Vitamin C is one of the most commonly supplemented nutrients. Although it is probably best known for its importance to immunity, vitamin C research has revealed multiple other functions within the body.
In the 1920s, vitamin C was first identified by the prospective Nobel laureate Albert Szent-Györgyi from Szeged University in Hungary, who unravelled the role of this essential vitamin for the treatment and prevention of scurvy resulting from vitamin C deficiency.
Before its discovery, around 50% of sailors developed scurvy, a condition now recognised as associated with vitamin C deficiency. It was noted that scurvy could be ameliorated by the consumption of citrus fruits, especially limes, during sea voyages and so lemon or lime juice became part of sailors’ daily rations.
Vitamin C is water soluble, which is an important factor in its function. It is also known as ascorbate or ascorbic acid.1
Functions of vitamin C
Antioxidant: One of the most powerful functions of vitamin C is as a water-soluble antioxidant (i.e. a reducing agent). When vitamin C reduces (or quenches) free radicals, it becomes oxidised itself. However, it is able to be recycled back to its reduced form by bioflavonoids and glutathione and is therefore described as being able to be oxidised reversibly. The biological role of vitamin C is related to both its antioxidant function and involvement in a multitude of both enzymatic and non-enzymatic processes. Because of its ability to donate electrons, ascorbic acid scavenges reactive oxygen species as well as singlet oxygen. High tissue levels of ascorbate provide substantial antioxidant protection where free radicals are encountered. This antioxidant activity is one of the main properties that makes vitamin C protective for cardiovascular and cognitive health.2,3
Immune support: Vitamin C has multiple effects on the immune system and has been shown to be supportive for a number of different immune cells. Leukocytes including lymphocytes can actively accumulate vitamin C against a concentration gradient demonstrating the importance of vitamin C in these cells. Vitamin C has functional as well as developmental effects on immune cells. In fact, vitamin C has a key role in both innate and adaptive immune responses.1,4
Natural Killer Cells – in clinical studies, vitamin C treatment of healthy subjects promoted and enhanced natural killer cell activities.
Monocytes/macrophages – it has been shown that monocytes contain a high concentration of vitamin C suggestsing the regulatory role of this vitamin in monocyte and macrophage functions. In support, an in vitro study revealed that intracellular accumulation of pharmacologic vitamin C concentrations could effectively inhibit apoptotic pathways in human monocytes. Vitamin C may also regulate distinct genes expressed in human macrophages, which are induced by the presence of lipopolysaccharide (found on the cell wall of gram-negative bacteria). In vitro studies have demonstrated that vitamin C application to monocytes derived from human whole blood diminished secretion of pro-inflammatory cytokines such as IL-6 and tumour necrosis factor (TNF)-α. These studies demonstrate the wide effect vitamin C has on macrophages and monocytes alone, not only supporting but also modulating immune function and inflammation.
Neutrophils – the exposure of neutrophils to oxidants inhibits their motility, which is related to oxidation of membrane lipids affecting cell membrane fluidity. In order to protect themselves from oxidative damage, neutrophils accumulate millimolar (mM) concentrations of vitamin C, resulting in improved cellular motility and migration in response of chemotactic stimuli and, subsequently, in enhanced phagocytosis of microbes.
Antimicrobial: Not only does vitamin C protect from pathogens by supporting immune function but it also acts directly as an antimicrobial. It is known that several bacteria can ferment vitamin C, whereas the presence of this vitamin exposes other species to oxidative stress, which may result in bacterial growth inhibition. The potent antibacterial effects of vitamin C are, at least in part, due to its low pH.5
- inhibits the growth of Staphylococcus aureus and Streptococci even under neutral pH conditions
- has potent growth-inhibitory effects against multi-drug resistant (MDR) bacteria such as MRSA and proven synergistic effects with natural or synthetic antibiotic compounds, this could open novel avenues for combatting infections with emerging MDR bacterial species
- also acts on viruses, parasites, and fungi.
Energy: Vitamin C is also essential for normal energy production by supporting mitochondrial function. It is needed for two dioxygenase enzymes involved in the biosynthesis of carnitine, an essential cofactor in the transport of long-chain fatty acids into the mitochondria. It thus plays an important role in the production of energy via beta-oxidation as impaired carnitine metabolism, including due to insufficient vitamin C supply, can be responsible for weakness or muscle aching.6
In one study, twenty obese adults received an oral dose of either 500mg of vitamin C or a placebo daily for four weeks. Ratings of perceived exertion during moderate exercise and general fatigue scores were significantly decreased in subjects receiving vitamin C. In another study, 44 workers who received an oral dose of 6g vitamin C daily for two weeks reported lower perceived fatigue and exhibited significantly increased blood vitamin C. These findings were confirmed when vitamin C was provided by the intravenous route, a non-physiological but relevant route of administration for research or medical purposes. In a randomised trial, 141 office workers aged 20–49 years received 10g vitamin C or a placebo in one intravenous injection. Fatigue scores two hours and one day after intervention were significantly lower in the vitamin C-treated group and especially in those who had the lowest baseline serum vitamin C.
Collagen synthesis: Vitamin C is essential for the formation of collagen. Specifically, vitamin C has been shown to stabilise collagen mRNA, thus increasing collagen protein synthesis for repair of the damaged skin. Vitamin C acts as a co-factor for the proline and lysine hydroxylases that stabilise the collagen molecule tertiary structure, and it also promotes collagen gene expression. In the skin, collagen formation is carried out mostly by the fibroblasts in the dermis, resulting in the generation of the basement membrane and dermal collagen matrix.7
Preclinical studies demonstrated that vitamin C has the potential to accelerate bone healing after a fracture, increase type I collagen synthesis, and reduce oxidative stress parameters. No adverse effects were reported with vitamin C supplementation in either animal models or human participants; thus, oral vitamin C appears to be a safe supplement but lacks clinical evidence compared with controls. Because of the limited number of human studies, it was concluded that further clinical investigations are needed before vitamin C is recommended as a post injury supplement.7
There are many functions and benefits to health of vitamin C but does it have any effect on mortality? Epidemiological studies have shown that vitamin C status is associated with a reduced incidence of death in certain populations. In the EPIC-Norfolk prospective population study, plasma concentration of ascorbic acid was inversely related to mortality from all-causes as well as from cardiovascular disease and ischaemic heart disease. While a study based on an NHANES II database found an inverse relationship between dying from any cause and low ascorbic acid in men, there was no association in women. In research looking at the elderly population, vitamin C concentration was shown to be inversely associated with subsequent mortality in both males and females while in another study ascorbic acid concentration was inversely associated with mortality from stroke but not from coronary heart disease.1
It is suggested that supplementation with vitamin C reduces hyperglycaemia and lowers blood pressure in people with hypertension by enhancing the formation of prostaglandin E1, prostacyclin and endothelial nitric oxide in addition to restoring essential fatty acid metabolism to normal and enhancing the formation of lipoxin A4, a potent anti-inflammatory, vasodilator and antioxidant. These actions are in addition to the ability of vitamin C to function as an antioxidant.1–3
It is well established that vitamin C inhibits oxidation of LDL-protein, thereby reducing the risk of atherosclerosis, but the cardiovascular outcomes related to this action and other actions of vitamin C are not fully understood. Studies have linked vitamin C to improvements in lipid profiles, arterial stiffness, and endothelial function. Overall, current research suggests that vitamin C deficiency is associated with a higher risk of mortality from CVD and that vitamin C may slightly improve endothelial function and lipid profiles in some groups, especially those with low plasma vitamin C levels.
In an NHANES II study, serum vitamin C was inversely related with the prevalence of coronary heart disease and stroke. In cross-sectional studies, blood pressure in middle aged and elderly as well as in young adults was found to be inversely associated with blood vitamin C.1
Vitamin C has long been associated with supporting immune function and therefore preventing or reducing duration of infections. Studies have demonstrated that supplementation with vitamin C appears to be able to both prevent and treat respiratory and systemic infections. Prophylactic prevention of infection requires dietary vitamin C intakes that provide at least adequate (i.e. 100-200 mg/day), to optimise cell and tissue levels. In contrast, treatment of established infections requires significantly higher (gram) doses of the vitamin to compensate for the increased inflammatory response and metabolic demand. Controlled trials found a statistically significant dose-response, for the duration of common cold symptoms, with up to 6-8 g/day of vitamin C. The negative findings of some therapeutic common cold studies might be explained by the low doses of 3-4 g/day of vitamin C. A further three controlled trials found that vitamin C prevented pneumonia.4,5,8
Vitamin C plays an important role in maintaining skin health and can promote the differentiation of keratinocytes and decrease melanin synthesis, leading to antioxidant protection against UV-induced photo-damage. Normal skin needs high concentrations of vitamin C, which plays many roles in the skin, including the formation of the skin barrier and collagen in the dermis, the ability to counteract skin oxidation, and the modulation of cell signal pathways of cell growth and differentiation.9
Research has shown that vitamin C has been effective for:
- acne scars – improves skin hardness, smoothness, and post-inflammatory pigmentation
- allergic contact dermatitis – reduces the sensitivity to ap-phenylenediamine (PPD)-containing hair dye
- psoriatic – supports normal keratinocytes
- genital herpes – improves immunity and natural defences and reduces the persistence of HPV infection
- vitiligo – increases hyperpigmentation at pigment diminished spots6
Natural sources of vitamin C include citrus fruits, kiwi, mango, strawberries, papaya, tomatoes, green leafy vegetables, and broccoli. Interestingly, the vast majority of vertebrates can synthesise vitamin C from glucose, but a few mammals, including guinea pigs and humans, have lost this ability due to a lack of the enzyme L-glucono-γ-lactone oxidase, which is necessary for the synthesis of vitamin C in vivo. Therefore, humans need to obtain vitamin C from diet.2
- Whilst vitamin C’s main function is as an antioxidant, it also has important roles in many enzymatic and non-enzymatic reactions.
- Vitamin C supports immune function by upregulating immune cells. Vitamin C has been associated with prevention and reduced duration of respiratory tract infections.
- Vitamin C also possesses anti-microbial properties by inhibiting the growth of certain bacteria including Staphylococcus, Streptococci spp. and MRSA resistant bacteria. In addition, it can inhibit fungi and virus replication.
- Vitamin C supports normal energy production by regulating enzymes which are involved in burning fat for energy by the mitochondria.
- Vitamin C has been shown to be protective against cardiovascular disease and hypertension partly due to its antioxidant capability but also by supporting blood vessel function and modulating inflammation.
- Vitamin C plays an important role in maintaining skin health and can promote the differentiation of keratinocytes and decrease melanin synthesis, leading to antioxidant protection against UV-induced photo-damage. Normal skin needs high concentrations of vitamin C, which plays many roles in the skin, including the formation of the skin barrier and collagen in the dermis, the ability to counteract skin oxidation, and the modulation of cell signal pathways of cell growth and differentiation.
If you have questions regarding the topics that have been raised, or any other health matters, please do contact me (Helen) by phone or email at any time.
firstname.lastname@example.org or 01684 310099
Helen Drake and the Cytoplan Editorial Team
- (PDF) Vitamin C and Disease: Insights from the Evolutionary Perspective | Csaba Tóth – Academia.edu. https://www.academia.edu/34133850/Vitamin_C_and_Disease_Insights_from_the_Evolutionary_Perspective?email_work_card=title. Accessed February 25, 2020.
- Ashor AW, Siervo M, Lara J, Oggioni C, Afshar S, Mathers JC. Effect of vitamin C and vitamin e supplementation on endothelial function: A systematic review and meta-analysis of randomised controlled trials. Br J Nutr. 2015;113(8):1182-1194. doi:10.1017/S0007114515000227
- Ashor AW, Lara J, Mathers JC, 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(1):9-20. doi:10.1016/j.atherosclerosis.2014.04.004
- Carr AC, Maggini S. Vitamin C and immune function. Nutrients. 2017;9(11). doi:10.3390/nu9111211
- Mousavi S, Bereswill S, Heimesaat MM. Immunomodulatory and antimicrobial effects of vitamin C. Eur J Microbiol Immunol. 2019;9(3):73-79. doi:10.1556/1886.2019.00016
- Bendich A, Machlin LJ, Scandurra O, Burton GW, Wayner DDM. The antioxidant role of vitamin C. Adv Free Radic Biol Med. 1986;2(2):419-444. doi:10.1016/S8755-9668(86)80021-7
- Pullar JM, Carr AC, Vissers MCM. The roles of vitamin C in skin health. Nutrients. 2017;9(8). doi:10.3390/nu9080866
- Hemilä H. Vitamin C and infections. Nutrients. 2017;9(4). doi:10.3390/nu9040339
- Wang K, Jiang H, Li W, Qiang M, Dong T, Li H. Role of vitamin C in skin diseases. Front Physiol. 2018;9(JUL). doi:10.3389/fphys.2018.00819