By: Susan Albert. Vitamin K Fat soluble vitamin Stands between life and death Coenzyme Family of...
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What is the Relationship Between Vitamin K and Cancer? By: Susan Albert
By: Susan Albert. Vitamin K Fat soluble vitamin Stands between life and death Coenzyme Family of compounds Phylloquinone (K1) Menaquiones (K2) Menadione
Vitamin K Fat soluble vitamin Stands between life and death
Coenzyme Family of compounds Phylloquinone (K1) Menaquiones (K2)
Menadione (K3) (Insel P., Turner, E., Ross, D., 2007)
Slide 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)
Slide 4
Bone Formation Inactive osteocalcin (substrate) Vitamin K
Calcium Mechanism of action: carboxylation Active osteocalcin
(product) (Insel et al., 2007)
Slide 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)
Slide 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)
SourceGramsServingmcg Kale85~ cup694 Spinach85~ 3 cups410 Turnip
greens85~3 cups213 Broccoli85~ cup120 Romaine lettuce85~ 1 cups87
Beef liver853 oz3.3 (Insel et al., 2007)
Slide 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)
Slide 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)
Slide 9
Quick Review Sources of vitamin K? Functions? What are the
three types?
Slide 10
What is the relationship between vitamin K and cancer?
Slide 11
Nimptsch, K., Rohrmann, S., Kaaks, R., & Linseisen, J.
(2010). American Journal of Clinical Nutrition, 91(5),
1348-1358.
Slide 12
Overview Study Design Prospective cohort study 24,340
participants 11, 438 men & 12,902 women Enrollment until 2008
Objective Location of study
Slide 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
Slide 14
Results Q1Q2Q3Q4P value K1
Cases/non-cases129/5956104/5982111/5975115/5969 HR*10.880.890.93
95% CI(0.68,1.14)(0.69,1.16)(0.71,1.22)0.70 K2
Cases/non-cases156/5928114/597290/599698/5986 HR*10.770.640.72 95%
CI(0.60, 0.99)(0.49, 0.85)(0.53, 0.98)0.03 Cancer Mortality Note:
adapted from Nimptsch et al., 2010 * Age and sex stratified
Slide 15
Results Q1Q2Q3Q4P value K1 HR*11.061.301.190.54 K2
HR*10.620.430.380.002 Lung Cancer Incidence Note: adapted from
Nimptsch et al., 2010 * Age and sex stratified
Slide 16
Results Q1Q2Q3Q4P Value K1 HR*10.891.00 0.84 K2
HR*10.790.670.650.03 Prostate Cancer Incidence Note: adapted from
Nimptsch et al., 2010 * Age and sex stratified
Slide 17
Other cancers Cancer typeP value for trend (K1) P value for
trend (K2) Colorectal0.500.57 Premenopausal breast cancer 0.580.70
Postmenopausal breast cancer 0.510.57 Cancer Incidence Note:
adapted from Nimptsch et al., 2010
Slide 18
Strengths and Weaknesses Strengths Hypothesis Large sample size
Statistics Planning and organization Validity Weaknesses
Validity
Slide 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
Slide 20
What is the relationship between vitamin K and cancer?
Slide 21
Sarin, S.K., Kumar, M., Hissar, S., Pandey, C., & Sharma,
B.C. (2006). Journal of Gastroenterology & Hematology, 21(9),
1478-1482.
Slide 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
Slide 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
Slide 24
Baseline Characteristics CharacteristicsVitamin K( n=23)Placebo
(n=19)P-Value Age (years) Mean +/- SD50.7 +/- 11.951.7 +/- 8.40.859
Median4854 Range27-7241-69 Sex n (%) Male 18 (78.3) 15(78.9) 1.000
Female 5(21.7) 4(21.1) Etiology n (%) Hepatitis B 17(73.9) 15(78.9)
0.895 Hepatitis C 4 (17.4) 3(15.8) Other 2 (8.7) 1 (5.3) Note:
adapted from Sarin et al., 2006
Slide 25
Results Groupn (%)Survival (months) median (range) 1-year
survival n (%) High dose K3 Complete response1 (4.3)371/1 (100)
Partial response3 (13)14 (11-28)2/3 (66.7) Objective response4
(17.4)21 (11-37)3/4 (75) Non-responsive19 (82.6)5 (1-16)4/19 (21.1)
Stable disease4 (17.4)12.5 (3-16)3/4 (75) Progressive disease15
(65.2)3.5(1-13)1/14 (6.7) Placebo19 (100)5(1.5-21)3/19(15.8) Note:
adapted from Sarin et al., 2006 Survival of patients with advanced
heptacellular carcinoma treated with high dose K3 or placebo
Slide 26
Causes of death in patients with advanced hepatocellular
carcinoma treated with high dose K3 or placebo TreatmentCancer
related n (%) Hepatic failure n (%) Hemorrhage n (%) High dose K313
(56.5)6 (26.1)4 (17.4) Placebo14 (73.7)4 (21.1)1 (5.3) Note:
adapted from Sarin et al., 2006
Slide 27
Kaplan-Meier survival curves
Slide 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
Slide 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
Slide 30
Final Conclusions The relationship between vitamin K and
cancer
Slide 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
Slide 32
Overview Study design Experimental Seven pancreatic cancer cell
lines Objective Location
Slide 33
Method and Statistics Method Descriptive statistics Mean
Standard deviation Inferential Statistics Kruskal-Wallis test
Mann-Whitney U test
Slide 34
Results
Slide 35
Strengths and Weaknesses Strengths Purpose Evidence of planning
and organization Statistics clearly stated Weaknesses Weaknesses
Controlled environment Statistics Future research
Slide 36
Verdict Vitamin K1 No relationship Vitamin K2 Lung cancer
incidence Prostate cancer incidence Overall cancer mortality
Vitamin K3 More research needed
Slide 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