Renal Insufficiency, Vitamin B ₁₂ Status, and Population Attributable Risk for Mild Hyperhomocysteinemia Among Coronary Artery Disease Patients in the Era of Folic Acid–Fortified Cereal Grain Flour

Abstract

Abstract-Fortification of enriched cereal grain flour products with folic acid has drastically reduced the prevalence of deficient plasma folate status, a major determinant of plasma total homocysteine (tHcy) levels. We hypothesized that even more liberally defined "suboptimal" plasma folate status might no longer contribute importantly to the population attributable risk (PAR) for mild hyperhomocysteinemia, a putative atherothrombotic risk factor. We determined fasting plasma tHcy, folate, vitamin B 12 , and pyridoxal 5Ј-phosphate levels, along with serum creatinine and albumin levels, in 267 consecutive patients (aged 61Ϯ9 [meanϮSD] years, 76.4% men and 26.6% women) with stable coronary artery disease (CAD) who were nonusers of vitamin supplements or had abstained from supplement use for at least 6 weeks before examination. Subjects were evaluated a minimum of 3 months after the implementation of flour fortification was largely completed. Relative risk estimates for the calculation of PAR were derived from a multivariable-adjusted logistic regression model with Ն12 mol/L tHcy as the dependent variable and with age, sex, pyridoxal 5Ј-phosphate (continuous), albumin (continuous), Ͻ5 ng/mL folate, Ͻ250 pg/mL vitamin B 12 , and Ն1.3 mg/dL creatinine as the independent variables. The prevalence of Ն12 mol/L plasma tHcy was 11.2% (30 of 267 patients). PAR estimates (percentage) for Ն12 mol/L tHcy were as follows: Ͻ5 ng/mL folate (Ͻ1%), Ͻ250 pg/mL vitamin B 12 (24.5%), and Ն1.3 mg/dL creatinine (37.5%

B-vitamins, homocysteine metabolism and CVD

“…They have shown that once folate status has been optimised a clear dependence of tHcy on vitamin B 12 status emerges that is not observed in the presupplementation period and coincides with the loss of a correlation between tHcy and folate status. These findings are consistent with recent evidence from the USA that shows that in the era of folicacid fortification of grain foods it is vitamin B 12 status (and not folate status) that is now the major nutritional determinant of tHcy in that population (Liaugaudas et al 2001).…”

C-reactive protein, vitamin B12 and C677T polymorphism of N-5,10-methylenetetrahydrofolate reductase gene are related to insulin resistance and risk factors for metabolic syndrome in Chinese population

“…Oral supplement of 0.5 mg vitamin B12 daily further reduced Hcy level by another 3% to 10%. [32][33][34] It will be very interesting to explore whether supplementation of folic acid and vitamin B12 to patients with MS-associated T2DM can reduce the levels of uric acid and hs-CRP in individuals with the TT genotype and whether changing in capital lifestyle in conjunction with drug treatment can alter the characteristics of MS. Further epidemiological studies on the correlations of MTHFR gene polymorphism with MS in other ethnic populations are required.…”

Total Homocysteine Lowering Treatment Among Coronary Artery Disease Patients in the Era of Folic Acid-Fortified Cereal Grain Flour

“…Participants lived in the Pawtucket and Providence, RI, metropolitan areas and underwent their baseline examinations between October 1997, and May 1999. 5 Information regarding previous vitamin supplement use was obtained by standardized interview, and subjects were either nonusers of any supplements containing folic acid, or they had abstained from using such supplements for at least 6 weeks by the time of their examination. However, all participants were examined at least three to four months after the widespread availability in New England (John Watson, President, Watson Foods, New Haven, Conn, written communication, 1997) of cereal grain flour products fortified with folic acid at 140 g per 100 g flour.…”

“…T he prevalence of both deficient plasma folate status, [1][2][3][4][5] and elevated fasting total plasma levels of the putatively atherothrombotic 6 sulfur amino acid homocysteine (tHcy), 1,4,5 have been dramatically reduced since the recent advent of United States 7 and Canadian 8 initiatives to fortify all enriched cereal grain flour products with physiological amounts (ie, 140 g/100 g flour) of folic acid. Presently, there are three large, randomized, controlled trials of tHcy-lowering for the potential reduction of arteriosclerotic cardiovascular disease outcomes ongoing in the United States and Canada.…”

“…Presently, there are three large, randomized, controlled trials of tHcy-lowering for the potential reduction of arteriosclerotic cardiovascular disease outcomes ongoing in the United States and Canada. 9 The considerable (nutritional) biochemical effects [1][2][3][4][5] of cereal grain flour fortification with folic acid could substantially reduce the statistical power of these ongoing cardiovascular disease prevention studies. All three trials assume the patient groups assigned to active treatment will achieve the same mean tHcy-lowering treatment effects (ie, a mean reductions of Ϸ33%, or 4 to 6 mo/L) previously reported 10 in the absence of the large potential background effect of folic acid-fortified cereal grain flour.…”