Effects of vitamin C on the immune system

by Harri Hemilä

This text is based on pages 61-62 of Hemilä (2006).
This document has up to date links to documents that are available via the net.
Harri Hemilä
Department of Public Health
University of Helsinki,  Helsinki, Finland
Home:  http://www.mv.helsinki.fi/home/hemila

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Version May 29, 2012

Vitamin C and infections Effects on the immune system In the intensive search for specific molecules participating in the defense against viruses and bacteria, vitamin C has not been particularly interesting as it is not specifically and firmly linked to any single immunological mechanism. Still, it is possible that as an efficient reducing agent vitamin C has non-specific effects on diverse parts of the immune system (Hemilä 1992a, 1997a, 2003a).

Upon activation, phagocytes release a set of oxidizing agents intended to kill viruses and bacteria. Many of these oxidants appear to be harmful to the host cells, and in some cases the oxidizing agents produced during viral and bacterial infections seem to play a substantial role in the pathogenesis (Goode & Webster 1993; Peterhans 1997; Akaike et al. 1998). Vitamin C is an efficient water-soluble antioxidant and may protect host cells against the oxidants released by phagocytes, for example (Hemilä et al. 1984; Frei et al. 1989; Hemilä 1992a, 1992b, 1997a). Phagocytes have a specific transport system by which the oxidized form of vitamin C (dehydroascorbic acid) is imported into the cells, where reduced vitamin C is regenerated (Wang et al. 1997; Nualart et al. 2003). If the major role of vitamin C in the immune system is that of a physiological antioxidant protecting various host cells against oxidative stress during an infection, it could have important effects in certain conditions even though the mechanisms are apparently nonspecific.

A number of authors have reviewed the literature on vitamin C and the immune system (Bourne 1949; Thomas & Holt 1978; Gross & Newberne 1980; Beisel 1982; Leibovitz & Siegel 1981; Cunningham-Rundles et al. 1993; Jariwalla & Harakeh 1996; Hemilä 1992a, 1997a;  Webb & Villamor 2007). Overall, more than 100 studies have examined the effect of vitamin C on various parts of the immune system (Hemilä 1997a;  Webb & Villamor 2007). The concentration of vitamin C in phagocytes and lymphocytes is far higher than in plasma, indicating that it may have functional roles in these immune system cells. In various experimental settings, vitamin C has affected random migration and chemotaxis of phagocytes (Goetzl et al. 1974), transformation of influenza virus-infected lymphocytes (Manzella & Roberts 1979), production of interferon (Siegel 1974), and replication of viruses (Atherton et al. 1978; Bissell et al. 1980; Harakeh et al. 1990). In guinea pigs, vitamin C deficiency suppressed the development of tuberculin skin reactivity (Mueller & Kies 1962; Zweiman et al. 1966). Recently, vitamin C was reported to affect the gene expression of monocyte adhesion molecules (Rayment et al. 2003). In some studies it affected complement and immunoglobulin levels, but the literature is quite inconsistent on these topics.

Although the great majority of studies found effects suggesting benefits from vitamin C on the immune system, one study with 5 subjects found that 2 g/day vitamin C impaired in vitro bactericidal activity of leukocytes when using E. coli as the test organism (Shilotri & Bhat 1977). The significance of this solitary report is unclear.

Even if vitamin C had a role in the immune system, it is possible that the level of vitamin C intake is important only in particular conditions. For example, if vitamin C intake is important only in the low range of intakes, it is possible that the variation in intake does not affect the immune system in the ordinary Western population. Still, it might be a limiting factor in populations with low vitamin C intakes.

If the fundamental question is whether vitamin C intake affects the incidence and severity of infections, then laboratory measures of the immune system are only surrogate markers. Since there are quite a few examples where the effect on a clinical outcome diverged from the effect on a surrogate end point (Fleming & DeMets 1996; DeGruttola et al. 1997), the effects on surrogate end points should be considered cautiously. Neither are the physiological mechanisms usually crucial in epidemiological reasoning when considering potential cause and effect relationships, since what is biologically plausible depends upon the biological knowledge of the day and in many cases this understanding is quite limited and changes with time (Hill 1965). Nevertheless, the extensive literature on the effects of vitamin C on the immune system provides a meaningful conceptual framework to consider whether this vitamin might have effects on infections.


NOTE: All the links in the main text should be freely accessible at least as an abstract, but some links below require a permission from publisher for any access.

Akaike T, Suga M, Maeda H (1998) Free radicals in viral pathogenesis. Proc Soc Exp Biol Med 217:64-7  * see also: J Clin Invest (1990);85:739-45  

Atherton JG, Kratzing CC, Fisher A (1978) The effect of ascorbic acid on infection of chick-embryo ciliated tracheal organ cultures by coronavirus. Arch Virol 56:195-9

Beisel WR (1982) Single nutrients and immunity: vitamin C. Am J Clin Nutr 35(Feb suppl):423-8, 460-1

Bissell MJ, Hatie C, Farson DA, et al. (1980) Ascorbic acid inhibits replication and infectivity of avian RNA tumor virus. Proc Natl Acad Sci USA 77:2711-5   PMC

Bourne GH (1949) Vitamin C and immunity. Br J Nutr 2:341-7

Cunningham-Rundles WF, Berner Y, Cunningham-Rundles S (1993) Interaction of vitamin C in lymphocyte activation: current status and possible mechanisms of action. In: Nutrient Modulation of the Immune Response [Cunningham-Rundles S, ed]. NY: Marcel Decker. pp 91-103

DeGruttola V, Fleming T, Lin DY, Coombs R (1997) Validating surrogate markers – are we being naive? J Infect Dis 175:237-46  PubMed 

Fleming TR, DeMets DL (1996) Surrogate end points in clinical trials: are we being misled? Ann Intern Med 125:605-13

Frei B, England L, Ames BN (1989) Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 86:6377-81  PMC

Goetzl EJ, Wasserman SI, Gigli I, et al. (1974) Enhancement of random migration and chemotactic response of human leukocytes by ascorbic acid. J Clin Invest 53:813-8 

Goode HF, Webster NR (1993) Free radicals and antioxidants in sepsis. Crit Care Med 21:1770-6  PubMed

Gross RL, Newberne PM (1980) Role of nutrition in immunologic function: vitamin C. Physiol Rev 60:255-60, 290-302

Harakeh S, Jariwalla RJ, Pauling L (1990) Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells. Proc Natl Acad Sci USA 87:7245-9   PMC

Hemilä H, Roberts P, Wikström M (1984) Activated polymorphonuclear leucocytes consume vitamin C. FEBS Letters 178:25-30

Hemilä H (1992a) Vitamin C and the common cold. Br J Nutr 67:3-16  Manu with links to Refs   CH

Hemilä H (1992b) Vitamin C, neutrophils and the symptoms of the common cold [letter]. Pediatr Infect Dis J 11:779  Manu with links to Refs 

Hemilä H (1997a) Vitamin C and infectious diseases. In: Vitamin C in Health and Disease [Packer L, Fuchs J, eds]. NY: Marcel Dekker. pp 471-503

Hemilä H (2003a) Vitamin C, respiratory infections, and the immune system. Trends Immunol 24:579-580

Hemilä H (2006) Do vitamins C and E affect respiratory infections? [PhD Thesis]  University of Helsinki, 2006    OtherAddress

Hemilä H, Roberts P, Wikström M (1984) Activated polymorphonuclear leucocytes consume vitamin C. FEBS Lett 178:25-30

Hill AB (1965) The environment and disease: association or causation? Proc R Soc Med 58:295-300

Jariwalla RJ, Harakeh S (1996) Antiviral and immunomodulatory activities of ascorbic acid. Subcell Biochem 25:215-31

Leibovitz B, Siegel BV (1981) Ascorbic acid and the immune system. Adv Exp Med Biol 135:1-25

Manzella JP, Roberts NJ (1979) Human macrophage and lymphocyte responses to mitogen stimulation after exposure to influenza virus, ascorbic acid, and hyperthermia. J Immunol 123:1940-4

Mueller PS, Kies MW (1962) Suppression of tuberculin reaction in the scorbutic guinea pig. Nature 195:813

Nualart FJ, Rivas CI, Montecinos VP, et al. (2003) Recycling of vitamin C by a bystander effect. J Biol Chem 278:10128-33

Peterhans E (1997) Oxidants and antioxidants in viral diseases. J Nutr 127:962S-5S 

Perla D, Marmorston J (1937) Role of vitamin C in resistance. Part I Arch Pathol 23:543-75    Part II  683-712

Rayment SJ, Shaw J, Woollard KJ, et al. (2003) Vitamin C supplementation in normal subjects reduces constitutive ICAM-1 expression. Biochem Biophys Res Commun 308:339-45 

Shilotri PG, Bhat KS (1977) Effect of mega doses of vitamin C on bactericidal activity of leukocytes. Am J Clin Nutr 30:1077-81

Siegel BV (1975) Enhancement of interferon production by poly(rI).poly(rC) in mouse cell cultures by ascorbic acid. Nature 254:531-2  * see also: Infect Immun (1974);10:409-10 

Thomas WR, Holt PG (1978) Vitamin C and immunity: an assessment of the evidence. Clin Exp Immunol 32:370-9     CH

Wang Y, Russo TA, Kwon O, et al. (1997) Ascorbate recycling in human neutrophils: induction by bacteria. Proc Natl Acad Sci USA 94:13816-9   PMC

Webb AL, Villamor E (2007)  Update: effects of antioxidant and non-antioxidant vitamin supplementation on immune function.  Nutr Rev 65:181-217    PubMed

Zweiman B, Besdine RW, Hilreth EA (1966) The effect of the scorbutic state on tuberculin hypersensitivity in the guinea pig. Part I. J Immunol 96:296-300

Copyright: © 2006-2009 Harri Hemilä. This text is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.  

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