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Immunity research is advancing, but supplement brands must be cautious

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Learn how cautious supplement brands need to be when using new research relating to immunity and particularly COVID-19.

With the COVID-19 vaccine rollout proceeding slowly and no cure for the coronavirus in sight, researchers are examining every last molecule in hopes of finding something—anything—that might alleviate symptoms, battle the infection or provide potent immune support. Even as the global pandemic has shuttered testing facilities, stalled clinical trials and strained access to basic lab supplies, scientists worldwide remain determined to help to ease the pain of this unprecedented health crisis.  

For the supplement industry, however, results in the lab are only one part of the process. A wave of new science is coming, and the question becomes not only whether an ingredient is effective but also how the supplement industry will market it with regulators watching more closely than ever.

Researchers, mainly from academia but also within the industry, are studying a broad range of dietary supplement ingredients for potential health benefits tangential to this virus. They’re not seeking COVID-19 treatments necessarily, but rather viable adjuncts to optimize immunity or support recovery from infection. 

“There is a mad scramble going on,” says Thomas Brendler, founder and CEO of herbal products consultancy Plantaphile. “A quick Google Scholar search of ‘COVID-19/SARS/CoV-2/herbal supplements’ for 2020 alone gives me close to 3,000 hits. I can back this up by what I’ve seen published and what I’ve personally peer-reviewed over the last year.”

There is immense scientific interest in immune health standbys like zinc and vitamins C and D, as well as CBD, adaptogens and branded ingredients. Botanicals, especially, are getting a close look. Researchers are probing herbs rooted in traditional Chinese medicine, Ayurveda and other traditional systems, as well as anything with known antiviral, immunomodulatory, anti-inflammatory, antioxidant or other pertinent properties. 

As for the type of COVID-19-related research underway or planned, it runs the gamut from literature reviews, computer modeling and in vitro studies all the way to randomized, controlled human clinicals. “A good proportion of the research is reviewing hypotheses, but I am also seeing a lot of experimental work being done, the majority of it preclinical,” Brendler says. “The most advanced studies are likely coming out of Asia because traditional Chinese medicine was applied pretty much instantly at the beginning of the outbreak.”

In fact, human-trial data have already produced a win in Thailand. On Dec. 30 the nation’s health ministry approved a pilot project using Andrographis paniculata to treat early-stage COVID-19 infection. Other human clinicals underway include a Spanish study looking at milk thistle and an Iranian study investigating licorice, both for relieving respiratory symptoms. Meanwhile, a Mexican trial is assessing Artemisia annua, AKA sweet wormwood or sweet Annie, which contains artemisinin, used in antimalaria drugs. 

But, as Brendler notes, the bulk of the science happening right now is nowhere near the human-testing phase; much of it is not on that trajectory anyway. Thus, most early-stage data won’t inform COVID-19 treatment protocols anytime soon, if ever. Still, this research is critically important. It can yield valuable information about specific ingredients’ mechanisms of action or dietary supplements’ potential to support immune health—data that could benefit the industry even after this current crisis subsides. 

In late December Phytotherapy Research published a paper titled “Botanical drugs and supplements affecting the immune response in the time of COVID-19: Implications for research and clinical practice.” Authored by Brendler and 12 other experts, it explores Indian frankincense, turmeric, umckaloabo, echinacea, elder, licorice, herbal adaptogens, salicylate-yielding herbs and medicinal fungi—not as treatments, but as safe options “when taken before onset, during initial infection or in convalescence,” Brendler says.

“Though none of these botanicals have been clinically tested for COVID-19, one can hypothesize, based on known mechanisms of action, that they may alleviate one symptom or another,” he explains. “But that is as far as one can ethically take it at this point. There are many places where botanicals could potentially play a role, but nobody should make recommendations about treating COVID-19.” 

As research continues to ramp up and more findings materialize in the coming years, there will likely be new discoveries and deeper understandings that will excite the dietary supplement industry. But in the COVID-19 era—as always—it remains imperative for companies selling products to approach any emerging science cautiously, interpret it correctly and communicate it accurately, ethically and legally.

Dealing with the same old regulatory roadblocks

While new research may produce promising findings pertaining to COVID-19—and even lead to approved natural treatments—that doesn’t mean U.S. dietary supplement companies can use this data to market their products. DSHEA hasn’t budged. Disease and drug claims, both expressed and implied, remain off limits to this industry. FDA and FTC have made this crystal clear, aggressively pursuing companies that deceptively claim their products can treat, cure, prevent or diagnose COVID-19. 

“Since early April 2020, we’ve issued 340 warning letters and brought three cases to federal court,” says Richard Cleland, assistant director of advertising practices at the FTC. “COVID-19 claims are keeping us very busy and will continue to for some time.” And now the feds possess even more punishing power. As part of the stimulus bill Congress passed in late December, FTC gained the authority to collect civil penalties of up to $43,792 per violation from companies making deceptive COVID-19 claims.

Of course, reputable industry players understand and respect DSHEA and wouldn’t dare to make COVID-19 claims anyway. As frustrating as staying within the structure/function confines can be, they know never to include virus, infection, disease or any related verbiage in their marketing. They also steer clear of activity-denoting terms such as antiviral, anti-inflammatory or antibacterial, none of which dietary supplements can legally claim to be.

But what about those ingredients that do have antiviral, anti-inflammatory or other can’t-talk-about-them properties—and have science to prove it? Obviously, companies want to trumpet the research-backed potential of their products, and it would be nice to get more specific than the token “supports immune health” or “promotes a healthy immune system.” 

Too bad.

“Even with COVID-19, we’re left with the same rigid legal framework we’ve always had—full stop,” says Diane McEnroe, partner at Sidley Austin LLP. “If you talk about an ingredient in labeling, you are limited to structure/function attributes and cannot talk about explicitly or implied disease prevention.”

But semantics aside, if an ingredient’s antiviral or other activity has only been demonstrated in a petri dish or animal model, as is the case for many, that alone is a problem. Unless an ingredient has been competently and reliably tested in humans, claiming that it will act the same way inside the human body is risky. And until that ingredient has been tested in humans for specific COVID-19-related endpoints, its effects most certainly cannot be conflated to coronavirus. 

“Proof of real-life effectiveness for medicinal action that meets scientific standards requires clinical trials,” says Steven Dentali, Ph.D., of industry consultancy Dentali Botanical Sciences. “In vitro or animal studies don’t necessarily translate to people. Antiviral activity doesn’t mean activity against all viruses. Anti-inflammatory action in a test tube doesn’t mean it will work in a person—and if it does, the science can’t just be extended to all cases where inflammation is an issue.”

Basically, when it comes to what the supplement industry can and can’t say about science as it relates to products, the regulations haven’t changed just because COVID-19 has changed the world. “FDA and FTC mean business in the same way they did during H1N1, where companies were preying on fears and taking advantage of a health crisis,” McEnroe says. “They’ve pushed out a number of double-headed warning letters, and within those, you’ll definitely find companies talking about emerging science.”

The danger of overselling science

Despite the clear risks, some dietary supplement brands and ingredient suppliers do utilize preclinical data to market their products. 

“We quite often see companies lead from in-vitro studies or, as we’re seeing with COVID-19, computer model studies to see if a metabolite in a botanical ingredient might bind to a viral protein,” says Stefan Gafner, Ph.D., chief science officer of American Botanical Council. “That is the danger: when there is potential for a botanical to be beneficial, and then an herbal product manufacturer jumps to the conclusion that it has been tried and established, but the data do not correspond to what is going on in human body.”

For some companies that latch onto early-stage data, they might not fully understand the scientific rigor required or what the regulations allow. In many cases, however, this is a strategic profit-seeking decision—especially in situations where media has hyped the results of a study. “The problem is industry loves it when the media gloms onto early-stage preclinical data,” says Frank Jaksch, co-founder and chairman of ChromaDex. “They use it as a jumping-off ground when they probably wouldn’t have jumped otherwise.”

When this happens, the industry gets raspberry ketones and green coffee extract—overhyped inredients that disappear once the true state of the science became clear. Jaksch says even resveratrol fell prey to unfounded fervor. “It didn’t go away, but it never lived up to its promise,” he explains. “There was literally no human data, only very early preclinical studies.” Jaksch calls CBD “the current example of overhype in advance of legit data to support the claims companies are making.”

The danger for companies in touting early science is, of course, facing legal ramifications. But it can also affect a brand’s credibility, both within industry and among consumers. Unfortunately, these situations can also erode trust in the industry at large. “If one fly-by-night supplement company gets hit, everyone gets hit,” Brendler says. “You can be as responsible and ethical as you want, but you’ll still be judged on the bad eggs.”

A marketing conundrum 

With such tight restrictions on claims, and with the perils of overselling science clear, how can brands tell a compelling story about product efficacy without wading into trouble? It’s complicated. Although it’s legal for companies to disseminate preclinical data in a nonpromotional fashion, says McEnroe, they must do so in a way that doesn’t exaggerate the findings or their connection to the product.

“Sharing in-vitro data of any kind has the potential to mislead if not accompanied by appropriate disclaimers or other clear explanation of the relevance of that data to real-world effectiveness,” Dentali says. “If a reasonable consumer would likely draw conclusions beyond what the science demonstrates, then it is incumbent upon the company to ensure that the information is properly qualified so that it is not misunderstood.” 

However, as Dentali points out, detailing proposed mechanisms of action typically doesn’t make for good marketing copy. Nor do lengthy disclaimers about the state of the science, which could wind up undermining the message or, worse, bring attention to the fact that a claim is essentially unsubstantiated. 

“It’s tricky,” Brendler says. “On one hand, manufacturers are obligated to substantiate any claims they put on their product, so anybody doing this halfway ethically should have full substantiation on file for every product. That said, that information does not necessarily use language suitable for the consumer—it’s way too technical and scientific. Of course, one can create romance language based on science, but that is a fine art and should be done with extreme caution and within the stipulations and boundaries of the regulatory frameworks.” 

Given the challenges, is it best for brands to just avoid sharing early-stage science altogether? Not necessarily. When done cautiously and correctly, it can be a solid means of consumer education. “Absolutely, there is value in informing the consumer—there is way too little of that going on,” Brendler says. “Not many manufacturers actually make the effort, though it definitely can be done, I believe.”

The key is to not make that information promotional and to avoid the temptation to use emerging science as the basis for product claims, especially when it comes to immune health and other areas that regulators are watching closely. “You have to let the scientific data speak for itself and not link it to any particular ingredient or product,” Gafner says. “That is the difficult tightrope walk companies have to do, as clinical studies are very difficult to use as a marketing tool.”

With the entire world hungry for solutions for COVID-19, it may be especially tempting for companies to get lax about regulations and co-opt promising preclinical data to sell products—particularly if a certain ingredient captures media attention. Thus, in the coming years, the supplement industry should exercise extreme restraint from jumping on unjustified bandwagons and stoking the fires around ingredients not ready for primetime, which could jeopardize their credibility in the future. Now, as ever, the industry stands to benefit from emerging science, but it must be patient, keep playing by the rules and not let potential dollar signs skew smart decision-making. 

This article was featured in the Nutrition Business Journal's Guest Editor Issue. It was edited by Rhen Al-Mondhiry, a lawyer at Amin Talati Wasserman.

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