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“Should we all (or should anyone) be taking ashwagandha?”

Honestly, I have no idea. Every single time I type “ashwagandha” I have to triple check to make sure I spelled it right.

As I sit down to research and write this, I know nothing about ashwagandha. I just know that more and more athletes are starting to take it and ask me my opinion on it.

So, let’s dive in.

What does the science say?

Now, forget about what the public says. What does the science say?

Our 4 main questions today are:

Is ashwagandha safe?
Is ashwagandha effective at reducing anxiety and enhancing mood?
Is ashwaganha effective at improving sleep?
Is ashwagandha effective at improving performance?

Before we get into that, we need to establish some background knowledge.

The background: What’s the physiology?

Our last deep dive, which was on caffeine, had a singular mechanism of action and we had high certainty in our understanding of how it worked.

With ashwagandha… not so much. We do, however, have some thoughts.

1) HPA Axis Modulation

HPA stands for Hypothalamic-Pituitary-Adrenal Axis.

The HPA axis is your body’s main stress response system, essentially a command chain starting in your brain. Here’s how it operates under normal conditions.

When you feel stressed, your hypothalamus sends an alert to your pituitary gland (both the hypothalamus and the pituitary gland are in your brain).
The pituitary then releases a hormone (corticotropin releasing hormone) that tells your adrenal glands to release cortisol.
Cortisol is the main stress hormone; it floods your body with energy and heightens your focus to deal with the threat.
Once the threat is gone, the cortisol in your blood signals the brain to stop the alarm, acting as the system’s “off-switch.”

This system, however, was designed to deal with stressors that are transient, like not getting eaten by a bear.

Today’s stressors are normally prolonged and drawn out, like worrying if you’re going to get offered that scholarship or pass that test.

That results in the HPA axis essentially never shutting down and constantly flooding you with cortisol.

Researchers think that an active component of ashwagandha, called withanolides, may reduce the sensitivity of the hypothalamus to stress.

With less stress-sensitivity, the hypothalmus sends a weaker signal to the pituitary gland, which in turn sends a weaker signal to the adrenal glands, which ultimately leads to less cortisol being dumped into your blood stream.

Less cortisol = less stress.

2) GABA Agonist

GABA stands for gamma-aminobutyric acid.

GABA is the primary inhibitory neurotransmitter in the brain. Its job is to really slow down neural activity.

Researchers propose that the withanolides in ashwagandha can bind to GABA receptors in the brain and mimic the effects of GABA itself.

This increased inhibition in the brain may lead to a feeling of calmness, reduced anxiety, and make it easier to fall asleep.

3) Antioxidant & Anti-inflammatory Mechanisms

“Free radicals” and “NF-κB” are the key concepts here.

Free radicals cause damage and that damage flips the “on-switch” for inflammation. Here’s how it works:

Free radicals are highly unstable molecules, like tiny, out-of-control “wrecking balls” bouncing around in your cells.
To become stable, they crash into other molecules, like your DNA, and “steal” parts from them in a process called oxidation.
This theft causes cellular damage, which we call “oxidative stress.”
This damage is a major trigger that activates NF-κB, which is a protein that acts as the main “on-switch” for inflammation inside your cells.
Once “on,” NF-κB travels into the cell’s nucleus and tells your DNA to produce pro-inflammatory chemicals, causing pain, swelling, and redness.
Here’s the catch: the process of inflammation itself creates even more free radicals as a byproduct.
This creates a cycle where damage causes inflammation, and inflammation causes more damage.

Researchers propose that ashwagandha breaks this cycle in two ways:

Antioxidant Action (The Cleanup Crew): The withanolides can neutralize free radicals directly, sacrificing themselves so the “wrecking balls” don’t damage your cells. It also appears to boost your body’s own natural antioxidant enzymes, encouraging your cells to produce more of their own “cleanup crew” to handle oxidative stress.
Anti-inflammatory Action (The Off-Switch): The withanolides are also thought to physically block NF-κB. By preventing the “on-switch” from being flipped, it keeps your cells from getting the signal to start pumping out those pro-inflammatory chemicals in the first place.

Less oxidative damage means there’s less reason to flip the inflammation switch, and blocking the switch itself stops the cycle from continuing.

That’s cool and all, but does it work?

Remember, our 4 main questions today are:

Is ashwagandha safe?
Is ashwagandha effective at reducing anxiety and enhancing mood?
Is ashwaganha effective at improving sleep?
Is ashwagandha effective at improving performance?

To answer these 4 questions, I have 4 studies for us to work through. Then, at the end, we’ll form a cohesive narrative and I’ll give my current stance.

Let’s dive into our first study:

1) Effects of Ashwagandha (Withania Somnifera) on stress and anxiety: A systematic review and meta-analysis (by Arumugam and others in 2024).

“Can I trust the results?”
- Yes, mostly.
  - Pros: rigorous systematic review, 897 total participants, high-quality inclusion criteria (only looked at RCTs), all 13 trials included a placebo control.
  - Cons: varying methodological quality of underlying primary research, small sample size of some of the underlying primary research, risk of incomplete outcome data and selective outcome reporting in primary research, a lot of heterogeneity (as there was no control for dose-response relationship and dosages varied substantially).
“What did the study find?”
- Significant reduction in stress
  - Mean Difference (MD) of -4.72 on the Perceived Stress Scale.
    - No Cohen’s d were reported for this systematic review, just raw mean differences. Which means we need the context of the test itself to determine the degree of effect size.
    - So, I looked up the Minimal Clinically Important Difference (MCID) for these tests.
      - Statistical Effect Size (like Cohen’s d) measures statistical magnitude (the “how big?” from a researcher’s view).
      - MCID measures clinical relevance (the “so what?” from a patient’s view). A result that meets the MCID threshold is clinically meaningful. It has just crossed the line from being a change “only a statistician could see” to one that a “real person would notice.”
      - For the PSS (likely a 0-40 scale, but not specified in the text), the MCID is likely somewhere between 2.5 to 4 points.
  - High heterogeneity (I² = 86%)
    - I² interpretation: 25% = low, 50% = moderate, 75% = high
    - Individual study effects ranged from −11.80 to− 1.63
    - When looking at the forest plot, you can see the 95% confidence interval bar is outside of the 95% confidence interval of any other study for the outlier study
- Significant reduction in anxiety
  - MD of -2.19 on the Hamilton Anxiety Scale
    - HAS (0-56 scale) has MCID likely around 2-3 points
  - Moderate heterogeneity (I² = 41%)
- Statistically significant reduction in serum cortisol levels with a MD of -2.58.
  - They didn’t even report the units they used for serum cortisol levels, so I can’t really interpret these.
  - It’s likely in micrograms per deciliter. A healthy person’s peak cortisol levels are typically between 5 to 25 micrograms/dL, which would make a 2.58 point drop quite meaningful.
    - However, it might be in nmol/L, which peak between 140-690 nmol/L which would make a 2.58 point drop quite meaningless.
- Adverse effects associated with Ashwagandha were limited.
  - “Nine studies reported no adverse effects throughout the intervention. Four studies reported some adverse events such as diarrhea, anorexia, nausea, abdominal pain, rashes, and deranged liver and kidney function tests. However, healthcare providers should consider the reported adverse events, albeit minor, and exercise caution while recommending Ashwagandha, particularly for patients with pre-existing gastrointestinal or hepatic conditions.”
“Can I use these results in my context?”
- The population was almost completely adults, with a few 16 and 17 year olds in there. So, kind of.

Next study!

2) Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress? A systematic review and meta-analysis of randomized controlled trials (by Akhgarjand and others in 2022)

“Can I trust the results?”
- Yes, mostly.
  - Pros: rigorous systematic review, dose-response meta-analysis, 1,002 total participants, high-quality inclusion criteria (only looked at RCTs), assessed risk of bias using the Cochrane guideline, explicitly rated the certainty of evidence using the GRADE approach.
  - Cons: varying methodological quality of underlying primary research (trials rated good, fair, and poor), serious inconsistency, certainty of the evidence was rated low for both anxiety and stress outcomes
“What did the study find?”
- Significant reduction in stress
  - SMD of -1.75.
  - High heterogeneity (I² = 83.1%)
    - The heterogeneity disappeared in studies performed on healthy subjects.
  - A significant non-linear effect was detected on stress at doses ranging from 300–600 mg/d. (The sweet spot for stress is in that 300-600mg/d range.)
- Significant reduction in anxiety
  - Standardized Mean Difference (SMD) of -1.55.
    - SMD > 0.8 = large
    - Healthy people, people 40 years or older, and supplementation doses ≥600 mg/d) had the greatest benefit
  - High heterogeneity (I² = 93.8%)
    - Massive outlier on the forest plot.
  - The study found a favorable non-linear dose-response effect on anxiety until 12,000 mg/d of Ashwagandha dose. (The more, the better; up to 12,000mg/d.)
    - HOWEVER, the vast majority of the studies were significantly below that and we can’t draw conclusions from one outlier study that had 12,000 mg
- High heterogeneity in results resulted in the authors concluding that the certainty of evidence was low.
“Can I use these results in my context?”
- The population was all 25-48 years old. So, kind of.

Now, let’s take a look at sleep. Next study!

3) Effect of Ashwagandha (Withania somnifera) extract on sleep: A systematic review and meta-analysis (by Cheah and others in 2021)

“Can I trust the results?”
- Yes, mostly.
  - Pros: rigorous systematic review, followed PRISMA guidelines, comprehensive database search (including grey literature), independent data extraction and risk of bias assessment, included a placebo control in all five trials, assessed the quality of evidence using the rigorous GRADE methodology, and found moderate quality evidence for the overall sleep outcome.
  - Cons: small total sample size (400 participants), serious imprecision due to not meeting the optimal information size, serious inconsistency, for overall sleep, risk of bias in primary research (unclear allocation concealment and blinding in some studies).
“What did the study find?”
- Significant improvement in overall sleep
- Standardized Mean Difference (SMD) of -0.59.
  - The beneficial effects were found to be more prominent in specific subgroups: adults diagnosed with insomnia, those receiving a treatment dosage ≥600 mg/day, and those receiving treatment for a duration ≥8 weeks.
“Can I use these results in my context?”
- The population was all adults. So, kind of.

And let’s wrap it up with one last study. This time, let’s look at performance.

4) Effects of Ashwagandha (Withania Somnifera) on Physical Performance: Systematic Review and Bayesian Meta-Analysis (by Bonilla and others in 2021)

“Can I trust the results?”
- Yes, mostly.
  - Pros: rigorous systematic review, employed a Bayesian meta-analysis (a more intuitive, direct, and flexible statistical approach found to be superior in modeling uncertainty and heterogeneity), conducted a pre-specified subgroup meta-analysis on strength/power, cardiorespiratory fitness, and fatigue/recovery, low-to-moderate overall risk of bias was detected in the trials, all included a placebo control, independent bias assessment was conducted by two authors
  - Cons: low number of studies in each subgroup, limited databases were used for extraction (PubMed, ScienceDirect, and Google Scholar), heterogeneity led to excluding outliers to derive a more stable estimate, the quantitative analysis included multiple effect sizes from single studies (i.e., multiple outcomes and/or multiple treatment arms), which requires caution in interpreting the pooled effect
“What did the study find?”
- Significant improvement in strength and power:
  - Pooled effect size was medium (μ = 0.67),
    - Bayesian model suggests Ashwagandha is very likely to be meaningful on strength/power-related variables (98.3% probability).
    - Hedges’ g (same reference ranges as Cohen’s d) was used as the effect size metric.
  - Low heterogeneity (diamond ratio = 1.11)
    - Diamond ratio interpretation: 1.0 = none, 1.5 = moderate, >2.0 = high
- Significant improvement in cardiorespiratory fitness
  - Pooled effect size was very large (μ = 1.89)
    - Bayesian model suggests the probability of the effect size being greater than 0.20 is absolutely high (100%).
  - High heterogeneity
    - Diamond ratio = 3.74, before excluding outliers
    - Diamond ratio = 1.41, after excluding outliers
- Significant improvement in fatigue and recovery
  - Pooled effect size was very large (μ = -1.18)
    - Bayesian model suggests the probability of the effect size being greater than 0.20 is very high (99.9%).
  - High heterogeneity
    - Diamond ratio = 1.89, after excluding outliers

“Can I use these results in my context?”
- Kind of. We don’t have answers to other variables that could manipulate the outcomes. We know these were all healthy adults, but were they athletic? Were they already getting enough sleep? Were they previously over-stressed?

What’s actually important here?

We have strong reason to believe that ashwagandha supplementation reduces stress.
We have strong reason to believe that ashwagandha supplementation reduces anxiety.
We have some reason to believe that ashwagandha supplementation improves sleep.
We have some reason to believe that ashwagandha supplementation improves physical performance.
We have minimal reason to be concerned with safety of ashwagandha supplementation.
- From a 2025 narrative review: Six cases of liver injury attributed to ashwagandha supplementation have been documented.
  - All cases had a similar pattern with jaundice and other symptoms which occurred 2 to 12 weeks into supplementing Ashwagandha or Ashwagandha-containing supplements, with daily doses ranging from 450 mg to 1350 mg.
  - All cases were reversible, with liver tests normalizing after 1–9 months after cessation of supplementation.
  - Although most research data indicates that Ashwagandha supplementation is safe and tolerable, more data is needed to evaluate safety of higher doses and longer periods of supplementation, especially regarding its impact on hepatotoxicity.
We have no information on the long-term effects of ashwaghanda. The longest supplementation protocols measured were 6 months in one study and 3 months in 3 studies.
It seems that root extract is more rich in bioactive molecules than the whole leaf extract. (KSM-66 is root extract.)

My stance: “Should we all be taking ashwagandha?”

If someone:

struggles with stress and anxiety,
is near physical maturity,
takes around 600 mg/day
and cycles 6 weeks on and 2 weeks off (as a hedge against long-term unknowns),

then it seems likely that it might be helpful.

Other than that, there isn’t enough data to warrant any risk.

Introducing the Attia categories

You’ve probably noticed that the answer to “Does it work?” is rarely a simple yes or no. It’s usually a messy mix of “statistically significant” yet “clinically confusing.”

To help us stop guessing and start categorizing, I am adopting a framework developed by Dr. Peter Attia. It emphasizes that in science, “proven” isn’t binary; it is a spectrum of confidence.

Moving forward, I will use these five categories to grade the interventions we discuss, ensuring we know the difference between high-quality science and clever marketing.

Proven: Interventions supported by robust, reproducible human data where the probability of them being ineffective is near zero (creatine, whey protein, strength training, etc.).
Promising: Treatments backed by strong mechanistic logic, animal data, or early human data that look effective but lack definitive long-term human trials.
Fuzzy: Topics where the data is inconsistent, contradictory, or confusing, making it currently impossible to determine clear benefit or harm.
Noise: Hyped interventions where the signal is too weak to form a conclusion because the “evidence” relies mostly on anecdotes, theory, or low-quality studies.
Nonsense: Approaches that have been rigorously tested and proven not to work, despite continued popularity and marketing.

I’d place ashwagandha squarely in the promising category.

Let’s wrap it up with a couple important things…

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Everything in these newsletters, podcasts, social media, and on our website is for educational purposes only and should not be taken as medical advice for you or your athlete. Consult directly with a healthcare professional.

Thanks so much for your help in spreading the word about athlete development!

Be >,

Zach

Dr. Zach Guiser, PT, DPT, CSCS