Skip to main content

Nutritional disturbance in acid–base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney

  • Jean-Philippe Bonjour (a1)

The nutritional acid load hypothesis of osteoporosis is reviewed from its historical origin to most recent studies with particular attention to the essential but overlooked role of the kidney in acid–base homeostasis. This hypothesis posits that foods associated with an increased urinary acid excretion are deleterious for the skeleton, leading to osteoporosis and enhanced fragility fracture risk. Conversely, foods generating neutral or alkaline urine would favour bone growth and Ca balance, prevent bone loss and reduce osteoporotic fracture risk. This theory currently influences nutrition research, dietary recommendations and the marketing of alkaline salt products or medications meant to optimise bone health and prevent osteoporosis. It stemmed from classic investigations in patients suffering from chronic kidney diseases (CKD) conducted in the 1960s. Accordingly, in CKD, bone mineral mobilisation would serve as a buffer system to acid accumulation. This interpretation was later questioned on both theoretical and experimental grounds. Notwithstanding this questionable role of bone mineral in systemic acid–base equilibrium, not only in CKD but even more in the absence of renal impairment, it is postulated that, in healthy individuals, foods, particularly those containing animal protein, would induce ‘latent’ acidosis and result, in the long run, in osteoporosis. Thus, a questionable interpretation of data from patients with CKD and the subsequent extrapolation to healthy subjects converted a hypothesis into nutritional recommendations for the prevention of osteoporosis. In a historical perspective, the present review dissects out speculation from experimental facts and emphasises the essential role of the renal tubule in systemic acid–base and Ca homeostasis.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Nutritional disturbance in acid–base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Nutritional disturbance in acid–base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Nutritional disturbance in acid–base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney
      Available formats
The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution licence .
Corresponding author
*Corresponding author: Dr Jean-Philippe Bonjour, fax +41 22 38 29 973, email
Hide All
1Smith HW (1961) From Fish to Philosopher. Garden City, NY: Anchor Books, Doubleday.
2Barzel US & Jowsey J (1969) The effects of chronic acid and alkali administration on bone turnover in adult rats. Clin Sci 36, 517524.
3Heaney RP (2001) Protein intake and bone health: the influence of belief systems on the conduct of nutritional science. Am J Clin Nutr 73, 56.
4Cordain L, Eaton SB, Sebastian A, et al. (2005) Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr 81, 341354.
5Davenport HW (1958) The ABC of Acid–Base Chemistry, 4th ed.Chicago, IL: University of Chicago Press.
6Valtin H (1979) Renal Dysfunction: Mechanisms Involved in Fluid and Solute Imbalance. Boston, MA: Little, Brown and Company.
7Vormann J & Goedecke T (2006) Acid–base homeostasis: latent acidosis as a cause of chronic diseases. Swiss J Integr Med 18, 255266.
8Frassetto LA, Morris RC Jr & Sebastian A (1996) Effect of age on blood acid–base composition in adult humans: role of age-related renal functional decline. Am J Physiol 271, F1114F1122.
9Fenton TR, Eliasziw M, Tough SC, et al. (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, 88.
10Fenton TR, Tough SC, Lyon AW, et al. (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, 41.
11Stewart PA (1978) Independent and dependent variables of acid–base control. Respir Physiol 33, 926.
12Stewart PA (1983) Modern quantitative acid–base chemistry. Can J Physiol Pharmacol 61, 14441461.
13Kurtz I, Kraut J, Ornekian V, et al. (2008) Acid–base analysis: a critique of the Stewart and bicarbonate-centered approaches. Am J Physiol Renal Physiol 294, F1009F1031.
14Relman AS (1954) What are acids and bases? Am J Med 17, 435437.
15Christiensen HN (1959) Anion–cation balance. In Diagnostic Biochemistry: Quantitative Distribution of Body Constituents and their Physiological Interpretation, pp. 128134. New York: Oxford University Press.
16Weiner ID & Hamm LL (2007) Molecular mechanisms of renal ammonia transport. Annu Rev Physiol 69, 317340.
17Hamm LL, Alpern RJ & Preisig PA (2008) Cellular mechanisms of renal tubular acidification. In Seldin and Giebisch's The Kidney, 4th ed. [Alpern RJ and Hebert SC, editors]. London: Academic Press.
18Koeppen BM (2009) The kidney and acid–base regulation. Adv Physiol Educ 33, 275281.
19Weiner ID & Verlander JW (2011) Role of NH3 and NH4+ transporters in renal acid–base transport. Am J Physiol Renal Physiol 300, F11F23.
20Bernard C (1865) Introduction à l'étude de la médecine expérimentale (Introduction to the Study of Experimental Medicine). Paris: Garnier Flammarion.
21Relman AS, Lennon EJ & Lemann J Jr (1961) Endogenous production of fixed acid and the measurement of the net balance of acid in normal subjects. J Clin Invest 40, 16211630.
22Goodman AD, Lemann J Jr, Lennon EJ, et al. (1965) Production, excretion, and net balance of fixed acid in patients with renal acidosis. J Clin Invest 44, 495506.
23Lemann J Jr, Litzow JR & Lennon EJ (1966) The effects of chronic acid loads in normal man: further evidence for the participation of bone mineral in the defense against chronic metabolic acidosis. J Clin Invest 45, 16081614.
24Litzow JR, Lemann J Jr & Lennon EJ (1967) The effect of treatment of acidosis on calcium balance in patients with chronic azotemic renal disease. J Clin Invest 46, 280286.
25Morgan EF, Barnes GL & Einhorn TA (2008) The bone organ system: form and function. In Osteoporosis, 3rd ed., pp. 325 [Marcus R, Feldman D, Nelson DA and Rosen CJ, editors]. Amsterdam, Boston: Elsevier, Academic Press.
26Rizzoli R & Bonjour JP (2006) Physiology of calcium and phosphate homeostasis. In Dynamics of Bone and Cartilage Metabolism: Principles and Clinical Applications, 2nd ed., pp. 345360 [Seibel MJ, Robins SP and Bilezikian JP, editors]. San Diego, CA: Academic Press.
27Lutz 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, 281288.
28Ball D & Maughan RJ (1997) Blood and urine acid–base status of premenopausal omnivorous and vegetarian women. Br J Nutr 78, 683693.
29Fenton TR & Lyon AW (2011) Milk and acid–base balance: proposed hypothesis versus scientific evidence. J Am Coll Nutr 30, 471S475S.
30Oh MS (1991) Irrelevance of bone buffering to acid–base homeostasis in chronic metabolic acidosis. Nephron 59, 710.
31Uribarri J, Douyon H & Oh MS (1995) A re-evaluation of the urinary parameters of acid production and excretion in patients with chronic renal acidosis. Kidney Int 47, 624627.
32Oh MS & Carroll HJ (2008) External balance of electrolytes and acids and alkalis. In Seldin and Giebisch's The Kidney, 4th ed. [Alpern RJ and Hebert SC, editors]. London: Academic Press.
33Oh MS (2000) New perspectives on acid–base balance. Semin Dial 13, 212219.
34Uribarri J (2000) Acidosis in chronic renal insufficiency. Semin Dial 13, 232234.
35Hruska KA & Mathew S (2009) Chronic Kidney Disease Mineral Bone Disorder (CKD-MBD). In Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 7th ed., pp. 343353 [Rosen CJ, Compston JE and Lian JB, editors]. Washington, DC: The American Society for Bone and Mineral Research.
36Barzel US (1969) The effect of excessive acid feeding on bone. Calcif Tissue Res 4, 94100.
37Arnett TR & Dempster DW (1986) Effect of pH on bone resorption by rat osteoclasts in vitro. Endocrinology 119, 119124.
38Bushinsky DA & Frick KK (2000) The effects of acid on bone. Curr Opin Nephrol Hypertens 9, 369379.
39Bushinsky DA, Smith SB, Gavrilov KL, et al. (2003) Chronic acidosis-induced alteration in bone bicarbonate and phosphate. Am J Physiol Renal Physiol 285, F532F539.
40Frick KK, Krieger NS, Nehrke K, et al. (2009) Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1. J Bone Miner Res 24, 305313.
41Barzel US (1995) The skeleton as an ion exchange system: implications for the role of acid–base imbalance in the genesis of osteoporosis. J Bone Miner Res 10, 14311436.
42Lanham-New SA (2008) The balance of bone health: tipping the scales in favor of potassium-rich, bicarbonate-rich foods. J Nutr 138, 172S177S.
43Wynn E, Krieg MA, Aeschlimann JM, et al. (2009) Alkaline mineral water lowers bone resorption even in calcium sufficiency: alkaline mineral water and bone metabolism. Bone 44, 120124.
44Pizzorno J, Frassetto LA & Katzinger J (2010) Diet-induced acidosis: is it real and clinically relevant? Br J Nutr 103, 11851194.
45Feskanich D, Willett WC, Stampfer MJ, et al. (1996) Protein consumption and bone fractures in women. Am J Epidemiol 143, 472479.
46Meyer HE, Pedersen JI, Loken EB, et al. (1997) Dietary factors and the incidence of hip fracture in middle-aged Norwegians. A prospective study. Am J Epidemiol 145, 117123.
47Mussolino ME, Looker AC, Madans JH, et al. (1998) Risk factors for hip fracture in white men: the NHANES I Epidemiologic Follow-up Study. J Bone Miner Res 13, 918924.
48Munger RG, Cerhan JR & Chiu BC (1999) Prospective study of dietary protein intake and risk of hip fracture in postmenopausal women. Am J Clin Nutr 69, 147152.
49Hannan MT, Tucker KL, Dawson-Hughes B, et al. (2000) Effect of dietary protein on bone loss in elderly men and women: The Framingham Osteoporosis Study. J Bone Miner Res 15, 25042512.
50Sellmeyer DE, Stone KL, Sebastian A, et al. (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 Osteoporotic Fractures Research Group. Am J Clin Nutr 73, 118122.
51Promislow JH, Goodman-Gruen D, Slymen DJ, et al. (2002) Protein consumption and bone mineral density in the elderly: The Rancho Bernardo Study. Am J Epidemiol 155, 636644.
52Wengreen HJ, Munger RG, West NA, et al. (2004) Dietary protein intake and risk of osteoporotic hip fracture in elderly residents of Utah. J Bone Miner Res 19, 537545.
53Dargent-Molina P, Sabia S, Touvier M, et al. (2008) Proteins, dietary acid load, and calcium and risk of postmenopausal fractures in the E3N French women prospective study. J Bone Miner Res 23, 19151922.
54Wynn E, Lanham-New SA, Krieg MA, et al. (2008) Low estimates of dietary acid load are positively associated with bone ultrasound in women older than 75 years of age with a lifetime fracture. J Nutr 138, 13491354.
55Darling AL, Millward DJ, Torgerson DJ, et al. (2009) Dietary protein and bone health: a systematic review and meta-analysis. Am J Clin Nutr 90, 16741692.
56Misra D, Berry SD, Broe KE, et al. (2011) Does dietary protein reduce hip fracture risk in elders? The Framingham Osteoporosis Study. Osteoporos Int 22, 345349.
57Shi L, Libuda L, Schonau E, et al. (2012) Long 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, 10261031.
58Oh MS (1989) A new method for estimating G-I absorption of alkali. Kidney Int 36, 915917.
59Remer 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, 13561361.
60Berkemeyer S & Remer T (2006) Anthropometrics provide a better estimate of urinary organic acid anion excretion than a dietary mineral intake-based estimate in children, adolescents, and young adults. J Nutr 136, 12031208.
61Remer T, Dimitriou T & Manz F (2003) Dietary potential renal acid load and renal net acid excretion in healthy, free-living children and adolescents. Am J Clin Nutr 77, 12551260.
62Remer T & Manz F (1995) Potential renal acid load of foods and its influence on urine pH. J Am Diet Assoc 95, 791797.
63Frassetto LA, Todd KM, Morris RC Jr, et al. (1998) Estimation of net endogenous noncarbonic acid production in humans from diet potassium and protein contents. Am J Clin Nutr 68, 576583.
64Grases F, Costa-Bauza A & Prieto RM (2006) Renal lithiasis and nutrition. Nutr J 5, 23.
65Moe OW, Pearle MS & Sakhaee K (2011) Pharmacotherapy of urolithiasis: evidence from clinical trials. Kidney Int 79, 385392.
66Sebastian A, Harris ST, Ottaway JH, et al. (1994) Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. N Engl J Med 330, 17761781.
67Sellmeyer 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, 20082012.
68Maurer M, Riesen W, Muser J, et al. (2003) Neutralization of Western diet inhibits bone resorption independently of K intake and reduces cortisol secretion in humans. Am J Physiol Renal Physiol 284, F32F40.
69Frassetto L, Morris RC Jr & Sebastian A (2005) Long-term persistence of the urine calcium-lowering effect of potassium bicarbonate in postmenopausal women. J Clin Endocrinol Metab 90, 831834.
70Rafferty K, Davies KM & Heaney RP (2005) Potassium intake and the calcium economy. J Am Coll Nutr 24, 99106.
71Jehle S, Zanetti A, Muser J, et al. (2006) Partial neutralization of the acidogenic Western diet with potassium citrate increases bone mass in postmenopausal women with osteopenia. J Am Soc Nephrol 17, 32133222.
72Macdonald HM, Black AJ, Aucott L, et al. (2008) 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 88, 465474.
73Rafferty K & Heaney RP (2008) Nutrient effects on the calcium economy: emphasizing the potassium controversy. J Nutr 138, 166S171S.
74Ceglia L, Harris SS, Abrams SA, et al. (2009) Potassium bicarbonate attenuates the urinary nitrogen excretion that accompanies an increase in dietary protein and may promote calcium absorption. J Clin Endocrinol Metab 94, 645653.
75Dawson-Hughes B, Harris SS, Palermo NJ, et al. (2009) Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women. J Clin Endocrinol Metab 94, 96102.
76Mardon J, Habauzit V, Trzeciakiewicz A, et al. (2008) 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, 718724.
77Jehle S, Hulter HN & Krapf R (2013) 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 98, 207217.
78Cannata-Andia JB, Roman-Garcia P & Hruska K (2011) The connections between vascular calcification and bone health. Nephrol Dial Transplant 26, 34293436.
79Wang L, Manson JE & Sesso HD (2012) Calcium intake and risk of cardiovascular disease: a review of prospective studies and randomized clinical trials. Am J Cardiovasc Drugs 12, 105116.
80Frassetto LA, Hardcastle AC, Sebastian A, et al. (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, 13151322.
81Fenton TR, Eliasziw M, Lyon AW, et al. (2008) Meta-analysis of the quantity of calcium excretion associated with the net acid excretion of the modern diet under the acid–ash diet hypothesis. Am J Clin Nutr 88, 11591166.
82Fenton TR, Lyon AW, Eliasziw M, et al. (2009) Meta-analysis of the effect of the acid–ash hypothesis of osteoporosis on calcium balance. J Bone Miner Res 24, 18351840.
83McLean RR, Qiao N, Broe KE, et al. (2011) Dietary acid load is not associated with lower bone mineral density except in older men. J Nutr 141, 588594.
84Hill AB (1965) The environment and disease: association or causation? Proc R Soc Med 58, 295300.
85Muhlbauer 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, 12301236.
86New SA, MacDonald HM, Campbell MK, et al. (2004) Lower estimates of net endogenous non-carbonic acid production are positively associated with indexes of bone health in premenopausal and perimenopausal women. Am J Clin Nutr 79, 131138.
87Macdonald HM, New SA, Fraser WD, et al. (2005) Low dietary 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, 923933.
88New SA (2002) Nutrition Society Medal lecture. The role of the skeleton in acid–base homeostasis. Proc Nutr Soc 61, 151164.
89Sebastian A, Frassetto LA, Sellmeyer DE, et al. (2002) Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors. Am J Clin Nutr 76, 13081316.
90Bonjour JP (2011) Calcium and phosphate: a duet of ions playing for bone health. J Am Coll Nutr 30, 438S448S.
91Fenton TR, Lyon AW, Eliasziw M, et al. (2009) Phosphate decreases urine calcium and increases calcium balance: a meta-analysis of the osteoporosis acid–ash diet hypothesis. Nutr J 8, 41.
92Miller PD, Schwartz EN, Chen P, et al. (2007) Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment. Osteoporos Int 18, 5968.
93Coresh J, Astor BC, Greene T, et al. (2003) Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 41, 112.
94Eustace JA, Astor B, Muntner PM, et al. (2004) Prevalence of acidosis and inflammation and their association with low serum albumin in chronic kidney disease. Kidney Int 65, 10311040.
95Looker AC, Orwoll ES, Johnston CC Jr, et al. (1997) Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res 12, 17611768.
96Hsu CY & Chertow GM (2002) Elevations of serum phosphorus and potassium in mild to moderate chronic renal insufficiency. Nephrol Dial Transplant 17, 14191425.
97Hsu CY, Cummings SR, McCulloch CE, et al. (2002) Bone mineral density is not diminished by mild to moderate chronic renal insufficiency. Kidney Int 61, 18141820.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 480
Total number of PDF views: 624 *
Loading metrics...

Abstract views

Total abstract views: 5590 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 23rd February 2018. This data will be updated every 24 hours.