NutriDex

The Supplement Research Compendium
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Vitamin K1 (Phylloquinone)

The clotting and bone-carboxylation vitamin from leafy greens

Strong evidence 🍊Vitamin

✚ Updated · How we grade evidence

Evidence tier
Strong
Research weight
Citations
8 verified / 8
Classification
Vitamin
❝
What the evidence says. Multiple high-quality RCTs / meta-analyses with consistent effects.

What is Vitamin K1 (Phylloquinone)?

Vitamin K1 (Phylloquinone) is a vitamin used for essential cofactor for hepatic synthesis of functional clotting factors ii, vii, ix and x — corrects/prevents coagulopathy in deficiency. NutriDex grades the human evidence as Strong. Vitamin K1 (phylloquinone) is the predominant dietary form of vitamin K and an essential cofactor for the gamma-carboxylation of clotting factors II, VII, IX and X, as well as bone proteins (osteocalcin) and matrix Gla protein. Frank deficiency is rare in healthy adults but causes impaired coagulation and bleeding; it is a real risk in newborns (hemorrhagic disease of the newborn), fat-malabsorption, and with certain antibiotics, which is why a single intramuscular dose is given at birth. In non-deficient adults, supplementation reliably lowers undercarboxylated osteocalcin, but the largest RCTs (ECKO, 5 mg K1 for 2-4 years) show no protection of bone mineral density, and trials of 500 mcg K1 found no slowing of coronary-artery calcification progression. Benefits beyond correcting deficiency or optimizing carboxylation status are not established for the general population.

Purported Benefits

✓Essential cofactor for hepatic synthesis of functional clotting factors II, VII, IX and X — corrects/prevents coagulopathy in deficiency
✓Standard newborn prophylaxis: a single IM dose prevents vitamin K deficiency bleeding (hemorrhagic disease of the newborn)
✓Reverses warfarin over-anticoagulation and treats vitamin-K-dependent bleeding (clinical antidote)
✓Reliably reduces undercarboxylated osteocalcin and matrix Gla protein, improving vitamin-K carboxylation biomarkers
✓Treats deficiency in fat-malabsorption states (cholestasis, cystic fibrosis, short-bowel, severe IBD)
✓Note: does NOT preserve bone mineral density or prevent coronary-artery calcification in non-deficient adults in large RCTs

Evidence by outcome

The same supplement can be well-proven for one use and unproven for another — here is the human evidence graded outcome by outcome.

OutcomeEvidenceEffectStudies
Corrects/prevents coagulopathy in deficiencyEssential clotting cofactor; repletion reliably corrects vitamin-K-dependent bleeding. Established physiology, not a general-population effect. Strong ↑ benefit · large 2
Reverses warfarin over-anticoagulationClinical antidote; large vitamin K loads predictably alter INR. Well-established, though based on review-level evidence here. Strong ↑ benefit · large 1
Reduces undercarboxylated osteocalcin (biomarker)RCTs reliably lower ucOC, but this is a carboxylation biomarker, not a clinical endpoint. Strong ↑ benefit · moderate 2
Preserves bone mineral densityECKO (5 mg, 2-4y) and other RCTs show no BMD protection in non-deficient adults despite biomarker change. Strong — no effect · negligible 3
Prevents coronary-artery/vascular calcification3-year RCT and 14-RCT meta-analysis found no consistent benefit on calcification in non-deficient adults. Moderate — no effect · negligible 2

Dosing & Compounds

Typical Dose
Adequate Intake (AI; no RDA set): 120 mcg/day for adult men, 90 mcg/day for adult women (including pregnancy/lactation). Typical supplements supply ~80-500 mcg; bone/clinical studies have used 1-5 mg K1. No Tolerable Upper Intake Level (UL) has been established because no toxicity has been observed from dietary or supplemental phylloquinone in people not on anticoagulants.
Active Compounds
Phylloquinone (vitamin K1) tablets/drops — the supplemental and pharmaceutical form (e.g., phytonadione)Injectable/oral phytonadione (Mephyton, Konakion) for clinical reversal and newborn prophylaxisDietary: dark leafy greens (kale, spinach, collards, Swiss chard, broccoli, Brussels sprouts)Dietary: vegetable oils (soybean, canola, olive) and foods made with them

Safety & Cautions

Phylloquinone has very low toxicity and no UL; no adverse effects have been documented from high oral or dietary intake in healthy people. The dominant clinical concern is the interaction with vitamin K antagonist anticoagulants (warfarin/coumarins): changes in vitamin K intake — including supplements and large vegetable meals — alter INR and warfarin effect, so intake should be kept consistent. IV phytonadione has rarely caused anaphylactoid reactions, so it is given slowly/diluted. Phylloquinone does not interact dangerously with DOACs and is not associated with the cancer/CVD harm signals seen with some other supplements. Educational only — always check with your doctor or pharmacist before combining Vitamin K1 (Phylloquinone) with any medicine.

Vitamin K1 (Phylloquinone) drug interactions

Known or theoretical interactions between Vitamin K1 (Phylloquinone) and common medications — educational, not exhaustive. Always check with your doctor or pharmacist before combining Vitamin K1 (Phylloquinone) with any medicine.

Caution
Warfarin
Vitamin K1 REDUCES warfarin's effect (lowers INR); inconsistent intake destabilizes anticoagulation.
Warfarin inhibits vitamin K epoxide reductase; phylloquinone replenishes vitamin K to make clotting factors. NIH ODS — Vitamin K

Key Studies

meta-analysis Vlasschaert 2023 (Front Nutr, vascular calcification meta-analysis) ✓ Full text
Systematic review/meta-analysis of 14 RCTs found no consistent benefit of vitamin K supplementation on vascular calcification and called for more rigorous trials.
meta-analysis Mott 2019/2022 (Bone Mineral Density & Fracture meta-analysis) ✓ Full text
Systematic review/meta-analysis concluding vitamin K (K1 and K2) effects on BMD and fracture risk are inconsistent, with most benefit signals from K2 trials and lower-quality data.
systematic review Violi 2016 (Medicine, systematic review) ✓ Full text
Systematic review of dietary vitamin K and vitamin K antagonist anticoagulation found large vitamin K loads alter INR, supporting consistent intake for warfarin patients.
RCT Cheung 2008 (ECKO Trial, PLoS Medicine) ✓ Full text
RCT of 440 osteopenic postmenopausal women; 5 mg/day K1 for 2-4 years did not protect bone mineral density at lumbar spine or hip vs placebo (no significant between-group difference).
RCT Booth 2008 (Am J Clin Nutr) ✓ PubMed
RCT in 452 healthy older adults; 500 mcg/day K1 for 3 years reduced undercarboxylated osteocalcin but did not alter bone turnover, BMD, or geometry.
RCT Shea 2009 (Am J Clin Nutr) ✓ Full text
3-year RCT (n=388 healthy older men/women); 500 mcg/day phylloquinone showed no overall difference in coronary-artery calcium progression vs control in intention-to-treat analysis.
authoritative body NIH ODS Vitamin K (Health Professional) ✓ Source
Sets AI at 120 mcg/day (men) and 90 mcg/day (women) and states no UL exists because no toxicity has been observed from high vitamin K intake.
authoritative body Institute of Medicine DRI (vitamin K) ✓ Full text
Dietary Reference Intakes report establishing AI values and documenting that data were insufficient to set an RDA or UL for vitamin K.
8 sources cited · 8 verified Search all studies on PubMed ↗

Common questions about Vitamin K1 (Phylloquinone)

What is Vitamin K1 (Phylloquinone) used for?

Vitamin K1 (Phylloquinone) is most often taken for Essential cofactor for hepatic synthesis of functional clotting factors II, VII, IX and X — corrects/prevents coagulopathy in deficiency, Standard newborn prophylaxis: a single IM dose prevents vitamin K deficiency bleeding (hemorrhagic disease of the newborn), Reverses warfarin over-anticoagulation and treats vitamin-K-dependent bleeding (clinical antidote), Reliably reduces undercarboxylated osteocalcin and matrix Gla protein, improving vitamin-K carboxylation biomarkers. The clotting and bone-carboxylation vitamin from leafy greens

Does Vitamin K1 (Phylloquinone) work — what does the evidence say?

Strong evidence. Multiple high-quality RCTs / meta-analyses with consistent effects. Vitamin K1 (phylloquinone) is the predominant dietary form of vitamin K and an essential cofactor for the gamma-carboxylation of clotting factors II, VII, IX and X, as well as bone proteins (osteocalcin) and matrix Gla protein. Frank deficiency is rare in healthy adults but causes impaired coagulation and bleeding; it is a real risk in newborns (hemorrhagic disease of the newborn), fat-malabsorption, and with certain antibiotics, which is why a single intramuscular dose is given at birth. In non-deficient adults, supplementation reliably lowers undercarboxylated osteocalcin, but the largest RCTs (ECKO, 5 mg K1 for 2-4 years) show no protection of bone mineral density, and trials of 500 mcg K1 found no slowing of coronary-artery calcification progression. Benefits beyond correcting deficiency or optimizing carboxylation status are not established for the general population.

What is the typical dose of Vitamin K1 (Phylloquinone)?

Adequate Intake (AI; no RDA set): 120 mcg/day for adult men, 90 mcg/day for adult women (including pregnancy/lactation). Typical supplements supply ~80-500 mcg; bone/clinical studies have used 1-5 mg K1. No Tolerable Upper Intake Level (UL) has been established because no toxicity has been observed from dietary or supplemental phylloquinone in people not on anticoagulants.

Is Vitamin K1 (Phylloquinone) safe? Any cautions or side effects?

Phylloquinone has very low toxicity and no UL; no adverse effects have been documented from high oral or dietary intake in healthy people. The dominant clinical concern is the interaction with vitamin K antagonist anticoagulants (warfarin/coumarins): changes in vitamin K intake — including supplements and large vegetable meals — alter INR and warfarin effect, so intake should be kept consistent. IV phytonadione has rarely caused anaphylactoid reactions, so it is given slowly/diluted. Phylloquinone does not interact dangerously with DOACs and is not associated with the cancer/CVD harm signals seen with some other supplements.

How many studies support Vitamin K1 (Phylloquinone)?

NutriDex cites 8 sources for Vitamin K1 (Phylloquinone), graded "Strong".

Does Vitamin K1 (Phylloquinone) interact with any medications?

Yes — known or theoretical interactions include: Blood thinners (warfarin, DOACs) (caution). This is educational and not exhaustive; always check with your doctor or pharmacist before combining Vitamin K1 (Phylloquinone) with any medicine.

Cite this page
APA

Peh, D. (2026). Vitamin K1 (Phylloquinone): Benefits, Dosage, Side Effects & Evidence. NutriDex — The Supplement Research Compendium. Retrieved 26 Jun 2026, from https://nutridex.info/s/vitamin-k1

BibTeX
@misc{nutridex_vitamin_k1,
  author       = {Peh, Daryl},
  title        = {Vitamin K1 (Phylloquinone): Benefits, Dosage, Side Effects \& Evidence},
  year         = {2026},
  howpublished = {NutriDex --- The Supplement Research Compendium},
  url          = {https://nutridex.info/s/vitamin-k1},
  note         = {Reviewed by Dr Daryl Peh, MBBS Singapore, MMed FM. Accessed 2026-06-26}
}

For medical claims, citing the underlying primary studies linked above is preferred. NutriDex is an educational reference, not medical advice.

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