Skip to main content
    • Aa
    • Aa
  • Access
  • Cited by 2
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Jeremias, J.T. Nogueira, S.P. Brunetto, M.A. Pereira, G.T. Loureiro, B.A. Ferreira, C.S. Gomes, M.O.S. and Carciofi, A.C. 2013. Predictive formulas for food base excess and urine pH estimations of cats. Animal Feed Science and Technology, Vol. 182, Issue. 1-4, p. 82.

    Robey, Ian F. and Nesbit, Lance A. 2013. Investigating Mechanisms of Alkalinization for Reducing Primary Breast Tumor Invasion. BioMed Research International, Vol. 2013, p. 1.


Diet-induced acidosis: is it real and clinically relevant?

  • Joseph Pizzorno (a1), Lynda A. Frassetto (a2) and Joseph Katzinger (a3)
  • DOI:
  • Published online: 15 December 2009

The concept of diet-induced ‘acidosis’ as a cause of disease has been a subject of interest for more than a century. The present article reviews the history of our evolving understanding of physiological pH, the physiological support for the concept of ‘acidosis’, the causes of acidosis, how it is recognised, its short-term effects as well as the long-term clinical relevance of preventative measures, and the research support for normalisation of pH. Further, we suggest differentiation of the terms ‘acidosis’ and ‘acidaemia’ as a way to resolve the conflation of these topics which has led to confusion and controversy. The available research makes a compelling case that diet-induced acidosis, not diet-induced acidaemia, is a real phenomenon, and has a significant, clinical, long-term pathophysiological effect that should be recognised and potentially counterbalanced by dietary means.

  • 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.

      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.

      Diet-induced acidosis: is it real and clinically relevant?
      Your Kindle email address
      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 Dropbox account. Find out more about sending content to Dropbox.

      Diet-induced acidosis: is it real and clinically relevant?
      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 Google Drive account. Find out more about sending content to Google Drive.

      Diet-induced acidosis: is it real and clinically relevant?
      Available formats
Corresponding author
*Corresponding author: Dr Joseph Pizzorno, fax +1 206 368 8570, email
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

1EJ Lennon , J Lemann Jr & JR Litzow (1966) The effects of diet and stool composition on the net external acid balance of normal subjects. J Clin Invest 45, 16011607.

2AD Goodman , J Lemann Jr, EJ Lennon , (1965) Production, excretion, and net balance of fixed acid in patients with renal acidosis. J Clin Invest 44, 495506.

3I Kurtz , JA Kraut , V Ornekian , (2008) Acid–base analysis: a critique of the Stewart and bicarbonate-centered approaches. Am J Physiol Renal Physiol 294, F1009F1031.

4F Manz (2001) History of nutrition and acid–base physiology. Eur J Nutr 40, 189199.

5DA Story (2004) Bench-to-bedside review: a brief history of clinical acid–base. Crit Care 8, 253258.

6LA Frassetto , RC Morris Jr & A Sebastian (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, F521F525.

10SL Gluck (1998) Acid–base. Lancet 352, 474479.

14A Brandao-Burch , JC Utting , IR Orriss , (2005) Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization. Calcif Tissue Int 77, 167174.

17KK Frick , NS Krieger , K Nehrke , (2009) Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1. J Bone Miner Res 24, 305313.

18T Buclin , M Cosma , M Appenzeller , (2001) Diet acids and alkalis influence calcium retention in bone. Osteoporos Int 12, 493499.

19WS Yancy Jr, MK Olsen , T Dudley , (2007) Acid–base analysis of individuals following two weight loss diets. Eur J Clin Nutr 61, 14161422.

20L Frassetto , RC Morris Jr, DE Sellmeyer , (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, 200213.

21A Sebastian , ST Harris , JH Ottaway , (1994) Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. N Engl J Med 330, 17761781.

22L Frassetto , RC Morris Jr & A Sebastian (2005) Long-term persistence of the urine calcium-lowering effect of potassium bicarbonate in postmenopausal women. J Clin Endocrinol Metab 90, 831834.

23PJ Osther (2006) Effect of acute acid loading on acid–base and calcium metabolism. Scand J Urol Nephrol 40, 3544.

25PJ Osther , J Bollerslev , AB Hansen , (1993) Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium, bone and citrate metabolism. Urol Res 21, 169173.

26S Domrongkitchaiporn , W Stitchantrakul & W Kochakarn (2006) Causes of hypocitraturia in recurrent calcium stone formers: focusing on urinary potassium excretion. Am J Kidney Dis 48, 546554.

27L Borghi , T Schianchi , T Meschi , (2002) Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med 346, 7784.

28A Trinchieri , R Lizzano , F Marchesotti , (2006) Effect of potential renal acid load of foods on urinary citrate excretion in calcium renal stone formers. Urol Res 34, 17.

29WE Mitch , R Medina , S Grieber , (1994) Metabolic acidosis stimulates muscle protein degradation by activating the adenosine triphosphate-dependent pathway involving ubiquitin and proteasomes. J Clin Invest 93, 21272133.

31J Du & WE Mitch (2005) Identification of pathways controlling muscle protein metabolism in uremia and other catabolic conditions. Curr Opin Nephrol Hypertens 14, 378382.

32JA Kraut & NE Madias (2007) Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol 2, 162174.

39T Remer & F Manz (1995) Potential renal acid load of foods and its influence on urine pH. J Am Diet Assoc 95, 791797.

40DS Michaud , RP Troiano , AF Subar , (2003) Comparison of estimated renal net acid excretion from dietary intake and body size with urine pH. J Am Diet Assoc 103, 10011007.

41SJ Whiting & JA Muirhead (2005) Measurement of net acid excretion by use of paper strips. Nutrition 21, 961963.

42R Jajoo , L Song , H Rasmussen , (2006) Dietary acid-base balance, bone resorption, and calcium excretion. J Am Coll Nutr 25, 224230.

43F Pietschmann , NA Breslau & CY Pak (1992) Reduced vertebral bone density in hypercalciuric nephrolithiasis. J Bone Miner Res 7, 13831388.

48BA Ince , EJ Anderson & RM Neer (2004) Lowering dietary protein to U.S. recommended dietary allowance levels reduces urinary calcium excretion and bone resorption in young women. J Clin Endocrinol Metab 89, 38013807.

49T Remer (2001) Influence of nutrition on acid–base balance – metabolic aspects. Eur J Nutr 40, 214220.

52P Frings-Meuthen , N Baecker & M Heer (2008) Low-grade metabolic acidosis may be the cause of sodium chloride-induced exaggerated bone resorption. J Bone Miner Res 23, 517524.

53JA Kellum (2000) Determinants of blood pH in health and disease. Crit Care 4, 614.

54AM Sharma , A Kribben , S Schattenfroh , (1990) Salt sensitivity in humans is associated with abnormal acid–base regulation. Hypertension 16, 407413.

55J Lemann Jr, RW Gray & JA Pleuss (1989) Potassium bicarbonate, but not sodium bicarbonate, reduces urinary calcium excretion and improves calcium balance in healthy men. Kidney Int 35, 688695.

57RM Bersin , K Chatterjee & AI Arieff (1989) Metabolic and hemodynamic consequences of sodium bicarbonate administration in patients with heart disease. Am J Med 87, 714.

59R Coppoolse , TJ Barstow , WW Stringer , (1997) Effect of acute bicarbonate administration on exercise responses of COPD patients. Med Sci Sports Exerc 29, 725732.

62K Sakhaee , NM Maalouf , SA Abrams , (2005) Effects of potassium alkali and calcium supplementation on bone turnover in postmenopausal women. J Clin Endocrinol Metab 90, 35283533.

63DE Sellmeyer , M Schloetter & A Sebastian (2002) Potassium citrate prevents increased urine calcium excretion and bone resorption induced by a high sodium chloride diet. J Clin Endocrinol Metab 87, 20082012.

64B Teucher , JR Dainty , CA Spinks , (2008) Sodium and bone health: the impact of moderately high and low salt intakes on calcium metabolism in postmenopausal women. J Bone Miner Res 23, 14771485.

65F Vescini , A Buffa , G La Manna , (2005) Long-term potassium citrate therapy and bone mineral density in idiopathic calcium stone formers. J Endocrinol Invest 28, 218222.

66S Jehle , A Zanetti , J Muser , (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.

68B Dawson-Hughes , SS Harris , NJ Palermo , (2009) Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women. J Clin Endocrinol Metab 94, 96102.

70TR Fenton , AW Lyon , M Eliasziw , (2009) Meta-analysis of the effect of the acid-ash hypothesis of osteoporosis on calcium balance. J Bone Miner Res 24, 18351840.

71J Lemann Jr (1999) Relationship between urinary calcium and net acid excretion as determined by dietary protein and potassium: a review. Nephron 81, Suppl. 1, 1825.

72JE Zerwekh , CV Odvina , LA Wuermser , (2007) Reduction of renal stone risk by potassium-magnesium citrate during 5 weeks of bed rest. J Urol 177, 21792184.

73PO Schwille , A Schmiedl , U Herrmann , (1999) Magnesium, citrate, magnesium citrate and magnesium-alkali citrate as modulators of calcium oxalate crystallization in urine: observations in patients with recurrent idiopathic calcium urolithiasis. Urol Res 27, 117126.

74LA Frassetto , E Nash , RC Morris Jr, (2000) Comparative effects of potassium chloride and bicarbonate on thiazide-induced reduction in urinary calcium excretion. Kidney Int 58, 748752.

75Y Kato , S Yamaguchi , S Yachiku , (2004) Changes in urinary parameters after oral administration of potassium-sodium citrate and magnesium oxide to prevent urolithiasis. Urology 63, 712.

76B Ettinger , CY Pak , JT Citron , (1997) Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis. J Urol 158, 20692073.

77E Löfberg , A Gutierrez , B Anderstam , (2006) Effect of bicarbonate on muscle protein in patients receiving hemodialysis. Am J Kidney Dis 48, 419429.

79L Frassetto , RC Morris Jr & A Sebastian (1997) Potassium bicarbonate reduces urinary nitrogen excretion in postmenopausal women. J Clin Endocrinol Metab 82, 254259.

80F Douroudos II, IG atouros , V Gourgoulis , (2006) Dose-related effects of prolonged NaHCO3 ingestion during high-intensity exercise. Med Sci Sports Exerc 38, 17461753.

81D Bishop & B Claudius (2005) Effects of induced metabolic alkalosis on prolonged intermittent-sprint performance. Med Sci Sports Exerc 37, 759767.

82L McNaughton , K Backx , G Palmer , (1999) Effects of chronic bicarbonate ingestion on the performance of high-intensity work. Eur J Appl Physiol Occup Physiol 80, 333336.

83GH Raymer , GD Marsh , JM Kowalchuk , (2004) Metabolic effects of induced alkalosis during progressive forearm exercise to fatigue. J Appl Physiol 96, 20502056.

84AM Lindh , MC Peyrebrune , SA Ingham , (2008) Sodium bicarbonate improves swimming performance. Int J Sports Med 29, 519523.

85D Ball , PL Greenhaff & RJ Maughan (1996) The acute reversal of a diet-induced metabolic acidosis does not restore endurance capacity during high-intensity exercise in man. Eur J Appl Physiol Occup Physiol 73, 105112.

86A Cupisti , M Meola , C D'Alessandro , (2007) Insulin resistance and low urinary citrate excretion in calcium stone formers. Biomed Pharmacother 61, 8690.

87M Daudon , O Traxer , P Conort , (2006) Type 2 diabetes increases the risk for uric acid stones. J Am Soc Nephrol 17, 20262033.

88MA Cameron , NM Maalouf , B Adams-Huet , (2006) Urine composition in type 2 diabetes: predisposition to uric acid nephrolithiasis. J Am Soc Nephrol 17, 14221428.

89NM Maalouf , MA Cameron , OW Moe , (2007) Low urine pH: a novel feature of the metabolic syndrome. Clin J Am Soc Nephrol 2, 883888.

90N Abate , M Chandalia , JAV Cabo-Chan Jr, (2004) The metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance. Kidney Int 65, 386392.

91F Birklein , M Weber , M Ernst , (2000) Experimental tissue acidosis leads to increased pain in complex regional pain syndrome (CRPS). Pain 87, 227234.

92B Duan , LJ Wu , YQ Yu , (2007) Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity. J Neurosci 27, 1113911148.

93H Cadiou , M Studer , NG Jones , (2007) Modulation of acid-sensing ion channel activity by nitric oxide. J Neurosci 27, 1325113260.

94WZ Wang , XP Chu , MH Li , (2006) Modulation of acid-sensing ion channel currents, acid-induced increase of intracellular Ca2+, and acidosis-mediated neuronal injury by intracellular pH. J Biol Chem 281, 2936929378.

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? *