Safety assessment of docosahexaenoic acid in X-linked retinitis pigmentosa: The 4-year DHAX trial

Investigative Ophthalmology and Visual Science

Volumn 55, Issue 8, 2014, Pages 4958-4966

  Hughbanks Wheaton, Dianna K ^a,b   Birch, David G ^a,b   Fish, Gary E ^c   Spencer, Rand ^c   Shirlene Pearson, N ^d   Takacs, Alison ^a   Hoffman, Dennis R ^a,b  

^a RETINA FOUNDATION OF THE SOUTHWEST   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c TEXAS RETINA ASSOCIATES   (United States)

^d Pearson Statistical Consulting and Expert Witness Testimony   (United States)

Author keywords

Adverse events; Biosafety; Fatty acids

Indexed keywords

ADVERSE EVENTS; BIOSAFETY; FATTY ACIDS;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; CHILD; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DIETARY SUPPLEMENTS; DOCOSAHEXAENOIC ACIDS; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTRORETINOGRAPHY; FOLLOW-UP STUDIES; GENETIC DISEASES, X-LINKED; HUMANS; MALE; OXIDATIVE STRESS; RETINITIS PIGMENTOSA; TIME FACTORS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84906057121     PISSN: 01460404     EISSN: 15525783     Source Type: Journal    
DOI: 10.1167/iovs.14-14437     Document Type: Article

References (52)

1. Heckenlively JR. Retinitis Pigmentosa. Philadelphia, PA: Lippincott; 1988.
2. Bird AC. X-linked retinitis pigmentosa. Br J Ophthalmol. 1975; 59:177-199.
3. Fishman GA, Farber MD, Derlacki DJ. X-linked retinitis pigmentosa. Profile of clinical findings. Arch Ophthalmol. 1988;106:369-375.
4. Birch DG, Anderson JL, Birch EE. Early abnormalities of rod function in children with X-linked retinitis pigmentosa. Clin Vision Sci. 1993;8:329-335.
5. Hoffman DR. Fatty acids and visual dysfunction. In: Chow CK, ed. Fatty Acids in Foods and Their Health Implications. New York, NY: Marcel Dekker; 2000:817-842.
6. Hoffman DR, Birch DG. Docosahexaenoic acid in red blood cells of patients with X-linked retinitis pigmentosa. Invest Ophthalmol Vis Sci. 1995;36:1009-1018.
7. Hoffman DR, DeMar JC, Heird WC, Birch DG, Anderson RE. Impaired synthesis of DHA in patients with X-linked retinitis pigmentosa. J Lipid Res. 2001;42:1395-1401.
8. Fliesler SJ, Anderson RE. Chemistry and metabolism of lipids in the vertebrate retina. Prog Lipid Research. 1983;22:79-131.
9. Treen M, Uauy RD, Jameson DM, Thomas V, Hoffman DR. Effect of docosahexaenoic acid on membrane fluidity and function in intact cultured Y-79 retinoblastoma cells. Arch Biochem Biophys. 1992;294:564-570.
10. Litman BJ, Mitchell DC. A role for phospholipid polyunsaturation in modulating membrane protein function. Lipids. 1996; 31:S193-S197.
11. Rotstein NP, Aveldano MI, Barrantes FJ, Politi LE. Docosahexaenoic acid is required for the survivial of rat retinal photoreceptor in vitro. J Neurochem. 1996;66:1851-1859.
12. Kim H-Y, Akbar M, Lau A, Edsall L. Inhibition of neuronal apoptosis by docosahexaenoic acid (22:6n-3). Role of phosphatidylserine in antiapoptotic effect. J Biol Chem. 2000;275: 35215-35223.
13. Anderson RE, Maude M, Alvarez RA, Acland G, Aguirre GD. A hypothesis to explain the reduced blood levels of docosahexaenoic acid in inherited retinal degenerations caused by mutations in genes encoding retina-specific proteins. Lipids. 1999;34:S235-S237.
14. Gu X, Meer SG, Miyagi M, et al. Carboxyethylpyrrole protein adducts and autoantibodies, biomarkers for age-related macular degeneration. J Biol Chem. 2003;278:42027-42035.
15. Knapp HR. Dietary fatty acids in human thrombosis and hemostastis. Am J Clin Nutr. 1997;65:1687S-1698S.
16. Jacobson TA, Glickstein SB, Rowe JD, Soni PN. Effects of eicosapentaenoic acid and docosahexaenoic acid on lowdensity lipoprotein cholesterol and other lipids: a review. J Clin Lipidol. 2012;6:5-18.
17. Bays H. Clinical overview of Omacor: a concentrated formulation of omega-3 polyunsaturated fatty acids. Am J Cardiol. 2006;98:71i-76i.
18. Hoffman DR, Locke KG, Wheaton DH, Fish GE, Spencer R, Birch DG. A randomized, placebo-controlled clinical trial of docosahexaenoic acid supplementation for X-linked retinitis pigmentosa. Am J Ophthalmol. 2004;137:704-718.
19. Berson EL, Rosner B, Sandberg MA, et al. Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment. Arch Ophthalmol. 2004;122: 1306-1314.
20. Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Willett WC. ω-3 intake and visual acuity in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2012;130: 707-711.
21. Wheaton DH, Hoffman DR, Locke KG, Watkins RB, Birch DG. Biological safety assessment of docosahexaenoic acid supplementation in a randomized clinical trial for X-linked retinitis pigmentosa. Arch Ophthalmol. 2003;121:1269-1278.
22. Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment. Arch Ophthalmol. 2004;122: 1297-1305.
23. Hoffman DR, Hughbanks-Wheaton DK, Pearson NS, et al. Fouryear placebo-controlled trial of docosahexaenoic acid in Xlinked retinitis pigmentosa (DHAX trial): a randomized clinical trial. JAMA Ophthalmol. 2014;132:866-873.
24. 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. 2007;85:1457-1464.
25. Hoffman DR, Theuer RC, Castañeda YS, et al. Maturation of visual acuity is accelerated in breast-fed term infants fed baby food containing DHA-enriched egg yolk. J Nutrition. 2004; 134:2307-2313.
26. Lipillonne A, Groh-Wargo S, Gonzalez CHL, Uauy R. Lipid needs of preterm infants: updated recommendations. J Pediatr. 2013;162:S37-S47.
27. Lloyd-Still JD, Powers CA Hoffman DR, et al. Bioavailability and safety of a high dose of docosahexaenoic acid triacylglycerol of algal origin in cystic fibrosis patients; a randomized controlled study. Nutrition. 2006;22:36-46.
28. DeFelice C, Signorini C, Durand T, et al. Partial rescue of Rett syndrome by ω-3 polyunsaturated fatty acids (PUFAs) oil. Genes Nutr. 2012;7:447-458.
29. Paker AM, Sunness JS, Brereton NH, et al. Docosahexaenoic acid therapy in peroxisomal diseases. Neurology. 2010;75: 826-830.
30. Kyle DJ, Arterburn LM. Single cell oil sources of docosahexaenoic acid: clinical studies. In: Simopoulos AP, ed. The Return of Omega-3 Fatty Acids Into the Food Supply. I. Land-Based Animal Food Products and Their Health Effects. New York, NY: Basel Karger; 1998:116-131.
31. Hoffman DR, Birch EE, Birch DG, et al. Impact of early dietary intake and blood lipid composition of long-chain polyunsaturated fatty acids on later visual development. J Ped Gastroenterol Nutr. 2000;31:540-553.
32. Bui MH. Simple determination of retinol, α-tocopherol, and carotenoids (lutein, all-trans-lycopene, α-and β-carotenes) in human plasma by isocratic liquid chromatography. J Chromatogr B Biomed Appl. 1994;654:129-133.
33. Whitehead TP, Thorpe GHG, Maxwell SRJ. Enhanced chemiluminescent assay for antioxidant capacity in biological fluids. Anal Chim Acta. 1992;266:265-177.
34. Holvoet P, Mertens A, Verhamme P, et al. Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2001;21:844-848.
35. Russell-Smith NC, Flower RJ, Cardinal DC. Measuring platelet and leucocyte aggregation/adhesion responses in very small volumes of whole blood. J Pharmacol Meth. 1981;6:315-333.
36. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502.
37. Division of AIDS (DAIDS) Regulatory Support Center. Division of AIDS table for grading severity of adult and pediatric adverse events, version 1.0, December 2004; clarification August 2009. Available at: http://rsc.tech-res.com/document/ safetyandpharmacovigilance/table_for_grading_severity_of_ adult_pediatric_adverse_events.pdf. Accessed March 19, 2014.
38. Xin W, Wei W, Lin Z, et al. Fish oil and atrial fibrillation after cardiac surgery: a meta-analysis of randomized controlled trials. PLoS One. 2013;8:e72913.
39. Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM. n-3 Fatty acid dietary recommendation and sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr. 2006;83: 1526S-1535S.
40. National Health and Nutrition Examination Survey. Daily intake of nutrients by food source: 2007-2010. Available at: http://www.ers.usda.gov/data-products/food-consumption-andnutrient-intakes.aspx. Accessed July 22, 2014.
41. Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med. 2008;233:674-688.
42. Okuyama H, Kobayashi T, Watanabe S. Dietary fatty acids-the N-6/N-3 balance and chronic elderly diseases. Excess linoleic acid and relative N-3 deficiency syndrome seen in Japan. Prog Lipid Res. 1996;35:409-457.
43. Gomez Candela C, Bermejo Lopez LM, Loria Kohen V. Importance of a balanced omega 6/omega 3 ratio for the maintenance of health. Nutritional recommendations. Nutr Hosp. 2011;26:323-329.
44. Parkinson AJ, Cruz AL, Heyward WL, et al. Elevated concentrations of plasma ω-3 polyunsaturated fatty acids among Alaskan Eskimos. Am J Clin Nutr. 1994;59:384-388.
45. Rotstein NP, Politi LE, German OL, Girotti R. Protective effect of docosahexaenoic acid on oxidative stress-induced apoptosis of retina photoreceptors. Invest Ophthalmol Vis Sci. 2003;44: 2252-2259.
46. Yavin E, Brand A, Green P. Docosahexaenoic acid abundance in the brain: a biodevice to combat oxidative stress. Nutr Neurosci. 2002;5:149-157.
47. Signorini C, de Felice C, Leoncini S, et al. F4-neuroprostanes mediate neurological severity in Rett syndrome. Clinica Chimica Acta. 2011;412:1399-1406.
48. Kyle DJ. Production and use of a single cell oil which is highly enriched in docosahexaenoic acid. Lipid Technol. 1996;8:106.
49. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747-2757.
50. Harris WS. Expert opinion: omega-3 fatty acids and bleeding-cause for concern? Am J Cardiol. 2007;99:44c-46c.
51. Villani AM, Crotty M, Cleland LG, et al. Fish oil administration in older adults: is there potential for adverse events? A systematic review of the literature. BMC Geriatrics. 2013;13: 41.
52. DeCaterina R, Madonna R, Bertolotto A. Schmidt EB. n-3 Fatty acids in the treatment of diabetic patients. Diabetes Care. 2007;30:1012-1026.