Blondin DP, Péronnet F, Haman F. Effects of ingesting [ 13 C]glucose early or late into cold exposure on substrate utilization. J Appl Physiol 109: 654 -662, 2010. First published July 22, 2010 doi:10.1152/japplphysiol.00440.2010.-One of the factors limiting the oxidation of exogenous glucose during cold exposure may be the delay in establishing a shivering steady state (ϳ60 min), reducing glucose uptake into skeletal muscle. Therefore, using indirect calorimetry and isotopic methodologies in non-cold-acclimatized men, the main purpose of this study was to determine whether ingesting glucose at a moment coinciding with the maximal shivering intensity could increase the utilization rate of the ingested glucose. 13 C-enriched glucose was ingested (800 mg/min) from the onset (G0) or after 60 min (G60) of cold exposure when the thermogenic rate was stabilized to low-intensity shivering (ϳ2.5 times resting metabolic rate). For the same quantity of glucose ingested, the oxidation rate of exogenous glucose was 35% higher in G60 (159 Ϯ 17 vs. 118 Ϯ 17 mg/min in G0) between minutes 60 and 90. By the end of cold exposure, exogenous glucose oxidation was significantly greater in G0, reaching 231 Ϯ 14 mg/min, ϳ15% higher than the only rates previously reported. This considerably reduced the utilization of endogenous reserves over time and compared with the G60 condition. This study also demonstrates a fall in muscle glycogen utilization, when glucose was ingested from the onset of cold exposure (from ϳ150 to ϳ75 mg/min). Together, these findings indicate the importance of ingesting glucose immediately on exposure to a cold condition, relying on shivering thermogenesis and sustaining that consumption for as long as possible. This substrate not only provides an auxiliary fuel source for shivering thermogenesis, but, more importantly, preserves the limited endogenous glucose reserves. energy metabolism; shivering thermogenesis; heat loss; plasma glucose oxidation; stable isotopes DURING SHIVERING, CARBOHYDRATE (CHO) represent a substantial source of metabolic substrate, with its utilization accounting for up to ϳ80% of total heat production (Ḣ ) (15). Given the limited CHO reserves, several cold-exposure studies have focused on the effects of CHO ingestion on whole body fuel selection. Evidence from this research has shown that the ingestion of food rich in CHO alters substrate utilization to varying degrees (1,8,33). During very-low-(8) to lowintensity shivering (33), CHO ingestion has been shown to increase CHO utilization and reduce lipid oxidation. However, more recent findings demonstrated that, when proteins are also considered in the energy balance, ingesting glucose at a rate of 400 or 800 mg/min over 2 h of cold exposure does not alter total CHO, lipid, or protein utilization (1). Using isotopic methodologies, combined with indirect calorimetry, this latter study also showed that exogenous glucose oxidation peaked and reached a plateau at a rate of ϳ195 mg/min at the lower ingestion rate of 400 mg/min. Interestingly,...