ABSTRACT
BACKGROUND: In a previous human intervention study, we observed an improved vitamin K status after 8 weeks of intake of a yogurt that was fortified with vitamin K2 (as menaquinone-7, MK-7) and enriched with vitamins C and D3, magnesium and polyunsaturated fatty acids. It was hypothesized that the added nutrients contributed to this improvement. Here we report on a study in which we compared the fasting plasma concentrations of MK-7 from (a) yogurt enriched with MK-7, vitamins D3 and C, magnesium, n-3 poly unsaturated fatty acids (n-3 PUFA) and fish oil (yogurt Kplus), (b) yogurt fortified with MK-7 only (yogurt K) and (c) soft gel capsules containing only MK-7. SUBJECTS/METHODS: For 42 days, healthy men and postmenopausal women between 45 and 65 years of age daily consumed either yogurt K, yogurt Kplus or capsules. Circulating MK-7, 25-hydroxy vitamin D (25(OH)D) and markers for vitamin K status (uncarboxylated osteocalcin (ucOC) and desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP)) were assessed. Plasma MK-7 was also measured during the washout period of 2 weeks. MK-7 and dp-ucMGP were measured in citrated plasma, and 25(OH)D3 and ucOC were measured in the serum. RESULTS: The increase in plasma MK-7 with the yogurt Kplus product was more pronounced than the increase in MK-7 with the capsules. Circulating dp-ucMGP and ucOC were significantly lowered after consumption of the yogurt products and the MK-7 capsules, reflecting vitamin K status improvement. No significant differences in fasting plasma concentrations of various biomarkers between the yogurts were found. CONCLUSIONS: Dairy matrix and nutrient composition may affect MK-7 delivery and improvement of vitamin K status. Yogurt fortified with MK-7 is a suitable matrix to improve the nutritional status of the fat-soluble vitamins.
Subject(s)
Diet , Dietary Fats/pharmacology , Dietary Supplements , Food, Fortified , Micronutrients/pharmacology , Vitamin K 2/analogs & derivatives , Yogurt , Ascorbic Acid/pharmacology , Biological Availability , Calcium-Binding Proteins/blood , Capsules , Cholecalciferol/pharmacology , Dairy Products , Extracellular Matrix Proteins/blood , Fasting , Fatty Acids, Omega-3/pharmacology , Female , Humans , Magnesium/pharmacology , Male , Middle Aged , Nutritional Status , Osteocalcin/blood , Postmenopause , Reference Values , Vitamin K 2/blood , Vitamin K 2/pharmacokinetics , Matrix Gla ProteinABSTRACT
Vitamin K's recommended dietary allowance (RDA) is based on the hepatic requirement for clotting factor synthesis, but substantial concentrations of undercarboxylated extra-hepatic Gla-proteins are found in the circulation of non-supplemented individuals. This suggests that vitamin K intake above the RDA is required for an optimal extra-hepatic vitamin K status. Circulating uncarboxylated osteocalcin (ucOC) and desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) are considered markers of the vitamin K status in bone and the vasculature, respectively. We measured these markers in 896 samples of healthy volunteers and defined target groups for vitamin K supplementation based on increased levels indicative of tissue-specific vitamin K deficiency. We studied the response to vitamin K supplements at different states of vitamin K deficiency by measuring the circulating dp-ucMGP level in samples from two short-term trials on menaquinone-7 (MK-7, vitamin K2) supplementation in 42 children and 68 adults. Children had high ucOC levels (3.4-96.9 ng ml(-1)); other age groups had values in the range of 1.5-5.0 ng ml(-1). From the age of 40 years, dp-ucMGP levels gradually increased. Children and adults with more pronounced vitamin K deficiency gave the highest responses to MK-7 supplementation. Children and adults above 40 years showed the largest tissue-specific vitamin deficiency and accordingly may benefit from MK-7 supplementation to improve their extra-hepatic vitamin K status.
Subject(s)
Vitamin K Deficiency/drug therapy , Vitamin K/administration & dosage , Vitamin K/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Calcium-Binding Proteins/blood , Child , Child, Preschool , Dietary Supplements/analysis , Extracellular Matrix Proteins/blood , Female , Healthy Volunteers , Humans , Male , Middle Aged , Osteocalcin/blood , Vitamin K Deficiency/blood , Young Adult , Matrix Gla ProteinABSTRACT
BACKGROUND AND OBJECTIVE: Despite the worldwide use of vitamin K antagonists (VKAs), there is limited knowledge of the influence of dietary vitamin K on anticoagulation control. In view of the increasing nutraceutical availability of menaquinone-7 (MK-7; vitamin K2 ) and its promotion for bone and cardiovascular health, it is important to determine the posology for the interference of supplemental MK-7 with VKA therapy. PATIENTS: Eighteen healthy men and women were anticoagulated for 4 weeks with acenocoumarol, and 15 of them attained a target International Normalized Ratio (INR) of 2.0. In the six subsequent weeks, subjects were given increasing doses of MK-7 (10, 20 and 45 µg day(-1) ) while continuing acenocoumarol treatment at established individual doses. RESULTS: Apart from the INR, acenocoumarol treatment significantly increased the levels of uncarboxylated factor II (ucFII), uncarboxylated osteocalcin (ucOC), and desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP), and decreased endogenous thrombin generation (ETP). A daily intake of 45 µg of MK-7 significantly decreased the group mean values of both the INR and ucFII by ~ 40%. Daily intakes of 10 and 20 µg of MK-7 were independently judged by two hematologists to cause a clinically relevant lowering of the INR in at least 40% and 60% of subjects, respectively, and to significantly increase ETP by ~ 20% and ~ 30%, respectively. Circulating ucOC and dp-ucMGP were not affected by MK-7 intake. CONCLUSIONS: MK-7 supplementation at doses as low as 10 µg (lower than the usual retail dose of 45 µg) significantly influenced anticoagulation sensitivity in some individuals. Hence, the use of MK-7 supplements needs to be avoided in patients receiving VKA therapy.
