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

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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.

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Acknowledgments

The authors thank the Comparative Biology Unit and the Nutrition Evaluation Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University for their help with the study. The research study was supported by the Boston Claude D. Pepper Older Americans Independence Center (5P30AG031679). Additional support was provided by the Tufts Clinical and Translational Science Institute Grant (UL1 RR025752) from the National Center for Research Resources and the Gerald J. and Dorothy R. Friedman Foundation. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Research Resources. This material is also based upon work supported by the USDA, Agricultural Research Service, under agreement No. 58-1950-7-707. Any opinions, findings, conclusion, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Dept of Agriculture.

Conflict of interest

The authors LC, DAR, RP, LLP, SSH, DS, RAF, and BDH have no conflict of interest to disclose.

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Authors and Affiliations

  1. Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center, Box 268, 800 Washington Street, Boston, MA, 02111, USA

    Lisa Ceglia

  2. Bone Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA, 02111, USA

    Lisa Ceglia, Susan S. Harris & Bess Dawson-Hughes

  3. Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA, 02111, USA

    Donato A. Rivas, Rachele M. Pojednic & Roger A. Fielding

  4. The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, and Tufts Clinical and Translational Science Institute, 800 Washington Street, Box #63, Boston, MA, 02111, USA

    Lori Lyn Price

  5. Comparative Biology Unit, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111, USA

    Donald Smith

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  1. Lisa Ceglia
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  8. Bess Dawson-Hughes
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Correspondence to Lisa Ceglia.

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This study was performed at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111.

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Ceglia, L., Rivas, D.A., Pojednic, R.M. et al. Effects of alkali supplementation and vitamin D insufficiency on rat skeletal muscle. Endocrine 44, 454–464 (2013). https://doi.org/10.1007/s12020-013-9976-0

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