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High dietary fat and cholesterol exacerbates chronic vitamin C deficiency in guinea pigs

  • Henriette Frikke-Schmidt (a1), Pernille Tveden-Nyborg (a1), Malene Muusfeldt Birck (a1) and Jens Lykkesfeldt (a1)
Abstract

Vitamin C deficiency – or hypovitaminosis C defined as a plasma concentration below 23 μm – is estimated to affect hundreds of millions of people in the Western world, in particular subpopulations of low socio-economic status that tend to eat diets of poor nutritional value. Recent studies by us have shown that vitamin C deficiency may result in impaired brain development. Thus, the aim of the present study was to investigate if a poor diet high in fat and cholesterol affects the vitamin C status of guinea pigs kept on either sufficient or deficient levels of dietary ascorbate (Asc) for up to 6 months with particular emphasis on the brain. The present results show that a high-fat and cholesterol diet significantly decreased the vitamin C concentrations in the brain, irrespective of the vitamin C status of the animal (P < 0·001). The brain Asc oxidation ratio only depended on vitamin C status (P < 0·0001) and not on the dietary lipid content. In plasma, the levels of Asc significantly decreased when vitamin C in the diet was low or when the fat/cholesterol content was high (P < 0·0001 for both). The Asc oxidation ratio increased both with low vitamin C and with high fat and cholesterol content (P < 0·0001 for both). We show here for the first time that vitamin C homoeostasis of brain is affected by a diet rich in fat and cholesterol. The present findings suggest that this type of diet increases the turnover of Asc; hence, individuals consuming high-lipid diets may be at increased risk of vitamin C deficiency.

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Corresponding author
*Corresponding author: Professor J. Lykkesfeldt, fax +45 35 35 35 14, email jopl@life.ku.dk
References
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1Khaw, KT, Bingham, S, Welch, A, et al. (2001) Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition. Lancet 357, 657663.
2Ginter, E (2007) Chronic vitamin C deficiency increases the risk of cardiovascular diseases. Bratisl Lek Listy 108, 417421.
3Cunningham, JJ, Ellis, SL, McVeigh, KL, et al. (1991) Reduced mononuclear leukocyte ascorbic acid content in adults with insulin-dependent diabetes mellitus consuming adequate dietary vitamin C. Metabolism 40, 146149.
4Jenab, M, Riboli, E, Ferrari, P, et al. (2006) Plasma and dietary vitamin C levels and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Carcinogenesis 27, 22502257.
5Fairfield, KM & Fletcher, RH (2002) Vitamins for chronic disease prevention in adults: scientific review. JAMA 287, 31163126.
6Lykkesfeldt, 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.
7Tveden-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.
8Harrison, FE, Hosseini, AH, Dawes, SM, et al. (2009) Ascorbic acid attenuates scopolamine-induced spatial learning deficits in the water maze. Behav Brain Res 205, 550558.
9Tveden-Nyborg, P & Lykkesfeldt, J (2009) Does vitamin C deficiency result in impaired brain development in infants? Redox Rep 14, 26.
10Rice, ME & Russo-Menna, I (1998) Differential compartmentalization of brain ascorbate and glutathione between neurons and glia. Neuroscience 82, 12131223.
11Kuo, CH, Yonehara, N & Yoshida, H (1979) Subcellular ascorbic acid in scorbutic guinea pig brain. J Nutr Sci Vitaminol (Tokyo) 25, 913.
12Diliberto, EJ Jr & Allen, PL (1980) Semidehydroascorbate as a product of the enzymic conversion of dopamine to norepinephrine. Coupling of semidehydroascorbate reductase to dopamine-beta-hydroxylase. Mol Pharmacol 17, 421426.
13Rebec, GV & Pierce, RC (1994) A vitamin as neuromodulator: ascorbate release into the extracellular fluid of the brain regulates dopaminergic and glutamatergic transmission. Prog Neurobiol 43, 537565.
14Lee, JY, Chang, MY, Park, CH, et al. (2003) Ascorbate-induced differentiation of embryonic cortical precursors into neurons and astrocytes. J Neurosci Res 73, 156165.
15Harrison, FE, Yu, SS, Van Den Bossche, KL, et al. (2008) Elevated oxidative stress and sensorimotor deficits but normal cognition in mice that cannot synthesize ascorbic acid. J Neurochem 106, 11981208.
16Mosdol, A, Erens, B & Brunner, EJ (2008) Estimated prevalence and predictors of vitamin C deficiency within UK's low-income population. J Public Health (Oxf) 30, 456460.
17Hampl, JS, Taylor, CA & Johnston, CS (2004) Vitamin C deficiency and depletion in the United States: the Third National Health and Nutrition Examination Survey, 1988 to 1994. Am J Public Health 94, 870875.
18Wrieden, WL, Hannah, MK, Bolton-Smith, C, et al. (2000) Plasma vitamin C and food choice in the third Glasgow MONICA population survey. J Epidemiol Community Health 54, 355360.
19Bjorkhem, I & Kallner, A (1976) Hepatic 7-alpha-hydroxylation of cholesterol in ascorbate-deficient and ascorbate-supplemented guinea pigs. J Lipid Res 17, 360365.
20Dunn, WA, Rettura, G, Seifter, E, et al. (1984) Carnitine biosynthesis from gamma-butyrobetaine and from exogenous protein-bound 6-N-trimethyl-l-lysine by the perfused guinea pig liver. Effect of ascorbate deficiency on the in situ activity of gamma-butyrobetaine hydroxylase. J Biol Chem 259, 1076410770.
21Nelson, PJ, Pruitt, RE, Henderson, LL, et al. (1981) Effect of ascorbic acid deficiency on the in vivo synthesis of carnitine. Biochim Biophys Acta 672, 123127.
22Ha, TY, Otsuka, M & Arakawa, N (1990) The effect of graded doses of ascorbic acid on the tissue carnitine and plasma lipid concentrations. J Nutr Sci Vitaminol (Tokyo) 36, 227234.
23Fernandez, ML (2001) Guinea pigs as models for cholesterol and lipoprotein metabolism. J Nutr 131, 1020.
24Frikke-Schmidt, H & Lykkesfeldt, J (2009) Role of marginal vitamin C deficiency in atherogenesis: in vivo models and clinical studies. Basic Clin Pharmacol Toxicol 104, 419433.
25Cos, E, Ramjiganesh, T, Roy, S, et al. (2001) Soluble fiber and soybean protein reduce atherosclerotic lesions in guinea pigs. Sex and hormonal status determine lesion extension. Lipids 36, 12091216.
26Lykkesfeldt, 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.
27Lykkesfeldt, J (2002) Measurement of ascorbic acid and dehydroascorbic acid in biological samples. In Current Protocols in Toxicology, pp. 7.6.17.6.15 [Maines, M, Costa, LG, Hodson, E and Reed, JC, editors]. New York: John Wiley & Sons.
28Sattler, W, Mohr, D & Stocker, R (1994) Rapid isolation of lipoproteins and assessment of their peroxidation by high-performance liquid chromatography postcolumn chemiluminescence. Methods Enzymol 233, 469489.
29Martin, J & White, IN (1991) Fluorimetric determination of oxidised and reduced glutathione in cells and tissues by high-performance liquid chromatography following derivatization with dansyl chloride. J Chromatogr 568, 219225.
30Ginter, E (1978) Marginal vitamin C deficiency, lipid metabolism, and atherogenesis. Adv Lipid Res 16, 167220.
31Odermarsky, M, Lykkesfeldt, J & Liuba, P (2009) Poor vitamin C status is associated with increased carotid intima-media thickness, decreased microvascular function, and delayed myocardial repolarization in young patients with type 1 diabetes. Am J Clin Nutr 90, 447452.
32Christen, S, Finckh, B, Lykkesfeldt, J, et al. (2005) Oxidative stress precedes peak systemic inflammatory response in pediatric patients undergoing cardiopulmonary bypass operation. Free Radic Biol Med 38, 13231332.
33Lykkesfeldt, J, Loft, S & Poulsen, HE (1995) Determination of ascorbic acid and dehydroascorbic acid in plasma by high-performance liquid chromatography with coulometric detection – are they reliable biomarkers of oxidative stress? Anal Biochem 229, 329335.
34Sharma, P, Pramod, J, Sharma, PK, et al. (1990) Effect of vitamin C deficiency and excess on the liver: a histopathological and biochemical study in guinea pigs fed normal or high cholesterol diet. Indian J Pathol Microbiol 33, 307313.
35Sharma, P, Pramod, J, Sharma, PK, et al. (1988) Effect of vitamin C administration on serum & aortic lipid profile of guineapigs. Indian J Med Res 87, 283289.
36Satinder, , Sarkar, AK, Majumdar, S, et al. (1987) Effect of ascorbic acid deficiency on the development of experimental atherosclerosis. Indian J Med Res 86, 351360.
37Kothari, LK & Sharma, P (1988) Aggravation of cholesterol induced hyperlipidemia by chronic vitamin C deficiency: experimental study in guinea pigs. Acta Biol Hung 39, 4957.
38Nambisan, B & Kurup, PA (1975) Ascorbic acid and glycosaminoglycan and lipid metabolism in guinea pigs fed normal and atherogenic diets. Atherosclerosis 22, 447461.
39Ginter, E, Bobek, P, Babala, J, et al. (1969) The effect of ascorbic acid on the lipid metabolism of guinea-pigs fed an atherogenic diet. Cor Vasa 11, 6573.
40Ginter, E, Babala, J & Cerven, J (1969) The effect of chronic hypovitaminosis C on the metabolism of cholesterol and atherogenisis in guinea pigs. J Atheroscler Res 10, 341352.
41Ohara, Y, Peterson, TE & Harrison, DG (1993) Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest 91, 25462551.
42Reilly, MP, Pratico, D, Delanty, N, et al. (1998) Increased formation of distinct F2 isoprostanes in hypercholesterolemia. Circulation 98, 28222828.
43Furukawa, S, Fujita, T, Shimabukuro, M, et al. (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114, 17521761.
44Michels, AJ & Hagen, TM (2009) Hepatocyte nuclear factor 1 is essential for transcription of sodium-dependent vitamin C transporter protein 1. Am J Physiol Cell Physiol 297, C1220C1227.
45Fernandez, ML & Volek, JS (2006) Guinea pigs: A suitable animal model to study lipoprotein metabolism, atherosclerosis and inflammation. Nutr Metab (Lond) 3, 17.
46West, KL & Fernandez, ML (2004) Guinea pigs as models to study the hypocholesterolemic effects of drugs. Cardiovasc Drug Rev 22, 5570.
47Dietrich, M, Traber, MG, Jacques, PF, et al. (2006) Does gamma-tocopherol play a role in the primary prevention of heart disease and cancer? A review. J Am Coll Nutr 25, 292299.
48Mawatari, S, Ohnishi, Y, Kaji, Y, et al. (2003) High-cholesterol diets induce changes in lipid composition of rat erythrocyte membrane including decrease in cholesterol, increase in alpha-tocopherol and changes in fatty acids of phospholipids. Biosci Biotechnol Biochem 67, 14571464.
49Bezaire, V & Langin, D (2009) Regulation of adipose tissue lipolysis revisited. Proc Nutr Soc 68, 350360.
50Martensson, J, Han, J, Griffith, OW, et al. (1993) Glutathione ester delays the onset of scurvy in ascorbate-deficient guinea pigs. Proc Natl Acad Sci U S A 90, 317321.
51Martensson, J & Meister, A (1991) Glutathione deficiency decreases tissue ascorbate levels in newborn rats: ascorbate spares glutathione and protects. Proc Natl Acad Sci U S A 88, 46564660.
52Jiang, Q, Lykkesfeldt, J, Shigenaga, MK, et al. (2002) Gamma-tocopherol supplementation inhibits protein nitration and ascorbate oxidation in rats with inflammation. Free Radic Biol Med 33, 15341542.
53Hill, KE, Motley, AK, May, JM, et al. (2009) Combined selenium and vitamin C deficiency causes cell death in guinea pig skeletal muscle. Nutr Res 29, 213219.
54Bertinato, J, Hidiroglou, N, Peace, R, et al. (2007) Sparing effects of selenium and ascorbic acid on vitamin C and E in guinea pig tissues. Nutr J 6, 7.
55Barja, G, Lopez-Torres, M, Perez-Campo, R, et al. (1994) Dietary vitamin C decreases endogenous protein oxidative damage, malondialdehyde, and lipid peroxidation and maintains fatty acid unsaturation in the guinea pig liver. Free Radic Biol Med 17, 105115.
56Chakraborty, S, Nandi, A, Mukhopadhyay, M, et al. (1994) Ascorbate protects guinea pig tissues against lipid peroxidation. Free Radic Biol Med 16, 417426.
57Lykkesfeldt, J (2002) Increased oxidative damage in vitamin C deficiency is accompanied by induction of ascorbic acid recycling capacity in young but not mature guinea pigs. Free Radic Res 36, 567574.
58Burton, GW, Wronska, U, Stone, L, et al. (1990) Biokinetics of dietary RRR-alpha-tocopherol in the male guinea pig at three dietary levels of vitamin C and two levels of vitamin E. Evidence that vitamin C does not “spare” vitamin E in vivo. Lipids 25, 199210.
59Sato, K, Niki, E & Shimasaki, H (1990) Free radical-mediated chain oxidation of low density lipoprotein and its synergistic inhibition by vitamin E and vitamin C. Arch Biochem Biophys 279, 402405.
60Frei, B (1991) Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage. Am J Clin Nutr 54, 1113S1118S.
61Hughes, RE, Hurley, RJ & Jones, PR (1971) The retention of ascorbic acid by guinea-pig tissues. Br J Nutr 26, 433438.
62Lykkesfeldt, J, Christen, S, Wallock, LM, et al. (2000) Ascorbate is depleted by smoking and repleted by moderate supplementation: a study in male smokers and nonsmokers with matched dietary antioxidant intakes. Am J Clin Nutr 71, 530536.
63Lykkesfeldt, J, Loft, S, Nielsen, JB, et al. (1997) Ascorbic acid and dehydroascorbic acid as biomarkers of oxidative stress caused by smoking. Am J Clin Nutr 65, 959963.
64Lykkesfeldt, J, Prieme, H, Loft, S, et al. (1996) Effect of smoking cessation on plasma ascorbic acid concentration. BMJ 313, 91.
65Lykkesfeldt, J, Viscovich, M & Poulsen, HE (2003) Ascorbic acid recycling in human erythrocytes is induced by smoking in vivo. Free Radic Biol Med 35, 14391447.
66Subar, AF, Harlan, LC & Mattson, ME (1990) Food and nutrient intake differences between smokers and non-smokers in the US. Am J Public Health 80, 13231329.
67Lykkesfeldt, J (2006) Smoking depletes vitamin C: should smokers be recommended to take supplements. In Cigarette Smoke and Oxidative Stress, pp. 237260 [Halliwell, BB and Poulsen, HE, editors]. Berlin/Heidelberg: Springer Verlag.
68Panel on Dietary Antioxidants and Related Compounds (2000) Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. A Report of the Institute of Medicine. Washington, DC: National Academy Press.
69Cundiff, DK (2002) Diet and tobacco use: analysis of data from the diabetic control and complications trial, a randomized study. MedGenMed 4, 2.
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