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

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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.
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
... Both vitamin C and zinc give a complementary powerful antioxidant protection against endogenously and exogenously reactive oxygen species (ROS) [1] . There is a true scientific rationale that the combination of vitamin C and zinc can play an important role in the immune functions and also to reduce the risk of diseases [2] . ...
... Moreover, the increase in total serum globulins in the present experiment is mainly due to the increase in gamma globulins which well known that it's mainly composed from immunoglobulin. This type is produced by the plasma cell that is the mature stage of B lymphocyte cells [50] which exhibit a significant increase by the supplementation [1,54] . The second explanation for increasing the total proteins and globulins in serum of intact and ovariectomized rabbits supplemented with complementary vitamin C and zinc, could be associated to the antioxidative action of them [1,55] . ...
... This type is produced by the plasma cell that is the mature stage of B lymphocyte cells [50] which exhibit a significant increase by the supplementation [1,54] . The second explanation for increasing the total proteins and globulins in serum of intact and ovariectomized rabbits supplemented with complementary vitamin C and zinc, could be associated to the antioxidative action of them [1,55] . They protect the body from the deleterious and damaging effect of free radicles (ROS), that cause oxidation of LDL and the oxidative damage of DNA and proteins [56,57] . ...
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The present experiment was investigated to study the complementary effect of vitamin C and Zinc supplementation on some parameters related to the immune system in intact and ovariectomized rabbits. Twenty female rabbits (7-8 weeks) have been used in this study. Ten of them had been subjected to ovariectomy and the other ten were left with intact ovaries. After recovery from the operation and acclimatization, the rabbits were divided into four equal groups as follow: Group one (G1): Intact rabbits received distilled water. Group two (G2): Intact rabbits received complementary vitamin C and Zinc with the dose (10.166 mg/kg/B.W) orally and daily. Group three (G3): Ovariectomized rabbits received distilled water. Group four (G4): Ovariectomized rabbits received complementary vitamin C and Zinc. The daily supplementation of complementary vitamin C and Zinc induces a significant increase in total leukocytes (14.06 and 11.08 × 10 3 /mm 3) in both intact and ovariectomized rabbits respectively. Moreover, the Arneth , s index reveals a significant higher percentage of neutrophils of four and five lobes in both supplemented groups. The total percentage of mature cells was (27.9% and 14.1%) for G2 and G4 respectively in comparison with (9.0% and 8.3%) for G1 and G3 respectively. There is a significant increase in eosinophil's and lymphocytes percentages in Ovariectomized rabbits only. However, the result also revealed a significant increase in total protein and total gamma concentration in both intact and ovariectomized rabbits that supplemented with complementary vitamin C and Zinc. In conclusion, the results from this experiment confirm and for the first time that the complementary vitamin C and Zinc supplementation to rabbits has an important protective role on the immune system in ovariectomized rabbits. This supplementation can overcome the deleterious effect of ovariectomy and ovarian hormones deficiency on bodies' immunity.
... Participation in 29 met-analysis studies shows that frequent ascorbic acid prophylaxis does not decrease common cold incidence in normal people by eleven thousand seven hundred and seven (11,707). However, six RTCs of ascorbic acid supplementation in 642, soldiers, skiers, and marathon runners showed a reduction in the frequency of the common cold [35]. ...
... Antimicrobial activities are increased, accompanying protein serum is promoted, and IFN g syntheses are stimulated [52,53].Due to its ability to neutralise free radicals, ascorbic acid helps to keep the cellular redox balance in check (R-O). Achieving equilibrium within the short reaction time of the body's inherent resistance mechanism [35,52,53]. White (T) blood cells, particularly venom T cell receptor TCR cells, proliferate and differentiate in the plasma units, which helps produce antibodies via the proliferation and differentiation process [52]. ...
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Vitamin C stands as an essential water-soluble vitamin, antioxidant and has been shown to enhance immunity. SARS-CoV-2 has been spreading rapidly across the worldwide, several cellular processes of innate and adaptive immunity are aided by vitamin C, which strengthens the immune system overall. Multiple lines of evidence in the literature associate vitamin C with antioxidant, anti-inflammatory, anticoagulant and immunomodulatory actions. Pneumonia and sepsis patients had poor ascorbic acid status and high oxidative stress, according to many studies. Pneumonia patients who get vitamin C may have less severe symptoms and a longer course of the illness if they do. To standardize plasma levels in sepsis patients, gram measurements of the vitamin must be administered intravenously (IV). This intervention has been shown in a few trials to reduce mortality. COVID-19 management in China and the United States has exhibited remarkable results when using a high percentage of intravenous vitamins C. It's acceptable to include vitamin C in the COVID-19 treatment protocol as a secondary measure based on the current active clinical studies looking at the impact of vitamin C on the management of COVID-19. Patients with hypovitaminosis C or severe respiratory illnesses, such as COVID-19, may benefit from taking vitamin C, due to its good safety profile, simplicity of use, and potential for rapid production scaling. The study's goal was to see whether high dosage intravenous vitamin C had any impact on individuals with severe COVID-19 (HDIVC). Finally we discuss recent research that has been published on the efficacy of vitamin C administration in the treatment of viral infection and life-threatening conditions. The purpose of this manuscript is to summarise existing research on the efficacy of vitamin C as a treatment for COVID-19 and to discuss possible explanations for why it may work in some individuals but not in others.
... Vitamin C can increase the serum levels of B and T antibodies in the adaptive immune system and play an active role in the differentiation and proliferation of lymphocytes. 52,53,56,57) Vitamin D Vitamin D has many effects on innate immune cells. One of them is that it increases numbers in monocytes, macrophages, dendritic cells. ...
... Food contributes to physical barriers in the natural immune system: the production and activity of antimicrobial proteins that function in the body; growth, differentiation, and motility of congenital cells are of great importance; phagocytic and lethal activities of neutrophils and macrophages such as oxidative explosion; and anti-inflammatory effects such as cytokine production and antioxidant activity. Nutrients also have functions in the adaptive immune system, including T-and B-lymphocyte differentiation, proliferation, homeostasis, and controls the production of cytokines, B antibodies, and memory cells (Tables 1, 2 andFigure 1).17,24,41,[43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] Therefore, immune function is negatively affected in the case of insufficient micronutrients and macronutrients, resulting in a potential decrease in the immunity against infections.21,[41][42][43] ...
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... Other studies of vitamin C supplementation on soccer players have shown that vitamin C intake and exercise can increase IgA levels (38). The authors' studies have shown that vitamin C can boost the immune system, decrease the risk of infectious diseases, significantly decrease cortisol, improve immune system indicators and be a barrier to infectious diseases by increasing IgA and IgG levels (39). Vitamin C is essential for producing white blood cells (WBCs) and includes positive effects in preventing URTI. ...
... Zinc has been reported to effectively inhibit the RNA synthesis activity of nidoviruses, including coronavirus (SARS-CoV), in vitro (53). Furthermore, Zn helps regulate thymulin activity, increase T cell count, increase normal immune cell cytotoxicity, decrease infections in children, decrease pneumonia and decrease duration and severity of cold symptoms (39,54). Risks of diseases such as bacterial, viral and fungal infections (especially diarrhea), pneumonia, diarrhea and respiratory diseases increase in Zn deficiency (Table 1) (55). ...
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... The The samples were air-dried for a period of three weeks after which fresh ones were obtained again for comparative study. The samples were collected during the flowering period, because it was expected that the vitamin content would be at its highest level at that time [10]. The fresh and dried samples were taken directly to the laboratory and analysis was done immediately upon arrival. ...
... Zinc has also been shown to have an antioxidant potential through the non-enzymatic stabilization of biomembrane and biostructures. The protective effects of zinc could be attributed to its ability to reduce collagen accumulation in liver as well as it exerts critical physiological role in regulating the structure and function of cells (Wintergerst et al., 2006). While Anderson et al., (1980) concluded that Zinc is required for the adequate formation and function of the antioxidant enzyme superoxide dismutase and various metallothionins. ...
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The antioxidant role of vitamin Cand zinc in ovariectomized rabbits with metabolic disorder
... The The samples were air-dried for a period of three weeks after which fresh ones were obtained again for comparative study. The samples were collected during the flowering period, because it was expected that the vitamin content would be at its highest level at that time [10]. The fresh and dried samples were taken directly to the laboratory and analysis was done immediately upon arrival. ...
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... The The samples were air-dried for a period of three weeks after which fresh ones were obtained again for comparative study. The samples were collected during the flowering period, because it was expected that the vitamin content would be at its highest level at that time [10]. The fresh and dried samples were taken directly to the laboratory and analysis was done immediately upon arrival. ...
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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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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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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.
  • E S Wintergerst
  • S Maggini
  • D H Hornig
Wintergerst ES, Maggini S & Hornig DH (2007) Ann Nutr Met 51, 301-323.
  • E S Wintergerst
  • S Maggini
  • D H Hornig
Wintergerst ES, Maggini S & Hornig DH (2006) Ann Nutr Met 50, 85-94.