Journal of Bone and Mineral Metabolism

, Volume 32, Issue 5, pp 469–475 | Cite as

The acid–ash hypothesis revisited: a reassessment of the impact of dietary acidity on bone

  • Rachel NicollEmail author
  • John McLaren Howard
Review Article


The acid–ash hypothesis states that when there are excess blood protons, bone is eroded to provide alkali to buffer the net acidity and maintain physiologic pH. There is concern that with the typical Western diet, we are permanently in a state of net endogenous acid production, which is gradually reducing bone. While it is clear that a high acid-producing diet generates increased urinary acid and calcium excretion, the effect of diet does not always have the expected results on BMD, fracture risk and markers of bone formation and resorption, suggesting that other factors are influencing the effect of acid/alkali loading on bone. High dietary protein, sodium and phosphorus intake, all of which are necessary for bone formation, were thought to be net acid forming and contribute to low BMD and fracture risk, but appear under certain conditions to be beneficial, with the effect of protein being driven by calcium repletion. Dietary salt can increase short-term markers of bone resorption but may also trigger 1,25(OH)2D synthesis to increase calcium absorption; with low calcium intake, salt intake may be inversely correlated with BMD but with high calcium intake, salt intake was positively correlated with BMD. With respect to the effect of phosphorus, the data are conflicting. Inclusion of an analysis of calcium intake may help to reconcile the contradictory results seen in many of the studies of bone. The acid–ash hypothesis could, therefore, be amended to state that with an acid-producing diet and low calcium intake, bone is eroded to provide alkali to buffer excess protons but where calcium intake is high the acid-producing diet may be protective.


Bone mineral Acid–ash hypothesis Diet 


Conflict of interest

All authors have no conflicts of interest.


  1. 1.
    Bushinsky DA, Frick KK (2000) The effects of acid on bone. Curr Opin Nephrol Hypertens 9:369–379PubMedCrossRefGoogle Scholar
  2. 2.
    New SA (2002) The role of the skeleton in acid-base homeostasis. Proc Nutr Soc 61:151–164PubMedCrossRefGoogle Scholar
  3. 3.
    Lina BA, Kuijpers MH (2004) Toxicity and carcinogenicity of acidogenic or alkalogenic diets in rats: effects of feeding NH(4)Cl, KHCO3 or KCl. Food Chem Toxicol 42:135–153PubMedCrossRefGoogle Scholar
  4. 4.
    Louden JD, Roberts RR, Goodship TH (1999) Acidosis and nutrition. Kidney Int Suppl 73:S85–S88PubMedCrossRefGoogle Scholar
  5. 5.
    Schwalfenberg GK (2012) The alkaline diet: is there evidence that an alkaline pH diet benefits health? J Environ Public Health 2012:727630PubMedCentralPubMedGoogle Scholar
  6. 6.
    Wiederkehr M, Krapf R (2001) Metabolic and endocrine effects of metabolic acidosis in humans. Swiss Med Wkly 131:127–132PubMedGoogle Scholar
  7. 7.
    Krapf R, Vetsch R, Vetsch W, Hulter HN (1992) Chronic metabolic acidosis increases the serum concentration of 1,25-dihydroxyvitamin D in humans by stimulating its production rate. Critical role of acidosis-induced renal hypophosphatemia. J Clin Invest 90:2456–2463PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Lemann J, Bushinsky DA, Hamm LL (2003) Bone buffering of acid and base in humans. Am J Physiol Renal Physiol 285:F811–F832PubMedGoogle Scholar
  9. 9.
    Jehle S, Krapf R (2010) Effects of acidogenic diet forms on musculoskeletal function. J Nephrol 23:S77–S84PubMedGoogle Scholar
  10. 10.
    Kraut JA, Coburn JW (1994) Bone acid and osteoporosis. N Eng J Med 330:1821–1822CrossRefGoogle Scholar
  11. 11.
    Oh MS (2000) New perspectives on acid-base balance. Semin Dial 13:212–219PubMedCrossRefGoogle Scholar
  12. 12.
    Meghji S, Morrison MS, Henderson B, Arnett TR (2001) pH dependence of bone resorption: mouse calvarial osteoclasts are activated by acidosis. Am J Physiol Endocrinol Metab 280:E112–E119PubMedGoogle Scholar
  13. 13.
    Krieger NS, Sessler NE, Bushinsky DA (1992) Acidosis inhibits osteoblastic and stimulates osteoclastic activity in vitro. Am J Physiol 262:F442–F448PubMedGoogle Scholar
  14. 14.
    Arnett TR, Dempster DW (1986) Effect of pH on bone resorption by rat osteoclasts in vitro. Endocrinology 119:119–124PubMedCrossRefGoogle Scholar
  15. 15.
    Remer T, Manz F (1994) Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein. Am J Clin Nutr 59:1356–1361PubMedGoogle Scholar
  16. 16.
    Remer T, Manz F (1995) Potential renal acid load of foods and its influence on urine pH. J Am Diet Assoc 95:791–797PubMedCrossRefGoogle Scholar
  17. 17.
    Lanham-New SA (2008) The balance of bone health: tipping the scales in favour of potassium-rich bicarbonate-rich foods. J Nutr 138:172S–177SPubMedGoogle Scholar
  18. 18.
    Wynn E, Krieg MA, Lanham-New SA, Burckhardt P (2010) Postgraduate Symposium: Positive influence of nutritional alkalinity on bone health. Proc Nutr Soc 69:166–173PubMedCrossRefGoogle Scholar
  19. 19.
    Fenton TR, Tough SC, Lyon AW, Eliasziw M, Hanley DA (2011) Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill’s epidemiologic criteria for causality. Nutr J 10:41PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Jehle S, Zanetti A, Muser J, Hulter HN, Krapf R (2006) Partial neutralisation of the acidogenic Western diet with potassium citrate increases bone mass in postmenopausal women with osteopenia. J Am Soc Nephrol 17:3213–3222PubMedCrossRefGoogle Scholar
  21. 21.
    Frassetto L, Morris RC, Sellmeyer DE, Todd K, Sebastian A (2001) Diet, evolution and aging—the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet. Eur J Nutr 40:200–213PubMedCrossRefGoogle Scholar
  22. 22.
    Moseley K, Weaver C, Appel L, Sebastain A, Sellmeyer DE (2013) Potassium citrate supplementation results in sustained improvement in calcium balance in older men and women. J Bone Miner Res 28:497–504Google Scholar
  23. 23.
    Brandao-Burch A, Utting JC, Orriss IR, Arnett TR (2005) Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralisation. Calcif Tissue Int 77:167–174PubMedCrossRefGoogle Scholar
  24. 24.
    Bushinsky DA, Smith DB, Gavrilov KL, Gavrilov LF, Li J, Levi-Setti R (2002) Acute acidosis-induced alteration in bone bicarbonate and phosphate. Am J Physiol Renal Physiol 283:F1091–F1097PubMedGoogle Scholar
  25. 25.
    Krieger NS, Frick KK, Bushinsky DA (2004) Mechanism of acid-induced bone resorption. Curr Opin Nephrol Hypertens 13:423–436PubMedCrossRefGoogle Scholar
  26. 26.
    Bushinsky DA, Lam BC, Nespeca R, Sessier NE, Grynpas MD (1993) Decreased bone carbonate content in response to metabolic, but not respiratory acidosis. Am J Physiol 265:F530–F536PubMedGoogle Scholar
  27. 27.
    New SA, MacDonald HM, Campbell MK, Martin JC, Garton MJ, Robins SP, Reid DM (2004) Lower estimates of net endogenous con-carbonic acid production are positively associated with indexes of bone health in premenopausal and peromenopausal women. Am J Clin Nutr 79:131–138PubMedGoogle Scholar
  28. 28.
    Macdonald HM, New SA, Fraser WD, Campbell MK, Reid DM (2005) Low potassium intakes and high dietary estimates of net endogenous acid production are associated with low bone mineral density in premenopausal women and increased markers of bone resorption in postmenopausal women. Am J Clin Nutr 81:923–933PubMedGoogle Scholar
  29. 29.
    Shi L, Libuda L, Schonau E, Frassetto L, Remer T (2012) Longer term higher urinary calcium excretion within the normal physiologic range predicts impaired bone status of the proximal radius in healthy children with higher potential renal acid load. Bone 50:1026–1031PubMedCrossRefGoogle Scholar
  30. 30.
    Buclin T, Cosma M, Appenzeller M, Jacquet AF, Decosterd LA, Biollaz J, Burckhardt P (2001) Diet acids and alkalis influence calcium retention in bone. Osteoporosis Int 12:493–499CrossRefGoogle Scholar
  31. 31.
    Lin PH, Ginty F, Appel LJ, Aickin M, Bohannon A, Garnero P et al (2003) The DASH diet and sodium reduction improve markers of bone turnover and calcium metabolism in adults. J Nutr 133:3130–3136PubMedGoogle Scholar
  32. 32.
    Chen YM, Ho SC, Woo JL (2006) Greater fruit and vegetable intake is associated with increased bone mass among postmenopausal Chinese women. Br J Nutr 96:745–751PubMedCrossRefGoogle Scholar
  33. 33.
    Muhlbauer RC, Lozano A, Reinli A (2002) Onion and a mixture of vegetables, salads and herbs affect bone resorption in the rat by a mechanism independent of their base excess. J Bone Miner Res 17:1230–1236PubMedCrossRefGoogle Scholar
  34. 34.
    New SA, Robins SP, Campbell MK, Martin JC, Garton MJ, Bolton-Smith C et al (2000) Dietary influences on bone mass and bone metabolism: further evidence of a positive link between fruit and vegetable consumption and bone health. Am J Clin Nutr 71:142–151PubMedGoogle Scholar
  35. 35.
    New SA, Bolton-Smith C, Grubb DA, Reid DM (1997) Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women. Am J Clin Nutr 65:1831–1839PubMedGoogle Scholar
  36. 36.
    Fenton TR, Lyon AW, Eliasziw M, Tough SC, Hanley DA (2009) Meta-analysis of the effect of the acid ash hypothesis of osteoporosis on calcium balance. J Bone Miner Res 24:1835–1840PubMedCrossRefGoogle Scholar
  37. 37.
    Fenton TR, Eliasziw M, Tough SC, Lyon AW, Brown JP, Hanley DA (2010) Low urine pH and acid excretion do not predict bone fractures or the loss of bone mineral density: a prospective cohort study. BMC Musculoskelet Disord 11:88PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    McLean RR, Qiao N, Broe KE, Tucker KL, Casey V, Cupples LA et al (2011) Dietary acid load is not associated with lower bone mineral density except in older men. J Nutr 141:588–594PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Frassetto LA, Hardcastle AC, Sebastian A, Aucott L, Fraser WD, Reid DM, Macdonald HM (2012) No evidence that the skeletal non-response to potassium alkali supplements in healthy postmenopausal women depends on blood pressure or sodium chloride intake. Eur J Clin Nutr 66:1315–1322Google Scholar
  40. 40.
    Heaney RP (2002) Protein and calcium: antagonists or synergists? Am J Clin Nutr 75:609–610PubMedGoogle Scholar
  41. 41.
    Cao JJ, Nielsen FH (2010) Acid diet (high-meat protein) effects on calcium metabolism and bone health. Curr Opin Clin Nutr Metab Care 13:698–702PubMedCrossRefGoogle Scholar
  42. 42.
    Lutz J (1984) Calcium balance and acid-base status of women as affected by increased protein intake and by sodium bicarbonate ingestion. Am J Clin Nutr 39:281–288PubMedGoogle Scholar
  43. 43.
    Schuette SA, Zemel MB, Linkswiler HM (1980) Studies on the mechanism of protein-induced hypercalciuria in older men and women. J Nutr 110:305–315PubMedGoogle Scholar
  44. 44.
    Whiting SJ, Anderson DJ, Weeks SJ (1997) Calciuric effects of protein and potassium bicarbonate but not of sodium chloride or phosphate can be detected acutely in adult women and men. Am J Clin Nutr 65:1465–1472PubMedGoogle Scholar
  45. 45.
    Darling AL, Millward DJ, Torgerson DJ, Hewitt CE, Lanham-New SA (2009) Dietary protein and bone health: a systematic review and meta-analysis. Am J Clin Nutr 90:1674–1692PubMedCrossRefGoogle Scholar
  46. 46.
    Kerstetter JE, Kenny AM, Insogna KL (2011) Dietary protein and skeletal health: a review of recent human research. Curr Opin Lipidol 22:16–20PubMedCrossRefGoogle Scholar
  47. 47.
    Meng X, Zhu K, Devine A, Kerr DA, Binns CW, Prince RL (2009) A 5-year cohort study of the effects of high protein intake on lean mass and BMC in elderly postmenopausal women. J Bone Miner Res 24:1827–1834PubMedCrossRefGoogle Scholar
  48. 48.
    Beasley JM, Ichikawa LE, Ange BA, Spangler L, LaCroix AZ, Ott SM, Scholes D (2010) Is protein intake associated with bone mineral density in young women? Am J Clin Nutr 91:1311–1316PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Hunt JR, Johnson LK, Roughead ZK (2009) Dietary protein and calcium interact to influence calcium retention: a controlled feeding study. Am J Clin Nutr 89:1357–1365PubMedCrossRefGoogle Scholar
  50. 50.
    Nieto R, Haro A, Delgado-Andrade C, Seiquer I, Aguilera JF (2012) Dietary protein excess does not influence calcium and phosphorus absorption and retention in Iberian pigs growing from 50 to 100 kg body weight. J Anim Sci 90:167–169PubMedCrossRefGoogle Scholar
  51. 51.
    Bihuniak JD, Simpson CA, Sullivan RR, Caseria DM, Kerstetter JE, Insogna KL (2013) Dietary protein-induced increases in urinary calcium are accompanied by similar increases in urinary nitrogen and urinary urea: a controlled clinical trial. J Acad Nutr Diet 113:447–451PubMedCrossRefGoogle Scholar
  52. 52.
    Ho-Pham LT, Nguyen ND, Nguyen TV (2009) Effect of vegetarian diets on bone mineral density: a Bayesian meta-analysis. Am J Clin Nutr 90:943–950PubMedCrossRefGoogle Scholar
  53. 53.
    Frassetto LA, Todd KM, Morris RC, Sebastian A (2000) Worldwide incidence of hip fracture in elderly women: relation to consumption of animal and vegetable foods. J Gerontol A Biol Sci Med Sci 55:M585–M592PubMedCrossRefGoogle Scholar
  54. 54.
    Sellmeyer DE, Stone KL, Sebastian A, Cummings SR (2001) A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. Study of Osteoporosis Fractures Research Group. Am J Clin Nutr 73:118–122PubMedGoogle Scholar
  55. 55.
    Sahni S, Cupples LA, McLean RR, Tucker KL, Broe KE, Kiel DP, Hannan MT (2010) Protective effect of high protein and calcium intake on the risk of hip fracture in the Framingham offspring cohort. J Bone Miner Res 25:2770–2776PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Calvez J, Poupin N, Chesneau C, Lassale C, Tome D (2012) Protein intake, calcium balance and health consequences. Eur J Clin Nutr 66:281–295PubMedCrossRefGoogle Scholar
  57. 57.
    Dawson-Hughes B, Harris SS (2002) Calcium intake influences the association of protein intake with rates of bone loss in elderly men and women. Am J Clin Nutr 75:773–779PubMedGoogle Scholar
  58. 58.
    Gaffney-Stomberg E, Sun BH, Cucchi CE, Simpson CA, Gundberg C, Kerstetter JE, Insogna KL (2010) The effect of dietary protein on intestinal calcium absorption in rats. Endocrinology 151:1071–1078PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Kerstetter JE, O’Brien KO, Insogna KL (1998) Dietary protein affects intestinal calcium absorption. Am J Clin Nutr 68:859–865PubMedGoogle Scholar
  60. 60.
    Kerstetter JE, O’Brien KO, Caseria DM, Wall DE, Insogna KL (2005) The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women. J Clin Endocrinol Metab 90:26–31PubMedCrossRefGoogle Scholar
  61. 61.
    Cao JJ, Johnson LK, Hunt JR (2011) A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting markers of bone resorption or formation in postmenopausal women. J Nutr 141:391–397PubMedCrossRefGoogle Scholar
  62. 62.
    Frassetto LA, Morris RC Jr, Sebastian A (2007) Dietary sodium chloride intake independently predicts the degree of hyperchloremic metabolic acidosis in healthy humans consuming a net acid-producing diet. Am J Physiol Renal Physiol 293:F521–F525PubMedCrossRefGoogle Scholar
  63. 63.
    Sellmeyer DE, Schloetter M, Sebastian A (2002) Potassium citrate prevents increased urine calcium excretion and bone resorption induced by a high sodium chloride diet. J Clin Endocrinol Metab 87:2008–2012PubMedCrossRefGoogle Scholar
  64. 64.
    Frassetto LA, Morris RC Jr, Sellmeyer DE, Sebastian A (2008) Adverse effects of sodium chloride on bone in the aging human population resulting from habitual consumption of typical American diets. J Nutr 138:419S–422SPubMedGoogle Scholar
  65. 65.
    Jones G, Beard T, Parameswaran V, Greenaway T, von Witt R (1997) A population-based study of the relationship between salt intake, bone resorption and bone mass. Eur J Clin Nutr 51:561–565PubMedCrossRefGoogle Scholar
  66. 66.
    Teucher B, Fairweather-Tait S (2003) Dietary sodium as a risk factor for osteoporosis: where is the evidence? Proc Nutr Soc 62:859–866PubMedCrossRefGoogle Scholar
  67. 67.
    Devine A, Criddle RA, Dick IM, Kerr DA, Prince RL (1995) A longitudinal study of the effect of sodium and calcium intakes on regional bone density in postmenopausal women. Am J Clin Nutr 62:740–745PubMedGoogle Scholar
  68. 68.
    Breslau NA, McGuire JL, Zerwekh JE, Pak CYC (1982) The role of dietary sodium on renal excretion and intestinal absorption of calcium and on vitamin D metabolism. J Clin Endocrinol Metab 55:369–373PubMedCrossRefGoogle Scholar
  69. 69.
    Breslau NA, Sakhaee K, Pak CYC (1985) Impaired adaptation to salt-induced urinary calcium losses in postmenopausal osteoporosis. Trans Assoc Am Physicians 98:107–115PubMedGoogle Scholar
  70. 70.
    Bedford JL, Barr SI (2011) Higher urinary sodium, a proxy for intake, is associated with increased calcium excretion and lower hip bone density in healthy young women with lower calcium intakes. Nutrients 3:951–961PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Teucher B, Dainty JR, Spinks CA, Majsak-Newman G, Berry DJ, Hoogewerff JA et al (2008) Sodium and bone health: impact of moderately high and low salt intakes on calcium metabolism in postmenopausal women. J Bone Miner Res 23:1477–1485PubMedCrossRefGoogle Scholar
  72. 72.
    Ilich JZ, Brownbill RA, Coster DC (2010) Higher habitual sodium intake is not detrimental for bone in older women with adequate calcium intake. Eur J Appl Physiol 109:745–755PubMedCrossRefGoogle Scholar
  73. 73.
    Classen HG, Schutte K, Schimatschek HF (1995) Different effects of three high-dose oral calcium salts on acid-base metabolism, plasma electrolytes and urine parameters or rats. Methods Find Exp Clin Pharmacol 17:437–442PubMedGoogle Scholar
  74. 74.
    Dawson-Hughes B, Harris SS, Palermo NJ, Castaneda-Sceppa C, Rasmussen HM, Dallal GE (2009) Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women. J Clin Endocrinol Metab 94:96–102PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Stauber A, Radanovic T, Stange G, Murer H, Wagner CA, Biber J (2005) Regulation of intestinal phosphate transport II. Metabolic acidosis stimulates Na+ -dependent phosphate absorption and expression of the Na+ -Pi cotransporter NaPi-IIb in small intestine. Am J Physiol Gastrointest Liver Physiol 288:G501–G506PubMedCrossRefGoogle Scholar
  76. 76.
    Supplee JD, Duncan GE, Bruemmer B, Goldberg J, Wen Y, Henderson JA (2011) Soda intake and osteoporosis risk in postmenopausal American-Indian women. Public Health Nutr 14:1900–1906PubMedCrossRefGoogle Scholar
  77. 77.
    Frick KK, Bushinsky DA (1998) Chronic metabolic acidosis reversibly inhibits extracellular matrix gene expression in mouse osteoblasts. Am J Physiol 275:F840–F847PubMedGoogle Scholar
  78. 78.
    Bushinsky DA (1995) Stimulated osteoclastic and suppressed osteoblastic activity in metabolic but not respiratory acidosis. Am J Physiol 268:C80–C88PubMedGoogle Scholar
  79. 79.
    Krieger NS, Bushinsky DA (2011) Pharmacological inhibition of intracellular calcium release blocks acid-induced bone resorption. Am J Physiol Renal Physiol 300:F91–F97PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Frick KK, LaPlante K, Bushinsky DA (2005) RANK ligand and TNF-alpha mediate acid-induced bone calcium efflux in vitro. Am J Physiol Renal Physiol 289:F1005–F1011PubMedCrossRefGoogle Scholar
  81. 81.
    Krieger NS, Frick KK, LaPlante Strutz K, Michalenka A, Bushinsky DA (2007) Regulation of COX-2 mediates acid-induced bone calcium efflux in vitro. J Bone Miner Res 22:907–917PubMedCrossRefGoogle Scholar
  82. 82.
    Krieger NS, Bushinsky DA, Frick KK (2003) Cellular mechanisms of bone resorption induced by metabolic acidosis. Semin Dial 16:463–466PubMedCrossRefGoogle Scholar
  83. 83.
    Frick KK, Bushinsky DA (2003) Metabolic acidosis stimulates RANKL RNA expression in bone through a cyclo-oxygenase-dependent mechanism. J Bone Miner Res 18:1317–1325PubMedCrossRefGoogle Scholar
  84. 84.
    Krieger NS, Frick KK, Bushinsky DA (2002) Cortisol inhibits acid-induced bone resorption in vitro. J Am Soc Nephrol 13:2534–2539PubMedCrossRefGoogle Scholar
  85. 85.
    Bushinsky DA, Riordon DR, Chan JS, Krieger NS (1997) Decreased potassium stimulates bone resorption. Am J Physiol 272:F774–F780PubMedGoogle Scholar
  86. 86.
    Bushinsky DA (1996) Metabolic alkalosis decreases bone calcium efflux by suppressing osteoclasts and stimulating osteoblasts. Am J Physiol 271:F216–F322PubMedGoogle Scholar

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan 2014

Authors and Affiliations

  1. 1.Department of Public Health and Clinical Medicine and Heart CentreUmea UniversityUmeåSweden
  2. 2.AcumenTiverton, DevonUK

Personalised recommendations