Folic acid and homocysteine — a silent enemy of blood vessels?

Aim of the study: B vitamin therapy lowers plasma total homocysteine concentrations, and might be a beneficial intervention for stroke prevention; however, cyanocobalamin (a form of vitamin B12) can accelerate decline in renal function and increase the risk of cardiovascular events in patients with impaired renal function.

Results: Although early trials did not show benefit in reduction of stroke, these results might have been due to harm in participants with impaired renal function. In patients with diabetic nephropathy, cyanocobalamin is harmful, whereas B vitamins appear to reduce cardiovascular events in study participants with normal renal function. Our meta-analysis of individual patient data from two large trials of B vitamin therapy (VISP and VITATOPS) indicates that patients with impaired renal function who are exposed to high-dose cyanocobalamin do not benefit from therapy with B vitamins for the prevention of stroke (risk ratio 1·04, 95% CI 0·84-1·27), however, patients with normal renal function who are not exposed to high-dose cyanocobalamin benefit significantly from this treatment (0.78, 0·67-0·90; interaction p=0·03).

Aim of the study: Hyperhomocysteinaemia has been identified from epidemiological studies as an independent risk factor for cardiovascular disease. Plasma total homocysteine is elevated in renal impairment, which may be a consequence of cardiovascular disease.

Results: However, it is also likely that plasma total homocysteine promotes cardiovascular disease, particularly through effects on endothelial function and coagulation pathways. It is influenced by complex interactions between B-group vitamins, especially folate, and polymorphisms in various genes involved in homocysteine metabolism. Supplementation with folate and other B-group vitamins effectively lowers total plasma homocysteine and improves endothelial function. The results of clinical trials to assess effects on cardiovascular morbidity and mortality are awaited.

Aim of the study: Atherosclerosis is a chronic disease that can seriously endanger human life. Folic acid supplementation modulates several disorders, including atherosclerosis, via its antiapoptotic and antioxidative properties.

Results: The results show aggravated atherosclerotic lesions in the HF+DEF group. Folic acid supplementation increased concentrations of serum folate. Further, folic acid supplementation increased high-density lipoprotein-cholesterol, decreased plasma homocysteine levels, and improved antioxidant capacity in atherogenic rats. These findings are consistent with the hypothesis that folic acid alleviates atherogenesis by reducing plasma homocysteine levels and improving antioxidant capacity in rats fed a high-fat diet.

Aim of the study: Folate supplementation is critical for preventing neural tube defects, while 5-methyltetrahydrofolate (5-MTHF), the predominant circulating form of folate, may offer a pharmacokinetic advantage. However, comparative data in this populations remain limited.

Results: Ninety-six participants completed the trial (48 per group). Both interventions significantly increased RBC folate (FA: +262.00 ng/mL [IQR: 245.50]; 5-MTHF: +244.50 ng/mL [IQR: 233.50]; p = 0.714) and reduced plasma homocysteine with no significant differences between groups. However, 5-MTHF supplementation resulted in a greater increase in plasma 5-MTHF compared to the FA group (Median change: +5.67 ng/mL [IQR: 5.93] vs. +3.12 ng/mL [IQR: 6.47]; unadjusted p = 0.027; baseline-adjusted p = 0.055), a difference of borderline statistical significance. Median UMFA accumulation was approximately twice as high in the FA group, but the difference failed to reach significance due to non-normal distribution. The bioavailability of 5-MTHF was comparable to folic acid across different BMI categories, with a stronger trend toward higher bioavailability among normal-weight women (p = 0.182) than overweight women (p = 0.304).