Looking to buy Ashwagandha? Buy from Amazon.comWhy the buy link?
Follow this Page for updates
Withania Somnifera, Indian Ginseng, Winter Cherry, Dunal, Solanaceae
Withania coagulans (Different Plant)
Limited human studies use 2-5g of Ashwagandha root powder daily, with the lower range for general vitality and the higher range for libido and vitality. This is similar to traditional usage of Ashwagandha root extract in Ayurveda.
Concentrated (X:1 extract) capsules can also be used, using the Withanolide and Withanoside content as a marker of purity.
Looking to buy Ashwagandha? Buy from Amazon.com or BodyBuilding.com
The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Ashwagandha has in your body, and how strong these effects are.
|Grade||Level of Evidence|
|A||Robust research conducted with repeated double blind clinical trials|
|B||Multiple studies where at least two are double-blind and placebo controlled|
|C||Single double blind study or multiple cohort studies|
|D||Uncontrolled or observational studies only|
|Level of Evidence ||Effect||Change||Magnitude of Effect Size ||Scientific Consensus||Comments|
Appears to enhance seminal quality, needs more studies against comparators
Was effective in infertile men, may not be effective in increasing testosterone in otherwise healthy men.
Not overly notable, but a decrease has reached statistical significance
An increase in luteinizing hormone has been detected with ashwagandha supplementation.
Unable to aid psychogenic erectile dysfunction more than placebo
Minor T-cell activation following ingestion of Ashwagandha tinctures, needs to be replicated.
|D||Natural Killer Cell Activity|
A slight increase in natural killer cell activity has been noted with ashwagandha supplementation.
May have diuretic effects, although not to a remarkable degree.
Decreases in total cholesterol have been seen due to ashwagandha ingestion.
A decrease in blood glucose has been noted with ashwagandha.
A slight decrease in LDL-C has been noted following ashwagandha supplementation.
A slight decrease in triglycerides has been noted with ashwagandha.
Looking to buy Ashwagandha? Buy from Amazon.com or BodyBuilding.com
It is classified as an Adaptogen (compound able to reduce the biochemical effects of a perceived stress) and as a Rasayana, which is a term used to refer to the highest class of Ayurveda. It has been traditionally used to treat almost all forms of ailment such as analgesia, astringent, adaptogen, anti-inflammatory, anti-stress, antispasmodic, anti-diabetes, immuno-stimulant and cardioprotective. The root or root extract are commonly used, although the fruits of the Ashwagandha plant (the Wintercherries) also have therapeutic potential.
There has been reported to be high variability in the amount of active withanolides in common nutritional supplements, which may be due either to lack of standardization of root powder.
Withanolides are present in all plants in the Solanaceae family of plants, of which Withania Somnifera(Ashwagandha) is the highest in concentrations.
Unless otherwise standardized to a certain percentage, the amount of active Withanolide A (seen as the primary ingredient) and Withaferin-A are 1% of dry weight of the leaves (with negligible content in the roots) of Withania Somnifera.
All the active withanosides share a backbone similar to testosterone, and vary depending on the configuration of the outer ring.
Natural Killer (NK) Cells appear to have increased activity in persons who are both selected for low baseline NK cell activity, and who drink a polyherbal Ayurvetic tea containing Ashwagandha. Increased NK cell activity has also been attributed to Ashwagandha in isolation, after 3-day consumption of 12mL Ashwagandha liquid format in otherwise healthy persons in a pilot study.
In mice subject to stress (in this study, cold stress), Ashwagandha at 512.5mcg daily was able to increase phagocytosis by macrophages to near control levels although it was outperformed by beta-glucans from Maitake.
At least one study has noted seemingly synergistic effects between Maitake (mushroom source of glucans) and Ashwagandha in stressed animals, as the reduction of perceived stress secondary to Ashwagandha's adaptogenic abilities itself reduced impairment of the immune system. These effects were seen at a relatively low dose, at 512.5mcg daily in mice, and the expected rise of corticosterone seen with stressors is not seen with Ashwagandha preloading.
Ashwagandha has been demonstrated to possess cancer-selective cytoxicity (able to destroy tumor cells at concentrations that are non-toxic to regular cells) when it looks at either the Withiferin A content or an extract known as i-factor, which is Withanone. Withiferin A had 4-fold higher cytotoxicity in cancer cells relative to contol, and Withanone as well as the i-extract (blend of nutraceuticals from Ashwagandha) appear to possess 33 to 38-fold higher cytotoxicity in cancer cells, with the extract being more potent. Interestingly, the prescence of Withanone has been shown to be protective against Withaferin A induced toxicity in normal cells.
Five canonical pathways seem to be implicated. p53 signalling, GM-CFS signaling, death receptor signaling, apoptosis signaling and G2-M DNA damage regulation pathway. All fractions tested influenced p53 and had p53 involved in cytotoxicity, whereas only i-extract influenced G2-M.
A later study suggested that cytotoxicity from Ashwagandha is mediated in the nucleus prior to the above signalling pathways mostly via the four genes TPX2, ING1, TFAP2A and LHX3; with three others less influential. TPX2 is a protein regulator of Aurora-A (and this pathway seems to be regulated by withanone), TFAP2A involved with Bcl-2 and SMAD signalling, LHX3 involved in cellular determination and oncogenesis, and ING1 (Inhibitor of Growth 1) both a determinator of cellular senscence as well as regulator of p53 signalling via acetylation and stablilization. All of these genes seem to be influenced by oxidative stress, and thus anti-oxidant enzyme induction may mediate these effects. Other explanations still exist, such as Withanone being able to prevent the sequestering of p53 in the nucleus from the pro-carcinogenic protein, mortalin. This latter mechanism has been noted before to cause selective cancer cell killing.
Ashwagandha appears to have a few different pathways of cytotoxicity in cancer cells, and interestingly can destroy cancer cells in preference to normal cells; not many studies have been done in vivo with animals or humans however, and the anti-cancer effects of Ashwagandha (and the active component in this regard, Withanone) is preliminary
Withanone, isolated from Ashwagandha, caused downregulation of p21WAF1 in non-cancerous human fibroblasts; a protein downstream of p53 involved in cellular senescence. Withaferin-A was able to increase expression of p21WAF1 in isolation, but could not when co-incubated with Withanone.
Fibroblasts treated with Withanone (2.5ug/mL) underwent 10-12 more population doublings than did control cells, correlated to a 20% increase in cellular lifespan; and were replicated in MRC5 cells (isolated from live lung culture). This was hypothesized to be secondary to a decrease in cellular sensence, as there was approximately a 20% decrease in autofluorescence (indicative of cellular damage accumulation) and similar reductions in beta-galactosidase activity.
Withanone has been demonstrated to increase cell viability (survival) when cells are insulted by either UV rays or by H2O2, although not to control levels. Overall reductive capacity of a cell also appears to be increased (as evidenced by up to 40% increases in Glucose-6-phosphate dehydrogenase activity).
It was mentioned in the discussion of one study that a trial of older men in India (50-59 years) given 3g Ashwagandha daily for a year enabled a greater amount of hair melanin content to be preserved, which should theoretically preserve hair color to a degree. Mentioned in the text entitled Clinical applications of Ayurvedic and Chinese herbs: monographs for the western herbal practitioner, the study (Kuppurajan, K, et al; 1980) cannot be located online.
Ashwagandha can beneficially influence Alzheimer's disease pathology indirectly via the liver tissue, increasing Low-density Lipoprotein related protein levels. In middle-aged and older mice, 30 day treatment of Ashwagandha at 1g/kg bodyweight of an extract (containing 75% withanolides, 20% withanosides) was able to reduce beta-amyloid pigmentation in the cortex (77%) and hippocampus (78%) of middle-aged mice, and of aged mice (49% in cortex, 52% in hippocampus) and all tested groups saw reductions in beta-amyloid oligomers. Ashwagandha does not affect amyloid precursor protein processing whatsoever, and the benefits seen due to a normalization of sLRP:RAGE (to be discussed). Neprilysins and sLRP are both increased after Ashwagandha ingestion, but inhibition of Neprilysin upregulation does not inhibit the therapeutic benefit.
The mechanism was through upregulation of LDL-related protein (LRP) in the liver and increasing mRNA about 2-fold and increasing circulating levels, soluble LRP which sequesters beta-amyloid pigment tissue into systemic circulation and away from the brain. Soluble LRP (sLRP) tends to be decreased in Alzheimer's Disease, and an abnormal ratio of low sLRP to high RAGE (Receptor for Advanced Glycemic End Products) appears to contribute to Alzheimer's Pathology.
Has been demonstrated to greatly benefit symptoms and pathology of Alzheimer's disease after oral administration, but a high dose of concentrated withanolides/withanosides was used in the animal study
Even without clearance of beta-amyloid pigmentation, Ashwagandha constituents (Withanoside IV and Sominone) can reduce neurodegeneration induced by this pigment and possesses metabolites that may act as acetylcholinesterase inhibitors (Withalide A mostly, although others are implicated) although the effects seem to be heterogenous across the brain; increasing acetylcholinesterase in the globus pallidus and decreasing activity in other areas of the basal forebrain nuclei and other components may offer protection from toxins that work via acetylcholinesterase inhibition such as Propoxur.
Has other properties that may confer some additional benefit to Alzheimer's disease, although more applied studies need to be done on the matter
Ashwagandha root extract, as well as isolated Withanolide A, have been demonstrated to reduce excitotoxicity-induced memory loss by preserving (or otherwise upregulating) anti-oxidant enzymes in rats. The reduction of NMDA receptor expression (seen during memory loss) was also significantly reversed with Ashwagandha and has been traced back to preventing a degree of the abnormalities unto Hsp70 that glutamate excitotoxicity induces.
Ashwagandha has been demonstrated to, after reserpine-induced toxicity resulting in tardive dyskinesia in mice, to dose-dependently reduce symptoms (orofacial) of tardive dyskinesia. This reversal of symptoms has also been seen with haloperidol-induced dyskinesia and both are suspected to benefit symptoms secondary to increased anti-oxidant enzyme expression.
Parkinson's Disease has also been shown to have beneficial symptom reduction and increased circulating catecholamines, possibly secondary to an observed increase in the anti-oxidant enzymes catalase and glutathione peroxidase. Huntington's disease has also shown benefit from the induction of these two enzymes, and established causation using 3-nitropropinoic acid as a research neurotoxin. Along these lines, dopaminergic neurons are also protected via Ashwagandha during periods of morphine withdrawal; which tend to be associated with significant localized atrophy in dopaminergic neurons.
Cholinergic antagonists and induced memory loss (such as reserpine) have also been shown to have their effects reversed somewhat with Ashwagandha in vivo, able to attenuate decreases in Brain-Derived Neurotrophic factor (BDNF) at 100mg/kg bodyweight intake of Withaferin-A/Withanone rich Ashwagandha extract, and increase BDNF levels above that of control at higher doses.
It is possible that these inductions of anti-oxidant enzymes are secondary to induction of Heme-Oxygenase 1, which is from Ashwagandha acting on KEAP-1 to induce activation of Nrf2; however, this lead is one in vitro study with industry funding and a PLoS entry demonstrating that Ashwagandha (specifically, the isolated withanone) was able to inhibit premature oxidant-induced senescence of cells via inducing Nrf2 and the Anti-oxidant response element and keep levels of anti-oxidant enzymes fairly stable near control levels at 10uM. This induction was greater than that recorded by Genistein, a soy isoflavone.
An underlying mechanism(s) related to the anti-oxidant enzymes appears to mediate protection from a variety of cognitive diseases associated with oxidative stress. This may be Nrf2 induction, which would suggest that the effects are similar to many other polyphenolic compounds
In mice treated with beta-amyloid (Aβ 25-35), the bioactive Withanoside IV (at 10umol/kg daily oral ingestion) via its in vivo metabolite Sominone was able to attenuate dendritic and synaptic reductions in the toxin-treated mice, while increasing axon and neuronal immunostaining (via NH-2) beyond that of control which indicates neurogenesis rather than merely preventing decline. Although this in vivo study did not note dendritic immunostaining greater than control (possibly due to negative influences form Aβ 25-35), dendritic extension has been seen in human neuroblastoma cells at 5ug/mL (methanolic extract) attributed to the Withanolide A and Withanosides IV and VI content although additional research suggests the latter two influence dendrites more and Withanolide A influencing axon length more and were able to elongate and potentiate dopaminergic neurons. These results suggest Ashwagandha possesses both rehabilitative benefit and could also benefit those without cognitive impairment, although applied studies have not yet been undergone in humans.
Appears to induce growth of dendrites and axons (parts of neurons) and appears to be active in mice after oral administration; may be a promising therapeutic or cognitive enhancement strategy
Ashwagandha has been used effectively in reducing anxiety, depression, and parameters thereof in rats (biochemical, such as tribulin; experimental, such as social interaction) at 20-50mg/kg oral ingestion of the withanolide glycosides; this was comparable to 0.5mg/kg lorazepam (a benzodiazepine) for anxiety, and 10mg/kg imipramine (anti-depression). The reduction in anxiety seen with Ashwagandha works synergistically with drinking Alcohol, and appears to reduce the social anxiety associated with prolonged social isolation.
When tested in humans at either 250mg daily (in two doses of 125mg at lunch and dinner) or 125mg (125mg at lunch, placebo at dinner) all standardized to 11.90% withanolide glycosides, 1.05% withaferin A, and 40.25% oligosaccharides with 3.44% polysaccharides over 60 days in 98 persons (18-60) with chronic stress and without any other medication saw significant improvements over placebo in regards to 11 parameters of anxiety such as forgetfulness, feelings of impending doom, irritability, sleeplessness, fatigue, dry mouth, loss of hunger, headaches and muscle pain, and inability to concentrate. Although the higher dose group (250mg) appeared to have more benefit than the lower dose group (125mg), the differences between the two were not clinically significant.
Rat studies suggest that Ashwagandha is validated in its usage traditionally as an Anti-Hikkikomori herb (Mood stabilizer in social isolation)
At least one study has suggested that Withania Somnifera (Ashwagandha) can help with Obsessive-Compulsive Disorder. Based on the assumption that Ashwagandha has traditionally been used to cure 'mood disturbances', a study was conducted on mouse marble-burying behaviour (an established research model for OCD) and found that 10-100mg/kg bodyweight ethanolic extract of Withania Somnifera was able to reduce OCD-like symptoms; with 25 and 50mg/kg being seen as best, as 10mg/kg was statistically ineffective and 100mg/kg associated with sedation (the anti-OCD effects still held true, but sedation was suggestive of impairment and lowered internal validity somewhat). Ashwagandha was about as effective at 10mg/kg as Fluoxetine at 5mg/kg bodyweight (both dosed too low to be significantly different than control) yet the combination of the two abolished OCD-like behaviour while pairing Ashwagandha with ritanserin (a serotonergic antagonist) negated the benefits of both; suggesting Ashwagandha benefits OCD via serotonergic mechanisms.
Ashwagandha may have a GABA-ergic mechanism of action and benzodiazepine-like effects; two studies have been conducted in sleep-disturbed mice, and both studies used 0.5mg diazepam (a benzodiazepine) as a comparative agent to 100-200mg/kg (injections) of Ashwagandha, and the effects on sleep latency, slow wave and REM sleep, as well as total waking and sleeping time were remarkably similar (with perhaps diazepine being insignificantly better at reducing sleep latency) and not additive. Picrotoxin (GABAA antagonist) reversed the benefits on sleep with Ashwagandha, and Muscimol (GABAA agonist) potentiated these benefits on sleep.
Sedation is a common side-effect in some studies when overdose on, actually. One study on aphrodisia found mice given 3g/kg bodyweight had less copulation (despite Ashwagandha being an aphrodisiac) due to over-sedation and a study on Obsessive-Compulsive Disorder had to disregard the highest dose group (100mg/kg) as that dose, despite showing benefit in symptoms, had a great reduction in motor recruitment.
A lack of efficacy of oral Ayurveda has been observed twice in Geriatric populations (whereas the practise of Yoga was able to benefit), but the oral Ayurveda preparation is highly confounded.
Ashwagandha is sometimes used as an aphrodisiac, which may be vicariously through its 'adaptogenic' stress reduction (as chronic stress induces sexual dysfunction). One study using a moderate dose in mice (25-50mg/kg bodyweight for 21 days) noted both reductions in stress and decreases in the reductions in sexual activity induced by chronic stress; in a relatively dose-dependent manner. Another study using 3g/kg in mice daily did note reductions in libido, hypothesized to be secondary to sedative effects of Ashwagandha and the larger dose used.
When 5g of Withania Somnifera root powder is supplemented into otherwise infertile men, all measured seminal parameters (motility, anti-oxidation status, count, concentration, and volume) increase, although not to the levels of the fertile control group. All nutrient counts, such as Vitamin C and fructose, also increase.
A mechanisms behind this pro-seminal effect may be protection from oxidative-induced damage.
One human study has been conducted on 'psychogenic erectile dysfunction' (lack of erections due to anxiety and fear of failure) in persons with DSM-IV confirmed Male Erectile Disorder Psychogenic type, and 2g of Ashwagandha root extract taken with meals for 60 days was ineffective in treating this condition. Ashwagandha was associated with significant benefit on all measured parameters (International Index of Erectile Dysfunction), but placebo group matched this benefit.
There is little to no evidence for usage of Ashwagandha as a testosterone boosting compound in healthy men, only infertile. This aforementioned study used 5g of basic Ashwagandha root powder daily for 6 months and found increases in testosterone in the three tested infertile groups (Asthenozoospermic rose to 121% of baseline, Oligozoospermic to 140% of baseline, and Normozoospermic to 114% of baseline) yet no group surpassed the fertile control groups testosterone level, although normozoospermic was insignificantly different after the end of the trial. A slight increase in testosterone was seen in non-diabetic rats used as a control, alongside a much larger spike in progesterone.
Preliminary evidence that Ashwagandha can normalize reduced testosterone levels in men, but no evidence looking at elevating testosterone beyond baseline levels in healthy individuals
The one study to note LH levels in infertile men noted an increase and a trend towards normalization when compared to fertile men. A study in diabetic rats who had two control groups (non-intervention, Ashwagandha intervention) found LH spikes about three-fold higher with 6.25% Ashwagandha (as assessed on a weight basis of food intake) from 0.2mIU/mL to 0.6mIU/mL after four weeks.
The one study to note FSH levels noted a decline in tested infertile men, signalling a trend to normalization when compared to the fertile control. These effects have been noted in diabetic mice, and a slight decrease is also seen in control mice with no health complications.
In animals, Ashwagandha has been shown to increase circulating T4 levels with no influence on T3 (at 1.4g/kg root extract daily in mice for 20 days) and another study noted both hormones (T3 and T4) increased under the same protocol. The latter study was conducted in male mice, and tested females showed different results; when female mice were tested in isolation, the same increase in hepatic anti-oxidant enzymes (catalase up by 12%) and decrease in lipid peroxidation (34%) was seen, and increased T4 (lesser active thyroid hormone) by approximately 60% without significantly influencing T3 (more active hormone). Ashwagandha has also been investigated as a combination with Guggulsterone gum and Bauhinia Bark (from Bauhinia Purpurea) and appears to be well-tolerated; and a rise in T3 was recorded with this blend possibly due to the Bauhinia.
Beyond that, Ashwagandha possibly has benefit as an adjunct therapy. While Metformin administration can alleviate many effects of experimentally induced type II diabetes, it further reduces circulating T4 levels; Ashwagandha administration at 1.4g/kg ameliorated these adverse changes.
At least one human case study has noted a medically relevant case of hyperthyroidism after usage of a supplement containing Ashwagandha.
Seems to have the ability to stimulate T4 production at the level of the thyroid, but there may be a gender difference in regards to T3 where men can produce more in response to Ashwagandha than women; more studies would be needed for conclusison
Ashwagandha has been associated with a decrease in circulating cholesterol levels and increased fecal cholesterol excretion in rats, but is confounded with the inclusion of other herbs. It has, however, been noted to do these same effects in isolation.
In a research model of type I diabetes (alloxan-induced), Ashwagandha was able to attenuate adverse changes in LDL, HDL, total cholesterol, and triglycerides to a comparable potency at 200mg/kg as glibenclamide (anti-diabetic drug) dosed at 0.6mg/kg.
In diabetic animals, both the root and leaf of Ashwagandha is also able to decrease circulating liver enzymes at 200mg/kg by 45% (AST and ALT), 31% (ACP) and 16% (ALP).
Bioaccumulation of cadmium, a hepatotoxic mineral (in excess), has been reduced and the oxidative damage attenuated with herbal adaptogens (of which includes ashwagandha) at low (0.1% of the diet) dosages. Ashwagandha in isolation appears to be able to prevent this toxicity as well.
Via the liver, Ashwagandha has been implicated in reversing the pathology of Alzheimer's Disease; more can be read in the Neurology section.
In a model of type I diabetes (mice injected with streptocozin), Withania Somnifera at 6.25% of the diet may raise fasting blood glucose slightly but significantly.
One study in rats noted that 6.25% Ashwagandha (on a food weight basis) could attenuate the adverse changes in lutenizing hormone and follicle-stimulating hormone associated with diabetes. No effects were seen on estrogen and progresterone (despite the latter dropping in the experimental group of diabetes) and testosterone changes were not related to the state of diabetes.
Doses of Ashwagandha (100-200mg/kg) have been shown to reduce adverse changes to glucose metabolism after oral ingestion in rats. The higher dose of 200mg/kg was as effective as 0.6mg/kg glibenclamide (anti-diabetic drug) at reducing blood glucose and HbA1c (to near control levels, although not completely) and increasing hepatic liver glycogen and hemoglobin levels. A decrease in glucose-6-phosphatase activity is also seen in the livers of diabetic animals treated with Ashwagandha, to a similar potency to glibenclamide.
Perment is a poly-Ayurvedic formula consisting of equal parts (125mg each) of four herbs; Ashwagandha, Clitoria Ternatea, Bacopa Monnieri, and Asparagus Racemosus. It is apparently used clinically for its anti-depressive and anxiolytic effects, and is effective in rat models of chronic unpredictable manageable stress. The combination of the four herbs shows synergism in this regard, but whether synergism exists between all four or just 2-3 herbs is not demonstrated.
The acute LD50 for Ashwagandha extract (2% pure alkaloids) was found to be 465mg/kg in rats and 432mg/kg in mice. Whereas other studies using alcohol extracts of Ashwagandha found LD50 values around 1750+/-41mg/kg, 1076 +/- 78 mg/kg and 1564 +/- 92 mg/kg for Ashwagandha, sitoindosides VII and VIII, and withaferin-A respectively. In vitro results suggest no toxicity to human blood cells (erythrocytes)
In a subchronic toxicity study using a 10:1 ratio of Panax Ginseng to Ashwagandha taken at 8.50mg/kg, 12.75mg/kg, and 17.00mg/kg bodyweight in rats (4, 6, and 8 times the therapeutic dose) noted that despite increased food intake (70-80% in experimental, 41% in control) there was no abnormal serum parameter indicative of toxicological signs; liver weight increased, but it was uncertain as to whether this was due to the intervention per se or the increased food intake observed. An increase in haematopoesis was seen 1.7-1.9 gm% which led to an increase of 2-2.1million/cumm in RBC count.
At least one confirmed case has established causation with ashwagandha at 5g oral ingestion daily for 10 days (a treatment dosage for libido) caused a burning/itching sensation on the penis mucous membrane, and slight discoloration and reddening of the head and prepuce.
(Common misspellings for Ashwagandha include ashwaganda, ashwhagandha, ashwaghanda, ashwhaghanda)
(Common phrases used by users for this page include ashwagandha therapeutic dose, ashwagandha sperm quality, ashwagandha powder daily dosage, ashwagandha clinical, ashwaganda for sleep, ashwaganda case study invertility)