Effects of L-Isoleucine and L-Valine on Hot Flushes and Serum Homocysteine

Abstract

OBJECTIVE To investigate whether L-isoleucine was effective in the treatment of hot flushes and whether L-isoleucine, L-valine, or the combination of both amino acids reduced fasting serum homocysteine. METHODS After a 1-week baseline period, 100 postmenopausal women experiencing at least five moderate-severe hot flushes per day were randomized with equal probability to one of four groups (phase 1/phase 2): placebo/L-valine, placebo/L-valine and L-isoleucine, L-isoleucine/L-valine, and L-isoleucine/L-valine and L-isoleucine. Phase 1 was 12 weeks long, and phase 2 was 10 weeks long. Patients took five capsules by mouth, twice a day throughout the study, with each capsule containing 500 mg of compound. Data were obtained from daily hot flush diaries, fasting blood work, and several questionnaires. The primary outcome variable was the percent change in hot flush composite score from baseline to week 12. RESULTS In phase 1 of the study, there were no significant differences between the L-isoleucine and placebo groups for any of the outcome measures. At week 12, there was a mean 13.9% decrease in hot flush composite score compared with baseline in the L-isoleucine group and a mean 25% decrease in the placebo group (P=.28). In phase 2 of the study, there was no significant change in fasting serum homocysteine levels associated with any of the amino acid therapies. CONCLUSION L-isoleucine therapy appears to be ineffective in the treatment of hot flushes in postmenopausal women. L-isoleucine and L-valine, either alone or in combination, appear to have no effect on fasting serum homocysteine levels.

Minimum Trial Duration to Reasonably Assess Long-Term Efficacy of Nonhormonal Hot Flash Therapies

“…Indeed, previous hot flash RCTs of similar power showed no significant baseline hot flash frequency differences among the treatment groups. 10,11,14,16,17 Even if one hypothetically considered baseline hot flash frequency differences between the groups in the Evans et al study, 8 such differences could not explain the variable treatment effects observed over time in this study. In other words, any hypothetical, and historically unlikely, baseline group difference that may have accounted for the observed efficacy at early time points should have also accounted for efficacy at later time points.…”

Variation in menopausal vasomotor symptoms outcomes in clinical trials: a systematic review

“…Of these, 330 were excluded; 59 included fewer than 20 women per study arm and 54 were not an RCT; 126 did not clearly state a sample size calculation; 52 did not measure vasomotor symptoms as the primary outcome; 39 were secondary analysis. Following these exclusions, 214 RCT were included…”

Effects of isoflavones and amino acid therapies for hot flashes and co-occurring symptoms during the menopausal transition and early postmenopause: A systematic review

“…There were four categories of interventions: soy isoflavones 15-19 , other isoflavones 20-26 , isoflavone combinations 27-29 , and amino acids 30-31 .…”