Cardiovascular Disease Death Before Age 65 in 168 Countries Correlated Statistically with Biometrics, Socioeconomic Status, Tobacco, Gender, Exercise, Macronutrients, and Vitamin K (Cundiff DK and Agutter PS)

A study using multiple regression analysis of worldwide cohort data has recently been published in Cureus as a way of dealing with major cardiovascular disease (CVD) risk factors, among which the deficiency of Vitamin K2 plays a crucial role.

The research has been conducted by collecting publicly accessible data of food commodity availability and deriving nutrient profiles including Vitamin K2 for people from 168 countries. Nutrition scientists and cardiologists hotly dispute on the diet optimal for the prevention of CVD, and the data presented in this paper supports the hypothesis that Vitamin K2 (especially the long chain menaquinones: MK-4–MK-13) plays a central role in CVD etiology, epidemiology, and pathogenesis. Animal trials and human observational studies that have been performed in Europe and in the US in the recent years, have demonstrated that vitamin K2 deficiency (either caused by poor diet or by warfarin) contributes to CVD by stiffening and calcifying coronary arteries and other vessels. Vitamin K2’s role in keeping calcium out of arteries and into bones may account for its beneficial role in reducing high blood pressure as well as the number of early CVD deaths.

The authors collected female and male cohort data on early death from CVD (ages 15–64 years), insufficient physical activity, tobacco, biometric CVD risk markers, socioeconomic risk factors for CVD, and gender. The outcome measures included (1) univariate correlations of early death from CVD with each risk factor, (2) a multiple regression-derived formula relating early death from CVD (dependent variable) to macronutrient profile, vitamin K1 and K2 and other risk factors (independent variables), (3) for each risk factor appearing in the multiple regression formula, the portion of CVD risk attributable to that factor, and (4) similar univariate and multivariate analyses of body mass index (BMI), fasting blood sugar (FBS) (simulated from diabetes prevalence), systolic blood pressure (SBP), and cholesterol/ HDL-C ratio (simulated from serum cholesterol) (dependent variables) and dietary and other risk factors (independent variables). The results of this trial showed that female and male cohorts in countries that have vitamin K2 < 5μg per 2000 kcal/day per capita (n = 70) had about 2.2 times the rate of early CVD deaths as people in countries with > 24μg/day of vitamin K2 per 2000 kcal/day (n = 72). The present study also found that Vitamin K2 was inversely correlated with early CVD death (r = –0.41, P < 0.0001) to the same degree that tobacco use was positively correlated (r = 0.41, P < 0.0001).

The researchers noted that inadequate vitamin K2 intake was the dominant dietary problem in poor countries. The complete lack of a statistical effect of vitamin K1 on early CVD deaths (r = –0.04 P = 0.45) or SBP (r = –0.01 P = 0.93) further supports the hypothesis that the molecular differences between Vitamin K1 (phylloquinone) and Vitamin K2 (menaquinones) account for why Vitamin K-dependent proteins (VKDP) in arterial walls require Vitamin K2 and not Vitamin K1 to prevent the deposition of calcium and the stiffening of arterial walls.

To that end, the authors suggested that health regulatory agencies of countries should more inclusively measure Vitamin K2 levels (MK-4–MK-13) in foods and should designate levels for adequate intakes (AIs) for Vitamin K2. Public health programs should be considered to increase the intake of Vitamin K2-containing fermented plant foods such as sauerkraut, miso, and natto.

Dr. Katarzyna Maresz, president of the International Science and Health Foundation, emphasized that carrying out tests of the activity of VKDP such as dpucMG or ucOC should become a common practice among medical doctors in order to recognize and treat Vitamin K deficiency. “The proposition that Vitamin K2 should be systematically quantified in food products is not the best in my opinion. However, it is important to point that the different production procedures will influence Vitamin K2 content. The number of products to test is extremely big,” says Dr. Maresz. “However, it is important to open the eyes of nutritionists and add Vitamin K2 info to nutrition tables,” she concludes.

Dr. Maresz also remarks on another aspect of the present study: “The authors did not include in the paper the data from a 3-year clinical study [Knapen MH et al], which shows that Vitamin K2 supplementation improves arterial elasticity. Moreover, Kurnatowska study [Kurnatowska et al] showed that Vitamin K2 and Vitamin D3 supplementation is beneficial for cardiovascular system in CKD [chronic kidney disease] patients.”


  1. Cundiff DK, Agutter PS (August 24, 2016) Cardiovascular Disease Death Before Age 65 in 168 Countries Correlated Statistically with Biometrics, Socioeconomic Status, Tobacco, Gender, Exercise, Macronutrients, and Vitamin K. Cureus 8(8): e748. DOI 10.7759/cureus.748
  2. Knapen MH, Braam LAJL, Drummen NE, Bekers O, Hoeks APG, Vermeer C. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women: double-blind randomised clinical trial. Thrombosis and Haemostasis. 2015 113 5: 1135-1144. doi: 10.1160/TH14-08-0675.
  3. Kurnatowska I, Grzelak P, Masajtis Zagajewska A, Kaczmarska M, Stefańczyk L, Vermeer C, Maresz K, Nowicki M. Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stage 35. Pol Arch Med Wewn. 2015 Jul 15. pii: AOP_15_066. [Epub ahead of print]
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