Effects of alkali supplementation and vitamin D insufficiency on rat skeletal muscle

Data on the independent and potential combined effects of acid–base balance and vitamin D status on muscle mass and metabolism are lacking. We investigated whether alkali supplementation with potassium bicarbonate (KHCO₃), with or without vitamin D₃ (±VD₃), alters urinary nitrogen (indicator of muscle proteolysis), muscle fiber cross-sectional area (FCSA), fiber number (FN), and anabolic (IGF-1, Akt, p70s6k) and catabolic (FOXO3a, MURF1, MAFbx) signaling pathways regulating muscle mass. Thirty-six, 20-month-old, Fischer 344/Brown-Norway rats were randomly assigned in a 2 × 2 factorial design to one of two KHCO₃-supplemented diets (±VD₃) or diets without KHCO₃ (±VD₃) for 12 weeks. Soleus, extensor digitorum longus (EDL), and plantaris muscles were harvested at 12 weeks. Independent of VD₃ group, KHCO₃ supplementation resulted in 35 % lower mean urinary nitrogen to creatinine ratio, 10 % higher mean type I FCSA (adjusted to muscle weight), but no statistically different mean type II FCSA (adjusted to muscle weight) or FN compared to no KHCO₃. Among VD₃-replete rats, phosphorylated-Akt protein expression was twofold higher in the KHCO₃ compared to no KHCO₃ groups, but this effect was blunted in rats on VD₃-deficient diets. Neither intervention significantly affected serum or intramuscular IGF-1 expression, p70s6k or FOXO3a activation, or MURF1 and MAFbx gene expression. These findings provide support for alkali supplementation as a promising intervention to promote preservation of skeletal muscle mass, particularly in the setting of higher vitamin D status. Additional research is needed in defining the muscle biological pathways that are being targeted by alkali and vitamin D supplementation.