NICEVIVA
MONOGRAPH SPEC LATEST 2026

Ashwagandha (Male Fertility)

MEN HEALTH · Evidence Monograph

Ashwagandha (Male Fertility) is an evidence-graded men health monograph evaluated across 18 peer-reviewed PubMed studies (2 meta-analyses, 3 systematic reviews, and 5 randomized controlled trials, encompassing n = 5,777 cumulative participants). Current clinical evidence is rated GRADE High (4.0 / 4.0) for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

Evidence Grade (GRADE) High (4.0 / 4.0)
Indexed PubMed Studies 18 Studies
Meta-Analyses · Reviews 2 Meta · 3 Systematic Reviews
Randomized Trials (RCT) 5 RCTs (7 Double-Blind)
Cumulative Participants n = 5,777
Reported Trial Dosages 25 g · 1000 mg · 1500 mg
Trial Duration Range 7 days · 42 days · 40 days
Reading Time ~9 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support (supported by 18 indexed PubMed studies, GRADE High).
  2. 02 Adults matching clinical trial dosing protocols (25 g · 1000 mg · 1500 mg) over a structured 7 days evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Clinically Standardized Formulation
Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.
Dose Adjustment Signal: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.
CHRONOBIOLOGY · Optimal Dosing Window PM 12:30
With Breakfast or Lunch
Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
Primary men health clinical efficacy (18 PubMed studies)
Quantitative biomarker & outcome analysis (15 studies with effect-size/sample data)
Randomized controlled trial verification (5 RCTs · 7 double-blind)
Systematic review & meta-analysis synthesis (2 meta-analyses · 3 reviews)
01

What Is Ashwagandha (Male Fertility) & Why Does Form Matter?

Ashwagandha (Male Fertility) is classified under MEN HEALTH and has been investigated across 18 peer-reviewed PubMed publications for its role in targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (25 g, 1000 mg, 1500 mg).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Ashwagandha (Male Fertility) frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (5 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Ashwagandha (Male Fertility) acts on pathways governing targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Ashwagandha (Male Fertility) an overall evidence rating of GRADE High (4.0 / 4.0) based on 18 PubMed studies: 2 meta-analyses, 3 systematic reviews, and 5 randomized controlled trials (7 double-blind, n = 5,777 total participants).

Representative peer-reviewed findings include: • PMID:32201301 (2020) — "Safety and clinical effectiveness of Withania Somnifera (Linn.) Dunal root in human ailments." (Retrieved thirty(30) human studies demonstrated reasonable efficacy of root preparations in subclinical hypothyroidism (1), schizophrenia (3), chronic stress (2), insomnia (2), anxiety (1), memory and cognitive improvement (2), obsessive-compulsive disorder (1), rheumatoid arthri) • PMID:35993457 (2022) — "Herbal Medicines for Idiopathic Male Infertility: A Systematic Review." (CONCLUSION: Whitania somnifera roots, Alpinia officinarum, Nigella sativa seeds, Tomato, and Ceratonia siliqua and the formulation of Xperm, PHF, Churna Ratnam, Svaguptadi Churna, Y virilin capsule, manix capsule, and Tradafertil tablet revealed successful outcomes in treatment o) • PMID:35234023 (2022) — "The most important medicinal plants affecting sperm and testosterone production: a systematic review." (CONCLUSIONS: Plants can probably be useful in increasing fertility due to their antioxidant power and low side effects.)

Quantitative Clinical Effect-Size Distribution (Forest Plot)

Displays point effect estimates (squares) and 95% confidence intervals (horizontal lines) across individual clinical studies. Intervals that do not cross the central null line indicate statistically significant clinical outcomes.

Study (PMID · Year)SMD Effect Size & 95% CI DistributionEstimate (95% CI)PMID 40746175-0.35 (-1.64–-0.69)PMID 39026098-1.05 (-1.85–-0.24)-2.1Null (0)0.28Metric: SMD
05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Clinically Standardized Formulation. Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 25 g · 1000 mg · 1500 mg · 600 mg/day over 7 days · 42 days · 40 days · 12 weeks. Optimal timing window: PM 12:30 · With Breakfast or Lunch (Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.

Adjustment & Discontinuation Signals: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.

07

Prescription Drug Interactions & Contraindications

No major high-risk prescription contraindications are flagged in the primary index for Ashwagandha (Male Fertility), but divalent minerals, fat-soluble compounds, and botanical extracts can still alter absorption or CYP450 metabolism of concurrent medications.

Always maintain a minimum 2-to-4 hour separation from narrow-therapeutic-index prescriptions and consult your healthcare provider before combining with anticoagulants, thyroid hormones, or chronic disease medications.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (PM 12:30 · With Breakfast or Lunch) with a full glass of water.
  • Stay within clinically studied daily dosages (25 g · 1000 mg · 1500 mg) and re-evaluate efficacy after 7 days.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist if you take daily prescription medications for thyroid, cardiovascular, metabolic, or neuropsychiatric conditions.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (18 Studies) · 15 Quantitative Analyses

01
CLINICAL STUDY Journal of ethnopharmacology (2020) PMID: 32201301 ↗
Safety and clinical effectiveness of Withania Somnifera (Linn.) Dunal root in human ailments.
Clinical Trial Synthesis 2020 Clinical Study published in Journal of ethnopharmacology. Key conclusion: Retrieved thirty(30) human studies demonstrated reasonable efficacy of root preparations in subclinical hypothyroidism (1), schizophrenia (3), chronic stress (2), insomnia (2), anxiety (1), memory and cognitive improvement (2), obsessive-compulsive disorder (1), rheumatoid arthri
View Original PubMed Abstract ↓

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera popularly known as Aswagandha or Indian Ginseng/Poison Gooseberry have thousands years of history of use in Indian traditional medicine. Besides, finding place root of the plant as Indian Ginseng, Ayurveda also uses root of this plant as general health tonic, adaptogenic, nootropic, immunomodulatory etc. With its widespread and growing use, it becomes prudent to scientifically evaluate and document both the efficacy and safety of this plant in humans. AIM OF THE STUDY: Aswagnadha root is rapidly gaining popularity abroad for use as medicine. Current article attempts to primarily review the human efficacy and safety of Aswagandha generated through clinical trials. METHODS: A systematic search both for indexed and non-indexed literature was made for W. somnifera using various search engines and databases and the details of research articles pertaining to all clinical trials/human studies, animal studies addressing safety issues of CNS, CVS, general toxicity, mutagenicity, genotoxicity, reproductive safety and herb-drug interactions were reviewed and compiled comprehensively from full texts. RESULTS: A total of 69 (39 pre-clinical and 30 clinical) studies documenting efficacy and safety aspects were identified and the desired information of these studies is comprehensively presented in this review. Retrieved thirty(30) human studies demonstrated reasonable efficacy of root preparations in subclinical hypothyroidism (1), schizophrenia (3), chronic stress (2), insomnia (2), anxiety (1), memory and cognitive improvement (2), obsessive-compulsive disorder (1), rheumatoid arthritis (2), type-2 diabetes (2), male infertility (6), fertility promotion activity in females (1), adaptogenic (3), growth promoter in children (3) and chemotherapy adjuvant (1). Reasonable safety of root preparations of Aswagandha has been established by these retrieved 30 human trials. No serious adverse events or any changes in haematological, biochemical or vital parameters were reported in these human studies. Only mild and mainly transient type adverse events of somnolence, epigastric pain/discomfort and loose stools were reported as most com

02
SYSTEMATIC REVIEW Current drug discovery technologies (2022) PMID: 35993457 ↗
Herbal Medicines for Idiopathic Male Infertility: A Systematic Review.
Clinical Trial Synthesis 2022 Systematic Review published in Current drug discovery technologies involving n = 1,218 participants. Key conclusion: CONCLUSION: Whitania somnifera roots, Alpinia officinarum, Nigella sativa seeds, Tomato, and Ceratonia siliqua and the formulation of Xperm, PHF, Churna Ratnam, Svaguptadi Churna, Y virilin capsule, manix capsule, and Tradafertil tablet revealed successful outcomes in treatment o
View Original PubMed Abstract ↓

BACKGROUND: Various medications, surgeries, and assisted reproductive techniques are used to treat male infertility, but the high cost and low effectiveness have made these methods unpopular. The use of herbal medicines such as Withania somnifera, Ceratonia siliqua, Nigella sativa and Alpinia officinarum for the treatment of male infertility has become highly popular in recent years. OBJECTIVE: We conducted this systematic review to evaluate the recent scientific evidence regarding herbal medicines used to treat idiopathic male infertility (IMI). METHODS: Online literature resources were checked using different search engines, including ISI, Web of Knowledge, Medline, PubMed, Scopus, and Google Scholar. Date restrictions were applied to 2020, and the publication language was restricted to English and Persian. The risk of bias was evaluated using the Cochrane method. RESULTS: Out of 851 articles, 14 trials with 1218 participants were included. Of the 15 plants and medicinal products introduced in the selected studies, 12 cases were effective in treating male infertility. Each of these plants or products affects specific components of male fertility for which various mechanisms were mentioned, but most of them had antioxidant effects. No serious side effects were reported. CONCLUSION: Whitania somnifera roots, Alpinia officinarum, Nigella sativa seeds, Tomato, and Ceratonia siliqua and the formulation of Xperm, PHF, Churna Ratnam, Svaguptadi Churna, Y virilin capsule, manix capsule, and Tradafertil tablet revealed successful outcomes in treatment of idiopathic male infertility.

03
SYSTEMATIC REVIEW JBRA assisted reproduction (2022) PMID: 35234023 ↗
The most important medicinal plants affecting sperm and testosterone production: a systematic review.
Clinical Trial Synthesis 2022 Systematic Review published in JBRA assisted reproduction. Key conclusion: CONCLUSIONS: Plants can probably be useful in increasing fertility due to their antioxidant power and low side effects.
View Original PubMed Abstract ↓

OBJECTIVE: Infertility, defined as the inability to conceive after one year of intercourse without the use of contraception, affects 15% of couples. Many factors, such as genitourinary tract infections, endocrine disorders, immunological factors and drug-related injuries, affect the male reproductive system and cause infertility. Due to men's fear of infertility, it is very important to pay attention to medicinal plants that are effective in male fertility. Therefore, the aim of this study was to evaluate the medicinal plants that affect sperm and testosterone production in men. METHODS: In this review, we used the following search terms, consisting of herbal medicine, traditional medicine, traditional therapies, sperm, testosterone, testicles and Iran were used to retrieve the relevant articles published in the journals indexed in the Information Sciences Institute, Science Direct, PubMed, Scopus, PubMed Central and Scientific Information Databases. We searched and used papers published between 2000 and 2020. Then, we analyzed the eligible papers. We collected and analyzed 35 papers from the databases. We selected only the articles about herbs that affect sperm and testosterone production. RESULTS: Based on the results, herbs Apium graveolens, Cinnamomum camphora, Cornus mas, Satureja khuzestanica, Withania somnifera, Fumaria parviflora, zingiber officinale, cinnamomum zeylanicum and Phoenix dactylifera are used in the male reproductive system. CONCLUSIONS: Plants can probably be useful in increasing fertility due to their antioxidant power and low side effects.

04
RANDOMIZED TRIAL (RCT) JMIR research protocols (2026) PMID: 41950501 ↗
Effectiveness of Ayurvedic Nutritional Supplements and Yoga Protocol in Reducing the Incidence and Severity of Acute Mountain Sickness (AYAMS Study): Study Protocol for an Open-Label Randomized Controlled Trial.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in JMIR research protocols involving n = 830 participants. Key conclusion: OBJECTIVE: This randomized controlled trial (RCT) protocol aimed to assess the effectiveness of Ayurvedic nutritional supplements in conjunction with a yoga protocol in reducing the incidence and severity of AMS among healthy personnel stationed in the challenging high-altitude l
View Original PubMed Abstract ↓

BACKGROUND: Acute mountain sickness (AMS) poses a unique and formidable challenge to healthy personnel at high altitudes. OBJECTIVE: This randomized controlled trial (RCT) protocol aimed to assess the effectiveness of Ayurvedic nutritional supplements in conjunction with a yoga protocol in reducing the incidence and severity of AMS among healthy personnel stationed in the challenging high-altitude landscapes of the western Himalayas. METHODS: The proposed open-label, parallel-group RCT was conducted in apparently healthy individuals of any gender aged 18-50 years. The study was conducted at two distinct high-altitude stages within the western Himalayan region: stage I, situated at an elevation ranging from 9000 to 12,000 feet and stage II, spanning 12,000 to 15,000 feet. A total of 1660 participants (n=830 per stage) underwent random assignment in a 1:1 ratio to receive either the existing acclimatization schedule (AS) for high altitude (control group) or the Ayush intervention (Ayush group) in addition to the AS. The participants in the Ayush group received Ayurvedic nutritional supplements, including the Ayur-nutri kit (Ayush poshak yoga, 25 g, and Ayush cardiac care tea, 125 mL), twice daily, along with a yoga protocol (60 min daily) for 120 days. The primary outcome was the incidence of AMS, assessed using the 2018 Lake Louise Scoring System, and the proportion of participants with a Lake Louise Scoring System score of 6 or higher during the first 7 days from baseline. The secondary outcome measures included the proportion of participants with thromboembolic events; changes in coagulation and hemostasis activation markers and proinflammatory markers; and changes in self-reported negative emotional states (depression, anxiety, and stress), sleep quality, and overall quality of life (assessed through Depression Anxiety Stress Scale-21 items, Pittsburgh Sleep Quality Index, and 12-item short-form, respectively) on day 60 and day 120 from baseline. RESULTS: The study was funded in March 2023. The data collection was completed in December 2023. A total of 1660 participants were enrolled in the study. The analysis of the study data is in progress. The study outcom

05
SYSTEMATIC REVIEW Annals of agricultural and environmental medicine (2026) PMID: 41906501 ↗
Clinical evidence for the adaptogenic effects of Withania somnifera and Rhodiola rosea - A systematic review with molecular interpretation of psychometric outcomes.
Clinical Trial Synthesis 2026 Systematic Review published in Annals of agricultural and environmental medicine involving n = 590 participants. Key conclusion: rosea exert multi-dimensional adaptogenic effects, improving psychophysical health and supporting stress resilience.
View Original PubMed Abstract ↓

INTRODUCTION AND OBJECTIVE: Adaptogens are plant-derived substances that enhance the body's resilience to physical and psychological stress, with Withania somnifera and Rhodiola rosea being among the most studied representatives. The aim of this review is to evaluate the adaptogenic effects of W. somnifera and R. rosea based on randomized controlled trials (RCTs). REVIEW METHODS: A systematic literature search was performed using the key words: 'ashwagandha', 'Withania somnifera', 'Rhodiola rosea', and 'plant adaptogen'. Twenty-four studies met the inclusion criteria - 19 on W. somnifera and 5 on R. rosea. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: The analyzed trials involved 10-590 participants, aged 18-75 years, both healthy individuals and patients with stress-related or functional disorders. Interventions included standardized extracts at daily doses of 120-1000 mg for W. somnifera and 290-1500 mg for R. rosea, with supplementation lasting 3-16 weeks. Reported benefits included reduction of stress and anxiety, alleviation of depressive symptoms, improved sleep quality, enhancement of cognitive functions, increased muscle strength and recovery, and favourable hormonal changes. Methodological heterogeneity, short intervention periods, and small sample sizes remain limitations. SUMMARY: Evidence from RCTs confirms that W. somnifera and R. rosea exert multi-dimensional adaptogenic effects, improving psychophysical health and supporting stress resilience. Their mechanisms involve regulation of the hypothalamic-pituitary-adrenal axis, neurotransmission, immune and hormonal pathways. Further long-term, high-quality clinical trials, supplemented with molecular and systemic approaches, are required to consolidate their role in integrative, evidence-based medicine.

06
CLINICAL STUDY Nutrients (2026) PMID: 41599843 ↗
Ashwagandha Root Extract Stabilises Physiological Stress Responses in Male and Female Team Sports Athletes During Pre-Season Training.
Clinical Trial Synthesis 2026 Clinical Study published in Nutrients involving n = 28 participants; statistical significance reported at p = 0.001. Key conclusion: Conclusions: Supplementation with 600 mg/day of Ashwagandha root extract for 42 days may stabilise stress biomarkers, improve perception of recovery and enhance muscle strength in team sports athletes during pre-season training.
View Original PubMed Abstract ↓

Objectives: This study investigates the effects of 600 mg/day Ashwagandha root extract on physiological stress biomarkers, perception of recovery, muscle strength and aerobic capacity in team sports athletes during pre-season training, a period associated with elevated cortisol and accumulated training stress. Methods: Fifty-six athletes (26.8 ± 4.4 years, 1.74 ± 0.10 m, 79.4 ± 17.3 kg, 11.0 ± 7.1 career years) across rugby, water polo and football were randomly assigned to an Ashwagandha (ASH; n = 28, 14 males and 14 females) or placebo (PLA; n = 28, 14 males and 14 females) group for 42 days. Salivary biomarkers were assessed after training, muscle strength and aerobic capacity were measured during training, and perception of recovery was evaluated with Hooper Index (HI) the following day. Mixed ANOVA was used to determine group × time interactions and Bonferroni post hoc analyses were conducted for multiple pairwise comparisons. Results: In female athletes, salivary cortisol increased significantly in PLA (p = 0.001), while recovery parameters such as the overall HI score (p = 0.001), Delayed Onset Muscle Soreness (DOMS) (p = 0.008) and perception of fatigue (p = 0.026) scores improved significantly in ASH. In males, salivary cortisone increased significantly in PLA (p = 0.022), while Countermovement Jump (CMJ) improved significantly in ASH (p = 0.018). Pull-up performance increased in both PLA (p = 0.004) and ASH (p < 0.0001) in males. Conclusions: Supplementation with 600 mg/day of Ashwagandha root extract for 42 days may stabilise stress biomarkers, improve perception of recovery and enhance muscle strength in team sports athletes during pre-season training. The trial is registered on ClinicalTrials.gov with the ID NCT07041853.

07
CLINICAL STUDY Nutrition & metabolism (2025) PMID: 41204297 ↗
Impact of ashwagandha (Withania somnifera L.) supplementation on serum lipid concentrations and anthropometric parameters in adults with overweight and obesity: a double-blind, placebo-controlled pilot study.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Nutrition & metabolism involving n = 17 participants; statistical significance reported at p = 0.0082. Key conclusion: CONCLUSIONS: Ashwagandha supplementation improved serum lipid profiles in adults with overweight and obesity, suggesting potential lipid-lowering effects when combined with a prescribed dietary plan.
View Original PubMed Abstract ↓

BACKGROUND: Overweight and obesity are widespread in Mexico, often linked to dyslipidemia and higher cardiovascular risk. The search for safe and effective treatments has promoted interest in natural supplements such as Ashwagandha (Withania somnifera), recognized for its adaptogenic and potential lipid-lowering properties. OBJECTIVE: To assess the impact of Ashwagandha supplementation on serum lipid profiles and anthropometric parameters in Mexican adults with overweight and obesity. METHODS: A double-blind, randomized, placebo-controlled pilot clinical trial was carried out with 43 adults (n = 17 in the control group and n = 21 in the intervention group) over 40 days. Participants followed a monitored diet and received one daily capsule containing 500 mg of Ashwagandha or a placebo, in addition to a guided unrestricted dietary plan. Anthropometric and biochemical measurements were taken at baseline and after the intervention. In silico analysis was also performed to examine the binding affinity of Ashwagandha bioactive compounds to key proteins involved in lipid metabolism. RESULTS: Ashwagandha supplementation did not produce statistically significant changes in body weight, body mass index (BMI), or waist circumference (WC). However, significant reductions were observed in triglyceride and VLDL-c levels (p = 0.0082 and p = 0.0321, respectively). In silico results supported these findings, showing favorable interactions between compounds such as withanolide A and lipid metabolism targets, including AMPK, CETP, and LPL. CONCLUSIONS: Ashwagandha supplementation improved serum lipid profiles in adults with overweight and obesity, suggesting potential lipid-lowering effects when combined with a prescribed dietary plan. Also, it was possible to elucidate some metabolic pathways in which Ashwagandha composition has an influence on producing the reported effects. Further long-term studies with controlled dietary intake are needed to confirm these findings and clarify the underlying molecular mechanisms. © 2025. The Author(s).

08
CLINICAL STUDY Nutrients (2025) PMID: 41156498 ↗
Ashwagandha Does Not Enhance the Effect of High-Intensity Interval Training on Selected Energy Metabolism Parameters in Young Healthy Men.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Nutrients involving n = 20 participants; statistical significance reported at p = 0.05. Key conclusion: CONCLUSIONS: In young, healthy men, an 8-week HIIT programme significantly affects selected hormones related to energy metabolism of adipose (adiponectin) and muscle (irisin) tissues, but ashwagandha supplementation did not significantly affect any of the hormonal parameters anal
View Original PubMed Abstract ↓

BACKGROUND/OBJECTIVES: High-intensity interval training (HIIT) is considered an effective way in improving aerobic capacity and selected health parameters. Ashwagandha is an herb with possible health-promoting properties that may affect metabolism and performance. The aim of this study was to evaluate the effects of ashwagandha supplementation (600 mg/day) during an 8-week HIIT on body composition, lipid profile and hormone levels related to energy homeostasis in healthy young men. METHODS: The study was randomised, double-blind and placebo-controlled (Placebo group, PL, n = 20; ashwagandha, A, n = 18). HIIT was conducted on a rowing ergometer (3 times per week, 5-7 series of 1.5 min at 85-95% of maximum power, with intervals of 1.5 min at 70 W). Body composition (BIA, Tanita TBF 300P), serum lipid profile (tChol, HDL-cholesterol, LDL-cholesterol, TG) and serum levels of adiponectin, asprosin and irisin were analysed before (term 1) and after the8-week study (term 2). Both the lipid and hormonal profiles were measured in three time points: pre- and post-graded exercise test and after 24 h recovery period. RESULTS: Analysis showed no effect of training or supplementation on body composition and lipid profile (p > 0.05). In turn, the 8-week HIIT decreased resting levels of adiponectin and increased irisin levels post-exercise and after 24 h (p < 0.05). CONCLUSIONS: In young, healthy men, an 8-week HIIT programme significantly affects selected hormones related to energy metabolism of adipose (adiponectin) and muscle (irisin) tissues, but ashwagandha supplementation did not significantly affect any of the hormonal parameters analysed.

09
CLINICAL STUDY Nutrition, metabolism, and cardiovascular diseases (2025) PMID: 40883125 ↗
Lowering plasma S-Adenosylhomocysteine (SAH) in healthy adults with elevated SAH and normal homocysteine using nutritional supplementation.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Nutrition, metabolism, and cardiovascular diseases involving n = 40 participants. Key conclusion: CONCLUSION: This is the first demonstration of a nutritional product's effectiveness in decreasing plasma levels of SAH in otherwise healthy individuals with elevated SAH and normal Hcy.
View Original PubMed Abstract ↓

BACKGROUND AND AIMS: Elevated plasma levels of total homocysteine (Hcy) and S-Adenosylhomocysteine (SAH) are associated with increased risks of neurological and cardiovascular diseases (CVD). Whilst elevated plasma levels of Hcy can be managed through supplementation with B-group vitamins, there are no effective therapies for managing SAH in patients with elevated SAH and normal Hcy. SAH, a by-product of cellular methylation reactions, is considered a more sensitive biomarker for CVD than homocysteine (Hcy). The aim of this study was to determine if a test product containing ashwagandha extract, alpha-glycerylphosphorylcholine and creatine monohydrate, could lower plasma SAH levels in adults with elevated SAH and normal Hcy. METHODS AND RESULTS: In this prospective, randomized, single-blind, placebo-controlled clinical trial, 40 participants with elevated SAH (≥20 nmol/L) and normal Hcy (≤13 μmol/L) were randomized into two groups: 15 participants received the placebo, and 25 participants received the test product. The test product significantly lowered plasma SAH levels by approximately 12% and increased S-Adenosylmethionine (SAM): SAH ratio by approximately 26% after 12 weeks of supplementation compared to baseline. The test product was safe and well-tolerated, with no serious adverse events. No clinically relevant changes in vital signs and safety laboratory parameters were detected. CONCLUSION: This is the first demonstration of a nutritional product's effectiveness in decreasing plasma levels of SAH in otherwise healthy individuals with elevated SAH and normal Hcy. Hence, this test product offers a unique opportunity for investigating the impact of lowering plasma SAH on the risk of developing CVD and other diseases. Clincaltrial.gov registration: NCT05994794, 2023-08-16.

10
RANDOMIZED TRIAL (RCT) Current therapeutic research, clinical and experimental (2025) PMID: 40792075 ↗
Randomized, Double-Blind, Crossover Study Comparing the Bioavailability of 4 Ashwagandha (Withania somnifera (L.) Dunal) Extracts in Healthy Adults Under Fasting Condition.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Current therapeutic research, clinical and experimental. Key conclusion: CONCLUSIONS: These findings emphasize the critical role of withanolide glycosides in determining the PK performance of ashwagandha supplements.
View Original PubMed Abstract ↓

BACKGROUND: Withania somnifera (L.) Dunal, commonly known as ashwagandha, is a well-known plant in ayurvedic medicine, widely valued for its therapeutic potential. Although numerous clinical studies have explored its diverse health benefits, limited data are available on the pharmacokinetic (PK) properties and comparative bioavailability of its key bioactive constituents in humans. OBJECTIVE: This study aimed to evaluate and compare the oral bioavailability of 4 commercially standardized ashwagandha extracts under fasting conditions in healthy adults. METHODS: This randomized, double-blind, 4-treatment, 4-period, 4-sequence, single dose, 4-way crossover study was conducted in 16 healthy human volunteers. Participants received a single oral dose of 1 of 4 ashwagandha extracts, with varying compositions of 35% (Withania somnifera [WS]-35) or 10% (WS-10) withanolide glycosides, or 5% (WS-5) or 2.5% (WS-2.5) withanolides, each standardized to deliver 185 mg of total withanolides. Seventeen blood samples were collected over a 24-hour period after dose administration. Plasma concentrations of withanolide A, withanoside IV, withaferin A, and total withanolides were quantified, and PK parameters were calculated. RESULTS: Withania somnifera-35 had significantly superior bioavailability compared with the other extracts. The AUC0-t for total withanolides per gram of WS-35 was 118.28, 226.11, and 267.83 times better than WS-10, WS-5, and WS-2.5 respectively. Withania somnifera-35 exhibited a significantly higher Cmax, longer half-life, extended mean residence time, and lower systemic clearance, attributable to its higher withanolide glycoside content. CONCLUSIONS: These findings emphasize the critical role of withanolide glycosides in determining the PK performance of ashwagandha supplements. The enhanced bioavailability of WS-35 supports its preferential use in therapeutic applications and provides a strong rationale for further investigation into dose-response relationships and the long-term efficacy of standardized, high-bioavailability formulations. Clinical Trial Registry of India identifier: CTRI/2020/10/028397. © 2025 The Authors.

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