The nutritional role of Vitamin K goes beyond coagulation of blood: An interview with Professor Sarah Booth of Tufts University

By Rob Winwood

The two most common forms of vitamin K are the phylloquinones (vitamin K₁) and menaquinones (vitamin K₂). Vitamin K₁ is found in green vegetables (i.e. parsley, spinach cauliflower), whereas vitamin K₂ is derived from animal sources (i.e. cheese, meat) and some fermented foods. Vitamin K plays an essential, and well-known role in the blood clotting process. However, Professor Sarah Booth at the Friedman School of Nutrition Science and Policy at Tufts University, Boston, USA, has investigated other important roles that it may have in human metabolism and health. Vitamin K exerts its blood clotting effect by being an enzymatic co-factor in the gamma carboxylation of vitamin K dependent (VKD) proteins. This same mechanism also occurs in other tissues of the body. In this way, Professor Booth believes that vitamin K and the VKD’s may play an important role in the regulation of calcification, energy metabolism, and inflammation (1).

A true assessment of vitamin K intake levels is difficult because whereas most food composition databases include phylloquinones (vitamin K₁), they do not include menaquinones (vitamin K₂). The Institute of Medicine (IOM) in the USA has set adequate intake (AI) for total vitamin K at 90 and 120 µg per day for adult women and men respectively (2).

The mineralisation of the human vascular system increases the risk of cardiovascular disease. Specifically, coronary artery calcification (CAC) is considered to be an independent predictor of CVD and mortality due to CVD. A vitamin K dependant protein called matrix Gla protein (MGP) is important in this process as it inhibits calcification (3).

A randomised controlled trial (RCT) looking at the effect of an intervention of vitamin K_1, calcium and vitamin D in postmenopausal women for three years demonstrated improved elasticity and compliance in the carotid artery (4). The authors proposed that the effect was due to reduced deposition of calcium caused by an increase in the vitamin K-dependent carboxylation of MGP. Professor Booth was involved in a subsequent RCT, which specifically looked at the effect of vitamin K₁ supplementation in reducing arterial calcification on older men and women (5). The team supplemented a cohort of 388 healthy older men and women with a high dose of vitamin K₁ (500 µg per day) for three years. The degree of artery calcification was determined by computed tomography (Agaston score).  In the participants who had some existing arterial calcification, there was a 6 percent reduction in further progression of calcification of the coronary artery when compared with placebo at the end of the intervention. However, curiously, there was no effect if the participants had no pre-existing arterial calcification condition. Also, there appeared to be no association between calcification and serum MGP concentrations, so the mechanism of the achieved reduction is unknown.

More recently, Professor Booth’s team turned its attention to vitamin K status in relation of lower extremity function (e.g. walking, sitting, getting in the bath or putting on socks) in the elderly (6). Her team conducted an RCT of a cohort of 1,089 community-dwelling older adults (average age 74 years) assessing lower extremity function (using a physical performance test battery) in relation to vitamin K₁ and MGP status. Over a four to five year observation period, they found that participants who had a blood plasma vitamin K₁ of 1 nM or more, had better results in the physical performance test battery and could walk faster. A possible reason for this improvement is that vitamin K₁ is known to reduce levels of inflammatory cytokines. Inflammation is a characteristic of the ageing process that often leads to a reduction in mobility.

Vitamin K has also been associated with bone loss and reduction in the risk of hip fracture in the elderly, but the results of RCTs have been equivocal. MK-4, a form of phylloquinone is used at doses of 45mg/d for the treatment of osteoporosis in Japan. However, whilst there is good evidence that MK-4 promotes bone turnover, recent trials have failed to show any protective effect in terms of bone mass density of the hip point (1). More positively, it has been suggested that vitamin K may have a role protecting against insulin resistance.

While Professor Booth has provided an excellent scientific foundation, it is clear that much further work needs to be done in this area if we wish to fully understand all the potential benefits of vitamin K.

A special thank you to Professor Sarah Booth at the Friedman School of Nutrition Science and Policy at Tufts University, in Boston, MA for providing perspective on this topic.

1. Booth SL; “Roles for Vitamin K Beyond Coagulation” Annu Rev Nutr 2009; 29: 5.1-5.22 .
2. Kyla Shea M & Booth SL; “Concepts and Controversies in Evaluating Vitamin K Status in Population-Based Studies”; Nutrients 2016; 8,8,doi: 10.3390/nu8010008 .
3. Luo G, Ducy P, McKee MD et al., “Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein”; Nature 1997; 386: 78-81.
4. Braam LA, Hoeks AP, Brouns F et al.; ”Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in post-menopausal women : a follow up study” ; Tromb Heamost 2004 ; 91 : 373-80.
5. Kyla Shea M, O’Donnell CJ, Hoffman U et al.; Vitamin K supplementation and progression of coronary artery calcium in older men and women”; Am J Clin Nutr 2009; 89:1799-807.
6. Kyla Shea M, Loeser RF, Hsu F-C. et al; “Vitamin K Status and Lower Extremity Function in Older Adults: The Health Aging and Body Composition Study”; J Gerentol A Biol Sci Med Sci 2015 Nov 17, 1-8. doi: 1093/Gerona/glv209