A short-chain menaquinone found in small amounts in animal foods and produced in tissue from vitamin K1. Supplements supply it synthetically, and in Japan the same molecule is licensed as a prescription osteoporosis medicine at 45 mg/day.
MK-4 is the vitamin K form with the most human outcome data and the most awkward evidence base. Japanese trials of menatetrenone at 45 mg/day — a pharmacological dose roughly 400 times the dietary Adequate Intake for vitamin K — reported reduced fracture rates in osteoporosis, and the drug is approved there on that basis. Trials outside Japan, including a large randomised trial in postmenopausal women, have not reproduced the fracture benefit. Retail MK-4 supplements typically supply 1–5 mg, which is neither the dietary amount nor the studied drug dose, and has no trial evidence of its own. MK-4 also has a very short half-life, measured in hours, so once-daily dosing leaves most of the day without elevated blood levels.
Sold as
Capsule, Softgel in oil, Drops, Prescription menatetrenone (Japan), Combination with vitamin D3
Also known as
Menatetrenone, Menaquinone-4, MK-4
Regulation: A prescription drug for osteoporosis in Japan at 45 mg/day; a dietary supplement in the US and much of Europe at far lower doses with no pre-market efficacy review. No Tolerable Upper Intake Level exists for any form of vitamin K.
What the research used
The amounts, forms and durations published trials of Vitamin K2 (MK-4) actually administered.
These are the amounts published trials administered — not a recommendation, and not a dose to copy. Trial participants were screened, supervised and given a characterised preparation. What is in a retail bottle is frequently not what was studied, and the amount that suits one person is not general advice.
Studied for Japanese osteoporosis trials
45 mg
Limited
Menatetrenone, three divided doses daily · 1–3 years
A pharmacological dose used as a licensed medicine in Japan. Fracture reductions were reported in Japanese trials; a large trial outside Japan did not reproduce them, and the difference has never been satisfactorily explained.
Studied for Typical retail supplement
1–5 mg
Not enough
Capsule, often combined with vitamin D3
Between 20 and 100 times the dietary Adequate Intake for vitamin K but a small fraction of the studied drug dose. No trial has tested this range for any outcome.
This is general information about food, not medical advice. It cannot diagnose, treat or replace guidance from a clinician who knows your history.
When it was taken
Each window says whether a trial compared it against an alternative, or whether it is convention and pharmacology. Most timing advice is the second kind.
1 of 2 timings below were actually compared in a trial. The rest reflect convention or pharmacology.
🍽️With food
Moderate
Fat-soluble and much better absorbed with a meal containing fat, as absorption studies show for all vitamin K forms.
Timing was tested. A trial compared this window against another and reported a difference.
🔀Split through the day
Limited
MK-4 has a blood half-life of only a few hours, which is why the Japanese trials used three doses a day. Once-daily retail dosing does not reproduce that exposure pattern — pharmacokinetic reasoning, not a tested comparison of schedules.
Timing was not directly compared. This reflects convention or how the compound behaves in the body, not a trial showing this window works better.
The evidence in depth
Best supported: Limited
What each association actually rests on, and the papers behind it. A rating describes the state of the research, not how promising the supplement sounds. How we rate evidence.
Some trials report fewer fractures with high-dose menatetrenone in Japanese populations with osteoporosis, but the effect on bone mineral density is small and trials outside Japan have been null. Whether the retail doses sold as supplements do anything at all for bone is untested.
What may be going on: Carboxylation of osteocalcin, allowing it to bind calcium in bone matrix. Blood levels of undercarboxylated osteocalcin fall reliably with supplementation, which is a marker rather than an outcome.
Limited evidence. Early human work, or mostly lab and animal research.
There is not enough evidence that MK-4 affects arterial calcification or cardiovascular events. The vascular hypothesis rests on matrix Gla protein biology and observational data on menaquinone intake, not on trials of this compound.
Not enough evidence. Not enough human research to say anything useful yet.
Randomised controlled trial · Journal of the American Society of Nephrology : JASN · 2020 · PMID 31704740
Deep research mode adds each paper’s own conclusion and stated limitations.
Things to know
Interactions, contraindications and dose limits, most serious first. Concentrated extracts interact with medication in ways the whole plant does not, so this section carries more weight here than it does on a food page.
All vitamin K forms oppose warfarin and related anticoagulants, and supplemental doses are far larger than dietary intake, so starting or stopping one can move the INR substantially. Anyone anticoagulated should involve their clinic rather than adjusting intake alone. Direct oral anticoagulants such as apixaban and rivaroxaban do not work through vitamin K and are not affected in the same way.
Worth knowing
Retail doses are not the studied doses
The evidence people cite for MK-4 comes from a 45 mg/day prescription regimen given three times daily. A 5 mg once-daily capsule shares the molecule and almost nothing else about the exposure, which is the most commonly glossed-over fact in vitamin K2 marketing.
Avoid
Not established in pregnancy at supplemental doses
Dietary vitamin K is essential in pregnancy, but the high-dose Japanese osteoporosis regimen has not been studied in pregnant women and supplemental doses well above dietary intake are best discussed with a clinician.
Worth knowing
Often sold blended with vitamin D3
D3+K2 combinations are marketed on the reasoning that vitamin D increases calcium absorption and vitamin K directs it to bone. That sequence is plausible biochemistry; no trial has shown the combination outperforms vitamin D alone for fractures.
In the food catalogue
The whole-food form, where one exists. The evidence for a concentrated extract rarely transfers to the food, or the other way round — these are cross-links, not equivalents.