Vitamin D3 and K2: Why the Two Are Formulated Together
Vitamin D and vitamin K are two separate fat-soluble vitamins with two separate histories. They arrived on the same label relatively recently, and the reason is not marketing convenience.
They sit at either end of the same process.
Vitamin D: the UK problem
Vitamin D is produced in skin exposed to UVB radiation. It is then hydroxylated in the liver to 25-hydroxyvitamin D, the form measured in blood tests, and again in the kidney to the active hormone.
The UK's latitude creates a well-documented seasonal gap. Between roughly October and March, UVB does not reach the ground at an angle sufficient for cutaneous synthesis anywhere in the UK. Dietary sources, principally oily fish, egg yolk and fortified foods, contribute relatively little.
This is why the position here is unusually specific for a nutrient. Following the SACN review in 2016, UK guidance recommends that everyone consider a daily supplement containing 10 micrograms of vitamin D during autumn and winter, with year-round supplementation advised for people with limited sun exposure and those with darker skin.
Cholecalciferol, vitamin D3, is the form produced in human skin and is generally the form used in supplements. It has traditionally been derived from lanolin. D3V is a vegan-source cholecalciferol, which matters for anyone who has previously had to accept vitamin D2 as the plant-friendly option despite its less favourable profile in comparative studies.
Vitamin K2: the less familiar half
Vitamin K exists in two main families. K1, phylloquinone, comes from green leafy vegetables and is the form associated with the coagulation cascade. K2, the menaquinones, comes from fermented foods and some animal products, and is designated by the length of its side chain: MK-4, MK-7 and so on.
Vitamin K's biochemical function is specific and elegant. It acts as a cofactor for gamma-glutamyl carboxylase, the enzyme that carboxylates certain proteins so that they can bind calcium. Osteocalcin, in bone, and matrix Gla protein are among those vitamin K dependent proteins.
MK-7 is the form most commonly used in supplements, and the reason is pharmacokinetic. Sato and colleagues compared MK-4 and MK-7 in healthy volunteers and found that MK-7 was detectable in serum for substantially longer, consistent with a much longer half-life. MK-4 given orally at nutritional doses was not well reflected in serum at all.
VitaMK7 is a branded menaquinone-7 produced by fermentation, specified as all-trans. That specification is not cosmetic. MK-7 exists as cis and trans isomers, and the biological activity is associated with the trans form, so a defined all-trans material is a genuine quality distinction rather than a label ornament.
Why they are paired
The mechanistic reasoning is straightforward and worth stating carefully, because it is easy to overstate.
Vitamin D contributes to the normal absorption and utilisation of calcium. Vitamin K is the cofactor required to carboxylate the proteins that handle calcium once it is in circulation. Formulating them together follows the logic of the pathway.
That is a description of two established nutrient functions sitting adjacent to each other. It is not a claim about what the combination achieves, and no such combination claim is authorised on the GB register.
Knapen and colleagues have published the most cited MK-7 intervention work, including a three-year study in postmenopausal women examining bone measures and a separate study examining arterial stiffness. These are the reference points for anyone wanting to read the primary literature, and their limitations, principally population specificity, are noted in the papers themselves.
Delivery
This is a liquid liposomal formulation, using Lipoid phospholipids with the vitamins held in a phospholipid structure.
Both D3 and K2 are fat soluble, which means their absorption is normally dependent on dietary fat and bile. A phospholipid delivery system presents them already associated with lipid, which is the physical state the absorption pathway handles.
Ingredient Health Facts
Vitamin D
Vitamin D contributes to normal absorption and utilisation of calcium and phosphorus. Vitamin D contributes to normal blood calcium levels. Vitamin D contributes to the maintenance of normal bones. Vitamin D contributes to the maintenance of normal muscle function. Vitamin D contributes to the maintenance of normal teeth. Vitamin D contributes to the normal function of the immune system. Vitamin D has a role in the process of cell division.
Vitamin K
Vitamin K contributes to normal blood clotting. Vitamin K contributes to the maintenance of normal bones.
Dose and practical considerations
One millilitre provides 25 micrograms of vitamin D3, which is 500 percent of the Nutrient Reference Value, and 45 micrograms of vitamin K2, which is 60 percent.
The UK safe upper level for adults, per SACN, is 100 micrograms of vitamin D per day from all sources. A 25 microgram serving sits comfortably within that, though anyone taking multiple products containing vitamin D should total them.
The important interaction. Vitamin K antagonist anticoagulants, warfarin being the common example, work by interfering with vitamin K recycling. Anyone taking warfarin or a similar anticoagulant must speak to their GP or anticoagulation clinic before taking any vitamin K supplement. This warning should appear on the PDP as well as here.
Anyone with kidney disease, hyperparathyroidism, sarcoidosis or a history of high blood calcium should seek clinical advice before supplementing vitamin D.
Common questions
Why do D3 and K2 appear together? Vitamin D contributes to calcium absorption and utilisation. Vitamin K is the cofactor for the enzyme that carboxylates calcium-binding proteins. The two functions sit adjacent in the same pathway.
What is the difference between MK-4 and MK-7? Side chain length, and consequently half-life. MK-7 remains detectable in serum considerably longer after an oral dose.
Is vitamin D2 as good as D3? Comparative studies have generally found D3 more effective at raising and maintaining serum 25-hydroxyvitamin D. D3V provides D3 from a vegan source.
Do I need vitamin D in summer? UK guidance suggests most people can obtain enough from sunlight between late March and September, with supplementation advised in autumn and winter. Year-round supplementation is advised for some groups.
Can I take this with warfarin? Not without speaking to your GP or anticoagulation clinic first. Vitamin K directly affects how these medicines work.
References
- Scientific Advisory Committee on Nutrition. Vitamin D and Health. UK Government, 2016.
- NHS. Vitamins and minerals: Vitamin D. nhs.uk.
- Holick MF. Vitamin D deficiency. New England Journal of Medicine. 2007;357(3):266-281.
- Sato T, Schurgers LJ, Uenishi K. Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutrition Journal. 2012;11:93. doi:10.1186/1475-2891-11-93
- Knapen MHJ, Drummen NE, Smit E, Vermeer C, Theuwissen E. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporosis International. 2013;24(9):2499-2507.
- Knapen MHJ, Braam LAJLM, Drummen NE, et al. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. Thrombosis and Haemostasis. 2015;113(5):1135-1144.
- Tripkovic L, Lambert H, Hart K, et al. Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. American Journal of Clinical Nutrition. 2012;95(6):1357-1364.
- Manson JE, Cook NR, Lee IM, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease (VITAL). New England Journal of Medicine. 2019;380(1):33-44.
- Great Britain Nutrition and Health Claims Register. Department of Health and Social Care, gov.uk.
Food supplements are not a substitute for a varied and balanced diet and a healthy lifestyle.