Vitamin C, Inflammatory Bowel Disease and Polymorphisms
As our understanding of human genetics has grown, we are starting to appreciate the effect of how genes and environment interact. Researchers Shaghaghi and associates published an article on the effect that variations in a vitamin C transporter have on two forms of inflammatory bowel disease. Vitamin C is a major water-soluble antioxidant. It has been shown to reduce inflammation by scavenging reactive oxygen species to prevent cellular damage according to a review by Traber and Stevens. Buffinton and Doe found that levels of vitamin C were lower in people with inflammatory bowel disease, and this could hinder recovery of the intestinal lining.
The gene SLC23A1 produces one of two vitamin C transporters located in cells in the lining of the intestine. It is required for the body to absorb vitamin C. Various polymorphisms within this gene have been shown to affect levels of ascorbic acid. In the current study, the polymorphisms in position rs6596473, rs33972313 (reported on previously by TalkingNutrition) and rs10063949 were investigated.
The authors compared polymorphism types between 162 Crohn’s disease patients, 149 patients with ulcerative colitis, and 146 ethnicity-matched controls. They found that the rs10063949G allele was associated with increased risk of Crohn’s disease, with a stronger risk found when patients had two rather than one copy of the G-variant. There was also a significant association between haplotype CGG in the rs6596473, rs33972313, and rs10063949 single nucleotide polymorphisms and Crohn’s disease, which could indicate that general deficiencies in the vitamin C transporter increase risk of this disease.
These results show that reduced absorption of vitamin C into intestinal cells increases risk of Crohn’s disease. The authors suggest that dietary supplements containing an oxidized form of vitamin C, dehydroascorbate, could be tested in an intervention study as a possible therapy for Crohn’s disease. This form of vitamin C uses another means of entering the cell and the SLC23A1 protein is not involved. This could potentially help intestinal cells repair damage done by inflammatory bowel disease, and also correct low vitamin C levels that are frequently found in people with Crohn’s disease.
Mandana Amir Shaghaghi, Charles N Bernstein, Alejandra Serrano León, Hani El-Gabalawy, and Peter Eck. Polymorphisms in the sodium-dependent ascorbate transporter gene SLC23A1 are associated with susceptibility to Crohn disease. Am J Clin Nutr 2014 ajcn.068015; First published online November 27, 2013. doi:10.3945/ajcn.113.068015
Buffinton GD, Doe WF. Altered ascorbic acid status in the mucosa from inflammatory bowel disease patients. Free Radic Res. 1995 Feb;22(2):131-43. http://www.ncbi.nlm.nih.gov/pubmed/7704184
Cahill LE, El-Sohemy A. Vitamin C transporter gene polymorphisms, dietary vitamin C and serum ascorbic acid. J Nutrigenet Nutrigenomics. 2009;2(6):292-301. doi: 10.1159/000314597. Epub 2010 Jun 30. http://www.ncbi.nlm.nih.gov/pubmed/20588054
Filippi J, Al-Jaouni R, Wiroth JB, Hébuterne X, Schneider SM. Nutritional deficiencies in patients with Crohn's disease in remission. Inflamm Bowel Dis. 2006 Mar;12(3):185-91. http://www.ncbi.nlm.nih.gov/pubmed/16534419
Timpson NJ, Forouhi NG, Brion MJ, Harbord RM, Cook DG, Johnson P, McConnachie A, Morris RW, Rodriguez S, Luan J, Ebrahim S, Padmanabhan S, Watt G, Bruckdorfer KR, Wareham NJ, Whincup PH, Chanock S, Sattar N, Lawlor DA, Davey Smith G. Genetic variation at the SLC23A1 locus is associated with circulating concentrations of L-ascorbic acid (vitamin C): evidence from 5 independent studies with >15,000 participants. Am J Clin Nutr. 2010 Aug;92(2):375-82. doi: 10.3945/ajcn.2010.29438. Epub 2010 Jun 2. http://www.ncbi.nlm.nih.gov/pubmed/20519558
Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med. 2011 Sep 1;51(5):1000-13. doi: 10.1016/j.freeradbiomed.2011.05.017. Epub 2011 May 25. http://www.ncbi.nlm.nih.gov/pubmed/21664268
Zanon-Moreno V, Ciancotti-Olivares L, Asencio J, Sanz P, Ortega-Azorin C, Pinazo-Duran MD, Corella D. Association between a SLC23A2 gene variation, plasma vitamin C levels, and risk of glaucoma in a Mediterranean population. Mol Vis. 2011;17:2997-3004. Epub 2011 Nov 17. http://www.ncbi.nlm.nih.gov/pubmed/22171153