Question 1

Why does the calculator refuse to dose warfarin / VKA users?

Accepted Answer

Warfarin and other vitamin K antagonists work by inhibiting VKORC1, the enzyme that recycles vitamin K in the K-cycle. Adding K2 supplementation changes the antagonism dose-response and shifts INR — sometimes dramatically. Any K supplementation in a VKA user requires consistent dose plus INR monitoring plus dose adjustment by the prescribing clinician. The calculator hard-stops this scenario and redirects to anticoagulation-clinic supervision; it is not a 'cautious recommendation' situation.

Question 2

MK-7 or MK-4 — which form?

Accepted Answer

MK-7 (menaquinone-7) has a 72-hour half-life, can be dosed once daily, and is the form behind most Western postmenopausal-bone, vascular, and CKD evidence. Standard supplemental dose is 100–360 µg/day depending on goal. MK-4 (menatetrenone) has a 1–2 hour half-life, must be split 2–3× daily, and is the specific form behind the Japanese 45 mg/day prescription fracture-prevention protocol (Glakay). The calculator forces MK-4 only on the 'Japan Rx fracture' goal; for all other goals MK-7 is the evidence-aligned choice.

Question 3

Why is the Japanese 45 mg/day fracture protocol flagged for non-Japanese populations?

Accepted Answer

Cockayne 2006 (PMID 16801507) pooled 7 Japanese RCTs and found dramatic fracture reduction at MK-4 45 mg/day: hip OR 0.23, vertebral OR 0.40, all-nonvertebral OR 0.19. But Binkley 2009 (PMID 19113922) tested the same MK-4 45 mg/day regimen in 381 North American postmenopausal women over 12 months and found NO change in BMD or geometry — despite the expected ucOC reduction. Genetic, dietary (notably natto consumption), or duration factors are not fully characterized. The calculator surfaces this 'western-replication-null' flag so users can confirm population fit before committing to a prescription-tier regimen.

Question 4

Did the AVADEC trial show K2+D3 prevents heart disease?

Accepted Answer

No. AVADEC (Diederichsen 2022, PMID 35465686) is the largest hard-endpoint K2+D3 trial — 365 men with aortic valve calcification (AVC) score >300 randomized to MK-7 720 µg + D3 25 µg/day vs placebo for 24 months. The primary endpoint (change in AVC score) was NULL: 275 vs 292 AU progression, P=0.64. Coronary artery calcification, valve area, and peak jet velocity all also unchanged. The dp-ucMGP biomarker DID normalize (-212 vs +45 pmol/L, P<0.001) — confirming the mechanism but not the clinical translation. The calculator's 'vascular + D3' goal surfaces this honestly; the framing is 'mechanism supported, clinical endpoint not validated' rather than 'proven cardiovascular benefit.'

Question 5

Do I need K2 if I'm not on high-dose D3?

Accepted Answer

For most healthy adults eating leafy greens with fat, no. The calculator returns a null-benefit redirect when goal is 'dietary adequacy' AND you're not on high-dose D3 — because (1) K1 90–120 µg/day from food meets adequacy, and (2) supplementation in replete adults shows no clear benefit on bone or vascular outcomes. K2 utility rises sharply in three contexts: postmenopausal bone with elevated ucOC, vascular calcification on high-dose D3 (D3 increases calcium turnover and K2 routes it correctly), and CKD/hemodialysis (where functional K2 deficiency is structural). Pick a different goal if one of those applies; otherwise focus on diet.

Question 6

What's the all-trans isomer purity issue with MK-7?

Accepted Answer

MK-7 has a stereochemistry — only the all-trans isomer is biologically active. Independent lab surveys have found roughly 2/3 of US MK-7 supplement products fail the >98% all-trans specification (some are ~50% cis-isomer, which has lower bioactivity). The practical fix is to choose products with a Certificate of Analysis showing >98% all-trans — MenaQ7 is the most common branded source that meets this. Without that COA, you may be paying for a product where half the material doesn't carry the K2 effect.