Menaquinone-7 (MK-7) is the most bioavailable form of vitamin K2 that activates proteins directing calcium to bones while preventing arterial calcification, supporting both skeletal strength and cardiovascular health.
Alternative Names: MK-7, Vitamin K2-7, Vitamin K2 (MK-7)
Categories: Vitamin, Fat-soluble vitamin, Menaquinone
Primary Longevity Benefits
- Bone health
- Cardiovascular health
- Calcium regulation
- Arterial flexibility
Secondary Benefits
- Joint health
- Cognitive function
- Insulin sensitivity
- Reduced inflammation
- Dental health
- Skin health
Mechanism of Action
Menaquinone-7 (MK-7) is a long-chain form of vitamin K2 that functions as an essential cofactor for the enzyme gamma-glutamyl carboxylase, which activates vitamin K-dependent proteins through carboxylation. The primary mechanism of MK-7 revolves around its role in activating two critical proteins: osteocalcin and Matrix Gla Protein (MGP). When osteocalcin is carboxylated by MK-7, it gains the ability to bind calcium and incorporate it into the bone matrix, thereby promoting bone mineralization and strength. This process is crucial for maintaining bone density and reducing the risk of osteoporosis.
Simultaneously, MK-7 activates MGP, which serves as a potent inhibitor of vascular calcification. Activated MGP prevents calcium from depositing in arterial walls and soft tissues, instead directing it to bones where it belongs. This dual action creates what researchers call the ‘calcium paradox’ – ensuring calcium is deposited in bones (where it’s beneficial) rather than in arteries (where it’s harmful). MK-7’s long side chain of seven isoprenoid units gives it superior bioavailability and longer half-life in circulation (approximately 72 hours) compared to other vitamin K forms, allowing for stable blood levels with daily supplementation.
Beyond calcium regulation, MK-7 influences several other biological pathways. It modulates inflammatory processes by inhibiting nuclear factor-kappa B (NF-κB) signaling and reducing pro-inflammatory cytokine production. MK-7 also supports insulin sensitivity by activating osteocalcin, which stimulates pancreatic beta cells to release insulin and adiponectin. In the brain, MK-7 activates Gas6 (Growth Arrest Specific Protein 6), a vitamin K-dependent protein that supports neuronal health, myelination, and protection against oxidative stress.
Additionally, MK-7 may influence gene expression through the Steroid and Xenobiotic Receptor (SXR), regulating genes involved in bone metabolism, cellular growth, and detoxification processes. Unlike vitamin K1 (phylloquinone), which primarily supports blood coagulation in the liver, MK-7’s longer side chain allows for more efficient transport to extrahepatic tissues like bone, vasculature, and brain, explaining its broader physiological effects throughout the body.
Optimal Dosage
Disclaimer: The following dosage information is for educational purposes only. Always consult with a healthcare provider before starting any supplement regimen, especially if you have pre-existing health conditions, are pregnant or nursing, or are taking medications.
The optimal dosage of Menaquinone-7 (MK-7) ranges from 45-180 μg (micrograms) per day for most adults. For general health maintenance and prevention, 45-100 μg daily is typically sufficient. For targeted therapeutic effects on bone and cardiovascular health, higher doses of 100-180 μg daily are often recommended.
By Condition
| Condition | Dosage | Notes |
|---|---|---|
| General health maintenance | 45-100 μg daily | Lower doses are appropriate for individuals with adequate dietary intake of vitamin K2 from fermented foods. |
| Bone health/Osteoporosis prevention | 100-180 μg daily | Clinical studies showing benefits for bone mineral density typically use doses in this range. May be combined with vitamin D3 and calcium for synergistic effects. |
| Cardiovascular health | 150-180 μg daily | Higher doses have been shown to reduce arterial stiffness and slow progression of arterial calcification in research studies. |
| Dental health | 45-100 μg daily | May help strengthen tooth enamel and reduce risk of dental caries. |
| Individuals on anticoagulant therapy | Consult healthcare provider | Even low doses (10 μg) can affect anticoagulation therapy. Medical supervision is essential. |
| Nocturnal leg cramps | 100 μg daily | Emerging research suggests potential benefits for reducing frequency and severity of leg cramps. |
By Age Group
| Age Group | Dosage | Notes |
|---|---|---|
| Infants (0-12 months) | Not established | Supplementation not typically recommended unless directed by a healthcare provider. |
| Children (1-13 years) | Not established | Limited research on supplementation in this age group. Focus on dietary sources. |
| Adolescents (14-18 years) | 45-90 μg daily | May be beneficial during periods of rapid bone growth and development. |
| Adults (19-50 years) | 45-100 μg daily | For general health maintenance and prevention. |
| Adults (51+ years) | 90-180 μg daily | Higher doses may be beneficial due to increased risk of bone and cardiovascular issues with aging. |
| Pregnant/lactating women | Consult healthcare provider | Limited research on safety during pregnancy and lactation. |
Bioavailability
Absorption Rate
Menaquinone-7 (MK-7) has superior bioavailability compared to other forms of vitamin K, with approximately 60-70% absorption when taken with a fat-containing meal. Its long side chain of seven isoprenoid units makes it more lipophilic and allows for better incorporation into mixed micelles in the small intestine.
Enhancement Methods
Take with a meal containing healthy fats to enhance absorption, Oil-based or emulsified formulations improve bioavailability, Microencapsulation technology can protect MK-7 from degradation in the stomach, Liposomal delivery systems may enhance cellular uptake, Combining with medium-chain triglycerides (MCT) oil can improve absorption, Fermented food sources (like natto) provide naturally enhanced bioavailability
Timing Recommendations
MK-7 is best absorbed when taken with the largest meal of the day, preferably one containing healthy fats. Unlike many supplements, the long half-life of MK-7 (approximately 72 hours) means it maintains stable blood levels with once-daily dosing, making timing less critical than with shorter-acting nutrients. For individuals taking medications that may interact with vitamin K (such as warfarin), consistent timing and dosing are essential to maintain stable anticoagulation. Morning or evening administration is equally effective, though some individuals report taking it in the evening to coincide with dinner, which is often the largest meal of the day.
For those taking calcium supplements, taking MK-7 at the same time may help direct calcium to bones rather than soft tissues.
Safety Profile
Safety Rating
Side Effects
- Rare and generally mild gastrointestinal discomfort
- Allergic reactions (extremely rare)
- Potential interference with anticoagulant medications (warfarin/Coumadin)
- No serious adverse effects reported in clinical trials using doses up to 180 μg daily
Contraindications
- Individuals on vitamin K antagonist anticoagulant therapy (e.g., warfarin) without medical supervision
- Known hypersensitivity to menaquinone-7 or any component of the formulation
- Caution advised during pregnancy and lactation due to limited safety data
Drug Interactions
- Vitamin K antagonist anticoagulants (warfarin/Coumadin) – MK-7 can reduce the effectiveness of these medications
- Antibiotics – May reduce vitamin K production by gut bacteria, potentially enhancing MK-7 effects
- Bile acid sequestrants (cholestyramine, colestipol) – May reduce absorption of fat-soluble vitamins including MK-7
- Orlistat and other lipase inhibitors – May reduce absorption of fat-soluble vitamins including MK-7
- No significant interactions with other common medications have been reported
Upper Limit
No official upper limit has been established for MK-7. Toxicological studies have demonstrated safety at doses far exceeding typical supplemental amounts. A 90-day toxicity study found no adverse effects at doses up to 4500 mg/kg/day in rats, establishing this as the No Observed Adverse Effect Level (NOAEL). For human supplementation, doses up to 1000 μg (1 mg) daily have been used in research settings without reported adverse effects.
However, most clinical benefits are achieved at much lower doses (45-180 μg daily), making higher doses unnecessary for most individuals.
Regulatory Status
Fda Status
In the United States, Menaquinone-7 (MK-7) is regulated as a dietary supplement ingredient under the Dietary Supplement Health and Education Act (DSHEA) of 1994. It is not approved as a drug for the prevention or treatment of any disease. The FDA allows qualified health claims related to vitamin K and bone health, though not specifically for MK-7. Manufacturers must ensure product safety and cannot make disease treatment claims.
MK-7 derived from natto fermentation has Generally Recognized as Safe (GRAS) status for certain food applications.
International Status
Eu: The European Food Safety Authority (EFSA) has approved MK-7 as a safe ingredient in food supplements. In 2009, EFSA established an Adequate Intake (AI) for vitamin K of 70 μg/day for adults, though this does not distinguish between K1 and K2 forms. The European Commission has authorized certain health claims related to vitamin K’s contribution to normal blood clotting and maintenance of normal bones, which apply to MK-7 as a form of vitamin K.
Canada: Health Canada has approved MK-7 as a Natural Health Product (NHP) ingredient. It is included in the Natural Health Products Ingredients Database with approved claims for bone health and blood coagulation. The recommended daily allowance is similar to European standards.
Australia: The Therapeutic Goods Administration (TGA) regulates MK-7 as a complementary medicine ingredient. It is listed in the Australian Register of Therapeutic Goods (ARTG) and can be used in listed medicines with appropriate evidence levels for claims.
Japan: In Japan, MK-7 has Food for Specified Health Uses (FOSHU) status when derived from natto. Japan has a long history of natto consumption and recognizes the health benefits of MK-7 for bone and cardiovascular health.
China: The National Medical Products Administration (NMPA) regulates MK-7 as a health food ingredient. New regulations implemented in recent years have increased scrutiny of health claims and quality standards for supplements containing MK-7.
Synergistic Compounds
| Compound | Synergy Mechanism | Evidence Rating |
|---|---|---|
| Vitamin D3 (Cholecalciferol) | Vitamin D3 increases production of vitamin K-dependent proteins (like osteocalcin and MGP) that require activation by MK-7. D3 also enhances calcium absorption, while MK-7 ensures proper calcium utilization and distribution to bones rather than soft tissues. This complementary relationship optimizes bone mineralization while preventing vascular calcification. | 5 – Strong evidence from multiple clinical studies and mechanistic research |
| Calcium | MK-7 directs calcium to bones and teeth where it’s needed while preventing deposition in arteries and soft tissues. This relationship is crucial for maximizing the benefits of calcium supplementation while minimizing potential cardiovascular risks. | 4 – Good evidence from clinical and observational studies |
| Magnesium | Magnesium is required for vitamin D metabolism and activation, which in turn supports the vitamin K-dependent protein system. Magnesium also supports bone formation and helps prevent arterial calcification, complementing MK-7’s actions. | 3 – Moderate evidence from mechanistic studies and limited clinical data |
| Zinc | Zinc supports bone formation and mineralization processes that work alongside MK-7’s activation of osteocalcin. Zinc also plays a role in matrix metalloproteinase activity, which is involved in bone remodeling. | 3 – Moderate evidence primarily from mechanistic studies |
| Boron | Boron enhances vitamin D metabolism and reduces urinary calcium excretion, complementing MK-7’s role in calcium utilization for bone health. | 2 – Limited evidence from preliminary studies |
| Vitamin A | Vitamin A works with vitamin K2 to support proper bone remodeling and prevent excessive bone breakdown. Both nutrients influence osteoblast and osteoclast activity. | 3 – Moderate evidence from cellular and animal studies |
| Omega-3 fatty acids (EPA/DHA) | Omega-3s reduce inflammation and support cardiovascular health through mechanisms complementary to MK-7’s prevention of arterial calcification. Both nutrients support endothelial function and vascular flexibility. | 3 – Moderate evidence from observational and limited intervention studies |
| Vitamin E (mixed tocopherols) | Vitamin E’s antioxidant properties may help protect MK-7 from oxidation and enhance its stability. Both nutrients support cardiovascular health through different mechanisms. | 2 – Limited evidence primarily from theoretical mechanisms |
| Vitamin C | Vitamin C is essential for collagen formation in bone matrix, complementing MK-7’s role in bone mineralization. Vitamin C also supports cardiovascular health through antioxidant mechanisms. | 2 – Limited evidence from mechanistic studies |
| Menaquinone-4 (MK-4) | MK-4 and MK-7 are both forms of vitamin K2 but have different tissue distributions and half-lives. MK-4 accumulates preferentially in certain tissues like the brain and reproductive organs, while MK-7 has better bioavailability and longer half-life in circulation. | 3 – Moderate evidence from pharmacokinetic studies |
Antagonistic Compounds
| Compound | Interaction Type | Evidence Rating |
|---|---|---|
| Vitamin K antagonist anticoagulants (Warfarin/Coumadin) | Direct pharmacological antagonism. Warfarin works by inhibiting the recycling of vitamin K, which is necessary for blood clotting. MK-7 supplementation can reduce warfarin’s anticoagulant effect, potentially increasing clotting risk. Even low doses of MK-7 (10 μg) can significantly affect INR (International Normalized Ratio) values in patients on warfarin therapy. | 5 – Strong evidence from clinical studies and established pharmacological mechanism |
| Broad-spectrum antibiotics | Indirect antagonism. Antibiotics can disrupt gut microbiota that naturally produce vitamin K2, potentially enhancing the effects of supplemental MK-7. This may lead to unexpected changes in vitamin K status, particularly relevant for individuals on anticoagulant therapy. | 3 – Moderate evidence from clinical observations and mechanistic understanding |
| Bile acid sequestrants (Cholestyramine, Colestipol) | Absorption inhibition. These medications bind to bile acids in the intestine, which can reduce the absorption of fat-soluble vitamins including MK-7. Taking MK-7 at least 4 hours apart from these medications is recommended. | 3 – Moderate evidence based on known mechanisms of fat-soluble vitamin absorption |
| Orlistat and lipase inhibitors | Absorption inhibition. By reducing fat absorption in the intestine, these medications can decrease the absorption of fat-soluble vitamins including MK-7. | 3 – Moderate evidence based on pharmacological mechanism and clinical observations |
| Mineral oil laxatives | Absorption inhibition. Regular use of mineral oil can reduce absorption of fat-soluble vitamins including MK-7. | 2 – Limited evidence from case reports and theoretical mechanisms |
| High-dose vitamin E supplements | Potential competitive absorption. Very high doses of vitamin E might theoretically compete with other fat-soluble vitamins including MK-7 for absorption mechanisms, though clinical significance is uncertain. | 1 – Theoretical concern with limited supporting evidence |
| Excessive vitamin A supplementation | Potential antagonism at bone level. Very high doses of vitamin A may counteract some of the bone-beneficial effects of vitamin K2, though this interaction is complex and dose-dependent. | 2 – Limited evidence primarily from animal studies |
| Calcium supplements without vitamin K2 | Suboptimal utilization. While not a direct antagonism, calcium supplementation without adequate vitamin K2 may lead to inappropriate calcium deposition in soft tissues rather than bones. | 3 – Moderate evidence from observational studies and mechanistic research |
Cost Efficiency
Relative Cost
Medium to high compared to other vitamin supplements
Cost Per Effective Dose
For standard MK-7 supplements (100 μg daily dose), the typical cost ranges from $0.30 to $1.50 per day, depending on brand, quality, and formulation. Premium brands with specialized delivery systems or higher potencies (150-180 μg) may cost $1.00-$2.00 per day. Bulk or subscription purchases can reduce costs by 10-30%.
Value Analysis
MK-7 represents good value despite its relatively higher cost compared to some other supplements. Several factors contribute to this assessment: First, the long half-life of MK-7 (approximately 72 hours) means once-daily dosing is sufficient to maintain stable blood levels, unlike some nutrients that require multiple daily doses. Second, the effective dose range (45-180 μg) is relatively small, meaning a little goes a long way. Third, MK-7 addresses multiple health systems simultaneously (bone, cardiovascular, possibly cognitive), potentially replacing several targeted supplements.
Fourth, the preventive health benefits, particularly for cardiovascular calcification and bone density maintenance, may offset significant healthcare costs associated with these conditions later in life. Fifth, the production process for high-quality MK-7 (bacterial fermentation) is relatively complex and resource-intensive, justifying some of the premium pricing. For maximum cost efficiency, consumers should look for: supplements containing the all-trans form of MK-7 (the most bioactive isomer); products with third-party testing for potency verification; formulations that include complementary nutrients like vitamin D3 for synergistic effects; and oil-based or enhanced-absorption formulations that maximize bioavailability. When comparing cost, the price per microgram of active MK-7 is a more relevant metric than the price per capsule, as potencies vary significantly between products.
Stability Information
Shelf Life
Properly formulated and packaged MK-7 supplements typically have a shelf life of 2-3 years from the date of manufacture. However, this can vary based on formulation, packaging, and storage conditions. Microencapsulated or stabilized formulations may have extended shelf life.
Storage Recommendations
Store in a cool, dry place away from direct sunlight and heat sources. Optimal temperature range is 59-77°F (15-25°C). Refrigeration is not necessary but may extend potency in hot climates. Keep container tightly closed to protect from moisture and oxygen exposure. For oil-based or liquid formulations, refrigeration after opening may help maintain freshness. Avoid storing in bathrooms or other humid environments.
Degradation Factors
Exposure to ultraviolet light and direct sunlight – MK-7 is photosensitive and can degrade when exposed to UV radiation, High temperatures – Heat accelerates oxidation and isomerization processes that reduce potency, Oxygen exposure – Oxidation is a primary degradation pathway for MK-7, Humidity – Can accelerate degradation, especially in powder formulations, pH extremes – MK-7 is most stable at neutral to slightly acidic pH, Presence of oxidizing agents or certain minerals in formulations, Improper packaging – Permeable packaging materials can allow oxygen and moisture penetration, Extended storage beyond expiration date – Gradual loss of potency occurs over time even under ideal conditions
Sourcing
Synthesis Methods
- Bacterial fermentation using Bacillus subtilis var. natto – The primary commercial production method, mimicking the natural process used to make natto
- Synthetic chemical synthesis – Less common for MK-7 compared to other vitamin K forms
- Genetically modified bacterial production – Emerging method using optimized bacterial strains for higher yield
- Extraction from natto – Direct extraction from fermented soybeans, though less efficient for commercial scale
Natural Sources
- Natto (fermented soybeans) – The richest known food source, containing 800-1000 μg per 100g
- Other fermented soybean products (tempeh, miso) – Moderate amounts
- Fermented cheeses (especially aged varieties like Gouda, Brie, Edam) – 50-80 μg per 100g
- Sauerkraut – Small amounts
- Certain animal products (egg yolks, organ meats) – Small amounts
- Some fermented dairy products (kefir, certain yogurts) – Small amounts
Quality Considerations
When selecting MK-7 supplements, several quality factors should be considered. First, verify the form of MK-7 – the all-trans form is biologically active, while cis isomers have reduced activity. Look for products specifying ‘all-trans MK-7’ or ‘trans MK-7’ on the label. Source matters significantly – MK-7 derived from natto fermentation (using Bacillus subtilis) is considered the gold standard and most closely resembles the natural form found in food. Synthetic versions may have different isomer ratios and potentially lower biological activity. Purity is crucial – high-quality supplements should be free from contaminants, allergens, and unnecessary additives. For those with soy allergies or sensitivities, look for products that specify ‘soy-free’ if the MK-7 is derived from natto fermentation. Stability is another important consideration – MK-7 is sensitive to light, heat, and oxygen. Quality products use protective packaging and stabilizing technologies to maintain potency throughout shelf life. Dosage accuracy is essential – reputable manufacturers conduct third-party testing to verify that the actual MK-7 content matches label claims. Finally, bioavailability enhancers like MCT oil or other healthy fats in the formulation can improve absorption. Certifications from organizations like USP, NSF, or GMP provide additional assurance of quality manufacturing practices.
Historical Usage
While Menaquinone-7 (MK-7) as a specific isolated compound is a relatively recent addition to the supplement market, its natural food sources have a rich historical usage spanning centuries. The most significant traditional source of MK-7 is natto, a fermented soybean food that has been consumed in Japan since at least the Edo period (1603-1867), though some historical records suggest its origins may date back to the Heian period (794-1185). Natto was traditionally prepared by wrapping cooked soybeans in rice straw, which naturally contains Bacillus subtilis bacteria that ferment the soybeans and produce MK-7 as a byproduct. This fermentation process was developed long before the discovery of microorganisms or vitamins.
The regions of Japan with the highest traditional natto consumption have historically shown lower rates of osteoporosis and cardiovascular disease, though this connection was not scientifically understood until recent decades. Other fermented foods rich in various menaquinones, including cheese and fermented vegetables, have been dietary staples in many traditional cultures worldwide. The scientific identification of vitamin K occurred much later, with Henrik Dam discovering the vitamin in 1929 (receiving the Nobel Prize in 1943), though he identified vitamin K1 (phylloquinone) rather than the K2 forms (menaquinones). The distinction between K1 and K2 was not clearly established until the 1970s, and the specific identification of MK-7 as a particularly bioavailable and effective form of vitamin K2 emerged primarily in research from the 1990s and early 2000s.
The first commercial MK-7 supplements derived from natto appeared on the market in the early 2000s, with clinical research on its benefits for bone and cardiovascular health accelerating in the 2010s. Today, MK-7 is recognized as one of the most important forms of vitamin K2 for human health, with its usage expanding from traditional food sources to targeted supplementation for specific health benefits.
Scientific Evidence
Evidence Rating
Key Studies
Meta Analyses
Huang ZB, Wan SL, Lu YJ, Ning L, Liu C, Fan SW. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials. Osteoporos Int. 2015;26(3):1175-1186., Marles RJ, Roe AL, Oketch-Rabah HA. US Pharmacopeial Convention safety evaluation of menaquinone-7, a form of vitamin K. Nutr Rev. 2017;75(7):553-578., van Ballegooijen AJ, Pilz S, Tomaschitz A, Grübler MR, Verheyen N. The Synergistic Interplay between Vitamins D and K for Bone and Cardiovascular Health: A Narrative Review. Int J Endocrinol. 2017;2017:7454376.
Ongoing Trials
MenaQ7® K2 Cardio Study – Investigating high-dose MK-7 supplementation on cardiovascular parameters in healthy adults, Vitamin K2 supplementation in patients with aortic valve calcification – Clinical trial investigating effects on progression of calcification, MK-7 supplementation in children with low bone mineral density – Evaluating safety and efficacy in pediatric populations, Vitamin K2 and D3 co-supplementation for cognitive function in older adults – Investigating potential neuroprotective effects
Disclaimer: The information provided is for educational purposes only and is not intended as medical advice. Always consult with a healthcare professional before starting any supplement regimen, especially if you have pre-existing health conditions or are taking medications.