Skip to main content

Comparative effects of oral aromatic and branched-chain amino acids on urine calcium excretion in humans



In 30 adults, increasing intake of aromatic amino acids increased calcium excretion and serum IGF-1, but not indices of bone turnover, when compared with similar increases in intake of branched-chain amino acids. The mechanisms involved are not certain but these findings suggest a role for the calcium sensor receptor.


In contrast to branched-chain amino acids (BCAAs), aromatic amino acids (AAAs) bind to the calcium sensing receptor (CaR) and thus have an increased potential to affect calcium homeostasis. In this study we compare the effects of increased intake of AAAs versus BCAAs on calcium excretion, serum IGF-1, markers of bone turnover, and 4-hr calcium excretion after an oral calcium load.


After two weeks on low-protein metabolic diets, 30 healthy subjects were randomized to a fivefold increase in intake of AAAs or BCAAs for two weeks. Changes in calcium excretion and other measures were compared in the two groups.


With the increase in amino acid intake, 24-hr calcium excretion (P = 0.027), IGF-1 (P = 0.022), and 4-hr calcium excretion after an oral load (P = 0.023) increased significantly in the AAA relative to the BCAA group. Group changes in turnover markers did not differ significantly.


In comparison with BCAAs, AAAs promoted calcium excretion. The calciuria does not appear to result from increases in bone resorption and may occur by increasing calcium absorption. The AAAs also increased circulating levels of IGF-1. Collectively these findings raise the possibility that AAAs may selectively influence calcium homeostasis through their interactions with the CaR.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. 1.

    Hegsted M, Schuette SA, Zemel MB et al (1981) Urinary calcium and calcium balance in young men as affected by level of protein and phosphorus intake. J Nutr 111:553–562

    PubMed  CAS  Google Scholar 

  2. 2.

    Frassetto 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 68:576–583

    PubMed  CAS  Google Scholar 

  3. 3.

    Sprague SM, Krieger NS, Bushinsky DA (1994) Greater inhibition of in vitro bone mineralization with metabolic than respiratory acidosis. Kidney Int 46:1199–1206

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Arnett TR, Spowage M (1996) Modulation of the resorptive activity of rat osteoclasts by small changes in extracellular pH near the physiological range. Bone 18:277–279

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Bushinsky DA (1996) Metabolic alkalosis decreases bone calcium efflux by suppressing osteoclasts and stimulating osteoblasts. Am J Physiol 271:F216–F222

    PubMed  CAS  Google Scholar 

  6. 6.

    Kerstetter JE, O’Brien KO, Insogna KL (1998) Dietary protein affects intestinal calcium absorption. Am J Clin Nutr 68:859–865

    PubMed  CAS  Google Scholar 

  7. 7.

    Kerstetter JE, O’Brien KO, Caseria DM et al (2005) The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women. J Clin Endocrinol Metab 90:26–31

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Conigrave AD, Quinn SJ, Brown EM (2000) L-amino acid sensing by the extracellular Ca2+-sensing receptor. Proc Natl Acad Sci USA 97:4814–4819

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Cheng I, Qureshi I, Chattopadhyay N et al (1999) Expression of an extracellular calcium-sensing receptor in rat stomach. Gastroenterology 116:118–126

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Geibel JP, Wagner CA, Caroppo R et al (2001) The stomach divalent ion-sensing receptor scar is a modulator of gastric acid secretion. J Biol Chem 276:39549–39552

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Ray JM, Squires PE, Curtis SB et al (1997) Expression of the calcium-sensing receptor on human antral gastrin cells in culture. J Clin Invest 99:2328–2333

    PubMed  CAS  Google Scholar 

  12. 12.

    Busque SM, Kerstetter JE, Geibel JP et al (2005) L-type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells. Am J Physiol-Gastrointest Liver Physiol 289:G664–G669

    PubMed  CAS  Google Scholar 

  13. 13.

    Isley WL, Underwood LE, Clemmons DR (1983) Dietary components that regulate serum somatomedin-C concentrations in humans. J Clin Investiga 71:175–182

    CAS  Article  Google Scholar 

  14. 14.

    Schurch MA, Rizzoli R, Slosman D et al (1998) Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial. Ann Int Med 128:801–809

    PubMed  CAS  Google Scholar 

  15. 15.

    Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (2005) Dietary reference intakes: energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. Institute of Medicine-Washington, DC 1060–1061

  16. 16.

    Jorgensen K (1957) Titrimetric determination of the net excretion of acid/base in urine. Scand J Clin Lab Invest 9:28–291

    Google Scholar 

  17. 17.

    Chan JC (1972) The rapid determination of urinary titratable acid and ammonium and evaluation of freezing as a method of preservation. Clin Biochem 5:94–98

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Maurer 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 284:F32–F40

    CAS  Google Scholar 

  19. 19.

    Sebastian A, Morris RC Jr (1994) Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. New Engl J Med 330:1776–1781

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Broadus AE, Dominguez M, Bartter FC (1978) Pathophysiological studies in idiopathic hypercalciuria: use of an oral calcium tolerance test to characterize distinctive hypercalciuric subgroups. J Clin Endocrinol Metab 47:751–760

    PubMed  CAS  Article  Google Scholar 

  21. 21.

    Harvey JA, Zobitz MM, Pak CY (1988) Dose dependency of calcium absorption: a comparison of calcium carbonate and calcium citrate. J Bone Miner Res 3:253–258

    PubMed  CAS  Article  Google Scholar 

  22. 22.

    Thissen JP, Ketelslegers JM, Underwood LE (1994) Nutritional regulation of the insulin-like growth factors. Endocrine Reviews 15:80–101

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Noguchi T (2000) Protein nutrition and insulin-like growth factor system. Br J Nutr 84(Suppl 2):S241–S244

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Canaff L, Petit JL, Kisiel M et al (2001) Extracellular calcium-sensing receptor is expressed in rat hepatocytes. coupling to intracellular calcium mobilization and stimulation of bile flow. J Biol Chem 276:4070–4079

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Law WM Jr, Heath H III (1985) Familial benign hypercalcemia (hypocalciuric hypercalcemia). Clinical and pathogenetic studies in 21 families. Ann Int Med 102:511–519

    PubMed  Google Scholar 

  26. 26.

    Cecconi E, Bogazzi F, Cetani F et al (2003) Impaired GH secretion to provocative stimuli in two families with hypocalciuric hypercalcaemia. Clin Endocrinol 59:604–606

    Article  CAS  Google Scholar 

Download references


We are grateful to the staff of the Metabolic Research Unit at Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University for assistance in carrying out this study. BD-H, SH, HMR, and GED contributed to the design, analysis, and writing of the manuscript. BD-H obtained the funding. None of the authors had any conflicts of interest.

Author information



Corresponding author

Correspondence to B. Dawson-Hughes.

Additional information

This material is based on work supported by a Discovery Grant from Dairy Management, Inc. and by the U.S. Department of Agriculture under agreement No. 59-1950-9001. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors, and do not necessarily reflect the view of the U.S. Department of Agriculture.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Dawson-Hughes, B., Harris, S.S., Rasmussen, H.M. et al. Comparative effects of oral aromatic and branched-chain amino acids on urine calcium excretion in humans. Osteoporos Int 18, 955–961 (2007).

Download citation


  • Aromatic amino acids
  • Bone turnover
  • Branched-chain amino acids
  • Calcium excretion
  • IGF-1