Vitamin B-6 deficiency causes mild elevation in plasma homocysteine, but the mechanism has not been clearly established. Serine is a substrate in one-carbon metabolism and in the transsulfuration pathway of homocysteine catabolism, and pyridoxal phosphate (PLP) plays a key role as coenzyme for serine hydroxymethyltransferase (SHMT) and enzymes of transsulfuration. In this study we used [2H3]serine as a primary tracer to examine the remethylation pathway in adequately nourished and vitamin B-6-deficient rats [7 and 0.1 mg pyridoxine (PN)/kg diet]. [2H3]Leucine and [1-13C]methionine were also used to examine turnover of protein and methionine pools, respectively. All tracers were injected intraperitoneally as a bolus dose, and then rats were killed (n = 4/time point) after 30, 60 and 120 min. Rats fed the low-PN diet had significantly lower growth and plasma and liver PLP concentrations, reduced liver SHMT activity, greater plasma and liver total homocysteine concentration, and reduced liver S-adenosylmethionine concentration. Hepatic and whole body protein turnover were reduced in vitamin B-6-deficient rats as evidenced by greater isotopic enrichment of [2H3]leucine. Hepatic [2H2]methionine production from [2H3]serine via cytosolic SHMT and the remethylation pathway was reduced by 80.6% in vitamin B-6 deficiency. The deficiency did not significantly reduce hepatic cystathionine-β-synthase activity, and in vivo hepatic transsulfuration flux shown by production of [2H3]cysteine from the [2H3]serine increased over twofold. In contrast, plasma appearance of [2H3]cysteine was decreased by 89% in vitamin B-6 deficiency. The rate of hepatic homocysteine production shown by the ratio of [1-13C]homocysteine/[1-13C]methionine areas under enrichment vs. time curves was not affected by vitamin B-6 deficiency. Overall, these results indicate that vitamin B-6 deficiency substantially affects one-carbon metabolism by impairing both methyl group production for homocysteine remethylation and flux through whole-body transsulfuration.
The long-term impact of dietary carbohydrate type, in particular sucrose, on insulin resistance and the development of diabetes and atherosclerosis is not established. Current guidelines for the healthy population advise restriction of sucrose intake. We investigated the effect of high- versus low-sucrose diet (25 vs. 10%, respectively, of total energy intake) in 13 healthy subjects aged 33 ± 3 years (mean ± SE), BMI 26.6 ± 0.9 kg/m2, in a randomized crossover design with sequential 6-week dietary interventions separated by a 4-week washout. Weight maintenance, eucaloric diets with identical macronutrient profiles and fiber content were designed. All food was weighed and distributed. Insulin action was assessed using a two-step euglycemic clamp; glycemic profiles were assessed by the continuous glucose monitoring system and vascular compliance by pulse-wave analysis. There was no change in weight across the study. Peripheral glucose uptake and suppression of endogenous glucose production were similar after each diet. Glycemic profiles and measures of vascular compliance did not change. A rise in total and LDL cholesterol was observed. In this study, a high-sucrose intake as part of an eucaloric, weight-maintaining diet had no detrimental effect on insulin sensitivity, glycemic profiles, or measures of vascular compliance in healthy nondiabetic subjects.
Red meat from grass-fed animals, compared with concentrate-fed animals, contains increased concentrations of long-chain (LC)n-3 PUFA. However, the effects of red meat consumption from grass-fed animals on consumer blood concentrations of LCn-3 PUFA are unknown. The aim of the present study was to compare the effects on plasma and platelet LCn-3 PUFA status of consuming red meat produced from either grass-fed animals or concentrate-fed animals. A randomised, double-blinded, dietary intervention study was carried out for 4 weeks on healthy subjects who replaced their habitual red meat intake with three portions per week of red meat (beef and lamb) from animals offered a finishing diet of either grass or concentrate (n20 consumers). Plasma and platelet fatty acid composition, dietary intake, blood pressure, and serum lipids and lipoproteins were analysed at baseline and post-intervention. Dietary intakes of totaln-3 PUFA, as well as plasma and platelet concentrations of LCn-3 PUFA, were significantly higher in those subjects who consumed red meat from grass-fed animals compared with those who consumed red meat from concentrate-fed animals (P < 0·05). No significant differences in concentrations of serum cholesterol, TAG or blood pressure were observed between groups. Consuming red meat from grass-fed animals compared with concentrate-fed animals as part of the habitual diet can significantly increase consumer plasma and platelet LCn-3 PUFA status. As a result, red meat from grass-fed animals may contribute to dietary intakes of LCn-3 PUFA in populations where red meat is habitually consumed.