Skip to main content
SpringerLink
Log in

Vitamin E: Interactions with Vitamin K and Other Bioactive Compounds

  • Chapter
  • First Online:
Vitamin E in Human Health

Part of the book series: Nutrition and Health ((NH))

Abstract

Nutrient functions often depend on those of other nutrients and/or bioactive compounds. These critical nutrient-nutrient interactions are often overlooked in observational studies and challenging to address in randomized clinical trials. As dietary guidance is issued to the general public primarily in the form of food components of the diet, such nutrient-nutrient interactions merit consideration in understanding the functions of a given nutrient. Vitamin E is no exception. An adverse interaction between vitamin E and another fat-soluble vitamin, vitamin K, was first detected over 50 years ago. Given both nutrients’ critical involvement in coagulation, in extreme cases, this interaction can result in abnormal blood clotting. There is also emerging evidence that vitamin E interacts with other bioactive compounds.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mohajeri MH, Eckert GP, Pauly JR, Butt CM. Pharmacology: the pharmacodynamics of nutrients and nutrient interactions in biological functions. Biomed Res Int. 2015;2015:974572.

    Article  Google Scholar 

  2. Traber MG. Vitamin E and K interactions – a 50-year-old problem. Nutr Rev. 2008;66:624–9.

    Article  Google Scholar 

  3. Suttie JW. Vitamin K in health and disease. Boca Raton: CRC Press, Taylor and Francis Group; 2009.

    Book  Google Scholar 

  4. Elder SJ, Haytowitz DB, Howe J, Peterson JW, Booth SL. Vitamin K contents of meat, dairy, and fast food in the U.S. diet. J Agric Food Chem. 2006;54:463–7.

    Article  CAS  Google Scholar 

  5. Fu X, Shen X, Finnan EG, Haytowitz DB, Booth SL. Measurement of multiple vitamin K forms in processed and fresh-cut pork products in the U.S. food supply. J Agric Food Chem. 2016;64:4531–5.

    Article  CAS  Google Scholar 

  6. Fu X, Harshman SG, Shen X, et al. Multiple vitamin K forms exist in dairy foods. Curr Dev Nutr. 2017;1:e000638.

    Article  Google Scholar 

  7. Walther B, Karl JP, Booth SL, Boyaval P. Menaquinones, bacteria, and the food supply: the relevance of dairy and fermented food products to vitamin K requirements. Adv Nutr. 2013;4:463–73.

    Article  CAS  Google Scholar 

  8. Shea MK, Booth SL. Fat soluble vitamins: an overview. Scientific America Nutrition; 2018 (in press).

    Google Scholar 

  9. Cheung A, Suttie JW. Synthesis of menaquinone-2 derivatives as substrates for the liver microsomal vitamin K-dependent carboxylase. Biofactors. 1988;1:61–5.

    CAS  PubMed  Google Scholar 

  10. Corrigan JJ Jr, Marcus FI. Coagulopathy associated with vitamin E ingestion. JAMA. 1974;230:1300–1.

    Article  Google Scholar 

  11. Corrigan JJ Jr, Ulfers LL. Effect of vitamin E on prothrombin levels in warfarin-induced vitamin K deficiency. Am J Clin Nutr. 1981;34:1701–5.

    Article  CAS  Google Scholar 

  12. Corrigan JJ Jr. The effect of vitamin E on warfarin-induced vitamin K deficiency. Ann N Y Acad Sci. 1982;393:361–8.

    Article  CAS  Google Scholar 

  13. Frank J, Weiser H, Biesalski HK. Interaction of vitamins E and K: effect of high dietary vitamin E on phylloquinone activity in chicks. Int J Vitam Nutr Res. 1997;67:242–7.

    CAS  PubMed  Google Scholar 

  14. Dowd P, Zheng ZB. On the mechanism of the anticlotting action of vitamin E quinone. Proc Natl Acad Sci U S A. 1995;92:8171–5.

    Article  CAS  Google Scholar 

  15. Nowicka B, Kruk J. Occurrence, biosynthesis and function of isoprenoid quinones. Biochim Biophys Acta. 2010;1797:1587–605.

    Article  CAS  Google Scholar 

  16. Yamanashi Y, Takada T, Kurauchi R, Tanaka Y, Komine T, Suzuki H. Transporters for the intestinal absorption of cholesterol, vitamin E, and vitamin K. J Atheroscler Thromb. 2017;24:347–59.

    Article  CAS  Google Scholar 

  17. Goncalves A, Margier M, Roi S, et al. Intestinal scavenger receptors are involved in vitamin K1 absorption. J Biol Chem. 2014;289:30743–52.

    Article  CAS  Google Scholar 

  18. Goncalves A, Roi S, Nowicki M, et al. Fat-soluble vitamin intestinal absorption: absorption sites in the intestine and interactions for absorption. Food Chem. 2015;172:155–60.

    Article  CAS  Google Scholar 

  19. Nassir F, Wilson B, Han X, Gross RW, Abumrad NA. CD36 is important for fatty acid and cholesterol uptake by the proximal but not distal intestine. J Biol Chem. 2007;282:19493–501.

    Article  CAS  Google Scholar 

  20. Rhainds D, Brissette L. The role of scavenger receptor class B type I (SR-BI) in lipid trafficking. Defining the rules for lipid traders. Int J Biochem Cell Biol. 2004;36:39–77.

    Article  CAS  Google Scholar 

  21. Reboul E, Klein A, Bietrix F, et al. Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. J Biol Chem. 2006;281:4739–45.

    Article  CAS  Google Scholar 

  22. Takada T, Yamanashi Y, Konishi K, et al. NPC1L1 is a key regulator of intestinal vitamin K absorption and a modulator of warfarin therapy. Sci Transl Med. 2015;7:275ra23.

    Article  CAS  Google Scholar 

  23. Reboul E, Soayfane Z, Goncalves A, et al. Respective contributions of intestinal Niemann-Pick C1-like 1 and scavenger receptor class B type I to cholesterol and tocopherol uptake: in vivo v. in vitro studies. Br J Nutr. 2012;107:1296–304.

    Article  CAS  Google Scholar 

  24. Narushima K, Takada T, Yamanashi Y, Suzuki H. Niemann-pick C1-like 1 mediates alpha-tocopherol transport. Mol Pharmacol. 2008;74:42–9.

    Article  CAS  Google Scholar 

  25. Booth SL, Tucker KL, McKeown NM, Davidson KW, Dallal GE, Sadowski JA. Relationships between dietary intakes and fasting plasma concentrations of fat-soluble vitamins in humans. J Nutr. 1997;127:587–92.

    Article  CAS  Google Scholar 

  26. Institute of Medicine. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press; 2001.

    Google Scholar 

  27. Gao X, Wilde PE, Lichtenstein AH, Bermudez OI, Tucker KL. The maximal amount of dietary alpha-tocopherol intake in U.S. adults (NHANES 2001–2002). J Nutr. 2006;136:1021–6.

    Article  CAS  Google Scholar 

  28. Harshman SG, Finnan EG, Barger KJ, et al. Vegetables and mixed dishes are top contributors to phylloquinone intake in US adults: data from the 2011–2012 NHANES. J Nutr. 2017;147:1308–13.

    Article  CAS  Google Scholar 

  29. Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. Washington, DC: National Academies Press; 2000.

    Google Scholar 

  30. Kantor ED, Rehm CD, Du M, White E, Giovannucci EL. Trends in dietary supplement use among US adults from 1999–2012. JAMA. 2016;316:1464–74.

    Article  Google Scholar 

  31. Traber MG. Mechanisms for the prevention of vitamin E excess. J Lipid Res. 2013;54:2295–306.

    Article  CAS  Google Scholar 

  32. Shearer MJ, Newman P. Metabolism and cell biology of vitamin K. Thromb Haemost. 2008;100:530–47.

    Article  CAS  Google Scholar 

  33. Edson KZ, Prasad B, Unadkat JD, et al. Cytochrome P450-dependent catabolism of vitamin K: omega-hydroxylation catalyzed by human CYP4F2 and CYP4F11. Biochemistry. 2013;52:8276–85.

    Article  CAS  Google Scholar 

  34. McDonald MG, Rieder MJ, Nakano M, Hsia CK, Rettie AE. CYP4F2 is a vitamin K1 oxidase: an explanation for altered warfarin dose in carriers of the V433M variant. Mol Pharmacol. 2009;75:1337–46.

    Article  CAS  Google Scholar 

  35. Traber MG. Vitamin E regulatory mechanisms. Annu Rev Nutr. 2007;27:347–62.

    Article  CAS  Google Scholar 

  36. Sontag TJ, Parker RS. Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. J Biol Chem. 2002;277:25290–6.

    Article  CAS  Google Scholar 

  37. Azzi A, Gysin R, Kempna P, et al. Regulation of gene expression by alpha-tocopherol. Biol Chem. 2004;385:585–91.

    Article  CAS  Google Scholar 

  38. Landes N, Birringer M, Brigelius-Flohe R. Homologous metabolic and gene activating routes for vitamins E and K. Mol Asp Med. 2003;24:337–44.

    Article  CAS  Google Scholar 

  39. Tabb MM, Sun A, Zhou C, et al. Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. J Biol Chem. 2003;278:43919–27.

    Article  CAS  Google Scholar 

  40. Farley SM, Leonard SW, Labut EM, et al. Vitamin E decreases extra-hepatic menaquinone-4 concentrations in rats fed menadione or phylloquinone. Mol Nutr Food Res. 2012;56:912–22.

    Article  CAS  Google Scholar 

  41. Farley SM, Leonard SW, Taylor AW, et al. omega-Hydroxylation of phylloquinone by CYP4F2 is not increased by alpha-tocopherol. Mol Nutr Food Res. 2013;57:1785–93.

    CAS  PubMed  Google Scholar 

  42. Al Rajabi A, Booth SL, Peterson JW, et al. Deuterium-labeled phylloquinone has tissue-specific conversion to menaquinone-4 among Fischer 344 male rats. J Nutr. 2012;142:841–5.

    Article  Google Scholar 

  43. Thijssen HH, Drittij-Reijnders MJ. Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4. Br J Nutr. 1994;72:415–25.

    Article  CAS  Google Scholar 

  44. Thijssen HH, Drittij-Reijnders MJ, Fischer MA. Phylloquinone and menaquinone-4 distribution in rats: synthesis rather than uptake determines menaquinone-4 organ concentrations. J Nutr. 1996;126:537–43.

    Article  CAS  Google Scholar 

  45. Nakagawa K, Hirota Y, Sawada N, et al. Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature. 2010;468:117–21.

    Article  CAS  Google Scholar 

  46. Okano T, Shimomura Y, Yamane M, et al. Conversion of phylloquinone (vitamin K1) into menaquinone-4 (vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice. J Biol Chem. 2008;283:11270–9.

    Article  CAS  Google Scholar 

  47. Shearer MJ, Newman P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res. 2014;55:345–62.

    Article  CAS  Google Scholar 

  48. Hanzawa F, Sakuma E, Nomura S, Uchida T, Oda H, Ikeda S. Excess alpha-tocopherol decreases extrahepatic phylloquinone in phylloquinone-fed rats but not menaquinone-4 in menaquinone-4-fed rats. Mol Nutr Food Res. 2014;58:1601–9.

    Article  CAS  Google Scholar 

  49. Tovar A, Ameho CK, Blumberg JB, Peterson JW, Smith D, Booth SL. Extrahepatic tissue concentrations of vitamin K are lower in rats fed a high vitamin E diet. Nutr Metab (Lond). 2006;3:29.

    Article  Google Scholar 

  50. Farley SM, Leonard SW, Stevens JF, Traber MG. Deuterium-labeled phylloquinone fed to alpha-tocopherol-injected rats demonstrates sensitivity of low phylloquinone-containing tissues to menaquinone-4 depletion. Mol Nutr Food Res. 2014;58:1610–9.

    Article  CAS  Google Scholar 

  51. Booth SL, Golly I, Sacheck JM, et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr. 2004;80:143–8.

    Article  CAS  Google Scholar 

  52. Horwitt MK. Vitamin E: a reexamination. Am J Clin Nutr. 1976;29:569–78.

    Article  CAS  Google Scholar 

  53. Shea MK, Booth SL. Concepts and controversies in evaluating vitamin K status in population-based studies. Nutrients. 2016;8:E8.

    Article  Google Scholar 

  54. Leung VW, Shalansky SJ, Lo MK, Jadusingh EA. Prevalence of use and the risk of adverse effects associated with complementary and alternative medicine in a cohort of patients receiving warfarin. Ann Pharmacother. 2009;43:875–81.

    Article  CAS  Google Scholar 

  55. Kim JM, White RH. Effect of vitamin E on the anticoagulant response to warfarin. Am J Cardiol. 1996;77:545–6.

    Article  CAS  Google Scholar 

  56. Stanger MJ, Thompson LA, Young AJ, Lieberman HR. Anticoagulant activity of select dietary supplements. Nutr Rev. 2012;70:107–17.

    Article  Google Scholar 

  57. Segal R, Pilote L. Warfarin interaction with Matricaria chamomilla. CMAJ. 2006;174:1281–2.

    Article  Google Scholar 

  58. Broniatowski M, Flasinski M, Hac-Wydro K. Antagonistic effects of alpha-tocopherol and ursolic acid on model bacterial membranes. Biochim Biophys Acta. 2015;1848:2154–62.

    Article  CAS  Google Scholar 

  59. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345:1583–92.

    Article  CAS  Google Scholar 

  60. Cheung MC, Zhao XQ, Chait A, Albers JJ, Brown BG. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol. 2001;21:1320–6.

    Article  CAS  Google Scholar 

  61. Singh U, Otvos J, Dasgupta A, de Lemos JA, Devaraj S, Jialal I. High-dose alpha-tocopherol therapy does not affect HDL subfractions in patients with coronary artery disease on statin therapy. Clin Chem. 2007;53:525–8.

    Article  CAS  Google Scholar 

  62. Niki E. Interaction of ascorbate and alpha-tocopherol. Ann N Y Acad Sci. 1987;498:186–99.

    Article  CAS  Google Scholar 

  63. Cook NR, Albert CM, Gaziano JM, et al. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women’s Antioxidant Cardiovascular Study. Arch Intern Med. 2007;167:1610–8.

    Article  CAS  Google Scholar 

  64. Gaziano JM, Glynn RJ, Christen WG, et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2009;301:52–62.

    Article  CAS  Google Scholar 

  65. Sesso HD, Buring JE, Christen WG, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2008;300:2123–33.

    Article  CAS  Google Scholar 

  66. Traber MG, Stevens JF. Vitamins C and E: beneficial effects from a mechanistic perspective. Free Radic Biol Med. 2011;51:1000–13.

    Article  CAS  Google Scholar 

  67. La Fata G, Seifert N, Weber P, Mohajeri MH. Vitamin E supplementation delays cellular senescence in vitro. Biomed Res Int. 2015;2015:563247.

    PubMed  PubMed Central  Google Scholar 

  68. Sunde RA, Thompson KM, Fritsche KL, Evenson JK. Minimum selenium requirements increase when repleting second-generation selenium-deficient rats but are not further altered by vitamin E deficiency. Biol Trace Elem Res. 2017;177:139–47.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA

    M. Kyla Shea & Sarah L. Booth

Authors
  1. M. Kyla Shea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah L. Booth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Kyla Shea .

Editor information

Editors and Affiliations

  1. University of Hohenheim, Institute of Nutritional Sciences, Stuttgart , Germany

    Peter Weber

  2. University of Applied Sciences Fulda, Nutritional, Food and Consumer Sciences, Fulda, Germany

    Marc Birringer

  3. Friedman School of Nutrition Science and Policy, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA

    Jeffrey B. Blumberg

  4. University Medical Center Groningen, Hanzeplain 1, Groningen, The Netherlands

    Manfred Eggersdorfer

  5. University of Hohenheim, Institute of Nutritional Sciences, Stuttgart , Germany

    Jan Frank

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Shea, M.K., Booth, S.L. (2019). Vitamin E: Interactions with Vitamin K and Other Bioactive Compounds. In: Weber, P., Birringer, M., Blumberg, J., Eggersdorfer, M., Frank, J. (eds) Vitamin E in Human Health. Nutrition and Health. Humana Press, Cham. https://doi.org/10.1007/978-3-030-05315-4_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-05315-4_19

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-030-05314-7

  • Online ISBN: 978-3-030-05315-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation