ashwagandha ( withania somnifera ) ( ws ) has been described in ayurvedic literature as a rasayana drug and is ascribed with the properties of balya and mamsavivardhan . in traditional clinical practice , our previous study of ws in peri- and post - menopausal women showed improvement in the quality of life , fatigability , and weakness . primary objective of this exploratory study , under reverse pharmacology , was to evaluate effects of incremental doses of ws on physiological , biochemical functions and vital signs in normal volunteers and assess its safety and tolerability . secondary objective was to evaluate effects of ws on body fat% , lean body weight , muscle strength , and exercise tolerance . after approval of the institutional ethics committee for research on human subjects ( ecrhs ) and written informed consent from each volunteer , 18 volunteers ( 12 m and 6f ) were enrolled for the study within 14 days of the screening for physical examination , routine biochemical tests including organ function tests , x - ray chest , and electrocardiogram . volunteers of either sex in the age group of 18 to 30 years , bmi within 19 to 30 kg / m , with no history of any medication / health promoting supplements / exercise program in the preceding 1 month were included . ws extract was available as gelatine capsules in the sizes of 250 and 500 mg in a plastic container with plastic lid containing silica gel . the capsules were stored in at room temperatures ( 24 - 32c ) and protected from light . each volunteer received three doses increased every 10 days . thus , 750 mg / day ( equivalent to 6 g of crude pulverized roots of ws ) was administered orally for first 10 days , 1000mg / day ( equivalent to 8 g ) for next 10 days , and 1250mg / day ( equivalent to 10 g ) for last 10 days . the dosing schedule was as follows : 250 mg in the morning and 500 mg at night from day1 to 10 ; 500 mg in the morning and 500 mg at night from day 11 to day 20 ; and 500 mg in the morning and 750 mg at night from day 21 to day 30 . the activity was assessed for exercise tolerance ( by cycle ergometer ) , muscle strength ( by hand grip force , quadriceps force , and back extensor force ) , and body fat percentage and lean body weight ( by measuring skin fold thickness at four areas such as biceps , triceps , subscapular , and suprailiac with a skin fold caliper in millimeters ) . tolerability was assessed by careful recording of adverse events and judging their causal relationship to the test drug . complete hemogram , liver function tests , renal function tests , fasting sugar , lipid profile , and ecg were performed at baseline , 11 , 21 , and 31 day to assess clinical safety profile . safety and tolerability data were analyzed using mcnemar 's test and data on muscle strength , fat% , and exercise tolerability was analyzed using paired t test to compare before and after the exercises . for ayurvedic parameters , mean age of the 18 volunteers was 24.33  2.14 years ( range : 20 - 27 years ) . mean height was 165.94  7.43 cm ( range : 155 - 175 cm ) . baseline mean weight was 66.65  8.79 kg ( range : 56 - 91 kg ) , and mean bmi was 24.28  2.70 all volunteers were non - smokers , non - tobacco chewers , and non - alcoholic . no clinically significant change was found in pulse , temperature , systolic and diastolic blood pressure . average mean body weight and bmi of the volunteers did not show significant change throughout the study . hematological parameters such as total white blood cells count , differential count , red blood cells count , hemoglobin , platelets count , and esr remained within normal range in all the visits for all the volunteers . no significant change was observed in serum bilirubin , proteins , albumin , alanine transaminase , aspartate transaminase , and alkaline phosphatase at all the visits in each of the volunteers and it remained within normal range . no significant change in serum uric acid and fasting blood sugar was seen throughout the study . however , average serum creatinine had increased and blood urea nitrogen had decreased at visit 5 as compared with visit 1 [ table 1 ] . renal function tests , s. uric acid , and fasting blood sugar significant decrease was seen in total cholesterol at visit 5 as compared to visit 1 , and decreasing trend in each follow - up visit was observed in triglycerides . however , no significant change in serum hdl , ldl , and vldl cholesterol was seen [ table 2 ] . . hand grip force , quadriceps force , and back extensor force showed an increase from visits 2 to 5 . the increase in quadriceps force and back extensor force was gradual and statistically significant [ table 3 ] . assessment of physical parameters cycle ergometer exercise assessment for heart rate , respiratory rate , maximum heart rate intensity percentage , energy expended post - exercise , distance covered in six minutes , speed reached in six minutes , and performance power percentage remained within normal range ; however , the modified borg 's score indicative of breathlessness index has shown gradual improvement [ table 3 ] . assessment of lean body weight has shown gradual increase in every visit , whereas fat percentage has shown gradual decrease from visit 2 to visit 5 [ table 3 ] . this volunteer study has essentially ensured the hematological and biochemical organ function safety of ws in higher doses from 6 to 10 g of crude pulverized roots of ws administered in aqueous extract form . although the doses were given in gradual incremental schedule , each dose was administered for 10 days and no immediate intolerance or any adverse effects were observed in vital functions such as body temperature , pulse rate , respiratory rate , systolic and diastolic blood pressure . the duration of sleep although did not exhibit significant change , the quality of sleep reportedly improved in 6 volunteers . in ayurvedic literature and traditional practice , ( sleep induction ) is one of the important clinical indications and products of ws for sleep are available in indian market . the volunteer who reported diverse clinical symptoms on third day of drug administration was withdrawn from the drug on sixth day and all the symptoms disappeared within a couple of days . the symptoms manifested were unusual increase in appetite , libido , and hallucinogenic effects with vertigo . although clinical / experimental studies have demonstrated anxiolytic , antidepressant , and neuroprotective activity[1214 ] of ws extracts or active molecules , the hallucinogenic activity reported in this volunteer needs further investigation . ws although is stated in ayurvedic literature for enhancing the libido , the unusually heightened sexual desire within 3 days of drug administration is difficult to explain . interestingly , as per ayurvedic protocol , this volunteer has a kapha pradhan prakruti , and shukrasar , rasasar , and asthisar physical status . this finding may illustrate significance in understanding the constitution of an individual before administering ayurvedic drug . assessment of activity for muscle strength , exercise tolerance , fat percentage , and lean body weight was undertaken in view of its traditional medical use . stepwise increment in groups of muscle force at three different locations such as upper extremity , lower extremity , and trunk along with gradual increase in serum creatinine levels within normal range suggest muscle mass promotive activity . the increase in creatinine is less likely due to adversity of renal function since blood urea nitrogen is concomitantly decreased . these findings support the classical description and traditional practices of ws being mentioned and used as mamsawardhak . in past , a volunteer study has shown improvement in hand grip strength with ws . the loss of muscle mass , strength , and muscle performance in postmenopausal and aging population need attention . our team has been studying sarcopenia at menopausal transition and beyond . the decreasing trend in fat% and simultaneous increase in lean body weight compliment the findings of muscle promotive activity . it was noteworthy that total body weight and bmi did not change significantly ; further interesting was to note the significant reduction in total cholesterol and gradual decreasing trend in triglycerides . lipid - lowering activity of ws has been reported earlier in hypercholesterolemic subjects within 30 days . another interesting finding was gradual improvement in modified borg 's score of breathlessness observed post - cycle ergometer exercise . recently , improvement is reported in the physical performance and strength parameters in healthy volunteers receiving ws aqueous extract 500 mg / day for 8 weeks . the volunteer study demonstrates that ws , when given in the form of aqueous extract in capsules with gradual escalating doses from 750 to 1250mg / day , was well tolerated . this study has also demonstrated muscle strengthening , lipid lowering , and improved quality of sleep in view of its traditional use as balya .
ashwagandha ( withania somnifera ) ( ws ) , a  rasayana  drug , is recommended for balavardhan and mamsavardhan . 
 the study was intended to evaluate dose - related tolerability , safety , and activity of ws formulation in normal individuals . 
 the design was prospective , open - labeled , variable doses in volunteers . 
 eighteen apparently healthy volunteers ( 12m:6f , age:18 - 30 years , and bmi : 19 - 30 ) were enrolled . 
 after baseline investigations , they received ws capsules ( rx ) ( aqueous extract , 8:1 ) daily in two divided doses with increase in daily dosage every 10 days for 30 days ( 750 mg / day 10 days , 1 000 mg / day  10 days , 1 250 mg / day  10 days ) . 
 volunteers were assessed for symptoms / signs , vital functions , hematological and biochemical organ function tests . 
 muscle activity was measured by hand grip strength , quadriceps strength , and back extensor force . 
 exercise tolerance was determined using cycle ergometry . 
 lean body weight and fat% were computed from skin fold thickness measurement . 
 adverse events were recorded , as volunteered by the subjects . repeated measures anova , mcnemar 's test , and paired t test were employed . 
 all but one volunteer tolerated ws without any adverse event . 
 one volunteer showed increased appetite , libido , and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study . in six subjects , improvement in quality of sleep was found . 
 organ function tests were in normal range before and after the intervention . 
 reduction in total- and ldl- cholesterol and increase of strength in muscle activity was significant . 
 total body fat percentage showed a reduction trend . 
 ws , in escalated dose , was tolerated well . 
 the formulation appeared safe and strengthened muscle activity . in view of its traditional rasayana use 
 , further studies are planned to evaluate potential of this drug in patients of sarcopenia .