Abstract
The effect of dietary docosahexaenoic acid (DHA) in the absence of eicosapentaenoic acid (EPA) has been studied infrequently in humans under controlled conditions. This 120-d study followed healthy, adult male volunteers who lived in the metabolic research unit (MRU) of the Western Human Nutrition Research Center for the entire study. The basal (low-DHA) diet consisted of natural foods (30 en% fat, 15 en% protein, and 55 en% carbohydrate), containing <50 mg/d of DHA, and met the recommended daily intake for all essential nutrients. The high-DHA (intervention) diet was similar except that 6 g/d of DHA in the form of a triglyceride containing 40% DHA replaced an equal amount of safflower oil in the basal diet. The subjects (ages 20 to 39) were within −10 to +20% of ideal body weight, nonsmoking, and not allowed alcohol in the MRU. Their exercise level was constant, and their body weights were maintained within 2% of entry level. They were initially fed the low-DHA diet for 30 d. On day 31, six subjects (intervention, group A) were placed on the high-DHA diet; the other four subjects (controls, group B) remained on the low-DHA diet. Platelet aggregation in platelet-rich plasma was determined using ADP, collagen, and arachidonic acid. No statistical differences could be detected between the amount of agonist required to produce 50% aggregation of platelet-rich plasma before and after the subjects consumed the high-DHA diet. The prothrombin time, activated partial thromboplastin time, and the antithrombin-III levels in the subjects were determined, and, again, there were no statistically significant differences in these three parameters when their values were compared before and after the subjects consumed the high-DHA diet. In addition, the in vivo bleeding times did not show any significant difference before and after the subjects consumed the high-DHA diet (9.4 ±3.1 min before and 8.0±3.4 min after). Platelets from the volunteers exhibited more than a threefold increase in their DHA content from 1.54±0.16 to 5.48±1.21 (wt%) during the DHA feeding period. The EPA content of the subjects’ platelets increased from 0.34±0.12 to 2.67±0.91 (wt%) during the high-DHA diet despite the absence of EPA in the subjects’ diets. The results from this study on blood clotting parameters and in vitro platelet aggregation suggest that adding 6 g/d of dietary DHA for 90 d to a typical Western diet containing less than 50 mg/d of DHA produces no observable physiological changes in blood coagulation, platelet function, or thrombotic tendencies in healthy, adult males.
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Abbreviations
- APTT:
-
activated partial thromboplastin time
- DHA:
-
docosahexaenoic acid
- EPA:
-
eicosapentaenoic acid
- MRU:
-
metabolic research unit
- PRP:
-
platelet-rich plasma
- PT:
-
prothrombin time
References
Bang, H.O., and Dyerberg, J. (1972) Plasma Lipids and Lipoproteins in Greenlandie West Coast Eskimos, Acta Med. Scand. 192, 85–94.
Bang, H.O., Dyerberg, J., and Sinclair, H.M. (1980) The Composition of Eskimo Food in Northwestern Greenland, Am. J. Clin. Nutr. 33, 2657–2661.
Bang, H.O., and Dyerberg, J. (1980) The Bleeding Tendency in Eskimos, Dan. Med. Bull. 27, 202–205.
Goodnight, S.H., Harris, W.S., and Connor, W.E. (1981) The Effects of Dietary ω3 Fatty Acids on Platelet Composition in Man, A Prospective, Controlled Study, Blood 58, 880–885.
Sanders, T.A.B., and Younger, K.M. (1981) The Effect of Dietary Supplements of ω3 Polyunsaturated Fatty Acids on the Fatty Acid Composition of Platelets and Plasma Choline Phosphoglycerides, Br. J. Med. 225 (Suppl. 1) 99–104.
Sanders, T.A.B., and Roshanai, F. (1983) The Influence of Different Types of ω3 Polyunsaturated Fatty Acids on Blood Lipids and Platelet Function in Healthy Volunteers, Clin. Sci. 64, 91–99.
Nestel, P.J., Connor, W.E., Reardon, M.F., Connor, S., Wong, S., and Boston, R. (1984) Suppression by Diets Rich in Fish Oil of Very Low Density Lipoprotein Production in Man, J. Clin. Invest. 74, 82–89.
Harris, W.S., Connor, W.E., and McMurry, M.P. (1983) The Comparative Reduction of Plasma Lipids and Lipoproteins by Dietary Polyunsaturated Fats, Salmon Oil Versus Vegetable Oils, Metabolism 32, 179–184.
Harris, W.S., Connor, W.E., Alam, N., and Illingworth, D.R. (1988) Reduction of Postprandial Triglyceridemia in Humans by Dietary n-3 Fatty Acids, J. Lipid Res. 29, 1451–1460.
Sanders, T.A.B., Naismith, D.J., Haines, A.P., and Vickers, M. (1981) Cod Liver Oil, Platelet Fatty Acids, and Bleeding Time, Lancet, i, 1189–1190.
Goodnight, S.H., Harris, W.S., Connor, W.E., and Illingsworth, D.R. (1982) Polyunsaturated Fatty Acids, Hyperlipidemia, and Thrombosis, Arteriosclerosis 2, 87–113.
Saynor, R., Verel, D., and Gillott, T. (1984) The Long-Term Effect of Dietary Supplementation with Fish Lipid Concentrates on Serum Lipids, Bleeding Time, Platelets, and Angina, Atherosclerosis 50, 3–10.
Berge, R.K., Willumsen, N., Skorve, J., Asiedu, D., Demoz, A., Rustan, A.C., and Froyland, L. (1993) The Triglyceride-Lowering Effect of Omega-3 Fatty Acids. Is It All in Eicosapentaenoic Acid? Program Abstracts. 1st International Congress of International Society for the Study of Fatty Acids and Lipids, “Fatty Acids and Lipids from Cell Biology to Human Disease”, Lugano, Switzerland, June 30–July 3, 1992, Fondazione Giovanni Lorenzini, Milan, Italy, p. 77.
Dyerberg, J., Bang, H.O., Stoffersen, E., Moncada, S., and Vane, J.R. (1978) Eicosapentaenoic Acid and the Prevention of Thrombosis and Atherosclerosis? Lancet ii, 117–119.
Hirai, A., Hamazaki, T., Terano, T., Nishikawa, T., Tamura, Y., and Kumagai, A. (1980) Eicosapentaenoic Acid and Platelet Function in Japanese, Lancet ii, 1132–1133.
Von Schacky, C., and Weber, P.C. (1985) Metabolism and Effects on Platelet Function of the Purified Eicosapentaenoic and Docosahexaenoic Acids in Humans, J. Clin. Invest. 76, 2446–2450.
Schlenk, H., Sand, D.M., and Gellerman, J.L. (1969) Retroconversion of Docosahexaenoic Acid in the Rat, Biochim. Biophys. Acta 187, 201–207.
Brossard, N., Corset, M., Pachiaudi, C., Riou, J.P., Tayot, J.L., and Lagarde, M. (1996) Retroconversion of [13C]22, 6n3 in Humans and Rats After a Single Dose of [13C]22, 6n3-Triacylgylcerols, Am. J. Clin. Nutr. 64, 577–586.
Sprecher, H. (1996) New Advances in Fatty Acid Biosynthesis, Nutr. 12 (Suppl. 1), S5–7.
Sprecher, H. (1996) Regulation of the Biosynthesis of 4, 7, 10, 13, 16, 19-Docosahexaenoic Acid, J. Biol. Chem. 271, 16020–16025.
The Composition of Foods (USDA Handbook 8) (1992) Consumer and Food Economic Institute, U.S. Department of Agrculture, Washington, D.C.
National Research Council, Recommended Dietary Allowances (1989), 10th edn. National Academy Press, Washington, D.C..
Nelson, G.J., Kelley, D.S., Emken, E.A., Phinney, S.D., Kyle, D., and Ferretti, A. (1997) A Human Arachidonic Acid Feeding Study Conducted in a Metabolic Research Unit, Rationale and Design, Lipids 32, 415–420.
Nelson, G.J., Schmidt, P.C., Bartolini, G., Kelley, D.S., and Kyle, D. (1997) The Effect of Dietary Arachidonic Acid on Platelet Function, Platelet Fatty Acid Composition and Blood Coagulation in Humans, Lipids 32, 421–425.
Kelley, D.S., Taylor, P.C., Nelson, G.J., Schmidt, P.C., Mackay, B.E., and Kyle, D. (1997) The Effect of Dietary Arachidonic Acid on Human Immune Response, Lipids 32, 441–448.
Houghie, C. (1983) in Hematology, 3rd edn., pp. 1662–1667, McGraw Hill, New York.
Nelson, G.J. (1972) Handling, Extraction and Storage of Blood Samples, in Blood Lipids and Lipoproteins (Nelson, G.J., ed.) pp. 3–24, Wiley-Interscience, New York.
Nelson, G.J. (1975) Quantitative Analytical Methods for Blood Lipids, in Analysis of Lipids and Lipoproteins (Perkins, E.G., ed.) pp. 1–22, American Oil Chemists’ Society, Champaign.
Nelson, G.J., Kelley, D.S., and Hunt, J.E. (1986) Effect of Nutritional Status on the Fatty Acid Composition of Rat Liver and Cultured Hepatocytes, Lipids 21, 454–459.
Nelson, G.J., Kelley, D.S., Schmidt, P.C., and Serrato, C.M. (1987) The Effect of Fat-Free, Saturated and Polyunsaturated Fat Diets on Rat Liver and Plasma, Lipids 22, 88–94.
Nelson, G.J., Kelley, D.S., Schmidt, P.C., and Serrato, C.M. (1987) The Influence of Dietary Fat on the Lipogenic Activity and Fatty Acid Composition of Rat White Adipose Tissue, Lipids 22, 334–338.
Kromhout, D., Bosschieter, E.B., and de Lezzene-Coulander, C. (1985) The Inverse Relationship Between Fish Comsumption and 20-Year Mortality from Coronary Heart Disease, New Engl. J. Med. 312, 1205–1209.
Norell, S.E., Ahlbom, A., Feychting, M., and Pedersen, N.L. (1986) Fish Consumption and Mortality from Coronary Heart Disease, Br. Med. J. 293, 426.
Siscovick, D.S., Raghunathan, T.E., King, I., Weinmann, E., Wicklund, K.G., Albright, J., Bovberg, V., Arbogast, P., Smith, H., Kushi, L.H., Cobb, L.A., Copass, M.K., Psaty, B.M., Memaitre, R., Retzlaff, B., Childs, M., and Knopp, R.H. (1995) Dietary Intake and Cell Membrane Levels of Long-Chain n-3 Polyunsaturated Fatty Acids and the Risk of Primary Cardiac Arrest, J. Am. Med. Assoc. 274, 1363–1367.
Nelson, G.J., Schmidt, P.C., and Corash, L. (1991) Effect of a Salmon Diet on Platelet Aggregation and the Fatty Acid Composition of Platelets, Plasma and Erythrocytes in Normal Adult Men, Lipids, 26, 87–96.
Conquer, J.A., and Holub, B.J. (1997) Dietary Docosahexaenoic Acid as a Source of Eicosapentaenoic Acid in Vegetarians and Omnivores, Lipids 32, 341–345.
Sanders, T.A.B., and Hinds, A. (1992) The Influence of Fish Oil High in Docosahexaenoic Acid on Plasma Lipoprotein and Vitamin E Concentrations and Haemostatic Function in Healthy Male Volunteers, Br. J. Nutr. 68, 163–173.
Nelson, G.J., Schmidt, P.C., Bartolim, G., Kelley, D.S., and Kyle, D. (1997) The Effect of Dietary Docosahexaenoic Acid on Plasma Lipoproteins and Tissue Fatty Acid Composition in Humans, Lipids 32, 1137–1146.
Jonnalagadda, S.S., Egan, S.K., Heimbach, J.T., Harris, S.S., and Kris-Etherton, P.M. (1995) Fatty Acid Consumption Patterns of Americans, 1987–1988, The USDA Nationwide Food Consumption Survey, Nutr. Res. 15, 1767–1781.
Ferretti, A., Nelson, G.J., Schmidt, P.C., Bartolini, G., Kelley, D.S., and Flanagan (1997) The Effect of Dietary Docosahexaenoic Acid on the Synthesis of Vasoactive Eicosanoids in vivo, Nutr. Biochem., in press.
Von Schacky, C., Fischer, S., and Weber, P.C. (1985) Long-Term Effects of Dietary Marine ω3 Fatty Acids upon Plasma and Cellular Lipids, Platelet Function and Eicosanoid Formation in Humans, J. Clin. Invest. 76, 1626–1631.
Thorngren, M., and Gustafson, A. (1981) Effect of 11-Week Increase in Dietary Eicosapentaenoic Acid on Bleeding Time, Lipids and Platelet Aggregation, Lancet ii, 1190–1193.
Saynor, R., and Verel, D. (1982) Eicosapentaenoic Acid, Bleeding Time, and Serum Lipids, Lancet ii, 272.
Saynor, R., Verel, D., and Gillott, T. (1984) The Long-Term Effect of Dietary Supplementation with Fish Lipid Concentrate on Serum Lipids, Bleeding Time, Platelets and Angina, Atherosclerosis 50, 3–10.
Van Houwelingen, A.C., Hornstra, G., Kromhout, D., and de Lezenne Coulander, C. (1989) Habitual Fish Consumption, Fatty Acids of Serum Phospholipids and Platelet Function, Atherosclerosis 75, 157–165.
Harris, W.S., Silveira, S., and Dujovne, C.A. (1990) The Combined Effect of n-3 Fatty Acids and Aspirin on Hemostatic Parameters in Man, Thromb. Res. 57, 517–526.
Buchanan, G.R., Uauy, R., Holtkamp, C., and Nickell, M. (1990) Bleeding Time (BT) Measurements in Healthy Very Low Birth Weight Neonates (VLBWN) between 10 and 120 Days of Age, Ped. Res. 27, (Suppl.), 262A.
Emken, E.A., Adlof, R.O., Rohwedder, W.K., and Gulley, R.M. (1992) Dietary Linoleic Acid Influence Desaturation and Acylation of Deuterium-Labeled Linoleic and Linolenic Acids in Young Adult Males, Biochim. Biophys. Acta 1212, 277–288.
Cunnane, S.C. (1995) Metabolism and Function of α-Linolenic Acid in Humans, in Flaxseed in Human Nutrition, AOCS Press, Champaign, pp. 99–127.
Steinberg, D. (1991) Antioxidants and Atherosclerosis, Circulation 84, 1420–1425.
Witzum, J.L. (1994) The Oxidation Hypothesis of Atherosclerosis, Lancet 344, 793–795.
McCord, J.M. (1985) Oxygen-Derived Free Radicals in Post-ischemic Tissue Injury, N. Engl. J. Med. 312, 159–163.
Halliwell, B., and Gutteridge, J.M. (1986) Oxygen Free Radicals and Iron in Biology and Medicine, Some Problems and Concepts, Arch. Biochem. Biophys. 246, 501–514.
Harman, D. (1994) Aging, Prospects for Further Increases in the Functional Life Span, Age 17, 119–146.
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Nelson, G.J., Schmidt, P.S., Bartolini, G.L. et al. The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids 32, 1129–1136 (1997). https://doi.org/10.1007/s11745-997-0145-6
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DOI: https://doi.org/10.1007/s11745-997-0145-6