Endocrine

, Volume 44, Issue 2, pp 454–464 | Cite as

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

  • Lisa Ceglia
  • Donato A. Rivas
  • Rachele M. Pojednic
  • Lori Lyn Price
  • Susan S. Harris
  • Donald Smith
  • Roger A. Fielding
  • Bess Dawson-Hughes
Original Article

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.

Keywords

Skeletal muscle Potassium bicarbonate Vitamin D Metabolic acidosis 

References

  1. 1.
    J.F. Aloia, D.M. McGowan, A.N. Vaswani, P. Ross, S.H. Cohn, Relationship of menopause to skeletal and muscle mass. Am. J. Clin. Nutr. 53, 1378–1383 (1991)PubMedGoogle Scholar
  2. 2.
    V.A. Hughes, W.R. Frontera, R. Roubenoff, W.J. Evans, M.A. Singh, Longitudinal changes in body composition in older men and women: role of body weight change and physical activity. Am. J. Clin. Nutr. 76, 473–481 (2002)PubMedGoogle Scholar
  3. 3.
    J. Vormann, T. Remer, Dietary, metabolic, physiologic, and disease-related aspects of acid-base balance: foreword to the contributions of the second International Acid-Base Symposium. J. Nutr. 138, 413S–414S (2008)PubMedGoogle Scholar
  4. 4.
    T. Remer, F. Manz, Potential renal acid load of foods and its influence on urine pH. J. Am. Diet. Assoc. 95, 791–797 (1995)PubMedCrossRefGoogle Scholar
  5. 5.
    R.D. Lindeman, J. Tobin, N.W. Shock, Longitudinal studies on the rate of decline in renal function with age. J. Am. Geriatr. Soc. 33, 278–285 (1985)PubMedGoogle Scholar
  6. 6.
    B. Dawson-Hughes, S.S. Harris, L. Ceglia, Alkaline diets favor lean tissue mass in older adults. Am. J. Clin. Nutr. 87, 662–665 (2008)PubMedGoogle Scholar
  7. 7.
    M.K. Abramowitz, T.H. Hostetter, M.L. Melamed, Association of serum bicarbonate levels with gait speed and quadriceps strength in older adults. Am. J. Kidney Dis. 58, 29–38 (2011)PubMedCrossRefGoogle Scholar
  8. 8.
    B. Williams, E. Layward, J. Walls, Skeletal muscle degradation and nitrogen wasting in rats with chronic metabolic acidosis. Clin. Sci. (Lond.) 80, 457–462 (1991)Google Scholar
  9. 9.
    R.C. May, R.A. Kelly, W.E. Mitch, Metabolic acidosis stimulates protein degradation in rat muscle by a glucocorticoid-dependent mechanism. J. Clin. Invest. 77, 614–621 (1986)PubMedCrossRefGoogle Scholar
  10. 10.
    W.W. Souba, R.J. Smith, D.W. Wilmore, Glutamine metabolism by the intestinal tract. J. Parenter. Enteral Nutr. 9, 608–617 (1985)CrossRefGoogle Scholar
  11. 11.
    W.G. Guder, D. Haussinger, W. Gerok, Renal and hepatic nitrogen metabolism in systemic acid base regulation. J. Clin. Chem. Clin. Biochem. 25, 457–466 (1987)PubMedGoogle Scholar
  12. 12.
    W.E. Mitch, Cellular mechanisms of catabolism activated by metabolic acidosis. Blood Purif. 13, 368–374 (1995)PubMedCrossRefGoogle Scholar
  13. 13.
    J.L. Bailey, B. Zheng, Z. Hu, S.R. Price, W.E. Mitch, Chronic kidney disease causes defects in signaling through the insulin receptor substrate/phosphatidylinositol 3-kinase/Akt pathway: implications for muscle atrophy. J. Am. Soc. Nephrol. 17, 1388–1394 (2006)PubMedCrossRefGoogle Scholar
  14. 14.
    L. Frassetto, R.C. Morris Jr, A. Sebastian, Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women. J. Clin. Endocrinol. Metab. 82, 254–259 (1997)PubMedCrossRefGoogle Scholar
  15. 15.
    L. Ceglia, S.S. Harris, S.A. Abrams, H.M. Rasmussen, G.E. Dallal, B. Dawson-Hughes, Potassium bicarbonate attenuates the urinary nitrogen excretion that accompanies an increase in dietary protein and may promote calcium absorption. J. Clin. Endocrinol. Metab. 94, 645–653 (2009)PubMedCrossRefGoogle Scholar
  16. 16.
    B. Dawson-Hughes, C. Castaneda-Sceppa, S.S. Harris, N.J. Palermo, G. Cloutier, L. Ceglia, G.E. Dallal, Impact of supplementation with bicarbonate on lower-extremity muscle performance in older men and women. Osteoporos. Int. 21, 1171–1179 (2010)PubMedCrossRefGoogle Scholar
  17. 17.
    R. Smith, G. Stern, Myopathy, osteomalacia and hyperparathyroidism. Brain 90, 593–602 (1967)PubMedCrossRefGoogle Scholar
  18. 18.
    M. Visser, D.J. Deeg, P. Lips, Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J. Clin. Endocrinol. Metab. 88, 5766–5772 (2003)PubMedCrossRefGoogle Scholar
  19. 19.
    M.B. Snijder, N.M. van Schoor, S.M. Pluijm, R.M. van Dam, M. Visser, P. Lips, Vitamin D status in relation to one-year risk of recurrent falling in older men and women. J. Clin. Endocrinol. Metab. 91, 2980–2985 (2006)PubMedCrossRefGoogle Scholar
  20. 20.
    J.W. Prineas, A.S. Mason, R.A. Henson, Myopathy in metabolic bone disease. Br. Med. J. 1, 1034–1036 (1965)PubMedCrossRefGoogle Scholar
  21. 21.
    G.D. Schott, M.R. Wills, Muscle weakness in osteomalacia. Lancet 1, 626–629 (1976)PubMedCrossRefGoogle Scholar
  22. 22.
    H. Glerup, K. Mikkelsen, L. Poulsen, E. Hass, S. Overbeck, H. Andersen, P. Charles, E.F. Eriksen, Hypovitaminosis D myopathy without biochemical signs of osteomalacic bone involvement. Calc. Tiss. Int. 66, 419–424 (2000)CrossRefGoogle Scholar
  23. 23.
    D. Seigfried, J. Arruda, N. Kurtzman, Influence of vitamin D on bicarbonate reabsorption, in Phosphate Metabolism, ed. by S.G. Massry (Plenum Press, New York and London, 1978), pp. 395–404Google Scholar
  24. 24.
    R.A. Peraino, E. Ghafary, D. Rouse, B.J. Stinebaugh, W.N. Suki, Effect of 25-hydroxycholecalciferol on renal handling of sodium, calcium, and phosphate during bicarbonate infusion. Miner. Electrolyte Metab. 1, 321–329 (1978)Google Scholar
  25. 25.
    H. Kawashiwa, J.A. Kraut, K. Kurokawa, Metabolic acidosis suppresses 25-hydroxyvitamin in D3–1alpha-hydroxylase in the rat kidney. Distinct site and mechanism of action. J Clin Invest 70, 135–140 (1982)CrossRefGoogle Scholar
  26. 26.
    S.W. Lee, J. Russell, L.V. Avioli, 25-hydroxycholecalciferol to 1,25-dihydroxycholechalciferol: conversion impaired by systemic metabolic acidosis. Science 175, 994–996 (1977)CrossRefGoogle Scholar
  27. 27.
    P.G. Reeves, F.H. Nielsen, G.C. Fahey Jr, AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J. Nutr. 123, 1939–1951 (1993)PubMedGoogle Scholar
  28. 28.
    J. Mardon, V. Habauzit, A. Trzeciakiewicz, M.J. Davicco, P. Lebecque, S. Mercier, J.C. Tressol, M.N. Horcajada, C. Demigne, V. Coxam, Long-term intake of a high-protein diet with or without potassium citrate modulates acid-base metabolism, but not bone status, in male rats. J. Nutr. 138, 718–724 (2008)PubMedGoogle Scholar
  29. 29.
    L. Doyle, K.D. Cashman, The effect of nutrient profiles of the Dietary Approaches to Stop Hypertension (DASH) diets on blood pressure and bone metabolism and composition in normotensive and hypertensive rats. Br. J. Nutr. 89, 713–724 (2003)PubMedCrossRefGoogle Scholar
  30. 30.
    A.A. Welch, A. Mulligan, S.A. Bingham, K.T. Khaw, Urine pH is an indicator of dietary acid-base load, fruit and vegetables and meat intakes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study. Br. J. Nutr. 99, 1335–1343 (2008)PubMedCrossRefGoogle Scholar
  31. 31.
    J.L. Greger, S.M. Kaup, A.R. Behling, Calcium, magnesium and phosphorus utilization by rats fed sodium and potassium salts of various inorganic anions. J. Nutr. 121, 1382–1388 (1991)PubMedGoogle Scholar
  32. 32.
    Z. Ren, M. Pae, M. Dao, D. Smith, S. Meydani, D. Wu, Dietary supplementation with tocotrienols enhances immune function in C57BL/6 mice. J. Nutr. 140, 1335–1341 (2010)PubMedCrossRefGoogle Scholar
  33. 33.
    M.H. Brooke, K.K. Kaiser, Muscle fiber types: how many and what kind? Arch. Neurol. 23, 369–379 (1970)PubMedCrossRefGoogle Scholar
  34. 34.
    L. Ceglia, S. Niramitmahapanya, L.L. Price, S.S. Harris, R.A. Fielding, B. Dawson-Hughes, An evaluation of the reliability of muscle fiber cross-sectional area and fiber number measurements in rat skeletal muscle. Biol. Proced. Online 15, 6 (2013)PubMedCrossRefGoogle Scholar
  35. 35.
    G.B. Forbes, G.J. Bruining, Urinary creatinine excretion and lean body mass. Am. J. Clin. Nutr. 29, 1359–1366 (1976)PubMedGoogle Scholar
  36. 36.
    R. Swaminathan, J.A. Bradley, G.H. Hill, D.B. Morgan, The nitrogen to creatinine ratio in untimed samples of urine as an index of protein catabolism after surgery. Postgrad. Med. J. 55, 858–861 (1979)PubMedCrossRefGoogle Scholar
  37. 37.
    S.J. Wassner, J.B. Li, A. Sperduto, M.E. Norman, Vitamin D deficiency, hypocalcemia, and increased skeletal muscle degradation in rats. J. Clin. Invest. 72, 102–112 (1983)PubMedCrossRefGoogle Scholar
  38. 38.
    H.A. Bischoff-Ferrari, T. Dietrich, E.J. Orav, F.B. Hu, Y. Zhang, E.W. Karlson, B. Dawson-Hughes, Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or = 60 y. Am. J. Clin. Nutr. 80, 752–758 (2004)PubMedGoogle Scholar
  39. 39.
    S. Schiaffino, C. Mammucari, Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Skelet. Muscle 1, 4 (2011)PubMedCrossRefGoogle Scholar
  40. 40.
    H.A. Franch, S. Raissi, X. Wang, B. Zheng, J.L. Bailey, S.R. Price, Acidosis impairs insulin receptor substrate-1-associated phosphoinositide 3-kinase signaling in muscle cells: consequences on proteolysis. Am. J. Physiol. Renal Physiol. 287, F700–F706 (2004)PubMedCrossRefGoogle Scholar
  41. 41.
    H.N. Hulter, Effects and interrelationships of PTH, Ca2+, vitamin D, and Pi in acid-base homeostasis. Am. J. Physiol. 248, F739–F752 (1985)PubMedGoogle Scholar
  42. 42.
    N. Buitrago, R. Arango, Boland, 1alpha,25(OH)2D3-dependent modulation of Akt in proliferating and differentiating C2C12 skeletal muscle cells. J. Cell. Biochem. 113, 1170–1181 (2012)PubMedCrossRefGoogle Scholar
  43. 43.
    Q.G. Zhou, F.F. Hou, Z.J. Guo, M. Liang, G.B. Wang, X. Zhang, 1,25-Dihydroxyvitamin D improved the free fatty-acid-induced insulin resistance in cultured C2C12 cells. Diabetes Metab. Res. Rev. 24, 459–464 (2008)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Lisa Ceglia
    • 1
    • 2
  • Donato A. Rivas
    • 3
  • Rachele M. Pojednic
    • 3
  • Lori Lyn Price
    • 4
  • Susan S. Harris
    • 2
  • Donald Smith
    • 5
  • Roger A. Fielding
    • 3
  • Bess Dawson-Hughes
    • 2
  1. 1.Division of Endocrinology, Diabetes, and MetabolismTufts Medical CenterBostonUSA
  2. 2.Bone Metabolism LaboratoryJean Mayer USDA Human Nutrition Research Center on Aging at Tufts UniversityBostonUSA
  3. 3.Nutrition, Exercise Physiology, and Sarcopenia LaboratoryJean Mayer USDA Human Nutrition Research Center on Aging at Tufts UniversityBostonUSA
  4. 4.The Institute for Clinical Research and Health Policy StudiesTufts Medical Center, and Tufts Clinical and Translational Science InstituteBostonUSA
  5. 5.Comparative Biology UnitJean Mayer USDA Human Nutrition Research Center on Aging at Tufts UniversityBostonUSA

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