A peptide is just a short string of amino acids. Insulin and oxytocin are peptides. And GLP-1 medications are peptides. But the wellness/biohacking peptides are essentially completely unstudied in humans. In most cases we are going from rodent studies to giving them to humans. RFK Jr. has signaled that he will allow compounding of some of these products, and if so, that means they are likely going to be everywhere. Since they are unstudied, we do not know the consequences of these drugs, so that is concerning.

I hope you find this informative. Dr. Colenso-Semple is a wealth of information, and believed women deserve science, not marketing!

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If you are like me, you have probably been inundated with content about protein in the news, on podcasts, and on social media, all extolling its almost magical benefits. Weight loss, brain health, bone health, muscle health, longevity…protein can do it all. (But can it do my laundry? I digress).

Is everything you put in your mouth filled with protein? WHY NOT? IT IS THE ONE DIETARY INGREDIENT TO RULE THEM ALL.

The protein pressure is real, but how much protein do we need?

This is a common question, and it’s no wonder as in 2025 we approached protein monism, where protein is everything and everything is protein. (Monism is an idea or doctrine where there is only one thing or one kind of thing).

Obviously, we need protein. Just like we need fats, carbohydrates, and vitamins, etc. But we also need to enjoy our meals and not feel like life is one big hunt for the next protein bolus that we can hopefully choke down. Let’s start with what people really need, because 2025 was filled with some pretty serious protein myths, such as women in menopause need more protein per kg of body weight than anyone else or if you have 20 g or less of protein in a meal that it gets turned into sugar. It seemed like a lot of people were engaged in protein one-upmanship in the fight for attention on social media.

The evidence-based recommendation for protein is 1.2-1.6 g/kg/day. This means that someone who weighs 80 kg needs 96-128 g per day. A competitive athlete may need a little more (maybe 1.6-1.8 g/kg/day). It’s ideal to divide the protein into three meals, aiming for at least 20-30g per meal, but total protein matters more than timing throughout the day. (There are probably nuances in how protein should be divided up throughout the day for competitive athletes.) In North America, many people fall short on protein at breakfast, so finding ways to get a little extra protein here could help many people meet their protein goals. Elizabeth Ward and Hilary Wright (@MenopauseDietPlan on Instagram) recently posted some easy protein- and fiber-filled breakfast options (click here).

Adequate dietary protein can protect against sarcopenia (muscle loss with age), and when combined with resistance training, helps us build muscle. There is also evidence that protein can help with fat loss, help someone feel full, and, when people are getting enough calcium, can help maintain bone mass. No real expert is arguing that protein isn’t important, but those of use who don’t profit from the protein-hype machine are also not promoting it as a magical health elixir. Dr. Stuart Phillips, a PhD and internationally respected expert in protein and muscles, refers to protein as “the (thin) layer of icing) or the sprinkles on the icing.” You can read a recent article of his here: “2025 Was the Year Protein Jumped the Shark.” When we are talking about muscle gains with protein, we mean complete protein, not collagen.

Mel Robbins apparently also noticed the protein conversation, and announced this week that she is entering the protein market. Here are some quotes from her about her new product, Pure Genius:

“TODAY I am launching my first-ever product and it’s something that I’m so proud of because there is absolutely nothing like it in the world until now.”

“It’s something I needed in my own life, and couldn’t find, so I partnered with some of the world’s leading nutritional and scientific experts to create it.”

“unlike any other protein you’ve ever had, It’s a protein shot containing 23 g of complete protein in a 3 oz bottle…”

(The name Pure Genius immediately made me think of Wile E. Coyote, who claimed he was a Super Genius.)

Here is the product:

To me, the copy put out by Robbins read like this was completely her idea, or her idea along with some other doctors she had interviewed on her podcast, and then they worked to design a novel product and bring it to market because there was nothing like it. I’m surprised she couldn’t find a protein shot, as there are quite a few on the market, not to mention protein bars, protein powders, protein drinks, and protein cereals, etc. But then again, it’s hard for me to believe that there is a market for yet another type of lipstick or yoga pants, and yet capitalism finds a way to deliver new products and make it seem like there is nothing like them. Also, when you have a large audience, I suspect it is easier to muscle into a crowded market.

I get that it is standard marketing hyperbole for brands to claim their product, be it jeans or bras or massive-lash mascara or whatever is UNLIKE ANYTHING ELSE. But it’s quite a flex to claim that your 23 g protein shot is so novel that it is “unlike any other protein,” and yet be very much like a 23 g protein shot that was introduced in March of 2025, called Genius Shot. So similar, in fact, that the old Instagram account for Genius Shot directs to Pure Genius Protein.

I was first alerted to this by Beth Wilkas Feraco (a great follow on Instagram, you can find her here), but many others soon chimed in wondering how Pure Genius, by Mel Robbins, was substantively different from Genius Shot, by Dr. Mike Israetel? I went over to Dr. Israetel’s Instagram, and sure enough, this is a post of his from March 2025: 23 g of complete protein in about 3 ounces.

The math isn’t mathing regarding the claim of “absolutely nothing like it in the world until now.” It’s completely fair to find a business opportunity with a brand you love or be approached by one that may be struggling (I don’t presume to know the nature of connection, only that it seems there is one). But claiming there was nothing like it before is not, in my opinion, transparent. And honestly, if it were just this, I’d be rolling my eyes and not writing about it, because, while expensive, Genius Shot delivered a whack of high-quality protein for 90 calories in 3 ounces.

The problem is that when you get people’s attention, you get their attention. Pure Genius was then checked by several coaches, registered dietitians, and Dr. Kevin Klatt, who is a PhD, metabolism researcher, and registered dietitian, and they all noticed that Pure Genius has less complete protein than Genius Shot (there are details on the math behind calculating this below). I spent a little time messaging Dr. Klatt about this, and I shared his post about it on Instagram. I learned something very interesting from him about protein labeling that I want to share with you.

(Side note, if you want an expert’s take on the new food pyramid, check out Dr. Klatt’s Substack).

The protein that was the star of Genius Shot was beta-lactoglobulin or BLG, which is the major whey protein of cow and sheep’s milk. It is highly concentrated and dissolves well, so it is a good way to get a lot of protein in a small volume.

The image above is the nutritional label for the old Genius Shot. The amount per serving column is the amount of protein, any protein, in the serving; this can be a complete protein, like BLG, or an incomplete protein, like collagen. As the only protein here is BLG, we can assume that all 23 g is BLG. We can double check this with the percent daily value (%DV), the column on the right-hand side in the image. This %DV is calculated based on a maximum of 50 g. Dr. Klatt told me that it is corrected for protein quality using a metric called PDCAAS (Protein Digestibility Corrected Amino Acid Score), which measures protein quality based on amino acid content and digestibility. BLG is a complete protein with a PDCASS of 1, meaning it counts as 1 gram per gram toward the percent daily value. This is why 23 g of protein in Genius Shot is 46% of the daily value, because 23 is 46% of 50.

The promotion for Mel Robbins Pure Genius claims “23 g of complete protein,” as well as collagen for hair and skin benefits. (As an aside, the science supporting collagen supplements for skin and hair is weak.) Collagen is an incomplete protein (it lacks tryptophan and is low in leucine, which is critical for muscle protein synthesis).

Now let’s look at the nutrition facts and ingredients for Pure Genius (screenshot from January 7, 2026).

There are two sources of protein, BLG and collagen. Pure Genius still has 23 g of protein, so some of those grams must be collagen.

You can see the %DV for protein for Pure Genius is 32%, lower than the 46% for Genius Shot. This is because the PDCAAS score for collagen is zero, meaning the protein in collagen does not count towards the %DV. Since 32% of 50 g is 16 g, this means, according to their own labeling, the Pure Genius protein shot is 16 g of complete protein, not 23 g. There is no other way to do the math. The %DV of protein decreased because the high-quality protein was diluted with collagen.

Why make Pure Genius lower in complete protein than Genius Shot? Who knows? Perhaps because they believe the collagen hype (which is primarily based on industry-funded data), and I suspect focusing on hair and skin may help them stand out as a product for women. Collagen is likely cheaper than BLG, so replacing BLG with collagen, in theory, should increase the profit per bottle.

There will be some people who complain that I, and others, are attacking Robbins because she is a woman, and no one attacks men for introducing similar products. I’m not attacking anyone, I am reviewing a product, and pointing out that it doesn’t appear to be as novel as claimed and explaining the protein component doesn’t match some of the marketing. I review products aimed at women, so I’m going to be writing about women investors because this market interests them. For those who are interested, here is one example of a product created by men that I appropriately lambasted.

Pure Genius isn’t a bad product, but it has 16 g of complete protein, about one-third less than the label implies. While it’s accurate for the front label to say 23 g of protein, you, the consumer, always need to do due diligence with protein products and check the %DV if the amount of complete protein matters to you. Given protein is more the icing on the cake, it’s unlikely a 7 g difference in complete protein is going to make a big difference for most people, but if your sole reason for taking a protein shot is to maximize protein for your muscles, Pure Genius’ own labeling says they don’t deliver 23 g of complete protein, and that may matter to you, especially given the price of $4 a shot. For comparison, Oikos has a protein drink with 23 g of complete protein for 120 calories and also has 40% of your daily calcium, and some vitamin D, and it’s $2.99 for a bottle. Although at 7 ounces, unlike Pure Genius, it is not TSA-friendly for travel. Many Greek yoghurts or Skyr have 15-16 g of complete protein per serving and have other nutritional benefits, and are less than half the price of Pure Genius. Then again, price may not matter to some, and if people love Pure Genius and it works for them, then great.

I am not at all opposed to protein-supplemented products, and I have my favorites. I just strongly believe that people deserve to know what they are buying.

As Dr. Klatt said, you shouldn’t have to know labeling regulations and do math to know how much complete protein you are actually getting. Transparency matters. And the amount of complete protein in a product may matter for some people. Personally, I don’t want to pay for collagen as I don’t find the data compelling.

There is also another issue. Going forward, for listeners of Mel Robbins, the fact that she now sells a protein and collagen product also opens her up to the risk of bias. Will she be more likely to invite guests who overhype protein or collagen? It gets really sticky when products enter the picture. It will be interesting to see how many times protein and collagen are mentioned in her upcoming episodes.

Meanwhile, I wonder if the proteinification of everything will ever run its course? After all, once everyone is saturated with protein content, another AMAZING superfood or supplement will be needed to move the needle for clicks and products. Who knows, maybe 2026 will be the Year of Fiber (it has always been important, but it is ripe for a wellness make-over). Although given the MAHA food pyramid, I suppose there are plenty of wild cards. Here’s hoping 2026 is NOT the Year of Beef Tallow.

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References

Stuart M. Phillips, Stéphanie Chevalier, and Heather J. Leidy. 2016. Protein “requirements” beyond the RDA: implications for optimizing health. Applied Physiology, Nutrition, and Metabolism. 41(5): 565-572. https://doi.org/10.1139/apnm-2015-0550

Here is the link to the Independent Auditor’s Report in natural products in Canada https://www.oag-bvg.gc.ca/internet/English/parl_cesd_202104_02_e_43806.html

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Ask Dr. Jen

I’ve been hearing that creatine supplements are essential for bone and muscle health as we age. Should every woman in menopause be taking them? Thanks!

-Via The Vajenda

Everywhere you turn, on social media anyway, it seems that there is a meno-influencer recommending creatine as the new magic cure for aging. Unlike many other supplements, creatine has been studied in clinical trials, providing us with more data than is typically available for many other supplements.

So what does the evidence show? Is the hype worth it? Read on, so you can decide for yourself.

What is Creatine?

Creatine is a naturally occurring substance made from amino acids. Humans get about half of the creatine they need from diet, and the rest is made in the liver and kidneys. Most of our creatine is stored in skeletal muscle. Creatine plays a critical role in supplying energy and in metabolism. Most people can easily get the creatine they need from their diet.

Creatine Supplements - The Basics

Creatine supplementation increases creatine levels in muscles and has been shown in numerous studies to improve energy availability, especially during maximal effort, which enhances the ability to perform high-intensity exercise. When combined with resistance training, it increases lean mass. It may also improve training adaptations and post-exercise recovery by stimulating growth factors and activating satellite cells. This is why you may have seen it promoted by athletes, either as an advertisement or simply as part of their regimen. It is particularly useful for activities that involve sprinting or bursts of energy, such as hockey or soccer, or for resistance training to increase muscle mass. Creatine supplementation may also reduce muscle recovery time, which may allow a professional athlete to train harder.

There are several decades of safety data on creatine supplements, and studies with doses of up to 30 g per day for five years have shown that supplementation does not pose a health risk. There has been concern about the effects on kidney function, and for an otherwise healthy person with normal kidney function, there appears to be no cause for concern.

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Creatine: Protecting Bone and Muscle Health in Menopause. What Does the Data Show?

Creatine may well help an athlete gain a competitive edge, but what about women in menopause looking to protect bone and muscle health? After all, some data suggest that creatine may provide energy to bone and may stimulate osteoblasts, which are cells that build bone. In addition, when muscle pulls on bone, it also provides a stimulus to build bone. Therefore, if creatine helps someone build more muscle, might it also give an additional boost to the bones? And can creatine help women maintain muscle mass and prevent sarcopenia, which is the gradual loss of muscle mass and strength over time?

What’s truly exciting is that unlike other supplements where I would be trying to make sense of some truly dismal studies, we actually have some quality studies with creatine! Even for women in menopause! I KNOW!!!!

So let’s look at the data.

There are pilot studies and shorter-term studies that suggest a benefit of creatine on bone health. For example, a study of 33 women found that 5 g a day of creatine for women who were also doing a supervised resistance training program had a 3.4% improvement in bone density at the femoral neck (a 5% increase reduces fracture risk by 25%). But we won’t be discussing the preliminary work as we actually have long-term studies to discuss.

(I KNOW!!!)

Creatine Supplementation and Resistance Training

This study (Gualano et al) enrolled women aged 60 years or older with osteopenia or osteoporosis. These women had not been doing regular exercise, and were considered “apparently vulnerable” (which was defined as “people who commonly complain of being 'slowed up' or have disease symptoms.”)

The women were randomized to one of four groups: placebo, creatine, placebo plus resistance training, and creatine plus resistance training. The creatine dose was 20 g a day for 5 days (loading dose), then 5 g a day. The resistance training was twice-a-week for 24-weeks in an intrahospital gym and was supervised by two fitness professionals. The training program included the following exercises: leg press, leg extension, squat, seated row, bench press, lat-pull down, and sit-ups.

After 24 weeks, there was no change in bone density or bone markers for any of the participants, so no benefit or creatine over placebo for bone health with or without resistance training.

Muscle strength was assessed with a 1-RM (the maximum weight for one rep) for the leg press and bench press. After 24 weeks, there were similar gains for the leg press for the creatine plus resistance training and the resistance training alone groups, which were both statistically better than placebo. Regarding the 1-RM bench press, the creatine plus resistance training had a statistically significant improvement versus the other three groups.

Regarding physical function tests, creatine and resistance training groups had superior gains in one of the tests versus the two groups without resistance training, and in one of the tests. In the either test all groups performed the same after 24 weeks.

The groups that took creatinine and did resistance training had the most gain in lean mass compared to the other three groups–in absolute numbers that translated into a 1.31% increase in lean mass or a 0.3 kg increase over 24 weeks. The groups that took creatine by itself or took placebo and did resistance training had a smaller gain in lean mass. The group that faired the worst was the placebo group with no resistance training, who lost an average of 1.2% of their lean mass (an average of 0.2 kg).

The study is small, with only 15 women completing each group, but it is well-designed. I think of it as an excellent exploratory study which provides a useful guide for future studies. One question that arises from this study is with longer use would there be greater gains in lean muscle mass for creatine plus resistance training versus resistance training alone?

Verdict: Creatine plus resistance training and resistance training without creatine can help with building lean mass and strength. Creatine plus resistance training may provide a small additional benefit in some measures. Creatine with or without resistance training did not benefit bone. Admittedly, 24 weeks may not be long enough to see a bone benefit, but there were blood markers for bone turnover, so if there was a small effect at a cellular level that should have been picked up. It’s also possible, of course, the study may not have had enough participants.

Creatine and Bone Health: A 2-Year Study Without Resistance Training

In this randomized double-blind placebo-controlled trial (Sales et al) postmenopausal women with osteopenia who were younger than age 70 received either 3 g of creatine monohydrate daily or a placebo. The women tracked their physical activity, but there was no activity intervention. Bone health was tracked with a bone density scan (DEXA), specialized CT scans, and blood tests for markers of bone health. The women were also evaluated using physical function and muscle strength tests, and their muscle mass was assessed. A total of 170 women completed the two-year study.

What did they find? Two years of creatine had no beneficial effect on bone health or physical function by any of the measures tested. This study also tracked lean mass as well as fractures and falls. The authors concluded that, “these findings suggest that the therapeutic effects attributed to Cr supplementation in conditions characterized by bone and muscle loss are primarily mediated by enhancements in the adaptive effects of exercise training, and cannot be achieved by Cr alone.”

Verdict: A well-designed, randomized, placebo-controlled trial shows that 3 g of creatine per day for 2 years in women not participating in resistance training provides no benefit for bone or muscle health. Many women in the study were getting the recommended amount of aerobic exercise a week, and this did not affect results.

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Two-Year Randomized Trial of Creatine and Resistance Training

This study was done by the same group that showed had shown some benefit to bone health with one year of creatine supplementation and resistance training (Cilibeck et al). This new study enrolled 237 postmenopausal women (mean age of 59 years). The women were randomized to receive creatine (0.14 g/kg/day) or placebo (a higher dose than the original study, as a 70 kg woman would be taking 9.8 g/day). All participants engaged in supervised resistance training three days a week, supervised brisk walking three days a week, and unsupervised walking three days a week. Outcomes included bone density, bone measurements by ultrasound, lean mass, strength, and walking speed. A total of 86 women who took creatine and 88 who took the placebo completed the study.

After 2 years, creatine monohydrate supplementation with resistance training did not impact bone density at any of the sites measured when compared with resistance training alone. Creatine supplementation did provide some benefit to the structural properties of bone in some of the imaging measurements, but also in some other measurements, there was no benefit. The authors speculated that the creatine may have stimulated bone remodeling, and in some areas that may have led to bone formation, but in other areas there could also have been more breakdown of bone. While some of these beneficial changes are expected to improve bone resilience, the changes observed were below the threshold for fracture prevention.

Creatine, when combined with resistance training, increased lean mass and also increased walking speed over placebo. While these changes were statistically significant, it’s also important to look at the actual numbers–the creatine plus resistance training group increased lean mass by an average of 2.1 kg over 2 years, and the increase for the placebo plus resistance training group was 1.8 kg over 2 years, a difference of 0.3 kg. With walking speed, the creatine group took 1.5 seconds off their time for walking 80 meters versus only 0.1 second for the placebo. Creatinine did not provide any additional benefits over resistance training alone for measures of strength (hack squat and bench press strength). The authors hypothesized that they didn't see any benefit in strength with creatine supplementation in the current study because of “the large beneficial effect of resistance training alone on muscular strength,” and the “hack squat strength measure is quite variable,” which could obscure a small effect.

The study has some limitations. There was a relatively low compliance with the protocol, and a fair number of people who stopped the study. Also, the authors monitored kidney and liver function closely, and any potential concerns led to a reduction in dose, although the authors attempted to account for that in their analysis and the benefits of creatine and the lack of benefits (depending on the measure studied) remained the same. To me, this likely represents how an average woman might use creatine, because taking something every day is hard and if someone has some changes in liver or kidney function, their doctor will almost certainly ask them to reduce their creatine or even stop it so they can see if there is any link.

Verdict: No benefit of 2 years of creatinine on bone density, but the change in some bone markers should be evaluated in a longer-term study. Creatine increased lean mass over placebo, and while this change was statistically significant, whether a net increase of 0.3 kg of lean mass over resistance training alone is clinically significant (meaning does it prevent sarcopenia or reduce falls) is unknown.

Other Data

Several meta-analyses have looked at creatine and older populations, and the data is pretty consistent with creatine providing an added benefit for muscle mass and strength over resistance training alone. Whether this translates into reduce sarcopenia is not known. However, a more recent meta-analysis that looked at studies that only included older women found only an improvement in strength with creatine plus resistance training, not muscle mass, but this did not include the two-year trial from 2022 which was published later.

The benefits with muscle mass and/or strength haven’t yet translated into studies that have shown a reduction in end points like sarcopenia, fractures, or falls, but it’s also important to add that we may need longer-term studies to see these changes (and of course longer-term studies may also not show benefit, so we shouldn’t speculate).

While changes in muscle strength and/or lean mass in studies may be statistically significant, and may well be important to professional athletes where a 0.1% difference can make a difference, we don’t yet know if the small changes seen in muscle mass and strength with creatine plus resistance training over resistance training alone are clinically meaningful for the general population.

A recent meta-analysis (Burke et al) looked at the amount of muscle that is actually gained and reported a 0.10-0.16 cm change with a combination of creatine supplementation and resistance training “on changes in the upper and lower body muscle thickness.” There is also some data that suggests some people are creatine responders while others are not, so some people may see more gains over others.

Summary

• Every woman in menopause does not need to take creatine for bone or muscle health. However, adding in resistance training will benefit almost every woman.

• If you are not doing resistance training, there seems to be no value to taking a creatine supplement for the specific purposes of bone or muscle health. I would be suspicious of people telling you that it is proven to protect against osteoporosis or sarcopenia as a stand alone therapy. In fact, it could be harmful to tell women that creatine itself can be beneficial as it may lead people to erroneously believe they can just take the supplement without the exercise to get the benefit for muscle health. That’s why I think it’s unethical for meno-influencers to push creatine without first explaining it should be considered an add-on therapy to those committed to a resistance training program. It is not a stand alone therapy. (Basically, you’re wasting your money taking creatine if you aren’t also participating in a resistance training regimen.)

• Women in menopause who are regularly engaging in resistance training may see an additive benefit in strength and/or lean mass from daily use of creatine, but whether those gains are meaningful medically, for example a reduced risk of sarcopenia or falls over resistance training alone isn’t known (remember, resistance training alone is incredibly powerful). An individual can decide whether a 0.3 kg improvement in lean mass over 2 years with creatinine plus resistance training over resistance training alone is of value to them. Some people may wish to take it to see if it improves athletic performance or improves recovery. As some people may see more results than others, that may explain reports of why some find it helps a lot and others not at all.

• Creatine seems very safe, even in doses up to 30 g a day (although side effects may be more common with higher doses). The typical dose for someone wanting to see if creatine gives them an added benefit to resistance training is 3-5 g a day. The idea of needing a loading dose for several days has largely been discarded.

• Creatine does not harm the kidneys. However, creatine supplements can raise the blood level of creatinine, which is a test that we use to monitor the health of the kidneys, and so anyone with kidney disease should first discuss their proposed use of creatine with their doctor. The effects of creatine for people with known kidney disease are less certain as we don’t have long term studies of this population. However, it is reassuring that there were no adverse kidney effects in women in menopause in the two long term studies.

• A creatine supplement should ALWAYS be third-party verified for safety. There are many reports of sports supplements that contain pharmaceuticals and even banned substances. ONLY take a product with a seal from a recognized third-party tester, a claim on the website that says “third party testing” without the name of the testing company is about as good as a statement that says “my mom tested this and she says it’s great!” USP-Verified, NSF, and Informed Sport are three recognized companies for third party testing, but with creatine, because it’s a sports supplement, you will get an extra level of safety if the product says it is NSF certified for sport, or verified by Informed Sport, as this means there has been additional testing or banned substances. The label should be on the packaging and easy to see, if it’s not, give it a pass, regardless of who is promoting it. Here is a good list from Men’s Health of creatine products with price, and the pros and cons of each product, as well as information about the third-party testing. There is definitely a lower cost alternative for someone wanting to give it a try for three months. Another resource to compare creatine supplements is ConsumerLabs.com, and I believe many libraries offer a subscription.

It’s clearly possible to do quality clinical trials with supplements. My guess the reason that researchers have devoted the time and effort into studying creatine is that the basic science suggested a valid hypothesis (important first step), the original preliminary studies were well-done and looked promising, and then each subsequent study showed benefit or a new angle to evaluate. As the quality of the data improved, so did the ability to get funding. And so on. For example, the two-year clinical trial for resistance training with and without creatine received funding from the Canadian Institutes of Health Research and the Canada Foundation for Innovation.

The reason many supplements with bold claims never progress beyond preliminary studies is the hypothesis was never robust, the preliminary studies showed no benefit, or the preliminary studies were low quality. Why would an ethical researcher want to commit precious time, energy, and funding here? Just something to consider the next time you see supplements promoted based on small, short-term studies or even based on animal data.

I know the latest thing is creatine for brain health, and I will tackle that data in another post. Meanwhile, there are actual evidence-based things you can do for brain health, which I covered in this post.

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References

Kreider, R.B., Kalman, D.S., Antonio, J. et al. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr 14, 18 (2017). https://doi.org/10.1186/s12970-017-0173-z

Devries MC, Phillips SM. Creatine supplementation during resistance training in older adults-a meta-analysis. Med Sci Sports Exerc. 2014 Jun;46(6):1194-203. doi: 10.1249/MSS.0000000000000220. PMID: 24576864.

Gualano B, Macedo AR, Alves CR, Roschel H, Benatti FB, Takayama L, de Sá Pinto AL, Lima FR, Pereira RM. Creatine supplementation and resistance training in vulnerable older women: a randomized double-blind placebo-controlled clinical trial. Exp Gerontol. 2014 May;53:7-15. doi: 10.1016/j.exger.2014.02.003. Epub 2014 Feb 13. PMID: 24530883.

Sales LP, Pinto AJ, Rodrigues SF, Alvarenga JC, Gonçalves N, Sampaio-Barros MM, Benatti FB, Gualano B, Rodrigues Pereira RM. Creatine Supplementation (3 g/d) and Bone Health in Older Women: A 2-Year, Randomized, Placebo-Controlled Trial. J Gerontol A Biol Sci Med Sci. 2020 Apr 17;75(5):931-938. doi: 10.1093/gerona/glz162. PMID: 31257405.

Cilibeck PD, Candow DG, Gordon JJ, Duff WRD, Mason R, Shaw K, Taylor-Gjevre R, Nair B, Zello GA. A 2-yr Randomized Controlled Trial on Creatine Supplementation during Exercise for Postmenopausal Bone Health. Med Sci Sports Exerc. 2023 Oct 1;55(10):1750-1760.

Candow DG, Chilibeck PD, Forbes SC. Creatine supplementation and aging musculoskeletal health. Endocrine. 2014 Apr;45(3):354-61. doi: 10.1007/s12020-013-0070-4. Epub 2013 Nov 5. PMID: 24190049.

Stares A, Bains M. The Additive Effects of Creatine Supplementation and Exercise Training in an Aging Population: A Systematic Review of Randomized Controlled Trials. J Geriatr Phys Ther. 2020 Apr/Jun;43(2):99-112. doi: 10.1519/JPT.0000000000000222. PMID: 30762623.

Burke R, Piñero A, Coleman M, Mohan A, Sapuppo M, Augustin F, Aragon AA, Candow DG, Forbes SC, Swinton P, Schoenfeld BJ. The Effects of Creatine Supplementation Combined with Resistance Training on Regional Measures of Muscle Hypertrophy: A Systematic Review with Meta-Analysis. Nutrients. 2023 Apr 28;15(9):2116. doi: 10.3390/nu15092116. PMID: 37432300; PMCID: PMC10180745.

Dos Santos EEP, de Araújo RC, Candow DG, Forbes SC, Guijo JA, de Almeida Santana CC, Prado WLD, Botero JP. Efficacy of Creatine Supplementation Combined with Resistance Training on Muscle Strength and Muscle Mass in Older Females: A Systematic Review and Meta-Analysis. Nutrients. 2021 Oct 24;13(11):3757. doi: 10.3390/nu13113757. PMID: 34836013; PMCID: PMC8619193.

Turmeric has been in the news, or rather, complications from turmeric supplements, as 57-year-old Katie Mohan told NBC News her story about turmeric-induced liver injury, which multiple news sites have since picked up. Ms. Mohan’s age is relevant given the highly targeted marketing of turmeric supplements to women for menopause-related symptoms. There has been a rise in liver injury associated with turmeric/curcumin supplements, and this appears to coincide with the introduction of products designed to enhance the absorption of turmeric or curcumin.^1-4 (Curcumin is a compound found in turmeric).

Readers of The Vajenda know that I have previously written about turmeric here. For those who are newer readers, welcome, and, I have a series on supplements (access here), where I explain issues with regulation and review products.

While some people may hear about supplements from their health care professional, the increasing commercialization of menopause appears to have spawned a growing number of menopause influencers and celebrities either endorsing specific menosupplements on social media, selling their own products, or partnering with companies to create/sell “curated” supplements. When these influencers have academic degrees, like MD or PhD, the consumer may think these products are backed by quality research and have been rigorously tested in the way that pharmaceuticals are tested, but in the United States, there is no testing required to bring a supplement to market (read more about that here).

When consumers investigate the webpages for many supplements there is typically a list of academic references, adding a veneer of scientific legitimacy. However, on closer inspection, these references often contain low-quality studies, irrelevant publications, or, quite frankly, garbage. Many consumers are unfamiliar with how to interpret scientific studies, and may trust the person with the academic credentials that this list of references represents robust science.

Two popular menopause/wellness influencers on social media who have reached minor celebrity status and who have legitimacy in the space courtesy of their academic degrees, Mary Claire Haver, M.D., and Stacy Sims, PhD, each promote a turmeric supplement. Given the rise of turmeric-related liver injury, I feel it is in the public’s interest to see the promoted science behind these products.

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Dr. Mary Claire Haver - The ‘Pause Nutrition Turmeric Supplement

If a prospective buyer wants more information about turmeric, they are directed to the “ 'Pause Blog, Turmeric 101.” Here we find the following claims about curcumin, supported by several references:

Here’s the list of sources:

References 1, 4, 6, 7, and 8 are rodent studies, which are preclinical work and irrelevant when it comes to evaluating the efficacy and safety of a product for human women. Can you imagine the uproar if we approved vaccines or a new pharmaceutical for hot flashes based on rodent studies? There should be three phases or layers of human trials that happen after the rodents, but before a product is offered en masse to people.

Reference 2 is a review article about turmeric and ginger from 2011.⁵ There are more recent review articles in higher impact journals that conclude that we still don’t have good data to support using turmeric.^6-7 The problem with review articles is most of the studies of turmeric or curcumin have issues, so it’s possible to cherry pick and come up with a more positive review depending on the rigor of the approach. Regardless, Dr. Haver’s claim that curcumin has a role in ”a normal inflammatory response” is so vague it’s meaningless. It’s important to note that many supplements are marketed based on blood tests that are supposedly markers of health, as is done here with “markers of aging,” but what actually matters are meaningful health outcomes like a lower risk of high blood pressure or reduced rate of stroke. Biomarkers are smoke and mirrors.

Reference 3 is used to support Haver’s claim that curcumin can decrease hot flashes and is a randomized, blinded, clinical trial of curcumin vs. vitamin E vs. placebo over 8 weeks from Iran.⁸ The first two sentences in the introduction are nonsensical and should have been flagged before publication to clarify what the authors actually meant, which makes me concerned about the quality of the peer review. The Greene Climacteric Scale, a standard scale, was used to report changes in symptoms; regarding vasomotor symptoms (aka hot flashes and night sweats), all groups improved equally and there is no difference between the 26 women who took curcumin and the 28 who took placebo group. In addition, the women taking curcumin, vitamin E, and the placebo were all equally “extremely satisfied” with the outcome on the scale used in the study. The authors themselves conclude, “In other domains, significant improvement occurred in all groups compared to the baseline (except for the sexual domain); however, there was no significant difference between the curcumin and vitamin E groups with the placebo group.” I am not sure how anyone who read this study carefully and understood it would have used it to support turmeric/curcumin for hot flashes.

The next clinical trial is also from Iran and also compares curcumin and vitamin E with a placebo over eight weeks.⁹ According to Dr. Haver, this supports the use of turmeric for hot flashes as well as for “mood and a positive outlook on life.” The sample size is small (30 women took curcumin) and the groups differed in a significant way from each other–only 55% of the women who were given the placebo reported they were satisfied with their life at baseline versus 74% who took placebo. While the investigators report that the women who took curcumin had substantially fewer hot flashes/week at week 4 and 8 versus those who took a placebo, there was no difference in menopause symptoms between groups in the Greene Climacteric Scale, which includes questions about hot flashes. It’s problematic that the authors did not report out the component of the Greene Climacteric Scale that measures vasomotor symptoms to compare with with the self reported measurements for hot flashes. This should have been addressed in the discussion, but was not. Regarding mood, the authors conclude, “Curcumin and vitamin E had no significant effect on anxiety in postmenopausal women in the present study.” Not sure how this study can support Haver’s claim that turmeric has a benefit on mood or a positive outlook on life, and in my opinion it’s pretty sketchy to use it to support a benefit for hot flashes.

I did not bother to read the rat study supporting turmeric for improving “mood and a positive outlook on life,” because even if one can measure if a rat has a positive outlook on life, how would that apply to a woman?

There’s a reason the 2023 Menopause Society Position Statement on nonhormonal therapy for hot flashes doesn’t include turmeric or curcumin, the data just isn’t there.¹⁰

If a medical student submitted Dr. Haver’s blog to me as an assignment, I would fail them. It’s no surprise that the consumer watchdog group, Truth in Advertising, sent Dr. Haver a letter of concern in October 2024 about how she markets her supplements. You can find the letter here.

Dr. Sim’s Momentous Peri & Post Menopause Support Stack

Momentous has a Peri & Post Menopause Support Stack that is five supplements including turmeric and was “formulated with Dr. Sims.” Apparently, “research unequivocally supports each element” in their stack.

For those who don't know, Dr. Sims’ registered trademark is “Women are not small men,^®”

Surely, the science here will be robust. Unequivocal, in fact. After all, Momentous claims there are six credible reviews and studies to support this supplement stack of five products for peri and post menopausal women. Only one paper for turmeric is listed. Hope it’s a good one!

It’s a study done on men!

I shit you not, this pilot study of turmeric on 19 men aged 18-39 who followed “a muscle-damaging protocol” is apparently unequivocally “credible” to support the use of turmeric for “the unique needs of women during and after menopause.”

I’m not going down the antioxidant-muscle-soreness rabbit hole here, but most studies and a Cochrane review don’t support a clinically meaningful effect.¹¹

There are four other references for the “science” of turmeric on another page on the Momentous site. To be clear, Sims' name is not on this page, but if a consumer decides to poke around the website, they would find these references, which might make someone think, “Wow, there really is good science women!” Three of these are small studies are on men, and one is on rat prostates.

For fun, I looked up the reference for the Alpha GPC supplement in the Peri & Post Menopause Stack…it’s a study of seven men, mean age of 30.1 years, with two years of resistance training experience. I guess this unequivocally supports the use of this product for women ages 40 and up.

Irony is dead, killed by the supplement industry.

The Commercialization of Menopause

At this point, there will be someone on the interwebs who thinks I’m mean. Don’t complain that I’m mean, prove me wrong with science. Do you want to know what I think is mean? Promoting a turmeric supplement to vulnerable women in perimenopause and menopause that is six times the price of one from Costco, and the best references that can be dredged up, are, in my opinion, drinking game material.

Take a shot every time you read mice, rats, or men!

What is the risk of liver toxicity associated with turmeric/curcumin supplements? Who knows, understudied. Are particular people more vulnerable? Who knows. While LiverTox estimates the risk of liver toxicity might be in the 1 in 10,000 to 1 in 100,000 range, we don’t really know.¹ Now those numbers may seem small to you, but according to a recent study, an estimated 11,400,151 Americans took a turmeric/curcumin supplement within the previous 30 days; if the 1/100,000 is accurate then 114 people could be at risk of liver toxicity.¹² If there is is 1 in 10,000 risk, then it is 1,140 people. How many cases of liver toxicity are acceptable for a product with no robust evidence?

With 11 million Americans reportedly taking turmeric, and almost certainly more than half of them women, you can see why this product is appealing to sell for menopause–the market is already built in. I investigated a turmeric supplement to see what the profit margin might be, and I can get a turmeric supplement for about $7.27 a bottle. If I sell 8,333 bottles, which is the smallest number I can order, I net a profit of $195,302. It just takes a few emails to do this. The company that makes the product can design the label, bottle the product, store the inventory, and I can link it to a Shopify site for sales. With enough followers eager to follow my protocols, this could be like printing money.

I have no idea about the profit from a company like Momentous, but Altheletetech News reported that the “Utah-based brand tripled its revenue from 2022 and projects to double its revenue again this year.”

I also have no idea what kind of money people get from partnering with companies like Momentous. However, I have seen an email from a recruiter looking for partners for supplement brands, and they claimed that some medical doctors are making $20,000 a month for about 10 hours of work, where the work is helping to craft advertising messages that resonate with their followers and promotion on social media.

Some may ask why I didn’t notify Haver or Sims them before I published this article. I am not their unpaid research assistant. When I find minor errors or I question a reference used by a medical professional on social media, I contact the person personally out of professional courtesy for clarification. But commercializing menopause through products is an entirely different situation. I don’t tell pharmaceutical or consumer brand companies, like Vagisil, when I am going to write about their products, so why would I tell people who sell supplements, which are simply unregulated pharmaceuticals? If someone is selling a product or has verified one with their expertise, it is their responsibility to vet their references. If they stand by these references, well, you the reader can decide what you think about that.

I have two major concerns. One is when there is no good data to support any benefit for turmeric/curcumin use in human women for menopause, you the consumer are assuming all the risks with no proven benefits. We also don’t know if specific products or doses are a concern. It’s buyer beware. And while the risks may be small, if it’s your liver that is injured, then you may feel very differently about that risk.

The other is the commercialization of menopause via supplements and the false sense of security consumers get from products marketed by those with academic credentials and a list of references that, in the end, are just slick marketing of mostly irrelevant citations.

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References

1. LiverTox, Turmeric https://www.ncbi.nlm.nih.gov/books/NBK548561/

2. Lombardi N, Crescioli G, Maggini V, et al. Acute liver injury following turmeric use in Tuscany: An analysis of the Italian Phytovigilance database and systematic review of case reports. Br J Clin Pharmacol. 2021; 87: 741–753. https://doi.org/10.1111/bcp.14460

3. Adverse effects associated with the consumption of food supplements containing turmeric, ANSES (the French Agency for Food, Environmental and Occupational Health & Safety) https://www.anses.fr/en/content/adverse-effects-associated-consumption-food-supplements-containing-turmeric

4. Australian Government Therapeutic Goods Administration, Medicines containing turmeric or curcumin - risk of liver injury, Safety Advisory. https://www.tga.gov.au/news/safety-alerts/medicines-containing-turmeric-or-curcumin-risk-liver-injury

5. Al-Suhaimi EA, Al-Riziza NA, Al-Essa RA. Physiological and therapeutical roles of ginger and turmeric on endocrine functions. Am J Chin Med. 2011;39(2):215-31. doi: 10.1142/S0192415X11008762. PMID: 21476200.

6. Kathryn M. Nelson, Jayme L. Dahlin, Jonathan Bisson, James Graham, Guido F. Pauli, and Michael A. Walters. The Essential Medicinal Chemistry of Curcumin Miniperspective. Journal of Medicinal Chemistry 2017 60 (5), 1620-1637 DOI: 10.1021/acs.jmedchem.6b00975

7. Liu S, Liu J, He L, Liu L, Cheng B, Zhou F, Cao D, He Y. A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health. Molecules. 2022 Jul 8;27(14):4400. doi: 10.3390/molecules27144400. PMID: 35889273; PMCID: PMC9319031.

8. Farshbaf-Khalili A, Ostadrahimi A, Mirghafourvand M, Ataei-Almanghadim K, Dousti S, Iranshahi AM. Clinical Efficacy of Curcumin and Vitamin E on Inflammatory-Oxidative Stress Biomarkers and Primary Symptoms of Menopause in Healthy Postmenopausal Women: A Triple-Blind Randomized Controlled Trial. J Nutr Metab. 2022 Jun 9;2022:6339715. doi: 10.1155/2022/6339715. PMID: 35719707; PMCID: PMC9203212.

9. Ataei-Almanghadim K, Farshbaf-Khalili A, Ostadrahimi AR, Shaseb E, Mirghafourvand M. The effect of oral capsule of curcumin and vitamin E on the hot flashes and anxiety in postmenopausal women: A triple blind randomised controlled trial. Complement Ther Med. 2020 Jan;48:102267. doi: 10.1016/j.ctim.2019.102267. Epub 2019 Nov 26. PMID: 31987231.

10. Shufelt, Chrisandra L. MD, MS, FACP, NCMP; Brown, Vivien MDCM, CCFP, FCFP, NCMP; Carpenter, Janet S. PhD, RN, FAAN; Chism, Lisa Astalos DNP, APRN, NCMP, FAANP; Faubion, Stephanie S. MD, MBA, FACP, NCMP, IF; Joffe, Hadine MD, MSc; Kling, Juliana M. MD, MPH, NCMP, FACP, IF; Soares, Claudio N. MD, PhD, FRCPC, MBA; Thurston, Rebecca C. PhD, FABMR. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause 30(6):p 573-590, June 2023. | DOI: 10.1097/GME.0000000000002200

11. Ranchordas MK, Rogerson D, Soltani H, Costello JT. Antioxidants for preventing and reducing muscle soreness after exercise: a Cochrane systematic review. Br J Sports Med. 2020 Jan;54(2):74-78. doi: 10.1136/bjsports-2018-099599. Epub 2018 Jul 27. PMID: 30054340.

12. Likhitsup A, Chen VL, Fontana RJ. Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults. JAMA Netw Open. 2024;7(8):e2425822. doi:10.1001/jamanetworkopen.2024.25822

I published this post a year ago, but I have many new followers (welcome!), and it’s an important topic, so I wanted to share it again in case you missed it the first time around or if you are game for a re-read, because sadly it’s very timely.

On Monday, January 20, 2025, many aspects of health care in the United States are likely to change for the worse. A self-serving, anti-vaxxer who ignores science in favor of personal profit (Robert F. Kennedy Jr.) will almost certainly be in charge of the Department of Health and Human Services. Dr. Marty Makary, a forced birther whose telemedicine company sells compounded GLP-1s, is poised to take charge of the Food and Drug Administration. In 2023, Makary said to Congress, “Nothing speaks more to the intellectual dishonesty of public health leaders than their complete dismissal of natural immunity.” Perhaps he forgot about the 350,000 people in the United States who died from COVID-19 in 2020 alone? I shouldn’t have to say this, but the rush to make a vaccine happened because natural immunity wasn’t exactly working out for hundreds of thousands of people. Hey, nothing says “I respect the sanctity of life” more than being indifferent to the deaths of hundreds of thousands of people because it interferes with your contrarian views.

Both Kennedy and Makary are deep in the MAHA movement, which I can best describe as a mob of anti-science, pro-supplement super grifters. While it’s true the FDA is relatively toothless when it comes to holding supplement companies accountable, they still provide some critical consumer protection, but this could easily be weakened or even evaporate altogether. For example, we rely on the FDA for safety alerts when health concerns regarding supplements are raised. We rely on the FDA to investigate harm related to supplements, bar dangerous products from entering the country, and even seize adulterated or mislabeled products. And we rely on the FDA to ensure that tampons are being made safely.

Now consider all the supplement shills involved with the MAHA movement. Do you have faith that if one of their products is linked with liver failure, the Trump FDA will intervene? Or what if one of them wants to sell a new tampon infused with an herb? Do you think Trump’s FDA will visit the factory in Bulgaria to see how the product is made or seize any product entering the United States because it hasn’t been studied for safety? I don’t.

Big Supplement has a terrible back story in the United States, and what we need here is more regulation, not less, but I don’t think that’s in the cards. So, with that in mind, I think this post is an essential primer on how we got where we are supplement-wise because, sadly, I think history is about to repeat itself.

(This is a shortened version of the original post; I have removed some material unrelated to regulations. If you want to read the original, you can find it here).

The Shit Show Before the Shit Show

Adulterated and contaminated foods were all too common in the 1800s. If a cherry wasn’t red enough, add dye to the bottle, and if it’s toxic, who cares? Need a medication that makes people feel better? Add fortified wine. Want to dye your lashes? Who cares if the active ingredient causes blindness? And yes, these are all real examples. 

Then, in 1906, in an attempt to protect the American public, The Pure Food and Drug Act was passed, requiring accurate labeling and listing of additional, potentially harmful ingredients. While an important step, many dangerous over-the-counter cosmetics and medications remained, including Radithor, radioactive water (no, really), and Koremlu, a permanent hair-removing cream that contained thallium acetate (a rat poison that has since been banned due to its extreme toxicity to humans). Even when applied to the upper lip, the result could be hair loss all over the body, paralysis, and damaged vision. Yes, known poisons were on the market disguised as helpful remedies, people suffered, and the government had little recourse. 

A bill was introduced in the early 1930s to create more regulation, which was sorely needed,  but it went nowhere until, sadly, in 1937, a predictable tragedy struck. S.E. Massengill Co., in response to the demand for a liquid form of an antibiotic, sulfanilamide, created Elixir Sulfanilamide, primarily intended for children. The problem was the solvent, diethylene glycol, is highly toxic (it’s in antifreeze). Over 100 people in 15 states, many of whom were children, died. The Food and Drug Administration launched a massive cross-country investigation to track every ounce sold. It was awful because the company initially sent telegrams to pharmacies just stating there was a recall, omitting the key information that the medication was a poison that could be fatal even in very small amounts, so there was little urgency with the recall. 

Here’s a quote from the FDA commissioner at the time, Walter Campbell, pleading for more regulation:

"These unfortunate occurrences may be expected to continue because new and relatively untried drug preparations are being manufactured almost daily at the whim of the individual manufacturer and the damage to public health cannot accurately be estimated. The only remedy for such a situation is the enactment by Congress of an adequate and comprehensive national Food and Drugs Act, which will require that all medicines placed upon the market shall be safe to use under the directions for use. ..."

Honestly, when you consider that supplements are a growing cause of liver damage, Ayurvedic medicines are routinely contaminated with lead, and many supplements contain medications banned by the FDA, that quote from 1937 is sadly still on the nose today. 

Spurred on by the public outcry over Elixir Sulfanilamide, the 1938 Food, Drug, and Cosmetic Act was passed into law. The law required manufacturers to prove the drugs were safe and effective, prohibited false claims about efficacy, and legislated factory inspections. This is also where homeopathic remedies found their way into a sort of no-man’s land of medication. Senator Royal Copeland, a physician who became a homeopath, added homeopathic remedies in such a way that essentially excluded them from proof of efficacy as they had already “met” safety standards. 

Laws work for a while but must be updated or rewritten as beliefs change, new technology brings new products, and people find ways around the law. The 1960s and 1970s saw an explosion of the “natural” movement; health food stores began popping up everywhere, and vitamins, food additives, herbal products, and other remedies flooded the market. It became clear that more regulation was needed, but governments are rarely proactive regarding health; instead, they are reactive regarding tragedy. In 1989, another preventable mass poisoning occurred when over 1,500 people were affected by eosinophilia myalgia due to supplements containing L-tryptophan, and thirty-eight died. The exact source was never identified but was hypothesized to be a contaminant created or introduced during manufacturing. L-tryptophan products were removed from the market, and the illnesses stopped. This event spurred renewed interest in increasing regulation. In 1991, the FDA started implementing regulations to protect consumers and hold these companies to safety and advertising standards. 

The Dietary Supplement Health and Education Act of 1994

Not surprisingly, the industry pushed back. Legal battles ensued. Senator Orin Hatch, a Republican from Utah, stepped in and crafted a bill to let supplement companies essentially do whatever they wanted with the Dietary Supplement Health and Education Act of 1994, or DSHEA. Hatch was from Utah, a haven for supplements and multilevel marketing, which earned it the nickname  “cellulose valley.” Hatch was apparently a personal believer in supplements. Although the cynic in me thinks if supplement companies are among your biggest donors and your son is a lobbyist for a supplement company, you might develop a public taste for them. Apparently, Hatch displayed supplements in his office. Before Hatch stepped in, supplements in the United States were a $9 billion-a-year business; now it’s $50 billion. 

Hatch removed all regulations, not just for vitamins and minerals (think vitamin B12 or iron, things people might actually need to supplement their diets), but herbs, botanicals, amino acids…you name it. As long as the product doesn't make a specific medical claim, for example, ‘“treats yeast infections,” and somewhere, even in the tiniest print, has the get-out-of-jail free card statement, “These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease,” the product can literally be dirt scooped up from someone’s backyard, and it is perfectly legal. 

So yes, someone could remake Elixir Sulfanilamide and sell it because the American government doesn’t require any safety testing or proof the product contains what it claims. And lest you think the idea of antifreeze in supplements is absurd today, in late 2023, the FDA warned that multiple supplements labeled as tejocote (Crataegus mexicana) root were really yellow oleander (Cascabela thevetia), a poisonous plant that can kill even with very small doses. Nine of the ten products tested contained yellow oleander. Let’s say that one more time, 90% of products tested were poison. The investigation and subsequent warning to the public was the result of a toddler ingesting some of the product and ending up in the emergency room with heart problems. 

Here’s the real kicker. Products labeled as tejocote have been known since at least 2021 to contain the poisonous yellow oleander, and there have already been several reports of serious cardiac complications from ingesting products labeled as tejocote.  

In any other industry (other than gun manufacturing), if a known poison/manufacturing flaw that puts lives at risk had been identified, something would have happened. For example, all Boeing 737 Max 900 planes were grounded after part of the fuselage blew out of one plane at 16,000 feet. Hundreds or even thousands of people could be harmed by an unsafe supplement, so the carnage could easily be on the same scope as an aviation incident. but because it’s a supplement, maybe the FDA sends a warning letter to the manufacturer. That lacks the negative PR punch of a plane grounding and is certainly not very scary for a multimillion-dollar product. 

(And for my Canadian friends, don’t think things are much better. Even though supplements must be licensed by Health Canada, which means they have been “found to be safe, effective and of high quality,” Health Canada does no testing and relies on the word of the manufacturer.)

Once in a while, if an outcome is especially tragic, the FDA will sue a manufacturer or even file criminal charges. For example, two former dietary supplement company executives were sent to prison, and two companies paid over $10 million in fines over the fraudulent and dangerous Jack3d and OxyElite Pro supplements. Two U.S. Army soldiers died after taking Jack3, which contains the stimulant dimethylamylamine or DMAA, which is an amphetamine. DMAA was banned in 2013 but is still widely available. In fact, some guy at the website “Lift Vault” is only too happy to tell you where you can get it. 

According to Kyle, the “real” reason it’s hard to get DMAA isn’t that it killed two people and is illegal in the United States, but that it’s the result of a “rocky relationship the FDA and other regulatory agencies have with DMAA and DMHA.”

Killing two people and illegal…rocky relationship. It’s the same thing, right?

Adulteration of supplements with active pharmaceuticals is common. Some of these pharmaceuticals are dangerous because the compound is dangerous, like DMAA, and sometimes, they are contaminated with approved pharmaceuticals. I’ve written previously about a study of “sports enhancers,” and 12% contained an ingredient banned by the Food and Drug Administration (FDA). One supplement contained four banned ingredients, and one even contained a substance that has never been approved for human use anywhere. Even if the added pharmaceutical isn't itself dangerous, there is a risk of negative medication interactions that can’t be predicted. And of course, not every person can safely take every pharmaceutical. Supplements for weight loss, metabolism boosters, muscle building, and libido seem to be the most common ones that are adulterated with pharmaceuticals. Still, of course, you never know because the system is designed, so you can’t know. A supplement for hot flashes could contain estrogen, so it may actually work, but then you are taking estrogen, and you don’t know how much. Could you get a blood clot? What about endometrial cancer? Real possibilities for harm. 

Don’t Forget the Dangerous Microbials

As there is no enforcement of good manufacturing practices, contamination of products by harmful bacteria, mold, and yeast is a real concern (echos of L-tryptophan, which is now back on the market, by the way, and there has since been a case report of eosinophilia myalgia). A study by V.H. Tournas looked at 183 dietary supplements, and “Potentially toxigenic molds were found in alfalfa, coriander, echinacea, garlic, ginkgo, juniper, licorice, psyllium and St. John's wort supplements.” Products containing kratom have been contaminated with Salmonella, resulting in 50 people needing hospitalization, and probiotics have been linked with liver abscesses. Contamination with microorganisms is a concern for everyone, but especially risky to immunosuppressed people. 

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Then there is Heavy Metal Contamination…

Studies tell us that 20% of Ayurvedic products are contaminated with lead. Really, 20%. If 20% of chickpeas were contaminated with lead, chickpeas would be banned, and the story would be on the front page above the fold of every newspaper. But it’s a supplement, so have at it. A study from Canada showed that of 121 supplements tested, 5% exceeded the safe level of arsenic, and 1.7% exceeded the levels for lead, cadmium, and aluminum. In many studies, there are heavy metals, although not enough in an individual product to be a concern. However, considering many people take more than one supplement, the possibility of tipping over into concerning exposure is very real. 

Supplements are so lucrative it’s actually painful.

Thinking back to the DMAA disaster, one manufacturer initially refused to destroy or turn over their stock to the FDA. When the FDA was ultimately successful, the amount destroyed was worth more than $8 million on the market. That’s one product line from one company. The the top ten menopause supplements generated $3,363,997 in sales on Amazon in one month. One month (read more about that here). It’s easy to see why supplements are so appealing, business-wise. But how can they make American healthy again if they don’t diagnose, treat, cure, or prevent disease?

I bet either the requirement for a supplement disclaimer will be gone in a year, or there will simply be no ramifications for those who decide to skip this fine print. When that happens, you can say you read it here.

Sigh.

Supplements are Untested, Unregulated Pharmaceuticals

There is no greater example of buyer-beware in medicine than supplements. The FDA is barely looking out for you as it is because they have been so hamstrung by legislation.

Buying a supplement is like buying gas from a guy selling it out of a can on the side of the road; all you can do is hope that it’s actually something that can cure an empty tank and not something that could wreck your engine or cause your car to blow up. 

References

The 1906 Food and Drugs Act and Its Enforcement https://www.fda.gov/about-fda/changes-science-law-and-regulatory-authorities/part-i-1906-food-and-drugs-act-and-its-enforcement

Ballentine C. Sulfanimamide Disaster. FDA Consumer Magazine, June 1981 https://www.fda.gov/files/about%20fda/published/The-Sulfanilamide-Disaster.pdf

1938 Food, Drug, Cosmetic Act https://www.fda.gov/about-fda/changes-science-law-and-regulatory-authorities/part-ii-1938-food-drug-cosmetic-act

Pray WS. Orrin Hatch and the Dietary Supplement Health and Education Act: Pandora’s Box Revisited. Journal of Child Neurology. 2012;27(5):561-563. doi:10.1177/0883073812441064

Podolsky SH, Kesselheim AS. Regulating Homeopathic Products — A Century of Dilute Interest

N Engl J Med 2016; 374:201-203

Swygert LA, Back EE, Auerbach SB, Sewell LE, Falk H. Eosinophilia-myalgia syndrome: mortality data from the US national surveillance system. J Rheumatol. 1993;20:1711–17.

Eosinophilia-myalgia syndrome and L-tryptophan-containing products--New Mexico, Minnesota, Oregon, and New York, 1989. Centers for Disease Control (CDC) MMWR Morb Mortal Wkly Rep. 1989;38:785–8. 

Allen JA, Peterson A, Sufit R, Hinchcliff ME, Mahoney JM, Wood TA, Miller FW, Whitfield ML, Varga J. Post-epidemic eosinophilia-myalgia syndrome associated with L-tryptophan. Arthritis Rheum. 2011 Nov;63(11):3633-9. doi: 10.1002/art.30514.

Belongia EA, Hedberg CW, Gleich GJ, White KE, Mayeno AN, Loegering DA, Dunnette SL, Pirie PL, MacDonald KL, Osterholm MT. An investigation of the cause of the eosinophilia-myalgia syndrome associated with tryptophan use. N Engl J Med. 1990 Aug 9;323(6):357-65. 

Hiltzik M. Orin Hatch is Leaving the Senate, but his Deadliest Law Will Live On. LA Times Accessed 01/17/24 https://www.latimes.com/business/hiltzik/la-fi-hiltzik-hatch-20180105-story.html

Shin D, Kang HS, Park EM, Kim J, Kwon J, Suh J, Moon G. Authentication of tejocote (Crataegus mexicana) dietary supplements based on DNA barcoding and chemical profiling. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2021 Dec;38(12):1985-1994.

Berland N, Kababick J, Santos C, Calello DP. Notes from the Field: Online Weight Loss Supplements Labeled as Tejocote (Crataegus mexicana) Root, Substituted with Yellow Oleander (Cascabela thevetia) - United States, 2022. MMWR Morb Mortal Wkly Rep. 2023 Sep 15;72(37):1016-1017. 

White CM. Dietary Supplements Pose Real Dangers to Patients. Annals of Pharmacotherapy. 2020;54(8):815-819. doi:10.1177/1060028019900504

Tournas VH. Microbial contamination of select dietary supplements. J Food Safe 2009;29:430-442.

Genuis SJ, Schwalfenberg G, Siy AK, Rodushkin I. Toxic element contamination of natural health products and pharmaceutical preparations. PLoS One. 2012;7:e49676.

Us Department of Justice, Press Release. Two Individuals And Two Companies Sentenced In Scheme To Fraudulently Sell Popular Dietary Supplements. https://www.justice.gov/opa/pr/two-individuals-and-two-companies-sentenced-scheme-fraudulently-sell-popular-dietary

I get asked a lot about supplements that claim to promote hair growth. If your Instagram is anything like mine, you probably also get fed a lot of advertisements and posts from brand partners promoting these products.

Many people take supplements to promote hair growth, even knowing the data is generally weak because they figure the product is likely safe and will cover all their bases. It’s a bit of a “What’s the harm?” approach. But as I’ve written before, supplements are a rising cause of liver failure. As supplements aren’t studied rigorously, we can’t explain risks as we can with pharmaceuticals; instead, researchers have to cobble together data from other sources. For example, looking at people who needed a liver transplant, between 1995 and 2003, supplements were the cause of 2.5% of non-acetaminophen-related liver failure, and between 2013 and 2020, that number jumped to 24.1%. That’s quite a dramatic leap.

I’ve been meaning to write about Nutrafol for a while, which is a “hair growth nutraceutical.” As a report was recently published linking Nutrafol with a severe case of drug-related liver injury, it seems like now is a good time to take a closer look.

The case was written up in the American Journal of Gastroenterology and details a 26-year-old woman who presented with jaundice, a yellowing of the skin, and the whites of the eyes that can be a sign of liver disease. Her blood tests indicated liver injury, and a thorough exam, blood work, and imaging studies ruled out medical conditions and viral infections as the cause. She reported drinking mullerian leaf tea, and her dermatologist had recommended Nutrafol, which she had been taking for five months. Based on the timeline and the test results, her medical team felt that Nutrafol was the most likely cause of her liver failure. She stopped it and fortunately recovered.

Let’s break it down.

What exactly is a nutraceutical? I love this description from Wikipedia:

Nutraceutical is a marketing term used to imply a pharmaceutical effect from a compound or food product that has not been scientifically confirmed or approved to have clinical benefits. In the United States, nutraceuticals are considered and regulated as a subset of foods (such as dietary supplements) by the Food and Drug Administration (FDA).

There are no internationally defined properties of nutraceuticals. Due to the vague, undiscriminating evidence for the biological effects of nutraceutical products, experts have proposed abandoning the term.

We have a case report of liver injury almost certainly due to Nutrafol, but is that single case a cause for concern? As we don't have any actual safety data, it’s impossible to put this case into perspective. Is it a one-in-a-million risk or one-in-a-thousand? Was this patient uniquely vulnerable, or is everyone at the same risk?

Despite not having quality studies for Nutrafol, I believe there are enough red flags to be concerned. Before we begin, it’s worth mentioning that Nutrafol has a whopping 23 ingredients (if I counted correctly, the font is small), so it’s possible that the ingredients are not toxic individually but may be in combination. Who knows? That’s the problem when there is a mega data void. Imagine if a pharmaceutical company created a medication with 23 active ingredients and pushed it out into the world without safety data. There would be an uproar! But of course, that’s not allowed because, unlike supplements, pharmaceuticals actually have to show data about safety and efficacy.

The case report discusses the ingredients in Nutrafol and their association with liver injury. The most likely culprits (but again, it could be a combination of ingredients) are:

• Turmeric, as turmeric-induced liver injury is well-reported (which I've previously written about here)

• Ashwagandha and horsetail, and while there is less evidence linking these two with liver injury, the consensus is that they are “probably linked” with liver injury

• Saw palmetto is another potentially concerning ingredient, and while even less is known about the risk, it is a possibility.

  

Other potential safety concerns about Nutrafol that were not mentioned in the case report include:

• Two proprietary blends. The liver-injuring substances mentioned above are in these blends, meaning the actual amounts are unknown. It would be a good idea to know precisely how much potentially harmful substance is in a product, but you can’t say with proprietary blends as they are secret recipes. Proprietary blends are often linked with reports of liver injury. This should be a big, bright red warning flag about Nutrafol.

• Excessive amounts of vitamin A (as beta-carotene). Vitamin A supplements, including beta-carotene, are associated with increased mortality. As vitamin A deficiency is rare, there is no need for a vitamin A supplement.

• High levels of selenium, which is unnecessary as selenium deficiency is also rare, and selenium supplements have been linked with a variety of serious health complications as well as…wait for it…hair loss. It’s worth noting that the recommended upper daily limit of selenium from food and supplements combined is 400 mcg, but Nutrafol has 200 mcg. If the product is incorrectly formulated and contains more selenium than it claims, or someone gets a lot of selenium from their diet, there is a risk of excessive intake. The folks at the website PerfectHairHealth.com tested the Nutrafol product for men, which also has 200 mcg of selenium, and their test showed it had 274 mcg, so more than expected. You can read more about their take on Nutrafol here.

Another issue is that I can’t find an independent third-party testing seal on the website proving that the product contains what it claims and is free from impurities and harmful substances. I could not find Nutrafol on the USP or NSF sites, two of the standard third-party testing organizations. The Nutrafol website states:

We test the final product for label claim, microbiological safety, and heavy metals, a process that is reviewed by Quality Assurance to ensure it meets all established specifications.

This testing is performed at our manufacturers' in-house laboratory and a third-party ISO/IEC 17025:2017 certified laboratory.

In-house testing doesn’t count here because it’s not independent. While the statement on their website suggests they have third-party testing, it feels unnecessarily vague. Which organization? It’s important to know so a consumer can understand the scope of the testing and make an informed choice. I emailed Nutrafol to clarify, and while I have been redirected twice to different emails, there has still been no response to my inquiry. As Nutrafol is available on Amazon, which requires 3rd party testing of supplements, I suspect the testing has been done, but I’d like to see proof for myself. I will update you if I hear back.

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Nutrafol contains biotin, so it’s worth mentioning that no quality studies support biotin for treating or preventing hair loss. If someone loses their hair, it is worth testing to ensure they don’t have a biotin deficiency, but because a deficiency can cause hair loss, it does not mean that excessive biotin can treat hair loss. Here’s my analogy: running out of gas is bad, but overfilling the tank is not helpful. According to the NIH Office of Dietary Supplements, “Biotin deficiency is rare, and severe biotin deficiency in healthy individuals eating a normal mixed diet has never been reported.” Biotin supplements can also interfere with testing for thyroid conditions and with some blood tests used to diagnose heart conditions.

What about studies that specifically evaluate Nutrafol? The website claims there are“20 clinical studies,” which sounds impressive, but below the claim about 20 clinical studies is a list of 13 references, and while I may not be a mathematician, I still know that 13 is not 20.

When consumers read “20 clinical studies,” they naturally think it means 20 quality peer-reviewed clinical trials, which sounds super impressive. However, several of the references above say “data on file,” which doesn't cut it (maybe they think people aren't going to read the fine print, but I learned to use progressive eyeglasses for a reason!). I cannot access the “randomized, placebo-controlled trials” in reference nine, as apparently, they are also in a file at Nutrafol. It’s irrelevant if a company has this data in its bat cave. If it’s not published in a peer-reviewed journal, I might as well assume it just doesn’t exist.

For fun, I decided to look up a few of their other references, and wow. What a collection. The first one is from 1975 and isn't even a clinical trial. There are studies of some of the individual ingredients, and one is in what I consider a predatory, or at least very low-quality, journal. There is also a review article on curcumin, and one of the co-authors, Bharat B. Aggarwal, PhD, is currently ranked at #27 on the Retraction Watch Leader Board for most retracted papers. Nice touch!

I did find three published peer-reviewed clinical trials, all funded by the manufacturer. Two are single-blinded, and as there is no placebo arm, so to me, they are the equivalent of, “My mom liked my supplement.” One of the papers is a six-month randomized-double blinded, placebo-controlled trial of women who felt they had hair loss, although the study is small and funded by the manufacturer. Interestingly, the exclusion criteria in the paper includes “hair loss disorders,” but isn’t that sort of the point of taking a hair growth supplement? I noticed this issue was also mentioned by the folks at PerfectHairHealth.com, who pointed out that the study criteria over at ClinicalTrials.gov exclude most people with hair loss disorders. They suggested that excluding anyone with an actual hair loss disorder would increase the likelihood that the participants could have a nutritional deficiency contributing to their hair loss, meaning the deck may have been stacked to include people who are most likely to benefit from a supplement (and therefore could also very likely have been helped with a much cheaper product). This paper also claims it’s a safety study, but the methods section doesn’t mention how they monitored safety beyond asking about adverse effects. I was looking for liver tests and selenium levels.

(Looking up and reading the articles in that reference section is several hours of my life that I will never get back).

Look, you couldn’t pay me to take Nutrafol for hair loss (which I’ve been experiencing and will write about soon, so stay tuned. I provide this context to emphasize that I have spent a lot of time lately thinking about what I will and will not take). I would never take a product with a proprietary blend or turmeric. In addition, Nutrafol is inadequately studied, and there is no real safety data, which is especially concerning given the high amounts of vitamin A and selenium. The one randomized double-blinded trial that I found seems to have excluded the most common causes of hair loss, and now, a case report links the product to liver failure.

Like many supplements—sorry, I mean nutraceuticals—there is a lot of flashy advertising and little else behind the curtain. Sadly, people are paying a lot of money to play the liver injury lottery, and really, we all deserve better.

References

Dugal J, Malhi A, Singh Y, Hsu M, Gill A, Patel P, Tun KM. Nutrafol's Hair Gains and Liver Strains. The American Journal of Gastroenterology 119(10S):p S2733-S2734, October 2024. | DOI: 10.14309/01.ajg.0001046328.13395.e1

Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database of Systematic Reviews 2012, Issue 3. Art. No.: CD007176. DOI: 10.1002/14651858.CD007176.pub2

Fact Sheet on Vitamin A and Carotene. National Insitutes of Health, Office of Dietary Supplements https://ods.od.nih.gov/factsheets/VitaminA-Consumer/

Fact Sheet on Selenium. National Insitutes of Health, Office of Dietary Supplements https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional%20/

Civas, E. and Akpınar, Ü. (2024), Selenium in the supplement as the probable cause of hair loss and nail dystrophy. J Cosmet Dermatol, 23: 361-363. https://doi.org/10.1111/jocd.15902

Wandrey F, Pickel C, Jongsma E, Ewald CY, Grothe T. Evaluation of the collagen-boosting effects of a Moldavian dragonhead extract. J Comm Med and Pub Health Rep 2021;2(7): https://doi.org/10.38207/jcmphr20210102 (Note, possible predatory journal)

Jagetia GC, Aggarwal BB. "Spicing up" of the immune system by curcumin. J Clin Immunol. 2007 Jan;27(1):19-35. doi: 10.1007/s10875-006-9066-7. Epub 2007 Jan 9. PMID: 17211725. (Co-author Aggarwal has had multiple articles retracted).

Sivamani RK, Ablon G, Nong Y, Maloh J, Hazan A, Raymond I. A Prospective, Multi-Center Study to Evaluate the Safety and Efficacy of a Vegan Nutraceutical to Improve Hair Growth and Quality in Females Following a Plant-Based Diet. J Drugs Dermatol. 2024 Aug 1;23(8):661-668. doi: 10.36849/JDD.8421. PMID: 39093662.

Stephens TJ, Berkowitz S, Marshall T, Kogan S, Raymond I. A Prospective Six-month Single-blind Study Evaluating Changes in Hair Growth and Quality Using a Nutraceutical Supplement in Men and Women of Diverse Ethnicities. J Clin Aesthet Dermatol. 2022 Jan;15(1):21-26. PMID: 35309272; PMCID: PMC8903234.

Ablon G, Kogan S. A Six-Month, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of a Nutraceutical Supplement for Promoting Hair Growth in Women With Self-Perceived Thinning Hair. J Drugs Dermatol. 2018 May 1;17(5):558-565. PMID: 29742189.

It seems that the pressure from social media to take various supplements comes and goes in waves, or perhaps it might even be. better to call them fads. Right now, the focus seems to be on magnesium, specifically magnesium for bone health.  

Before we get into the magnesium and bone question, I think it’s fair to point out that we should be highly skeptical of supplement fads. The doctors, naturopaths, functional nutritionists, chiropractors, coaches, and wellness warriors who are financially invested in supplements need a continuous supply of ever-changing products to feed their machine, as it were. Once everyone is taking creatine, or collagen, or turmeric, or whatever they are selling, they need a new, amazing supplement because A) sales taper off because people can only hear about creatine or turmeric or whatever so many times before they start to tune out, and B) the placebo effect wears off, so there needs to be the next “new thing.” But here’s the deal: reliable science, of which there is very little to none for most supplements, often takes decades of work, so the pace at which “new” and “miraculous” supplements are perpetually recommended far outstrips the capacity of scientific study, meaning you should always be skeptical!

With that preamble, on to the question at hand. Can magnesium supplements prevent osteoporosis?

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Magnesium and Bone: What’s The Connection?

While most people think of bone, they think of calcium, but about 60% of the body's magnesium is stored in bone. Magnesium is important for bone structure, and some of the magnesium in the bone is metabolically active and enters the blood, where it participates in a wide range of essential functions. Magnesium is also indirectly involved in bone health via its effect on calcium and vitamin D. Low magnesium can reduce parathyroid hormone, decreasing calcium levels. Regarding vitamin D, magnesium is important for absorption, and the enzymes that produce and metabolize vitamin D also require magnesium.

Magnesium is important for health for many other reasons; for example, it is involved in over 300 enzymatic reactions, but here, we will just focus on bone health. 

Magnesium: Some Basics

Clearly, magnesium is important for bone health. How does this affect the risk for osteoporosis?

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Sometimes, it feels like social media is rapidly becoming one big supplement ad. In addition to traditional ads, there are soft sales from doctors and other healthcare professionals who clearly profit from the supplements because they are either selling their own product or they are sharing discount codes, often something like #GynoApproved. Some may not be directly financially profiting; they are just posting about them to ride the popularity of supplements on social media as they know the posts and videos they create about the topic get more attention and views, which drives followers that are most definitely a currency. So many healthcare providers are trying to get in on the menopause gold rush that it’s become a supplement minefield.  Unlike some doctors who base their supplement choices on less rigorous evidence, I demand that supplements actually have some proven benefits. For example, I am not a rodent; I am a human woman, so rat studies aren’t going to sway me. I also don’t want low-quality studies or studies published in questionable journals. I demand the same evidence from supplements as I do from pharmaceuticals because I’m worth it.

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I don’t typically like discussing what I do because it's an anecdote, but since I frequently get this request, I thought I would explain the reasoning behind what I take or mostly don’t take. This doesn't mean that you should do what I do, but perhaps you might be interested in how I think about it. But remember, I am using lots of *I* words here.

Before we go any further, I have an entire section of The Vajenda dedicated to supplements, and it’s called Supplements & Such (very creative, I know…insert eye roll emoji). There, you can find information on how I group supplements (this is an important primer), the backstory behind the lack of legislation for supplements in the United States, and reviews of different products, to name just a few of the topics. 

In this post, I’m writing about supplements for generally healthy people, meaning for primary prevention. There are some evidence-based reasons to take supplements for primary prevention that I won’t discuss here because they don't apply to me. For example, I'm not trying to get pregnant, so I don't need a folic acid supplement. I also have no idea about the literature for professional athletes/bodybuilders, so what I write here may not apply.

The following is my answer to someone asking what supplements I, a reasonably physically active and healthy woman in her 50s, take for preventative health care. 

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Here’s my list:

Vitamin D, 1,000 IU, and I do this reluctantly because studies have consistently failed to show significant benefit from routine supplementation (excluding people with true vitamin D deficiency). There is a lot of bias and shoddy science among the biggest promoters of the supposed low vitamin D epidemic, and there is a good summary here in the New York Times for anyone interested. The latest Endocrine Society guidelines recommend against routine supplementation for people ages 50-70 years (my age group) for those who can get 600 IU a day from their diet. The VITAL study showed no benefit from Vitamin D supplementation in reducing fractures with or without calcium. I had my vitamin D level tested after I broke my ribs as part of the workup, and my level was barely normal by the new cut-off: I was 23 ng/ml, and normal is ≥ 20 ng/ml (50 mmol/l). Because my level is barely normal and I have osteopenia, my endocrinologist persuaded me to take it. I was conflicted because vitamin D supplements don't tend to increase bone density in clinical trials, except for those with very low baseline levels of < 12 ng/ml (<30 nmol/L). Some data shows people with higher levels tend to have better bone health, but there are lots of confounders. There is likely no downside to taking 1,000 IU a day. I take Nature Made, which is third-party verified and cheap. 

Is This Really a Supplement? Maybe, kind of?

Protein: At the Menopause Society meeting, we were quoted that women should consume 1.2 g/kg of protein daily, but I think there is enough evidence to suggest that 1.6 g/kg is a better target, especially when combined with resistance training. Diet-wise, I struggle the most here. For me, 1.6 g/kg is about 125 g a day, but when I first started tracking protein, I was in the 60-70 g/day range, which was eye-opening and showed the benefit of at least checking once or twice. It has taken time and dedicated effort to restructure my diet accordingly. I’ve reached the 100-105 g range, and recently, I have surpassed 120 g fairly consistently. I sometimes make smoothies with skyr (Icelandic yogurt) and protein powder (I use Simply Tera’s Whey Powder, vanilla because every other protein powder tastes disgusting to me), and I find Barebells protein bars extremely palatable, as well as Fairfield protein shakes and Ensure Max 30 g Protein shakes, so I guess you could loosely call those supplements (the Ensure also has 650 mg of calcium!). Protein bars and these shakes are also great for travel as they don’t have to be refrigerated. I’ve been playing around with some high-protein flours and now have a few recipes for higher-protein dinner rolls and pizza crusts, and look, getting an extra five or more grams of protein from something I love is a win-win. If people are interested, I will post some of my high-protein recipe modifications. 

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Here are some of the most common supplements that I get asked about that I do NOT take:

Calcium: The recommendation in the United States is 1,200 mg a day for women over age 50, and I get between 800-1,200 mg a day. Calcium absorption is believed to reduce with age, partly due to lower vitamin D, but I'm taking that, so it shouldn't be an issue. There aren’t good studies showing that calcium supplementation reduces fractures for people eating a typical diet. In the Women’s Health Initiative, calcium combined with vitamin D did not significantly reduce hip or wrist fractures compared with placebo. While there were some beneficial changes in a few markers of bone health, these were not statistically significant. Admittedly, the WHI may not apply to me as this study was postmenopausal women at typical risk of fracture, and I'm at higher risk, but other data suggests that calcium supplements only provide about a 1% increase in bone density, which is limited to the first year of use. There is also a small but definite increased risk of kidney stones with a calcium supplement, an extra 5 cases per 10,000 women per year. While this is a small increase in risk, I have one kidney, and a kidney stone would be a bigger deal for me. Also, if I took a calcium supplement for 30 years, at five extra stones a year, that means when I’m 88, I would have had a 1.5% lifetime risk of a calcium supplement-induced kidney stone. The general consensus is that it’s best to get calcium from a diet, but if there is a dietary requirement shortfall, make up the remainder with a supplement. How do I get to 800-1,200 mg? I have a lot of milk, coconut and soy milk with added calcium, feta cheese, and skyr or yogurt. I often have a glass of So Delicious Coconut Milk when I walk in the door. I like the taste; it only has 45 calories, and it adds 130 mg of calcium to my diet. I cook rice in it as well, and it just gives it a hint of coconut.

Collagen: There is no good data supporting collagen supplements for muscle or bone health, which would be my primary concern. While low-quality data supports it for skin health, the data is, well, lower-quality, so it’s not enough for me to bother with. I’m sticking with sunscreen and Retin-A, which have a lot of quality evidence. 

Creatine: This may show a very small benefit for the muscles, but the effect is less for older people, and even for younger people, the benefit is likely so slight that it’s probably not clinically significant. Here’s part of a conclusion from a recent meta-analysis: 

A pooled analysis of the current data suggests that creatine supplementation promotes a small increase in skeletal muscle hypertrophy in both the upper and lower body musculature when combined with a regimented resistance training program. Those considering creatine supplementation for the goal of regional muscle hypertrophy should consider the practical significance of the small magnitude of effect. Furthermore, young adults appear to derive a greater hypertrophic benefit compared to older individuals, but the magnitude of this difference is relatively modest, calling into question the practical relevance of this finding

I’ve heard a lot of chatter recently about creatine supplements for memory, but the data here is weak, and I’m not going to take something daily that has a weak effect when there are many things with great data for brain health (see this post). Like most people, I am busy, and I don’t want to waste money, time, and energy on interventions with little supporting proof. When a supplement reaches a threshold that makes it into guidelines for the prevention of dementia, then I’ll consider it. Until then, I will stick with robust science.  

Fiber: I consistently get > 25 g of fiber a day, so I don’t supplement here. For those who can’t get to that goal or who are struggling with constipation, psyllium husk is the winner, hands down. You can get that from Metamucil or one of my favorite cereals, Bran Buds. There is no reason to waste your money on expensive, designer fiber supplements. 

Omega-3 fatty Acids: the VITAL trial probably gives us the best data here, and the conclusion from the paper is, “supplementation with n−3 fatty acids did not result in a lower incidence than placebo of the primary end points of major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) and invasive cancer of any type.” While some people wonder if people who don’t eat any fish might benefit from an omega-3 supplement, I don’t think the data is very robust. Also, I make a pretty concerted effort to have fatty fish twice a week. I asked Dr. Danielle Belardo about the benefits of omega-3 supplements for people who don’t eat fish, as she is a preventative cardiologist and a vegan, and she says there is no good evidence to support supplementation for heart health, even for those who don’t eat fish. In fact, she told me that a “healthful plant-based diet does not demonstrate lower omega levels as compared with omnivores.” There may be benefits with a purified form of EPA for people with elevated triglycerides and who also have diabetes or who have coronary artery disease, but that’s not the situation we are discussing here. 

Final thoughts…

I really do my best to get all my nutrition from my food because that seems to be the one consistent message in every study. It’s a simple idea but not easy to execute, and I think that’s important to recognize. I also have a super supportive husband who does more than 50% of the grocery shopping and cooking, and that helps a lot. And I have my easy backups, like protein shakes or high-fiber Mission tortillas (18 g of fiber and 5 g of protein, not bad!), and Kodiak Cakes Protein cakes (pancake mix) to help fill in the gaps. 

(I have no sponsorships with any of the food items that I have mentioned; I am just sharing what I like because I have benefited so much from others sharing what they like with me.) 

I love this quote from the Harvard Health Blog, as it sums this all up quite well:

How food, and its component molecules, affect the body is largely a mystery. That makes the use of supplements for anything other than treating a deficiency questionable.

Gunter’s corollary is that many people are looking to capitalize on this mystery, especially for women in menopause.

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References

1. Bouillon, R., Manousaki, D., Rosen, C. et al. The health effects of vitamin D supplementation: evidence from human studies. Nat Rev Endocrinol 18, 96–110 (2022). https://doi.org/10.1038/s41574-021-00593-z

2. Marie B Demay, Anastassios G Pittas, Daniel D Bikle, Dima L Diab, Mairead E Kiely, Marise Lazaretti-Castro, Paul Lips, Deborah M Mitchell, M Hassan Murad, Shelley Powers, Sudhaker D Rao, Robert Scragg, John A Tayek, Amy M Valent, Judith M E Walsh, Christopher R McCartney, Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 109, Issue 8, August 2024, Pages 1907–1947, https://doi.org/10.1210/clinem/dgae290

3. US Preventive Services Task Force; Grossman DC, Curry SJ, Owens DK, Barry MJ, Caughey AB, Davidson KW, Doubeni CA, Epling JW Jr, Kemper AR, Krist AH, Kubik M, Landefeld S, Mangione CM, Silverstein M, Simon MA, Tseng CW. Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2018 Apr 17;319(15):1592-1599. doi: 10.1001/jama.2018.3185. PMID: 29677309.

4. Manson JE, Crandall CJ, Rossouw JE, et al. The Women’s Health Initiative Randomized Trials and Clinical Practice: A Review. JAMA. 2024;331(20):1748–1760. doi:10.1001/jama.2024.6542

5. Livingston G, Huntley J, Liu KY, et al. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission. The Lancet 2024, July 31. 

6. LeBoff MS, Chou SH, Ratliff KA, et al. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med 2022;387:299-309.

7. Manson JE, Cook NR, Lee IM, et al., on behalf of the VITAL Research Group. Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med 2019;380:23-32.

8. Omega-3 fatty Acids, Fact Sheets for Health Professionals, NIH https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/#:~:text=The%20AHA%20does%20not%20recommend,and%20those%20with%20preexisting%20CVD.

9. McMorris T, Hale BJ, Pine BS, Williams TB. Creatine supplementation research fails to support the theoretical basis for an effect on cognition: Evidence from a systematic review. Behav Brain Res. 2024 May 28;466:114982. doi: 10.1016/j.bbr.2024.114982. Epub 2024 Apr 4. PMID: 38582412.

10. Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D. Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Exp Gerontol. 2018 Jul 15;108:166-173. doi: 10.1016/j.exger.2018.04.013. Epub 2018 Apr 25. PMID: 29704637; PMCID: PMC6093191.

11. Prokopidis K, Giannos P, Triantafyllidis KK, Kechagias KS, Forbes SC, Candow DG. Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2023 Mar 10;81(4):416-427. doi: 10.1093/nutrit/nuac064. PMID: 35984306; PMCID: PMC9999677.

12. Nunes E. A., Colenso-Semple L., McKellar S. R., Yau T., Ali M. U., Fitzpatrick-Lewis D., Sherifali D., Gaudichon C., Tomé D., Atherton P. J., Robles M. C., Naranjo-Modad S., Braun M., Landi F., and Phillips S. M. (2022) Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults, Journal of Cachexia, Sarcopenia and Muscle, 13, 795–810, https://doi.org/10.1002/jcsm.12922

In 2023, a group of researchers looked up the 10 most popular “liver cleansing” supplements on Amazon (“liver-cleansing” is in quotations because it is a fake-ass concept). They picked a day, identified the top ten 10 products, and then calculated the number of units sold and the revenue for the previous month using a tool called AMZScout. There were 115,256 units sold with $2,442,963 a month in revenue. None of the ingredients in these 10 products were recommended by the American Association for the Study of Liver Diseases or the European Association for the Study of Liver. So yes, you read that right: $2,442,963 per month for products that are, at best, just a waste of money but could also be a ticket to liver damage or a host of other health problems. The researchers also used Fakespot.com, a Chrome plugin, to look for fake reviews. There was an average of 11,526 reviews per product (that’s a lot!), and the mean rating was 4.42 stars (also a lot). Fakespot.com calculated that only 65.04% of the product reviews were genuine. 

I thought to myself, Jen, this might be illuminating to do with the top 10 menopause supplements! So, we picked August 27, 2024, paid for AMZScout, and got to work. We double-checked the sales data results for accuracy with those published by Amazon (they were quite close). My husband (aka @drjenadjacent, aka Todd), given his lengthy career in tech and marketing, knows a lot about online sales and reviews and wasn’t convinced about the accuracy of Fakespot.com, so I skipped that part and just went straight for the money, as it were. 

What do you think? Is there more money in menopause than liver cleansing?  

The menopause gold rush is real: the top ten menopause supplements generated $3,363,997 in sales on Amazon in one month, easily beating $2,442,963 for “liver cleansing.” In just one month, 93,543 units were sold, which is fewer units sold but much more money to be made. The unit price ranged from $13.99 (Estroven Sleep Cool for Menopause Relief) to $89.00 (BB Company Slim Gut Bundle). The average price per unit for the top 10 menopause supplements was $36.89 vs. $26.45 for the liver supplements. Remember, this is just from one month from Amazon by unit volume; this does not include other online retailers, brick-and-mortar stores, and all of those suppliers with their own Shopify or e-commerce site. 

Take that liver cleansing; menopause wins…or really loses. 

The numbers here represent total sales; profit will be less. You can see how much profit people can make selling supplements on my post here, where I created Dr. Jen’s Menopause Taming Turmeric Supplement. In that experiment, if I were to sell 8333 units of my turmeric supplement for $35 a bottle, I could make a $195,760 profit after covering my expenses. The profit was about 70% a bottle. If we estimate that Amazon takes 15%, that leaves about $2,859,357 for the companies selling these untested, unregulated pharmaceuticals. There is no reason to believe these companies are doing any worse than I would from my turmeric supplement, so that leaves about $2 million a month in profit from selling 10 products for menopause on one e-commerce platform. 

How Bad Are These Top Ten?

Not one product in the top 10 contains an ingredient recommended in the 2023 Menopause Society Guide to Non-Hormonal Therapy, so there’s that. 

I identified some red flags to help spot ingredients and claims that are more likely to be problematic health-wise:

• Green tea leaf extract is associated with liver failure.

• Turmeric is associated with liver failure, and despite extensive study, there is no data to show that it is useful in menopause (or really anywhere except cooking). Read more about turmeric here. 

• Black cohosh is associated with liver failure, and results do not reliably show it is helpful for hot flashes. Also, in one study, 25% of products that claimed to have black cohosh were adulterated with another plant and contained no black cohosh. Yikes!!!

• Proprietary blends or “secret recipes” only have to state the total amount, not how much of each herb or spice, so the consumer has no idea what they are truly taking. These products are all about marketing and focus on making the product look special. In fact, the names of these blends often sound scientific, where no science exists, so they only provide the illusion of science. It’s pure smoke and mirrors. Proprietary blends often contain multiple ingredients, which has also been identified as a risk for liver injury. 

• For products that make claims about weight loss, study after study after study has shown there is a higher risk of adulteration, sometimes even with poisonous substances. In one study looking at supplements that were adulterated, 40.9% of them marketed for weight loss were adulterated. What do they contain? Sibutramine, which is a substance included in a drug removed from the market due to cardiac complications, is a common additive, but antidepressants, stimulants, and even oleander (a poison) have been identified. Also, no supplement has been proven to be safe and effective for weight loss. 

An incredible 80% of products triggered my short list of red flags! Only two of the top ten made it past this simple screening: Estroven Multi-Symptom and Gaia Herbs. Estroven Multi-Symptom is 4 mg of Rhapontic rhubarb root extract. The few studies looking at this product are of low quality and can’t be used to draw conclusions. It is not recommended in the 2023 Menopause Society Guidelines. Gaia Herbs contains Vitex agnus-castus (Chaste Berry) extract and agnuside, which is a chemical compound found in Vitex agnus-castus. It is advertised as “hormone balancing,” which is gibberish, as medically, there is no such thing, and I think it’s best to stay away from products advertised with gibberish. The highest quality study showed no difference in reducing hot flashes versus placebo with a product that combined Hypericum perforatum with Vitex agnus-castus. Other studies are of even lower quality. Vitex is also not recommended in the 2023 Menopause Society Guidelines. 

Remember, placebo-controlled trials for hot flashes have a high placebo response rate. For example, in the studies for fezolinetant, 37% of people who took the placebo reported a 50% reduction in hot flashes. And the more someone pays for a product, the more likely the placebo response. In addition, studies for supplements and hot flashes are typically 12 weeks, but a longer duration is needed to help tease out the placebo effect. It is possible that all the glowing anecdotes are placebo responses, and without appropriate studies, we’ll never know. This benefits the manufacturer, not you, the consumer. 

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Doesn’t Amazon Require Third-Party Testing?

Yes, they do as of April 2024, which may help ensure that supplements contain the ingredients they claim and are free of contaminants. As an aside, it’s a very sad statement that Amazon is doing more to protect consumers than the U.S. government. While I am sure the motive was protecting Amazon from injuries and, hence, lawsuits related to these products, the consumer does benefit. 

Annual testing is required, but it isn’t known how annual testing compares with batch testing, which is the safest and the standard with pharmaceuticals, but annual testing is far superior to no testing. Products sold for sexual enhancement, weight management, sports nutrition, and body-building must also be tested for “undeclared active pharmaceutical ingredients.” Whether menopause products that advertise themselves with weight loss euphemisms, like “sexy midsection curves,” will fall in the weight loss category isn’t known. This policy also means there is no requirement for products that claim to treat hot flashes to prove that they don’t contain hormones, gabapentin, or any other medication that has been shown to treat hot flashes.

Remember, the third-party testing requirement applies only to retailers that sell on the Amazon platform. If products are being sold on Shopify or some other e-commerce platform or in a brick-and-mortar store, unless the products have an accepted third-party verification label or you’ve checked with the companies that do the verification to see if a specific product has been tested, all bets are off.  

But here’s the thing: Third-party testing here means that the product contains what it claims and isn’t contaminated with bacteria or fungi, not that the product is effective and safe for humans. For example, when researching Amberen, I saw that the web page states that the product can “increase exogenous estrogen levels.” 

I am highly skeptical that a product without hormones can increase estrogen levels. And as expected, the references were not the most, um, inspiring. For example, one is from a journal mostly printed in Russian that I was able to track down (fortunately, the article in question was in English), but my computer would not let me download it for “security reasons.” The study is problematic for many reasons. For example, they provided no demographic data on the participants and included women ages 40-61 but didn’t break them down by menopausal status (pre or post); the authors simply said, “Thus, in general, most participants in this distribution were in the stages of early menopause,” but this is useless information because they did not say how many participants or define early menopause. Issues aside, this article claimed that estradiol levels increase by 4 four, which is not only a bold claim but, if true, would be highly concerning because it could put people at risk for endometrial cancer or be harmful to people with breast cancer. To be clear, I highly doubt Amberen can do this, but third-party testing can’t resolve these safety considerations brought up by the company’s own claims. 

Here’s another example that third-party testing doesn't resolve: green tea leaf extract, turmeric, and black cohosh are associated with liver failure, and yet they’re not considered harmful substances by Amazon or, apparently, by many people who make supplements. This is alarming, considering we have no idea about the risk of liver failure with these products or what dose is concerning. We also don’t even know if these products even work. And we don’t know any of this because people who sell these products choose not to do the studies. There is simply no way for the consumer to assess the balance of benefits versus risks for green tea leaf extract, turmeric, or black cohosh, which should be unacceptable but is perfectly legal in the United States and many other countries. 

There is real money in menopause supplements

It’s clear why the market is flooded. Given that no R&D is required, all someone has to do is email a company that makes these products, set up a Shopify site (and they will even hook you up with a designer for your e-store), and, if you have a large media or social media presence, you are on your way to making hundreds of thousands or even millions of dollars a year with less than 40 hours of work. Everything can be outsourced to a 3rd party expert at a relatively minimal expense. I know because I went through the exercise of doing it, and you can read about my Menopause Taming Turmeric Supplements here. And it’s clear that for those who want to expand their market beyond their own social media reach, Amazon is a very attractive place to move product. 

The right answer to insufficient research isn’t to join the patriarchy and sell understudied, unstudied, and potentially harmful products to women. The right answer, when faced with a lack of research, is to raise the money and do the fucking research. It’s clear that almost everyone selling these products is making enough profit to do this. The lack of quality studies means people who sell these products, whether they are a big-name supplement company or a doctor or a celebrity, aren’t champions for women; they are “entrepreneurs” and profiteers who are more concerned about their own bottom line than getting definitive answers to help women. 

References

Eltelbany, Ahmed; Hamid, Osama; Nanah, Rama; Paleti, Swathi. Liver Cleansing Imposters: An Analysis of Popular Online Liver Supplements. The American Journal of Gastroenterology 118(10S):p S1008-S1009, October 2023. | DOI: 10.14309/01.ajg.0000954920.30407.c4

NAMS POSITION STATEMENT. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause 2023;30:573-590.

van Die MD, Burger HG, Bone KM, Cohen MM, Teede HJ. Hypericum perforatum with Vitex agnus-castus in menopausal symptoms: a randomized, controlled trial. Menopause 2009;16:156-163. doi: 10.1097/gme.0b013e31817fa9e0

Rotem C, Kaplan B. Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: randomized, controlled, double-blind pilot study. Gynecol Endocrinol 2007;23:117-122. doi: 10.1080/09513590701200900

Hafizi S, Abbassian A, Tabarrai M. The effect of Jazar supplement on quality of life and sexual function in postmenopausal women: a doubleblind, randomized, placebo-controlled trial. Evid Based Complement Alternat Med 2021:8854182. doi: 10.1155/2021/8854182

Newmaster, S.G., Grguric, M., Shanmughanandhan, D. et al. DNA barcoding detects contamination and substitution in North American herbal products. BMC Med 11, 222 (2013). https://doi.org/10.1186/1741-7015-11-222.

Baker DA, Stevenson DW, Little DP: DNA barcode identification of black cohosh herbal dietary supplements. J AOAC Int 2012, 95:1023–1034

White CM. Continued Risk of Dietary Supplements Adulterated With Approved and Unapproved Drugs: Assessment of the US Food and Drug Administration's Tainted Supplements Database 2007 Through 2021. J Clin Pharmacol. 2022 Aug;62(8):928-934. doi: 10.1002/jcph.2046. Epub 2022 Mar 31. PMID: 35285963.

Cohen  PA, Travis  JC, Keizers  PHJ, Deuster  P, Venhuis  BJ.  Four experimental stimulants found in sports and weight loss supplements: 2-amino-6-methylheptane (octodrine), 1,4-dimethylamylamine (1,4-DMAA), 1,3-dimethylamylamine (1,3-DMAA) and 1,3-dimethylbutylamine (1,3-DMBA).  Clin Toxicol (Phila). 2018;56(6):421-426. doi:10.1080/15563650.2017.1398328

Maevsky EI, Peskov AB, Uchitel ML, Pogorelov AG, Saharova NY, Vihlyantseva EF, Bogdanova LA, Kondrashova MN. A succinate-based composition reverses menopausal symptoms without sex hormone replacement therapy. Adv Gerontol. 2008;21(2):298-305. PMID: 18942377.

I’ve written a few times about how menopause is the new frontier to exploit via supplements. Celebrities and doctors are trying to cash in, so why let the naturopaths get all that supplement cash? If you want to be alarmed about how easy it is for a doctor to make a fortune selling supplements, read this post.

Given the weak legislation around supplements, those who sell them are able to make bold promises that aren’t backed by science. And what’s worse is an accurate discussion of risk is almost always missing from the Instagram reels and slick Shopify sites selling these unstudied pharmaceutics. I get it, when you are trying to make a buck, highlighting a product's risks isn't exactly a good business model, but it’s unethical to discuss a medication, never mind sell one, without discussing potential risks.

Often when we discuss supplements we focus on the fact that their purported benefits aren’t supported by science. Which is important, but of course, the corollary is, when there is no science showing a product works, there is also no safety data. In comparison, understanding risk is an essential part of getting a pharmaceutical approved by the Food and Drug Administration (FDA) because not only do the clinical trials that study the drug report on side effects and complications, but all pharmaceuticals have what’s called post-marketing surveillance, which is the monitoring of drugs after they go to market. This is important because clinical trials may not be long enough to capture all the risks or have enough patients. This doesn’t mean that our FDA-approved medications are unsafe; instead, if a severe complication has a risk of one in 10,000, that might not be captured until hundreds of thousands of people take the medication. This process allows the FDA to look for safety signals that appear after a drug goes to market.

As quality clinical trials are rare with supplements and post-market surveillance nonexistent, evaluating their risk is challenging, if not impossible. Instead, investigators are basically left picking up the pieces when people have serious complications, assuming the complication is even reported. This is even more difficult because many supplements have multiple ingredients. Which one is the cause, or is it a case of the sum being worse than the individual products? Supplements can also contain harmful bacteria or fungi or may not even contain what they claim and then can even be adulterated with harmful substances (in some cases, drugs that have never been tested on humans!). This means that when someone gets sick after taking a supplement, unless the pills in the specific bottle are analyzed, the actual source of the harm can't be known—good for supplement manufacturers, bad for you.

Despite these limitations, it’s clear that liver injury from herbal and dietary supplements (which we will refer to as supplements going forward) is a growing concern. It’s such an issue that the NIH convened a meeting about this in 2017. And it’s no wonder they called a meeting because the risk of supplement-related liver injury and liver injury severe enough that liver transplantation is needed has increased dramatically over the past 20 years. Some estimates suggest supplements may cause up to 43% of non-acetaminophen drug-induced liver injury in the United States and 19% of non-acetaminophen drug-induced acute liver failure.

A relatively recent study gives us an insight into the rise of the most severe cases of liver injury related to supplements, those that lead to the need for a liver transplant, and I want to highlight this work. A group of researchers looked at people waiting for a liver transplant on the United Network for Organ Sharing (UNOS), and they looked specifically at those whose liver injury was medication related, either pharmaceutical, an over-the-counter-medication, or a supplement, to see if there were any trends over time. They divided people into three groups by the year they were put on the waitlist: 1995-2003, 2004-2012, and 2013-2020. They also further divided people into acetaminophen (aka Tylenol®) vs all other medications, and then in the “other” category, they looked specifically at supplements.

Over 26 years, a total of 267,615 people were listed for a liver transplant (1995-2020), and 2,146 had liver failure due to a medication where the medication was identified. The average age was 32-35 years (depending on the years in question, it rose from 32 at the beginning of the study to 35 at the end). I’ll be honest; this surprised and saddened me because that means there are a lot of young people who need a liver transplant due to medication. Looking at those whose liver failure was due to supplements, the average age was 42 and was stable across all three of the time frames. Apart from age, what do we know about this group whose liver failure was due to supplements?

Of the 61 cases of liver failure due to supplements, 21 occurred in California, which means 34% of supplement-related liver failure occurred in the state with 12% of the American population. While we can’t know for sure, this is likely due to greater cultural acceptance of supplements in California. During the first time block, 1995-2003, White women were the predominant group affected, but in the last time frame analyzed, the group had become more racially and ethnically diverse. It isn’t known if this is due to changing patterns in supplement use or if changes in access to medical care might have played a role, as this later time frame overlapped with Medicaid expansion and so people who previously had difficulty accessing medical care and who suffered from health inequalities due to structural racism were now able to receive medical care and be waitlisted.

Depending on the year, between 74-79% of those on the waitlist because of a medication reaction were women, but looking at those with supplement-related liver failure, there was a dramatic shift in distribution by sex. Between 1995-2003 there were no men with supplement-related liver failure on the transplant list, and by the last time block (2013-2020), men accounted for 49% of supplement-related liver failure. My guess is this is due to the flood of bodybuilding products targeting men and the rise of Instagram as an influencer-driven marketing tool for these products. This makes me think of the old Virginia Slims “You’ve Come A Long Way, Baby” cigarette ads aimed at women, but instead of hiding lung cancer with a veneer of feminism, supplement influencers targeting men are hiding liver failure with a veneer of masculinity.

If more men are taking riskier supplements, of course, they will make up a greater percentage on the waitlist. However, it is still vital for people to know that overall, women have a greater risk of medication-related liver failure than men. This is just one of the reasons why adequately studying medication for women is essential and, of course, why supplements pose a greater risk for women. We are trying to correct the systemic understudying of drugs on women, and supplements turn back that clock. Selling and promoting supplements for women’s health is performative feminism. Real feminism is studying products to make sure they are effective and ensuring the medication supply is safer for women. Remember that the next time you see a health care provider or influencer shilling her untested supplement as a faux take-charge-of-your-menopause/menstruation/fertility empowerment.

In the study at hand, acetaminophen was the most common cause of drug-related liver failure. From 1995-2003 it was the cause of 66.8% of the drug-induced liver injury that led to the need for a transplant; from 2004-2012, it was 78.4%; and from 2013-2020 it was 70.9%. After acetaminophen, the three most common classes of medications that caused liver failure necessitating a transplant were antimicrobials, drugs for epilepsy, and supplements. Looking just at these non-acetaminophen severe liver injuries, the percentage due to supplements rose eightfold. That’s right 8x! The most commonly implicated products were green tea extract, weight loss supplements, muscle-building supplements, Hydroxycut, and Oxylite Pro.

Here is a chart showing the percentage of non-acetaminophen-related liver failure leading to being waitlisted for a liver transplant and how that changed over time in the study:

The researchers also looked more closely at FDA-approved medications that led to liver failure and found something very interesting. Cases of liver failure were linked to older medications. The authors raised the possibility that the FDA approval process has become more attuned to preventing liver injury, resulting in greater safety.

Don’t women deserve that same safety from supplements?

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A lot of people might think, well, acetaminophen causes a lot of liver failure, so why should I worry about supplements? They seem relatively safe in comparison. Remember, many of the acetaminophen-related cases are overdoses, so the drug was not taken as directed, either accidentally or intentionally. In addition, some of these people with acetaminophen-related liver failure will not have had access to emergency treatment for acetaminophen overdose, meaning their liver failure might have been prevented with prompt care. This doesn’t apply to supplements, which you can’t know how to take correctly as they are unstudied. And here’s another critical point–we know acetaminophen is an effective pain reliever, but, for comparison, we don’t know that Dr. Marie Clare Haver’s ‘Pause-Life Turmeric Supplement or Dr. Vonda’s NOVA MD Advanced Menopause Support can do a damned thing.

The trend for supplements and liver failure is alarming. What else do you call an 8x increase in the risk of liver failure from products with no evidence of any real health benefit? Unfortunately, we have yet to determine exactly why these products harm people. Are they contaminated, and if so, with what? Or do they contain what they claim and the risk is related to the stated ingredients? All these unknowns could be solved with regulation and an ethical supplement industry, so remember that when you see doctors, naturopaths, celebrities, health coaches, chiropractors, influencers, and whoever else is in the rogue’s gallery of supplement shills pushing their products. It’s a choice to be unsafe and to profit from the gaps in medicine.

I can’t solve these big systemic issues, but what I can do is warn people that there is a pattern emerging: the risk of supplements causing liver failure that leads to needing a transplant is rising. It’s always buyer beware, but consumers should be extra aware that any supplements marketed for weight loss or muscle building and those with green tea extract are especially associated with liver failure that requires transplantation. As these products are untested for safety and efficacy, if someone is selling you one of them, is it your health or your wallet that interests them?

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I have been reviewing different supplements targeting women’s health concerns, so let me know if you like those posts and if you’d like to see more. You can find all of my posts about supplements here.

References

Navarro VJ, Khan I, Björnsson E, Seeff LB, Serrano J, Hoofnagle JH. Liver injury from herbal and dietary supplements. Hepatology. 2017 Jan;65(1):363-373. doi: 10.1002/hep.28813. Epub 2016 Nov 17. PMID: 27677775; PMCID: PMC5502701.

Vega M, Verma M, Beswick D, Bey S, Hossack J, Merriman N, et al. The incidence of drug‐ and herbal and dietary supplement‐ induced liver injury: preliminary findings from gastroenterologist‐ based surveillance in the population of the state of Delaware. Drug Saf 2017;40:783‐787.

Björnsson E, Bergman OM, Björnsson HK, Kyaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144:1419–1425.

Ghabril, Marwan; Ma, Jiayi; Patidar, Kavish R.; Nephew, Lauren; Desai, Archita P; Orman, Eric S; Vuppalanchi, Raj; Kubal, Shekhar; Chalasani, Naga. Eight‐Fold Increase in Dietary Supplement–Related Liver Failure Leading to Transplant Waitlisting Over the Last Quarter Century in the United States. Liver Transplantation 28(2):p 169-179, February 2022. | DOI: 10.1002/lt.26246

I’m genuinely curious if it’s true that I should take a probiotic alongside an antibiotic to reduce the risk of developing a yeast infection.

-Via Instagram

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Short Take

I don’t recommend it.

Tell me More…

Let’s tackle this in three parts.

How Common are Vaginal Yeast Infections After Antibiotics

Post-antibiotic vaginal yeast infections are commonly reported, and some experts estimate the risk may be as high as 10-30%, although we actually have very little quality data about this phenomenon as it is so understudied. Many symptoms and conditions that are very bothersome are considered insignificant because they are not life-threatening and they only affect women. One of the better studies that evaluated women before and after they took antibiotics found that 20% developed a yeast infection. In this study, the two major risk factors for a yeast infection after antibiotics were being colonized with yeast before starting the antibiotics and reporting being prone to yeast infections after antibiotics.

Studies like this one are important because observational studies can be problematic as many women self-diagnose and self-treat treat or are treated by their providers without receiving a correct diagnosis via testing. This means when someone reports having had a yeast infection, we don’t know if that report is accurate as self-diagnosis of a yeast infection can be incorrect up to 50% of the time. Unfortunately, many medical providers don’t perform much better when they don’t do the appropriate testing. Even in many prospective studies, women have often simply been asked about their symptoms, and so instead of receiving the appropriate test to get an accurate diagnosis, all vaginal and vulvar mayhem is assumed to be yeast. Fortunately, this is changing.

There are some studies that look at vaginal colonization after antibiotics, meaning the presence of yeast but no symptoms. Most people believe colonization is necessary before infection, so this finding supports an antibiotic-yeast connection. Some studies show an increase in yeast after antibiotics, but others do not. It’s rare to find several studies evaluating the same antibiotic, so it’s not possible to know if some antibiotics are more likely to lead to an increase vaginal colonization with yeast, hence the discrepancies between studies, or if there are other reasons for the difference.

Bottom Line: Based on limited data, about 20% of women get a yeast infection after a course of antibiotics (not an insignificant number!), and some women may be more prone than others.

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What Causes Post-Antibiotic Yeast Infections?

The dogma has long been that antibiotics kill the “good bacteria” (primarily lactobacilli) that control the vaginal ecosystem, including keeping the normally present yeast in check. When the good bacteria are killed by the antibiotics, the yeast is now free to overgrow. However, there are some issues with this theory. Here are the main two, which basically drive truck-like holes in the hypothesis:

• We don’t have studies that tell us antibiotics kill off vaginal lactobacilli.

• We don’t think the lactobacilli in the vaginal microbiome play a big role in preventing yeast infections, as women with recurrent vaginal yeast infections aren’t lacking lactobacilli.

If antibiotics lead to yeast infections, it is almost certainly unrelated to lactobacilli. However, antibiotics can damage or affect the microbiome in other ways, and these changes could allow the “Hey, I’m along for the ride” vaginal yeast to become more aggressive (meaning invasive), hence causing an infection.

The fact that many women do not develop a yeast infection after antibiotics and that some women seem to be more vulnerable to this phenomenon suggests that there are likely individual risk factors at play, for example, genetics or other factors that increase the risk of colonization with yeast (for example, estrogen therapy, either in contraception or vaginal estrogen), or skin conditions, like lichen sclerosus.

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What About Probiotics?

Since lactobacilli don’t appear to be involved with yeast infections, that pours cold water on the idea that probiotics could help. In 2019, Dr. Jack Sobel, a doctor and infectious diseases expert who probably knows more about vaginal yeast than any other human alive, wrote that using oral or vaginal probiotics to prevent antibiotic-related yeast infections represents “a leap of faith of extrapolation based on zero data and proof of efficacy.”

Studies tell us that oral probiotics don’t do a good job of colonizing the vagina, so even if probiotics were the thing, that method of delivery would be pointless.

The lactobacilli species that dominate the vaginal microbiome are crispatus, iners, gasseri, jensenii, and vaginalis, although reuteri, rhamnosus, and gallinarum can be found. Most commercial products don’t have crispatus and iners, which are the most commonly isolated species from healthy vaginal microbiomes. So, there’s that. There is a product called Lactin-V, which is vaginal lactobacillus crispatus. Lactin-V is still under investigation and has shown early promise for preventing bacterial vaginosis, but it is not yet commercially available. I believe the company is ultimately aiming for FDA approval, but I am not “in the know.” There is a new OTC vaginal probiotic called Seed, which also contains lactobacillus crispatus, but currently, there are no clinical trials with this product for the treatment or prevention of infections, so it can’t be recommended. Regardless, as we don't believe the loss of lactobacilli is a cause of post-antibiotic yeast infection/symptoms, this would also not be a time to consider this product.

Most of the existing studies looking at probiotics to treat/prevent vaginal yeast infections are generally of lower quality, but based on the evidence (such as it is), a recent meta-analysis concluded that probiotics didn’t appear to hold much promise for vaginal yeast infections in general. This fits with what we know. One prospective placebo-controlled clinical trial evaluated two different probiotics for preventing yeast infections after treatment for urinary tract infections. The study used an oral probiotic containing Lactobacillus rhamnosus and Bifidobacterium longum and a vaginal probiotic containing L. rhamnosus, L. delbrueckii, L. acidophilus, and Streptococcus thermophilus, and neither were effective. There is some preliminary evidence that supports vaginal lactobacillus crispatus for the prevention of urinary tract infections, but more work is needed.

Ultimately, developing a prescription product for any probiotic that appears to be effective would be ideal. Research to get FDA approval would be required, so we’d really know if it works. In addition, these products are not cheap, and you deserve more than any company’s claims about effectiveness. And with a prescription product, there would be regulatory requirements, so we would really know that it contains what it claims.

The best course of action for someone with a history of yeast infections after antibiotics is to be evaluated the next time symptoms occur after antibiotics so they can be formally tested for yeast to ensure the diagnosis is correct. Once the diagnosis has been confirmed, oral fluconazole or over-the-counter anti-fungal medications can be used to prevent an infection. I recommend oral fluconazole (150 mg) once a week while taking an antibiotic, but a vaginal over-the-counter weekly therapy could also be used.

Bottom Line: Based on the data, probiotics, either oral or vaginal, will not prevent a yeast infection after antibiotics.

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As always, the information here is not direct medical advice. If you have questions, leave them below. I try to reply to the easier ones directly in the comments (obviously, again, not individual medical advice). For those questions that are more complex, I tuck them away to try to incorporate them in future posts, as I am always looking for “Ask Dr. Jen” questions.

References

Shukla, A., Sobel, J.D. Vulvovaginitis Caused by Candida Species Following Antibiotic Exposure. Curr Infect Dis Rep 21, 44 (2019). https://doi.org/10.1007/s11908-019-0700-y

Tabrizi SN, Pirotta MV, Rudland E, Garland SM. Detection of Candida species by PCR in self-collected vaginal swabs of women after taking antibiotics. Mycoses. 2006 Nov;49(6):523-4. doi: 10.1111/j.1439-0507.2006.01312.x. PMID: 17022774.

Rocha RM, Zanni PC, de Souza Bonfim-Mendonça P, Gimenes F, Alczuk SS, Svidzinski TI, Consolaro ME. Effect of norfloxacin therapy for acute, uncomplicated lower urinary tract infection on vaginal Candida prevalence. Int Urogynecol J. 2016 May;27(5):773-80. doi: 10.1007/s00192-015-2884-5. Epub 2015 Nov 13. PMID: 26564224.

Pirotta M, Gunn J, Chondros P, Grover S, O'Malley P, Hurley S, Garland S. Effect of lactobacillus in preventing post-antibiotic vulvovaginal candidiasis: a randomised controlled trial. BMJ. 2004 Sep 4;329(7465):548. doi: 10.1136/bmj.38210.494977.DE. Epub 2004 Aug 27. PMID: 15333452; PMCID: PMC516107.

van de Wijgert J, Verwijs MC. Lactobacilli-containing vaginal probiotics to cure or prevent bacterial or fungal vaginal dysbiosis: a systematic review and recommendations for future trial designs. BJOG. 2020 Jan;127(2):287-299. doi: 10.1111/1471-0528.15870. Epub 2019 Aug 8. PMID: 31299136.

Pirotta MV, Garland SM 2006. Genital Candida Species Detected in Samples from Women in Melbourne, Australia, before and after Treatment with Antibiotics. J Clin Microbiol 44:https://doi.org/10.1128/jcm.00218-06

Varsha Gupta, Paola Mastromarino, Ritu Garg, Effectiveness of Prophylactic Oral and/or Vaginal Probiotic Supplementation in the Prevention of Recurrent Urinary Tract Infections: A Randomized, Double-Blind, Placebo-Controlled Trial, Clinical Infectious Diseases, Volume 78, Issue 5, 15 May 2024, Pages 1154–1161, https://doi.org/10.1093/cid/ciad766

There is a growing body of evidence that the gut microbiome plays an important role in many aspects of human health, such as hormone health, immune function, metabolism, inflammation, and even bone health. More and more papers have been popping up about the microbiome and bone health, so much so that it feels as if we are at the start of an exponential increase in research looking at how to modulate the gut microbiome to prevent osteoporosis. 

Given this trend and considering that probiotics are already big moneymakers with little to no hard evidence of value for most conditions and menopause has proven to be a gold rush for supplement scammers, I thought it might be interesting to look at some of the data on the gut microbiome and bone health and walk through a new study. There is some really cool science here, but it’s certainly not anywhere near ready for prime time.

Gut Microbiome 101

Our intestines are host to a community of microbes known collectively as the gut microbiome, which includes bacteria, viruses, and fungi. Before we go any further, it’s important to stress that we don’t know what we don’t know about the gut microbiome. We are on the precipice of a brave new world of research, and as technology improves, we will undoubtedly learn more. Here’s a good example using the vaginal microbiome. In the early 1990s, when I was in OB/GYN, we thought it was lactobacillus acidophilus all the way for vaginal health. This was the golden ticket for vaginal health. And then DNA technology became a thing, and all of a sudden, we could identify bacteria we had no idea existed in the vagina because it couldn’t be cultured in a lab. Now, we know a lot more about the vaginal microbiome, and one of those things is that lactobacillus acidophilus isn’t a big deal; it was just easy to grow in the lab, but we couldn’t know that until the technology had advanced far enough to figure that out. Think of our current knowledge of the microbiome as the first few maps of a new world, and we have no idea how complete the maps are or what we may discover as exploration proceeds.

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It seems that a healthy gut microbiome is diverse, and while there are communities of bacteria that are associated with a healthier microbiome, people can have quite different microbiomes and still be healthy. The best thing for a diverse microbiome seems to be a fiber-rich diet, and a typical “Western” diet is probably the least healthy as far as the microbiome (and almost every health metric, really) is concerned. The microbiome can change throughout the day and also have seasonal variations, and can also change positively in response to exercise. The microbiome also changes with age. In one study, people whose microbiome changed the most with age had better blood markers of health, were more mobile, and were overall in better health. This suggests that what is good for you microbiome-wise at age 20 or 30 might not be at age 70. But it is also important to remember that a lot of what we know is observational data, and healthier people might move more, make more meals at home, or take fewer antibiotics or other medications, which could result in their microbiome being different. 

While some studies suggest that the gut microbiome may become less diverse with menopause, the data is conflicting. A recent study, albeit a small one, looked at the microbiome of women before and after their ovaries were removed and found there was no change in bacterial diversity. Whether the women took hormone replacement or not also didn’t impact their microbiome. Most microbiome studies on menopause are painfully small, so it’s really important not to jump to conclusions. We need more work here.

There are so many unknowns with the microbiome that it’s important to be highly skeptical of bold claims.  

The Gut Microbiome and Bone Health

The link between the gut microbiome and bone health is often called the “gut-bone axis,” which sounds like a strategic alliance between regions in an alternate timeline of Earth. But really, a strategic alliance is a good way of thinking about how our organs interact. But how can the bacteria in your gut affect your bones? The very idea seems fantastical. 

And that’s the great thing about science: it can explain events that seem fantastical (with enough funding, that is). 

Research on the gut-bone axis kicked into high gear about 10 years ago with studies on germ-free mice, which are mice without a microbiome. It turns out that germ-free mice have better bone density than mice with a regular microbiome, and when germ-free mice receive a fecal transplant from regular mice, their bone mass decreases and becomes like regular mice's.

Fantastical, indeed!

But why? How?

The protective impact of the absence of gut bacteria wasn’t related to estrogen levels. The proxy for this was the weight of the uterus, which was the same for germ-free and regular mice (apparently, it’s challenging to obtain estrogen levels in mice, a tidbit I am tucking away for when I come up with my Menses and Menopause Trivia Game). Interestingly, calcium absorption was also the same in germ-free and regular mice, so that, too, was not the mechanism behind an increase in bone mass. The impact of the gut microbiome on bone health appeared to be via changes in the immune system that ultimately reduced levels of TNF-α (tumor necrosis factor-alpha), a signaling molecule that stimulates osteoclasts, cells that break down bone. If the signal to break down bone is reduced, the result is more bone.

Interestingly, when germ-free mice have their estrogen removed, either with medication or their ovaries removed, they still don’t lose their bone mass. This doesn’t mean we should be wiping out microbiomes to prevent osteoporosis, but it does suggest the gut microbiome poses a potential avenue for preventing osteoporosis. The fact that germ-free mice with menopause don’t develop poor bone health makes sense when you consider that a major mechanism of menopause bone loss is due to an increase in TNF-α. Estrogen inhibits TNF-α, so in menopause, without the suppressive effect of estrogen on that inflammatory pathway, we see osteoclast activity picking up and accelerated bone loss. Going back to the germ-free mice, reducing estrogen wouldn’t negatively affect bone health because TNF-α was already suppressed given the lack of a microbiome. So fascinating!

This is the kind of basic science research that is needed to move forward in designing therapies. So, the next question is, can a therapy be designed to alter the microbiome so that osteoporosis can be prevented without major risks?

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The Most Recent Study

Researchers from Sweden evaluated the impact of two different doses of the probiotic Limosilactobacillus reuteri ATCC PTA 6475 (L reuteri) daily for two years vs. placebo in a randomized controlled trial for bone health. This probiotic was chosen because, in previous studies, it reduced bone loss in a mouse model and also in a study of older postmenopausal women, although the magnitude of the effect was not large. 

As a side note, it is great to see a study for a supplement that lasted for two years. Too often, these studies are short-term, so even when the results are positive, they don’t really mean much. Another good thing about this study is the investigators used bone density, not just blood tests that evaluate bone turnover, which is a proxy for bone health (less turnover is a good sign). While these blood tests are valuable, what we really want to see is changes in bone density (and also, in an ideal world, a reduced risk of fracture). The researchers also examined protein and calcium intake, which could affect bone mass. 

The overall results showed no protective effect of the probiotic on any marker of bone health. However, one finding of note is that those with an increased BMI had an improvement in bone density, with both the high and low-dose probiotics, less so at one year but more significantly by the end of the second year. The magnitude of the effect increased with increasing BMI. This is an interesting finding as gut dysbiosis is more common among those with obesity, and taken together with results from another study showing some benefit for bone health with the same bacteria for women ages 75-80, who statistically are more likely to have gut dysbiosis, one hypothesis that could be generated is the probiotic L. reuteri may not be helpful for those with a diverse microbiome, but could be helpful for bone health when there is dysbiosis (an imbalance or disruption of the microbiome). The researchers appropriately caution that these results are exploratory at best. This is data on which to build more studies, not run out and slap together a supplement to sell (although it wouldn’t surprise me if someone did that). 

What Does This Mean for Me?

First, it does not mean anyone should take a probiotic for bone health! 

Most human data on the microbiome and bone health is observational, so we must be careful before creating new treatment protocols. While we do have some good lab science that shows inflammation that negatively affects bone can originate in the gut, how to use that information to actually protect bone health requires quality randomized trials. First of all, you don’t want to waste money on probiotic supplements that can’t help. But more importantly, probiotic supplements are not risk-free. For example, people who are immune suppressed can develop serious infections from the bacteria in probiotics. When people take probiotics after a course of antibiotics to try to “re-set” their microbiome, what typically happens is the gut gets colonized with the probiotic bacteria, which paradoxically delays the return of the baseline, native bacteria (not considered a good thing). And there is some literature that suggests some probiotics can carry genes for antibiotic resistance, which could theoretically increase antibiotic resistance. 

Instead of spending hundreds of dollars to test your microbiome and/or on probiotics, based on what we know at this time, the best way to cultivate a healthy microbiome for bone health is the eternally unsexy and, hence, less Instagramable advice of sticking to a diet high in fiber (with an emphasis on protein sources from plants and fish) that also includes fermented foods, quit smoking, only take antibiotics when needed, and of course, exercise. 

In the meantime, I will sit back and hopefully (funding and researchers willing) watch this exciting new research unfold.

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References

Allaband C, McDonald D, Vázquez-Baeza Y, Minich JJ, Tripathi A, Brenner DA, Loomba R, Smarr L, Sandborn WJ, Schnabl B, Dorrestein P, Zarrinpar A, Knight R. Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for Clinicians. Clin Gastroenterol Hepatol. 2019 Jan;17(2):218-230. doi: 10.1016/j.cgh.2018.09.017. Epub 2018 Sep 18. PMID: 30240894; PMCID: PMC6391518.

Wang Y, Jiang Y, Deng Y, Yi C, Wang Y, Ding M, Liu J, Jin X, Shen L, He Y, Wu X, Chen X, Sun C, Zheng M, Zhang R, Ye H, An H, Wong A. Probiotic Supplements: Hope or Hype? Front Microbiol. 2020 Feb 28;11:160. doi: 10.3389/fmicb.2020.00160. PMID: 32184760; PMCID: PMC7058552.

Montassier, E., Valdés-Mas, R., Batard, E. et al. Probiotics impact the antibiotic resistance gene reservoir along the human GI tract in a person-specific and antibiotic-dependent manner. Nat Microbiol 6, 1043–1054 (2021). https://doi.org/10.1038/s41564-021-00920-0

Preidis GA, Weizman AV, Kashyap PC, Morgan RL. AGA Technical Review on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology. 2020 Aug;159(2):708-738.e4. doi: 10.1053/j.gastro.2020.05.060. Epub 2020 Jun 9. PMID: 32531292; PMCID: PMC8018518.

Peters BA, Santoro N, Kaplan RC, Qi Q. Spotlight on the Gut Microbiome in Menopause: Current Insights. Int J Womens Health. 2022 Aug 10;14:1059-1072. doi: 10.2147/IJWH.S340491. PMID: 35983178; PMCID: PMC9379122.

Wilmanski, T., Diener, C., Rappaport, N. et al. Gut microbiome pattern reflects healthy ageing and predicts survival in humans. Nat Metab 3, 274–286 (2021). https://doi.org/10.1038/s42255-021-00348-0

Stuart H. Ralston, R. Graham G. Russell, Maxine Gowen, Estrogen inhibits release of tumor necrosis factor from peripheral blood mononuclear cells in postmenopausal women, Journal of Bone and Mineral Research, Volume 5, Issue 9, 1 September 1990, Pages 983–988, https://doi.org/10.1002/jbmr.5650050912

Lyu, Z., Hu, Y., Guo, Y. et al. Modulation of bone remodeling by the gut microbiota: a new therapy for osteoporosis. Bone Res 11, 31 (2023). https://doi.org/10.1038/s41413-023-00264-x

Sjögren K, Engdahl C, Henning P, Lerner UH, Tremaroli V, Lagerquist MK, Bäckhed F, Ohlsson C. The gut microbiota regulates bone mass in mice. J Bone Miner Res. 2012 Jun;27(6):1357-67. doi: 10.1002/jbmr.1588. PMID: 22407806; PMCID: PMC3415623.

Nilsson AG, Sundh D, Bäckhed F, Lorentzon M. Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial. J Intern Med. 2018 Sep;284(3):307-317. doi: 10.1111/joim.12805. Epub 2018 Jul 22. PMID: 29926979.

Suez J, Zmora N, Zilberman-Schapira G, Mor U, Dori-Bachash M, Bashiardes S, Zur M, Regev-Lehavi D, Ben-Zeev Brik R, Federici S, Horn M, Cohen Y, Moor AE, Zeevi D, Korem T, Kotler E, Harmelin A, Itzkovitz S, Maharshak N, Shibolet O, Pevsner-Fischer M, Shapiro H, Sharon I, Halpern Z, Segal E, Elinav E. Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT. Cell. 2018 Sep 6;174(6):1406-1423.e16. doi: 10.1016/j.cell.2018.08.047. PMID: 30193113.

In this subsection of The Vajenda, you’ll find a table of contents (this post) and posts about vitamins, minerals, probiotics, vaginal products, and a whole host of special mixes, as well as background information about legislation or lack thereof (in the United States anyway). And, of course, plenty of information about risks. If the supplement industry isn’t going to provide you with informed consent, then I’m stepping up!

Most of the supplements you’ll read about here are understudied; for some, the data amounts to little more than a hypothesis. Sometimes people think, well, I want to be cutting edge, so I’m okay trying something new, but it’s important not to confuse a novel hypothesis for cutting-edge. Cutting-edge therapy is my 20-year-old son having open heart surgery where a valve was replaced without needing a blood transfusion and being able to walk a mile just two weeks later. The surgery, multiple post-operative protocols, and even the choice of valves weren’t just an idea his surgeon dreamed up; his cutting-edge therapy was the tip of a massive research iceberg that started with many intriguing hypotheses.

Medicine is littered with incredible harm from so-called disruptive or novel medications and interventions that were never evaluated appropriately. The Rely tampon is a classic example (unstudied super absorbent material led to toxic shock syndrome and some deaths), there is the medication thalidomide (unstudied in pregnancy, which led to miscarriages and severe birth deformities), and the Dalkon shield (inadequately studied IUD, which led to severe infections and some deaths), and many more. It’s important not to confuse “cutting edge” with inadequately studied products quickly foisted on people courtesy of unfettered capitalism. And it’s equally as important to note how many of these unstudied/inadequately studied products and medications were meant for women.

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With supplements, it’s hard to know the dangers because there is so little research, so in many cases, the waters are essentially uncharted. In addition, supplements are a supplement adulteration, often with pharmaceuticals or even completely novel drugs, is a real concern. There is also microbial contamination, and many supplements don’t contain the amount of active ingredient that the label claims. For example, in a study published in JAMA (2024), researchers looked at the accuracy of labeling for products containing galantamine, a medication used to treat dementia (primarily Alzheimer's disease), but it has some off-label indications as well. Galantamine offered a unique opportunity to compare the accuracy of labeling for a prescription product versus a supplement, as galantamine is available as both a prescription (regulated) and as a supplement (unregulated). With the regulated prescription (generics were chosen), galantamine in the pills was between 97.5% and 104.2% of the amount indicated on the label, which is not an uncommon margin of error, and there was no bacterial contamination. However, with the unregulated, over-the-counter supplement version, the amount of galantamine ranged from less than 2% to as much as 110% percent of what was printed on the label, and only one product contained what is claimed with the same margin of error as the prescription products. In addition, three or 30% of the supplements were contaminated with genes for the enterotoxin produced by Bacillus cereus sensu stricto, which is a cause of food poisoning.

What about third-party validation? While it may help, especially when it comes to identifying contaminants or adulteration, it may not guarantee the product contains the amount of product that it claims. You can read more about that in this post on prenatal vitamins. 

We also don’t know how supplements might negatively affect the body or interact with other medications. For example, turmeric/curcumin interferes with iron metabolism and can cause iron deficiency. How many other supplements negatively affect a different bodily function?

Trying a supplement that isn’t recommended in any guideline is not wrong. It’s your body and your choice. What is wrong is for a medical provider, coach, or person with a supplement store to misrepresent supplements as being “science-backed,” “doctor-approved,” or “expert-recommended” when quality studies supporting effectiveness and safety are lacking. And it’s wrong not to inform you of the risks. You can make an informed choice only when you are given accurate information.

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With that preamble, here is Gunter’s Guide to Supplements and Such. As I write about more products, I’ll add them to the Table of Contents below with a hyperlink. If you have specific products you’d like me to write about, leave the request in the comments! And as always, the information here is not individual medical advice.

Gunter’s Guide to Supplements and Such

The Basics

***START HERE*** -> What is a supplement anyway? This post breaks down the basics of the different types of products. Really, read this first because there are some cases where supplements are indicated, and the language can be confusing (which the industry counts on)

The Death-Strewn Backstory of Big Supplement, how we got here (in the United States)

My Open-Minded Approach to Alternative Medicine. Really!

Homeopathic remedies, do you know what they are? Many people do not. Read this post before taking any.

Supplement companies often use podcasts to gain influence. An important read about advertising and using trusted podcasters to whitewash supplements.

The Money

The Money in Menopause Supplements.  I created my own supplement to show how much someone can make selling supplements and how easy it is.

Avenir Nutrition, a company that makes a useless product that glorifies binge drinking, is making millions in sales. Read about their cash claims here. It seems that cultivating a large, engaged following on social media can be wildly profitable. 

Adulteration and Contamination

Lead poisoning in Ayurvedic Medicine. It’s a huge issue.

Mislabeling and dangerous ingredients in sports enhancers. One product even contained a compound that has NEVER BEEN TESTED IN HUMANS (yes, I am shouting).

Products

1. Bone

   Magnesium and Osteoporosis

2. Hair Growth

   Nutrafol, in-depth review here

3. Hangovers/Alcohol/Liver

   The Liver Shield, a supplement that claims to support the liver and help you recover from drinking.

   Z-Biotics. A product that claims it can prevent hangovers.

4. Menopause

   Dr. Kellyann & ME Peri plus Menopause, promoted by Drew Barrymore 

5. Menstrual-Related Concerns

   Castor Oil Packs for Menstrual Pain

   Flo vitamins for PMS 

6. Muscle

   Creatine

   How much protein do women really need?

7. Probiotics

   Can probiotics prevent osteoporosis?

8. Pregnancy

   Mislabeling of prenatal vitamins. This is one of the most pressing reasons we need legislation because prenatal vitamins are among the few medically recommended supplements.

   Folic acid: Why you need a prenatal vitamin with folic acid and not “natural” folate or methylfolate. Most designer prenatal vitamins do not have folic acid! 

9. Vaginal Products

   Vaginal boric acid, this is one of those products that is taken advantage of as it does have a legitimate use for two conditions. However, it is inappropriately promoted to balance the vaginal pH, which it cannot do. 

References

Tucker J, Fischer T, Upjohn L, Mazzera D, Kumar M. Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings. JAMA Netw Open. 2018;1(6):e183337. doi:10.1001/jamanetworkopen.2018.3337

Ghabril, M, Ma J, Patidar K, et. al. Eight‐Fold Increase in Dietary Supplement–Related Liver Failure Leading to Transplant Waitlisting Over the Last Quarter Century in the United States. Liver Transplantation 28(2):p 169-179, February 2022. | DOI: 10.1002/lt.26246

Cohen PA, Jacobs B, Van Hoorde K, Vanhee C. Accuracy of Labeling of Galantamine Generic Drugs and Dietary Supplements. JAMA. 2024;331(11):974–976. doi:10.1001/jama.2024.0328

Turmeric is the common name for Curcuma longa. Most people are familiar with using the underground stem (rhizome) in cooking, and many have also probably heard about it as part of some traditional medicine. Like many plants, turmeric contains bioactive compounds, most notably a class called curcuminoids, which includes curcumin. It is curcumin that gives turmeric its distinctive yellow color. Both turmeric and curcumin are promoted as natural medications or supplements, and the benefit of turmeric is believed to be due to curcuminoids, primarily curcumin. The global turmeric/curcumin supplement market was $70 million/year in 2020, estimated to be $112 million/year in 2025. Yes, for one supplement. It is aptly referred to as the golden spice.

To see how much an individual could make from turmeric, I set up my own supplement and distribution system (read about that here). If I charge $35 a bottle, I net $15 a bottle. If I can sell just 8,333 bottles, I can cover my start-up costs and net $195,760. It’s easy to see how someone with a million followers on Instagram or a popular podcast could leverage that large presence to make hundreds of thousands of dollars a year just selling turmeric or curcumin. 

“He who controls the spice controls the universe” is a quote from Dune (1994) that seems to apply to turmeric today.

Recently, turmeric has received more attention courtesy of Dr. Marie Claire Haver, an OB/GYN and menopause specialist with a supplement business. Given her promotion of turmeric for menopause and the money to be made, I felt it was worth a closer look. 

Are menopausal women wasting their money with turmeric products, like those sold by Dr. Haver, or is there something to turmeric? 

The Biology of Turmeric and Curcumin 

For a substance like turmeric to provide medicinal value beyond the gut, it must be absorbed into the blood. When ingested, about 99% of turmeric remains in the gut and heads out of the body with stool. This means that almost none of it gets into the blood, which also means that turmeric in reasonable doses is nontoxic, although adulteration with lead can be a concern with turmeric spice and turmeric supplements (which are much higher amounts than used in cooking). Contamination with lead can come from the soil where the turmeric is grown, or turmeric/curcumin can be purposely adulterated with lead chromate to enhance the yellow color. 

Curcumin is a highly problematic molecule. In addition to being poorly absorbed, it’s challenging to study in a lab. Curcumin is classified as one of the pan-assay interference compounds, or PAINS, which means it can interfere with lab tests in various ways (and means the acronym PAINS is very accurate). I asked Kevin Klatt, PhD, RD, a research scientist and instructor in Nutrition Sciences and Toxicology at Berkeley, who told me, “PAINS are a problem because, in science, we can rarely observe what is happening biologically, but rather we develop assays with specific readouts that tell us what is happening biologically (e.g., a color change, increased fluorescent signal) and curcumin interferes with these readouts.” This kind of interference can lead researchers to believe that curcumin might be doing something when, in reality, it’s just messing with the test results, so the results may be spurious. There is also concern about curcumin being unstable. 

Compounds that are absorbed poorly, that may be unstable, and that create unreliable results are generally not good candidates for medications. This means studying curcumin requires the utmost scientific rigor; otherwise, the results will be meaningless. Science needs reproducibility and reliability, not crap shoots. The problems inherent in studying curcumin are laid out in detail in a 2017 review of the biology of curcumin in the Journal of Medicinal Chemistry that calls the substance “an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead.” The way curcumin can respond in the lab can make weak research leads look more robust than they are, leading to research that is destined to fail because it was built on a false premise. This sucks up precious research funding. 

There are also issues with many papers evaluating curcumin. Bharat B. Aggarwal, PhD, was a biochemist from MD Anderson Cancer Center who co-authored over 120 papers on curcumin. In 2012, the U.S. Department of Health and Human Services' Office of Research Integrity notified MD Anderson about concerns regarding image manipulation in 65 of his papers. By 2022, at least 30 of his papers had been retracted due to concerns about scientific misconduct; apparently, more are problematic. Dr. Aggarawal is currently at #27 on the Retraction Watch Leader Board for most retracted papers, yet people continue to cite his work in articles about turmeric or curcumin! In addition, many studies about curcumin from other authors have been flagged as potentially originating from paper mills. 

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Does Turmeric/Curcumin do Anything Medical? 

From 1995 to 2017, the NIH funded curcumin with over $150 million, yet we have no quality data to make a solid recommendation for any indication. 

There are many studies of varying quality, but very few are high-quality, randomized, double-blind placebo control trials. There is no orderly progression from basic science or lab research to Phase 1, then Phase 2, and then Phase 3 clinical trials, as we demand with pharmaceuticals. In addition, many studies use different formulations, so comparing the results meaningfully isn’t possible. We need quality Phase 3 studies to recommend a pharmaceutical, so why should we hold turmeric/curcumin to a lower standard? There have been over $150 million in NIH funding, and it’s a $70 million-dollar-a-year and growing business, so the absence of quality studies can’t be for want of money.  

There is a recent scoping review of curcumin (2023). A scoping review is a lay-of-the-land kind of review; it is not the kind of rigorous scientific review we see with a systemic review, which is a deep dive into the data to attempt to answer a specific question. Scoping reviews are generally done when the data isn’t strong enough yet to support a systemic review. While many of the studies included were randomized double-blinded placebo-controlled trials, the quality of these studies wasn’t interrogated. Some studies included in the review were small (as few as 3 or 4 participants), most were short-term, and there was no evaluation of study methods, statistical analysis, or potential bias (this is typical of a scoping review). In addition, formulations of curcumin were not consistent between studies. Conclusions about benefits aren’t possible with scoping reviews, and these publications should not be used to guide therapy. The result of the scoping review suggests that maybe curcumin might have benefits for arthritis and for people with metabolic syndrome, but additional research is needed with high-quality clinical trials.  

However, another review (2022) looking at the data had a much harsher conclusion:

Through a review and summary of the clinical research on curcumin and case reports of adverse effects, we found that the clinical transformation of curcumin is not successful, and excessive intake of curcumin may have adverse effects on the kidneys, heart, liver, blood and immune system, which leads us to warn that curcumin has a long way to go from basic research to application transformation.

And: 

However, compared with a large number of exciting preclinical studies on curcumin, the clinical studies on curcumin are rather dull.

And therein lies one of the issues with low quality studies that are typical of so-called alternative medicine. If you consider low-quality studies, the results look more promising, but when stricter criteria are applied, the results become underwhelming. 

Dr. Klatt agreed with me about the state of the literature. He told me that robust clinical trials with curcumin are: 

“often lacking, with a few small, high risk of bias trials in diseases like inflammatory bowel disease and osteoarthritis suggesting small clinical benefit. To date, no societies are recommending curcumin, partly due to the lack of RCTs, and partly due to the challenges in having standardized formulations (i.e. giving a similar amount of curcuminoids across batches) that are shelf-stable. One of the problems in the curcumin research space is that few trials have measured outcomes that are clinically relevant - for example, you can find trials that show a certain curcumin formulation slightly lowers an inflammatory marker like hsCRP or an oxidative stress marker, but these have limited prognostic capacity in many disease states. Whether the curcumin is actually improving validated disease metrics (e.g. histology, pain scores, remission rates/duration, disease events) is often unknown. Unfortunately, claims around inflammation, metabolism, and oxidative stress are recognizable by the public and imply a clinical benefit where one rarely has been demonstrated.”

In simpler terms, we just don’t have the kind of quality clinical trials we need to make recommendations. This is shocking, considering the funding. 

A common reason to recommend turmeric or curcumin is arthritis. The 2019 guidelines on osteoarthritis from the American College of Rheumatology (ACR) don’t mention turmeric or curcumin. Interestingly, Dr. Haver recommends turmeric for bone mineral density, but neither of her two provided references for turmeric supports that claim. The Menopause Society 2021 Position Statement on Osteoporosis doesn’t mention turmeric or curcumin. There are a few small, low-quality, short-term studies suggesting turmeric/curcumin might benefit bone density, but we shouldn’t make clinical recommendations based on that kind of data. In one of the studies I found, two authors worked for the company that made the curcumin, and one was a consultant for the company. Many women in menopause are concerned about their bone health, and in my opinion, it is predatory to suggest turmeric as a viable therapy and then conveniently sell it.

Dr. Haver also recommends turmeric to treat exercise-induced muscular pain to improve recovery, but a 2017 Cochrane review of antioxidant supplements for muscle soreness after exercise, which included curcumin supplements, concluded, “There is moderate to low‐quality evidence that high dose antioxidant supplementation does not result in a clinically relevant reduction of muscle soreness after exercise at up to 6 hours or at 24, 48, 72 and 96 hours after exercise.” I added the bold for emphasis. 

Also, no supplement is recommended in the Menopause Society’s latest guidelines for treating hot flashes.

Liver Injury

As curcumin isn’t absorbed well, there has been an explosion of different formulations to improve absorption and bioavailability, such as combining turmeric or curcumin with piperine (from black pepper) or formulating the curcumin in nanoparticles or encasing it in lipids. Some claim that these methods might increase absorption by 2000%. But here’s the catch. Turmeric and curcumin have been considered relatively benign because absorption was so bad, so what might happen when it’s actually absorbed? 

Curcumin can negatively affect iron metabolism, and there are reports of iron deficiency. This may be an issue for those who already have low iron levels, which is a common issue for women. There is a concern that if absorbed curcumin might be toxic to more than cancer cells as there is also data showing it can be toxic to human kidney cells and macrophages (a type of white blood cell). A recent animal study evaluating curcumin nanoparticles shows that while low and medium doses of curcumin nanoparticles were safe for rodents, high doses damaged the liver, spleen, kidneys, lungs, and pancreas. This means these new curcumin products with enhanced absorption/bioavailability need rigorous safety data (and, of course, data showing they actually work) before they are used. Like we demand of any new drug. 

The biggest safety concern with turmeric/curcumin appears to be liver injury, and there are multiple reports from many countries:

• The Italian Ministry of Health banned health claims regarding turmeric and curcumin supplements, spurred on by more than 20 cases of turmeric/curcumin-related hepatitis.

• The French Agency for Food, Environmental and Occupational Health & Safety reports over 100 cases of adverse effects (15 cases of hepatitis) related to turmeric and/or curcumin.

• In Australia, there have been at least 18 cases of liver injury related to turmeric/curcumin, including one fatality.

• At least 10 cases of liver injury related to turmeric/curcumin have been reported in the United States, with one death. The most common scenario was a woman “using turmeric for arthritis, pain relief, and/or general health.”

Contamination with lead or dyes as a cause of the liver injury has been ruled out, so it seems to be the curcumin. In addition, the rising numbers of liver injuries seem to parallel the flood of new products designed to enhance curcumin absorption. 

Currently, only 0.5% of drug-related liver injuries are due to turmeric/curcumin, but there has been an alarming bump that parallels the recent introduction of newer products. As they have not been studied meaningfully, from a safety standpoint, this is all buyer beware.  

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Unknowns

Could a formulation of turmeric/curcumin with enhanced absorption be safe and effective for some medical conditions? Sure. We must always be open to quality data; that is the amazing meandering path of science. However, an equally plausible hypothesis is that no meaningful benefit will be found. This is why we do research. It’s concerning that over $150 million in American taxpayer dollars later, we still don’t have good data for curcumin. In 2022, endometriosis received $27 million in NIH funding, but it has traditionally been much lower than that. It’s hard to play research favorites, but it’s also hard to see money go to support funding for a molecule that has resulted in less than spectacular results, and yet we still don’t understand the basic biology of a disease that affects 10% of women.

Some have wondered if curcumin's beneficial effects might be via an effect on the gut microbiome, and that avenue is largely unexplored. So yes, it’s possible. Again, we need data. 

Products with enhanced absorption need quality studies to show they work and rigorous safety testing, but those are not the kind of studies we have come to expect from the supplement industry. And because the supplement industry doesn’t have to do those studies, it’s up to the taxpayers to fund them, which diverts funding from other diseases and therapies.

Women Deserve Data

I am so tired of inadequately tested products being foisted on women. Those who sell turmeric or curcumin supplements don’t fund rigorous studies because they don’t have to. Look, they are already making a small fortune selling them, so why risk a negative result? Not doing that work means you think women don’t deserve quality data. Also, there’s the issue of spending $420 ($35/bottle x 12 bottles per year) or so dollars a year on a product with dismal data. To anyone who sells turmeric or curcumin supplements, if you think your product is effective and safe, prove it.

The fact that turmeric is a plant doesn’t mean it’s effective or safe. When turmeric is used as a spice in cooking it is almost certainly in lower doses than supplements, rarely ingested every single day, and it is mixed with other nutrients that may further reduce absorption. In addition, and probably most importantly, turmeric in food is not mixed with agents designed to enhance absorption.

If you are taking a turmeric/curcumin supplement that doesn’t have something to enhance absorption, you are likely just paying for expensive feces. If you are taking a product designed to enhance absorption, you should be mindful of your iron status and know that you are paying to play the liver injury lotto with no quality data to prove that the product can help you meaningfully. I think you deserve better than that. 

References

Lowe, D. Science.org Curcumin will Waste Your Time https://www.science.org/content/blog-post/curcumin-will-waste-your-time (of note the author has his PhD in organic chemistry)

Kathryn M. Nelson, Jayme L. Dahlin, Jonathan Bisson, James Graham, Guido F. Pauli, and Michael A. Walters. The Essential Medicinal Chemistry of Curcumin Miniperspective. Journal of Medicinal Chemistry 2017 60 (5), 1620-1637

DOI: 10.1021/acs.jmedchem.6b00975 https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.6b00975

Newman, D. J. (2021). Problems that Can Occur when Assaying Extracts to Pure Compounds in Biological Systems. Current Therapeutic Research, 95, 100645. https://doi.org/10.1016/j.curtheres.2021.100645

Dahlin, J. L., Auld, D. S., Rothenaigner, I., Haney, S., Sexton, J. Z., Nissink, J. W. M., Walsh, J., Lee, J. A., Strelow, J. M., Willard, F. S., Ferrins, L., Baell, J. B., Walters, M. A., Hua, B. K., Hadian, K., & Wagner, B. K. (2021). Nuisance compounds in cellular assays. Cell Chemical Biology, 28(3), P356-370. https://doi.org/10.1016/j.chembiol.2021.01.021

Retraction Watch https://retractionwatch.com/2013/04/10/md-andersons-bharat-aggarwal-threatens-to-sue-retraction-watch/

Nowak KL, Farmer-Bailey H, Wang W, You Z, Steele C, Cadnapaphornchai MA, Klawitter J, Patel N, George D, Jovanovich A, Soranno DE, Gitomer B, Chonchol M. Curcumin Therapy to Treat Vascular Dysfunction in Children and Young Adults with ADPKD: A Randomized Controlled Trial. Clin J Am Soc Nephrol. 2022 Feb;17(2):240-250. doi: 10.2215/CJN.08950621. Epub 2021 Dec 14. Erratum in: Clin J Am Soc Nephrol. 2022 Jun;17(6):877-878. PMID: 34907021; PMCID: PMC8823928.

Yan Jiao, John Wilkinson, IV, Xiumin Di, Wei Wang, Heather Hatcher, Nancy D. Kock, Ralph D'Agostino, Jr, Mary Ann Knovich, Frank M. Torti, Suzy V. Torti. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator. Blood 2009;113:462–469.

Ridley D. https://hbw.citeline.com/RS152886/Italian-Ministry-Of-Health-Bans-Turmeric-Health-Claims-Updates-Product-Labeling#:~:text=Following%20recent%20cases%20of%20use,labeling%20protocols%20for%20these%20products.

https://cot.food.gov.uk/First%20draft%20statement%20on%20the%20potential%20risk%20to%20human%20health%20of%20turmeric%20and%20curcumin#:~:text=ANSES%20(the%20French%20Agency%20for,supplements%20containing%20turmeric%20or%20curcumin.

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee Arthritis & RheumatologyVol. 72, No. 2, February 2020, pp 220–233

Panknin TM, Howe CL, Hauer M, Bucchireddigari B, Rossi AM, Funk JL. Curcumin Supplementation and Human Disease: A Scoping Review of Clinical Trials. Int J Mol Sci. 2023 Feb 24;24(5):4476. doi: 10.3390/ijms24054476. PMID: 36901908; PMCID: PMC10003109.

Liu S, Liu J, He L, Liu L, Cheng B, Zhou F, Cao D, He Y. A Comprehensive Review on the Benefits and Problems of Curcumin with Respect to Human Health. Molecules. 2022 Jul 8;27(14):4400. doi: 10.3390/molecules27144400. PMID: 35889273; PMCID: PMC9319031.

Munn, Z., Peters, M.D.J., Stern, C. et al. Systematic review or scoping review? Guidance for authors when choosing between a systematic or scoping review approach. BMC Med Res Methodol 18, 143 (2018). https://doi.org/10.1186/s12874-018-0611-x

Lombardi N, Crescioli G, Maggini V, et al. Acute liver injury following turmeric use in Tuscany: An analysis of the Italian Phytovigilance database and systematic review of case reports. Br J Clin Pharmacol. 2021; 87: 741–753. https://doi.org/10.1111/bcp.14460

It seems there are an ever-increasing number of health influencers promoting bespoke supplements on social media. This spectrum includes celebrities, naturopaths, podcasters, PhDs, and even medical doctors. I’m not talking about advertisements for an already established supplement company via posts that raise “awareness,” which might come with a “15% off code.” Here, I’m referring to health influencers with their own line of supplements. While a few of these products might be straight-up vitamins or minerals that may have an evidence-based place for some people (think calcium or vitamin D, although almost always less expensive elsewhere), most of these bespoke supplements are concoctions that suggest a health benefit but often have very little, if any supporting research. Instead of the rigorous research you deserve, we typically find cherry-picked, low-quality studies, social media posts, and websites filled with 5-star anecdotes from “satisfied customers.” This is especially insidious when the influencer is a medical doctor or someone with expertise in the biomedical field because they transfer their perceived expertise to the product they sell.

There are definitely some supplement trailblazers, for example, Dr. Steve Gundry and the naturopath Jolene Brighten, who have had their own products for years. It’s a feat worthy of Barnum for people like Brighten to claim that medications like the birth control pill are under-tested and unsafe (it is well-tested and extremely safe), all the while selling untested, unregulated pharmaceuticals (which is how you should think of supplements).

While supplements targeting women have been around for a long time, it feels like menopause is having a supplement moment. Drew Barrymore introduced her Dr. Kellyann &ME Peri + Menopause supplement, designed by a naturopath who is also a bone broth wizard. But Ms. Barrymore isn’t the only one tapping into the menopause supplement gold rush. Alloy, the online menopause platform, has its own branded synbiotic. Dr. Marie Claire Haver, an OB/GYN, has her ‘Pause Nutrition line of supplements. And Dr. Vonda Wright, an orthopedic surgeon, has NovaMD, which includes a product called Advanced Menopause Support, which she claims can help with all kinds of menopause symptoms, and yet each claim requires an asterisk to direct you to the disclaimer that there is no proof this product can treat anything. Always believe the asterisks!

The veracity of the health claims for all of these menopause products and their safety is for another post. But, in case you are considering NovaMD Advanced Menopause Support, you should know the 2023 Menopause Society Guidelines did not recommend a single supplement for hot flashes and that green tea extract, an ingredient in the product, is associated with liver injury.

For a good reason, we require pharmaceutical companies to report how much money they pay physicians, but there is zero reporting in the supplement game for any kind of health influencer, from health coaches all the way to medical doctors. I know the people who sell the useless Liver Shield supplement that promotes binge drinking claimed in writing that they were on track to be in the tens of millions of dollars in sales in 2024, but I didn’t have any data on menopause products. So, I decided to see how easy and profitable it might be to tap into the menopause gold rush myself and sell a bespoke “Dr Jen” product in my very own shop. Theoretically, of course!

The World of Private Labeling

There are two ways to source a supplement. One is to have your own manufacturing facility, and the other is to pay someone to make it for you. It seems that most companies have someone else make it. Even the big names. For example, Pharmavite in California makes supplements for a limited range of big-name companies: Nature Made, Megafood, Equelle, Uqora, and Bonefide.

Private labeling is the concept of a company making a specific product for someone else. And it isn’t just for big players like Nature Made. There are companies that will help anyone start a private-label supplement. There is another option called white labeling, which is a mass-produced product that is then sold to multiple retailers who put their own labels on it. However, this is not a way to get a product with a specific set of ingredients. It seems that most influencer supplements are likely private label, so that will be Dr Jen’s route.

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Dr Jen’s Menopause Taming Turmeric Supplement

Since turmeric was recently mentioned in Woman’s World magazine as something that might be beneficial in menopause, I decided that would be my product as women may be looking for it. Also, tons of supplements and supporting scammy articles pop up when I google turmeric, so the market has been well-primed for me. I think it’s good to have an entry-level product that seems to be sold everywhere and recommended in a magazine by an OB/GYN, as that lends a veneer of legitimacy.

I decided on a turmeric supplement that consists of 500 mg of turmeric root extract and 5mg of black pepper fruit extract per pill, and the daily dose would be two pills. How did I come up with that formulation? I spent about five minutes googling turmeric supplements and copied what seemed to be a common formula. I did zero research (wow, this is an awesome business so far). As there are quite a few supplements with this or very similar formulations, I wondered if it were a common practice to see what is selling and come up with something identical or different in a meaningless way (although who knows, as all this shit is essentially unstudied, maybe it’s a meaningful change!). The black pepper is supposed to enhance the absorption of turmeric.

A Google search brought up multiple companies that provide private-label supplements. These companies will manufacture my pills (or gummies or elixirs, etc), although where the products are made wasn’t clear. Some companies will make my formulation and even handle the shelving and shipping, so I don’t have to worry about renting a warehouse or figuring out how to ship. I just need to create a Shopify website and drive my social media followers to my site to learn about the amazing benefits of Dr. Jen’s Menopause Taming Turmeric supplements.

I did not have to prove I was a doctor or have any data to back up the benefits of my proposed product to get a quote; I just told them my ingredients, and the two companies I contacted said fine. The emails were sent from my husband’s email, so there was no way to trace the request to a physician.

Price Quote for Dr. Jen’s Menopause Taming Turmeric Supplement

These numbers came from a quote from a private-label supplement manufacturer that does everything. I chose this route because I want to show how little effort is required to be up and running. The company will make the product, design a label that meets the FDA language standards, store the product, and even connect with my Shopify account. If someone wants to source their own storage, there are probably cheaper ways, but I chose the easy path. Here is my cost to make Dr. Jen’s Menopause Taming Turmeric Supplement. I chose a high-end label because I’m fancy like that.

I chose a gelcap formulation, which is more expensive, but I think it looks bespoke. The lowest minimum volume that the manufacturer would accept is 8333 bottles. If I went with a regular capsule instead of a gelcap, I could order less and have less upfront cost. Also, if I ordered more bottles, the price per bottle of 60 gel caps could drop from $6.77 to $4.99, increasing my profit by almost $2 a bottle. Buying in greater volume means I have to put out more cash up front, but it also gives me greater profit. However, there is so much profit, even at lower volumes, that I don’t really need to worry.

There are a few minor costs not included here. There is a one-time upfront design cost for the label and some monthly storage charges. None of these are significant, and might add a few pennies per bottle.

The only other upfront cost is setting up and designing a Shopify website. That can range from $2000 to $20,000 (source: Shopify website). A simple shop with 10 items or so can be nicely designed for about $5000, but I’m paying $10,000 fictitious dollars for my website because image is everything in this kind of business. With the Shopify model, my supplements are stored by the private label manufacturer for a relatively small fee. The manufacturer works with Shopify or whatever other retail website I might choose to complete the sale.

The total startup costs for Dr. Jen’s Menopause Taming Turmeric supplements would be:

This will cost me $73K to get started, which is a lot. I could lose it all. (If I went with regular capsules instead of gelcaps, I could get started for only $28K due to lower minimum order quantities). So what is the risk here? How much do I have to sell to break even? First, we need to understand the entire cost model on a per-bottle basis to figure that out. That breaks down as follows:

And now, on the revenue side. Nature Made charges $13.99 a bottle for their turmeric, but they don’t have fancy advertising or menopause brand (although they are still likely making a great profit at this price based on their production scale). The naturopath Jolene Brighten sells her “women’s hormone support” for $63.95 for one month’s supply, and a few of Dr. Steve Gundry’s products seem to be about $49.95. More than $40 sounds steep to me, so I will copy Dr. Marie Claire Haver’s pricing for her turmeric supplement and charge $35 a bottle, $31.50 if you subscribe and save.

For every bottle I sell at $35, I make a $24.93 profit. If someone subscribes, I make a $21.43 profit per bottle, but that’s okay because I think a repeat customer will likely spend more over time. Shipping is extra, but if someone spends over $100 on my supplements, I am happy to pay for shipping.

How risky is this for me? Remember, I am putting out $73k upfront for my order, storage, and Shopify. To recover the $73K, I will need to sell one of the two to break even:

• 2929 bottles at $35 a bottle ($24.93 profit/bottle)

or

• 292 yearly subscriptions ($31.50 a bottle, so $21.43 x 12 or $247.16 profit/year)

Let’s go with the single bottles; I need to sell 2929, or just over one-third of my order, to cover my initial investment. Not bad.

If I have a large social media presence, making this sale should be easy. For example, with 250,000 followers on Instagram, I would need 1.1% of my followers to buy just one bottle to break even. If I have one million followers on Instagram, I just need 0.3% to buy a bottle of my Menopause Taming Turmeric Supplement to break even. To be clear, that last number is not 3 percent; it is one-tenth of 3 percent. But with turmeric mentioned in Women’s World, I’m no longer limited to my social media footprint.

Once I sell my entire 8333 initial run, I will have made $195,760. I didn’t need a staff or a warehouse; there was no factory to inspect, government forms to fill out, licenses to acquire, or payroll to meet. It took about 5 minutes on Google, some emails, and paying someone (theoretically) to set up my Shopify.

It might seem like a lot of sales, but if I had one million Instagram followers, I would just need to convince about 0.8% of them to buy one bottle to make that $195,302 profit.

I make more if I order more than 8,333 bottles for my first run. And, of course, my profit margin grows with my next order because setting up my Shopify was a one-time expense. Even if I keep ordering lots of 8,333 bottles, my cost per run is now $63,021, so I am making about $205k per production run. For one supplement.

And, of course, if I am a celebrity like Drew Barrymore, I can get even more press coverage, and the sky really is the limit.

But These Are Bespoke Products!

The influencers and celebrities selling these products will claim they are made for their customers’ needs. Yes, they are made with a particular customer in mind, but this says nothing about efficacy or safety. Also, no one selling supplements knows their turmeric farmer or green tea farmer, ya know? This is America. Anyone can make a supplement and sell it. Anyone. The only real requirement for success is having a large social media following, being in health care, or preferably both. Remember, with supplements, there is no requirement that they actually work. In case you are wondering, the science behind turmeric is pretty sketchy, which I will cover in a future post.

Like Lifting Up the Floorboards and Finding an Oil Well That’s Ready to Go

We priced Dr. Jen’s Menopause Taming Turmeric Supplements with two companies, and the pricing seemed to be in the same ballpark. Other supplements might cost more or less, and I don’t know what business model people selling supplements are actually following, so to be clear, this model I am presenting is only for my theoretical supplement. There is probably a wide range of profit per product. Some people may only make $15 a pop, but for another supplement, it could possibly be $30 or more. But even at a $15 profit, if you can sell 1,000 bottles a month, that’s $180,000 a year for doing next to nothing. If I am someone like Dr. Sood, an anesthesiologist and one of the creators of the liver condom, and I have 2.3 million followers on TikTok, if I can convince 3% of my followers to buy just one bottle of a product with a $15 profit, I’ve made $1,035,000. Followers are a currency that can be potentially converted into supplement sales.

There are many variables like volume ordered, the company, storage, and the actual product itself, so I have no idea how much money anyone makes selling supplements. The model I chose was about three months for everything to get stocked and ready for customers to buy. It doesn’t appear to take much time or effort, and certainly, no research, to start a potentially very profitable supplement business, so it’s no wonder we are seeing health influencers getting in on the action. Why limit yourself to making just $5,000 for an advertisement here and there for other people’s products or even charge $1,000 for an in-office consultation? That’s nothing compared to what supplements can offer if you have a sales strategy and a market. After all, there is only so much time in the day to see patients or make content. But supplements? It’s a business with almost no effort and an exponential potential for profit. Americans spend about $45 billion a year on supplements, so there’s a lot of action to get in on.

Selling bespoke menopause supplements isn’t championing women; it’s cashing in on the menopause gold rush, and the same holds true whether you are a celebrity, a doctor, a naturopath, or a health coach. If the evidence showed these products worked, they would be in the guidelines instead of being sold with an asterisk about the product being unstudied and untested. And so, Dr. Jen’s Menopause Taming Turmeric will never see the light of day. But stay tuned for an in-depth look at turmeric! I wanted to learn about what I almost (okay, not really) sold.

References

1. Hu J, Webster D, Cao J, Shao A. The safety of green tea and green tea extract consumption in adults - Results of a systematic review. Regul Toxicol Pharmacol. 2018 Jun;95:412-433. doi: 10.1016/j.yrtph.2018.03.019. Epub 2018 Mar 24. PMID: 29580974.

2. Oketch-Rabah HA, Roe AL, Rider CV, et al. United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts. Toxicol Rep. 2020 Feb 15;7:386-402. doi: 10.1016/j.toxrep.2020.02.008. PMID: 32140423; PMCID: PMC7044683.

3. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause 2023:30: 573-590.

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If you’ve listened to a podcast, there is a pretty decent chance you’ve heard an ad for a supplement or a probiotic, be it a regular advertisement injected between segments or something read by the host. (Some hosts even have their own line of supplements, but that’s another story altogether). It’s a smart advertising move. Podcasts are often well-researched, and the hosts are seen as either experts in their fields, experts at deep dives into topics, or both, hence their value. Via the close association with the podcast, the research skills and integrity of the hosts are transferred to the unstudied, unregulated product, which now seems more beneficial, wholesome, and backed by science, even when the data says otherwise. Many hosts are influencers, so they often have additional trust with their audience. I call this phenomenon of supplement advertising on podcasts podwashing, a riff on sportswashing. 

Sportswashing is the practice of organizations or governments gaining influence through the sponsorship of sports and athletes. We tend to see sports as fair and wholesome, and athletes are beloved, so oppressive governments and regimens can seem more benign by their association with sports. Sportswashing is the subject of the World Corrupt podcast, featuring Tommy Vietor (a cofounder of Crooked Media) and Roger Bennett (of Men in Blazers Media Network) as hosts. Season two tackles Saudi Arabia’s growing influence in the world of soccer. For those who don’t know, Crooked Media is a political media company founded by former Obama staffers (among their podcasts are the popular Pod Save America and Pod Save the World). They do a lot of great work getting factual information out to the public and also counteracting misinformation. If I wanted to podwash my supplement or probiotic, I’d definitely want to advertise with Crooked Media. 

It is not surprising, but sad all the same, that World Corrupt, a well-researched, educational, and entertaining podcast, is brought to you by Z-Biotics, a probiotic that claims to prevent the ill effects of drinking too much alcohol and whose advertising, in my opinion, promotes or at least minimizes binge drinking. In addition, the science behind the product doesn’t add up, and it hasn’t been studied in humans. Instead, before Z-Biotics launched publicly, they “gave out over 5,000 free samples” and “saw no consistent complaints attributable to the product.” (Giving out 5,000 free samples for feedback isn’t a scientific method; it’s marketing). Their batch testing involves the CEO/co-founder drinking “a bottle out of every batch himself, just to make sure nothing is off and no mistakes are made in manufacturing.”  

Neato. Super science-y.

A product with big claims and little data with the potential for promoting binge drinking, paying to sponsor a podcast about sportswashing hit me as very meta and not in a good way. Here’s a quote from the April 6, 2024, episode that ran right before an advertisement for Z-Biotics:

“That exact quandary, Rog, the money versus reputation question, is what we're going to talk about after this break.

My left eye is twitching. Badly. 

Z-Biotics doesn’t just have a company-produced ad injected into the podcast; no, we get the guys we have grown to trust reading the copy. Here's part of one:

Roger: Rough mornings after drinking, the inevitable sequel to night with drinks and the sequel, Tommy. Oh, it's never as good as the original, is it?

Tommy: No, except for The Godfather. Here's how it works. When you drink, alcohol gets converted into a toxic byproduct in your gut. It's this byproduct, not dehydration, that's to blame for your rough next day. Z-Biotics produces an enzyme to break this byproduct down. Just remember to make Z-Biotics your first drink of the night, drink responsibly, and you'll feel your best tomorrow.

What is Z-Biotics?

It is the probiotic B. subtilis ZB183™, which is genetically engineered to produce the enzyme acetaldehyde dehydrogenase. The company claims that if you drink it before you drink alcohol, it will accelerate the breakdown of acetaldehyde in the gastrointestinal tract, “setting you up for a better day after drinking.” Their central hypothesis is that it is the acetaldehyde produced in the gut accumulates and enters the body, causing a hangover. Sorry, the “particularly rough feelings you get the day after drinking.” 

However, the accepted science does not support acetaldehyde being responsible for a hangover/rough morning the next day. According to the Alcohol Hangover Research Research Group (Feb 2024), “previous studies often focused on the quick removal of acetaldehyde or incorrectly viewed the hangover as a consequence of dehydration. It is therefore not surprising that no proven effective and safe hangover treatments are currently marketed.” 

Let’s take a closer look, shall we? 

Alcohol Metabolism

When we drink, the alcohol enters our stomach and then intestines, where it is absorbed into a vein that takes blood directly to the liver. Here in the liver, the alcohol is metabolized, which means it is broken down into other substances for removal. The enzyme alcohol dehydrogenase first converts alcohol to acetaldehyde, a toxic (harmful) substance. However, acetaldehyde is quickly converted by another enzyme, acetaldehyde dehydrogenase, into acetate, which is further broken down into carbon dioxide and water. 

The liver chugs along, metabolizing alcohol as fast as it can, about one drink per hour, give or take, based on various factors. If the liver is presented with too much alcohol and it can’t keep up, the result is intoxication. Some alcohol remains in the gut, where it is also metabolized. The gut isn’t quite as good at converting acetaldehyde into acetate, so some acetaldehyde accumulates in the gut, and some is absorbed and heads to the liver.

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What Causes a Hangover/Feeling Awful the Day After Drinking

A hangover is a constellation of awful symptoms, and according to the Alcohol Hangover Research Group, it is a “common consequence of excessive alcohol consumption.” A hangover only occurs when the blood alcohol has risen and come back down to zero, so it is the next morning phenomenon or an after-effect of drinking. The biology of hangovers is surprisingly complicated and not well understood. They appear to be multifactorial, which basically means many biological processes are likely involved, but we don’t know precisely because it’s complicated and/or understudied. That’s a far cry from Z-Biotics claim about acetaldehyde. Some factors that appear to be central to creating the hangover experience are:

• Inflammation from the alcohol or one of the breakdown products

• Oxidative stress (the presence of unstable molecules called free radicals, which can damage cells)

• The genetics of alcohol metabolism

• Congeners, which are compounds that develop due to fermentation and distilling (for example, the substance that makes rum dark or the small amounts of methanol in alcohol). 

Other factors that may be involved are sleep disruption and gastrointestinal tract irritation. 

Most of the studies, such as they are, suggest that the faster alcohol is metabolized, which means the quicker acetaldehyde is produced, the less severe the hangover. This points to alcohol triggering the biological cascade that leads to a hangover, not acetaldehyde. People with a genetic variation of acetaldehyde dehydrogenase that causes them to break down acetaldehyde more slowly can get flushing, nausea, headache, and feeling unwell from high levels of acetaldehyde, but this is not the same thing as feeling ill the next day. 

I am but a Gynecologist, So I Asked Some Liver Specialists

I first turned to Dr. Abby Philips, a hepatologist (liver specialist), who told me via email that “Acetaldehyde does not directly cause hangovers, and there is no strong evidence available for us to claim that reducing or quickly breaking down acetaldehyde reduces hangovers after alcohol use.” A hangover, he wrote, is “multifactorial.”

Because I am me, I asked another hepatologist. They are generally very smart and entertaining, so I enjoy listening to them. Next up on my list was Dr. Kaveh Hoda, who told me, "The awfulness of a hangover is multifactorial.” Dr. Hoda mentioned that alcohol also affects sleep and irritates the gastrointestinal tract, which may play a role.  

Dr. Philips also explained that acetate (one of the byproducts of alcohol metabolism) may even play a role in the "bad feeling and headache post-alcohol use.” This means that without studies, it’s possible that accelerating acetaldehyde metabolism could worsen a hangover. When something is unstudied, we don’t know what we don’t know. 

Dr. Philips and Dr. Hoda confirmed what I had read in numerous articles, in the Proceedings of the 12th Alcohol Hangover Research Group Meeting, and in the book Proof: The Science of Booze, written by Adam Rogers. If acetaldehyde plays a role in hangovers or “rough mornings,” the available evidence suggests it’s minor at best. There is also no robust evidence to suggest that acetaldehyde production in the gut plays a major role in hangovers. 

Acetaldehyde production in the gut may be responsible for some of the gastrointestinal side effects of drinking, like diarrhea. It may also be part of the risk of colon cancer associated with drinking, but this isn’t certain because alcohol is also directly toxic to the gastrointestinal tract. Might a probiotic that accelerates acetaldehyde metabolism in the gut reduce diarrhea after drinking or have other protective effects by reducing acetaldehyde in the bowel? It’s possible, but as of right now, that would be an untested hypothesis. 

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Show Me The Research

Sometimes, we are unsure exactly how a product works, but quality, peer-reviewed studies show it does. Let’s look at the evidence; although it’s important to note that Z-Biotics isn’t a medication, while I might hold them to the same rigorous criteria for safety and efficacy as medications, our government does not.

The folks at Z-Biotics have published a peer-reviewed safety study showing their product wasn’t harmful to rats, which is an essential first step, although they seem to regret it. From their website:

We should all obviously just take the word of a for-profit company that their product couldn’t possibly have an unanticipated ill effect on mammals (that is written in heavy sarcasm font).

It is true that supplements don’t require ANY testing to go to market. However, probiotics are apparently considered a food ingredient, and a new one must pass a safety bar, albeit a low one, before it can go to market in the United States. 

On their website, Z-Biotics claims to have data showing that their product can reduce acetaldehyde levels in vitro (essentially in a test tube), but I can’t find a peer-reviewed study to support this claim. To ensure I wasn’t missing anything, I emailed the people at Z-Biotics, and I am correct; the only published paper is the rat study. They told me they were “finalizing a paper that shows the acetaldehyde breakdown kinetics in gut-simulated conditions in vitro” and would share the preprint with me confidentially. I don’t read these kind of papers confidentially. Proving that Z-Biotics can break down acetaldehyde in a simulated model is another important step, but to be clear, the ability of the product to break down acetaldehyde in a lab isn’t something I’m questioning. Call me old-fashioned, but I believe that you should have human data when you sell a product to humans. 

I asked about human trials, knowing that one of the co-founders, Zack Abbott, Ph.D. has experience in clinical trial design, and this was the reply answer: 

We would like to do this, and we hope to be able to eventually. Given the extremely difficult nature of designing a quality study taking into account different human physiologies and responses to alcohol and perceptions of pain and discomfort the next day, we struggled to be able to design a truly rigorous scientific in vivo study in humans that would meet our standards and also be eligible for IRB approval, given the relatively strict limits they set on BAC levels for human studies. For instance, it is very difficult to obtain approval for a study in which a person’s BAC goes above 0.08-0.1, which is essentially right at the threshold of intoxication, and really only the very beginning of where people might start to feel symptoms the next day. The signal-to-noise ratio at that level of intoxication is very low, and so it would be difficult to get a reliable response from people. Sampling colonic acetaldehyde would be very invasive and unpleasant (and expensive), and so as a small company we’ve opted to not do a sub-par or extremely invasive study just yet.

There is a lot to unpack here. 

My conclusion from this reply is that their target audience isn’t someone who has some stomach irritation from one drink; it’s someone who expects to be intoxicated, meaning heavy or binge drinking, which puts their advertising in a different light, especially the jokey sell on World Corrupt.

As for it being too challenging to get IRB approval for a human study involving alcohol intoxication, these studies do exist. That is how we know that several therapies are ineffective. However, admittedly, there are challenges with these kinds of studies. I asked Dr. Ryan Marino, a toxicologist, who told me that he “had an active study getting people intoxicated on alcohol as recently as 2019, and was looking at both metabolic products and cognitive effects, which is what they would need to do. It’s definitely possible, especially if there is an actual question, which this supplement’s claim seems to be.” In fact, while he said it was difficult, he was able “to get approval to get people to ethanol levels >0.20,” but it did require “demonstrating that we were a legitimate group using a legitimate lab, etc.” 

(Dr. Marino added that he didn’t think Z-Biotics would do anything medically for a hangover). 

Of course, there is a less expensive step BEFORE human studies–animal studies, specifically drunken rodents. Yes, there are animal models for studying the effects of alcohol and for sampling different body fluids and organs to test benefits or ill effects. In fact, I found a study from 2023 evaluating the impact of a genetically engineered probiotic on drunkenness and the ill effects of alcohol in mice. 

In this fascinating study, researchers genetically engineered a probiotic to express the enzyme ADH1B, which is a very effective variant of alcohol dehydrogenase (the first enzyme in the alcohol metabolism process). ADH1B apparently has the ability to convert alcohol into acetaldehyde about 100 times faster than regular ADH. The researchers introduced the gene for human ADH1B into Lactococcus lactis, a food-grade probiotic used in the dairy industry, and then tested the probiotic on mice. The mice treated with this probiotic were less likely to appear intoxicated, they recovered faster from alcohol exposure, and they had fewer resulting health problems than untreated mice. This study is also another strike against the Z-Biotics hypothesis because faster alcohol metabolism (meaning faster production of acetaldehyde) was beneficial. 

When interviewed about their findings by the American Society for Microbiology, one of the paper’s authors, Meng Dong, Ph.D., said the next steps were to investigate whether the potential benefits of the genetically modified probiotic extended to humans. One goal is to reduce “acute alcohol-induced liver and intestinal damage.”  

It’s absolutely possible to study the beneficial effects of a genetically engineered probiotic on alcohol-related complications in a rodent model. Then again, doing so risks proving your product is ineffective. 

Podwashing

In my opinion, it’s pretty despicable to have no data to prove your product has the intended clinical effect in mammals, never mind humans, and yet make bold claims about a grand mission to improve everyday living while also advertising that someone could drink three or ten drinks (yes, ten) and, if they take your product, not have to “spend a whole day recovering.”

At this point, I am compelled to point out that binge drinking is five or more drinks for men and four or more for women on the same occasion over 2-to 3 hours at least once in the past month, and heavy drinking is five or more drink/day or 15 drinks per week for men four or more on any day or eight or more drinks per week for women. Binge drinking and heavy drinking are associated with many health issues, including liver disease and liver failure, high blood pressure, stroke, heart disease, dementia, memory problems, and multiple cancers, including liver, breast, rectum, mouth, and esophagus. Even a single episode of binge drinking can have adverse effects on health. 

But even what we might think of as small amounts of alcohol carries risk, and according to the World Health Organization (WHO), there is no safe level of alcohol consumption. Of the two million new cases of breast cancer worldwide each year, about 100,000 are attributable to alcohol. And it doesn’t take much alcohol. In Europe, 25% of alcohol-related breast cancers are related to as little as one bottle of beer or 200 ml or 6.7 ounces of wine a day. Many people don’t like to hear this, but the evidence is what it is, and having this information is how you make informed decisions in your own life. 

Apart from the lack of evidence showing Z-Biotics has its intended effect, the risk here is that claims to reduce or prevent hangover symptoms or those “rough feelings” from drinking could encourage people to drink more than they usually would or lead someone to think the ill effects of binge drinking, heavy drinking, or even any drinking could be biohacked away. Even if Z-Biotics did work as it claims (and to be clear, there is no scientific evidence yet to suggest it can), the person taking it would still have the negative health consequences of drinking.  

According to Crunchbase, Z-Biotics raised $27.6 million in total venture funding and $22.4 million in its most recent round. Use some of that money to prove me wrong! How a company raises 27 million dollars based in part on a product with a medically questionable hypothesis that is untested in animal models and humans and is apparently too complicated/ethically challenging to study in humans yet fine to sell to humans for $12 a bottle ($7.17/bottle for a monthly 12-pack subscription) would make an interesting podcast episode. In fact, an entire Podcast dedicated to supplement and probiotic companies, their research, VC funding, the marketing of their products, and, of course, their podwashing would be really interesting. 

But I’m not sure Crooked Media is up to the task. It might affect their sponsorships. 

Hey, it’s a money versus reputation question.

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References

Zakhari S. Overview: how is alcohol metabolized by the body? Alcohol Res Health. 2006;29(4):245-54. PMID: 17718403; PMCID: PMC6527027.

Tellez-Monnery K, Balikji J, Carrere L, Czerniczyniec A, Devenney LE, Guerra JI, Kiani P, Lores-Arnaiz S, Merlo A, Stock A-K, et al. Proceedings of the 12th Alcohol Hangover Research Group Meeting, in Buenos Aires, Argentina. Proceedings. 2024; 95(1):1. https://doi.org/10.3390/proceedings2024095001

Pittler MH, Verster JC, Ernst E. Interventions for preventing or treating alcohol hangover: systematic review of randomised controlled trials. BMJ. 2005 Dec 24;331(7531):1515-8. doi: 10.1136/bmj.331.7531.1515. PMID: 16373736; PMCID: PMC1322250.

Mackus M, van de Loo AJ, Garssen J, Kraneveld AD, Scholey A, Verster JC. The Association between Ethanol Elimination Rate and Hangover Severity. Int J Environ Res Public Health. 2020 Jun 17;17(12):4324. 

Joris C. Verster, The alcohol hangover–a puzzling phenomenon, Alcohol and Alcoholism. 2008;43:124–126, https://doi.org/10.1093/alcalc/agm163

Merlo A, Mackus M, van de Loo AJAE, van Neer RHP, Vermeulen SA, Thijssen SS, Knipping K, Bruce G, Garssen J, Verster JC. An evening of alcohol consumption negatively impacts next-day immune fitness in both hangover-sensitive drinkers and hangover-resistant drinkers. Addict Behav. 2023 Oct;145:107776.

Mackus M, van de Loo AJ, Garssen J, Kraneveld AD, Scholey A, Verster JC. The Association between Ethanol Elimination Rate and Hangover Severity. Int J Environ Res Public Health. 2020 Jun 17;17(12):4324. 

Salaspuro M. Microbial metabolism of ethanol and acetaldehyde and clinical consequences. Addict Biol. 1997 Jan;2(1):35-46. doi: 10.1080/13556219772840. PMID: 26735439.

Hangover, Chapter 8. Proof: The Science of Booze. Rogers, A. Houghton Mifflin Harcourt. May 27, 2014.

Naidu BA, Kannan K, Santhosh Kumar DP, Oliver JWK, Abbott ZD. Lyophilized B. subtilis ZB183 Spores: 90-Day Repeat Dose Oral (Gavage) Toxicity Study in Wistar Rats.  Journal of Toxicology, 2019, https://doi.org/10.1155/2019/3042108.

Karadayian AG, Mac Laughlin MA, Cutrera RA. Estrogen blocks the protective action of melatonin in a behavioral model of ethanol-induced hangover in mice. Physiol Behav. 2012 Sep 10;107(2):181-6. 

American Society Microbiology Press Release https://asm.org/press-releases/2023/april/a-protective-probiotic-blunts-the-ill-effects-of-a#:~:text=An%20enzyme%20called%20ADH1B%20accelerates,had%20fewer%20resulting%20health%20problems.

Jiang X,Yan C, Zhang H,Chen L,Jiang R,Zheng K, Jin W,Ma H,Liu X, Dong M,2023.Oral Probiotic Expressing Human Ethanol Dehydrogenase Attenuates Damage Caused by Acute Alcohol Consumption in Mice. Microbiol Spectr11:e04294-22.https://doi.org/10.1128/spectrum.04294-22

World Health Organization, Alcohol is One of the Biggest Risk Factors for Breast Cancer https://www.who.int/europe/news/item/20-10-2021-alcohol-is-one-of-the-biggest-risk-factors-for-breast-cancer#:~:text=There%20is%20no%20safe%20level,100%20ml%20each)%20every%20day.

Seitz HK, Becker P. Alcohol metabolism and cancer risk. Alcohol Res Health. 2007;30(1):38-41, 44-7. PMID: 17718399; PMCID: PMC3860434.

Bala, S., Marcos, M., Gattu, A., Catalano, D., & Szabo, G. (2014). Acute Binge Drinking Increases Serum Endotoxin and Bacterial DNA Levels in Healthy Individuals. PLOS ONE, 9(5), e96864. https://doi.org/10.1371/journal.pone.0096864

Castor oil packs for painful periods and endometriosis pain are popular on social media right now. Is there any evidence to support their use? 

What is Castor Oil

Castor oil is a vegetable oil extracted from castor beans, which are the seeds of the Ricinus communis plant. It has been used for thousands of years as an emollient for the skin, oil for lamps, and various medicinal reasons. When taken orally, it can cause vomiting and diarrhea, which is likely why it was considered medicinal, either because people believed it restored “balance” or simply because the drama of the vomiting/diarrhea provided the illusion of effectiveness. Just because people used something medicinally thousands of years ago doesn’t mean it has the ascribed medicinal properties. 

One very important thing to know about Ricinus communis is that the seeds (castor beans) contain ricin, a deadly poison. Ricin is absent in commercial preparations as it is removed while producing commercial castor oil, but this is why you should NEVER attempt to make castor oil at home. 

What are the Uses of Castor Oil?

The only known medical use is as an oral therapy for constipation, so the Food and Drug Administration FDA classifies it as a laxative. Specifically, it’s a stimulant laxative that stimulates the bowel to contract, pushing stool along. It is generally recognized as safe and effective for this reason, but the diarrhea can be violent, so it’s not commonly used. You may see claims that castor oil is FDA-approved for constipation, but that isn’t exactly correct, as over-the-counter (OTC) medications are not FDA-approved. Instead, the FDA has a monograph listing the acceptable ingredients, doses, and formulations for OTC drugs and their acceptable applications. If an OTC product conforms to that recipe book, it can be sold without FDA pre-approval.

Castor oil is also found in many cosmetics, where it functions as an emollient, emulsion stabilizer, and surfactant. Castor oil is also occlusive, meaning it creates a physical barrier on the skin that prevents water loss, helping keep the skin hydrated. 

How is Castor Oil Used for Menstrual and Endometriosis Pain?

The oil is applied to the abdomen, and then a cloth wrap is used to hold it in place, or the castor oil is applied directly to the wrap first, which is then placed against the skin. Some people apply a hot water bottle over top, and others don’t. There are also disposable, self-adhesive castor oil pads like these on Amazon. Notice the bullshit about a “liver detox.” 

What About Castor Oil For Pain?

No data supports its use, and I can’t find that it has been studied meaningfully. What we know about the chemistry also doesn’t support the topical use of castor oil for pain as ricinoleic acid, the main fatty acid in castor oil doesn’t penetrate through the skin, so it can’t access muscles or fat or enter the bloodstream. Any benefit from castor oil packs likely comes from massage (if it’s being massaged into the skin), the pressure from the wrapping, or the heat (if used). The ritual of applying a castor oil pack might be self-care, which could also make someone feel better. If it gives time to pause and do some slow, deep breaths (diaphragmatic breathing), that may also help with pain. And there is always the possibility of a placebo response. I don’t want to downplay how applying an oil, wrapping, or heat might make some people feel better, but there is no evidence to suggest that topical castor oil is better than any other vegetable oil or that the oil is doing anything biological for pain. 

There are some naturopaths, chiropractors, and influencers who apparently believe castor oil can activate mysterious parts of the immune or endocrine system or penetrate the skin and do something “medicinal” (what specifically from a pain perspective is never stated). Given its widespread and longstanding use in cosmetics, we'd likely know if a bioactive chemical from castor oil could be absorbed to treat pain (or do anything else). I double-checked with Dr. Michelle Wong, who has her Ph.D. in chemistry and is a science educator and cosmetic chemist (you may know her as Lab Muffin, and she is well worth the follow on social media), and she told me castor oil would “only get into the very top layers” of the skin. 

The origin of castor oil for menstrual pain/endometriosis pain likely came from the belief that it can induce labor when taken orally, but how something could stimulate painful uterine contractions in pregnancy and yet make them less painful during menstruation is quite the conundrum. 

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What’s The Harm of Castor Oil Packs?

If someone tried them and found they helped, great, but as a doctor, I couldn’t recommend them over a hot water bottle. I could recommend a TENS unit, as those have been shown to help reduce menstrual pain. 

If heat is used with a castor oil pack (the same goes for a hot water bottle or heating pad), it’s important to be mindful of chronic long-term heat exposure, as this can produce a rash on the skin called erythema ab igne. To prevent this, heat shouldn’t be used for more than 15 minutes at a time, and if mottling or redness persists on the skin once the heat is withdrawn, stopping exposure to heat is necessary. 

The real harm with castor oil packs is the disinformation that is often (really often) found on websites that promote their use. Take a look at this kit, making bullshit claims about liver detox, lymphatic drainage, balancing hormones, and so on. None of these benefits are remotely plausible. It reads like an untrained AI was asked to write the copy.

Other health claims about castor oil packs that I have seen from a motley crew of naturopaths, menstrual coaches, and chiropractors include the following:

• “Detoxification,” which I guess is a more general detox than the liver detox? The words “detox” and “detoxification” should function like a pop-up warning to let you know that you are in a medical bullshit zone.

• “Treatment of constipation and loose stools,” a.k.a. covering your bases. The idea that there is one product (a laxative, no less) that, when applied topically, can treat both constipation and loose stools is ludicrous.

• “Treat fatty liver and gallstones”…nope, nope, nope.  

• “Regulate periods.” I mean, no. Not possible with human physiology.

• Shrink uterine fibroids. The idea here, I suppose, is there is something “special” in castor oil that can either recruit special fibroid-destroying chemicals or seep through the skin, fat, and muscles of the abdominal wall, then penetrate the uterus but dissolve only the fibroids while leaving the rest of the uterus untouched. This is biologically absurd. How naturopaths, chiropractors, and influencers would know about this miraculous yet secret substance, and yet its existence has been ignored by the world of science is…something.  

I could go on with the “That’s Incredible!” list of the miracle wonders of castor oil, but I sprained my eyes rolling back into my head. I guess you can’t sell oil and special wraps if you are honest and say, “Some people find this makes them feel better.”

The real harm of castor oil packs is that they could be a gateway into the wide world of serious medical disinformation. 

Summary

If you want to use castor oil packs, know that the oil doesn’t penetrate deeper than your skin. However, the pressure from the wrap, the feel of the oil, the heat (if used), or the time spent caring for yourself may help. Just be wary of people who promote castor oil packs as medicine because they are often peddling disinformation. While castor oil is a fine emollient and will likely leave your skin feeling soft, the benefits of the oil itself are only skin-deep. 

References

Final report on the safety assessment of Ricinus Communis (Castor) Seed Oil, Hydrogenated Castor Oil, Glyceryl Ricinoleate, Glyceryl Ricinoleate SE, Ricinoleic Acid, Potassium Ricinoleate, Sodium Ricinoleate, Zinc Ricinoleate, Cetyl Ricinoleate, Ethyl Ricinoleate, Glycol Ricinoleate, Isopropyl Ricinoleate, Methyl Ricinoleate, and Octyldodecyl Ricinoleate. Int J Toxicol. 2007;26 Suppl 3:31-77. doi: 10.1080/10915810701663150

Elboim-Gabyzon M, Kalichman L. Transcutaneous Electrical Nerve Stimulation (TENS) for Primary Dysmenorrhea: An Overview. Int J Womens Health. 2020 Jan 8;12:1-10. doi: 10.2147/IJWH.S220523.

It is always hard to write about medical bullshit because the energy it takes to debunk it is infinitely more significant than the lack of effort and research it took to create it. A good faith argument is honest and uses science, which is hard to apply to unstudied supplements sold as cure-alls…like this one…

My feed has been littered with ads for this product for the past 48 hours. Apparently, Dr. Kellyann and Ms. Barrymore have found the one true elixir that can “support hormonal weight management goals” (no idea what that fucking word salad means), “ease hot flashes,” “promote a healthy mood,” “promote digestive health,” AND “help get your sleep back on track.” And you can get this menopause alchemy, all for the low, low price of $179.95 for three months! 

Wow, the cure for EVERYTHING MENOPAUSE IN ONE PILL! 

TAKES A BIG BREATH. SERENITY NOW! SERENITY NOW!

Establishes some inner peace…

Ahem.

The General Claims

Any supplement that can help you lose weight, treat hot flashes, correct sleep, and help your gut and your mood is a fucking miracle in a bottle. This is a big red flag. The “can treat everything including unclogging your kitchen sink” is a standard snake oil sell-job, which is simply taking a page from the patent medicines that were heavily advertised with wild claims and patient testimonials in the 1800s and early 1900s. The claims made about the “Dr. Kellyann &ME Peri + Menopause” product reminded me of Lydia Pinkham’s Vegetable Tonic from 1837, a common patent medicine that was a “A Woman’s Cure for Women’s Ills” and could 

Give quick relief and effect a permanent cure in all cases of irregularity, faintness, headaches, cirrhosis, megrims, displacements, periodic bearing down pains, dizziness, palpitations, depression, pains in the back, and those dull and listless days when you feel fit for nothing.

If a product could do all of this, Big Pharma would have marketed the shit out of this years ago.

Verdict: Extraordinary claims require extraordinary evidence, which, spoiler alert, we will not find.

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The Inventor

Who is Dr. Kellyann?

She is a naturopath and bone broth wizard. She also seems to think people can boost their immune system as she co-wrote a whole “For Dummies” book about the topic. Boosting your immune system is not a thing, and I guess those “For Dummies” books might not have the most robust backing research. Really stretch out the “o” in robust when you read that last sentence.

Verdict: The creator of the product is not a recognized medical expert. 

The Product

The first ingredient is chromium, and this is what the NIH Office of Dietary Supplements has to say about this ingredient:

Scientists do not currently think that chromium is necessary for good health, and chromium deficiency has not been reported in healthy people. However, in 2001 scientists did consider chromium to be an essential nutrient, and they set recommended amounts based on the evidence available at that time.

The recommended daily intake for chromium is 25 mcg. 

Here is the product label for the peri & me or whatever supplement.

I can find no clinical trials for chromium in menopause for hot flashes, weight loss, sleep, etc. Chromium has been looked at for weight loss, control of blood sugar for people with diabetes, high cholesterol, and for PCOS and the results, such as they are, are not robust enough to make any recommendations. For example, regarding weight loss, the NIH Department of Dietary Supplements states 

Some chromium supplements are marketed for weight loss and to reduce body fat and increase muscle mass. However, clinical trials have found only a very small benefit. This benefit is unlikely to make any difference in health or appearance.

The real issue here is not the chromium but the three proprietary blends!!! Three! The Hormonal Health Blend, the Menopause Symptom Relief Complex, and the Digestive Wellness Complex. One exclamation mark for each proprietary blend.

A proprietary blend is basically a secret recipe of herbs and spices that might as well be translated as, “it’s super secret and we won’t share it with you but trust us that that it actually works and is safe, even though we provide no actual proof”. The amount listed tells you the total weight of the combined products, not how much of each individual ingredient, so you have no idea exactly what you are taking. Products that contain proprietary blends are not recommended and are considered riskier when it comes to causing liver damage. When I previously interviewed Dr. Ryan Marino, a toxicologist, he confirmed that proprietary blends are particularly problematic. 

Verdict: Promise me you won’t take this. It has three proprietary blends. 

Drilling Down on the Claims

Another red flag is when products claim they can help you lose weight or “boost” your metabolism. First of all, it’s medically illiterate to make this claim, as you can’t actually boost your metabolism. I know you see ads about this all the time, but it is not possible. Secondly, and more concerning, is that these products may be more likely to be adulterated with pharmaceuticals or even untested compounds! You can read about a summary of some of these kinds of products and the concerns they raise here. 

Verdict: Red flag #4

Supporting Research on the Site

All the supposed health claims on the site, such as “88% Of Women In User Group Felt Improvement In Fatigue Levels,” have an asterisk, which, if you scroll down to the bottom, takes you to this peach of a comment:

Sigh. They may as well have said, we gave it to some friends. 

There is no scientific literature quoted, not even in a predatory journal! 

People have asked me about a few other similar products and if maybe those who make them turn later around and put their profits into research. Not that I have ever seen. Also, using money from selling supplements to study that supplement injects a significant amount of bias and would need the level of scrutiny we see with studies from Pharma. People need to study the supplement first before bringing it to market if they want to help people.

Verdict: This is going from bad to worse. 

What Do the Guidelines Say?

I am sure you will be shocked to learn that none of the ingredients in Dr. Kellyann &ME Peri + Menopause supplement made it into the 2023 Menopause Society position statement on non-hormone therapy. How Dr. Kellyann can have knowledge about the secret blend of herbs and spices in her supplement that is unknown to actual experts boggles the mind (please read that with the heaviest of sarcasm).

Verdict: Red flag #6. I think. I’m losing count.

There is REAL potential for harm here. 

I just read a case report from 2023 of a woman who developed drug induced liver injury (DILI) from taking MenoFit, a supplement which includes a proprietary blend, and claims to reduce hot flashes, improve sleep, boost metabolism etc (sounds familiar, hey?). You need to be VERY WARY of these kinds of products.  

You can read more here about supplements and how to think about them. It can be confusing as a very limited number are recommended, for example, iron for iron deficiency or prenatal vitamins.  

A good rule of thumb is to avoid multi-ingredient supplements that are not multivitamins, especially those with proprietary blends, and/or make claims about weight loss/boosting metabolism. These have not tested in any meaningful studies and harm can come from several ways: the listed ingredients themselves may be harmful, they may be contaminated with bacteria or fungi, or they can be adulterated with other substances, even active pharmaceuticals or completely untested compounds or straight-up poisons. Read this post about how many of them don’t contain what they claim. This is REALLY a buyer-beware situation. And even more concerning, women seem to be at higher risk for drug-induced liver injury when compared with men. 

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What can I say about Drew Barrymore being a brand ambassador, for a multi ingredient supplement created by a naturopath that contains three proprietary blends and makes a wild range of medically unsubstantiated claims, including the ability to boost metabolism? 

Nothing positive.

Supplements are BIG BUSINESS, given how easy they are to make, sell, and then promote on social media. How big a business? Glad you asked. A recent study looked at the top ten liver supplements sold on Amazon. Not one of the sixty-five ingredients that were identified in these products is recommended by either the American Association for the Study of Liver Diseases or the European Association for the Study of Liver. So, I mean, there’s that. Also, 35% of the reviews were fake, so there’s also that. But how much money in sales did these ten supplements generate on Amazon in one month? $2.4 million dollars. Yes, $2.4 million in one month on one platform for ten useless products that cost very little to bring to market. It’s really depressing.

Cashing in on the menopause gold rush isn’t championing women’s health, it’s nothing more than garden variety misogyny because in my opinion you must have little regard for women to exploit the gaps in medicine so egregiously. If you cared about women, you would do a modicum of research, not sell an untested supplement with a proprietary blend!

Who knows, maybe there is more money in supplements than being an actor and talk show host. It honestly wouldn’t surprise me.

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References

NIH Office Dietary Supplements Fact Sheet Chromium https://ods.od.nih.gov/factsheets/Chromium-HealthProfessional/

Navarro VJ, Khan I, Björnsson E, et al. Liver injury from herbal and dietary supplements. Hepatology. 2017;65(1):363–73.

Navarro VJ, Barnhart H, Bonkovsky HL, et al. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology. 2014;60(4):1399–408.

Lu RJ, Zhang Y, Tang FL, et al. Clinical characteristics of drug-induced liver injury and related risk factors. Exp Ther Med. 2016;12(4):2606–16.

Dadlani A, Anudu A, Marginean EC. Unexpected Drug-Induced Liver Injury Associated With MenoFit: A Synbiotic Menopause Supplement. ACG Case Reports Journal 10(9):p e01153, September 2023. DOI: 10.14309/crj.0000000000001153

NAMS POSITION STATEMENT. The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause 2023;30:573-590. DOI: 10.1097/GME.0000000000002200

Eltelbany, Ahmed, Hamid, Osama, Nanah, Rama, Paleti, Swathi.iver Cleansing Imposters: An Analysis of Popular Online Liver Supplements. The American Journal of Gastroenterology 118(10S):p S1008-S1009, October 2023. | DOI: 10.14309/01.ajg.0000954920.30407.c4

The U.S. Government Accountability Office (GAO) recently published a report on prenatal vitamins, comparing the ingredients listed on the label with what was found when the supplements were tested, as well as testing for potentially harmful contaminants. This kind of work is necessary because individuals who are trying to conceive, are pregnant, or breastfeeding need to know if prenatal vitamins contain what they claim so they can be assured they are getting the expected health benefits from these products. In addition, there have been reports of contamination of prenatal vitamins with heavy metals and fungi, but we don’t have a good idea about the scope of the problem. For example, in a study published in 2018 from Canada, 51 prenatal vitamins from 26 brands were tested, and 20 samples exceeded the threshold for lead, which they set at 0.5 mcg/day (this is the level from Proposition 65 in California). Yes, 40% of the samples. One product had 4.0 mcg Three samples had toxic levels of thallium, and three had levels of inorganic arsenic over the accepted safe range! In 2021, Spotlight on America tested over 220 prenatal vitamins, and 25 exceeded the 0.5 mcg/day Prop 65 limit for lead.

And to the Canadians who keep insisting the supply of supplements is safer in Canada, the products in the Canadian study were all bought from brick and mortar stores in Edmonton.

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The Report From the GAO

Twelve types of prenatal supplements (four gummies, four soft gels, and four tablets) were tested for six key nutrients listed on their labels. Three doses of each product were tested. Folic acid, iodine, and iron were selected because they are recommended for their health benefits in pregnancy. Vitamin A, Vitamin C, and Vitamin E were selected because while small doses are recommended, high doses in pregnancy could be harmful. The study examined whether these ingredients were present in the acceptable range set out by the U.S. Pharmacopeia (USP) and/or whether the product contained more than the tolerable upper limit. USP guidelines refer to acceptable manufacturing practices. For example, according to USP guidelines, it is acceptable for a product with vitamin A to contain anywhere from 100% to 165% of the stated label for a tablet or softgel. Tolerable safe limits are a level that could be concerning to your health. 

Important side note. Two of the twelve (products F and I) contained methylfolate, not folic acid, so they were tested for methylfolate. However, the report lists all results as folic acid. I emailed Karen L. Howard, Ph.D., the Director of Science and Technology Assessment at the U.S. Government Accountability Office, for clarity. She explained that while the results for the methylfolate-containing supplements say a percentage for folic acid, that was for simplicity’s sake in the reporting; the results should be interpreted as a percentage of methylfolate on the label.

The report also evaluated the presence of four heavy metals, lead, arsenic, cadmium, and mercury, as they are associated with harmful effects on fetal development. 

Here is a graphic from the reports showing the levels of nutrients in the key supplements; I have modified it so you can see which supplements had methylfolate.

Here are some key findings:

• Only one product, a prenatal gummy, contained everything it claimed within the accepted deviation from the amounts on the label. It did not have iron, as gummies don’t typically contain iron due to the difficulties in manufacturing it in that form. 

• A total of six prenatal vitamins didn’t contain enough folic acid, four because they had less folic acid than stated on the product label, and two had none because they had methylfolate. One of the supplements with folic acid had 50% less of what the label stated it should contain. The consequence here is some prenatal vitamins are not delivering enough folic acid to reduce the risk of neural tube defects. 

• All the supplements with iron contained iron in the acceptable range. 

• The amount of vitamin E in the supplements ranged from 28 to 332% of what the labels claimed, and four products had vitamin E that exceeded the USP range. High doses of vitamin E  are associated with pregnancy complications, including fetal loss or neonatal death.

• Vitamin A was the nutrient that was most frequently outside the USP standard, with nine of the 12 products or a staggering 75! Fortunately, most had too little as opposed to too much. Still, two products had more vitamin A, and this is always a potential concern as 1,300 mcg of RAE (retinol activity ingredients) is recommended in a prenatal supplement. The tolerable upper limit is 3,000 mg RAE daily; one product tested was slightly over this value. Doses of > 7,500 mg RAE of vitamin A within 60 days of conception are associated with miscarriage and spontaneous abortion, so good manufacturing practices here are essential.

• No products had concerning levels of lead, arsenic, or cadmium and the amount of lead conformed to the Prop 65 standard of less than 0.5 mcg per day. This was a small sampling, so we don’t know if the situation would be better or worse if more doses from more batches were tested.

We don’t know the reason for the variability in the products. Vitamins are apparently hard to make in a shelf-stable way, and so this is one possibility, but this is no excuse. It is a reason to turn some of the massive amounts of profits from making vitamins into research and development to correct this problem. Without legislation, this is unlikely to happen. Science can often solve these manufacturing issues, but sometimes, it can take decades of research. Look, it used to be impossible to give progesterone orally because of absorption issues, and then, through research and development, scientists figured it out, and now we have oral progesterone. But the drive to do this came from Pharma, and they had to prove they did what they claimed to the FDA. Many topical progesterone supplements that can't be absorbed and are scams are sold as supplements, which is the difference between oversight and no oversight.

Heavy metals, which do show up in some studies but didn’t here, can come from a variety of sources. While contamination during manufacturing or even purposeful addition (like with Ayurvedic medicines) can be one source, it can also be from bioaccumulation; basically, the heavy metals build up in the raw product that is used to make the supplement. For example, the natural sources used for some calcium supplements include shells, bones, and rock, which can be a lead source. This is no excuse; companies can and should test their products and look for sources with lower risks of lead contamination. 

The GAO doesn’t release the names of products, so I can’t tell you which products had too little folic acid or the one with the highest vitamin A level. I asked Dr. Karen Howard from the GAO if any of the products had third-party testing verification labels to see if that was predictive of label accuracy. This is what she told me:

According to our analysis, third-party verification is not a guarantee of conformity to the amounts on the label. Five of the 12 prenatal supplement products we tested stated on their labels that they had undergone some form of third-party verification. We found that, on average, these five verified products performed similarly to the non-verified products, although none of the products with third-party verification had nutrient levels present in amounts that may cause a health concern.

Sigh. 

More About Third Parties…

I decided to take a peek at ConsumerLabs.com and Consumer Reports to see what they recommended regarding prenatal vitamins…and I received a couple of shocks. 

ConsumerLabs.com mentioned that 29% of multivitamins tested had labeling inaccuracies. Their top pick for prenatal vitamins is MegaFood Baby & Me 2. HOWEVER, which is in capital letters for a reason: MegaFood Baby & Me 2 has 612 mg of L-5-methyltetrahydrofolate, NOT folic acid. I was shocked, as only folic acid is recommended by the CDC to prevent neural tube defects. You can read more about the different types of folate and why folic acid is recommended here. 

I contacted ConsumerLabs.com and asked why they recommended a product without folic acid. I received a reply from Dr. Cooperman, the President and Founder, who told me via email that the National Academies recommend “that pregnant women get 600 mcg DFE (dietary folate equivalents) daily from supplemental folate, which would mean either folic acid or another synthetic form, such as methylfolate,” and that "600 mcg DFE (dietary folate equivalents) is equal to about 360 mcg of folic acid or methylfolate.”

In my email, I mentioned that the CDC and ACOG recommend folic acid, and his response:  

“It may be that the organizations you mention focus on "folic acid," as there is more research on folic acid than with methylfolate. We are agnostic as to the synthetic form -- MegaFood happened to use methylfolate rather than folic acid. There is, however, a potential advantage to methylfolate over folic acid, in that a small percentage of the population may, due to genetics, be less able to utilize folic acid than methylfolate -- although any real advantage has yet to be proven. We liked MegaFood mainly due to other features, such as providing a significant amount of choline.”

This was disappointing. You know who isn’t agnostic about folic acid vs methylfolate or other non folic acid forms of folate? The experts at the Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists. This is because we have clinical trials showing folic acid reduces neural tube defects, and there are no clinical trials showing that non folic acid forms of folate in supplements, like methylfolate, reduce neural tube defects. This means that people taking a supplement with a form of folate other than folic acid cannot be sure they are getting the needed benefit. There is no upside, with a big potential downside. Why should you, the consumer, bear the risk with an untested form of folate when a tested and safe form is available? 

The evidence also does not support the claim that people with an MTHFR genetic variation do better with methylfolate. The experts at the CDC say that people with an MTHFR variation can get all the folate they need from folic acid. 

When I asked Dr. Shannon Clark, a board-certified OB/GYN and maternal-fetal medicine specialist about the recommendation from Consumerlabs.com, she replied, 

Folic acid is the only form of folate found in prenatals/supplements that has been proven through numerous studies, including RTCs to help prevent against neural tube defects in the fetus, some of which are lethal. While these companies try to say methylfolate is better or equivalent to folic acid, we don’t know this to be true.

Dr. Clark recommends that consumers “make sure the nutrition and supplements facts label specifically says “folic acid” followed by the amount of micrograms.”

Next, I went to Consumer Reports, which did not report safety testing but had lists of prenatal supplements based on their labeling. I was shocked to see that many products, like Ritual and Pink Stork Prenatal, were recommended even though they do not contain folic acid but rather one of the other folates. Even worse, these non-folic acid-containing products were labeled by Consumer Reports as containing folic acid! The language about folate is confusing, so absolute clarity is essential.

See a screenshot from Consumer Reports below to the left and the Pink Stork product label to the right.

I emailed Consumer Reports.com and sent them the information from the CDC, and I am pleased to say that they were very responsive and, after reviewing the data, amended their page and now clearly state which prenatal vitamins contain folic acid and which do not! Click here to see the list.

An updated screenshot from Consumer Reports.

They also added this nice comment at the end of their report. 

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What Can You Do?

Some supplements are needed, and prenatal vitamins are one of the best examples. Unfortunately, they are also a great example of why products need to be tested and safe because pregnant people shouldn’t have to play folic acid, vitamin, and heavy metal roulette. We need more studies to understand how common contamination is with these products and how often they deviate from the amounts listed on the labels. 

This system of relying on third-party testing also needs further exploration. The GAO did not tell me which third-party testing labels were included on the products tested or how much they deviated, so it’s impossible to say more. I would still choose a supplement with one of the most known third-party testers, Pharmacopeia Convention (USP, label should say USP verified), NSF International, and ConsumerLabs, although I think the GAO should let the public know which products were verified and by whom. I am also disappointed in ConsumerLab's position on folic acid, as this is not supported by the relevant experts.

If you want to know which prenatal vitamins Dr. Clark, who is an expert, recommends, go to her Instagram. You can find her here. 

I have no grand words or a neat summary here. Regarding supplements, unfettered capitalism is the opposite of consumer protection (probably for all of medicine, for that matter). I’ll end with the summary from the GAO, and if this bothers you as much as it bothers me, call your Representative and Senator. Dietary supplements need oversight. You have the right to know what you are putting in your body.

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References

1. FIGO Toxic Chemicals and Environmental Contaminants in Prenatal Vitamins. https://www.figo.org/resources/figo-statements/toxic-chemicals-and-environmental-contaminants-prenatal-vitamins

2. Prenatal Supplements; Amount of Some Key Nutrients Different from Product Labels. GAO-24-106689  Q&A Report to the Chair, Subcommittee on Human Rights and the Law, Committee on the Judiciary, U.S.Senate. Dec 12, 2023. https://www.gao.gov/assets/d24106689.pdf

3. Schwalfenberg G, Rodushkin I, Genuis SJ. Heavy metal contamination of prenatal vitamins. Toxicol Rep. 2018 Mar 6;5:390-395. doi: 10.1016/j.toxrep.2018.02.015.

4. CDC MTHFR Gene, Folic Acid, and Preventing Neural Tube Defects. https://www.cdc.gov/ncbddd/folicacid/mthfr-gene-and-folic-acid.html

5. Bourgoin BP, Evans DR, Cornett JR, Longard SM, Quattrone AJ. Lead Content in 70 Brands of Dietary Calcium Supplements. Am J Pub Health 1993;83:1155-1160.

6. Lashbrook A. How to Choose a Prenatal Vitamin, Consumer Reports 2023, April https://www.consumerreports.org/health/supplements/how-to-choose-a-prenatal-vitamin-a1197384921/ 

7. Multivitamin and Multimineral Supplements Review ConsumerLabs.com https://www.consumerlab.com/reviews/multivitamin-review-comparisons/multivitamins/#results