Mark my words: long COVID will be a magnet for quacks.
The nebulous syndrome—or perhaps family of syndromes—that sometimes sticks to a COVID survivor, crippling them with fatigue, shortness of breath, and difficulty thinking (among an endless list of symptoms) is bound to become a significant healthcare headache and a life-altering burden for a substantial number of people. As months go by, desperate minds will turn to whatever is offered to them: energy healing, colourful crystals, and supplements. If COVID long haulers are not already familiar with the word “adaptogen,” the magical spice of the wellness world, they will hear it from the mouths of friends and relatives trying to help.
Already, some questionable nutritionists are playing matchmakers between adaptogens and people with long COVID. A clinical trial of one particular adaptogen is underway in the United Kingdom to see if it can help with symptoms and activities of daily living, while one of the biggest names in the adaptogen research space has published the results of his pilot trial pitting an adaptogen blend against a placebo.
Adaptogens are meant to help us adapt to stressful situations and avoid the bodily damage that comes from stress, and these herbs, mushrooms, and foodstuffs have themselves adapted and survived a number of medicinal philosophies: first, the folk medicines that predated modern science; then, secret Soviet military research; and finally, and most awkwardly, the world of evidence-based medicine, which has not been kind to their extraordinary claims.
Because if you believe the hype around adaptogens, you might think they are witchcraft.
Ginseng and tonic
Imagine what stress does to you. At first, there is alarm: an immediate response to prime the body against this stressor. Then there is resistance to the stress, but eventually the body exhausts itself. We can’t live in high stress forever. Or could we?
Adaptogens, as described by Soviet scientists in the middle of the 20thcentury, are substances that must abide by a number of rules, not unlike Isaac Asimov’s Three Laws of Robotics. Rule #1: an adaptogen must have a non-specific activity, meaning it must help you adapt to a wide variety of stressors, including physical, chemical, and biological agents. Rule #2: an adaptogen must have a normalizing influence, meaning it increases what needs to go up in one person and decreases what needs to go down in another. And rule #3: an adaptogen must do no harm.
You may think that adaptogens are stimulants, much like caffeine. Advocates for adaptogens would disagree. Caffeine gives you a boost but eventually, if you don’t reach for another cup, you will crash. Adaptogens, by instead supporting the body’s stress response, are not supposed to make you crash. They are claimed to have no side effects, no negative impact on sleep, and no risk of creating addiction, tolerance, or abuse. Some have even said they act as “mild stress vaccines.”
Your skeptical alarm bell might ring louder when I tell you that adaptogens have had a thick gloop of marketing smeared all over them. Product labels and social media influencers will parade limitless claims: adaptogens are said to sharpen your memory, boost your sex drive, rid yourself of exhaustion, help stabilize your blood sugar, and fight cancer. They might also assemble your IKEA furniture for you and help you with your financial investments if they had opposable thumbs and direct access to your bank account.
These mysterious adaptogenic molecules did not fall from the Siberian sky in the 1940s, however. Adaptogens were in fact repackaged herbal remedies, the products of ancient healing traditions, that Soviet scientists thought helped bodies adapt to stress. Especially the bodies of soldiers.
As with competitive sports, wars can benefit greatly from an edge. During the Second World War, the Soviet Union became particularly interested in the investigations that had been done of Asian folk medicines, particularly the use of a woody vine by Nanai hunters who lived in parts of modern Russia and China. This vine is called schisandra or, to give it its full Latin name, Schisandra chinensis. The Nanai people used it as a tonic, meaning a substance that invigorates the body and mind, so Soviet pilots and submariners were given schisandra to boost their energy and calm their nerves down.
The Soviets spent decades researching schisandra and other adaptogens, writing down the results of over 1,500 studies, but most of these are not listed in the major databases that allow scientific papers to be searchable nowadays. It has been reported by researchers in the field that the quality of these Soviet studies, by modern standards, is lacking and the diagnoses used by these scientists were somewhat questionable. The word “schizophrenia,” for example, was often overused and misapplied.
If you are stressed out and go looking for adaptogens, the ones you are likely to encounter include various unrelated plants referred to as ginseng. In fact, the word “ginseng” seems to have become synonymous with “plant-based tonic.” There’s Chinese ginseng (Panax ginseng) and its cousin-in-name-only Siberian ginseng (Eleutherococcus senticosus), which was discovered when a cheaper alternative to the expensive ginseng root was sought. Then there is American ginseng, Malaysian ginseng, Peruvian ginseng, even Indian ginseng better known as ashwagandha (Withania somnifera), an evergreen shrub that was recommended by the Indian government to treat COVID-19.
Natural adaptogens also include a green plant you have probably encountered while eating at a Thai restaurant: holy basil. If adaptogens really are the magic bullets they are portrayed as, I would imagine the Thai people would be champions at surviving stress unscathed.
A big hit on the adaptogen circuit, and hailing from the high altitudes of Europe and Asia, is golden root (Rhodiola rosea), a plant so popular it is being threatened by the massive harvesting operations needed to meet demand, which has led to substitutions.
Reishi and cordyceps mushrooms are also said to have adaptogenic benefits, as well as green tea, ginger and garlic, and a number of synthetic substances like bromantan, which figures on the World Anti-Doping Agency’s list of prohibited substances as a stimulant.
To embrace the claims of efficacy that surround adaptogens like health halos is to brush aside, through ignorance or willful dismissal, the many, many problems adaptogens have, which wellness skeptics will recognize as the problems of herbalism more generally.
No green light for adaptogens
Adaptogens are supposed to be a category unto themselves, different from substances that regulate the immune system (immunomodulators) or that improve our memory and thinking (nootropics). But many adaptogens have been shown to have immunomodulatory or nootropic activity, so the boundaries of the adaptogen classification melt rather easily.
The boundaries of what we define as stress are also quite flexible in the context of selling adaptogens. And while we may think that tweaking our stress response must be beneficial, we would do well to remember that wellness gurus have oversimplified biology before: see antioxidants.
Adaptogens also clash with modern medicine. They are mixtures. Golden root alone contains polyphenols, glycosides, organic acids, essential oils, alcohols, proteins, sugars, and fats. Some claim that the adaptogenic power of these plants lies in specific families of molecules, like tetracyclic triterpenoids or complex phenolics, because they are claimed to be similar to chemicals our bodies naturally produce and that help us respond to stress, like corticosteroids and neurotransmitters called catecholamines.
Others argue the hundreds of chemicals found in adaptogens like ginseng and ashwagandha must be ingested together, as they work synergistically. It’s not any one molecule in the plant; it’s all of them. Because the molecular composition of plants varies based on the climate, soil composition, the presence or absence of infections, the fertilizer used, and many more factors, however, you just don’t know if the adaptogenic dose you got from last year’s ginseng harvest will be the same as this year’s. And given how loosely regulated the natural health product industry is to begin with, you may get a boost from consuming one of these adaptogens, not because of the plant itself, but because of contamination with actual drugs, like the steroid prednisone. With acetaminophen tablets, you know the dose is constant. With natural products like adaptogens, you simply do not know what you are buying.
And lest you still believe there is good evidence for the outsized claims the all-natural crowd makes with respect to adaptogens, I hope you are a large rat. Promising data on adaptogens come from animal studies, a necessary first step but far from relevant to human beings, with some studies resorting to intraperitoneal injections of adaptogens. I don’t know of anyone who injects themselves with Siberian ginseng straight in the abdomen, nor would I recommend it.
The relatively few studies done in humans tend to be disappointing. They often lack randomization, recruit only healthy people, and they don’t specify the dose of the herb that was tested. Reviews of the evidence often conclude that, at best, adaptogens may helpwith stress and fatigue and that more studies are needed. At worst, there is no indication they have the claimed clinical benefit. The number of participants in human trials is almost always small and the treatment and follow-up periods are short, with no long-term, properly documented safety data on the consumption of these plants. You might wonder why safety is important, since the Third Law of Adaptogens is that they must do no harm. The reality is that plants contain chemicals, and chemicals can harm us. Ashwagandha, the Indian ginseng that was sold by some as a treatment for COVID-19, may actually cause abortions. Adaptogens are not innocuous.
Which brings us back to the adaptogen trial done on people dealing with long COVID, who were given either a placebo or a liquid containing golden root, schisandra, and Siberian ginseng. This liquid, called ADAPT-232/Chisan®, is made by the Swedish Herbal Institute, which funded the trial, and the corresponding author on the paper is the head of research and development for the institute. The “follow the money” crowd would do well to keep this in mind.
Despite the inherent bias and the spin given to the results (“this pilot study demonstrates that Chisan®/ADAPT-232 can increase physical performance in Long COVID”), the findings are overall disappointing, with the real meat being buried in the supplemental section. Long COVID symptoms significantly decreased over the three-week period the participants were followed for. Fatigue, headaches, difficulty breathing, sweatiness, loss of smell and taste, hair loss, pain, attention deficit, memory issues, and mood disorders—all went down… but they decreased equally for those on the adaptogen mixture and for those on the placebo.
It’s only when the authors start to slice and dice the data that they extract some weak sauce that will undoubtedly be spotlit by marketers: the adaptogen mixture was better than placebo when it came to coughing and daily walk time, and when looking at blood levels of creatinine and interleukin-6. Also, it was better than placebo at reducing fatigue and pain… for half of the participants only… and specifically on days 9 and 11 of the trial. It’s hard to slice more thinly than this. None of it is scientifically filling.
The best summary of the adaptogen market I have read—and which can easily apply to the natural product industry as a whole—comes from Dr. Rashmi Mullur, an assistant professor of medicine at UCLA, who was interviewed by Vox about adaptogens and the people who sell them: “They can just say it works. They can sell it or they can spend a bunch of money to study it and potentially find that it has no benefit. There’s too much risk.”
You can spin negative findings into gold when your remuneration is on the line. But really, why even study a product thoroughly when you can simply appeal to magical thinking and make profits along the way?
Take-home message:
- Adaptogens are supposed to be substances, often plants (like ginseng and golden root), that help the body adapt to stress with no side effect
- Their long-term safety has not been demonstrated, and consumers should keep in mind that the regulation of this market is poor and some adaptogenic herbs are known to have potentially serious side effects
- Evidence for their effectiveness usually comes from animal studies and a few published studies in humans, which tend to be small and lacking in rigour
