Plasma metabolite abundances are associated with urinary enterolactone excretion in healthy participants on controlled diets.

Enterolignans, products of gut bacterial metabolism of plant lignans, have been associated with reduced risk of chronic diseases, but their association with other plasma metabolites is unknown. We examined plasma metabolite profiles according to urinary enterolignan excretion in a cross-sectional analysis using data from a randomized crossover, controlled feeding study. Eighty healthy adult males and females completed two 28-day feeding periods differing by glycemic load, refined carbohydrate, and fiber content. Lignan intake was calculated from food records using a polyphenol database. Targeted metabolomics was performed by LC-MS on plasma from fasting blood samples collected at the end of each feeding period. Enterolactone (ENL) and enterodiol, were measured in 24 h urine samples collected on the penultimate day of each study period using GC-MS. Linear mixed models were used to test the association between enterolignan excretion and metabolite abundances. Pathway analyses were conducted using the Global Test. Benjamini-Hochberg false discovery rate (FDR) was used to control for multiple testing. Of the metabolites assayed, 121 were detected in all samples. ENL excretion was associated positively with plasma hippuric acid and melatonin, and inversely with epinephrine, creatine, glycochenodeoxycholate, and glyceraldehyde (P < 0.05). Hippuric acid only satisfied the FDR of q < 0.1. END excretion was associated with myristic acid and glycine (q < 0.5). Two of 57 pathways tested were associated significantly with ENL, ubiquinone and terpenoid-quinone biosynthesis, and inositol phosphate metabolism. These results suggest a potential role for ENL or ENL-metabolizing gut bacteria in regulating plasma metabolites.

Modulation of human serum glutathione S-transferase A1/2 concentration by cruciferous vegetables in a controlled feeding study is influenced by GSTM1 and GSTT1 genotypes.

Glutathione S-transferases (GST) detoxify a wide range of carcinogens. Isothiocyanates (ITC), from cruciferous vegetables, are substrates for and inducers of GST. GST variants may alter ITC clearance such that response to crucifers varies by genotype. In a randomized cross-over trial, we tested the hypothesis that changes in serum GSTA1/2 concentration in response to cruciferous vegetable feeding depends on GSTM1/GSTT1 genotype. Thirty-three men and 34 women (age 20-40 years) ate four 14-day controlled diets--basal (vegetable-free), basal supplemented with two different doses of crucifers ("single dose" and "double dose"), and single-dose cruciferous-plus-apiaceous vegetables--fed per kilogram of body weight. Fasting bloods from days 0, 7, 11, and 14 of each diet period were analyzed for serum GSTA1/2 by ELISA. GSTA1/2 increased with single- and double-dose cruciferous compared with basal diet (10% and 13%, respectively; P = 0.02 and 0.004), but cruciferous-plus-apiaceous did not differ from basal (P = 0.59). Overall, GSTA1/2 was higher in GSTM1-null/GSTT1-null than GSTM1+/GSTT1+ individuals (4,198 +/- 338 and 3,372 +/- 183 pg/mL; P = 0.03). The formal interaction of genotype-by-diet was not statistically significant, but the GSTA1/2 increase during the single-dose cruciferous diet was among GSTM1-null/GSTT1-null individuals (by 28%; P = 0.008), largely explained by GSTM1-null/GSTT1-null men (by 41%; P = 0.01). GSTA1/2 increased during the double-dose cruciferous diet in both GSTM1-null/GSTT1-null men (by 35%; P = 0.04) and GSTM1+/GSTT1+ men (by 26%; P = 0.01) but not in women. In summary, cruciferous vegetable supplementation increased GSTA1/2, but the effect was most marked in GSTM1-null/GSTT1-null men.

Serum beta-glucuronidase activity in response to fruit and vegetable supplementation: a controlled feeding study.

BACKGROUND: Fruit and vegetable (F&V) intake may lower the risk of some cancers. One hypothesized, but understudied, chemopreventive mechanism is that plant food constituents inhibit beta-glucuronidase, an acid hydrolase that deconjugates glucuronides. METHODS: We conducted a crossover feeding trial in 63 healthy women and men ages 20 to 40 years to examine the effect of diet on serum beta-glucuronidase activity. Participants were randomized to two 2-week experimental diets with an intervening washout period: a diet high in selected citrus fruit, crucifers, and soy (F&V) and a diet devoid of fruits, vegetables, and soy (basal). Serum beta-glucuronidase activity was measured during the preintervention, F&V, and basal periods. Linear mixed models were used to obtain effect estimates and 95% confidence intervals (95% CI). RESULTS: We observed statistically significantly higher beta-glucuronidase activity during the F&V than the basal diet (ratio, F&V versus basal diet, 1.09; 95% CI, 1.05-1.13; P < 0.01). These results were probably due to decreased beta-glucuronidase activity during the basal diet (ratio, basal period versus preintervention, 0.93; 95% CI, 0.87-0.98; P = 0.01) rather than increased enzyme activity during the F&V diet (ratio, F&V period versus preintervention, 1.01; 95% CI, 0.96-1.06; P = 0.64). Response to the experimental diet did not differ by sex (P(interaction) = 0.30), but there was a suggestion of a short-term diet effect at 8 versus 15 days (P(interaction) = 0.06). CONCLUSION: This intervention of selected F&V did not lower beta-glucuronidase activity. Further investigation is needed regarding what other foods and phytochemicals may influence beta-glucuronidase activity and effect modifiers of this relation.