MikroScore
Science-backed ingredient evidence
Strong Evidence Safety: Safe Study dose: 25 mg/day

Vitamin D3 + K2

Also known as: Cholecalciferol, Vitamin D, Menaquinon, MK-7, Vitamin K2

Summary Strong Evidence

Low vitamin D levels are common in northern climates. Supplementation is comparatively well studied in deficiency; K2 is often combined but has weaker standalone evidence.

EU Health Claims: Approved

EFSA has approved extensive claims for vitamin D: normal immune function, bone, muscle, teeth, and calcium absorption. For vitamin K2 (menaquinone), claims are approved for normal blood clotting and bone maintenance.

AI Summary

Quick verdict

Low vitamin D levels are common in northern climates. Supplementation is comparatively well studied in deficiency; K2 is often combined but has weaker standalone evidence.

What the evidence supports

For vitamin D3, hundreds of RCTs and EFSA-approved claims exist (bone, immune function, muscles). The VITAL trial (n=25,871) and D-HEALTH study provide solid human data.

What is NOT supported

Long-term safety and rare adverse effects in humans remain insufficiently studied.

EU/EFSA status

Approved. EFSA has approved extensive claims for vitamin D: normal immune function, bone, muscle, teeth, an…

Safety

Safe

This AI summary is generated from the structured data on this page.

Why D3 + K2 Together?

Vitamin D3 promotes intestinal calcium absorption — one of its most established effects. Vitamin K2 (as MK-7) is proposed to direct absorbed calcium into bone rather than vessel walls. The mechanism: K2 activates osteocalcin (for bone mineralisation) and matrix Gla protein (inhibits vascular calcification), both dependent on carboxylation by vitamin K.

The combination is biologically plausible and widely marketed. Important context: the evidence base for D3 is substantially stronger and broader than for K2. Those supplementing K2 should understand that its effects are well argued but not equivalent in robustness to D3 data.

Vitamin D3: Why It Matters

Deficiency is the rule, not the exception

In northern and central Europe, estimates suggest 40–60% of the population have insufficient 25(OH)D levels (<50 nmol/L) in winter. Risk factors include darker skin, older age, limited outdoor activity, and obesity. This makes vitamin D one of the few supplements where targeted supplementation in confirmed deficiency is clearly indicated.

What vitamin D3 does in the body

Vitamin D3 (cholecalciferol) is biochemically not a vitamin but a prohormone. Via the liver it is converted to 25(OH)D (calcidiol), and in the kidneys to active 1,25(OH)₂D (calcitriol). Calcitriol binds to the vitamin D receptor (VDR), expressed in nearly all cells — hence the broad physiological effects:

  • Calcium and phosphate absorption (EFSA-approved)
  • Bone and tooth mineralisation (EFSA-approved)
  • Normal immune function (EFSA-approved): VDR is expressed on immune cells; active vitamin D modulates innate and adaptive immune responses
  • Muscle strength (EFSA-approved): improvements in muscle strength in older individuals with deficiency have been shown in RCTs

Evidence on broader effects

The VITAL trial (n=25,871, 5.3-year follow-up) is the largest RCT to date. Result: 2,000 IU/day reduced cancer mortality by 25% in a subgroup analysis (not the total population), but had no clear effect on heart attack frequency overall. The D-HEALTH study (n=421, 60,000 IU/month) showed positive effects on glucose metabolism and blood pressure.

Important: These benefits were observed primarily in people with deficiency or low baseline levels. In those with already adequate levels (25(OH)D >75 nmol/L), the additional benefit is much more uncertain.

Vitamin K2: The Evidence

K2 exists in two relevant sub-forms:

  • MK-4 (short half-life <4 h): requires 3× daily dosing; found mainly in animal products
  • MK-7 (half-life ~70 h): once daily is sufficient; found mainly in natto (fermented soy); most bioavailable form for supplementation

What the studies show

The Rotterdam cohort (n=4,807) showed a 41% reduction in heart attack risk with the highest K2 intake — a striking result, but an observational study. RCTs on vascular calcification exist but are smaller and shorter (often 3 years). A meta-analysis shows consistent reduction in calcification progression with K2, but the absolute effect size remains unclear.

For bone density and fracture risk: EFSA has approved K2 claims based on bone protein dependence on K. RCTs with MK-7 show effects on bone turnover markers (osteocalcin carboxylation), but clinical significance for fracture risk is still being investigated.

Dosage and Practical Recommendations

Vitamin D3:

  • Deficiency correction: 1,000–2,000 IU/day is generally sufficient for normalisation
  • Supplementation without confirmed deficiency: 800–1,000 IU/day (when sun exposure is limited)
  • Do not self-dose above 4,000 IU/day without blood monitoring — vitamin D is fat-soluble and accumulates
  • Taking with a fat-containing meal improves absorption by ~30–50%

Vitamin K2:

  • Typical RCT doses: 90–360 µg MK-7/day
  • With a diet rich in vegetables and fermented products, supplementation is not automatically necessary

EFSA Status

Vitamin D has one of the broadest EFSA authorisations of any supplement. Approved claims include: normal immune function, normal bone and teeth, normal muscle function, normal calcium absorption.

Vitamin K2: EFSA has approved claims for normal blood clotting and bone maintenance.

Safety and Important Warnings

Vitamin D3 is very well tolerated at normal doses (≤2,000 IU/day). Toxicity occurs almost exclusively with very high sustained intake (>10,000 IU/day over months), with hypercalcaemia as the main risk.

Vitamin K2 and anticoagulants: Anyone taking vitamin K antagonists (warfarin, acenocoumarol, phenprocoumon) must not supplement vitamin K2 without medical supervision. K2 directly influences the coagulation cascade and can substantially alter the efficacy of these medications.

Honest Limitations

  • Supplementation at normal levels: At 25(OH)D levels >75 nmol/L, the additional benefit of D3 supplementation is very uncertain. Many positive studies enrolled individuals with low baseline levels.
  • K2 long-term data: Most K2 RCTs run <3 years. Fracture risk endpoints have been directly measured in few studies.
  • Combination products: Whether D3+K2 combined works better than D3 alone has not been directly compared in large RCTs.
  • Product quality: In vitamin D softgels, actual dosing can vary substantially by formulation and storage conditions.

Key Studies

Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer (VITAL)

Manson JE et al. (2019)

RCT, n=25,871: 2,000 IU vitamin D/day reduced cancer mortality by 25% in a subgroup analysis. No significant effect on cardiovascular events in the overall population.

PubMed PMID 30415637

Vitamin D Deficiency

Holick MF (2007)

Landmark review in NEJM: vitamin D is synthesised in the skin by UV-B; 25(OH)D &lt;50 nmol/L is considered deficiency. An estimated 1 billion people worldwide are inadequately nourished.

PubMed PMID 17634462

Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study

Geleijnse JM et al. (2004)

Prospective cohort, n=4,807: higher K2 intake (MK-7 to MK-9) was associated with 41% lower heart attack risk. K1 intake showed no comparable effect.

PubMed PMID 15514282

Vitamin K2 and Vascular Calcification: A Systematic Review

Dalmeijer GW et al. (2012)

Systematic review: observational studies consistently show an association between high K2 intake and less vascular calcification; RCT evidence is still limited.

PubMed PMID 22516723
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Editorial notice: For most ingredients described here, no health claims are approved in the EU (Regulation (EC) 1924/2006). Evidence levels are editorial assessments of research quality — not health promises. This content is not a substitute for medical advice and does not constitute a recommendation to treat, alleviate, or prevent any disease.