Vitamin (K)ardiovascular health?

As you age, there’s a lot to look forward to: career development, watching your children and grandchildren grow, and retirement, are some things that come to mind. But along with the good, there’s also the bad. For post-menopausal women, an increased risk of heart attack or stroke is among the bad. The drop in estrogen after menopause is an independent risk factor^[1] for cardiovascular disease in women. Hormone replacement therapy comes with its own set of risks^[2] and its efficacy at reducing cardiovascular disease is controversial^[3], though. So, is there another way to lower cardiovascular disease risk in women?

Some studies are starting to suggest that vitamin K may be one possible route. There are different forms of vitamin K (shown in Figure 1) known as vitamers. Vitamin K1, also known as phylloquinone, is found in leafy green vegetables^[4]. There is also a group of vitamin K2 vitamers, known as the menaquinones (MKs). This is a family of molecules that differ through how many isoprene units make up their side chain. The name of a specific type of vitamin K2 is based on the length of this side chain. So, vitamin K2 with seven units in its side chain is called MK-7. The forms of vitamin K2 have different physiological effects than vitamin K1, which largely benefits clotting and was named for the German term “koagulation.”

Figure 1: The K vitamins

Recent observational^[5] evidence^[6] suggests that dietary intake of MKs may be associated with a lower risk of cardiovascular disease. Interestingly, these studies found no such association with the intake of vitamin K1. Another observational study^[7] found that the higher-chain MKs, specifically MK-7, MK-8, and MK-9, were particularly associated with decreased cardiovascular disease risk. Many of the MKs, especially the longer-chain ones, are found in meat and cheese^[4], with MK-7 mostly found^[8] in a type of fermented soybean from Japan called natto (a food that is unappetizing to those unaccustomed to the slimy texture and funky taste), although it can also be found increasingly as a dietary supplement.

In terms of interventional trials for the prevention of cardiovascular risk factors, only vitamin K1 has been tested to date, with mixed results and at five to ten times the recommended daily allowance. One trial^[9] found some effect on blood vessel elasticity when combined with vitamin D, and another^[10] found no effect in its primary endpoint measuring artery hardening, but found some promise in a subgroup analysis of those who were highly adherent to the supplementation regimen.

For vitamin K2, things look different, though. The observational studies mentioned above suggest that vitamin K2 intake that is associated with decreased cardiovascular disease risk, not K1. Furthermore, one of the MKs, MK-7, has been found^[11] to have properties that suggest it would make a better supplement than vitamin K1. Specifically, it lasts longer in the blood stream, is absorbed well, and may be more potent by some measures such as inducing bone-building. But up until now, no interventional studies tested the effect of MK supplementation on cardiovascular outcomes. The purpose of the trial we’re reviewing here was to fill this hole in the research.

There are two different kinds of vitamin K: vitamin K1 and vitamin K2. Vitamin K2 also has different subtypes depending on the length of its chemical side chain. These are known as the menaquinone Ks, or MKs. Observational studies have suggested that a high dietary intake of MKs are associated with a reduced risk of cardiovascular disease, but this hypothesis has not been tested in a clinical trial up until this one.