HED: Vitamin K2: The Forgotten Vitamin


When one thinks of vitamin K (if they do at all), blood clotting likely comes to mind. While this is an important role, research has confirmed far greater capabilities in the goal of true human health.

There has been a rash of well-publicized studies, in particular the results of a 2013 JAMA-published study (1), that have linked calcium and vitamin D, which increases the absorption of calcium, to an increase in cardiovascular risk—showing that too much calcium is being deposited into arterial walls, creating a build-up of plaque—and this has led to calcium sales dropping 30% over the last three years.

What’s missing from this analysis is the vitamin K status of the study participants. Because what has been proven in studies (2) is that vitamin K, specifically vitamin K2, inhibits soft tissue calcification, reducing deaths from cardiovascular disease. Further, vitamin K2 has been clinically proven beneficial for bone health.

The Vitamin K Family
Although the name suggests differently, vitamin K is not a single compound. It consists of a group of fat-soluble vitamins that are essential for the body to have normal coagulation, or blood clotting, as well as to utilize calcium for healthy bones, arteries and soft tissues. The vitamin K family is divided into vitamin K1 (one molecule or phylloquinone) and vitamin K2 (a group of molecules or menaquinones).

While Vitamin K1 is needed for proper blood coagulation, Vitamin K2 is essential to build and maintain strong bones, as well as to avoid calcium deposits in the arteries, promoting cardiovascular health. Vitamin K2 exists in several forms, the most common ones are the synthetic menaquinone-4 (MK-4) and the natural or synthetic menaquinone-7 (MK-7).

All K vitamins are similar in structure: they share a “quinone” ring. However, they differ in the saturation and number of attached carbon-hydrogen atomes in the sidechain, called “isoprenoid residues” (3). These differences are especially pronounced in the vitamin K2 group, which includes menaquinones with different lengths of the side chain. The length is marked in the name of the particular menaquinone chain (for example MK-4 means that four isoprenoid residues are attached to the main ring). The length influences their abilities to reach different tissues within the body: the longer side chain (7-9 units) of the vitamin K, the better its potential. Consequently, the superior amongst all K vitamins are the long-chain menaquinones — especially MK-7 (4) They are completely absorbed, and remain in the blood for the longest time, and are therefore more available for all tissues when needed.

Where bone health is concerned, Vitamin K2 activates osteocalcin, a protein required to bind calcium to the mineral matrix, thus strengthening the skeleton. In circulation, Vitamin K2 allows the Matrix Gla Protein (MGP) to accomplish its desired goal: taking calcium away from the arteries (where it could have calamitous effects) and putting it in the bone (where the effects are far more beneficial).

Due to vitamin K’s activation of MGP and osteocalcin, calcium is ushered away from the arteries (high calcification correlates to increased death from cardiovascular disease), directing it and binding it to the bone mineral matrix. So the better one’s K status, the better their heart and bone health.


Vitamin K2 Through Diet
While vitamin K1 is found in green leafy vegetables, such as broccoli, spinach and kale, and is easy to incorporate into one’s diet, the more beneficial vitamin K2 is difficult to come by through diet alone.

Natural vitamin K2 is found in bacterially fermented foods like mature cheeses and curd. The MK-4 form of vitamin K2 is often found in relatively small quantities in meat and eggs. The best source of natural vitamin K2 is the traditional Japanese dish “natto,” which is made of fermented soybeans. Natto provides an unusually rich source of natural vitamin K2 as long-chain menaquinone-7.

Epidemiological trials show the benefits of eating food rich in vitamin K, especially vitamin K2, and the positive health impact on the populations and cultures regularly consuming traditional food sources of vitamin K.

In one such trial of a Dutch population, the dietary intake of phylloquinone (K1) and menaquinone (K2) was followed by 4,807 subjects for seven to 10 years (2). The relative risk of mortality due to coronary heart disease was reduced significantly with increased intake of dietary menquinones (K2) from food such as cheese, but not with intake of phylloquinone (K1) from vegetables.

For another epidemiological study, the health status of 944 Japanese women (aged between 20 and 79 years) was followed for three years, and natto intake was suggested to be responsible for preventing post-menopausal osteoporosis due to the effects of MK-7 (5).

Even though studies have found that natto consumption in Japan has been linked to significant improvement in K vitamins status and bone health, the intense smell and “controversial” taste make this soyfood a less attractive source of vitamin K2 for the Western population.

The Supplemental Solution
While it is a noble to try to attain K2 through the diet, it has been more frequently suggested that Americans are sub-clinically deficient in vitamin K2 (6). In general, the typical Western diet contains insufficient amounts of vitamin K2 to adequately activate MGP, which means about 30% of vitamin K2-activated proteins remain inactive. This amount only increases with age. Further, vitamin K2 is nearly non-existent in processed “junk” food, and even in a healthy Western diet.

Due to the deficiency of K vitamins in most people for optimal bone and cardiovascular health as a result of the Western diet, supplementation is recommended. Vitamin K2 is preferable to K1 as K2 intake has been linked to both bone and cardiovascular health, and the most desirable form of K2 is natural vitamin K2 as MK-7, as this is the most bioavailable, bioactive and longest lasting form of vitamin K available. One MK-7 product called MenaQ7® from NattoPharma has been tested by VitaK Research at the Maastricht University in the Netherlands, the World’s largest research institute dedicated to vitamin K, for safety and efficacy in humans.

Despite the strong epidemiological evidence showing that dietary intake of vitamin K2 may improve overall health status, it was not until a three-year ‘breakthrough’ study of MenaQ7 – completed in 2012 – that there had been a clinical trial to show that only a long-term (more than one year) supplement if vitamin K, especially MK-7, improves bone mineral density, bone mineral concentration and bone strength (7).

The study was a double-blind, randomized, clinical trial evaluating the results of a three-year regular intake of natural MK-7 in a 180 mcg daily dose by a group of 244 healthy post-menopausal Dutch women, 55 to 65 years old, randomly assigned to receive either MenaQ7 or identical-looking placebo capsules, daily.

This study is considered by the medical community to be a breakthrough because it shows clinically, for the first time, statistically significant protection with vitamin K against osteoporosis and cardiovascular deterioration with aging. Specifically, with regards to bone preservation, the study showed significant protection of the vertebrae and the hip (femoral neck) against osteoporosis and fractures due to bone degeneration. This was achieved with only 180 mcg/daily of MenaQ7, which is considered a ‘nutritional dose,’ meaning it is a dose that can be obtained from a healthy balanced diet.

Importantly, the three-year study showed, for the first time, substantial benefits of nutritional vitamin K2, as compared to the placebo group, in preventing age-related stiffening of arteries.

So for those seeking to sure up their skeletal structure and keep their circulatory systems flowing with ease, vitamin K2 needs to be kept top of mind.


1 Xiao et al, JAMA, 2013.

2 Geleijnse et al, Rotterdam study, 2004.

3 Shearer MJ, Physiology, 2003.

4 Schurgers LJ, et al, Blood. 2007.

5 Ikeda et al, Japanese population-based osteoporosis study, 2006.

6 Theuwissen et al, Food & Function, 2013.

7 Knapen et al, Osteoperosis International, 2013.


Katarzyna Maresz is currently a Scientific Coordinator and President of International Science and Health Foundation.  A master’s graduate at the Jagiellonian University, Pharmacy Faculty (specialization: Medical Analytics, 1998), she holds a PhD in Biological Sciences at the Medical Faculty of the Jagiellonian University (2002). Dr. Maresz held her practice at the Laboratory of Cellular and Molecular Immunology, Blood Research Institute, in Milwaukee, WI (2003-06), and was a post-doctoral fellow within the Marie-Curie Programme at the Department of Biochemistry, Biophysics and Biotechnology at the Jagiellonian University (2008-12).





Posted May 1, 2014