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Vitamin K

Last Revision: December 3, 2018.

Estimated reading time: 6 minutes

CASRN: 84-80-0 11104-38-4 863-61-6

Chemical structureChemical structureChemical structure

Drug Levels and Effects

Summary of Use during Lactation

Vitamin K is naturally found in human milk. Maternal vitamin K supplementation increases milk vitamin K levels and can improve vitamin K status in breastfed infants who receive intramuscular vitamin K shortly after birth. Maternal vitamin K supplementation should not be considered a substitute for vitamin K prophylaxis administered directly to the newborn.[1] Late vitamin K-deficiency bleeding, including intracranial hemorrhage, can occur from 2 to 12 weeks and up to 6 months postpartum in breastfed infants.[2] When vitamin K is given by injection to a nursing mother, the U.S. manufacturer recommends the use of unpreserved phytonadione injection to avoid infant exposure to benzyl alcohol, although amounts in milk are likely to be trivial.

Drug Levels

Maternal Levels. Vitamin K is naturally present in human milk in concentrations of 1 to 9 mcg/L (2.2 to 20 nmol/L).[3][4] Similar levels have been reported in colostrum.[3] Levels are approximately 1 mcg/L higher in hindmilk than foremilk.[5] Vitamin K1 (phylloquinone) is the predominant form in plasma and milk and derives from maternal dietary plant sources. Vitamin K2 (menaquinones) are also present in milk, mainly as menatetrenone (menaquninone-4; MK-4), at approximately one-half the levels of vitamin K1. [4][6] Since MK-4 can be synthesized from phylloquinone in the mother, dietary phylloquinone is the main source of milk MK-4.[6] It can also be derived from maternal dietary poultry in countries where vitamin K3 (menadione), a chemical precursor of MK-4, is used in poultry feed.[7] Other menaquinones are synthesized by some bacteria. Their milk levels can be increased in mothers who consume certain fermented foods.[4] The reported average milk/plasma ratio of phylloquinone is 4 to 8, while that of MK-4 is 15.[6][8][9] The higher M/P ratio of MK-4 is consistent with its known wider tissue distribution in the body.[10] Relevant published information regarding vitamin K milk levels in mothers taking MK-4 supplements was not found as of the revision date.

Four lactating mothers were given 0.1, 0.5, 1, or 3 mg single doses of oral vitamin K1. Milk was sampled at baseline and then at random times over 2 days after administration in 3 of the mothers and at fixed 6-hour intervals over 1 day in the fourth mother. Baseline milk levels were 2 to 3 mcg/L. Peak milk vitamin K1 levels occurred at 12 to 24 hours after administration in all subjects. The highest level reported was approximately 150 mcg/L, occurring 18 hours after a 3 mg dose. Menaquinone levels were not measured.[5]

Eleven lactating mothers between 2 and 6 months postpartum were given a single oral 20 mg vitamin K1 supplement and their milk was collected at 0, 12, 24, 48, 96 hours, and 1 week after administration. The average peak milk vitamin K1 level was approximately 130 mcg/L at 12 hours after administration compared to 1.1 mcg/L at baseline. By 48 hours the average milk level had decreased to 35 mcg/L, and returned to baseline after 1 week. Menaquinone levels were not measured.[11]

Twenty exclusively breastfeeding mothers were given either 2.5 or 5 mg of oral vitamin K1 once daily for 6 weeks beginning within 3 days of delivery. Breastmilk samples were collected at baseline and 18 to 24 hours after a dose (peak level) at 2 and 6 weeks. Average milk vitamin K1 levels were approximately 1 mcg/L at baseline in both groups, increasing to 27 and 59 mcg/L at 2 weeks, and 22 and 44 mcg/L at 6 weeks, in the 2.5 mg and 5 mg groups, respectively. The same investigators then gave 5 mg or placebo to twenty-two different exclusively breastfeeding mothers on the same postpartum schedule, but for 12 weeks instead of 6 weeks. At 2, 6 and 12 weeks, average milk vitamin K1 levels were approximately 80 mcg/L in the 5 mg group and 1 mcg/L in the placebo group. Menaquinone levels were not measured.[8] Using the milk levels reported in this study, an exclusively breastfed infant would receive 12 mcg/kg daily of vitamin K1 from a daily 5 mg maternal vitamin K1 dose.

Six lactating mothers of preterm infants ranging from 26 to 30 weeks gestation were given 2.5 mg of oral vitamin K1 once daily for 2 weeks beginning at 2 weeks postpartum. Breastmilk vitamin K1 was measured at baseline, then daily for 14 days. Milk was collected 6 times a day during routine pumping. Reported levels thus represent a daily average level in the mothers' milk. The average baseline milk level was 3 mcg/L. This increased to 22.6 mcg/L after 1 day, then gradually increased daily to 64.2 mcg/L on day 6 with no further significant changes. Menaquinone levels were not measured.[9] Based on the highest average level reported in this study, an exclusively maternal breastmilk fed preterm infant would receive 9 mcg/kg daily from a maternal vitamin K1 dose of 2.5 mg daily.

Thirty-one lactating mothers were given 0, 0.8, 2, or 4 mg of oral vitamin K1 once daily beginning on postpartum day 4 and continuing until day 16. Milk was sampled at baseline, and then prior to administration on days 8, 16, and 19. At baseline, the average milk vitamin K1 level was 6 to 7 mcg/L and the average milk MK-4 level was 2 to 3 mcg/L in all groups. Milk levels did not significantly change in the control (0 mg) group over time. On day 8 the average vitamin K1 levels were 23.3, 41.3, and 88.7 mcg/L, and MK-4 levels were 2.7, 3.8, 9.9 mcg/L in the 0.8, 2 and 4 mg groups, respectively. On day 16 average vitamin K1 levels were 24.5, 60.6, and 139.6 mcg/L, and MK-4 levels were 3.5, 5.5, and 16.5 mcg/L, respectively. On day 19, three days after maternal supplement discontinuation, average levels decreased to 12.4, 12.1, and 44.9 mcg/L, and MK-4 decreased to levels of 3.2, 3.0 and 9.0 mcg/L, respectively. Only the 4 mg group still had levels higher than the control group on day 19. The authors reported a highly significant correlation between vitamin K1 and MK-4 milk levels.[6] Using the highest average milk levels of both vitamin K1 and MK-4 reported in this study, an exclusively breastfed infant would receive a daily dosage of 23 mcg/kg of total vitamin K from a maternal 4 mg daily vitamin K1 supplement.

Infant Levels. Twenty-two exclusively breastfeeding mothers were given either 5 mg of oral vitamin K1 or placebo once daily for 12 weeks beginning within 3 days of delivery. All infants were given 1 mg of intramuscular vitamin K1 at birth. Average infant plasma vitamin K1 levels were between 2 and 3 mcg/L at 2, 6, and 12 weeks in the 5 mg group compared to between 0.2 and 0.4 mcg/L in the placebo group. Average infant PIVKA-II (des-gamma-carboxy-prothrombin) levels at 12 weeks were 0.42 mcg/L in the 5 mg group compared to 1.48 mcg/L in the placebo group (upper limit of normal is 2 mcg/L). The higher level in the placebo group suggests a relative vitamin K deficiency. Infant prothrombin times at 2, 6, and 12 weeks were not different between the two groups.[8]

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

References

1.
Shahrook S, Ota E, Hanada N et al. Vitamin K supplementation during pregnancy for improving outcomes: A systematic review and meta-analysis. Sci Rep. 2018;8:11459. [PMC free article: PMC6065418] [PubMed: 30061633]
2.
Ng E, Loewy AD. Position Statement: Guidelines for vitamin K prophylaxis in newborns: A joint statement of the Canadian Paediatric Society and the College of Family Physicians of Canada. Can Fam Physician. 2018;64:736-9. [PMC free article: PMC6184976] [PubMed: 30315016]
3.
Greer FR. Vitamin K status of lactating mothers and their infants. Acta Paediatr Suppl. 1999;88:95-103. [PubMed: 10569231]
4.
Kojima T, Asoh M, Yamawaki N et al. Vitamin K concentrations in the maternal milk of Japanese women. Acta Paediatr. 2004;93:457-63. [PubMed: 15188971]
5.
von Kries R, Shearer M, McCarthy PT et al. Vitamin K1 content of maternal milk: Influence of the stage of lactation, lipid composition, and vitamin K1 supplements given to the mother. Pediatr Res. 1987;22:513-7. [PubMed: 3684378]
6.
Thijssen HH, Drittij MJ, Vermeer C et al. Menaquinone-4 in breast milk is derived from dietary phylloquinone. Br J Nutr. 2002;87:219-26. [PubMed: 12064330]
7.
Booth SL. Vitamin K: Food composition and dietary intakes. Food Nutr Res. 2012;56:5505. [PMC free article: PMC3321250] [PubMed: 22489217]
8.
Greer FR, Marshall SP, Foley AL et al. Improving the vitamin K status of breastfeeding infants with matenal vitamin K supplements. Pediatrics. 1997;99:88-92. [PubMed: 8989344]
9.
Bolisetty S, Gupta JM, Graham GG, Salonikas C, Naidoo D. Vitamin K in preterm breastmilk with maternal supplementation. Acta Paediatr. 1998;87:960-2. [PubMed: 9764891]
10.
Hirota Y, Tsugawa N, Nakagawa K et al. Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1) in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2) in rats. J Biol Chem. 2013;288:33071-80. [PMC free article: PMC3829156] [PubMed: 24085302]
11.
Greer FR, Marshall S, Cherry J et al. Vitamin K status of lactating mothers, human milk, and breast-feeding infants. Pediatrics. 1991;88:751-6. [PubMed: 1896278]

Substance Identification

Substance Name

Vitamin K

CAS Registry Number

84-80-0 11104-38-4 863-61-6

Drug Class

  • Breast Feeding
  • Vitamins
  • Antifibrinolytic Agents

Disclaimer: Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

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