The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis

Abstract

Objective: Folate and vitamin B 12 are two vital regulators in the metabolic process of homocysteine, which is a risk factor of atherothrombotic events. Low folate intake or low plasma folate concentration is associated with increased stroke risk. Previous randomized controlled trials presented discordant findings in the effect of folic acid supplementation-based homocysteine lowering on stroke risk. The aim of the present review was to perform a meta-analysis of relevant randomized controlled trials to check the how different folate fortification status might affect the effects of folic acid supplementation in lowering homocysteine and reducing stroke risk. Design: Relevant randomized controlled trials were identified through formal literature search. Homocysteine reduction was compared in subgroups stratified by folate fortification status. Relative risks with 95 % confidence intervals were used as a measure to assess the association between folic acid supplementation and stroke risk. Setting: The meta-analysis included fourteen randomized controlled trials, Subjects: A total of 39 420 patients. Results: Homocysteine reductions were 26·99 (SD 1·91) %, 18·38 (SD 3·82) % and 21·30 (SD 1·98) %, respectively, in the subgroups without folate fortification, with folate fortification and with partial folate fortification. Significant difference was observed between the subgroups with folate fortification and without folate fortification (P = 0·05). The relative risk of stroke was 0·88 (95 % CI 0·77, 1·00, P = 0·05) in the subgroup without folate fortification, 0·94 (95 % CI 0·58, 1·54, P = 0·82) in the subgroup with folate fortification and 0·91 (95 % CI 0·82, 1·01, P = 0·09) in the subgroup with partial folate fortification. Conclusions: Folic acid supplementation might have a modest benefit on stroke prevention in regions without folate fortification.

High Homocysteine Levels are Closely Associated with the Categories of Coronary Artery Diseases as well as Low Status of Folic Acid and Vitamin B12

“…Moreover, SAP patients had the third higher level of Hcy, whose were significantly higher than controls (p<0.01). However, the levels of folic acid and vitamin B 12 had opposite results, whose in AMI group had the lowest, while in controlled group had the highest. …”

“…Categorical variables were expressed as percentage and compared by χ 2 -test. The correlation study between Hcy and folic acid as well as vitamin B 12 were performed on the measured data by using Pearson correlation a coefficient. A p-value < 0.05 was considered as significant.…”

“…Patients with the following diseases were excluded from this study: cancer, liver diseases, renal insufficiency, blood diseases, hyperthyroidism, thyroid dysfunction, systemic lupus erythematosus, malnutrition, pregnant woman, and supplemented folic acid and vitamin B 12 . Participating subjects were explained their participation rights and written informed consent was obtained, and were asked about excessive drinking (yes or no, it was defined as yes at least once a week and drinking over 45 degrees of alcohol more than 200 mL) and smoking habits (yes or no, nonsmokers including never smoking and stop smoking more than one year).…”

“…Vitamin B 12 deficiency and HHcy are related to cardiovascular risk factors in patients with coronary artery disease [14]. In present study, we evaluate the correlations between Hcy and folic acid as well as vitamin B 12 , and explore the associations of Hcy with the categories of CAD as well as the levels of folic acid and vitamin B 12 in patients with atherosclerotic CAD.…”

“…Genetic or nutritional deficiencies in Hcy metabolism lead to hyperhomocysteinemia (HHcy) and cause endothelial dysfunction, a hallmark of atherosclerosis [11]. Folic acid and vitamin B 12 play an important role in regulating the metabolic process of Hcy [12]. Current studies have shown that folic acid supplementation can significantly improve endothelial dysfunction in patients with CAD [13].…”