title: Menaquinone-4 in breast milk is derived from dietary phylloquinone.
abstract: The effect of maternal phylloquinone supplementation on vitamin K in breast milk was studied to establish: (1) if phylloquinone is the source of menaquinone-4 in breast milk; (2) the dose-effect relationship between intake and obtainable levels. Four groups of lactating mothers with a full-term healthy infant participated and took oral phylloquinone supplements of 0.0 (n 8), 0.8 (n 8), 2.0 (n 8), and 4.0 (n 7) mg/d for 12d, starting at day 4 post-partum. Milk samples were collected on days 4, 8, 16, and 19. Blood samples were collected on days 4 and 16. Vitamin K and vitamin E concentrations, the latter for reason of comparison, were assayed. Phylloquinone and menaquinone-4 were present in all milk samples: 5.84 (SD 2.31) and 2.98 (SD 1.51) nmol/l (n 31) respectively, in colostrum (day 4 sample). A strong correlation between the vitamers was found (r 0.78, P<0.001). Breast-milk phylloquinone levels were raised in a dose-dependent manner: 4-, 12-, and 30-fold on day 16 for the 08, 2.0, and 4.0 mg group respectively. In addition, menaquinone-4 levels were higher: 2.5- (P<0.05) and 7-fold (P<0.001) in the 2.0 and 4.0 mg groups respectively. Plasma of supplemented subjects contained 3-, 5-, and 10-fold higher phylloquinone levels on day 16. Detectable menaquinone-4 was found in ten of thirty-one day 4 plasma samples. All day 16 plasma samples of the 4mg supplemented group contained the vitamin. There was no correlation between the K-vitamers in plasma. Vitamin E and phylloquinone appear to differ in their distribution in breast milk, milk:plasma concentration ratios were < or =1 and 3-5 for vitamin E and phylloquinone respectively. The milk:plasma concentration ratio of menaquinone-4 was >10. In conclusion, dietary phylloquinone is a source of menaquinone-4 in breast milk. Phylloquinone supplementation to lactating mothers may be of benefit to the newborn infant, since both phylloquinone and menaquinone-4 are raised by supplementation.
authors.affiliation: Department of Pharmacology, University of Maastricht, The Netherlands. h.thijssen@farmaco.unimaas.nl
authors.forename: H H W
authors.initials: HH
authors.lastname: Thijssen
authors.forename: M J
authors.initials: MJ
authors.lastname: Drittij
authors.forename: C
authors.initials: C
authors.lastname: Vermeer
authors.forename: E
authors.initials: E
authors.lastname: Schoffelen
mesh_terms: D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008895:Milk, Human / Q000378:metabolism*; D014810:Vitamin E / Q000097:blood / Q000493:pharmacokinetics; D010837:Vitamin K 1 / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D000933:Antifibrinolytic Agents; D024482:Vitamin K 2; D014810:Vitamin E; C030814:menatetrenone; D010837:Vitamin K 1