Vitamin C

The requirement for dietary vitamin C is based on its role as an antioxidant, and was determined by estimating the quantity of dietary vitamin C needed to maximise its concentration in neutrophils, where it reduces reactive oxygen species produced during phagocytosis.[1]

Cardiovascular Disease (CVD)

The hypothesis that vitamin C may play a role in CVD prevention also draws support from the vitamin’s antioxidant capabilities. The epidemiological evidence relating fruit and vegetable intake to reduced risk of CVD may be explained, at least in part, by antioxidant content, and especially the role of these antioxidants in preventing oxidative changes to LDL.[2] Oxidized LDL is a target for scavenger receptors, which incorporate it into plaque.[3] Therefore, the prevention of LDL oxidation by vitamin C may prevent atherosclerosis, thereby mediating a potential role in CVD risk reduction.

Various other functions of vitamin C may also bolster the hypothesis that vitamin C can reduce cardiovascular risk. For example, vitamin C has been shown to reduce monocyte adhesion to the endothelium.[4] Adhesion of circulating monocytes to endothelial cells is one key in the formation of atheromas, and is considered one of the early signs of the development of atherosclerosis.[4] Additionally, vitamin C has been shown to improve nitric oxide production of the endothelium, which, in turn, increases vasodilation, reducing blood pressure.[5] Furthermore, vitamin C may prevent apoptosis of vascular smooth muscle cells, which helps keep plaques more stable if atherosclerosis has developed.[6]

One meta-analysis that showed promising results with vitamin C supplementation looked at its effects on blood pressure. This analysis looked at 29 trials with a median dose of 500 mg daily vitamin C. The median duration of supplementation in these trials was only eight weeks, but in these short-term studies, it was shown that vitamin C supplementation reduced both systolic and diastolic blood pressure.[7]

Meta-analysis have also been undertaken and show benefits of vitamin C alongside vitamin E in reducing arterial stiffness and improving endothelial function.[8,9]

Importantly, multiple studies have documented increases in cardiovascular risk associated with the use of supplemental vitamin C, even when taken in doses of about 1000 mg per day.[10,11]

Skin

Nutritional status is vital for maintaining normal functioning of the skin during collagen synthesis and keratinocyte differentiation.[12] Additionally, many of the components of our antioxidant defences such as vitamins C and E and selenium are obtained from the diet, and these are likely to be important for protection against UV-induced damage.[13,14] Beauty from the inside, via nutrition, may be more effective than topical application of vitamin C.[15] However, similarly to CHD, vitamin C in isolation is only minimally effective, and most studies showing a benefit use a multi-component intervention.[16,17,18] In particular, a synergy exists between vitamin C and vitamin E, with the combination being particularly effective.[16] These results indicate the need for complete oxidant scavenging and recycling. In order to provide effective protection from UV irradiation. This combination also decreases the inflammation induced by excessive UV exposure.

The immune system

Vitamin C is an efficient water-soluble antioxidant and may protect host cells against the actions of reactive oxygen species (ROS) released by phagocytes. Phagocytes have a specific transport system by which the oxidized form of vitamin C (dehydroascorbic acid) is imported into the cell where it is converted into the reduced form of vitamin C.[19,20]

Increased ROS production during the immune response to pathogens can explain the decrease in vitamin C levels seen in several infections. There is evidence that plasma, leukocyte and urinary vitamin C levels decrease in the common cold and in other infections.[21,22] Hume and Weyers (1973) reported that vitamin C levels in leukocytes halved when subjects contracted a cold and returned to the original level one week after recovery.[23] Vitamin C levels are also decreased by pneumonia.[24,25,26,27]

Decreases in vitamin C levels during various infections imply that vitamin C administration might have a treatment effect on many patients with infections. There is no reason to assume that the saturation of plasma or leukocyte vitamin C levels during infections is reached by the 0.2 g/day intake of vitamin C that applies to healthy people (see above). In particular, Hume and Weyers (1973) showed that supplementation at the level of 0.2 g/day was insufficient to normalize leukocyte vitamin C levels in common cold patients, but when 6 g/day of vitamin C was administered for a short duration, the decline in leukocyte vitamin C induced by the common cold was essentially abolished.[23]

Safety

Doses of 1000mg or more vitamin C should not be taken long term, for reasons given in the studies above. Oral vitamin C supplementation is also not to be taken during cancer treatment due to its antioxidant effects. Intravenous vitamin C treatments are currently being evaluated for safety and efficacy.

References

1. Institute of Medicine . Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. The National Academies Press; Washington, DC, USA: 2000.
2. Salvayre R., Negre-Salvayre A., Camar C. Oxidative theory of atherosclerosis and antioxidants. Biochimie. 2015;125:281–296. doi: 10.1016/j.biochi.2015.12.014.
3. Li D., Mehta J.L. Oxidized LDL, a critical factor in atherogenesis. Cardiovasc. Res. 2005;68:353–354. doi: 10.1016/j.cardiores.2005.09.009.
4. Weber C., Erl W., Weber K., Weber P.C. Increased Adhesiveness of Isolated Monocytes to Endothelium Is Prevented by Vitamin C Intake in Smokers. Circulation. 1996;93:1488–1492. doi: 10.1161/01.CIR.93.8.1488.
5. D’uscio L.V., Milstien S., Richardson D., Smith L., Katusic Z.S. Long-term vitamin C treatment increases vascular tetrahydrobiopterin levels and nitric oxide synthase activity. Circ. Res. 2003;92:88–95. doi: 10.1161/01.RES.0000049166.33035.62.
6. Siow R.C.M., Richards J.P., Pedley K.C., Leake D.S., Mann G.E. Vitamin C Protects Human Vascular Smooth Muscle Cells Against Apoptosis Induced by Moderately Oxidized LDL Containing High Levels of Lipid Hydroperoxides. Arterioscler. Thromb. Vasc. Biol. 1999;19:2387–2394. doi: 10.1161/01.ATV.19.10.2387.
7. Juraschek S.P., Guallar E., Appel L.J., Miller E.R., III Effects of vitamin C supplementation on blood pressure: A meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 2012;95:1079–1088. doi: 10.3945/ajcn.111.027995.
8. Ashor A.W., Siervo M., Lara J., Oggioni C., Mathers J. Antioxidant Vitamin Supplementation Reduces Arterial Stiffness in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J. Nutr. 2014;144:1594–1602. doi: 10.3945/jn.114.195826.
9. Ashor A.W., Lara J., Mathers J.C., Siervo M. Effect of vitamin C on endothelial function in health and disease: A systematic review and meta-analysis of randomised controlled trials. Atherosclerosis. 2014;235:9–20. doi: 10.1016/j.atherosclerosis.2014.04.004.
10. Lee D.-H., Folsom A.R., Harnack L., Halliwell B., Jacobs D.R. Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? Am. J. Clin. Nutr. 2004;80:1194–1200.
11. Waters D.D., Alderman E.L., Hsia J., Howard B.V., Cobb F.R., Rogers W.J., Ouyang P., Thompson P., Tardif J.C., Higginson L. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: A randomized controlled trial. JAMA. 2002;288:2432–2440. doi: 10.1001/jama.288.19.2432.
12. Park K. Role of micronutrients in skin health and function. Biomol Ther (Seoul). 2015 May; 23(3):207-17.
13. Placzek M, Gaube S, Kerkmann U, Gilbertz KP, Herzinger T, Haen E, Przybilla B. Ultraviolet B-induced DNA damage in human epidermis is modified by the antioxidants ascorbic acid and D-alpha-tocopherol. J Invest Dermatol. 2005 Feb; 124(2):304-7.
14. Zussman J, Ahdout J, Kim J. Vitamins and photoaging: do scientific data support their use? J Am Acad Dermatol. 2010 Sep; 63(3):507-25.
15. Marini A. Beauty from the inside. Does it really work? Hautarzt. 2011 Aug; 62(8):614-7.
16. Fuchs J, Kern. Modulation of UV-light-induced skin inflammation by D-alpha-tocopherol and L-ascorbic acid: a clinical study using solar simulated radiation. Free Radic Biol Med. 1998 Dec; 25(9):1006-12.
17. Murray J.C., Burch J.A., Streilein R.D., Iannacchione M.A., Hall R.P., Pinnell S.R. A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation. J. Am. Acad. Dermatol. 2008;59:418–425. doi: 10.1016/j.jaad.2008.05.004.
18. Lin F.H., Lin J.Y., Gupta R.D., Tournas J.A., Burch J.A., Selim M.A., Monteiro-Riviere N.A., Grichnik J.M., Zielinski J., Pinnell S.R. Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin. J. Investig. Dermatol. 2005;125:826–832. doi: 10.1111/j.0022-202X.2005.23768.x.
19. Wang Y., Russo T.A., Kwon O., Chanock S., Rumsey S.C., Levine M. Ascorbate recycling in human neutrophils: Induction by bacteria. Proc. Natl. Acad. Sci. USA. 1997;94:13816–13819. doi: 10.1073/pnas.94.25.13816.
20. Nualart F.J., Rivas C.I., Montecinos V.P., Godoy A.S., Guaiquil V.H., Golde D.W., Vera J.C. Recycling of vitamin C by a bystander effect. J. Biol. Chem. 2003;278:10128–10133. doi: 10.1074/jbc.M210686200.
21. Hemilä H. Ph.D. Thesis. University of Helsinki; Helsinki, Finland: 2006. [(accessed on 17 March 2017)]. Do vitamins C and E affect Respiratory Infections? Available online: https://hdl.handle.net/10138/20335.
22. Hemilä H. Vitamin C and the common cold. Br. J. Nutr. 1992;67:3–16. doi: 10.1079/BJN19920004.
23. Hume R., Weyers E. Changes in leucocyte ascorbic acid during the common cold. Scott. Med. J. 1973;18:3–7. doi: 10.1177/003693307301800102.
24. Mochalkin N.I. Ascorbic acid in the complex therapy of acute pneumonia. Voenno-Meditsinskii Zhurnal. 1970;9:17–21. (In Russian).
25. Hunt C., Chakravorty N.K., Annan G., Habibzadeh N., Schorah C.J. The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. Int. J. Vitam. Nutr. Res. 1994;64:212–219.
26. Hemilä H., Louhiala P. Vitamin C for preventing and treating pneumonia. Cochrane Database Syst. Rev. 2013;8:CD005532.
27. Hemilä H., Louhiala P. Vitamin C for Preventing and Treating Pneumonia. [(accessed on 17 March 2017)]; Available online: http://www.mv.helsinki.fi/home/hemila/CP.