Estrogen supplementation reduces whole body leucine and carbohydrate oxidation and increases lipid oxidation in men during endurance exercise

Healthy active men exhibit higher rates of carbohydrate (CHO) and leucine oxidation and lower rates of lipid oxidation compared with their female counterparts both at rest and during moderate intensity endurance exercise. We postulated that this reduced dependence on amino acids as a fuel source in women was due to the female sex hormone estrogen. In a randomized, double-blind, placebo-controlled, cross-over design, we investigated the effect of supplementing 12 recreationally active men with estrogen on whole body substrate oxidation and leucine kinetics at rest and during moderate intensity endurance exercise. Subjects cycled for 90 min at an intensity of 65% maximum O(2) consumption after 8 d of either estrogen supplementation ( 2 mg 17 beta-estradiol/d) or placebo ( polycose). After a 2-wk washout period, they repeated the test after 8 d of the alternate treatment. On the test day, after a primed continuous infusion of L-[(13)C] leucine, O(2) consumption, CO(2) production, steady-state breath (13)CO(2), and plasma alpha-[(13)C] ketoisocaproate enrichments were measured at rest and at 60, 75, and 90 min during exercise in the postabsorptive state. Exercise increased energy expenditure more than 5-fold, CHO oxidation more than 6-fold, lipid oxidation more than 4-fold, and leucine oxidation 2.2-fold ( all P < 0.0001), whereas it decreased the ratio of lipid to CHO oxidation by 50 - 70% ( P = 0.003) compared with values at rest. Estrogen supplementation decreased respiratory exchange ratio during exercise ( P = 0.03). Estrogen supplementation significantly decreased CHO oxidation by 5 - 16% ( P = 0.04) and leucine oxidation by 16% ( P = 0.01), whereas it significantly increased lipid oxidation by 22 - 44% ( P = 0.024) at rest and during exercise. We conclude that estrogen influences fuel source selection at rest and during endurance exercise in recreationally active men, characterized by a reduced dependence on amino acids and CHO and an increased reliance on lipids as a fuel source.