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Ashwagandha · Withania somnifera
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In one pass Ashwagandha is the root of a plant that Indian traditional medicine has used for about three thousand years; on today's shelves it is sold for stress and sleep. Not this — Ashwagandha is a testosterone booster — Pooled randomized trials show testosterone rises only about 14-15% — still within the body's normal range of variation.
Educational content, not medical advice — consult a clinician.
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Chapter 1
How it claims to ease stress
Ashwagandha is the root of a plant that Indian traditional medicine has used for about three thousand years; on today's shelves it is sold for stress and sleep. In stressed adults, a few small (RCTs, where people are assigned by chance to the herb or to a placebo) found that after about two months, stress scores and cortisol measured in a morning blood draw fell further than in people on the placebo. The trials were small and mostly run in India, and the result still needs larger trials to confirm it.
The claim is that it inserts itself into the chain of the stress response. When stress arrives, the hypothalamus deep in the brain signals the pituitary; the pituitary releases a signal into the blood that tells the adrenal glands to pour cortisol out. Your heart speeds up, blood sugar is pushed up, and you tense. Ashwagandha is thought to soften that push, but which step it actually moves has not been measured directly in people.
"Natural" does not mean harmless. A small number of people develop drug-induced liver injury after taking it, and it does not track how much they took. If your skin or the whites of your eyes turn yellow, or your urine turns as dark as strong tea, stop taking it immediately and see a doctor as soon as possible.
The claim is that it inserts itself into the chain of the stress response. When stress arrives, the hypothalamus deep in the brain signals the pituitary; the pituitary releases a signal into the blood that tells the adrenal glands to pour cortisol out. Your heart speeds up, blood sugar is pushed up, and you tense. Ashwagandha is thought to soften that push, but which step it actually moves has not been measured directly in people.
"Natural" does not mean harmless. A small number of people develop drug-induced liver injury after taking it, and it does not track how much they took. If your skin or the whites of your eyes turn yellow, or your urine turns as dark as strong tea, stop taking it immediately and see a doctor as soon as possible.
Mechanism · Why its compounds resemble cortisol
Ashwagandha's main actives are called withanolides, a class of steroidal lactones whose skeleton belongs to the same family as the body's own steroid hormones. The three most studied are withaferin A, withanolide A and withanone.Here is a shape problem: a withanolide's skeleton looks like that of a glucocorticoid, and cortisol itself is a glucocorticoid.
For a cell to hear cortisol, it uses a receiver called GR (the glucocorticoid receptor). Cortisol floats over and docks on GR, GR carries it into the nucleus, and a batch of genes switches on. The hypothalamus and pituitary carry the same receiver, and they use it to count whether there is enough cortisol in the blood; if there is, they send less signal upstream. That is the stress chain's built-in brake.
So there is a conjecture: a molecule that looks like cortisol but does not push as hard, if it can dock on the receivers on the brake side, would make the upstream read enough, and a little less would be sent. This is the path that makes the most molecular sense of lowering cortisol. It is still a hypothesis, not a process seen directly in people.
Besides the GR path, cell and animal experiments report that withanolides act on (gamma-aminobutyric acid, the signal that quiets neurons) and on the dopamine and serotonin systems. That is why it is also sold for sleep, and this too has not been measured directly in people.
Other constituents
Withanosides: withanolides with a sugar attachedAlkaloids: present in small amounts; Indian tradition used them for sedation
Root and leaf: a difference that affects safety
Traditional use and most clinical trials use the root, because the root is high in withanolides and low in impurities such as alkaloids. Leaf extracts carry more withaferin A. That sounds stronger, but withaferin A is also the member of this family that is most toxic to cells. Some commercial products mix leaf and root, and some researchers suspect this is linked to some adverse-event cases; the liver-injury chapter later comes back to it. Proprietary extracts such as KSM-66 and Sensoril are standardized, and the evidence chapter later compares them.
Background · What the word adaptogen means
Ashwagandha is often put in the adaptogen class. The word is neither a botanical category nor a pharmacological one; it is a functional label coined in the Soviet period. The pharmacologist Lazarev proposed it in 1947, and Brekhman and Dardymov gave it a systematic definition in 1969, in three clauses:It is non-toxic at ordinary dosesIt works against many kinds of stressor, without picking the kindIt has a normalizing action: it pulls the body back toward balance, pressing down what is too high and lifting what is too low
The first two can still be tested; the third is the loosest part of the idea. Pulling a deviation back does have a physiological counterpart, the negative-feedback brake that cortisol applies to the stress chain. But a claim that high goes down and low goes up is almost impossible to falsify in an experiment: whichever way the number moves, it can be counted as right. So whether an adaptogen claim carries weight does not rest on the label. It rests on whether a clinical trial behind it named a direction, a population and an endpoint in advance.
Other plants often put on adaptogen lists are rhodiola, ginseng, cordyceps, holy basil and schisandra. The word has no formal recognition from the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) and lives mostly in marketing and integrative medicine. Still, several of these plants have been tested in , and ashwagandha has been tested the most.
Background · What the plant is
A few facts to lay down first:Latin name Withania somnifera, a shrub in the nightshade family (Solanaceae)The main medicinal part is the root; leaves and berries have different uses and a different safety profile3000 years of Ayurvedic use, mainly in India, Nepal and South AsiaThe name comes from Sanskrit and joins two images: the smell of a horse and giving you the strength of a horse
The name deserves a second look. It describes not an ingredient but an expectation. For three thousand years the root was taken as a vitality tonic, and the phrase natural stress relief on today's shelf carries the same expectation. An expectation is not evidence. What comes next is to set the expectation and what was actually measured side by side.
Background · Why it has the most trials
Ashwagandha has more than any other adaptogen, for several reasons stacked together:1. Indian government support: the AYUSH ministry (which oversees Ayurveda, yoga and other traditional medicine) funds modern research on traditional remedies, and many trials run in Indian hospitals.
2. It fits the chronic-stress theme of the era: many people are stressed, sleep badly or are anxious, demand for natural, cortisol-regulating products is large, and ashwagandha sells straight into that market.
3. Commercial drive: KSM-66 (Ixoreal Biomed) is a standardized extract developed by an Indian company that has paid for several trials; Sensoril (Natreon) is another standardized extract. A patented extract plus trials gives both academic data and a commercial moat.
4. Signals in several fields: stress and anxiety (the core), sleep, male fertility and testosterone (limited evidence), muscle strength and exercise performance, cognition and memory, and subclinical thyroid problems. More than one indication means more room for marketing.
5. Growing popularity in the West: in recent years it spread fast through social-media wellness content and podcasts, moving from a niche herb to a routine shelf product. This point is different from the first four. Those explain why the research exists; this one only explains why you keep seeing it. Selling well has never been evidence.
These reasons explain why it is popular, not whether it works for you. What decides the effect is the quality of the trials, the dose, the extract form and the specific problem you want to solve.
Chapter 2
How it may lower cortisol
The stress response is a chain with three links. The hypothalamus deep in the brain first releases CRH (corticotropin-releasing hormone). The pituitary picks it up and puts ACTH (adrenocorticotropic hormone) into the blood. ACTH travels in the bloodstream to the adrenal glands and makes them build and release cortisol. Cortisol spreads through the whole body: it speeds the heart, pushes blood sugar up, and moves digestion and repair to the back of the queue. The racing heart, the sleeplessness and the tight stomach you feel are that last step.
Cortisol also docks back on the hypothalamus and pituitary and says enough; that is the chain's built-in brake. When stress never lets up, the usual change is not a high number on one day but a flattening of the wave that should be high in the morning and low at night.
Ashwagandha is thought to act at the top of the chain, so that a little less CRH and ACTH is sent. Human trials measured only the result, less cortisol in the blood; the middle step has not been measured directly. The drowsiness it causes may come from a different route: cell and animal experiments suggest its compounds act on , the brain system that quiets neurons.
Cortisol also docks back on the hypothalamus and pituitary and says enough; that is the chain's built-in brake. When stress never lets up, the usual change is not a high number on one day but a flattening of the wave that should be high in the morning and low at night.
Ashwagandha is thought to act at the top of the chain, so that a little less CRH and ACTH is sent. Human trials measured only the result, less cortisol in the blood; the middle step has not been measured directly. The drowsiness it causes may come from a different route: cell and animal experiments suggest its compounds act on , the brain system that quiets neurons.
Evidence · How much cortisol actually fell
The chain's formal name is the axis (hypothalamic–pituitary–adrenal axis), and ashwagandha's main hypothesized mechanism sits here: withanolides may reduce CRH and ACTH release, so cortisol climbs less when stress arrives.The human data come from randomized, double-blind, placebo-controlled trials in stressed adults. Both trials below measured serum cortisol from a morning blood draw:
Chandrasekhar 2012 (Indian J Psychol Med): 64 adults with a history of chronic stress took 600 mg a day of the KSM-66 root extract (300 mg twice a day) for 60 days. Serum cortisol fell 27.9% from baseline, against 7.9% in the placebo group.Lopresti 2019 (Medicine): 60 healthy adults who reported high stress took 240 mg a day of a different standardized extract (Shoden) for 60 days. Fasting morning cortisol fell 23%, while the placebo group rose 0.5%.
Both trials were small and ran for only two months. They point the same way, but larger independent trials need to repeat them.
Why "morning serum" gets its own label
Cortisol rides a roller coaster every day: it peaks about half an hour after waking, then falls all day and is lowest in the second half of the night. So the sentence how much cortisol dropped means nothing without the sampling time. The same person drawn at 8 a.m. and at 3 p.m. can differ by far more than any supplement moves it. Serum measures the total, including the share held by carrier proteins; saliva measures only the small free share, and the two cannot be converted directly. When you see a percentage, first ask what time of day and which sample.
One link on the chain is still missing
Inhibiting CRH and ACTH release names a result, not a process. The route in which a withanolide skeleton that resembles a glucocorticoid docks on the receivers at the negative-feedback end is the most coherent explanation so far, but it remains a hypothesis. What the human trials measured is less cortisol in the blood; the middle step, less CRH sent, has not been measured directly in people. That is the difference between a clear mechanism and a repeatable result, and it is worth keeping the two apart yourself.
Mechanism · Why it can make you drowsy
Besides pressing cortisol down, withanolides may take a completely separate road: in cell and animal experiments they partly bind the -A receptor. This road has not been measured directly in people, and everything below is reasoned from the mechanism.GABA (gamma-aminobutyric acid) is the brain's main brake-pedal signal. Its receiver, GABA-A, is not an ordinary switch but a chloride channel. GABA docks, the channel opens, negatively charged chloride ions flood into the neuron, and the inside of the cell becomes a little more negative. The more negative it is, the harder that neuron is to fire. When a whole patch of brain is a little harder to fire, what you notice is that the tension lets go, your thoughts stop looping, and sleep comes more easily.
Benzodiazepine sleeping pills (BZDs) work through this same channel, which is why the literature often describes withanolides as mild benzodiazepine-like sedation. If this road holds in people, it explains three things that look unrelated:
Why its effect on anxiety and falling asleep is often easier for the person to feel than any change in a cortisol numberWhy daytime drowsiness is one of its common side effects: the same action shows up at a time you do not want itWhy it should not be taken with sleeping pills or sedatives: if two things push the same channel, the result can go deeper than a simple sum
This side road and lowering cortisol are two parallel hypothesized paths, not two ways of describing one event. So a person who sleeps more easily after taking it while their cortisol barely moves is still a coherent picture.
Mechanism · Three less mature pathways
Besides the two main lines, the axis and (the signal that quiets neurons), three more paths come up again and again, at a much earlier stage of evidence.③ Neurotransmitters
Some animal studies suggest ashwagandha may raise serotonin and dopamine, and some small randomized trials in people saw depression and anxiety scores improve. Take the words animal studies seriously. Between a transmitter level measured in rodent brain tissue and a person feeling a bit better lie dose conversion, whether the compound crosses the blood–brain barrier, and the large placebo share inside any score improvement.
④ Antioxidant and anti-inflammatory action
In the test tube and in animals, withanolides show anti-inflammatory activity (they inhibit and COX-2), and some small trials saw mild drops in blood markers of inflammation such as and .
Those two names are worth taking apart. NF-κB is a switch protein inside the cell: when an inflammatory signal arrives, it is released, moves into the nucleus and switches on a batch of inflammatory genes. COX-2 is an enzyme made afterward; it turns arachidonic acid into prostaglandins, the molecules that make a spot red, hot and sore. So inhibiting NF-κB and COX-2 means running a little less of the inflammatory program upstream, not wiping inflammation out.
⑤ Thyroid
Sharma 2018 (J Altern Complement Med): 50 adults with subclinical hypothyroidism (thyroid hormones still in the normal range but already high) took 600 mg a day for 8 weeks; and rose and TSH fell. It was a small randomized double-blind trial and needs repeating.
The direction of this chain is worth stating clearly. TSH (thyroid-stimulating hormone) is the pituitary's make a little more order to the thyroid, and when thyroid hormones (T3 and T4) rise, they press TSH back down. So T3 and T4 up with TSH down is an internally consistent pair: the push is coming from the thyroid end, not the pituitary. Thyroid hormone turns up the metabolic rate of the whole body: a faster heart, more heat, more energy spent. For someone who is already hyperthyroid (already palpitating, heat-intolerant, losing weight), pushing the same way adds to the problem instead of correcting it, which is why people with hyperthyroidism should not use it. That conclusion is reasoned from the direction of the effect and has not been tested in hyperthyroid patients; whether people with Hashimoto's thyroiditis or subclinical hypothyroidism benefit is also only early evidence.
Evidence · Which claims have support
Matching the mechanisms against the evidenceSupported by small randomized trials: lower stress scores and lower morning serum cortisol (27.9% in Chandrasekhar 2012, 23% in Lopresti 2019), with several trials pointing the same wayStill hypotheses: neurotransmitters, anti-inflammatory action, thyroid, sexual function; early evidence that needs repeatingNo human data at all: marketing claims such as anti-aging, skin whitening and fat loss
Does lower cortisol mean less stress?
Lowering cortisol is not a health gain in itself. Cortisol is a normal stress response, and too little causes problems too: adrenal insufficiency (Addison's disease) is the disease of not having enough. What may matter more is whether the rhythm, high in the morning and low at night, recovers. Whether ashwagandha works mainly through that route has not been tested in the trials so far.
Why the rhythm deserves more attention than the number
The morning wave of cortisol is not a problem; it is a function. It releases stored sugar from the liver, holds blood pressure up and pushes you from sleep into waking. At night it falls, and only then do repair and the immune cells get to work. When long-term stress flattens this curve, people feel a typical pair: cannot get up in the morning, cannot fall asleep at night. Their total energy has not shrunk; the timing of when it is released has shifted. So a lab slip that says only cortisol high or cortisol low often tells you less than the answer to what time of day do you feel strongest.
Using ashwagandha instead of dealing with the sources of stress (work, sleep, relationships, money) is treating a plant extract as a cure-all, a common marketing trap.
In practice · Where it fits in handling stress
The link between cortisol and stress is more complicated than the popular version. A few points that are easy to miss:1. "High cortisol means stress" is a simplification
In healthy people, a short rise in cortisol under stress is an adaptive response and a good thing. Chronic stress more often disrupts the cortisol rhythm, flattening or even inverting it, without necessarily raising the average. Among people with depression, stress-related fatigue or chronic fatigue syndrome, studies have found that a sizable share actually have low cortisol and a sluggish response.
2. Who lowering cortisol makes sense for
People truly under long-term stress: bringing it down may help them recoverPeople whose cortisol is already normal: pushing it lower may be pointless or even harmful
That may explain why ashwagandha varies so much between people: the effect is clear in stressed groups and blurry in healthy comparison groups.
3. Limits of the trial design
Most ashwagandha trials enroll people with high stress scores, not ordinary healthy people. Extending the results to healthy people calls for caution: someone with plenty of energy and no obvious anxiety is unlikely to gain much. Some worry it could even blunt a normal stress response; that is a guess that has not been tested.
4. Handling stress itself
Recovery rests on rhythm plus the right amount of challenge, not on staying low-stress all the time. Heart rate variability (, the small variation between heartbeats, usually larger when you are relaxed) is another common stress measure that you can track at home. Real stress interventions include:
Sleeping 7–9 hours: the most basic step, which no supplement replacesRegular exercise: cortisol rises during a session, and over the long run it comes downMindfulness and meditation: randomized trials have seen cortisol fallSocial connection and time in natureLess caffeine, and less screen time before bed
5. A reasonable place for ashwagandha
An add-on on top of the basics above, not a replacementTry it for 4–8 weeks and watch whether sleep, heart rate variability and your own stress rating changeIf nothing changes, stop; do not keep taking it on faithSevere anxiety, depression or post-traumatic stress disorder (PTSD): see a professional rather than trying ashwagandha first
For stress, sleep, exercise and how you organize your life are the foundation; a supplement can only sit on top of it.
rosmond-2005-psychoneuroendocrinology
Chapter 3
Evidence for stress, sleep and muscle
The evidence on ashwagandha does not fit into a flat it works or it doesn't. Some conclusions have been measured by several groups independently, some rest on one small study, and some have never been measured at all, while marketing writes all three in the same confident voice.
The most trials are on stress and anxiety: several small in stressed adults point the same way, with stress and anxiety scores and morning serum cortisol falling further than on placebo. Sleep has trial support too: people with insomnia who took it for ten weeks fell asleep faster. For strength training, people doing resistance training gained more strength than the placebo group in two small trials. The weak spots these share: few participants, mostly run in India, and in many trials the extract was supplied or funded by the manufacturer.
There is a signal for male testosterone and fertility, but it is still weak. Thyroid, cognition and memory, depression add-on and obsessive-compulsive disorder rest on single or small studies. Longevity, anti-aging, skin whitening, direct fat loss and boosting immunity have no human data.
The most trials are on stress and anxiety: several small in stressed adults point the same way, with stress and anxiety scores and morning serum cortisol falling further than on placebo. Sleep has trial support too: people with insomnia who took it for ten weeks fell asleep faster. For strength training, people doing resistance training gained more strength than the placebo group in two small trials. The weak spots these share: few participants, mostly run in India, and in many trials the extract was supplied or funded by the manufacturer.
There is a signal for male testosterone and fertility, but it is still weak. Thyroid, cognition and memory, depression add-on and obsessive-compulsive disorder rest on single or small studies. Longevity, anti-aging, skin whitening, direct fat loss and boosting immunity have no human data.
Evidence · Trials on stress, sleep and strength
Certainty of evidence for this layer: low to moderate. There are several pointing the same way, but each is small, most were run in India, and in many the extract was supplied or funded by the manufacturer.Stress and anxiety is where the evidence is densest: several randomized trials consistently saw stress and anxiety scores fall and serum cortisol fall (by 27.9% in Chandrasekhar 2012). A 2014 review by Pratte pooled 5 randomized controlled trials, and their conclusions pointed the same way.
Sleep: people with insomnia who took it for 10 weeks saw sleep efficiency (the share of time in bed actually spent asleep) rise from 75.6% to 83.5%, and they fell asleep faster (Langade 2019, N=60); the placebo group improved too, just less. Another 8-week trial in stressed but healthy adults also saw better sleep quality on a self-rating scale (Salve 2019). The mechanism may involve the route through (the signal that quiets neurons) and the cortisol rhythm; neither has been measured directly.
Male testosterone and fertility: a signal exists but needs caution. Lopresti 2019 (Am J Men's Health) ran a crossover trial in middle-aged and older overweight men with mild fatigue, each taking the extract and a placebo for 8 weeks in turn. Salivary testosterone rose 14.7% more than during the placebo period, but fatigue, vigor and sexual well-being did not differ between the two. Ambiye 2013, a small pilot study in men with low sperm counts, reported large gains in sperm concentration, semen volume and motility. The numbers are striking and need larger trials to repeat them. It counts as an add-on with a signal, not a replacement for proper reproductive medicine.
Why salivary testosterone should be discounted
Saliva can only show the small free share of testosterone, the part not held by binding proteins, which is the part that can actually enter cells. It drifts with the time of sampling, with whether the mouth is bleeding and with saliva flow; serum measures the total and is far more stable. So a rise in salivary testosterone in one person may not appear at the same size in serum. When you see a hormone percentage, first check which sample it came from.
Muscle strength: in Wankhede 2015, young men new to strength training took 600 mg a day during 8 weeks of training, and their bench press, leg strength and arm and chest muscle size grew more than in the placebo group. Ziegenfuss 2018 pointed the same way. Both were small trials.
Why lowering cortisol might relate to muscle
This route is reasoned from the mechanism; the two trials did not measure it. In muscle, cortisol pushes toward breakdown: it encourages muscle protein to be split into amino acids and sent to the liver to make sugar, while holding back the building side. Muscle is being built and broken down at the same time every day, and the growth you see is only the difference. So if the breakdown side is pressed a little lower, the difference comes out a little more positive even when building does not change. But training itself raises cortisol briefly, and that is a normal response, so this cannot be read as the lower the cortisol, the more muscle you grow.
Evidence · Thin evidence and no evidence
Only single or small studies: subclinical thyroid problems (Sharma 2018), cognition and memory (Choudhary 2017 and others), depression add-on (Chengappa 2013, in bipolar disorder), and obsessive-compulsive disorder (Jahanbakhsh 2016).Claims with no human data: longevity, anti-aging, skin whitening, skin health, direct fat loss, boosting immunity.
Shared limits of these trials
Most had fewer than 100 participants and were done in IndiaIn many, the extract was supplied or funded by the maker of KSM-66 (Ixoreal Biomed). That does not cancel the results, but it raises the risk of publication biasThere are no long-term data beyond 6 monthsFew trials have been run in Western populationsNo specific indication has been approved by the FDA or EMA; it is a dietary supplement, not a drug
How manufacturer funding turns into bias
It is not as crude as changing the data, and usually nobody does. It happens like this: a trial comes out negative, so nobody has a reason to finish writing it up, submit it and push it through review. Negative results are already harder to publish, and the funder has even less reason to push. Years later, the literature holds only the trials that came out positive. Then someone writes a review and honestly reports highly consistent conclusions. The consistency is real, but it is consistency after a sieve.
What that means for you
A pile of small positive trials that point the same way is worth less than one large independent trial with a reliable effect sizeEffect sizes in this kind of literature are usually overestimated, and the true value is often smallerBut overestimated is not fake: it is not a reason to reject, only a reason to lower your expectationsWhat actually removes this kind of bias is a replication with a pre-registered protocol, independent funding and enough participants, and ashwagandha is still short of that
In practice · Choosing an extract form
Ashwagandha is not one thing; the market splits into at least 4 kinds:① Whole root powder, the traditional form
The traditional dose is 5–10 g/day, taken with warm milk and honey, with a withanolide content of 0.2–0.5%. It is the whole plant material and cheap, but the dose is hard to standardize, and modern randomized trials rarely use it.
② KSM-66 (Ixoreal Biomed), the standardized extract used in the most randomized trials
Withanolide content ≥ 5% (standardized)Root only, no leaf; water extraction, not ethanolMost modern randomized trials use itTypical dose 300 mg twice a day, or 600 mg/dayMany brands buy KSM-66 as their raw material
③ Sensoril (Natreon), another standardized extract
Withanolides ≥ 10% (a higher concentration)Contains leaf and root; its safety is debatedTypical dose 125–250 mg/day (relatively low)Used in some randomized trials
④ Self-standardized generic extracts, most cheap products
The label says it contains X% withanolides, but the real content varies (third-party testers such as ConsumerLab have found gaps repeatedly). Be careful with products that lack third-party certification; they may also contain impurities or heavy metals.
Choosing between KSM-66 and Sensoril:
Stress and anxiety: most randomized trials used KSM-66 at 600 mg/daySleep: both KSM-66 at 300 mg and Sensoril at 250 mg have dataMale testosterone and muscle: KSM-66 at 600 mg/daySubclinical thyroid problems: the early data used KSM-66
Dose ceiling and safety
The highest dose in randomized trials was 1000 mg/day, and 300–600 mg is usually enough. Traditional adaptogen use leans toward small doses over a long time; still, do not take it for more than 12 weeks without a break. Long-term data are missing, so pausing for a while is the conservative approach.
A 4-week trial run:
1. Record a baseline first: a stress score (PSS-10, the 10-item Perceived Stress Scale), a sleep diary and how energetic you feel
2. Take KSM-66 at 600 mg/day for 4 weeks
3. Measure again: set yourself a threshold in advance, for example continue for another 4 weeks if things improve by ≥ 20%, and stop if nothing changed
4. Do not use it for more than 12 weeks in a row
5. Watch for side effects: stomach upset, drowsiness or any change in your body; if your skin turns yellow or your urine looks like strong tea, stop immediately and see a doctor as soon as possible
Chapter 4
Side effects and who should avoid it
Natural means safe is a serious mistake here: ashwagandha has real pharmacological activity. Before and while you take it, let a doctor or pharmacist know, and do not let social media push you into buying and taking it casually.
The two most common effects are not serious: stomach upset (nausea, diarrhea) and daytime drowsiness. The drowsiness is the same thing as its possible action on the brain's braking system run by , the signal that quiets neurons (this comes from cell and animal experiments), just showing up at a time you do not want it.
What deserves real attention is liver injury. It is rare, but it has happened; most people in the reports took the dose on the label, so there is no this little is safe line, and people who already had chronic liver disease fared worst. The signs to recognize are yellow skin or yellow whites of the eyes, urine as dark as strong tea, itchy skin, pain in the upper right abdomen, and unexplained extreme tiredness. If these appear, stop taking it immediately and see a doctor as soon as possible.
These groups should not use it: people who are pregnant or trying to conceive, people with hyperthyroidism, people with existing liver disease, anyone having surgery within two weeks, and children and teenagers. It may also interact with sedatives and sleeping pills, diabetes drugs, blood pressure drugs and thyroid medication.
The two most common effects are not serious: stomach upset (nausea, diarrhea) and daytime drowsiness. The drowsiness is the same thing as its possible action on the brain's braking system run by , the signal that quiets neurons (this comes from cell and animal experiments), just showing up at a time you do not want it.
What deserves real attention is liver injury. It is rare, but it has happened; most people in the reports took the dose on the label, so there is no this little is safe line, and people who already had chronic liver disease fared worst. The signs to recognize are yellow skin or yellow whites of the eyes, urine as dark as strong tea, itchy skin, pain in the upper right abdomen, and unexplained extreme tiredness. If these appear, stop taking it immediately and see a doctor as soon as possible.
These groups should not use it: people who are pregnant or trying to conceive, people with hyperthyroidism, people with existing liver disease, anyone having surgery within two weeks, and children and teenagers. It may also interact with sedatives and sleeping pills, diabetes drugs, blood pressure drugs and thyroid medication.
Safety · Side effects and signs of liver injury
Common side effects: stomach upset (nausea, diarrhea), daytime drowsiness (consistent with a possible action on , the signal that quiets neurons, and often eased by lowering the dose), mild headache, and an odd taste in the mouth. In Chandrasekhar 2012, side effects were mild and similar in the two groups.Rare but important: drug-induced liver injury ()
A case series from Iceland and the US (Björnsson 2020) and one from India (Philips 2023): people taking ashwagandha developed acute liver injury, with raised transaminases, raised bilirubin and jaundiceMost recovered after stopping, but the literature also includes a case that needed a liver transplantBjörnsson 2020 (Liver International): 5 cases of liver injury attributed to ashwagandhaThe mechanism is unknown. Some suspect individual susceptibility, but in both series the products that were tested showed no adulteration or other toxic compoundsPeople who already had chronic liver disease fared worst; most people in the reports took the dose on the labelIf you have a history of liver disease, do not use it; checking and (two transaminases) while you take it is a reasonable precaution
Transaminases up, bilirubin up: what is happening in the body
Transaminases (ALT, AST) normally stay inside liver cells and do their work there. A little can be measured in blood, leaking from normal cell turnover. When the blood level suddenly jumps several-fold, the meaning is direct: the membranes of a great many liver cells have broken, and their contents have poured into the blood. So transaminases are not a measure of how well the liver is working; they are a measure of whether liver cells are being torn open right now.
Bilirubin takes another road. It is the residue that heme leaves behind when red blood cells retire; the liver processes it and sends it through the bile ducts into the gut. When that exit route is blocked or the processing stalls, bilirubin builds up in the blood. The skin and the whites of the eyes turn yellow, and the pigment that should have colored the stool leaves through the urine instead, which turns as dark as strong tea. That is why the pair yellowing plus tea-colored urine is the outward sign most worth recognizing: it points to a problem on the exit route, not just feeling a bit tired.
Most reports of ashwagandha-related liver injury are cholestatic, meaning they lean toward that exit-route side. If you notice yellowing or tea-colored urine, stop taking it immediately and see a doctor as soon as possible.
Safety · Thyroid, pregnancy and autoimmunity
② Thyroid functionAshwagandha may raise and (the basis of the trial in subclinical hypothyroidism)Hyperthyroidism: do not use it. The reason is the direction in which it pushes T3 and T4; it has not been tested in hyperthyroid patientsHashimoto's thyroiditis, or taking levothyroxine: monitoring is needed, and the medication dose may have to come downA normal thyroid: usually no effect, though sensitive people are exceptions
Why this matters most for people on levothyroxine
Levothyroxine is T4 added from outside. Its dose is worked backward from how much your own thyroid can still make, and the doctor tunes it to just right by rechecking (thyroid-stimulating hormone). If a plant then pushes T3 and T4 up from another side, the two forces add up, and the result is overshooting rather than topping up: palpitations, shaky hands, sleeplessness, unexplained weight loss. The trouble is that these symptoms are easy to read as stress, and stress is why you were taking it. So if you add it, the prescribing doctor has to know, and the rechecked TSH has to decide.
③ Pregnancy and breastfeeding
Traditional Ayurveda also used it in pregnancy, but in different preparationsThe modern concern: withanolides have a steroid structure and could in theory affect hormones and the uterusAnimal studies: high doses can induce miscarriageThe advice is not to use it in pregnancy; easing stress is not worth an unknown risk
④ Autoimmune disease
Ashwagandha may modulate the immune system and could in theory worsen some autoimmune diseases (lupus, multiple sclerosis, rheumatoid arthritis, Hashimoto's thyroiditis). The data are mixed and the real risk is unknown. If you have a diagnosed autoimmune disease, talk to your doctor before deciding.
The direction is worth laying out. In autoimmune disease the immune system mistakes the body's own tissue for an invader, and treatment usually aims to turn it down; the selling point boost your immunity is about turning it up. The two point in opposite directions. So in this group of diseases, something whose direction of action has not even been measured clearly should not be your own decision in front of a shelf.
Safety · Interactions and who should avoid it
⑤ Drug interactionsSedatives (benzodiazepines, sleeping pills, opioids): sedation may add up, which can be dangerousDiabetes drugs: ashwagandha may lower blood sugar, and together with the medication it may cause low blood sugarBlood pressure drugs: similarly, it may add to the lowering effectThyroid medication: see the thyroid section aboveImmunosuppressants: in theory it may work against themStop 2 weeks before surgery (in theory it may deepen anesthesia, and some worry about bleeding)
The first item deserves a closer look. Going by the mechanism suggested in cell and animal experiments, sedatives and ashwagandha may be pushing the same kind of chloride channel. When one channel is pushed by two things at once, the result is not necessarily a simple sum of two sedations; it can go deeper than you expect. Being a bit drowsy in the daytime turning into shallower breathing at night is a completely different matter.
Who should not use it:
Women who are pregnant or trying to conceivePeople with hyperthyroidism (Graves' disease and others); the reason is the direction of its effect, not a result measured in hyperthyroid patientsPeople on thyroid medication without monitoringPeople with existing liver disease, or taking drugs that can harm the liverAnyone having surgery within two weeksAnyone under 18 (no safety data)
Use with caution, after talking to a doctor: autoimmune diseases (lupus, multiple sclerosis, type 1 diabetes, rheumatoid arthritis, Hashimoto's thyroiditis); people taking several medicines for chronic conditions; people with diagnosed depression or anxiety who are on medication (talk to the psychiatrist).
Why it has to be stopped before surgery
Anesthesia is a whole set of drugs that press the central nervous system down, and several of them also act through , the signal that quiets neurons. If you walk into the operating room carrying something that may be pushing the same channel, the anesthesiologist does not know; the doses they have prepared were calculated for without this thing. So stopping is not just in case; it keeps the numbers right for the person giving the drugs. For the same reason, telling every doctor and dentist what you take is the cheapest step there is.
Red flag · What the liver-injury cases show
The reports of liver injury from ashwagandha are enough to break the idea that natural means safe.Björnsson 2020 (Liver International): 5 cases of acute liver injury attributed to ashwagandha, 3 from Iceland and 2 from the US Drug-Induced Liver Injury Network (DILIN). Latency was 2–12 weeks, not only after two or three months: some people were affected in the second week. They had jaundice, itching, lethargy and abdominal discomfort with raised transaminases, in a cholestatic or mixed pattern. None of the 5 progressed to liver failure; in 4, liver tests returned to normal 1–5 months after stopping, and 1 was lost to follow-up.
Philips 2023 (Hepatology Communications, India):
Several centers found 23 cases of liver injury linked to ashwagandha; the 8 who had taken a single-ingredient product were reported case by caseOf those 8, 5 already had chronic liver disease, and 3 developed acute-on-chronic liver failure; all 3 diedThe pattern was mostly cholestatic (jaundice plus a rise in ALP and , two enzymes tied to the bile ducts); in the others the injury dragged on but mostly resolved on its own, and 1 person developed chronic injuryThe tested products contained only the plant's own compounds, with no adulteration or contaminationIn the literature the authors reviewed, there is also 1 reported case that needed an emergency liver transplant (the patient survived)Mechanism hypotheses: individual genetic differences in drug-metabolizing enzymes (CYP, UGT); leaf-containing extracts (more withaferin A) may harm the liver more than pure rootIt is an idiosyncratic reaction with no clear dose threshold, which makes it hard to predict
Compared with liver injury from other "natural" products: green tea extract (high in ) is one of the main liver-toxic herbs; He Shou Wu (Polygonum multiflorum) has multiple reports; black cohosh (a menopause supplement) has many cases; and there are green coffee bean, Hydroxycut (a weight-loss product) and multi-ingredient gym supplements.
In the US DILIN registry, the share of acute drug-induced liver injury caused by herbs and dietary supplements has been rising for years. The real number may be higher, because regulation is loose and users often do not tell their doctors.
Practical advice:
1. While taking ashwagandha, watch for jaundice, upper abdominal pain, tea-colored urine and extreme tiredness
2. Ideally, test , , ALP and bilirubin before starting, after 4 weeks and after 12 weeks, especially if you take several supplements
3. If anything worries you, stop taking it immediately and see a doctor
4. Tell every doctor and dentist that you take ashwagandha, to avoid drug interactions and anesthesia risk
Conclusion: ashwagandha is not safe and harmless; it is relatively safe for most people when used sensibly. Its rare but real liver injury makes it unsuitable as something to take every day just in case. It belongs only within a plan that has a specific purpose, monitoring and a time limit.
Chapter 5
How it compares with rhodiola, ginseng
When you put ashwagandha back in a row of similar plants, the most useful dividing line is not which one is stronger but which direction it pushes.
Ashwagandha pushes down: calming, helping sleep, pressing the stress response back. Rhodiola and ginseng push up: alertness and less fatigue. Get the direction backwards and you feel more drained, or you cannot sleep at night. It is not that the plant does nothing; you picked the wrong tool.
So choose by the problem you want to solve. For stress, anxiety or trouble sleeping, ashwagandha has the most trials; for fatigue, low energy in the morning or scattered attention, look at rhodiola or ginseng. Rhodiola is traditionally used for coping with high altitude, but the trial cited here tested stress-related fatigue, not altitude sickness, so do not count on it to prevent altitude sickness.
Try one at a time. They may act on similar pathways, and if you start several and react, you cannot tell which one caused it or which one to stop. All of these are add-ons; what really sets your stress level is still sleep, exercise, diet and your connections with other people.
Ashwagandha pushes down: calming, helping sleep, pressing the stress response back. Rhodiola and ginseng push up: alertness and less fatigue. Get the direction backwards and you feel more drained, or you cannot sleep at night. It is not that the plant does nothing; you picked the wrong tool.
So choose by the problem you want to solve. For stress, anxiety or trouble sleeping, ashwagandha has the most trials; for fatigue, low energy in the morning or scattered attention, look at rhodiola or ginseng. Rhodiola is traditionally used for coping with high altitude, but the trial cited here tested stress-related fatigue, not altitude sickness, so do not count on it to prevent altitude sickness.
Try one at a time. They may act on similar pathways, and if you start several and react, you cannot tell which one caused it or which one to stop. All of these are add-ons; what really sets your stress level is still sleep, exercise, diet and your connections with other people.
Evidence · What rhodiola and ginseng trials show
Rhodiola (Rhodiola rosea, which grows in cold mountains and high latitudes)Actives: salidroside and rosavinTraditional use: the cold highlands of Russia and Scandinavia, against fatigue and for tolerating altitudeCharacter: stimulating (alertness, less fatigue, sharper thinking), the opposite of ashwagandha's calming characterTrials: in Olsson 2009, adults with stress-related fatigue (burnout) took a standardized extract (SHR-5) for 4 weeks; their burnout scores and several attention measures beat placebo, and their cortisol response after waking changed too. Other short-term fatigue and cognition trials are mostly small, so the certainty of evidence is moderate to lowDose: 200–600 mg of standardized extract (3% rosavin, 1% salidroside)Timing: take it in the morning to start the day; do not take it in the evening, since it easily causes insomniaAltitude: this is a traditional use, but the trial above tested stress-related fatigue, not altitude sickness
Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius)
Actives: ginsenosides; hundreds have been identified, and only a few such as Rb1 and Rg1 are commonly studiedTradition: East Asia and North America, over 2000 yearsCharacter: gently stimulating, close to rhodiolaTrials: some randomized trials on cognition were positive (Park 2014 and others); American ginseng has data on blood sugar after meals in people with diabetes (a series of studies by Vuksan from 2000 on); Barton 2013, a multicenter randomized double-blind trial, found that people with cancer-related fatigue who took American ginseng for 8 weeks improved more than on placebo; red ginseng has limited evidence for male erectile functionVarieties (by the traditional Chinese medicine classification): Korean red ginseng is warming, Chinese white ginseng neutral, American ginseng coolingDose: 200–400 mg of standardized extract
What the percentages on a standardized extract are telling you
The two percentages in brackets in the rhodiola list mean that in every hundred parts of the powder, three are rosavin and one is salidroside. Where the plant grew, when it was harvested and which solvent was used all make that ratio drift; standardization means the maker pulls it to a fixed value, so that how many milligrams you took lines up with how much of the active compounds you swallowed.
That is also why milligrams alone mean little: two bottles of the same weight, one labeled with its active-compound percentage and one not, can differ several-fold in what you actually take in. When you buy this kind of product, whether the label carries that percentage is far more useful than the brand name.
Evidence · Where other adaptogens stand
Holy basil (tulsi, Ocimum sanctum): a classic Ayurvedic adaptogen that, like ashwagandha, leans toward calming and stress regulation, but with fewer data; it is mostly used as a tea or an extract.Cordyceps: a fungus. Traditional Cordyceps sinensis forms when a ghost-moth caterpillar is infected; modern products mostly use cultivated Cordyceps militaris. The marketing centers on energy, and exercise performance; the randomized-trial evidence is weak to moderate, with a possible small gain in high-intensity exercise performance.
Schisandra: an East Asian plant said to have five flavors (sour, sweet, bitter, pungent and salty); there are animal data on fatigue and liver protection, and very few randomized trials in people.
Eleuthero (Eleutherococcus senticosus, nicknamed Siberian ginseng, though it is not a true ginseng): used in the Soviet era by athletes and cosmonauts; there are data on fatigue, but of uneven quality.
What separates these from the first two is the layer the evidence sits on
The difference is not whether it does anything but who has been measured. Three gaps separate animal data from human trials: dose conversion (rodents metabolize much faster), the route of dosing (a tube into a rat's stomach is not you swallowing a capsule), and the endpoint (the activity of an enzyme in the liver is not the same thing as whether you have energy tomorrow). So a sentence like animal studies show liver protection should not be read as it protects the liver. It means this is a lead worth testing in people, and that step has not been taken.
The ATP in the cordyceps entry works the same way. ATP is the cell's common energy currency, but related to ATP does not mean you will feel more energetic: almost everything in the body is related to ATP. In marketing, the word's job is to make you think energy, not to point to a specific site of action.
In practice · How to choose, and why not stack
Choose by purpose:Stress, anxiety, sleep: ashwagandha has the most trials (mostly with KSM-66)Fatigue, poor focus, low energy in the morning: rhodiola or ginsengExercise recovery: ashwagandha has small strength-training trials; some people add rhodiola for enduranceHigh altitude: rhodiola is a traditional choice, but none of the trials cited here tested altitude sickness; preventing altitude sickness calls for the standard measuresCancer-related fatigue: American ginseng has one larger randomized trial; discuss it with your oncologistDiabetes add-on: American ginseng has small studies on blood sugar after meals
But all of these are add-ons, not the core. The core is sleep, exercise, diet, handling stress and social connection; adaptogens and other supplements are only a layer on top.
Think carefully before stacking several adaptogens: they may act on similar pathways (the axis, neurotransmitters, antioxidant systems), and stacking can amplify side effects. Trying one at a time and watching for 4–8 weeks is more scientific than starting a whole set at once.
One at a time is not only about safety
Start three at once and you run into a problem with no solution. If something works, you do not know which one is doing it, so you have to keep taking all three. If a side effect appears, you do not know which one to stop, so you stop all three and start over. One at a time buys you knowing what to do in the next round, which is worth far more than the few weeks you would save.
And these plants do not even point the same way: one presses down and one lifts up, so taking them together is one foot on the gas and one on the brake. Where your body ends up is not up to you.
Background · Does the adaptogen idea hold up
Is adaptogen actually a useful clinical concept? Researchers still disagree.The case for it:
Mechanistically, the axis really can be modulated by various plants; this is not fantasyClinically, several plants (ashwagandha, rhodiola, ginseng) have been tested in randomized trials on stress and fatigue measuresThe European Medicines Agency (EMA) grants some plants Traditional Herbal Registration (THR), which does not require modern randomized trials but does require decades of documented traditional use
The case against it:
The concept is too broad: helping the body return to balance fits almost any effective drug, so it lacks specificityIt is hard to measure: resistance to stress has no objective biomarker beyond cortisol and Publication bias: adaptogen randomized trials tend to be small, and positive results are more likely to be publishedAlternative-medicine packaging: the word adaptogen is applied to many plants with no randomized-trial data at all, so the real and the fake get mixed together
How regulators see it: in the US, adaptogen is not a disease or sign category the FDA recognizes, and these products are sold as dietary supplements under the 1994 Dietary Supplement Health and Education Act (DSHEA). The structure-function claim loophole lets a label say supports the stress response but not treats anxiety. The THR registration the EMA grants some plants acknowledges traditional use only and is not validation by modern medicine.
A balanced position:
Accept that several plants (ashwagandha, rhodiola, ginseng) have some randomized-trial data and can be considered as add-onsReject the claim that adaptogens can cure or prevent a disease; that is marketing overreachReal stress management means sleep, exercise, diet, psychological coping and social connection, plus therapy or medication when needed; together these have far larger effects than all the adaptogens combined
3 principles of use:
1. A specific goal: not I hope to be healthier but my stress score is high, and I want to try it for 4–8 weeks and see what changes
2. Measure a baseline and track it: without trying you will not know, and trying without measuring leaves you not knowing either
3. Time-limited use: cycles of 4–12 weeks with breaks in between; no dependence, no indefinite use
One last image: an adaptogen is like a key that sometimes opens a door. But you do not need this key to get into the room where real change in health happens, because that door is always open: it is enough sleep, regular exercise, a varied diet and staying connected with people. The key is an add-on; do not let marketing convince you the door is locked without it.
References · 13
- Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha root in reducing stress and anxiety in adults. Indian Journal of Psychological Medicine, 34(3), 255–262. 64 adults with chronic stress, single-centre, randomized double-blind: 300 mg high-concentration full-spectrum root extract twice daily or placebo for 60 days. Scores on all stress scales fell significantly more than on placebo (P < 0.0001); serum cortisol fell 27.9% from baseline vs 7.9% on placebo, a significant difference; adverse effects were mild and comparable in both groups (abstract, PMID 23439798; full text, PMC3573577). 10.4103/0253-7176.106022
- Lopresti, A. L., Smith, S. J., Malvi, H., & Kodgule, R. (2019). An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: a randomized, double-blind, placebo-controlled study. Medicine, 98(37), e17186. 60 stressed healthy adults, 240 mg/day standardized extract (Shoden) or placebo for 60 days; all completed. HAM-A fell more than on placebo (P = .040), DASS-21 only near-significantly (P = .096); fasting morning cortisol fell 23% vs a 0.5% rise on placebo (P < .001) and DHEA-S fell 8.2% vs +2.5%; testosterone rose in men over time but not significantly vs placebo (P = .158). The lead author had earlier study funding from Arjuna Natural (abstract, PMID 31517876; full text, PMC6750292). 10.1097/MD.0000000000017186
- Salve, J., et al. (2019). Adaptogenic and anxiolytic effects of ashwagandha root extract in healthy adults: a double-blind, randomized, placebo-controlled clinical study. Cureus, 11(12), e6466. 8-week RCT, 60 stressed healthy adults (PSS above 20): ashwagandha root extract 125 mg or 300 mg twice daily (250 or 600 mg/day) vs placebo; 58 completed. PSS fell with 250 mg/day (P < 0.05) and 600 mg/day (P < 0.001); serum cortisol fell with both; sleep quality improved vs placebo (abstract, PMID 32021735). 10.7759/cureus.6466
- Lopresti, A. L., Drummond, P. D., & Smith, S. J. (2019). A randomized, double-blind, placebo-controlled, crossover study examining the hormonal and vitality effects of ashwagandha (Withania somnifera) in aging, overweight males. American Journal of Men's Health, 13(2), 1557988319835985. 16-week crossover in overweight men aged 40-70 with mild fatigue, 8 weeks each of placebo and ashwagandha extract (Shoden beads, 21 mg withanolide glycosides/day): 57 enrolled, 50 completed the first period, 43 all 16 weeks. Fatigue, vigour and sexual and psychological wellbeing improved over time with NO significant between-group difference; salivary DHEA-S rose 18% more (p = .005) and testosterone 14.7% more (p = .010) than on placebo; cortisol and estradiol did not differ (abstract, PMID 30854916). 10.1177/1557988319835985
- Ambiye, V. R., Langade, D., Dongre, S., Aptikar, P., Kulkarni, M., & Dongre, A. (2013). Clinical evaluation of the spermatogenic activity of the root extract of ashwagandha (Withania somnifera) in oligospermic males: a pilot study. Evidence-Based Complementary and Alternative Medicine, 2013, 571420. 10.1155/2013/571420
- Wankhede, S., Langade, D., Joshi, K., Sinha, S. R., & Bhattacharyya, S. (2015). Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial. Journal of the International Society of Sports Nutrition, 12, 43. 10.1186/s12970-015-0104-9
- Sharma, A. K., Basu, I., & Singh, S. (2018). Efficacy and safety of ashwagandha root extract in subclinical hypothyroid patients: A double-blind, randomized placebo-controlled trial. Journal of Alternative and Complementary Medicine, 24(3), 243-248. N=50; 600 mg/day × 8 weeks lowered TSH and raised T3/T4 in subclinical hypothyroidism. 10.1089/acm.2017.0183
- Langade, D., Kanchi, S., Salve, J., Debnath, K., & Ambegaokar, D. (2019). Efficacy and safety of Ashwagandha (Withania somnifera) root extract in insomnia and anxiety: a double-blind, randomized, placebo-controlled study. Cureus, 11(9), e5797. 60 patients with insomnia at one Indian hospital, randomized 2:1 to 300 mg high-concentration full-spectrum root extract (n = 40) or starch placebo (n = 20), twice daily for 10 weeks; sleep by actigraphy. Sleep onset latency improved in both groups but was shorter on ashwagandha at 10 weeks (29.00 vs 33.94 min, p = 0.019); sleep efficiency went from 75.63 to 83.48 vs 75.14 to 79.68 on placebo; sleep quality was better (p = 0.002). The abstract gives the per-protocol set as 58, then as 29 + 19, which do not add up (abstract, PMID 31728244). 10.7759/cureus.5797
- Ziegenfuss, T. N., Kedia, A. W., Sandrock, J. E., Raub, B. J., Kerksick, C. M., & Lopez, H. L. (2018). Effects of an aqueous extract of Withania somnifera on strength training adaptations and recovery: the STAR trial. Nutrients, 10(11), 1807. 38 recreationally active men randomized double-blind to placebo (n = 19) or 500 mg/day Sensoril, an aqueous root-and-leaf extract (n = 19), during a 12-week, 4-day/week resistance program. 1-RM squat +19.1 vs +10.0 kg (p = 0.009) and bench press +12.8 vs +8.0 kg (p = 0.048); the android/gynoid fat ratio favoured the extract; no other between-group differences in body composition, recovery or affect scales. Funded by Natreon, Inc. (abstract and funding, PMID 30463324). 10.3390/nu10111807
- Björnsson, H. K., Björnsson, E. S., Avula, B., Khan, I. A., et al. (2020). Ashwagandha-induced liver injury: A case series from Iceland and the US Drug-Induced Liver Injury Network. Liver International, 40(4), 825-829. Five cases of cholestatic/mixed liver injury after 2-12 weeks of ashwagandha use; all self-limited. 3 cases from Iceland (2017-2018) and 2 from the US DILIN (2016); mean age 43; jaundice after 2-12 weeks; cholestatic or mixed injury; pruritus and hyperbilirubinaemia lasted 5-20 weeks; no hepatic failure; liver tests normalized in 1-5 months in 4 (1 lost to follow-up); chemical analysis confirmed ashwagandha with no other toxic compound; 4 were also taking other supplements (rhodiola possibly co-causal in one). Full text: the Icelandic daily doses were 450-1350 mg as recorded from the label, and no patient had recently raised the dose (abstract, PMID 31991029; full text, PMC8041491). pubmed.ncbi.nlm.nih.gov/31991029
- Philips, C. A., Valsan, A., et al. (2023). Ashwagandha-induced liver injury — A case series from India and literature review. Hepatology Communications, 7(10), e0270. 23 herb-induced liver injury cases; cholestatic predominant; patients with pre-existing chronic liver disease had severe (fatal) outcomes. Retrospective multicentre Indian series, January 2019 to December 2022: of 23 patients with ashwagandha liver injury, the 8 on single-ingredient products are reported in detail (multiherbal or co-hepatotoxic exposures excluded); mostly men, cholestatic hepatitis commonest; 5 had underlying chronic liver disease, 3 of them presented with acute-on-chronic liver failure and all 3 died; the other injuries were prolonged but self-limiting, one became chronic. Chemical analysis found only natural phytochemicals, no adulteration or contamination. Full text: patients took ashwagandha per practitioner advice or product labeling (abstract, PMID 37756041; full text, PMC10531359). 10.1097/HC9.0000000000000270
- Olsson, E. M., von Schéele, B., & Panossian, A. G. (2009). A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract SHR-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta Medica, 75(2), 105-112. 10.1055/s-0028-1088346
- Barton, D. L., Liu, H., Dakhil, S. R., et al. (2013). Wisconsin ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2. Journal of the National Cancer Institute, 105(16), 1230-1238. 10.1093/jnci/djt181