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When Is Low Potential Renal Acid Load (PRAL) Beneficial for Bone?

  • Thomas RemerEmail author
  • Danika Krupp
  • Lijie Shi
Chapter
  • 1.4k Downloads

Abstract

Potential metabolic influences of dietary acid load on bone health have been discussed controversially. Here, we review the available findings in adults and healthy children regarding certain methodological aspects including (i) appropriate use of urinary biomarkers – potential renal acid load (PRAL) and net acid excretion (NAE), (ii) problems in the interpretation of results on calcium balance and bone turnover markers, and (iii) possible influences of selection bias regarding baseline diets of the population groups of randomized controlled trials. Based on the available evidence, it is concluded that calcium balance measurements and bone turnover markers are no adequate and sensitive tools to evaluate the modest but long-term prevailing influence of nutrition on bone status. Findings in children and adults exclusively conducted on the most reliable outcomes, that is, bone densitometric structure analyses, suggest that a low-PRAL diet may be especially relevant in certain population groups, for example, in children with higher dietary protein intakes, in postmenopausal women with impaired bone status, and probably in adults on a habitually acidifying nutrition. The mechanisms mediating detrimental bone effects of higher dietary acid loads under discussion include changes in endocrine–metabolic milieu, for example, impairment of GH/IGF-1 axis and higher glucocorticoid secretion as well as direct bone–cell-related changes by higher acid load. In conclusion, to identify moderate alterations in bone status exerted through nutritional influences, not only appropriate assessments of dietary proton load but also outcome measurements that are closely related to long-term bone structure are required.

Keywords

Dietary acid load Biomarker Potential renal acid load Net acid excretion Bone Calcium balance 

Abbreviations

BMD

Bone mineral density

DEXA

Dual-energy X-ray absorptiometry

NAE

Net acid excretion

NEAP

Net endogenous acid production

OA

Organic acids

pQCT

Peripheral quantitative computed tomography (pQCT)

PRAL

Potential renal acid load

RCT

Randomized controlled trial

References

  1. 1.
    Remer T, Manz F. Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein. Am J Clin Nutr. 1994;59(6):1356–61.PubMedGoogle Scholar
  2. 2.
    Groen BB, Res PT, Pennings B, Hertle E, Senden JM, Saris WH, et al. Intragastric protein administration stimulates overnight muscle protein synthesis in elderly men. Am J Physiol Endocrinol Metab. 2012;302(1):E52–60.PubMedCrossRefGoogle Scholar
  3. 3.
    Darling AL, Millward DJ, Torgerson DJ, Hewitt CE, Lanham-New SA. Dietary protein and bone health: a systematic review and meta-analysis. Am J Clin Nutr. 2009;90(6):1674–92.PubMedCrossRefGoogle Scholar
  4. 4.
    Kalhoff H, Manz F. Nutrition, acid–base status and growth in early childhood. Eur J Nutr. 2001;40(5):221–30.PubMedCrossRefGoogle Scholar
  5. 5.
    Proctor DN, Balagopal P, Nair KS. Age-related sarcopenia in humans is associated with reduced synthetic rates of specific muscle proteins. J Nutr. 1998;128(2 Suppl):351S–5.PubMedGoogle Scholar
  6. 6.
    Remer T, Krupp D, Shi L. Dietary protein’s and dietary acid load’s influence on bone health. Crit Rev Food Sci Nutr. [in press].Google Scholar
  7. 7.
    Berkemeyer S, Remer T. 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. 2006;136(5):1203–8.PubMedGoogle Scholar
  8. 8.
    Remer T, Manz F, Alexy U, Schoenau E, Wudy SA, Shi L. Long-term high urinary potential renal acid load and low nitrogen excretion predict reduced diaphyseal bone mass and bone size in children. J Clin Endocrinol Metab. 2011;96(9):2861–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Frassetto LA, Lanham-New SA, Macdonald HM, Remer T, Sebastian A, Tucker KL, et al. Standardizing terminology for estimating the diet-dependent net acid load to the metabolic system. J Nutr. 2007;137(6):1491–2.PubMedGoogle Scholar
  10. 10.
    Fenton TR, Eliasziw M, Tough SC, Lyon AW, Brown JP, Hanley DA. 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. 2010;11:88.PubMedCrossRefGoogle Scholar
  11. 11.
    Frassetto L, Morris Jr RC, Sebastian A. Long-term persistence of the urine calcium-lowering effect of potassium bicarbonate in postmenopausal women. J Clin Endocrinol Metab. 2005;90(2):831–4.PubMedCrossRefGoogle Scholar
  12. 12.
    Lemann J, Litzow JR, Lennon EJ. Studies of the mechanism by which chronic metabolic acidosis augments urinary calcium excretion in man. J Clin Invest. 1967;46(8):1318–28.PubMedCrossRefGoogle Scholar
  13. 13.
    Sebastian A, Harris ST, Ottaway JH, Todd KM, Morris Jr RC. Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. N Engl J Med. 1994;330(25):1776–81.PubMedCrossRefGoogle Scholar
  14. 14.
    Fenton TR, Lyon AW, Eliasziw M, Tough SC, Hanley DA. Meta-analysis of the effect of the acid-ash hypothesis of osteoporosis on calcium balance. J Bone Miner Res. 2009;24(11):1835–40.PubMedCrossRefGoogle Scholar
  15. 15.
    Rafferty K, Davies KM, Heaney RP. Potassium intake and the calcium economy. J Am Coll Nutr. 2005;24(2):99–106.PubMedGoogle Scholar
  16. 16.
    Hunt JR, Johnson LK, Fariba Roughead ZK. Dietary protein and calcium interact to influence calcium retention: a controlled feeding study. Am J Clin Nutr. 2009;89(5):1357–65.PubMedCrossRefGoogle Scholar
  17. 17.
    Rauch F, Schonau E, Woitge H, Remer T, Seibel M. Urinary excretion of hydroxy-pyridinium cross-links of collagen reflects skeletal growth velocity in normal children. Exp Clin Endocrinol. 1994;102(2):94–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Wallace JD, Cuneo RC, Lundberg PA, Rosen T, Jorgensen JO, Longobardi S, et al. Responses of markers of bone and collagen turnover to exercise, growth hormone (GH) administration, and GH withdrawal in trained adult males. J Clin Endocrinol Metab. 2000;85(1):124–33.PubMedCrossRefGoogle Scholar
  19. 19.
    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(11):3213–22.PubMedCrossRefGoogle Scholar
  20. 20.
    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(2):465–74.PubMedGoogle Scholar
  21. 21.
    Frassetto LA, Hardcastle AC, Sebastian A, Aucott L, Fraser WD, Reid DM, et al. 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. 2012;66:1315–22.PubMedCrossRefGoogle Scholar
  22. 22.
    Tucker KL, Hannan MT, Kiel DP. The acid–base hypothesis: diet and bone in the Framingham Osteoporosis Study. Eur J Nutr. 2001;40(5):231–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Macdonald HM, New SA, Golden MH, 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(1):155–65.PubMedGoogle Scholar
  24. 24.
    Kaptoge S, Welch A, McTaggart A, Mulligan A, Dalzell N, Day NE, et al. Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age. Osteoporos Int. 2003;14(5):418–28.PubMedCrossRefGoogle Scholar
  25. 25.
    Pedone C, Napoli N, Pozzilli P, Lauretani F, Bandinelli S, Ferrucci L, et al. Quality of diet and potential renal acid load as risk factors for reduced bone density in elderly women. Bone. 2010;46(4):1063–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Pedone C, Napoli N, Pozzilli P, Lauretani F, Bandinelli S, Ferrucci L, et al. Author reply – quality of diet and potential renal acid load as risk factors for reduced bone density in elderly women. Bone. 2011;48(2):416.CrossRefGoogle Scholar
  27. 27.
    Remer T, Shi L, Alexy U. Potential renal acid load may more strongly affect bone size and mass than volumetric bone mineral density. Bone. 2011;48(2):414–5; author reply 6.PubMedCrossRefGoogle Scholar
  28. 28.
    Alexy U, Remer T, Manz F, Neu CM, Schoenau E. Long-term protein intake and dietary potential renal acid load are associated with bone modeling and remodeling at the proximal radius in healthy children. Am J Clin Nutr. 2005;82(5):1107–14.PubMedGoogle Scholar
  29. 29.
    Fenton TR, Tough SC, Lyon AW, Eliasziw M, Hanley DA. Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill’s epidemiologic criteria for causality. Nutr J. 2011;10:41.PubMedCrossRefGoogle Scholar
  30. 30.
    Green J, Maor G. Effect of metabolic acidosis on the growth hormone/IGF-I endocrine axis in skeletal growth centers. Kidney Int. 2000;57(6):2258–67.PubMedCrossRefGoogle Scholar
  31. 31.
    Ordonez FA, Santos F, Martinez V, Garcia E, Fernandez P, Rodriguez J, et al. Resistance to growth hormone and insulin-like growth factor-I in acidotic rats. Pediatr Nephrol. 2000;14(8–9):720–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Brungger M, Hulter HN, Krapf R. Effect of chronic metabolic acidosis on the growth hormone/IGF-1 endocrine axis: new cause of growth hormone insensitivity in humans. Kidney Int. 1997;51(1):216–21.PubMedCrossRefGoogle Scholar
  33. 33.
    Wiederkehr MR, Kalogiros J, Krapf R. Correction of metabolic acidosis improves thyroid and growth hormone axes in haemodialysis patients. Nephrol Dial Transplant. 2004;19(5):1190–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Sicuro A, Mahlbacher K, Hulter HN, Krapf R. Effect of growth hormone on renal and systemic acid–base homeostasis in humans. Am J Physiol. 1998;274(4 Pt 2):F650–7.PubMedGoogle Scholar
  35. 35.
    Maurer M, Riesen W, Muser J, Hulter HN, Krapf R. Neutralization of Western diet inhibits bone resorption independently of K intake and reduces cortisol secretion in humans. Am J Physiol Renal Physiol. 2003;284(1):F32–40.PubMedGoogle Scholar
  36. 36.
    Yakar S, Rosen CJ, Beamer WG, Ackert-Bicknell CL, Wu Y, Liu JL, et al. Circulating levels of IGF-1 directly regulate bone growth and density. J Clin Invest. 2002;110(6):771–81.PubMedGoogle Scholar
  37. 37.
    Canalis E, Delany AM. Mechanisms of glucocorticoid action in bone. Ann N Y Acad Sci. 2002;966:73–81.PubMedCrossRefGoogle Scholar
  38. 38.
    Arnett T. Regulation of bone cell function by acid–base balance. Proc Nutr Soc. 2003;62(2):511–20.PubMedCrossRefGoogle Scholar
  39. 39.
    Geng W, Hill K, Zerwekh JE, Kohler T, Muller R, Moe OW. Inhibition of osteoclast formation and function by bicarbonate: role of soluble adenylyl cyclase. J Cell Physiol. 2009;220(2):332–40.PubMedCrossRefGoogle Scholar
  40. 40.
    Street D, Nielsen JJ, Bangsbo J, Juel C. Metabolic alkalosis reduces exercise-induced acidosis and potassium accumulation in human skeletal muscle interstitium. J Physiol. 2005;566(Pt 2):481–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.DONALD Study at the Research Institute of Child Nutrition, Nutritional EpidemiologyUniversity of BonnDortmundGermany

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