Dietary Vitamin K Intake and the Risk of Pancreatic Cancer

A Prospective Study of 101,695 American Adults

Dao-Wu Yu; Qu-Jin Li; Long Cheng; Peng-Fei Yang; Wei-Ping Sun; Yang Peng; Jie-Jun Hu; Jing-Jing Wu; Jian-Ping Gong; Guo-Chao Zhong


Am J Epidemiol. 2021;190(10):2029-2041. 

In This Article

Abstract and Introduction


No epidemiologic studies have been conducted to assess the association of intake of dietary vitamin K with the risk of pancreatic cancer. We used prospective data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial between 1993 and 2009 to fill this gap. A total of 101,695 subjects were identified. Dietary intakes of phylloquinone (vitamin K1), menaquinones (vitamin K2), and dihydrophylloquinone (dihydrovitamin K1) were assessed using a food frequency questionnaire. Cox regression was applied to calculate hazard ratios and 95% confidence intervals. During a mean follow-up of 8.86 years (900,744.57 person-years), 361 cases of pancreatic cancer were documented. In the fully adjusted model, dietary intakes of phylloquinone (for quartile 4 vs. quartile 1, hazard ratio (HR) = 0.57, 95% confidence interval (CI): 0.39, 0.83; P for trend = 0.002) and dihydrophylloquinone (for quartile 4 vs. quartile 1, HR = 0.59; 95% CI: 0.41, 0.85; P for trend = 0.006), but not menaquinones (for quartile 4 vs. quartile 1, HR = 0.93; 95% CI: 0.65, 1.33; P for trend = 0.816), were found to be inversely associated with the risk of pancreatic cancer in a nonlinear dose–response manner (all P values for nonlinearity < 0.05), and this was not modified by predefined stratification factors and remained in sensitivity analyses. In conclusion, dietary intakes of phylloquinone and dihydrophylloquinone, but not menaquinones, confer a lower risk of pancreatic cancer. Future studies should confirm our findings.


Pancreatic cancer is the fourth leading cause of cancer-related mortality in the US population, with a 5-year survival rate of less than 10%.[1] Hence, it is essential and urgent to identify modifiable risk factors that can decrease the burden of this cancer. The well-established risk factors for pancreatic cancer include cigarette smoking, type 2 diabetes mellitus, and obesity.[2] Apart from these traditional risk factors, dietary habits have been also indicated to play a moderate role in the etiology of pancreatic cancer.[3,4]

Vitamin K, a fat-soluble vitamin, physiologically functions as a cofactor for γ-glutamyl-carboxylase[5] and occurs in 2 natural forms in foods: phylloquinone (vitamin K1) and menaquinones (vitamin K2). Phylloquinone is a major form of dietary vitamin K and is predominantly found in green leafy vegetables and vegetable oils, whereas menaquinones are primarily found in fermented products and meat.[6] Dihydrophylloquinone is a hydrogenated form of dietary vitamin K that is formed during the industrial hydrogenation of phylloquinone-rich plant oils;[7] the major sources of dihydrophylloquinone include margarine, mayonnaise, fast-food, or heated French fries.[7]

Interestingly, beyond its classic function in blood coagulation, vitamin K has been found in experimental studies to have antitumor effects on various cancer cells;[8–11] moreover, epidemiologic studies found that dietary vitamin K intake was inversely associated with risks of type 2 diabetes mellitus[12] and metabolic syndrome,[13] 2 well-known risk factors for cancer.[14,15] Together, these findings indicate that vitamin K may play a favorable role against carcinogenesis.[16,17] Indeed, results from large prospective studies have shown an inverse association between dietary menaquinone intake and risks of prostate and lung cancers.[18,19]

However, to our knowledge, the association of dietary vitamin K intake with the risk of pancreatic cancer has not been investigated previously. Hence, we conducted a prospective study to examine the hypothesis that dietary intakes of phylloquinone, menaquinones, and dihydrophylloquinone were inversely associated with the risk of pancreatic cancer in a US population.