Supplements are a Rising Cause of Liver Failure

Selling and promoting unstudied supplements for women's health is performative feminism

Robert Nicholas/Getty Images

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 drug-induced liver injury in the United States and 19% of 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?

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?

****

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