Vitamin K–containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7

Abstract

Vitamin K is a cofactor in the production of blood coagulation factors (in the liver), osteocalcin (in bone), and matrix Gla protein (cartilage and vessel wall). Accumulating evidence suggests that for optimal bone and vascular health, relatively high intakes of vitamin K are required. The synthetic short-chain vitamin K 1 is commonly used in food supplements, but recently the natural long-chain menaquinone-7 (MK-7) has also become available as an over-the-counter (OTC) supplement. The purpose of this paper was to compare in healthy volunteers the absorption and efficacy of K 1 and MK-7. Serum vitamin K species were used as a marker for absorption and osteocalcin carboxylation as a marker for activity. Both K 1 and MK-7 were absorbed well, with peak serum concentrations at 4 hours after intake. A major difference between the 2 vitamin K species is the very long half-life time of MK-7, resulting in much more stable serum levels, and accumulation of MK-7 to higher levels (7-to 8-fold) during prolonged intake. MK-7 induced more complete carboxylation of osteocalcin, and hematologists should be aware that preparations supplying 50 g/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way.

Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs Fermentation-Derived MK-7 in Randomised Controlled Trials

“…However, vitamin K 1 quickly disappears from the circulation (half-life ~1 -2 h). MK-7, by contrast, has a half-life of days [9]. This difference may be due to differences in molecular structure, causing differences in uptake, transport in blood, distribution, and metabolism.…”

“…Subjects were screened during week -2 relative to the start of supplementation. Men and women meeting all the following inclusion criteria were eligible to participate in the bioavailability or functional study: · Age 18 -65 years · BMI: 18.5 -27 kg/m 2 · Signed informed consent Subjects meeting any of the following exclusion criteria were ineligible to participate in the bioavailability or functional study: · Chronic disease (except allergy) · Use of vitamin K supplements within the last month · Current treatment with vitamin K antagonists (e. g. warfarin) · Current daily chronic drug treatment (except contraceptives) · Current pregnancy, confirmed by measurement of serum human chorionic gonadotropin by Advia Centaur XP immunoassay (Siemens AS, Oslo, Norway) by Fürst AS (Oslo, Norway) · Current lactation · C-reactive protein (CRP) >10 mg/L, serum creatinine >90 µmol/L (women) or >105 µmol/L (men), alanine aminotransferase (ALAT) >45 U/L (women) or >70 U/L (men) or serum total cholesterol >7 mmol/L · Drug abuse · Current participation in another clinical study · Inability to comply with the protocol, in the opinion of the investigator Based on the sample size of a previous bioavailability study of MK-7 [9], we aimed to include 16 subjects in the bioavailability study. 19 subjects satisfied the eligibility criteria and agreed to participate in the bioavailability study.…”

“…Assuming a linear increase in MK-7 uptake with increasing MK-7 dose [9], we recalculated the geometric mean ratios and 90 % CIs for AUC (0 -48 h) , AUC (0-72 h) and C max with an adjustment factor of 1.09 for the synthetic MK-7 data. The ratio for AUC (0 -48 h) was 94 % and the 90 % CI was 81 -108.…”

“…There is also a large difference in steady-state concentration: the serum concentration of MK-7 is substantially higher than that of vitamin K 1 when subjects are given equimolar amounts. The longer half-life of MK-7 means that it remains longer in the blood and is far more accessible to extra-hepatic tissues such as bone and blood vessel walls, probably promoting more efficacious carboxylation of OC and MGP [9].…”

“…The extent of OC carboxylation may be the most sensitive marker of human vitamin K status [8,9]. In healthy adults, about 30 % of circulating OC is undercarboxylated [10,11].…”