Auddy
B, Hazra J, Mitra A, Abedon B, Ghosal S. A standardized Withania somnifera extract significantly reduces stress-related
parameters in chronically stressed humans: A double-blind, randomized,
placebo-controlled study. JANA.
2008;11(1):50-56.
Ashwagandha
(Withania somnifera) has an
antistress adaptogenic effect. According to Ayurvedic medicine, it promotes
stress relief, restores homeostasis, and increases resistance to adverse
environmental factors. However, it has not been evaluated in a randomized,
controlled trial of chronically stressed people. Hence, the objective of this
study was to evaluate the effect of ashwagandha on indicators of stress and
anxiety in chronically stressed adults.
Men and women (n = 130,
aged 18 to 60 years) with a Bengali version of a modified Hamilton anxiety (mHAM-A) scale for stress
score of 24 to 42 participated in this double-blind, randomized,
placebo-controlled study between November 2004 and October 2006. The study was
conducted at the Central Research Institute (Ayurveda), Ministry of Health and
Family Welfare, Bidhan Nagar, Kolkata,
India. Patients
were treated with placebo (excipients) or 125 mg/day, 250 mg/day, or 500 mg/day
ashwagandha (Sensoril®; Natreon Inc.; New Brunswick,
New Jersey and Essentra®; NutraGenesis, LLC; Brattleboro, Vermont)
for 60 days. Ashwagandha was standardized to a minimum of 8% withanolide
glycosides and 32% oligosaccharides, and a maximum of 2% withaferin A. Stress
and anxiety were assessed with the mHAM-A and blood was drawn to measure
biochemical markers of stress and anxiety.
A total of 32 patients
dropped out of the study including 10 who were lost to follow-up, 6 from
protocol violations, and 4 due to doctor's decisions. The other 12 withdrew due
to lack of efficacy, and 9 of these were in the placebo group. Dropouts were
not included in the analysis. Patients treated with ashwagandha had improved
well-being at day 30 and 60. There was a statistically significant
dose-dependent improvement in mHAM-A scores of patients in the ashwagandha
groups, whereas the placebo group had no significant improvement over the
course of the study. Even the lowest dose (125 mg/day) had a significant
decrease (P < 0.001) in mean sum mHAM-A score from baseline (29.9) to Day 30
(18.1, -39.5%) to Day 60 (11.3, -62.2%) compared to placebo.
Similarly, there was a
dose-dependent effect on the biochemical parameters of stress. Between baseline
and Day 60, the 125 mg/day group decreased significantly (P < 0.05) more
than the placebo group for mean serum cortisol (-14.5%), serum very low-density
lipoprotein cholesterol (VLDL-C) (-8.9%), systolic blood pressure (-1.6%),
diastolic blood pressure (-5.6%), and (P < 0.001) serum C-reactive protein
(-31.6%) and pulse rate (-6.0%), and increased significantly (P < 0.05) more
than the placebo group for mean serum dehydroepiandrosterone sulfate (DHEAS)
(13.2%) and hemoglobin (6.3%). In addition to these improvements, the 250
mg/day group had significantly (P < 0.05) greater reductions, compared to
the placebo group, in mean fasting blood glucose (-4.7%), serum total cholesterol (-7.0%), serum triglycerides (-9.5%), and
serum LDL-C (-9.0%). In addition to all of the aforementioned improvements, the
500 mg/day group had a significantly (P < 0.001) greater increase in mean
serum high-density lipoprotein cholesterol (HDL-C) compared to the placebo group
(17.3%). Cardiac risk ratios for the 2 higher doses were significantly less (P
< 0.05) than for placebo after 60 days. There was no significant change over
time in the placebo group for any biochemical parameter. There were no adverse
events reported for any group.
The authors conclude
that all doses tested support traditional claims of an antistress-adaptogenic
effect. In this study, the cortisol levels declined over the course of the
study in patients treated with ashwagandha. This indicates that ashwagandha may
be working through the hypothalamic-pituitary-adrenal axis. Cortisol also
regulates blood sugar levels. Patients in the 250 and 500 mg/day groups had
reductions in fasting blood glucose. Also, chronic stress reduces serum DHEAS,
a marker of stress. Patients in this study treated with ashwagandha had
increased concentrations of DHEAS at study end compared with the placebo group.
Chronic stress is associated with high levels of serum C-reactive protein, a
systemic marker of inflammation associated with various chronic diseases. All
doses of ashwagandha decreased levels of serum C-reactive protein. The authors
conclude that daily use of ashwagandha may help people with chronic stress with
no adverse side effects. Long-term safety and efficacy need to be determined.