Elevated plasma homocysteine and cysteine are associated with endothelial dysfunction across menopausal stages in healthy women

Keller AC1Klawitter J2Hildreth KL3Christians U4Putnam K5Kohrt WM6Reusch JEB7Moreau KL8.

J Appl Physiol (1985). 2019 Mar 21. doi: 10.1152/japplphysiol.00819.2018. [Epub ahead of print]


Hyperhomocysteinemia is associated with endothelial dysfunction and increased cardiovascular disease (CVD). We determined whether elevated homocysteine (Hcy) and markers of Hcy metabolism were associated with the previously reported endothelial dysfunction across stages of the menopause transition. Brachial artery flow-mediated dilation (FMD) and plasma concentrations of Hcy, cysteine and methionine were measured in healthy women (n=128) 22-70 years of age categorized as premenopausal (n=35), perimenopausal (early, n=16 and late, n=21) and postmenopausal (early, n=21 and late, n=35). Dietary intake of micronutrients involved in Hcy metabolism (e.g., vitamins B6, B12, folate) were assessed in a subpopulation of women. Hcy and cysteine concentrations were progressively higher, and methionine was progressively lower across menopausal stages (all p<0.005). The higher Hcy and cysteine concentrations correlated with lower circulating estradiol levels (r= -0.49 and -0.50, respectively, both P<0.001). FMD was inversely correlated with Hcy (r=-0.25, p=0.004) and cysteine (r=-0.39, p<0.001) and positively correlated with methionine concentrations (r=0.25, p=0.005). Dietary intake of vitamins B6 and B12 (both p<0.05) were lower in postmenopausal women. Vitamin B12 intake correlated with FMD (r=0.22, P=0.006). These data suggest that declines in estradiol across stages of the menopause transition may lead to elevations in Hcy and cysteine that may contribute to endothelial dysfunction in postmenopausal women. Future studies should examine whether targeting Hcy metabolism during the perimenopausal to early postmenopausal period with interventions, including diet, attenuates or reverses the decline in endothelial function in women.


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