Abstract
OBJECTIVE—To test the efficacy of tyrosine supplementation, as an adjunct to dietary treatment, on neuropsychological test performance in individuals with phenylketonuria. DESIGN—A randomised controlled trial of tyrosine supplementation using a double blind crossover procedure with three four week phases. SETTING—The Hospital for Sick Children, Toronto. PARTICIPANTS—21 individuals with phenylketonuria (ages 6 to 28 years, mean 11.3). INTERVENTION—Participants were given 100 mg/kg body weight/d of L-tyrosine or L-alanine (placebo). RESULTS—At baseline, performance on several of the neuropsychological test measures was correlated with tyrosine levels. Dietary supplements of tyrosine increased plasma tyrosine concentrations; however, no change in test performance was found across the tyrosine and placebo phases of the study. CONCLUSIONS—Tyrosine supplementation of this type does not appear to alter neuropsychological performance in individuals with phenylketonuria.
Full Text
The Full Text of this article is available as a PDF (109.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BECK L. H., BRANSOME E. D., Jr, MIRSKY A. F., ROSVOLD H. E., SARASON I. A continuous performance test of brain damage. J Consult Psychol. 1956 Oct;20(5):343–350. doi: 10.1037/h0043220. [DOI] [PubMed] [Google Scholar]
- Berry H. K., O'Grady D. J., Perlmutter L. J., Bofinger M. K. Intellectual development and academic achievement of children treated early for phenylketonuria. Dev Med Child Neurol. 1979 Jun;21(3):311–320. doi: 10.1111/j.1469-8749.1979.tb01623.x. [DOI] [PubMed] [Google Scholar]
- Bessman S. P. The justification theory: the essential nature of the non-essential amino acids. Nutr Rev. 1979 Jul;37(7):209–220. doi: 10.1111/j.1753-4887.1979.tb06668.x. [DOI] [PubMed] [Google Scholar]
- Brunner R. L., Jordan M. K., Berry H. K. Early-treated phenylketonuria: neuropsychologic consequences. J Pediatr. 1983 Jun;102(6):831–835. doi: 10.1016/s0022-3476(83)80007-9. [DOI] [PubMed] [Google Scholar]
- Cabalska B., Duczyńska N., Borzymowska J., Zorska K., Koślacz-Folga A., Bozkowa K. Termination of dietary treatment in phenylketonuria. Eur J Pediatr. 1977 Nov 4;126(4):253–262. doi: 10.1007/BF00477051. [DOI] [PubMed] [Google Scholar]
- Christensen H. N. Where do the depleted plasma amino acids go in phenylketonuria? Biochem J. 1986 Jun 15;236(3):929–930. doi: 10.1042/bj2360929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clarke J. T., Gates R. D., Hogan S. E., Barrett M., MacDonald G. W. Neuropsychological studies on adolescents with phenylketonuria returned to phenylalanine-restricted diets. Am J Ment Retard. 1987 Nov;92(3):255–262. [PubMed] [Google Scholar]
- Diamond A., Ciaramitaro V., Donner E., Djali S., Robinson M. B. An animal model of early-treated PKU. J Neurosci. 1994 May;14(5 Pt 2):3072–3082. doi: 10.1523/JNEUROSCI.14-05-03072.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diamond A. Phenylalanine levels of 6-10 mg/dl may not be as benign as once thought. Acta Paediatr Suppl. 1994 Dec;407:89–91. doi: 10.1111/j.1651-2227.1994.tb13462.x. [DOI] [PubMed] [Google Scholar]
- GUROFF G., KING W., UNDENFRIEND S. The uptake of tyrosine by rat brain in vitro. J Biol Chem. 1961 Jun;236:1773–1777. [PubMed] [Google Scholar]
- Glaeser B. S., Melamed E., Growdon J. H., Wurtman R. J. Elevation of plasma tyrosine after a single oral dose of L-tyrosine. Life Sci. 1979 Jul 16;25(3):265–271. doi: 10.1016/0024-3205(79)90294-7. [DOI] [PubMed] [Google Scholar]
- Gordon M., Mettelman B. B. The assessment of attention: I. Standardization and reliability of a behavior-based measure. J Clin Psychol. 1988 Sep;44(5):682–690. doi: 10.1002/1097-4679(198809)44:5<682::aid-jclp2270440504>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
- Hannay H. J., Levin H. S. Selective reminding test: an examination of the equivalence of four forms. J Clin Exp Neuropsychol. 1985 Jun;7(3):251–263. doi: 10.1080/01688638508401258. [DOI] [PubMed] [Google Scholar]
- Knudsen G. M., Hasselbalch S., Toft P. B., Christensen E., Paulson O. B., Lou H. Blood-brain barrier transport of amino acids in healthy controls and in patients with phenylketonuria. J Inherit Metab Dis. 1995;18(6):653–664. doi: 10.1007/BF02436753. [DOI] [PubMed] [Google Scholar]
- Koch R., Azen C., Friedman E. G., Williamson M. L. Paired comparisons between early treated PKU children and their matched sibling controls on intelligence and school achievement test results at eight years of age. J Inherit Metab Dis. 1984;7(2):86–90. doi: 10.1007/BF01805813. [DOI] [PubMed] [Google Scholar]
- Krause W., Halminski M., McDonald L., Dembure P., Salvo R., Freides D., Elsas L. Biochemical and neuropsychological effects of elevated plasma phenylalanine in patients with treated phenylketonuria. A model for the study of phenylalanine and brain function in man. J Clin Invest. 1985 Jan;75(1):40–48. doi: 10.1172/JCI111695. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lou H. C., Güttler F., Lykkelund C., Bruhn P., Niederwieser A. Decreased vigilance and neurotransmitter synthesis after discontinuation of dietary treatment for phenylketonuria in adolescents. Eur J Pediatr. 1985 May;144(1):17–20. doi: 10.1007/BF00491918. [DOI] [PubMed] [Google Scholar]
- Lou H. C., Lykkelund C., Gerdes A. M., Udesen H., Bruhn P. Increased vigilance and dopamine synthesis by large doses of tyrosine or phenylalanine restriction in phenylketonuria. Acta Paediatr Scand. 1987 Jul;76(4):560–565. doi: 10.1111/j.1651-2227.1987.tb10521.x. [DOI] [PubMed] [Google Scholar]
- Mazzocco M. M., Yannicelli S., Nord A. M., van Doorninck W., Davidson-Mundt A. J., Greene C. L. Cognition and tyrosine supplementation among school-aged children with phenylketonuria. Am J Dis Child. 1992 Nov;146(11):1261–1264. doi: 10.1001/archpedi.1992.02160230019009. [DOI] [PubMed] [Google Scholar]
- McKean C. M. The effects of high phenylalanine concentrations on serotonin and catecholamine metabolism in the human brain. Brain Res. 1972 Dec 12;47(2):469–476. doi: 10.1016/0006-8993(72)90653-1. [DOI] [PubMed] [Google Scholar]
- Murray J. E. Carrier-mediated transfer of amino acids from blood to brain. An in vivo study in the rat. Neurology. 1973 Sep;23(9):940–944. doi: 10.1212/wnl.23.9.940. [DOI] [PubMed] [Google Scholar]
- NEAME K. D. Phenylalanine as inhibitor of transport of amino-acids in brain. Nature. 1961 Oct 14;192:173–174. doi: 10.1038/192173a0. [DOI] [PubMed] [Google Scholar]
- Nord A. M., McCabe L., McCabe E. R. Biochemical and nutritional status of children with hyperphenylalaninaemia. J Inherit Metab Dis. 1988;11(4):431–432. doi: 10.1007/BF01800437. [DOI] [PubMed] [Google Scholar]
- Oldendorf W. H. Saturation of blood brain barrier transport of amino acids in phenylketonuria. Arch Neurol. 1973 Jan;28(1):45–48. doi: 10.1001/archneur.1973.00490190063008. [DOI] [PubMed] [Google Scholar]
- PETERSON L. R., PETERSON M. J. Short-term retention of individual verbal items. J Exp Psychol. 1959 Sep;58:193–198. doi: 10.1037/h0049234. [DOI] [PubMed] [Google Scholar]
- Pennington B. F., van Doorninck W. J., McCabe L. L., McCabe E. R. Neuropsychological deficits in early treated phenylketonuric children. Am J Ment Defic. 1985 Mar;89(5):467–474. [PubMed] [Google Scholar]
- Petrides M., Milner B. Deficits on subject-ordered tasks after frontal- and temporal-lobe lesions in man. Neuropsychologia. 1982;20(3):249–262. doi: 10.1016/0028-3932(82)90100-2. [DOI] [PubMed] [Google Scholar]
- Pietz J., Landwehr R., Kutscha A., Schmidt H., de Sonneville L., Trefz F. K. Effect of high-dose tyrosine supplementation on brain function in adults with phenylketonuria. J Pediatr. 1995 Dec;127(6):936–943. doi: 10.1016/s0022-3476(95)70031-5. [DOI] [PubMed] [Google Scholar]
- Ris M. D., Williams S. E., Hunt M. M., Berry H. K., Leslie N. Early-treated phenylketonuria: adult neuropsychologic outcome. J Pediatr. 1994 Mar;124(3):388–392. doi: 10.1016/s0022-3476(94)70360-4. [DOI] [PubMed] [Google Scholar]
- Seashore M. R., Friedman E., Novelly R. A., Bapat V. Loss of intellectual function in children with phenylketonuria after relaxation of dietary phenylalanine restriction. Pediatrics. 1985 Feb;75(2):226–232. [PubMed] [Google Scholar]
- Shue K. L., Douglas V. I. Attention deficit hyperactivity disorder and the frontal lobe syndrome. Brain Cogn. 1992 Sep;20(1):104–124. doi: 10.1016/0278-2626(92)90064-s. [DOI] [PubMed] [Google Scholar]
- Smith I., Beasley M. G., Ades A. E. Intelligence and quality of dietary treatment in phenylketonuria. Arch Dis Child. 1990 May;65(5):472–478. doi: 10.1136/adc.65.5.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith I., Beasley M. G., Wolff O. H., Ades A. E. Behavior disturbance in 8-year-old children with early treated phenylketonuria. Report from the MRC/DHSS Phenylketonuria Register. J Pediatr. 1988 Mar;112(3):403–408. doi: 10.1016/s0022-3476(88)80320-2. [DOI] [PubMed] [Google Scholar]
- Smith I., Beasley M. Intelligence and behaviour in children with early treated phenylketonuria. A report from the MRC/DHSS phenylketonuria register. Eur J Clin Nutr. 1989;43 (Suppl 1):1–5. [PubMed] [Google Scholar]
- Snodgrass S. R., Cutler R. W., Kang E. S., Lorenzo A. V. Transport of neutral amino acids from feline cerebrospinal fluid. Am J Physiol. 1969 Oct;217(4):974–980. doi: 10.1152/ajplegacy.1969.217.4.974. [DOI] [PubMed] [Google Scholar]
- Waisbren S. E., Schnell R., Levy H. L. Intelligence and personality characteristics in adults with untreated atypical phenylketonuria and mild hyperphenylalaninemia. J Pediatr. 1984 Dec;105(6):955–958. doi: 10.1016/s0022-3476(84)80088-8. [DOI] [PubMed] [Google Scholar]
- Weglage J., Pietsch M., Funders B., Koch H. G., Ullrich K. Deficits in selective and sustained attention processes in early treated children with phenylketonuria--result of impaired frontal lobe functions? Eur J Pediatr. 1996 Mar;155(3):200–204. doi: 10.1007/BF01953938. [DOI] [PubMed] [Google Scholar]
- Welsh M. C., Pennington B. F., Ozonoff S., Rouse B., McCabe E. R. Neuropsychology of early-treated phenylketonuria: specific executive function deficits. Child Dev. 1990 Dec;61(6):1697–1713. [PubMed] [Google Scholar]