Ashwagandha, an herbal supplement commonly used in traditional Indian medicine, is the latest fad herb trending on social media. It is also an excelent example of everything that is wrong with the herbal supplement industry.
Herbs are Drugs
The biggest problem with the herbal supplement industry and the rhetoric used to promote it is that it ignores the primary reality of herbal products – herbs are drugs. That is it – they are nothing more or less than pharmacological agents. This means they can cause drug-drug interactions, and they can have all the usual side effects and risks that pharmaceutical can have. They also are not very good drugs, because they have multiple potentially active ingredients, we don’t always know what they are, and they vary considerably among various preparations and even crop to crop.
The fact that there are multiple active ingredients is often marketed as an advantage, with the notion that there is a positive synergistic effect among these ingredients. But why would that be? Plants evolve chemicals to be toxins, to keep animals from eating them. There are no evolutionary pressures to be useful as medicinals. Polypharmacy is also tricky business, and is far more likely to enhance toxicity than any beneficial effect. Often the alleged benefits of herbal polypharmacy are explicitly supernatural in explanation, having to do with chakras, life energy, and a spiritual origin of the plants themselves. Looked at scientifically, however, the messy and variable polypharmacy of herbs should be viewed with extreme caution.
The supplement industry is also famously poorly regulated. There are problems with substitution, contamination, and adulteration. This has significant risks to the consumer. But it also means that clinical trials performed with verified and measured extracts will not necessarily translate to any product on the shelf.
Herbal drugs also have the potential for drug toxicity, even without contamination. The safety of herbs is often falsely assumed, based on the appeal to nature fallacy, but also on the fact that we simply lack adequate evidence for safety and toxicity. Ashwagandha, for example, is associated with cases of liver injury, a common drug toxicity.
What we should do is isolate and purify specific active ingredients, study them in isolation, and if they have a medically safe and exploitable effect, they can be provided at a known dose with a known safety profile, pharmacokinetics, bioavailability, risks, and interactions. Of course then, they are a normal pharmaceutical, and not a magical herb that can be marketed as “natural”.
Hyping Preliminary Evidence
The herbal industry thrives on preliminary scientific results. We have spent years and thousands of articles explaining in careful detail why preliminary medical evidence is unreliable and a poor predictor of actual safety and efficacy. It is quite possible that any particular herbal product may have useful medical effects – again, they are drugs. There is a potential mechanism by which they may have an effect. Also, some effects are easy to observe, which is why most cultures have managed to find local plants that act as hallucinogens. But subtle subjective effects and long term risks and altered health outcomes require careful scientific study.
What we see with Ashwagandha is the same pattern. Studies go back decades, and yet we have not yet managed to definitely answer the question of safety and efficacy. Herbal products seem to be stuck in this preliminary phase of evidence, perhaps by design.
Recent systematic reviews show similar results:
The current systematic review and dose-response meta-analysis of RCTs revealed a beneficial effect in both stress and anxiety following Ashwagandha supplementation. However, further high-quality studies are needed to firmly establish the clinical efficacy of the plant.
The individual studies are mostly small studies, often with methodological issues, and often with subjective outcomes. Again, it’s quite possible there is one or more active ingredients in Ashwagandha that has anxiolytic properties. But as we know from studies looking at anti-anxiety medications, preliminary positive results are often false positives, and it takes large rigorous trials to determine if an effect is real. The studies I looked at generally don’t assess blinding, which is problematic with an herb which can have many active ingredients, some of which may have noticeable effects. Without using an active placebo to conceal who is getting the treatment, or assessing blinding, we have no way of knowing.
We are often therefore left with the “more studies are needed” conclusion, and that status never seems to change.
Extrapolating from Basic Science
This is the aspect of the herbal industry (and the CAM industry in general) that I find most frustrating. What happens is that the substance in question is given even to animals or to cells in a culture, and then stuff happens. Whatever happens can be interpreted as a potentially beneficial effect. Immune function is an almost ubiquitous target.
Immune activity, first of all, is highly reactive. It seems to change and react to almost any stimuli. Anything that increases any marker of immune activity can be spun as “boosting” the immune system. Anything that decreases any marker of immune activity can be spun as “anti-inflammatory”. Sometimes both of these things are claimed at the same time. Of course, we could just as easily present increasing immune activity as causing inflammation and decreasing immune activity as “suppressing” the immune system. These interpretations are just as valid, and in fact are always the case. Even beneficial anti-inflammatories suppress the immune system, and anything that “boosts” the immune system can have negative inflammatory effects.
This is because the immune system is a double-edged sword. It fights off invaders, infections, and cancers, but it causes inflammatory stress and damage. Just increasing or decreasing immune activity is not inherently beneficial or harmful, and can be either. It all depends on the details, the targeting and regulation of immune activity. Even experts in immunology, designing a treatment for an inflammatory disease, have made wrong predictions in the past about net effects (see alpha-interferon and MS).
The same is true of steroids. Reducing corticosteroid levels in the body may be a marker of reduced stress, but these steroids exist in the body for a reason. They are part of a delicately regulated system kept in careful homeostatic balance. Altering this system in any one direction is not inherently good or bad. The same is also true of oxidative stress and anti-oxidants. This is another good example of simplistic herbal thinking – oxygen is good, except when it’s bad.
Is Ashwagandha a useful herb or just another herbal snake oil? I don’t know, no one does, and I think that’s the point. As an herbal treatment Ashwagandha has some plausibility, because (say it with me) it’s a drug, or actually a combination of multiple drugs. I find the pre-clinical data completely unconvincing, for the reasons I stated above. Stuff happens, it could be useful, it could be harmful. It could also be inconsequential.
The clinical evidence is also unconvincing. Like most other herbs, Ashwagandha is living in the world of preliminary evidence, like being stuck in scientific purgatory. I believe that is a feature not a bug of the CAM/herbal world. There is just enough evidence to use for marketing and promotion, without ever having the kind of evidence that would confidently indicate whether or not the herb actually worked for a specific indication. When we do sometime get that level of evidence (from NIH studies, for example) the results are usually disappointing.
Reports of liver damage are also very concerning. This is not something that should be casually dismissed. Long term use is also not reassuring. Most over the counter use likely involves small doses or low bioavailability. Low doses are less likely to have toxicity, but also less likely to have a beneficial effect. When you ramp up the concentrations and dosage to get an effect, that is where the toxicity also comes in. What matters is – is there a safe dose range? We can only know this if we carefully measure dosage, which is impossible with messy and variable herbs.
Which brings me to the ultimate conclusion – the problem is inherent to the herbal supplement industry itself. Using herbs as drugs has inherent problems. There is simply no advantage to this approach (except for the companies selling dubious products with unsupported claims). Herbs should be treated as the drugs they are – purified, studied, and regulated. Otherwise the probability of harm vastly outweighs the probability of benefit for the health consuming public. Although the most likely outcome is simply wasting billions of dollars on useless products.