Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Randomised controlled trial of essential fatty acid supplementation in phenylketonuria

European Journal of Clinical Nutrition volume 60, pages 915–920 (2006)Cite this article

Abstract

Objective:

The long-chain polyunsaturated fatty acids (LC-PUFA) status of children with PKU is often compromised. LC-PUFA, which are important fatty acids in the development of the CNS, can be synthesised endogenously from the parent essential fatty acids (EFA) provided dietary intakes are adequate. This study was designed to assess the biochemical effect over a 20-week period of a phe-free protein substitute that has been supplemented with a balanced blend of n-3 and n-6 EFAs on LC-PUFA status of children with PKU.

Design, setting and subjects:

Fifty three community-living children aged 1–10 years diagnosed with PKU in the newborn period were recruited from seven tertiary centres in the UK and France and randomised to a fat-free control formula or the EFA-supplemented test-treatment formula in an open, prospective study. Forty four children completed the study (20 controls, 24 test-treatments). Fatty acid status was assessed at entry and 20-weeks follow-up. Three day dietary diaries were recorded at 20 weeks' follow-up. The safety, efficacy and palatability of the test-treatment formula were also assessed.

Results:

The test-treatment group had significantly higher intakes of fat and EFA than the control group. There was a significant between group difference (P=0.04) in increases in median docosahexaenoic acid (DHA) concentrations in erythrocyte phospholipids, which increased by 19% in the test-treatment group and by 0.5% in the control group over the study period. Growth and phe control were satisfactory in all subjects.

Conclusions:

Supplementing the diets of children with PKU with a balanced blend of n-6 and n-3 EFA improves DHA status without compromising AA status.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  • Agostoni C, Massetto N, Biasucci G, Rottoli A, Bonvissuto M, Bruzzese M-G et al. (2000). Effects of long-chain polyunsaturated fatty acid supplementation on fatty acid status and visual function in treated children with hyperphenylalaninemia. J Pediatr 137, 504–509.

    Article  CAS  Google Scholar 

  • Agostoni C, Riva E, Biasucci G, Luotti D, Bruzzese MG, Marangoni F et al. (1995). The effects of n-3 and n-6 polyunsaturated fatty acids on plasma lipids and fatty acids of treated phenylketonuric children. Prostaglandins Leukot Essent Fatty Acids 53, 401–404.

    Article  CAS  Google Scholar 

  • Beblo S, Reinhardt H, Muntau AC, Mueller-Felber W, Roscher AA, Koletzko B (2001). Fish oil supplementation improves visual evoked potentials in children with phenylketonuria. Neurology 57, 1488–1491.

    Article  CAS  Google Scholar 

  • Burgard P (2000). Development of intelligence in early treated phenylketonuria. Eur J Pediatr 159 (Suppl 2), S74–S79.

    Article  Google Scholar 

  • Cleary MA, Walter JH, Wraith JE, Jenkins JP, Alani SM, Tyler K et al. (1994). Magnetic Resonance Imaging of the brain in phenylketonuria. Lancet 344, 87–90.

    Article  CAS  Google Scholar 

  • Cockburn F, Clark BJ, Caine EA, Harvie A, Farquharson J, Jamieson EC et al. (1996). Fatty acids in the stability of the neuronal membrane: Relevance to PKU. Int Pediatr 11, 56–60.

    Article  Google Scholar 

  • Freeman JV, Cole TJ, Chinn S, Jones PRM, White EM, Preece MA (1993). Cross-sectional stature and weight reference curves for the UK, 1990. Arch Dis Child 73, 17–24.

    Article  Google Scholar 

  • Galli C, Agostoni C, Mosconi C, Riva E, Salari P-C, Giovannini M (1991). Reduced plasma C-20 and C-22 polyunsaturated fatty acids in children with phenylketonuria during dietary intervention. J Pediatr 119, 562–567.

    Article  CAS  Google Scholar 

  • Gregory J, Lowe S (2000). National Diet and Nutrition Survey: young people aged 4 to 18 years. Volume 1: Report of the diet and nutrition survey. HMSO: London.

    Google Scholar 

  • Gregory JR, Collins DL, Davies PSW, Hughes JM, Clarke PC (1995). National Diet and Nutrition Survey: children aged 1½ - 4½ years. Volume 1: Report of the diet and nutrition survey. HMSO: London.

    Google Scholar 

  • Infante JP, Huszagh V (2001). Impaired arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acid synthesis by phenylalanine metabolites as etiological factors in the neuropathology of phenylketonuria. Mol Genet Metabol 72, 185–198.

    Article  CAS  Google Scholar 

  • Makrides M, Neumann MA, Byard RW, Simmer K, Gibson RA (1994). Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants. Am J Clin Nutr 60, 189–194.

    Article  CAS  Google Scholar 

  • Medical Research Council Working Party on Phenylketonuria (1993). Recommendations on the Dietary Management of Phenylketonuria. Arch Dis Child 68, 426–427.

  • Moseley K, Koch R, Moser AB (2002). Lipid status and long-chain polyunsaturated fatty acid concentrations in adults and adolescents with phenylketonuria on phenylalanine-restricted diet. J Inher Metab Dis 25, 56–64.

    Article  CAS  Google Scholar 

  • Sanjurjo P, Perteagudo L, Rodriguez Soriano J, Vilaseca A, Campistol J (1994). Polyunsaturated fatty acid status in patients with phenylketonuria. J Inher Metab Dis 17, 704–709.

    Article  CAS  Google Scholar 

  • Smith I, Beasley MG, Ades AE (1991). Effect on intelligence of relaxing the low phenylalanine diet in phenylketonuria. Arch Dis Child 66, 311–316.

    Article  CAS  Google Scholar 

  • Thompson AJ, Smith I, Brenton D, Youl BD, Rylance G, Davidson DC et al. (1990). Neurological deterioration in young adults with phenylketonuria. Lancet 336, 602–605.

    Article  CAS  Google Scholar 

  • Villasana D, Butler IJ, Williams JC, Roongta SM (1989). Neurological deterioration in adult phenylketonuria. J Inher Metab Dis 12, 451–459.

    Article  CAS  Google Scholar 

  • Weglage J, Pietsch M, Funders B, Koch HG, Ullrich K (1995). Neurological findings in early treated phenylketonuria. Acta Paediatr 84, 411–415.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank the parents, children and the health care professionals at the following centres who participated in the trial: Hôpital D'enfants Brabois, Nancy, France; Royal Manchester Children's Hospital, Manchester, UK; Birmingham Children's Hospital, Birmingham, UK; R Thom, ER Trimble, Royal Belfast Hospital for Sick Children, Belfast, UK; J Sarles, Hôpital Timone Enfants, Marseille, France; Hôpital Robert Debré, Paris, France; DC Davidson, Alder Hey Children's Hospital, Liverpool, UK. The authors are grateful to David Percy (School of Accounting, Economics and Management Science, University of Salford, Manchester, UK) who carried out the statistical analysis of the data and Helen Rose and Catherine Deering (R&D Department, SHS International Ltd, Liverpool, UK) for their assistance with the preparation of this article.

Author information

Authors and Affiliations

  1. Department of Metabolic Medicine, Great Ormond St. Hospital for Sick Children, London, UK

    M A Cleary

  2. Department of Pediatrics, Hôpital D'enfants Brabois, Nancy, France

    F Feillet & M Vidailhet

  3. Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, UK

    F J White

  4. Birmingham Children's Hospital, Birmingham, UK

    A MacDonald

  5. Royal Belfast Hospital for Sick Children, Belfast, UK

    A Grimsley

  6. Hôpital Timone Enfants, Marseille, France

    N Maurin

  7. Hôpital Robert Debré, Paris, France

    H Ogier de Baulny

  8. Alder Hey Children's Hospital, Liverpool, UK

    P J Rutherford

Authors
  1. M A Cleary
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F Feillet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F J White
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Vidailhet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A MacDonald
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Grimsley
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N Maurin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H Ogier de Baulny
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P J Rutherford
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M A Cleary.

Additional information

Sources of financial support: SHS International Ltd, 100 Wavertree Boulevard, Wavertree Technology Park, Liverpool, L7 9PT, UK.

Guarantor: MA Cleary.

Contributors: All contributors are clinicians or dietitians from the seven recruiting centres. All contributors were involved in the development of the study protocol. The principal investigator (MC) produced the initial draft of the manuscript and the dietitians (FW, AM, AG, PR) collected and analysed the diet diaries. The other contributors provided additional information and comments on the drafts of the manuscript.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cleary, M., Feillet, F., White, F. et al. Randomised controlled trial of essential fatty acid supplementation in phenylketonuria. Eur J Clin Nutr 60, 915–920 (2006). https://doi.org/10.1038/sj.ejcn.1602401

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1602401

Keywords

This article is cited by

Search

Advanced search

Quick links