Omega-3 Uzun Zincirli Çoklu Doymamış Yağ Asitleri ve Fenilketonüri

Beyin, retina ve diğer sinir dokuları uzun zincirli çoklu doymamış yağ asitlerinden (UZÇDYA) zengindir. Birçok klinik ve epidemiyolojik çalışma ile omega-3 UZÇDYA’ların çocukluk çağındaki nöral gelişim üzerine olumlu etkileri olduğu kanıtlanmıştır. Uzun zincirli ÇDYA’lar, diyetle alımları yeterli olduğu sürece temel elzem yağ asitlerinden endojen olarak sentezlenebilirler. Aynı zamanda, et, balık, yumurta, karaciğer ve süt ürünleri gibi proteinden zengin besinler eikosapentaenoik asit (EPA) ve dokosaheksaenoik asit (DHA) gibi UZÇDYA’ların en belirgin diyetsel kaynaklarıdır. Bununla birlikte, klasik fenilketonürili (FKÜ) hastalar yüksek plazma fenilalanin düzeyleri ve nörolojik hasarı önlemek için diyet protein alımında sıkı ve ömür boyu süren bir sınırlamaya gereksinme duyarlar. Bu katı metabolik kontrol sadece düşük miktarda vitamin ve mineral sağlamakla kalmaz, genellikle doymuş yağ asitleri ve ÇDYA’ların da düşük miktarda alınmasına neden olur. Bu nedenle, FKÜ’lü hastaların sağlıklı kontrollerle karşılaştırıldığında UZÇDYA alımları daha az olmakta ve daha düşük plazma ve eritrosit UZÇDYA düzeylerine sahip olmaktadırlar. Bebeklik ve çocukluk döneminde, UZÇDYA’lar normal nörogelişim için önemlidir. Yetersizliği, okul öncesi ve okul çağındaki FKÜ’lü çocuklarda erken dönemde saptanabilen merkezi sinir sistemi işlev bozukluklarına katkıda bulunabilir. Ayrıca, UZÇDYA yetersizliğinin kronik nörolojik, inflamatuvar ve metabolik bozukluklara neden olabileceği de ileri sürülmektedir. Diğer taraftan, randomize kontrollü çalışmalardan elde edilen veriler, FKÜ’lü hastalardaki UZÇDYA durumunun diyet desteği ile iyileştirilebileceğini önermektedir. Bu derleme yazıda, fenilalaninden kısıtlı diyetler ile UZÇDYA arasındaki ilişki incelenmiş ve FKÜ’lü hastalar için UZÇDYA’ların önemi ele alınmıştır.

Omega-3 Long-Chain Polyunsaturated Fatty Acids and Phenylketonuria

The brain, retina and other nervous tissues are rich in long chain polyunsaturated fatty acids (LCPUFA). Many clinical and epidemiological studies have proven omega-3 LCPUFA to produce positive effects on neural development in childhood. Long-chain PUFA can be synthesised endogenously from the parent essential fatty acids when dietary intakes are adequate. Protein-rich foods such as meat, fish, eggs, liver and milk products are also the predominant dietary sources of LCPUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, patients with classical phenylketonuria (PKU) require strict lifelong limitation of dietary protein intake to avoid high plasma concentrations of phenylalanine and neurological damage. This type of strict metabolic control usually provides not only lower amounts of vitamins and minerals but also lower amounts of saturated fatty acids and PUFA. Therefore, PKU patients have very low LCPUFA intakes and reduced LCPUFA concentrations in plasma and erythrocytes as compared to healthy controls. During infancy and childhood, LCPUFA are important for normal neurodevelopment. A deficiency may contribute to disturbances in the function of thecentral nervous system, which are detectable as early as in preschool and school-age children with PKU. Moreover, it has been suggested that the LCPUFA deficiency may lead to chronic neurological, inflammatory and metabolic disorders. On the other hand, data from randomized controlled trials suggest that LCPUFA status in patients with PKU may be improved by dietary supplementation. In this review, the association between phenylalanine restricted diets and LCPUFA was investigated and the importance of LCPUFA for patients with PKU was discussed.

PDF

___

1. Burr G, Burr M. A new deficiency disease produced by the rigid exclusion of fat from the diet. J Biol Chem 1929;82:345-67.
2. Bang HO, Dyerberg J. Plasma lipids and lipoproteins in Greenlandic west coast Eskimos. Acta Med Scand 1972;192:85-94
3. Dyerberg J, Bang HO, Hjorne N. Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr 1975;28:958-66.
4. Koletzko B, Sauerwald T, Demmelmair H, Herzog M, von Schenck U, Böhles H, et al. Dietary long chain polyunsaturated fatty acid supplementation in infants with phenylketonuria: A randomized controlled trial. J Inherit Metab Dis 2007;30:326-32.
5. Lohner S, Fekete K, Decsi T. Lower n-3 long-chain polyunsaturated fatty acid values in patients with phenylketonuria: A systematic review and metaanalysis. Nutr Res 2013;33:513-20.
6. Campoy C, Escolano-Margarit MV, Anjos T, Szajewska H, Uauy R. Omega 3 fatty acids on child growth, visual acuity and neurodevelopment. Br J Nutr 2012;107:85- 106.
7. Koletzko B, Beblo S, Demmelmair H, Hanebutt FL. Omega-3 LC-PUFA supply and neurological outcomes in children with phenylketonuria (PKU). J Pediatr Gastroenterol Nutr 2009;48:2-7.
8. Bone A, Kuehl AK, Angelino AF. A neuropsychiatric perspective of phenylketonuria I: Overview of phenylketonuria and its neuropsychiatric sequelae. Psychosomatics 2012;53:517–23.
9. Konukoğlu D. Omega-3 ve omega-6 yağ asitlerinin özellikleri, etkileri ve kardiyovasküler hastalıklar ile ilişkileri. Türk Aile Hek Derg 2008;12:121-9.
10. European Food Safety Authority (EFSA). Scientific opinion on dietary reference values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol. EFSA Journal 2010;8:1461.
11. Gezer C, Samur G. Omega-3 yağ asitlerinin bilişsel gelişimdeki rolü. Bes Diy Derg 2012;40:43-9.
12. Abu-Ouf NM, Jan MM. The influence of fish oil on neurological development and function. Can J Neurol Sci 2014;41:13-8.
13. Brenna JT, Varamini B, Jensen RG, Diersen-Schade DA, Boettcher JA, Arterburn LM. Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am J Clin Nutr Neurosci 2007;85:1457-64.
14. Yuhas R, Pramuk K, Lien EL. Human milk fatty acid composition from nine countries varies most in DHA. Lipids 2006;41:851-8.
15. Food and Agriculture Organization & World Health Organization. Fats and Oils in Human Nutrition. Vol Paper no. 57. Rome: FAO; 1994.
16. World Health Organization. Diet, Nutrition and the Prevention of Chronic Diseases. Consultation JWFE (eds). Geneva: WHO;2003.
17. Kris-Etherton PM, Innis S. Position of the American Dietetic Association and Dietitians of Canada: Dietary fatty acids. J Am Diet Assoc 2007;107:1599-611.
18. European Food Safety Authority (EFSA). Scientific opinion on nutrient requirements and dietary intakes of infants and young children in the European Union. EFSA Journal 2013;11:3408.
19. Hacettepe Üniversitesi Sağlık Bilimleri Fakültesi Beslenme ve Diyetetik Bölümü. Türkiye’ye Özgü Besin ve Beslenme Rehberi. Yenilenmiş 1. Baskı. Ankara: Hacettepe Üniversitesi Sağlık Bilimleri Fakültesi Beslenme ve Diyetetik Bölümü; 2015.
20. Koletzko B, Lien E, Agostoni C, Böhles H, Campoy C, Cetin I, et al. The roles of longchain polyunsaturated fatty acids in pregnancy, lactation and infancy: Review of current knowledge and consensus recommendations. J Perinat Med 2008;36:5-14.
21. Agostoni C, Braegger C, Decsi T, Kolacek S, Mihatsch W, Moreno LA, et al. Supplementation of n-3 LCPUFA to the diet of children older than 2 years: A commentary by the espghan committee on nutrition. J Pediatr Gastroenterol Nurt 2011;53:2-10.
22. European Food Safety Authority (EFSA). Scientific opinion on the tolerable upper intake level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). EFSA Journal 2012;10:2815.
23. Calder PC. Mechanisms of action of (n-3) fatty acids. J Nutr 2012;142:592-9.
24. Infante JP, Huszagh VA. Impaired arachidonic (20:4n6) and docosahexaenoic (22:6n-3) acid synthesis by phenylalanine metabolites as etiological factors in the neuropathology of phenylketonuria. Mol Genet Metab 2001;72:185-98.
25. Cornejo V, Concha M, Cabello JF, Raimann E. Lipids composition diet in phenylketonuric children with early diagnosis. Arch Latinoam Nutr 2005;55:332-5.
26. LaVoie SM, Harding CO, Gillingham MB. Normal fatty acid concentrations in young children with phenylketonuria (PKU). Top Clin Nutr 2009;24:333-40.
27. Giovannini M, Verduci E, Radaelli G, Lammardo A, Minghetti D, Cagnoli G, et al. Long-chain polyunsaturated fatty acids profile in plasma phospholipids of hyperphenylalaninemic children on unrestricted diet. Prostaglandins Leukot Essent Fatty Acids 2011;84:39-42.
28. Gramer G, Haege G, Langhans CD, Schuhmann V, Burgard P, Hoffmann GF. Long-chain polyunsaturated fatty acid status in children, adolescents and adults with phenylketonuria. Prostaglandins Leukot Essent Fatty Acids 2016;109:52-7.
29. Russo GL. Dietary n-6 and n-3 polyunsaturated fatty acids: From biochemistry to clinical implications in cardiovascular prevention. Biochem Pharmacol 2009;77:937-46.
30. Riediger ND, Othman RA, Suh M, Moghadasian MH. A systemic review of the roles of n-3 fatty acids in health and disease. J Am Diet Assoc 2009;109:668-79.
31. Agostoni C, Marangoni F, Riva E, Giovannini M, Galli C. Plasma arachidonic acid and serum thromboxane B2 concentrations in phenylketonuric children negatively correlate with dietary compliance. Prostaglandins Leukot Essent Fatty Acids 1997;56:219-22.
32. Mütze U, Beblo S, Kortz L, Matthies C, Koletzko B, Bruegel M, et al. Metabolomics of dietary fatty acid restriction in patients with phenylketonuria. PLoS One 2012;7(8):e43021. 33. Htun P, Nee J, Ploeckinger U, Eder K, Geisler T, Gawaz M, et al. Fish-free diet in patients with phenylketonuria is not associated with early atherosclerotic changes and enhanced platelet activation. PLoS One 2015;10(8):e0135930.
34. MacDonald A, Rocha JC, van Rijn M, Feillet F. Nutrition in phenylketonuria. Mol Genet Metab 2011;104:10-8.
35. Brumm VL, Grant ML. The role of intelligence in phenylketonuria: A review of research and management. Mol Genet Metab 2010;99:18-21.
36. VanZutphen K, Packman W, Sporri L, Needham M, Morgan C, Weisiger K, et al. Executive functioning in children and adolescents with phenylketonuria. Clin Genet 2007;72:13-8.
37. Blau N, van Spronsen FJ, Levy HL. PhenylketonuriaLancet 2010;376:1417-27.
38. Beblo S, Reinhardt H, Demmelmair H, Muntau AC, Koletzko B. Effect of fish oil supplementation on fatty acid status, coordination, and fine motor skills in children with phenylketonuria. J Pediatr 2007;150:479- 84.
39. Koletzko B, Beblo S, Demmelmair H, Müller-Felber W, Hanebutt FL. Does dietary DHA improve neural function in children? Observations in phenylketonuria. Prostaglandins Leukot Essent Fatty Acids 2009;81:159- 64.
40. Agostoni C, Scaglioni S, Bonvissuto M, Bruzzese MG, Giovanini M, Riva E. Biochemical effects of supplemented long-chain polyunsaturated fatty acids in hyperphenylalaninemia. Prostaglandins Leukot Essent Fatty Acids 2001;64:111-5.
41. Agostoni C, Verduci E, Massetto N, Fiori L, Radaelli G, Riva E, et al. Long term effects of long chain polyunsaturated fats in hyperphenylalaninemic children. Arch Dis Child 2003;88:582-3.
42. Koçum Y, Köksal G, Özel HG, Coşkun T. Fenilketonürili hastalara omega-3 yağ sitleri verilmesinin antropometrik ölçümler, biyokimyasal parametreler ve bilişsel gelişimdeki etkisinin incelenmesi. VIII Uluslararası Katılımlı Beslenme ve Metabolik Hastalıklar Kongre Kitabı 2005;G2S5:21.
43. Jans JJ, de Sain-van der Velden MG, van Hasselt PM, van den Hurk DT, Vaz FM, Visser G, et al. Supplementation with a powdered blend of PUFAs normalizes DHA and AA levels in patients with PKU. Mol Genet Metab 2013;109:121-4.
44. Acosta PB, Yannicelli S. The Ross Metabolic Formula System Nutrition Support Protocols. 4th edition. Columbus, Ohio: Abbott Laboratories;2001.