Vitamin C Overview

Vitamin C (or L-ascorbic acid) has been postulated to have an important role in reduction in oxidative stress and prevention of cancer and heart disease, and in boosting the immune system (1, 6). (The immune boosting effects has been thought to be associated to Vitamin C’s enhancement of non-heme iron (6); although there is research opposing this view (7).) Vitamin C deficiency, as is well known, causes scurvy which is typically seen after 1 month of dietary deficiency largely due to impaired collagen biosynthesis (1). Unfortunately, despite the importance of Vitamin C, studies attempting to show that supplementation was advantageous have been equivocal (2). For one, vitamin C absorption from oral administration appears to be highly regulated such that amounts ingested over normal intake appear to be excreted (1). (Of recent note, interest in intravenous vit C has shown some potential benefits) (2). More over, there are complex interaction Vitamin C has with trace metals that may confound outcomes (see below, and in 7).

Vitamin C is synthesized endogenously in most animals, however humans and primates have lost this capability, and so for us it is an essential dietary component (1). The USDA Dietary Reference Intakes for Vitamin C indicate that the Recommended Daily Allowance for males 19+ years old is 90 mg and females of the same age range is 75 ug/d. Of note, for smokers, there is an additional 35 mg/day recommended. Food sources of vitamin C include fruits and vegetables, especially citrus, tomatoes, potatoes, red and green peppers, kiwifruit, broccoli, strawberries, Brussels sprouts, and cantaloupe. According to the 2001–2002 National Health and Nutrition Examination Survey (NHANES), mean intakes of vitamin C are 105.2 mg/day for adult males and 83.6 mg/day for adult females, meeting the currently established RDA for most nonsmoking adults.

However, large variability, excluding significant environmental factors, have been found in circulating ascorbic acid in populations, and significant differences in response to dietary vitamin C noted (3). As mentioned in the assigned paper (4), single chain polymorphisms (SNPs) in the detoxifying enzyme glutathione S-transferase M1 (GSTM1) may impact ascorbic acid function and have been associated with serum ascorbic acid concentrations (3). GSTs containing glutathione act synergistically with ascorbic acid as antioxidants and these agents seem to protect each other from oxidation (3), thus being a potential rationale for maintaining serum ascorbic acid levels. Although studies have been inconsistent, one study suggested that the presence of the SNP in those who did not meet the RDA had a 4-12-fold greater risk of ascorbic acid deficiency than those without the SNP (3). This SNP appears wide spread with evidence that this mutation may be in about 50% of the population (4).

Authors Garry Buettner and Beth Anne Jurkiewicz highlight the potential adverse impact of low ascorbic acid serum concentration in these people with this SNP. There is a “cross-over” effect for ascorbate in the presence of catalytic metals from pro-oxidant at low concentrations to anti-oxidant at higher concentrations (7 with my italics). This suggests that if you recommend vitamin C supplements, that you avoid supplements with trace irons or other metals like silica. Additionally, looking for reasons for low levels of serum vitamin C may be justifiable given the pro-oxidative effects that may result.

Although vitamin C deficiency is not typically seen as a common public health problem, there are some reports that vitamin C deficiency remains an issue (5) The identification of the SNP described above may need more research, however appears to be an interesting line of clinical investigation.

(1)        NIH Vitamin A Fact Sheet for Health Professionals: https://www.nal.usda.gov/fnic/ascorbic-acid-vitamin-c

(2)        Yan MA et al. High-Dose Parenteral Ascorbate Enhanced Chemosensitivity of Ovarian Cancer and Reduced Toxicity of Chemotherapy. Science Translational Medicine  05 Feb 2014: Vol. 6, Issue 222, pp. 22

(3)        Da Costa, et al. Genetic Determinants of Dietary Antioxidant Status. Progress in Molecular Biology and Translational Science Volume 108, 2012, Pages 179-200

(4)        Costa V et al, Nutritional genomics era: opportunities toward a genome-tailored nutritional regimen. Journal of Nutritional Biochemistry 21 (2010) 457–467

(5)        Scurvy is a serious public health problem. Slate.com, Nov 20, 2015: http://www.slate.com/articles/health_and_science/medical_examiner/2015/11/scurvy_is_common_and_should_be_diagnosed_and_treated.html

(6)        Vitamin C and iron interactions:

a.         Haliberg L etal. The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl. 1989;30:103-8.

b.         Morris ER. An overview of current information on bioavailability of dietary iron to humans. Fed Proc. 1983 Apr;42(6):1716-20

c.         Lynch SR et al. Interaction of vitamin C and iron. Ann N Y Acad Sci. 1980;355:32-44.

(7)        Garry R. Buettner and Beth Anne Jurkiewicz. Catalytic Metals, Ascorbate and Free Radicals: Combinations to Avoid. RADIATION RESEARCH 145, 532-541 (1996)

(8)        Cook JD. Effect of ascorbic acid intake on nonheme-iron absorption from a complete diet. Am J Clin Nutr. 2001;73:93–8.