15 clinical trials were conducted in India, 5 in the U.S., 1 in Iran, and 1 in Australia.
Evidence shows that falsified data or fake clinical trials are a problem in medical literature. Especially from specific countries.
For example, 62% of closely-inspected Indian trials submitted to Anaesthesia had false data. 46% of closely-inspected Indian trials were found to be fatally flawed. The potential reasons for this are numerous. (R)
Similarly, our review on the effect of beet juice on blood pressure discovered a geographic bias as well.
Compared to trials conducted in the rest of the world:
Trials conducted in the U.S. or U.K. were 1.85 times more likely to find that beets lowered blood pressure significantly better than placebo/control.
In this particular case, financial conflicts of interest may explain our finding.
(U.S. and U.K. trials were more likely to have connections to commercial interests.)
What about the trials on ashwagandha’s effects on anxiety, stress, or sleep?
In the 6 clinical trials conducted in the U.S. and Australia:
37.5% of results showed ashwagandha worked better than placebo for anxiety, stress, or sleep.
In the 16 clinical trials conducted in India and Iran:
77.8% of results showed ashwagandha worked better than placebo for anxiety, stress, or sleep.
In other words, as compared to trials conducted in the U.S. and Australia:
Trials conducted in India and Iran were 2.1 times more likely to report that ashwagandha improved anxiety, stress, or sleep.
There could be multiple explanations for this. Our analysis isn’t an implication that there’s outright data manipulation of any sort as we didn’t examine for this.
Genetic, environmental, and cultural differences between populations can also influence clinical trial results. (R)
One thing is very clear from this analysis:
Further high quality trials outside of India are necessary to clarify ashwagandha’s effect on anxiety, stress, and sleep in different populations.
Financial conflicts of interest often correlate to favorable clinical trial results. (R)
Where data allowed, we found that 38.1% (8 of 21) clinical trials reported significant financial conflicts of interest.
Often, this meant funding from an ashwagandha-related supplement company. Or, it meant one of the researchers had a stake in an ashwagandha-related company.
Of the trials with no stated financial conflicts of interest:
68.2% of results showed ashwagandha worked better than placebo for anxiety, stress, or sleep.
Of the trials with stated financial conflicts of interest:
69.2% of results showed ashwagandha worked better than placebo for anxiety, stress, or sleep.
In other words:
Trials with financial conflicts of interest were slightly more likely to report favorable results vs. trials with no stated conflicts of interest.
This is likely a conservative estimate.
That’s because undisclosed conflicts of interest are a common problem in medical literature. (R)
That means many of the trials that stated “no conflicts of interest” may not have done so honestly.
We discovered as much in our review on the effect of beet juice on blood pressure.
Highest Reliability Results
We filtered the clinical trials that we found to match the following criteria:
- Randomized, double-blind, placebo-controlled trials
- Trials where the placebo was indistinguishable from ashwagandha (details: Smell of Horse)
- Trials with no reported financial conflicts of interest
We accounted for abstract bias (details: Abstract Bias).
Only 5 clinical trials met all such criteria (“higher reliability trials”).
The other 17 trials did not meet one or more of these criteria (“lower reliability trials”).
Of the higher reliability trials:
66.7% of results showed ashwagandha worked better than placebo for anxiety, stress, or sleep.
Of the lower reliability trials:
69.0% of results showed ashwagandha worked better than placebo for anxiety, stress, or sleep.
Lower reliability trials were slightly more likely to report favorable results for ashwagandha.
The results and conclusions in study abstracts can be misleading. (R)
For example, a study may claim that ashwagandha lowers stress.
But the data in the trial itself fails to support such an assertion.
A reader who skims the abstract alone may walk away thinking that ashwagandha helps beat stress.
Where data allowed, we found that 28.6% (6 of 21) clinical trials in this review had a misleading abstract.
Most often, the misdirection had to do with the following:
The abstract claimed that ashwagandha helped improve anxiety, stress, or sleep.
The data actually showed that ashwagandha didn’t improve anxiety, stress, or sleep better than placebo.
Where did the misdirection occur?
1. People who took ashwagandha experienced an improvement in anxiety, stress, or sleep.
2. But so did the people who took a placebo.
3. The effect of ashwagandha wasn’t significantly different from placebo.
The abstract stated #1 without mentioning #3.
Smell of Horse
Ashwagandha translates as “smell of horse”. Where “ashwa” means horse, and “gandha” means smell. As this suggests, ashwagandha roots have a distinct horse-like smell. (R, R, R)
Researchers investigating ashwagandha’s effects on anxiety, stress, and sleep recognize this fact. (R)
To be properly masked, a placebo needs to be as indistinguishable from ashwagandha as possible.
Of the 21 trials we had enough data on for this subanalysis:
Only 28.6% (6 of 21) trials explicitly mentioned they controlled for ashwagandha’s distinct smell.
(These 6 trials also ensured that the ashwagandha treatment matched the placebo for color, size, shape, etc.)
In other words:
In up to 71.4% of clinical trials, the study’s subjects may have been able to determine if they got a treatment or “placebo” due to ashwagandha’s unique smell. This might have altered the results in unknown ways.
What happened to the placebos in the other 15 trials?
We don’t know.
Perhaps the researchers controlled for the smell but didn’t mention it in the paper. Perhaps they didn’t control for the smell. In that case, the participants may have known if they got ashwagandha or placebo. This would, of course, influence the results.
This is nothing new.
Inadequately masked placebos are a recognized problem in clinical literature. (R)
Of the 6 (“smell-controlled”) trials:
75.0% of results showed ashwagandha worked better than placebo for anxiety, stress, or sleep.
Of the 15 (possibly “non-smell-controlled”) trials:
66.7% of results showed ashwagandha worked better than placebo for anxiety, stress, or sleep.
Trials that explicitly mentioned they controlled for ashwagandha’s smell were more likely to report that it was superior to placebo.
The term “double-blind” (“double-masked”) doesn’t have a standardized definition.
Many people assume “double-blind” implies that the study’s subjects didn’t know if they got treatment or placebo. This isn’t always the case.
There are up to 11 types of individuals that could be blinded in a clinical trial.
This includes doctors, patients, statisticians, technicians, outcomes assessors, etc. (R)
Therefore, the term “double-blind” is often ambiguous, not defined, or even misused.
We were able to closely examine 21 clinical trials for this section’s analysis.
Of these 21 trials:
20 (95.2%) claimed to be “double-blind”. For many, this automatically implies the study’s subjects were “blind”.
(The subjects supposedly didn’t know if they got ashwagandha or placebo).
Of these 20 “double-blind” trials:
25.0% (5 of 20) did not state that the study subjects were “blinded”. This could simply have been an omission and the subjects were actually blinded. Or it might mean the study’s subjects knew that they got ashwagandha or placebo, while other trial participants (e.g. statisticians) were blinded instead.
15 double-blind trials confirmed that the study’s subjects were, indeed, “blind”.
Of the 15 double-blind trials where the subjects were confirmed to be “blind”:
73.1% of results showed ashwagandha worked better than placebo for anxiety, stress, or sleep.
Of the 5 double-blind trials where the subjects may not have been “blind”:
62.5% of results showed ashwagandha worked better than placebo for anxiety, stress, or sleep.
Double-blind trials that confirmed the subjects were blind were more likely to report that ashwagandha is superior to placebo.
Our literature review and analysis sought to answer the following clinical question:
“How does the consumption of isolated ashwagandha affect patient-centered measures of anxiety, stress, or sleep?”
Primary intervention of interest: Withania somnifera (L.) Dunal (Solanaceae) isolated from other likely active ingredients.
Primary outcomes of interest: questionnaire-based measures of anxiety or psychological distress, questionnaire-based and actigraphic measures of sleep quality or quantity.
The purpose of this literature review was to determine the direction of the effect that ashwagandha supplements have on a person’s anxiety, stress, or sleep.
We included studies that focused exclusively on the extracts and powders of the Withania somnifera plant, namely the roots and/or leaves.
We excluded any studies where the ashwagandha intervention was mixed with another product or supplement, such as another herb— unless the non-primary intervention comparator arm(s) excluded the ashwagandha product in an otherwise generally equivalent fashion, thereby allowing us to isolate the effect of ashwaganda in such cases.
We included studies where the primary or secondary endpoint data was derived from a questionnaire-based measure of anxiety or any form of psychological stress. Examples include, but are not limited to, the Hamilton Anxiety Rating Scale (HAM-A) and the Perceived Stress Scale (PQSI), respectively.
We included studies where the primary or secondary endpoint data was derived from a questionnaire-based measure of sleep quality or quantity, such as the Pittsburg Sleep Quality Index (PQSI) or an actigraphic measure of sleep quality or quantity.
We excluded endpoint data on measures of anxiety, stress, or sleep that were part of a composite (overall) score that did not allow us to isolate an individual score for each of anxiety, stress, or sleep.
We excluded endpoint data on non-patient-centered approximations of anxiety, stress, or sleep, such as—but not limited to—biomarker levels (e.g. cortisol), variations in heart rate, changes in blood pressure, and similar surrogate outcomes.
In order to gather the best available evidence for any potential cause-and-effect relationship pertinent to the clinical question, we focused on data solely from published, peer-reviewed, clinical trials and any meta-analyses thereof. This means we excluded observational and basic science literature and any meta-analyses thereof, any interim analyses, conference abstracts, whitepapers, and other non-peer-reviewed data.
We excluded all studies published in a non-English language.
We excluded all studies focused on individuals under the age of 18 years.
Our clinical question, and primary interventions/outcomes of interest, largely defined our search strategy.
An initial literature search was conducted in November of 2023, using three distinct searches to maximize the number of relevant clinical trials we could find.
(See the Last Literature Review date in the beginning of this article to see when we last searched for any new trial data on this topic.)
Using PubMed, search #1 used search terms focused on identifying published studies where the primary intervention was any ashwagandha-based product (higher specificity, lower sensitivity intervention search) using a combination of keywords and wildcards. We didn’t use any keywords relevant to the primary outcomes of interest in order to maximize the sensitivity of this part of the search (lower specificity, higher sensitivity outcomes search).
The search terms were applied to the titles and abstracts of PubMed’s database.
Filters for clinical trials on humans, practice guidelines, and errata/retractions were applied.
Search #1 yielded 82 results.
Using PubMed, search #2 focused on maximizing the specificity of the outcomes search. Clinical trials related to anxiety, stress, and sleep were specifically searched for using a combination of keywords and wildcards while focusing on the primary intervention (ashwagandha) of interest at the same time.
Search #2 yielded 167 results.
Search #3 was a “sweep”.
The sweep is an acknowledgement that PubMed doesn’t contain all studies of interest (or may not at the time of our search) and that PubMed filters are imperfect and, on occasion, miscategorize or fail to categorize studies of interest. Moreover, search #1 and #2 are neither perfect nor exhaustive searches on their own.
Using search #1 and #2, we identified 9 systematic reviews and meta-analyses (SRMAs) of relevance to our clinical question.
We examined all of the studies included in these SRMAs of interest and identified a small number of clinical trials of interest missed by search #1 and #2.
Our literature review did not include studies published in a language other than English.
Our search and analysis focused on patient-centered (questionnaire and actigraphic-based) measures of anxiety, psychological distress, and sleep.
We excluded surrogate measures that may be of relevance in some cases, such as changes in cortisol and blood pressure. Inclusion of such surrogate markers may have changed the results of this analysis. However, while the use of surrogate endpoints for anxiety, stress, and sleep may be useful in select cases, such relationships are not always well-correlated and may have little to do with the subjective (lived) patient experience. (R)
Our search may have missed trials where “ashwagandha” (or related terms) weren’t mentioned in the title/abstract but were actually used in the trial. We believe that our third search (the “sweep”) largely addressed such sensitivity/specificity concerns. However, we cannot exclude the possibility that the sweep also missed trials of interest, especially those with primary interventions or primary outcomes of interest not mentioned in the title nor abstract.
Virtually all of the trials that found that ashwagandha had a beneficial effect on anxiety, stress, or sleep mentioned this fact in the title/abstract. This means we likely found nearly all of the trials with a beneficial effect. Trials that didn’t find a beneficial effect were less likely to report this lack of effect in the title/abstract. Therefore, we believe that if we missed any relevant trials, it was likely trials that did not find a difference between ashwagandha and placebo. This means that ashwagandha may be less effective than our analysis suggests. In other words, we believe that our analysis might be systematically biased in favor of ashwagandha as a result of our review’s limitations.
We declare no conflicts of interest. We do not sell any supplements and this review hasn’t been sponsored by, nor is it affiliated with, any outside entity in any way.