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Menaquinone-4 in breast milk is derived from dietary phylloquinone

Published online by Cambridge University Press:  09 March 2007

H. H. W. Thijssen*
Departments of Pharmacology, University of Maastricht, Maastricht, The Netherlands
M.-J. Drittij
Departments of Pharmacology, University of Maastricht, Maastricht, The Netherlands
C. Vermeer
Biochemistry, University of Maastricht, Maastricht, The Netherlands
E. Schoffelen
Centre of Midwifery, Maastricht, The Netherlands
*Corresponding author: Dr H.H.W. Thijssen, fax +31 43 388 41 49, email
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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 12 d, 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 0·8, 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 4 mg 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 ≤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.

Research Article
Copyright © The Nutrition Society 2002


Billeter, M & Martius, C (1960) Über die Umwandlung von Phylloquinon (Vitamin K1) in Vitamin K2(20) im Tierkörper (About the conversion of phylloquinone (vitamin K1) in to vitamin K2(20) in animal tissue). Biochemisches Zeitschrift 333, 430439.Google Scholar
Boersma, ER, Offringa, PJ, Muskiet, FAJ, Chase, WM & Simmons, IJ (1991) Vitamin E, lipid fractions in, and fatty acid composition of colostrum, transitional milk, and mature milk: an international comparative study. American Journal of Clinical Nutrition 53, 11971204.CrossRefGoogle ScholarPubMed
Booth, SL & Suttie, JW (1998) Dietary intake and adequacy of vitamin K. Journal of Nutrition 128, 785788.CrossRefGoogle ScholarPubMed
Bosiletty, S, Gupta, JM, Graham, GG, Salonikas, C & Naidoo, D (1998) Vitamin K in preterm breastmilk with maternal supplementation. Acta Paediatrica 87, 960962.Google Scholar
Buitenhuis, HC, Soute, BAM & Vermeer, C (1990) Comparison of the vitamins K1, K2, and K3 as cofactors for the hepatic vitamin K-dependent carboxylase. Biochimica et Biophysica Acta 1034, 170175.CrossRefGoogle ScholarPubMed
Chappell, JE, Francis, T & Clandinin, MT (1985) Vitamin A and E content of human milk at early stages of lactation. Early Human Development 11, 157167.CrossRefGoogle Scholar
Conly, JM & Stein, K (1992) The production of menaquinones (vitamin K2) by intestinal bacteria and their role in maintaining coagulation homeostasis. Progress in Food and Nutrition Science 16, 307343.Google ScholarPubMed
Cornelissen, EAM, von Kries, R, Loughnan, P & Schubiger, G (1997) Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K. European Journal of Pediatry 156, 126130.CrossRefGoogle ScholarPubMed
Davidson, RT, Foley, AL, Engelke, JA & Suttie, JW (1998) Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria. Journal of Nutrition 128, 220223.CrossRefGoogle Scholar
Dialameh, GH, Taggart, WV, Matshiner, JT & Olson, RE (1971) Isolation and characterization of menaquinone-4 as a product of menadione metabolism in chicks and rats. International Journal of Vitamin and Nutrition Research 41, 391400.Google ScholarPubMed
Fournier, B, Sann, L, Guillaumont, M & Leclercq, M (1987) Variations of phylloquinone concentration in human milk at various stages of lactation and in cow's milk at various seasons. American Journal of Clinical Nutrition 45, 551558.CrossRefGoogle ScholarPubMed
Greer, FR (1995) Vitamin K deficiency and hemorrhage in infancy. Clinical Perinatology 22, 759777.CrossRefGoogle ScholarPubMed
Greer, FR, Marshall, SP, Foley, AL & Suttie, JW (1997) Improving the vitamin K status of breastfeeding infants with maternal vitamin K supplements. Pediatry 99, 8892.CrossRefGoogle ScholarPubMed
Hachey, DL, Thomas, MR, Emken, EA, Garza, C, Brown-Booth, L, Adlof, RO & Klein, PD (1987) Human lactation: maternal transfer of dietary triglycerides labeled with stable isotopes. Journal of Lipid Research 28, 11851192.Google ScholarPubMed
Hagstrom, JN, Bovill, EG, Soll, RF, Davidson, KW & Sadowski, JA (1995) The pharmacokinetics and lipoprotein fraction distribution of intramuscular vs oral vitamin K1 supplementation in women of childbearing age: effects on hemostasis. Thrombosis and Haemostasis 74, 14861490.Google ScholarPubMed
Haroon, Y, Bacon, DS & Sadowski, JA (1986) Liquid-chromatographic determination of vitamin K1 in plasma, with fluorometric detection. Clinical Chemistry 32, 19251929.Google ScholarPubMed
Harzer, G, Haug, M, Dieterich, I & Gentner, PR (1983) Changing patterns of human milk lipids in the course of lactation and during the day. American Journal of Clinical Nutrition 37, 612621.CrossRefGoogle ScholarPubMed
Hiraike, H, Kimura, M & Itokawa, Y (1988) Distribution of K vitamins (phylloquinone and menaquinones) in human placenta and maternal and umbilical cord plasma. American Journal of Obstetrics and Gynecology 158, 564569.CrossRefGoogle ScholarPubMed
Indyk, HE & Woollard, DC (1997) Vitamin K in milk and infant formulas: determination and distribution of phylloquinone and menaquinone-4. Analyst 122, 465469.CrossRefGoogle ScholarPubMed
Jie, K-SG, Bots, ML, Vermeer, C, Witteman, JCM & Grobbee, DE (1995) Vitamin K intake and osteocalcin levels in women with and without aortic atherosclerosis: a population-based study. Atherosclerosis 116, 117123.CrossRefGoogle ScholarPubMed
Kindberg, C, Suttie, JW, Uchida, K, Hirauchi, K & Nakao, H (1987) Menaquinone production and utilization in germ-free rats after inoculation with specific organisms. Journal of Nutrition 117, 10321035.CrossRefGoogle ScholarPubMed
King, JC (2000) Physiology of pregnancy and nutrient metabolism. American Journal of Clinical Nutrition 71S, 218S225S.Google Scholar
Kohlmeier, M, Salomon, A, Saupe, J & Shearer, M (1996) Transport of vitamin K to bone in humans. Journal of Nutrition 126, 1192S1196S.CrossRefGoogle ScholarPubMed
Meydan, M (1995) Vitamin E. Lancet 345, 170175.CrossRefGoogle Scholar
Neville, MC, Keller, R, Seacat, J, Lutes, V, Neifert, M, Casey, C, Allen, J & Archer, P (1988) Studies in human lactation: milk volumes in lactating women during the onset of lactation and full lactation. American Journal of Clinical Nutrition 48, 13751386.CrossRefGoogle ScholarPubMed
Ronden, JE (1998) Absorption, tissue distribution and bioactivity of vitamin K and related compounds in the rat. PhD Thesis, University of Maastricht.Google Scholar
Ronden, JE, Drittij-Reijnders, MJ, Vermeer, C & Thijssen, HHW (1998) Intestinal flora is not an intermediate in the phylloquinone–menaquinone-4 conversion in the rat. Biochimica et Biophysica Acta 1379, 6975.CrossRefGoogle Scholar
Ramotar, K, Conly, JM, Chubb, H & Louie, TJ (1984) Production of menaquinones by intestinal anaerobes. Journal of Infectious Disease 150, 213218.CrossRefGoogle ScholarPubMed
Shearer, MJ (1992) Vitamin K metabolism and nutriture. Blood Reviews 6, 92104.CrossRefGoogle ScholarPubMed
Sutor, AH, Von Kries, R, Cornelissen, EAM & McNinh, AW (1999) Vitamin K deficiency bleeding (VKDB) in infancy. Thrombosis and Haemostasis 81, 456461.Google ScholarPubMed
Suttie, JW (1995) The importance of menaquinones in human nutrition. Annual Reviews of Nutrition 15, 399417.CrossRefGoogle ScholarPubMed
The Netherlands Nutrition Centre (1998) Dutch Food Intake in 1997–1998. Den Haag: Voedingscentrum.Google Scholar
Thijssen, HHW & Drittij-Reijnders, MJ (1994) Vitamin K distribution in rat tissue: dietary phylloquinone is a source of tissue menaquinone-4. British Journal of Nutrition 72, 415425.CrossRefGoogle ScholarPubMed
Thijssen, HHW & Drittij-Reijnders, MJ (1996) Vitamin K status in human tissues: tissue-specific accumulation of phylloquinone and menaquinone-4. British Journal of Nutrition 75, 121127.CrossRefGoogle ScholarPubMed
Thijssen, HHW, Drittij-Reijnders, MJ & Fischer, MAJG (1996) Phylloquinone and menaquinone-4 distribution in rats: synthesis rather than uptake determines menaquinone-4 organ concentrations. Journal of Nutrition 126, 537543.CrossRefGoogle ScholarPubMed
Trumbo, P, Yates, AA, Schlicker, S & Poos, M (2001) Dietary reference intakes: Vitamin A, vitamin K, arsenic, boron, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium and zinc. Journal of the American Dietetic Association 101, 294301.CrossRefGoogle ScholarPubMed
Will, BH, Usui, Y & Suttie, JW (1992) Comparative metabolism and requirement of vitamin K in chicks and rats. Journal of Nutrition 122, 23542360.CrossRefGoogle ScholarPubMed
Von Kries, R, Shearer, M, McCarthy, PT, Haug, M, Harzer, G & Gobel, U (1987) Vitamin K1 content of maternal milk: influence of the stage of lactation, lipid composition, and vitamin K1 supplements given to the mother. Pediatric Research 22, 513517.CrossRefGoogle Scholar