Nuclear Magnetic Resonance-Based Metabolomics Enable Detection of the Effects of a Whole Grain Rye and Rye Bran Diet on the Metabolic Profile of Plasma in Prostate Cancer Patients

Prostate cancer (PC) is the most common cancer in the Western world and the second most important cancer causing male deaths, after lung cancer, in the United States and Britain. Lifestyle and dietary changes are recommended for men diagnosed with early-stage PC. It has been shown that a diet rich in whole grain (WG) rye reduces the progression of early-stage PC, but the underlying mechanism is not clear. This study sought to identify changes in the metabolic signature of plasma in patients with early-stage PC following intervention with a diet rich in WG rye and rye bran product (RP) compared with refined white wheat product (WP) as a tool for mechanistic investigation of the beneficial health effects of RP on PC progression. Seventeen PC patients received 485 g RP or WP in a randomized, controlled, crossover design during a period of 6 wk with a 2-wk washout period. At the end of each intervention period, plasma was collected after fasting and used for (1)H NMR-based metabolomics. Multilevel partial least squares discriminant analysis was used for paired comparisons of multivariate data. A metabolomics analysis of plasma showed an increase in 5 metabolites, including 3-hydroxybutyric acid, acetone, betaine, N,N-dimethylglycine, and dimethyl sulfone, after RP. To understand these metabolic changes, fasting plasma homocysteine, leptin, adiponectin, and glucagon were measured separately. The plasma homocysteine concentration was lower (P = 0.0171 and that of leptin tended to be lower (P = 0.07) after RP intake compared to WP intake. The increase in plasma 3-hydroxybutyric acid and acetone after RP suggests a shift in energy metabolism from anabolic to catabolic status, which could explain some of the beneficial health effects of WG rye, i.e., reduction in prostate-specific antigen and reduced 24-h insulin secretion. In addition, the increase in betaine and N,N-dimethylglycine and the decrease in homocysteine show a favorable shift in homocysteine metabolism after RP intake. J. Nutr. 141: 2126-2132, 2011.