Subtle changes in thyroid indices during a placebo-controlled study of an extract of Withania somnifera in persons with bipolar disorder

Laboratory indices of thyroid function (TSH, Free T4, and T3) were measured in a randomized clinical trial in which Ashwagandha (ASW) was used to improve cognitive function in patients with bipolar disorder. This was done in light of a case-report of ASW-associated thyrotoxicosis, and data from mice administered ASW that showed significant increases in thyroxine levels. Ten (of the original 60) patients showed abnormal results in one of the thyroid measures either at the beginning or end of the 8-week study. One ASW- treated patient had subclinical hypothyroidism (TSH - 5.7 mIU/L) at baseline that normalized, and all three ASW treated patients experienced T4 increases from baseline (7%, 12%, and 24%). Six of 7 placebo-assigned patients showed decreases in T4 from baseline (4% to 23%), and one patient's TSH moved from the normal to subclinical hypothyroid range (6.96 mIU/L). As thyroid indices were done for safety, and not the primary goal of the original study, only 16.7% had abnormal thyroid indices, and as there was no sub-stratification for treatment assignment by thyroid status, unequal numbers of subjects received ASW (n = 3) or placebo (n = 7). In spite of these limitations, the subtle laboratory changes noted in thyroid indices in an 8-week study suggest that ASW may increase thyroxine levels, and therefore vigilance regarding hyperthyroidism may be warranted. Nonetheless, the thyroid enhancing properties of ASW may also represent a clinical opportunity for the treatment of subclinical hypothyroidism, and these results suggest the need for further study of the effects of ASW on thyroid indices, especially in those with bipolar and unipolar mood disorders.