A Review of the Applications of Vitamin C to Treat Human Diseases

Abstract

Vitamin C, a ubiquitous water-soluble vitamin, has been demonstrated to have several biological activities, including the promotion of collagen production, enhancement of immunity, facilitation of iron absorption, and improvement of fat metabolism. Thus, it has a multitude of applications in the medical field, such as whitening, antioxidation, and the prevention of a wide range of diseases. Conversely, its lack of stability and low permeability limit its applicability. This review presents a summary of the physicochemical properties, delivery strategies, and biological activities of vitamin C. Additionally, this review provides an overview of its preventive and therapeutic effects on diseases such as cataracts, tumors, and cardiovascular conditions. Finally, this review explores the prospective applications of vitamin C as a pharmaceutical agent. A variety of vitamin C derivatives and delivery systems have been developed to overcome the instability and low permeability of vitamin C. However, several challenges persist, including the uncertain efficacy of derivatives and the complexities associated with the implementation of delivery systems. It is anticipated that future advancements will facilitate the development of delivery forms and the utilization of vitamin C in novel applications.

Keywords

vitamin C - ascorbic acid - free radicals - antioxidant - biological activities

^# These authors contributed equally to this work.

Publication History

Received: 18 September 2023

Accepted: 09 September 2024

Article published online:
21 October 2024

• References

• 1 Caritá AC, Fonseca-Santos B, Shultz JD, Michniak-Kohn B, Chorilli M, Leonardi GR. Vitamin C: one compound, several uses. Advances for delivery, efficiency and stability. Nanomedicine 2020; 24: 102117
• 2 Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA 1999; 281 (15) 1415-1423
• 3 Lykkesfeldt J, Michels AJ, Frei B, Vitamin C. Vitamin C. Adv Nutr 2014; 5 (01) 16-18
• 4 Kinlin LM, Weinstein M. Scurvy: old disease, new lessons. Paediatr Int Child Health 2023; 43 (04) 83-94
• 5 Palmieri B, Vadalà M, Laurino C. Nutrition in wound healing: investigation of the molecular mechanisms, a narrative review. J Wound Care 2019; 28 (10) 683-693
• 6 Carr AC, Lykkesfeldt J. Factors affecting the vitamin C dose-concentration relationship: implications for global vitamin C dietary recommendations. Nutrients 2023; 15 (07) 1657
• 7 Wang A, Luo J, Zhang T, Zhang D. Dietary vitamin C and vitamin C derived from vegetables are inversely associated with the risk of depressive symptoms among the general population. Antioxidants 2021; 10 (12) 1984
• 8 Frei B, Birlouez-Aragon I, Lykkesfeldt J. Authors' perspective: what is the optimum intake of vitamin C in humans?. Crit Rev Food Sci Nutr 2012; 52 (09) 815-829
• 9 Grosso G, Bei R, Mistretta A. et al. Effects of vitamin C on health: a review of evidence. Front Biosci (Landmark Ed) 2013; 18 (03) 1017-1029
• 10 Ma N, Siegfried C, Kubota M. et al. Expression profiling of ascorbic acid-related transporters in human and mouse eyes. Invest Ophthalmol Vis Sci 2016; 57 (07) 3440-3450
• 11 Corpe CP, Eck P, Wang J, Al-Hasani H, Levine M. Intestinal dehydroascorbic acid (DHA) transport mediated by the facilitative sugar transporters, GLUT2 and GLUT8. J Biol Chem 2013; 288 (13) 9092-9101
• 12 Washko PW, Wang Y, Levine M. Ascorbic acid recycling in human neutrophils. J Biol Chem 1993; 268 (21) 15531-15535
• 13 Subramanian VS, Sabui S, Moradi H, Marchant JS, Said HM. Inhibition of intestinal ascorbic acid uptake by lipopolysaccharide is mediated via transcriptional mechanisms. Biochim Biophys Acta Biomembr 2018; 1860 (02) 556-565
• 14 Tsiaoussis GI, Christaki E, Apidianakis Y. I can C clearly now: how EPEC inhibits gut vitamin C transport by dysregulating SVCT. Dig Dis Sci 2021; 66 (07) 2140-2142
• 15 Subramanian VS, Srinivasan P, Wildman AJ, Marchant JS, Said HM. Molecular mechanism(s) involved in differential expression of vitamin C transporters along the intestinal tract. Am J Physiol Gastrointest Liver Physiol 2017; 312 (04) G340-G347
• 16 Levine M, Padayatty SJ, Espey MG. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv Nutr 2011; 2 (02) 78-88
• 17 Rivers JM. Safety of high-level vitamin C ingestion. Int J Vitam Nutr Res Suppl 1989; 30: 95-102
• 18 Padayatty SJ, Levine M. Vitamin C: the known and the unknown and Goldilocks. Oral Dis 2016; 22 (06) 463-493
• 19 Gęgotek A, Skrzydlewska E. Ascorbic acid as antioxidant. Vitam Horm 2023; 121: 247-270
• 20 Ahmed TA, Aljaeid BM. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery. Drug Des Devel Ther 2016; 10: 483-507
• 21 Alishahi A, Mirvaghefi A, Tehrani MR. et al. Chitosan nanoparticle to carry vitamin C through the gastrointestinal tract and induce the non-specific immunity system of rainbow trout (Oncorhynchus mykiss). Carbohydr Polym 2011; 86 (01) 142-146
• 22 Thapa Magar K, Boafo GF, Li X, Chen Z, He W. Liposome-based delivery of biological drugs. Chin Chem Lett 2022; 33 (02) 587-596
• 23 Xiao Q, Li X, Liu C. et al. Liposome-based anchoring and core-encapsulation for combinatorial cancer therapy. Chin Chem Lett 2022; 33 (09) 4191-4196
• 24 Maurya VK, Shakya A, McClements DJ. et al. Vitamin C fortification: need and recent trends in encapsulation technologies. Front Nutr 2023; 10: 1229243
• 25 Wechtersbach L, Ulrih NP, Cigic B. Liposomal stabilization of ascorbic acid in model systems and in food matrices. Lebensm Wiss Technol 2012; 45 (01) 43-49
• 26 Łukawski M, Dałek P, Borowik T. et al. New oral liposomal vitamin C formulation: properties and bioavailability. J Liposome Res 2020; 30 (03) 227-234
• 27 Jiao Z, Wang X, Yin Y, Xia J, Mei Y. Preparation and evaluation of a chitosan-coated antioxidant liposome containing vitamin C and folic acid. J Microencapsul 2018; 35 (03) 272-280
• 28 Davis JL, Paris HL, Beals JW. et al. Liposomal-encapsulated ascorbic acid: influence on vitamin C bioavailability and capacity to protect against ischemia-reperfusion injury. Nutr Metab Insights 2016; 9: 25-30
• 29 Gopi S, Balakrishnan P. Evaluation and clinical comparison studies on liposomal and non-liposomal ascorbic acid (vitamin C) and their enhanced bioavailability. J Liposome Res 2021; 31 (04) 356-364
• 30 Callender SP, Mathews JA, Kobernyk K, Wettig SD. Microemulsion utility in pharmaceuticals: implications for multi-drug delivery. Int J Pharm 2017; 526 (1–2): 425-442
• 31 Sawant RR, Vaze O, D'Souza GG, Rockwell K, Torchilin VP. Palmitoyl ascorbate-loaded polymeric micelles: cancer cell targeting and cytotoxicity. Pharm Res 2011; 28 (02) 301-308
• 32 Xiao W, Fu Q, Zhao Y. et al. Ascorbic acid-modified brain-specific liposomes drug delivery system with “lock-in” function. Chem Phys Lipids 2019; 224: 104727
• 33 Luo Q, Jiang M, Kou L. et al. Ascorbate-conjugated nanoparticles for promoted oral delivery of therapeutic drugs via sodium-dependent vitamin C transporter 1 (SVCT1). Artif Cells Nanomed Biotechnol 2018; 46 (sup1): 198-208
• 34 Inoue Y, Hibino M, Murata I, Kanamoto I. A nanocarrier skin-targeted drug delivery system using an ascorbic acid derivative. Pharm Res 2017; 35 (01) 1
• 35 Kishimoto Y, Saito N, Kurita K, Shimokado K, Maruyama N, Ishigami A. Ascorbic acid enhances the expression of type 1 and type 4 collagen and SVCT2 in cultured human skin fibroblasts. Biochem Biophys Res Commun 2013; 430 (02) 579-584
• 36 Abdullah M, Jamil RT, Attia FN. Vitamin C (Ascorbic Acid). 2023 May 1. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing LLC; 2024
• 37 De Giorgi F, Fumagalli M, Scietti L, Forneris F. Collagen hydroxylysine glycosylation: non-conventional substrates for atypical glycosyltransferase enzymes. Biochem Soc Trans 2021; 49 (02) 855-866
• 38 Chugaeva UY, Raouf M, Morozova NS, Mahdavian L. Effects of L-ascorbic acid (C₆H₈O₆: Vit-C) on collagen amino acids: DFT study. Amino Acids 2023; 55 (11) 1655-1664
• 39 Dengler VL, Galbraith M, Espinosa JM. Transcriptional regulation by hypoxia inducible factors. Crit Rev Biochem Mol Biol 2014; 49 (01) 1-15
• 40 Strowitzki MJ, Cummins EP, Taylor CT. Protein hydroxylation by hypoxia-inducible factor (HIF) hydroxylases: unique or ubiquitous?. Cells 2019; 8 (05) 384
• 41 Fischer AP, Miles SL. Ascorbic acid, but not dehydroascorbic acid increases intracellular vitamin C content to decrease Hypoxia Inducible Factor -1 alpha activity and reduce malignant potential in human melanoma. Biomed Pharmacother 2017; 86: 502-513
• 42 Piersma B, Wouters OY, de Rond S, Boersema M, Gjaltema RAF, Bank RA. Ascorbic acid promotes a TGFβ1-induced myofibroblast phenotype switch. Physiol Rep 2017; 5 (17) e13324
• 43 Kuiper C, Dachs GU, Currie MJ, Vissers MC. Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. Free Radic Biol Med 2014; 69: 308-317
• 44 Vissers MC, Gunningham SP, Morrison MJ, Dachs GU, Currie MJ. Modulation of hypoxia-inducible factor-1 alpha in cultured primary cells by intracellular ascorbate. Free Radic Biol Med 2007; 42 (06) 765-772
• 45 Carr AC, Maggini S. Vitamin C and immune function. Nutrients 2017; 9 (11) 1211
• 46 Nikolich-Žugich J. The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol 2018; 19 (01) 10-19
• 47 Netea MG, Schlitzer A, Placek K, Joosten LAB, Schultze JL. Innate and adaptive immune memory: an evolutionary continuum in the host's response to pathogens. Cell Host Microbe 2019; 25 (01) 13-26
• 48 Valacchi G, Muresan XM, Sticozzi C. et al. Ozone-induced damage in 3D-Skin Model is prevented by topical vitamin C and vitamin E compound mixtures application. J Dermatol Sci 2016; 82 (03) 209-212
• 49 Zhong S, Zhou Q, Yang J. et al. Relationship between the cGAS-STING and NF-κB pathways-role in neurotoxicity. Biomed Pharmacother 2024; 175: 116698
• 50 Liu ZQ. Anti-oxidant in china: a thirty-year journey. Am J Chin Med 2019; 47 (05) 1005-1024
• 51 Morante-Palacios O, Godoy-Tena G, Calafell-Segura J. et al. Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells. Nucleic Acids Res 2022; 50 (19) 10981-10994
• 52 Qi T, Sun M, Zhang C, Chen P, Xiao C, Chang X. Ascorbic acid promotes plasma cell differentiation through enhancing TET2/3-mediated DNA demethylation. Cell Rep 2020; 33 (09) 108452
• 53 Bhoot HR, Zamwar UM, Chakole S, Anjankar A. Dietary sources, bioavailability, and functions of ascorbic acid (vitamin C) and its role in the common cold, tissue healing, and iron metabolism. Cureus 2023; 15 (11) e49308
• 54 Houten SM, Wanders RJ. A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation. J Inherit Metab Dis 2010; 33 (05) 469-477
• 55 Pekala J, Patkowska-Sokoła B, Bodkowski R. et al. L-carnitine–metabolic functions and meaning in humans life. Curr Drug Metab 2011; 12 (07) 667-678
• 56 Lee H, Ahn J, Shin SS, Yoon M. Ascorbic acid inhibits visceral obesity and nonalcoholic fatty liver disease by activating peroxisome proliferator-activated receptor α in high-fat-diet-fed C57BL/6J mice. Int J Obes (Lond) 2019; 43 (08) 1620-1630
• 57 Conway FJ, Talwar D, McMillan DC. The relationship between acute changes in the systemic inflammatory response and plasma ascorbic acid, alpha-tocopherol and lipid peroxidation after elective hip arthroplasty. Clin Nutr 2015; 34 (04) 642-646
• 58 Tragni V, Primiano G, Tummolo A. et al. Personalized medicine in mitochondrial health and disease: molecular basis of therapeutic approaches based on nutritional supplements and their analogs. Molecules 2022; 27 (11) 3494
• 59 Yuan Y, Liu C, Chen X. et al. Vitamin C inhibits the metabolic changes induced by tet1 insufficiency under high fat diet stress. Mol Nutr Food Res 2021; 65 (16) e2100417
• 60 Piskin E, Cianciosi D, Gulec S, Tomas M, Capanoglu E. Iron absorption: factors, limitations, and improvement methods. ACS Omega 2022; 7 (24) 20441-20456
• 61 Hsieh Y-HPHaYP. Valence state of iron in the presence of ascorbic acid and ethylenediaminetetraacetic acid. J Agric Food Chem 1997; 45 (04) 1126-1129
• 62 Bergamaschi G, Di Sabatino A, Pasini A. et al. Intestinal expression of genes implicated in iron absorption and their regulation by hepcidin. Clin Nutr 2017; 36 (05) 1427-1433
• 63 Ganasen M, Togashi H, Takeda H. et al. Structural basis for promotion of duodenal iron absorption by enteric ferric reductase with ascorbate. Commun Biol 2018; 1: 120
• 64 Luo X, Hill M, Johnson A, Latunde-Dada GO. Modulation of Dcytb (Cybrd 1) expression and function by iron, dehydroascorbate and Hif-2α in cultured cells. Biochim Biophys Acta 2014; 1840 (01) 106-112
• 65 Lane DJ, Bae DH, Merlot AM, Sahni S, Richardson DR. Duodenal cytochrome b (DCYTB) in iron metabolism: an update on function and regulation. Nutrients 2015; 7 (04) 2274-2296
• 66 von Siebenthal HK, Moretti D, Zimmermann MB, Stoffel NU. Effect of dietary factors and time of day on iron absorption from oral iron supplements in iron deficient women. Am J Hematol 2023; 98 (09) 1356-1363
• 67 Cook JD, Monsen ER. Vitamin C, the common cold, and iron absorption. Am J Clin Nutr 1977; 30 (02) 235-241
• 68 Lee CM, Afshari NA. The global state of cataract blindness. Curr Opin Ophthalmol 2017; 28 (01) 98-103
• 69 Kupfer C. Bowman lecture. The conquest of cataract: a global challenge. Trans Ophthalmol Soc U K (1962) 1985; 104 (Pt 1): 1-10
• 70 Lee B, Afshari NA, Shaw PX. Oxidative stress and antioxidants in cataract development. Curr Opin Ophthalmol 2024; 35 (01) 57-63
• 71 Llop SM, Papaliodis GN. Cataract surgery complications in uveitis patients: a review article. Semin Ophthalmol 2018; 33 (01) 64-69
• 72 Alkadi H. A review on free radicals and antioxidants. Infect Disord Drug Targets 2020; 20 (01) 16-26
• 73 Thiagarajan R, Manikandan R. Antioxidants and cataract. Free Radic Res 2013; 47 (05) 337-345
• 74 Kodera S, Hirata A, Miura F. et al. Model-based approach for analyzing prevalence of nuclear cataracts in elderly residents. Comput Biol Med 2020; 126: 104009
• 75 Ishikawa Y, Hashizume K, Kishimoto S. et al. Effect of vitamin C depletion on UVR-B induced cataract in SMP30/GNL knockout mice. Exp Eye Res 2012; 94 (01) 85-89
• 76 Bejarano E, Weinberg J, Clark M, Taylor A, Rowan S, Whitcomb EA. Redox regulation in age-related cataracts: roles for glutathione, vitamin C, and the NRF2 signaling pathway. Nutrients 2023; 15 (15) 3375
• 77 Lim JC, Caballero Arredondo M, Braakhuis AJ, Donaldson PJ. Vitamin C and the lens: new insights into delaying the onset of cataract. Nutrients 2020; 12 (10) 3142
• 78 Wei L, Liang G, Cai C, Lv J. Association of vitamin C with the risk of age-related cataract: a meta-analysis. Acta Ophthalmol 2016; 94 (03) e170-e176
• 79 Choi JH, Lee E, Heo YR. The association between dietary vitamin A and C intakes and cataract: data from korea national health and nutrition examination survey 2012. Clin Nutr Res 2020; 9 (03) 163-170
• 80 Braakhuis AJ, Donaldson CI, Lim JC, Donaldson PJ. Nutritional strategies to prevent lens cataract: current status and future strategies. Nutrients 2019; 11 (05) 1186
• 81 Fan X, Xiaoqin L, Potts B, Strauch CM, Nemet I, Monnier VM. Topical application of L-arginine blocks advanced glycation by ascorbic acid in the lens of hSVCT2 transgenic mice. Mol Vis 2011; 17: 2221-2227
• 82 Fan X, Sell DR, Hao C. et al. Vitamin C is a source of oxoaldehyde and glycative stress in age-related cataract and neurodegenerative diseases. Aging Cell 2020; 19 (07) e13176
• 83 van Gorkom GNY, Lookermans EL, Van Elssen CHMJ, Bos GMJ. The effect of vitamin C (ascorbic acid) in the treatment of patients with cancer: a systematic review. Nutrients 2019; 11 (05) 977
• 84 Peng H, Wu X, Wen Y. Plasma circulating vitamin C levels and risk of endometrial cancer: a bi-directional mendelian randomization analysis. Front Med (Lausanne) 2022; 9: 792008
• 85 Campbell EJ, Vissers MCM, Wohlrab C. et al. Pharmacokinetic and anti-cancer properties of high dose ascorbate in solid tumours of ascorbate-dependent mice. Free Radic Biol Med 2016; 99: 451-462
• 86 Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A 1976; 73 (10) 3685-3689
• 87 Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A 1978; 75 (09) 4538-4542
• 88 Creagan ET, Moertel CG, O'Fallon JR. et al. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med 1979; 301 (13) 687-690
• 89 Moertel CG, Fleming TR, Creagan ET, Rubin J, O'Connell MJ, Ames MM. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N Engl J Med 1985; 312 (03) 137-141
• 90 Padayatty SJ, Sun H, Wang Y. et al. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med 2004; 140 (07) 533-537
• 91 Stephenson CM, Levin RD, Spector T, Lis CG. Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. Cancer Chemother Pharmacol 2013; 72 (01) 139-146
• 92 Zhang J, Simpson CM, Berner J. et al. Systematic identification of anticancer drug targets reveals a nucleus-to-mitochondria ROS-sensing pathway. Cell 2023; 186 (11) 2361-2379.e25
• 93 Heer CD, Davis AB, Riffe DB. et al. Superoxide dismutase mimetic GC4419 enhances the oxidation of pharmacological ascorbate and its anticancer effects in an H₂O₂-dependent manner. Antioxidants 2018; 7 (01) 18
• 94 Chen H, He W, Guo Z. An H₂O₂-responsive nanocarrier for dual-release of platinum anticancer drugs and O₂: controlled release and enhanced cytotoxicity against cisplatin resistant cancer cells. Chem Commun (Camb) 2014; 50 (68) 9714-9717
• 95 Tovmasyan A, Sampaio RS, Boss MK. et al. Anticancer therapeutic potential of Mn porphyrin/ascorbate system. Free Radic Biol Med 2015; 89: 1231-1247
• 96 Gao X, Wei K, Hu B, Xu K, Tang B. Ascorbic acid induced HepG2 cells' apoptosis via intracellular reductive stress. Theranostics 2019; 9 (14) 4233-4240
• 97 Yun J, Mullarky E, Lu C. et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 2015; 350 (6266): 1391-1396
• 98 Guo D, Liao Y, Na J. et al. The involvement of ascorbic acid in cancer treatment. Molecules 2024; 29 (10) 2295
• 99 Magrì A, Germano G, Lorenzato A. et al. High-dose vitamin C enhances cancer immunotherapy. Sci Transl Med 2020; 12 (532) eaay8707
• 100 Du J, Cullen JJ, Buettner GR. Ascorbic acid: chemistry, biology and the treatment of cancer. Biochim Biophys Acta 2012; 1826 (02) 443-457
• 101 Rawal M, Schroeder SR, Wagner BA. et al. Manganoporphyrins increase ascorbate-induced cytotoxicity by enhancing H₂O₂ generation. Cancer Res 2013; 73 (16) 5232-5241
• 102 Camarena V, Wang G. The epigenetic role of vitamin C in health and disease. Cell Mol Life Sci 2016; 73 (08) 1645-1658
• 103 Vissers MCM, Das AB. Potential mechanisms of action for vitamin C in cancer: reviewing the evidence. Front Physiol 2018; 9: 809
• 104 Lee KE, Hahm E, Bae S, Kang JS, Lee WJ. The enhanced tumor inhibitory effects of gefitinib and L-ascorbic acid combination therapy in non-small cell lung cancer cells. Oncol Lett 2017; 14 (01) 276-282
• 105 Shimpo K, Nagatsu T, Yamada K. et al. Ascorbic acid and adriamycin toxicity. Am J Clin Nutr 1991; 54 (6, suppl): 1298S-1301S
• 106 Fritz H, Flower G, Weeks L. et al. Intravenous vitamin C and cancer: a systematic review. Integr Cancer Ther 2014; 13 (04) 280-300
• 107 Ausman LM. Criteria and recommendations for vitamin C intake. Nutr Rev 1999; 57 (07) 222-224
• 108 Kubota Y, Iso H, Date C. et al; JACC Study Group. Dietary intakes of antioxidant vitamins and mortality from cardiovascular disease: the Japan Collaborative Cohort Study (JACC) study. Stroke 2011; 42 (06) 1665-1672
• 109 Stepaniak U, Micek A, Grosso G. et al. Antioxidant vitamin intake and mortality in three Central and Eastern European urban populations: the HAPIEE study. Eur J Nutr 2016; 55 (02) 547-560
• 110 Knekt P, Ritz J, Pereira MA. et al. Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts. Am J Clin Nutr 2004; 80 (06) 1508-1520
• 111 Tveden-Nyborg P, Lykkesfeldt J. Does vitamin C deficiency increase lifestyle-associated vascular disease progression? Evidence based on experimental and clinical studies. Antioxid Redox Signal 2013; 19 (17) 2084-2104
• 112 Zoulikha M, Xiao Q, Boafo GF, Sallam MA, Chen Z, He W. Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome. Acta Pharm Sin B 2022; 12 (02) 600-620
• 113 Oudemans-van Straaten HM, Spoelstra-de Man AM, de Waard MC. Vitamin C revisited. Crit Care 2014; 18 (04) 460
• 114 Panday S, Kar S, Kavdia M. How does ascorbate improve endothelial dysfunction? - a computational analysis. Free Radic Biol Med 2021; 165: 111-126
• 115 Brown AA, Hu FB. Dietary modulation of endothelial function: implications for cardiovascular disease. Am J Clin Nutr 2001; 73 (04) 673-686
• 116 Mortensen A, Lykkesfeldt J. Does vitamin C enhance nitric oxide bioavailability in a tetrahydrobiopterin-dependent manner? In vitro, in vivo and clinical studies. Nitric Oxide 2014; 36: 51-57
• 117 Yuyun MF, Ng LL, Ng GA. Endothelial dysfunction, endothelial nitric oxide bioavailability, tetrahydrobiopterin, and 5-methyltetrahydrofolate in cardiovascular disease. Where are we with therapy?. Microvasc Res 2018; 119: 7-12
• 118 Ginter E. Chronic vitamin C deficiency increases the risk of cardiovascular diseases. Bratisl Lek Listy 2007; 108 (09) 417-421
• 119 Zhang PY, Xu X, Li XC. Cardiovascular diseases: oxidative damage and antioxidant protection. Eur Rev Med Pharmacol Sci 2014; 18 (20) 3091-3096
• 120 Pandya V, Hunsaker JJH, La'ulu SL. et al. Excessively low cholesterol and triglyceride levels in an apparently healthy patient. Clin Biochem 2021; 96: 78-81
• 121 Das UN. Vitamin C for type 2 diabetes mellitus and hypertension. Arch Med Res 2019; 50 (02) 11-14
• 122 Yuan X, Li X, Ji Z. et al. Effects of vitamin C supplementation on blood pressure and hypertension control in response to ambient temperature changes in patients with essential hypertension. Clin Exp Hypertens 2019; 41 (05) 414-421
• 123 Guan Y, Dai P, Wang H. Effects of vitamin C supplementation on essential hypertension: a systematic review and meta-analysis. Medicine (Baltimore) 2020; 99 (08) e19274
• 124 Xu JX, Su L, Chen L, Lin JX. Protection from vascular endothelial dysfunction in acute glycemic load-induced primary hypertension by vitamin C and E. Genet Mol Res 2014; 13 (03) 7246-7255
• 125 Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol 2015; 71: 40-56
• 126 Wang K, Jiang H, Li W, Qiang M, Dong T, Li H. Role of vitamin C in skin diseases. Front Physiol 2018; 9: 819
• 127 Pullar JM, Carr AC, Vissers MCM. The roles of vitamin C in skin health. Nutrients 2017; 9 (08) 866
• 128 Ebanks JP, Wickett RR, Boissy RE. Mechanisms regulating skin pigmentation: the rise and fall of complexion coloration. Int J Mol Sci 2009; 10 (09) 4066-4087
• 129 Patrizi A, Raone B, Neri I. Atopiclair. Expert Opin Pharmacother 2009; 10 (07) 1223-1230
• 130 Tang MB, Leong KF, Ou LS. et al. Cost-effectiveness study of pediatric atopic dermatitis in Asia: atopiclair vs. regular emollient (AD-ATOP). J Drugs Dermatol 2015; 14 (02) 169-175
• 131 Copley-Merriman C, Zelt S, Clark M, Gnanasakthy A. Impact of measuring patient-reported outcomes in dermatology drug development. Patient 2017; 10 (02) 203-213
• 132 Foucher C, Bisson JF, Guy M. et al. A new moisturiser improves DNCB-induced atopic dermatitis-like symptoms and restores skin barrier function in BALB/c mice. Antiinflamm Antiallergy Agents Med Chem 2023; 22 (01) 49-57
• 133 Iinuma K, Noguchi N, Nakaminami H, Sasatsu M, Nishijima S, Tsuboi I. Susceptibility of Propionibacterium acnes isolated from patients with acne vulgaris to zinc ascorbate and antibiotics. Clin Cosmet Investig Dermatol 2011; 4: 161-165
• 134 Stamford NP. Stability, transdermal penetration, and cutaneous effects of ascorbic acid and its derivatives. J Cosmet Dermatol 2012; 11 (04) 310-317
• 135 Lee CA, Baek JS, Kwag DG, Lee HJ, Park J, Cho CW. Enhancement of skin permeation of vitamin C using vibrating microneedles. Transl Clin Pharmacol 2017; 25 (01) 15-20
• 136 Al-Niaimi F, Chiang NYZ. Topical vitamin C and the skin: mechanisms of action and clinical applications. J Clin Aesthet Dermatol 2017; 10 (07) 14-17
• 137 Sun S, Li J, Wang S. et al. CHIT1-positive microglia drive motor neuron ageing in the primate spinal cord. Nature 2023; 624 (7992): 611-620
• 138 Bedhiafi T, Idoudi S, Fernandes Q. et al. Nano-vitamin C: a promising candidate for therapeutic applications. Biomed Pharmacother 2023; 158: 114093
• 139 Enescu CD, Bedford LM, Potts G, Fahs F. A review of topical vitamin C derivatives and their efficacy. J Cosmet Dermatol 2022; 21 (06) 2349-2359
• 140 Zhu YZ. Study on incompatibility of vitamin C [in Chinese]. Guide of China Medicine. 2014; 12 (28) 398-399