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Prospects for studying the pharmacokinetics, pharmacodynamics and pharmacogenetics of vitamin C in patients with neurological diseases and mental disorders

https://doi.org/10.52667/2712-9179-2021-1-2-63-82

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Abstract

Ascorbic acid (vitamin C) is a vital nutrient that belongs to the group of antioxidants. Vitamin C plays an important role in the functioning of the central (CNS) and peripheral nervous system (PNS), including maturation and differentiation of neurons, formation of myelin, synthesis of catecholamines, modulation of neurotransmission and antioxidant protection. Neurological diseases and mental disorders are characterized by increased generation of free radicals. At the same time, the highest concentrations of vitamin C are found in the brain and neuroendocrine tissues. It is believed that vitamin C can affect the age of debut and the course of many neurological diseases and mental disorders. However, its potential therapeutic role continues to be studied. The efficacy and safety of vitamin C is likely influenced by the pharmacogenetic profile of the patient, including the carriage of single-nucleotide variants (SNVS), candidate genes associated with vitamin C metabolism in the human body in normal and neuropsychic disorders. The purpose of this thematic review is to update current knowledge about the role of vitamin C pharmacogenetics in the efficacy and safety of its use in neurological diseases (amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Huntington's disease, Alzheimer's disease, etc.) and mental disorders (depression, anxiety, schizophrenia, etc.). Special attention is paid to the possibility of translating the results of pharmacogenetic studies into real clinical practice in neurology and psychiatry.

About the Authors

P. S. Goncharova
V.M. Bekhterev National Medical Research Center of Psychiatry and Neurology
Russian Federation

Polina S. Goncharova

192019, Saint Petersburg



T. K. Davydova
Yakut Science Centre of Complex Medical Problems
Russian Federation

Tatiana K. Davydova

677000, Yakutsk



N. G. Zhukova
Siberian State Medical University
Russian Federation

Natalia G. Zhukova

634050 Tomsk



References

1. Du, J.; Cullen, J.J.; Buettner, G.R. Ascorbic acid: Chemistry, biology and the treatment of cancer. Biochimica et Biophysica Acta 2012, 1826, 443–457. doi: 10.1016/j.bbcan.2012.06.003.

2. Kocot, J.; Luchowska-Kocot, D.; Kiełczykowska, M.; Musik, I.; Kurzepa, J. Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders? Nutrients, 2017, 9(7), 659. doi:10.3390/nu9070659.

3. Tolbert, B.M; Ward, J.B. Dehydroascorbic acid. In: Ascorbic Acid: Chemistry, Metabolism, and Uses. American Chemical Society, 1982 (P.A. Seib and B.M. Tolbert, eds.), pp. 101–123, Washington, D.C.

4. Lewin, S. Vitamin C: Its Molecular Biology and Medical Potential. Academic Press, London, 1976,

5. Washko, P.W., Welch, R.W., Dhariwal, K.R., Wang, Y., Levine, M. Ascorbic acid and dehydroascorbic acid analyses in biological samples. Analytical Biochemistry, 1992, 204 (1):1-14. doi: 10.1016/0003-2697(92)90131-p.

6. Said, H.M. Intestinal absorption of water-soluble vitamins in health and disease. Biochemical Journal, 2011, 437, 357–372. doi: 10.1042/BJ20110326.

7. Traber, M.G.; Stevens, J.F. Vitamins C and E: Beneficial effects from a mechanistic perspective. Free Radical Biology & Medicine, 2011, 51, 1000–1013. doi: 10.1016/j.freeradbiomed.2011.05.017.

8. Doseděl, M.; Jirkovský, E.; Macáková, K.; Krčmová, L.; Javorská, L.; Mercolini, L; Remião, F; Nováková, L; Mladěnka, P; Pourová, J. Vitamin C—Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination. Nutrients, 2021 13(2), 615. doi:10.3390/nu13020615

9. 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 in Immunology. 2016, 6, 8–10. doi:10.1016/j.rinim.2016.01.001

10. Riemersma, R.A.; Carruthers, K.F.; Elton, R.A.; Fox, K.A. Vitamin C and the risk of acute myocardial infarction. The American Journal of Clinical Nutrition, 2000, 71, 1181–1186. doi: 10.1093/ajcn/71.5.1181.

11. 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). The American Journal of Clinical Nutrition. 2009, 90, 1252–1263. doi:10.3945/ajcn.2008.27016

12. Dhariwal, K.R.; Hartzell, W.O.; Levine, M. Ascorbic acid and dehydroascorbic acid measurements in human plasma and serum. The American Journal of Clinical Nutrition. 1991, 54, 712–716. doi: 10.1093/ajcn/54.4.712.

13. Motoyama, T.; Kawano, H.; Kugiyama, K.; Hirashima, O.; Ohgushi, M.; Yoshimura, M.; Ogawa, H.; Yasue, H. Endotheliumdependent vasodilation in the brachial artery is impaired in smokers: Effect of vitamin C. American Journal of Physiology. 1997, 273, 1644–1650. doi: 10.1152/ajpheart.1997.273.4.H1644.

14. 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.

15. 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. Proceedings of the National Academy of Sciences. USA 1996, 93, 3704–3709. doi: 10.1073/pnas.93.8.3704.

16. Levine, M.; Padayatty, S.J.; Espey, M.G. Vitamin C: A concentration-function approach yields pharmacology and therapeutic discoveries. Advances in Nutrition. 2011, 2, 78–88. doi: 10.3945/an.110.000109

17. 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. Annals of Internal Medicine. 2004, 140, 533–537. doi: 10.7326/0003-4819-140-7-200404060-00010

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

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

20. 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. Molecular Aspects of Medicine. 2013, 34, 436–454. doi: 10.1016/j.mam.2012.12.002.

21. 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. Proceedings of the National Academy of Sciences. USA 2007, 104, 8749–8754. doi: 10.1073/pnas.0702854104

22. Berger, M.M. Vitamin C requirements in parenteral nutrition. Gastroenterology. 2009, 137, 70–78. doi: 10.1053/j.gastro.2009.08.012

23. Hart, A.; Cota, A.; Makhdom, A.; Harvey, E.J. The Role of Vitamin C in Orthopedic Trauma and Bone Health. American Journal of Orthodontics and Dentofacial Orthopedics. 2015, 44, 306–311. PMID: 26161758

24. Waly, M.I.; Al-Attabi, Z.; Guizani, N. Low Nourishment of Vitamin C induces glutathione depletion and oxidative stress in healthy young adults. Preventive Nutrition and Food Science. 2015, 20, 198–203. doi: 10.3746/pnf.2015.20.3.198

25. Redfern, C. P. F. Vitamin A and its natural derivatives. Methods in Enzymology 2020, 637:1-25. doi:10.1016/bs.mie.2020.02.002

26. Oliveira, M.R.D. The neurotoxic effects of vitamin A and retinoids. Anais Da Academia Brasileira de Ciências. 2015, 87(2 suppl), 1361–1373. doi:10.1590/0001-3765201520140677

27. Fitzgerald, K. C.; O’Reilly, É. J.; Fondell, E.; Falcone, G. J.; McCullough, M. L.; Park, Y.; Kolonel, L.N.; Ascherio, A. Intakes of vitamin C and carotenoids and risk of amyotrophic lateral sclerosis: Pooled results from 5 cohort studies. Annals of Neurology. 2013, 73(2), 236–245. doi:10.1002/ana.23820

28. Wang, M.; Liu, Z.; Sun, W.; Yuan, Y.; Jiao, B.; Zhang, X.; Shen, L.; Jiang, H.; Xia, K.; Tang, B.; Wang, J. Association between vitamins and amyotrophic lateral sclerosis: A Center-Based Survey in Mainland China. Frontiers in Neurology. 2020, 11:488. doi:10.3389/fneur.2020.00488

29. Eldridge, C.F.; Bunge, M.B.; Bunge, R.P.; Wood, P.M. Differentiation of axon-related Schwann cells in vitro. I. Ascorbic acid regulates basal lamina assembly and myelin formation. Journal of Cell Biology. 1987, 105, 1023–1034. doi: 10.1083/jcb.105.2.1023.

30. Sawicka-Glazer, E.; Czuczwar, S.J. Vitamin C: A new auxiliary treatment of epilepsy? Pharmacol. Rep. 2014, 66, 529–533. doi: 10.1016/j.pharep.2014.02.016

31. Warner, T.A.; Kang, J.Q.; Kennard, J.K.; Harrison, F.E. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer’s disease. Epilepsy Research. 2015, 110, 20–25. doi: 10.1016/j.eplepsyres.2014.11.017

32. Dixit, S.; Bernardo, A.; Walker, J.M.; Kennard, J.A.; Kim, G.Y.; Kessler, E.S.; Harrison, F.E. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice. ACS Chemical Neuroscience. 2015, 6, 570–581. doi: 10.1021/cn500308h

33. Ward, M.S.; Lamb, J.; May, J.M.; Harrison, F.E. Behavioral and monoamine changes following severe vitamin C deficiency. Journal of Neurochemistry. 2013, 124, 363–375. doi: 10.1111/jnc.12069

34. Sarkar, S.; Mukherjee, A.; Swarnakar, S.; Das, N. Nanocapsulated ascorbic acid in combating cerebral ischemia reperfusion— induced oxidative injury in rat brain. Current Alzheimer Research. 2016, 13, 1363–1373. doi: 10.2174/1567205013666160625082839

35. Murakami, K.; Murata, N.; Ozawa, Y.; Kinoshita, N.; Irie, K.; Shirasawa, T.; Shimizu, T. Vitamin C restores behavioral deficits and amyloid-β oligomerization without affecting plaque formation in a mouse model of Alzheimer’s disease. J. Alzheimers Dis. 2011, 26, 7–18. doi: 10.3233/JAD-2011-101971.

36. He, X.B.; Kim, M.; Kim, S.Y.; Yi, S.H.; Rhee, Y.H.; Kim, T.; Lee, E.H.; Park, C.H.; Dixit, S.; Harrison, F.E.; et al. Vitamin C facilitates dopamine neuron differentiation in fetal midbrain through TET1- and JMJD3-dependent epigenetic control manner. Stem Cells. 2015, 33, 1320–1332. doi: 10.1002/stem.1932.

37. Camarena, V.; Wang, G. The epigenetic role of vitamin C in health and disease. Cellular and Molecular Life Sciences. 2016, 73, 1645–1658. doi: 10.1007/s00018-016-2145-x.

38. Minor, E.A.; Court, B.L.; Young, J.I.; Wang, G. Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenasemediated generation of 5-hydroxymethylcytosine. Journal of Biological Chemistry. 2013, 288, 13669–13674. doi: 10.1074/jbc.C113.464800

39. Jinsmaa, Y.; Sullivan, P.; Sharabi, Y.; Goldstein, D.S. DOPAL is transmissible to and oligomerizes alpha-synuclein in human glial cells. Autonomic Neuroscience: Basic and Clinical. 2016, 194, 46–51. doi: 10.1016/j.autneu.2015.12.008

40. Ballaz, S.; Morales, I.; Rodríguez, M.; Obeso, J.A. Ascorbate prevents cell death from prolonged exposure to glutamate in an in vitro model of human dopaminergic neurons. Journal of Neuroscience Research. 2013, 91, 1609–1617. doi: 10.1002/jnr.23276

41. Ide, K.; Yamada, H.; Umegaki, K.; Mizuno, K.; Kawakami, N.; Hagiwara, Y.; Matsumoto, M.; Yoshida, H.; Kim, K.; Shiosaki, E.; Yokochi, T.; Harada, K. Lymphocyte vitamin C levels as potential biomarker for progression of Parkinson’s disease. Nutrition. 2015, 31, 406–408. doi: 10.1016/j.nut.2014.08.001

42. Mariam, I.; Ali, S.; Rehman, A. Ikram-Ul-Haq. l-Ascorbate, a strong inducer of l-dopa (3,4-dihydroxy-l-phenylalanine) production from pre-grown mycelia of Aspergillus oryzae NRRL-1560. Biotechnology and Applied Biochemistry. 2010, 55, 131–137. doi: 10.1042/BA20090248.

43. Acuña, A.I.; Esparza, M.; Kramm, C.; Beltrán, F.A.; Parra, A.V.; Cepeda, C.; Toro, C.A.; Vidal, R.L.; Hetz, C.; Concha, I.I.; et al. A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington’s disease in mice. Nature Communications. 2013, 4, 2917. doi: 10.1038/ncomms3917.

44. Miller, B.R.; Dorner, J.L.; Bunner, K.D.; Gaither, T.W.; Klein, E.L.; Barton, S.J.; Rebec, G.V. Up-regulation of GLT1 reverses the deficit in cortically evoked striatal ascorbate efflux in the R6/2 mouse model of Huntington’s disease. Journal of Neurochemistry. 2012, 121, 629–638. doi: 10.1111/j.1471-4159.2012.07691.x.

45. Rebec, G.V. Dysregulation of corticostriatal ascorbate release and glutamate uptake in transgenic models of Huntington’s disease. Antioxidants & Redox Signaling. 2013, 19, 2115–2128. doi: 10.1089/ars.2013.5387.

46. Polachini, C.R.; Spanevello, R.M.; Zanini, D.; Baldissarelli, J.; Pereira, L.B.; Schetinger, M.R.; da Cruz, I.B.; Assmann, C.E.; Bagatini, M.D.; Morsch, V.M. Evaluation of delta aminolevulinic dehydratase activity, oxidative stress biomarkers, and Vitamin D levels in patients with multiple sclerosis. Neurotoxicity Research. 2016, 29, 230–242. doi: 10.1007/s12640-015-9584-2.

47. Tavazzi, B.; Batocchi, A.P.; Amorini, A.M.; Nociti, V.; D’Urso, S.; Longo, S.; Gullotta, S.; Picardi, M.; Lazzarino, G. Serum metabolic profile in multiple sclerosis patients. Multiple Sclerosis International. 2011, 2011, 167156. doi: 10.1155/2011/167156

48. Hejazi, E.; Amani, R.; SharafodinZadeh, N.; Cheraghian, B. Comparison of antioxidant status and Vitamin D levels between multiple sclerosis patients and healthy matched subjects. Multiple Sclerosis International. 2014, 2014, 539854. doi: 10.1155/2014/539854

49. Babri, S.; Mehrvash, F.; Mohaddes, G.; Hatami, H.; Mirzaie, F. Effect of intrahippocampal administration of vitamin C and progesterone on learning in a model of multiple sclerosis in rats. Advanced Pharmaceutical Bulletin. 2015, 5, 83–87. doi: 10.5681/apb.2015.011.

50. Blasco, H.; Corcia, P.; Moreau, C.; Veau, S.; Fournier, C.; Vourc’h, P.; Emond, P.; Gordon, P.; Pradat, P.F.; Praline, J.; Devos, D.; Nadal-Desbarats, L.; Andres, C.R. 1H-NMR-based metabolomic profiling of CSF in early amyotrophic lateral sclerosis. PLoS ONE. 2010, 5, e13223. doi: 10.1371/journal.pone.0013223

51. Nagano, S.; Fujii, Y.; Yamamoto, T.; Taniyama, M.; Fukada, K.; Yanagihara, T.; Sakoda, S. The efficacy of trientine or ascorbate alone compared to that of the combined treatment with these two agents in familial amyotrophic lateral sclerosis model mice. Experimental Neurology. 2003, 179, 176–180. doi: 10.1016/s0014-4886(02)00014-6

52. Netzahualcoyotzi, C.; Tapia, R. Degeneration of spinal motor neurons by chronic AMPA-induced excitotoxicity in vivo and protection by energy substrates. Acta Neuropathologica Communications. 2015, 3, 27. doi: 10.1186/s40478-015-0205-3

53. Spasojević, I.; Stević, Z.; Nikolić-Kokić, A.; Jones, D.R.; Blagojević, D.; Spasić, M.B. Different roles of radical scavengers—Ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. Redox Report. 2010, 15, 81–86. doi: 10.1179/174329210X12650506623320.

54. Moretti, M.; Budni, J.; Ribeiro, C.M.; Rieger, D.; Leal, R.B.; Rodrigues, A.L. Subchronic administration of ascorbic acid elicits antidepressant-like effect and modulates cell survival signaling pathways in mice. Journal of Nutritional Biochemistry. 2016, 38, 50–56. doi: 10.1016/j.jnutbio.2016.09.004.

55. Rosa, P.B.; Neis, V.B.; Ribeiro, C.M.; Moretti, M.; Rodrigues, A.L.S. Antidepressant-like effects of ascorbic acid and ketamine involve modulation of GABAA and GABAB receptors. Pharmacological reports: PR. 2016, 68, 996–1001. doi: 10.1016/j.pharep.2016.05.010

56. Zhao, B.; Fei, J.; Chen, Y.; Ying, Y.L.; Ma, L.; Song, X.Q.; Wang, L.; Chen, E.Z.; Mao, E.Q. Pharmacological preconditioning with vitamin C attenuates intestinal injury via the induction of heme oxygenase-1 after hemorrhagic shock in rats. PLoS ONE. 2014, 9, 99134. doi: 10.1371/journal.pone.0099134

57. Hughes, R.N.; Lowther, C.L.; van Nobelen, M. Prolonged treatment with vitamins C and E separately and together decreases anxiety-related open-field behavior and acoustic startle in hooded rats. Pharmacology Biochemistry and Behavior. 2011, 97, 494– 499. doi: 10.1016/j.pbb.2010.10.010

58. Kori, R.S.; Aladakatti, R.H.; Desai, S.D.; Das, K.K. Effect of Drug Alprazolam on Restrained Stress Induced Alteration of Serum Cortisol and Antioxidant Vitamins (Vitamin C and E) in Male Albino Rats. J. Clin. Diagn. Res. 2016, 10, AF07–AF09. doi: 10.7860/JCDR/2016/21355.8380

59. Boufleur, N.; Antoniazzi, C.T.; Pase, C.S.; Benvegnú, D.M.; Dias, V.T.; Segat, H.J.; Roversi, K.; Roversi, K.; Nora, M.D.; Koakoskia, G.; Rosa, G.J.; Barcellos, L.J.G.; Bürger, M.E. Neonatal handling prevents anxiety-like symptoms in rats exposed to chronic mild stress: Behavioral and oxidative parameters. Stress. 2013, 16, 321–330. doi: 10.3109/10253890.2012.723075

60. Konarzewska, B.; Stefańska, E.; Wendołowicz, A.; Cwalina, U.; Golonko, A.; Małus, A.; Kowzan, U.; Szulc, A.; Rudzki, L.; Ostrowska, L. Visceral obesity in normal-weight patients suffering from chronic schizophrenia. BMC Psychiatry. 2014, 14, 35. doi: 10.1186/1471-244X-14-35

61. Magalhães, P.V.; Dean, O.; Andreazza, A.C.; Berk, M.; Kapczinski, F. Antioxidant treatments for schizophrenia. Cochrane database of systematic reviews. 2016, 2, CD008919. doi: 10.1002/14651858.CD008919.pub2.

62. Heiser, P.; Sommer, O.; Schmidt, A.J.; Clement, H.W.; Hoinkes, A.; Hopt, U.T.; Schulz, E.; Krieg, J.C.; Dobschütz, E. Effects of antipsychotics and vitamin C on the formation of reactive oxygen species. Journal of Psychopharmacology. 2010, 24, 1499–1504. doi: 10.1177/0269881109102538.

63. Wang, M.; Liu, Z.; Sun, W.; Yuan, Y.; Jiao, B.; Zhang, X.; Shen, L.; Jiang, H.; Xia, K.; Tang, B.; Wang, J. Association Between Vitamins and Amyotrophic Lateral Sclerosis: A Center-Based Survey in Mainland China. Frontiers in Neurology. 2020, 18;11:488. doi:10.3389/fneur.2020.00488

64. Nieves, J. W.; Gennings, C.; Factor-Litvak, P.; Hupf, J.; Singleton, J.; Sharf, V.; Oskarsson, B.; Fernandes Filho, J. A. M.; Sorenson, E. J.; D'Amico, E.; Goetz, R.; Mitsumoto, H. Association between dietary intake and function in amyotrophic lateral sclerosis. JAMA Neurology. 2016, 73(12), 1425. doi:10.1001/jamaneurol.2016.3401

65. Pupillo, E.; Bianchi, E.; Chiò, A.; Casale, F.; Zecca, C., Beghi, E.; Tortelli, R. Amyotrophic lateral sclerosis and food intake. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. 2017, 19(3-4), 267–274. doi:10.1080/21678421.2017.1418002

66. Wang, M.; Liu, Z.; Sun, W.; Yuan, Y.; Jiao, B.; Zhang, X.; Shen, L.; Jiang, H.; Xia, K.; Tang, B.; Wang, J. Association between vitamins and amyotrophic lateral sclerosis: A Center-Based Survey in Mainland China. Frontiers in Neurology. 2020, 11:488. doi:10.3389/fneur.2020.00488

67. Blasco, H.; Corcia, P.; Moreau, C.; Veau, S.; Fournier, C.; Vourc’h, P., Emond, P.; Gordon, P.; Pradat, P-F.; Praline, J.; Devos, D.; Nadal-Desbarats, L.; Andres, C. R. 1H-NMR-based metabolomic profiling of CSF in early amyotrophic lateral sclerosis. PLoS ONE. 2010, 5(10), e13223. doi:10.1371/journal.pone.0013223

68. Spasojević, I.; Stević, Z.; Nikolić-Kokić, A.; Jones, D.R.; Blagojević, D.; Spasić, M.B. Different roles of radical scaven-gers—Ascorbate and urate in the cerebrospinal fluid of amyotrophic lateral sclerosis patients. Redox Report. 2010, 15, 81–86. doi: 10.1179/174329210X12650506623320.

69. Netzahualcoyotzi, C.; Tapia, R. Degeneration of spinal motor neurons by chronic AMPA-induced excitotoxicity in vivo and protection by energy substrates. Acta Neuropathologica Communications. 2015, 3, 27. doi: 10.1186/s40478-015-0205-3.

70. Nagano, S.; Fujii, Y.; Yamamoto, T.; Taniyama, M.; Fukada, K.; Yanagihara, T.; Sakoda, S. The efficacy of trientine or ascor-bate alone compared to that of the combined treatment with these two agents in familial amyotrophic lateral sclerosis model mice. Experimental Neurology. 2003, 179, 176–180. doi: 10.1016/s0014-4886(02)00014-6.

71. Fitzgerald, K. C.; O’Reilly, É. J.; Fondell, E.; Falcone, G. J.; McCullough, M. L.; Park, Y.; Kolonel, L.N.; Ascherio, A. Intakes of vitamin C and carotenoids and risk of amyotrophic lateral sclerosis: Pooled results from 5 cohort studies. Annals of Neurology. 2013, 73(2), 236–245. doi:10.1002/ana.23820

72. Goncharova, P.S.; Davydova, T.K.; Popova, T.E.; Novitsky, M.A.; Petrova, M.M.; Gavrilyuk, O.A.; Al-Zamil, M.; Zhukova, N.G.; Nasyrova, R.F., Shnayder, N.A. Nutrient Effects on Motor Neurons and the Risk of Amyotrophic Lateral Sclerosis. Nutrients 2021, 13, 3804. https://doi.org/10.3390/nu13113804

73. Vanderslice, J.T. and Higgs, D.J. Vitamin C content of foods: sample variability. Am. J. Clin. Nutr. 54, 1323S–1327S, Bilic, N. Assay for both ascorbic and dehydroascorbic aciin dairy foods by high-performance liquid chromatography using precolumn derivatization with methoxy- and ethoxy-1,2-phenylenediamine. Journal of Chromatography. 1991, 543, 367–374. doi: 10.1093/ajcn/54.6.1323s.

74. Stevenson, N.R. Active transport of L-ascorbic acid in the human ileum. Gastroenterology. 1974, 67, 952–956. PMID: 4473393

75. Stewart, J.S.; Booth, C.C. Ascorbic acid absorption in malabsorption. Clinical Science. 1964, 27, 15–22. PMID: 14203254

76. Karasov. W.H.; Darken, B.W.; Bottum, M.C.Dietary regulation of intestinal ascorbate uptake in guinea pigs American Journal of Physiology. 1991, 260, pp. G108-G118. doi: 10.1152/ajpgi.1991.260.1.G108.

77. Rumsey, S. C.; Levine, M. Absorption, transport, and disposition of ascorbic acid in humans. The Journal of Nutritional Biochemistry. 1998, 9(3), 116–130. doi:10.1016/s0955-2863(98)00002-3

78. Bianchi, J.; Rose, R.C. Dehydroascorbic acid and cell membranes: Possible disruptive effects. Toxicology. 1986, 40, 75–82. doi: 10.1016/0300-483x(86)90047-8.

79. Rose, R.C. Transport of ascorbic acid and other watersoluble vitamins. Biochimica et Biophysica Acta. 1988, 947, 335–366. doi: 10.1016/0304-4157(88)90014-7.

80. Sabry, J.H.; Fisher, K.H.; Dodds, M.L. Human utilization of dehydroascorbic acid. Journal of Nutrition. 1958, 68, 457–466. doi: 10.1093/jn/64.3.457.

81. Rumsey, S. C.; Levine, M. Absorption, transport, and disposition of ascorbic acid in humans. The Journal of Nutritional Biochemistry, 1998, 9(3), 116–130. doi:10.1016/s0955-2863(98)00002-3

82. Rowland, M.; Tozer, T.M. Clinical pharmacokinetics: concepts and applications. Lea and Febiger, 1989, Philadelphia, USA

83. Levine, M.; Conry-Cantilena, C.; Wang, Y.; Welch, R.W.; Washko, P.W.; Dhariwal, K.R.; Park, J.B.; Lazarev, A.; Graumlich, J.; King, J.; Cantilena, L.R. Vitamin C pharmacokinetics in healthy volunteers: Evidence for a Recommended Dietary Allowance. Proceedings of the National Academy of Sciences. 1996, 93, 3704–3709. doi: 10.1073/pnas.93.8.3704.

84. 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. Pharmaceutical Research. 1997, 14, 1133–1139. doi: 10.1023/a:1012186203165

85. Mangels, A.R.; Block, G.; Frey, C.M.; Patterson, B.H.; Taylor, P.R.; Norkus, E.P.; Levander, O.A. The bioavailability to humans of ascorbic acid from oranges, orange juice and cooked broccoli is similar to that of synthetic ascorbic acid. Journal of Nutrition. 1993, 123, 1054–1061. doi: 10.1093/jn/123.6.1054.

86. Vinson, J.A.; Bose, P. Comparative bioavailability to humans of ascorbic acid alone or in a citrus extract. The American Journal of Clinical Nutrition. 1988, 48, 601–604. doi: 10.1093/ajcn/48.3.601

87. Levine, M.; Conry-Cantilena, C.; Wang, Y.; Welch, R.W.; Washko, P.W.; Dhariwal, K.R.; Park, J.B.; Lazarev, A.; Graumlich, J.; King, J.; Cantilena, L.R. Vitamin C pharmacokinetics in healthy volunteers: Evidence for a Recommended Dietary Allowance. Proceedings of the National Academy of Sciences. 1996, 93, pp. 3704-3709. doi: 10.1073/pnas.93.8.3704.

88. Vanderslice, J.T.; Higgs, D.J.; Beecher, G.R.; Higgs, H.E.; Bouma, J. On the presence of dehydroascorbic acid in human plasma. International Journal for Vitamin and Nutrition Research. 1992, 62, 101–102. PMID: 1587701

89. Dhariwal, K.R.; Hartzell, W.O.; Levine, M. Ascorbic acid and dehydroascorbic acid measurements in human plasma and serum. The American Journal of Clinical Nutrition. 1991, 54, 712–716. doi: 10.1093/ajcn/54.4.712

90. Washko, P.W.; Wang, Y.; Levine, M. Ascorbic acid recycling in human neutrophils. Journal of Biological Chemistry. 1993, 268, 15531–15535. PMID: 8340380

91. Evans, R.M.; Currie, L.; Campbell, A. The distribution of ascorbic acid between various cellular components of blood, in normal individuals, and its relation to the plasma concentration. British Journal of Nutrition. 1982, 47, 473–482. doi: 10.1079/bjn19820059.

92. Welch, R.W.; Wang, Y.; Crossman, A.; Jr., Park J.B.; Kirk, K.L.; Levine, M. Accumulation of vitamin C (ascorbate) and its oxidized metabolite dehydroascorbic acid occurs by separate mechanisms. Journal of Biological Chemistry. 1995, 270, 12584–12592. doi: 10.1074/jbc.270.21.12584.

93. Welch, R.W.; Bergsten, P.; Butler, J.D.; Levine, M. Ascorbic acid accumulation and transport in human fibroblasts. Biochemical Journal. 1993, 294, 505–510. doi: 10.1042/bj2940505.

94. Bergsten, P; Yu, R.; Kehrl, J.; Levine, M. Ascorbic acid transport and distribution in human B lymphocytes. Archives of Biochemistry and Biophysics. 1995, 317, 208–214. doi: 10.1006/abbi.1995.1155.

95. Jacob, R.A.; Pianalto, F.S.; Agee, R.E. Cellular ascorbate depletion in healthy men. Journal of Nutrition. 1992. 122, 1111–1118. doi: 10.1093/jn/122.5.1111.

96. Dreyer, R.; Rose, R.C. Lacrimal gland uptake and metabolism of ascorbic acid. Proc. Soc. Exp. Biol. Med. 1993, 202, 212–216. doi: 10.3181/00379727-202-43529.

97. Kasahara, E.; Kashiba, M.; Jikumaru, M.; Kuratsune, D.; Orita, K.; Yamate, Y.; Hara, K.; Sekiyama, A.; Sato. F.E.; Inoue, M. Dynamic aspects of ascorbic acid metabolism in the circulation: analysis by ascorbate oxidase with a prolongedin vivohalf-life. Biochemical Journal. 2009, 421(2), 293–299. doi:10.1042/bj20090286

98. Inoue, M. [Inter-organ metabolism and transport of glutathione]. Tanpakushitsu Kakusan Koso. 1984, 29, 695–707.

99. Helbig, H.; Korbmacher, C.; Wohlfarth, J.; Berweck, S.; Kuhner, D.; Wiederholt, M. Electrogenic Na1-ascorbate cotransport in cultured bovine pigmented ciliary epithelial cells. American Journal of Physiology. 1989, 256, C44–C49. doi: 10.1152/ajpcell.1989.256.1.C44.

100. Keller, K.; Mueckler, M. Different mammalian facilitative glucose transporters expressed in Xenopus oocytes. Biochimica et Biophysica Acta. 1990, 49, 1201–1203. PMID: 2097992

101. Vera, J.C.; Rivas, C.I.; Zhang, R.H.; Farber, C.M.; Golde, D.W. Human HL-60 myeloid leukemia cells transport dehydroascorbic acid via the glucose transporters and accumulate reduced ascorbic acid. Blood. 1994, 84, 1628–1634. PMID: 8068952

102. Kern, H.L.; Zolot, S.L. Transport of vitamin C in the lens. Current Eye Research. 1987, 6, 885–896. doi: 10.3109/02713688709034857.

103. Ingermann, R.L.; Stankova, L.; Bigley, R.H.; Bissonnette, J.M. Effect of monosaccharide on dehydroascorbic acid uptake by placental membrane vesicles. The Journal of Clinical Endocrinology and Metabolism. 1998, 67, 389–394. doi: 10.1210/jcem-67-2-389

104. Kanai, Y.; Lee, W.S.; You, G.; Brown, D.; Hediger, M.A. The human kidney low affinity Na1/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. Journal of Clinical Investigation. 1994, 93, 397–404. doi: 10.1172/JCI116972

105. Vera, J.C.; Rivas, C.I.; Fischbarg, J.; Golde, D.W. Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid. Nature. 1993, 364, 79–82, 64. doi: 10.1038/364079a0

106. Rumsey, S.C.; Kwon, O.; Xu, G.W.; Burant, C.F.; Simpson, I.; Levine, M. Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. Journal of Biological Chemistry. 1997, 272, 18982–18989. doi: 10.1074/jbc.272.30.18982.

107. Welch, R.W.; Wang, Y.; Crossman Jr, A.; Park, J.B.; Kirk, K.L.; Levine, M. Accumulation of vitamin C (ascorbate) and its oxidized metabolite dehydroascorbic acid occurs by separate mechanisms. Journal of Biological Chemistry. 1995, 270, pp. 12584-12592. doi: 10.1074/jbc.270.21.12584.

108. Doseděl, M.; Jirkovský, E.; Macáková, K.; Krčmová, L.; Javorská, L.; Mercolini, L.; Remião, F.; Nováková, L.; Mladěnka, P.; Pourová, J. Vitamin C—sources, physiological role, kinetics, deficiency, use, toxicity, and determination. Nutrients, 2021, 13(2), 615. doi:10.3390/nu13020615

109. 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.

110. 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.

111. 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.

112. 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

113. 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. Nature Medicine. 2002, 8, 514–517. doi: 10.1038/0502-514

114. Hornig, D. Distribution of ascorbic acid, metabolites and analogues in man and animals. Annals of the New York Academy of Sciences. 1975, 258, pp. 103-118. doi: 10.1111/j.1749-6632.1975.tb29271.x.

115. Keith, M.O.; Pelletier, O. Ascorbic acid concentrations in leukocytes and selected organs of guinea pigs in response to increasing ascorbic acid intake. The American Journal of Clinical Nutrition. 1974, 27, pp. 368-372. doi: 10.1093/ajcn/27.4.368.

116. Kallner, A.; Hartmann, D.; Hornig, D. Steady-state turnover and body pool of ascorbic acid in man. The American Journal of Clinical Nutrition. 1979, 32, pp. 530-539. doi: 10.1093/ajcn/32.3.530.

117. Jacob, R.A.; Pianalto, F.S.; Agee, R.E. Cellular ascorbate depletion in healthy men. Journal of Nutrition. 1992, 122, pp. 1111-1118. doi: 10.1093/jn/122.5.1111

118. Hornig, D.; Weber, F.; Wiss, O. Autoradiographic distribution of (1-14C) ascorbic acid and (1-14C) dehydroascorbic acid in male guinea pigs after intravenous injection. International Journal for Vitamin and Nutrition Research. 1972, 42, pp. 223-241. PMID: 5053849

119. Mieyal, J.J.; Starke, D.W.; Gravina, S.A.; Dothey, C.; J.S. Chung, J.S. Thioltransferase in human red blood cells: Purification and properties. Biochemistry. 1991, 30, pp. 6088-6097. doi: 10.1021/bi00239a002.

120. Park, J.M.; Levine, M. Purification, cloning, and expression of dehydroascorbic acid reduction activity from human neutrophils: Identification as glutaredoxin. Biochemical Journal. 1996, 315 (1996), pp. 931-938. doi: 10.1042/bj3150931.

121. Melhorn, R.J. Ascorbate- and dehydroascorbic acid-mediated reduction of free radicals in the human erythrocyte. Journal of Biological Chemistry. 1991, 266, pp. 2724-2731. PMID: 1993652

122. Evans, R.M.; Currie, L.; Campbell, A. The distribution of ascorbic acid between various cellular components of blood, in normal individuals, and its relation to the plasma concentration. British Journal of Nutrition. 1982, 47, pp. 473-482. doi: 10.1079/bjn19820059

123. Hellman, L.; Burns, J.J. Metabolism of L-ascorbic acid-1-C14 in man. Journal of Biological Chemistry. 1957, 230, pp. 923-930. PMID: 13525409

124. Omaye, S.T.; Tillotson, J.A.; Sauberlich, H.E. Metabolism of L-ascorbic acid in the monkey P.A. Seib, B.M. Tolbert (Eds.), Ascorbic acid: chemistry, metabolism and uses. American Chemical Society, Washington, DC (1982), 317-334

125. Wang, Y.H.; Dhariwal, K.P.; Levine, M. Ascorbic acid bioavailability in humans. Ascorbic acid in plasma, serum, and urine. Annals of the New York Academy of Sciences. 1992, 669, pp. 383-386. doi: 10.1111/j.1749-6632.1992.tb17130.x.

126. Levine, M.; Dhariwal, K.R.; Welch, R.W.; Wang, Y.; Park, J.B. Determination of optimal vitamin C requirements in humans. The American Journal of Clinical Nutrition. 1995, 62 (suppl), pp. 1347S-1356S. doi: 10.1093/ajcn/62.6.1347S.

127. Frei, B.; Stocker, R.; England, L.; Ames B.N. Ascorbate: the most effective antioxidant in human blood plasma. Advances in Experimental Medicine and Biology. 1990, 264, 155-163. doi: 10.1007/978-1-4684-5730-8_24.

128. 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.

129. Granger, M.; Eck, P. Dietary vitamin C in human health. Advances in Food and Nutrition Research. 2018, 83, 281–310. doi: 10.1016/bs.afnr.2017.11.006.

130. Daruwala, R.; Song, J.; Koh, W.S.; Rumsey, S.C.; Levine, M. Cloning and functional characterization of the human sodiumdependent vitamin C transporters hSVCT1 and hSVCT2. FEBS Lett. 1999, 460, 480–484. doi: 10.1016/s0014-5793(99)01393-9.

131. Liang, W.J.; Johnson, D.; Jarvis, S.M. Vitamin C transport systems of mammalian cells. Molecular Membrane Biology. 2001, 18, 87– 95. doi: 10.1080/09687680110033774.

132. Levine, M.; Wang, Y.; Padayatty, S.J.; Morrow, J. A new recommended dietary allowance of vitamin C for healthy young women. Proceedings of the National Academy of Sciences. 2001, 98, 9842–9846. doi: 10.1073/pnas.171318198.

133. 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. Journal of Biological Chemistry. 2005, 280, 5211–5220. doi: 10.1074/jbc.M412925200

134. Bowers-Komro, D.M.; McCormick, D.B. Characterization of ascorbic acid uptake by isolated rat kidney cells. Journal of Nutrition. 1991, 121, pp. 57-64. doi: 10.1093/jn/121.1.57

135. Friedman, G.J.; Sherry, S.; Ralli, E. The mechanism of excretion of vitamin C by the human kidney at low and normal plasma levels of ascorbic acid. Journal of Clinical Investigation. 1940, 19, pp. 685-689. doi: 10.1172/JCI101171.

136. Oreopoulos, D.G.; Lindeman, R.D.; VanderJagt, D.J.; Tzamaloukas, A.H.; Bhagavan, H.N.; Garry, P.J. Renal excretion of ascorbic acid: Effect of age and sex. American College of Nutrition.1993, 12, pp. 537-542. doi: 10.1080/07315724.1993.10718349.

137. Toggenburger, G.; Hausermann, M.; Mutsch, B.; Genoni, G.; Kessler, M.; Weber, F.; Hornig, D.; O’Neill, B.; Semenza, G. Na+- dependent, potential-sensitive L-ascorbate transport across brush border membrane vesicles from kidney cortex. Biochimica et Biophysica Acta. 1981, 646, pp. 433-443. doi: 10.1016/0005-2736(81)90312-6.

138. Food and Nutrition Board (U.S.R.C.) Recommended dietary allowances. National Academy Press, Washington, DC, 1985.

139. Baker, E.M.; Hodges, R.E.; Hood, J.; Sauberlich, H.E.; March, S.C. Metabolism of ascorbic-1–14C acid in experimental human scurvy. The American Journal of Clinical Nutrition. 1969, 22, 549-558. doi: 10.1093/ajcn/22.5.549.

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

141. Bianchi, J.; Rose, R.C. Na+-independent dehydro-L-ascorbic acid uptake in renal brush-border membrane vesicles. Biochimica et Biophysica Acta. 1985, 819. 75-82. doi: 10.1016/0005-2736(85)90197-x.

142. Bianchi, J.; Rose, R.C. Transport of L-ascorbic acid and dehydro-L-ascorbic acid across renal cortical basolateral membrane vesicles. Biochimica et Biophysica Acta. 1985, 820,265-273. doi: 10.1016/0005-2736(85)90120-8.

143. Rose, R.C.; Choi, J.L.; M.J. Koch, M.J. Intestinal transport and metabolism of oxidized ascorbic acid (dehydroascorbic acid). American Journal of Physiology.1988, 254. G824-G828. doi: 10.1152/ajpgi.1988.254.6.G824.

144. Kallner, A.; Hornig, D.; Pellikka, R. Formation of carbon dioxide from ascorbate in man. The American Journal of Clinical Nutrition. 1985, 41. 609-613. doi: 10.1093/ajcn/41.3.609.

145. Baker, E.M.; Halver, J.E.; Johnsen, D.O.; Joyce, B.E.; Knight, M.K.; Tolbert, B.M. Metabolism of ascorbic acid and ascorbic-2- sulfate in man and the subhuman primate. Annals of the New York Academy of Sciences.1975, 258. 72-80. doi: 10.1111/j.1749-6632.1975.tb29269.x.

146. Mydlik, M.; Derzsiova, K.; Pribylincova, V.; Zvara, V.; Takac, M. Urinary excretion of vitamin C in chronic renal failure and after renal transplantation. International Urology and Nephrology.1986, 18. 457-462. doi: 10.1007/BF02084119

147. Hellman, L.; Burns, J.J. Metabolism of L-ascorbic acid-1-C14 in man. Journal of Biological Chemistry. 1958, 230, 923–930. PMID: 13525409

148. 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. Journal of Clinical Investigation. 2010, 120, 1069–1083. doi: 10.1172/JCI39191

149. 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.

150. 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. Pharmaceutical Research. 1997, 14, 1133–1139. doi: 10.1023/a:1012186203165

151. 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. The American Journal of Clinical Nutrition. 2010, 92, 375–382. doi: 10.3945/ajcn.2010.29438.

152. Michels, A.J.; Hagen, T.M.; Frei, B. Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function. Annual Review of Nutrition. 2013, 33, 45–70. doi: 10.1146/annurev-nutr-071812-161246.

153. 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. American Journal of Epidemiology. 2006, 163, 245–254. doi: 10.1093/aje/kwj035

154. 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 & Nutrition. 2013, 8, 549–560. doi: 10.1007/s12263-013-0346-6

155. Amir Shaghaghi, M.; Bernstein, C. N.; Serrano León, A.; El-Gabalawy, H.; Eck, P. Polymorphisms in the sodium-dependent ascorbate transporter gene SLC23A1 are associated with susceptibility to Crohn disease. The American Journal of Clinical Nutrition. 2013, 99(2), 378–383. doi:10.3945/ajcn.113.068015

156. Said, H. M.; Nexo, E. Intestinal Absorption of Water-Soluble Vitamins: Cellular and Molecular Mechanisms. Physiology of the Gastrointestinal Tract. 2018, 1201–1248. doi:10.1016/b978-0-12-809954-4.00054-2

157. Liu, E. S.; Jüppner, H. Vitamin D. In: Clinical Disorders of Phosphate Homeostasis. 2018, 229–247. doi:10.1016/b978-0-12-809963-6.00070-5

158. Piersma, B.; Wouters, O. Y.; de Rond, S.; Boersema, M.; Gjaltema, R. A. F.; Bank, R. A. Ascorbic acid promotes a TGFβ 1-induced myofibroblast phenotype switch. Physiological Reports. 2017, 5(17), e13324. doi:10.14814/phy2.13324

159. Gupta, I., Ganguly, S., Rozanas, C. R., Stuehr, D. J., & Panda, K. (2016). Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis. Proceedings of the National Academy of Sciences, 113(29), E4208–E4217. doi:10.1073/pnas.1600056113

160. Kvaratskhelia, M.; George, S. J.; Thorneley, R. N. F. Salicylic Acid Is a Reducing Substrate and Not an Effective Inhibitor of Ascorbate Peroxidase. Journal of Biological Chemistry. 2016, 272(34), 20998–21001. doi:10.1074/jbc.272.34.20998

161. Eck, P., Kwon, O., Chen, S., Mian, O., & Levine, M. (2013). The human sodium-dependent ascorbic acid transporters SLC23A1 and SLC23A2 do not mediate ascorbic acid release in the proximal renal epithelial cell. Physiological Reports, 1(6). doi:10.1002/phy2.136

162. Zanon-Moreno, V.; Garcia-Medina, J. J.; Sanz-Solana, P.; Pinazo-Duran, M. D.; Corella, D. SLC23A2 Gene Variation, Vitamin C Levels, and Glaucoma. Handbook of Nutrition, Diet and the Eye. 2014, 549–556. doi:10.1016/b978-0-12-401717-7.00056-3

163. Ashor, A. W.; Siervo, M.; Mathers, J. C. Vitamin C, Antioxidant Status, and Cardiovascular Aging. Molecular Basis of Nutrition and Aging. 2016, 609–619. doi:10.1016/b978-0-12-801816-3.00043-1


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Goncharova P.S., Davydova T.K., Zhukova N.G. Prospects for studying the pharmacokinetics, pharmacodynamics and pharmacogenetics of vitamin C in patients with neurological diseases and mental disorders. Personalized Psychiatry and Neurology. 2021;1(2):63-82. https://doi.org/10.52667/2712-9179-2021-1-2-63-82

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