Ashwagandha

Goli Nutrition isn't taking any chances.

The dietary supplement company notes that ashwagandha is an "ancient Indian herb...recognized for its medicinal properties for over 5,000 years" while quickly adding that it's "heavily backed by modern science". In 2021, the company hired Jennifer Lopez to tell you she takes their product to relax (though in the ad, she looks chill even before she pops one of the gummies). And, the company offers testimonials from unnamed customers who seem to plagiarize each other (see the circled boxes in the screenshot below).

There you have it: Traditional wisdom, modern science, J.Lo, and ordinary citizens. How could ashwagandha not be good for you?

This newsletter was spurred by a new review of research on the supplement. I'll be discussing this review as well as older data. The point of the newsletter is to answer some questions raised by the label on the bottle you see below. If ashwagandha has been "clinically studied to reduce stress and occasional anxiety", what were the results? Should ashwagandha be "pharmacist recommended"? If so, for what?

Why is this important?

The dietary supplement industry is currently valued at around $160 billion dollars in the U.S., and ashwagandha, easily found at pharmacies, grocery stores, etc., has become one of the five most lucrative herbal products on the retail market. Meanwhile, authoritative sources ranging from the National Institutes of Health to National Geographic suggest that ashwagandha may lower anxiety and stress while improving sleep. (NIH even indicates this on a fact sheet for health professionals.) The same cautiously positive message has been aired on Good Morning America, and, less cautiously, on TikTok. And then of course there's J.Lo.

In short, lots of people are hearing (and apparently believing) that ashwagandha is good for your health. We should check whether that's what the data says.

What is ashwagandha?

Ashwagandha is an evergreen shrub that grows in tropical and subtropical areas of India, the Middle East, and Africa. The name combines the Sanskrit words for "horse" (ashwa) and "smell" (gandha), because the root of the plant reputedly smells like wet horse.

Ashwagandha has been taken medicinally for thousands of years. In the Ayurvedic and Unani medicine systems of India, it was used as an adaptogen (a crude term for anything that supports overall well-being while increasing resistance and adaptability to disease). Currently, ashwagandha is marketed in countries such as the U.S. as a means of reducing anxiety and stress, promoting relaxation, and improving sleep, but a ton of other claims are occasionally made, ranging from better memory and attention to enhanced athletic performance and sexual functioning.

Medicine vs. supplements

In the U.S., medicines are FDA-approved, meaning, among other things, that they've undergone rigorous testing for effectiveness and safety.

Supplements are not approved by the FDA for the prevention or treatment of any disease. Rather, as the FDA itself notes, once a supplement comes to market, the agency simply monitors its safety (in the limited sense of inspecting manufacturing facilities, investigating complaints of harm, etc.) and ensures that companies aren't making unwarranted health claims.

Are supplements less trustworthy than medicines? I think this is a fair generalization. Although FDA approval doesn't guarantee that a product is safe and effective, it does tell you at least that the product has undergone rigorous testing, and expert panels have probably agreed (more or less) on the findings.

The fact that a supplement isn't FDA-approved doesn't mean that benefits haven't been scientifically demonstrated. Folic acid supplements are clearly needed during pregnancy. For some people, vitamins correct deficiencies they can't otherwise address via dietary changes. These are cases where supplementing one's regular diet is beneficial.

The problem with supplements is that manufacturers aren't required to demonstrate safety and effectiveness via rigorous research. Roughly speaking, anything that's not already proven to be harmful can be sold as a supplement and described as good for you, so long as the wording is careful not to overpromise (by the FDA's arguably lax standards).

The result is that many supplements have no clear health benefits. The science behind them is weak at best. The fact that ashwagandha supplements are sold at CVS and promise health benefits doesn't offer much assurance that they'll actually improve your health.

(For more on supplements and the supplement industry, see Dr. Andrea Love's overview in this April 2024 Immunologic post.)

A new review

The review, co-authored by Shiyi Guo (Liaoning Polytechnic University, China) and Mohammad Rezaei (Tehran University of Medicine, Iran) was published last month in Frontiers in Nutrition.

(I could write an entire newsletter on Frontiers journals. Long story short, some of the studies they publish are methodologically strong and well-received by experts; others are crap that reflect widely panned, ethically questionable editorial practices.)

Guo and Rezaei concluded that ashwagandha improves antioxidant response and athletic performance.

A key problem with this review is its unstinting positivity. Ashwagandha is said to be effective and safe, and there's zero acknowledgment that any of the studies might be limited.

I looked at the studies, and they are limited indeed. Sometimes the reviewers don't even summarize them properly. For example, Guo and Rezaei write the following:

"Ashwagandha has been shown in studies to enhance muscular strength and coordination as well as cardiorespiratory endurance in healthy, normal individuals (12, 13)."

Sounds great, but…

Study 13 actually only shows that ashwagandha is safe. This study contains no measures of strength, coordination, endurance, or anything else but clinical safety (no adverse physical effects were found) and tolerability (participants didn't report any subjective side effects).

Study 12 is not just bad. It's bad in a funny way. I mean chuckle-out-loud funny.

Here's the gist of it: For 30 days, participants received ashwagandha supplements. At the beginning of the study, and then three more times during the 30-day period, they spent extended time in the lab using an exercise bike, performing muscle strength activities, and undergoing measurement of variables like body fat. There was no control group.

By the end of the study, participants showed slight gains in cardiovascular performance on the bike and in muscular strength, as well as slight reductions in body fat. Conclusion: Ashwagandha makes you cardiovascularly healthier, stronger, and leaner.

Are you chuckling yet? Since there was no control group, we have no idea whether  ashwagandha helped. All we can be sure of is that the more people exercised in the lab, the stronger and healthier they got.

Basically, the researchers gave people a supplement, enlisted them in a month-long fitness program, and wound up with fitter people. Amazing, right?

All of the studies that Guo and Rezaei reviewed are either flawed in some fundamental way such as this one, or they focus on animals, or they were conducted in vitro (think of a Petri dish).

Bottom line: There's not a shred of evidence in this review that ashwagandha is good for you.

Some studies do show that ashwagandha has antioxidant properties, but that's no reason to take the supplement, because (a) there's zero evidence in the review that these properties translate into health benefits, and (b) lots of edible things have antioxidant properties (broccoli, beans, basil, blueberries, blackberries, black plums, black tea.... the list of "b" foods alone goes on for a while). Saying that you should take ashwagandha because it contains antioxidants is like saying you should eat chinchilla meat because it contains protein. Sure, it contains protein, but you will never, ever need to eat chinchilla.

Does ashwagandha have other health benefits?

Guo and Rezaei only studied antioxidant properties and athletic performance. Dozens of studies have explored other potential benefits.

Rather than attempting to read all of these studies, I chose 15 peer-reviewed examples at random from a 2021 review published in Current Pharmacology. This review, led by Dr. Alex Speers at Oregon Health and Science University, has been cited by the NIH as well as popular magazines such as National Geographic and Fortune. Speers and colleagues' main conclusion is that that ashwagandha reduces anxiety, stress, and sleep disturbances.

Although the review is well-written, none of the 15 studies came close to offering compelling evidence in favor of ashwagandha. (I didn't consider quality of journal or whether authors had conflicts of interest. Rather, my focus was on methods and findings. My only criterion in choosing studies was that they explored health outcomes among people – in other words, no animal or in vitro studies). Here are some of the shortcomings I identified:

• small samples (all 15 studies)

• small effects (all 15 studies)

• lack of a control group (4 studies)

• inadequate consideration of pre-existing differences between control and placebo groups (12 studies)

• egregious statistical flaws (11 studies. Examples: failure to correct for multiple comparisons, failure to use repeated-measures analyses for RM data, clearly underpowered analyses, etc.)

To illustrate, I'll close with some remarks on one of the strongest of these 15 studies.  

This study, published in the journal Medicine in 2019, claimed to show that ashwagandha alleviates anxiety, because a group of 30 adults who took the supplement improved significantly more than a group of 30 who took a placebo.

One of the key limitations of this study is that the effects of ashwagandha were too small to be clinically meaningful.

Over a 60-day period, the ashwagandha group showed a decline in mean anxiety scores of 4.2 points on a 56-point scale. The placebo group showed a decline of 2.36 points on the same scale. In short, both groups became less anxious, for whatever reason, but the extent of improvement was 1.84 points greater, on average, for those who took ashwagandha.

A 1.84 difference on this 56-point scale is clinically meaningless. Not because it seems like a small number, mathematically speaking, but because the scale that was used, the Hamilton Anxiety Rating Scale (HAM-A) is not expected to be precise enough to make reliable distinctions at that level of granularity.

To generate a HAM-A score, an interviewer rates a person on 14 symptoms such as anxious mood ("worries, anticipation of the worst...") and genitourinary symptoms ("frequency of micturition [peeing], urgency of micturition..."). For each symptom, the interviewer chooses a rating that could range from 0 to 4 (0 = not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe).

You can imagine why the measure might be a bit limited in precision. The interviewee says things like, "I worry about my job every day", and "I expect to be awfully feeble when I'm old", and the interviewer then has to assign a rating for anxious mood. The person does sound anxious, but is their anxiety "moderate", "severe", or "very severe"? Inter-rater reliabilities for the HAM-A (below .85) don't justify much faith in 1.84 point differences on the scale.

Finally, this study loses credibility owing to a number of honking presentation errors that raise questions about the editorial process. For instance, below is a screen shot of the results for HAM-A scores (anxiety) and DASS-21 scores (stress). You don't need to read these; just note the mistaken reference to HAM-A scores that I circled in the DASS-21 section.

There are a bunch of other problems I won't get into. Just keep in mind: This is one of the strongest of the studies I reviewed...

Conclusion: Should we be taking ashawagandha?

No.

1. Although the research I saw indicated that ashawagandha is safe, these were small-sample studies that haven't considered long-term effects. Denmark banned ashawagandha in 2023 on the grounds that the supplement might cause damage to thyroid and sex hormones, and other European countries are considering whether to follow suit. Although Denmark's ban was based on one of its own unversities' risk assessments, and those data have been questioned recently, I think you might attach a question mark to the ashawagandha safety issue.

2. Some of the data does suggest positive biochemical effects (lowering of cortisol levels, moderation of oxidative stress, blocking of inflammatory responses, etc). This seems like good news, but (a) the effects are small, (b) they could be produced by other minor dietary changes, and (c) there's no evidence linking these changes to actual changes in health.

3. There's no clear evidence that ashawagandha makes people healthier in any respect. Perhaps it does, but the data hasn't shown it yet.

I hope scientists continue to explore the possibilities. Although people have made mistakes that endured for thousands of years (e.g., assuming the sun revolves around the earth), it seems suggestive at least that ashawagandha has had such a long history in traditional medicines. Also, it's intriguing that one of the reported side effects is drowsiness. Although drowsiness doesn't necessarily translate into longer or better quality sleep, this effect hints that ashawagandha could turn out to be a useful sleep aid.

That's a hint at best, because studies demonstrating better sleep after taking the supplement are terrible, methodologically speaking. Meanwhile, lots of other lifestyle changes can improve sleep (and if you prefer chemicals, you can buy melatonin, a prescription medicine in the U.K. and Europe but still available as a supplement in the U.S.).

Final thought

In a MedPage Today editorial published this Monday, Drs. Andrea Love and Katie Suleta commented on the double-edged sword of the growing wellness industry. While the industry has broadened our perspective on health and well-being, Love and Suleta note that it "has a more nefarious side too. Wellness companies use the same strategies as evidence-based medicine to sell tests for diseases that don't exist and treatments that don't work, recommended by individuals who aren't qualified."

Love and Suleta use the supplement industry as one example of their concerns. As they point out, "companies bulk up the perceived legitimacy of [supplements] with buzzy phrases like "science backed" which sound like there might be clinical data, but often refer to Petri dish or animal studies on an isolated ingredient."

Definitely one reason to be skeptical of ashwagandha products is that the manufacturers' "buzzy phrases" are based in part on Petri dish/animal data. The other reason is that the studies with humans they refer to have been small, flawed, and untrustworthy on the whole. Ashwagandha sounds cool, but there's just no good evidence that it's beneficial.

I wish I could end with a happier conclusion, but I'd rather be honest.

Thanks for reading!