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Influence of fish oil or folate supplementation on the time course of plasma redox markers during pregnancy

  • Corinna Franke (a1), Hans Demmelmair (a1), Tamas Decsi (a2), Cristina Campoy (a3), Milagros Cruz (a3), Juan A. Molina-Font (a3), Klaus Mueller (a4) and Berthold Koletzko (a1)...


Maternal supplementation with long-chain PUFA, to improve infant neurological development, might cause additional increase of oxidative stress. Pregnant women aged 18–41 years were randomised into one of four supplementation groups. From week 22 on, they received supplements containing either modified fish oil (n 69), 5-methyl-tetrahydro-folate (n 65), both (n 64), or placebo (n 72). Plasma Trolox-equivalent antioxidative capacity (TEAC), concentrations of α-tocopherol, retinol, β-carotene, free thiol groups, uric acid and thiobarbituric acid-reactive substances (TBARS) were determined at weeks 20 and 30 and at delivery. The studied antioxidants showed no significant differences between the four supplementation groups. At week 30 plasma TBARS levels were found to be significantly higher in the fish oil group (0·80 (sem 0·04) μmol/l) than in the folate (0·67 (sem 0·03) μmol/l; P = 0·024) and control (0·69 (sem 0·04) μmol/l; P = 0·01) groups. Concentrations of retinol and free thiol groups decreased during pregnancy, whereas uric acid increased and β-carotene as well as TEAC showed only minor changes. Fish oil supplementation during the second half of pregnancy appears not to decrease antioxidant status. The increased TBARS levels at week 30 may indicate a period of increased oxidative stress in plasma at this time.


Corresponding author

*Corresponding author: Professor Berthold Koletzko, fax +49 89 5160 3336, email


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1Jenkins, C, Wilson, R, Roberts, J, et al. (2000) Antioxidants: their role in pregnancy and miscarriage. Antioxid Redox Signal 2, 623628.
2Sugino, N, Takiguchi, S, Kashida, S, et al. (2000) Superoxide dismutase expression in the human corpus luteum during the menstrual cycle and in early pregnancy. Mol Hum Reprod 6, 1925.
3Mutlu-Turkoglu, U, Ademoglu, E, Ibrahimoglu, L, et al. (1998) Imbalance between lipid peroxidation and antioxidant status in preeclampsia. Gynecol Obstet Invest 46, 3740.
4Perkins, AV (2006) Endogenous anti-oxidants in pregnancy and preeclampsia. Aust NZ J Obstet Gynaecol 46, 7783.
5Kim, YJ, Hong, YC, Lee, KH, et al. (2005) Oxidative stress in pregnant women and birth weight reduction. Reprod Toxicol 19, 487492.
6Koletzko, B, Agostoni, C, Carlson, SE, et al. (2001) Long chain polyunsaturated fatty acids (LC-PUFA) and perinatal development. Acta Paediatr 90, 460464.
7Willatts, P & Forsyth, JS (2000) The role of long-chain polyunsaturated fatty acids in infant cognitive development. Prostaglandins Leukot Essent Fatty Acids 63, 95100.
8Decsi, T & Koletzko, B (2005) n-3 Fatty acids and pregnancy outcomes. Curr Opin Clin Nutr Metab Care 8, 161166.
9Lakin, V, Haggarty, P, Abramovich, DR, et al. (1998) Dietary intake and tissue concentration of fatty acids in omnivore, vegetarian and diabetic pregnancy. Prostaglandins Leukot Essent Fatty Acids 59, 209220.
10Makrides, M, Duley, L & Olsen, SF (2006) Marine oil, and other prostaglandin precursor, supplementation for pregnancy uncomplicated by pre-eclampsia or intrauterine growth restriction The Cochrane Database of Systematic Reviews 2006, issue 3, CD003402.
11Olsen, SF, Osterdal, ML, Salvig, JD, et al. (2007) Duration of pregnancy in relation to fish oil supplementation and habitual fish intake: a randomised clinical trial with fish oil. Eur J Clin Nutr 61, 976985.
12Gitto, E, Reiter, RJ, Karbownik, M, et al. (2002) Causes of oxidative stress in the pre- and perinatal period. Biol Neonate 81, 146157.
13Herrera, E (2002) Lipid metabolism in pregnancy and its consequences in the fetus and newborn. Endocrine 19, 4355.
14Homocysteine Lowering Trialists' Collaboration (2005) Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr 82, 806812.
15Böhles, H, Arndt, S, Ohlenschlager, U, et al. (1999) Maternal plasma homocysteine, placenta status and docosahexaenoic acid concentration in erythrocyte phospholipids of the newborn. Eur J Pediatr 158, 243246.
16Hayden, MR & Tyagi, SC (2004) Homocysteine and reactive oxygen species in metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: the pleiotropic effects of folate supplementation. Nutr J 3, 4.
17Krauss-Etschmann, S, Shadid, R, Campoy, C, et al. (2007) Effects of fish-oil and folate supplementation of pregnant women on maternal and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial. Am J Clin Nutr 85, 13921400.
18Brigelius-Flohe, R, Kelly, FJ, Salonen, JT, et al. (2002) The European perspective on vitamin E: current knowledge and future research. Am J Clin Nutr 76, 703716.
19Tsuchihashi, H, Kigoshi, M, Iwatsuki, M, et al. (1995) Action of β-carotene as an antioxidant against lipid peroxidation. Arch Biochem Biophys 323, 137147.
20Ames, BN, Cathcart, R, Schwiers, E, et al. (1981) Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A 78, 68586862.
21Iciek, M, Chwatko, G, Lorenc-Koci, E, et al. (2004) Plasma levels of total, free and protein bound thiols as well as sulfane sulfur in different age groups of rats. Acta Biochim Pol 51, 815824.
22Franke, C, Verwied-Jorky, S, Campoy, C, et al. (2008) Dietary intake of natural sources of docosahexaenoic acid and folate in pregnant women of three European cohorts. Ann Nutr Metab 53, 167174.
23Knight, J, Smith, S, Kinder, V, et al. (1988) Urinary lipoperoxides quantified by liquid chromatography, and determination of reference values for adults. Clin Chem 34, 11071110.
24Hess, D, Keller, HE, Oberlin, B, et al. (1991) Simultaneous determination of retinol, tocopherols, carotenes and lycopene in plasma by means of high-performance liquid chromatography on reversed phase. Int J Vit Nutr Res 61, 232238.
25Quinlan, G, Evans, T & Guttridge, J (2005) Oxidative damage to plasma proteins in adult respiratory distress syndrome. Free Rad Res 20, 289298.
26Motchnik, PA, Frei, B & Ames, BN (1994) Measurement of antioxidants in human blood plasma. Methods Enzymol 234, 269279.
27Uotila, J, Tuimala, R, Aarnio, T, et al. (1991) Lipid peroxidation products, selenium-dependent glutathione peroxidase and vitamin E in normal pregnancy. Eur J Obstet Gynecol Reprod Biol 42, 95100.
28Little, RE & Gladen, BC (1999) Levels of lipid peroxides in uncomplicated pregnancy: a review of the literature. Reprod Toxicol 13, 347352.
29Toescu, V, Nuttall, SL, Martin, U, et al. (2002) Oxidative stress and normal pregnancy. Clin Endocrinol (Oxf) 57, 609613.
30Patrick, TE, Hubel, CA & Roberts, JM (2004) Evidence of increased oxidative stress, unexplained by lipid changes, is present in nulliparous black women from early gestation. Hypertens Pregnancy 23, 91100.
31Janero, DR (1990) Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 9, 515540.
32Herrera, E, Ortega, H, Alvino, G, et al. (2004) Relationship between plasma fatty acid profile and antioxidant vitamins during normal pregnancy. Eur J Clin Nutr 58, 12311238.
33Cao, G & Prior, RL (1998) Comparison of different analytical methods for assessing total antioxidant capacity of human serum. Clin Chem 44, 13091315.
34Van den Berg, R, Haenen, GRMM, van den Berg, H, et al. (1999) Applicability of an improved Trolox equivalent antioxidant capacity (TEAC) assay for evaluation of antioxidant capacity measurements of mixtures. Food Chem 66, 511517.
35Schofield, D & Braganza, JM (1996) Shortcomings of an automated assay for total antioxidant status in biological fluids. Clin Chem 42, 17121714.
36Bruinse, HW & van den Berg, H (1995) Changes of some vitamin levels during and after normal pregnancy. Eur J Obstet Gynecol Reprod Biol 61, 3137.
37Cikot, RJ, Steegers-Theunissen, RP, Thomas, CM, et al. (2001) Longitudinal vitamin and homocysteine levels in normal pregnancy. Br J Nutr 85, 4958.
38Clagett-Dame, M & DeLuca, HF (2002) The role of vitamin A in mammalian reproduction and embryonic development. Annu Rev Nutr 22, 347381.
39Foulon, T, Richard, MJ, Payen, N, et al. (1999) Effects of fish oil fatty acids on plasma lipids and lipoproteins and oxidant–antioxidant imbalance in healthy subjects. Scand J Clin Lab Invest 59, 239248.
40Faure, H, Preziosi, P, Roussel, AM, et al. (2006) Factors influencing blood concentration of retinol, α-tocopherol, vitamin C, and β-carotene in the French participants of the SU.VI.MAX trial. Eur J Clin Nutr 60, 706717.
41Chappell, LC, Seed, PT, Kelly, FJ, et al. (2002) Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function. Am J Obstet Gynecol 187, 777784.
42Powers, RW, Bodnar, LM, Ness, RB, et al. (2006) Uric acid concentrations in early pregnancy among preeclamptic women with gestational hyperuricemia at delivery. Am J Obstet Gynecol 194, 160.
43Becker, BF (1993) Towards the physiological function of uric acid. Free Radic Biol Med 14, 615631.
44Glantzounis, GK, Tsimoyiannis, EC, Kappas, AM, et al. (2005) Uric acid and oxidative stress. Curr Pharm Des 11, 41454151.
45Sanchez-Lozada, LG, Nakagawa, T, Kang, DH, et al. (2006) Hormonal and cytokine effects of uric acid. Curr Opin Nephrol Hypertens 15, 3033.
46Lain, KY, Markovic, N, Ness, RB, et al. (2005) Effect of smoking on uric acid and other metabolic markers throughout normal pregnancy. J Clin Endocrinol Metab 90, 57435746.
47Wisdom, SJ, Wilson, R, Mckillop, JH, et al. (1991) Antioxidant systems in normal pregnancy and in pregnancy hypertension. Am J Obstet Gynecol 165, 17011704.
48Raijmakers, MT, Roes, EM, Steegers, EA, et al. (2001) Umbilical cord and maternal plasma thiol concentrations in normal pregnancy. Clin Chem 47, 749751.
49Myatt, L & Cui, X (2004) Oxidative stress in the placenta. Histochem Cell Biol 122, 369382.
50Walsh, SW (1998) Maternal–placental interactions of oxidative stress and antioxidants in preeclampsia. Semin Reprod Endocrinol 16, 93104.
51Koletzko, B, Cetin, I & Brenna, JT (2007) Dietary fat intakes for pregnant and lactating women. Br J Nutr 98, 873877.
52Simopoulos, AP, Leaf, A & Salem, N Jr (2000) Workshop statement on the essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids 63, 109121.



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