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Prolonged maternal vitamin C deficiency overrides preferential fetal ascorbate transport but does not influence perinatal survival in guinea pigs

  • Janne G. Schjoldager (a1), Pernille Tveden-Nyborg (a1) and Jens Lykkesfeldt (a1)


Human and guinea pig fetuses are completely dependent on an adequate maternal vitamin C (vitC) intake. Shortage of micronutrients can have negative implications for fetal health and pregnancy outcome; however, knowledge of maternal vitC deficiency's impact on fetal development is sparse and reports of pregnancy outcome have been divergent. The present study investigated whether maternal vitC deficiency affects pregnancy outcome and plasma vitC distribution between the mother and the offspring in a guinea pig model. A total of eighty pregnant Dunkin Hartley guinea pigs were randomised into two weight-stratified groups receiving either a deficient (100 mg/kg DEF) or a control (923 mg/kg CTRL) diet. VitC levels were measured in plasma during pregnancy and postpartum, and in the plasma and brain of newborns. Pregnancy outcome was recorded with respect to birth weight and perinatal survival and were similar between groups. Plasma vitC in dams declined throughout gestation in both groups (P< 0·01). Compared with maternal plasma vitC, plasma vitC of newborn pups was found to be significantly lower in the DEF group (P< 0·001) and higher in the CTRL group (P< 0·001), respectively. Brain vitC levels were significantly reduced in DEF newborn pups (P< 0·001). The present results indicate that preferential transport of vitC from the mother to the fetus is overridden during sustained maternal vitC deficiency, maintaining maternal vitC concentration at the expense of the offspring. This contradicts the notion that a fetus is protected from vitC deficiency by the placental Na-dependent vitC co-transporter, SVCT2, thus fetal development may be susceptible to the negative effects of maternal vitC deficiency.

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Corresponding author

*Corresponding author: Professor J. Lykkesfeldt, fax +45 353 53514, email


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1Guesnet, P & Alessandri, JM (2011) Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) – implications for dietary recommendations. Biochimie 93, 712.
2Birch, EE, Carlson, SE, Hoffman, DR, et al. (2010) The DIAMOND (DHA Intake And Measurement Of Neural Development) Study: a double-masked, randomized controlled clinical trial of the maturation of infant visual acuity as a function of the dietary level of docosahexaenoic acid. Am J Clin Nutr 91, 848859.
3Lozoff, B (2011) Early iron deficiency has brain and behavior effects consistent with dopaminergic dysfunction. J Nutr 141, 740S746S.
4Roth, C, Magnus, P, Schjolberg, S, et al. (2011) Folic acid supplements in pregnancy and severe language delay in children. JAMA 306, 15661573.
5Christian, P, Murray-Kolb, LE, Khatry, SK, et al. (2010) Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in Nepal. JAMA 304, 27162723.
6Christian, P (2010) Micronutrients, birth weight, and survival. Annu Rev Nutr 30, 83104.
7McDonald, SD, Han, Z, Mulla, S, et al. (2010) Overweight and obesity in mothers and risk of preterm birth and low birth weight infants: systematic review and meta-analyses. Br Med J 341, c3428.
8Tveden-Nyborg, P & Lykkesfeldt, J (2009) Does vitamin C deficiency result in impaired brain development in infants? Redox Rep 14, 26.
9Tveden-Nyborg, P, Vogt, L, Schjoldager, JG, et al. (2012) Maternal vitamin C deficiency during pregnancy persistently impairs hippocampal neurogenesis in offspring of guinea pigs. PLOS One 7, e48488.
10Tveden-Nyborg, P, Johansen, LK, Raida, Z, et al. (2009) Vitamin C deficiency in early postnatal life impairs spatial memory and reduces the number of hippocampal neurons in guinea pigs. Am J Clin Nutr 90, 540546.
11Lykkesfeldt, J, Trueba, GP, Poulsen, HE, et al. (2007) Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain. Br J Nutr 98, 11161119.
12Sotiriou, S, Gispert, S, Cheng, J, et al. (2002) Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival. Nat Med 8, 514517.
13Frikke-Schmidt, H, Tveden-Nyborg, P, Lykkesfeldt, J, et al. (2011) Vitamin C in human nutrition. In Vitamins for Prevention of Human Diseases, 1st ed., pp. 323347 [Hermann, W and Obeid, R, editors]. Berlin/New York: Walter de Gruyter GmbH & Co. KG.
14Duarte, TL & Lunec, J (2005) Review: when is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C. Free Radic Res 39, 671686.
15Teel, HM, Burke, BS & Draper, R (1938) Vitamin C in human pregnancy and lactation I studies during pregnancy. Am J Dis Child 56, 10041010.
16Dejmek, J, Ginter, E, Solansky, I, et al. (2002) Vitamin C, E and A levels in maternal and fetal blood for Czech and gypsy ethnic groups in the Czech Republic. Int J Vitam Nutr Res 72, 183190.
17de Oliveira, AM, Rondo, PHD & Barros, SBD (2004) Concentrations of ascorbic acid in the plasma of pregnant smokers and nonsmokers and their newborns. Int J Vitam Nutr Res 74, 193198.
18Prasad, PD, Huang, W, Wang, H, et al. (1998) Transport mechanisms for vitamin C in the JAR human placental choriocarcinoma cell line. Biochim Biophys Acta 1369, 141151.
19Biondi, C, Pavan, B, Dalpiaz, A, et al. (2007) Expression and characterization of vitamin C transporter in the human trophoblast cell line HTR-8/SVneo: effect of steroids, flavonoids and NSAIDs. Mol Hum Reprod 13, 7783.
20Huppertz, B (2008) The anatomy of the normal placenta. J Clin Pathol 61, 12961302.
21Carter, AM (2007) Animal models of human placentation – a review. Placenta 28, S41S47.
22Enders, AC (1965) A comparative study of fine structure of trophoblast in several hemochorial placentas. Am J Anat 116, 2967.
23Frei, B, Birlouez-Aragon, I & Lykkesfeldt, J (2012) Authors' perspective: what is the optimum intake of vitamin C in humans? Crit Rev Food Sci Nutr 52, 815829.
24Levine, M, Conry-Cantilena, C, Wang, YH, et al. (1996) Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A 93, 37043709.
25Smith, JL & Hodges, RE (1987) Serum levels of vitamin C in relation to dietary and supplemental intake of vitamin C in smokers and nonsmokers. Ann N Y Acad Sci 498, 144152.
26Schleicher, RL, Carroll, MD, Ford, ES, et al. (2009) Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003–2004 National Health and Nutrition Examination Survey (NHANES). Am J Clin Nutr 90, 12521263.
27Villalpando, S, Montalvo-Velarde, I, Zambrano, N, et al. (2003) Vitamins A, and C and folate status in Mexican children under 12 years and women 12–49 years: a probabilistic national survey. Salud Publica Mex 45, S508S519.
28Lykkesfeldt, J (2006) Smoking depletes vitamin C: should smokers be recommended to take supplements? In Cigarette Smoke & Oxidative Stress, pp. 237260 [Halliwell, B and Poulsen, HE, editors]. Berlin: Springer.
29Lykkesfeldt, J & Moos, T (2005) Age-dependent change in vitamin C status: a phenomenon of maturation rather than of ageing. Mech Ageing Dev 126, 892898.
30Tveden-Nyborg, P, Hasselholt, S, Miyashita, N, et al. (2012) Chronic vitamin C deficiency does not accelerate oxidative stress in ageing brains of guinea pigs. Basic Clin Pharmacol Toxicol 110, 524529.
31Lykkesfeldt, J (2012) Ascorbate and dehydroascorbic acid as biomarkers of oxidative stress: validity of clinical data depends on vacutainer system used. Nutr Res 32, 6669.
32Lykkesfeldt, J (2000) Determination of ascorbic acid and dehydroascorbic acid in biological samples by high-performance liquid chromatography using subtraction methods: reliable reduction with tris[2-carboxyethyl] phosphine hydrochloride. Anal Biochem 282, 8993.
33Lykkesfeldt, J (2007) Ascorbate and dehydroascorbic acid as reliable biomarkers of oxidative stress: analytical reproducibility and long-term stability of plasma samples subjected to acidic deproteinization. Cancer Epidemiol Biomarkers Prev 16, 25132516.
34Hissin, PJ & Hilf, R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74, 214226.
35Lykkesfeldt, J (2001) Determination of malondialdehyde as dithiobarbituric acid adduct in biological samples by HPLC with fluorescence detection: comparison with ultraviolet–visible spectrophotometry. Clin Chem 47, 17251727.
36Pate, SK, Lukert, BP & Kipp, DE (1996) Tissue vitamin C levels of guinea pig offspring are influenced by maternal vitamin C intake during pregnancy. J Nutr Biochem 7, 524528.
37Wegger, I & Palludan, B (1994) Vitamin C deficiency causes hematological and skeletal abnormalities during fetal development in swine. J Nutr 124, 241248.
38Bates, CJ, Cowen, TD & Tsuchiya, H (1988) Growth, ascorbic acid and iron contents of tissues of young guinea-pigs whose dams received high or low levels of dietary ascorbic acid or Fe during pregnancy and suckling. Br J Nutr 60, 487497.
39Norkus, EP, Bassi, J & Rosso, P (1979) Maternal–fetal transfer of ascorbic acid in the guinea pig. J Nutr 109, 22052212.
40Haig, D (1993) Genetic conflicts in human pregnancy. Q Rev Biol 68, 495532.
41Haig, D (2004) Evolutionary conflicts in pregnancy and calcium metabolism – a review. Placenta 25, S10S15.
42Lund, CJ & Kimble, MS (1943) Some determinants of maternal and plasma vitamin C levels. Am J Obstet Gynecol 46, 635647.
43Harrison, FE, Dawes, SM, Meredith, ME, et al. (2010) Low vitamin C and increased oxidative stress and cell death in mice that lack the sodium-dependent vitamin C transporter SVCT2. Free Radic Biol Med 49, 821829.
44Ames, BN (2006) Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci U S A 103, 1758917594.
45Mccann, JC & Ames, BN (2009) Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr 90, 889907.
46Mccann, JC & Ames, BN (2011) Adaptive dysfunction of selenoproteins from the perspective of the triage theory: why modest selenium deficiency may increase risk of diseases of aging. FASEB J 25, 17931814.
47Zalani, S, Rajalakshmi, R & Parekh, LJ (1989) Ascorbic acid concentration of human fetal tissues in relation to fetal size and gestational age. Br J Nutr 61, 601606.
48Das, S & Powers, HJ (1998) The effects of maternal intake and gestational age on materno-fetal transport of vitamin C in the guinea-pig. Br J Nutr 80, 485491.
49Braestrup, PW (1938) The content of reduced ascorbic acid in blood plasma in infants, especially at birth and in the first days of life. J Nutr 16, 363373.
50Hamil, BM, Munks, B, Moyer, EZ, et al. (1947) Vitamin C in the blood and urine of the newborn and in the cord and maternal blood. Am J Dis Child 74, 417433.
51Norkus, EP & Rosso, P (1981) Effects of maternal intake of ascorbic acid on the postnatal metabolism of this vitamin in the guinea pig. J Nutr 111, 624630.
52Ikonomidou, C & Kaindl, AM (2011) Neuronal death and oxidative stress in the developing brain. Antioxid Redox Sign 14, 15351550.
53Harrison, FE, Meredith, ME, Dawes, SM, et al. (2010) Low ascorbic acid and increased oxidative stress in gulo( − / − ) mice during development. Brain Res 1349, 143152.
54Gitto, E, Reiter, RJ, Karbownik, M, et al. (2002) Causes of oxidative stress in the pre- and perinatal period. Biol Neonate 81, 146157.
55Buonocore, G, Perrone, S, Longini, M, et al. (2003) Non protein bound iron as early predictive marker of neonatal brain damage. Brain 126, 12241230.
56Luo, ZC, Fraser, WD, Julien, P, et al. (2006) Tracing the origins of “fetal origins” of adult diseases: programming by oxidative stress? Med Hypotheses 66, 3844.
57Zhang, C, Williams, MA, King, IB, et al. (2002) Vitamin C and the risk of preeclampsia – results from dietary questionnaire and plasma assay. Epidemiology 13, 409416.
58Siega-Riz, AM, Promislow, JHE, Savitz, DA, et al. (2003) Vitamin C intake and the risk of preterm delivery. Am J Obstet Gynecol 189, 519525.
59Lee, BE, Hong, YC, Lee, KH, et al. (2004) Influence of maternal serum levels of vitamins C and E during the second trimester on birth weight and length. Eur J Clin Nutr 58, 13651371.
60Catov, JM, Bodnar, LM, Olsen, J, et al. (2011) Periconceptional multivitamin use and risk of preterm or small-for-gestational-age births in the Danish National Birth Cohort. Am J Clin Nutr 94, 906912.
61Hasan, R, Olshan, AF, Herring, AH, et al. (2009) Self-reported vitamin supplementation in early pregnancy and risk of miscarriage. Am J Epidemiol 169, 13121318.
62Roberts, JM, Myatt, L, Spong, CY, et al. (2010) Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med 362, 12821291.
63Hauth, JC, Clifton, RG, Roberts, JM, et al. (2010) Vitamin C and E supplementation to prevent spontaneous preterm birth a randomized controlled trial. Obstet Gynecol 116, 653658.
64Spinnato, JA, Freire, S, Silva, JLPE, et al. (2007) Antioxidant therapy to prevent preeclampsia – a randomized controlled trial. Obstet Gynecol 110, 13111318.
65Rumbold A, Middleton P, Pan N, et al. (2011) Vitamin supplementation for preventing miscarriage. The Cochrane Database of Systematic Reviews, CD004073.
66Wang, YZ, Ren, WH, Liao, WQ, et al. (2009) Concentrations of antioxidant vitamins in maternal and cord serum and their effect on birth outcomes. J Nutr Sci Vitaminol (Tokyo) 55, 18.
67Lykkesfeldt, J & Poulsen, HE (2010) Is vitamin C supplementation beneficial? Lessons learned from randomised controlled trials. Br J Nutr 103, 12511259.
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