Vitamin K — Health Benefits, Food Sources, Uses, & Dosage
Introduction
Vitamin K is a fat-soluble vitamin found in certain foods and available as a supplement. Vitamin K is found in three forms:
- Vitamin K1 (phylloquinone): Vitamin K1 is mainly found in green leafy vegetables as it is directly involved in photosynthesis and is the main dietary form of the vitamin; intestinal microbiota can also produce it in small quantities (1, 2).
- Vitamin K2 (menaquinone): Vitamin K2 is mainly produced by gut bacteria and can also be found in several animal-based and fermented foods (1). Vitamin K2 differs from vitamin K1 due to a 3-substituted lipophilic side chain (2).
- Vitamin K3 (menadione): Vitamin K3 is a synthetic water-soluble form of vitamin K shown to damage liver cells in laboratory studies. Due to its toxicity, it is no longer available for use in humans (1, 3).
Vitamin K plays a major role in the organism as a coenzyme for vitamin K-dependent carboxylase required to synthesize several proteins crucial for hemostasis (blood clotting), bone metabolism, and more (1, 4).
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Absorption & Metabolism
Like dietary fats and fat-soluble vitamins A, D, and E, consumed vitamin K is incorporated into mixed micelles (via the action of bile and pancreatic enzymes) and absorbed in the small intestine. Afterward, vitamin K is incorporated into chylomicrons, transported to the liver, and repackaged into very low-density lipoproteins or VLDL cholesterol (1).
In the bloodstream, vitamin K is carried in lipoproteins; however, small amounts of the vitamin itself may also be found. The metabolism and excretion of vitamin K are rapid, accounting for the vitamin’s low blood levels and tissue stores. The organism absorbs only 30-40% of vitamin K and excretes 20% in the urine and 40-50% in the feces (1).
Some amounts of vitamin K are produced by gut bacteria, and the absorption and transport of this vitamin K are not fully understood. Research indicates substantial quantities of vitamin K2 are found in the large intestines. The amount of vitamin K obtained in this manner is unclear; researchers believe that this vitamin K2 may satisfy at least some of the body’s requirements for the vitamin (1).
Vitamin K is stored mainly in the liver and can also be found in bones, brain, heart, and pancreas (1, 5).
Recommended Intakes
Around 97-98% of healthy people meet the recommended daily vitamin K levels (5).
According to the 2020–2025 Dietary Guidelines for Americans, the recommended daily value for vitamin K is 90 mcg for women and 120 mcg for men over 18 (6).
The recommended daily value of vitamin K for 9-13-year-olds is 60 mcg; for 14-18-year-olds, it is 75 mcg (6).
Food Sources
The primary dietary sources of vitamin K are green leafy vegetables. The table below demonstrates the vitamin K levels of several foods (per 100g serving).
| Spinach | 493.6 mcg |
| Collard greens | 406.6 mcg |
| Turnip greens | 367.6 mcg |
| Kale | 817 mcg |
| Broccoli | 101.6 mcg |
| Brussels sprouts | 177 mcg |
| Mustard greens | 592.7 mcg |
| Parsley, fresh | 1640 mcg |
| Natto | 23.1 mcg |
| Canola oil | 71.3 mcg |
| Olive oil | 60.2 µg |
| Soybean oil | 24.7 mcg |
Some vitamin K levels can also be found in other vegetables, meat, liver, soy products, eggs, nuts, cereals, and oils (5).
Vitamin K on Human Health
Coagulation
Vitamin K is required for the biosynthesis of vitamin K-dependent clotting factors in the liver. It is required to synthesize pro-hemorrhagic factors FII (prothrombin, clotting factor II), FVII, FIX, and FX, and antithrombotic proteins C and S. Vitamin K is also a co-factor for vitamin K-dependent carboxylation, including various enzymes and allowing the coagulation factors to bind calcium ions, facilitating the cascade pathways. Vitamin K deficiency impairs the coagulation cascades and increases the risk of bleeding (1, 2, 4).
Usually, those who take anticoagulants or have bleeding disorders routinely assess vitamin K status. The clinically significant indicator of vitamin K status is prothrombin time (blood clotting time).
Osteoporosis
Osteopenia is defined by low bone mineral density or low bone mass, and osteoporosis is defined by porous and fragile bones, increasing the risk of sudden fractures. Even though consuming adequate amounts of calcium and vitamin D minimizes the risk of osteoporosis, adequate vitamin K intake may also play a role in reducing the risk.
Vitamin K is a cofactor for the gamma-carboxylation of many proteins, including osteocalcin, one of the main proteins involved in bone mineralization. Some research found an association between high undercarboxylated osteocalcin levels and lower bone mineral density. Some studies link higher vitamin K intake with higher bone mineral density and lower hip fracture incidence (1).
Coronary Heart Disease
Vascular calcification (pathological deposition of minerals in the vascular system) is a risk factor for coronary heart disease as it affects vascular elasticity.
A vitamin K-dependent protein called matrix Gla-protein (MGP) is found in vascular smooth muscle, bone, and cartilage. MGP may play a role in preventing vascular calcification. According to a hypothesis, inadequate vitamin K levels lead to undercarboxylated MGP, potentially increasing the risk of vascular calcification and coronary heart disease (1).
Alzheimer’s disease & Inflammation
A study connected the scientific research and clinical studies of vitamin K2 and the pathogenesis of Alzheimer’s disease. A study concluded that there may be evidence that vitamin K2 slows the progression of Alzheimer's disease and potentially contributes to its prevention. The potential mechanism may be due to the vitamin’s antioxidant effects and suppression of proinflammatory agents, leading to decreased neuroinflammation and neurodegeneration (7, 8).
Vitamin K Deficiency
Low vitamin K levels are almost impossible in healthy people with healthy dietary habits. Vitamin K deficiency is rarely symptomatic; minimal or trivial traumas may cause bleeding and hemorrhage. As vitamin K is required for bone mineralization, its deficiency may contribute to osteoporosis (1, 9).
Vitamin K deficiency can occur during the first weeks of infancy due to low placental transfer, low vitamin content of breast milk, and low bacterial synthesis, causing vitamin K deficiency bleeding (VKDB), a classic hemorrhagic disease of the newborn (1, 9).
Clinically significant vitamin K deficiency in adults is associated with certain disorders and diseases. Conditions that may lead to vitamin K deficiency (1, 10):
- Chronic illness
- Malnutrition (poor nutrition)
- Alcoholism
- Multiple abdominal surgeries
- Long-term parenteral nutrition
- Malabsorption (difficulty in the digestion or absorption of nutrients): cystic fibrosis, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), celiac disease, chronic pancreatitis, biliary obstruction, primary biliary cholangitis or cirrhosis, short bowel syndrome
- Liver diseases
- Disseminated intravascular coagulation (DIC)
- Polycythemia vera
- Nephrotic syndrome
- Leukemia
Vitamin K Toxicity & Allergy
No known toxicity is associated with high doses of vitamin K; thus, there is no maximal daily intake dose.
Allergy to vitamin K may be present, milder during oral administration and potentially severe during intravenous administration. There is a documented association between intravenous vitamin K1 administration and bronchospasm and cardiac arrest (2).
According to studies, higher vitamin K2 intake does not increase the risk of blood clots (2).
Vitamin K3 is very toxic and may cause allergic reactions, hemolytic anemia, and death of the liver cells (2).
Contraindications
Vitamin K should be used cautiously in neonates, people with hereditary hypoprothrombinemia, kidney disease, cases of over-anticoagulation caused by heparins, and hypersensitivity to the vitamin (2).
Interactions With Medications
Interactions between vitamin K and several medications have been observed.
Warfarin and Similar Anticoagulants
Vitamin K is involved in blood clotting, whereas Warfarin (Coumadin) and several anticoagulants, such as phenprocoumon, acenocoumarol, and tioclomarol, have the opposite effects - they slow the clotting process.
Maintaining a consistent daily intake of vitamin K from food and supplements is recommended to avoid bleeding or making blood clots (1).
Antibiotics
Antibiotics, particularly cephalosporin antibiotics, may destroy vitamin K-producing bacteria in the gut while also inhibiting vitamin K’s action in the body.
Vitamin K supplements are rarely needed, mainly when the antibiotics are used beyond several weeks and accompanied by inadequate vitamin K intake (1).
Bile Acid Sequestrants
Bile acid sequestrants, such as cholestyramine (Questran) and colestipol (Colestid), prevent the reabsorption of bile acids, thus reducing the absorption of fat-soluble vitamins such as vitamin K. Its clinical significance is yet unclear; however, it is suggested that vitamin K status be monitored in people taking these medications for many years (1).
Orlistat
Orlistat is a weight-loss drug that reduces the absorption of dietary fat, and consequently, the absorption of fat-soluble vitamins may also be reduced. The combination of orlistat and warfarin therapy may significantly increase prothrombin time and the risk of bleeding. Otherwise, the effect of orlistat on vitamin K is insignificant; nevertheless, clinicians may recommend a multivitamin supplement containing vitamin K (1).
Other Medications
Salicylates (such as aspirin), anticonvulsants (such as phenytoin, barbiturates, carbamazepine), sulfonamides (such as sulfasalazine acetazolamide xr), antituberculosis medication (eg, rifampin, isoniazid), high doses of vitamins A and E and mineral oils (10).
Summary
Vitamin K is a fat-soluble vitamin found in green leafy vegetables in large amounts and available as a supplement. Vitamin K can be found in three forms: Vitamin K1 or phylloquinone (mainly found in leafy green vegetables), vitamin K2 or menaquinone (produced by gut bacteria), and vitamin K3 or menadione (considered toxic and not available as a supplement).
Vitamin K is required to synthesize several proteins crucial for blood clotting, bone metabolism, and more.
Several medications, such as warfarin and other anticoagulants, antibiotics (cephalosporins), bile acid sequestrants, and orlistat, may interact with vitamin K, reducing its absorption.
References
- https://ods.od.nih.gov/factsheets/VitaminK-HealthProfessional/
- https://www.ncbi.nlm.nih.gov/books/NBK551578/
- https://emedicine.medscape.com/article/2088738
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714837
- https://medlineplus.gov/ency/article/002407.htm
- Dietary Guidelines for Americans, 2020-2025
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308377/
- https://www.mdpi.com/2072-6643/12/1/138
- https://emedicine.medscape.com/article/126354-overview
- https://emedicine.medscape.com/article/2088738-overview
