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| Date: 02-13-2015 | HC# 011551-514 |
Re: Systematic Review of Ashwagandha for the Treatment of Anxiety
Pratte
MA, Nanavati KB, Young V, Morley CP. An alternative treatment for anxiety: a
systematic review of human trial results reported for the Ayurvedic herb
ashwagandha (Withania somnifera). J Altern Complement Med.
2014;20(12):901-908.
Ashwagandha
(Withania somnifera, Solanaceae; WS)
root is used in Ayurvedic medicine as a broad-spectrum remedy or tonic, and has
been shown to have anti-inflammatory, antioxidant, and anxiolytic properties.
The purpose of this systematic review was to evaluate human studies of WS as a
treatment for anxiety.
The
PubMed, SCOPUS, CINAHL, Google Scholar, Google, and AYUSH Research Portal
databases were searched using the key words ashwagandha or withania in
combination with mental health terms such as anxiety, behavior, mood, and
stress. The searches were limited to English language reports of randomized,
controlled clinical trials evaluating WS as a treatment for anxiety. Studies investigating
formulas containing WS, review articles, and duplicate publications were
excluded.
Five
studies met the inclusion/exclusion criteria. Validity and risk of bias for
each study was evaluated using the Cochrane Collaboration risk-of-bias tool. A
meta-analysis could not be conducted because the trials had different primary outcome
measures and durations (six to 12 weeks), and evaluated different doses (12,000
mg/day raw herb, 125-2,500 mg/day extract), dosage schedules (one to three
times daily), and formulations (raw root, ethanol extracts, or water extracts
containing 1.5%, 5%, or 12% withanolides).
One
study evaluated 39 patients who were treated with 500 mg twice daily (1000
mg/day) of placebo or WS root ethanol extract (manufacturer and composition not
reported) for six weeks. The dose was increased every two weeks as necessary,
up to a maximum of 2,500 mg/day. There was a significant improvement on the
Hamilton Anxiety Scale (HAM-A) in the WS group compared with the placebo group (P
= 0.026). The risk of bias was rated as high. Limitations of the study were the
relatively small sample size and short study duration, inconsistent dosing
(500-2,500 mg/day), and 48.7% drop-out rate.
The second study
included 130 patients who were treated with 125 mg/day or 250 mg/day Sensoril®
(Natreon Inc; New Brunswick, New Jersey); 500 mg/day Essentra® (NutraGenesis
LLC; Brattleboro, Vermont); or placebo for 60 days. The Sensoril and Essentra
products contained root and leaf material derived from a withaferin A and withanolide glycoside-predominant genetically uniform WS
chemotype and extracted using a water-based protocol. The product composition cited
in the review (minimum of 8% withanolide glycosides and 32% oligosaccharides) is
not consistent with the data reported in the original article (11.90% withanolide glycosides, 1.05% withaferin A, and 40.25%
oligosaccharides).
There was a significant WS dose-dependent increase on the modified HAM-A (P
< 0.001) compared to placebo. The risk of bias was rated as unclear. Limitations
of the study were the 24.6% drop-out rate and potential reporting bias (two authors
were employed by the company funding the trial).
The
third study included 81 patients who were treated with naturopathic counseling
plus 300 mg twice daily (600 mg/day) WS root extract standardized to 1.5%
withanolides (manufacturer not reported) or psychotherapy plus placebo for 12
weeks. Beck Anxiety Inventory scores significantly improved in the WS group
compared with the placebo group (P < 0.0001). The risk of bias was rated as
high. Limitations of the study were the 21% drop-out rate, the lack of a true
control group, and potential performance bias because the therapists could not
be blinded.
The
fourth study included 64 patients who were treated with 300 mg twice daily (600
mg/day) WS root extract containing at least 5% withanolides (KSM-66®;
Ixoreal Biomed; Hyderabad, Telangana, India) or placebo for 60 days. KSM-66 is
produced using an alcohol-free and synthetic solvent-free "green
chemistry" extraction process. There was significant improvement on the
Perceived Stress Scale and in cortisol levels in the WS group compared with the
placebo group (P < 0.0001 and P = 0.0006, respectively). The risk of bias
was rated as unclear. A limitation of the study was the relatively small sample
size.
The
fifth study included 86 patients who were treated with anupana (milk) plus 4 g raw
WS root (source not provided) or placebo three times daily (12,000 mg/day) for
60 days. To prepare the WS treatment, dried root was pulverized, combined with equal
quantities of sugar syrup, sieved (40#), and dried to create granules (chemical
composition/standardization was not reported). Changes in HAM-A scores were not
significant compared with placebo, except for the anxious mood domain (P <
0.001). The risk of bias was rated as unclear.
All
five studies concluded that WS was safe. Adverse events in the WS groups were
mild and did not differ in frequency or duration compared with the control
groups.
In summary, WS
significantly improved measures of anxiety compared to the control in most
trials. However, most of the studies were methodologically flawed and
underpowered, and none attained a low risk-of-bias rating. In addition, the
primary outcomes for all of these studies were patient-reported measures. The
authors suggest that the addition of objective data obtained from blinded
diagnostic interviews and the assessment of biomarkers would strengthen future
studies. They also point out several limitations of this review, including the
exclusion of studies published in other languages and trials evaluating the
traditional use of WS (Ayurvedic formulas containing WS).
The authors conclude
that while these "somewhat promising but early, and possibly biased,
results" suggest that WS may significantly improve symptoms of stress,
"additional research in larger samples and in more
clinical contexts is essential to validate its therapeutic capabilities for
widespread use." In addition, the optimal WS preparation form,
chemical composition, dose, and dosage schedule for the treatment of anxiety remains
to be determined.
—Heather S. Oliff, PhD
