Introduction: Low dietary intake of vitamin E is a global public health issue. RRR-α-tocopherol (RRR-αT) is the only naturally occurring vitamin E stereoisomer, but the equimolecular mixture of all eight stereoisomers, synthetic vitamin E (S-αT), is commonly consumed. The objective of this study was to evaluate bioavailability and antioxidant activity of RRR-αT versus S-αT, in both mother and fetus, after maternal supplementation during pregnancy. Methods: Female rats (7 weeks of age) received a modified AIN-93G diet supplemented with 75 IU/kg of RRR-αT (NVE, n = 20) or S-αT (SVE, n = 17). At delivery, the levels of αT, stereoisomer distribution, and antioxidant capacity were analyzed in maternal and fetal plasma. Results: NVE administration significantly increased the proportion of RRR-αT stereoisomer in maternal and fetal plasma. The percentage of RRR-αT increased from 32.76% to 88.33% in maternal plasma, and 35.25% to 97.94% in fetal plasma, in the NVE group compared to SVE. Fetal plasma from the NVE group was found to have higher total antioxidant capacity compared to SVE. Lastly, fetal plasma RRR-αT stereoisomer percentage was positively associated with expression levels of scavenger receptor class B type 1 (SR-B1) in the placenta. Conclusions: Both natural and synthetic sources of vitamin E showed similar bioavailability. Still, NVE supplementation increased the proportion of RRR-αT and promoted higher antioxidant activity in fetal plasma at birth. Placental SR-B1 might be involved in the stereoselective transfer of RRR-αT stereoisomer across the placenta and may improve αT bioactivity in the fetus.

Debier C. Vitamin E during pre- and postnatal periods. Vitam Horm. 2007;76:357–73.
Arkkola T, Uusitalo U, Pietikainen M, Metsala J, Kronberg-Kippila C, Erkkola M, et al. Dietary intake and use of dietary supplements in relation to demographic variables among pregnant finnish women. Br J Nutr. 2006 Nov;96(5):913–20.
Olza J, Aranceta-Bartrina J, Gonzalez-Gross M, Ortega RM, Serra-Majem L, Varela-Moreiras G, et al. Reported dietary intake and food sources of zinc, selenium, and vitamins A, E and C in the Spanish population: findings from the ANIBES study. Nutrients. 2017 Jul 6;9(7):697.
Moyersoen I, Lachat C, Cuypers K, Ridder KD, Devleesschauwer B, Tafforeau J, et al. Do current fortification and supplementation programs assure adequate intake of fat-soluble vitamins in Belgian infants, toddlers, pregnant women, and lactating women? Nutrients. 2018 Feb 16;10(2):223.
Busso D, David A, Penailillo R, Echeverria G, Rigotti A, Kovalskys I, et al. Intake of vitamin E and C in women of reproductive age: results from the Latin American study of nutrition and health (ELANS). Nutrients. 2021 Jun 7;13(6):1954.
Perrone S, Santacroce A, Picardi A, Buonocore G. Fetal programming and early identification of newborns at high risk of free radical-mediated diseases. World J Clin Pediatr. 2016 May 8;5(2):172–81.
Mutalip SSM. Chapter 26 - vitamin E and reproductive health. In: Patel VB, editor. Molecular nutrition. Academic Press; 2020. p. 543–59.
McLaughlin PJ, Weihrauch JL. Vitamin E content of foods. J Am Diet Assoc. 1979 Dec;75(6):647–65.
Jiang Q. Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radic Biol Med. 2014 Jul;72:76–90.
Medicine Io . Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: The National Academies Press; 2000.
Harris PL, Ludwig MI. Relative vitamin E potency of natural and of synthetic alpha-tocopherol. J Biol Chem. 1949 Jul;179(3):1111–5.
Acuff RV, Thedford SS, Hidiroglou NN, Papas AM, Odom TA Jr. Relative bioavailability of RRR- and all-rac-alpha-tocopheryl acetate in humans: studies using deuterated compounds. Am J Clin Nutr. 1994 Sep;60(3):397–402.
Traber MG, Elsner A, Brigelius-Flohe R. Synthetic as compared with natural vitamin E is preferentially excreted as alpha-CEHC in human urine: studies using deuterated alpha-tocopheryl acetates. FEBS Lett. 1998 Oct 16;437(1–2):145–8.
Lauridsen C, Engel H, Craig AM, Traber MG. Relative bioactivity of dietary RRR- and all-rac-alpha-tocopheryl acetates in swine assessed with deuterium-labeled vitamin E. J Anim Sci. 2002 Mar;80(3):702–7.
Jensen SK, Lashkari S, Kristensen NB. Pharmacokinetics of alpha-tocopherol stereoisomers in plasma and milk of cows following a single dose injection of all-rac-alpha-tocopheryl acetate. Food Chem. 2020 Apr 25;310:125931.
Ranard KM, Erdman JW Jr. Effects of dietary RRR alpha-tocopherol vs all-racemic alpha-tocopherol on health outcomes. Nutr Rev. 2018 Mar 1;76(3):141–53.
Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG, NC3Rs Reporting Guidelines Working Group. Animal research: reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol. 2010 Aug;160(7):1577–9.
Reeves PG, Nielsen FH, Fahey GC Jr. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr. 1993 Nov;123(11):1939–51.
Gázquez A, Sánchez-Campillo M, Barranco A, Rueda R, Chan JP, Kuchan MJ, et al. Calcifediol during pregnancy improves maternal and fetal availability of vitamin D compared to vitamin D3 in rats and modifies fetal metabolism. Front Nutr. 2022;9:871632.
Jensen SK, Engberg RM, Hedemann MS. All-rac-alpha-tocopherol acetate is a better vitamin E source than all-rac-alpha-tocopherol succinate for broilers. J Nutr. 1999 Jul;129(7):1355–60.
Jensen SK, Norgaard JV, Lauridsen C. Bioavailability of alpha-tocopherol stereoisomers in rats depends on dietary doses of all-rac- or RRR-alpha-tocopheryl acetate. Br J Nutr. 2006 Mar;95(3):477–87.
Drotleff AM, Ternes W. Determination of RS,E/Z-tocotrienols by HPLC. J Chromatogr A. 2001 Feb 16;909(2):215–23.
Ruiz-Alcaraz AJ, Liu HK, Cuthbertson DJ, McManus EJ, Akhtar S, Lipina C, et al. A novel regulation of IRS1 (insulin receptor substrate-1) expression following short term insulin administration. Biochem J. 2005 Dec 01;392(Pt 2):345–52.
Amazan D, Cordero G, Lopez-Bote CJ, Lauridsen C, Rey AI. Effects of oral micellized natural vitamin E (D-alpha-tocopherol) v. synthetic vitamin E (DL-alpha-tocopherol) in feed on alpha-tocopherol levels, stereoisomer distribution, oxidative stress and the immune response in piglets. Animal. 2014 Mar;8(3):410–9.
Prieto-Sanchez MT, Ruiz-Palacios M, Blanco-Carnero JE, Pagan A, Hellmuth C, Uhl O, et al. Placental MFSD2a transporter is related to decreased DHA in cord blood of women with treated gestational diabetes. Clin Nutr. 2017 Apr;36(2):513–21.
Arnao MB, Cano A, Acosta M. Methods to measure the antioxidant activity in plant material. A comparative discussion. Free Radic Res. 1999;31(Suppl l):89–96.
Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem. 1996 Jul 15;239(1):70–6.
Weiser H, Riss G, Kormann AW. Biodiscrimination of the eight alpha-tocopherol stereoisomers results in preferential accumulation of the four 2R forms in tissues and plasma of rats. J Nutr. 1996 Oct;126(10):2539–49.
Meglia GE, Jensen SK, Lauridsen C, Persson Waller K. Alpha-tocopherol concentration and stereoisomer composition in plasma and milk from dairy cows fed natural or synthetic vitamin E around calving. J Dairy Res. 2006 May;73(2):227–34.
Horn M, Gunn P, Van Emon M, Lemenager R, Burgess J, Pyatt NA, et al. Effects of natural (RRR alpha-tocopherol acetate) or synthetic (all-rac alpha-tocopherol acetate) vitamin E supplementation on reproductive efficiency in beef cows. J Anim Sci. 2010 Sep;88(9):3121–7.
Mahan DC, Kim YY, Stuart RL. Effect of vitamin E sources (RRR- or all-rac-alpha-tocopheryl acetate) and levels on sow reproductive performance, serum, tissue, and milk alpha-tocopherol contents over a five-parity period, and the effects on the progeny. J Anim Sci. 2000 Jan;78(1):110–9.
Weiss WP, Hogan JS, Wyatt DJ. Relative bioavailability of all-rac and RRR vitamin E based on neutrophil function and total alpha-tocopherol and isomer concentrations in periparturient dairy cows and their calves. J Dairy Sci. 2009 Feb;92(2):720–31.
Kuchan MJ, Jensen SK, Johnson EJ, Lieblein-Boff JC. The naturally occurring alpha-tocopherol stereoisomer RRR-alpha-tocopherol is predominant in the human infant brain. Br J Nutr. 2016 Jul;116(1):126–31.
Kuchan MJ, DeMichele SJ, Schimpf KJ, Chen X. α-Tocopherol stereoisomer profiles in matched human maternal and umbilical cord plasma. Curr Dev Nutr. 2021 Jun;5(6):nzab073.
Acuff RV, Dunworth RG, Webb LW, Lane JR. Transport of deuterium-labeled tocopherols during pregnancy. Am J Clin Nutr. 1998 Mar;67(3):459–64.
Hatzopoulos AK, Rigotti A, Rosenberg RD, Krieger M. Temporal and spatial pattern of expression of the HDL receptor SR-BI during murine embryogenesis. J Lipid Res. 1998 Mar;39(3):495–508.
Chatuphonprasert W, Jarukamjorn K, Ellinger I. Physiology and pathophysiology of steroid biosynthesis, transport and metabolism in the human placenta. Front Pharmacol. 2018;9:1027.
Miettinen HE, Rayburn H, Krieger M. Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)-deficient mice. J Clin Invest. 2001 Dec;108(11):1717–22.
Mardones P, Rigotti A. Cellular mechanisms of vitamin E uptake: relevance in alpha-tocopherol metabolism and potential implications for disease. J Nutr Biochem. 2004 May;15(5):252–60.
Witt W, Kolleck I, Fechner H, Sinha P, Rustow B. Regulation by vitamin E of the scavenger receptor BI in rat liver and HepG2 cells. J Lipid Res. 2000 Dec;41(12):2009–16.
Traber MG, Burton GW, Ingold KU, Kayden HJ. RRR- and SRR-alpha-tocopherols are secreted without discrimination in human chylomicrons, but RRR-alpha-tocopherol is preferentially secreted in very low density lipoproteins. J Lipid Res. 1990 Apr;31(4):675–85.
Hosomi A, Arita M, Sato Y, Kiyose C, Ueda T, Igarashi O, et al. Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs. FEBS Lett. 1997 Jun 2;409(1):105–8.
Jialal I, Fuller CJ, Huet BA. The effect of alpha-tocopherol supplementation on LDL oxidation. A dose-response study. Arterioscler Thromb Vasc Biol. 1995 Feb;15(2):190–8.
Miller NJ, Paganga G, Wiseman S, Van Nielen W, Tijburg L, Chowienczyk P, et al. Total antioxidant activity of low density lipoproteins and the relationship with alpha-tocopherol status. FEBS Lett. 1995 May 29;365(2–3):164–6.
Reaven PD, Witztum JL. Comparison of supplementation of RRR-alpha-tocopherol and racemic alpha-tocopherol in humans. Effects on lipid levels and lipoprotein susceptibility to oxidation. Arterioscler Thromb. 1993 Apr;13(4):601–8.
Devaraj S, Adams-Huet B, Fuller CJ, Jialal I. Dose-response comparison of RRR-alpha-tocopherol and all-racemic alpha-tocopherol on LDL oxidation. Arterioscler Thromb Vasc Biol. 1997 Oct;17(10):2273–9.
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