Group of vitamins and bacterial metabolites
Vitamin K2 or menaquinone (MK) (/ˌmɛnəˈkwɪnoʊn/) is one of three types of vitamin K, the other two being vitamin K1 (phylloquinone) and K3 (menadione). K2 is both a tissue and bacterial product (derived from vitamin K1 in both cases) and is usually found in animal products or fermented foods.
The number n of isoprenyl units in their side chain differs and ranges from 4 to 13, hence vitamin K2 consists of various forms. It is indicated as a suffix (-n), e. g. MK-7 or MK-9.
The most common in the human diet is the short-chain, water-soluble menatetrenone (MK-4), which is commonly found in animal products. However, at least one published study concluded that "MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels." The MK-4 in animal (including human) tissue is made from dietary plant vitamin K1. This process can be accomplished by animal tissues alone, as it proceeds in germ-free rodents.
Long-chain menaquinones (longer than MK-4) include MK-7, MK-8 and MK-9 and are more predominant in fermented foods such as natto and cheonggukjang. They are bioavailable: oral consumption of MK-7 "significantly increases serum MK-7 levels and therefore may be of particular importance for extrahepatic tissues".
Longer-chain menaquinones (MK-10 to MK-13) are produced by anaerobic bacteria in the colon, but they are not well absorbed at this level and have little physiological impact.
When there are no isoprenyl side chain units, the remaining molecule is vitamin K3. This is usually made synthetically, and is used in animal feed. It was formerly given to premature infants, but due to inadvertent toxicity in the form of hemolytic anemia and jaundice, it is no longer used for this purpose. K3 is now known to be a circulating intermediate in the animal production of MK-4: K1 is absorbed into the gut and converted into blood K3 and target tissues convert K3 into MK-4.
Safety at a Glance
- Toxicity: Vitamin K2 has no established tolerable upper intake level due to its very low toxicity. No adverse effects have been...
- Start with a low dose and wait for onset before redosing
- Test your substance with reagent kits when possible
- Never use alone — have a sober person present
If someone is in crisis, call 911 or Poison Control: 1-800-222-1222
Dosage
Oral
Duration
Oral
Total: 48 hrs – 72 hrsPharmacology
Vitamin K2 serves as a cofactor for gamma-glutamyl carboxylase, which converts specific glutamic acid residues in vitamin K-dependent proteins to gamma-carboxyglutamic acid (Gla) residues. These Gla residues enable calcium binding. Key K2-dependent proteins include: osteocalcin (produced by osteoblasts, directs calcium into bone matrix), matrix Gla protein (MGP, the most potent inhibitor of arterial calcification), Gas6 (Growth arrest-specific 6, involved in cell survival, myelination, and neuroprotection), and protein S (neuroprotective signaling through TAM receptors).
In the brain, vitamin K2 is present as MK-4, concentrated in the cerebral cortex, hippocampus, and striatum. MK-4 activates Gas6/TAM receptor signaling, which promotes oligodendrocyte survival and myelination, protects neurons from oxidative stress-induced apoptosis, and supports synaptic function. K2 also supports brain sphingolipid metabolism, as it is a cofactor for the production of sulfatides and gangliosides that are major components of myelin.
The menaquinone-7 (MK-7) form has a half-life of approximately 72 hours (compared to 1-2 hours for K1), providing sustained activation of extrahepatic K-dependent proteins. MK-4 has a shorter half-life but is the predominant form in the brain.
Interactions
No documented interactions.
History
Vitamin K was discovered in 1929 by Danish biochemist Henrik Dam, who observed that chicks fed a fat-extracted diet developed hemorrhagic disease. He named the factor Koagulationsvitamin (vitamin K). Dam shared the Nobel Prize in Physiology or Medicine in 1943 with Edward Doisy, who determined the chemical structure of vitamins K1 and K2.
The distinction between K1 and K2 was initially considered pharmacologically unimportant, as both support coagulation. The paradigm shifted with the discovery of non-coagulation vitamin K-dependent proteins. The identification of osteocalcin's K-dependence by Paul Price in 1980 and matrix Gla protein by Cees Vermeer's group in the 1990s established K2's unique roles in bone and vascular health.
The Rotterdam Study (2004), a large prospective cohort study, demonstrated that high dietary vitamin K2 (but not K1) intake was associated with significantly reduced coronary heart disease, aortic calcification, and all-cause mortality. This landmark finding established K2 as independently important for cardiovascular health and catalyzed the supplement industry's interest in K2.
Harm Reduction
Vitamin K2 is well-tolerated at standard supplement doses. The MK-7 form at 100-200mcg daily is the most commonly recommended. It is contraindicated in patients on warfarin or other vitamin K-dependent anticoagulants, as it directly counteracts the mechanism of these drugs and can cause dangerous clotting. Consult a physician before combining K2 with any blood-thinning medication. K2 is fat-soluble and should be taken with a meal containing dietary fat. There is no established upper limit for K2, but doses above 500mcg daily have limited additional benefit. Fermented foods like natto are natural dietary sources of MK-7.
Toxicity & Safety
Vitamin K2 has no established tolerable upper intake level due to its very low toxicity. No adverse effects have been reported at supplemental doses up to 45 mg/day MK-4 (used in Japanese osteoporosis treatment). Critical interaction: vitamin K antagonizes warfarin and other vitamin K antagonist anticoagulants. Patients on these medications must maintain consistent K intake and should consult their physician before supplementing.
Addiction Potential
No addiction potential.
Tolerance
| Full | Not applicable — nutritional supplement |
| Half | N/A |
| Zero | N/A |
Cross-tolerances
Legal Status
This substance is not a controlled or scheduled substance in any major jurisdiction. It is widely available as a dietary supplement, food additive, or over-the-counter product in the United States, United Kingdom, European Union, Canada, and Australia. In the US, it falls under the Dietary Supplement Health and Education Act (DSHEA) of 1994 and is regulated by the FDA as a dietary supplement rather than a drug. Manufacturers are responsible for ensuring safety and accurate labeling, but pre-market approval is not required.
In the European Union, it is regulated under the Food Supplements Directive (2002/46/EC) and may be subject to maximum permitted levels set by individual member states. In the United Kingdom, it falls under the Food Supplements (England) Regulations 2003 and similar devolved legislation. In Australia, it is typically listed on the Australian Register of Therapeutic Goods (ARTG) as a complementary medicine or is available as a food product. In Canada, it may be classified as a Natural Health Product (NHP) requiring a product license from Health Canada.
No prescription is required in any of these jurisdictions, and there are no criminal penalties associated with possession, purchase, or use.
Tips (6)
Take Vitamin K2 consistently at the same time each day for best results. Many vitamins and nutrients need to build up to steady-state levels before you notice benefits. Give it at least 2-4 weeks.
Quality varies enormously between Vitamin K2 supplement brands. Look for products with third-party testing (USP, NSF, ConsumerLab). Cheaper brands may contain fillers, incorrect doses, or contaminants.
Vitamin K2 is primarily important as a companion to vitamin D3 supplementation. D3 increases calcium absorption, while K2 activates proteins (osteocalcin and matrix GLA protein) that direct that calcium into bones rather than soft tissues. If you supplement D3, you almost certainly need K2.
Vitamin K2 comes in two main forms: MK-4 (short-acting, requires multiple daily doses of 1-5mg) and MK-7 (long-acting, effective at 100-200mcg once daily). MK-7 is generally preferred for supplementation due to its longer half-life and lower required dose. Both direct calcium to bones and away from arteries.
Vitamin K2 is generally safe, but it directly affects blood clotting through a different pathway than vitamin K1. If you are on warfarin or other vitamin K-sensitive anticoagulants, do NOT supplement K2 without consulting your doctor, as it can dangerously alter your INR levels.
Follow evidence-based dosing for Vitamin K2 rather than megadose protocols. More is not always better with supplements, and some have toxicity at high doses. The recommended daily allowance exists for a reason.
Community Discussions (1)
See Also
References (3)
- PubChem: Vitamin K2
PubChem compound page for Vitamin K2 (CID: 5282367)
pubchem - Vitamin K2 - TripSit Factsheet
TripSit factsheet for Vitamin K2
tripsit - Vitamin K2 - Wikipedia
Wikipedia article on Vitamin K2
wikipedia