Date: May 6, 2019
Author: Markham Heid
Earlier this year, federal authorities announced plans to strengthen oversight of the supplement industry.
“The growth in the number of adulterated and misbranded products — including those spiked with drug ingredients not declared on their labels, misleading claims, and other risks — creates new potential dangers,” said U.S. Food and Drug Administration (FDA) commissioner Dr. Scott Gottlieb in a February press release.
Heightened oversight is needed, Gottlieb argued, because expansion and change within the supplement industry has made it difficult for his agency to keep pace. “What was once a $4 billion industry comprised of about 4,000 unique products, is now an industry worth more than $40 billion, with more than 50,000 — and possibly as many as 80,000 or even more — different products available to consumers,” he said.
From multivitamins and botanicals to probiotics and protein powders, roughly three out of four Americans now take some kind of supplement on a regular basis. Since the days of palliative tonics and snake-oil salesmen, Americans have been readily lured by the promise of health or longevity in the form of a drink, pill, or powder. While the terminology has evolved — “biohacking” and “nutraceuticals” are some of the buzzwords du jour — the implied benefits of most supplements still outpace or ignore the science. And despite recent studies that find supplements are frequently contaminated or that the best way to get nutrients is through food, Americans’ interest in supplements is only growing. And experts say many supplement users don’t recognize or appreciate the risks that accompany the use of these products.
“Pill use among every age group is at an all-time high,” says Dr. Mark Moyad, the Jenkins/Pomkempner director of preventive and alternative medicine at the University of Michigan. “There isn’t a medical condition or symptom you can name that doesn’t have a supplement you can take to treat or prevent it.”
“There’s a huge disconnect between people’s perception of supplements and the reality, and that can be really destructive.”
In some respects, the growth of the supplement industry is a good thing. As America’s population has grown older, fatter, and sicker, Moyad says there’s potential for targeted supplement use to fill in some nutrient shortfalls caused by unhealthy eating habits or disease-related deficiencies. There’s also little doubt that some groups — notably pregnant women and older adults — can benefit from taking certain supplements, he says.
“But the idea that you can take 10 pills a day and fix everything or live forever is faulty,” he says. “There’s a huge disconnect between people’s perception of supplements and the reality, and that can be really destructive.”
“Most supplements on the market are not tested for either efficacy or safety,” says Dr. JoAnn Manson, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston. She mentions heavy metal contamination and other concerns related to poor manufacturing practices, and compares the current regulatory environment to “the Wild West.” Just last year, a JAMA report found unapproved pharmaceutical ingredients have turned up in hundreds of products.
If you’re taking a handful of supplements without a doctor’s oversight, she says, “there’s the potential for almost anything to happen.”
In the mid-1980s, researchers at Seattle’s Fred Hutchinson Cancer Research Center, and elsewhere, were optimistic about the disease-fighting potential of antioxidants and vitamins.
Two in particular — beta-carotene and vitamin A — had shown promise in early dietary studies. “Beta-carotene is an antioxidant and a natural component of green and orange-yellow vegetables,” says Dr. Gilbert Omenn, who back then was at Fred Hutchinson and is now a professor of human genetics and molecular medicine at the University of Michigan. “Vitamin A was shown to reduce cell division and the proliferation of cancer cells.”
After gaining study approval from the National Cancer Institute, Omenn and his colleagues recruited more than 18,000 men and women who were at high risk for lung cancer. They randomly divided these volunteers into two groups; one took a placebo while the other swallowed a daily supplement containing 30 mg of beta-carotene and 25,000 IU of vitamin A.
Omenn says the goal of his government-funded study, which was known as CARET, was to lower cancer incidence. “We had beta-carotene for its antioxidant properties and vitamin A for its antiproliferative effect, and we thought it would be a nice combination,” he says.
The results of CARET were so disastrous that the trial had to be terminated almost two years early. Rather than lowering rates of lung cancer, the supplement had the opposite effect. Among the people taking it, “we saw one additional cancer case per thousand people,” Omenn says. That may not sound like a lot, but in the world of cancer statistics, an increase of one case per 100,000 people is significant.
“What we observed was maybe the most potent carcinogenic effect ever discovered,” he says. “It was truly shocking.”
What went wrong? It turns out that, when confronted with an overabundance of certain antioxidants, the human body may convert them into prooxidants, which have the potential to activate cancer pathways. “Something fundamental we didn’t understand in advance was that, in living systems, antioxidants are not antioxidants in all situations,” Omenn says.
Troublingly, another group of researchers more or less replicated Omenn and his team’s work in a later trial that looked at the effect of vitamin E and selenium supplements on prostate cancer incidence. Again, people at high risk for cancer were randomly assigned either a placebo or a daily supplement. And again, the study had to be ended early because cancer rates soared.
The lesson here isn’t that supplements give people cancer. Rather, it’s that approaching supplements as though they’re all upside is a misguided and potentially harmful operating philosophy. When you swallow a capsule packed with concentrated amounts of a vitamin, nutrient, or other substance — a practice that did not become widespread until very recently — you can get into trouble. “To this day, there remain people who believe vitamins and organic compounds are inherently safe and that our studies were flawed,” Omenn says. “But clearly, that’s not true.”
Omenn says that heavy doses of vitamin A can also promote bone pain or swelling, headaches, and skin problems among adults. Taken during pregnancy, large doses of vitamin A can cause birth defects, he says.
While individual supplements are unlikely to pack dangerous levels of vitamin A, people who take multiple supplements with overlapping ingredients may be playing with fire. “I see patients who come in with a whole bag of supplements they’re taking — an immune booster, something for hair, something for vision, something for skin — but if you look at the ingredients, you see they’re all the same,” says Dr. Zhaoping Li, a professor of medicine and director of clinical nutrition at UCLA Medical Center. “So someone is taking three or four things with vitamin A, and also a multivitamin with vitamin A, and all these can add up.”
Li explains that fat-soluble vitamins can accumulate in the body and cause liver toxicity. She says that, on rare occasions, she’s seen patients who needed liver transplants due to supplement overuse. But a more typical reaction to this sort of nutrient overdose could be elevated levels of inflammation accompanied by GI side effects like nausea and bloating, she says. “But these are nonspecific symptoms,” she adds, meaning doctors who see people with these issues probably wouldn’t associate them with supplement overuse.
While specifics vary from one product to the next, nearly all supplements come with some level of risk — including some of the most popular pills on the market today.
“When you talk about fish oil and omega-3, it’s very difficult and expensive to preserve the goodness of the fatty acids and to put it in capsules,” says Chandan Sen, associate vice president of research at the Indiana University School of Medicine. If fish oil is not properly preserved, he says, it becomes oxidized and potentially harmful. Taking such a product has “a similar impact on the body as taking over-fried cooking oil,” he explains.
Sen has written extensively on the risk and role of supplements. He says heavy-metal contamination is a common and well-documented issue associated with herbal products. He, and others, also point out that, time and again, research has shown that taking concentrated doses of food-derived or plant-derived nutrients does not confer the same benefits as eating the foods or plants themselves.
“In the cancer world, we tell people to avoid processed foods, and supplements by definition are processed foods.”
“It’s often harder for the body to metabolize an isolated vitamin or nutrient on its own,” says Lorenzo Cohen, a distinguished professor and director of the Integrative Medicine Program at the University of Texas MD Anderson Cancer Center in Houston. Cohen says that whole, unprocessed foods contain “a whole pharmacology” of different compounds and chemicals that together have a synergistic effect not found when those same chemicals are isolated and taken as supplements. It’s this synergy, he says, that seems to provide the greatest health benefit and the least amount of risk.
“Take curcumin, which is popular in the cancer world,” he says. Curcumin is found in turmeric root, and some research has found that it has antioxidant and anti-inflammatory properties. “When you consume curcumin as ground up turmeric powder and use it in cooking, you’re getting it with this rich soup of different phytochemicals and other constituents that are probably helpful,” he explains. On the other hand, taking concentrated curcumin in a capsule — even if its paired with other ingredients to boost its bioavailability — doesn’t seem to have the same effect, and it may come with risks, he says.
“In the cancer world, we tell people to avoid processed foods, and supplements by definition are processed foods,” he adds.
Sen echoes many of these warnings. “There’s evidence that berry anthocyanins may have potent anticancer chemopreventive effects,” he says. “But these anthocyanins have a very specific chemical structure.” When supplement makers try to extract these structures and put them into pills or powder, they often end up with a very different structure, he explains.
Sen says he’s interacted with many supplement companies. And his experience, by and large, has been that most of them spend far, far more of their budget on product marketing than on proper research and development. “This is clearly not in the best interest of consumers,” he says.
A common scenario, he explains, is that a small study performed in a “limited” experimental environment — for example, in cell cultures or in animals — will link a certain plant chemical with a potential health benefit. The media reports on this finding, and then a supplement maker rushes to manufacture a supplement using the relevant chemical, which they’ll claim is “science-backed.”
“The current legal landscape permits this,” he says. “To regulate everything is not the answer, but the barrier of entry into the marketplace for supplements is very low.”
In his February press release, FDA’s Gottlieb detailed plans to beef up his agency’s research efforts and product-reporting requirements. The FDA has since announced plans to heighten public awareness of adulterated products. But experts say these changes, while welcome, won’t address many of their core concerns.
“There are really no laws that make supplement companies go through the FDA in the first place,” says Joanna Sax, a professor of law at California Western School of Law who has published papers on the supplement industry.
Sax explains that, unlike prescription drugs or over-the-counter medications, nutrition and health supplements are legally categorized as food products. This makes them exempt from many forms of oversight. “Drugs have to be tested for safety and efficacy before they go to market,” she says. “But in most cases, the FDA can remove a supplement from the market only if there’s a demonstrated harm, and they don’t know if there’s a harm until that harm has already happened.”
The FDA’s authority comes from Congress, she adds, and so their power to prevent risky supplements from getting into consumers’ hands is limited. (The FDA declined to comment for this story.)
There’s a counterargument to be made that, were the FDA granted the power to demand pharmaceutical-level testing of supplements, many people would be denied affordable access to products that could provide them real and meaningful benefits.
“Pharmaceuticals need to be vetted for efficacy and safety, and approved by the FDA through a process that can take 10-plus years and many, many millions of dollars,” says Amy Brown, an associate professor in complementary and integrative medicine at the University of Hawaii at Manoa who has researched herb and dietary supplements. “This process is not possible for dietary supplements that are not patented,” she says. The costs would chase away most manufacturers.
Still, other experts say change is needed. “I absolutely do think there should be increased regulatory oversight and supplement makers should have to show that their products are safe,” says Brigham and Women’s Manson. “Many come with risks and very few benefits.”
Regardless of how supplements are regulated, experts say it’s time people started thinking of these products as akin to prescription drugs.
“There’s a lot of distrust of the drug industry, and I think some consumers trust supplements more because they see them as ‘natural’ and not made by the drug companies,” Sax says. The irony is that the recent growth in the consumer supplement industry has largely been fueled by drug companies entering the fold.
“It used to be supplements versus Big Pharma, but now they’ve merged — supplements are Big Pharma,” UM’s Moyad says. “The drug companies saw how big complementary health was getting and they wanted a piece of the action.”
“There is a desire to go from point A to point B as quickly and easily as possible, and taking pills to do that is very chic right now.”
Based on his 33 years in medicine — much of which he’s spent studying supplements — Moyad says he approaches these products with the same caution he applies to drugs. “I understand and respect the power of pills,” he says. Like prescription drugs, supplements can help people with a diagnosed medical condition or deficiency. And like pharmaceuticals, supplements come with risks and side effects, he says.
He also practices what he preaches. “My colleagues can’t believe I don’t take anything,” he says. “And I tell them I don’t take anything, first of all, because I don’t need to take anything, and also because I’m not willing to be a guinea pig in a clinical trial of one.”
Asked for examples of times when supplements are clearly beneficial, he says there’s strong evidence that some products can benefit those at high risk for macular degeneration or skin cancer. There’s also good evidence that supplements can treat some disease-related symptoms.
There’s also no question that certain patient groups — as well as adults who, by choice or by necessity, are deficient in certain vitamins or nutrients — can make up shortfalls with supplements. “I’m primarily vegan, so I take a vitamin B12 supplement,” MD Anderson’s Cohen says. But he adds that, for healthy adults looking to mitigate their disease risks, supplements offer more downside than upside. “In the best case, they’re just a waste of money and you pee them out,” he says. “The worst case is over time there’s some kind of accumulation and toxicity.”
Over and over again, he and other experts say that eating a range of healthy whole foods is a better, safer, more-effective approach than taking supplements.
“Eat at least five servings a day of fruits and vegetables, eat whole grains rather than refined grains, avoid processed foods, eat at least two servings of fish a week,” Manson says. “If you’re vegetarian, try to get fatty acids from oils and nuts and seeds.”
Moyad agrees. “I have yet to come across any product that someone could sell me that was the secret to health or longevity,” he says. “But all the boring shit — a healthy diet, a good night’s sleep, exercise — the evidence for that has only become stronger.”
“There is a desire to go from point A to point B as quickly and easily as possible, and taking pills to do that is very chic right now,” he says. “I think we’ll get to a place where some supplements could have incredible value in disease treatment, but people need to wake up to the fact that if they’re experimenting on themselves with these products today, they could wake up in a few years and have done real harm.”