Role of Vitamin-C and Vitamin-D as an Immunomodulatory Dietary Source in Prevention of Infectious Disease Such as Covid-19
SayaliPrashant Bawankule1
1. Intern, Dept. of Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (Meghe), Wardha-442001,
Maharashtra, India,[email protected] , +91 9764929226 Corresponding author’s name and address:
Sayali Prashant Bawankule, Intern, Dept. of Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi
(Meghe), Wardha-442001, Maharashtra, India.
Corresponding author’s email id: [email protected] Contact number of the corresponding author: +91 9764929226
Type of Article: Review Conflict of Interest: None
Funding: DMIMS
Ethical Approval: IEC, DMIMS, Wardha.
ABSTRACT BACKGROUND
It is necessary to take adequate and nutritious substances in the diet to fulfill the daily requirement. Carbohydrates, fats, proteins, minerals, vitamins are few of the integrants in the daily diet. Immunity is the multi gem and trailblazing connecting various cellular chains from organ to tissue and so on.
SUMMARY
This chain has explored to serve the antigens from the series of microorganisms like parasites, fungi, viruses, bacteria or carcinogenic cells. Components of WBC (White Blood Cell) like neutrophils and monocytes play vital role in enhancing immunity through wound healing. The above article kingpin the role of vitamin C nutritional function and its relation with immunity as an enhancing factor which can be utilized as a supplement and dietary component to fight against the preventive mode for pandemic diseases like Covid-19 in a systematic way. Antioxidant activity in function of cell cycle and internal health. Sapodilla, guava, orange, lime, mango, strawberry, broccoli and kiwi have an antioxidant property which gist the immunity. Vitamin C is potent immunity cell booster by preventing systemic infections and treating respiratory infections. The role of vitamin C and D per day to up heave the immunity as a preventive measure against various infections. The combine effect of both vitamin C and D can be best
preventive modality in order to maintain health hygiene and immunity and to stay disease free.
CONCLUSION
The above study is suggestive of the role of both vitamin C and D independently or combined as a dietary source to reduce the acute respiratory tract infection like COVID 19.
KEYWORDS: Immunity, vitamin C, Vitamin D, respiratory infections.
INTRODUCTION
Balanced diet is the exuberant factor of livelihood. The basic requirements of the body are obtained through healthy nutritious diet. Moreover few nutritional components are synthesized in body and others are absorbed through food. So it is necessary to take adequate and nutritious substances in the diet to fulfill the daily requirement. Carbohydrates, fats, proteins, minerals, vitamins are few of the integrants in the daily diet. Not only the palliative receptors yearning for sensations but there are many different systems in body ought to function with the help of these components some as an enzyme, some as cofactors and others as coenzymes etc. vitamins are also the component among these nutrients to be the most requisite for several systems. They cannot be formed in body. The external administration of vitamins is paramount for body.
Excessive or insufficiency both causes a several pathology leading to diseases. Likewise vitamin C is the prime factor. In the ruling pandemic vitamin C supplements are vigorously given due to its respiratory symptoms and its efficiency to relieve from it. Dietary uptake can also be a boon to succor as a preventive aspect these days. Vitamin C acts as both curative and preventive role.
Many studies are suggestive of the vitamin C and its role in boosting immunity.
Immunity is the multi gem and trailblazing connecting various cellular chains from organ to tissue and so on. This chain has explored to serve the antigens from the series of microorganisms like parasites, fungi, viruses, bacteria or carcinogenic cells. [1] Further classification of immunity involves cellular and epithelial obstacle of both specific and nonspecific types [1]. Multiple lofty nexus way these components are connected. Vitamin C plays an efficient role in numerous facets enhancing immunity specially triggering function of immune cells [2,3]. A tough barrier is created fraternizing the cells and the system.
Human body cannot produce Vitamin C among itself it is artificially synthesized or taken orally [4,5]. It also causes life-threatening disease like scurvy [6]. Scurvy diseased person is vulnerable to several infections related to pulmonary disorders and other fatal diseases [7,8]. Bleeding gums, bruising and healing The daily dose of vitamin c varies from age groups and slightly as per gender. Adult male needs 90 mg while female needs 75mg, in pregnancy the dose is 85mg, and lactation has 120mg. smoking alter these values as there is conjoint relation between smoking and respiratory disorders. Respiratory disorders have special reference to vitamin C and a chain ends up with relation of vitamin C and immunity. It increases the plasma concentration and reduces the risk of chronicity [9, 10]. Vitamin c requirement cannot be fulfilled many a times due to lack of healthy diet, poor dietary habits like smoking, alcohol, drug abuse, various diseases, pollutants or poverty [11, 12]. Vitamin C as an immune enhancer is convicted due to its antioxidant property by serving essential bio-components like carbohydrates, lipids, proteins, nucleic acid and prevents the cell synthesis due to exposure of pollutants and toxins [13].
Increases Amidated peptides helps in GnRHand as yet undiscovered cofactor function? [14].
Many current research have indicated the role of Vitamin C as a cofactor. [15]
Vitamin C also increases production of collagen and its stability. Wound healing through antioxidant constituents is the notable work of Vitamin C which boosts the early closure of injured wound. [16,17]
Components of White blood Cells (WBC) like neutrophils and monocytes play vital role in enhancing immunity through wound healing.[18]. The dietary foods as an immunomodulator suggest the role of vegetable nutritional value and function in fighting against various infectious diseases such as COVID 19.[19] the most susceptible group among society is newborn, pregnant and elderly aged people vulnerable to respiratory disorders as the immunity enhancer.
VITAMIN D
Vitamin D is an element with special immune boosting effect. Vitamin D is a hormone produce externally from the sunrays emiting ultraviolet rays or dietary supplements known as steroid hormone. Huge amount of population of variant ages grossly affect due to its inadequacy. Many studies have proved the relation between deficient vitamin D and its relation with infections [20, 21, 22]. Several studies have been performed to correlate the respiratory viruses and immune function performed by vitamin D [23].vitamin D slog inborn or specific type of immunity it eject a peptide in order to create mucosal defense against viruses of respiratory tract. The risk of infection doubles with the abrupt detoriaration of vitamin D. it was been noted that the patients with pneumonia gets severe and mortality and morbidity increases. Viruses duplicates and break the anti-inflammatory barriers and immune system. vitamin D balances the rennin-anginotensin system leading to reduced cytokine. These cytokine effect on on interferon γ and tumor necrosis factor α [24]. Special hinder in vitamin D is been found in immune homeostasis. Fatty substances oily fish such as salmon, sardines and mackerel, red meat, liver, egg yolks, cheese, butter, cereals are good source of vitamin D. along with diet vitamin D can be obtained through direct exposure to sun. the pores inhibit helper T cells.
VITAMINS AND DIETRY COMPONENTS
Present review was done by encapsulating quintessence of date back studies and begins invigorating facts relatable to vitamin C and D, its role in body and function in boosting the immunity. The above article kingpin the role of vitamin C and Dnutritional function and its relation with immunity as an enhancing factor which can be utilized as a supplement and dietary component to fight against the preventive mode for pandemic diseases like COVID-19 in a systematic way. The study excludes current status of pandemic, its pathogenesis related to self maintenance.There are many fruits like oranges, grapes, tangerines having adequate amount of ascorbic acid or Vitamin C. Sapodilla is the richest source of vitamin c 427g. The vitamin C and its role in boosting immunity and its function enhancing whole immune system. [25].
Antioxidant and anti-inflammatory function of sapodilla helps to increase the immunity and hence to fight against various respiratory disorders like COVID- 19.
Guava is another component having 380 mg of vitamin C with antioxidant property. The arched study of concentration of vitamin c to tissue and by mouth dose. Single orange consumption can met a need for one day. As orange is powerful antioxidant acting as a scavenger it helps to prevent from certain dreadful disorders by neutralizing harmful elements. Anti-carcinogenic property is also worth notable. It helps the absorption of iron. Lime has 48mg vitamin C, which the least amount amongst all citrus fruits. To meet the daily dietary need two to 3 limes are required and so is least preferred. Mango the most common fruit has 60 mg of vitamin C with
both anti-oxidant and anti- inflammatory property. Strawberry has 85mg, kiwi has 93 mg vitamin c, broccoli has 51 mg of vitamin C. All the dietary components has antioxidant property.
Table1. Nutritional function of components, amount of Vitamin C Sr.no Name of Component Vitamin C Nutritional function
1. Sapodilla 424 mg Antioxidant, Anti-inflammatory
2. Guava 380 mg Antioxidant
3. Orange 88 mg Antioxidant, Anti-inflammatory
4. Lime 48 mg Antioxidant
5. Mango 60 mg Antioxidant, Anti-inflammatory
6. Strawberry 85 mg Antioxidant
7. Broccoli 51 mg Antioxidant, anti-carcinogenic
8. Kiwi 93 mg Antioxidant
Antioxidant role of vitamin C is explained beautifully in an article. [25] Hence forth immunity has special course with vitamin C supplementation as a dietary mode in preventing dreadful scenario of the several decades. Vitamin D is has egg yolk, oyster, fatty fish, cod liver oil, milk, cereals, salmon
Table 2. Name of component containing vitamin D per 100gm and its nutritional function Sr.no Name of Component Vitamin D Nutritional function
1. Egg yolk 42IU Antioxidant, Anti-inflammatory
2. Salmon 447 IU Antioxidant, anti-viral
3. Mushroom 1022 IU Antioxidant, Anti-inflammatory 4. Fortified milk 124 IU Antioxidant
5. Orange juice 137 IU Antioxidant, Anti-inflammatory
6. Cereals 40 IU Antioxidant
Mushroom is the richest source of vitamin D having 1022 IU /100grams. Naturally obtaining mushrooms is available easily and can be used in the multiple forms for consumption.
Mushrooms are treated with UV light providing much amount of nutrients. Salmon is the fish having 447 IU/100 grams, salmons are available in the large water source. The higher the light exposed to salmon greater is the accumulation of vitamin D therein. The combine effect of mushroom and salmon can be the best solution for fostering the vitamin D as a dietary supplement. Egg yolk contains zinc and selenium. Egg is richest source of protein but other that this the vitamin D contain in 100grams is 42IU. Antioxidant and anti-inflammatory role of these substances render a mesmerizing role in enhancing immunity. Orange is citrus fruit with both vitamin C and D. orange juice is also considered as the source of vitamin D. fortified milk of soya and almondprovid similar amount of vitamin D. they are considered as a plant based milk.
Along with vitamin D calcium is another source which speeds up the innate cells.
.VITAMINS AND PATHOPHYSIOLOGY
Biological fluids including blood, plasma, lymph, Cerebro spinal fluid (CSF), Synovial fluid etc has vitamin C as water soluble antioxidants. Hunting the oxygen and nitrogen preferably prevent the oxidative damage. All living beings are copiously attacked by antigens. Due to micro size of these antigens, they settle in the amount of millions on a single head of cell. Vitamin c also acts as co antioxidant.The more the organisms found complex greater is the immunity activated. Most commonly consumed diet has enough nutrition along with essential components to be consumed externally to maintain healthy health and immunity. Antioxidant defense system is the other supernatural mechanism working in human body amongst other systems of body. Antioxidant activity in function of cell cycle and internal health. Sapodilla, guava, orange, lime, mango, strawberry, broccoli and kiwihave an antioxidant property which gist the immunity. Also anti- inflammatory property aid to induce the neutrophils which are the root source in enhancing immunity against damaged tissues by evoking the process of phagocytosis (killing of cells). The reduced vitamin c values in plasma may increase the chances of respiratory infections [26]. The fatality of respiratory diseases can be minimized by intake of vitamin c in patients [27]. Few study have shown the clear findings in x-ray due to intravenous administration of vitamin c in acute lung infection [28,29]. Supplementary dose of vitamin C 200mg in reducing the fatality and duration in symptoms of influenza and bodily tension [30]. The common symptoms of COVID 19 involve common cold and it has crucially proved the intake of vitamin c in depressing the cold and recovery. It reduces the risk of prolonged hospital stay. A study also has denoted the abundant decrease in ESR that is erythrocyte sedimentation rate by oral vitamin c intake [31]. Vitamin C depletion is amply fall during frightful disease. [32]. Ascorbic acid is pin point media for normal metabolism of body. Fresh fruit, citrus fruits and vegetables contain plenty of it. The alveolar fluid clearing and increasing the obstacle between bronchus and alveoli and enervate segregation of lymphocytes (neutrophils) as stated in animal study wherein animals having infection due to lung injury [33] vitamin c enumerate the normal functioning of lungs.
There are connecting links in between cells and their receptors to the immune-modulating system and several metabolic disorders [34]. Smoking and tobacco chewing permit the growth of various bacterial and viral infections [35,36]. Other functions of vitamin C are reducing Hypoxia- inducible factor [37] is the transcription factor that reacts to reduced oxygen content in environment. Reduce DNA and histone methylation[38] inculcate the epigenetic mechanisms. Increases carnitine due to huge intake of dairy and non-vegetarian foods.
Increase catecholamine is the basic work of vitamin c by adequately taking citrus fruits.
Increase collagens which improve the skin relives joint pins, prevent the bone density improve the muscle mass and promote the healthy heart functioning [39,40,41]. Wound healing is imposed with the help of vitamin c along with external injuries it heals the internal flora of gastro-intestinal tract that may damaged due to engulfing endotoxins and antibiotics. It protect the cell membranes and allow the oxidation and enlighten the cellular movements [42]. Animal study has indicated the amount of vitamin C in diet by executing the leucocytes [43]. In-vivo detoxification of immune cells by hitting the histamine concentration was seen by vitamin C supplementation [44]. Vitamin D deficient children found to asthmatic in the cord blood plasma.
It was found due to deficient vitamin D diet by the conceiving ladies resulting RSV LRTI [45].
The fitness of strong antigens related with the amount of UV light with respect to season and site. So the infections worsen day to day due to changing season and dietary regimen [46].
Migration and sudden climatic changes affect the production vitamin D so the external
supplements are necessary to rebuild the immunity. Inflammatory process gets shut down due to suppression of extra skeletal effects [47]. A parathyroid hormone depends on CVD and reduced lung function [48]. Heart failure and ARDS and pneumonia totally depends upon rennin anginotensin factor. Medical condition relates to fonder respiratory function with pro- inflammatory cytokine. Along with vitamin C and D, vitamin B12 deteriorate the effect of vitamin D. Magnesium vitamin B12 and vitamin D combined use as safe and effective mode to reduce COVID-19 symptoms [49]. Serum 25- hydroxyvitamin D concentration can be increased through these components by adding vitamin C and oral supplements of vitamin D3. The metabolism of vitamin D implies the basic role of Mg (magnesium) in the renal and hepatic reaction by enzymes as a cofactor [50]. Daily supplementsup to 100- 250 microgram/day has increased the concentration of Serum 25- hydroxyvitamin D. the increase dose of 100 micrograms/day can be safely given to adults. Antimicrobial activity of vitamin C aid the increased production of glutathione helps in treatment and prevention of COVID-19 [51]. Daily dose of 10mg of vitamin C provides the collagen synthesis and prevent scurvy and are susceptible to several infections by successively decreasing the immune response. The processed food with added doses of vitamins does not shuffle the body mechanism. The vitamins are water soluble so can be excreted out to reduce intoxication by itself [52,53]. Antioxidants in the body are triggered by vitamin C and D to act wisely against several antigens and to activate both specific and nonspecific type of immunity[54,55].
Conclusion:
Inclusively it has been noted the role of vitamin in boosting both innate and adaptive type of immunity. Vitamin C is a formidable antioxidant protecting the human body against external and internal oxidative ultimatum in fostering the immunity. Increase in phagocytic and formation of oxidant at the site of infection bracing the amount of vitamin C. apoptosis of few neutrophils by vivifying macrophagial activity by preventing the damage of host tissues. Vitamin C is potent immunity cell booster by preventing systemic infections and treating respiratory infections.
Sapodilla is the best dietary component having antioxidant activity aid in consumption of vitamin C.Broccoli is the vegetable containing abundant vitamin c and other nutrients can be utilized in the form of salad in order to increase the bodily requirement of vitamins and the fruits can be used in the form of juices.Kiwi is the fruit used for increasing the thrombocytes (platelets) in several diseases like dengue, thrombocytopenia etc. Multiple decades have expressed the consequences of vitamin C through diet incorporating the immunity. Antioxidant and anti- inflammatory activity of the above components increases the aversion to infectious diseases. So these components and the others containing vitamin c should be avail in preventing the COVID 19 pandemic and the other infectious diseases. Rapid absorption is fostered by vitamin C or ascorbic acid so it is given as a supplement with several antibiotics. So absorption is another important factor that can be utilized as a pre-dietary element in food for daily consumption.
Production of interferons facilitates the defense mechanism to work as a whole. Vitamin C is found 80times in plasma of immune system. Antioxidant activity suppresses the inflammation as in shout up the immunity. It shortens the duration of the symptoms and severity of disease and making up the respiratory function. The above research has summarized the role of vitamin C per day to up heave the immunity.Vitamin D resides very close to respiratory flora thus activating the dendric cells (DCs). Dendric cells engulf the viruses by phagocytic and micropinocytosis activity boosting the immune system rapidly. It activates the PRRs. As in vitamin C cytokine activated , vitamin d produce chemokines (CXCL8, CXCL9, CXCL10 AND IL-15). The role of neutrophils is much clear as it forms an envelope around to protect the respiratory cells from
hosts. The further spread of the disease is prevented by dietary supplement by minimizing the further growth of viruses. Mushroom is found to be the best source of vitamin D. salmon is the fish to be utilized with fatty oily stuffs with ample of vitamin D and antiviral property helps to boost the immunity. The combination of these components ,may help to render the markers and fulfill the daily requirement. Egg yolk is the product to be used which help to gear the interleukin 6 elevation and breakdown the sequel of growing viruses. The spikes of glycoprotein shed down with consumption of vitamin D. The combine effect of both vitamin C and D can be best preventive modality in order to maintain health hygiene and immunity and to stay disease free.
The above study is suggestive of the role of both vitamin C and D independently or combined as a dietary source to reduce the acute respiratory tract infection like COVID 19.
REFERENCES:
1. Parkin J, Cohen B. An overview of the immune system. The Lancet. 2001 Jun 2;357(9270):1777-89.
2. Maggini S, Wintergerst ES, Beveridge S, Hornig DH. Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses. British Journal of Nutrition. 2007 Oct;98(S1):S29-35.
3. Webb AL, Villamor E. Update: effects of antioxidant and non-antioxidant vitamin supplementation on immune function. Nutrition reviews. 2007 May 1;65(5):181-217.
4. Burns JJ. Missing step in man, monkey and guinea pig required for the biosynthesis of L- ascorbic acid. Nature. 1957 Sep;180(4585):553-.
5. Nishikimi M, Fukuyama R, Minoshima S, Shimizu N, Yagi K. Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. Journal of Biological Chemistry. 1994 May 6;269(18):13685-8.
6. Sauberlich HE, Packer L, Fuchs J. Vitamin C in health and disease.
7. Hemila H. Vitamin C and infections. Nutrients.
8. Carr AC, McCall C. The role of vitamin C in the treatment of pain: new insights. Journal of translational medicine. 2017 Dec;15(1):1-4.
9. Levine M, Dhariwal KR, Welch RW, Wang Y, Park JB. Determination of optimal vitamin C requirements in humans. The American journal of clinical nutrition. 1995 Dec 1;62(6):1347S-56S.
10. Carr AC, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. The American journal of clinical nutrition. 1999 Jun 1;69(6):1086-107.
11. Maggini S, Beveridge S, Sorbara PJ, Senatore G. Feeding the immune system: the role of micronutrients in restoring resistance to infections. CAB Reviews: Perspectives in Agriculture, Veterinary Science, Nutrition and Natural Resources. 2008;3(098):1-21.
12. Huskisson E, Maggini S, Ruf M. The role of vitamins and minerals in energy metabolism and well-being. Journal of international medical research. 2007 May;35(3):277-89.
13. Carr A, Frei B. Does vitamin C act as a pro‐oxidant under physiological conditions?. The FASEB journal. 1999 Jun;13(9):1007-24.
14. Englard S, Seifter S. The biochemical functions of ascorbic acid. Annual review of nutrition. 1986 Jul;6(1):365-406.
15. Young JI, Züchner S, Wang G. Regulation of the epigenome by vitamin C. Annual review of nutrition. 2015 Jul 17;35:545-64.
16. Desneves KJ, Todorovic BE, Cassar A, Crowe TC. Treatment with supplementary
arginine, vitamin C and zinc in patients with pressure ulcers: a randomised controlled trial. Clinical nutrition. 2005 Dec 1;24(6):979-87.
17. Taylor TV, Rimmer S, Day B, Butcher J, Dymock IW. Ascorbic acid supplementation in the treatment of pressure-sores. The Lancet. 1974 Sep 7;304(7880):544-6.
18. Martin P. Leibovich.(2005). Inflammatory cells during wound repair: the good, the bad and the ugly. Trends in Cell Biology.;15(11):599-607.
19. Selkar R, Rajput D. Immunomodulator dietary foods as a promising preventive tool against infectious diseases such as COVID-19. ijrps [Internet]. 2020Dec.9 [cited 2021Feb.8];11(SPL1):1411-5.
20. Webb AL, Villamor E. Update: effects of antioxidant and non-antioxidant vitamin supplementation on immune function. Nutrition reviews. 2007 May 1;65(5):181-217.
21. Infante M, Ricordi C, Sanchez J, Clare-Salzler MJ, Padilla N, Fuenmayor V, Chavez C, Alvarez A, Baidal D, Alejandro R, Caprio M. Influence of vitamin D on islet autoimmunity and beta-cell function in type 1 diabetes. Nutrients. 2019 Sep;11(9):2185 22. Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-Hughes B, Lips P,
Munns CF, Lazaretti-Castro M, Giustina A, Bilezikian J. Skeletal and extraskeletal actions of vitamin D: current evidence and outstanding questions. Endocrine reviews.
2019 Aug;40(4):1109-51.
23. Martineau AR, James WY, Hooper RL, Barnes NC, Jolliffe DA, Greiller CL, Islam K, McLaughlin D, Bhowmik A, Timms PM, Rajakulasingam RK. Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial. The lancet Respiratory medicine.
2015 Feb 1;3(2):120-30.
24. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, Bhattoa HP.
Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020 Apr;12(4):988.
25. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK, Levine M. Vitamin C as an antioxidant: evaluation of its role in disease prevention. Journal of the American college of Nutrition. 2003 Feb 1;22(1):18-35.
26. Bakaev VV, Duntau AP. Ascorbic acid in blood serum of patients with pulmonary tuberculosis and pneumonia. The International Journal of Tuberculosis and Lung Disease.
2004 Feb 1;8(2):263-6.
27. Hunt C, Chakravorty NK, Annan G, Habibzadeh N, Schorah CJ. The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. International journal for vitamin and nutrition research. 1994 Mar 2;64(3):212-9.
28. Bharara A, Grossman C, Grinnan D, Syed A, Fisher B, DeWilde C, Natarajan R.
Intravenous vitamin C administered as adjunctive therapy for recurrent acute respiratory distress syndrome. Case reports in critical care. 2016 Nov 7;2016.
29. Fowler III AA, Kim C, Lepler L, Malhotra R, Debesa O, Natarajan R, Fisher BJ, Syed A, DeWilde C, Priday A, Kasirajan V. Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome. World journal of critical care medicine. 2017 Feb 4;6(1):85.
30. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane database of systematic reviews. 2013(1).
31. Mochalkin NI. Ascorbic acid in the complex therapy of acute pneumonia. Voenno- MeditsinskiiZhurnal. 1970 Sep;9:17-21.
32. Carr AC, Shaw GM, Natarajan R. Ascorbate-dependent vasopressor synthesis: a rationale
for vitamin C administration in severe sepsis and septic shock?. Critical Care. 2015 Dec;19(1):1-8.
33. Fisher BJ, Kraskauskas D, Martin EJ, Farkas D, Wegelin JA, Brophy D, Ward KR, Voelkel NF, Natarajan R. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. American Journal of Physiology-Lung Cellular and Molecular Physiology. 2012 Jul 1.
34. Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nature medicine. 2012 Mar;18(3):363-74.
35. Bagaitkar J, Demuth DR, Scott DA. Tobacco use increases susceptibility to bacterial infection. Tobacco induced diseases. 2008 Jun;4(1):1-0.
36. Arcavi L, Benowitz NL. Cigarette smoking and infection. Archives of internal medicine.
2004 Nov 8;164(20):2206-16.
37. Kuiper C, Vissers M. Ascorbate as a co-factor for Fe-and 2-oxoglutarate dependent dioxygenases: physiological activity in tumor growth and progression. Frontiers in oncology. 2014 Dec 10;4:359.
38. Young JI, Züchner S, Wang G. Regulation of the epigenome by vitamin C. Annual review of nutrition. 2015 Jul 17;35:545-64.
39. Rhie GE, Shin MH, Seo JY, Choi WW, Cho KH, Kim KH, Park KC, Eun HC, Chung JH.
Aging-and photoaging-dependent changes of enzymic and nonenzymic antioxidants in the epidermis and dermis of human skin in vivo. Journal of investigative dermatology.
2001 Nov 1;117(5):1212-7.
40. Shindo Y, Witt E, Han D, Epstein W, Packer L. Enzymic and non-enzymic antioxidants in epidermis and dermis of human skin. Journal of Investigative Dermatology. 1994 Jan 1;102(1):122-4.
41. McArdle F, Rhodes LE, Parslew R, Jack CI, Friedmann PS, Jackson MJ. UVR-induced oxidative stress in human skin in vivo: effects of oral vitamin C supplementation. Free Radical Biology and Medicine. 2002 Nov 15;33(10):1355-62.
42. Anderson R. Ascorbate-mediated stimulation of neutrophil motility and lymphocyte transformation by inhibition of the peroxidase/H2O2/halide system in vitro and in vivo.
The American journal of clinical nutrition. 1981 Sep 1;34(9):1906-11.
43. Ganguly R, Durieux MF, Waldman RH. Macrophage function in vitamin C-deficient guinea pigs. The American journal of clinical nutrition. 1976 Jul 1;29(7):762-5.
44. Johnston CS, Barkyoumb GM, Schumacher SS. Vitamin C supplementation slightly improves physical activity levels and reduces cold incidence in men with marginal vitamin C status: A randomized controlled trial. Nutrients. 2014 Jul;6(7):2572-83.
45. Belderbos ME, Houben ML, Wilbrink B, Lentjes E, Bloemen EM, Kimpen JL, Rovers M, Bont L. Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis. Pediatrics. 2011 Jun 1;127(6):e1513-20.
46. Coussens AK. The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease. Photochemical & Photobiological Sciences. 2017;16(3):314-38.
20. Dankers W, Colin EM, van Hamburg JP, Lubberts E. Vitamin D in autoimmunity:
molecular mechanisms and therapeutic potential. Frontiers in immunology. 2017 Jan 20;7:697.
47. Gruber-Bzura BM. Vitamin D and influenza—prevention or therapy?. International journal of molecular sciences. 2018 Aug;19(8):2419.
48. Shi Y, Liu T, Yao LI, Xing Y, Zhao X, Fu J, Xue X. Chronic vitamin D deficiency induces lung fibrosis through activation of the renin-angiotensin system. Scientific reports. 2017 Jun 12;7(1):1-0.
49. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. bmj. 2017 Feb 15;356.
50. Uwitonze AM, Razzaque MS. Role of magnesium in vitamin D activation and function. J Am Osteopath Assoc. 2018 Mar 1;118(3):181-9.
51. Mousavi S, Bereswill S, Heimesaat MM. Immunomodulatory and antimicrobial effects of vitamin C. European Journal of Microbiology and Immunology. 2019 Sep;9(3):73-9.
52. Juneja, S., S. Dangore-Khasbage, and R.R. Bhowate. ―Role of Vitamin d in Prevention of Corona Virus Infection (Covid-19).‖ International Journal of Research in Pharmaceutical
Sciences 11, no. Special Issue 1 (2020): 407–10.
https://doi.org/10.26452/ijrps.v11iSPL1.2737.
53. Kamble, A., R.S. Ambad, M. Padamwar, A. Kakade, and M. Yeola. ―To Study the Effect of Oral Vitamin d Supplements on Wound Healing in Patient with Diabetic Foot Ulcer and Its Effect on Lipid Metabolism.‖ International Journal of Research in Pharmaceutical Sciences 11, no. 2 (2020): 2701–6. https://doi.org/10.26452/ijrps.v11i2.2290.
54. Wagh, S.P., S.P. Bhagat, N. Bankar, and K. Jain. ―Role of Vitamin-c Supplementation in Type II Diabetes Mellitus.‖ International Journal of Current Research and Review 12, no.
13 (2020): 61–64. https://doi.org/10.31782/IJCRR.2020.121311.
55. Boharupi, G., and P. Shelotkar. ―Immunomodulatory Measures to Strengthen the Body during Covid Outbreak.‖ International Journal of Research in Pharmaceutical Sciences 11, no. Special Issue 1 (2020): 774–78. https://doi.org/10.26452/ijrps.v11iSPL1.3081.
