Vitamin D: a history spanning over a century

Vitamin D is one of the most extensively studied nutrients, playing a key role in maintaining human health. The history of its research spans over 100 years, encompassing stages from the description of rickets and osteomalacia to the deciphering of molecular mechanisms of action and the recognition of its pleiotropic effects. Despite a significant body of accumulated data, debates persist to this day regarding optimal target levels of 25(OH)D, indications for prescribing vitamin D supplements, and the clinical significance of its extraskeletal effects. This review sequentially examines the main historical milestones in the discovery of vitamin D, the contributions of foreign and Russian scientists, modern concepts of its biochemistry and metabolism, and its role in regulating bone, metabolic, endocrine, immune, cardiovascular, and nervous system homeostasis. Special attention is given to the problem of the high prevalence of vitamin D deficiency in the Russian Federation, caused by geographical, climatic, and dietary factors. The article summarizes current international and Russian clinical guidelines, discusses approaches to the prevention and correction of vitamin D deficiency, and outlines promising directions for future research.

1. Suplotova LA, Avdeeva VA, Pigarova EA Rozhinskaya LYa, Troshina EA. Vitamin D deficiency in Russia: the first results of a registered, non-interventional study of the frequency of vitamin D deficiency and insufficiency in various geographic regions of the country. Problems of Endocrinology. 2021;67(2):84-92. (In Russ.). doi: https://doi.org/10.14341/probl12736

2. Karonova TL, Golovatyuk KA, Mikhaylova AA, Suplotova LA, Troshina EA, Rozhinskaya LYa. The first Russian multicenter non-interventional registry Phase III Study of vitamin D deficiency and insufficiency prevalence among adults in Russian Federation. Osteoporosis and Bone Diseases. 2023;26(1):13-23. (In Russ.). doi: https://doi.org/10.14341/osteo12964.

3. Zaharova IN, Maltsev SV, Borovik TE, Yatsyk GV, Malyavskaya SI, et al. Results of a multicenter research «Rodnichok» for the study of vitamin D insufficiency in infants in Russia. Pediatria n.a. G.N. Speransky. 2015;94(1). (In Russ.).

4. Jones G. 100 years of vitamin D: Historical aspects of vitamin D. Endocr Connect. 2022;11(4):e210594. doi: https://doi.org/10.1530/EC-21-0594

5. Huldschinsky K. The Ultra-Violet Light Treatment of Rickets. Alpine Press. 1928.3–19

6. Mellanby E. An experimental investigation of rickets. Nutrition Reviews. 1976;34:338–340. doi: https://doi.org/10.1111/j.1753-4887.1976.tb05815.x

7. McCollum EV, Simmonds N, Becker JE, Shipley PG. Studies on experimental rickets: XXI. An experimental demonstration of the existence of a vitamin which promotes calcium deposition. J. Biol. Chem. 1922;53:293–312. doi: https://doi.org/10.1111/j.1753-4887.1975.tb07097.x

8. Steenbock H, Black A. Fat-soluble vitamins. XVII. The induction of growth-promoting and calcifying properties in a ration by exposure to ultraviolet light. Journal of Biological Chemistry. 1924;61:405-422

9. Nenakhov IG. Nikolay Ivanovich Lunin - osnovatel’ vitaminologii i uchenyy, vnesshiy znachitel’nyy vklad v razvitiye gigiyeny pitaniya. Nauchno-meditsinskiy vestnik Tsentral’nogo Chernozem’ya. 2019;77:122-125. (In Russ.).

10. Namazova-Baranova LS, Albitskiy VYu. Velikiy russkiy pediatr Georgiy Nestorovich Speranskiy: k 150-letiyu so dnya rozhdeniya. Pediatriya. Zhurnal im. G.N. Speranskogo. 2023;102(1):8-11. (In Russ.). doi: https://doi.org/10.24110/0031-403X-2023-102-1-8-11

11. Maltsev SV, Safina LZ. Lepsky: an outstanding figure in the russian paediatrics (on the occasion of the 140th anniversary of the birth). Meditsinskiy sovet. 2018;(17):273-279.(In Russ.). doi: https://doi.org/10.21518/2079-701X-2018-17-273-278

12. Tur AF. Rakhit u detej. Moskva: Medgiz; 1951. (In Russ.).

13. Mikirtichan GL. Klassiki sovetskoy pediatrii Yuliya Fominichna Dombrovskaya i Aleksandr Fyodorovich Tur. Rossiyskiy pediatricheskiy zhurnal. 2017;20(4):250-256.(In Russ.). doi: https://doi.org/10.18821/1560-9561-2017-20-4-250-256

14. Andreeva AV, Samburov GO, Spasenkov BA. Istoriya sozdaniya severnoy nauchnoy pediatricheskoy shkoly (k 110-letiyu so dnya rozhdeniya professora Marii Vladimirovny Pikkel’). Byulleten Natsionalnogo nauchno-issledovatelskogo instituta obshchestvennogo zdorov’ya imeni N.A. Semashko. 2021;1:92-99. (In Russ.)].

15. Igor’ Mikhaylovich Vorontsov (k 70-letiyu so dnya rozhdeniya). Pediatriya (im. G.N. Speranskogo). 2005;(4):84. (In Russ.).

16. Windaus A, Brockmann H, Schroff KH. Über das Vorkommen des Vitamins D₃ in der Leber von Haifischen. Hoppe-Seyler’s Z Physiol Chem. 1936;243:1–4

17. Norman AW, Myrtle JF, Midgett RJ, Nowicki HG, Williams V, Popják G. 1,25-Dihydroxycholecalciferol: Identification of the proposed active form of vitamin D₃. Science. 1971;173(3991):51–54. doi: https://doi.org/10.1126/science.173.3991.51

18. Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab. 2010;95(2):471–478. doi: https://doi.org/ 10.1210/jc.2009-1773

19. Jones G, Prosser DE, Kaufmann M. 25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): Its important role in the degradation of vitamin D. Arch Biochem Biophys. 2012;523(1):9–18. doi: https://doi.org/10.1016/j.abb.2011.11.003

20. Pike JW, Meyer MB. Genomic actions of 1,25-dihydroxyvitamin D₃. Vitam Horm. 2012;89:49–85

21. Tuckey RC, Cheng CYS, Slominski AT. The serum vitamin D metabolome: What we know and what is still to discover. J Steroid Biochem Mol Biol. 2019;186:4-21. doi: https://doi.org/10.1016/j.jsbmb.2018.09.003

22. Lesnyak OM, Baranova IA, Belova KYu, Gladkova EN, Evstigneeva LP, et al. Osteoporosis in Russian Federation: Epidemiology, Socio-Medical and Economical Aspects (Review). Traumatology and Orthopedics of Russia. 2018;24(1):155-168. (In Russ.). doi: https://doi.org/10.21823/2311-2905-2018-24-1-155-168

23. [Markova TN, Markov DS, Markelova TN, Nigmatullina SR, Baimkina EV, et al. Rasprostranennost defitsita vitamina D i faktorov riska osteoporoza u lits molodogo vozrasta. Vestnik Chuvashskogo universiteta. 2012;(3):441-446. (In Russ.).

24. Skripnikova IA, Sorokin MYu. Diagnosis, treatment and prevention of vitamin d deficiency (discussion based on the clinical recommendations of the endocrine society 2011). Osteoporosis and Bone Diseases. 2012;15(1):34-37. (In Russ.). doi: https://doi.org/10.14341/osteo2012134-37

25. Suplotova LA, Avdeeva VA, Sudnitsyna AS, Rozhinskaya LYa. Hyperparathyroidism and vitamin d: relationship difficulties. Osteoporosis and Bone Diseases.2022;25(1):23-28. (In Russ.). doi: https://doi.org/10.14341/osteo12944

26. Nikitinskaya OA, Toroptsova NV. Sotsialnaya programma «Osteoskrinig Rossiya» v deistvii. Farmateka. 2012;(6):90-93.(In Russ.).

27. Toroptsova NV, Nikitinskaya OA, Demin NV, Benevolenskaya LI. Profilaktika postmenopauzalnogo osteoporoza: rezultaty tryokhletnego nablyudeniya. Nauchno-prakticheskaya revmatologiya. 2006;(5):25–32.(In Russ.).

28. Wamberg L, Christiansen T, Paulsen SK, Fisker S, Rask P, et al. Expression of vitamin D-metabolizing enzymes in human adipose tissue-the effect of obesity and diet-induced weight loss. Int J Obes. 2013;37(5):651-657. doi:

29. Pigarova EA, Dzeranova LK. Obesity, diabetes and vitamin D. Obesity and metabolism. 2024;21(3):316-324.(In Russ.)]. doi:

30. Volkova NI, Kiseleva TP, Markova TN, Remizov OV, Skakun LA, Tyulganova VL, Yavlyanskaya VV. Vitamin D deficiency in overweight patients: current strategies and practical aspects. Problemy Endokrinologii. 2025;71(1):92-98.. doi: https://doi.org/10.14341/probl13557

31. Karonova TL, Grineva EN, Mikheeva EP, Belyaeva OD, Krasilnikova EI, Nikitina IL. The level of vitamin D and its relationship with the amount of fatty tissue and adipocytokine content in the women of reproductive age. Problemy endokrinologii. 2012;58(6):19-23. doi: https://doi.org/10.14341/probl201258619-23

32. Rock CL, Emond JA, Flatt SW. Weight loss is associated with increased serum 25-hydroxyvitamin D in overweight or obese women. Obesity. 2012;20(11):2296-301. doi: https://doi.org/10.1038/oby.2012.57.

33. Cheng S, Massaro JM, Fox CS. Adiposity, Cardiometabolic Risk, and Vitamin D Status: The Framingham Heart Study. Diabetes. 2010;59(1):242-8. doi: https://doi.org/10.2337/db091011

34. Dzgoeva FKh, Radaeva OA, Krasnoglazova KA, Arkhipkin AA, Mamieva EK, Smetanina SA. Serum levels of 25(OH)D and visfatin as markers of NAFLD in obesity and overweight. Russian Medical Inquiry. 2025;9(10):702–709. doi: https://doi.org/10.32364/2587-6821-2025-9-10-2

35. Nikitina IL, Todieva AM, Karonova TL, Vasilieva EYu, Budanova MB. Vitamin D deficiency in children with obesity — who is at the highest risk? Voprosi detskoi dietologii. 2013;11(3):15-20.

36. Nikitina IL, Todiyeva AM, Karonova TL. Metabolic risks in children with obesity and deficit of vitamin D. Practical medicine. 2017;5(106) 48-52.

37. Borges JLC, Miranda ISM, Sarquis MMS, Borba V, Maeda SS, Lazaretti-Castro M. Obesity, Bariatric Surgery, and Vitamin D. J Clin Densitom. 2018;21(2):157–62

38. Pilz S, Kienreich K, Rutters F. Role of vitamin D in the development of insulin resistance and type 2 diabetes. Current Diabetes Reports. 2012;13(2):261-270. doi: https://doi.org/10.1007/s11892-012-0358-4

39. Pigarova EA, Dzeranova LK. Obesity, diabetes and vitamin D. Obesity and metabolism. 2024;21(3):316-324.

40. Mirhosseini N, Vatanparast H, Mazidi M, Kimball SM. The effect of improved serum 25-hydroxyvitamin D status on glycemic control in diabetic patients: a meta-analysis. J Clin Endocrinol Metab. 2017;102(9):3097-3110.

41. Zhang B, Zhao W, Tu J, Wang X, Hao Y, Wang H, Zhao Y, Mizuno K, Tseng Y, Bu H. The relationship between serum 25-hydroxyvitamin D concentration and type 2 diabetic peripheral neuropathy: A systematic review and a meta-analysis. Medicine (Baltimore). 2019;98(48):e18118. doi: https://doi.org/10.1097/MD.0000000000018118

42. Stepanova AP, Karonova TL. Effect of vitamin D therapy on the severity of pain in patients with type 2 diabetes mellitus and diabetic peripheral neuropathy. Osteoporosis and Bone Diseases. 2020;23(2):165-166.(In Russ.).

43. Harris E. Meta-analysis: Vitamin D therapy reduced type 2 diabetes. JAMA. 2023;329(9):703. doi: https://doi.org/10.1001/jama.2023.1550

44. Golzarand M, Hollis BW, Mirmiran P, Wagner CL, Shab-Bidar S. Vitamin D supplementation and body fat mass: a systematic review and meta-analysis. Eur J Clin Nutr. 2018;72(10):1345-1357. doi: .

45. Perna S. Is vitamin D supplementation useful for weight loss programs? A systematic review and meta-analysis of randomized controlled trials. Medicina (Kaunas). 2019;55(7):368. doi: https://doi.org/10.3390/medicina55070368

46. Andreeva AT, Gavrilova VI, Ustyuzhanina AO, Bystrova AA, Kokina MA, Karonova TL. Effects of vitamin on glucose metabolism in patients with prediabetes. Consilium Medicum. 2020;22(4):47-54.(In Russ.). doi: https://doi.org/ 10.26442/20751753.2020.4.200115.

47. Povaliaeva AA, Pigarova EA, Dzeranova LK, Rozhinskaya LYa. The relationship of vitamin D status with the development and course of diabetes mellitus type 1. Obesity and metabolism. 2020;17(1):82-87.(In Russ.). doi: https://doi.org/10.14341/omet12206

48. Pigarova EA, Dzeranova LK. High prevalence of low vitamin D levels in endocrine disorders. Obesity and metabolism. 2021;18(4):398-405.(In Russ.). doi: https://doi.org/ 10.14341/omet12799

49. Povaliaeva AA, Rozhinskaya LYa, Zhukov SA, Pigarova EA, Dzeranova LK, et al. Vitamin D Metabolism Alteration in Acromegaly and Its Impact on Calcium-Phosphorus Metabolism. Journal of the Endocrine Society. 2021;5(1):A651–A652. doi: https://doi.org/10.1210/jendso/bvab048.1329

50. Povaliaeva AA, Pigarova EA, Dzeranova LK, Rozhinskaya LYa, Mel’nichenko GA. Vitamin D metabolism in hypercorticism and acromegaly. Problems of Endocrinology. 2019;65(6):444-450. doi: https://doi.org/10.14341/probl12099

51. Sytaya YuS. Key mechanisms of the relationship between vitamin D and cardiovascular disease. Russian Journal of Cardiology. 2022;27(1):4602. doi: https://doi.org/10.15829/1560-4071-2022-4602

52. Belyaeva OD, Du J, Ionova ZhI, Karonova TL, Polunicheva EV, et al. The severity of coronary artery defeat in coronary heart disease patients with different variants of the vitamin D receptor gene and the level of vitamin D sufficiency. The Scientific Notes of the Pavlov University. 2022;29(2):41-51. doi: https://doi.org/10.24884/1607-4181-2022-29-2-41-51

53. Cheng X, Chen Z, Fang Y, Zhang Q, Chen B, Xi W, Pan Z, Guo L. Effect of vitamin D supplementation for major adverse cardiovascular events: a meta-analysis based on randomised controlled trials. Br J Nutr. 2025;134(2):124-133. doi: https://doi.org/10.1017/S0007114525103954

54. Wassif GA, Alrehely MS, Alharbi DM, Aljohani AA. The Impact of Vitamin D on Neuropsychiatric Disorders. Cureus. 2023;15(10):e47716. doi: https://doi.org/10.7759/cureus.47716

55. Machekhina LV, Balashova AV, Tkacheva ON, Mamchur AA, Erema VV, et al. Vitamin D and Geriatric Assessment: A Cross-Sectional Study of a Centenarian Cohort in the Central Region of the Russian Federation. Russian Journal of Geriatric Medicine. 2024;(1):21-29. doi: https://doi.org/10.37586/2686-8636-1-2024-21-29.

56. Karonova TL, Andreeva AT, Golovatuk KA. Low 25(OH)D level is associated with severe course and poor prognosis in COVID-19. Nutrients. 2021;13(9): 3021. doi: https://doi.org/10.3390/nu13093021

57. Kaya MO, Pamukcu E, Yakar B. The role of vitamin D deficiency on COVID-19: a systematic review and meta-analysis of observational studies. Epidemiology and Health. 2021;(43):e2021074. doi: https://doi.org/10.4178/epih.e2021074

58. Karonova TL, Golovatyuk KA, Kudryavtsev IV, Chernikova AT, Mikhaylova AA, et al. Effect of cholecalciferol supplementation on the clinical features and inflammatory markers in hospitalized COVID-19 patients: a randomized, open-label, single-center study. Nutrients. 2022;14(13):2602. doi: https://doi.org/10.3390/nu14132602.

59. Zhang Y, Li J, Yang M, Wang Q. Effect of vitamin D supplementation on COVID-19 patients: A systematic review and meta-analysis. Front Nutr. 2023;10:1131103. doi: https://doi.org/10.3389/fnut.2023.1131103

60. Gulick RM, Pau AK, Daar E, Evans L, Gandhi RT, et al. NIH COVID-19 Treatment Guidelines Panel; National Institutes of Health COVID-19 Treatment Guidelines Panel: Perspectives and Lessons Learned. Ann Intern Med. 2024;177(11):1547-1557. doi: https://doi.org/10.7326/ANNALS-24-00464

61. Gorelov AV, Petrov VA, Usenko DV. Role of vitamin D in the prevention of acute respiratory infections: a systematic review and meta-analysis. Infectious Diseases. 2023;21(1):119–124. doi: https://doi.org/10.20953/1729-9225-2023-1-119-124.

62. Grant WB, Lahore H, McDonnell SL, Baggerly CA, French CB, Aliano JL, Bhattoa HP. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020;12(4):988. doi: https://doi.org/10.3390/nu12040988

63. Zhao SS, Mason A, Gjekmarkaj E, Yanaoka H, Burgess S. Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis. Semin Arthritis Rheum. 2023;62:152238. doi: https://doi.org/10.1016/j.semarthrit.2023.152238

64. Ranjbar M, Rahimlou M, Fallah M, Djafarian K, Mohammadi H. Effects of vitamin D supplementation in patients with rheumatoid arthritis: а systematic review and meta-analysis. Heliyon. 2025;11(3):e42463. doi: https://doi.org/10.1016/j.heliyon.2025.e42463

65. Yasuda T, Okamoto Y, Hamada N, Miyashita K, Takahara M, et al. Serum vitamin D levels are Decreased and associated with thyroid volume in female patients with newly onset Graves’ Disease. Endocrine. 2012;42:739-741. doi: https://doi.org/10.1007/s12020-012-9679-y

66. Zhang H, Liang L, Xie Z. Low vitamin D status is associated with increased thyrotropin-receptor antibody titer in Graves’ Disease. Endocr Pract. 2015;21:258-263. doi: https://doi.org/10.4158/EP14191.OR

67. Mazokopakis EE, Papadomanolaki MG, Tsekouras KC, Evangelopoulos AD, Kotsiris DA, Tzortzinis AA. Is vitamin D related to pathogenesis and treatment of Hashimoto’s thyroiditis? Hell J Nucl Med. 2015;18:222-227

68. Demay MB, Pittas AG, Bikle DD, Diab DL, Kiely ME, et al. Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2024;109(8):1907-1947. doi: https://doi.org/10.1210/clinem/dgae290

69. Pigarova EA, Rozhinskaya LYa, Belaya ZhE, Dzeranova LK, Karonova TL, et al. Russian association of endocrinologists recommendations for diagnosis, treatment and prevention of vitamin D deficiency in adults. Problems of endocrinology. 2016;62(4):60-84.

70. Sahota O, Mundey MK, San P, Godber IM, Lawson N, Hosking DJ. The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis. Bone. 2004;35(1):312-9. doi: https://doi.org/10.1016/j.bone.2004.02.003

71. Priemel M, von Domarus C, Klatte TO, Kessler S. Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res. 2010;25(2):305-12. doi: https://doi.org/ 10.1359/jbmr.090728

72. Bakhtiyarova S, Lesnyak O, Kyznesova N, Blankenstein MA, Lips P. Vitamin D status among patients with hip fracture and elderly control subjects in Yekaterinburg, Russia. Osteoporos Int. 2006;17(3):441-6. doi: https://doi.org/10.1007/s00198-005-0006-9

73. Novikova TV, Zazerskaya IE, Kuznetsova LV, Vasilyeva MYu, Rudenko KA. Serum 25-Hydroxycalciferol Levels in Cholecalciferol Prophylaxis During Breastfeeding. Obstetrics and gynecology. 2022;3:97-103. doi: https://doi.org/10.18565/aig.2022.3.97-103

74. Belaya ZhE, Pigarova EA, Rozhinskaya LYa, Arutyunov GP, Gilyarevsky SR, et al. Resolution of the National interdisciplinary expert council «The use of high-dose vitamin D for the prevention and treatment of vitamin D deficiency, including in comorbid patients, in the use of endocrinologists, rheumatologists, gerontologists and internists/GPS». Osteoporosis and Bone Diseases. 2024;27(1):10-20. (In Russ.). doi: https://doi.org/10.14341/osteo13171

75. Troshina EA, Pigarova EA, Karonova TL, Dzgoeva FKh, Radzinskiy VE, et al. Optimal serum 25(OH)D levels in relation to musculoskeletal, metabolic, neurological, autoimmune and infectious diseases. Problems of Endocrinology. 2025;71(6):40-49. (In Russ.). doi: https://doi.org/10.14341/probl13687