Dietary Vitamin K

Overview

Vitamin K refers to a group of fat-soluble vitamins with a common 2-methyl-1,4-naphthoquinone structure. The two main dietary forms are vitamin K1 (phylloquinone), found in green leafy vegetables, and vitamin K2 (menaquinones, MK-n), produced by bacteria and found in fermented foods and animal products. Vitamin K serves as an essential cofactor for gamma-carboxylation of specific proteins involved in coagulation and bone metabolism. HealthKit tracks dietary vitamin K intake in micrograms.

Biological Functions

Vitamin K is essential for the post-translational modification (gamma-carboxylation) of vitamin K-dependent proteins:

• Blood coagulation: Activates clotting factors II (prothrombin), VII, IX, and X, as well as anticoagulant proteins C, S, and Z
• Bone metabolism: Activates osteocalcin (bone Gla protein), essential for calcium binding to bone matrix; activates matrix Gla protein (MGP), inhibiting soft tissue calcification
• Vascular health: Matrix Gla protein prevents arterial calcification
• Cell signaling: Emerging roles in cell proliferation, apoptosis, and inflammation
• Brain function: Involved in sphingolipid metabolism; potential neuroprotective effects

Vitamin K cycle: Vitamin K is recycled through the vitamin K epoxide reductase (VKORC1) pathway, allowing small dietary amounts to sustain coagulation function. Warfarin inhibits this cycle.

Health Significance

Adequate vitamin K is essential for proper blood clotting and is increasingly recognized for its role in bone and cardiovascular health. Clinical deficiency causing bleeding is rare in adults but is a concern in newborns. The interaction between vitamin K and anticoagulant therapy is critically important in clinical practice.

Clinical Interpretation Guidelines

When reviewing patient vitamin K intake data:

• Critical for warfarin patients: Vitamin K intake directly affects INR; consistent daily intake is essential
• Assess dietary sources: Dark green leafy vegetables are the primary source
• Consider K1 vs K2: Most food databases report primarily K1; K2 from fermented foods may not be captured
• Evaluate antibiotic use: Prolonged antibiotics can reduce gut bacterial K2 synthesis
• Note malabsorption conditions: Fat malabsorption significantly impacts vitamin K status
• Review bleeding symptoms: Unexplained bruising or bleeding may indicate deficiency

Deficiency

Clinical vitamin K deficiency is rare in adults due to:

• Wide distribution in foods
• Gut bacterial synthesis of vitamin K2
• Efficient recycling via the vitamin K cycle
• Low daily requirements

Symptoms and conditions (when deficiency occurs):

• Prolonged prothrombin time (PT) and elevated INR
• Easy bruising
• Bleeding from mucous membranes, GI tract, or wounds
• Hemorrhagic disease of the newborn (VKDB)
• Increased risk of osteoporosis and fractures (with chronic low status)

Vitamin K Deficiency Bleeding (VKDB) in newborns:

• Early (0-24 hours): Rare, associated with maternal medications
• Classical (1-7 days): Presents as GI, umbilical, or circumcision bleeding
• Late (2-12 weeks): Often presents as intracranial hemorrhage; associated with exclusive breastfeeding without prophylaxis

At-risk populations:

• Newborns (especially exclusively breastfed without prophylaxis)
• Patients with fat malabsorption (cystic fibrosis, celiac disease, cholestatic liver disease, short bowel)
• Patients on prolonged antibiotic therapy
• Those with liver disease (reduced clotting factor synthesis)
• Patients receiving total parenteral nutrition without vitamin K
• Those taking vitamin K antagonists (warfarin)
• Individuals with very restricted diets avoiding green vegetables

Toxicity/Excess

No Tolerable Upper Intake Level (UL) has been established for vitamin K due to lack of documented toxicity.

Safety profile of K1 and K2:

• No adverse effects reported from high dietary or supplemental intake of K1 or K2
• Large doses do not affect coagulation in individuals not on anticoagulants
• Does not cause hypercoagulability or increased thrombosis risk in healthy individuals

Menadione (synthetic K3) concerns:

• Water-soluble synthetic form not recommended for human use
• Can cause hemolytic anemia, hyperbilirubinemia, and liver toxicity
• Not present in food or standard supplements

Clinical note: While K1 and K2 are safe, patients on warfarin must avoid sudden large changes in vitamin K intake as this will affect INR stability.

Food Sources

Vitamin K1 (phylloquinone) - excellent sources:

• Kale (1 cup raw: ~472 mcg)
• Spinach (1 cup raw: ~145 mcg; cooked: ~888 mcg)
• Collard greens (1/2 cup cooked: ~530 mcg)
• Swiss chard (1 cup raw: ~299 mcg)
• Broccoli (1/2 cup cooked: ~110 mcg)
• Brussels sprouts (1/2 cup cooked: ~109 mcg)
• Lettuce, green leaf (1 cup: ~46 mcg)
• Parsley (1/4 cup: ~246 mcg)
• Green peas (1/2 cup: ~21 mcg)

Vitamin K1 - other sources:

• Vegetable oils: Soybean oil (1 tbsp: ~25 mcg), canola oil (~16 mcg)
• Green beans, asparagus, cabbage
• Kiwi, avocado (small amounts)

Vitamin K2 (menaquinones):

• Natto (fermented soybeans): Exceptionally high (~1000 mcg MK-7 per 100g)
• Hard and soft cheeses (~50-75 mcg/100g, varies widely)
• Egg yolks (~32 mcg/100g)
• Chicken, beef liver (modest amounts)
• Butter (small amounts)
• Fermented vegetables (sauerkraut - varies)

Bioavailability considerations:

• K1 absorption is 5-10% from raw vegetables; improves with cooking and dietary fat
• K2 (especially longer-chain MK-7) has better absorption and longer half-life than K1
• Requires dietary fat for optimal absorption
• Gut bacteria produce MK-7 through MK-13, but contribution to human requirements is unclear

Special Populations

Newborns: AAP and WHO recommend prophylactic vitamin K injection at birth (0.5-1 mg IM) to prevent VKDB. Oral regimens are less effective but used in some countries. Exclusively breastfed infants are at highest risk (breast milk is low in vitamin K).

Pregnancy: AI is 75-90 mcg (same as non-pregnant women of same age). No evidence that pregnancy increases requirements. Some medications crossing the placenta may affect fetal vitamin K status.

Lactation: Breast milk is relatively low in vitamin K regardless of maternal intake. Maternal supplementation modestly increases breast milk content but does not eliminate need for infant prophylaxis.

Elderly: May benefit from adequate vitamin K for bone health. Some research suggests higher vitamin K intake is associated with reduced fracture risk and cardiovascular calcification, though evidence is evolving.

Patients on warfarin: CRITICAL - must maintain consistent vitamin K intake, not eliminate it. Sudden large increases or decreases in vitamin K intake cause INR instability. Education should emphasize consistency rather than avoidance. Typical target: 80-120 mcg/day with minimal variation.

Patients with osteoporosis: Some evidence supports vitamin K2 (especially MK-4 and MK-7) for bone health, but results are mixed. Japan has approved high-dose MK-4 for osteoporosis treatment.

Drug Interactions

Vitamin K antagonists (most critical interaction):

• Warfarin (and other coumarins): Inhibits VKORC1, blocking vitamin K recycling
  • Dietary vitamin K directly opposes warfarin effect
  • Sudden increase in vitamin K intake decreases INR (increased clotting)
  • Sudden decrease in vitamin K intake increases INR (bleeding risk)
  • Management: Maintain consistent daily intake; avoid dramatic changes
• Large doses of vitamin K can reverse warfarin anticoagulation

Drugs that decrease vitamin K status:

• Broad-spectrum antibiotics: Reduce gut bacterial vitamin K synthesis (especially prolonged use)
• Cholestyramine and colestipol: Reduce fat-soluble vitamin absorption
• Orlistat: Decreases fat absorption
• Anticonvulsants: Some may interfere with vitamin K metabolism
• High-dose vitamin A or E: May interfere with vitamin K function at very high doses

Drugs potentially affected by vitamin K:

• Aspirin and other antiplatelet agents: Vitamin K does not directly interact but both affect hemostasis
• Direct oral anticoagulants (DOACs): Rivaroxaban, apixaban, edoxaban, dabigatran - do NOT interact with vitamin K (do not inhibit VKORC1)

Clinical notes for warfarin management:

• Do not advise patients to avoid green vegetables; advise consistency
• If INR is subtherapeutic, assess for recent increase in vitamin K intake
• If INR is supratherapeutic, assess for recent decrease in vitamin K intake or antibiotic use

Caveats & Limitations

• HealthKit data reflects user-reported intake, not vitamin K status or clotting function
• Most food databases emphasize K1; K2 content often incomplete or missing
• Gut bacterial synthesis contributes variably to vitamin K status and is not captured
• Individual vitamin K needs vary based on genetic polymorphisms (VKORC1, CYP4F2)
• Accuracy depends on logging completeness, particularly of green vegetables
• Cannot determine if intake is adequate without clinical assessment (PT/INR if concerns)
• For warfarin patients, daily consistency matters more than absolute amount