Clinical safety and tolerability evaluation of Withania somnifera (L.) Dunal (Ashwagandha) root extract in healthy human volunteers.

BACKGROUND: Withania somnifera (L.) Dunal, known as Ashwagandha, is an adaptogen with significant importance in Ayurveda for its potential health benefits in strength ('balavardhan') and muscle growth ('mamsavardhan'). Despite numerous studies on its efficacy, limited research is reported on its clinical safety and tolerability in healthy individuals. OBJECTIVE: This research evaluated the tolerability and safety of standardized Withania somnifera root extract (WSE) capsules (AgeVel®/Witholytin®) at 1000 mg/day dose upon oral administration in healthy male participants. METHOD: A non-randomized, open-label, single-treatment clinical study included eighteen healthy male participants aged 18 to 60. The participants were administered a dose of 500 mg of the WSE capsules twice daily for four weeks. Each capsule contained not less than 7.50 mg of total withanolides. The study evaluated various indicators in a cohort of healthy participants throughout the trial, including vital signs, organ function tests, urine analysis, X-ray and ECG, cardiorespiratory endurance, body fat percentage, lean body weight, adverse events profile, and tolerability of the WSE capsules. RESULTS: The participant's physical, hematological, and biochemical characteristics were normal, and no significant alterations or irregularities were observed in safety metrics like liver, kidney, and thyroid functions after administering AgeVel®/Witholytin®. CONCLUSION: This study found that healthy male participants could consume a standardized WSE at a daily dosage of 1000 mg for four weeks without any adverse effects. Future research should focus on long-term safety assessments in male and female participants.

Clinical pharmacokinetic evaluation of Withania somnifera (L.) Dunal root extract in healthy human volunteers: A non-randomized, single dose study utilizing UHPLC-MS/MS analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal; (Solanaceae), commonly known as Ashwagandha, is one of the most significant medicinal herbs in 'Ayurveda', a traditional Indian medicine used for centuries with evidence in scriptures. Ashwagandha was mentioned in old Ayurvedic medical literature such as Charaka Samhita and Sushruta Samhita for improving weight and strength, with multiple citations for internal and exterior usage in emaciation and nourishing the body. Ethnopharmacological evidence revealed that it was used to relieve inflammation, reduce abdominal swelling, as a mild purgative, and treat swollen glands. The root was regarded as a tonic, aphrodisiac, and emmenagogue in the Unani tradition of the Indian medicinal system. Further, Ashwagandha has been also described as an Ayurvedic medicinal plant in the Ayurvedic Pharmacopoeia of India extending informed therapeutic usage and formulations. Despite the widespread ethnopharmacological usage of Ashwagandha, clinical pharmacokinetic parameters are lacking in the literature; hence, the findings of this study will be relevant for calculating doses for future clinical evaluations of Ashwagandha root extract. AIM: This study aimed to develop a validated and highly sensitive bioanalytical method for quantifying withanosides and withanolides of the Ashwagandha root extract in human plasma to explore its bioaccessibility. Further to apply a developed method to perform pharmacokinetics of standardized Withania somnifera (L.) Dunal root extract (WSE; AgeVel®/Witholytin®) capsules in healthy human volunteers. METHODS: A sensitive, reliable, and specific ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS/MS) method was developed and validated for the simultaneous quantification of five major withanosides and withanolides (withanoside IV, withanoside V, withanolide A, withaferin A, and 12-deoxy-withastramonolide) in human plasma. Further for the study, eighteen healthy male volunteers (18-45 years) were enrolled in a non-randomized, open-label, single period, single treatment, clinical pharmacokinetic study and given a single dose (500 mg) of WSE (AgeVel®/Witholytin®) capsules containing not less than 7.5 mg of total withanolides under fasting condition. Later, pharmacokinetic profiles were assessed using the plasma concentration of each bioactive constituent Vs. time data. RESULTS: For all five constituents, the bioanalytical method demonstrated high selectivity, specificity, and linearity. There was no carryover, and no matrix effect was observed. Furthermore, the inter-day and intra-day precision and accuracy results fulfilled the acceptance criteria. Upon oral administration of WSE capsules, Cmax was found to be 0.639 ± 0.211, 2.926 ± 1.317, 2.833 ± 0.981, and 5.498 ± 1.986 ng/mL for withanoside IV, withanolide A, withaferin A, and 12-deoxy-withastramonolide with Tmax of 1.639 ± 0.993, 1.361 ± 0.850, 0.903 ± 0.273, and 1.375 ± 0.510 h respectively. Further, withanoside V was also detected in plasma; but its concentration was found below LLOQ. CONCLUSION: The novel and first-time developed bioanalytical method was successfully applied for the quantification of five bio-active constituents in human volunteers following administration of WSE capsules, indicating that withanosides and withanolides were rapidly absorbed from the stomach, have high oral bioavailability, and an optimum half-life to produce significant pharmacological activity. Further, AgeVel®/Witholytin® was found safe and well tolerated after oral administration, with no adverse reaction observed at a 500 mg dose.

Efficacy and safety assessment of protein supplement - micronutrient fortification in promoting health and wellbeing in healthy adults - a randomized placebo-controlled trial.

Protein supplements are extensively used for muscle building, weight loss, recovery from exercise, improving endurance & cardio-performance. Major challenge with protein supplement is undigested protein and impaired gut health which results in nausea, dehydration, diarrhea, constipation, indigestion, stomach pain, and decreased appetite. Several studies have linked plant protein with reduced metabolic syndrome incidence. Probiotics can improve gut health as well. The objective of the study is to assess the efficacy and safety of protein supplement in promoting health and wellbeing in healthy adults. The present trial is a double blind, multi-center, randomized, placebo controlled, clinical trial involving 60 healthy individuals. The treatment duration was of 90 days. The subjects were randomized to receive either protein supplement treatment or placebo control. Protein supplement significantly improved quality-of-life score by 85.76%, VO2 max by 42.92%, distance covered in 6 minutes, 100% individuals with at least 25% reduction in low energy events as compared to the control group. Protein supplement treatment reduced body weight (1.94 kg), waist circumference (2.46 cm), body mass index, waist circumference, hip circumference and body fat. Remarkable and significant improvement in digestive and sleep quality score, percent skeletal muscle was observed among protein supplement treated group. There were no clinically significant changes in hematological, biochemical and vital parameters; indicating safety of protein supplement. Present study concluded that protein supplement is safe and efficacious in weight management, improving high energy events, aerobic capacity, quality of life, digestive behavior score and sleep quality. This study ensures consumers about safety and effectiveness of protein supplement.

Efficacy and Safety of Aspirin, Promethazine, and Micronutrients for Rapid Clinical Recovery in Mild to Moderate COVID-19 Patients: A Randomized Controlled Clinical Trial.

Introduction In the present study, the combination of two tablets, one with Aspirin and Promethazine and the other with vitamin D3, C, and B3 along with zinc and selenium supplementation was proposed as an intervention (APMV2020). The ingredients in the formulation represent a precise, tailored therapy for the symptoms of COVID-19, combined with natural constituents to help the body itself build immunity to recover from infection. The present study was conducted to clinically validate the safety and efficacy of the APMV2020 tablets. Trial design The present trial is a randomized, multicentric, controlled clinical trial involving 260 mild to moderate COVID-19 patients. The treatment duration was of 10 days. Methodology The subjects were randomized to receive either the control intervention (clinical management protocol for COVID-19 advocated by the Indian Council of Medical Research (ICMR) or the test intervention (treatment with APMV2020 tablets along with the standard control treatment. The assessment days were baseline, days five and 10. Results APMV2020 significantly (<0.05) improved symptoms of COVID-19 like cough, myalgia, headache, and anosmia as compared to the control group. APMV2020 treatment also reduced inflammatory markers like lactate dehydrogenase (LDH), ferritin, and C-reactive protein (CRP). Conclusion APMV2020 can prove as a good candidate to be integrated into the COVID-19 management protocol. As it can offer speedy clinical recovery to reduce the burden on healthcare infrastructure, second, the combination shows significant anti-inflammatory potential to improve prognosis, and lastly, the immunomodulatory properties offer long-term protection that can help in combating long COVID symptoms and complications.

Correction: Efficacy and Safety of Aspirin, Promethazine, and Micronutrients for Rapid Clinical Recovery in Mild to Moderate COVID-19 Patients: A Randomized Controlled Clinical Trial.

[This corrects the article DOI: 10.7759/cureus.25467.].

Safety and efficacy of ozone therapy in mild to moderate COVID-19 patients: A phase 1/11 randomized control trial (SEOT study).

INTRODUCTION: The Corona virus disease 19 (COVID-19) has accounted for multiple deaths and economic woes.While the entire medical fraternity and scientists are putting their best feet forward to find a solution to contain this deadly pandemic, there is a growing interest in integrating other known alternative therapies in to standard care. This study is aimed at evaluating the safety and efficacy of ozone therapy (OT), as an adjuvant to the standard of care (SOC). METHODS: In the current randomized control trial, 60 patients with mild to moderate score NEWS score were included in two parallel groups (n = 30/group). The interventional group (OZ) received ozonized rectal insufflation and minor auto haemotherapy, daily along with SOC, while the control group (ST) received SOC alone. The main outcome measures included changes in clinical features, oxygenation index (SpO2), NEWS score, Reverse transcription polymerase chain reaction(RT-PCR), inflammatory markers, requirement of advanced care, and metabolic profiles. RESULTS: The OZ group has shown clinically significant improvement in the mean values of all the parameters tested compared to ST Group. However, statistical significance were only observed in RT-PCR negative reaction (P = 0.01), changes in clinical symptoms (P < 0.05) and requirement for Intensive care (P < 0.05). No adverse events were reported in OZ group, as against 2 deaths reported in ST group. CONCLUSION: OT when integrated with SOC can improve the clinical status and rapidly reduce the viral load compared to SOC alone, which facilitate early recovery and check the need for advanced care and mortality as demonstrated in this study.

An Open Label, Randomized, Comparative, Parallel Group, Multicenter, Prospective, Interventional, Clinical Study to Evaluate Efficacy and Safety of "AHPL/AYTOP/0113" in Comparison with "Framycetin Sulphate Cream" in Acute Wounds.

OBJECTIVES: The main objective of the present study was to assess efficacy and safety of AHPL/AYTOP/0113 cream, a polyherbal formulation in comparison with Framycetin sulphate cream in acute wounds. METHODOLOGY: It was an open label, randomized, comparative, parallel group and multi-center clinical study. Total 47 subjects were randomly assigned to Group-A (AHPL/AYTOP/0113 cream) and 42 subjects were randomly assigned to Group-B (Framycetin sulphate cream). All the subjects were advised to apply study drug, thrice daily for 21 days or up to complete wound healing (whichever was earlier). All the subjects were called for follow up on days 2, 4, 7, 10, 14, 17 and 21 or up to the day of complete wound healing. Data describing quantitative measures are expressed as mean ± SD. Comparison of variables representing categorical data was performed using Chi-square test. RESULTS: Group-A subjects took significantly less (P < 0.05) i.e., (mean) 7.77 days than (mean) 9.87 days of Group-B subjects for wound healing. At the end of the study, statistically significant better (P < 0.05) results were observed in Group-A than Group-B in mean wound surface area, wound healing parameters and pain associated with wound. Excellent overall efficacy and tolerability was observed in subjects of both the groups. No adverse event or adverse drug reaction was noted in any subject of both the groups. CONCLUSION: AHPL/AYTOP/0113 cream proved to be superior to Framycetin sulphate cream in healing of acute wounds.