Astral Codex Ten - How Trustworthy Are Supplements?
[Epistemic status: not totally sure of any of this, I welcome comments by people who know more.] Not as in “do supplements work?”. As in “if you buy a bottle of ginseng from your local store, will it really contain parts of the ginseng plant? Or will it just be sugar and sawdust and maybe meth?” There are lots of stories going around that 30% or 80% or some other very high percent of supplements are totally fake, with zero of the active ingredient. I think these are misinformation. In the first part of this post, I want to review how this story started and why I no longer believe it. In the second and third, I’ll go over results from lab tests and testimonials from industry insiders. In the fourth, I’ll try to provide rules of thumb for how likely supplements are to be real. I. Two Big Studies That Started The Panic Around Fake SupplementsThese are Newmaster (2013) and an unpublished study sponsored by NY attorney general Eric Schneiderman in 2015. Both used a similar technique called DNA barcoding, where scientists check samples (in this case, herbal supplements) for fragments of DNA (in this case, from the herbs the supplements supposedly came from). Both found abysmal results. Newmaster found that a third of herbal supplements tested lacked any trace of the relevant herb, instead seeming to be some other common plant like rice. Schneiderman’s study was even more damning, finding that eighty percent of herbal supplements lacked the active ingredient. These results were extensively and mostly uncritically signal-boosted by mainstream media, for example the New York Times (1, 2) and NPR (1, 2), mostly from the perspective that supplements were a giant scam and needed to be regulated by the FDA. The pro-supplement American Botanical Council struck back, publishing a long report arguing that DNA barcoding was completely inappropriate here. Many herbal supplements are plant extracts, meaning that the plant has one or two medically useful chemicals, and supplement manufacturers purify those chemicals without including a bunch of random leaves and stems and things. Sometimes these purified extracts don’t include plant DNA; other times the purification process involves heating and chemical reactions that degrade the DNA beyond the point of detectability. Meanwhile, since supplements may include only a few mg of the active ingredient, it’s a common practice to spread it through the capsule with a “filler”, with powdered rice being among the most common. So when DNA barcoders find that eg a ginseng supplement has no ginseng DNA, but lots of rice DNA, this doesn’t mean anything sinister is going on. Wouldn’t you expect scientific experts and attorney generals to know this sort of thing already? The American Botanical Council certainly did, and its report was pretty scathing:
You may also enjoy reading the part of the report where they just list every single nitpicky mistake the authors have ever made and how angry they are about all of them:
So far, this seems like a pretty normal scientific dispute. But I think subsequent events pretty firmly supported the Botanical Council’s side. Attorney General Schneiderman tried to leverage his study into a lawsuit against supplement manufacturers. He got a lot of pushback, with even anti-supplement scientists coming out against his data (1, 2). GNC, one of the companies that failed the original study, sent the same supplements to a respected third-party lab, who said all of them seemed totally fine. The end result of the lawsuit seemed inconclusive to me - GNC agreed to test its products better, and the Attorney General declared victory - but people who know more about law and the industry suggest this was a face-saving measure allowing the Attorney General to gracefully retreat. The Forbes article was Supplement Companies Sitting Pretty After AG’s Blunder. Meanwhile, Dr. Steven Newcomer, lead author of the original study, has had one of his other DNA barcoding papers retracted for suspected fraud. Science magazine did an investigative report on him, claiming that:
It paints a picture of Newmaster as founding a DNA barcoding company, then publishing fraudulent studies to prove DNA barcoding was better than all other testing methods, or that companies who refused to use his DNA barcoding had fake or contaminated products. The particular 2013 study indicting the supplement industry has not been retracted, with the journal defaulting to an internal investigation by Newmaster’s university that found no wrongdoing, but Science suggests the internal investigation was biased and we shouldn’t trust it. Overall I don’t have very much confidence in this. But at least Attorney General Schneiderman, while not doing very well scientifically, hasn’t been completely discredited as a human being, right?
Oops, it looks like Schneiderman is among the approximately 100% of New York elected officials who have resigned after being accused of egregious sexual harassment. According to Wikipedia, he was most recently spotted retraining to become a meditation teacher, which is not how I expected this saga to end. Maybe he can recommend his students take herbs! Anyway, as far as I know none of the media sources that signal-boosted the original false information have ever apologized or covered any of this, and many of the people I talk to are still letting the original media blitz shape their opinions. I think at this point those studies are clearly untrustworthy and shouldn’t be determining our beliefs here. II. What Consumer Review Laboratory Sites SayA few companies do Consumer Reports style analyses of supplement brands. For a fee (or sometimes for free, supported by ads), they will analyze supplements and tell you what they find. The two biggest sites I know of in this space are LabDoor and ConsumerLab. Many people have pointed out that LabDoor is a bad company. They have zero transparency and nobody knows exactly how they test products. Their ranking system is also bad: they subtract points for companies that go slightly over the amount of product on a label (eg they say they have 100 mg active ingredient, but actually have 120 mg). But it’s impossible to always hit an exact target (eg 100 mg of ingredient) and reputable companies will make sure that they’re more likely to exceed the target by a little bit (eg have 120 mg) rather than go below it. These kinds of mild excesses aren’t dangerous and are considered industry standard, but LabDoor unfairly penalizes them as much as serious errors. But as long as we look at their raw data, we should be able to avoid their rating problems. And the same people are positive about ConsumerLab. So I think looking at data from both these companies could be a good way to figure out how accurate supplement labels are. Like most labs, these don’t use the questionable DNA barcoding techniques mentioned in Part I. They use primarily chromatography and spectroscopy, normal well-validated methods for these kinds of tests. Still, there are some complications. Most herbs have dozens of closely related chemicals in them. Someone does a study suggesting that one of them is good for you, and then supplement makers try to extract that one. But other times supplement makers disagree, or prefer to extract some very-closely-related chemical which probably does the same thing as the first chemical. Depending on how they do this, they might fail a test which is too myopically focused on amount of the first chemical present. Easy Mode: Magnesium Magnesium is a metal. There is no complicated extraction process. There’s no debate over which ingredient is the active one. It’s just magnesium. You either have it or you don’t. Some suppliers bind it to different molecules, and others do special things to make it bioavailable, but something that claims to have 100 mg magnesium should always have 100 mg magnesium. Labdoor analyzes 30 brands of magnesium supplement. 25 earn As, 3 earn Cs, and 2 flunk. Of the two that flunk, one has only 60% as much magnesium as claimed, and the other has almost 3x as much magnesium as claimed. No product has an unsafe amount of heavy metals, although the worst have between a third and half of the government’s safety limit. ConsumerLab analyzes twelve magnesium brands. Eleven pass and one fail. The failure had only about 80% as much magnesium as claimed. The brand that Labdoor said had 3x the claimed amount of magnesium was completely fine according to ConsumerLab, although Labdoor checked the neutral flavor and ConsumerLab checked the raspberry flavor. The company involved claims to have done an investigation and found that their supplement had the amount they claimed, so it’s possible Labdoor was in error here. Overall this seems good, with almost all brands having close to their labelled amount of ingredient, and the worst having 60-80%. One brand may have gone way above labelled amount, but this is questionable and I suspect a testing error. Hard Mode: Bacopa and Ashwagandha Bacopa and ashwagandha are Ayurvedic (Indian traditional medicine) herbs used for stress. I’m listing them as hard mode because turning it into a supplement usually involves extracting active chemicals (called withanolamides) from the plant. If there were problems with herbal medicines, this would be where we would expect to find them. Labdoor has bacopa but not ashwagandha, and ConsumerLab has vice versa, so I’m combining them for this investigation. Labdoor investigates three brands of bacopa, giving two Bs and one C. These grades are only lower than As because they find the brands have slightly more bacopa than promised on the label. As mentioned above, this shouldn’t be considered an error and a more reasonable version of LabDoor would probably have given As to all of these. ConsumerLab investigates fifteen brands of ashwagandha. They approved 11, were “uncertain” about 3, and rejected 1. One “uncertain” company was uncertain because they claimed to be extracting different chemicals than the ones ConsumerLab was set up to detect - but it was a reputable brand and I give them the benefit of the doubt here; two others had accurate labels but may or may not have been underdosing. The reject was Himalaya Ashwagandha, which claimed to have 3 mg of the active ingredient, but really had 3.3 mg. This would normally qualify as okay, but ConsumerLab says that based on the extraction process they used they should have had 4.4, and they are confused why this didn’t happen. I have trouble holding this against Himalaya given that their label is basically correct. Himalaya also gets dinged because apparently a reasonable dose of this product would be 6 mg, which they do not reach. But their tagline for this page is “Only 56% Of Products Passed Tests”, and I see discussion on Reddit about how “only 3 products passed”. I’m pretty confused by this; maybe this is true of an earlier version of the page, but they’ve since updated it and products have gotten much better since then? Pending figuring out what’s going on with the ashwagandha, my impression here is that most supplements have very close to what they say on the label. When they don’t, it’s more likely to be deviations of 25-50%, rather than complete fraud where the pill is full of rice or sawdust or something. I looked through several other supplements on these sites and these results are typical, although maybe slightly better than average. The most concerning category was mushrooms, where about 25% of brands used some mycelium (the “roots” of a mushroom, which have fewer health-promoting chemicals than the above-ground part) instead of or in addition to the mushroom itself. This is a known issue with mushroom supplements; not enough people know the difference for companies to be consistently incentivized to get it right. III. MYASD From Nootropics DepotNootropics Depot is a supplement company that actively engages with the supplement community on Reddit. A big part of the engagement is their CEO, who goes by the Reddit username MisterYouAreSoDumb, talking about his experiences running the company and answering customer questions. A common feature of his experiences is worrying that his competitors are doing a bad job with lab testing, or getting an unfair advantage by skimping on active ingredient in their product. His writings on this have shaped my understanding of this area and I wouldn’t feel comfortable posting this essay without including some of them. Obviously these are potentially biased (he owns a competing company!) but I still find them useful. I’m going to err on the side of posting many of his very long comments, because I love this stuff - but if you get bored, read one or two and then skip down to the conclusion section. Here’s MYASD on Magtein, a special patented bioavailable form of magnesium:
More on milk thistle:
On tongkat ali:
On fadogia, a plant which Joe Rogan’s podcast recently promoted as a testosterone-booster:
And in response to someone asking him directly how bad the industry was, and whether lots of vitamins from reputable brands had no active ingredient:
On which competitors he respects:
He also has a very long and fascinating comment about turkesterone which this margin is unfortunately too small to contain. Believe it or not, I am restraining myself in terms of how many MYASD comments I post - you can go here for more, including his adventures with payment processors, lawsuits, and cryptocurrencies. The results from the consumer lab companies seemed very promising - almost everyone was good. MYASD’s experiences seem like the opposite - almost everyone seems bad. How do we reconcile these? I think some of the difference is in what supplements we’re talking about. MYASD admits that most simple vitamins, minerals, and amino acids are fine. He finds the most problems with tongkat ali, fadogia, and (offscreen) maca and turkesterone. These are all testosterone/libido/strength boosting supplements for men. My guess is that the most reputable companies avoid these, the consumer base is less discerning, and so these are genuinely worse than other products. That still leaves the mushrooms, milk thistle, Magtein, and several other products he talks about that I haven’t reposted here. We already talked about mushrooms. The milk thistle seems like a special case - it sounds like the industry standard is flawed there. Magtein sounds like companies competing to sell an expensive product for the lowest possible price and having an easy substitution available. IV. ConclusionClaims from the mainstream media that most supplements are completely fake and don’t even contain the active ingredient are probably completely wrong. Most simple supplements, including vitamins, minerals, and amino acids, are very likely to have the amount of product shown on the label. A few less reputable brands might differ by 25%, rarely 50%, practically never less than that. Botanicals are more complicated. Commonly-used botanicals from reputable brands are usually about as trustworthy as vitamins, but there are lots of complications around extraction processes and sometimes you might get 50% more or less than you thought. Less-commonly-used botanicals are less clear; you still will rarely find outright sugar pills, but you may find people bungling the chemistry, not caring too much about exact amounts, or selling mushroom mycelium instead of fruiting body. “Male enhancement” products are their own special class of danger zone, as are anything that’s been featured on The Joe Rogan Experience; you should be extra careful to buy from only the most reputable companies. I trust Nootropics Depot, Thorne, NOW, and Jarrow, in that order, but you’ll want to do your own research and maybe check ConsumerLab for the particular product you’re buying. But zooming out: what is the proper dose of the antidepressant Lexapro? Trick question - it depends on the person - I have seen people need anywhere between 2.5 and 30 mg of it. So how do I prescribe it to someone? I usually tell them to start at 5 mg, then go up or down depending on whether it seems to be working, causing side effects, etc. A lot of herbal supplements are similar. If this is your strategy, a 25% labeling error isn’t going to matter much, is it? If my patients get their Lexapro from a sketchy company that actually has only 4 mg in a 5 mg pill, they’re still going to go up to 20 mg or down to 2 mg or whatever it is the end up needing, based on how it affects them. It will cause problems if they ever change brands, but probably not very many problems. And all of these substances have a wide enough therapeutic index that you’re not going to get toxicity from a 25% mislabeling. So although it’s correct for the industry to obsess over getting this right for purposes of honesty and reputation, as a consumer I don’t personally worry about it as much except for rare substances where specific doses are constant between people and make a big difference, or where you’re not supposed to feel anything (eg decreases heart attack risk over ten years) and so you can’t titrate the dose to effects. If it’s just something that’s supposed to make you less anxious, check how anxious you get! You’re a free subscriber to Astral Codex Ten. For the full experience, become a paid subscriber. |
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