Clinical evidence on ashwagandha and endocrine function

Introduction

Ashwagandha (Withania somnifera), an evergreen shrub belonging to the Solanaceae family, is one of the most prominent botanical agents utilized in traditional Ayurvedic and Unani medicine systems ¹²³. Historically prescribed as a "rasayana" or rejuvenator to promote vitality and longevity, the botanical is functionally classified in modern phytotherapy as an adaptogen - a pharmacological compound purported to increase physiological resilience to biological, physical, and chemical stressors while restoring systemic homeostasis ¹⁴⁵. Over the past two decades, the application of ashwagandha has shifted from traditional use in the Indian subcontinent to mainstream global consumption, driven largely by an expanding body of clinical research investigating its neuroendocrine effects.

The scientific and clinical interest in ashwagandha centers primarily on its capacity to modulate human hormonal pathways. Current research focuses heavily on its efficacy in reducing perceived stress and serum cortisol, its androgenic potential to elevate testosterone and dehydroepiandrosterone-sulfate (DHEA-S) in men, and its distinct stimulatory effects on thyroid function ⁶⁷⁸. As global sales and consumption have surged - with the market value approaching nearly one billion dollars annually - so too has regulatory scrutiny ⁹. National health authorities in several European jurisdictions have recently evaluated the safety profile of the botanical, weighing its established clinical benefits in stress management against emerging pharmacovigilance reports of hepatotoxicity, thyrotoxicosis, and potential endocrine disruption ¹⁰¹¹¹². This report systematically examines the clinical evidence regarding ashwagandha's physiological impact on stress, cortisol, testosterone, and thyroid hormones, alongside an analysis of its safety profile and global regulatory status.

Central Neuroendocrine Mechanisms of Action

The pharmacological activity of ashwagandha is primarily attributed to a diverse group of naturally occurring steroidal lactones known collectively as withanolides. Key bioactive constituents include withaferin A, withanolide D, as well as various alkaloids (such as withanine and somniferine) and sitoindosides ³⁵¹³. Rather than acting as direct, exogenous hormone substitutes, these bioactive constituents appear to exert their physiological effects via central regulatory pathways, modifying the signaling cascades that govern the broader endocrine system ⁶⁷. Clinical evidence suggests that ashwagandha acts centrally via GABAergic pathways to modulate the neuroendocrine system, suppressing stress hormones which subsequently relieves inhibition on gonadal and thyroid axes.

Modulation of the Hypothalamic-Pituitary-Adrenal Axis

The most thoroughly documented mechanism of ashwagandha is its modulation of the hypothalamic-pituitary-adrenal (HPA) axis, the primary neuroendocrine system that dictates the body's physiological response to stress ³⁷. During periods of acute or chronic stress, the hypothalamus secretes corticotropin-releasing hormone (CRH). This hormone travels to the anterior pituitary gland, stimulating the release of adrenocorticotropic hormone (ACTH). ACTH subsequently enters the systemic circulation and prompts the adrenal cortex to synthesize and secrete glucocorticoids, predominantly cortisol ¹⁴¹⁰.

Preclinical and human studies indicate that ashwagandha exerts GABA-mimetic activity at the hypothalamic level, structurally interacting with gamma-aminobutyric acid (GABA) receptors to enhance central inhibitory signaling ⁷¹⁴¹⁶. This increased GABAergic tone exerts an inhibitory effect on the HPA axis, suppressing the excessive release of CRH and ACTH. By limiting the upstream signaling molecules, ashwagandha limits downstream cortisol production, preventing the sustained hyperactivation of the adrenal glands that characterizes chronic psychological and physical stress ³¹⁶.

Interactions with the Hypothalamic-Pituitary-Gonadal Axis

The human reproductive system, governed by the hypothalamic-pituitary-gonadal (HPG) axis, is exquisitely sensitive to stress ⁷. From an evolutionary biology perspective, reproduction is an energy-intensive process that is downregulated during periods of perceived environmental threat or scarcity. Physiologically, elevated systemic cortisol directly suppresses the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus ⁷¹⁶. This suppression cascades downward, reducing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland, ultimately diminishing sex steroid synthesis in the gonads ⁷.

By attenuating HPA axis hyperactivation and lowering serum cortisol, ashwagandha provides a permissive environment for the HPG axis to operate optimally. The reduction in circulating stress hormones removes the inhibitory brake on GnRH, facilitating an increase in LH, which subsequently stimulates testosterone production in men ⁷¹⁶. Furthermore, the potent antioxidant properties of withanolides protect Leydig cells - the primary site of testosterone synthesis in the testes - from oxidative stress and lipid peroxidation, ensuring these cells can effectively respond to LH signaling ¹¹¹².

Regulation of the Hypothalamic-Pituitary-Thyroid Axis

While the HPA and HPG axes operate with a degree of inverse correlation, the hypothalamic-pituitary-thyroid (HPT) axis is also deeply integrated into stress adaptation and systemic metabolism. Chronically elevated cortisol suppresses the HPT axis, reducing the production of thyroxine (T4) by the thyroid gland and inhibiting the peripheral conversion of T4 into the more biologically active triiodothyronine (T3) ¹⁹²⁰.

Ashwagandha appears to support and stimulate thyroid function through two distinct, parallel pathways. First, the reduction of cortisol via HPA-axis modulation removes the glucocorticoid-induced suppression of thyroid hormone synthesis ²⁰. Second, clinical and animal evidence suggests that withanolides may directly stimulate the thyroid gland. This direct action increases the biosynthesis of T4 and facilitates its conversion to T3, independently of the cortisol-mediated relief pathway ¹³²⁰. This dual mechanism explains why ashwagandha can exert pronounced effects on circulating thyroid hormones.

Clinical Efficacy for Stress and Anxiety

The primary, and most robustly supported, clinical application of ashwagandha is the amelioration of psychological stress, anxiety, and stress-related fatigue. Clinical trials consistently measure these outcomes using both subjective psychometric questionnaires - such as the Perceived Stress Scale (PSS), the Hamilton Anxiety Rating Scale (HAM-A), and the Depression, Anxiety, and Stress Scale (DASS-21) - as well as objective biochemical markers, predominantly morning serum cortisol and DHEA-S.

Meta-Analytical Evidence on Perceived Stress

Multiple systematic reviews and meta-analyses published in leading academic journals between 2022 and 2026 confirm that ashwagandha root extract significantly reduces anxiety and stress symptomology compared to placebo. A highly cited 2022 meta-analysis by Akhgarjand et al., published in Phytotherapy Research, pooled data from 12 randomized controlled trials (RCTs) involving 1,002 participants. The researchers found a significant reduction in both anxiety (Standardized Mean Difference [SMD]: -1.55) and stress levels (SMD: -1.75) compared to placebo ¹³¹⁴. The authors conducted non-linear dose-response analyses and noted a favorable effect for stress reduction at daily dosages between 300 mg and 600 mg ¹³.

Subsequent meta-analyses have reinforced these psychometric findings. A 2024 review by Arumugam et al. encompassing nine RCTs and 558 patients confirmed significant improvements in PSS scores and HAM-A scores following ashwagandha administration ¹⁵. More recently, a 2025 analysis by Bachour et al. of 15 studies (873 patients) demonstrated sustained improvements at eight weeks of treatment, with significant reductions in the HAM-A score and the PSS scale ¹⁶. Furthermore, an umbrella review by Alsanie et al. in 2026 evaluating 22 RCTs noted significant improvements across stress, anxiety, and depressive symptoms, concluding that supplementation exhibits a strong dose-response relationship for psychological variables ²⁵²⁶.

While the vast majority of analyses confirm subjective stress reduction, some variations in the data exist. Albalawi (2025) conducted a targeted meta-analysis that found a statistically significant reduction in biological cortisol but failed to find a corresponding significant reduction in perceived stress scores on the PSS ¹⁷. This discrepancy highlights a potential disconnect between physiological biomarkers and psychological perception in certain patient cohorts, suggesting that while ashwagandha predictably downregulates the HPA axis, subjective improvements in mental state may depend heavily on external environmental factors, baseline psychiatric conditions, and the duration of therapy ¹⁷.

Dose-Response and Extract Variations

The clinical literature features several proprietary, standardized extracts of ashwagandha, which introduces some heterogeneity into the data. The most frequently studied extract is KSM-66, which is derived exclusively from the root of the plant and standardized to contain at least 5% withanolides ¹⁸²⁹. Other prominent extracts include Sensoril, which utilizes both roots and leaves and is standardized to higher withanolide glycoside concentrations, and Shoden, a purified extract containing up to 35% withanolide glycosides ⁸¹⁹³¹.

Clinical trials suggest that lower doses of highly concentrated extracts can achieve similar physiological results to higher doses of standard root powder. For instance, a double-blind, placebo-controlled study evaluating the Shoden extract demonstrated that a relatively low dose of 240 mg per day over 60 days was sufficient to achieve statistically significant reductions in HAM-A anxiety scores and lower circulating cortisol levels in stressed adults ⁸. Conversely, trials utilizing Sensoril have confirmed that doses as low as 125 mg per day can effectively attenuate chronic stress parameters in a dose-dependent manner ²⁰. However, some practitioners and researchers advocate for standard root-only extracts administered at higher volumes (typically 300 mg to 600 mg daily), citing a more extensive history of traditional safety and broader replication in peer-reviewed literature ⁵²⁹.

Physiological Biomarker Dynamics: Cortisol and DHEA-S

The subjective improvements in mood, resilience, and sleep quality observed in clinical trials are closely mirrored by tangible reductions in serum cortisol and its associated steroidal hormones. In healthy adults experiencing high baseline stress, 60 to 90 days of ashwagandha supplementation generally results in substantial declines in morning fasting cortisol ⁸.

In a 60-day, double-blind, placebo-controlled study involving 60 chronically stressed adults, supplementation with 240 mg of standardized ashwagandha extract yielded a 23% reduction in morning cortisol and an 8.2% decrease in DHEA-S, compared to nominal baseline fluctuations in the placebo group ⁸. Another clinical trial involving 130 chronically stressed participants taking 300 mg of extract over 60 days recorded reductions in serum cortisol of up to 27.9% ²¹.

The simultaneous reduction of DHEA-S alongside cortisol is a critical neuroendocrine finding. DHEA-S is an endogenous steroid hormone produced by the adrenal cortex. A reduction in both cortisol and DHEA-S indicates a comprehensive moderating effect on overall HPA axis hyperactivity, rather than isolated interference with cortisol synthesis pathways ⁸. The data indicates that ashwagandha does not suppress adrenal output indiscriminately; it acts as a true adaptogen, lowering cortisol in hyper-aroused states while preventing complete adrenal exhaustion ²².

It is important to contextualize the magnitude of these cortisol reductions. In clinical research concerning stress management interventions, mindfulness meditation and relaxation techniques typically yield moderate effect sizes for cortisol reduction (g = ~0.34) ³⁵³⁶. By comparison, the pharmacological intervention of ashwagandha consistently produces large effect sizes in cortisol attenuation, rivaling or exceeding the physiological benefits of intensive cognitive-behavioral stress management programs ¹⁵²³.

Impact on Testosterone and Male Reproductive Health

The relationship between ashwagandha and testosterone is clinically established, though its hormonal effects exhibit a high degree of sexual dimorphism. The botanical consistently demonstrates androgenic properties in men - particularly those presenting with high psychological stress, systemic fatigue, or clinical infertility - but it does not exert similar testosterone-elevating effects in women ⁵⁸²⁴.

Androgen Response Disparities Between Sexes

A comprehensive 2026 meta-analysis assessing the hormonal health impacts of ashwagandha across 23 RCTs and 1,706 participants concluded that supplementation significantly increases testosterone levels in men. The pooled data demonstrated a mean difference of +57.43 ng/dL in male participants taking the botanical compared to those on placebo ⁵²⁴. Conversely, the same robust analysis found no significant increase in testosterone among female participants (+5.09 ng/dL, statistically non-significant), confirming that ashwagandha does not induce virilization or inappropriate androgen excess in women ⁵.

The male-specific androgenic response was further detailed in a 16-week randomized, double-blind, placebo-controlled crossover study involving 57 men aged 40 - 70 presenting with mild fatigue. The cohort received either a standardized ashwagandha extract or a placebo for an 8-week period. The results demonstrated that ashwagandha intake was associated with a 14.7% greater increase in salivary testosterone and an 18% greater increase in DHEA-S compared to the placebo phase ³⁹²⁵.

Despite these clear hormonal shifts, the researchers noted no statistically significant between-group differences in subjective psychometric measures of fatigue, physical vigor, or sexual well-being at the end of the 8-week intervention ³⁹²⁵. This specific finding suggests that while a 15% increase in testosterone is physiologically measurable and statistically significant, it may not immediately translate into distinct clinical symptom resolution or enhanced libido for aging, eugonadal men who lack a severe baseline deficiency ³⁹²⁵.

Clinical Contexts for Testosterone Elevation

The magnitude of testosterone elevation achieved through ashwagandha supplementation appears highly dependent on the baseline physiological and psychological state of the patient. Ashwagandha acts as a secondary, supportive androgen booster; it does not introduce exogenous hormones into the bloodstream, nor does it override natural endocrine feedback loops. Instead, it optimizes the endogenous environment to allow the testes to produce testosterone at their genetic potential. This effect is most pronounced in three specific clinical populations:

1. Stress-Induced Hypogonadism: In men whose testosterone production is artificially suppressed by high circulating cortisol and chronic stress, ashwagandha provides significant benefit. By lowering cortisol, the herb reduces the glucocorticoid-mediated negative feedback on the HPG axis. This allows luteinizing hormone (LH) signaling from the pituitary to recover, which in turn stimulates the Leydig cells to resume normal testosterone synthesis ⁷¹².
2. Resistance-Trained Athletes: Physical exercise, particularly intense resistance training, inherently stresses the body. In a clinical trial of 57 healthy, resistance-trained young men, supplementation with 600 mg/day of root extract for 8 weeks boosted testosterone by approximately 15% ⁵. This hormonal optimization correlated with significant secondary gains, including increased muscle strength, larger muscle cross-sectional area, improved exercise recovery, and reduced body fat percentages compared to the placebo group undergoing the identical training regimen ⁵¹¹.
3. Male Factor Infertility: Ashwagandha exhibits profound benefits for populations of oligospermic (low sperm count) and stressed infertile men. In a 90-day trial involving 46 oligospermic men, administration of 675 mg/day of a standardized root extract increased serum testosterone by 17%. More importantly, this hormonal shift was accompanied by dramatic improvements in reproductive viability: a 167% increase in sperm count, a 53% increase in semen volume, and a 57% improvement in sperm motility ⁵¹⁸. These reproductive benefits are attributed not only to elevated androgens but also to the herb's antioxidant capacity, which actively reduces oxidative stress and lipid peroxidation within the testicular tissue, protecting developing spermatozoa ¹¹¹⁹¹⁸.

Clinical Relevance of Modest Androgen Increases

While a 15% to 17% increase in endogenous testosterone is less dramatic than the supraphysiological spikes achieved via pharmaceutical testosterone replacement therapy (TRT), it remains clinically relevant. Research conducted by the Veterans Affairs (VA) health system investigating testosterone thresholds indicates that even modest increases in circulating testosterone can yield measurable improvements in metabolic health and body composition for aging men ²⁶²⁷. Studies show that elevating testosterone - even within the lower boundaries of the normal physiological range - can support a reduction in Hemoglobin A1c (HbA1c), improve fasting blood glucose levels, and increase total fat-free mass (lean muscle) ²⁶. Therefore, the androgenic support provided by ashwagandha, while subtle, can contribute meaningfully to long-term metabolic and musculoskeletal health.

Thyroid Function and Autoimmune Considerations

The biochemical interaction between ashwagandha and the thyroid gland is an area of intense clinical interest, representing both a significant therapeutic opportunity and a tangible pharmacological risk. While the herb's ability to lower cortisol and support testosterone is generally viewed as benign for the vast majority of healthy adults, its direct and potent stimulatory effect on thyroid hormone synthesis mandates specific clinical caution.

Treatment of Subclinical Hypothyroidism

Ashwagandha has demonstrated notable clinical efficacy in the management of subclinical hypothyroidism. This endocrine condition is characterized by an elevated thyroid-stimulating hormone (TSH) level occurring alongside normal reference ranges of circulating T3 and T4, often manifesting clinically as mild fatigue, weight gain, and cognitive slowing ⁷¹⁹⁴³.

In a pivotal 2018 double-blind, randomized, placebo-controlled trial conducted by Sharma et al., 50 adult patients diagnosed with subclinical hypothyroidism (defined as a TSH between 4.5 and 10 IU/L) were administered 600 mg of ashwagandha root extract daily (divided into two 300 mg doses) for an 8-week period ¹⁹⁴⁴⁴⁵. The intervention yielded highly significant, progressive alterations in thyroid indices compared to the placebo group.

After 4 weeks, patients began showing measurable improvements, which compounded over the remainder of the trial. By the end of the 8-week period, the patients taking ashwagandha exhibited a massive 41.5% increase in serum T3, a 19.6% increase in T4, and a corresponding 17.4% reduction in TSH ¹⁹⁴³⁴⁵. These shifts effectively normalized overall thyroid function in the majority of the treatment group, bringing them back into optimal physiological ranges. The placebo group saw no significant improvements in any thyroid parameter. The dual mechanism underlying this profound outcome is believed to be a combination of central HPA-axis downregulation (removing cortisol-induced HPT suppression) and a direct stimulatory effect of withanolides on the thyroid gland's cellular machinery ¹³¹⁹²⁰.

Implications for Hashimoto's Thyroiditis

Hashimoto's disease is an autoimmune condition where the body's immune system erroneously attacks the thyroid gland, leading to progressive tissue destruction and subsequent hypothyroidism. For patients with Hashimoto's, the clinical guidance regarding ashwagandha use is highly nuanced and occasionally debated among integrative endocrinologists.

The primary concern stems from ashwagandha's immunomodulatory characteristics. Depending on the physiological environment and how the herb is consumed, it can act as an immune stimulant. Specifically, when taken with dietary fats, ashwagandha has been shown to stimulate a T-helper 1 (Th1) immune response ⁴³⁴⁶. In states of autoimmune disease, there is often an existing overstimulation of the Th1 response and an understimulation of the counteracting Th2 response. Theoretically, stimulating immune activity in a patient whose immune system is actively destroying their thyroid could exacerbate the autoimmune flare and worsen the disease progression ²⁰⁴⁷.

However, many clinical practitioners find that the net effect of ashwagandha in Hashimoto's patients is overwhelmingly positive. The herb possesses potent systemic anti-inflammatory properties, specifically the inhibition of nuclear factor kappa B (NF-kappaB), a protein complex that controls the transcription of DNA and plays a critical role in regulating the immune response to infection and autoimmune inflammation ⁴³⁴⁶. Furthermore, because chronic stress and elevated cortisol aggravate Hashimoto's symptoms and further suppress residual thyroid function, the adaptogenic stress relief provided by ashwagandha often results in significant symptomatic improvement regarding energy levels and brain fog ⁴⁵⁴⁷.

Endocrinology consensus suggests that while ashwagandha is not strictly contraindicated in Hashimoto's disease, it should not be utilized as a standalone cure for autoimmunity. Patients utilizing the herb require close physician monitoring of their thyroid peroxidase (TPO) antibodies, TSH, and free T4 panels to ensure the immunomodulatory effects do not accidentally trigger a hyperthyroid shift or accelerate tissue degradation ²⁰⁴⁸.

Risks of Thyrotoxicosis and Hyperthyroidism

The exact thyroid-stimulating properties that make ashwagandha beneficial for subclinical hypothyroidism render it distinctly dangerous for patients with pre-existing hyperthyroidism or Graves' disease ²⁰⁴⁹. In these populations, the unmonitored addition of a thyroid-stimulating botanical can push T3 and T4 output to pathological levels, triggering severe hyperthyroid symptoms including tachycardia, tremors, severe anxiety, and dangerous unintentional weight loss ²⁰.

Medical literature contains several rare but documented case reports of thyrotoxicosis - a severe and potentially life-threatening state of excess thyroid hormone - induced directly by ashwagandha supplementation. A literature review identified instances of thyrotoxicosis in women ranging in age from 32 to 73 years old who were consuming ashwagandha extracts ¹. One notable case involved a 47-year-old patient who developed fatigue, low TSH, and abnormally elevated T3 and T4 after two months of unmonitored ashwagandha use. Following the complete cessation of the supplement, the patient's thyroid parameters normalized within 15 days, confirming the botanical as the causative agent ²⁸.

Furthermore, for hypothyroid patients actively taking prescription thyroid hormone replacement therapies (such as levothyroxine), ashwagandha can unpredictably compound the effects of the medication. The endogenous stimulation of T3 and T4 by the herb, combined with the exogenous hormones provided by the drug, can easily push a patient out of their carefully calibrated therapeutic range, necessitating frequent blood monitoring and potential medication adjustments ¹²⁰⁴⁹.

Safety Profile and Hepatotoxicity

In standard, controlled clinical trials lasting 8 to 12 weeks, ashwagandha root extract is consistently reported to be safe and highly tolerated by adult participants. The most frequently observed adverse effects in trial settings are mild, transient, and non-severe, typically including minor gastrointestinal discomfort, loose stools, nausea, mild headaches, and daytime drowsiness ¹⁵¹. However, the exponential rise in global over-the-counter consumption has generated much broader, real-world pharmacovigilance data. This extended data set has revealed severe, albeit rare, adverse events concerning liver function that have prompted significant action from national regulatory agencies.

Characteristics of Herb-Induced Liver Injury

While generally recognized as safe, emerging medical literature has identified ashwagandha as a potential causative agent for herb-induced liver injury (HILI). A comprehensive systematic review published in 2024 evaluated 37 published case reports of severe liver injury explicitly associated with ashwagandha consumption ⁵².

The demographic data from these cases revealed an average patient age of 41 years (ranging from 16 to 75), with a slight male predominance (22 males to 15 females). The clinical presentation of hepatotoxicity was stark: 78% of affected patients presented with severe jaundice, and 51% experienced pruritis (intense itching due to bile salt accumulation). Approximately 30% of patients reported prodromal symptoms such as nausea, vomiting, profound malaise, or abdominal pain prior to the onset of jaundice ⁵².

Laboratory evaluations of liver enzymes confirmed significant hepatic distress. The average peak aspartate aminotransferase (AST) reached 377 U/L, and average peak alanine aminotransferase (ALT) soared to 562 U/L. The predominant clinical pattern of liver injury was hepatocellular (49%), indicating direct damage to the liver parenchyma, followed by mixed injury patterns (24%) and cholestatic injury (19%), which affects bile flow ⁵².

While the vast majority of cases resolved either spontaneously upon the immediate cessation of the supplement or through pharmacological intervention with corticosteroids or N-acetylcysteine, the outcomes were not universally benign. The review noted that the hepatotoxicity progressed to severe outcomes in a small fraction of patients, resulting in one individual requiring a full liver transplantation and three reported fatalities directly linked to ashwagandha-induced liver failure ⁵².

Root Versus Leaf Extract Safety Profiles

The mechanism behind ashwagandha's occasional hepatotoxicity remains a subject of intense scientific debate, but recent toxicological evaluations strongly point toward issues of botanical adulteration and the use of non-root plant parts in commercial supplements. Traditionally, Ayurvedic medicine utilized only the root of the Withania somnifera plant for internal consumption ²²⁹. However, modern commercial pressures have led some manufacturers to include leaves and aerial parts of the plant in their extracts to artificially inflate the total withanolide percentage and reduce production costs.

Advanced computational AI analyses, utilizing Natural Language Processing (NLP) and Quantitative Structure-Activity Relationship (QSAR) models, have systematically evaluated the safety profiles of different parts of the ashwagandha plant at the molecular level. These models indicate that the root of Withania somnifera exhibits a superior safety profile regarding liver and reproductive toxicity compared to the leaves or aerial parts ²⁹⁵⁴. The predictive models suggest that the vast majority of molecules capable of posing a liver toxicity risk are localized almost exclusively in the non-root parts of the plant. When assessing purely root-derived molecules, ashwagandha performed better than the average for both edible plants and other common herbal supplements ²⁹⁵⁴³⁰.

Acknowledging this stark discrepancy in plant chemistry, national regulators are beginning to alter supplement manufacturing guidelines. In April 2026, the Food Safety and Standards Authority of India (FSSAI) issued a strict regulatory advisory explicitly prohibiting the use of ashwagandha leaves and their extracts in all foods and dietary supplements ³¹. The directive limits permissible ashwagandha products strictly to root extracts in an effort to minimize adulteration, improve industry transparency, and mitigate the risks of severe hepatotoxicity ³¹.

Global Regulatory Actions and Bans

The combination of the herb's potent endocrine-altering effects and emerging reports of liver toxicity has led to a polarized regulatory landscape. While the United States Food and Drug Administration (FDA) continues to classify ashwagandha generally as a botanical dietary supplement with minimal pre-market scrutiny, European health authorities have adopted a far more aggressive, precautionary stance.

The Danish Veterinary and Food Administration Ban

The most severe regulatory action taken against ashwagandha occurred in April 2023, when Denmark became the first European Union nation to enact a complete ban on the sale of ashwagandha in food and dietary supplements ⁹¹¹¹². The Danish Veterinary and Food Administration (DVFA) ordered the immediate withdrawal of all products containing the herb from the domestic market.

This sweeping prohibition was predicated entirely on a 2020 risk assessment authored by the Technical University of Denmark (DTU). The DTU report concluded that a safe lower limit for ashwagandha consumption could not be mathematically established due to poor data quality in existing literature and the lack of molecular standardization across commercially available extracts ¹⁰¹¹¹². The assessment cited profound concerns regarding the herb's established capacity to cause hormonal disruption - specifically noting its documented ability to alter sex hormones and stimulate the thyroid gland. Furthermore, the DTU report referenced historical, traditional Ayurvedic literature suggesting the plant possesses abortifacient properties, prompting regulatory fears of severe reproductive toxicity for pregnant women ⁹¹¹¹².

Scientific Pushback and Broadening Pharmacovigilance

The Danish ban has generated significant controversy and backlash within the scientific community and the botanical supplement industry. Critics of the DTU report point out a critical methodological flaw: the university did not generate any new toxicological data or conduct new clinical trials. Instead, the authors extrapolated risks by synthesizing historical texts and evaluating preclinical animal models that were exposed to excessively high, non-physiological doses of the extract ²¹¹.

Pharmacognosy researchers, including experts from the University of Mississippi's National Center for Natural Products Research, have publicly scrutinized the ban, arguing that the DTU report lacked the solid scientific foundation required to justify prohibition ⁹. These researchers highlight that numerous modern clinical trials have consistently demonstrated a 'No Observed Adverse Effect Level' (NOAEL) for standardized root extracts at common therapeutic doses, and that decades of widespread global consumption have not yielded epidemiological evidence of the plant acting as an abortifacient in humans ²⁹.

Despite this pushback, the precautionary approach is spreading across Europe. Following Denmark's lead, regulatory bodies in other nations have issued strong public advisories. In 2024, the French National Agency for Food, Environmental and Occupational Health Safety (ANSES) issued formal guidance warning against ashwagandha consumption for specific vulnerable populations, explicitly including pregnant women, children under 18, and individuals with a history of liver disease, thyroid conditions, or hyperandrogenism ¹⁰⁵⁷. Similarly, the Netherlands Pharmacovigilance Centre (Lareb) documented multiple domestic cases of liver toxicity and has advised against broad consumption ¹⁰³². Currently, the European Medicines Agency's Committee on Herbal Medicinal Products (EMA HMPC) continues to actively monitor the safety dossier and adverse event reports of the botanical, though it has not yet recommended an EU-wide ban ⁵⁷³³³⁴.

Conclusion

The clinical evidence surrounding ashwagandha confirms its pharmacological efficacy as a potent adaptogen capable of significant central neuroendocrine modulation. Through central GABAergic activity, it exerts a reliable inhibitory effect on the HPA axis, resulting in reproducible, dose-dependent reductions in serum cortisol and perceived psychological stress that rival behavioral interventions. In men, this suppression of circulating cortisol facilitates a permissive environment for the HPG axis, consistently elevating testosterone levels by approximately 15% and significantly improving reproductive biomarkers in infertile populations, while demonstrating no androgenic effect in women.

Regarding the thyroid, ashwagandha offers a distinct, dual-pathway stimulatory effect on the HPT axis, successfully normalizing T3, T4, and TSH in patients suffering from subclinical hypothyroidism. However, this exact mechanism poses a tangible risk of thyrotoxicosis in healthy or hyperthyroid individuals and deeply complicates its concurrent use alongside standard prescription thyroid replacement therapies.

While controlled clinical trials emphasize the botanical's safety and high tolerability, expanding real-world pharmacovigilance highlights a rare but severe risk of herb-induced liver injury. Toxicological evidence suggests this hepatotoxicity is primarily associated with poorly standardized extracts or those adulterated with the leaves of the plant. This dichotomy between clinical utility and toxicological risk has fueled regulatory polarization, culminating in complete market bans in certain European jurisdictions. Moving forward, the clinical and therapeutic utility of ashwagandha relies on strict manufacturing adherence to root-only, standardized extracts, paired with careful physician monitoring for patients presenting with pre-existing thyroid, hepatic, or autoimmune conditions.