Background Studying the impact of dietary carbohydrates and fat on markers of one-carbon metabolism could provide important insight into distinct metabolic adaptations and how diets affects disease risk. Objective To determine changes in plasma one-carbon metabolites and B-vitamers on isocaloric diets differing in carbohydrate processing or amount. Methods 193 individuals with obesity were randomized to equal energy- and protein diets either with more processed, acellular carbohydrates (A-HCLF, comparator arm), minimally processed cellular carbohydrates (C-HCLF) (both designed with 45 energy percent (E%) carbohydrates and 38 E% fat), or a low-carbohydrate, high-fat diet (LCHF) designed with 8 E% carbohydrate and ∼75 E% fat including 30 E% saturated fat. Addressing secondary outcomes of the trial, we analyzed changes in plasma one-carbon metabolites and B-vitamers, and dietary B-vitamin intakes after 3, 6, 9 and 12 months, using constrained linear mixed effect modelling (cLMM). Results After 3 months, the relative change score following the LCHF diet was significantly different from the A-HCLF comparator for plasma α-hydroxybutyrate (LCHF/A-HCLF: +41.3%*/−1.56%, p<0.001; *: significant within-group change), methylmalonic acid (MMA) (−5.69%*/+8.64%*, p <0.001), methionine (−7.81%*/+1.44%, p =0.001), nicotinamide (−19.7%*/+14.0%, p=0.007), 1-Methylnicotinamide (mNAM) (−14.1%*/+14.1%, p=0.003), pyridoxal (−2.42%/+18.9%*), 4-pyridoxic acid (−12.4%*/+21.4%*, p<0.001), and cysteine (−3.00%*/+1.10%). Between-group differences for most of these metabolites remained significant after 6 and 9 months. Comparing C-HCLF to A-HCLF, significant differences in relative change scores were found for mNAM after 3 (C-HCLF/A-HCLF: −11.5%/+14.1%, p=0.012) and 9 (−14.9%*/+18.6%, p=0.001) months. Plasma changes in one-carbon metabolites and B-vitamers showed weak correlations with dietary B-vitamins. Conclusion Compared with A-HCLF, the LCHF diet was followed by significantly different changes in plasma α-hydroxybutyrate, MMA, methionine, nicotinamide, mNAM, pyridoxal, 4-pyridoxic acid and cysteine. These shifts were largely independent of vitamin consumption, and may rather reflect ketoadaptive mechanisms, including enhanced fatty acid oxidation and upregulated antioxidant defense. Carbohydrate quality had less impact on the one-carbon metabolites. Clinical Trial Registry number NCT03401970 ( https://clinicaltrials.gov/study/NCT03401970 )
Bråtveit et al. (Mon,) studied this question.