Substrate metabolism and metabolic flexibility in male astronauts onboard the International Space Station: The ENERGY study

Abstract Simulated microgravity is known to induce a shift in fasting fuel selection in favor of carbohydrate use and in detriment of lipids, and to reduce metabolic flexibility (MF), i.e., the capacity to adjust fuel oxidation to changes in substrate availability and energy demand. Given their potential adverse effects on performance and health, we aimed to determine whether such metabolic alterations occur in astronauts during long-term spaceflights. We further explored the associations with diet, physical activity, and body composition. Before and after at least three months onboard the International Space Station, respiratory quotient (RQ), carbohydrate and fat oxidation were measured by indirect calorimetry before and following a standardized meal in 11 male astronauts (age=45.7 [SD 7.7] years, BMI=24.3 [2.1] kg/m²). MF was determined by 0-to-260 min postprandial incremental area under the curve (iAUC) of nutrient oxidation and the difference between maximal postprandial and fasting RQ (ΔRQ). The food quotient (FQ) was calculated from diet logs. Fat (FM) and fat-free mass (FFM) were measured by hydrometry and physical activity by accelerometry and diary logs. Three months in space increased fasting RQ (P=0.01) and carbohydrate oxidation (P=0.04), and decreased fasting lipid oxidation (P<0.01). An increase in FQ (P<0.001) indicated a shift in diet composition. Spaceflight-induced changes in RQ adjusted on ground RQ were associated with inflight FQ (P<0.01). No changes were noted in mean postprandial nutrient oxidation or ΔRQ. Individual postprandial lipid oxidation iAUC was negatively associated with changes in FFM and inflight aerobic exercise, and positively with changes in FM. The opposite was observed with postprandial carbohydrate oxidation. Changes in ΔRQ were negatively and positively related to FM and FFM changes, respectively. In conclusion, the shift in fasting substrate oxidation observed during spaceflight is essentially driven by dietary modifications. Between-astronaut variability in postprandial substrate oxidation depends on body composition changes and inflight physical activity.