Frequently Asked Questions:
Vitamin K is not a single compound – it consists of a group of essential fat-soluble vitamins. The vitamin K family is divided into vitamin K1 – one molecule (phylloquinone) – and vitamin K2 – a group of molecules (menaquinones). 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 share a “quinone” ring. However, they differ in the saturation and number of attached carbon-hydrogen atomes in the sidechain, called “isoprenoid residues.” 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 (ex: MK-4 means 4 isoprenoid resides are attached to the main ring), and the length influences their abilities to reach different tissues within the body. In other words, the longer the side chain, the better it is absorbed and longer it remains in the blood.
Vitamin K1, or phylloquinone, is produced by plants and algae, while vitamin K2, or menaquinone, is predominantly of microbial origin. As vitamin K2 is difficult to obtain through diet alone, supplementation is recommended.
There are three forms of K vitamins presently available in dietary supplements: synthetic vitamin K1, synthetic menaquinone-4 (MK-4), and natural or synthetic vitamin K2 as menaquinone-7 (MK-7). Recent studies show that natural vitamin K2 as MK-7 is consistently found to be much more effective compared to both vitamin K1 and MK-4. This is mainly due to significantly greater bioavailability (well absorbed) and bioactivity (half-life time).
More specifically, vitamin K2 is comprised of a family of molecules distinguished from K1 by unsaturated side chains of isoprenoid units that vary in length from 1 to 14 repeats. One will often see “vitamin K2 as menaquinone-7” or “MK-7” because this means that the active, health-supporting “repeat” is the seventh menaquinone.
Vitamin K1 has always been known as the “coagulation” vitamin because it helps keep the body’s blood-clotting mechanism functioning in a healthy manner. Vitamin K2, meanwhile, activates inactive proteins in the body that keep systems healthy.
There are many proteins in the body responsible for processes that keep systems healthy, but these proteins need to be activated, which is where vitamin K2 comes into play. Vitamin K2 has been shown to activate 17 inert proteins. When these proteins encounter vitamin K2, they bond and begin working. For example, vitamin K2 activates a protein called osteocalcin, which works to moderate a healthy bone turnover process, ensuring that as much bone is built to replace the bone that is broken down. Another protein that vitamin K2 encourages to work is Matrix Gla protein (MGP), which helps keep cardiovascular arteries pliable and healthy by discouraging calcium from adhering to arterial walls, calcifying (or hardening) them.
The largest body of research has focused on vitamin K2’s beneficial influence on bone and cardiovascular health based on the activation of osteocalcin and MGP, but there are numerous studies planned and under way to demonstrate the precise manner in which K2 activates the 15 other proteins, and the specific benefit for human health.
A small amount of vitamin K2 is present in the colon, where it is synthesized by the intestinal microflora. Vitamin K2 is primarily found in animal products, such as meat, dairy, and eggs, and fermented foods like cheese, yogurt, and natto, a Japanese traditional dish of fermented soybeans. (Note: K2 is only found in “real” cheese, that is, rind cheeses that are sliced from a wheel, not processed cheese, or “cheeze” foods. Food processing strips the vitamin out, and some of these chemical “cheezes” never had nutrients such as K2 to begin with.)
Cultured cheese like Gouda can provide up to 50 mcg of menaquinone-7 (vitamin K2) per 100 g of cheese consumed. But the richest source of natural vitamin K2 is the traditional Japanese dish natto, which provides a uniquely ample store of natural vitamin K2 as long-chain menaquinone-7 (MK-7).
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. Due to this deficiency, supplementation is recommended.
Current daily recommendations for K vitamins are based exclusively on vitamin K1 and the requirement for proper blood clotting, which is 1 mcg vitamin K1 per kg of body weight (daily). But this amount of vitamin K1 is insufficient for the optimal function of vitamin K-dependent proteins in other tissues like bone and vasculature – since vitamin K1 has a short half-life time, or bioactivity, the recommended dose will not reach these peripheral tissues.
Studies have shown that vitamin K2 as menaquinone-7 (MK-7) is effective at very low doses and experts recommend just 45 mcg per day to maintain healthy bone and cardiovascular health.
However, a recent study, published in the peer-reviewed journal Osteoporosis International, followed 244 healthy post-menopausal women who took 180 mcg of vitamin K2 as MK-7 (menaquinone-7) daily for 3 years. The researchers found that there was statistically significant protection against cardiovascular deterioration, as well as and improved bone status. (NOTED: 180 mcg/daily of MK-7 is considered a ‘nutritional dose,’ meaning it is a dose that can/should be obtained from a healthy balanced diet.)
As with everything, one can get too much of a good thing. Eating more vitamin K2-containing foods is encouraged as part of a healthy diet. When supplementation is used to fill vitamin-K2 gaps, it is recommended to always follow label dosing instructions.
Inside the human body, liver stores of vitamin K normally comprise about 90% menaquinones (K2) and 10% phylloquinone (K1). Vitamin K is extensively metabolized in the liver and excreted in the urine and bile. Researchers found that about 20% of an injected dose of phylloquinone was recovered in the urine, while about 40-50% was excreted in the feces through the bile. It seems likely, therefore, that about 60-70% of the amount of K1 absorbed from food will ultimately be lost to the body by excretion. These results suggest that the body stores of vitamin K need to be constantly replenished.
Further, researchers conducted a study with 15 volunteers, who took both vitamin K2 and K2 as MK-7 (menaquinone-7), and collected their blood samples at the beginning and 8 more precise times for up to 96 hours. In a related study, 10 people received both vitamin K2 and MK-7, the latter in increasing doses. The research team showed that the viability (half-life) of MK-7 in plasma lasted several times longer compared to the vitamin K2 when similar levels of either form were consumed.
A vitamin K insufficiency does not lead to dramatic, intensely painful, debilitating symptoms of deficiencies of other vitamins, such as vitamins C (scurvy), B1 (beri beri), or D (rickets). While insufficient vitamin K1 can lead to improper blood clotting, or bleeding more than one should after a cut, insufficient levels of K2 can lead to the decline in bone health status (potentially osteoporosis) and calcification of the cardiovascular arteries, making them stiff and inelastic – symptoms that are not immediately or obviously detectable.
There are 3 factors that can increase vitamin K2 insufficiency: poor nutrition and use of antibiotics that deteriorate gut flora; poor absorption of K2 from the gut due to aging or chronic gastrointestinal (GI) infections; and age-related compromised bioavailability of K2. If any of these factors correlate with one’s lifestyle, they should consider the possibility that they are vitamin K2 deficient.
Oral anticoagulants work by a mechanism that inhibits vitamin K. Vitamin K1, due to its ability to support healthy blood clotting, may interact or interfere with anti-coagulants such as warfarin. Researchers concluded in one study that vitamin K2 (MK-7) supplementation at doses as low as 10 μg (lower than usual retail dose of 45 μg) significantly influenced anticoagulation sensitivity in some individuals. Thus, the researchers recommended avoiding use of MK-7 supplements if on vitamin K-antagonist therapy.
However, it has been shown that patients on oral anti-coagulant therapy who took up to 50 mcg of vitamin K2 as MK-7 per day have more complete activation of osteocalcin without interfering with the effect of the blood thinner. In other words, taking a small amount of MK-7 allows one to avoid the side effects of these medications without interfering with their intended benefits.
On the basis of the latest insights and in order to remain on the safe side, it is recommended that patients on conventional blood thinners consult with their doctor before taking a vitamin K2 supplement, since taking more than 50 mcg might interfere with the prescription.
Monitoring vitamin K status can help reduce risk of osteoporotic bone fractures and cardiovascular disease. One’s vitamin K status can be measured directly by looking at blood levels of inactive (also known as “undercarboxylated”) osteocalcin. It is more difficult for a doctor to discern K status in the blood because the very little vitamin K one consumes is stored in the body. So, looking at levels of a K-dependent protein, such as osteocalcin, is more accurately reflective of one’s K2 status – the more inactive osteocalcin, the lower the range of K2; higher levels of active osteocalcin, K2 status is likely quite sufficient.