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| Date: 09-15-2015 | HC# 031555-528 |
Gannon JM, Forrest PE, Chengappa KNR. Subtle changes in thyroid indices during a placebo-controlled study of an extract of Withania somnifera in persons with bipolar disorder. J Ayurveda Integr Med. 2014;5(4):241-245.
The pathogenesis of bipolar disorder may involve a dysfunction of the hypothalamic-pituitary-thyroid axis. For that reason, thyroid hormones are often monitored in people with bipolar disorder. Ashwagandha (Withania somnifera, Solanaceae) root and leaf extract is used in Ayurvedic medicine as an adaptogen—a substance that diminishes or alleviates stress. There is a case report of ashwagandha treatment associated with thyrotoxicosis,1a hypermetabolic syndrome where excess thyroid hormones (triiodothyronine [T3] or thyroxine [T4]) are produced and released into the blood. In addition, 2 animal studies found that ashwagandha induces an increase in thyroid hormones. In light of these findings, the purpose of this post-hoc analysis was to evaluate the serum levels of thyroid hormones in patients with bipolar disorder who participated in a 2013 randomized, placebo-controlled, double-blind trial of ashwagandha.2
Briefly, patients (n=60) with bipolar I, bipolar II, or bipolar disorder not otherwise specified (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, DSM-IV) received 500 mg/day ashwagandha (Sensoril®; Natreon Inc.; New Brunswick, New Jersey) leaf/root extract or placebo for 8 weeks, in addition to their existing medication regimen (i.e., medications for bipolar disorder, comorbid psychiatric conditions, and other medical conditions). Patients received 250 mg/day ashwagandha for the first week and 250 mg 2x/day for the next 7 weeks. For this study, the blood samples drawn at baseline and at the end of the clinical trial were analyzed to determine the levels of thyroid-stimulating hormone (TSH), total T3, and free T4.
A total of 12 patients (20%) had thyroid hormone levels that were outside the reference range (i.e., normal range) either at baseline or at the end of the study. However, 2 of these patients were excluded from the analysis due to changes in the T4 reference range midway through the study. Therefore, the data for 10 patients (16.7%) were analyzed. At baseline, 1 patient in the placebo group had pre-existing hypothyroidism (low thyroid hormones) and was receiving treatment. Three patients in the ashwagandha group and 7 patients in the placebo group had values outside of the reference range.
One patient in the ashwagandha group had an elevated TSH level at baseline which returned to normal at the study's end. In contrast, 1 patient in the placebo group had a normal TSH at baseline and an elevated TSH at the end of the study. One patient in the ashwagandha group had a high T3 index at baseline which returned to normal by the end of the study. Of the 2 patients in the placebo group that had an elevated T3 at baseline, 1 patient had a normal level at the end of the study, while T3 remained elevated in the other patient. The third patient in the ashwagandha group had an abnormally low T4 index at baseline which increased 7% (slightly short of the normal range) by the study's end. Four patients in the placebo group had abnormal T4 values; 3 patients with normal levels at baseline were hypothyroid at the study's end, while 1 patient had low T4 levels at both time points.
Compared to baseline, all 3 patients in the ashwagandha group had increased free T4 levels (7-24%) at the end of the study. In the placebo group, 6 out 7 patients had a 4-23% decrease in T4 at the study's end.
Of the remaining 48 patients who had normal laboratory values throughout the study, there were no significant differences between the ashwagandha group and placebo group in mean TSH, T3, or T4 indices. Nonetheless, the greater numerical increase in mean T4 values in the ashwagandha group compared to placebo could be indicative of a trend towards a significant effect on T4 levels.
These equivocal findings are confounded by the fact that the parent study was not designed to measure change in thyroid function as a primary outcome. Therefore, the analysis was underpowered with imbalanced numbers in the groups (n=3, ashwagandha and n=7, placebo), and the measures of the thyroid indices were not repeated for accuracy—i.e., the results may have been random or the observed (nonsignificant) changes may have been due to the various bipolar medication cocktails taken by the patients, or drug-herb interactions.
Erring on the side of caution, the authors conclude that at best, these results suggest that ashwagandha might potentially elevate T4 levels, but well-designed, prospective studies with adequate sample sizes and rigorous laboratory testing are required to confirm this hypothesis. However, in consideration of the case report of thyrotoxicosis, the authors recommend vigilance in clinical practice.
—Heather S. Oliff, PhD
References
1van der Hooft CS, Hoekstra A, Winter A, de Smet PA, Stricker BH. Thyrotoxicosis following the use of ashwagandha. [Article in Dutch]. Ned Tijdschr Geneeskd. 2005;149(47):2637-2638.
2Chengappa KNR, Bowie CR, Schlicht PJ, Fleet D, Brar JS, Jindal R. Randomized placebo-controlled adjunctive study of an extract of Withania somnifera for cognitive dysfunction in bipolar disorder. J Clin Psychiatry. 2013;74(11):1076-1083.
