Discussion
CFS, obesity, overweight, fatigue
OBESITY, ADVERSE EFFECTS, OBESE
In this 12-week, randomized, double-blind, placebo-controlled trial on overweight or mildly obese men and women aged 40–75 years, supplementing with 200 mg of an ashwagandha root extract (Witholytin®) twice daily was associated with a significant reduction in their stress levels based on the PSS (primary outcome measure); however, the improvements were not significantly different to participants taking a placebo. Based on the CFS, there was a significant reduction in self-reported fatigue symptoms in the ashwagandha group compared to the placebo group, and participants taking ashwagandha also experienced a significant increase in HRV, as measured by RMSSD, compared to the placebo group. However, there were no significant between-group differences in other self-report outcome measures. In the men taking ashwagandha, there was a significant increase in the blood concentrations of FT and LH compared to the placebo group, and a trend suggesting a greater increase in MDA concentrations. Moreover, there was a trend of a greater increase in estradiol concentrations in women taking ashwagandha. However, there were no significant between-group differences in changes in DHEA-S, TT, HbA1c, fasting glucose, and grip strength. Ashwagandha intake was well-tolerated, with both groups experiencing a similar number of self-reported adverse effects. Further evidence of the safety of ashwagandha supplementation over 12 weeks is demonstrated by findings of no significant changes in blood safety measures comprising full blood count, liver function, and renal function, and anthropometric measurements comprising BMI, waist and hip circumference.In this study, there were no significant between-group differences in changes in the PSS, the primary outcome measure and a validated self-report measure of perceived stress in adults. However, this finding contrasts with other studies investigating the effects of ashwagandha using the PSS, which have found positive (stress-reducing) effects on PSS scores over time (Despite no significant difference between the groups in the change of PSS scores (primary outcome), there was a statistically significant between-group difference in change in HRV over time. However, this finding needs to be tentatively considered since there was a statistically significant 18.8% reduction in HRV in the placebo group, and only a non-significant increased trend of 9.1% in the ashwagandha group. HRV is the measurement of time between successive beats of the heart and provides a measure of the interplay between the parasympathetic and sympathetic nervous systems. HRV is inversely associated with cortisol concentrations (A significant reduction in fatigue symptoms in the ashwagandha group compared to the placebo group, as measured by the CFS, was identified in the present study. The positive result from the CFS is supported by a meta-analysis examining the effects of ashwagandha on physical performance, which included fatigue symptoms. The results of the review from 13 studies and 615 adults concluded that the pooled effect of ashwagandha administration was large (effect size of 1.18) and that future studies demonstrating positive effects in terms of fatigue reduction were likely to be meaningful (Despite ashwagandha being associated with increases in FT and estradiol concentrations over time in men and women, respectively, concentrations in these sex hormones remained within normal ranges. It is important to note that in men, estradiol concentrations increased by 28% and 29% in the ashwagandha and placebo groups, respectively. Despite these similar changes, at week 12, estradiol concentrations in men taking ashwagandha were slightly above normal ranges. Similar increases in estradiol occurred in both the placebo and ashwagandha groups, with baseline estradiol concentrations being slightly higher in the ashwagandha group. Moreover, since BMI and obesity in men are associated with increased estradiol concentrations and aromatase activity (A further observation in men was a trend suggesting a between-group difference in changes in MDA concentrations. This was signified by an 85% increase in MDA concentrations from baseline to week 12 in the ashwagandha group and only a 5% increase in the placebo group. As there was substantial variability in MDA concentrations over time in the ashwagandha group at week 12, this finding should be interpreted cautiously. In a previous ashwagandha study, MDA concentrations were reduced by 18% following 6 months of supplementation in healthy adults (In women, there was no statistically significant between-group difference in estradiol concentrations; however, the ashwagandha group did experience a significant 59% increase in estradiol concentrations from baseline to week 12. Even though the sample sizes were too small to formulate robust conclusions, an exploratory analysis of changes in estradiol concentrations in perimenopausal women taking ashwagandha (The significant increase in LH in men in the ashwagandha group compared to the placebo group is unexpected as there is generally a negative feedback relationship between FT and LH (