Effect of L-methionine on hot flashes in postmenopausal women: a randomized controlled trial

Based on a common mechanism of action with gabapentin, we investigated the effects of L-methionine on hot flashes in postmenopausal women.

After a 1-week baseline period, 51 postmenopausal women experiencing at least five moderate-severe hot flashes per day were randomized to one of three groups in a 13:13:25 ratio: placebo/placebo, placebo/L-methionine, or L-methionine/L-methionine, respectively (phase 1/phase 2). Phase 1 was 12 weeks long, and phase 2 was 8 weeks long. Participants took 1 g PO BID in phase 1 and 2 g PO BID in phase 2 of either L-methionine or placebo. All participants also took folate 1 mg and methylcobalamin 0.5 mg a day to help minimize the L-methionine-induced elevation in serum homocysteine. The primary outcome variable was the percent change in hot flash composite score from baseline to week 12 obtained from participants' daily hot flash diaries.

In phases 1 and 2, there were no significant differences between the L-methionine and placebo groups for any of the hot flash outcome measures. At week 12, there was a mean of 37.4% decrease in hot flash composite score compared with baseline in the L-methionine group and a mean of 33.4% decrease in the placebo group (P = 0.60). There were expected significant increases in fasting serum homocysteine (1.7 and 5.8 micromol/L) and fasting serum methionine (13.9 and 22.3 micromol/L) at weeks 12 and 20, respectively, associated with the two doses of L-methionine therapy relative to placebo therapy.

L-methionine therapy seems to be ineffective in the treatment of hot flashes in postmenopausal women.