Generic placeholder image

Current Bioactive Compounds

Author(s): Anthony Olofinnade, Adejoke Onaolapo*, Olakunle Onaolapo and Olugbenga Olowe

DOI: 10.2174/1573407217666210813143547

DownloadDownload PDF Flyer Cite As
Pleiotropic Beneficial Effects of Dietary L-Ascorbic Acid Fortification in Middle-Aged Mice

Article ID: e251121195658 Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Background: An enhanced knowledge of the multiple effects of ascorbic acid (AA) in health can broaden our understanding of the impacts of its deficiency.

Methods: Mice (10-12 month old) were either fed standard rodent feed or AA-fortified diet at 100, 200 and 300 mg/kg of feed, respectively for 8 weeks. On completion of the study, animals were sacrificed, following which haematological, inflammatory/apoptotic marker, oxidative stress markers, and markers of hepatic/renal integrity were assessed.

Results: Across the groups, AA fortified diet was associated with an increase in food consumption; however, body weight reduction occurred at the lowest concentration, while weight gain was observed at the higher concentrations. Haematological indices (white cell count, granulocytes, lymphocytes, and red cell count) increased at the highest concentration; while some other red cell parameters decreased. A concentration-dependent improvement in antioxidant status, with the greatest benefit at the highest concentration, was observed. Also, a concentration-dependent modulation of inflammatory markers, lipid peroxidation, lipid profile, and biochemical markers of liver and kidney function was observed.

Conclusion: Dietary fortification with AA in middle-aged mice impacted several measurable parameters in a concentration dependent manner. In addition to its antioxidant effects, it was also associated with anti-inflammatory and anti-apoptotic effects.

Keywords: Apoptosis, inflammation, haematological, micronutrient fortification, nutraceutical, oxidative stress.

Graphical Abstract

[1]
Ramakrishnan, U.; Goldenberg, T.; Allen, L.H. Do multiple micronutrient interventions improve child health, growth, and development? J. Nutr., 2011, 141(11), 2066-2075.
[http://dx.doi.org/10.3945/jn.111.146845] [PMID: 21956959]
[2]
Bailey, R.L.; West, K.P., Jr; Black, R.E. The epidemiology of global micronutrient deficiencies. Ann. Nutr. Metab., 2015, 66(Suppl. 2), 22-33.
[http://dx.doi.org/10.1159/000371618] [PMID: 26045325]
[3]
Verma, A. Food fortification: A complementary strategy for improving micronutrient malnutrition (MNM) status. Food Sci. Res. J., 2015, 6, 381-389.
[http://dx.doi.org/10.15740/HAS/FSRJ/6.2/381-389]
[4]
WHO/United Nations General Assembly Proclaims the Decade of Action on Nutrition. 2016. Available from: https://www.who.int/nutrition/decade-of-action/en/
[5]
World Health Organization and Food and Agriculture Organization of the United Nations Guidelines on food fortification with micronutrients. 2006.
[6]
FAO: Food and Agriculture Organization of the United Nations, World Health Organization (WHO) Second International Conference on Nutrition: Conference Outcome Document: Rome Declaration on Nutrition. FAO; Rome, Italy: WHO; Geneva, Switzerland 2014. Available from: http://www.fao.org/3/a-ml542e.pdf
[7]
Aryeetey, R. Optimism for the UN Proclamation of the Decade of Action on Nutrition: An African Perspective. Glob. Health Sci. Pract., 2016, 4(2), 354-355.
[http://dx.doi.org/10.9745/GHSP-D-16-00117] [PMID: 27353630]
[8]
Wirth, J.P.; Laillou, A.; Rohner, F.; Northrop-Clewes, C.A.; Macdonald, B.; Moench-Pfanner, R. Lessons learned from national food fortification projects: experiences from Morocco, Uzbekistan, and Vietnam. Food Nutr. Bull., 2012, 33(4)(Suppl.), S281-S292.
[http://dx.doi.org/10.1177/15648265120334S304] [PMID: 23444709]
[9]
Chadare, F.J.; Idohou, R.; Nago, E.; Affonfere, M.; Agossadou, J.; Fassinou, T.K.; Kénou, C.; Honfo, S.; Azokpota, P.; Linnemann, A.R.; Hounhouigan, D.J. Conventional and food-to-food fortification: An appraisal of past practices and lessons learned. Food Sci. Nutr., 2019, 7(9), 2781-2795.
[http://dx.doi.org/10.1002/fsn3.1133] [PMID: 31576203]
[10]
Method, A.; Tulchinsky, T.H. Food fortification: African countries can make more progress. Adv. Nutri. Food Technol., 2015, S22-S28.
[11]
Nyumuah, R.O.; Hoang, T.C.; Amoaful, E.F.; Agble, R.; Meyer, M.; Wirth, J.P.; Locatelli-Rossi, L.; Panagides, D. Implementing large-scale food fortification in Ghana: lessons learned. Food Nutr. Bull., 2012, 33(4), S293-S300.
[http://dx.doi.org/10.1177/15648265120334S305] [PMID: 23444710]
[12]
Bhagwat, S.; Gulati, D.; Sachdeva, R.; Sankar, R. Food fortification as a complementary strategy for the elimination of micronutrient deficiencies: case studies of large scale food fortification in two Indian States. Asia Pac. J. Clin. Nutr., 2014, 23(Suppl. 1), S4-S11.
[http://dx.doi.org/10.6133/apjcn.2014.23.s1.04] [PMID: 25384726]
[13]
De-Regil, L.M.; Suchdev, P.S.; Vist, G.E.; Walleser, S.; Peña-Rosas, J.P. Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age (Review). Evid. Based Child Health, 2013, 8(1), 112-201.
[http://dx.doi.org/10.1002/ebch.1895] [PMID: 23878126]
[14]
Institute of Medicine (US) Committee on International Nutrition-Vitamin C in Food Aid Commodities Washington (DC); National Academies Press: US, 1997.
[15]
Florentino, R.F.; Pedro, M.R. Rice fortification in the Philippines. In: Combating Iron Deficiency Through Food Fortification Technology; INACG: Washington, DC, 1990.
[16]
Carr, A.C.; Frei, B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am. J. Clin. Nutr., 1999, 69(6), 1086-1107. a
[http://dx.doi.org/10.1093/ajcn/69.6.1086] [PMID: 10357726]
[17]
Lykkesfeldt, J.; Tveden-Nyborg, P. The pharmacokinetics of vitamin C nutrients. 2019.
[18]
Naidu, K.A. Vitamin C in human health and disease is still a mystery? An overview. Nutr. J., 2003, 2, 7.
[http://dx.doi.org/10.1186/1475-2891-2-7] [PMID: 14498993]
[19]
Devaki, S.J.; Raveendran, R.L. Vitamin C: Sources, Functions, Sensing and Analysis, Vitamin C. 2017. Available from: https://www.intechopen.com/books/vitamin-c/vitamin-c-sources-functions-sensing-and-analysis
[20]
Carr, A.; Frei, B. Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J., 1999, 13(9), 1007-1024.
[http://dx.doi.org/10.1096/fasebj.13.9.1007] [PMID: 10336883]
[21]
Levine, M.; Conry-Cantilena, C.; Wang, Y.; Welch, R.W.; Washko, P.W.; Dhariwal, K.R.; Park, J.B.; Lazarev, A.; Graumlich, J.F.; King, J.; Cantilena, L.R. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc. Natl. Acad. Sci. USA, 1996, 93(8), 3704-3709.
[http://dx.doi.org/10.1073/pnas.93.8.3704] [PMID: 8623000]
[22]
Institute of Medicine (US) Panel on Dietary Antioxidants and Related Compounds Washington (DC); National Academies Press: US, 2000.
[23]
Carr, A.C.; Lykkesfeldt, J. Discrepancies in global vitamin C recommendations: a review of RDA criteria and underlying health perspectives. Crit. Rev. Food Sci. Nutr., 2020, 1-14.
[http://dx.doi.org/10.1080/10408398.2020.1744513] [PMID: 32223303]
[24]
Frei, B.; Trabe, M.G. The new US dietary reference for vitamins C and E. Redox Rep., 2001, 6(1), 5-9.
[http://dx.doi.org/10.1179/135100001101535978] [PMID: 11333117]
[25]
Onaolapo, A.Y.; Onaolapo, O.J.; Nwoha, P.U. Alterations in behaviour, cerebral cortical morphology and cerebral oxidative stress markers following aspartame ingestion. J. Chem. Neuroanat., 2016, 78, 42-56.
[http://dx.doi.org/10.1016/j.jchemneu.2016.08.006] [PMID: 27565676]
[26]
Onaolapo, A.Y.; Onaolapo, O.J.; Nwoha, P.U. Aspartame and the hippocampus: Revealing a bi-directional, dose/time-dependent behavioural and morphological shift in mice. Neurobiol. Learn. Mem., 2017, 139, 76-88.
[http://dx.doi.org/10.1016/j.nlm.2016.12.021] [PMID: 28049023]
[27]
Onaolapo, O.J.; Odeniyi, A.O.; Jonathan, S.O.; Samuel, M.O.; Amadiegwu, D.; Olawale, A.; Tiamiyu, A.O.; Ojo, F.O.; Yahaya, H.A.; Ayeni, O.J.; Onaolapo, A.Y. An investigation of the anti- Parkinsonism potential of co-enzyme Q10 and co-enzyme Q10 /levodopa-carbidopa combination in mice. Curr. Aging Sci., 2019.
[http://dx.doi.org/10.2174/1874609812666191023153724] [PMID: 31702498]
[28]
Olofinnade, A.T.; Onaolapo, T.M.; Oladimeji, S.; Fatoki, A.M.; Balogun, C.I.; Onaolapo, A.Y.; Onaolapo, O.J. An Evaluation of the Effects of Pyridoxal Phosphate in Chlorpromazineinduced Parkinsonism using Mice. Cent. Nerv. Syst. Agents Med. Chem., 2020, 20(1), 13-25.
[http://dx.doi.org/10.2174/1871524920666200120142508] [PMID: 31987026]
[29]
Onaolapo, O.J.; Adekola, M.A.; Azeez, T.O.; Salami, K.; Onaolapo, A.Y. l-Methionine and silymarin: A comparison of prophylactic protective capabilities in acetaminophen-induced injuries of the liver, kidney and cerebral cortex. Biomed. Pharmacother., 2017, 85, 323-333.
[http://dx.doi.org/10.1016/j.biopha.2016.11.033] [PMID: 27889232]
[30]
Mollica, A.; Stefanucci, S.; Macedonio, G.; Locatelli, M.; Onaolapo, O.J.; Onaolapo, A.Y.; Adegoke, J.; Olaniyan, M.; Novellino, E. Capparis spinosa L: In vivo and in vitro evaluation of the anti- diabetic and anti-hyperlipidaemic activity. J. Funct. Foods, 2017, 35, 32-42.
[http://dx.doi.org/10.1016/j.jff.2017.05.001]
[31]
Mollica, A.; Zengin, G.; Stefanucci, A.; Ferrante, C.; Menghini, L.; Orlando, G.; Brunetti, L.; Locatelli, M.; Dimmito, M.P.; Novellino, E.; Wakeel, O.K.; Ogundeji, M.O.; Onaolapo, A.Y.; Onaolapo, O.J. Nutraceutical potential of Corylus avellana daily supplements for obesity and related dysmetabolism. J. Funct. Foods, 2018, 47, 562-574.
[http://dx.doi.org/10.1016/j.jff.2018.06.016]
[32]
Clinical Diagnosis and Measurement by Laboratory Methods, 16th ed; W. B. Saunders and Co: Philadelphia, PA, 1974, p. 260.
[33]
Searcy, R.L.; Reardon, J.E.; Foreman, J.A. A new photometric method for serum urea nitrogen determination. Am. J. Med. Technol., 1967, 33(1), 15-20.
[PMID: 6037908]
[34]
Nishikimi, M.; Appaji, N.; Yagi, K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem. Biophys. Res. Commun., 1972, 46(2), 849-854.
[http://dx.doi.org/10.1016/S0006-291X(72)80218-3] [PMID: 4400444]
[35]
Miller, N.J.; Rice-Evans, C.; Davies, M.J.; Gopinathan, V.; Milner, A. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin. Sci. (Lond.), 1993, 84(4), 407-412.
[http://dx.doi.org/10.1042/cs0840407] [PMID: 8482045]
[36]
Ghiselli, A.; Serafini, M.; Natella, F.; Scaccini, C. Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Free Radic. Biol. Med., 2000, 29(11), 1106-1114.
[http://dx.doi.org/10.1016/S0891-5849(00)00394-4] [PMID: 11121717]
[37]
Bartosz, G. Non-enzymatic antioxidant capacity assays: Limitations of use in biomedicine. Free Radic. Res., 2010, 44(7), 711-720.
[http://dx.doi.org/10.3109/10715761003758114] [PMID: 20446897]
[38]
Pinchuk, I.; Shoval, H.; Dotan, Y.; Lichtenberg, D. Evaluation of antioxidants: scope, limitations and relevance of assays. Chem. Phys. Lipids, 2012, 165(6), 638-647.
[http://dx.doi.org/10.1016/j.chemphyslip.2012.05.003] [PMID: 22721987]
[39]
Re, R.; Pellegrini, N.; Proteggente, A.; Pannala, A.; Yang, M.; Rice-Evans, C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med., 1999, 26(9-10), 1231-1237.
[http://dx.doi.org/10.1016/S0891-5849(98)00315-3] [PMID: 10381194]
[40]
Shea, T.B.; Rogers, E.; Ashline, D.; Ortiz, D.; Sheu, M.S. Quantification of antioxidant activity in brain tissue homogenates using the ‘total equivalent antioxidant capacity’. J. Neurosci. Methods, 2003, 125(1-2), 55-58.
[http://dx.doi.org/10.1016/S0165-0270(03)00028-1] [PMID: 12763230]
[41]
Canoy, D.; Wareham, N.; Welch, A.; Bingham, S.; Luben, R.; Day, N.; Khaw, K.T. Plasma ascorbic acid concentrations and fat distribution in 19,068 British men and women in the European Prospective Investigation into Cancer and Nutrition Norfolk cohort study. Am. J. Clin. Nutr., 2005, 82(6), 1203-1209.
[http://dx.doi.org/10.1093/ajcn/82.6.1203] [PMID: 16332652]
[42]
Johnston, C.S.; Beezhold, B.L.; Mostow, B.; Swan, P.D. Plasma vitamin C is inversely related to body mass index and waist circumference but not to plasma adiponectin in nonsmoking adults. J. Nutr., 2007, 137(7), 1757-1762.
[http://dx.doi.org/10.1093/jn/137.7.1757] [PMID: 17585027]
[43]
Garcia, O.P.; Ronquillo, D.; Caamano, M.C.; Camacho, M.; Long, K.Z.; Rosado, J Zinc, vitamin A, and vitamin C status are associated with leptin concentrations and obesity in Mexican women: results from a cross-sectional study. Nutr Metab (Lond), 2012, 9, 59-10.
[44]
Naylor, G.J.; Grant, L.; Smith, C. A double blind placebo controlled trial of ascorbic acid in obesity. Nutr. Health, 1985, 4(1), 25-28.
[http://dx.doi.org/10.1177/026010618500400104] [PMID: 3914623]
[45]
Jung, E.Y.; Jun, S.C.; Chang, U.J.; Suh, H.J. L-ascorbic acid addition to chitosan reduces body weight in overweight women. Int. J. Vitam. Nutr. Res., 2014, 84(1-2), 5-11.
[http://dx.doi.org/10.1024/0300-9831/a000187] [PMID: 25835230]
[46]
Larsen, S.C.; Angquist, L.; Ahluwalia, T.S.; Skaaby, T.; Roswall, N.; Tjønneland, A.; Halkjær, J.; Overvad, K.; Pedersen, O.; Hansen, T.; Linneberg, A.; Husemoen, L.L.; Toft, U.; Heitmann, B.L.; Sørensen, T.I. Dietary ascorbic acid and subsequent change in body weight and waist circumference: associations may depend on genetic predisposition to obesity--a prospective study of three independent cohorts. Nutr. J., 2014, 13, 43.
[http://dx.doi.org/10.1186/1475-2891-13-43] [PMID: 24886192]
[47]
Jun, S.C.; Jung, E.Y.; Hong, Y.H.; Park, Y.; Kang, Dh.; Chang, U.J.; Suh, H.J. Anti-obesity effects of chitosan and psyllium husk with L-ascorbic acid in guinea pigs. Int. J. Vitam. Nutr. Res., 2012, 82(2), 113-120.
[http://dx.doi.org/10.1024/0300-9831/a000100] [PMID: 23065836]
[48]
Njoku, P.C. Effect of dietary ascorbic acid (vitamin C) supplementation on the performance of broiler chickens in a tropical environment. Anim. Feed Sci. Technol., 1985, 6(1–2), 17-24.
[49]
Alvarez, M.R.; Kravetz, F.O. Effect of ascorbic acid on food preference and consumption in captive capybaras (Hydrochoerushydrochaeris). Braz. Arch. Biol. Technol., 2009, 2, 3.
[http://dx.doi.org/10.1590/S1516-89132009000300011]
[50]
Johnston, C.S.; Corte, C.; Swan, P.D. Marginal vitamin C status is associated with reduced fat oxidation during submaximal exercise in young adults. Nutr Metab, 2006, 3, 35-10.
[http://dx.doi.org/10.1186/1743-7075-3-35]
[51]
Steiber, A.; Kerner, J.; Hoppel, C.L. Carnitine: a nutritional, biosynthetic, and functional perspective. Mol. Aspects Med., 2004, 25(5-6), 455-473.
[http://dx.doi.org/10.1016/j.mam.2004.06.006] [PMID: 15363636]
[52]
Das, S.S.; Srivastava, L.M. Effect of ascorbic acid on lipid profile and lipid peroxidation in hypercholesterolemic rabbits. Nutr. Res., 1997, 17(2), 231-241.
[http://dx.doi.org/10.1016/S0271-5317(96)00254-0]
[53]
Eteng, M.U.; Ibekwe, H.A.; Amatey, T.E.; Bassey, B.J.; Uboh, F.U.; Owu, D.U. Effect of vitamin C on serum lipids and electrolyte profile of albino Wistar rats. Niger. J. Physiol. Sci., 2006, 21(1-2), 15-19.
[PMID: 17242728]
[54]
Karakilcik, A.Z.; Halat, R.; Zerin, M.; Celik, H.; Nazligul, Y. Effects of vitamin C and exercise on lipid profile, platelet and erythrocyte indices in young soccer players. J. Sports Med. Phys. Fitness, 2014, 54(5), 665-671.
[PMID: 25270787]
[55]
El Mashad, G.M.; ElSayed, H.M.; Nosair, N.A. Effect of vitamin C supplementation on lipid profile, serum uric acid, and ascorbic acid in children on hemodialysis. Saudi J. Kidney Dis. Transpl., 2016, 27(6), 1148-1154.
[http://dx.doi.org/10.4103/1319-2442.194602] [PMID: 27900959]
[56]
McRae, M.P. The efficacy of vitamin C supplementation on reducing total serum cholesterol in human subjects: a review and analysis of 51 experimental trials. J. Chiropr. Med., 2006, 5(1), 2-12.
[http://dx.doi.org/10.1016/S0899-3467(07)60127-X] [PMID: 19674666]
[57]
McRae, M.P. Vitamin C supplementation lowers serum low-density lipoprotein cholesterol and triglycerides: a meta-analysis of 13 randomized controlled trials. J. Chiropr. Med., 2008, 7(2), 48-58.
[http://dx.doi.org/10.1016/j.jcme.2008.01.002] [PMID: 19674720]
[58]
Carr, T.P.; Parks, J.S.; Rudel, L.L. Hepatic ACAT activity in African green monkeys is highly correlated to plasma LDL cholesteryl ester enrichment and coronary artery atherosclerosis. Arterioscler. Thromb., 1992, 12(11), 1274-1283.
[http://dx.doi.org/10.1161/01.ATV.12.11.1274] [PMID: 1420087]
[59]
Montano, C.E.; Fernandez, M.L.; McNamara, D.J. Regulation of apolipoprotein B-containing lipoproteins by vitamin C level and dietary fat saturation in guinea pigs. Metabolism, 1998, 47(7), 883-891.
[http://dx.doi.org/10.1016/S0026-0495(98)90131-7] [PMID: 9667240]
[60]
Hillstrom, R.J.; Yacapin-Ammons, A.K.; Lynch, S.M. Vitamin C inhibits lipid oxidation in human HDL. J. Nutr., 2003, 133(10), 3047-3051.
[http://dx.doi.org/10.1093/jn/133.10.3047] [PMID: 14519782]
[61]
Yousef, M.I.; Salem, M.H.; Kamel, K.I.; Hassan, G.A.; El-Nouty, F.D. Influence of ascorbic acid supplementation on the haematological and clinical biochemistry parameters of male rabbits exposed to aflatoxin B1. J. Environ. Sci. Health B, 2003, 38(2), 193-209.
[http://dx.doi.org/10.1081/PFC-120018449] [PMID: 12617557]
[62]
Karakilcik, A.Z.; Zerin, M.; Arslan, O.; Nazligul, Y.; Vural, H. Effects of vitamin C and E on liver enzymes and biochemical parameters of rabbits exposed to aflatoxin B1. Vet. Hum. Toxicol., 2004, 46(4), 190-192.
[PMID: 15303390]
[63]
Shekoohi-Shooli, F.; Mortazavi, S.M.; Shojaei-Fard, M.B.; Nematollahi, S.; Tayebi, M. Evaluation of the Protective Role of Vitamin C on the Metabolic and Enzymatic Activities of the Liver in the Male Rats After Exposure to 2.45 GHz Of Wi-Fi Routers. J. Biomed. Phys. Eng., 2016, 6(3), 157-164.
[PMID: 27853723]
[64]
Gillis, K.; Stevens, K.K.; Bell, E.; Patel, R.K.; Jardine, A.G.; Morris, S.T.W.; Schneider, M.P.; Delles, C.; Mark, P.B. Ascorbic acid lowers central blood pressure and asymmetric dimethylarginine in chronic kidney disease. Clin. Kidney J., 2018, 11(4), 532-539.
[http://dx.doi.org/10.1093/ckj/sfx158] [PMID: 30094018]
[65]
Karahan, S.; Afsar, B.; Kanbay, M. Ascorbic acid: a promising agent in chronic kidney disease? Clin. Kidney J., 2018, 11(4), 530-531.
[http://dx.doi.org/10.1093/ckj/sfy044] [PMID: 30094017]
[66]
Dröse, S.; Brandt, U. Molecular mechanisms of superoxide production by the mitochondrial respiratory chain. Adv. Exp. Med. Biol., 2012, 748, 145-169.
[http://dx.doi.org/10.1007/978-1-4614-3573-0_6] [PMID: 22729857]
[67]
Chen, A.Y.; Lü, J.M.; Yao, Q.; Chen, C. Entacapone is an antioxidant more potent than vitamin C and vitamin E for scavenging of hypochlorous acid and peroxynitrite, and the inhibition of oxidative stress-induced cell death. Med. Sci. Monit., 2016, 22, 687-696.
[http://dx.doi.org/10.12659/MSM.896462] [PMID: 26927838]
[68]
Padayatty, S.J.; Katz, A.; Wang, Y.; Eck, P.; Kwon, O.; Lee, J.H.; Chen, S.; Corpe, C.; Dutta, A.; Dutta, S.K.; Levine, M. Vitamin C as an antioxidant: Evaluation of its role in disease prevention. J. Am. Coll. Nutr., 2003, 22(1), 18-35.
[http://dx.doi.org/10.1080/07315724.2003.10719272] [PMID: 12569111]
[69]
Wong, S.K.; Chin, K.Y.; Ima-Nirwana, S.; Vitamin, C. Vitamin C: A review on its Role in the management of metabolic syndrome. Int. J. Med. Sci., 2020, 17(11), 1625-1638.
[http://dx.doi.org/10.7150/ijms.47103] [PMID: 32669965]
[70]
Aditi, A.; Graham, D.Y. Vitamin C, gastritis, and gastric disease: a historical review and update. Dig. Dis. Sci., 2012, 57(10), 2504-2515.
[http://dx.doi.org/10.1007/s10620-012-2203-7] [PMID: 22543844]
[71]
Mikirova, N.; Casciari, J.; Riordan, N.; Hunninghake, R. Clinical experience with intravenous administration of ascorbic acid: achievable levels in blood for different states of inflammation and disease in cancer patients. J. Transl. Med., 2013, 11, 191.
[http://dx.doi.org/10.1186/1479-5876-11-191] [PMID: 23947403]
[72]
Ellulu, M.S.; Rahmat, A.; Patimah, I.; Khaza’ai, H.; Abed, Y. Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial. Drug Des. Devel. Ther., 2015, 9, 3405-3412.
[http://dx.doi.org/10.2147/DDDT.S83144] [PMID: 26170625]
[73]
Fadime, E.P. Vitamin C: An Antioxidant Agent, Vitamin C. 2017. Available from: https://www.intechopen.com/books/vitamin-c/vitamin-c-an-antioxidant-agent
[74]
Majewicz, J.; Rimbach, G.; Proteggente, A.R.; Lodge, J.K.; Kraemer, K.; Minihane, A.M. Dietary vitamin C down-regulates inflammatory gene expression in apoE4 smokers. Biochem. Biophys. Res. Commun., 2005, 338(2), 951-955.
[http://dx.doi.org/10.1016/j.bbrc.2005.10.029] [PMID: 16248984]
[75]
Kong, E.H.; Ma, S.Y.; Jeong, J.Y.; Kim, K.H. Effects of L-ascorbic acid on the production of pro-inflammatory and anti-inflammatory cytokines in C57BL/6 mouse splenocytes. Kosin Med. J., 2015, 30, 41-49.
[http://dx.doi.org/10.7180/kmj.2015.30.1.41]
[76]
Mikirova, N. Intravenous high-dose ascorbic acid reduces the expression of inflammatory markers in peripheral mononuclear cells of subjects with metabolic syndrome. J. Transl. Sci., 2016, 2(3), 188-195.
[http://dx.doi.org/10.15761/JTS.1000140]
[77]
Qing, Z.; Xiao-Hui, W.; Xi-Mei, W.; Chao-Chun, Z. Vitamin C deficiency aggravates tumor necrosis factor α-induced insulin resistance. Eur. J. Pharmacol., 2018, 829, 1-11.
[http://dx.doi.org/10.1016/j.ejphar.2018.03.044] [PMID: 29625084]
[78]
Mohanty, J.G.; Nagababu, E.; Rifkind, J.M. Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging. Front. Physiol., 2014, 5, 84.
[http://dx.doi.org/10.3389/fphys.2014.00084] [PMID: 24616707]
[79]
Sureda, A.; Batle, J.M.; Tauler, P.; Ferrer, M.D.; Tur, J.A.; Pons, A. Vitamin C supplementation influences the antioxidant response and nitric oxide handling of erythrocytes and lymphocytes to diving apnea. Eur. J. Clin. Nutr., 2006, 60(7), 838-846.
[http://dx.doi.org/10.1038/sj.ejcn.1602388] [PMID: 16482080]
[80]
Raval, J.S.; Fontes, J.; Banerjee, U.; Yazer, M.H.; Mank, E.; Palmer, A.F. Ascorbic acid improves membrane fragility and decreases haemolysis during red blood cell storage. Transfus. Med., 2013, 23(2), 87-93.
[http://dx.doi.org/10.1111/tme.12013] [PMID: 23406333]
[81]
Radosinska, J.; Jasenovec, T.; Puzserova, A.; Krajcir, J.; Lacekova, J.; Kucerova, K.; Kalnovicova, T.; Tothova, L.; Kovacicova, I.; Vrbjar, N. Promotion of whole blood rheology after vitamin C supplementation: focus on red blood cells 1. Can. J. Physiol. Pharmacol., 2019, 97(9), 837-843.
[http://dx.doi.org/10.1139/cjpp-2018-0735] [PMID: 30983394]
[82]
Nyoro, K.I.; Seriki, A.S.; Odetola, O.A. Comparative Effects of Ascorbic Acid and Aspirin on Platelet Count and Aggregation in Albino Wistar Rats. EC Pharmacology and Toxicology, 2018, 10, 880-890.
[83]
Mohammed, B.M.; Sanford, K.W.; Fisher, B.J.; Martin, E.J.; Contaifer, D., Jr; Warncke, U.O.; Wijesinghe, D.S.; Chalfant, C.E.; Brophy, D.F.; Fowler Iii, A.A.; Natarajan, R. Impact of high dose vitamin C on platelet function. World J. Crit. Care Med., 2017, 6(1), 37-47.
[http://dx.doi.org/10.5492/wjccm.v6.i1.37] [PMID: 28224106]