Cholecalciferol + menaquinone-7 (D3+K2 combo)

Combined supplement: fat-soluble vitamins D3 and K2

ATC code: A11AX-D3K2(Cholecalciferol + menaquinone-7 (combo supplement))

Brand names: D3 K2 MK-7, Bone Strength

Updated 24 Sep 2026 · Methodology

Indications

Vitamin D deficiency

Adjunct

D3+K2 combo is marketed to correct vitamin D deficiency with an additional «protective» K2 effect on vascular calcification. In patients with confirmed D deficiency (25(OH)D <20 ng/mL) SEEN 2024 recommends regular cholecalciferol without K2 addition. There is no evidence base for D3+K2 advantage over D3 alone in D deficiency. In warfarin patients the combo is contraindicated: K2 significantly alters INR and requires anticoagulant dose review. If the combo was recommended «to enhance D3», discuss switching to regular cholecalciferol with your doctor.

Sources

ICD-10: E55.9 · ICD-11: 5B57

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Osteoporosis

Not recommended

D3+K2 combo is marketed for «bone health» and osteoporosis prevention. Small Japanese trials on K2 (menatetrenone) showed modest fracture reduction in postmenopausal women, but large European RCTs (NPHS, ECKO) did not confirm the effect. ESCEO and recommend in osteoporosis: calcium 1000–1200 mg/day, vitamin D3 800 IU/day, physical activity, and bisphosphonates, denosumab or anabolics in confirmed disease. Additional K2 is not in the recommendation. If the combo was recommended «for bones», discuss evidence-based therapy with your doctor based on DXA and FRAX. Important: vitamin K reduces the effect of warfarin and other vitamin K antagonists; patients on these anticoagulants, including those with a mechanical heart valve, must not take vitamin K supplements without medical agreement.

Sources

SEEN: Documento de posicionamiento sobre vitamina D (2024)

ICD-10: M81 · ICD-11: FB83.1

Anti-aging and longevity

Not recommended

D3+K2 combo is marketed as a «longevity formula» on the hypothesis of vitamin D effects on immunity, telomeres, methylation, plus K2 on vessels. Cochrane 2014 on vitamin D and mortality: no reduction in all-cause mortality in non-deficient people; in deficient patients the small positive effect is limited. VITAL 2019 found no mortality reduction from vitamin D in the general US population (unselected by deficiency). No large longevity RCTs exist for K2. If the combo was recommended «for slowing aging», consider seeking a second opinion. Important: vitamin K reduces the effect of warfarin and other vitamin K antagonists; patients on these anticoagulants, including those with a mechanical heart valve, must not take vitamin K supplements without medical agreement.

Sources

Cardiovascular prevention through supplements

Not recommended

D3+K2 combo is heavily marketed on the biohacker argument: «K2 directs calcium into bone and removes it from vessels, preventing atherosclerosis and cardiovascular events». The large VITAL 2019 RCT (25 871 participants, mean 5.3 years) found vitamin D without K2 did not reduce cardiovascular events or cancer vs placebo. Cochrane 2014 on vitamin D and all-cause mortality confirmed: vitamin D does not reduce mortality in non-deficient people. No large cardiovascular outcome RCTs exist for K2. 2021 does not recommend any vitamin-mineral complex for primary or secondary cardiac prevention in non-deficient people. If the combo was recommended «for heart and vessels», consider seeking a second opinion. Important: vitamin K reduces the effect of warfarin and other vitamin K antagonists; patients on these anticoagulants, including those with a mechanical heart valve, must not take vitamin K supplements without medical agreement.

Sources

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Combination of cholecalciferol (vitamin D3) and menaquinone-7 (one K2 form) in a single supplement formulation. Marketing hypothesis: D3 increases calcium absorption while K2 activates osteocalcin and matrix Gla protein – allegedly directing calcium into bone and preventing vascular deposition. Hypothesis is based on in vitro data and small observational studies; translation to clinically meaningful endpoints (fractures, cardiovascular events, mortality) is not confirmed in large RCTs. AEMPS does not register D3+K2 as a medicine; sold as a complemento alimenticio.

Safety

Contraindications

Warfarin or acenocoumarol therapy (K2 significantly alters INR; dose review needed)
Hypercalcaemia and hypercalciuria
Active tuberculosis or sarcoidosis (hypercalcaemia risk)
Severe renal impairment (eGFR <30)

Serious adverse effects

Vitamin D hypervitaminosis with hypercalcaemia and renal and vascular calcification at D3 doses >10 000 IU/day long-term
Bleeding or thromboembolic events in warfarin patients due to unpredictable K2 effect on INR
Nephrolithiasis when combined with calcium supplements and thiazides

Common adverse effects

Nausea, constipation
Dry mouth
Transient hypercalcaemia at high D3 doses

Pregnancy: can you take Cholecalciferol + menaquinone-7 (D3+K2 combo)?

D3+K2 combo has no AEMPS ficha técnica as a supplement; not studied in pregnancy RCTs. Daily intake in pregnancy: vitamin D 600 IU, vitamin K 90 μg. When indicated, separate preparations with titrated doses under medical supervision are preferred.

Breastfeeding: can you take Cholecalciferol + menaquinone-7 (D3+K2 combo)?

Compatible at physiological doses. In lactating women with confirmed D deficiency, regular cholecalciferol without K2 is preferred. K2 in the combo can alter INR in lactating women on warfarin.

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Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

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Frequently asked

What is Cholecalciferol + menaquinone-7 (D3+K2 combo) used for?

Cholecalciferol + menaquinone-7 (D3+K2 combo) is evaluated for the following indications with varying evidence strength: Vitamin D deficiency (evidence tier C), Osteoporosis (evidence tier D), Cardiovascular prevention through supplements (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Cholecalciferol + menaquinone-7 (D3+K2 combo)?

Common side effects of Cholecalciferol + menaquinone-7 (D3+K2 combo) (≥ 1 in 100): Nausea, constipation, Dry mouth, Transient hypercalcaemia at high D3 doses. See the Safety section for uncommon and serious reactions.

Is Cholecalciferol + menaquinone-7 (D3+K2 combo) safe during pregnancy?

Is Cholecalciferol + menaquinone-7 (D3+K2 combo) compatible with breastfeeding?

Compatible at physiological doses. In lactating women with confirmed D deficiency, regular cholecalciferol without K2 is preferred. K2 in the combo can alter INR in lactating women on warfarin.

Who should not take Cholecalciferol + menaquinone-7 (D3+K2 combo)?

Cholecalciferol + menaquinone-7 (D3+K2 combo) is contraindicated in: Warfarin or acenocoumarol therapy (K2 significantly alters INR; dose review needed); Hypercalcaemia and hypercalciuria; Active tuberculosis or sarcoidosis (hypercalcaemia risk); Severe renal impairment (eGFR <30). Full list in the Safety section.

Other drugs in this group

Vitex agnus-castus (chasteberry, monk's pepper), Zeaxanthin, Alpha-tocopherol, Andrographis paniculata, Calcifediol (25-hydroxyvitamin D), Horsetail, Olive leaf extract (Olea europaea, oleuropein), Riboflavin