Vitamin K: Beyond Clotting

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Q & A with Sarah L. Booth, PhD
Senior Scientist and Director, Vitamin K Lab, Tufts University

Vitamin K is one of those nutrients that has lost its position as a vital component of nutritional therapy as it was thought that so little was required. But along with vitamin A this nutrient, due to more sophisticated investigation options is now getting some well deserved respect and it is becoming clear that it impacts on many aspects of health – maybe this will gain as much respect as Vitamin D in the coming years.[1],[2]


Focus: So, let’s talk about vitamin K. Why don’t we hear more about this fat soluble vitamin?

SB: The vitamin K research community is extremely small, and we don’t have the volume of publications that the other fat soluble nutrients have. We’re probably decades behind in research findings. Vitamin K was identified for its role in blood clotting but we need very little for blood clotting. The body seems to be exquisite at taking what it needs to support clotting, and we don’t have a public health problem associated with abnormal bleeding. Our current dietary recommendations for vitamin K are based on the amount that’s ideal for clotting—90 micrograms a day for women and 120 micrograms a day for men.

In addition, the amount of vitamin K that is in circulation in your blood is about 1/30,000th of vitamin E, for example. There’s very little in our circulation because, unlike the other fat soluble vitamins, it’s recycled. So we only began to be able to measure vitamin K reliably in the 1980’s, and science has a quirky way of waiting until technology is available to address important questions. That’s what we’re trying to do, and we’re the only lab in the United States that studies vitamin K nutrition.

Focus: Tell us about vitamin K and bone health.

SB: Vitamin K is required to support the function of proteins in the body that regulate calcification. At least 13 vitamin K dependent proteins have been discovered thus far. The protein that requires vitamin K in bone is called osteocalcin and it’s a very important protein. Our lab looked at the Framingham heart study, and the nurse’s health study, and we found that high intakes of vitamin K in older people was associated with a lower risk of hip fracture. We looked at blood samples and found that lower amounts of vitamin K in the blood were linked with lower bone mineral density. This is a very consistent finding. One study in the Netherlands found that vitamin D, vitamin K and calcium together correlated with less bone loss at the hip than just vitamin D and calcium alone. Other studies have not found the same beneficial effect. The contradiction might be due to the fact that the women in the Netherlands were just entering menopause, and around the onset of menopause women do not seem as receptive to the impact of Vitamin D and calcium on bone loss. The effect of those two nutrients seems more pronounced later on. I wonder if certain nutrients like vitamin K may be most beneficial during a very narrow window when menopause is beginning.

Focus: What about vitamin K and the heart?

SB: Preliminary research seems to show that vitamin K may slow calcification in the arteries. It doesn’t stop the onset of calcification but it does seem to slow it. However, though this preliminary research is very encouraging, it needs to be replicated several times before we can say that everybody should eat vitamin-K rich green leafies to slow the progression of arterial calcification.

Focus: And vitamin K may help protect against insulin resistance, right?

SB: Again, this is promising preliminary research. Cell studies suggest that high vitamin K actually slows the progression of insulin resistance but the work needs to be replicated.

Focus: How do you think vitamin K is linked with the other fat soluble vitamins?

SB: It’s well documented that vitamin E and vitamin K interact. Individuals on warfarin are advised to consume a constant amount of vitamin K, and to avoid extremely high doses of vitamin E. Over 1000 IU of vitamin E will interfere with the function of vitamin K and we’ve demonstrated that in humans. We’ve seen that vitamin D does work on vitamin K dependent proteins and so there may be a synergy between them, but we don’t have the data yet to support that. The same is true of vitamin A. There is data from long ago in animals where high intakes of vitamin A were detrimental to vitamin K but we haven’t studies on this in humans yet. We know that vitamins A and D work through the RXR receptor, but we’ve never explored whether vitamin K also does. Vitamin K might use that receptor as well. The fact is, all these fat soluble nutrients are absorbed in similar ways and share similar pathways, and as we move forward and advance our study of these nutrients in chronic disease, we may well find an overall synergy among all four of them.

References

[1] Vermeer Cees; Shearer Martin J; Zittermann Armin; Bolton-Smith Caroline; Szulc Pawel; Hodges Stephen; Walter Paul; Rambeck Walter; Stöcklin Elisabeth; Weber Peter Beyond deficiency: potential benefits of increased intakes of vitamin K for bone and vascular health. European journal of nutrition 2004;43(6):325-35.

[2] Cranenburg EC, Schurgers LJ, Vermeer C. Thromb Haemost. 2007 Jul;98(1):120-5. Vitamin K: the coagulation vitamin that became omnipotent. Thromb Haemost. 2007 Jul;98(1):120-5. View Abstract

References used for the interview

  1. Shea MK, Gundlberg C, Meigs JB, Dallal GE, Saltzman E, Yoshida M, Jacques PF, Booth SL. Y-Carobxylaion of osteocalcin and insulin resistance in older men and women. AM J CLin Nutr 2009;90:1230-5.
  2. Shea KM, O’Donnell CJ, Hoffmann U, Dallal GE, Dawson-Hughes B, Ordovas JM, Price PA, Williamson MK, Booth, SL. Vitamin K supplementation and progression of coronary artery calcium in older men and women. Am J Clin Nutr 2009:89:1799-807.
  3. LI, J, Lin JC, Wang H, Peterson JW, Furie BC, Furie B, Booth SL, Volpe JJ, SRosenberg PA. Novel role of vitamin K in preventing oxidative injury to developing oligodendrocytes and neurons. The Journal of Neuroscience, July 2, 2003: 23(13):5816-5826.
  4. Booth SL, Dallal G, Shea KM, Gundberg C, Pterson JW, Dawson-Hughes B. Effect of vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab, April 2008: 93(4): 1217-1223.
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2 Comments. Leave new

  • Hello, interested about the vitamin K & warfarin interaction. On the Natural Medicines Comprehensive database they cite a major interaction between K & warfarin and advise not to take K if on warfarin; that would make it difficult for an NT here to recommend vitamin K to any patient on warfarin. Would you agree with that or do you think food forms of K would be helpful?

    Reply
    • Hi Angela

      Orally, vitamin K1 (phytonadione) is used for preventing and treating hypoprothrombinaemia caused by vitamin K deficiency; to counteract excessive doses of oral anticoagulants; to prevent haemorrhagic disease of the new-born; to treat hypoprothrombinaemia induced by salicylates, sulphonamides, quinine, quinidine, or broad-spectrum antibiotic therapy; to prevent and treat osteoporosis; and relieve itching associated with primary biliary cirrhosis.

      Vitamin K2 (menaquinone) is used orally to treat osteoporosis and steroid-induced bone loss, and to lower total cholesterol in dialysis patients.

      Vitamin K3 (menadiol acetate) is used orally in combination with vitamin C for treating prostate and breast cancers.

      Vitamin K4 (menadiol sodium diphosphate) is used orally for treating hypoprothrombinaemia resulting from impaired absorption or synthesis of vitamin K.

      It seems that both Vit K1 and Vit K2 are both coagulants, and care needs to be taken when used with warfarin, particularly the dose however, the decision to supplement or not is not as straight forward as this may suggest.

      Warfarin anticoagulation.
      We can confidently say: Taking vitamin K1 (phytonadione) orally or parentally can counteract excessive warfarin anticoagulation.
      McKevoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

      However, Vitamin K might also be effective for stabilising anticoagulation in patients with low intake of vitamin K. Patients taking warfarin who have a low dietary vitamin K intake are significantly more likely to have an unstable international normalised ratio (INR), a standardised measure of clotting time, compared to patients who ingest higher amounts of vitamin K.
      Sconce E, Khan T, Mason J, et al. Patients with unstable control have a poorer dietary intake of vitamin K compared to patients with stable control of anticoagulation. Thromb Haemost 2005;93:872-5. View Abstract

      It is worth remembering that it is thought that vitamin K-depleted patients become more sensitive when vitamin K is ingested, even in small quantities, resulting in erratic or unstable INR. Particularly important in the interpretation of the first few INR readings.
      Kurnik D, Lobestein R, Rabinovitz H, et al. Over-the-counter vitamin K1-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K1-depleted patients. Thromb Haemost 2004; 92:1018-24. View Abstract

      Looking around further a retrospective study also suggests that unstable warfarin patients have improved INR stability if they take vitamin K at 100 mcg daily.
      Reese AM, Farnett LE, Lyons RM, et al. Low-dose vitamin K to augment anticoagulation control. Pharmacotherapy 2005;25:1746-51. View Abstract
      However, other clinical research found no significant differences in INR stability in warfarin patients taking vitamin K 100 mcg daily compared to placebo.
      Rombouts EK, Rosendaal FR. Van Der Meer FJ. Daily vitamin K supplementation improves anticoagulant stability. J Thromb Haemost 2007;5:2043-8. View Abstract

      The American College of Chest Physicians Guidelines currently recommend vitamin K 100-200 mcg daily for patients on long-term warfarin therapy who have unstable INR that is not attributed to other causes.
      Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:160S-98S. View Abstract

      So what can we conclude – Warfarin patients started on low-dose vitamin K should be monitored closely. Warfarin doses may need to be adjusted to compensate for the vitamin K intake.

      Phylloquinone (K1) or menaquinone (K2) are capable of blocking the blood thinning action of anticoagulants like warfarin, which work by interfering with the action of vitamin K. They also reverse the tendency of these drugs to cause arterial calcification in the long term. Experts now advise a reasonably constant dietary intake of vitamin K that meets current dietary recommendations (90-120 mcg/day) for patients on vitamin K antagonists like warfarin.
      Booth SL, Centurelli MA. Vitamin K: a practical guide to the dietary management of patients on warfarin. Nutr Rev. 1999 Sep;57(9 Pt 1):288-96. Review. View Abstract

      The key point is to be consistent in the dose and avoid large fluctuations, and this may well include taking care not to overindulge in vitamin K containing foods. Vitamin K is found in a number of foods, including leafy greens, cauliflower and, if you consider it a food, liver. However, the chief source of vitamin K is synthesis by bacteria in the large intestine.

      Drugs that deplete vitamin K are
      • Antibiotics
      • Anticonvulsants
      • Bile acid sequesterants
      • Mineral oil
      • Orilstat
      • Rifampin

      Reply

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