Duality of Tocopherol Isoforms and Novel Associations with Vitamins Involved in One-Carbon Metabolism: Results from an Elderly Sample of the LifeLines Cohort Study.

Whether the affinity of serum vitamin E with total lipids hampers the appropriate assessment of its association with age-related risk factors has not been investigated in epidemiological studies. We aimed to compare linear regression-derived coefficients of the association of non-indexed and total lipids-indexed vitamin E isoforms with clinical and laboratory characteristics pertaining to the lipid, metabolic syndrome, and one-carbon metabolism biological domains. We studied 1429 elderly subjects (non-vitamin supplement users, 60-75 years old, with low and high socioeconomic status) from the population-based LifeLines Cohort and Biobank Study. We found that the associations of tocopherol isoforms with lipids were inverted in total lipids-indexed analyses, which may be indicative of overcorrection. Irrespective of the methods of standardization, we consistently found positive associations of α-tocopherol with vitamins of the one-carbon metabolism pathway and inverse associations with characteristics related to glucose metabolism. The associations of γ-tocopherol were often opposite to those of α-tocopherol. These data suggest that tocopherol isoforms and one-carbon metabolism are related, with beneficial and adverse associations for α-tocopherol and γ-tocopherol, respectively. Whether tocopherol isoforms, or their interplay, truly affect the one-carbon metabolism pathway remains to be further studied.

Joint Effect of Hypertension and Elevated Serum Phosphorus on the Risk of Mortality in National Health and Nutrition Examination Survey-III.

BACKGROUND: Elevated serum phosphorus might aggravate the effect of hypertension on mortality. The objective of this study was to examine the joint effect of hypertension and serum phosphorus on the risk of mortality. METHODS AND RESULTS: A large prospective (n=15 833), population-based cohort of participants from the National Health and Nutritional Examination Survey III was examined to test potential synergism between hypertension, elevated serum phosphorus, and the risk of mortality. Interaction on additive scale and multiplicative scale was estimated. After a median follow-up of 14.3 years, 1691 cases of cardiovascular mortality and 3875 cases of all-cause mortality were identified. Interaction was observed between hypertension and elevated serum phosphorus on the additive scale for cardiovascular mortality (relative excess risk due to interaction, 0.99, 95% CI: 0.06; 1.92, adjusted for age, gender, race, and estimated glomerular filtration rate). No statistically significant interaction was found between hypertension and serum phosphorus for all-cause mortality on the additive scale. No significant interaction was detected on the multiplicative scale. In sensitivity analysis, excluding participants who died in first 2 years and adjustment for additional confounders resulted in essentially similar findings. CONCLUSIONS: The joint effect of hypertension and elevated serum phosphorus was larger than the sum of the independent effects on cardiovascular mortality but not on all-cause mortality. Future studies should investigate whether controlling elevated serum phosphorus in hypertensive individuals helps in prevention of extra risk of cardiovascular mortality.