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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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.
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.
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.
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.
Edwards MH, Dennison EM, Aihie Sayer A, Fielding R, Cooper C. Osteoporosis and sarcopenia in older age. Bone. 2015;80:126–30.
Kawao N, Kaji H. Interactions between muscle tissues and bone metabolism. J Cell Biochem. 2015;116:687–95.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Sprague SM, Krieger NS, Bushinsky DA. Greater inhibition of in vitro bone mineralization with metabolic than respiratory acidosis. Kidney Int. 1994;46:1199–206.
Arnett TR, Dempster DW. Effect of pH on bone resorption by rat osteoclasts in vitro. Endocrinology 1986;119:119–24.
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.
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.
Bushinsky DA. Metabolic alkalosis decreases bone calcium efflux by suppressing osteoclasts and stimulating osteoblasts. Am J Physiol. 1996;271(1:Pt 2):F216–22.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Dawson-Hughes B, Harris SS, Ceglia L. Alkaline diets favor lean tissue mass in older adults. Am J Clin Nutr. 2008;87:662–5.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
Remer T, Manz F. Potential renal acid load of foods and its influence on urine pH. J Am Diet Assn. 1995;95:791–7.
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.
Tucker KL. Osteoporosis prevention and nutrition. Curr Osteoporos Rep. 2009;7:111–7.
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.
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.
Ruderman NB, Berger M. The formation of glutamine and alanine in skeletal muscle. J Biol Chem. 1974;249:5500–6.
Cahill GF Jr. Starvation in man. N. Engl J Med. 1970;282:668–75.
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.
Aulick LH, Wilmore DW. Increased peripheral amino acid release following burn injury. Surgery 1979;85:560–5.
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.
Souba WW, Smith RJ, Wilmore DW. Glutamine metabolism by the intestinal tract. J Parent Enter Nutr. 1985;9:608–17.
Williamson DH. Muscle protein degradation and amino acid metabolism in human injury. Biochem Soc Trans. 1980;8:497.
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.
Williams B, Layward E, Walls J. Skeletal muscle degradation and nitrogen wasting in rats with chronic metabolic acidosis. Clin Sci. 1991;80:457–62.
Frassetto L, Morris RC Jr, Sebastian A. Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women. J Clin Endocrinol Metab. 1997;82:254–9.
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.
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.
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.
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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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