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4 Research Institute, The Hospital for Sick Children, and Departments of 5 Paediatrics and 6 Nutritional Sciences, University of Toronto, M5G 1X8 Toronto, Ontario, Canada; and 7 Department of Agriculture, Food, and Nutritional Sciences, University of Alberta, Edmonton, Alberta T6G 2P5, Alberta, Canada
* To whom correspondence should be addressed. E-mail: paul.pencharz{at}sickkids.ca.
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ABSTRACT |
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 TOP ABSTRACT LITERATURE CITED |
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Determination of amino acid requirements
Amino acid requirements should be determined by feeding graded levels of the test amino acid across a range of intakes, which includes the predicted mean requirement level (6). In the recently published Dietary Reference Intakes (DRI) for the Macronutrients, it was agreed that the isotope oxidation methods are currently the preferred method to determine amino acid requirements (7). Further, it was agreed that the indicator amino acid oxidation (IAAO) model was the best approach. The indicator model is shown in Figure 1. The data used by the DRI committee to define total aromatic amino acid requirements consisted of 3 studies, none of which is ideal. The first used direct amino acid oxidation to determine the minimum phenylalanine requirements in the presence of an excess of tyrosine (40 mg·kg–1·d–1) and studied subjects across a range of 7 levels of phenylalanine intake where each subject was studied at 6 different levels (3). A mean minimum phenylalanine requirement of 9.1 mg·kg–1·d–1 was determined with an upper 95% [CI] level of 14 mg·kg–1·d–1. A subsequent study using 24-h tyrosine balance as the physiological endpoint and only 3 levels of phenylalanine intake (high, medium, and low) concluded that an intake of 39 mg·kg–1·d–1 approximates the daily phenylalanine need (8). The third study was a determination of tyrosine requirements using [1-13C]-lysine as the indicator (9). The subjects of this study ingested a phenylalanine intake of 9 mg·kg–1·d–1, which approximates the mean minimum phenylalanine requirement and showed a tyrosine requirement of 6 mg·kg–1·d–1 when the phenylalanine intake was at 9 mg·kg–1·d–1, for a calculated mean total aromatic amino acid requirement of 15 mg·kg–1·d–1. In light of the lack of data, the DRI Committee decided to average the 2 values of 15 and 39 mg·kg–1·d–1 and suggested an average total aromatic amino acid requirement of 27 mg·kg–1·d–1. The only other data in humans using IAAO was in children with phenylketonuria who were shown to have mean tyrosine (10) and phenylalanine (11) requirements of 19 and 14 mg·kg–1·d–1, respectively, for a total mean aromatic amino acid requirement of 33 mg·kg–1·d–1.
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Because it was clear that total aromatic amino acid requirements were not known, we and others have conducted studies in adults in which the only source of aromatic amino acids was phenylalanine. In the first study, we used [1-13C]-lysine as the indicator and derived a mean requirement of 48 mg·kg–1·d–1 (12). Next, we attempted to utilize [1-13C]-leucine as an indicator amino acid to determine aromatic amino acids. Despite leucine being used as an indicator amino acid, its use, to our knowledge, had never been validated (6). We found that leucine is not a good indicator and that it was important to use a limited intake of leucine in order for the indicator to have any sensitivity (13). The derived mean estimate of total aromatic amino acid requirements was 42 mg·kg–1·d–1. Most recently, Kurpad et al. (14) have reported the use of 24-h indicator oxidation and balance using [1-13C]-leucine to determine total aromatic amino acid needs. Their estimate of the maximum mean phenylalanine requirement is 38 mg·kg–1·d–1. The main criticism of the Kurpad et al. (14) article is that their range of intakes is narrow and ranges from 19 to 47 mg·kg–1·d–1. In our work, we used phenylalanine intake ranging from 5 to 70 mg·kg–1·d–1. Because of the narrow upper end of their range, the Kurpad et al. (14) studies have only 2 data points above the requirement break-point. We in fact had a similar problem with our lysine indicator studies and had to add additional phenylalanine intake levels to define the requirement break-point with certainty. Had Kurpad et al. (14) used additional levels of phenylalanine intake above the break-point, we suggest that their break-point requirement value would have been higher and would have been similar to our own.
Aromatic amino acid requirement estimates are summarized in Table 1 and included for historical purposes are the 1985 FAO/WHO/UNU estimates based on nitrogen balance (15).
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As mentioned above, the minimum phenylalanine requirement has been defined as being 9.1 mg·kg–1·d–1 (3). From the 3 studies of the maximum phenylalanine requirement that range from 38 to 48 mg·kg–1·d–1, the proportion of the total aromatic amino acid requirement that can be met by tyrosine ranges between 76 and 81%. The study of Roberts et al. (9) casts a different light on the relation between phenylalanine and tyrosine. At a phenylalanine intake limited to 9 mg·kg–1·d–1, protein synthesis was optimized at a mean tyrosine intake of 6 mg·kg–1·d–1. This suggests that for optimal protein synthesis, the optimal dietary ratio of phenylalanine and tyrosine in mass units is 60:40. This ratio is similar to that seen in human tissue (7,16).
Three recent studies have established clearly that the requirement for phenylalanine (to meet the needs for phenylalanine plus tyrosine) is an average of 43 mg·kg–1·d–1. The optimal dietary ratio of phenylalanine to tyrosine is 60:40.
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FOOTNOTES |
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2 Supported by the Canadian Institutes of Health Research (grant MOP-10321).
3 Author disclosures: P. Pencharz, travel expenses to attend meeting paid by the Ajinomoto Company, Inc.; J. Hsu, no conflicts of interest; R. Ball, no conflicts of interest.
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LITERATURE CITED |
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1. Matthews DE. Proteins and amino acids. In: ME Shils, M Shike, AC Ross, B Caballero, RJ Cousins, editors. Modern nutrition in health and disease. 10th ed. Philadelphia: Lippincott, Williams & Wilkins; 2006. p. 23–61.
2. Tessari P, Deferrari G, Robaudo C, Vettore M, Pastorino N, De Biasi L, Garibotto G. Phenylalanine hydroxylation across the kidney in humans; rapid communication. Kidney Int. 1999;56:2168–72.[Medline]
3. Zello GA, Pencharz PB, Ball RO. Phenylalanine flux, oxidation and conversion to tyrosine in humans studied with L-[1-13C]-phenylalanine. Am J Physiol. 1990;259:E835–43.[Medline]
4. Ball RO, Courtney-Martin G, Pencharz PB. The in vivo sparing effect of cysteine on methionine requirements in animal models and adult humans. J Nutr. 2006;136:S1682–93.
5. Shiman R, Gray DW. Formation and fate of tyrosine. Intracellular partitioning of newly synthesized tyrosine in mammalian liver. J Biol Chem. 1998;273:34760–9.
6. Pencharz PB, Ball RO. Different approaches to define individual amino acid requirements. Annu Rev Nutr. 2003;23:101–16.[Medline]
7. Garlick P, Pencharz PB, Reeds P. Protein and amino acids. In: Dietary reference intakes for energy, carbohydrate. Fiber, fat, fatty acids, cholesterol, protein and amino acids. Chapter 10. Washington (DC): Institute of Medicine, National Academy of Sciences; 2002/2005. pp 589–768.
8. Basile-Filho A, Beaumier L, El-Khoury AE, Yu Y-M, Kenneway M, Gleason RE, Young VR. Twenty-four-hour L-[1-13C]tyrosine and L-[3,3-2H2]phenylalanine oral tracer studies at generous, intermediate, and low phenylalanine intakes to estimate aromatic amino acid requirements in adults. Am J Clin Nutr. 1998;67:640–59.[Abstract]
9. Roberts SA, Thorpe JM, Ball RO, Pencharz PB. Tyrosine requirement of healthy adult males receiving a fixed phenylalanine intake determined using amino acid oxidation. Am J Clin Nutr. 2001;73:276–82.
10. Bross R, Ball RO, Clarke JTR, Pencharz PB. Tyrosine requirements in children with classical PKU determined by indicator amino acid oxidation. Am J Physiol Endocrinol Metab. 2000;278:E195–201.
11. Courtney-Martin G, Bross R, Rafii M, Clarke JTR, Ball RO, Pencharz PB. Phenylalanine requirement in children with classical phenylketonuria determined by indicator amino acid oxidation. Am J Physiol Endocrinol Metab. 2002;283:E1249–56.
12. Hsu JW, Rafii M, Ball RO, Pencharz PB. The total aromatic amino acid requirements in healthy adult males determined by indicator amino acid oxidation. Am J Clin Nutr. 2006;83:82–8.
13. Hsu JW, Kriengsinyos W, Wykes LJ, Rafii M, Goonewardene LA, Ball RO, Pencharz PB. Leucine is not a good choice as an indicator amino acid for determining amino acid requirements in men. J Nutr. 2006;136:958–64.
14. Kurpad AV, Regan MM, Raj TDS, Rao VN, Gnanou J, Young VR. The daily phenylalanine requirements of healthy Indian adults. Am J Clin Nutr. 2006;83:1331–6.
15. FAO/WHO/UNU. Energy and protein requirements. Report of a joint FAO/WHO/UNU expert consultation, Geneva, Switzerland. World Health Organization. 1985; Technical Report Series 724.
16. Pencharz PB, House JD, Wykes LJ, Ball RO. What are the essential amino acids for the preterm and term infant? 10th Nutricia Symposium. Dordrecht (the Netherlands): Kluwer Academic Publishers; 1996;21: 278–296.
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