title: Effects of alkali supplementation and vitamin D insufficiency on rat skeletal muscle.
abstract: 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.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center, Box 268, 800 Washington Street, Boston, MA, 02111, USA, lisa.ceglia@tufts.edu.
authors.forename: Lisa
authors.initials: L
authors.lastname: Ceglia
authors.forename: Donato A
authors.initials: DA
authors.lastname: Rivas
authors.forename: Rachele M
authors.initials: RM
authors.lastname: Pojednic
authors.forename: Lori Lyn
authors.initials: LL
authors.lastname: Price
authors.forename: Susan S
authors.initials: SS
authors.lastname: Harris
authors.forename: Donald
authors.initials: D
authors.lastname: Smith
authors.forename: Roger A
authors.initials: RA
authors.lastname: Fielding
authors.forename: Bess
authors.initials: B
authors.lastname: Dawson-Hughes
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000468:Alkalies / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019587:Dietary Supplements; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D014807:Vitamin D / Q000097:blood; D014808:Vitamin D Deficiency / Q000378:metabolism / Q000473:pathology*
chemical_list: D000468:Alkalies; D014807:Vitamin D