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Acid–base balance of the diet—implications for bone and muscle

European Journal of Clinical Nutrition volume 74, pages 7–13 (2020)Cite this article

Abstract

Western diets are net acid-producing, based on their general characteristics of containing excessive amounts of grains in relation to their content of fruits and vegetables. The continuous consumption of acid-producing diets is countered by the renal excretion of the excess acid. However, when renal excretion is not adequate, as is the case in many older adults with mildly and moderately impaired renal function, other adaptations are employed to preserve neutrality. In adults who are unable to excrete the daily dietary acid load, the excess acid is buffered by bone. The mechanisms by which hydrogen ions affect bone have been well defined. Current evidence also indicates a role for muscle in preserving neutrality; however, the mechanism(s) by which this occurs have not been directly demonstrated. The evidence supporting the role of bone and muscle in defending against the development of frank metabolic acidosis are reviewed herein. This evidence stems from observational studies and randomized, controlled clinical trials. Gaps in the evidence that would be useful to fill are also indicated.

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Fig. 1: Mechanism by which hydrogen ions increase bone resorption and alkali release.

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References

  1. Hughes VA, Frontera WR, Wood M, Evans WJ, Dallal GE, Roubenoff R, et al. Longitudinal muscle strength changes in older adults: influence of muscle mass, physical activity, and health. J Gerontol A. 2001;56:B209–17.

    CAS  Google Scholar 

  2. Sehl ME, Yates FE. Kinetics of human aging: I. Rates of senescence between ages 30 and 70 years in healthy people. J Gerontol A. 2001;56:B198–208.

    CAS  Google Scholar 

  3. Riggs BL, Wahner HW, Seeman E, Offord KP, Dunn WL, Mazess RB, et al. Changes in bone mineral density of the proximal femur and spine with aging. Differences between the postmenopausal and senile osteoporosis syndromes. J Clin Invest. 1982;70:716–23.

    PubMed  PubMed Central  CAS  Google Scholar 

  4. Isaacson J, Brotto M. Physiology of mechanotransduction: how do muscle and bone “talk” to one another? Clin Rev Bone Miner Metab. 2014;12:77–85.

    PubMed  Google Scholar 

  5. Edwards MH, Dennison EM, Aihie Sayer A, Fielding R, Cooper C. Osteoporosis and sarcopenia in older age. Bone. 2015;80:126–30.

    PubMed  PubMed Central  CAS  Google Scholar 

  6. Kawao N, Kaji H. Interactions between muscle tissues and bone metabolism. J Cell Biochem. 2015;116:687–95.

    PubMed  CAS  Google Scholar 

  7. Pereira FB, Leite AF, de Paula AP. Relationship between pre-sarcopenia, sarcopenia and bone mineral density in elderly men. Arch Endocrinol Metab. 2015;59:59–65.

    PubMed  Google Scholar 

  8. Drey M, Sieber CC, Bertsch T, Bauer JM, Schmidmaier R. Osteosarcopenia is more than sarcopenia and osteopenia alone. Aging Clin Exp Res. 2016;28:895–9.

    PubMed  Google Scholar 

  9. Visser M, Goodpaster BH, Kritchevsky SB, Newman AB, Nevitt M, Rubin SM, et al. Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. J Gerontol A. 2005;60:324–33.

    Google Scholar 

  10. Lord SR, Ward JA, Williams P, Anstey KJ. Physiological factors associated with falls in older community-dwelling women. J Am Geriatr Soc. 1994;42:1110–7.

    PubMed  CAS  Google Scholar 

  11. Bischoff-Ferrari HA, Orav JE, Kanis JA, Rizzoli R, Schlogl M, Staehelin HB, et al. Comparative performance of current definitions of sarcopenia against the prospective incidence of falls among community-dwelling seniors age 65 and older. Osteoporos Int. 2015;26:2793–802.

    PubMed  CAS  Google Scholar 

  12. Rantanen T, Avlund K, Suominen H, Schroll M, Frandin K, Pertti E. Muscle strength as a predictor of onset of ADL dependence in people aged 75 years. Aging Clin Exp Res. 2002;14(3 Suppl):10–5.

    PubMed  Google Scholar 

  13. Rantanen T, Sakari-Rantala R, Heikkinen E. Muscle strength before and mortality after a bone fracture in older people. Scand J Med Sci Sports. 2002;12:296–300.

    PubMed  CAS  Google Scholar 

  14. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Min Res. 2007;22:465–75.

    Google Scholar 

  15. U.S. Department of Agriculture (USDA) and U.S. Department of Health and Human Services (HHS). Dietary guidelines for Americans. Washington, DC: U.S. Printing Office; 2010.

  16. Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc. 1985;33:278–85.

    PubMed  CAS  Google Scholar 

  17. Rowe JW, Andres R, Tobin JD, Norris AH, Shock NW. The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study. J Gerontol 1976;31:155–63.

    PubMed  CAS  Google Scholar 

  18. Davies DF, Shock NW. Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest. 1950;29:496–507.

    PubMed  PubMed Central  CAS  Google Scholar 

  19. Frassetto L, Sebastian A. Age and systemic acid-base equilibrium: analysis of published data. J Gerontol A Biol Sci Med Sci. 1996;51:B91–9.

    PubMed  CAS  Google Scholar 

  20. Wesson DE, Simoni J, Broglio K, Sheather S. Acid retention accompanies reduced GFR in humans and increases plasma levels of endothelin and aldosterone. Am J Physiol Renal Physiol. 2011;300:F830–7.

    PubMed  CAS  Google Scholar 

  21. Sprague SM, Krieger NS, Bushinsky DA. Aluminum inhibits bone nodule formation and calcification in vitro. Am J Physiol. 1993;264(5:Part 2):F882–90.

    PubMed  CAS  Google Scholar 

  22. Sudo H, Kodama HA, Amagai Y, Yamamoto S, Kasai S. In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria. J Cell Biol. 1983;96:191–8.

    PubMed  CAS  Google Scholar 

  23. Ecarot-Charrier B, Glorieux FH, van der RM, Pereira G. Osteoblasts isolated from mouse calvaria initiate matrix mineralization in culture. J Cell Biol. 1983;96:639–43.

    PubMed  CAS  Google Scholar 

  24. Bhargava U, Bar-Lev M, Bellows CG, Aubin JE. Ultrastructural analysis of bone nodules formed in vitro by isolated fetal rat calvaria cells. Bone 1988;9:155–63.

    PubMed  CAS  Google Scholar 

  25. Sprague SM, Krieger NS, Bushinsky DA. Greater inhibition of in vitro bone mineralization with metabolic than respiratory acidosis. Kidney Int. 1994;46:1199–206.

    PubMed  CAS  Google Scholar 

  26. Arnett TR, Dempster DW. Effect of pH on bone resorption by rat osteoclasts in vitro. Endocrinology 1986;119:119–24.

    PubMed  CAS  Google Scholar 

  27. Arnett TR, Spowage M. Modulation of the resorptive activity of rat osteoclasts by small changes in extracellular pH near the physiological range. Bone 1996;18:277–9.

    PubMed  CAS  Google Scholar 

  28. Krieger NS, Yao Z, Kyker-Snowman K, Kim MH, Boyce BF, Bushinsky DA. Increased bone density in mice lacking the proton receptor OGR1. Kidney Int. 2016;89:565–73.

    PubMed  PubMed Central  CAS  Google Scholar 

  29. Bushinsky DA. Metabolic alkalosis decreases bone calcium efflux by suppressing osteoclasts and stimulating osteoblasts. Am J Physiol. 1996;271(1:Pt 2):F216–22.

    PubMed  CAS  Google Scholar 

  30. Ludwig MG, Vanek M, Guerini D, Gasser JA, Jones CE, Junker U, et al. Proton-sensing G-protein-coupled receptors. Nature. 2003;425:93–8.

    PubMed  CAS  Google Scholar 

  31. Frick KK, Krieger NS, Nehrke K, Bushinsky DA. Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1. J Bone Miner Res. 2008;24:305–13.

    PubMed Central  Google Scholar 

  32. Dawson-Hughes B, Harris SS, Palermo NJ, Castaneda-Sceppa C, Rasmussen HM, Dallal GE. Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women. J Clin Endocrinol Metab. 2009;94:96–102.

    PubMed  CAS  Google Scholar 

  33. Dawson-Hughes B, Harris SS, Palermo NJ, Gilhooly CH, Shea MK, Fielding RA, et al. Potassium bicarbonate supplementation lowers bone turnover and calcium excretion in older men and women: a randomized dose-finding trial. J Bone Miner Res. 2015;30:2103–11.

    PubMed  PubMed Central  CAS  Google Scholar 

  34. Moseley KF, Weaver CM, Appel L, Sebastian A, Sellmeyer DE. Potassium citrate supplementation results in sustained improvement in calcium balance in older men and women. J Bone Miner Res. 2013;28:497–504.

    PubMed  PubMed Central  CAS  Google Scholar 

  35. Jehle S, Hulter HN, Krapf R. Effect of potassium citrate on bone density, microarchitecture, and fracture risk in healthy older adults without osteoporosis: a Randomized Controlled Trial. J Clin Endocrinol Metab. 2013;98:207–17.

    PubMed  CAS  Google Scholar 

  36. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older.[see comment]. N. Engl J Med. 1997;337:670–6.

    PubMed  CAS  Google Scholar 

  37. Jehle S, Zanetti A, Muser J, Hulter HN, Krapf R. Partial neutralization of the acidogenic Western diet with potassium citrate increases bone mass in postmenopausal women with osteopenia. J Am Soc Nephrol. 2006;17:3213–22.

    PubMed  CAS  Google Scholar 

  38. Macdonald HM, Black AJ, Sandison R, Aucott L, Hardcastle AJ, Lanham-New SA, et al. Two year double blind randomized controlled trial in postmenopausal women shows no gain in BMD with potassium citrate treatment. J Bone Min Res. 2006;21(Suppl 1):S15.

    Google Scholar 

  39. Tucker KL, Chen H, Hannan MT, Cupples LA, Wilson PW, Felson D, et al. Bone mineral density and dietary patterns in older adults: the Framingham Osteoporosis Study. Am J Clin Nutr. 2002;76:245–52.

    PubMed  CAS  Google Scholar 

  40. Jones G, Riley MD, Whiting S. Association between urinary potassium, urinary sodium, current diet, and bone density in prepubertal children. Am J Clin Nutr. 2001;73:839–44.

    PubMed  CAS  Google Scholar 

  41. New SA, Bolton-Smith C, Grubb DA, Reid DM. Nutritional influences on bonel mineral density: a cross-sectional study in premenopausal women. Am J Clin Nutr. 1997;65:1831–9.

    PubMed  CAS  Google Scholar 

  42. Chen Y, Ho SC, Lee R, Lam S, Woo J. Fruit intake is associated with better bone mass among Hong Kong Chinese early postmenopausal women. J Bone Min Res. 2001;16(Suppl 1):S386.

    Google Scholar 

  43. MacDonald HM, New SA, Golden MHN, Campbell MK, Reid DM. Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids. Am J Clin Nutr. 2004;79:155–65.

    PubMed  CAS  Google Scholar 

  44. Dawson-Hughes B, Harris SS, Ceglia L. Alkaline diets favor lean tissue mass in older adults. Am J Clin Nutr. 2008;87:662–5.

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Byberg L, Bellavia A, Orsini N, Wolk A, Michaelsson K. Fruit and vegetable intake and risk of hip fracture: a cohort study of Swedish men and women. J Bone Miner Res. 2015;30:976–84.

    PubMed  Google Scholar 

  46. Haring B, Crandall CJ, Wu C, LeBlanc ES, Shikany JM, Carbone L, et al. Dietary patterns and fractures in postmenopausal women: results from the women as health initiative. JAMA Intern Med. 2016;176(5):645–52.

    PubMed  PubMed Central  Google Scholar 

  47. Liu ZM, Leung J, Wong SY, Wong CK, Chan R, Woo J. Greater fruit intake was associated with better bone mineral status among Chinese elderly men and women: results of Hong Kong Mr. Os and Ms. Os studies. J Am Med Dir Assoc. 2015;16:309–15.

    PubMed  Google Scholar 

  48. Qiu R, Cao WT, Tian HY, He J, Chen GD, Chen YM. Greater intake of fruit and vegetables is associated with greater bone mineral density and lower osteoporosis risk in middle-aged and elderly adults. PLoS ONE. 2017;12:e0168906

    PubMed  PubMed Central  Google Scholar 

  49. Keast DR, O'Neil CE, Jones JM. Dried fruit consumption is associated with improved diet quality and reduced obesity in US adults: National Health and Nutrition Examination Survey, 1999–2004. Nutr Res. 2011;31:460–7.

    PubMed  CAS  Google Scholar 

  50. Macdonald HM, Black AJ, Aucott L, Duthie G, Duthie S, Sandison R, et al. Effect of potassium citrate supplementation or increased fruit and vegetable intake on bone metabolism in healthy postmenopausal women: a randomized controlled trial. Am J Clin Nutr. 2008;88:465–74.

    PubMed  CAS  Google Scholar 

  51. Lin P, Ginty F, Appel LJ. Impact of sodium intake and dietary patterns on biochemical markers of bone and calcium metabolism. J Bone Min Res. 2001;16(S1):S511.

    Google Scholar 

  52. Elders PJ, Netelenbos JC, Lips P, van Ginkel FC, Khoe E, Leeuwenkamp OR, et al. Calcium supplementation reduces vertebral bone loss in perimenopausal women: a controlled trial in 248 women between 46 and 55 years of age. J Clin Endocrinol Metab. 1991;73:533–40.

    PubMed  CAS  Google Scholar 

  53. Cao JJ, Whigham LD, Jahns L. Depletion and repletion of fruit and vegetable intake alters serum bone turnover markers: a 28-week single-arm experimental feeding intervention. Br J Nutr. 2018;120:500–7.

    PubMed  CAS  Google Scholar 

  54. Jennings A, Cashman KD, Gillings R, Cassidy A, Tang J, Fraser W, et al. A Mediterranean-like dietary pattern with vitamin D3 (10 microg/d) supplements reduced the rate of bone loss in older Europeans with osteoporosis at baseline: results of a 1-y randomized controlled trial. Am J Clin Nutr. 2018;108:633–40.

    PubMed  PubMed Central  Google Scholar 

  55. Remer T, Manz F. Potential renal acid load of foods and its influence on urine pH. J Am Diet Assn. 1995;95:791–7.

    CAS  Google Scholar 

  56. Garcia-Gavilan JF, Bullo M, Canudas S, Martinez-Gonzalez MA, Estruch R, Giardina S, et al. Extra virgin olive oil consumption reduces the risk of osteoporotic fractures in the PREDIMED trial. Clin Nutr. 2018;37:329–35.

    PubMed  CAS  Google Scholar 

  57. Tucker KL. Osteoporosis prevention and nutrition. Curr Osteoporos Rep. 2009;7:111–7.

    PubMed  Google Scholar 

  58. Franceschi RT, Iyer BS, Cui Y. Effects of ascorbic acid on collagen matrix formation and osteoblast differentiation in murine MC3T3-E1 cells. J Bone Miner Res. 1994;9:843–54.

    PubMed  CAS  Google Scholar 

  59. Basu S, Michaelsson K, Olofsson H, Johansson S, Melhus H. Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun. 2001;288:275–9.

    PubMed  CAS  Google Scholar 

  60. Ruderman NB, Berger M. The formation of glutamine and alanine in skeletal muscle. J Biol Chem. 1974;249:5500–6.

    PubMed  CAS  Google Scholar 

  61. Cahill GF Jr. Starvation in man. N. Engl J Med. 1970;282:668–75.

    PubMed  CAS  Google Scholar 

  62. Owen EE, Robinson RR. Amino acid extraction and ammonia metabolism by the human kidney during the prolonged administration of ammonium chloride. J Clin Invest. 1963;42:263–76.

    PubMed  PubMed Central  CAS  Google Scholar 

  63. Aulick LH, Wilmore DW. Increased peripheral amino acid release following burn injury. Surgery 1979;85:560–5.

    PubMed  CAS  Google Scholar 

  64. Askanazi J, Carpentier YA, Michelsen CB, Elwyn DH, Furst P, Kantrowitz LR, et al. Muscle and plasma amino acids following injury. Influence of intercurrent infection. Ann Surg. 1980;192:78–85.

    PubMed  PubMed Central  CAS  Google Scholar 

  65. Souba WW, Smith RJ, Wilmore DW. Glutamine metabolism by the intestinal tract. J Parent Enter Nutr. 1985;9:608–17.

    CAS  Google Scholar 

  66. Williamson DH. Muscle protein degradation and amino acid metabolism in human injury. Biochem Soc Trans. 1980;8:497.

    PubMed  CAS  Google Scholar 

  67. Garibotto G, Russo R, Sofia A, Sala MR, Sabatino C, Moscatelli P, et al. Muscle protein turnover in chronic renal failure patients with metabolic acidosis or normal acid-base balance. Min Electrolyte Metab. 1996;22:58–61.

    CAS  Google Scholar 

  68. Williams B, Layward E, Walls J. Skeletal muscle degradation and nitrogen wasting in rats with chronic metabolic acidosis. Clin Sci. 1991;80:457–62.

    PubMed  CAS  Google Scholar 

  69. Frassetto L, Morris RC Jr, Sebastian A. Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women. J Clin Endocrinol Metab. 1997;82:254–9.

    PubMed  CAS  Google Scholar 

  70. Dawson-Hughes B, Castaneda-Sceppa C, Harris SS, Palermo NJ, Cloutier G, Ceglia L, et al. Impact of supplementation with bicarbonate on lower-extremity muscle performance in older men and women. Osteoporos Int. 2010;21:1171–9.

    PubMed  CAS  Google Scholar 

  71. Ceglia L, Dawson-Hughes B. Increasing alkali supplementation decreases urinary nitrogen excretion when adjusted for same day nitrogen intake. Osteoporos Int. 2017;28:3355–9.

    PubMed  PubMed Central  CAS  Google Scholar 

  72. Neville CE, Young IS, Gilchrist SE, McKinley MC, Gibson A, Edgar JD, et al. Effect of increased fruit and vegetable consumption on physical function and muscle strength in older adults. Age. 2013;35:2409–22.

    PubMed  PubMed Central  CAS  Google Scholar 

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Funding

This work was supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS]) RO1 AR052322-01A1 and 1RO1AR060261 and by the U.S. Department of Agriculture, under agreement No. 58-1950-0-014. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the National Institutes of Health or the U.S. Department of Agriculture. This article is published as part of a supplement sponsored by NuOmix-Research k.s. The conference was financially supported by Protina Pharmazeutische GmbH, Germany and Sirius Pharma, Germany, and organized by NuOmix-Research k.s. Neither company had any role in writing of the manuscript.

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  1. Jean Mayer United States Department of Agriculture Human Nutrition Research Cenon Aging at Tufts University, 711 Washington St., Boston, MA, 02111, USA

    Bess Dawson-Hughes

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Correspondence to Bess Dawson-Hughes.

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Dawson-Hughes, B. Acid–base balance of the diet—implications for bone and muscle. Eur J Clin Nutr 74 (Suppl 1), 7–13 (2020). https://doi.org/10.1038/s41430-020-0691-7

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