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Immune-enhancing role of vitamin C and zinc and effect on clinical conditions

DOI:10.1017/S0029665108006927
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S Beveridge
S Beveridge
S Beveridge
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E S Wintergerst
E S Wintergerst
E S Wintergerst
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Silvia Maggini at Bayer
Silvia Maggini
D.H. Hornig
D.H. Hornig
D.H. Hornig
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Abstract

Vitamin C concentrations in the plasma and leukocytes rapidly decline during infections and stress. Supplementation of vitamin C was found to improve components of the human immune system such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity. Vitamin C contributes to maintaining the redox integrity of cells and thereby protects them against reactive oxygen species generated during the respiratory burst and in the inflammatory response. Likewise, zinc undernutrition or deficiency was shown to impair cellular mediators of innate immunity such as phagocytosis, natural killer cell activity, and the generation of oxidative burst. Therefore, both nutrients play important roles in immune function and the modulation of host resistance to infectious agents, reducing the risk, severity, and duration of infectious diseases. This is of special importance in populations in which insufficient intake of these nutrients is prevalent. In the developing world, this is the case in low- and middle-income countries, but also in subpopulations in industrialized countries, e.g. in the elderly. A large number of randomized controlled intervention trials with intakes of up to 1 g of vitamin C and up to 30 mg of zinc are available. These trials document that adequate intakes of vitamin C and zinc ameliorate symptoms and shorten the duration of respiratory tract infections including the common cold. Furthermore, vitamin C and zinc reduce the incidence and improve the outcome of pneumonia, malaria, and diarrhea infections, especially in children in developing countries.
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1
st
International Immunonutrition Workshop, Valencia, 3–5 October 2007, Valencia, Spain
Immune-enhancing role of vitamin C and zinc and effect on
clinical conditions
S. Beveridge
1
, E. S. Wintergerst
2
, S. Maggini
1
and D. Hornig
3
1
Bayer Consumer Care, Basel,
2
Bayer Diabetes Care, Basel, Switzerland and
3
Bayer Diabetes Care, Reinach, Switzerland
The present paper is intended to give an overview on the roles of vitamin C and Zn in immune functions. Vitamin C concentrations in the
plasma and leucocytes rapidly decline during infections and stress. Supplementation of vitamin C improves components of the human
immune system such as antimicrobial and natural killer (NK) cell activities, lymphocyte proliferation, chemotaxis and delayed-type
hypersensitivity. Vitamin C contributes to maintaining the redox integrity of cells and thereby protects them against reactive oxygen
species generated during the respiratory burst and in the inflammatory response. Similarly, Zn deficiency impairs cellular mediators of
innate immunity such as phagocytosis, NK cell activity, and the generation of oxidative burst. Thus, both nutrients play important and
complementary roles in immune function and the modulation of host resistance to infectious agents, reducing the risk, severity and
duration of infectious diseases. A deficiency in one of these essential nutrients weakens immunity since vitamin C is crucial for cellular
immunity and Zn for the production of antibodies.A large number of randomized controlled intervention trials with intakes of £1g
vitamin C and £30 mg Zn are available. These trials show that adequate intakes of vitamin C and Zn ameliorate symptoms and shorten the
duration of respiratory tract infections including the common cold. Natural defences can only provide full protection when the body has
sufficient Zn, as well as high levels of vitamin C.The physiological effects of vitamin C provide clear evidence and rationale for a number
of ways in which it might help to protect against infection. This evidence is termed mechanistic evidence because it stems from
knowledge of the chemical reactions and biochemical processes in which vitamin C is known to play an important role (Table). The
actions of Zn not only complement the actions of vitamin C to provide ‘double protection’ (Table), but may even have a synergistic effect.
Like vitamin C, in recent years research has proved that Zn is essential for effective immune defence at several different levels.
Table. Summary of the role of vitamin C and Zn in body defences
(1,2,3)
Defence Vitamin C Zn
Skin and mucosal barriers Collagen synthesis
Improved strength
Cellular proliferation
Maintains thickness
Neutrophils and macrophages Improved motility and chemotaxis
Enhanced killing
Overall improvement in phagocytosis
Lymphocytes Proliferation of stem cells
B- and T-cell differentiation
B- and T-cell interaction
B lymphocytes Antibody production
T lymphocytes Proliferation Proliferation and appropriate response
Destruction of infected tissue cells and tumours
Interferon Production enhanced
Adequate intakes of vitamin C and Zn are essential for health.This is of special importance in populations in which insufficient intake of
these nutrients is prevalent. The current belief is that regular prophylactic intakes of vitamin C at doses of ‡ 200 mg daily have no effect
on the incidence of the common cold, but may be beneficial in the reduction of the severity and duration of the symptoms, suggesting that
vitamin C plays some role in the respiratory defence mechanisms. However, the elderly, who have been shown to have a lowered vitamin
C status and may therefore be more prone to infections, individuals exposed to continuous oxidative stress, such as chronic smokers, and
individuals exposed to heavy physical exercise and/or cold environment may benefit from a moderate continuous vitamin C intake. Other
vulnerable population groups include children. As a result of the high prevalence of Zn deficiency, especially in children in developing
countries, and the impaired immune status, susceptibility to infectious diarrhoea, malaria and pneumonia is found to be substantially
increased. Large intervention trials with daily intakes of 10–30 mg Zn have shown that Zn supplementation could be an important
adjuvant therapy for treating these infectious diseases in children in developing countries. Given that both vitamin C and Zn have
an important and synergistic effect on immune function and the modulation of host resistance to infectious agents it is hence appropriate
and beneficial to combine the trace element Zn with a high dose of vitamin C in one supplement.
1. Wintergerst ES, Maggini S & Hornig DH (2006) Ann Nutr Met 50, 85–94.
2. Wintergerst ES, Maggini S & Hornig DH (2007) Ann Nutr Met 51, 301–323.
3. Maggini S, Wintergerst ES, Beveridge S & Hornig DH (2007) Br J Nutr 98, Suppl. 1, S29–S35.
Proceedings of the Nutrition Society (2008), 67 (OCE), E83 doi:10.1017/S0029665108006927
... Vitamin C: The immune-enhancing roles of vitamin C are well established [12,13]. Vitamin C regulates the immune system because of its antioxidant properties and its role in collagen synthesis required for stabilization of epithelial barriers. ...
... High vitamin C levels in neutrophils are necessary to counteract the extremely high levels of oxidative stress to which they are exposed following Reactive Oxygen Species (ROS) production [12,17,19]. ROS are generated during the respiratory burst to kill pathogens and are elevated in the inflammatory response. ...
... In children, low concentrations of circulating zinc are associated with an increased risk of respiratory tract morbidity. Zinc supplementation reduces both the risk and duration of pneumonia in children and is also beneficial in the management of infantile diarrhea [10,12,81]. Zinc supplementation to maintain a normal serum concentration may help to reduce the mean incidence of infections (i.e., common cold, cold sores and flu) [81] as well as the incidence of pneumonia and associated morbidity in the elderly [82]. ...
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... Among many physiological roles, vitamin C is important in immune function and wound healing, and has antioxidant, antiviral and anti-inflammatory properties [128,[151][152][153]. In their analysis of circulating levels of vitamin C within 24 h of ICU admission, Tomasa Irriguible and Bielsa Berrocal [151] found up to 82% of COVID-19 patients were deficient, with many showing levels of only 0.1 mg/dL (normal values are 0.4-2 mg/dL), and 18% having undetectable levels of vitamin C (below 0.1 mg/dL). ...
... In addition to having important roles in cell growth and differentiation, bone formation, wound healing, brain development and structural integrity, zinc is also integral for heathy immune function [128,152]. Since the body has no storage system for zinc, a steady supply is essential [152]. As with vitamins C and D, zinc levels have been found to be lower in COVID-19 patients than in healthy controls [155]; similarly, among hospitalized COVID-19 patients, zinc levels were lower among patients who died, compared to those who survived [144]. ...
... In addition to having important roles in cell growth and differentiation, bone formation, wound healing, brain development and structural integrity, zinc is also integral for heathy immune function [128,152]. Since the body has no storage system for zinc, a steady supply is essential [152]. As with vitamins C and D, zinc levels have been found to be lower in COVID-19 patients than in healthy controls [155]; similarly, among hospitalized COVID-19 patients, zinc levels were lower among patients who died, compared to those who survived [144]. ...
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... A basic concentration of vitamin C is needed for a natural and well-functional host defense system, and the pharmacological use of vitamin C is thought to enhance immune function 29,30 . The range of statistical relationship between the dosage of vitamin C and the concentration of immune cells emphasizes the unique role of vitamin C in the cellular immune response 31 . ...
... The range of statistical relationship between the dosage of vitamin C and the concentration of immune cells emphasizes the unique role of vitamin C in the cellular immune response 31 . Even so, vitamin C deficiency that has been experimentally induced impairs cellular 31,32 and humoral immune responses 29,33 . Also, both research for both in vivo and humans' models have demonstrated the influence of vitamin C on diverse populations of immune cells [34][35][36] . ...
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Objective: Rabies is a lethal zoonotic infection caused by the rabies virus. Interferon- (INF) and interleukins (ILs) are a cytokine that is primarily produced by cells of the immune system. Vitamin C is an essential micronutrient in various biological processes, especially immune responses, and plays an essential part. Vaccination can successfully activate immune responses to virus infection protection. This study aimed to investigate the effect of vitamin C administration on immune responses to an inactivated rabies vaccine. Materials and methods: Thirty male Balb/c mice weighing between 25-30 gm (8 weeks old) were used in the current experimental study and randomly equally divided into three groups. Group I: untreated healthy control group was inoculated with PBS as a negative control. Group II: vaccinated intradermally with rabies vaccine alone using a dose of 4 ml/animal at 0, 7, 21 days. Group III: In addition to the dose of vaccine, mice were injected single intraperitoneally with 10 mg of vitamin C with each dose of vaccine on days 0, 7, 21. At experimental end, serum levels of IFN-γ, IL-4, and IL-5 were measured. Results: The results revealed that vitamin C supplementation significantly elevated IFN-γ, IL-4, and IL-5 levels in vaccinated mice and treated with vitamin C (group III) compared to vaccinated group II and healthy control group I. Similarly, vitamin C supplementation exhibited strong positive correlations between IFN-γ and both IL-4 and IL-5 level in all experimental group. Taken together, these results showed that vitamin C is an important stimulator of interferon, interleukin-4 and -5 during inactivated rabies vaccine vaccination in mice. Conclusions: Our results supported the hypothesis that indicated the immunological improvement of vitamin C to the effectiveness of the inactivated rabies virus vaccination. High dose of vitamin C increases the levels of interferon and interleukin-4 and interleukin-5.
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... The deficiency of zinc causes dangerous effects and damage to immunity cellular mediators, such as natural killer cell activity and the production of cytokines [17]. Zinc is an inflammatory and anti-oxidative stress agent. ...
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... Zinc is an essential mineral apperceived by the public today as being of "incomparable biological and public health prominence," [1] and has been revealed to play an imperative role in curing of septic condition, proper functioning of mucosal cells, reduction of reactive oxygen species (ROS) [2] and as a cofactor for metalloenzymes. [3] Zinc 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 sexual maturation, [1] decreased spermatogenesis, ataxia, and lethargy. ...
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... Since early 1970s, there has been an increasing interest in the levels of several elements in composite diet and individual food items such as honey, meat, milk, wheat, water, fish and vegetables (Nath, 2000;Singh, 2004;Black, 2003;Cousins et al., 2004;Vyoral et al., 2005;Wintergerst et al., 2006). Also a great deal of research has been undertaken on the concentration of essential trace elements in biological materials such as fluids and tissues (Mandal et al., 2003;Samatha et al., 2005;Mehra and Juneja, 2005;Nowak and Chmielnicka, 2007;Were, 2008;Mogwasi, 2009). ...
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... Oxidation occurs due to inflammatory immune response to pathogens, therefore Vitamin C plays an essential role in immune function (Wintergerst et al., 2006). Vitamin C is also essential in the production of collagen formation in the body. ...
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... Individuals with zinc deficiency are more prone to viral infections (Read et al., 2019). Zinc is also thought to be essential for T-cell receptors that need the intracellular binding of tyrosine kinase, which is necessary for their growth and survival as well as activation of T-lymphocyte activation (Wintergerst et al., 2006). Zinc plays a crucial role in cytokine release and triggering CD8+ T-cell proliferation, as well as immune cell development and differentiation. ...
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... Also, VitC has direct antioxidant capacity and contributes to the cell protection from the damaging effects of ROS, e.g., during immune activation. For instance, VitC was shown to protect neutrophils from ROS generated during phagocytosis and prevent oxidative damage on lymphocytes and DNA (Wintergerst et al. 2006). ...
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Immune-Enhancing Role of Vitamin C and Zinc and Effect on Clinical Conditions
Article
Full-text available
  • Feb 2006
Vitamin C concentrations in the plasma and leukocytes rapidly decline during infections and stress. Supplementation of vitamin C was found to improve components of the human immune system such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity. Vitamin C contributes to maintaining the redox integrity of cells and thereby protects them against reactive oxygen species generated during the respiratory burst and in the inflammatory response. Likewise, zinc undernutrition or deficiency was shown to impair cellular mediators of innate immunity such as phagocytosis, natural killer cell activity, and the generation of oxidative burst. Therefore, both nutrients play important roles in immune function and the modulation of host resistance to infectious agents, reducing the risk, severity, and duration of infectious diseases. This is of special importance in populations in which insufficient intake of these nutrients is prevalent. In the developing world, this is the case in low- and middle-income countries, but also in subpopulations in industrialized countries, e.g. in the elderly. A large number of randomized controlled intervention trials with intakes of up to 1 g of vitamin C and up to 30 mg of zinc are available. These trials document that adequate intakes of vitamin C and zinc ameliorate symptoms and shorten the duration of respiratory tract infections including the common cold. Furthermore, vitamin C and zinc reduce the incidence and improve the outcome of pneumonia, malaria, and diarrhea infections, especially in children in developing countries.
View
Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses
Article
Full-text available
  • Nov 2007
Adequate intakes of micronutrients are required for the immune system to function efficiently. Micronutrient deficiency suppresses immunity by affecting innate, T cell mediated and adaptive antibody responses, leading to dysregulation of the balanced host response. This situation increases susceptibility to infections, with increased morbidity and mortality. In turn, infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing losses, and interfering with utilization by altering metabolic pathways. Insufficient intake of micronutrients occurs in people with eating disorders, in smokers (active and passive), in individuals with chronic alcohol abuse, in certain diseases, during pregnancy and lactation, and in the elderly. This paper summarises the roles of selected vitamins and trace elements in immune function. Micronutrients contribute to the body's natural defences on three levels by supporting physical barriers (skin/mucosa), cellular immunity and antibody production. Vitamins A, C, E and the trace element zinc assist in enhancing the skin barrier function. The vitamins A, B6, B12, C, D, E and folic acid and the trace elements iron, zinc, copper and selenium work in synergy to support the protective activities of the immune cells. Finally, all these micronutrients, with the exception of vitamin C and iron, are essential for antibody production. Overall, inadequate intake and status of these vitamins and trace elements may lead to suppressed immunity, which predisposes to infections and aggravates malnutrition. Therefore, supplementation with these selected micronutrients can support the body's natural defence system by enhancing all three levels of immunity.
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Contribution of Selected Vitamins and Trace Elements to Immune Function
Article
Adequate intakes of vitamins and trace elements are required for the immune system to function efficiently. Micronutrient deficiency suppresses immune functions by affecting the innate T-cell-mediated immune response and adaptive antibody response, and leads to dysregulation of the balanced host response. This increases the susceptibility to infections, with increased morbidity and mortality. In turn, infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing losses, and interfering with utilization by altering metabolic pathways. Insufficient intake of micronutrients occurs in people with eating disorders, in smokers (both active and passive), in individuals with chronic alcohol abuse, in patients with certain diseases, during pregnancy and lactation, and in the elderly. With aging a variety of changes are observed in the immune system, which translate into less effective innate and adaptive immune responses and increased susceptibility to infections. Antioxidant vitamins and trace elements (vitamins C, E, selenium, copper, and zinc) counteract potential damage caused by reactive oxygen species to cellular tissues and modulate immune cell function through regulation of redox-sensitive transcription factors and affect production of cytokines and prostaglandins. Adequate intake of vitamins B(6), folate, B(12), C, E, and of selenium, zinc, copper, and iron supports a Th1 cytokine-mediated immune response with sufficient production of proinflammatory cytokines, which maintains an effective immune response and avoids a shift to an anti-inflammatory Th2 cell-mediated immune response and an increased risk of extracellular infections. Supplementation with these micronutrients reverses the Th2 cell-mediated immune response to a proinflammatory Th1 cytokine-regulated response with enhanced innate immunity. Vitamins A and D play important roles in both cell-mediated and humoral antibody response and support a Th2-mediated anti-inflammatory cytokine profile. Vitamin A deficiency impairs both innate immunity (mucosal epithelial regeneration) and adaptive immune response to infection resulting in an impaired ability to counteract extracellular pathogens. Vitamin D deficiency is correlated with a higher susceptibility to infections due to impaired localized innate immunity and defects in antigen-specific cellular immune response. Overall, inadequate intake and status of these vitamins and minerals may lead to suppressed immunity, which predisposes to infections and aggravates malnutrition.
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  • Jan 2007
  • 301-323
  • E S Wintergerst
  • S Maggini
  • D H Hornig
Wintergerst ES, Maggini S & Hornig DH (2007) Ann Nutr Met 51, 301-323.
  • Jan 2006
  • 85-94
  • E S Wintergerst
  • S Maggini
  • D H Hornig
Wintergerst ES, Maggini S & Hornig DH (2006) Ann Nutr Met 50, 85-94.