Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much higher than its plasma concentrations, and compared to other vitamins. The role of vitamin C is well demonstrated by miscellaneous symptoms of its absence-scurvy. The only clinically well-documented indication for vitamin C is scurvy. The effects of vitamin C administration on cancer, cardiovascular diseases, and infections are rather minor or even debatable in the general population. Vitamin C is relatively safe, but caution should be given to the administration of high doses, which can cause overt side effects in some susceptible patients (e.g., oxalate renal stones). Lastly, analytical methods for its determination with advantages and pitfalls are also discussed in this review.

Department of Analytical Chemistry Faculty of Pharmacy Charles University 500 05 Hradec Králové Czech Republic

Department of Clinical Biochemistry and Diagnostics University Hospital Hradec Králové 500 05 Hradec Králové Czech Republic

Department of Pharmacognosy Faculty of Pharmacy Charles University 500 05 Hradec Králové Czech Republic

Department of Pharmacology and Toxicology Faculty of Pharmacy Charles University 500 05 Hradec Králové Czech Republic

Department of Social and Clinical Pharmacy Faculty of Pharmacy Charles University 500 05 Hradec Králové Czech Republic

Research group of Pharmaco Toxicological Analysis Alma Mater Studiorum University of Bologna 40126 Bologna Italy

UCIBIO REQUIMTE Laboratory of Toxicology Biological Sciences Department Faculty of Pharmacy University of Porto 4050 313 Porto Portugal

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Linster C.L., Van Schaftingen E. Vitamin C. Biosynthesis, recycling and degradation in mammals. FEBS J. 2007;274:1–22. doi: 10.1111/j.1742-4658.2006.05607.x. PubMed DOI

Granger M., Eck P. Dietary vitamin C in human health. Adv. Food Nutr. Res. 2018;83:281–310. doi: 10.1016/bs.afnr.2017.11.006. PubMed DOI

World Health Organization . Scurvy and its Prevention and Control in Major Emergencies/Prepared by Zita Weise Prinzo. World Health Organization; Geneva, Switzerland: 1999.

Englard S., Seifter S. The biochemical functions of ascorbic acid. Annu. Rev. Nutr. 1986;6:365–406. doi: 10.1146/annurev.nu.06.070186.002053. PubMed DOI

Levine M., Rumsey S., Daruwala R., Park J., Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999;281:1415–1423. doi: 10.1001/jama.281.15.1415. PubMed DOI

Padayatty S.J., Levine M. Vitamin C: The known and the unknown and Goldilocks. Oral. Dis. 2016;22:463–493. doi: 10.1111/odi.12446. PubMed DOI PMC

Sauberlich H.E., Tamura T., Craig C.B., Freeberg L.E., Liu T. Effects of erythorbic acid on vitamin C metabolism in young women. Am. J. Clin. Nutr. 1996;64:336–346. doi: 10.1093/ajcn/64.3.336. PubMed DOI

Hornig D. Distribution of ascorbic acid, metabolites and analogues in man and animals. Ann. N. Y. Acad. Sci. 1975;258:103–118. doi: 10.1111/j.1749-6632.1975.tb29271.x. PubMed DOI

Robertson W.B. D-Ascorbic acid and collagen synthesis. Biochim. Biophys. Acta. 1963;74:137–139. doi: 10.1016/0006-3002(63)91341-6. PubMed DOI

Zilva S.S. The behaviour of l-ascorbic acid and chemically related compounds in the animal body. The influence of generalised ether anaesthesia on their urinary excretion. Biochem. J. 1935;29:2366–2368. doi: 10.1042/bj0292366. PubMed DOI PMC

Davey M.W., Montagu M.V., Inzé D., Sanmartin M., Kanellis A., Smirnoff N., Benzie I.J.J., Strain J.J., Favell D., Fletcher J. Plant L-ascorbic acid: Chemistry, function, metabolism, bioavailability and effects of processing. J. Sci. Food Agr. 2000;80:825–860. doi: 10.1002/(SICI)1097-0010(20000515)80:7<825::AID-JSFA598>3.0.CO;2-6. DOI

EFSA Panel on Dietetic Products, Nutrition and Allergies Scientific opinion on dietary reference values for vitamin C. EFSA J. 2013;11:3418. doi: 10.2903/j.efsa.2013.3418. DOI

Fediuk K., Hidiroglou N., Madère R., Kuhnlein H.V. Vitamin C in Inuit traditional food and women’s diets. J. Food Compos. Anal. 2002;15:221–235. doi: 10.1006/jfca.2002.1053. DOI

Barros L., Ferreira M.-J., Queirós B., Ferreira I.C.F.R., Baptista P. Total phenols, ascorbic acid, β-carotene and lycopene in Portuguese wild edible mushrooms and their antioxidant activities. Food Chem. 2007;103:413–419. doi: 10.1016/j.foodchem.2006.07.038. DOI

Ferreira I., Barros L., Abreu R. Antioxidants in wild mushrooms. Curr. Med. Chem. 2009;16:1543–1560. doi: 10.2174/092986709787909587. PubMed DOI

Mattila P., Könkö K., Eurola M., Pihlava J.M., Astola J., Vahteristo L., Hietaniemi V., Kumpulainen J., Valtonen M., Piironen V. Contents of vitamins, mineral elements, and some phenolic compounds in cultivated mushrooms. J. Agric. Food Chem. 2001;49:2343–2348. doi: 10.1021/jf001525d. PubMed DOI

Williams D.J., Edwards D., Pun S., Chaliha M., Burren B., Tinggi U., Sultanbawa Y. Organic acids in Kakadu plum (Terminalia ferdinandiana): The good (ellagic), the bad (oxalic) and the uncertain (ascorbic) Food Res. Int. 2016;89:237–244. doi: 10.1016/j.foodres.2016.08.004. PubMed DOI

Rodrigues R.B., De Menezes H.C., Cabral L.M.C., Dornier M., Reynes M. An Amazonian fruit with a high potential as a natural source of vitamin C: The camu-camu (Myrciaria dubia) Fruits. 2001;56:345–354. doi: 10.1051/fruits:2001135. DOI

Mezadri T., Villaño D., Fernández-Pachón M.S., García-Parrilla M.C., Troncoso A.M. Antioxidant compounds and antioxidant activity in acerola (Malpighia emarginata DC.) fruits and derivatives. J. Food Compos. Anal. 2008;21:282–290. doi: 10.1016/j.jfca.2008.02.002. DOI

Gutzeit D., Baleanu G., Winterhalter P., Jerz G. Vitamin C content in sea buckthorn berries (Hippophaë rhamnoides L. ssp. rhamnoides) and related products: A kinetic study on storage stability and the determination of processing effects. J. Food Sci. 2008;73:615–620. doi: 10.1111/j.1750-3841.2008.00957.x. PubMed DOI

Roman I., Stănilă A., Stănilă S. Bioactive compounds and antioxidant activity of Rosa canina L. biotypes from spontaneous flora of Transylvania. Chem. Cent. J. 2013;7:73. doi: 10.1186/1752-153X-7-73. PubMed DOI PMC

Ariharan V.N., Kalirajan K., Devi V.N., Prasad P. An exotic fruit which forms the new natural source for vitamin-C. Rasayan J. Chem. 2012;5:356.

Gull J., Sultana B., Anwar F., Naseer R., Ashraf M., Ashrafuzzaman M. Variation in antioxidant attributes at three ripening stages of guava (Psidium guajava L.) fruit from different geographical regions of Pakistan. Molecules. 2012;17:3165–3180. doi: 10.3390/molecules17033165. PubMed DOI PMC

Vagiri M., Ekholm A., Öberg E., Johansson E., Andersson S.C., Rumpunen K. Phenols and ascorbic acid in black currants (Ribes nigrum L.): Variation due to genotype, location, and year. J. Agric. Food Chem. 2013;61:9298–9306. doi: 10.1021/jf402891s. PubMed DOI

Ellong E., Billard C., Adenet S., Rochefort K. Polyphenols, carotenoids, vitamin C content in tropical fruits and vegetables and impact of processing methods. Food Sci. Nutr. 2015;6:299–313. doi: 10.4236/fns.2015.63030. DOI

Domínguez-Perles R., Mena P., García-Viguera C., Moreno D.A. Brassica foods as a dietary source of vitamin C: A review. Crit. Rev. Food Sci. Nutr. 2014;54:1076–1091. doi: 10.1080/10408398.2011.626873. PubMed DOI

Martínez S., López M., González-Raurich M., Bernardo Alvarez A. The effects of ripening stage and processing systems on vitamin C content in sweet peppers (Capsicum annuum L.) Int. J. Food Sci. Nutr. 2005;56:45–51. doi: 10.1080/09637480500081936. PubMed DOI

Peñas E., Frias J., Sidro B., Vidal-Valverde C. Chemical evaluation and sensory quality of sauerkrauts obtained by natural and induced fermentations at different NaCl levels from Brassica oleracea Var. capitata Cv. Bronco grown in Eastern Spain. Effect of storage. J. Agric. Food Chem. 2010;58:3549–3557. doi: 10.1021/jf903739a. PubMed DOI

Külen O., Stushnoff C., Holm D.G. Effect of cold storage on total phenolics content, antioxidant activity and vitamin C level of selected potato clones. J. Sci. Food Agric. 2013;93:2437–2444. doi: 10.1002/jsfa.6053. PubMed DOI

Santos J., Herrero M., Mendiola J., Oliva-Teles M.T., Ibáñez E., Delerue-Matos C., Oliveira M. Fresh-cut aromatic herbs: Nutritional quality stability during shelf-life. LWT. 2014;59:101–107. doi: 10.1016/j.lwt.2014.05.019. DOI

Chakraborty S., Santra S. Biochemical composition of eight benthic alge collected from Sunderban. Indian J. Mar. Sci. 2008;37:329–332.

Zheng J., Yang B., Tuomasjukka S., Ou S., Kallio H. Effects of latitude and weather conditions on contents of sugars, fruit acids, and ascorbic acid in black currant (Ribes nigrum L.) juice. J. Agric. Food Chem. 2009;57:2977–2987. doi: 10.1021/jf8034513. PubMed DOI

Kallio H., Yang B., Peippo P. Effects of different origins and harvesting time on vitamin C, tocopherols, and tocotrienols in sea buckthorn (Hippophaë rhamnoides) berries. J. Agric. Food Chem. 2002;50:6136–6142. doi: 10.1021/jf020421v. PubMed DOI

Cardoso P.C., Tomazini A.P.B., Stringheta P.C., Ribeiro S.M.R., Pinheiro-Sant’Ana H.M. Vitamin C and carotenoids in organic and conventional fruits grown in Brazil. Food Chem. 2011;126:411–416. doi: 10.1016/j.foodchem.2010.10.109. DOI

Raghu V., Platel K., Srinivasan K. Comparison of ascorbic acid content of Emblica officinalis fruits determined by different analytical methods. J. Food Compos. Anal. 2007;20:529–533. doi: 10.1016/j.jfca.2007.02.006. DOI

Lešková E., Kubíková J., Kováčiková E., Košická M., Porubská J., Holčíková K. Vitamin losses: Retention during heat treatment and continual changes expressed by mathematical models. J. Food Compos. Anal. 2006;19:252–276. doi: 10.1016/j.jfca.2005.04.014. DOI

Wang J., Law C.L., Mujumdar A.S. The degradation mechanisms and kinetics of vitamin C in fruits and vegetables during thermal processing. In: Nema P.K., Kaur B.P., Mujumdar A.S., editors. Drying Technologies in Foods. CRC Press; Boca Raton, FL, USA: 2018. pp. 275–301.

Phillips K.M., Tarragó-Trani M.T., Gebhardt S.E., Exler J., Patterson K.Y., Haytowitz D.B., Pehrsson P.R., Holden J.M. Stability of vitamin C in frozen raw fruit and vegetable homogenates. J. Food Compos. Anal. 2010;23:253–259. doi: 10.1016/j.jfca.2009.08.018. DOI

Vandamme E.J., Revuelta J.L. Industrial Biotechnology of Vitamins, Biopigments, and Antioxidants. Wiley-VCH Verlag GmbH & Co. KGaA; Weinheim, Germany: 2016. Industrial fermentation of vitamin C; pp. 161–192.

Carr A.C., Vissers M.C. Synthetic or food-derived vitamin C—Are they equally bioavailable? Nutrients. 2013;5:4284–4304. doi: 10.3390/nu5114284. PubMed DOI PMC

Konczak I., Maillot F., Dalar A. Phytochemical divergence in 45 accessions of Terminalia ferdinandiana (Kakadu plum) Food Chem. 2014;151:248–256. doi: 10.1016/j.foodchem.2013.11.049. PubMed DOI

Justi K.C., Visentainer J.V., Evelázio de Souza N., Matsushita M. Nutritional composition and vitamin C stability in stored camu-camu (Myrciaria dubia) pulp. Arch. Latinoam. Nutr. 2000;50:405–408. PubMed

McCook-Russell K.P., Nair M.G., Facey P.C., Bowen-Forbes C.S. Nutritional and nutraceutical comparison of Jamaican Psidium cattleianum (strawberry guava) and Psidium guajava (common guava) fruits. Food Chem. 2012;134:1069–1073. doi: 10.1016/j.foodchem.2012.03.018. PubMed DOI

Najwa R., Azlan A. Comparison of vitamin C content in citrus fruits by titration and high performance liquid chromatography (HPLC) methods. Int. Food Res. J. 2017;24:726–733.

Njoku P.C., Ayuk A.A., Okoye C.V. Temperature effects on vitamin C content in citrus fruits. Pak. J. Nutr. 2011;10:1168–1169. doi: 10.3923/pjn.2011.1168.1169. DOI

Kevers C., Pincemail J., Tabart J., Defraigne J.O., Dommes J. Influence of cultivar, harvest time, storage conditions, and peeling on the antioxidant capacity and phenolic and ascorbic acid contents of apples and pears. J. Agric. Food Chem. 2011;59:6165–6171. doi: 10.1021/jf201013k. PubMed DOI

Roberts P., Jones D.L., Edwards-Jones G. Yield and vitamin C content of tomatoes grown in vermicomposted wastes. J. Sci. Food Agric. 2007;87:1957–1963. doi: 10.1002/jsfa.2950. DOI

Georgé S., Tourniaire F., Gautier H., Goupy P., Rock E., Caris-Veyrat C. Changes in the contents of carotenoids, phenolic compounds and vitamin C during technical processing and lyophilisation of red and yellow tomatoes. Food Chem. 2011;124:1603–1611. doi: 10.1016/j.foodchem.2010.08.024. DOI

Turkben C., Uylaser V., Incedayi B., Çelikkol I. Effects of different maturity periods and processes on nutritional components of rose hip (Rosa canina L.) J. Food Agric. Environ. 2010;8:26–30.

Singh G., Kawatra A., Sehgal S. Nutritional composition of selected green leafy vegetables, herbs and carrots. Plant. Foods Hum. Nutr. 2001;56:359–364. doi: 10.1023/A:1011873119620. PubMed DOI

Daruwala R., Song J., Koh W.S., Rumsey S.C., Levine M. Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2. FEBS Lett. 1999;460:480–484. doi: 10.1016/S0014-5793(99)01393-9. PubMed DOI

Lykkesfeldt J., Tveden-Nyborg P. The pharmacokinetics of vitamin C. Nutrients. 2019;11:2412. doi: 10.3390/nu11102412. PubMed DOI PMC

Burzle M., Suzuki Y., Ackermann D., Miyazaki H., Maeda N., Clemencon B., Burrier R., Hediger M.A. The sodium-dependent ascorbic acid transporter family SLC23. Mol. Aspects Med. 2013;34:436–454. doi: 10.1016/j.mam.2012.12.002. PubMed DOI

Liang W.J., Johnson D., Jarvis S.M. Vitamin C transport systems of mammalian cells. Mol. Membr. Biol. 2001;18:87–95. doi: 10.1080/09687680110033774. PubMed DOI

Levine M., Conry-Cantilena C., Yh W., Welch R., Washko P., Dhariwal K., Park J., Lazarev A., Graumlich J., King J., et al. Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Proc. Natl. Acad. Sci. USA. 1996;93:3704–3709. doi: 10.1073/pnas.93.8.3704. PubMed DOI PMC

Hornig D., Vuilleumier J.P., Hartmann D. Absorption of large, single, oral intakes of ascorbic acid. Int. J. Vitam. Nutr. Res. 1980;50:309–314. PubMed

Graumlich J.F., Ludden T.M., Conry-Cantilena C., Cantilena L.R., Jr., Wang Y., Levine M. Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion. Pharm. Res. 1997;14:1133–1139. doi: 10.1023/A:1012186203165. PubMed DOI

Kim Y., Kim M.-G. HPLC-UV method for the simultaneous determinations of ascorbic acid and dehydroascorbic acid in human plasma. Transl. Clin. Pharmacol. 2016;24:37–42. doi: 10.12793/tcp.2016.24.1.37. DOI

Huijskens M.J., Wodzig W.K., Walczak M., Germeraad W.T., Bos G.M. Ascorbic acid serum levels are reduced in patients with hematological malignancies. Results Immunol. 2016;6:8–10. doi: 10.1016/j.rinim.2016.01.001. PubMed DOI PMC

Riemersma R.A., Carruthers K.F., Elton R.A., Fox K.A. Vitamin C and the risk of acute myocardial infarction. Am. J. Clin. Nutr. 2000;71:1181–1186. doi: 10.1093/ajcn/71.5.1181. PubMed DOI

Schleicher R.L., Carroll M.D., Ford E.S., Lacher D.A. Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES) Am. J. Clin. Nutr. 2009;90:1252–1263. doi: 10.3945/ajcn.2008.27016. PubMed DOI

Dhariwal K.R., Hartzell W.O., Levine M. Ascorbic acid and dehydroascorbic acid measurements in human plasma and serum. Am. J. Clin. Nutr. 1991;54:712–716. doi: 10.1093/ajcn/54.4.712. PubMed DOI

Motoyama T., Kawano H., Kugiyama K., Hirashima O., Ohgushi M., Yoshimura M., Ogawa H., Yasue H. Endothelium-dependent vasodilation in the brachial artery is impaired in smokers: Effect of vitamin C. Am. J. Physiol. 1997;273:1644–1650. doi: 10.1152/ajpheart.1997.273.4.H1644. PubMed DOI

Padayatty S.J., Sun H., Wang Y., Riordan H.D., Hewitt S.M., Katz A., Wesley R.A., Levine M. Vitamin C pharmacokinetics: Implications for oral and intravenous use. Ann. Intern. Med. 2004;140:533–537. doi: 10.7326/0003-4819-140-7-200404060-00010. PubMed DOI

Levine M., Padayatty S.J., Espey M.G. Vitamin C: A concentration-function approach yields pharmacology and therapeutic discoveries. Adv. Nutr. 2011;2:78–88. doi: 10.3945/an.110.000109. PubMed DOI PMC

Levine M., Wang Y., Padayatty S.J., Morrow J. A new recommended dietary allowance of vitamin C for healthy young women. Proc. Natl. Acad. Sci. USA. 2001;98:9842–9846. doi: 10.1073/pnas.171318198. PubMed DOI PMC

Chen Q., Espey M.G., Sun A.Y., Lee J.H., Krishna M.C., Shacter E., Choyke P.L., Pooput C., Kirk K.L., Buettner G.R., et al. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc. Natl. Acad. Sci. USA. 2007;104:8749–8754. doi: 10.1073/pnas.0702854104. PubMed DOI PMC

May J.M., Harrison F.E. Role of vitamin C in the function of the vascular endothelium. Antioxid. Redox Sign. 2013;19:2068–2083. doi: 10.1089/ars.2013.5205. PubMed DOI PMC

Harrison F.E., Dawes S.M., Meredith M.E., Babaev V.R., Li L., May J.M. Low vitamin C and increased oxidative stress and cell death in mice that lack the sodium-dependent vitamin C transporter SVCT2. Free Radic. Biol. Med. 2010;49:821–829. doi: 10.1016/j.freeradbiomed.2010.06.008. PubMed DOI PMC

Sotiriou S., Gispert S., Cheng J., Wang Y., Chen A., Hoogstraten-Miller S., Miller G.F., Kwon O., Levine M., Guttentag S.H., et al. Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival. Nat. Med. 2002;8:514–517. doi: 10.1038/0502-514. PubMed DOI

May J.M., Qu Z.C. Transport and intracellular accumulation of vitamin C in endothelial cells: Relevance to collagen synthesis. Arch. Biochem. Biophys. 2005;434:178–186. doi: 10.1016/j.abb.2004.10.023. PubMed DOI

Prigge S.T., Mains R.E., Eipper B.A., Amzel L.M. New insights into copper monooxygenases and peptide amidation: Structure, mechanism and function. Cell. Mol. Life Sci. 2000;57:1236–1259. doi: 10.1007/PL00000763. PubMed DOI PMC

May J.M. Vitamin C transport and its role in the central nervous system. Subcell. Biochem. 2012;56:85–103. doi: 10.1007/978-94-007-2199-9_6. PubMed DOI PMC

Corpe C., Lee J.-H., Kwon O., Eck P., Narayanan J., Kirk K., Levine M. 6-Bromo-6-deoxy-L-ascorbic acid: An ascorbate analog specific for Na +-dependent vitamin C transporter but not glucose transporter pathways. J. Biol. Chem. 2005;280:5211–5220. doi: 10.1074/jbc.M412925200. PubMed DOI

Tolbert B.M., Ward J.B. Dehydroascorbic acid. In: Seib P.A., Tolbert B.M., editors. Ascorbic Acid: Chemistry, Metabolism, and Uses. American Chemical Society; Washington, DC, USA: 1982. pp. 101–123.

Banhegyi G., Braun L., Csala M., Puskas F., Mandl J. Ascorbate metabolism and its regulation in animals. Free Radic. Biol. Med. 1997;23:793–803. doi: 10.1016/S0891-5849(97)00062-2. PubMed DOI

Huang J., Agus D.B., Winfree C.J., Kiss S., Mack W.J., McTaggart R.A., Choudhri T.F., Kim L.J., Mocco J., Pinsky D.J., et al. Dehydroascorbic acid, a blood-brain barrier transportable form of vitamin C, mediates potent cerebroprotection in experimental stroke. Proc. Natl. Acad. Sci. USA. 2001;98:11720–11724. doi: 10.1073/pnas.171325998. PubMed DOI PMC

Schjoldager J.G., Paidi M.D., Lindblad M.M., Birck M.M., Kjærgaard A.B., Dantzer V., Lykkesfeldt J., Tveden-Nyborg P. Maternal vitamin C deficiency during pregnancy results in transient fetal and placental growth retardation in guinea pigs. Eur. J. Nutr. 2015;54:667–676. doi: 10.1007/s00394-014-0809-6. PubMed DOI

Hellman L., Burns J.J. Metabolism of L-ascorbic acid-1-C14 in man. J. Biol. Chem. 1958;230:923–930. doi: 10.1016/S0021-9258(18)70515-2. PubMed DOI

Corpe C.P., Tu H., Eck P., Wang J., Faulhaber-Walter R., Schnermann J., Margolis S., Padayatty S., Sun H., Wang Y., et al. Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice. J. Clin. Investig. 2010;120:1069–1083. doi: 10.1172/JCI39191. PubMed DOI PMC

Tsukaguchi H., Tokui T., Mackenzie B., Berger U.V., Chen X.Z., Wang Y., Brubaker R.F., Hediger M.A. A family of mammalian Na+-dependent L-ascorbic acid transporters. Nature. 1999;399:70–75. doi: 10.1038/19986. PubMed DOI

Timpson N.J., Forouhi N.G., Brion M.J., Harbord R.M., Cook D.G., Johnson P., McConnachie A., Morris R.W., Rodriguez S., Luan J., et al. Genetic variation at the SLC23A1 locus is associated with circulating concentrations of L-ascorbic acid (vitamin C): Evidence from 5 independent studies with >15,000 participants. Am. J. Clin. Nutr. 2010;92:375–382. doi: 10.3945/ajcn.2010.29438. PubMed DOI PMC

Michels A.J., Hagen T.M., Frei B. Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function. Annu. Rev. Nutr. 2013;33:45–70. doi: 10.1146/annurev-nutr-071812-161246. PubMed DOI PMC

Erichsen H.C., Engel S.A., Eck P.K., Welch R., Yeager M., Levine M., Siega-Riz A.M., Olshan A.F., Chanock S.J. Genetic variation in the sodium-dependent vitamin C transporters, SLC23A1, and SLC23A2 and risk for preterm delivery. Am. J. Epidemiol. 2006;163:245–254. doi: 10.1093/aje/kwj035. PubMed DOI

Duell E.J., Lujan-Barroso L., Llivina C., Munoz X., Jenab M., Boutron-Ruault M.C., Clavel-Chapelon F., Racine A., Boeing H., Buijsse B., et al. Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort. Genes Nutr. 2013;8:549–560. doi: 10.1007/s12263-013-0346-6. PubMed DOI PMC

Amir Shaghaghi M., Bernstein C.N., Serrano Leon A., El-Gabalawy H., Eck P. Polymorphisms in the sodium-dependent ascorbate transporter gene SLC23A1 are associated with susceptibility to Crohn disease. Am. J. Clin. Nutr. 2014;99:378–383. doi: 10.3945/ajcn.113.068015. PubMed DOI

Skibola C.F., Bracci P.M., Halperin E., Nieters A., Hubbard A., Paynter R.A., Skibola D.R., Agana L., Becker N., Tressler P., et al. Polymorphisms in the estrogen receptor 1 and vitamin C and matrix metalloproteinase gene families are associated with susceptibility to lymphoma. PLoS ONE. 2008;3:e2816. doi: 10.1371/journal.pone.0002816. PubMed DOI PMC

De Jong T.M., Jochens A., Jockel-Schneider Y., Harks I., Dommisch H., Graetz C., Flachsbart F., Staufenbiel I., Eberhard J., Folwaczny M., et al. SLC23A1 polymorphism rs6596473 in the vitamin C transporter SVCT1 is associated with aggressive periodontitis. J. Clin. Periodontol. 2014;41:531–540. doi: 10.1111/jcpe.12253. PubMed DOI

Wade K.H., Forouhi N.G., Cook D.G., Johnson P., McConnachie A., Morris R.W., Rodriguez S., Ye Z., Ebrahim S., Padmanabhan S., et al. Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with L-ascorbic acid. Am. J. Clin. Nutr. 2015;101:202–209. doi: 10.3945/ajcn.114.092981. PubMed DOI PMC

Wright M.E., Andreotti G., Lissowska J., Yeager M., Zatonski W., Chanock S.J., Chow W.H., Hou L. Genetic variation in sodium-dependent ascorbic acid transporters and risk of gastric cancer in Poland. Eur. J. Cancer. 2009;45:1824–1830. doi: 10.1016/j.ejca.2009.01.027. PubMed DOI PMC

Erichsen H.C., Peters U., Eck P., Welch R., Schoen R.E., Yeager M., Levine M., Hayes R.B., Chanock S. Genetic variation in sodium-dependent vitamin C transporters SLC23A1 and SLC23A2 and risk of advanced colorectal adenoma. Nutr. Cancer. 2008;60:652–659. doi: 10.1080/01635580802033110. PubMed DOI PMC

Chen A.A., Marsit C.J., Christensen B.C., Houseman E.A., McClean M.D., Smith J.F., Bryan J.T., Posner M.R., Nelson H.H., Kelsey K.T. Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer. Carcinogenesis. 2009;30:977–981. doi: 10.1093/carcin/bgp076. PubMed DOI PMC

Andrew A.S., Gui J., Sanderson A.C., Mason R.A., Morlock E.V., Schned A.R., Kelsey K.T., Marsit C.J., Moore J.H., Karagas M.R. Bladder cancer SNP panel predicts susceptibility and survival. Hum. Genet. 2009;125:527–539. doi: 10.1007/s00439-009-0645-6. PubMed DOI PMC

Casabonne D., Gracia E., Espinosa A., Bustamante M., Benavente Y., Robles C., Costas L., Alonso E., Gonzalez-Barca E., Tardon A., et al. Fruit and vegetable intake and vitamin C transporter gene (SLC23A2) polymorphisms in chronic lymphocytic leukaemia. Eur. J. Nutr. 2017;56:1123–1133. doi: 10.1007/s00394-016-1162-8. PubMed DOI

Zanon-Moreno V., Ciancotti-Olivares L., Asencio J., Sanz P., Ortega-Azorin C., Pinazo-Duran M.D., Corella D. Association between a SLC23A2 gene variation, plasma vitamin C levels, and risk of glaucoma in a Mediterranean population. Mol. Vis. 2011;17:2997–3004. PubMed PMC

Dalgard C., Christiansen L., Vogel U., Dethlefsen C., Tjonneland A., Overvad K. Variation in the sodium-dependent vitamin C transporter 2 gene is associated with risk of acute coronary syndrome among women. PLoS ONE. 2013;8:e70421. doi: 10.1371/journal.pone.0070421. PubMed DOI PMC

McDonough M., Loenarz C., Chowdhury R., Clifton I., Schofield C. Structural studies on human 2-oxoglutarate dependent oxygenases. Curr. Opin. Struct. Biol. 2010;20:659–672. doi: 10.1016/j.sbi.2010.08.006. PubMed DOI

Kuiper C., Vissers M.C. Ascorbate as a co-factor for fe- and 2-oxoglutarate dependent dioxygenases: Physiological activity in tumor growth and progression. Front. Oncol. 2014;4:359. doi: 10.3389/fonc.2014.00359. PubMed DOI PMC

Loenarz C., Schofield C.J. Physiological and biochemical aspects of hydroxylations and demethylations catalyzed by human 2-oxoglutarate oxygenases. Trends Biochem. Sci. 2011;36:7–18. doi: 10.1016/j.tibs.2010.07.002. PubMed DOI

Myllyla R., Kuutti-Savolainen E.R., Kivirikko K.I. The role of ascorbate in the prolyl hydroxylase reaction. Biochem. Biophys. Res. Commun. 1978;83:441–448. doi: 10.1016/0006-291X(78)91010-0. PubMed DOI

Islam M.S., Leissing T., Chowdhury R., Hopkinson R., Schofield C. 2-Oxoglutarate-dependent oxygenases. Annu. Rev. Biochem. 2018;87 doi: 10.1146/annurev-biochem-061516-044724. PubMed DOI

Young J.I., Zuchner S., Wang G. Regulation of the epigenome by vitamin C. Annu. Rev. Nutr. 2015;35:545–564. doi: 10.1146/annurev-nutr-071714-034228. PubMed DOI PMC

Cimmino L., Neel B.G., Aifantis I. Vitamin C in stem cell reprogramming and cancer. Trends Cell Biol. 2018;28:698–708. doi: 10.1016/j.tcb.2018.04.001. PubMed DOI PMC

Vasta J.D., Raines R.T. Collagen prolyl 4-hydroxylase as a therapeutic target. J. Med. Chem. 2018;61:10403–10411. doi: 10.1021/acs.jmedchem.8b00822. PubMed DOI PMC

Amer J., Zelig O., Fibach E. Oxidative status of red blood cells, neutrophils, and platelets in paroxysmal nocturnal hemoglobinuria. Exp. Hematol. 2008;36:369–377. doi: 10.1016/j.exphem.2007.12.003. PubMed DOI

Furusawa H., Sato Y., Tanaka Y., Inai Y., Amano A., Iwama M., Kondo Y., Handa S., Murata A., Nishikimi M., et al. Vitamin C is not essential for carnitine biosynthesis in vivo: Verification in vitamin C-depleted senescence marker protein-30/gluconolactonase knockout mice. Biol. Pharm. Bull. 2008;31:1673–1679. doi: 10.1248/bpb.31.1673. PubMed DOI

Monfort A., Wutz A. Breathing-in epigenetic change with vitamin C. EMBO Rep. 2013;14:337–346. doi: 10.1038/embor.2013.29. PubMed DOI PMC

Das A.B., Smith-Diaz C.C., Vissers M.C.M. Emerging epigenetic therapeutics for myeloid leukemia: Modulating demethylase activity with ascorbate. Haematologica. 2020;106 doi: 10.3324/haematol.2020.259283. PubMed DOI PMC

Lee Chong T., Ahearn E.L., Cimmino L. Reprogramming the epigenome with vitamin C. Front. Cell Dev. Biol. 2019;7:128. doi: 10.3389/fcell.2019.00128. PubMed DOI PMC

Ozer A., Bruick R.K. Non-heme dioxygenases: Cellular sensors and regulators jelly rolled into one? Nat. Chem. Biol. 2007;3:144–153. doi: 10.1038/nchembio863. PubMed DOI

Kuiper C., Dachs G.U., Currie M.J., Vissers M.C. 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. doi: 10.1016/j.freeradbiomed.2014.01.033. PubMed DOI

Wang T., Chen K., Zeng X., Yang J., Wu Y., Shi X., Qin B., Zeng L., Esteban M.A., Pan G., et al. The histone demethylases Jhdm1a/1b enhance somatic cell reprogramming in a vitamin-C-dependent manner. Cell Stem. Cell. 2011;9:575–587. doi: 10.1016/j.stem.2011.10.005. PubMed DOI

Zhang T., Huang K., Zhu Y., Wang T., Shan Y., Long B., Li Y., Chen Q., Wang P., Zhao S., et al. Vitamin C-dependent lysine demethylase 6 (KDM6)-mediated demethylation promotes a chromatin state that supports the endothelial-to-hematopoietic transition. J. Biol. Chem. 2019;294:13657–13670. doi: 10.1074/jbc.RA119.009757. PubMed DOI PMC

D’Oto A., Tian Q.W., Davidoff A.M., Yang J. Histone demethylases and their roles in cancer epigenetics. J. Med. Oncol. Ther. 2016;1:34–40. doi: 10.35841/medical-oncology.1.2.34-40. PubMed DOI PMC

Ge W., Wolf A., Feng T., Ho C.H., Sekirnik R., Zayer A., Granatino N., Cockman M.E., Loenarz C., Loik N.D., et al. Oxygenase-catalyzed ribosome hydroxylation occurs in prokaryotes and humans. Nat. Chem. Biol. 2012;8:960–962. doi: 10.1038/nchembio.1093. PubMed DOI PMC

Chowdhury R., Sekirnik R., Brissett N.C., Krojer T., Ho C.H., Ng S.S., Clifton I.J., Ge W., Kershaw N.J., Fox G.C., et al. Ribosomal oxygenases are structurally conserved from prokaryotes to humans. Nature. 2014;510:422–426. doi: 10.1038/nature13263. PubMed DOI PMC

Blaschke K., Ebata K.T., Karimi M.M., Zepeda-Martinez J.A., Goyal P., Mahapatra S., Tam A., Laird D.J., Hirst M., Rao A., et al. Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature. 2013;500:222–226. doi: 10.1038/nature12362. PubMed DOI PMC

Chen J., Guo L., Zhang L., Wu H., Yang J., Liu H., Wang X., Hu X., Gu T., Zhou Z., et al. Vitamin C modulates TET1 function during somatic cell reprogramming. Nat. Genet. 2013;45:1504–1509. doi: 10.1038/ng.2807. PubMed DOI

Minor E.A., Court B.L., Young J.I., Wang G. Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine. J. Biol Chem. 2013;288:13669–13674. doi: 10.1074/jbc.C113.464800. PubMed DOI PMC

Rasmussen K.D., Helin K. Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev. 2016;30:733–750. doi: 10.1101/gad.276568.115. PubMed DOI PMC

Zheng G., Dahl J.A., Niu Y., Fu Y., Klungland A., Yang Y.G., He C. Sprouts of RNA epigenetics: The discovery of mammalian RNA demethylases. RNA Biol. 2013;10:915–918. doi: 10.4161/rna.24711. PubMed DOI PMC

Gerken T., Girard C.A., Tung Y.C., Webby C.J., Saudek V., Hewitson K.S., Yeo G.S., McDonough M.A., Cunliffe S., McNeill L.A., et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science. 2007;318:1469–1472. doi: 10.1126/science.1151710. PubMed DOI PMC

Aas P.A., Otterlei M., Falnes P.O., Vagbo C.B., Skorpen F., Akbari M., Sundheim O., Bjoras M., Slupphaug G., Seeberg E., et al. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature. 2003;421:859–863. doi: 10.1038/nature01363. PubMed DOI

Ougland R., Rognes T., Klungland A., Larsen E. Non-homologous functions of the AlkB homologs. J. Mol. Cell Biol. 2015;7:494–504. doi: 10.1093/jmcb/mjv029. PubMed DOI

Ueda Y., Ooshio I., Fusamae Y., Kitae K., Kawaguchi M., Jingushi K., Hase H., Harada K., Hirata K., Tsujikawa K. AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells. Sci. Rep. 2017;7:42271. doi: 10.1038/srep42271. PubMed DOI PMC

Zou S., Toh J.D., Wong K.H., Gao Y.G., Hong W., Woon E.C. N(6)-Methyladenosine: A conformational marker that regulates the substrate specificity of human demethylases FTO and ALKBH5. Sci. Rep. 2016;6:25677. doi: 10.1038/srep25677. PubMed DOI PMC

Hudson D.M., Eyre D.R. Collagen prolyl 3-hydroxylation: A major role for a minor post-translational modification? Connect. Tissue Res. 2013;54:245–251. doi: 10.3109/03008207.2013.800867. PubMed DOI PMC

Trackman P.C. Enzymatic and non-enzymatic functions of the lysyl oxidase family in bone. Matrix Biol. 2016;52–54:7–18. doi: 10.1016/j.matbio.2016.01.001. PubMed DOI PMC

Qi Y., Xu R. Roles of PLODs in Collagen Synthesis and Cancer Progression. Front. Cell Dev. Biol. 2018;6 doi: 10.3389/fcell.2018.00066. PubMed DOI PMC

Hirota K., Semenza G.L. Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl hydroxylases. Biochem. Biophys. Res. Commun. 2005;338:610–616. doi: 10.1016/j.bbrc.2005.08.193. PubMed DOI

Strowitzki M.J., Cummins E.P., Taylor C.T. Protein hydroxylation by hypoxia-inducible factor (HIF) hydroxylases: Unique or ubiquitous? Cells. 2019;8:384. doi: 10.3390/cells8050384. PubMed DOI PMC

Keith B., Simon M.C. Hypoxia-inducible factors, stem cells, and cancer. Cell. 2007;129:465–472. doi: 10.1016/j.cell.2007.04.019. PubMed DOI PMC

Lando D., Peet D.J., Gorman J.J., Whelan D.A., Whitelaw M.L., Bruick R.K. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev. 2002;16:1466–1471. doi: 10.1101/gad.991402. PubMed DOI PMC

Feng T., Yamamoto A., Wilkins S.E., Sokolova E., Yates L.A., Münzel M., Singh P., Hopkinson R.J., Fischer R., Cockman M.E., et al. Optimal translational termination requires C4 lysyl hydroxylation of eRF1. Mol. Cell. 2014;53:645–654. doi: 10.1016/j.molcel.2013.12.028. PubMed DOI PMC

Plch J., Hrabeta J., Eckschlager T. KDM5 demethylases and their role in cancer cell chemoresistance. Int. J. Cancer. 2019;144:221–231. doi: 10.1002/ijc.31881. PubMed DOI

Lan F., Bayliss P.E., Rinn J.L., Whetstine J.R., Wang J.K., Chen S., Iwase S., Alpatov R., Issaeva I., Canaani E., et al. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature. 2007;449:689–694. doi: 10.1038/nature06192. PubMed DOI

Schulz W.A., Lang A., Koch J., Greife A. The histone demethylase UTX/KDM6A in cancer: Progress and puzzles. Int. J. Cancer. 2019;145:614–620. doi: 10.1002/ijc.32116. PubMed DOI

Chaturvedi S.S., Ramanan R., Lehnert N., Schofield C.J., Karabencheva-Christova T.G., Christov C.Z. Catalysis by the non-heme iron(II) histone demethylase PHF8 involves iron center rearrangement and conformational modulation of substrate orientation. ACS Catal. 2020;10:1195–1209. doi: 10.1021/acscatal.9b04907. PubMed DOI PMC

Wang C., Zhang Q., Hang T., Tao Y., Ma X., Wu M., Zhang X., Zang J. Structure of the JmjC domain-containing protein NO66 complexed with ribosomal protein Rpl8. Acta Crystallogr. D Biol. Crystallogr. 2015;71:1955–1964. doi: 10.1107/S1399004715012948. PubMed DOI PMC

Pandey D., Mohammad F., Weissmann S., Hallenborg P., Blagoev B., Helin K. P11.36 Ribosome hydroxylase Mina53 is required for Glioblastoma and is involved in regulation of translation rateand fidelity by regulating ribosomal biogenesis. Neuro-Oncology. 2019;21:iii51. doi: 10.1093/neuonc/noz126.182. DOI

Rebouche C.J. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann. N. Y. Acad. Sci. 2004;1033:30–41. doi: 10.1196/annals.1320.003. PubMed DOI

Tars K., Rumnieks J., Zeltins A., Kazaks A., Kotelovica S., Leonciks A., Sharipo J., Viksna A., Kuka J., Liepinsh E., et al. Crystal structure of human gamma-butyrobetaine hydroxylase. Biochem. Biophys. Res. Commun. 2010;398:634–639. doi: 10.1016/j.bbrc.2010.06.121. PubMed DOI

Wang Y., Reddy Y.V., Al Temimi A.H.K., Venselaar H., Nelissen F.H.T., Lenstra D.C., Mecinović J. Investigating the active site of human trimethyllysine hydroxylase. Biochem. J. 2019;476:1109–1119. doi: 10.1042/BCJ20180857. PubMed DOI

Moran G.R. 4-Hydroxyphenylpyruvate dioxygenase. Arch. Biochem. Biophys. 2005;433:117–128. doi: 10.1016/j.abb.2004.08.015. PubMed DOI

Vendelboe T.V., Harris P., Zhao Y., Walter T.S., Harlos K., El Omari K., Christensen H.E.M. The crystal structure of human dopamine β-hydroxylase at 2.9 Å resolution. Sci. Adv. 2016;2:e1500980. doi: 10.1126/sciadv.1500980. PubMed DOI PMC

Goldstein M., Fuxe K., Hokfelt T. Characterization and tissue localization of catecholamine synthesizing enzymes. Pharmacol. Rev. 1972;24:293–309. PubMed

Eipper B.A., Milgram S.L., Husten E.J., Yun H.Y., Mains R.E. Peptidylglycine alpha-amidating monooxygenase: A multifunctional protein with catalytic, processing, and routing domains. Protein Sci. 1993;2:489–497. doi: 10.1002/pro.5560020401. PubMed DOI PMC

Kolhekar A.S., Mains R.E., Eipper B.A. Peptidylglycine alpha-amidating monooxygenase: An ascorbate-requiring enzyme. Methods Enzymol. 1997;279:35–43. doi: 10.1016/s0076-6879(97)79007-4. PubMed DOI

Bousquet-Moore D., Mains R.E., Eipper B.A. Peptidylgycine α-amidating monooxygenase and copper: A gene-nutrient interaction critical to nervous system function. J. Neurosci. Res. 2010;88:2535–2545. doi: 10.1002/jnr.22404. PubMed DOI PMC

Martínez A., Montuenga L., Springall D., Treston A., Cuttitta F., Polak J. Immunocytochemical localization of peptidylglycine alpha-amidating monooxygenase enzymes (PAM) in human endocrine pancreas. J. Histochem. Cytochem. 1993;41:375–380. doi: 10.1177/41.3.8094086. PubMed DOI

Braas K.M., Harakall S.A., Ouafik L., Eipper B.A., May V. Expression of peptidylglycine alpha-amidating monooxygenase: An in situ hybridization and immunocytochemical study. Endocrinology. 1992;130:2778–2788. doi: 10.1210/endo.130.5.1572293. PubMed DOI

Morris K.M., Cao F., Onagi H., Altamore T.M., Gamble A.B., Easton C.J. Prohormone-substrate peptide sequence recognition by peptidylglycine α-amidating monooxygenase and its reflection in increased glycolate inhibitor potency. Bioorg. Med. Chem. Lett. 2012;22:7015–7018. doi: 10.1016/j.bmcl.2012.10.004. PubMed DOI

Jeng A.Y., Fujimoto R.A., Chou M., Tan J., Erion M.D. Suppression of substance P biosynthesis in sensory neurons of dorsal root ganglion by prodrug esters of potent peptidylglycine alpha-amidating monooxygenase inhibitors. J. Biol. Chem. 1997;272:14666–14671. doi: 10.1074/jbc.272.23.14666. PubMed DOI

Padayatty S.J., Katz A., Wang Y., Eck P., Kwon O., Lee J.H., Chen S., Corpe C., Dutta A., Dutta S.K., et al. Vitamin C as an antioxidant: Evaluation of its role in disease prevention. J. Am. Coll. Nutr. 2003;22:18–35. doi: 10.1080/07315724.2003.10719272. PubMed DOI

Gaut J.P., Belaaouaj A., Byun J., Roberts L.J., 2nd, Maeda N., Frei B., Heinecke J.W. Vitamin C fails to protect amino acids and lipids from oxidation during acute inflammation. Free Radic. Biol. Med. 2006;40:1494–1501. doi: 10.1016/j.freeradbiomed.2005.12.013. PubMed DOI

Johnston C.S., Cox S.K. Plasma-Saturating intakes of vitamin C confer maximal antioxidant protection to plasma. J. Am. Coll. Nutr. 2001;20:623–627. doi: 10.1080/07315724.2001.10719159. PubMed DOI

Carr A.C., Maggini S. Vitamin C and immune function. Nutrients. 2017;9:1211. doi: 10.3390/nu9111211. PubMed DOI PMC

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. doi: 10.1016/j.niox.2013.12.001. PubMed DOI

Oudemans-van Straaten H.M., Spoelstra-de Man A.M., de Waard M.C. Vitamin C revisited. Crit. Care. 2014;18:460. doi: 10.1186/s13054-014-0460-x. PubMed DOI PMC

Förstermann U., Sessa W.C. Nitric oxide synthases: Regulation and function. Eur. Heart J. 2012;33:829–837d. doi: 10.1093/eurheartj/ehr304. PubMed DOI PMC

Kim H.-L., Park Y. Maintenance of cellular tetrahydrobiopterin homeostasis. BMB Rep. 2010;43:584–592. doi: 10.5483/BMBRep.2010.43.9.584. PubMed DOI

Vasquez-Vivar J., Whitsett J., Martasek P., Hogg N., Kalyanaraman B. Reaction of tetrahydrobiopterin with superoxide: EPR-kinetic analysis and characterization of the pteridine radical. Free Radic. Biol. Med. 2001;31:975–985. doi: 10.1016/S0891-5849(01)00680-3. PubMed DOI

Wu F., Tyml K., Wilson J.X. Ascorbate inhibits iNOS expression in endotoxin- and IFN gamma-stimulated rat skeletal muscle endothelial cells. FEBS Lett. 2002;520:122–126. doi: 10.1016/S0014-5793(02)02804-1. PubMed DOI

Gokce N., Keaney J.F., Jr., Frei B., Holbrook M., Olesiak M., Zachariah B.J., Leeuwenburgh C., Heinecke J.W., Vita J.A. Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation. 1999;99:3234–3240. doi: 10.1161/01.CIR.99.25.3234. PubMed DOI

Bassenge E., Fink N., Skatchkov M., Fink B. Dietary supplement with vitamin C prevents nitrate tolerance. J. Clin. Investig. 1998;102:67–71. doi: 10.1172/JCI977. PubMed DOI PMC

Seo M.Y., Lee S.M. Protective effect of low dose of ascorbic acid on hepatobiliary function in hepatic ischemia/reperfusion in rats. J. Hepatol. 2002;36:72–77. doi: 10.1016/S0168-8278(01)00236-7. PubMed DOI

Jackson T.S., Xu A., Vita J.A., Keaney J.F., Jr. Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations. Circ. Res. 1998;83:916–922. doi: 10.1161/01.RES.83.9.916. PubMed DOI

Podmore I.D., Griffiths H.R., Herbert K.E., Mistry N., Mistry P., Lunec J. Vitamin C exhibits pro-oxidant properties. Nature. 1998;392:559. doi: 10.1038/33308. PubMed DOI

Aronovitch J., Godinger D., Samuni A., Czapski G. Ascorbic acid oxidation and DNA scission catalyzed by iron and copper chelates. Free Radic. Res. Commun. 1987;2:241–258. doi: 10.3109/10715768709065289. PubMed DOI

Hodges R.E., Hood J., Canham J.E., Sauberlich H.E., Baker E.M. Clinical manifestations of ascorbic acid deficiency in man. Am. J. Clin. Nutr. 1971;24:432–443. doi: 10.1093/ajcn/24.4.432. PubMed DOI

Bird T.A., Schwartz N.B., Peterkofsky B. Mechanism for the decreased biosynthesis of cartilage proteoglycan in the scorbutic guinea pig. J. Biol. Chem. 1986;261:11166–11172. doi: 10.1016/S0021-9258(18)67363-6. PubMed DOI

Fukushima R., Yamazaki E. Vitamin C requirement in surgical patients. Curr. Opin. Clin. Nutr. Metab. Care. 2010;13:669–676. doi: 10.1097/MCO.0b013e32833e05bc. PubMed DOI

Long C.L., Maull K.I., Krishnan R.S., Laws H.L., Geiger J.W., Borghesi L., Franks W., Lawson T.C., Sauberlich H.E. Ascorbic acid dynamics in the seriously ill and injured. J. Surg. Res. 2003;109:144–148. doi: 10.1016/S0022-4804(02)00083-5. PubMed DOI

Padayatty S.J., Levine M. Vitamin C and myocardial infarction: The heart of the matter. Am. J. Clin. Nutr. 2000;71:1027–1028. doi: 10.1093/ajcn/71.5.1027. PubMed DOI

Mayland C.R., Bennett M.I., Allan K. Vitamin C deficiency in cancer patients. Palliat. Med. 2005;19:17–20. doi: 10.1191/0269216305pm970oa. PubMed DOI

Leveque N., Robin S., Muret P., Mac-Mary S., Makki S., Humbert P. High iron and low ascorbic acid concentrations in the dermis of atopic dermatitis patients. Dermatology. 2003;207:261–264. doi: 10.1159/000073087. PubMed DOI

Ngo B., Van Riper J.M., Cantley L.C., Yun J. Targeting cancer vulnerabilities with high-dose vitamin C. Nat. Rev. Cancer. 2019;19:271–282. doi: 10.1038/s41568-019-0135-7. PubMed DOI PMC

Creagan E.T., Moertel C.G., O’Fallon J.R., Schutt A.J., O’Connell M.J., Rubin J., Frytak S. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N. Engl. J. Med. 1979;301:687–690. doi: 10.1056/NEJM197909273011303. PubMed DOI

Moertel C.G., Fleming T.R., Creagan E.T., Rubin J., O’Connell M.J., Ames M.M. 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;312:137–141. doi: 10.1056/NEJM198501173120301. PubMed DOI

Chen Q., Espey M.G., Krishna M.C., Mitchell J.B., Corpe C.P., Buettner G.R., Shacter E., Levine M. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues. Proc. Natl. Acad. Sci. USA. 2005;102:13604–13609. doi: 10.1073/pnas.0506390102. PubMed DOI PMC

Chen Q., Espey M.G., Sun A.Y., Pooput C., Kirk K.L., Krishna M.C., Khosh D.B., Drisko J., Levine M. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc. Natl. Acad. Sci. USA. 2008;105:11105–11109. doi: 10.1073/pnas.0804226105. PubMed DOI PMC

Fritz H., Flower G., Weeks L., Cooley K., Callachan M., McGowan J., Skidmore B., Kirchner L., Seely D. Intravenous vitamin C and cancer: A systematic review. Integr. Cancer Ther. 2014;13:280–300. doi: 10.1177/1534735414534463. PubMed DOI

Nauman G., Gray J.C., Parkinson R., Levine M., Paller C.J. Systematic review of intravenous ascorbate in cancer clinical trials. Antioxidants. 2018;7:89. doi: 10.3390/antiox7070089. PubMed DOI PMC

Klimant E., Wright H., Rubin D., Seely D., Markman M. Intravenous vitamin C in the supportive care of cancer patients: A review and rational approach. Curr. Oncol. 2018;25:139–148. doi: 10.3747/co.25.3790. PubMed DOI PMC

Perrone G., Hideshima T., Ikeda H., Okawa Y., Calabrese E., Gorgun G., Santo L., Cirstea D., Raje N., Chauhan D., et al. Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia. 2009;23:1679–1686. doi: 10.1038/leu.2009.83. PubMed DOI

Luo J., Shen L., Zheng D. Association between vitamin C intake and lung cancer: A dose-response meta-analysis. Sci. Rep. 2014;4:6161. doi: 10.1038/srep06161. PubMed DOI PMC

Xu X., Yu E., Liu L., Zhang W., Wei X., Gao X., Song N., Fu C. Dietary intake of vitamins A, C, and E and the risk of colorectal adenoma: A meta-analysis of observational studies. Eur. J. Cancer Prev. 2013;22:529–539. doi: 10.1097/CEJ.0b013e328364f1eb. PubMed DOI

Bandera E.V., Gifkins D.M., Moore D.F., McCullough M.L., Kushi L.H. Antioxidant vitamins and the risk of endometrial cancer: A dose-response meta-analysis. Cancer Causes Control. 2009;20:699–711. doi: 10.1007/s10552-008-9283-x. PubMed DOI PMC

Moser M.A., Chun O.K. Vitamin C and Heart Health: A review based on findings from epidemiologic studies. Int. J. Mol. Sci. 2016;17 doi: 10.3390/ijms17081328. PubMed DOI PMC

Ashor A.W., Brown R., Keenan P.D., Willis N.D., Siervo M., Mathers J.C. Limited evidence for a beneficial effect of vitamin C supplementation on biomarkers of cardiovascular diseases: An umbrella review of systematic reviews and meta-analyses. Nutr. Res. 2019;61:1–12. doi: 10.1016/j.nutres.2018.08.005. PubMed DOI

Hemila H. Vitamin C in clinical therapeutics. Clin. Ther. 2017;39:2110–2112. doi: 10.1016/j.clinthera.2017.08.005. PubMed DOI

Shi R., Li Z.H., Chen D., Wu Q.C., Zhou X.L., Tie H.T. Sole and combined vitamin C supplementation can prevent postoperative atrial fibrillation after cardiac surgery: A systematic review and meta-analysis of randomized controlled trials. Clin. Cardiol. 2018;41:871–878. doi: 10.1002/clc.22951. PubMed DOI PMC

Hemilä H., Suonsyrjä T. Vitamin C for preventing atrial fibrillation in high risk patients: A systematic review and meta-analysis. BMC Cardiovasc. Disord. 2017;17:49. doi: 10.1186/s12872-017-0478-5. PubMed DOI PMC

Putzu A., Daems A.M., Lopez-Delgado J.C., Giordano V.F., Landoni G. The Effect of vitamin C on clinical outcome in critically ill patients: A systematic review with meta-analysis of randomized controlled trials. Crit. Care Med. 2019;47:774–783. doi: 10.1097/CCM.0000000000003700. PubMed DOI

Hemila H. Vitamin C and infections. Nutrients. 2017;9:339. doi: 10.3390/nu9040339. PubMed DOI PMC

Hemila H., Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst. Rev. 2013 doi: 10.1002/14651858.CD000980.pub4. PubMed DOI PMC

Padhani Z.A., Moazzam Z., Ashraf A., Bilal H., Salam R.A., Das J.K., Bhutta Z.A. Vitamin C supplementation for prevention and treatment of pneumonia. Cochrane Database Syst. Rev. 2020;4 doi: 10.1002/14651858.CD013134.pub2. PubMed DOI PMC

Hemila H., Louhiala P. Vitamin C for preventing and treating pneumonia. Cochrane Database Syst. Rev. 2013 doi: 10.1002/14651858.CD005532.pub3. PubMed DOI

Fowler A.A., 3rd, Truwit J.D., Hite R.D., Morris P.E., DeWilde C., Priday A., Fisher B., Thacker L.R., 2nd, Natarajan R., Brophy D.F., et al. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: The CITRIS-ALI randomized clinical trial. JAMA. 2019;322:1261–1270. doi: 10.1001/jama.2019.11825. PubMed DOI PMC

Kuhn S.O., Meissner K., Mayes L.M., Bartels K. Vitamin C in sepsis. Curr. Opin. Anaesthesiol. 2018;31:55–60. doi: 10.1097/ACO.0000000000000549. PubMed DOI PMC

Jovic T.H., Ali S.R., Ibrahim N., Jessop Z.M., Tarassoli S.P., Dobbs T.D., Holford P., Thornton C.A., Whitaker I.S. Could vitamins help in the fight against COVID-19? Nutrients. 2020;12:2550. doi: 10.3390/nu12092550. PubMed DOI PMC

Carr A.C., Rowe S. The emerging role of vitamin C in the prevention and treatment of COVID-19. Nutrients. 2020;12:3286. doi: 10.3390/nu12113286. PubMed DOI PMC

Traxer O., Huet B., Poindexter J., Pak C.Y., Pearle M.S. Effect of ascorbic acid consumption on urinary stone risk factors. J. Urol. 2003;170:397–401. doi: 10.1097/01.ju.0000076001.21606.53. PubMed DOI

Hung K.C., Lin Y.T., Chen K.H., Wang L.K., Chen J.Y., Chang Y.J., Wu S.C., Chiang M.H., Sun C.K. The effect of perioperative vitamin C on postoperative analgesic consumption: A meta-analysis of randomized controlled trials. Nutrients. 2020;12:3109. doi: 10.3390/nu12103109. PubMed DOI PMC

Robitaille L., Mamer O.A., Miller W.H., Jr., Levine M., Assouline S., Melnychuk D., Rousseau C., Hoffer L.J. Oxalic acid excretion after intravenous ascorbic acid administration. Metabolism. 2009;58:263–269. doi: 10.1016/j.metabol.2008.09.023. PubMed DOI PMC

Padayatty S.J., Sun A.Y., Chen Q., Espey M.G., Drisko J., Levine M. Vitamin C: Intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS ONE. 2010;5:e11414. doi: 10.1371/journal.pone.0011414. PubMed DOI PMC

Baxmann A.C., Mendonça C.d.O.G., Heilberg I.P. Effect of vitamin C supplements on urinary oxalate and pH in calcium stone-forming patients. Kidney Int. 2003;63:1066–1071. doi: 10.1046/j.1523-1755.2003.00815.x. PubMed DOI

Robertson W.G., Scurr D.S., Bridge C.M. Factors influencing the crystallisation of calcium oxalate in urine—Critique. J. Cryst. Growth. 1981;53:182–194. doi: 10.1016/0022-0248(81)90064-6. DOI

Taylor E.N., Stampfer M.J., Curhan G.C. Dietary factors and the risk of incident kidney stones in men: New insights after 14 years of follow-up. J. Am. Soc. Nephrol. 2004;15:3225–3232. doi: 10.1097/01.ASN.0000146012.44570.20. PubMed DOI

Iwamoto N., Kawaguchi T., Horikawa K., Nagakura S., Hidaka M., Kagimoto T., Takatsuki K., Nakakuma H. Haemolysis induced by ascorbic acid in paroxysmal nocturnal haemoglobinuria. Lancet. 1994;343:357. doi: 10.1016/S0140-6736(94)91195-9. PubMed DOI

Karlsen A., Blomhoff R., Gundersen T.E. High-throughput analysis of vitamin C in human plasma with the use of HPLC with monolithic column and UV-detection. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2005;824:132–138. doi: 10.1016/j.jchromb.2005.07.008. PubMed DOI

Ko D.H., Jeong T.D., Kim S., Chung H.J., Lee W., Chun S., Min W.K. Influence of vitamin C on urine dipstick test results. Ann. Clin. Lab. Sci. 2015;45:391–395. PubMed

Nováková L., Solichová D., Pavlovicová S., Solich P. Hydrophilic interaction liquid chromatography method for the determination of ascorbic acid. J. Sep. Sci. 2008;31:1634–1644. doi: 10.1002/jssc.200700570. PubMed DOI

Szőcs A., Vancea S., Kiss I., Donáth-Nagy G. Quantification of plasma and leukocyte vitamin C by high performance liquid chromatography with mass spectrometric detection. J. Anal. Chem. 2020;75:1168–1176. doi: 10.1134/S1061934820090038. DOI

Lykkesfeldt J. Ascorbate and dehydroascorbic acid as biomarkers of oxidative stress: Validity of clinical data depends on vacutainer system used. Nutr. Res. 2012;32:66–69. doi: 10.1016/j.nutres.2011.11.005. PubMed DOI

Pullar J.M., Bayer S., Carr A.C. Appropriate handling, processing and analysis of blood samples is essential to avoid oxidation of vitamin C to dehydroascorbic acid. Antioxidants. 2018;7:29. doi: 10.3390/antiox7020029. PubMed DOI PMC

Bernasconi L., Saxer C., Neyer P., Huber A., Steuer C. Suitable preanalytical conditions for vitamin C measurement in clinical routine. J. Food Sci. Technol. 2018;3:280–287. doi: 10.25177/JFST.3.2.3. DOI

Fatima Z., Jin X., Zou Y., Kaw H.Y., Quinto M., Li D. Recent trends in analytical methods for water-soluble vitamins. J. Chromatogr. A. 2019;1606:360245. doi: 10.1016/j.chroma.2019.05.025. PubMed DOI

Dos Santos V.B., da Silva E.K.N., de Oliveira L.M.A., Suarez W.T. Low cost in situ digital image method, based on spot testing and smartphone images, for determination of ascorbic acid in Brazilian Amazon native and exotic fruits. Food Chem. 2019;285:340–346. doi: 10.1016/j.foodchem.2019.01.167. PubMed DOI

Dhara K., Debiprosad R.M. Review on nanomaterials-enabled electrochemical sensors for ascorbic acid detection. Anal. Biochem. 2019;586:113415. doi: 10.1016/j.ab.2019.113415. PubMed DOI

Spínola V., Llorent-Martínez E.J., Castilho P.C. Determination of vitamin C in foods: Current state of method validation. J. Chromatogr. A. 2014;1369:2–17. doi: 10.1016/j.chroma.2014.09.087. PubMed DOI

Sempionatto J.R., Khorshed A.A., Ahmed A., De Loyola E.S.A.N., Barfidokht A., Yin L., Goud K.Y., Mohamed M.A., Bailey E., May J., et al. Epidermal enzymatic biosensors for sweat vitamin C: Toward personalized nutrition. ACS Sens. 2020;5:1804–1813. doi: 10.1021/acssensors.0c00604. PubMed DOI

Romeu-Nadal M., Morera-Pons S., Castellote A.I., López-Sabater M.C. Rapid high-performance liquid chromatographic method for Vitamin C determination in human milk versus an enzymatic method. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2006;830:41–46. doi: 10.1016/j.jchromb.2005.10.018. PubMed DOI

Wang X., Li L., Li Z., Wang J., Fu H., Chen Z. Determination of ascorbic acid in individual liver cancer cells by capillary electrophoresis with a platinum nanoparticles modified electrode. J. Electroanal. Chem. 2014;712:139–145. doi: 10.1016/j.jelechem.2013.11.010. DOI

Munday M.R., Rodricks R., Fitzpatrick M., Flood V.M., Gunton J.E. A pilot study examining vitamin C levels in periodontal patients. Nutrients. 2020;12:2255. doi: 10.3390/nu12082255. PubMed DOI PMC

Robitaille L., Hoffer L.J. A simple method for plasma total vitamin C analysis suitable for routine clinical laboratory use. Nutr. J. 2016;15:40. doi: 10.1186/s12937-016-0158-9. PubMed DOI PMC

Akbari A., Chamkouri N., Zadabdollah A. Determination trace levels of vitamin C and folic acid in urine sample by ultrasound-assisted dispersive liquid-liquid microextraction method coupled HPLC-UV. Orient. J. Chem. 2016;32 doi: 10.13005/ojc/320623. DOI

Gazdik Z., Zitka O., Petrlova J., Adam V., Zehnalek J., Horna A., Reznicek V., Beklova M., Kizek R. Determination of vitamin C (ascorbic acid) using high performance liquid chromatography coupled with electrochemical detection. Sensors. 2008;8:7097–7112. doi: 10.3390/s8117097. PubMed DOI PMC

Li H., Tu H., Wang Y., Levine M. Vitamin C in mouse and human red blood cells: An HPLC assay. Anal. Biochem. 2012;426:109–117. doi: 10.1016/j.ab.2012.04.014. PubMed DOI PMC

Vovk T., Bogataj M., Roskar R., Kmetec V., Mrhar A. Determination of main low molecular weight antioxidants in urinary bladder wall using HPLC with electrochemical detector. Int. J. Pharm. 2005;291:161–169. doi: 10.1016/j.ijpharm.2004.07.053. PubMed DOI

Haswell L.E., Papadopoulou E., Newland N., Shepperd C.J., Lowe F.J. A cross-sectional analysis of candidate biomarkers of biological effect in smokers, never-smokers and ex-smokers. Biomarkers. 2014;19:356–367. doi: 10.3109/1354750X.2014.912354. PubMed DOI

Wang X., Li K., Yao L., Wang C., Van Schepdael A. Recent advances in vitamins analysis by capillary electrophoresis. J. Pharm. Biomed. Anal. 2018;147:278–287. doi: 10.1016/j.jpba.2017.07.030. PubMed DOI

Sun X., Niu Y., Bi S., Zhang S. Determination of ascorbic acid in individual rat hepatocyte by capillary electrophoresis with electrochemical detection. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2008;870:46–50. doi: 10.1016/j.jchromb.2008.05.035. PubMed DOI

Dong S., Zhang S., Cheng X., He P., Wang Q., Fang Y. Simultaneous determination of sugars and ascorbic acid by capillary zone electrophoresis with amperometric detection at a carbon paste electrode modified with polyethylene glycol and Cu(2)O. J. Chromatogr. A. 2007;1161:327–333. doi: 10.1016/j.chroma.2007.05.077. PubMed DOI

Zhao S., Huang Y., Liu Y.M. Microchip electrophoresis with chemiluminescence detection for assaying ascorbic acid and amino acids in single cells. J. Chromatogr. A. 2009;1216:6746–6751. doi: 10.1016/j.chroma.2009.08.008. PubMed DOI PMC

Sun X., Niu Y., Bi S., Zhang S. Determination of ascorbic acid in individual rat hepatocyte cells based on capillary electrophoresis with electrochemiluminescence detection. Electrophoresis. 2008;29:2918–2924. doi: 10.1002/elps.200700792. PubMed DOI

Olędzka I., Kaźmierska K., Plenis A., Kamińska B., Bączek T. Capillary electromigration techniques as tools for assessing the status of vitamins A, C and E in patients with cystic fibrosis. J. Pharm. Biomed. Anal. 2015;102:45–53. doi: 10.1016/j.jpba.2014.08.036. PubMed DOI

Georgakopoulos C.D., Lamari F.N., Karathanasopoulou I.N., Gartaganis V.S., Pharmakakis N.M., Karamanos N.K. Tear analysis of ascorbic acid, uric acid and malondialdehyde with capillary electrophoresis. Biomed. Chromatogr. 2010;24:852–857. doi: 10.1002/bmc.1376. PubMed DOI

Huang L., Tian S., Zhao W., Liu K., Guo J. Electrochemical vitamin sensors: A critical review. Talanta. 2021;222:121645. doi: 10.1016/j.talanta.2020.121645. PubMed DOI

Taleb M., Ivanov R., Bereznev S., Kazemi S.H., Hussainova I. Graphene-ceramic hybrid nanofibers for ultrasensitive electrochemical determination of ascorbic acid. Mikrochim. Acta. 2017;184:897–905. doi: 10.1007/s00604-017-2085-7. DOI

Hashemi S.A., Mousavi S.M., Bahrani S., Ramakrishna S., Babapoor A., Chiang W.H. Coupled graphene oxide with hybrid metallic nanoparticles as potential electrochemical biosensors for precise detection of ascorbic acid within blood. Anal. Chim. Acta. 2020;1107:183–192. doi: 10.1016/j.aca.2020.02.018. PubMed DOI

Zhao Y., Qin J., Xu H., Gao S., Jiang T., Zhang S., Jin J. Gold nanorods decorated with graphene oxide and multi-walled carbon nanotubes for trace level voltammetric determination of ascorbic acid. Mikrochim. Acta. 2018;186:17. doi: 10.1007/s00604-018-3138-2. PubMed DOI

Liu L., Zhai J., Zhu C., Han L., Ren W., Dong S. One-step synthesis of functional pNR/rGO composite as a building block for enhanced ascorbic acid biosensing. Anal. Chim. Acta. 2017;981:34–40. doi: 10.1016/j.aca.2017.05.023. PubMed DOI

Prasad B.B., Tiwari K., Singh M., Sharma P.S., Patel A.K., Srivastava S. Molecularly imprinted polymer-based solid-phase microextraction fiber coupled with molecularly imprinted polymer-based sensor for ultratrace analysis of ascorbic acid. J. Chromatogr. A. 2008;1198–1199:59–66. doi: 10.1016/j.chroma.2008.05.059. PubMed DOI

Karimi-Maleh H., Arotiba O.A. Simultaneous determination of cholesterol, ascorbic acid and uric acid as three essential biological compounds at a carbon paste electrode modified with copper oxide decorated reduced graphene oxide nanocomposite and ionic liquid. J. Colloid Interface Sci. 2020;560:208–212. doi: 10.1016/j.jcis.2019.10.007. PubMed DOI

Asif M., Aziz A., Wang H., Wang Z., Wang W., Ajmal M., Xiao F., Chen X., Liu H. Superlattice stacking by hybridizing layered double hydroxide nanosheets with layers of reduced graphene oxide for electrochemical simultaneous determination of dopamine, uric acid and ascorbic acid. Mikrochim. Acta. 2019;186:61. doi: 10.1007/s00604-018-3158-y. PubMed DOI

Mehdi Motaghi M., Beitollahi H., Tajik S., Hosseinzadeh R. Nanostructure electrochemical sensor for voltammetric determination of vitamin C in the presence of vitamin B6: Application to real sample analysis. Int. J. Electrochem. Sci. 2016;11:7849–7860. doi: 10.20964/2016.09.60. DOI

Eagle Biosciences Vitamin C HPLC Assay. [(accessed on 23 November 2020)]; Available online: https://eaglebio.com/wp-content/uploads/data-pdf/vic31-h100.pdf-package-insert.pdf.

Chromsystems Vitamin C in Plasma/Serum—Automated HPLC. [(accessed on 24 November 2020)]; Available online: https://chromsystems.com/en/vitamin-c-in-plasma-serum-automated-hplc-65765-f.html.

LeVatte M.A., Lipfert M., Zheng J., Wishart D.S. A fast, sensitive, single-step colorimetric dipstick assay for quantifying ascorbic acid in urine. Anal. Biochem. 2019;580:1–13. doi: 10.1016/j.ab.2019.05.015. PubMed DOI

Sigma-Aldrich Ascorbic Acid Assay Kit II. [(accessed on 23 November 2020)]; Available online: https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Bulletin/1/mak075bul.pdf.

Biovision Ascorbic acid colorimetric assay kit II (FRASC) [(accessed on 23 November 2020)]; Available online: https://www.biovision.com/documentation/datasheets/K671.pdf.

Vislisel J.M., Schafer F.Q., Buettner G.R. A simple and sensitive assay for ascorbate using a plate reader. Anal. Biochem. 2007;365:31–39. doi: 10.1016/j.ab.2007.03.002. PubMed DOI PMC

MyBiosource Human vitamin C (VC) Elisa Kit (Competitive ELISA) [(accessed on 23 November 2020)]; Available online: https://cdn.mybiosource.com/tds/protocol_manuals/000000-799999/MBS726748.pdf.

Cloud-Clone Corp Elisa Kit for Vitamin C (VC) [(accessed on 23 November 2020)]; Available online: http://www.cloud-clone.com/manual/ELISA-Kit-for-Vitamin-C--VC--CEA913Ge.pdf.

Nováková L., Solich P., Solichová D. HPLC methods for simultaneous determination of ascorbic and dehydroascorbic acids. Trends Analyt. Chem. 2008;27:942–958. doi: 10.1016/j.trac.2008.08.006. DOI

Tessier F., Birlouez-Aragon I., Tjani C., Guilland J.C. Validation of a micromethod for determining oxidized and reduced vitamin C in plasma by HPLC-fluorescence. Int. J. Vitam. Nutr. Res. 1996;66:166–170. PubMed

Gao X., Zhou X., Ma Y., Qian T., Wang C., Chu F. Facile and cost-effective preparation of carbon quantum dots for Fe3+ ion and ascorbic acid detection in living cells based on the “on-off-on” fluorescence principle. Appl. Surf. Sci. 2019;469:911–916. doi: 10.1016/j.apsusc.2018.11.095. DOI