Association between dietary macronutrient composition and plasma one-carbon metabolites and B-vitamin cofactors in patients with stable angina pectoris

Abstract Elevated plasma concentrations of several one-carbon metabolites are associated with increased CVD risk. Both diet-induced regulation and dietary content of one-carbon metabolites can influence circulating concentrations of these markers. We cross-sectionally analyzed 1928 patients with suspected stable angina pectoris (geometric mean age 61), representing elevated CVD risk, to assess associations between dietary macronutrient composition (food frequency questionnaire) and plasma one-carbon metabolites and related B-vitamin status markers (GC-MS/MS, LC-MS/MS, or microbiological assay). Diet-metabolite associations were modelled on the continuous scale, adjusted for age, sex, BMI, smoking, alcohol, and total energy intake. Average (geometric mean [95% prediction interval]) intake was 49 (38, 63) energy percent (E%) from carbohydrate, 31 (22, 45) E% from fat, and 17 (12, 22) E% from protein. The strongest associations were seen for higher protein intake, i.e., with higher plasma pyridoxal 5’-phosphate (PLP) (% change [95% confidence interval] 3.1 [2.1, 4.1]), cobalamin (2.9 [2.1, 3.7]), riboflavin (2.4 [1.1, 3.7]), and folate (2.1 [1.2, 3.1]), and lower total homocysteine (tHcy) (-1.4 [-1.9, -0.9]) and methylmalonic acid (MMA) (-1.4 [-2.0, -0.8]). Substitution analyses replacing mono- or polyunsaturated with saturated fatty acids demonstrated higher plasma concentrations of riboflavin (5.0 [0.9, 9.3] and 3.3 [1.1, 5.6]), tHcy (2.3 [0.7, 3.8] and 1.3 [0.5, 2.2]), and MMA (2.0 [0.2, 3.9] and 1.7 [0.7, 2.7]), and lower PLP (-2.5 [-5.3, 0.3] and -2.7 [-4.2, -1.2]). In conclusion, a higher protein intake, and replacing saturated with mono- and polyunsaturated fatty acids, was associated with a more favourable metabolic phenotype regarding metabolites associated with CVD risk.