Витамин К2: известный и неизвестный. Современный взгляд: возможности и перспективы

В настоящее время витамин К2 является одним из наиболее популярных микронутриентов как у исследователей, так и у практикующих врачей. Помимо хорошо известного участия в синтезе факторов свертывания, витамин К2 оказывает влияние на отложение кальция в костной ткани и внекостных структурах, защищая от развития остеопороза и кальцификации сосудов. За последние годы накапливается все больше данных о его участии в регуляции ключевых физиологических и патологических процессов в организме, таких как деление и дифференцировка клеток, углеводный обмен, воспаление, оксидативный стресс и др. В настоящем обзоре мы разбираем источники витамина К2, механизмы его действия и влияние на метаболизм.

1. Walther B, Karl JP, Booth SL, Boyaval P. Menaquinones, bacteria, and the food supply: the relevance of dairy and fermented food products to vitamin K requirements. Adv Nutr. 2013 Jul 1;4(4):463–73. doi: 10.3945/an.113.003855

2. Bus K, Szterk A. Relationship between Structure and Biological Activity of Various Vitamin K Forms. Foods. 2021 Dec 17;10(12):3136. doi: 10.3390/foods10123136

3. Dutch food composition database (NEVO). Netherlands Food Information Resource. https://nevo-online.rivm.nl/Home/En

4. Walther B., Chollet, M. Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet. In: Gordeladze J. O., editor. Vitamin K2 – Vital for Health and Wellbeing [Internet]. London: IntechOpen; 2017 [cited 2022 Jun 02]. Available from: https://www.intechopen.com/chapters/50921 doi: 10.5772/63712

5. Kozioł-Kozakowska A, Maresz K. The Impact of Vitamin K2 (Menaquionones) in Children’s Health and Diseases: A Review of the Literature. Children (Basel). 2022 Jan 5;9(1):78. doi: 10.3390/children9010078

6. Ambrożewicz E, Muszyńska M, Tokajuk G, Grynkiewicz G, Žarković N, Skrzydlewska E. Beneficial Effects of Vitamins K and D 3 on Redox Balance of Human Osteoblasts Cultured with Hydroxyapatite-Based Biomaterials. Cells. 2019 Apr 8;8(4):325. doi: 10.3390/cells8040325

7. Методические рекомендации МР 2.3.1.0253–21 «Нормы физиологических потребностей в энергии и пищевых веществах для различных групп населения Российской Федерации», утверждены руководителем Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека – Главным государственным санитарным врачом Российской Федерации 22.07.2021. https://www.rospotrebnadzor.ru/documents/details.php?ELEMENT_ID=18979

8. Vergnaud P, Garnero P, Meunier PJ, Bréart G, Kamihagi K, Delmas PD. Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: the EPIDOS Study. J Clin Endocrinol Metab. 1997 Mar;82(3):719–24. doi: 10.1210/jcem.82.3.3805

9. Hao G, Zhang B, Gu M, Chen C, Zhang Q, Zhang G, Cao X. Vitamin K intake and the risk of fractures: A meta-analysis. Medicine (Baltimore). 2017 Apr;96(17): e6725. doi: 10.1097/MD.0000000000006725

10. Mott A, Bradley T, Wright K, Cockayne ES, Shearer MJ, Adamson J, Lanham-New SA, Torgerson DJ. Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials. Osteoporos Int. 2019 Aug;30(8):1543–1559. doi: 10.1007/s00198-019-04949-0

11. Mott A, Bradley T, Wright K, Cockayne ES, Shearer MJ, Adamson J, Lanham-New SA, Torgerson DJ. Correction to Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials. Osteoporos Int. 2020 Nov;31(11):2269–2270. doi: 10.1007/s00198-020-05586-8. Erratum for: Osteoporos Int. 2019 Aug;30(8):1543–1559.

12. Su S, He N, Men P, Song C, Zhai S. The efficacy and safety of menatetrenone in the management of osteoporosis: a systematic review and meta-analysis of randomized controlled trials. Osteoporos Int. 2019;30:1175–86. https://doi.org/10.1007/s00198-019-04853-7

13. Huang ZB, Wan SL, Lu YJ, Ning L, Liu C, Fan SW. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials. Osteoporos Int. 2015;26:1175–86.

14. Morishita M, Nagashima M, Wauke K, Takahashi H, Takenouchi K. Osteoclast inhibitory effects of vitamin K2 alone or in combination with etidronate or risedronate in patients with rheumatoid arthritis: 2-year results. J Rheumatol. 2008 Mar;35(3):407–13.

15. Suzuki K, Tsuji S, Fukushima Y, Nakase T, Hamada M, Tomita T, Yoshikawa H. Clinical results of alendronate monotherapy and combined therapy with menatetrenone (VitK 2 ) in postmenopausal RA patients. Mod Rheumatol. 2013 May;23(3):450–5. doi: 10.1007/s10165–012–0678-x

16. AlHajri L, Ayoub A, Ahmed H, AlMulla M. Effect of Vitamin K2 Alone or in Combination on Various Bone Turnover Markers Amongst Postmenopausal Females. J Bone Metab. 2021 Feb;28(1):11–26. doi: 10.11005/jbm.2021.28.1.11

17. Hu L, Ji J, Li D, Meng J, Yu B. The combined effect of vitamin K and calcium on bone mineral density in humans: a meta-analysis of randomized controlled trials. J Orthop Surg Res. 2021 Oct 14;16(1):592. doi: 10.1186/s13018-021-02728-4

18. Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food Funct. 2020 Apr 30;11(4):3280–3297. doi: 10.1039/c9fo03063h.

19. Shishavan NG, Gargari BP, Kolahi S, Hajialilo M, Jafarabadi MA, Javadzadeh Y. Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial. J Am Coll Nutr. 2016 Jul;35(5):392–8. doi: 10.1080/07315724.2015.1026004

20. Ebina K, Shi K, Hirao M, Kaneshiro S, Morimoto T, Koizumi K, Yoshikawa H, Hashimoto J. Vitamin K2 administration is associated with decreased disease activity in patients with rheumatoid arthritis. Mod Rheumatol. 2013 Sep;23(5):1001–7. doi: 10.1007/s10165-012-0789-4

21. Abdel-Rahman MS, Alkady EA, Ahmed S. Menaquinone-7 as a novel pharmacological therapy in the treatment of rheumatoid arthritis: A clinical study. Eur J Pharmacol. 2015 Aug 15;761:273–8. doi: 10.1016/j.ejphar.2015.06.014.

22. Fiordellisi W, White K, Schweizer M. A Systematic Review and Meta-analysis of the Association Between Vitamin K Antagonist Use and Fracture. J Gen Intern Med. 2019 Feb;34(2):304–311. doi: 10.1007/s11606-018-4758-2.

23. Huang HK, Peng CC, Lin SM, Munir KM, Chang RH, Wu BB, Liu PP, Hsu JY, Loh CH, Tu YK. Fracture Risks in Patients Treated With Different Oral Anticoagulants: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2021 Apr 6;10(7): e019618. doi: 10.1161/JAHA.120.019618

24. Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100–5. doi: 10.1093/jn/134.11.3100

25. Gast GC, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis. 2009 Sep;19(7):504–10. doi: 10.1016/j.numecd.2008.10.004

26. Chen HG, Sheng LT, Zhang YB, Cao AL, Lai YW, Kunutsor SK, Jiang L, Pan A. Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis. Eur J Nutr. 2019 Sep;58(6):2191–2205. doi: 10.1007/s00394-019-01998-3

27. Lees JS, Chapman FA, Witham MD, Jardine AG, Mark PB. Vitamin K status, supplementation and vascular disease: a systematic review and meta-analysis. Heart. 2019 Jun;105(12):938–945. doi: 10.1136/heartjnl-2018–313955

28. Verma H, Garg R. Effect of Vitamin K Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis. Endocr Metab Immune Disord Drug Targets. 2019;19(1):13–25. doi: 10.2174/1871530318666180703125007

29. Witham MD, Lees JS, White M, Band M, Bell S, Chantler DJ, Ford I, Fulton RL, Kennedy G, Littleford RC, McCrea IV, McGlynn D, Panarelli M, Ralston MR, Rutherford E, Severn A, Thomson N, Traynor JP, Struthers AD, Wetherall K, Mark PB. Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial. J Am Soc Nephrol. 2020 Oct;31(10):2434–2445. doi: 10.1681/ASN.2020020225.

30. Karamzad N, Maleki V, Carson-Chahhoud K, Azizi S, Sahebkar A, Gargari BP. A systematic review on the mechanisms of vitamin K effects on the complications of diabetes and pre-diabetes. Biofactors. 2020 Jan;46(1):21–37. doi: 10.1002/biof.1569

31. Choi HJ, Yu J, Choi H, An JH, Kim SW, Park KS, Jang HC, Kim SY, Shin CS. Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care. 2011 Sep;34(9): e147. doi: 10.2337/dc11–0551

32. Li Y, Chen JP, Duan L, Li S. Effect of vitamin K2 on type 2 diabetes mellitus: A review. Diabetes Res Clin Pract. 2018 Feb;136:39–51. doi: 10.1016/j.diabres.2017.11.020

33. Dam V, Dalmeijer GW, Vermeer C, Drummen NE, Knapen MH, van der Schouw YT, Beulens JW. Association Between Vitamin K and the Metabolic Syndrome: A 10-Year Follow-Up Study in Adults. J Clin Endocrinol Metab. 2015 Jun;100(6):2472–9. doi: 10.1210/jc.2014–4449

34. Pan Y, Jackson RT. Dietary phylloquinone intakes and metabolic syndrome in US young adults. J Am Coll Nutr. 2009 Aug;28(4):369–79. doi: 10.1080/07315724.2009.10718099

35. Beulens JW, van der A DL, Grobbee DE, Sluijs I, Spijkerman AM, van der Schouw YT. Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes Care. 2010 Aug;33(8):1699–705. doi: 10.2337/dc09–2302

36. Shahdadian F, Mohammadi H, Rouhani MH. Effect of Vitamin K Supplementation on Glycemic Control: A Systematic Review and Meta-Analysis of Clinical Trials. Horm Metab Res. 2018 Mar;50(3):227–235. doi: 10.1055/s-0044–100616

37. Karamzad N, Faraji E, Adeli S, Carson-Chahhoud K, Azizi S, Pourghassem Gargari B. Effects of MK-7 Supplementation on Glycemic Status, Anthropometric Indices and Lipid Profile in Patients with Type 2 Diabetes: A Randomized Controlled Trial. Diabetes Metab Syndr Obes. 2020 Jun 26;13:2239–2249. doi: 10.2147/DMSO.S253014

38. Rahimi Sakak F, Moslehi N, Niroomand M, Mirmiran P. Glycemic control improvement in individuals with type 2 diabetes with vitamin K2 supplementation: a randomized controlled trial. Eur J Nutr. 2021 Aug;60(5):2495–2506. doi: 10.1007/s00394-020-02419-6

39. Lai Y, Masatoshi H, Ma Y, Guo Y, Zhang B. Role of Vitamin K in Intestinal Health. Front Immunol. 2022 Jan 5;12:791565. doi: 10.3389/fimmu.2021.791565

40. Ganbat D, Jugder BE, Ganbat L, Tomoeda M, Dungubat E, Takahashi Y, Mori I, Shiomi T, Tomita Y. The Efficacy of Vitamin K, A Member Of Naphthoquinones in the Treatment of Cancer: A Systematic Review and Meta-Analysis. Curr Cancer Drug Targets. 2021;21(6):495–513. doi: 10.2174/1568009621999210120182834

41. Okamoto H. 2008. Vitamin K and rheumatoid arthritis: critical review. IUBMB Life.2008 Jun;60(6):355–61. doi: 10.1002/iub.41