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Nutra Report Vegetarian Docosahexaenoic acid (DHA) and Triglyceride Reduction GENERAL INFORMATION: Active component[s]: DHA. Source material: Marine algae. Dosage route: Oral. Directions of use and/or Duration of use: A clinical literature search did not yield specific results pertaining to directions of use and/or duration of use. Target Population: Infants, children, adults. Risk Information: The following have been reported with DHA intake: gastrointestinal upset, belching, loose stools, dry mouth, fishy aftertaste, decreased libido, dizziness, headache, insomnia, anxiety, increased cholesterol, decreased blood glucose. Patients with allergy to fish, fish oil or marine products should use caution. Based on potential interactions, consult a health care practitioner prior to use if you are pregnant or breastfeeding, or if you are taking blood thinners, lipid lowering agents, blood pressure lowering agents and/or blood sugar lowering agents. HUMAN HEALTH INDICATIONS: Recommended Use or Purpose General Helps to lower levels of blood triglycerides. Adults 0.7-3 g per day (Conquer, 1996; Kelley, 2007; Maki, 2005; Neff, 2010; Stark, 2004; Theobald, 2004) DHA Docosahexaenoic acid [DHA; 22:6n-3] is a long-chain polyunsaturated omega-3 fatty acid. DHA has 22 carbons with six double bonds and is in the omega-3 family of polyunsaturated fatty acids. The omega-3 fatty acid family includes the essential fatty acid alpha-linolenic acid [18:3n-3], found in plant foods such as flax, soy and walnuts, as well as eicosapentaenoic acid [EPA] [20:5n-3], found in fish and marine oils. All fatty acids in this family have their first double bond three carbons from the methyl end. In North America, the recommended intake of alpha-linolenic acid is 1.1 g [females] and 1.6 g [males] (Food and © Nutrasource Diagnostics Inc. Page 1 120 Research Lane, Suite 203, Guelph, ON, N1G 0B4 CANADA T: 519.341.3367 | F: 888.531.3466 | E: [email protected] www.nutrasource.ca Nutra Report Nutrition Board, 2005). There is no specific recommendation for DHA, although The American Heart Association recommends 1000 mg EPA+DHA daily for individuals with cardiovascular disease [or 2-4 g daily for individuals with high levels of blood triglycerides] (Kris-Etherton, 2002) and general recommendations include increasing intake of pre-formed long-chain EPA plus DHA and/or intakes of EPA plus DHA at levels of approximately 10% of the total intake of omega-3 fatty acids (Food and Nutrition Board, 2005). Although DHA can be synthesized from alpha-linolenic acid, the conversion is low (Burdge, 2002a; Burdge, 2002b; Innis, 1994; Plourde, 2007). DHA is commonly found in fish and other marine foods, and is an important fatty acid in fish oil and omega-3 fatty acid supplements. However, vegetarian-source DHA can be isolated from marine algae. It has been shown that DHA from algal oil is bioequivalent to cooked salmon in providing DHA to plasma and red blood cells (Arterburn et al., 2008). Alternate sources of DHA are of interest to non-fish eaters [including vegetarians], populations in which increased EPA may be of concern [e.g. infants] and for those concerned with the potential decrease of fish stocks (Kyle, 1998; Sargent, 1999). Omega-3 fatty acids, including vegetarian DHA, have been incorporated or enriched in various foods and beverages in an effort to increase intake of these fatty acids (Arterburn et al., 2007; Lewis, 2000; Riediger, 2009). Many infant formulas on the market in North America contain 0.3-0.35% of fat as DHA, usually sourced from vegetarian algal oil. In the body, DHA is found in all cell membranes and plasma phospholipids, but is highest in the fluid membranes in the brain, retina and spermatozoa. Health benefits possibly associated with DHA include cardiovascular health, due to its presence in fish oil, as well as cognitive and neuropsychiatric health and male infertility, due to its presence in cell membranes in the body. DHA AND TRIGLYCERIDE LOWERING Various studies have investigated the effect of DHA on cardiovascular disease risk factors. Most studies were conducted in healthy individuals although some have studied hypertriglyceridemic patients. Algal DHA has been shown to reduce triglyceride levels in many studies (Conquer, 1996; Davidson, 1997; Geppert, 2006; Kelley, 2007; Maki, 2005; Neff, 2010; Stark, 2004). As commonly observed in fish oil studies, DHA may also increase total and LDL cholesterol (Davidson, 1997; Geppert, 2006; Kelley, 2007; Maki, 2005), however, this appears to be associated with a decrease in small dense LDL cholesterol [i.e., the more atherogenic sub-type of cholesterol] and an increase in the large, buoyant, less atherogenic subtype (Engler, 2005; Kelley, 2007; Maki, 2005; Neff, 2010; Theobald, 2004;) and an increase in HDL cholesterol (Conquer, 1996; Davidson, 1997; Geppert, 2006; Stark, 2004). Other risk factors that may be benefited by algal DHA intake include decreased heart rate (Stark, 2004). The mechanism by which DHA decreases triglyceride levels is not clear. Possibilities include increased lipoprotein lipase activity (Park, 2004; Park, 2003). © Nutrasource Diagnostics Inc. Page 2 120 Research Lane, Suite 203, Guelph, ON, N1G 0B4 CANADA T: 519.341.3367 | F: 888.531.3466 | E: [email protected] www.nutrasource.ca Nutra Report DHA AND COGNITIVE HEALTH It is well known that DHA undergoes rapid accretion in the brain during prenatal development and during the first postnatal year. Early studies in breastfed infants, a source of dietary DHA, found higher levels of DHA in the infant brain vs. formula fed [lacking DHA] infants. Given the importance of DHA for the developing infant, especially the premature infant, most, recent studies have investigated the effect of DHA in combination with arachidonic acid [AA, 20:4n-6]. Based on many reviews in the field, most authors are in support of addition of both DHA and AA to term and pre-term formula (Cheatham, 2006; Fleith, 2005; Heird, 2005; Wright, 2006). Based on a meta-analysis of 12 studies, DHA-supplemented formula increased visual acuity at four months in term infants (SanGiovanni, 2000). Fortification of formula with DHA also prevents the decline of blood DHA levels observed in infants fed formula lacking DHA (Clandinin, 1997; Smit, 2000). DHA has also been studied for its cognitive benefits in healthy individuals and in individuals with dementia. DHA is thought to play a role in amyloid-beta peptide signalling in Alzheimer's disease (Lukiw, 2009), perhaps following conversion to its metabolite neuroprotectin D1 (Lukiw, 2008). In persons with Alzheimer’s disease, levels of neuroprotectin D1 may be decreased in the hippocampal region (Lukiw, 2005). Although based on epidemiological study, DHA intakes are inversely correlated with dementia risk (Johnson, 2006; Schaefer, 2006) and patients with Alzheimer’s disease have been shown to have decreased DHA status (Conquer, 2000a), the effect of algal DHA in dementia or Alzheimer’s disease has not been studied extensively. The source of DHA was not indicated in a study by Terano in which mini mental state examination [MMSE] scores increased following six months of DHA use (Terano, 1999). In a study using algal DHA, however, a lack of benefit was observed in Alzheimer’s patients (Quinn, 2010). SAFETY AND TOXICITY: DHA has been safely administered in human clinical research at dosages of up to 4 g daily for up to 15 weeks in adults. DHA is commonly added to marketed infant formulas at levels of approximately 0.3% fat. Common adverse effects include increased total cholesterol or LDL cholesterol, suggesting caution in patients with increased cholesterol levels (Davidson, 1997; Kelley, 2007; Geppert, 2006; Maki, 2005). Also, some evidence suggests an association of omega-3 intake [including DHA] with increased levels of fasting glucose, suggesting caution in patients with diabetes or those using hypoglycemic agents (Woodman, 2002). Based on clinical trials, adverse effects to DHA supplementation are generally mild. Examples include gastrointestinal upset [gas, bloating], belching, loose stools, dry mouth, and fishy aftertaste (Kelley, 2007; Marangell, 2003; Mischoulon, 2008). In patients with depression, adverse effects include decreased libido, dizziness, headache, insomnia and anxiety (Marangell, 2003; Mischoulon, 2008). © Nutrasource Diagnostics Inc. Page 3 120 Research Lane, Suite 203, Guelph, ON, N1G 0B4 CANADA T: 519.341.3367 | F: 888.531.3466 | E: [email protected] www.nutrasource.ca Nutra Report Animal and/or in vitro/ex vivo toxicity literature indicates a lack of safety concern regarding algal DHA (Blum, 2007a; Blum, 2007b; Hadley, 2010; Hammond, 2002; Kroes, 2003; Lein, 2009). The no-adverseeffect level [NOAEL] in rats for DHASCO oil [algal DHA] was the highest dose level [1.25 g per kg per day] (Arterburn, 2000). CAUTIONS, WARNINGS, CONTRAINDICATIONS AND INTERACTIONS Consult a health care practitioner prior to use if you have a pre-existing medical condition, are taking prescription medication, or are pregnant or breastfeeding. For additional information from the clinical literature regarding interactions, please refer to the following tables: DRUG INTERACTION WITH DHA Anticoagulants and Antiplatelets Blood Pressure Lowering Agents DHA ethyl ester resulted in a decrease in collagen-induced platelet aggregation and thromboxane A2 levels (Woodman, 2003). However, DHA had no effect on blood coagulation, platelet function, or thrombotic tendencies (Nelson, 1997). Thus, DHA may interfere with medications [heparin, warfarin or clopidogrel] or natural health products [Ginkgo biloba, saw palmetto or garlic] that increase the risk of bleeding. DHA-rich oils have been shown to lower blood pressure (Kimura, 2002; Mori, 1999). Effect of algal DHA is unclear. Blood Sugar Omega-3 fatty acids may increase blood sugar and potentially exert additive effects with medications, herbs and dietary supplements that have hypoglycaemic properties. The effect of algal DHA is unclear. Carbamazepine Patients on carbamazepine had lower DHA levels (Yuen, 2008). Hormones DHA levels were higher in patients not using oral contraceptives (Giltay, 2004) and in those using hormone replacements (Stark, 2004). Lipid-Lowering Drugs DHA has been shown to decrease levels of blood triglycerides and increase levels of total, LDL and HDL cholesterol (Conquer, 1996; Kelley, 2007; Maki, 2005, Stark, 2004). © Nutrasource Diagnostics Inc. Page 4 120 Research Lane, Suite 203, Guelph, ON, N1G 0B4 CANADA T: 519.341.3367 | F: 888.531.3466 | E: [email protected] www.nutrasource.ca Nutra Report NATURAL HEALTH PRODUCTS INTERACTION WITH DHA [NHP] SUBSTANCES Eicosapentaenoic Acid [EPA] Supplementation with EPA alone [in the absence of DHA] can potentially result in a reduction in red blood cell DHA (Higashihara, 2008). Vitamin E DHA supplementation for four years may decrease vitamin E levels (Wheaton, 2003). FOOD INTERACTION WITH DHA Medium Chain Triglyceride Formula Use of an infant formula containing high levels of medium chain triglycerides may decrease plasma DHA (Carnielli, 1996). YOU MIGHT ALSO BY INTERESTED IN OUR REPORTS ON: Lipid Lowering: Acacia Gum and Blood Lipids Psyllium and Blood Lipids Guar gum and Blood lipids Coenzyme Q10 and Cholesterol Ginseng and Cardiovascular Health Fish Oil and Cardiovascular Disease Borage Oil and Cardiovascular Health © Nutrasource Diagnostics Inc. Page 5 120 Research Lane, Suite 203, Guelph, ON, N1G 0B4 CANADA T: 519.341.3367 | F: 888.531.3466 | E: [email protected] www.nutrasource.ca Nutra Report REFERENCES Arterburn, L.M., Oken, H.A., Bailey, Hall, E., Hamersley, J., Kuratko, C.N., and Hoffman, J.P. 2008. Algal-oil capsules and cooked salmon: nutritionally equivalent sources of docosahexaenoic acid. Journal of American Dietetic Association; 108(7): 1204-9. Arterburn, L.M., Oken, H.A., Hoffman, J.P., Bailey-Hall, E., Chung, G., Rom, D., Hamersley, J., and McCarthy, D. 2007. Bioequivalence of Docosahexaenoic acid from different algal oils in capsules and in a DHA-fortified food. Lipids; 42(11):1011-24 Arterburn, L.M., Boswell, K.D., Koskelo, E., Kassner, S.L., Kelly, C., and Kyle, D.J. 2000. A combined subchronic (90day) toxicity and neurotoxicity study of a single-cell source of docosahexaenoic acid triglyceride (DHASCO oil). Food and Chemical Toxicology; 38(1):35-49. Blum, R., Kiy, T., Waalkens-Berendsen, I., Wong, A.W., and Roberts, A. 2007a. One-generation reproductive toxicity study of DHA-rich oil in rats. Regulatory Toxicology and Pharmacology; 49(3):260-70. Blum, R., Kiy, T., Tanaka, S., Wong, A.W., and Roberts, A. 2007b. Genotoxicity and subchronic toxicity studies of DHA-rich oil in rats. Regulatory Toxicology and Pharmacology; 49(3):271-84. Burdge, G.C., Jones, A.E., Wootton, S.A. 2002a. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men*. British Journal of Nutrition; 88(4):355-63. Burdge, G.C and Wootton SA. 2002b. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. British Journal of Nutrition; 88(4):411-20. Carnielli, V.P., Rossi, K., Badon, T., Gregori, B., Verlato, G., Orzali, A., and Zacchello, F. 1996. Medium-chain triacylglycerols in formulas for preterm infants: effect on plasma lipids, circulating concentrations of medium-chain fatty acids, and essential fatty acids. American Journal of Clinical Nutrition; 64(2):152-8. Cheatham, C.L., Colombo, J., and Carlson, S.E. 2006. N-3 fatty acids and cognitive and visual acuity development: methodologic and conceptual considerations. America Journal of Clinical Nutrition; 83(6 Suppl):1458S-1466S. Clandinin, M.T., Van Aerde, J.E., Parrott, A., Field, C.J., Euler, A.R., and Lien, E. 1999. Assessment of feeding different amounts of arachidonic and docosahexaenoic acids in preterm infant formulas on the fatty acid content of lipoprotein lipids. Acta Paediatrica; 88(8):890-6. Clandinin, M.T., Van Aerde, J.E., Parrott, A., Field, C.J., Euler, A.R., and Lien, E.L. 1997. Assessment of the efficacious dose of arachidonic and docosahexaenoic acids in preterm infant formulas: fatty acid composition of erythrocyte membrane lipids. Paediatric Research; 42(6):819-25. Conquer, J.A., Tierney, M.C., Zecevic, J., Bettger, W.J., and Fisher, R.H. 2000a. Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment. Lipids; 35(12):1305-12. © Nutrasource Diagnostics Inc. Page 6 120 Research Lane, Suite 203, Guelph, ON, N1G 0B4 CANADA T: 519.341.3367 | F: 888.531.3466 | E: [email protected] www.nutrasource.ca Nutra Report Conquer, J.A. and Holub, B.J. 1996. 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. Journal of Nutrition; 126(12):3032-9. Davidson, M.H., Maki, K.C., Kalkowski, J., Schaefer, E.J., Torri, S.A., and Drennan, K.B. 1997. Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, doubleblind, placebo-controlled trial. Journal of American College of Nutrition; 16(3):236-43. Engler, M.M., Engler, M.B., Malloy, M.J., Paul, S.M., Kulkarni, K.R., and Mietus-Snyder, M.L. 2005. Effect of docosahexaenoic acid on lipoprotein subclasses in hyperlipidemic children (the EARLY study). American Journal of Cardiology; 1;95(7):869-71. Fleith, M. and Clandinin, M.T. 2005. Dietary PUFA for preterm and term infants: review of clinical studies. Critical Revues of Food Science and Nutrition; 45(3):205-29. Food and Nutrition Board. 2005. Institute of Medicine of the National Academies. Geppert, J., Kraft, V., Demmelmair, H., and Koletzko, B. 2006. Microalgal docosahexaenoic acid decreases plasma triacylglycerol in normolipidaemic vegetarians: a randomized trial. British Journal of Nutrition; 95(4):779-86. Giltay, E.J., Gooren, L.J., Toorians, A.W., Katan, M.B., and Zock, P.L. 2004. Docosahexaenoic acid concentrations are higher in women than in men because of estrogenic effects. American Journal of Clinical Nutrition; 80(5):116774. Hadley, K.B., Ryan, A.S., Nelson, E.B., Salem, N. Jr. 2010. Preclinical safety evaluation in rats using a highly purified ethyl ester of algal-docosahexaenoic acid. Food and Chemical Toxicology; 48(10):2778-84. Hammond, B.G., Mayhew, D.A., Kier, L.D., Mast, R.W., and Sander, W.J. 2002. Safety assessment of DHA-rich microalgae from Schizochytrium sp. Regulatory Toxicology and Pharmacology; 35(2 Pt 1):255-65. Heird, W.C. and Lapillonne, A. 2005. The role of essential fatty acids in development. Annual Reviews of Nutrition; 25:549-71. Higashihara, E., Nutahara, K., Horie, S., Muto, S., Hosoya, T., Hanaoka, K., Tuchiya, K., Kamura, K., Takaichi, K., Ubara, Y., Itomura, M., and Hamazaki, T. 2008. The effect of eicosapentaenoic acid on renal function and volume in patients with ADPKD. Nephrology, dialysis, transplantation; 23(9):2847-52. Johnson, E.J. and Schaefer, E.J. 2006. Potential role of dietary n-3 fatty acids in the prevention of dementia and macular degeneration. American Journal of Clinical Nutrition; 83(6Suppl):1494S-1498S. Innis, S.M. 1994. The 1993 Borden Award Lecture. Fatty acid requirements of the newborn. Canadian Journal of Physiology and Pharmacology; 72(12):1483-92. Kelley, D.S., Siegel, D., Vemuri, M., and Mackey, B.E. 2007. Docosahexaenoic acid supplementation improves fasting and postprandial lipid profiles in hypertriglyceridemic men. Americal Journal of Clinical Nutrition; 86(2):32433. © Nutrasource Diagnostics Inc. Page 7 120 Research Lane, Suite 203, Guelph, ON, N1G 0B4 CANADA T: 519.341.3367 | F: 888.531.3466 | E: [email protected] www.nutrasource.ca Nutra Report Kimura, S., Saito, H., Minami, M., Togashi, H., Nakamura, N., Ueno, K., Shimamura, K., Nemoto, M., and Parvez, H. 2002. Docosahexaenoic acid attenuated hypertension and vascular dementia in stroke-prone spontaneously hypertensive rats. Neurotoxicology and Teratology; 24(5):683-93. Kris-Etherton, P.M., Harris, W.S., Appel, L.J.; American Heart Association. Nutrition Committee. 2002. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation; 106(21):2747-57. Kroes, R., Schaefer, E.J., Squire, R.A., and Williams, G.M. 2003. A review of the safety of DHA45-oil. Food Chemistry and Toxicology; 41(11):1433-46. Kyle, D.J. and Arterburn, L.M. 1998. Single cell oil sources of docosahexaenoic acid: clinical studies. World Review of Nutrition Dietetics; 83:116-31. Lien, E.L. 2009. Toxicology and safety of DHA. Prostaglandins, Leukotrienes, and Essential Fatty Acids; 81(2-3):12532. Lewis, N.M., Seburg, S., and Flanagan, N.L. 2000. Enriched eggs as a source of N-3 polyunsaturated fatty acids for humans. Poultry Science; 79(7):971-4. Lukiw, W.J. 2009. Docosahexaenoic acid and amyloid-beta peptide signalling in Alzheimer's disease. World Reviews of Nutrition Dietetics; 99:55-70. Lukiw WJ, Bazan NG. Docosahexaenoic acid and the aging brain. J Nutr. 2008 Dec;138(12):2510-4. Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest. 2005 Oct;115(10):2774-83. Maki KC, Van Elswyk ME, McCarthy D, Hess SP, Veith PE, Bell M, Subbaiah P, Davidson MH. 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. 2005 Jun;24(3):189-99. Marangell LB, Martinez JM, Zboyan HA, Kertz B, Kim HF, Puryear LJ. A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Am J Psychiatry. 2003 May;160(5):996-8. Mischoulon D, Best-Popescu C, Laposata M, Merens W, Murakami JL, Wu SL, Papakostas GI, Dording CM, Sonawalla SB, Nierenberg AA, Alpert JE, Fava M. A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder. Eur Neuropsychopharmacol. 2008 Sep;18(9):639-45. Mori TA, Bao DQ, Burke V, Puddey IB, Beilin LJ. Docosahexaenoic acid but not eicosapentaenoic acid lowers ambulatory blood pressure and heart rate in humans. Hypertension. 1999 Aug;34(2):253-60. Neff LM, Culiner J, Cunningham-Rundles S, Seidman C, Meehan D, Maturi J, Wittkowski KM, Levine B, Breslow JL. Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution in overweight and obese adults. J Nutr. 2011 Feb;141(2):207-13. © Nutrasource Diagnostics Inc. Page 8 120 Research Lane, Suite 203, Guelph, ON, N1G 0B4 CANADA T: 519.341.3367 | F: 888.531.3466 | E: [email protected] www.nutrasource.ca Nutra Report Nelson GJ, Schmidt PS, Bartolini GL, Kelley DS, Kyle D. The effect of dietary docosahexaenoic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Lipids. 1997 Nov;32(11):1129-36. Park Y, Jones PG, Harris WS. Triacylglycerol-rich lipoprotein margination: a potential surrogate for whole-body lipoprotein lipase activity and effects of eicosapentaenoic and docosahexaenoic acids. Am J Clin Nutr. 2004 Jul;80(1):45-50 Park Y, Harris WS. Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance. J Lipid Res. 2003 Mar;44(3):455-63. Plourde M, Cunnane SC. Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements. Appl Physiol Nutr Metab. 2007 Aug;32(4):619-34. Review. Erratum in: Appl Physiol Nutr Metab. 2008 Feb;33(1):228-9. Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR Jr, Weiner M, Shinto L, Aisen PS. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010 Nov 3;304(17):1903-11. 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 Apr;109(4):668-79. SanGiovanni JP, Berkey CS, Dwyer JT, Colditz GA. Dietary essential fatty acids, long-chain polyunsaturated fatty acids, and visual resolution acuity in healthy fullterm infants: a systematic review. Early Hum Dev. 2000 Mar;57(3):165-88. Sargent JR, Tacon AG. Development of farmed fish: a nutritionally necessary alternative to meat. Proc Nutr Soc. 1999 May;58(2):377-83. Schaefer EJ, Bongard V, Beiser AS, Lamon-Fava S, Robins SJ, Au R, Tucker KL, Kyle DJ, Wilson PW, Wolf PA. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol. 2006 Nov;63(11):1545-50. Smit EN, Koopmann M, Boersma ER, Muskiet FA. Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosahexaenoic acid on breastmilk fatty acid composition. Prostaglandins Leukot Essent Fatty Acids. 2000 Jun;62(6):335-40. Stark KD, Holub BJ. 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. 2004 May;79(5):765-73. Terano T, Fujishiro S, Ban T, Yamamoto K, Tanaka T, Noguchi Y, Tamura Y, Yazawa K, Hirayama T. Docosahexaenoic acid supplementation improves the moderately severe dementia from thrombotic cerebrovascular diseases. Lipids. 1999;34 Suppl:S345-6. Theobald HE, Chowienczyk PJ, Whittall R, Humphries SE, Sanders TA. LDL cholesterol-raising effect of low-dose docosahexaenoic acid in middle-aged men and women. Am J Clin Nutr. 2004 Apr;79(4):558-63. © Nutrasource Diagnostics Inc. Page 9 120 Research Lane, Suite 203, Guelph, ON, N1G 0B4 CANADA T: 519.341.3367 | F: 888.531.3466 | E: [email protected] www.nutrasource.ca Nutra Report 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 Sep;121(9):1269-78. Woodman RJ, Mori TA, Burke V, Puddey IB, Barden A, Watts GF, Beilin LJ. Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Atherosclerosis. 2003 Jan;166(1):85-93. Woodman RJ, Mori TA, Burke V, Puddey IB, Watts GF, Beilin LJ. 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. 2002 Nov;76(5):1007-15. Wright K, Coverston C, Tiedeman M, Abegglen JA. Formula supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA): a critical review of the research. J Spec Pediatr Nurs. 2006 Apr;11(2):100-12. Yuen AW, Sander JW, Flugel D, Patsalos PN, Browning L, Bell GS, Koepp MM. Erythrocyte and plasma fatty acid profiles in patients with epilepsy: does carbamazepine affect omega-3 fatty acid concentrations? Epilepsy Behav. 2008 Feb;12(2):317-23. © Nutrasource Diagnostics Inc. Page 120 Research Lane, Suite 203, Guelph, ON, N1G 0B4 CANADA T: 519.341.3367 | F: 888.531.3466 | E: [email protected] www.nutrasource.ca 10