Should vitamin K2 also be recommended for statin users?

Writing in Expert Review of Clinical Pharmacology​​, Japanese scientists report that statins inhibit the synthesis of vitamin K2. K2 plays a critical role in the activation of matrix Gla protein (MGP) that in turn inhibits cardiovascular calcification, they said.

MGP binds calcium and protects blood vessels from calcification, but only when activated and that requires adequate intakes of vitamin K2. By inhibiting vitamin K2 synthesis in the body, statins may actually accelerate coronary artery calcification, according to researchers.

While CoQ10 is recommended to people on statins to offset the CoQ10-depleting effects of the medication, no such recommendations currently exist for vitamin K2, said Kate Quackenbush, director of communications for vitamin K2 supplier NattoPharma. “We feel vitamin K2 supplements should absolutely be recommended to people taking statins, but they currently are not,”​ she told us.

“This new paper speaks directly to statins interrupting the mechanism of action by which vitamin K2 inhibits calcification,” ​added Hogne Vik, NattoPharma’s CEO. “Conversely, research clearly demonstrates that increasing dietary vitamin K2, specifically vitamin K2 as menaquinone-7, can improve vitamin K2 levels in the blood and tissues, thus promoting cardiovascular health.”  ​

Effects on selenium containing proteins​

Led by Harumi Okuyama from Kinjo Gakuin University, the authors also note that the pharmaceuticals also inhibit the biosynthesis of selenium containing proteins, one of which is the antioxidant enzyme glutathione peroxidase which counters peroxidative stress.

“An impairment of selenoprotein biosynthesis may be a factor in congestive heart failure, reminiscent of the dilated cardiomyopathies seen with selenium deficiency,” ​they wrote. “Thus, the epidemic of heart failure and atherosclerosis that plagues the modern world may paradoxically be aggravated by the pervasive use of statin drugs. ​

“We propose that current statin treatment guidelines be critically re-evaluated.”​

Statin use​

Statin use has been increasing rapidly over the last few decades, rising from 2% of adults 45 years of age and over in 1988-94 to 25% in 2005–2008, according to the National Center for Health Statistics (NCH Stats​).  

Concerns about the side-effects of statin use are not new, and the US Food and Drug Administration issued a consumer update in 2014​ explaining that the medications have been linked to potential liver injury (rare, according to FDA), memory loss, muscle damage, and an increased risk of diabetes.

The Japanese authors claimed that the majority of clinicians still rely on meta-analyses published prior to 2004 that conclude statins are effective in lowering LDL-C levels and preventing coronary heart disease (CHD). However, papers published after 2004 “by scientists essentially free of conflict”​ indicated that “statins are ineffective in preventing CHD”​, they said.

“Severe and often irreversible adverse effects of statins and their pharmacological mechanisms have been discussed in this study, indicating that the applicability of statins should be severely restricted.”​

Vitamin K2 and cardiovascular health ​

With no sign that the mainstream medical community will move away from recommending statins, it may be prudent to add K2 to the supplement list for people taking the medications, given the cardiovascular benefits of vitamin K2.

Data from a long-term study published in Thrombosis and Haemostasis​ recently indicated that supplementation with vitamin K2 (NattoPharma’s MenaQ7) may inhibit age-related stiffening of the artery walls in healthy postmenopausal women.

A daily 180 microgram dose of vitamin K2 for three years was also associated with statistically significant improvement of vascular elasticity, wrote scientists from VitaK at the Maastricht University Holding (The Netherlands), and lead researcher on the study.

K forms​

There are two main forms of vitamin K: phylloquinone, also known as phytonadione, (vitamin K1) which is found in green leafy vegetables such as lettuce, broccoli and spinach, and makes up about 90% of the vitamin K in a typical Western diet; and menaquinones (vitamins K2), which make up about 10% of Western vitamin K consumption and can be synthesized in the gut by microflora.

Menaquinones (MK-n: with the n determined by the number of prenyl side chains) can also be found in the diet; MK-4 can be found in animal meat, MK-7, MK-8, and MK-9 are found in fermented food products like cheese, and natto is a rich source of MK-7.

Sources: Expert Review of Clinical Pharmacology​​
March 2015, Vol. 8, No. 2 , Pages 189-199 (doi:10.1586/17512433.2015.1011125)
“Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms”​
Authors: H. Okuyama, P.H. Langsjoen, T. Hamazaki, et al.