Toxicology and safety of DHA

Prostaglandins Leukotrienes and Essential Fatty Acids

Volumn 81, Issue 2-3, 2009, Pages 125-132

  Lien, Eric L ^a  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; DOCOSAHEXAENOIC ACID; GLUCOSE; LIPID; PLACEBO;

ARTICLE; BLEEDING TIME; BREAST MILK; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; FISH; FOOD INTAKE; FOOD SAFETY; GLYCEMIC CONTROL; HUMAN; HYPERLIPIDEMIA; IMMUNE RESPONSE; LIPID BLOOD LEVEL; MEDICAL LITERATURE; OXIDATION; PRIORITY JOURNAL; REPRODUCTIVE TOXICITY; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION; TOXICOLOGY;

ADULT; ANIMALS; BLOOD GLUCOSE; BLOOD PLATELETS; CHOLESTEROL; CLINICAL TRIALS, PHASE I AS TOPIC; DOCOSAHEXAENOIC ACIDS; FISH OILS; HUMANS; IMMUNITY; INFANT; LIPID METABOLISM; MILK, HUMAN;

ANIMALIA; RATTUS;

EID: 69549116606     PISSN: 09523278     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.plefa.2009.05.004     Document Type: Article

References (81)

1. Mori T.A., and Woodman R.J. The independent effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in humans. Curr. Opin. Clin. Nutr. Metab. Care 9 (2006) 95-104
2. Boswell K., Koskelo E.K., Carl L., et al. Preclinical evaluation of single-cell oils that are highly enriched with arachidonic acid and docosahexaenoic acid. Food Chem. Toxicol. 34 (1996) 585-593
3. Wibert G.J., Burns R.A., Diersen-Schade D.A., and Kelly C.M. Evaluation of single cell sources of docosahexaenoic acid and arachidonic acid: a 4-week oral safety study in rats. Food Chem. Toxicol. 35 (1997) 967-974
4. Hammond B.G., Mayhew D.A., Naylor M.W., Ruecker F.A., Mast R.W., and Sander W.J. Safety assessment of DHA-rich microalgae from Schizochytrium sp. I. Subchronic rat feeding study. Regul. Toxicol. Pharmacol. 33 (2001) 192-204
5. Kroes R., Schaefer E.J., Squire R.A., and Williams G.M. A review of the safety of DHA45-oil. Food Chem. Toxicol. 41 (2003) 1433-1446
6. Blum R., Kiy T., Tanaka S., Wong A.W., and Roberts A. Genotoxicity and subchronic toxicity studies of DHA-rich oil in rats. Regul. Toxicol. Pharmacol. 49 (2007) 271-284
7. Arterburn L.M., Boswell K.D., Koskelo E., Kassner S.L., Kelly C., and Kyle D.J. A combined subchronic (90-day) toxicity and neurotoxicity study of a single-cell source of docosahexaenoic acid triglyceride (DHASCO oil). Food Chem. Toxicol. 38 (2000) 35-49
8. Burns R.A., Wibert G.J., Diersen-Schade D.A., and Kelly C.M. Evaluation of single-cell sources of docosahexaenoic acid and arachidonic acid: 3-month rat oral safety study with an in utero phase. Food Chem. Toxicol. 37 (1999) 23-36
9. Hammond B.G., Mayhew D.A., Robinson K., Mast R.W., and Sander W.J. Safety assessment of DHA-rich microalgae from Schizochytrium sp. III. Single-generation rat reproduction study. Regul. Toxicol. Pharmacol. 33 (2001) 356-362
10. Blum R., Kiy T., Waalkens-Berendsen I., Wong A.W., and Roberts A. One-generation reproductive toxicity study of DHA-rich oil in rats. Regul. Toxicol. Pharmacol. 49 (2007) 260-270
11. Arterburn L.M., Boswell K.D., Henwood S.M., and Kyle D.J. A developmental safety study in rats using DHA- and ARA-rich single-cell oils. Food Chem. Toxicol. 38 (2000) 763-771
12. Hammond B.G., Mayhew D.A., Holson J.F., Nemec M.D., Mast R.W., and Sander W.J. Safety assessment of DHA-rich microalgae from Schizochytrium sp. II. Developmental toxicology evaluation in rats and rabbits. Regul. Toxicol. Pharmacol. 33 (2001) 205-217
13. Borzelleca J.F. Macronutrient substitutes: safety evaluation. Regul. Toxicol. Pharmacol. 16 (1992) 253-264
14. Yaqoob P., Sherrington E.J., Jeffery N.M., et al. Comparison of the effects of a range of dietary lipids upon serum and tissue lipid composition in the rat. Int. J. Biochem. Cell Biol. 27 (1995) 297-310
15. Rabbani P.I., Sheikh N.M., Chirtel S.J., Jackson R., and Ruffin G. Effects of long-term consumption of high doses of fish oil concentrates on clinical parameters in male and female rats. J. Nutr. Sci. Vitaminol. (Tokyo) 45 (1999) 553-565
16. Tamura M., and Suzuki H. Effect of docosahexaenoic acid and sardine oil diets on the ultrastructure of hepatocytes in adult mice. J. Nutr. Sci. Vitaminol. (Tokyo) 41 (1995) 477-483
17. Huang M.C., Chao A., Kirwan R., et al. Negligible changes in piglet serum clinical indicators or organ weights due to dietary single-cell long-chain polyunsaturated oils. Food Chem. Toxicol. 40 (2002) 453-460
18. Abril R., Garret J., Zeller S.G., Sander W.J., and W M.R. Safety assessment of DHA-rich microalgae from Schizochytrium sp. Part V. Target animal safety/toxicity study in growing swine. Regul. Toxicol. Pharmacol. 37 (2003) 73-82
19. Arterburn L.M., Boswell K.D., Lawlor T., Cifone M.A., Murli H., and Kyle D.J. In vitro genotoxicity testing of ARASCO and DHASCO oils. Food Chem. Toxicol. 38 (2000) 971-976
20. Hammond B.G., Mayhew D.A., Kier L.D., Mast R.W., and Sander W.J. Safety assessment of DHA-rich microalgae from Schizochytrium sp. IV. Mutagenicity studies. Regul. Toxicol. Pharmacol. 35 (2002) 255-265
21. Gibson R.A., Neumann M.A., and Makrides M. Effect of increasing breast milk docosahexaenoic acid on plasma and erythrocyte phospholipid fatty acids and neural indices of exclusively breast fed infants. Eur. J. Clin. Nutr. 51 (1997) 578-584
22. Yuhas R., Pramuk K., and Lien E.L. Human milk fatty acid composition from nine countries varies most in DHA. Lipids 41 (2006) 851-858
23. Brenna J.T., Varamini B., Jensen R.G., Diersen-Schade D.A., Boettcher J.A., and Arterburn L.M. Docosahexaenoic and arachidonic acid concentrations in human breast milk worldwide. Am. J. Clin. Nutr. 85 (2007) 1457-1464
24. Makrides M., Gibson R.A., Udell T., and Ried K. Supplementation of infant formula with long-chain polyunsaturated fatty acids does not influence the growth of term infants. Am. J. Clin. Nutr. 81 (2005) 1094-1101
25. Clandinin M.T., Van Aerde J.E., Parrott A., Field C.J., Euler A.R., and Lien E.L. Assessment of the efficacious dose of arachidonic and docosahexaenoic acids in preterm infant formulas: fatty acid composition of erythrocyte membrane lipids. Pediatr. Res. 42 (1997) 819-825
26. Lauritzen L., Hoppe C., Straarup E.M., and Michaelsen K.F. Maternal fish oil supplementation in lactation and growth during the first 2.5 years of life. Pediatr. Res. 58 (2005) 235-242
27. Helland I.B., Saugstad O.D., Smith L., et al. Similar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Pediatrics 108 (2001) E82
28. Kent J.C., Mitoulas L.R., Cregan M.D., Ramsay D.T., Doherty D.A., and Hartmann P.E. Volume and frequency of breastfeedings and fat content of breast milk throughout the day. Pediatrics 117 (2006) e387-e395
29. European Union Commission, Commission directive 2006/141/EC on infant formulae and follow-on formulae and amending Directive 1999/21/EC, Official Journal of the European Union 2006, Internet: 〈http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2006:40 1:0001:0033:EN:PDF:1-33〉.
30. Koletzko B., Baker S., Cleghorn G., et al. Global standard for the composition of infant formula: recommendations of an ESPGHAN coordinated international expert group. J. Pediatr. Gastroenterol. Nutr. 41 (2005) 584-599
31. Koletzko B., Lien E., Agostoni C., et al. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J. Perinat. Med. 36 (2008) 5-14
32. Mori T.A., Beilin L.J., Burke V., Morris J., and Ritchie J. Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease. Arterioscler. Thromb. Vasc. Biol. 17 (1997) 279-286
33. Bays H.E. Safety considerations with omega-3 fatty acid therapy. Am. J. Cardiol. 99 (2007) 35C-43C
34. Conquer J.A., and Holub B.J. Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects. J. Nutr. 126 (1996) 3032-3039
35. Nelson G.J., Schmidt P.S., Bartolini G.L., Kelley D.S., and Kyle D. The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids 32 (1997) 1129-1136
36. Park Y., and Harris W. EPA, but not DHA, decreases mean platelet volume in normal subjects. Lipids 37 (2002) 941-946
37. Agren J.J., Vaisanen S., Hanninen O., Muller A.D., and Hornstra G. Hemostatic factors and platelet aggregation after a fish-enriched diet or fish oil or docosahexaenoic acid supplementation. Prostaglandins Leukot. Essent. Fatty Acids 57 (1997) 419-421
38. Sanders T.A., Gleason K., Griffin B., and Miller G.J. Influence of an algal triacylglycerol containing docosahexaenoic acid (22:6n-3) and docosapentaenoic acid (22:5n-6) on cardiovascular risk factors in healthy men and women. Br. J. Nutr. 95 (2006) 525-531
39. Wheaton D.H., Hoffman D.R., Locke K.G., Watkins R.B., and Birch D.G. Biological safety assessment of docosahexaenoic acid supplementation in a randomized clinical trial for X-linked retinitis pigmentosa. Arch. Ophthalmol. 121 (2003) 1269-1278
40. Woodman R.J., Mori T.A., Burke V., et al. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Atherosclerosis 166 (2003) 85-93
41. Hirai A., Terano T., Makuta H., et al. Effect of oral administration of highly purified eicosapentaenoic acid and docosahexaenoic acid on platelet function and serum lipids in hyperlipidemic patients. Adv. Prostaglandin Thromboxane Leukot. Res. 19 (1989) 627-630
42. von Schacky C., and Weber P.C. Metabolism and effects on platelet function of the purified eicosapentaenoic and docosahexaenoic acids in humans. J. Clin. Invest. 76 (1985) 2446-2450
43. Eritsland J., Arnesen H., Seljeflot I., and Kierulf P. Long-term effects of n-3 polyunsaturated fatty acids on haemostatic variables and bleeding episodes in patients with coronary artery disease. Blood Coagul. Fibrinolysis 6 (1995) 17-22
44. Harris W.S., Silveira S., and Dujovne C.A. The combined effects of n-3 fatty acids and aspirin on hemostatic parameters in man. Thromb. Res. 57 (1990) 517-526
45. Mueller B.A., Talbert R.L., Tegeler C.H., and Prihoda T.J. The bleeding time effects of a single dose of aspirin in subjects receiving omega-3 fatty acid dietary supplementation. J. Clin. Pharmacol. 31 (1991) 185-190
46. Harris W.S. n-3 fatty acids and lipoproteins: comparison of results from human and animal studies. Lipids 31 (1996) 243-252
47. Ryan A.S., Keske M.A., Hoffman J.P., and Nelson E.B. Clinical overview of algal-docosahexaenoic acid (DHA): effects on triglyceride levels and other cardiovascular risk factors. Am. J. Ther. 16 (2009) 183-192
48. Agren J.J., Hanninen O., Julkunen A., et al. Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels. Eur. J. Clin. Nutr. 50 (1996) 765-771
49. Maki K.C., Van Elswyk M.E., McCarthy D., et al. Lipid responses to a dietary docosahexaenoic acid supplement in men and women with below average levels of high density lipoprotein cholesterol. J. Am. Coll. Nutr. 24 (2005) 189-199
50. Theobald H.E., Chowienczyk P.J., Whittall R., Humphries S.E., and Sanders T.A. LDL cholesterol-raising effect of low-dose docosahexaenoic acid in middle-aged men and women. Am. J. Clin. Nutr. 79 (2004) 558-563
51. Nelson G.J., Schmidt P.C., Bartolini G.L., Kelley D.S., and Kyle D. The effect of dietary docosahexaenoic acid on plasma lipoproteins and tissue fatty acid composition in humans. Lipids 32 (1997) 1137-1146
52. Grimsgaard S., Bonaa K.H., Hansen J.B., and Nordoy A. Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids. Am. J. Clin. Nutr. 66 (1997) 649-659
53. Rambjor G., Walen A., Windsor S., and Harris W. Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans. Lipids 31 (1996) S45-S49
54. Stark K.D., and Holub B.J. Differential eicosapentaenoic acid elevations and altered cardiovascular disease risk factor responses after supplementation with docosahexaenoic acid in postmenopausal women receiving and not receiving hormone replacement therapy. Am. J. Clin. Nutr. 79 (2004) 765-773
55. Geppert J., Kraft V., Demmelmair H., and Koletzko B. Microalgal docosahexaenoic acid decreases plasma triacylglycerol in normolipidaemic vegetarians: a randomised trial. Br. J. Nutr. 95 (2006) 779-786
56. Wu W.H., Lu S.C., Wang T.F., Jou H.J., and Wang T.A. Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women. Eur. J. Clin. Nutr. 60 (2006) 386-392
57. Mori T.A., Burke V., Puddey I.B., et al. Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am. J. Clin. Nutr. 71 (2000) 1085-1094
58. Kelley D.S., Siegel D., Vemuri M., and Mackey B.E. Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men. Am. J. Clin. Nutr. 86 (2007) 324-333
59. Davidson M.H., Maki K.C., Kalkowski J., Schaefer E.J., Torri S.A., and Drennan K.B. Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial. J. Am. Coll. Nutr. 16 (1997) 236-243
60. Engler M.M., Engler M.B., Malloy M., et al. Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study. Int. J. Clin. Pharmacol. Ther. 42 (2004) 672-679
61. Nestel P., Shige H., Pomeroy S., Cehun M., Abbey M., and Raederstorff D. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am. J. Clin. Nutr. 76 (2002) 326-330
62. Woodman R.J., Mori T.A., Burke V., Puddey I.B., Watts G.F., and Beilin L.J. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am. J. Clin. Nutr. 76 (2002) 1007-1015
63. Woodman R.J., Mori T.A., Burke V., et al. Docosahexaenoic acid but not eicosapentaenoic acid increases LDL particle size in treated hypertensive type 2 diabetic patients. Diabetes Care 26 (2003) 253
64. Kelley D.S., Siegel D., Vemuri M., Chung G.H., and Mackey B.E. Docosahexaenoic acid supplementation decreases remnant-like particle-cholesterol and increases the (n-3) index in hypertriglyceridemic men. J. Nutr. 138 (2008) 30-35
65. Rosenson R.S., Otvos J.D., and Freedman D.S. Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I) trial. Am. J. Cardiol. 90 (2002) 89-94
66. Wilson P.W. Relation of high-density lipoprotein subfractions and apolipoprotein E isoforms to coronary disease. Clin. Chem. 41 (1995) 165-169
67. Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J. Biol. Chem. 272 (1997) 20963-20966
68. Cosgrove J.P., Church D.F., and Pryor W.A. The kinetics of the autooxidation of polyunsaturated fatty acids. Lipids 22 (1987) 299-304
69. Mori T.A., Woodman R.J., Burke V., Puddey I.B., Croft K.D., and Beilin L.J. Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Free Radical Biol. Med. 35 (2003) 772-781
70. Thies F., Nebe-von-Caron G., Powell J.R., Yaqoob P., Newsholme E.A., and Calder P.C. Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y. Am. J. Clin. Nutr. 73 (2001) 539-548
71. Hartweg J., Perera R., Montori V., Dinneen S., Neil H.A., and Farmer A. Omega-3 polyunsaturated fatty acids (PUFA) for type 2 diabetes mellitus. Cochrane Database Syst. Rev. CD003205 (2008)
72. Friedberg C.E., Janssen M.J., Heine R.J., and Grobbee D.E. Fish oil and glycemic control in diabetes. a meta-analysis. Diabetes Care 21 (1998) 494-500
73. Food and Nutrition Board. IoMDrife, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients) (2002), National Academy Press, Washington, DC. http://www.nap (Internet: 〈http://www.nap〉. (Ed.), Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients): National Academy Press, Washington, DC, 2005)
74. Albers R., Antoine J.M., Bourdet-Sicard R., et al. Markers to measure immunomodulation in human nutrition intervention studies. Br. J. Nutr. 94 (2005) 452-481
75. Fritsche K. Fatty acids as modulators of the immune response. Annu. Rev. Nutr. 26 (2006) 45-73
76. Kelley D.S., Taylor P.C., Nelson G.J., and Mackey B.E. Dietary docosahexaenoic acid and immunocompetence in young healthy men. Lipids 33 (1998) 559-566
77. Kelley D.S., Taylor P.C., Nelson G.J., et al. Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 34 (1999) 317-324
78. Thies F., Nebe-von-Caron G., Powell J.R., Yaqoob P., Newsholme E.A., and Calder P.C. Dietary supplementation with gamma-linolenic acid or fish oil decreases T lymphocyte proliferation in healthy older humans. J. Nutr. 131 (2001) 1918-1927
79. Schwellenbach L.J., Olson K.L., McConnell K.J., Stolcpart R.S., Nash J.D., and Merenich J.A. The triglyceride-lowering effects of a modest dose of docosahexaenoic acid alone versus in combination with low dose eicosapentaenoic acid in patients with coronary artery disease and elevated triglycerides. J. Am. Coll. Nutr. 25 (2006) 480-485
80. Food and Drug Administration DoHaHS. Substances affirmed as generally recognized as safe: menhaden oil. Fed. Regist. 62 (1997) (FR 30751(6))
81. Munro I.C. Setting tolerable upper intake levels for nutrients. J. Nutr. 136 (2006) 490S-492S