Vitamin K2 is Inversely Associated with Coronary Heart Disease Risk

by | Jun 23, 2020 | 2020, Cardiovascular Health, Vitamin K

Written by Joyce Smith, BS. Intake of K2, but not K1, was associated with a lower risk of coronary heart disease (CHD).

vitamin KVitamin K is a fat soluble vitamin that includes K1 (phylloquinone), found in green leafy vegetables and vegetable oils and K2 (menaquinone) derived from dairy products, meat, and egg yolks 1. Vitamin K2 is a cofactor that participates in the conversion of glutamate into gammacarboxyglutamate (GLA ) 2, which is involved in blood coagulation 3 and  the inhibition of plaque calcification in both the inner endothelial lining (intima) and the  muscular middle layer (media) of arteries 4,5. While studies have shown a higher risk of CHD for patients with arterial calcification, observational studies have been inconsistent in demonstrating an inverse association between vitamin K and CHD 6. In our western diet, hard cheese (richer in K2 than soft cheese), is the most important source of K2 7. Concentrations of vitamin K range from 40 μg to 850 μg per 100 g, while reduced-fat cheeses often contain as little as 5%–22% of the vitamin K found in regular cheeses.8 Different lactic acid bacteria used in the  cheese-making process account for the variability in K2 content 9, with Norwegian cheeses claiming the highest K2 content. 10,11.

The current study 12 evaluates the association between intake of K1 and K2 and subsequent CHD events in a community of middle-aged adults in Norway. In the observational community-based Hordaland Health Study from 1997 – 1999 through 2009, researchers followed 2,987 Norwegian men and women, ages 46–49 years, to evaluate associations between intake of vitamin K and incident (new onset) CHD. They found that the Norwegian participants’ major dietary sources of K1 were vegetables (64%), fruits and berries (6%) and milk and milk products (6%), while sources of K2 were cheese (40%), other dairy products (14%), meat (24%) and eggs (13%).

During a median follow-up time of 11 years, researchers documented 112 incident CHD cases. They found no association between vitamin K1 intake and CHD (p for trend 0.64), while higher vitamin K2 intake was associated with lower CHD risk (p for trend 0.03). Adjusting for potential dietary confounders had no effect on K1 and only slightly reduced the association between K2 and CHD. Study results indicate an inverse association between vitamin K2 intake and CHD risk and no association between intake of vitamin K1 and CHD. In addition, the study validates that in healthy participants, supplementation with Vitamin K2 may potentially decrease the progression of hardening of the arteries.

Study strengths include results that can be generalizable to other middle-aged Western populations in which dairy products are the primary source of K2. Also, linking to a nationwide database allowed for a complete cohort follow-up and provided accurate baseline information on all participants’ CHS history. Among the limitations were the differences seen in K1 and K2 levels that may be due to biological differences. As well, the Food Frequency Questionnaire (FFQ) could not account for the different levels of K1 intake 13. Also, differentiating among the various sub-types of K2 was not possible. Since current dietary guidelines are based on insufficient knowledge, the research team reiterates the importance of more research on the association between K2 and CHD, as well as research that provides greater knowledge of the absorption, transportation and bioactivity of K2.

Source: Haugsgjerd, Teresa R., Grace M. Egeland, Ottar K. Nygård, Kathrine J. Vinknes, Gerhard Sulo, Vegard Lysne, Jannicke Igland, and Grethe S. Tell. “Association of dietary vitamin K and risk of coronary heart disease in middle-age adults: the Hordaland Health Study Cohort.” BMJ open 10, no. 5 (2020): e0

© BMJ Open 2020;10:e035953. doi:10.1136/bmjopen-2019-035953

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Posted June 23, 2020.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

References:

  1. Booth SL, Suttie JW. Dietary intake and adequacy of vitamin K. J Nutr. 1998;128(5):785-788.
  2. Levy RJ, Zenker JA, Lian JB. Vitamin K-dependent calcium binding proteins in aortic valve calcification. J Clin Invest. 1980;65(2):563-566.
  3. Suttie JW. Synthesis of vitamin K-dependent proteins. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 1993;7(5):445-452.
  4. Tintut Y, Demer LL. Recent advances in multifactorial regulation of vascular calcification. Curr Opin Lipidol. 2001;12(5):555-560.
  5. Vermeer C, Braam L. Role of K vitamins in the regulation of tissue calcification. Journal of bone and mineral metabolism. 2001;19(4):201-206.
  6. Rees K, Guraewal S, Wong YL, et al. Is vitamin K consumption associated with cardio-metabolic disorders? A systematic review. Maturitas. 2010;67(2):121-128.
  7. Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis. 2000;30(6):298-307.
  8. Fu X, Harshman SG, Shen X, et al. Multiple Vitamin K Forms Exist in Dairy Foods. Current developments in nutrition. 2017;1(6):e000638.
  9. Beulens JW, Booth SL, van den Heuvel EG, Stoecklin E, Baka A, Vermeer C. The role of menaquinones (vitamin K₂) in human health. Br J Nutr. 2013;110(8):1357-1368.
  10. Vermeer C, Raes J, van ‘t Hoofd C, Knapen MHJ, Xanthoulea S. Menaquinone Content of Cheese. Nutrients. 2018;10(4).
  11. Hojo K, Watanabe R, Mori T, Taketomo N. Quantitative measurement of tetrahydromenaquinone-9 in cheese fermented by propionibacteria. J Dairy Sci. 2007;90(9):4078-4083.
  12. Haugsgjerd TR, Egeland GM, Nygård OK, et al. Association of dietary vitamin K and risk of coronary heart disease in middle-age adults: the Hordaland Health Study Cohort. BMJ Open. 2020;10(5):e035953.
  13. Halder M, Petsophonsakul P, Akbulut AC, et al. Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease. Int J Mol Sci. 2019;20(4).