Vitamin C Physiology: The Known and the Unknown in Obesity

Büşra Totan^1, , Hatice Baygut¹ and Makbule Gezmen Karadağ¹

¹Department of Nutrition and Dietetics, Gazi University, Ankara, Türkiye

Cite this paper:
Büşra Totan, Hatice Baygut and Makbule Gezmen Karadağ. Vitamin C Physiology: The Known and the Unknown in Obesity. Journal of Food and Nutrition Research. 2019; 7(8):613-618. doi: 10.12691/jfnr-7-8-9

Abstract

Vitamin C is effective in strengthening the immune system, capillary blood vessels and protecting the dental health, as well as in the convenient use of iron, calcium, thiamine, riboflavin, folic acid, vitamin A and E in the body. Vitamin C also acts as a cofactor for 15 different enzymes, and shows antioxidant activity as a electron donor reducing agent. It acts as a powerful free radical scavenger by protecting tissues against oxidative stress and reduces inflammation. Obesity is defined as “mild inflammatory disease” due to the increase in inflammatory markers such as C reactive protein (CRP), tumor necrosis factor alpha (TNF) and IL-6. Since antioxidant enzyme activity and serum antioxidant levels decrease in obese individuals, the effect of antioxidant vitamins on weight loss is further investigated. In studies investigating the effectiveness of vitamin C in the treatment of obesity; vitamin C was found to reduce systemic inflammation by inhibiting CRP and TNF alpha pathways, shown to inhibit the hypoxia in adipose tissue with potential for protection against free radicals and decreasing lipid peroxidation. On the other hand, it was shown that vitamin C inhibits mature adipocyte formation and cell growth, inhibits lipolysis, and can be considered as a treatment model for obesity to offer solutions for abnormal fat accumulation. In this review, the action mechanism of vitamin C and its role in dietary treatment were investigated in order to prevent obesity complications and to provide weight loss.

Keywords:
obesity vitamin C mechanism inflammation

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Padayatty, S.C. Levine, M. 2016. Vitamin C physiology: the known and the unknown and Goldilocks. Oral Dis. 22(6):463-493.
[2]	Baysal, A. .2007. Beslenme. Ankara: Hatipoğlu Yayınevi. 244-253.
[3]	Corpe, C.P., Eck, P., Wang, J., Al-Hasani, H., Levine, M. 2013. Intestinal dehydroascorbic acid (DHA) transport mediated by the facilitative sugar transporters, GLUT2 and GLUT8. J Biol Chem. 288:9092-9101.
[4]	Wang, H., Dutta, B., Huang, W., Devoe, L.D., Leibach, F.H., Ganapathy, V., Prasad, P.D. 1999. Human Na(+)-dependent vitamin C transporter 1 (hSVCT1): primary structure, functional characteristics and evidence for a non-functional splice variant. Biochim Biophys Acta. 1461:1-9.
[5]	Aksoy, M. .2008. Beslenme Biyokimyası. Ankara: Hatiboğlu Yayınevi. 475-485.
[6]	Rutkowski, M., Grzegorczyk, K. 1999. Vitamin C in medicine: "normal concentration" in serum. Pol Merkur Lekarski. 6(31): 57-60.
[7]	Veedamali S. Subramanian, V.S., Sabui, S., Subramenium, G.A., Marchant, S.J., Said, H.M. Tumor Necrosis Factor alpha (TNF-α) reduces intestinal vitamin C uptake: a role for NF2κB mediated signaling. Am J Physiol Gastrointest Liver Physiol. 2018 Apr 6.
[8]	Pearson, J.F., Pullar, J.M., Wilson, R. Spittlehouse, J.K., Vissers, M.C. 2017. Vitamin C Status Correlates with Markers of Metabolic and Cognitive Health in 50-Year-Olds: Findings of the CHALICE Cohort Study. Nutrients. 9(831): 1-15.
[9]	German Nutrition Society (DGE). 2015. New Reference Values for Vitamin C Intake. Ann Nutr Metab. 67(1):13-20.
[10]	Türkiye Beslenme Rehberi. TÜBER-2015.
[11]	Handelman, G.J. 2011. New insight on vitamin C in patients with chronic kidney disease. J Ren Nutr. 21:110-112.
[12]	Ellulu, M.S. 2017. Obesity, cardiovascular disease, and role of vitamin C on inflammation: a review of facts and underlying mechanisms. Inflammopharmacol. 25:313-328.
[13]	Sorice, A., Guerriero, E., Capone, F., Colonna, C., Castello, G. And et al. 2014. Ascorbic Acid: Its Role in Immune System and Chronic Inflammation Diseases. Mini-Reviews in Medicinal Chemistry. 14(5):1-10.
[14]	Chen, Q., Espey, M.G., Sun, A.Y., Lee, J.H., Krishna, M.C., Shacter, E., and et al. 2007. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. PNAS. 104(21):8749-8754.
[15]	Ohno, S., Ohno, Y., Suzuki, N., Soma, G., Inoue, M. 2009. High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer. Antıcancer Research. 29:809-816.
[16]	Zhou, S.S., Chen, D.L., Zhou, C.Y. 2015. Vitamin paradox in obesity: Deficiency or excess? World J Diabetes. 6(10):1158-1167.
[17]	Fernández-Sánchez, A., Santillán, E.M., Bautista, M., Esquivel-Soto, J., Morales-González, A. and et al. 2011. Inflammation, Oxidative Stress, and Obesity. Int. J. Mol. Sci. 12(5):3117-3132.
[18]	Diaz, D.F. Campion, J. Milagro, FI. Coque N. Aliaga-Moreno MJ. Martinez J.A. 2010. Vitamin C inhibits leptin secretion and some glucose/lipid metabolic pathways in primary rat adipocytes. J Mol Endocrinol. 45(1):33-43.
[19]	Büyükuslu, N., Yiğitbaşı, T. 2015. Reaktif Oksijen Türleri ve Obezitede Oksidatif Stres. MÜSBED. 5(3):197-203.
[20]	Hancı T., Türkön, H., Aydoğdu, A.Ç., Yıldız, Ö., Karademirci, İ. 2012. Yüksek Duyarlıklı C-reaktif Protein (HSCRP) ve Obezite İlişkisi. Türk Klinik Biyokimya Derg. 10(1): 1-7.
[21]	Schectman, G., Byrd, J.C., Gruchow, H.W. 1989. The influence of smoking on vitamin C status in adults. Am J Public Health. 79(2):158-162.
[22]	Singh, R.B., Beegom, R., Rastogi, S.S., Gaoli, Z., Shoumin, Z. 1998. Association of low plasma concentrations of antioxidant vitamins, magnesium and zinc with high body fat per cent measured by bioelectrical impedance analysis in Indian men. Magnesium Research. 11(1):3-10.
[23]	Canoy, D., Wareham, N., Welch, A., Bingham, S., Luben, R., Day, N., and Khaw. K.T. 2005. Plasma ascorbic acid concentrations and fat distribution in 19,068 British men and women in the European prospective investigation into cancer and nutrition Norfolk cohort study. Am J Clin Nutr. 82(6):1203-1209.
[24]	Aasheim, E.T., Hofso, D., Hjelmesaeth, J., Birkeland, K.I., and Bohmer. T. 2008. Vitamin status in morbidly obese patients: a crosssectional study. Am J Clin Nutr. 87(2):362-369.
[25]	Rendo-Urteaga T, Puchau B, Chueca M, Oyarzabal M, Azcona-Sanjulian MC, Martinez JA, Marti A. 2013. Total antioxidant capacity and oxidative stress after a 10-week dietary intervention program in obese children. Eur J Pediatr. 173:609-616.
[26]	Naylor, G.J., Grant, L., Smith, C. 1985. A double blind placebo controlled trial of ascorbic acid in obesity. Nutr Health. 4:25-28.
[27]	Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., and et al. 2004. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 114(12):1752-1761.
[28]	Le Lay, S., Simard, G., Martinez, M.C., Andriantsitohaina, R. 2014. Oxidative stres and metabolic pathologies: from an adipocentric point of view. Oxid Med Cell Longev. 908539:1-18.
[29]	Sies, H., Stahl, W. 1995. Vitamins E and C, beta-carotene, and other carotenoids as antioxidants. Am J Clin Nutr. 62:1315-1321.
[30]	Niki, E. 1991. Action of ascorbic acid as a scavenger of active and stable oxygen radicals. Am J Clin Nutr. 54(6):1119-1124.
[31]	Keaney, J.F., Larson, M.G., Vasan, R.S., Wilson, P., Lipinska, I. 2003. Obesity and Systemic Oxidative Stress Clinical Correlates of Oxidative Stress in The Framingham Study. Arterioscler Thromb Vasc Biol. 23:434-439.
[32]	Perticone, F., Ceravolo, R., Candigliota, M., Ventura, G. Iacopino, S. et al. 2001. Obesity and Body Fat Distribution Induce Endothelial Dysfunction by Oxidative Stress Protective Effect of Vitamin C. Diabetes. 50:159-165.
[33]	Diaz, D.F. Lopez, P., Quintero, P., Martinez, J.A. 2014. Vitamin C in the Treatment and/or Prevention of Obesity. J Nutr Sci Vitaminol. 60:367-379.
[34]	Galili, O., Versari, D., Sattler, K.J., Olson, M.L., Mannheim, D. et al. 2007. Early experimental obesity is associated with endothelial dysfunction and oxidative stress. Am J Physiol Heart Circ Physiol. 292(2):904-911.
[35]	Zhang, Y.J., Gan, R.Y., Lis Zhou, Y., Li, A. And et al. 2015. Antioxidant Phytochemicals for the Prevention and Treatment of Chronic Diseases. Molecules. 20:21138-21156.
[36]	Ford, E.S., Liu, S., Mannino, D.M., Giles, W.H., Smith, S.J. 2003. C-reactive protein concentration and concentrations of blood vitamins, carotenoids, and selenium among United States adults. Eur J Clin Nutr. 57:1157-1163.
[37]	Jang, I.S., Ko, Y.H., Moon, Y.S., Sohn, S.H. 2014. Effects of vitamin C or E on the pro-inflammatory cytokines, heat shock protein 70 and antioxidant status in broiler chicks under summer conditions. Asian Aust J Anim Sci. 27:749-756.
[38]	Peluso, I., Villano, D.V., Roberts, S.A., Cesqui, E., Raguzzini, A., Borges, G. and et al. 2014. Consumption of mixed fruit-juice drink and vitamin C reduces postprandial stress induced by a high fat meal in healthy overweight subjects. Curr Pharm Des. 20:1020-1024.
[39]	Devi, S.A., Vani, R. Subramanyam, M.V., Reddy, S.S., Jeevaratnam, K. 2007. Intermittent hypobaric hypoxia‐induced oxidative stress in rat erythrocytes: protective effects of vitamin E, vitamin C, and carnitine. Cell Biochem Funct. 25:221-231.
[40]	Trayhurn, P.Hypoxia and adipose tissue function and dysfunction in obesity. Treatment of Chronic Diseases. Molecules 2015, 20, 21138–21156.
[41]	Suganami, T., Nishida, J., Ogawa, Y. 2005. A Paracrine Loop Between Adipocytes and Macrophages Aggravates Inflammatory Changes. Arterioscler Thromb Vasc Biol. 25(10):2062-2068.
[42]	Murer, S.B., Aeberli, I., Braegger, C.P., Gittermann, M., Hersberger, M. and et al. 2014. Antioxidant supplements reduced oxidative stress and stabilized liver function tests but did not reduce inflammation in a randomized controlled trial in obese children and adolescents. J Nutr. 144:193-201.
[43]	Franch, P.C., López‐Jaén, A.B., Mano‐Hernández, A.D., Sentandreu, E., Simó‐Jordá, R. 2010. Oxidative markers in children with severe obesity following low‐calorie diets supplemented with mandarin juice. Acta Paediatrica. 99: 1841-1846.
[44]	Diaz D.F., Campion, J., Arellano, A.V., Milagro, F.I., Moreno-Aliaga, M.J., Martinez, JA. 2012. Fat intake leads to differential response of rat adipocytes to glucose, insulin and ascorbic acid. Exp Biol Med (Maywood). 237(4):407-416.
[45]	Brauer, H.K., Kather, H. 1995. The stimulus-sensitive H2O2-generating system present in human fat-cell plasma membranes is multireceptor-linked and under antagonistic control by hormones and cytokines. Biochem J. 307(2):549-556.
[46]	Hasegawa, N., Niimi, N., Odani, F. 2002. Vitamin C is one of the lipolytic substances in green tea. Phytother Res. 16(1):891-892.
[47]	Campion, J., Milagro, F.I., Fernandez, D., Martinez, J.A. 2006. Differential gene expression and adiposity reduction induced by ascorbic acid supplementation in a cafeteria model of obesity. J Physiol Biochem. 62:71-80.
[48]	Diaz, D.F., Campion, J,. Milagro, F.I., Paternain, L., Solomon, A., Martinez, J.A. 2009. Ascorbic acid oral treatment modifies lipolytic response and behavioural activity but not glucocorticoid metabolism in cafeteria diet fed rats. Acta Physiol. 195(4):449-457.
[49]	Rahman, F., Frouh, F.A., Bordignon, B. et al. 2014. Ascorbic acid is a dose-dependent inhibitor of adipocyte differentiation, probably by reducing cAMP pool. Frontiers in Cell and Developmental Biology. 29(2):1-10.
[50]	Kaya,F., Belin,S., Bourgeois,P., Micaleff,J.,Blin, O., Fontés, M. 2007. Ascorbic acid inhibits PMP22 expression by reducing cAMP levels. Neuromuscul. Disord. 17:248-253.
[51]	Abdel-Wahab, Y.H., O’Harte, F.P., Mooney, M.H., Barnett, C.R., and Flatt. P.R. 2002. Vitamin C supplementation decreases insulin glycation and improves glucose homeostasis in obese hyperglycemic (ob/ob) mice. Metabolism. 51(4):514-517.
[52]	Cárcamo, J.M., Pedraza, A., Bórquez-Ojeda, O., Golde, D.W. 2002. Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation. Biochemistry.41(43):12995-3002.
[53]	Paolisso, G., Balbi, V., Volpe, C., Varricchio, G., Gambardella, A. And et al. 1995. Metabolic benefits deriving from chronic vitamin C supplementation in aged non-insulin dependent diabetics. J Am Coll Nutr. 14:387-392.
[54]	Aeberli, I., Molinari, L., Spinas, G., Lehmann, R., l’Allemand, D., Zimmermann, M.B. 2006. Dietary intakes of fat and antioxidant vitamins are predictors of subclinical inflammation in overweight Swiss children. Am J Clin Nutr. 84(4):748-755.
[55]	Larsen, SC., Ängquist, L., Ahluwalia, TS., Skaaby, T., Roswall, N., Tjønneland, A., Halkjær, J., Overvad, K., Pedersen, O., Hansen, T., and Linneberg. A. 2014. Dietary ascorbic acid and subsequent change in body weight and waist circumference: associations may depend on genetic predisposition to obesity-a prospective study of three independent cohorts. Nutrition journal. 13(1):43.
[56]	Wilson, R., Willis, J., Gearry, R., Skidmore, P., Fleming, E., Frampton, C., and Carr. A. 2017. Inadequate vitamin C status in prediabetes and type 2 diabetes mellitus: Associations with glycaemic control, obesity, and smoking. Nutrients. 9(9): 997.
[57]	Thornton, S.J., Wong, I.T., Neumann, R., Kozlowski, P. Wasan, K.M. 2011. Dietary supplementation with phytosterol and ascorbic acid reduces body mass accumulation and alters food transit time in a diet-induced obesity mouse model. Lipids in health and disease. 10(1):107.
[58]	Johnston, C.S., Beezhold, B.L., Mostow, B. and Swan, P.D. 2007. Plasma vitamin C is inversely related to body mass index and waist circumference but not to plasma adiponectin in nonsmoking adults. The Journal of Nutrition. 137(7):1757-1762.