Effect of folic acid supplementation on the progression of carotid intima-media thickness: A meta-analysis of randomized controlled trials

Institute of Biomedicine, Anhui Medical University, Hefei, China.
Atherosclerosis (Impact Factor: 3.99). 12/2011; 222(2):307-13. DOI: 10.1016/j.atherosclerosis.2011.12.007
Source: PubMed


We conducted a meta-analysis of relevant randomized trials to assess whether folic acid supplementation reduces the progression of atherosclerosis as measured by carotid intima-media thickness (CIMT).
This analysis included 2052 subjects from ten folic acid randomized trials with the change in CIMT reported as one of the end points. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effect models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity.
Our analysis showed that folic acid supplementation significantly reduces the progression of CIMT (WMD: -0.04 mm; 95%CI: -0.07, -0.02; P<0.001), particularly in subjects with chronic kidney disease (CKD) (WMD: -0.16 mm; 95%CI: -0.26, -0.07; P=0.0006) or high cardiovascular disease (CVD) risk (WMD: -0.05 mm; 95%CI: -0.11, 0.00; P=0.06) but not in subjects who were generally healthy with only elevated homocysteine concentrations (WMD:0.00 mm; 95%CI: -0.01, 0.01; P=0.35). Furthermore, meta-regression analysis of the data showed that the baseline CIMT levels (P=0.011) and the percent reduction of homocysteine (P<0.001) were positively related to the effect size. Consistently, a greater beneficial effect was seen in those trials with baseline CIMT levels ≥0.8 mm (WMD: -0.14 mm; 95%CI: -0.19, -0.08; P<0.0001), and a reduction in the homocysteine concentration ≥30% (WMD: -0.22 mm; 95%CI: -0.38, -0.06; P=0.009). In the corresponding comparison groups, the effect sizes were attenuated and insignificant.
Our findings indicate that folic acid supplementation is effective in reducing the progression of CIMT, particularly in subjects with CKD or high CVD risk and among trials with higher baseline CIMT levels or a larger homocysteine reduction.

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    • "Large epidemiological studies have shown a clear association between intake of vitamin B and CVD( 10 , 11 ), and intervention with folic acid fortification of grain products has resulted in reduction in stroke mortality outcomes( 12 ). Meta-analyses of folic acid supplementation studies have also indicated a protective effect( 13 , 14 ), although not convincing( 14 ). "
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    ABSTRACT: The association between diet and CVD cannot be assigned to a single nutrient, but rather to a set of nutrients and non-nutrients, and eating pattern analyses have become an important tool in investigation of this relationship. Our objective was to investigate eating patterns in relation to nutrient intake and serum concentration of folate, vitamin B12 and TAG in ninety-five healthy adult participants. Dietary information was collected by an FFQ, and eating patterns were obtained by principal components analyses of thirty-three food groups. Three eating patterns were extracted, a sweet eating pattern identified by intakes of cakes, snacks, sugar-sweetened drinks and chocolates; a prudent eating pattern identified by vegetables, fruits and olive oil; and a traditional food pattern identified by red meat, lean fish and cheese. Blood samples were collected in the morning after an overnight fast. Linear regression analyses adjusted for age, BMI and smoking showed a negative association between the sweet eating pattern scores and the serum concentration of folate (β = −2·31 (95 % CI −4·14, −0·45)) and a positive association with serum concentration of TAG (β = 0·35 (95 % CI 0·12, 0·57)). The prudent eating pattern scores were positively associated with the serum concentration of folate (β = 1·69 (95 % CI 0·44, 2·92)). In conclusion, a sweet eating pattern was associated with risk factors for CVD, whereas a prudent eating pattern was associated with protective factors.
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