Post-methionine Plasma Homocysteine Research Articles

Basal and post methionine plasma homocysteine in a rat model of cholestasis

Basal and post methionine plasma homocysteine in a rat model of cholestasis

Variability of fasting and post-methionine plasma homocysteine levels in normo-and hyperhomocysteinaemic individuals

To assess the variability of plasma homocysteine levels, fasting and post-methionine homocysteine levels were measured twice, at baseline and after follow-up of 1–4 months, in 16 individuals with normal and 26 with elevated homocysteine levels after methionine loading. The intra-individual coefficients of variation varied from 15 to 23% for fasting and post-methionine homocysteine levels, whether these levels were within the normal range or not. As a result, test–retest agreement was poor when subjects were dichotomized as having ‘normal’ or ‘abnormal’ homocysteine levels (itself a questionable concept). There was a relation between the average post-methionine homocysteine levels (at the first and second measurement) and the difference between both measurements (r=0.37, P=0.016). In normohomocysteinaemic individuals, delta (i.e., the difference between baseline and follow-up) fasting homocysteine and delta post-methionine homocysteine were correlated negatively with delta folate serum levels: r=−0.64, P=0.007 and r=−0.50, P=0.05, respectively. Individuals homozygous for the 677 C→T mutation in the 5,10-methylenetetrahydrofolate reductase gene showed a greater variation of fasting homocysteine levels than those homozygous for the wild type (P=0.017).In summary, we suggest that there is a substantial intra-individual variability in plasma homocysteine levels over time and that this variability is significantly related to the variability in serum folate levels, especially in normohomocysteinaemic individuals.

Hyperhomocysteinemia: a risk factor for placental abruption or infarction

Objective: To establish the prevalence of hyperhomocysteinemia in women with placental abruption or infarction. Design: Forty-six women with normal pregnancy outcome (controls) and 84 women with placental abruption or infarction (study group) were selected, and studied in the non-pregnant state. Homocysteine metabolism was investigated by a standardized oral methionine loading test. Hyperhomocysteinemia was defined as a concentration of fasting and/or postmethionine plasma homocysteine exceeding the estimated 97.5 percentile level of the controls. In the fasting state, the vitamin status was investigated by the measurement of serum and red cell folate, serum vitamin B12, and whole blood pyridoxal-5′-phosphate (PLP, an active form of vitamin B6). Results: Hyperhomocysteinemia was diagnosed in four controls (9%) and 26 women of the study group (31%, P < 0.05). The median concentrations of the vitamins studied were significantly lower in women of the study group as compared to the controls, except for red cell folate, where the median concentration was comparable in both groups. The median concentration of fasting plasma homocysteine, unlike post-methionine plasma homocysteine, was significantly higher in women who experienced placental abruption or infarction in their first pregnancy than in women who had the same event after one or more uncomplicated pregnancies. Conclusion: Hyperhomocysteinemia is associated with placental abruption or infarction.

Plasma homocysteine and menopausal status**

The aim of the study was to measure the concentrations of plasma homocysteine in premenopausal and postmenopausal women, and to examine a possible relationship between plasma homocysteine and oestrogen status. Homocysteine metabolism was studied by a standardized oral methionine loading test, and oestrogen status was assessed by the measurement of serum 17 beta-oestradiol. Forty-six premenopausal and 26 postmenopausal healthy women without a history of vascular disease or adverse pregnancy outcome were recruited by public advertisement. The main outcome measures were the concentrations of fasting and postmethionine plasma homocysteine, and serum 17 beta-oestradiol. Fasting plasma homocysteine concentrations (mean +/- SD) were significantly higher in postmenopausal women as compared to premenopausal women (12 +/- 4 mumol L-1 and 10 +/- 3 mumol L-1, respectively) as well as postmethionine plasma homocysteine concentrations (46 +/- 16 mumol L-1 and 32 +/- 9 mumol L-1, respectively). In premenopausal women, postmethionine plasma homocysteine was negatively and significantly correlated to serum 17 beta-oestradiol (r = -0.34). It is concluded that plasma homocysteine concentrations, both fasting and after methionine loading, are significantly higher in postmenopausal women than in premenopausal women. In premenopausal women, the higher concentrations of serum 17 beta-oestradiol may account in part for the lower concentrations of postmethionine plasma homocysteine.

Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology.

Mild homocysteinemia occurs surprisingly often in patients with premature vascular disease. We studied the possible enzymatic sources of this mild hyperhomocysteinemia and the control of homocysteine levels in plasma by treatment of patients with the cofactors and cosubstrates of homocysteine catabolism. We assessed homocysteine metabolism in 131 patients who had premature disease in their coronary, peripheral, or cerebrovascular circulation by using a standard oral methionine-load test. Impaired homocysteine metabolism occurred in 28 patients. We assayed levels of the primary enzymes of homocysteine catabolism in cultured skin fibroblast extracts from 15 of these 28 patients. The patients' cystathionine beta-synthase levels (3.68 +/- 2.52 nmol/h per milligram of cell protein, mean +/- SD) were markedly depressed compared with those from 31 healthy adult control subjects (7.61 +/- 4.49, P < .001). The patients' levels of 5-methyltetrahydrofolate: homocysteine methyltransferase were normal. While betaine: homocysteine methyltransferase was not expressed in skin fibroblasts, 24-hour urinary betaine and N,N-dimethylglycine measurements were consistent with normal or enhanced remethylation of homocysteine by betaine: homocysteine methyltransferase in the 13 patients tested. When treated daily with choline and betaine, pyridoxine, or folic acid, there was a normalization of the postmethionine plasma homocysteine level in 16 of 19 patients. Our results indicate that mild homocysteinemia in premature vascular disease may be caused by either a folate deficiency or deficiencies in cystathionine beta-synthase activity. It does not necessarily involve deficiencies of either 5-methyltetrahydrofolate:homocysteine methyltransferase or betaine:homocysteine methyltransferase. Effective treatment regimens are also defined.