Effect of Vitamin E Supplementation on Plasma Nitric Oxide in Menopausal Women with Hot Flashes: A Cross-Over, Randomized Clinical Trial

Background: Vitamin E serves a major role in increasing nitric oxide (NO) and reducing lipoperoxidation progression during the menopause transition. Objectives: This study aimed to determine the effect of Vitamin E on plasma nitric oxide in menopausal women with hot flashes (HFs). Methods: In this double-blind, randomized, cross-over clinical trial performed in a teaching hospital, 83 eligible menopausal women with HFs were randomly block allocated to Vitamin E (n = 42) and placebo (n = 41) groups. In phase I of the intervention, they were administered 400 IU per day of Vitamin E or placebo for 4-weeks. In the phase II, the group receiving Vitamin E was subsequently given placebo and vice versa after wash-out. Primary outcomes were the number and severity of hot flashes per day as determined by the recorded values by the women and using Modified Kupperman Index, respectively. The secondary outcome was plasma nitric oxide measured before and after the intervention in the two phases. Both outcomes were analyzed within and between placebo-vitamin E (P-E) and Vitamin E-placebo (E-P) groups, and in general by gathering Vitamin E and placebo groups in the two phases, separately. Data were analyzed using the Chi-Square test, independent t-test, Wilcoxon test, Mann-Whitney test, and Spearman's correlation coefficient. Results: The mean number of HFs indicated a significant decreasing trend from week II of the phase I to the end of the phase II within P-E and E-P groups compared to before the intervention. Median (interquartile range [IQR]) of HFs number changes was 2.03 (2.57) in the P-E group and 1.21 (2.21) in the E-P group at the end of the first week of phase II (P = 0.043). There was a very low significant positive correlation between changes in HFs and plasma nitric oxide level in weeks I (r = 0.262, P = 0.029) and II (r = 0.256, P = 0.034) in the Vitamin E group. Conclusions: Vitamin E and placebo were both effective in reducing HFs in menopausal women. It seems that the subjective effect of placebo contributed to this decline. Vitamin E had no effect on reducing HFs via increasing plasma level of nitric oxide. These results were not in line with our hypothesis. Further research is needed to understand this issue.