Fixed-drug eruption caused by ashwagandha (Withania somnifera): a widely used Ayurvedic drug.

A 28-year-old man with decreased libido received ashwagandha in the usual daily dosage of 5 g for 10 days. During this period, he experienced a burning and/or itching sensation as well as discoloration of the skin/mucous membrane confined to the penis. He had a similar type of eruption at the same site 6 months prior while taking ashwagandha. Examination of the skin surface was conspicuous and marked by the presence of a dusky, erythematous, oval, eroded plaque of 3 cm, affecting the glans penis and prepuce (Figure). The drug was withdrawn and topical 0.05% clobetasol propionate cream was administered along with cetrizine dihydrochloride, an H1-receptor blocker, 10 mg daily for 1 month. There was a perceptible amelioration of the lesion, resulting in residual greyish white pigmentation. He was prescribed oral drug provocation with 1 g of ashwagandha powder. Within 12 hours, a flare-up developed at the earlier site, confirming the causality.

Withania somnifera as a safer option to hydroxychloroquine in the chemoprophylaxis of COVID-19: Results of interim analysis.

OBJECTIVES: To study the efficacy and safety of Withania somnifera (WS, Ashwagandha) in the prophylaxis against COVID-19 in high risk health care workers (HCW) in comparison to hydroxychloroquine (HCQ). To evaluate the general physical and mental health benefits of Ashwagandha. METHODS: A 16 week randomized prospective, open-label, parallel efficacy, two arm, multi-centre study. The primary efficacy measure was 'failure of prophylaxis' as confirmed COVID-19 by quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) at any time during the study period. This study on 400 participants from three centres was designed to establish non-inferiority for WS to HCQ for prophylaxis against COVID-19 at 80 % power and significance p < 0.025, one-sided. The interim analysis was carried out on 160 participants after completion of 8 weeks. RESULTS: Participants in both the arms were well-matched at the baseline characteristics. Forty participants in the HCQ group and 26 participants in the WS group reported mild AE. The symptoms of confirmed COVID-19 were found to be 3.7 % (95 % CI 1.3-10.5 %) in the HCQ and 1.3 % (95 % CI 0.02-6.7 %) in the WS arm amongst the first 160 participants completing 8 weeks. CONCLUSION: Our intent was to explore a safer option to HCQ. We report that WS was not found inferior to HCQ and its efficacy was within the 15 % non-inferiority margin set a priori. WS as an immunomodulator has other clinical benefits including reducing mental stress. The final report of this study is expected by end of August 2021.

Safety and clinical effectiveness of Withania Somnifera (Linn.) Dunal root in human ailments.

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 common (>5%); and giddiness, drowsiness, hallucinogenic, vertigo, nasal congestion (rhinitis), cough, cold, decreased appetite, nausea, constipation, dry mouth, hyperactivity, nocturnal cramps, blurring of vision, hyperacidity, skin rash and weight gain were reported as less common adverse events. Pre-clinical chronic toxicity studies conducted up to 8 months also found root extracts to be safe. No mutagenicity or genotoxicity was reported for the root; only mild CNS depression and increase in thyroxine (T4) levels were reported with rootby some studies. Further, there was no in vitro and in vivo inhibition seen for CYP3A4 and CYP2D6, the two major hepatic drug metabolizing enzymes. CONCLUSION: Root of the Ayurvedic drug W. somnifera (Aswagandha) appears a promising safe and effective traditional medicine for management of schizophrenia, chronic stress, insomnia, anxiety, memory/cognitive enhancement, obsessive-compulsive disorder, rheumatoid arthritis, type-2 diabetes and male infertility, and bears fertility promotion activity in females adaptogenic, growth promoter activity in children and as adjuvant for reduction of fatigue and improvement in quality of life among cancer patients undergoing chemotherapy. Properly designed, randomized-controlled, large-size, prospective trials with standardized preparations are needed to ascertain efficacy of Aswagandha root in previously studied and other new indications.

Effects of an Aqueous Extract of Withania somnifera on Strength Training Adaptations and Recovery: The STAR Trial.

Withania somnifera (Ashwagandha) is an Ayurvedic herb categorized as having "rasayana" (rejuvenator), longevity, and revitalizing properties. Sensoril® is a standardized aqueous extract of the roots and leaves of Withania somnifera. Purpose: To examine the impact of Sensoril® supplementation on strength training adaptations. Methods: Recreationally active men (26.5 ± 6.4 years, 181 ± 6.8 cm, 86.9 ± 12.5 kg, 24.5 ± 6.6% fat) were randomized in a double-blind fashion to placebo (PLA, n = 19) or 500 mg/d Sensoril® (S500, n = 19). Body composition (DEXA), muscular strength, power, and endurance, 7.5 km cycling time trial, and clinical blood chemistries were measured at baseline and after 12 weeks of supplementation and training. Subjects were required to maintain their normal dietary habits and to follow a specific, progressive overload resistance-training program (4-day/week, upper body/lower body split). 2 × 2 mixed factorial ANOVA was used for analysis and statistical significance was set a priori at p ≤ 0.05. Results: Gains in 1-RM squat (S500: +19.1 ± 13.0 kg vs. PLA +10.0 ± 6.2 kg, p = 0.009) and bench press (S500: +12.8 ± 8.2 kg vs. PLA: +8.0 ± 6.0 kg, p = 0.048) were significantly greater in S500. Changes in DEXA-derived android/gynoid ratio (S500: +0.0 ± 0.14 vs. PLA: +0.09 ± 0.1, p = 0.03) also favored S500. No other between-group differences were found for body composition, visual analog scales for recovery and affect, or systemic hemodynamics, however, only the S500 group experienced statistically significant improvements in average squat power, peak bench press power, 7.5 km time trial performance, and perceived recovery scores. Clinical chemistry analysis indicated a slight polycythemia effect in PLA, with no other statistical or clinically relevant changes being noted. Conclusions: A 500 mg dose of an aqueous extract of Ashwagandha improves upper and lower-body strength, supports a favorable distribution of body mass, and was well tolerated clinically in recreationally active men over a 12-week resistance training and supplementation period.

[Thyrotoxicosis following the use of ashwagandha]. / Thyreotoxicose na gebruik van Ashwagandha.

A 32-year-old healthy woman developed thyrotoxicosis while taking capsules that contained ashwagandha herbal extract for symptoms of chronic fatigue. She was not taking any other remedies or medications. During the first few weeks, she took the capsules only occasionally without any symptoms, but after increasing the dose, she experienced clinical symptoms indicative of thyrotoxicosis. This was confirmed by laboratory assessment. The symptoms resolved spontaneously after discontinuation of the ashwagandha capsules and laboratory values normalised. To our knowledge, this relationship has not been reported previously in humans. Data from animal studies, however, have suggested that ashwagandha can increase serum concentrations of thyroid hormones. This case study suggests that thyrotoxicosis is a potentially serious side effect of ashwagandha.