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Folic acid responsive postmenopausal homocysteinemia
Insights
Elevated homocysteine-cysteine mixed disulfide (MDS) levels are found in postmenopausal women, increasing after methionine loads. Folic acid therapy significantly reduced these levels, suggesting a potential prophylactic role.
Area of Science:
- Cardiovascular Science
- Endocrinology
- Nutritional Science
Background:
- Homocysteinemia is linked to juvenile arteriosclerosis, thromboembolic issues, and osteoporosis.
- Plasma homocysteine (as homocysteine-cysteine mixed disulfide, MDS) is higher in patients with cardiovascular disease and in men versus premenopausal women.
- The study investigates MDS levels in relation to menopause and methionine loading.
Purpose of the Study:
- To compare fasting and post-methionine load plasma MDS levels in normal premenopausal women, postmenopausal women, and men.
- To assess the effect of folic acid therapy on plasma MDS concentrations in individuals with initially normal folate levels.
- To explore the potential link between moderate homocysteinemia and postmenopausal health issues.
Main Methods:
- Measurement of plasma MDS in fasting state and post-methionine load in normal men and premenopausal/postmenopausal women.
- Administration of folic acid (5 mg daily) for four weeks.
- Comparison of MDS levels before and after folic acid therapy.
Main Results:
- Postmenopausal women exhibited significantly higher fasting MDS concentrations than premenopausal women and younger men.
- After methionine load, postmenopausal women showed markedly higher MDS levels with no overlap compared to premenopausal women and older men.
- Folic acid therapy led to significant reductions in MDS levels (pre-load: -31%, post-load: -28%) despite normal initial folate status.
Conclusions:
- Moderate homocysteinemia may contribute to postmenopausal arteriosclerosis and osteoporosis.
- Folic acid supplementation could be a beneficial prophylactic measure for postmenopausal women.
- Further research is warranted to confirm the role of homocysteinemia and folic acid in postmenopausal vascular and bone health.
Abstract:
Homocysteinemia is associated with juvenile arteriosclerosis, recurrent thromboembolic complications and osteoporosis. Plasma homocysteine, measured as homocysteine-cysteine mixed disulfide (MDS), has in other than homocysteinemics been reported to be higher in patients with coronary heart or cerebrovascular disease than in controls, and higher in men than in premenopausal women. Here, in groups of normal men and normal premenopausal and postmenopausal women, we measured plasma MDS in the fasting state and four hours after a methionine load (100 mg/kg body weight), before and after four weeks of folic acid therapy at 5 mg daily. In their fasting plasma, postmenopausal women (n = 5) had significantly (P less than 0.05) higher MDS concentrations than premenopausal women (n = 5) and younger men (n = 5). After the methionine load MDS concentrations in postmenopausal women rose markedly, reaching levels significantly higher than those in younger men (P less than 0.05), and with no overlap with values in premenopausal women (P less than 0.01), or in older men (n = 5, P less than 0.01). Folic acid therapy resulted in substantial reductions (n = 15, P less than 0.01) of MDS concentrations both before the methionine load (-31%) and after (-28%), though subjects had initially had normal concentrations of serum and erythrocyte folates. We speculate that moderate homocysteinemia might contribute to postmenopausal arteriosclerosis and osteoporosis. Should this prove to be the case, folic acid might be a useful prophylactic.