Introduction
Vitamins D3 and K2 appear together on more supplement labels every year, and almost nobody explains why. Shoppers see the pairing, assume the science is settled, and buy on that assumption. The mechanism behind the pairing is real and well described. The clinical evidence for the pair is thinner than the marketing suggests. This article covers what each nutrient is and why the two are combined. It also covers what the trials measured, how much people take, and what the safety record shows. You will finish it able to decide whether the combination belongs in your own routine, and at what amount.
What Are Vitamins D3 and K2? A Closer Look
Vitamin D3 is cholecalciferol, the form your skin makes when ultraviolet B light strikes it. It is also the form used in most supplements and in fortified foods. Vitamin D3 is fat soluble, which means it is absorbed alongside dietary fat and stored in body tissue. A meta-analysis of randomized controlled trials in adults found that vitamin D3 raised serum 25-hydroxyvitamin D more than vitamin D2 did (Tripkovic et al., 2012).
Vitamin K2 is not one molecule but a family called menaquinones. Each member carries a side chain of a different length, and the number in its name gives that length. Menaquinone-7, written MK-7, is the long-chain form produced by bacterial fermentation. The richest food source is natto, a fermented soybean dish supplying 850 micrograms of MK-7 in a three-ounce serving (Office of Dietary Supplements, n.d.-b).
Vitamin K1, called phylloquinone, is the form found in leafy greens and a few vegetable oils. Booth and Suttie pooled eleven human intake studies of phylloquinone. Mean intake was nearly 80 micrograms daily in young adults and 150 micrograms in older adults (Booth & Suttie, 1998). That same review reported that menaquinones absorbed from the diet or the gut appear to supply only a minor part of the daily requirement. That gap between K1 and K2 is the reason a supplement would bother with a menaquinone at all.
Both nutrients are fat soluble and both are part of calcium metabolism, which is why they are paired together. A narrative review of animal and human work described the two vitamins as jointly central to that system (van Ballegooijen et al., 2017). How the body routes and holds calcium is a subject I keep returning to. I cover it in my article on IP6 and again in my article on calcium silicate clay. The body can make vitamin D3 if the skin is exposed to enough sunlight, but it cannot make enough vitamin K2 in useful amounts.
How common low vitamin D status is depends entirely on where the line is drawn. Using 30 nanograms per milliliter as the line, one analysis of 8,351 United States adults put the prevalence at 74 percent (Kim et al., 2008). A second analysis of 13,369 participants from those same survey years found only 23 percent at or above that cut point (Ginde et al., 2009). Using the lower Institute of Medicine cut points instead, 5.0 percent of 16,180 Americans were at risk of deficiency (Herrick et al., 2019). Both sets of numbers are real, and what separates them is the threshold rather than the population. A standardized reanalysis of NHANES later found United States concentrations stable from 1988 to 2006 and rising modestly after that (Schleicher et al., 2016).
Why Vitamins D3 and K2 Are Taken Together
The honest starting point is that the mechanism is better established than the clinical result. Vitamin D and vitamin K interact through a specific and well-mapped biochemical step. Whether adding vitamin K2 to vitamin D3 changes an outcome a healthy adult would notice has not been settled by trial. I will describe the mechanism first and then say exactly where the evidence stops.
Vitamin K is a cofactor in the production of three groups of proteins, and the location of each group matters. Clotting factors are made in the liver and osteocalcin is made in bone. Matrix Gla protein is made in cartilage and in the vessel wall (Schurgers et al., 2007). Each of those proteins must be carboxylated to work, and vitamin K is what supplies the carboxylation. Without enough vitamin K the proteins are still produced, but they remain uncarboxylated and inactive.
Vitamin D enters that picture one step upstream. A narrative review of animal and human studies described vitamin D as promoting the production of vitamin K-dependent proteins. Those proteins then require vitamin K for carboxylation in order to function (van Ballegooijen et al., 2017). Raising vitamin D therefore raises the demand for vitamin K rather than meeting it. That single sentence is the entire argument for putting vitamin D3 and K2 in one tablet.
Reading that same review through to its conclusion is where the certainty on page one falls apart. Its authors reported that most clinical trials of joint supplementation studied bone outcomes in postmenopausal women. They also reported that few intervention trials examined vascular outcomes at all. Their conclusion was that combined supplementation might be more effective than either nutrient alone, stated as a possibility rather than as a demonstrated result. I can find no trial testing the pair against vitamin D3 alone in healthy adults on a general health endpoint.
I am selling this combination, and I am telling you that its central claim is mechanistic. That is a deliberate choice. A reader who buys on a mechanism knows exactly what they bought, and a reader who buys on an implied trial result does not.
Benefits of D3 and K2 Backed by Science
The benefits of D3 and K2 have been measured, and the measurements are narrower than the category implies. Nearly the entire vitamin K2 trial record in this area rests on one cohort of Dutch women, studied twice. The vitamin D3 record is far larger and far more negative than most supplement pages admit. Both deserve to be read as they actually are.
One three-year randomized trial gave 180 micrograms of MK-7 daily or placebo to 244 healthy postmenopausal women. MK-7 improved vitamin K status in those women and slowed the age-related decline in bone mineral density. The effect appeared at the lumbar spine and the femoral neck (Knapen et al., 2013). The same trial found no such effect at the total hip. Its authors wrote that extending the result to other groups, including children and men, needs further investigation.
Those same 244 healthy postmenopausal women were also assessed for arterial stiffness across the three years. Carotid-femoral pulse wave velocity and the stiffness index decreased in the MK-7 group. Desphospho-uncarboxylated matrix Gla protein fell by half against placebo in those women (Knapen et al., 2015). Markers of acute-phase response and endothelial function did not change at all in them. The improvement concentrated in the women whose baseline stiffness was above the group median. Because that population is postmenopausal women, the pattern connects to what I set out in brain health for women over 50.
Vitamin D3 has been tested at a scale vitamin K2 has never approached, and the large trials have mostly returned nothing. The VITAL trial randomized 25,871 United States adults to 2,000 IU of vitamin D3 daily or placebo. Participants were men aged 50 and older and women aged 55 and older, followed a median of 5.3 years. Neither invasive cancer of any type nor major cardiovascular events occurred less often in the vitamin D group (Manson et al., 2019). The D-Health trial randomized 21,315 Australian adults aged 60 to 84 to monthly vitamin D3 or placebo. Its hazard ratio for major cardiovascular events was 0.91, with a confidence interval consistent with no effect (Thompson et al., 2023).
The cognitive question matters most to my readers, and it has an answer they will not enjoy. Two ancillary studies inside VITAL followed 3,424 adults aged 60 and older by telephone and 794 more in person. The pooled difference in annual rate of cognitive decline was 0.01 between vitamin D3 and placebo. That difference did not reach significance (Kang et al., 2021). Vitamin D3 did not slow cognitive decline in those community-dwelling older adults over two to three years. I report that plainly for the same reason I report every other null result in best supplements for memory loss.
Vitamins D3 and K2 Dosage: How Much, and What Is on My Label
Any honest vitamin D3 and K2 dosage discussion starts with the official intake figures rather than with a product. The Recommended Dietary Allowance for vitamin D is 15 micrograms, or 600 IU, for adults through age 70. Above that age it rises to 20 micrograms, or 800 IU. The Tolerable Upper Intake Level for adults is 100 micrograms, or 4,000 IU (Office of Dietary Supplements, n.d.-a). Vitamin K carries an Adequate Intake of 120 micrograms for men and 90 micrograms for women. No upper limit has been set for it (Office of Dietary Supplements, n.d.-b).
That vitamin K figure carries a caveat which changes how you should read it. It was built around blood clotting, which is the liver’s use of the vitamin. It was not built around carboxylation of osteocalcin and matrix Gla protein elsewhere in the body. Healthy volunteers given MK-7 showed more complete osteocalcin carboxylation than the same volunteers given vitamin K1 (Schurgers et al., 2007). An intake adequate for clotting is therefore not automatically adequate for the vitamin’s other jobs.
Form matters here at least as much as amount does. Healthy Japanese women given a single 420 microgram dose of MK-7 reached peak serum levels at six hours. The compound was still detectable in them at 48 hours. The same women given an identical dose of MK-4 showed no detectable serum MK-4 at any time point. Seven days of 60 micrograms daily did not change that result (Sato et al., 2012). In healthy volunteers, MK-7 also accumulated to serum levels seven to eight times higher than vitamin K1 during prolonged intake. The reason is its far longer half-life (Schurgers et al., 2007). Where each common MK-7 label amount came from, and what the trials behind it measured, is covered in my article on vitamin K2 MK-7.
The 2024 Endocrine Society clinical practice guideline contains the sentence most vitamin D sellers skip. Its panel suggested against empiric vitamin D supplementation above the Dietary Reference Intake in healthy adults younger than 75 (Demay et al., 2024). The same panel suggested against routine 25-hydroxyvitamin D testing in the populations it considered. It also found no clear evidence defining an optimal target level. For nonpregnant people older than 50 who do have an indication, it preferred daily dosing over intermittent high doses. Every prevalence figure earlier in this article therefore rests on a threshold that panel declined to endorse.
One chewable tablet of my own formula supplies 3,000 IU of vitamin D3 and 100 micrograms of vitamin K2 as MK-7 from natto. That vitamin D3 amount sits above the Recommended Dietary Allowance and below the Tolerable Upper Intake Level. The MK-7 amount sits below the 180 micrograms used in the two three-year trials, so I will not borrow their results for my label. Taking it with a meal is sensible enough. In one trial, 62 healthy older adults took a monthly vitamin D3 dose with no meal, a low-fat meal, or a high-fat meal. Absorption differed between those groups, and their 90-day 25-hydroxyvitamin D response did not (Dawson-Hughes et al., 2013). Matching a label to its trials is harder still on my Curcumin capsule, as I show in tetrahydrocurcumin vs curcumin.
Vitamins D3 and K2 Side Effects: What the Safety Record Shows
The most important of the vitamin D3 and K2 side effects has nothing to do with vitamin D. Authors of the MK-7 pharmacokinetic work in healthy volunteers issued a direct warning. Preparations supplying 50 micrograms per day or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way (Schurgers et al., 2007). My own tablet supplies 100 micrograms, which is double that threshold. Anyone taking warfarin or a similar vitamin K antagonist should speak with the prescribing clinician before starting any vitamin K2 product, mine included.
The NIH Office of Dietary Supplements makes the same point in different words. People taking warfarin need a consistent vitamin K intake from food and supplements. Sudden changes in either direction can shift the anticoagulant effect (Office of Dietary Supplements, n.d.-b). The issue is stability rather than quantity, since the drug is titrated against a person’s usual intake. No Tolerable Upper Intake Level has been set for vitamin K. The Food and Nutrition Board cited its low potential for toxicity as the reason.
Vitamin D carries the opposite kind of risk, which is the assumption that a bigger number must be a better one. A three-year trial randomized 311 community-dwelling healthy adults aged 55 to 70 to 400, 4,000, or 10,000 IU of vitamin D3 daily. Radial volumetric bone mineral density ended lower in the 4,000 IU group than in the 400 IU group. It ended lower still in the 10,000 IU group (Burt et al., 2019). Bone strength did not differ between the three groups. The authors concluded that their findings do not support the benefit of high-dose vitamin D for bone health.
Some people should not take supplemental vitamin D3 without medical supervision at all. D-Health excluded volunteers reporting hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia, or sarcoidosis (Thompson et al., 2023). That exclusion list is a reasonable guide for who should ask a physician first. Stacking several products that each contain vitamin D is the ordinary way a person crosses the upper limit without noticing. Anyone who is pregnant or nursing, or taking prescription medication, should check with a qualified clinician.
Should You Take D3 and K2 Together? My Own Answer
Should you take D3 and K2 together is a question I can only answer conditionally. If you already supplement vitamin D3, adding vitamin K2 has a mechanistic rationale, subject to the anticoagulant warning above. If you get regular midday sun on bare skin and eat natto several times a week, the case is much weaker. Food and sunlight come first, and no tablet changes that order.
Nearly all supplemental vitamin D3 on the market is extracted from lanolin, which is the grease in sheep wool. I have eaten a whole-food, plant-based diet since 1999, so a lanolin-derived tablet was never going to be something I would take myself. My formula uses vegan vitamin D3 from lichen instead. No trial has compared lichen-derived vitamin D3 with lanolin-derived vitamin D3 in humans. I therefore make no absorption claim about vegan vitamin D3 as a source, and say only that it is the one I chose.
The vitamin K2 in that tablet is MK-7 from natto, which is the form the pharmacokinetic work actually supports (Sato et al., 2012). The tablet is built with sunflower lecithin as its phospholipid carrier, the same sunflower lecithin I write about elsewhere, alongside citric acid. That lecithin is not only a carrier. Both actives are encapsulated inside it as a liposome, which is a shell of phospholipid like the one forming a cell membrane. My manufacturing partner builds that liposome as a dry powder under a patent-pending process, and the powder is then pressed into the chewable tablet. I weigh liposomal delivery in capsule form against its human trials in liposomal curcumin.
A 2022 study compared liposomal vitamin D3 against an oily formulation in human participants (Dałek et al., 2022). The report does not state how many participants took part. Plasma calcidiol rose rapidly on the liposomal version and did not rise on the oily one, most markedly in severely deficient participants. That preparation was a liquid rather than a dry powder, and it was not my formula. No trial has tested this specific tablet against a conventional tablet of the same two nutrients. I describe the technology and not the result. I make no absorption claim for my own tablet, and anyone quoting you a multiple without a head-to-head trial is quoting their marketing.
People ask me why Daily Brain Care does not simply contain vitamin D3 and K2. The honest reason is that these two nutrients are dose sensitive and personal. Sun exposure, latitude, season, skin tone, body weight, and medications all bear on the right amount. Building a fixed amount of each into a whole-food polysaccharide formula would force one number on everybody. That runs against how I think about formulation at Dr Lewis Nutrition®.
What I do myself is keep them separate and adjust them separately. I take Daily Brain Care every day at a fixed serving. Vitamins D3 and K2 are the part of the routine I adjust, with the season and with my bloodwork. That same logic runs through what I have written about healthy aging. Diet, training, and sleep do the heavy lifting, and a tablet is the last few percent. Decades of intense drug-free exercise training taught me which inputs actually compound, and none of them arrive in a bottle.
Conclusion
Vitamins D3 and K2 belong together for a reason that is biochemical rather than promotional. Vitamin D raises the body’s production of proteins that vitamin K must then activate. The trial evidence for the pair is real but narrow, and the large vitamin D3 trials have mostly returned null results. Knowing all of that, you can take the combination or skip it with your eyes open. If you want the pairing in a vegan, lichen-derived and natto-derived form, order our D3+K2 today.
Frequently Asked Questions
What are vitamins D3 and K2?
Vitamin D3 is cholecalciferol, the form of vitamin D that your skin makes from ultraviolet B light. It is also the form used in most supplements. Vitamin K2 is a family of menaquinones, of which MK-7 from fermented foods such as natto is the long-chain member. Both are fat-soluble vitamins that sit inside calcium metabolism.
What do D3 and K2 do?
Vitamin D promotes the production of vitamin K-dependent proteins, including osteocalcin in bone and matrix Gla protein in the vessel wall. Vitamin K then carboxylates those proteins, which is the step that switches them on. Neither nutrient completes that sequence by itself.
What are vitamins D3 and K2 good for?
Researchers have studied MK-7 for its role in bone mineral density and arterial elasticity in healthy postmenopausal women. They have studied vitamin D3 across very large trials with mostly null results. The pairing itself rests on a described mechanism rather than on a head-to-head trial. I state that limit rather than working around it.
How much D3 and K2 should you take?
The Recommended Dietary Allowance for vitamin D is 600 IU through age 70 and 800 IU above it. The adult upper limit is 4,000 IU. Vitamin K has an Adequate Intake of 120 micrograms for men and 90 micrograms for women. My own tablet supplies 3,000 IU of vitamin D3 and 100 micrograms of MK-7. Your clinician is the right person to help you set your own amount.
Are D3 and K2 bad for you?
Anyone taking warfarin or another vitamin K antagonist should talk to the prescribing clinician first. MK-7 at 50 micrograms daily or more can interfere with that treatment. High vitamin D intake is its own issue. A three-year trial in healthy adults found lower radial bone density on 4,000 and 10,000 IU daily than on 400 IU. Pregnancy, nursing, and prescription medication all warrant a conversation with a qualified clinician.
References
Booth, S. L., & Suttie, J. W. (1998). Dietary intake and adequacy of vitamin K. The Journal of Nutrition, 128(5), 785–788. https://doi.org/10.1093/jn/128.5.785
Burt, L. A., Billington, E. O., Rose, M. S., Raymond, D. A., Hanley, D. A., & Boyd, S. K. (2019). Effect of high-dose vitamin D supplementation on volumetric bone density and bone strength: A randomized clinical trial. JAMA, 322(8), 736–745. https://doi.org/10.1001/jama.2019.11889
Dałek, P., Drabik, D., Wołczańska, H., Foryś, A., Jagas, M., Jędruchniewicz, N., Przybyło, M., Witkiewicz, W., & Langner, M. (2022). Bioavailability by design - Vitamin D3 liposomal delivery vehicles. Nanomedicine: Nanotechnology, Biology and Medicine, 43, 102552. https://doi.org/10.1016/j.nano.2022.102552
Dawson-Hughes, B., Harris, S. S., Palermo, N. J., Ceglia, L., & Rasmussen, H. (2013). Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25-hydroxyvitamin D response to supplementation. Journal of Bone and Mineral Research, 28(8), 1778–1783. https://doi.org/10.1002/jbmr.1896
Demay, M. B., Pittas, A. G., Bikle, D. D., Diab, D. L., Kiely, M. E., Lazaretti-Castro, M., Lips, P., Mitchell, D. M., Murad, M. H., Powers, S., Rao, S. D., Scragg, R., Tayek, J. A., Valent, A. M., Walsh, J. M. E., & McCartney, C. R. (2024). Vitamin D for the prevention of disease: An Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism, 109(8), 1907–1947. https://doi.org/10.1210/clinem/dgae290
Ginde, A. A., Liu, M. C., & Camargo, C. A., Jr. (2009). Demographic differences and trends of vitamin D insufficiency in the US population, 1988–2004. Archives of Internal Medicine, 169(6), 626–632. https://doi.org/10.1001/archinternmed.2008.604
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Kang, J. H., Vyas, C. M., Okereke, O. I., Ogata, S., Albert, M., Lee, I.-M., D’Agostino, D., Buring, J. E., Cook, N. R., Grodstein, F., & Manson, J. E. (2021). Effect of vitamin D on cognitive decline: Results from two ancillary studies of the VITAL randomized trial. Scientific Reports, 11(1), 23253. https://doi.org/10.1038/s41598-021-02485-8
Kim, D. H., Sabour, S., Sagar, U. N., Adams, S., & Whellan, D. J. (2008). Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004). The American Journal of Cardiology, 102(11), 1540–1544. https://doi.org/10.1016/j.amjcard.2008.06.067
Knapen, M. H. J., Braam, L. A. J. L. M., Drummen, N. E., Bekers, O., Hoeks, A. P. G., & Vermeer, C. (2015). Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women: A double-blind randomised clinical trial. Thrombosis and Haemostasis, 113(5), 1135–1144. https://doi.org/10.1160/TH14-08-0675
Knapen, M. H. J., Drummen, N. E., Smit, E., Vermeer, C., & Theuwissen, E. (2013). Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporosis International, 24(9), 2499–2507. https://doi.org/10.1007/s00198-013-2325-6
Manson, J. E., Cook, N. R., Lee, I.-M., Christen, W., Bassuk, S. S., Mora, S., Gibson, H., Gordon, D., Copeland, T., D’Agostino, D., Friedenberg, G., Ridge, C., Bubes, V., Giovannucci, E. L., Willett, W. C., & Buring, J. E. (2019). Vitamin D supplements and prevention of cancer and cardiovascular disease. The New England Journal of Medicine, 380(1), 33–44. https://doi.org/10.1056/NEJMoa1809944
Office of Dietary Supplements. (n.d.-a). Vitamin D: Fact sheet for health professionals. National Institutes of Health. Retrieved September 13, 2026, from https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
Office of Dietary Supplements. (n.d.-b). Vitamin K: Fact sheet for health professionals. National Institutes of Health. Retrieved September 13, 2026, from https://ods.od.nih.gov/factsheets/VitaminK-HealthProfessional/
Sato, T., Schurgers, L. J., & Uenishi, K. (2012). Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutrition Journal, 11, 93. https://doi.org/10.1186/1475-2891-11-93
Schleicher, R. L., Sternberg, M. R., Lacher, D. A., Sempos, C. T., Looker, A. C., Durazo-Arvizu, R. A., Yetley, E. A., Chaudhary-Webb, M., Maw, K. L., Pfeiffer, C. M., & Johnson, C. L. (2016). The vitamin D status of the US population from 1988 to 2010 using standardized serum concentrations of 25-hydroxyvitamin D shows recent modest increases. The American Journal of Clinical Nutrition, 104(2), 454–461. https://doi.org/10.3945/ajcn.115.127985
Schurgers, L. J., Teunissen, K. J. F., Hamulyák, K., Knapen, M. H. J., Vik, H., & Vermeer, C. (2007). Vitamin K-containing dietary supplements: Comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood, 109(8), 3279–3283. https://doi.org/10.1182/blood-2006-08-040709
Thompson, B., Waterhouse, M., English, D. R., McLeod, D. S., Armstrong, B. K., Baxter, C., Duarte Romero, B., Ebeling, P. R., Hartel, G., Kimlin, M. G., Rahman, S. T., van der Pols, J. C., Venn, A. J., Webb, P. M., Whiteman, D. C., & Neale, R. E. (2023). Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial. BMJ, 381, e075230. https://doi.org/10.1136/bmj-2023-075230
Tripkovic, L., Lambert, H., Hart, K., Smith, C. P., Bucca, G., Penson, S., Chope, G., Hyppönen, E., Berry, J., Vieth, R., & Lanham-New, S. (2012). Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: A systematic review and meta-analysis. The American Journal of Clinical Nutrition, 95(6), 1357–1364. https://doi.org/10.3945/ajcn.111.031070
van Ballegooijen, A. J., Pilz, S., Tomaschitz, A., Grübler, M. R., & Verheyen, N. (2017). The synergistic interplay between vitamins D and K for bone and cardiovascular health: A narrative review. International Journal of Endocrinology, 2017, 7454376. https://doi.org/10.1155/2017/7454376
