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Vitamin K2D3 - The perfect pair for each other

Strong immunity is important as it can save and improve lives. And it depends on nutrition. Micronutrients including vitamins are essential for the body to function at its best. Vitamin K2 and D3 are fat-soluble vitamins that are widely known to support general immunity and perform important roles. Vitamin K2 and D3 have more recently gained the attention of the medical and research community.

Vitamin D – the sunshine vitamin

Vitamin D has a significant role in the immune system, without vitamin D, the system can’t be activated. Vitamin D also known as the “antibiotic vitamin” due to its anti-inflammatory, immune-regulating effect. Our body T cells remain dormant and couldn’t fight infections without vitamin D. Vitamin D has shown to significantly reduced influenza and colds in a 3- year clinical study (1). Vitamin D supplementation reduced the risk of acute respiratory disease up to 70% as compared to those with low vitamin D output status (2).

Vitamin K2

Vitamin K1 and K2 do not have the same structure, so do their biological activities. Vitamin K2 has the role that is beyond just blood clotting, but also regulates other important metabolic processes, such as calcification and inflammation. Vitamin K1 is easily found in a balanced diet, which is not the case for Vitamin K2. Although there is little evidence on vitamin K2 in impacting immune system as compared to vitamin D3, vitamin K2 has a positive effect on inflammation, which could contribute to a healthy immune inflammatory response. Higher vitamin K has been associated with lower inflammation overall and lower concentration of pro-inflammatory biomarkers. Vitamin K2 can help to keep inflammation under control, and thus switching off inflammatory chemical mediators throughout the body (3).

Vitamin K2D3 combination

Both Vitamin K2 and D3 are involved in metabolizing and depositing calcium in order to strengthen bones and improve their health. Vitamin D3 absorb calcium from the food content and increase its concentration in the blood. To direct calcium to the bones and away from the arteries, Vitamin K2 will determine where to take calcium in the body. Vitamin K2 activates two key proteins, osteocalcin and matrix Gla protein, through a chemical reaction called carboxylation. Osteocalcin will deposit calcium on the teeth and bones to solidify them and increase their strength. Vitamin K2 also promote the calcification of bones by reducing calcification of soft tissues such as kidneys and synthesis matrix GLA protein (4). Vitamin K2 also reduce elastic fibre degradation, thrombosis and inflammation.

Vitamin K2 and D3, the perfect pair for immune system regulation and health. (Adapted from McComsey 2021)

During the immune response to an infection, Vitamin D is needed to downregulate the expression of ACE2 receptors, thus reduce the opportunity of the virus to enter cells. Both vitamins K2D3 work synergistically to downregulate NK-kB signalling and the secretion of cytokines. This could avoid the dangerous cytokine storm and vitamin K2 on the other hand could prevent thrombosis and vascular damage, that play a role in COVID progresses.

Dofferhoff and co have measured the blood concentration of uncarboxylated matrix Gla protein in Covid-19 patients and found that the levels were higher compared to control patients, suggesting Covid-19 patients had lower levels of vitamin K2 (5). Another study also has shown the low vitamin K status was a predictor of mortality in hospitalized Covid-19 patients. Randomized clinical trials will be conducted to determine if vitamin K2 supplementation in Covid-19 patients can change the course of the disease and prevent death or long-term consequences. In a computational molecular dynamics (MD) simulation study, it found that vitamin K2 can bound to ACE2 binding domains and reduce the infectivity of the SARS-CoV-2 spike protein. Thus, for every doubling of uncarboxylated matrix Gla protein, there was a doubling of risk for Covid-19 severity (6). On the other hand, research shows low vitamin D levels appear to promote Covid-19 infections, and related hospitalizations and deaths. Vitamin D modulated thousands of genes and many aspects of immune function, both innate and adaptive, and thus vitamin D seems to be critical piece of Covid-19 and immunity puzzle (7).

Vitamin D and K2 support immune system’s response to Covid-19

(Adapted from McComsey 2021)

Supplementation with vitamin K2D3 represents an inexpensive and simple to use intervention that could help the immune system downregulate receptors that the virus needs and help prevent thrombosis and soft tissue calcification. Prevention is always better than cure. By focusing on prevention, we will be able to support our health in so many ways.



  1. Aloia JF, Li-Ng M. Re: epidemic influenza and vitamin D. Epidemiol Infect. 2007 Oct;135(7):1095-6; author reply 1097-8. doi: 10.1017/S0950268807008308. PMID: 17352842; PMCID: PMC2870688.

  2. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Griffiths CJ, Janssens W, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S Jr, Stelmach I, Kumar GT, Urashima M, Camargo CA Jr. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017 Feb 15;356:i6583. doi: 10.1136/bmj.i6583. PMID: 28202713; PMCID: PMC5310969.

  3. Harshman SG, Shea MK. The Role of Vitamin K in Chronic Aging Diseases: Inflammation, Cardiovascular Disease, and Osteoarthritis. Curr Nutr Rep. 2016 Jun;5(2):90-98. doi: 10.1007/s13668-016-0162-x. Epub 2016 Mar 31. PMID: 27648390; PMCID: PMC5026413.

  4. Van Ballegooijen AJ, Pilz S, Tomaschitz A, Grübler MR, Verheyen N. The Synergistic Interplay between Vitamins D and K for Bone and Cardiovascular Health: A Narrative Review. Int J Endocrinol. 2017;2017:7454376. doi: 10.1155/2017/7454376. Epub 2017 Sep 12. PMID: 29138634; PMCID: PMC5613455.

  5. Linneberg, A.; Kampmann, F.B.; Israelsen, S.B.; Andersen, L.R.; Jørgensen, H.L.; Sandholt, H.; Jørgensen, N.R.; Thysen, S.M.; Benfield, T. The Association of Low Vitamin K Status with Mortality in a Cohort of 138 Hospitalized Patients with COVID-19. Nutrients 2021, 13, 1985.

  6. Shoemark DK, Colenso CK, Toelzer C, Gupta K, Sessions RB, Davidson AD, Berger I, Schaffitzel C, Spencer J, Mulholland AJ. Molecular Simulations suggest Vitamins, Retinoids and Steroids as Ligands of the Free Fatty Acid Pocket of the SARS-CoV-2 Spike Protein*. Angew Chem Int Ed Engl. 2021 Mar 22;60(13):7098-7110. doi: 10.1002/anie.202015639. Epub 2021 Feb 22. PMID: 33469977; PMCID: PMC8013358.

  7. Davies G, Garami AR, Byers J. Evidence Supports a Causal Role for Vitamin D Status in Global COVID-19 Outcomes, 2020. medRxiv 2020.05.01.20087965; doi:

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