What is the Relationship Between Vitamin K and Cancer?

1. What is the Relationship Between Vitamin K and Cancer? By: Susan Albert

2. Vitamin K • Fat soluble vitamin • Stands between life and death • Coenzyme • Family of compounds • Phylloquinone (K1) • Menaquiones (K2) • Menadione (K3) (InselP., Turner, E., Ross, D., 2007)

3. Functions of Vitamin K • Blood clotting • Factor II, Factor VIII, Factor IX Inactive clotting factor X Vitamin K (adds carbon dioxide to glutamic acid) Calcium Factor Xa Prothrombin Thrombin (Gropper et al., 2009)

4. Inactive osteocalcin(substrate) Vitamin K Calcium Mechanism of action: carboxylation Active osteocalcin (product) • Bone Formation (Insel et al., 2007)

5. Recommendations • Deficiencies are extremely rare • No tolerable upper intake level • Adequate Intake (AI) • Men: 120 micrograms/day • Women: about 90 micrograms/day • Children: 30-55 micrograms/day (Insel et al., 2007)

6. Sources of Vitamin K Other sources: vegetable oils (soybean, cottonseed, canola, and olive), animal products (egg yolks, butter, various cheeses, liver), soybean products (tofu) (Insel et al., 2007)

7. Cancer • Breast • Colorectal • Lung • Liver (hepatocellular carcinoma) • Pancreatic • Prostate • Factors that increase risk: tobacco, diet, exposure to carcinogens in environment/workplace (Insel et al., 2007)

8. Mechanism of Action • Vitamin K-dependent carboxylation reactions • Potential Anticancer agent (Ohlsson et al., 2004) • Specific link to cancer is still unclear • Number proposed • Focus on oxidative capacity of K3 • Cell line research • K exerts inhibitory effects (Alternative Medicine Review, 2009)

9. Quick Review • Sources of vitamin K? • Functions? • What are the three types?

10. What is the relationship between vitamin K and cancer?

11. Dietary vitamin K in relation to cancer incidence and mortality: Results from Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg) Nimptsch, K., Rohrmann, S., Kaaks, R., & Linseisen, J. (2010). American Journal of Clinical Nutrition, 91(5), 1348-1358.

12. Overview • Study Design • Prospective cohort study • 24,340 participants • 11, 438 men & 12,902 women • Enrollment until 2008 • Objective • Location of study

13. Method and Statistics • Method • Baseline • Follow-up and outcome assessment • Descriptive • Mean • Standard deviation • Median • Range • Inferential • Cox proportional hazards regression model with hazard ratios • 95% confidence interval

14. Results Cancer Mortality Note: adapted from Nimptsch et al., 2010 * Age and sex stratified

15. Results Lung Cancer Incidence Note: adapted from Nimptsch et al., 2010 * Age and sex stratified

16. Results Prostate Cancer Incidence Note: adapted from Nimptsch et al., 2010 * Age and sex stratified

17. Other cancers Cancer Incidence Note: adapted from Nimptsch et al., 2010

18. Strengths and Weaknesses Strengths • Hypothesis • Large sample size • Statistics • Planning and organization • Validity Weaknesses • Validity

19. Conclusion • No relationship between K1 and K2 • Colorectal cancer incidence • Pre & post menopausal breast cancer incidence • No relationship between vitamin k1 • Prostate cancer incidence • Lung cancer incidence • Cancer mortality • Relationship between vitamin K2 • Prostate cancer incidence • Lung cancer incidence • Cancer mortality

20. What is the relationship between vitamin K and cancer?

21. High dose vitamin K3 infusion in advanced hepatocellular carcinoma Sarin, S.K., Kumar, M., Hissar, S., Pandey, C., & Sharma, B.C. (2006). Journal of Gastroenterology & Hematology,21(9), 1478-1482.

22. Overview • Study Design: randomized controlled clinical trial • Total participants: 42 • Placebo group (n=19) • High dose of vitamin K3 (n=23) • Objective • Location of study

23. Method & Statistics • Method • Baseline characteristics • Criteria to be included (4) • Treatment • Descriptive statistics • Median • Range • Mean • Standard deviation • Inferential statistics • Student t-test • Chi squared test • Kaplan-Meier survival curves

24. Baseline Characteristics Note: adapted from Sarin et al., 2006

25. Results Survival of patients with advanced heptacellular carcinoma treated with high dose K3 or placebo Note: adapted from Sarinet al., 2006

26. Causes of death in patients with advanced hepatocellular carcinoma treated with high dose K3 or placebo Note: adapted from Sarinet al., 2006

27. Kaplan-Meier survival curves

28. Strengths and Weaknesses Strengths • Purpose • Evidence of planning and organization • Statistics clearly stated • Population Weaknesses • First trial for those with advanced liver cancer • Demographics • Population • Small sample size

29. Conclusion • More research is needed • High doses do not affect overall survival • Vitamin K3 does not cure cancer • 1 patient achieved complete response • 13% partial response • 17.4% objective response • All patients died

30. Final Conclusions The relationship between vitamin K and cancer

31. Vitamins A and D but not E and K decreased the cell number in human pancreatic cell lines B. Ohlsson, E. Albrechtsson & J. Axelson

32. Overview • Study design • Experimental • Seven pancreatic cancer cell lines • Objective • Location

33. Method and Statistics • Method • Descriptive statistics • Mean • Standard deviation • Inferential Statistics • Kruskal-Wallis test • Mann-Whitney U test

34. Results

35. Strengths and Weaknesses Weaknesses • Controlled environment • Statistics • Future research Strengths • Purpose • Evidence of planning and organization • Statistics clearly stated Weaknesses

36. Verdict • Vitamin K1 • No relationship • Vitamin K2 • Lung cancer incidence • Prostate cancer incidence • Overall cancer mortality • Vitamin K3 • More research needed

37. Future Direction • American Cancer Society • Vitamin K1 and K2 (Nimptsch et al., 2010) • Biomarkers • More studies in humans • Vitamin K3 (Sarin et al., 2006). • Larger studies • Different dosages

38. Any questions?