Effect of Dietary Fat Content on Oral Bioavailability of Menatetrenone in Humans

Abstract

The purpose of this investigation was to determine the effects of fat content and frequency of meals on the oral bioavailability of menatetrenone (2-methyl-3-all-trans-tetraprenyl-1,4-naphthoquinone), a vitamin K2 with four isoprene units. In the first series of studies, menatetrenone (15 mg) was administered at breakfast time to 18 healthy male volunteers after meals with three different fat contents (meals A, B, and C) on three occasions in a crossover design. The three types of meals had almost the same calorie content (721-746 kcal) with varied fat contents (A, 8.8 g; B, 20.0 g; C, 34.9 g). The area under the plasma menatetrenone concentration-time curve within the first 24 h (AUC0-24) increased with increase of fat content: 371 +/- 194, 485 +/- 150, and 1024 +/- 341 ng.h/mL (mean +/- SD, n = 18) after meals A, B, and C, respectively. On the fourth occasion, the same dose of menatetrenone was administered to all volunteers after taking meal B, but in this case the lunch 5 h after drug administration was omitted from the protocol. The time profile of plasma menatetrenone showed a single peak when lunch was not taken, whereas it showed two peaks with lunch. On the fifth occasion, 12 out of 18 volunteers took the same dose of menatetrenone after a meal with the highest fat content (53.8 g of fat and 789 kcal; meal D), showing that AUC0-24 was almost the same as that for meal C, 1027 +/- 389 and 991 +/- 392 ng.h/mL (n = 12) for meals C and D, respectively. The oral bioavailability of lipid-soluble vitamin K was influenced by the fat content of a meal, although the increase in bioavailability seemed to reach a peak when the lipid content of the meal was > 35 g.

Combination of vitamin K2 and the angiotensin-converting enzyme inhibitor, perindopril, attenuates the liver enzyme-altered preneoplastic lesions in rats via angiogenesis suppression

“…However, the sensitivities of HCC cells and EC to VK were quite different. VK exerted a significant inhibitory effect on EC even at a dose of 1!10 K6 M (P!0.01), which was comparable to the serum concentration of the patients treated with VK [26]. On the other hand, this low dose did not have any effect on HCC proliferation.…”

Low-Dose Daily Intake of Vitamin K₂ (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trials

“…MK-7 doses were set at 50, 100, and 200 mg/d. Uematsu et al reported that simultaneous intake of fat improved vitamin K2 absorption (19). Each dose of MK-7 was dissolved in oil and then incorporated into mayonnaise.…”

Scientific Opinion on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol

“…Very low fat diets may increase the risk of an insufficient intake of PUFA, can impair the absorption of fatsoluble vitamins and be associated with insufficiency of other essential nutrients like zinc and B vitamins. The addition of 5 g fat to a diet providing only 5 g fat per day (total of 10g fat per day) was shown to significantly improve blood vitamin A concentrations and improve vitamin K availability (Jayarajan et al, 1980;Uematsu et al, 1996). Such low fat intakes are highly unlikely in European countries and no signs of deficiency have been observed at the lowest observed intakes in the European population including pregnant and lactating women.…”