The “K” in vitamin K is derived from the Danish and German “koagulation,” emphasizing its role in the coagulation process. The human body relies on vitamin K for blood coagulation and the regulation of calcium binding in bones and tissues.

Vitamin K deficiency is often seen in 8 percent to 31 percent of healthy adults but seldom leads to significant bleeding. Clinically significant bleeding is more likely in individuals with malabsorption syndromes, liver disease, or those taking medications that work via disrupting vitamin K metabolism (blood thinners like warfarin).

Furthermore, following an extremely low-fat diet is not ideal for vitamin K absorption, as this vitamin is better absorbed when consumed with fat. Ingesting a lot of mineral oil, sometimes used for constipation, might also diminish vitamin K absorption.

Symptoms and signs of vitamin K deficiency include:

• Delayed blood clotting or an extended prothrombin time (demonstrated in a test)
• Bleeding or hemorrhaging
• Osteopenia, a condition characterized by lower-than-normal bone mineral density (BMD) but not low enough to be classified as osteoporosis
• Osteoporosis
• Easy bruising: Insufficient vitamin K can make the blood vessels more fragile, increasing the likelihood of easy bruising.
• Heavier menstrual periods
• Blood in the urine
• Increased difficulty stopping bleeding after an injury or surgery
• Impaired scabbing
• Poor bone development

Complications

Complications of vitamin K deficiency include:

• • Bleeding disorders: Vitamin K deficiency can lead to uncontrolled bleeding and different bleeding disorders, including vitamin K deficiency bleeding (VKDB), which results in bleeding inside or outside the body of newborn babies. Internal bleeding, such as into the intestines or brain, can be challenging to detect. Babies without the vitamin K shot at birth can develop VKDB up to the age of 6 months with potentially devastating consequences. For instance, according to the U.S. Centers for Disease Control and Prevention (CDC), 20 percent of infants with VKDB don’t survive. Up to 50 percent who bleed after the first few weeks will bleed into the brain and risk having permanent brain damage.
  • Impaired bone development
  • Potential cardiovascular problems: Such problems include arterial calcification and vascular stiffness.

The body metabolizes vitamin K through a process that involves absorption, transportation, and utilization, including the following steps:

• As a fat-soluble vitamin, vitamin K’s absorption primarily occurs in the small intestine in the presence of dietary fats. The liver obtains vitamin K after it is absorbed via the small intestine. The liver then metabolizes the vitamin into various necessary clotting factors or stores it. From there, it gets incorporated into chylomicrons, assisting its absorption into the lymphatic system and blood vessels that lead to the liver.
• Some vitamin K is transported from the liver into the bloodstream, bound to lipoproteins. It is then delivered to various tissues and organs.
• While some excess vitamin K can be reabsorbed in the small intestine, the remainder is excreted in stool or urine.

The following are what vitamin K does for your body:

• Blood clotting: Vitamin K, often referred to as the clotting vitamin, is crucial for the production of clotting factors in the liver, which play a vital role in blood clotting, thus preventing continuous bleeding and facilitating wound healing. Maintaining a predictable intake of vitamin K is particularly important for individuals on anticoagulant medications such as warfarin, as significant fluctuations in intake can impact prothrombin time levels and potentially interfere with the effectiveness of the medication.
• Bone health: Vitamin K is essential for the production of bone proteins, including osteocalcin, which helps prevent bone weakening. Higher vitamin K intake is associated with a lower risk of hip fractures and less bone density loss, and low blood levels of vitamin K are linked with reduced bone density. However, clinical trials on vitamin K supplements and bone fractures have yielded conflicting results, possibly influenced by other factors such as calcium, vitamin D, and exercise, which may mask the potential benefits of vitamin K supplementation.
• Cardiovascular health: Vitamin K plays a role in the production of proteins that help prevent the calcification or hardening of heart arteries, a factor linked to heart disease. However, further studies are required before recommending a specific amount of vitamin K beyond the standard recommendation for addressing this condition.
• Better aging: Vitamin K is a micronutrient linked to protection against age-related diseases. While its known role involves the carboxylation of vitamin K-dependent proteins (VKDPs) in these diseases’ pathogenesis, vitamin K also acts as an anti-inflammatory by inhibiting inappropriate signaling of nuclear factor-kappa B, an ancient protein transcription factor that regulates innate immunity, and by providing protection against oxidative stress by preventing reactive oxygen species generation. Clinical evidence suggests that maintaining a high vitamin K status may offer protective effects in the inflammatory and mineralization processes associated with the development and progression of geriatric diseases.
• Cellular function regulation: Growth arrest-specific gene 6 protein (Gas6) is a vitamin K-dependent protein present in various body tissues such as the nervous system, heart, lungs, stomach, kidneys, and cartilage. Gas6 is implicated in cellular growth regulation and exhibits cell-signaling activities. Its roles span immune defense, cell adhesion, cell proliferation, and protection against cell death.

Vitamin K Prevents Certain Conditions

While adequate vitamin K intake is important for several aspects of health, and deficiency may lead to various health issues, it’s important to note that specific diseases are not solely prevented by vitamin K alone. Adequate vitamin K plays a role in preventing:

• Bleeding disorders
• Osteoporosis: Although vitamin K alone doesn’t prevent osteoporosis, maintaining proper levels supports overall bone health and optimal bone density. In Japan and some other countries, different types of vitamin K are commonly used as a treatment for osteoporosis.
• Diabetes: Vitamin K plays a crucial role in gamma-carboxylation, a form of carboxylation essential for various bodily functions. One significant aspect is its impact on beta cells, responsible for producing insulin, a vital hormone that regulates glucose levels. Diabetes can occur when there’s a shortage of beta cells or when they fail to produce sufficient insulin. Researchers have identified a new protein, ERGP, which relies on gamma-carboxylated vitamin K to function. This protein is vital for maintaining proper calcium levels in beta cells and preventing disruptions in insulin secretion. This is a discovery with potential implications for understanding and addressing diabetes.
• Cancer: Research on the impact of vitamin K on specific female malignancies, such as breast, cervical, and ovarian cancers, has mainly been conducted through lab and animal tests. In breast cancer, vitamin K has the potential to hinder cancer cell activity and impede tumor growth. In cervical cancer, it may trigger cancer cell death and inhibit tumor growth. In ovarian cancer, it can induce apoptotic cell death. Vitamin K2 has also been discovered to be able to inhibit the advancement of liver cancer. What’s more, human follow-up studies have shown a beneficial effect on prostate and pancreatic cancers.
• Geriatric diseases: Inadequate vitamin K intake may be a factor that increases the susceptibility to age-related conditions such as dementia, osteoporosis, and osteoarthritis.

There are three forms of vitamin K, including:

• Vitamin K1: Also called phylloquinone, vitamin K1 is predominantly found in foods, especially plants. It accounts for around 75 percent of total vitamin K dietary intake. In addition, phytonadione can be accessible for administration through oral, intravenous, subcutaneous, and intramuscular routes to treat vitamin K deficiency.
• Vitamin K2: Also known as menaquinone, vitamin K2 is synthesized by bacteria and yeast and is primarily present in animal or fermented products such as meat, cheese, and eggs. It can also be produced by gut microbiota. Menaquinones differ from phylloquinones in terms of their chemical structure, the body’s utilization of them, and their tissue distribution. The different subtypes of vitamin K2 include short-chain (including menaquinone-4 or MK-4) and long-chain (including MK-7, MK-8, and MK-9) menaquinones.
• Vitamin K3: Also called menadione, vitamin K3 is the artificial form of the vitamin. Menadione is industrially significant as an intermediate for phylloquinone synthesis. Since it transforms into the active K2 form within some animals’ bodies, it’s also used as an animal feed additive. In addition, menadione can also be used medically for humans.

Data on the bioavailability of various forms of vitamin K from food are limited. The absorption rate of free-form phylloquinone is about 80 percent, but its absorption rate from foods is much lower. Phylloquinone in plant foods is tightly bound to chloroplasts, making it less bioavailable than that from oils or supplements. For instance, the body absorbs only 4 percent to 17 percent as much phylloquinone from spinach as from a tablet. Consuming vegetables with some fat improves phylloquinone absorption, but it is still lower than that from oils.

Limited research suggests that long-chain MKs may have higher absorption rates than phylloquinone from green vegetables. In a comparative study between vitamin K1 and the subtype of K2, MK-7, both were readily absorbed within two hours after ingestion of vegetables and K2-rich food, respectively. However, postprandial serum concentrations of MK-7 were found to be 10-fold higher than K1. This is because one significant distinction between the two vitamin K forms is the notably greater half-life of MK-7, leading to more stable serum levels over time.

Dietary intake recommendations, including those for vitamin K and other nutrients, can be found in the Dietary Reference Intakes (DRIs), developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies.

As per the United Kingdom’s National Health Service (NHS), adults require around 1 microgram of vitamin K per day for each kilogram of their body weight. For instance, a person weighing 65 kilograms would need 65 micrograms daily.

Vitamin K supplements are offered in various forms, including capsules, tablets, liquid-filled capsules, solutions, and oil, with each containing different types of the vitamin. Due to the risk of side effects and potential interactions with medications, it is advisable to take vitamin K supplements only under the supervision of your doctor. The common types include the following:

• Vitamin K1 supplements contain the K1 form of the vitamin, including phylloquinone and phytonadione (a synthetic form of vitamin K1).
• Vitamin K2 supplements contain the K2 form (menaquinone), with subtype MK-4 or MK-7. MK-7 supplements are gaining popularity due to their higher bioavailability compared to other vitamin K forms, with increased sales and usage.
• Vitamin K complex supplements provide a combination of both vitamin K1 and K2 to offer a broader spectrum.
• Dietary supplements combining vitamin K and other nutrients: Vitamin K is also found in supplements in combination with other nutrients such as calcium, magnesium, or vitamin D. These supplements often offer a broader range of vitamin K doses compared to multivitamin supplements, with some providing very high amounts, such as 4,050 micrograms (5,063 percent of the daily value).
• Multivitamins: Many multivitamin supplements include vitamin K in their formulation, offering a mix of K1 and K2, typically at values less than 75 percent of the daily value.
• Vitamin K drops are liquid formulations of vitamin K, often used for infants or individuals who have difficulty swallowing pills.

The sale of vitamin K3 (menadione) as a human dietary supplement is prohibited in the United States due to documented instances of allergic reactions, hepatic cell damage, and other adverse events.

Vitamin K is found naturally in some foods, and most dietary intake in the United States comes from spinach, broccoli, iceberg lettuce, and lipids and oils, especially soybean and canola oils. As most diets in the United States offer a sufficient amount of vitamin K, most food products are not fortified with vitamin K, with the exception of some meal replacement shakes and bars. Infant formulas also contain supplemental vitamin K.

Vitamin K1 (Phylloquinone)

Phylloquinone is found in vegetables, particularly green leafy ones, vegetable oils, and certain fruits. The phylloquinone content in green vegetables is influenced by chlorophyll (a green pigment found in the cells of plants and other photosynthetic organisms) levels, with outer leaves having more phylloquinone than inner leaves. The absorption of phylloquinone from plant sources varies, and adding fat to a meal enhances its intestinal absorption. In addition, the hydrogenation of vegetable oils may decrease the absorption and biological effect of dietary phylloquinone.

• Spinach: Canned regular-pack spinach, including both solids and liquids (891 micrograms per cup)
• Turnip greens: Boiled and drained frozen turnip greens without salt (852 micrograms per cup)
• Garden cress: Raw garden cress (271 micrograms per cup)
• Broccoli: Boiled and drained frozen chopped broccoli (162 micrograms per cup)
• Kale: Raw (113 micrograms per cup)
• Soybean oil: 25 micrograms per tablespoon (A note of caution: Soybean has been genetically modified.)
• Lettuce: Raw iceberg lettuce (14 micrograms per cup)
• Canola oil: 10 micrograms per tablespoon (Note: Most commercially available canola oil comes from genetically modified crops.)
• Cashews: Dry roasted cashews (10 micrograms per ounce)

Vitamin K2 (Menaquinone)

Meat, dairy, and eggs have low levels of phylloquinone but contain moderate amounts of menaquinones. Natto, a traditional Japanese fermented soybean food, is the richest in menaquinones, and other fermented foods such as cheese and sauerkraut also contain them. The forms and quantities of vitamin K2 in these foods may vary depending on bacterial strains and fermentation conditions. Poultry and pork products may contain MK-4 due to animals converting the menadione added to their feed.

• Natto provides MK-7 (850 micrograms per 3 ounces)
• Rotisserie chicken breast provides MK-4 (13 micrograms per 3 ounces)
• Cheddar cheese provides MK-4 (8 micrograms per 3 ounces)
• Braised chicken liver provides MK-4 (6 micrograms per 3 ounces)
• Roasted or pan-broiled ham provides MK-4 (4 micrograms per 3 ounces)
• Hard-boiled egg provides MK-4 (4 micrograms per 1 large egg)

To obtain sufficient vitamin K from your diet, you can consume vitamin K-rich foods, cook with soybean or canola oil, snack on cashews, and try the unique-tasting Japanese food natto.

In addition to obtaining vitamin K from dietary sources and supplements, another way to get vitamin K is through the gut microbiota’s synthesis of vitamin K2.

After the neonatal period, different bacterial species in the gut produce various forms of menaquinones, with bacteroides species producing MK-10 and MK-11, enterobacteria producing MK-8, veillonella species producing MK-7, and Eubacterium lentum producing MK-6.

Although these menaquinones are abundant in the gut, their tight binding to bacterial membranes and lipophilic nature severely limits their bioavailability, and the primary source of functionally available vitamin K2 is still the diet. Research indicates that a short-term reduction in dietary vitamin K intake is not compensated by intestinal menaquinones.

To promote the production of vitamin K2 by your gut bacteria, you can take the following steps:

• Consume fermented foods: Consuming fermented foods rich in beneficial bacteria can support the production of vitamin K2 by gut bacteria. Examples include sauerkraut, kimchi, natto, and kefir.
• Eat prebiotic foods: Prebiotics are non-digestible fibers or compounds found in certain foods that can be consumed by beneficial bacteria in the gut and promote their growth and activity. Foods such as garlic, onions, leeks, asparagus, and bananas are good sources of prebiotics.
• Diversify your diet: A diverse and balanced diet supports a variety of gut bacteria, which may contribute to vitamin K2 production.
• Avoid overuse of antibiotics: Antibiotics can disrupt the balance of gut bacteria and destroy vitamin K-producing gut bacteria. Use antibiotics only when necessary and as prescribed by your doctor.
• Consider probiotic supplements: Probiotic supplements contain live beneficial bacteria.

A frequently used approach to assess vitamin K blood levels is by measuring prothrombin time (PT), which indicates the duration it takes for blood to coagulate.

Some hospitals directly measure serum vitamin K levels for more precise detection. In healthy individuals with sufficient vitamin K intake (50 to 150 micrograms daily), serum vitamin K1 ranges from 0.2 to 1.0 nanograms per milliliter. The timing of vitamin K intake helps in interpreting serum levels, with recent intake affecting serum vitamin K levels but not levels in tissues.

To correct a prolonged blood clotting time in adults, phytonadione (vitamin K1) can be given orally, under the skin, intramuscularly, or very slowly intravenously. The typical dose is 1 to 20 mg, and if needed, it can be repeated in 6 to 8 hours. For non-emergency situations in patients taking anticoagulants or for partial corrections, lower doses may be appropriate.

In infants with bleeding due to vitamin K deficiency, a single dose of 1 mg phytonadione under the skin or in the muscle is usually effective, and more may be given if needed.

In addition, while rare, giving phytonadione through an IV can lead to severe allergic reactions.

High-Risk Populations

Those at a higher risk for vitamin K deficiency include:

• Breastfed infants: Some develop a condition called vitamin K deficiency bleeding (VKDB), which has serious consequences such as life-threatening bleeding and death. Increasing the maternal dietary intake of vitamin K to 5 milligrams per day can enhance the relatively low vitamin K content in breast milk.
• Babies who didn’t receive a vitamin K shot at birth: Administering a vitamin K shot into the thigh muscle is one way to prevent vitamin K deficiency and VKDB in newborns. However, there has been some parental resistance to the shot due to safety concerns, more recently coinciding with a dip in childhood vaccinations.
• Babies whose mothers used specific medications during pregnancy:  Medications such as isoniazid and seizure medicines can interfere with the body’s utilization of vitamin K. Some health care providers suggest that pregnant women on anti-seizure medications take oral phytonadione (vitamin K1), either 10 milligrams once daily for one month or 20 milligrams once daily for two weeks leading up to delivery.
• People with liver disease: They have difficulty using stored vitamin K due to liver issues.
• People with malabsorption disorders, diarrhea, celiac disease, or cystic fibrosis

Vitamin K toxicity is very rare. There is no identified toxicity linked to elevated doses, whether obtained through diet or supplements, of vitamin K1 (phylloquinone) or vitamin K2 (menaquinone). For instance, vitamin K1 doses of up to 50 mg have been administered without any safety issues, though some sources say 25 to 30 milligrams is considered an extremely high amount. Vitamin K is rapidly metabolized and removed from the body through urine or stool, preventing it from reaching toxic levels even with high intakes, unlike some other fat-soluble vitamins. Therefore, no specific Tolerable Upper Intake Level (UL) has been established for vitamin K.

The only reported toxicity of vitamin K is associated with menadione (vitamin K3), which is not used in humans. Menadione toxicity is linked to its water-soluble properties, and the mechanism involves increased oxygen uptake in the liver, leading to lipid peroxidation (a process in which free radicals steal electrons from the lipids in cell membranes and result in cell damage) and hepatic cell damage.

Vitamin K3 toxicity can cause the following:

• Jaundice is a condition characterized by yellowing of the skin, mucous membranes, and eyes. It occurs when there is an excess of bilirubin, a yellow pigment produced during the breakdown of red blood cells, in the bloodstream.
• Hyperbilirubinemia refers to elevated levels of bilirubin in the blood.
• Hemolytic anemia is a type of anemia that occurs when red blood cells are destroyed more rapidly than the body can replace them. This increased destruction of red blood cells can lead to elevated bilirubin levels and, subsequently, jaundice.
• Kernicterus is a severe form of brain damage and may result in symptoms such as decreased movement, loss of appetite, seizures, deafness, mental retardation, and, in extreme cases, death. This condition is linked to elevated levels of bilirubin in the brain tissues.

Due to the associated risks, vitamin K3 is no longer sold over the counter.

Side Effects

Both vitamin K1 and vitamin K2 can potentially cause allergic reactions. Vitamin K1 has been associated with bronchospasm (a sudden constriction of the muscles in the walls of the bronchioles) and cardiac arrest when administered intravenously (IV). This is thought to be due to the solvent necessary for injection. On the other hand, oral forms of vitamin K1 or K2 have a high safety profile. It is difficult to find any reported severe reactions. 

Most adverse effects of vitamin K1 are associated with intravenous (IV), subcutaneous, and intramuscular administration, including dyspnea (difficulty breathing), chest tightness, and reactions at the injection site. Other allergic reactions include skin rash, itching and swelling (particularly of the face, tongue, or throat), and severe dizziness.

Prohibited in the United States, vitamin K3 is also capable of engaging in reduction-oxidation reactions and producing reactive oxygen species (ROS). This process can result in damage to DNA and other macromolecules.

People who should avoid vitamin K include:

• Individuals with Glucose-6-phosphate dehydrogenase (G6PD) deficiency should avoid injectable vitamin K, as it may trigger hemolysis, which is the destruction of red blood cells. There is not consistent evidence of any difficulty with dietary or oral forms.
• Those taking warfarin should avoid vitamin K due to possible interactions.
• Individuals undergoing dialysis for kidney diseases should consult their doctors before taking vitamin K, as it may have adverse effects.

Interactions with the following may occur while supplementing with vitamin K:

• Anticoagulants: For individuals taking vitamin K antagonists such as the blood-thinner warfarin, excessive intake of vitamin K may weaken the medications’ anticoagulant effect. Even low daily doses of MK-7 (10 to 20 micrograms) may affect anticoagulant stability. However, it is still advised for individuals on warfarin to aim for the recommended vitamin K intake (90 to 120 micrograms per day) and avoid significant vitamin K level fluctuations that could impact anticoagulant dose adjustment.
• Antibiotics: Antibiotics, especially cephalosporins such as cefoperazone, can eliminate vitamin K-producing gut bacteria, potentially lowering vitamin K levels. However, vitamin K supplements are generally unnecessary unless antibiotic use is prolonged and accompanied by inadequate vitamin K intake.
• Anticonvulsants and anti-TB drugs: The use of anti-vitamin K anticoagulants, anticonvulsants (e.g. phenytoin), and anti-tuberculosis drugs (e.g. rifampin and isoniazid) during pregnancy or breastfeeding may increase the risk of vitamin K deficiency in the newborn as they compete for its natural metabolism.
• Cholesterol-lowering medications: The use of cholesterol-lowering medications, such as cholestyramine and colestipol, may interfere with fat absorption and impact the absorption of vitamin K. They are also called bile acid sequestrants, since they achieve a lowered cholesterol level by preventing reabsorption of bile acids. Other substances with similar effects include mineral oil and the fat substitute olestra. The Food and Drug Administration mandates the addition of vitamin K and other fat-soluble vitamins (A, D, and E) to food products containing olestra.
• Orlistat: Orlistat, a weight-loss drug, may also interfere with fat absorption and vitamin K absorption, thus lowering the vitamin K level in the body. Patients prescribed orlistat are often advised to supplement it with a multivitamin containing fat-soluble vitamins.
• Vitamin A: An excessive amount of vitamin A seems to disrupt the absorption of vitamin K.
• Vitamin E: Vitamin E may hinder the activity of vitamin K-dependent carboxylase and disrupt the coagulation cascade. A study showed that supplementing with 1,000 IU/day of vitamin E for 12 weeks reduced the gamma-carboxylation of prothrombin, a vitamin K-dependent protein. Therefore, people deficient in vitamin K should avoid vitamin E supplements without medical supervision due to the increased risk of hemorrhage.
• Vitamin D: Vitamin K collaborates with vitamin D to maintain adequate calcium levels in bones, contributing to optimal bone growth and health. A well-balanced intake of these micronutrients is crucial for this synergistic effect.

The controversies surrounding vitamin K intake and supplementation include the following:

Optimal Intakes

Currently, there’s insufficient data available to establish a Recommended Dietary Allowance (RDA) or Estimated Average Requirement (EAR) for the daily intake of vitamin K. And the public uses a set of Adequate Intakes (AIs) for the time being. However, it remains uncertain whether the existing AIs for vitamin K are sufficient to maximize the gamma-carboxylation of vitamin K-dependent proteins in bones or to prevent osteoporosis. Also, additional research is needed before suggesting a precise dosage of vitamin K beyond the AIs to assist in preventing the calcification or hardening of heart arteries. In addition, individual variability should also play a role in determining the optimal vitamin K intakes for each person. For instance, genetic variations may influence how individuals metabolize and utilize vitamin K; age, overall health, and certain medical conditions may affect the body’s vitamin K requirements; and personal dietary habits may influence the vitamin K supplementation needed.

Most Effective Forms

Vitamin K1 and different subtypes of vitamin K2 are found in various foods. There’s ongoing debate regarding the effectiveness and bioavailability of these different forms. Although vitamin K1 is found in more abundance in the diet, vitamin K2 supplements have become popular. For instance, research indicates that vitamin K2 may be more effective in activating extra-hepatic vitamin K-dependent proteins compared to vitamin K1. And its subtype MK-7, in particular, exhibits greater bioavailability than other vitamin K forms.

Newborn Vitamin K Shots

The controversy regarding newborn vitamin K shots revolves around the administration of vitamin K injections to neonates, in order to prevent vitamin K deficiency bleeding (VKDB). The controversy arises from concerns about the necessity, safety, and potential side effects of the vitamin K injection. While some health care professionals argue that the injection is crucial to prevent VKDB and that the shots are considered safe and effective, some parents and groups express concerns about the use of injections in newborns, preferring alternative methods such as oral vitamin K supplementation. While some evidence suggests oral vitamin K given at birth reduces the chances of early-onset and classic VKDB, a single dose fails to prevent late-onset VKDB.

Specific parental concerns include worries about preservatives and the shots’ ingredients (e.g., aluminum), doubts about the necessity of intramuscular shots, and fears of high doses of injected vitamin K.