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

Guttuso, Thomas Jr MD1; McDermott, Michael P. PhD2; Ng, Phillip BS2; Kieburtz, Karl MD2

doi: 10.1097/gme.0b013e3181a2fa76

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

Methods: 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.

Results: 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 μmol/L) and fasting serum methionine (13.9 and 22.3 μmol/L) at weeks 12 and 20, respectively, associated with the two doses of L-methionine therapy relative to placebo therapy.

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

The efficacy of two doses of L-methionine therapy for treating hot flashes was evaluated in a randomized controlled trial. Neither dose of L-methionine was associated with a significant reduction in hot flashes; however, both doses were associated with significant increases in serum homocysteine.

From the 1University at Buffalo, Buffalo; and 2University of Rochester, Rochester, NY.

Received January 13, 2009; revised and accepted February 26, 2009.

Funding/support: This publication was made possible by Grant 1K23-AT-1709-01 from the National Center for Complementary and Alternative Medicine (NCCAM) and by the University of Rochester Clinical and Translational Science Institute and by Grant Numbers UL1 RR024160, KL2 RR024136, and TL1 RR024135 from the National Center for Research Resources (NCRR). Both Centers are components of the National Institutes of Health (NIH). This publication's contents are solely the responsibility of the authors and do not necessarily represent the official views of NCCAM, NCRR, or NIH.

Financial disclosure/conflicts of interest: Thomas Guttuso, Jr, is the inventor on US Patent 6,310,098, which is owned by the University of Rochester, covering the use of gabapentin and related compounds for treating hot flashes.

Address correspondence to: Thomas Guttuso, Jr, MD, University at Buffalo, 3435 Main Street, 311 BRB, Buffalo, NY 14214. E-mail:

©2009The North American Menopause Society