Abstract
Background:
Vegetarians are generally deficient in long-chain n-3 fatty acids. Long-chain n-3 fatty acids have a beneficial effect on plasma lipid levels, and some studies showed that they had breast cancer suppression effect. One of the biomarkers of breast cancer risk is the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16α-hydroxyestrone (16α-OHE1).
Objective:
To investigate the effect of docosahexaenoic acid (DHA, 22:6n-3) supplementation on blood lipids, estrogen metabolism and oxidative stress in vegetarians.
Design:
Single-blind, randomized, placebo-controlled trial.
Interventions:
Twenty-seven postmenopausal vegetarian women were recruited. After a 2-week run-in period with 6 g placebo corn oil, the subjects were subsequently randomized to receive either 6 g corn oil (n=13) or 6 g DHA-rich algae oil (2.14 g of DHA/day) (n=14) for 6 weeks. Two subjects in corn oil group withdrew before completion.
Main outcome measures:
Plasma lipids, urinary 2-OHE1 and 16α-OHE1, urinary F2-isoprostanes and plasma α-tocopherol.
Results:
Plasma LDL-DHA and EPA level increased significantly by DHA supplementation. DHA decreased plasma cholesterol (C) levels (P=0.04), but did not influence the levels of plasma TG, LDL-C and HDL-C, α-tocopherol, urinary F2-isoprostanes, 2-OHE1, 16α-OHE1 and ratio of 2-OHE1 to 16α-OHE1 as compared to corn oil.
Conclusion:
DHA supplementation at a dose of 2.14 g/day for 42 days decreases plasma cholesterol but neither does it show beneficial effects on estrogen metabolism, nor does it induce deleterious effects on the observed in vivo antioxidant or oxidative stress marker in postmenopausal vegetarian women.
Sponsorship:
A grant (# DOH89-TD-1062) from Department of Health, Executive Yuan, Taiwan.
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References
Bernard-Gallon D, Vissac-Sabatier C, Antoine-Vincent D, Rio PG, Maurizis JC, Fustier P et al. (2002). Differential effects of n–3 and n–6 polyunsaturated fatty acids on BRCA1 and BRCA2 gene expression in breast cell lines. Br J Nutr 87, 281–289.
Bradlow HL, Sepkovic DW, Klug T, Osborne MP (1998). Application of an improved ELISA assay to the analysis of urinary estrogen metabolites. Steroids 63, 406–413.
Brooks JD, Ward WE, Lewis JE, Hilditch J, Nickell L, Wong E et al (2004). Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy. Am J Clin Nutr 79, 318–325.
Cave WT (1997). Omega-3 polyunsaturated fatty acids in rodent models of breast cancer. Breast Cancer Res Treat 46, 239–246.
Chen HW, Tsai CW, Yang JJ, Liu CT, Kuo WW, Lii CK (2003). The combined effects of garlic oil and fish oil on the hepatic antioxidant and drug-metabolizing enzymes of rats. Br J Nutr 89, 189–200.
Conquer JA, Holub BJ (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. J Nutr 126, 3032–3039.
Dos Santos Silva I, Mangtani P, McCormack V, Bhakta D, Sevak L, McMichael AJ (2002). Lifelong vegetarianism and risk of breast cancer: a population-based case–control study among South Asian migrant women living in England. Int J Cancer 99, 238–244.
Dougherty RM, Galli C, Ferro-Luzzi A, Iacono JM (1987). Lipid and phospholipid fatty acid composition of plasma, red blood cells, and platelets and how they are affected by dietary lipids: a study of normal subjects from Italy, Finland, and the USA. Am J Clin Nutr 45, 443–455.
Fraser GE (1999). Associations between diet and cancer, ischemic heart disease, and all-cause mortality in non-Hispanic white California Seventh-day Adventists. Am J Clin Nutr 70, 532–538.
Harris WS (1997). n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 65 (Suppl), 1645S–1654S.
Higdon JV, Liu J, Du SH, Morrow JD, Ames BN, Wander RC (2000). Supplementation of postmenopausal women with fish oil rich in eicosapentaenoic acid and docosahexaenoic acid is not associated with greater in vivo lipid peroxidation compared with oils rich in oleate and linoleate as assessed by plasma malondialdehyde and F(2)-isoprostanes. Am J Clin Nutr 72, 714–722.
Huang Z, Guengerich FP, Kaminsky LS (1998). 16α-Hydroxylation of estrone by human cytochrome P4503A4/5. Carcinogenesis 19, 867–872.
Kabat GC, Chang CJ, Sparano JA, Sepkovic DW, Hu XP, Khalil A et al. (1997). Urinary estrogen metabolites and breast cancer: a case–control study. Cancer Epidemiol Biomaker Prev 6, 505–509.
Kall MA, Vang O, Clausen J (1996). Effects of dietary broccoli on human in vivo drug metabolizing enzymes: evaluation of caffeine, oestrone and chlorzoxazone metabolism. Carcinogenesis 17, 793–799.
Kaplan LA, Miller JA, Stein EA (1987). Simultaneous measurement of serum retinal, tocopherols, carotenes and carotenoids by high performance liquid chromatography. J Clin Lab Anal 1, 147–152.
Karmali RA (1989). n-3 fatty acids and cancer. J Intern Med 225 (Suppl 1), 197–200.
Lee HY, Woo J, Chen ZY, Leung SF, Peng XH (2000). Serum fatty acid, lipid profile and dietary intake of Hong Kong Chinese omnivores and vegetarians. Eur J Clin Nutr 54, 768–773.
Lepage G, Roy CC (1986). Direct transesterification of all classes of lipids in a one-step reaction. J Lipid Res 27, 114–120.
Li D, Sinclair A, Mann N, Turner A, Ball M, Kelly F et al. (1999). The association of diet and thrombotic risk factors in healthy male vegetarians and meat-eaters. Eur J Clin Nutr 53, 612–619.
Lu LJW, Cree M, Josyula S, Nagamani M, Grady JJ, Anderson KE (2000a). Increased urinary excretion of 2-hydroxyestrone but not 16α-hydroxyestrone in premenopausal women during a soya diet containing isoflavones. Cancer Res 60, 1299–1305.
Lu SC, Wu WH, Lee CA, Chou HF, Lee HR, Huang PC (2000b). LDL of Taiwanese vegetarians are less oxidizable than those of omnivores. J Nutr 130, 1591–1596.
Manjari V, Suresh Y, Sailaja Devi MM, Das UN (2001). Oxidant stress, anti-oxidants and essential fatty acids in South Indian vegetarians and non-vegetarians. Prostaglandins Leukot Essent Fatty Acids 64, 53–59.
Meydani M, Natiello Goldin B, Free N, Woods M, Schaefer E, Blumberg JB et al (1991). Effect of long-term fish oil supplementation on vitamin E status and lipid peroxidation in women. J Nutr 121, 484–491.
Mezzano D, Kosiel K, Martinez C, Cuevas A, Panes O, Aranda E et al. (2000). Cardiovascular risk factors in vegetarians. Normalization of hyperhomocysteinemia with vitamin B (12) and reduction of platelet aggregation with n-3 fatty acids. Thromb Res 100, 153–160.
Michnovicz JJ, Adlercreutz H, Bradlow HL (1997). Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst 89, 718–723.
Mori TA, Beilin LJ (2001). Long-chain omega 3 fatty acids, blood lipids and cardiovascular risk reduction. Curr Opin Lipidol 12, 11–17.
Mori TA, Woodman RJ, Burke V, Puddey IB, Croft KD, Beilin L (2003). Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Free Rad Biol Med 35, 772–781.
Morrow JD, Roberts II LJ (1996). The isoprostanes. Current knowledge and directions for future research. Biochem Pharmacol 51, 1–9.
Muti P, Bradlow HL, Micheli A, Krogh V, Freudenheim JL, Schunemann HJ et al. (2000). Estrogen metabolism and risk of breast cancer: A prospective study of the 2:16α-hydroxyestrone ratio in premenopausal and postmenopausal women. Epidemiology 11, 635–640.
Nelson GJ, Schmidt PC, Bartolini GL, Kelley DS, Kyle D (1997). The effect of dietary docosahexaenoic acid on plasma lipoproteins and tissue fatty acid composition in humans. Lipids 32, 1137–1146.
Nettleton JA, Greany KA, Thomas W, Wangen KE, Adlercreutz H, Kurzer MS (2005). The effect of soy consumption on the urinary 2:16-hydroxyestrone ratio in postmenopausal women depends on equol production status but is not influenced by probiotic consumption. J Nutr 135, 603–608.
Nourooz-Zadeh J, Halliwell B, Anggard EE (1997). Formation of a novel class of F3-isoprostanes during peroxidation of eicosapentaenoic acid (EPA). Adv Exp Med Biol 433, 185–188.
Nourooz-Zadeh J, Liu EH, Anggard E, Halliwell B (1998). F4-isoprostanes: a novel class of prostanoids formed during peroxidation of docosahexaenoic acid (DHA). Biochem Biophys Res Commun 242, 338–344.
Oostenbrug GS, Mensink RP, Hornstra G (1994). Effects of fish oil and vitamin E supplementation on copper-catalysed oxidation of human low density lipoprotein in vitro. Eur J Clin Nutr 48, 895–898.
Osborne MP, Karmali RA, Hershcopf RJ, Bradlow HL (1988). Omega-3 fatty acids: modulation of estrogen metabolism and potential for breast cancer prevention. Cancer Invest 6, 629–631.
Service RF (1998). New role for estrogen in cancer? Science 279, 1631–1633.
Suzukawa M, Abbey M, Howe PR, Nestel PJ (1995). Effects of fish oil fatty acids on low density lipoprotein size, oxidizability, and uptake by macrophages. J Lipid Res 36, 473–484.
Takahashi M, Tsuboyama-Kasaoka N, Nakatani T, Ishii M, Tsutsumi S, Aburatani H et al. (2002). Fish oil feeding alters liver gene expressions to defend against PPARalpha activation and ROS production. Am J Physiol-Gastr L 282, G338–G348.
Terry PD, Rohan TE, Wolk A (2003). Intakes of fish and marine fatty acids and the risks of cancers of the breast and prostate and of other hormone-related cancers: a review of the epidemiologic evidence. Am J Clin Nutr 77, 532–543.
Ursin G, Wilson M, Henderson BE, Kolonel LN, Monroe K, Lee HP et al. (2001). Do urinary estrogen metabolites reflect the differences in breast cancer risk between Singapore Chinese and United States African-American and white women? Cancer Res 61, 3326–3329.
Valdes E, Vega P, Avalos N, Orellana M (1995). Dietary fish oil and cytochrome P-450 monooxygenase activity in rat liver and kidney. Lipids 30, 955–958.
Wang HH, Hung TM, Wei J, Chiang AN (2004). Fish oil increases antioxidant enzyme activities in macrophages and reduces atherosclerotic lesions in apoE-knockout mice. Cardiovasc Res 61, 169–176.
Yamazaki H, Shaw PM, Guengerich FP, Shimada T (1998). Role of cytochromes P450 1A2 and 3A4 in the oxidation of estradiol and estrone in human liver microsomes. Chem Res Toxicol 11, 659–665.
Zock PL, Mensink RP, Harryvan J, de Vries JH, Katan MB (1997). Fatty acids in serum cholesteryl esters as quantitative biomarkers of dietary intake in humans. Am J Epidemiol 145, 1114–1122.
Acknowledgements
This study was supported by a grant (Grant# DOH89-TD-1062) from Department of Health, Executive Yuan, Taiwan. We thank reviewers for the suggestion in statistical analysis and Professor Sieh-Hwa Lin from National Taiwan Normal University for assistance in statistical analysis.
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Guarantor: WH Wu.
Contributors: WHW designed the study, contributed to method development, data interpretation and preparation of the manuscript. SCL initiated the study, obtained a research grant for the study and was responsible for all stages of the study. TFW was responsible for biochemical and statistical analyses and taking care of the study subjects. HJJ and TAW were the gynecologists involved in subject recruitment, sample processing and advised on protocol design. All authors contributed to the writing of the manuscript.
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Wu, W., Lu, S., Wang, T. et al. Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women. Eur J Clin Nutr 60, 386–392 (2006). https://doi.org/10.1038/sj.ejcn.1602328
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DOI: https://doi.org/10.1038/sj.ejcn.1602328
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