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Targeted plasma metabolome response to variations in dietary glycemic load in a randomized, controlled, crossover feeding trial in healthy adults.

ABSTRACT: Low versus high glycemic load (GL) diet patterns are inversely associated with obesity and chronic diseases such as cancer and cardiovascular disease. These associations persist beyond the protection afforded by increased fiber alone, representing an important gap in our understanding of the metabolic effects of GL. We conducted a randomized, controlled, crossover feeding trial of two 28-day diet periods of high and low GL. Using LC-MS, targeted metabolomics analysis of 155 metabolites was performed on plasma samples from 19 healthy adults aged 18-45 years. Fourteen metabolites differed significantly between diets (P < 0.05), with kynurenate remaining significant after Bonferroni correction (P < 4 × 10(-4)). Metabolites with the largest difference in abundance were kynurenate and trimethylamine-N-oxide (TMAO), both significantly higher after consumption of the low GL diet. Partial least squares-discriminant analysis showed clear separation between the two diets; however no specific pathway was identified in pathway analyses. We found significant differences in 14 plasma metabolites suggesting a differing metabolic response to low and high GL diets. Kynurenate is associated with reduced inflammation, and may be one mechanism through which protective effects of a low GL diet are manifested and warrants further evaluation. This trial was registered at clinicaltrials.gov as NCT00622661.

SUBMITTER: Barton S

PROVIDER: S-EPMC4558254 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Targeted plasma metabolome response to variations in dietary glycemic load in a randomized, controlled, crossover feeding trial in healthy adults.

Barton Sally S Navarro Sandi L SL Buas Matthew F MF Schwarz Yvonne Y Gu Haiwei H Djukovic Danijel D Raftery Daniel D Kratz Mario M Neuhouser Marian L ML Lampe Johanna W JW

Food & function 20150901 9

Low versus high glycemic load (GL) diet patterns are inversely associated with obesity and chronic diseases such as cancer and cardiovascular disease. These associations persist beyond the protection afforded by increased fiber alone, representing an important gap in our understanding of the metabolic effects of GL. We conducted a randomized, controlled, crossover feeding trial of two 28-day diet periods of high and low GL. Using LC-MS, targeted metabolomics analysis of 155 metabolites was perfo ...[more]

PMID: 26165375

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Project description:BackgroundLow-glycemic load dietary patterns, characterized by consumption of whole grains, legumes, fruits, and vegetables, are associated with reduced risk of several chronic diseases.MethodsUsing samples from a randomized, controlled, crossover feeding trial, we evaluated the effects on metabolic profiles of a low-glycemic whole-grain dietary pattern (WG) compared with a dietary pattern high in refined grains and added sugars (RG) for 28 d. LC-MS-based targeted metabolomics analysis was performed on fasting plasma samples from 80 healthy participants (n = 40 men, n = 40 women) aged 18-45 y. Linear mixed models were used to evaluate differences in response between diets for individual metabolites. Kyoto Encyclopedia of Genes and Genomes (KEGG)-defined pathways and 2 novel data-driven analyses were conducted to consider differences at the pathway level.ResultsThere were 121 metabolites with detectable signal in >98% of all plasma samples. Eighteen metabolites were significantly different between diets at day 28 [false discovery rate (FDR) < 0.05]. Inositol, hydroxyphenylpyruvate, citrulline, ornithine, 13-hydroxyoctadecadienoic acid, glutamine, and oxaloacetate were higher after the WG diet than after the RG diet, whereas melatonin, betaine, creatine, acetylcholine, aspartate, hydroxyproline, methylhistidine, tryptophan, cystamine, carnitine, and trimethylamine were lower. Analyses using KEGG-defined pathways revealed statistically significant differences in tryptophan metabolism between diets, with kynurenine and melatonin positively associated with serum C-reactive protein concentrations. Novel data-driven methods at the metabolite and network levels found correlations among metabolites involved in branched-chain amino acid (BCAA) degradation, trimethylamine-N-oxide production, and β oxidation of fatty acids (FDR < 0.1) that differed between diets, with more favorable metabolic profiles detected after the WG diet. Higher BCAAs and trimethylamine were positively associated with homeostasis model assessment-insulin resistance.ConclusionsThese exploratory metabolomics results support beneficial effects of a low-glycemic load dietary pattern characterized by whole grains, legumes, fruits, and vegetables, compared with a diet high in refined grains and added sugars on inflammation and energy metabolism pathways. This trial was registered at clinicaltrials.gov as NCT00622661.

Dataset Information

Targeted plasma metabolome response to variations in dietary glycemic load in a randomized, controlled, crossover feeding trial in healthy adults.

Publications

Targeted plasma metabolome response to variations in dietary glycemic load in a randomized, controlled, crossover feeding trial in healthy adults.

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