The monosaccharides glucose and fructose have been extensively investigated for their well-recognised roles in metabolism and human health. In contrast, galactose, the third major dietary monosaccharide, has received less attention in human volunteer research outside of its role in the pathophysiology of galactosaemias.
The acute ingestion of free galactose elicits a minimal or modest insulin response but a marked increase in blood galactose concentrations, which, depending on dose, largely returns to baseline within 2 hours. Galactose is mostly consumed within the human diet as lactose is present in milk and a well-established observation is that the co-ingestion of galactose with glucose (in free form or as lactose) partially or almost completely blunts the increase in blood galactose concentrations. We have confirmed this also occurs during exercise although the enhanced galactose clearance does not appear to increase it use as an exogenous fuel source (Odell et al, 2022).
Evidence suggests that the co-ingestion of glucose enhances splanchnic galactose extraction, with the liver, and its substantial expression of Leloir pathway enzymes, considered the major site of galactose metabolism. The prevailing view is that these effects are related to increases in blood glucose concentrations, and not the concomitant increase in blood insulin that occurs with galactose-glucose co-ingestion. However, data will be presented to suggest a role for insulin mediated plasma galactose clearance, although it is acknowledged that modulation of gastrointestinal transit by presence of other nutrients cannot be discounted.
Recent observations of postexercise muscle glycogen synthesis with aggressive galactose ingestion and evidence for skeletal-muscle expression of Leloir pathway enzymes suggested further research into the potential for extra-splanchnic galactose metabolism was warranted (Podlogar et al, 2023). Results from a collaborative project will be presented to provide evidence for galactose uptake in human skeletal muscle as determined using dynamic 2-(18)F-fluoro-2-deoxy-d-galactose ((18)F-FDGal) PET/CT approaches. Data will also be presented showing that less aggressive but still high galactose feeding modulated expression of genes related to galactose metabolism in skeletal muscle but did not stimulate short-term post-exercise muscle glycogen synthesis.
Collectively, recent investigations suggest the potential for galactose metabolism in skeletal muscle and its modulation by nutrients, insulin and/or exercise does exist, although its physiological significance requires further investigation.