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Vitamin K

Q: Is more vitamin K better?

No. For natural K1 and K2 there is no added benefit to megadosing; consistency matters more than quantity.

Q: Is vitamin K safe during pregnancy or breastfeeding?

Ordinary dietary amounts are considered compatible; high-dose forms should be specialist-directed. (A newborn’s vitamin K shot at birth is a separate, routine measure.)

Overview

Plain-English information for everyday use

1. What Is Vitamin K?

Key Takeaway

Vitamin K is a fat-soluble vitamin that helps your blood clot normally and helps activate proteins involved in normal bone; it comes as K1 (from greens) and K2 (from fermented and animal foods).

Vitamin KNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ is a fat-soluble vitamin your body uses to switch on certain proteins. It comes in two natural families: vitamin K1 (phylloquinone), the form in leafy green vegetables and the main type in most diets, and vitamin K2 (the menaquinones, such as MK-4 and MK-7), from fermented foods and some animal foods. A synthetic form called K3 (menadione) exists but is not used in human supplements.

Its best-established job is helping your blood clot normallyNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗; the same process also activates proteins involved in normal bone. The forms differ mainly in how long they stay in the bloodstream — MK-7 is the longest-lasting, while K1 and MK-4 clear within a few hours, which is why MK-7 is popular in once-a-day supplements.

Key Highlights

Fat-soluble vitamin essential for normal blood clotting
Activates proteins involved in normal bone and calcium handling
Two natural families: K1 (leafy greens) and K2 (natto, fermented and animal foods)
MK-7 is the longest-lasting form — well suited to once-daily use
No upper limit set for K1 or K2; menadione (K3) is not used in humans
Most relevant interaction is with warfarin — keep intake consistent

2. Signs You May Be Running Low

Key Takeaway

Outright vitamin K deficiency is uncommon in healthy adults; when it occurs the signs are bleeding-related, and the people most at risk are those with fat-absorption problems, certain medicines, and newborns.

Outright vitamin K deficiency is uncommon in healthy adultsCDC — Vitamin K Deficiency Bleeding: information for healthcare providers view ↗ — the vitamin is found across many foods, the body recycles it, and gut bacteria make some. Because its clearest role is in clotting, the signs that do appear are bleeding-related:

Bruising more easily than usual
Cuts or nosebleeds that are slow to stop
Bleeding gums

The people most likely to run low are those with conditions that block fat absorption, people on particular long-term medicines, and newbornsAmerican Academy of Pediatrics — Vitamin K and the Newborn Infant (Pediatrics, 2022) view ↗ — which is why a vitamin K shot is given routinely at birth. These signs have many causes and are not a diagnosis; if several show up together, talk with your healthcare provider.

3. Who Should Be Careful or Check With a Provider

Key Takeaway

If you take warfarin (a vitamin K antagonist), keep your vitamin K intake consistent and coordinate any change with your clinician; newer blood thinners are not affected. Menadione is excluded.

If you take warfarin (or another vitamin K antagonist), this matters most. Vitamin K is the direct counterweight to warfarin, so a sudden change in how much you get — from a supplement or even a big shift in leafy-green intakeNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ — can move your INR out of range. The goal is steady, consistent intake, not avoidance, and any supplement change should go through the clinician who manages your anticoagulation. The newer blood thinners (apixaban, rivaroxaban, dabigatran) and heparin do not interactNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ with vitamin K this way.

People with fat-absorption problems or who take orlistat, bile-acid binders, mineral oil, or long courses of antibiotics — these can lower vitamin K levelsNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗.
Anyone who is pregnant or breastfeedingNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗: ordinary dietary and supplement amounts are considered compatible, but high-dose forms should be specialist-directed.
Anyone considering menadione (vitamin K3)FDA — 21 CFR 573.620 (menadione permitted in animal feed only): it is not permitted in human supplements — look for K1, MK-4, or MK-7 instead.

Two points that cause confusion: injectable vitamin KFDA / DailyMed — Phytonadione prescribing information (boxed warning) view ↗ is a prescription medical product with its own cautions, used in clinics — its warnings do not apply to ordinary oral supplements. And the worry that "K2 causes clots" is not supported: in people not on a vitamin K antagonist, normal or even high K2 intake has not been shown to raise clotting riskNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗.

4. How to Get the Best Results

Key Takeaway

Take vitamin K with a meal containing some fat, favor consistency over big doses, store it away from light, and know you won't 'feel' it working — its effects are biochemical.

Vitamin K is fat-solubleNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗, so a few simple habits help your body take it up:

Take With a Meal Containing Fat

Take it with a meal that contains some fat rather than on an empty stomach.

Favor Consistency Over Big Doses

For natural K1 and K2, more is not better.

MK-7 Is Once-Daily

If you choose MK-7, once daily is fine because it lasts a long timeNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ in the body; K1 and MK-4 clear quickly.

Store Away From Light

Store it away from bright light, which breaks vitamin K downNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ over time.

If You Take Warfarin

Keep your intake steady and coordinate any change with your clinician.

One honest expectation-setter: you will not "feel" vitamin K working. Its effects are biochemicalNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ — measurable in lab markers, not as energy, mood, or any sensation.

5. Side Effects to Know About

Key Takeaway

Oral K1/MK-7 at normal amounts is very well tolerated, with no upper limit set for K1/K2; the serious reactions you may read about belong to the injectable form, and menadione is the toxic form that's banned.

For most healthy people, vitamin K from food and ordinary oral supplements (K1 or MK-7) is very well tolerated. No upper limitNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ has been set for K1 or K2 because they have not been shown to cause harm at high intakes — there is no recognized "vitamin K toxicity" from food or oral supplements in healthy people. As with any supplement, mild, occasional digestive upset is possible; taking it with food usually settles that.

If you read about serious reactions to vitamin K — such as severe allergic-type reactions or a newborn "gasping syndrome" — those are linked to the injectable formFDA / DailyMed — Phytonadione prescribing information (boxed warning) view ↗ given in medical settings, not to oral supplements. The one form with well-documented toxicity is menadione (K3)FDA — 21 CFR 573.620 (menadione permitted in animal feed only), and that is precisely the form not allowed in human supplements.

6. What the Research Suggests

Key Takeaway

The clearest evidence is that vitamin K is essential for normal blood clotting and supports normal bone; the bigger claims about long-term bone strength and heart health are genuinely mixed, and one 3-year trial found no benefit.

Here is a straight look at what the science actually shows — including where it is strong, where it is mixed, and where claims outpace the data.

Evidence: Strong

The best-supported themes are the simplest ones: vitamin K is essential for normal blood clotting, and adequate intake supports the maintenance of normal bones. These are the two relationships with the clearest backing — and the only two authorized for vitamin KEFSA — Dietary Reference Values for vitamin K (Scientific Opinion, 2017) view ↗ by European regulators.

Evidence: Mixed / Limited

Much of the popular interest goes further — asking whether K2 supplements measurably strengthen bone over the long run or keep calcium out of the arteries. Here the evidence is genuinely mixed: some studies show movement in laboratory markersNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗, but larger, longer trials have not consistently shown changes in outcomes people care about, such as bone-health outcomesMott et al. — Vitamin K, bone mineral density and fractures: updated systematic review & meta-analysis (2019) view ↗ or heart events; one three-year trialDiederichsen et al. — Vitamin K2 + D in aortic valve calcification (AVADEC RCT), Circulation 2022 view ↗ in older adults found no benefit on its cardiovascular measures. The practical takeaway: keep a healthy baseline; beyond that, the strongest marketing claims currently run ahead of the evidence, and a supplement is best understood as nutritional support, not a remedy for any specific condition.

7. Where to Find Vitamin K in Food

Key Takeaway

K1 comes mainly from leafy greens; K2 from natto and some cheeses, egg yolk, and meats. If you take warfarin, keep your greens intake consistent rather than avoiding them.

A balanced diet usually covers vitamin K easily. The two families come from different foodsNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗:

Vitamin K1: leafy greens lead by a wide margin — kale, collard greens, spinach, Swiss chard, broccoli — plus some vegetable oils.
Vitamin K2: natto (fermented soybeans) is by far the richest source of MK-7; smaller amounts come from some cheeses, egg yolks, and certain meats.

K1 from greens is absorbed better with a little fat, and vitamin K stands up well to cooking. If you take warfarin: you do not have to avoid greens — just keep your intake roughly consistentNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ week to week so your INR stays steady.

8. What Body Systems Vitamin K Supports

Key Takeaway

Vitamin K activates proteins involved in normal clotting, normal bone (osteocalcin), and calcium handling in blood vessels (matrix Gla protein) — descriptions of normal function, not promises of disease prevention.

Vitamin K works by switching on a small set of proteins. In plain terms, that touches a few normal, healthy systemsNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗:

🩸 Blood & Clotting

Its central, best-established role: activating the proteins that let blood clot normally.

🦴 Bones

It activates osteocalcin, a protein involved in normal bone.

🫀 Blood Vessels & Soft Tissue

It activates matrix Gla protein, which helps keep calcium directed toward bone rather than soft tissue. Whether supplements change long-term vascular outcomes is, as the research section notes, still unsettled.

These are descriptions of normal function, not promises that a supplement prevents disease.

9. Frequently Asked Questions

Key Takeaway

Common questions about K1 vs K2, whether you need a K2 supplement, taking vitamin K with a blood thinner or with vitamin D, whether more is better, and safety in pregnancy.

What’s the difference between vitamin K1 and K2?

They share the same core job but come from different foods and behave differently. K1, from leafy greens, is the main dietary form and the body’s priority for clotting. K2 comes from fermented and animal foods and stays in the blood longerNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗, especially MK-7.

Do I need a K2 supplement if I eat vegetables?

Eating greens supplies K1, which covers essential clotting needs. K2 is found in fewer foods, but whether adding it changes long-term health outcomes is not establishedMott et al. — Vitamin K, bone mineral density and fractures: updated systematic review & meta-analysis (2019) view ↗.

Can I take vitamin K with my blood thinner?

If it is warfarin, vitamin K directly affects how it works, so don’t start, stop, or change a supplement without the clinician who manages it. Newer blood thinnersNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ (apixaban, rivaroxaban, dabigatran) and heparin are not affected.

Is more vitamin K better?

No. For natural K1 and K2 there is no added benefitNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ to megadosing; consistency matters more than quantity.

Should I take vitamin K with vitamin D?

Many products combine D3 and K2, and both are fat-soluble. Just know the claim that the combination protects the heart or bones long-term is not provenNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗.

Is vitamin K safe during pregnancy or breastfeeding?

Ordinary dietary amounts are considered compatibleNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗; high-dose forms should be specialist-directed. (A newborn’s vitamin K shot at birth is a separate, routine measure.)

10. How to Choose a Quality Supplement — Bonus

Key Takeaway

Pick a recognized form (K1, MK-4, or MK-7), look for all-trans MK-7 and third-party testing, avoid menadione, and choose D3+K2 combinations on your needs rather than hype.

This is general, form-level guidance — not a recommendation of any brand:

Pick a Recognized Form

K1, MK-4, or MK-7. MK-7 is long-acting and common in once-daily products.

Look for Quality Signals

all-trans MK-7NIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ (the USP-grade, biologically active configuration) and third-party / independent testing.

Avoid Menadione (K3)

Avoid menadione (K3) for human useCDC — Vitamin K Deficiency Bleeding: information for healthcare providers view ↗.

D3 + K2 Combinations

D3 + K2 combinations are popular and fine to use — choose based on your own needsNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ rather than marketing claims.

11. Your Genes & Vitamin K — Bonus

Key Takeaway

Most 'vitamin K genetics' is really about warfarin dosing (VKORC1/CYP2C9), not supplements; there is no validated genotype-guided vitamin K supplement, and rare inherited bleeding disorders are specialist-managed.

VKORC1 & CYP2C9 — Warfarin Dosing

Most "vitamin K and genetics" information is really about the drug warfarin, not supplements. Variants in two genes (VKORC1 and CYP2C9NIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗) strongly affect how much warfarin a person needs, which is why genotype is sometimes used to guide warfarin dosing.

Rare Inherited Disorders

There is, however, no validated way to "personalize your vitamin K supplement by DNA test." Separately, there are rare inherited disordersNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ of the vitamin K system that cause bleeding; these are specialist-managed and not something a general supplement addresses.

12. Traditional Roots — Bonus

Key Takeaway

Vitamin K is a modern discovery (1929), so no traditional system used it as such; traditional foods like natto happened to be rich in it, but that recognition is modern and after-the-fact.

Vitamin K is a modern discoveryThe Nobel Prize in Physiology or Medicine 1943 (Dam & Doisy) — NobelPrize.org — first identified in 1929 — so no traditional medicine system used "vitamin K" as such. Traditional diets did include foods naturally rich in it (fermented soybeans like natto, aged cheeses, leafy greens), but recognizing those as vitamin K sources is a modern, after-the-fact understanding rather than inherited knowledge.

13. The Story Behind the Science — Bonus

Key Takeaway

Henrik Dam discovered vitamin K in 1929 and named it for 'Koagulation' (the only vitamin named for a function); today its marker effects are clear, but long-term supplement benefits for bone and heart remain unproven.

Vitamin K owes its letter to chemistry history: the Danish scientist Henrik Dam discovered it in 1929 and named it for "Koagulation" — making it the only vitamin named for a function. Dam shared the 1943 Nobel PrizeThe Nobel Prize in Physiology or Medicine 1943 (Dam & Doisy) — NobelPrize.org with Edward Doisy, who worked out its structure.

Where research stands today: vitamin K’s effects on laboratory markers are well established, but the long-term, real-world benefits of supplements for bone and heart health remain unprovenDiederichsen et al. — Vitamin K2 + D in aortic valve calcification (AVADEC RCT), Circulation 2022 view ↗ and are an active area of study.

14. Blood Tests That May Show Changes — Bonus

Key Takeaway

A vitamin K level isn't part of routine bloodwork, but a direct test can be ordered separately; functional markers are also used to gauge status. PT/INR is a clotting test central to warfarin monitoring, and vitamin K can affect a specialized liver lab marker (DCP).

Vitamin K is not on a standard blood panel, but a direct serum vitamin K (phylloquinone) level can be ordered separately through major labs — it mainly reflects your recent intake (such tests usually require fasting and avoiding vitamin K-rich foods and supplements beforehand), so it's used selectively rather than routinely. Status is gauged with specialized markersNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ — such as PIVKA-II, undercarboxylated osteocalcin, and dp-ucMGP — used mostly in research.

⚠️ Tests to Flag to Your Provider

The familiar clotting test, PT/INR, is not a vitamin K status test, but it is central to warfarin monitoringNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗, and large swings in vitamin K intake can change the INR. One more thing to flag to a provider: vitamin K can influence a specialized lab marker called DCP (PIVKA-II)Mayo Clinic Laboratories — DCP (PIVKA-II) test information used in certain liver testing, so mention any vitamin K supplement if that test is being interpreted.

If you take warfarin, or if a DCP/PIVKA-II liver test is being interpreted, tell your provider about any vitamin K supplement so the result is read correctly.

✓ Last Reviewed: June 2026

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Vitamin K

Clinical Reference — Technical Data

Clinician-facing reference: identity, mechanism, pharmacokinetics, evidence, dosing, interactions, adverse effects, cautions, monitoring, and quality.

CLINICAL SUMMARY

Vitamin K (phylloquinone K1; menaquinones K2 — MK-4, MK-7)

Fat-soluble vitamin and obligate cofactor for gamma-glutamyl carboxylase, activating vitamin K-dependent Gla proteins (hepatic factors II/VII/IX/X and protein C/S/Z; osteocalcin; matrix Gla protein; Gas6).

Overall Evidence

MODERATE

Clinical Research Areas

STRONGNormal blood clotting · and correcting low vitamin K status (EFSA-authorized role)
STRONGMaintenance of normal bone · second EFSA-authorized structure/function relationship
LIMITEDBone mineral density & vascular-calcium handling · biomarkers move; hard outcomes inconsistent
INSUFFICIENTCardiovascular endpoints, mortality, oncology, cognition, glucose · observational/confounded; no supportive hard-outcome RCT

Structure/function context — not FDA-evaluated disease indications.

Typical Intake Ranges

Dietary (AI): 90-120 ug/day (US IOM) / 70 ug/day (EFSA); no Tolerable Upper Intake Level for K1/K2
Supplemental: MK-7 commonly ~90-200 ug/day for biomarker effects
Medical / prescription: milligram-level intakes appear only in medical settings — outside dietary-supplement use

Key Safety Flags

🟠 CAUTION Warfarin (VKA): keep vitamin K intake consistent + INR monitoring; coordinate any change with the managing clinician
🟢 STANDARD No interaction with DOACs (apixaban, rivaroxaban, dabigatran), heparin, or antiplatelets
🟢 STANDARD No UL for K1/K2; no recognized oral toxicity in healthy adults
🟠 CAUTION Avoid menadione (K3) for human use (neonates, G6PD); the injectable form's boxed warning does not apply to oral supplements

Monitoring Quick-Ref

PT/INR: for VKA patients when vitamin K intake changes — a drug-effect monitor, not a status test
Functional markers: PIVKA-II / %ucOC / dp-ucMGP (research/specialist; no single gold standard)
Plasma phylloquinone: <0.15 ug/L supports deficiency; reflects recent intake

⚠️ Lab Interference

Vitamin K is the direct counterweight to warfarin — it lowers INR in VKA patients (a drug-effect monitor, not a status test). It also lowers DCP (PIVKA-II), which is an HCC tumor marker, so flag any vitamin K supplement to the lab when that test is interpreted. No documented interference with cardiac, thyroid, or hormone assays.

Bottom line: Vitamin K is an essential nutrient whose clearest role is supporting normal blood clotting; the bone and cardiovascular research rests on biomarker data with inconsistent or absent hard-outcome results and is not established. The main adult consideration is the warfarin interaction (consistency, not avoidance). Menadione is not used in humans. Acute medical uses of prescription vitamin K are separate from dietary supplements.

1. Chemical Identity & Forms

Key Takeaway

Vitamin K denotes 2-methyl-1,4-naphthoquinones differing by C-3 side chain: phylloquinone (K1), menaquinones (K2; MK-4, MK-7), and the human-prohibited synthetic menadione (K3). Phytonadione is both nutrient and Rx drug.

Vitamin K denotes a family of 2-methyl-1,4-naphthoquinones differing in the C-3 side chain. Phylloquinone (K1; phytonadione) is the predominant dietary form; menaquinones (K2; MK-n) — supplement-relevant MK-4 and long-chain MK-7 — differ by isoprenyl chain length; menadione (K3) is a synthetic provitamin restricted to animal feedFDA — 21 CFR 573.620 (menadione permitted in animal feed only) and not permitted in human supplements.

Phytonadione carries two regulatory identities: an essential nutrient under DSHEA and an FDA-approved prescription drugFDA / DailyMed — Phytonadione prescribing information (boxed warning) view ↗ (injectable, tablets). MK-4 is an approved prescription drug for skeletal indications in Japan (45 mg/day); MK-7 is an EFSA novel-food ingredient. Dietary K1/menadione can be converted to MK-4 in tissue via UBIAD1Nakagawa et al. — Identification of UBIAD1 as the human menaquinone-4 biosynthetic enzyme (Nature 2010); PMID 20953171 view ↗. All-trans MK-7 and USP-grade phytonadione are the quality benchmarks (§14).

Vitamer Identity

Vitamer	CAS	Formula	MW (g/mol)	Form / Role
Phylloquinone (K1)	84-80-0	C₃₁H₄₆O₂	450.70	Predominant dietary form (leafy greens); Rx phytonadione
Menaquinone-4 (K2, MK-4)	863-61-6	C₃₁H₄₀O₂	444.65	Tissue-converted form; approved Rx drug in Japan (45 mg/d)
Menaquinone-7 (K2, MK-7)	2124-57-4	C₄₆H₆₄O₂	649.0	Long-chain; fermented foods (natto); supplement form
Menadione (K3)	58-27-5	C₁₁H₈O₂	172.18	Synthetic provitamin; animal-feed only — excluded from human supplements

2. Mechanism of Action

Key Takeaway

Reduced vitamin K is the obligate cofactor for gamma-glutamyl carboxylase (GGCX), gamma-carboxylating 17 vitamin K-dependent proteins; the epoxide is recycled by VKORC1 — warfarin's target.

Vitamin K activity is cofactor-mediated. Reduced vitamin K is the obligate cofactor for gamma-glutamyl carboxylase (GGCX)Schurgers, Uitto & Reutelingsperger — Vitamin K-dependent carboxylation of matrix Gla-protein (Trends Mol Med 2013); PMID 23375872 view ↗, which gamma-carboxylates specific glutamate residues on vitamin K-dependent proteins (VKDPs), creating Ca2+-binding Gla proteins; vitamin K is oxidized to the epoxide and regenerated by VKORC1CPIC (Johnson et al.) — Pharmacogenetics-guided warfarin dosing: CYP2C9/VKORC1/CYP4F2, 2017 update (Clin Pharmacol Ther); PMID 28198005 view ↗ — the vitamin K cycle and warfarin’s pharmacologic target.

Of the 17 recognized VKDPsSchurgers et al. — The realm of vitamin K-dependent proteins: from coagulation toward calcification (Mol Nutr Food Res 2014); PMID 24668744 view ↗: procoagulant factors II/VII/IX/X and regulators protein C/S/Z (hemostasis); osteocalcinNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ (skeletal; ucOC is a status marker); matrix Gla proteinLuo et al. — Spontaneous calcification of arteries and cartilage in mice lacking matrix Gla protein (Nature 1997); doi 10.1038/386078a0 view ↗ (a local inhibitor of ectopic calcification — MGP-null mice calcify spontaneously, the animal basis of the vascular hypothesis); and Gas6/protein SSchurgers et al. — The realm of vitamin K-dependent proteins: from coagulation toward calcification (Mol Nutr Food Res 2014); PMID 24668744 view ↗ (TAM-receptor and cell-survival roles, incl. CNS). A non-canonical vitamin K / FSP1 axis suppresses ferroptosisMishima et al. — A non-canonical vitamin K cycle is a potent ferroptosis suppressor (Nature 2022); doi 10.1038/s41586-022-05022-3 view ↗ in models — mechanistic/preclinical, not an indication.

Vitamin K-Dependent (Gla) Proteins

Gla protein	Site / compartment	Function
Factors II, VII, IX, X	Liver → plasma	Procoagulant clotting factors
Protein C, Protein S, Protein Z	Liver → plasma	Anticoagulant / regulatory
Osteocalcin (bone Gla protein)	Bone (osteoblasts)	Binds calcium in bone matrix; ucOC is a skeletal status marker
Matrix Gla protein (MGP)	Vascular smooth muscle, cartilage	Local inhibitor of soft-tissue / vascular calcification
Gas6	Widespread (incl. CNS)	TAM-receptor ligand; cell survival and signaling

3. Pharmacokinetics (ADME)

Key Takeaway

Bile/lipase-dependent micellar absorption via chylomicrons; phylloquinone/MK-4 t1/2 ~1-2 h vs MK-7 ~3 days (rationalizing once-daily MK-7); CYP4F2-mediated omega-hydroxylation clears it.

Absorption requires bile and pancreatic lipase; vitamers enter mixed micelles, are taken up by enterocytes, packaged into chylomicrons, and delivered via lymph. Fractional absorptionNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ of phylloquinone from a plant matrix is low (~5-15%) and improves with dietary fat.

Turnover differs by vitamer and drives dosing: phylloquinone and MK-4 have short half-lives (~1-2 h), whereas MK-7’s ~3-day half-lifeSchurgers et al. — Synthetic vitamin K1 vs natto-derived MK-7; MK-7's longer half-life (Blood 2007); doi 10.1182/blood-2006-08-040709 view ↗ yields higher, more stable steady-state levels and greater extrahepatic carboxylation per dose. Hepatic clotting-factor carboxylation is prioritized over extrahepatic VKDPs when vitamin K is limited. Catabolism proceeds by CYP4F2 omega-hydroxylationEdson et al. — CYP4F2/CYP4F11 ω-hydroxylation (catabolism) of vitamin K (Biochemistry 2013); PMID 24138531 view ↗; excretion is predominantly biliary/fecal.

4. Organ System Effects

Key Takeaway

Effects follow VKDP distribution: hepatic/hematologic coagulation (established), skeletal osteocalcin, vascular/soft-tissue MGP, and preclinical CNS Gas6 roles. Whether supplementation beyond adequacy alters outcomes is graded in §6.

Effects follow VKDP distribution; the statements describe normal physiology of adequate status, with supplementation outcomes graded in §6 Schurgers et al. — The realm of vitamin K-dependent proteins: from coagulation toward calcification (Mol Nutr Food Res 2014); PMID 24668744 view ↗:

Hematologic/hepatic — the established effect: carboxylation of factors II/VII/IX/X and protein C/S/Z enabling normal coagulationNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗.
Skeletal — osteocalcin carboxylationSchurgers, Uitto & Reutelingsperger — Vitamin K-dependent carboxylation of matrix Gla-protein (Trends Mol Med 2013); PMID 23375872 view ↗; adequacy lowers circulating ucOC.
Cardiovascular/soft tissue — MGP carboxylationSchurgers, Uitto & Reutelingsperger — Vitamin K-dependent carboxylation of matrix Gla-protein (Trends Mol Med 2013); PMID 23375872 view ↗ contributes to local inhibition of vascular/cartilage calcification in mechanistic models.
Nervous system — brain MK-4 and Gas6/protein S signalingSchurgers et al. — The realm of vitamin K-dependent proteins: from coagulation toward calcification (Mol Nutr Food Res 2014); PMID 24668744 view ↗ are preclinical; clinical relevance unestablished.

Per §34, these are framed as the biology of the carboxylated proteins, not disease-modifying actions of a vitamin K product.

5. Clinical Study Intakes

Key Takeaway

Dietary adequacy 90-120 ug/day (no UL); supplemental MK-7 ~90-200 ug/day for biomarker effects, which develop over weeks. Milligram-level intakes (e.g., the 45 mg/day MK-4 studied for bone in Japan, or prescription phytonadione) belong to medical/prescription settings, not dietary supplements.

Intake ranges by context; medical and prescription uses are shown as distinct from dietary-supplement intake Schurgers, Uitto & Reutelingsperger — Vitamin K-dependent carboxylation of matrix Gla-protein (Trends Mol Med 2013); PMID 23375872 view ↗:

Dietary (adequacy)

IOM AI 90-120 ug/day; EFSA AI 70 ug/day; no ULNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ for K1/K2.

Functional (bone & vascular biomarkers)

MK-7 ~90-200 ug/day; ucOC improves ~4-12 wk and dp-ucMGP falls ~30-50% over 12-24 wkKnapen et al. — MK-7 180 mcg/d and arterial stiffness in postmenopausal women, 3-yr RCT (Thromb Haemost 2015); PMID 25694037 view ↗.

Medical, Prescription & Research Intakes

Clinical & prescription uses (not supplement uses): correcting diagnosed deficiency, reversing the effect of vitamin K antagonists, and newborn vitamin K administration are carried out by healthcare providers using FDA-approved prescription protocols (including intramuscular/intravenous routes) that are legally and functionally distinct from over-the-counter dietary supplements.

Bone research (outside the US): in some jurisdictions (e.g., Japan), MK-4 45 mg/dayMott et al. — Vitamin K supplementation, bone mineral density and fractures: systematic review & meta-analysis (Osteoporos Int 2019); PMID 31076817 view ↗ has been studied for skeletal health; bone-outcome evidence elsewhere is inconsistent (§6), and the US FDA has not evaluated this use.

Multi-form note: hepatic coagulation responses generalize across vitamers, but extrahepatic trial data are dominated by MK-7 (and MK-4 in Japan) and should not be extrapolated to low-dose K1.

6. Clinical Evidence

Key Takeaway

STRONG for supporting normal coagulation and correcting deficiency; LIMITED/conflicting for bone and vascular-calcification supplementation (biomarkers move, hard outcomes don't, AVADEC null); INSUFFICIENT for CV events, mortality, cancer, cognition.

Graded by indication (Three States Rule — positive, null, and adverse findings side by side); industry funding disclosed.

STRONG — Coagulation, deficiency, repletion. Vitamin K is required for normal coagulation; deficiency causes a bleeding tendency that corrects with repletion. In clinical settings, newborn vitamin K administrationAmerican Academy of Pediatrics — Vitamin K and the Newborn Infant (Pediatrics, 2022) view ↗ is a standard, guideline-endorsed measure that supports normal clotting factor levels at birth.

STRONG (reserved) — medical anticoagulation reversal. Clinicians administer phytonadione (with prescription clotting-factor products, in medical settings)Holbrook et al. — Evidence-based management of anticoagulant therapy, ACCP/CHEST 9th ed (Chest 2012); PMID 22315259 view ↗ to restore carboxylation, in clinician-directed situations.

LIMITED / CONFLICTING — Bone. A Japanese program reported maintained bone mineral density with MK-4 45 mg/day (Eisai-funded)Mott et al. — Vitamin K supplementation, bone mineral density and fractures: systematic review & meta-analysis (Osteoporos Int 2019); PMID 31076817 view ↗ and an early meta-analysis suggested benefitMott et al. — Vitamin K supplementation, bone mineral density and fractures: systematic review & meta-analysis (Osteoporos Int 2019); PMID 31076817 view ↗, but updated syntheses found inconsistent bone mineral density (BMD) outcomesMott et al. — Vitamin K supplementation, bone mineral density and fractures: systematic review & meta-analysis (Osteoporos Int 2019); PMID 31076817 view ↗ with several null Western RCTs. Carboxylation markers improve; hard outcomes do not consistently.

LIMITED / CONFLICTING — Vascular calcium handling. MK-7 lowers dp-ucMGP and some trials report slowed arterial-stiffness progression (Knapen 2015, MenaQ7/NattoPharma-fundedKnapen et al. — MK-7 180 mcg/d and arterial stiffness in postmenopausal women, 3-yr RCT (Thromb Haemost 2015); PMID 25694037 view ↗); in those study populations, biomarkers improve without consistent hard-outcome benefitGeng et al. — Vitamin K and vascular calcification in CKD: meta-analysis (Front Nutr 2023); PMID 36704782 view ↗, and the 3-year AVADEC trial showed no CV benefitDiederichsen et al. — AVADEC: vitamin K2 + D vs placebo on aortic valve calcification, RCT (Circulation 2022); PMID 35465686 view ↗. Animal MGP modelsLuo et al. — Spontaneous calcification of arteries and cartilage in mice lacking matrix Gla protein (Nature 1997); doi 10.1038/386078a0 view ↗ motivate but do not establish efficacy.

INSUFFICIENT — cardiovascular endpoints, mortality, oncology, cognition, glucose metabolism. Associations with lower CV events/mortality are observational and confoundedDiederichsen et al. — AVADEC: vitamin K2 + D vs placebo on aortic valve calcification, RCT (Circulation 2022); PMID 35465686 view ↗, with no supportive hard-outcome RCT. Net: certainty is high for supporting normal coagulation and correcting deficiency; low and conflicting for bone/vascular supplementation; insufficient for broader endpoints.

7. Pharmacogenomics & Genetics

Key Takeaway

Vitamin K PGx is about warfarin dose, not supplement response: VKORC1 (~30%), CYP2C9, CYP4F2. No validated genotype-guided supplementation. Rare VKCFD (GGCX/VKORC1) is a recessive bleeding disorder.

Warfarin Pharmacogenomics (VKORC1, CYP2C9, CYP4F2)

Critical framing: vitamin K pharmacogenomics concerns warfarin (the antagonist) dose, not response to vitamin K intake. VKORC1 c.-1639G>ACPIC (Johnson et al.) — Pharmacogenetics-guided warfarin dosing: CYP2C9/VKORC1/CYP4F2, 2017 update (Clin Pharmacol Ther); PMID 28198005 view ↗ alone explains ~30% of warfarin dose variability; with CYP2C9 and clinical factors, ~50%. CYP4F2*3CPIC (Johnson et al.) — Pharmacogenetics-guided warfarin dosing: CYP2C9/VKORC1/CYP4F2, 2017 update (Clin Pharmacol Ther); PMID 28198005 view ↗ reduces vitamin K clearance, so carriers need a modestly higher warfarin dose — the one variant whose mechanism touches vitamin K availability. CPIC/FDA operationalize these; allele frequencies differ by ancestry.

Hereditary Combined VKD Deficiency (VKCFD)

There is no validated genotype-guided vitamin K supplementation algorithm. Rare loss-of-function defects cause hereditary combined VKD clotting-factor deficiency (VKCFD)Schurgers, Uitto & Reutelingsperger — Vitamin K-dependent carboxylation of matrix Gla-protein (Trends Mol Med 2013); PMID 23375872 view ↗: type 1 GGCX, type 2 VKORC1 — a recessive bleeding disorder with possible skeletal anomalies, managed with high-dose vitamin K +/- plasma/PCC/rFVIIa.

8. Adverse Effects

Key Takeaway

Oral K1/MK-7 well tolerated (no UL; high-dose K2 hasn't raised thrombosis risk in non-anticoagulated subjects). Parenteral phytonadione carries an FDA boxed warning. Menadione is the toxic, human-excluded form.

Three States Rule, by form/route:

Oral K1 / MK-7: well tolerated; no ULMarles, Roe & Oketch-Rabah — USP safety evaluation of menaquinone-7 (Nutr Rev 2017); PMID 28838081 view ↗; high-dose K2 has not increased thrombosis/clotting risk in non-anticoagulated subjects.
Parenteral phytonadione: FDA boxed warningFDA / DailyMed — Phytonadione prescribing information (boxed warning) view ↗ for severe anaphylactoid reactions with IV/IM use; SC preferred.
Menadione (K3): documented dose-dependent toxicityFDA — 21 CFR 573.620 (menadione permitted in animal feed only) (oxidative hemolysis, hepatotoxicity; neonates/G6PD) — the form excluded from human supplements.

No recognized vitamin K toxicity syndrome arises from food or oral K1/K2 in healthy adults; the serious profile is route- and form-specific.

9. Drug Interactions

Key Takeaway

VKAs (warfarin) — MAJOR, bidirectional: consistency + INR monitoring, not avoidance. NO interaction with DOACs/heparin. Depleting agents (orlistat, sequestrants, NMTT cephalosporins, inducers); high-dose vitamin E antagonizes.

Vitamin K Antagonists (warfarin) — MAJOR, bidirectional

increased/fluctuating vitamin K antagonizes VKAs and destabilizes INR; abrupt reductions potentiate them. Management is consistency + INR monitoringHolbrook et al. — Evidence-based management of anticoagulant therapy, ACCP/CHEST 9th ed (Chest 2012); PMID 22315259 view ↗, not avoidance.

DOACs & Heparins — No Interaction

apixaban, rivaroxaban, edoxaban, dabigatran, heparin/LMWH do not act via the vitamin K cycleStatPearls — Anticoagulant Therapy in Pregnancy (warfarin teratogenicity; DOAC drug classes) view ↗.

Depletion / Functional Deficiency

orlistat, bile-acid sequestrants, mineral oil (malabsorption); broad-spectrum antibiotics; NMTT cephalosporins (additionally inhibit VKOR)NIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗; enzyme-inducing anticonvulsants/rifampin (maternal use → lower neonatal vitamin K status).

High-Dose Vitamin E

antagonizes vitamin K (raises PIVKA-II)Booth et al. — Effect of vitamin E supplementation on vitamin K status (Am J Clin Nutr 2004;80:143-8) view ↗, relevant with anticoagulation.

10. Important Warnings & Precautions

Key Takeaway

Hypersensitivity; menadione for human use (esp. neonates/G6PD); injectable-specific precautions. It does not correct the bleeding of severe liver disease. VKA patients must not self-supplement. See Block F (10a-10d).

Strong/absolute: hypersensitivity; menadione for human useFDA — 21 CFR 573.620 (menadione permitted in animal feed only) (neonates, G6PD). Injectable-specific: hereditary hypoprothrombinemia and heparin over-anticoagulation (phytonadione ineffective) plus the parenteral boxed-warning precautionsFDA / DailyMed — Phytonadione prescribing information (boxed warning) view ↗. Vitamin K does not correct the bleeding tendency of severe liver disease (a limitation of effectiveness, not a safety precaution). VKA patients must not self-supplementHolbrook et al. — Evidence-based management of anticoagulant therapy, ACCP/CHEST 9th ed (Chest 2012); PMID 22315259 view ↗ without the managing clinician. The clinical-decision-support panels follow in 10a-10d.

Patient Population Red Flags

Highest-priority: anticoagulated (VKA) patientsHolbrook et al. — Evidence-based management of anticoagulant therapy, ACCP/CHEST 9th ed (Chest 2012); PMID 22315259 view ↗ — any vitamin K change must route through anticoagulation management. NeonatesAmerican Academy of Pediatrics — Vitamin K and the Newborn Infant (Pediatrics, 2022) view ↗ should receive standard vitamin K administration at birth and never menadione. Pregnancy/Lactation are P-1 (compatible) at dietary/functional intakeNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ — the teratogen is the antagonist (fetal warfarin syndrome ~6%, Category X)StatPearls — Anticoagulant Therapy in Pregnancy (warfarin teratogenicity; DOAC drug classes) view ↗, not vitamin K. Malabsorptive and CKD/dialysisGeng et al. — Vitamin K and vascular calcification in CKD: meta-analysis (Front Nutr 2023); PMID 36704782 view ↗ patients warrant attention; G6PD deficiency contraindicates menadione (natural-form caution is precautionary).

Drug-Nutrient Depletion Table

Agents that reduce vitamin K status: orlistat / mineral oil / olestra (fat malabsorption); bile-acid sequestrants (bind bile/fat); broad-spectrum antibiotics (gut-flora menaquinone suppression); NMTT cephalosporinsNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ (flora + VKOR inhibition → hypoprothrombinemia); enzyme-inducing anticonvulsants/rifampin (maternal use → lower neonatal vitamin K status); and high-dose vitamin EBooth et al. — Effect of vitamin E supplementation on vitamin K status (Am J Clin Nutr 2004;80:143-8) view ↗ (antagonizes; raises PIVKA-II).

Lab Interference Panel

PT/INR: vitamin K antagonizes VKAs (lowers INR); deficiency prolongs PT — the operative VKA monitor, not a status test NIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗. DCP / PIVKA-IIMayo Clinic Laboratories — DCP (PIVKA-II) test information view ↗: vitamin K lowers it; it is an HCC tumor marker, so flag supplement use to the lab. %ucOC and dp-ucMGPGeng et al. — Vitamin K and vascular calcification in CKD: meta-analysis (Front Nutr 2023); PMID 36704782 view ↗ improve with adequate status (functional markers; research/specialist use). Plasma phylloquinone reflects recent intake (lipemia/light affect it; <0.15 ug/L supports deficiency). A direct serum/plasma phylloquinone (vitamin K1) level by LC–MS/MS is available commercially as a specialist send-out test and can be ordered separately; it reflects recent intake rather than long-term stores.

Monitoring Protocol Template + Discontinuation

VKA patients: INR at baseline and after any change in vitamin K intake; target consistency rather than eliminationHolbrook et al. — Evidence-based management of anticoagulant therapy, ACCP/CHEST 9th ed (Chest 2012); PMID 22315259 view ↗. Deficiency/repletion: PT/INR to confirm response (correction within hours); PIVKA-II where available; treat the underlying cause. Functional supplementation: status markers (ucOC, dp-ucMGP) change over weeks; clinical-outcome monitoring (BMD, vascular indices) only over months-to-years against the conflicting-evidence backdrop of §6. Discontinuation: no taper or rebound for nutritional K1/K2NIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗; for VKA patients coordinate timing, and medical reversal of anticoagulation is handled by the prescribing clinician.

11. Nutrient Synergies

Key Takeaway

D3+K2 is mechanistically complementary but not proven on hard bone/CV outcomes (present as rationale, not benefit). Dietary fat aids absorption. Negative: high-dose vitamin E antagonizes — avoid stacking with anticoagulation.

Vitamin D3 + K2

mechanistically complementary (D drives Gla-protein expression; K carboxylates them), but hard-outcome benefit is not establishedDiederichsen et al. — AVADEC: vitamin K2 + D vs placebo on aortic valve calcification, RCT (Circulation 2022); PMID 35465686 view ↗ — present as rationale, not proven benefit.

Dietary Fat

improves absorption of this fat-soluble vitaminNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗.

Negative — High-Dose Vitamin E (and very high vitamin A)

antagonize vitamin K statusNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗; avoid stacking with anticoagulation.

Form Selection

all-trans MK-7 for long half-life; MK-4 needs mg-range dosing — forms are not interchangeable at equal microgram doses.

12. Lab Monitoring & Repletion

Key Takeaway

No single gold-standard status marker: plasma phylloquinone (recent intake), PIVKA-II (sensitive functional), %ucOC (skeletal), dp-ucMGP (vascular). PT/INR corrects after phytonadione but isn't a status screen. DCP tumor-marker caveat.

No single gold-standard status marker exists; a panel is used. Plasma phylloquinoneNIH Office of Dietary Supplements — Vitamin K: Fact Sheet for Health Professionals view ↗ reflects recent intake; PIVKA-IIMayo Clinic Laboratories — DCP (PIVKA-II) test information view ↗ is a sensitive functional marker that rises before PT; %ucOC indexes the skeletal compartment and dp-ucMGP the vascular compartmentGeng et al. — Vitamin K and vascular calcification in CKD: meta-analysis (Front Nutr 2023); PMID 36704782 view ↗.

PT/INR corrects after phytonadione (diagnostically useful) but is normal until factors fall, so it is not a status screen. Repletion: oral phytonadione for uncomplicated deficiency; parenteral when malabsorption/bleeding risk; prescription clotting-factor products for major bleeding (medical settings)Holbrook et al. — Evidence-based management of anticoagulant therapy, ACCP/CHEST 9th ed (Chest 2012); PMID 22315259 view ↗ (vitamin K acts over hours). Note the DCP/PIVKA-II tumor-marker caveatMayo Clinic Laboratories — DCP (PIVKA-II) test information view ↗ (§10c).

Status & Functional Markers

Marker	Sample	Reference	Reflects
Plasma phylloquinone (K1)	Serum / plasma	<0.15 ug/L supports deficiency (lab-dependent)	Recent dietary intake
PIVKA-II / DCP	Serum / plasma	Low / undetectable normally (lab-dependent)	Hepatic status; sensitive functional marker (rises before PT); also an HCC tumor marker
%ucOC (undercarboxylated osteocalcin)	Serum	Lab-dependent (higher = poorer status)	Skeletal compartment status
dp-ucMGP	Plasma	Lab-dependent (higher = poorer status)	Vascular compartment status
PT / INR	Citrated plasma	INR ~0.8–1.1 (untreated)	Functional clotting-factor activity / warfarin effect; not a status screen (late indicator)

13. Traditional Medicine

Key Takeaway

A modern isolate (1929) — no traditional system used 'vitamin K' as a concept; this section is not applicable as inherited therapeutic knowledge. Traditional foods (natto, greens) supplied it incidentally.

Vitamin K is a modern isolate (discovered 1929)Nobel Prize in Physiology or Medicine 1943 (Dam & Doisy) — discovery of vitamin K, so traditional systems (TCM, Ayurveda, Unani, Western herbalism) did not employ “vitamin K” — this section is largely not applicable as inherited therapeutic knowledge. Traditional diets supplied it incidentally (natto is exceptionally MK-7-rich; greens/fermented cheeses supplied K1/K2); recognition of these as vitamin K sources is retrospective and modern.

14. Quality Control

Key Takeaway

Prefer all-trans MK-7 and USP-grade phytonadione; degrades with light and alkaline minerals; menadione prohibited for human use; EFSA authorizes only bone + coagulation claims; DSHEA disclaimer required.

Forms & potency: prefer all-trans MK-7 (cis is inactive) and USP-grade phytonadioneMarles, Roe & Oketch-Rabah — USP safety evaluation of menaquinone-7 (Nutr Rev 2017); PMID 28838081 view ↗; oil-based/microencapsulated forms improve stability.
Stability: vitamin K degrades with light and co-formulated alkaline minerals — favor tested products.
Contaminants/regulatory: menadione not permitted for human useFDA — 21 CFR 573.620 (menadione permitted in animal feed only); EFSA authorizes only bone and blood-coagulation claimsEFSA — Dietary Reference Values for vitamin K (Scientific Opinion, 2017) view ↗ (CV claims not authorized); US structure/function claims require the DSHEA disclaimerFDA — 21 CFR 101.93 (DSHEA structure/function claim disclaimer).

✓ Last Reviewed: June 2026

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.