Fasting and Post-methionine Homocysteine Levels in Alzheimer’s Disease and Vascular Dementia

The aim of the study is to compare the basal homocysteine levels in patients with impairment of cognitive status, and in controls, to evaluate if the methionine loading test is able to identify any differences between patients with Alzheimer’s disease and patients with vascular dementia. We enrolled 56 subjects, 20 with Alzheimer’s disease, 18 with vascular dementia, and 18 normal controls. The data shown that plasma homocysteine levels both basal and post-methionine load were significantly higher in the two groups of demented patients than in the control group. No significant differences were found between Alzheimer’s patients and vascular dementia patients. The homocysteine percent increase after a methionine loading test was significantly higher in the controls with respect to the two groups of demented patients. Only in Alzheimer’s patients were vitamin B12 basal levels negatively correlated with basal homocysteine levels (p<0.05), while positively correlated with the homocysteine percent increase after load (p<0.05). The study confirms the possible role of chronically elevated homocysteinemia in neuronal degeneration in demented patients. Even if the methionine loading test revealed an abnormal homocysteine metabolism in demented patients, it didn’t show any difference among patients with Alzheimer’s disease and vascular dementia.

Methionine-Loading and Random Homocysteine Tests Have No Added Value in Risk Assessment for Venous and Arterial Thrombosis.

Hyperhomocysteinemia is a risk factor for venous and arterial thrombosis. Different diagnostic strategies are used to identify subjects at risk of thrombosis, related to hyperhomocysteinemia. Measurements of fasting and methionine-loading levels are usually recommended. Alternatively, random homocysteine measurements may simplify the procedure. Random levels < 10 and > 20 μmol/l are considered to indicate normohomocysteinemia and hyperhomocysteinemia, respectively, while consecutive fasting and methionine-loading tests are required at levels 10–20 μmol/l. We performed a study to assess the most suitable strategy in a large cohort of families with hereditary (index) deficiencies of protein S, protein C or antithrombin. Random, fasting and methionine-loading homocysteine samples were measured in 713 relatives. According to predefined cut-off levels hyperhomocysteinemic and normohomocysteinemic relatives were identified and their absolute risks of thrombosis were compared. Relatives with random homocysteine levels > 20 μmol/l were not at risk of venous or arterial thrombosis compared to relatives with levels < 10 μmol/l (relative risks 0.9 [95% CI, 0.4–2.3] and 1.7 [0.5–5.7], respectively). Fasting hyperhomocysteinemia (homocysteine levels > 18.5 μmol/l) was associated with an increased risk of venous and arterial thrombosis (relative risks 2.6 [1.3–4.8] and 3.7 [1.5–8.4)], respectively) (Table). Relatives with normal fasting homocysteine levels, but methionine-loading hyperhomocysteinemia (homocysteine levels > 58.8 μmol/l) were not at risk; relative risk 0.8 (0.2–1.9) for venous thrombosis and 1.1 (0.2–3.9) for arterial thrombosis. Exclusion of relatives with an index deficiency did not alter the risk estimates, while annual incidences of normohomocysteinemic relatives decreased to 0.19% per year (0.12–0.29), which is comparable with the annual incidence in the normal population. As only fasting homocysteine identified subjects at risk of thrombosis, random homocysteine and methionine-loading tests can be omitted in clinical practice. Venous Thrombosis Observation Relatives Incidence/year (%) Relative Risk years with event (95% CI) (95% CI) * Methionine-loading performed in relatives with no fasting hyperhomocysteinemia Fasting Homocysteine No hyperhomocysteinemia 10408 55 0.53 (0.40–0.69) Reference Hyperhomocysteinemia 804 11 1.37 (0.68–2.45) 2.6(1.3–4.8) Methionine-loading test* No hyperhomocysteinemia 9341 50 0.54 (0.40–0.71) Reference Hyperhomocysteinemia 986 4 0.41 (0.11–1.04) 0.8(0.2–1.9) Arterial Thrombosis Fasting Homocysteine No hyperhomocysteinemia 11096 21 0.19 (0.12–0.29) Reference Hyperhomocysteinemia 1004 7 0.70 (0.28–1.44) 3.7(1.5–8.4) Methionine-loading test* No hyperhomocysteinemia10008 10008 19 0.19 (0.11–0.30) Reference Hyperhomocysteinemia 1000 2 0.20 (0.02–0.72) 1.1(0.2–3.9)

No added value of the methionine loading test in assessment for venous thrombosis and cardiovascular disease risk

SummaryHomocysteine isa risk factor for cardiovascular disease and venous thrombosis. Clinical guidelines differ in their recommendation whether or not to measure homocysteine after methionine loading. In this study, we investigated the added value of the methionine loading test next to fasting homocysteine levels for identifying subjects at risk for venous thrombosis or cardiovascular disease, using Receiver Operating Characteristic (ROC) curves.The analysis was performed in 185 patients with recurrent venous thrombosis, 130 patients with cardiovascular disease and 601 controls.The discriminatory power of the fasting homocysteine measurement alone for identifying subjects at risk of venous thrombosis expressed as the area under the ROC curve (AUC) was 0.61 (95%CI 0.56-0.66). Using both a fasting homocysteine measurement and a methionine loading test together yielded a similar AUC of 0.65 (95%CI 0.60-0.69), indicating no added value of methionine loading next to fasting homocysteine measurement in identifying subjects at risk for thrombosis. Similar results where found for cardiovascular disease, with anAUC of 0.62 (95%CI 0.57-0.67) for the fasting homocysteine measurement alone and an AUC of 0.62 (95%CI 0.57-0.67) for the combination of both the fasting and the postload homocysteine measurement. The methionine loading test has no added value next to measuring fasting homocysteine levels for identifying subjects at risk for venous thrombosis or cardiovascular disease and for that reason should not be used in clinical practice.

l-Folic Acid Supplementation in Healthy Postmenopausal Women: Effect on Homocysteine and Glycolipid Metabolism

Context: Hyperhomocysteinemia as well as alterations of glycemic and lipidic metabolism are recognized as risk factors for cardiovascular diseases. Objective: The aim of this study was to examine the effect of l-folic acid supplementation on homocysteine (Hcy) and related thiols, such as cysteine (Cys) and Cys-glycine (Cys-Glyc) pathways and their relationship to glucose, insulin, and lipidic metabolism in normoinsulinemic postmenopausal women. Design: This study was a randomized placebo, not double-blind, trial. Setting: The study was performed in an academic research center. Patients or Other Participants: Twenty healthy postmenopausal women were selected. No patient was taking drugs known to affect lipid or glucose metabolism. Intervention(s): Patients underwent two hospitalizations before and after 8 wk of l-acid folic (7.5 mg/d) or placebo administration. The glycemic metabolism was studied by an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Hcy metabolism was studied by a standardized oral methionine-loading test. Main Outcome Measure(s): Hcy, Cys, and Cys-Glyc, basally and after a methionine loading test, were measured. Basal insulin, glucose, and peptide C levels as well as area under the curve for insulin, area under the curve for peptide, hepatic insulin extraction, and metabolic index were assayed. The total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels and the cholesterol/HDL and LDL/HDL ratios were also measured. Results: The total basal Hcy concentration and the plasma postmethionine loading Hcy values were significantly decreased (P &lt; 0.01) in l-folic acid-treated patients, whereas postmethionine loading Cys-Glyc levels were markedly increased (P &lt; 0.02). Furthermore, l-folic acid intake induced a significant improvement in carbohydrate metabolism through an increase in fractional hepatic insulin extraction (P &lt; 0.05) and peripheral insulin sensitivity (P &lt; 0.02) in normoinsulinemic women. HDL levels considerably increased, inducing an improvement in other atherosclerotic indexes, such as cholesterol/HDL and LDL/HDL ratios (P &lt; 0.03). Conclusions: These results show that folic acid supplementation lowers plasma Hcy levels and improves insulin and lipid metabolism, reducing the risk of cardiovascular disease.

Evaluation of a shorter methionine loading test

We validated whether a shorter methionine loading test is as accurate as the original 6-h test in identifying hyperhomocysteinemic patients and investigated determinants of fasting and post-load homocysteine concentration. Plasma homocysteine was determined in EDTA-blood from women with a history of preeclampsia (n=106) after 12 h fasting and 3 and 6 h after an oral methionine load (0.1 g/kg body weight). The 677C > T polymorphism in the methylenetetrahydrofolate reductase (