Dr. Kumar’s Take:
This study from Nutrition Journal (2012) compared two forms of vitamin K2 head to head in people, not in animals: ten healthy Japanese women, aged 20 to 21, given menaquinone-4 (MK-4) or menaquinone-7 (MK-7) at nutritional doses. The result is blunt. MK-7 showed up in the blood, peaked at 6 hours, and was still detectable 48 hours later. MK-4 was not detectable in the serum of any subject at any time point after the single dose, and a week of daily MK-4 did not increase serum MK-4 levels. For anyone choosing a K2 supplement, or reading a label that lists MK-4, that matters. The authors conclude that MK-4 present in food does not contribute to vitamin K status as measured by serum vitamin K levels. This is a small, short study in ten young women, so I read it as a clear signal about absorption rather than the final word on what MK-4 does inside tissues, since vitamin K homologues can be converted to MK-4 in the body and MK-4 is thought to have functions beyond carboxylation.
Key Takeaways:
✔ A single 420 μg dose of MK-7 was well absorbed, reached its maximal serum level at 6 hours, and was still detectable 48 hours after intake.
✔ The same 420 μg dose of MK-4 was not detectable in the serum of any subject at any time point.
✔ Taking 60 μg daily for one week raised serum MK-7 significantly in every subject, while MK-4 supplementation did not raise serum MK-4 levels at all.
✔ The authors conclude that MK-4 from food does not contribute to vitamin K status measured by serum levels, while MK-7 may be of particular importance for extrahepatic tissues.
Actionable Tip:
If your goal is to raise circulating vitamin K2, choose MK-7, from natto or an MK-7 supplement, rather than MK-4 at nutritional doses. Take it with a meal that contains some fat, as the subjects here did: the doses were given within 10 minutes of a breakfast containing 13 to 17 g of fat.
Brief Summary:
This study looked at how two forms of vitamin K2 are absorbed in humans. Ten healthy female volunteers, aged 20 to 21 with a mean BMI of 20.4 kg/m², were recruited from Kagawa Nutrition University in Japan and randomized to receive either MK-4 or MK-7. Serum levels were measured by HPLC with fluorescence detection after on-line post-column zinc reduction. MK-7 entered the bloodstream and stayed there. MK-4 never appeared in the serum after the single large dose, and a week of daily intake at the recommended dietary intake level did not increase serum MK-4.
Study Design:
Two experiments were done, each in ten healthy women, aged 20 to 21, none of them taking any medication, and none allowed natto or vitamin supplements other than the study capsules:
- In the first study, subjects were randomized into two groups of five. Each received a single dose of MK-4 (420 μg; 945 nmol) or MK-7 (420 μg; 647 nmol) within 10 minutes of a standardized breakfast containing 13 to 17 g of fat. The 420 μg dose is equivalent to the MK-7 concentration in natto and is 7 times the recommended dietary intake of vitamin K for Japanese women aged 19 to 29. Blood was drawn at baseline and at 2, 4, 6, 8, 10, 24, 48, and 72 hours.
- In the second study, subjects were again randomized into two groups of five and took MK-4 (60 μg; 135 nmol) or MK-7 (60 μg; 92 nmol), equivalent to the recommended dietary intake, daily after supper for one week.
Purified MK-4 (98.5%) and MK-7 (98.7%) were used, packed in gelatin capsules and stored refrigerated in light-shielded bags, and re-analysis after the study confirmed neither had degraded during storage. The study was approved by the ethics committee of Kagawa Nutrition University, with informed consent per the Declaration of Helsinki.
Results:
- MK-7 was well absorbed after a single 420 μg dose, reaching its maximal serum level at 6 hours and remaining detectable up to 48 hours after intake.
- MK-4 was not detectable in the serum of any subject at any time point after the single 420 μg dose.
- After one week of 60 μg daily, MK-7 raised serum MK-7 levels significantly in all subjects.
- After one week of 60 μg daily, MK-4 supplementation did not increase serum MK-4 levels.
- The authors conclude that MK-4 present in food does not contribute to vitamin K status as measured by serum vitamin K levels, and that MK-7, by raising serum levels, may be of particular importance for extrahepatic tissues.
Why MK-4 and MK-7 Behave Differently
Both are vitamin K2, built on the same 2-methyl-1,4-naphthoquinone ring, and they differ in the length of the isoprenoid side chain at position 3. That difference tracks with where they come from and how they behave. MK-4 is found in animal products such as eggs, meat, and liver, where it derives from conversion of menadione fed to the animals. The long chain menaquinones, MK-7, MK-8, and MK-9, come from fermented foods such as cheese, curd, and sauerkraut, and the Japanese fermented food natto contains MK-7 at an exceptionally high concentration. Prior work cited by the authors attributes MK-7’s stronger and longer-lasting effect to its very long half-life in serum, which produces a better carboxylation grade of osteocalcin than vitamin K1. Vitamin K matters here because it is the cofactor for γ-glutamylcarboxylase, the enzyme that forms Gla proteins: the clotting factors made in the liver, and osteocalcin and matrix Gla protein made in bone and blood vessels.
Related Studies and Research
Examines the conversion efficiency of various dietary vitamin K forms into bioactive MK-4 in human tissues.: Tracks metabolic pathways converting dietary K to MK-4.
Compares bioavailability and serum retention of MK-7 versus MK-4 in healthy women.: Compares absorption profiles of two K2 forms.
Investigates combined vitamin D3 and K2 supplementation effects on bone mineral density over 18 months.: Assesses D+K synergy on skeletal outcomes.
Explores natto intake’s association with reduced bone loss rates in postmenopausal women.: Links fermented soy to slower bone turnover.
Review of MK-7 supplementation effects on bone quality, including compression and impact strength metrics.: Summarizes mechanical benefits of K2 on bone strength.
Frequently Asked Questions
Does it matter which form of vitamin K2 I take?
Based on this study, yes. At nutritional doses, MK-7 raised serum levels and MK-4 did not appear in the blood at all. If a supplement is meant to raise your circulating vitamin K2, MK-7 is the form that did it here.
What foods contain MK-4?
MK-4 is found in animal products such as eggs, meat, and liver, where it comes from menadione given to the animals.
Where does MK-7 come from?
Long chain menaquinones like MK-7 are found in fermented foods such as cheese, curd, and sauerkraut. Natto, a Japanese fermented soybean food, contains MK-7 at an exceptionally high concentration. The 420 μg single dose used in this study was chosen to match the MK-7 content of natto.
Should I take a vitamin K2 supplement?
That depends on your diet. If you eat little in the way of leafy greens or fermented foods, MK-7 is the form with evidence of absorption behind it in this trial. Talk to your doctor first, especially if you take blood thinners, since vitamin K drives production of clotting factors II, VII, IX, and X.
What’s the difference between MK-4 and MK-7?
They differ in side chain length. MK-7 has a very long serum half-life and accumulated in the blood in this study. MK-4 was undetectable in serum after the single dose, and a week of daily dosing did not increase serum MK-4, though it is still thought to have functions in tissues beyond carboxylation, and vitamin K homologues can be converted to MK-4 in the body.
Conclusion
In ten healthy young women, MK-7 was absorbed, peaked in serum at 6 hours, persisted for 48 hours, and rose significantly with a week of daily 60 μg dosing. MK-4 was not measurable in serum at any point after the single dose, and a week of daily dosing did not raise serum MK-4 levels. The authors’ conclusion is that MK-4 in food does not contribute to vitamin K status as measured by serum levels, while MK-7 does and may therefore matter most for tissues outside the liver. It is a small, short study, but if you are choosing a K2 supplement, that difference is the practical point.
