The ABCs of Vitamin K1, K2, and K3

Researchers have identified three main forms of vitamin K: Vitamin K1, vitamin K2, and vitamin K3. Furthermore, there are two principal forms of vitamin K2. Each has slight differences in chemical structure, but all seem to be used by the body. Vitamin K3 is not used in supplements for people, so the important forms are vitamins K1 and K2.

Vitamin K1

Known also as phylloquinone, Vitamin K1 is naturally found in leafy green vegetables, such as dark lettuce varieties, spinach, kale, and broccoli. It promotes normal blood coagulation and bone strength.¹ It’s available as a supplement, but does not appear to be as potent as vitamin K2.

Vitamin K2

Vitamin K2 occurs in several forms, but two appear to have the most biological activity: MK-4 and MK-7. Both are referred to as menaquinone, but the MK-4 type is also sometimes more specifically called menatetrenone.

The MK-4 form of vitamin K is naturally found in egg yolk, egg mayonnaise, chicken thighs, and dairy products. Substantial research shows that very high supplemental doses (45 mg daily) of the MK-4 form of vitamin K2 can improve bone mineral density and bone strength in post-menopausal women.²

The MK-7 form of vitamin K is naturally found in natto, a type of fermented soybean food. One ounce of natto provides about 250 mcg of MK-7.³ The MK-7 form of vitamin K2 is absorbed much better than vitamin K1. There is limited research directly comparing the absorption of MK-4 versus MK-7, but the research that does exist suggests MK-7 is more bioavailable and has a longer half-life in the body—meaning you can take smaller doses (micrograms versus millagrams) less frequently (once a day versus 3 times a day) to obtain similar blood levels.⁴

Unfortunately, there is very little human research directly comparing the health benefits or therapeutic effects of MK-4 and MK-7, so no one knows how large amounts of MK-4 might compare with small amounts of MK-7. Until we know more, it appears that either form of vitamin K2 can offer similar benefits when taken in the appropriate dose.

History and Basic Functions of Vitamin K

Vitamin K was discovered in the early 1930s by Henrik Dam, Ph.D., a Danish researcher who recognized its role in normal blood coagulation. He called it the “koagulationsvitamin,” and the “K” designation stuck. A few years later, Edward Doisy, Ph.D., an American researcher, delineated the chemical structure of vitamin K, and both he and Dam shared the 1943 Nobel Prize in medicine for their work.

Most of vitamin K’s benefits derive from its role in making several key proteins, including osteocalcin, which is needed for strong bones. More technically, vitamin K promotes the carboxylation of glutamic acid. To explain, carboxylation adds what chemists call a carboxyl group (COOH, containing one carbon, one hydrogen, and two oxygen atoms) to glutamic acid—a necessary step in the creation of several proteins. Without carboxylation, these proteins cannot do their jobs.

Health Benefits of Vitamin K

Bone Health

Rather than being pure calcium, bone actually consists of a matrix of calcium, phosphorus, magnesium, and protein. Production of one of the key proteins of the matrix, osteocalcin, depends on vitamin K. Indeed, numerous studies have shown that low intake of vitamin K interferes with normal bone development and increases the risk of broken bones and osteoporosis.

In recent years, both Dutch and Japanese researchers have used large amounts of vitamin K2 daily to treat and reverse osteoporosis in women.^{5 6} In fact, vitamin K (as MK-4) is an approved treatment for osteoporosis in Japan.⁷ Nearly all of these studies used 45 mg (not mcg) daily of the MK-4 form of vitamin K. (See The ABCs of Vitamin K1, K2, and K3 above.)

In one of the studies, Dutch researchers asked 325 postmenopausal women to take either 45 mg of vitamin K2 or placebos daily for three years. Bone density improved among women taking vitamin K2 but decreased among those taking placebos. An analysis of seven studies, published in the Archives of Internal Medicine, found that high-dose vitamin K2 supplements consistently reduced bone fractures in women by more than 60 percent.⁸

Vitamin K also reduces bone loss caused by cortisone, blood-thinning drugs, menopause, diabetes, and other health issues. In a number of studies, the bone-building benefits of vitamin K were enhanced with the addition of vitamin D supplements.^{9 10}

Cardiovascular

Increasing research suggests that vitamin K is an important nutrient for cardiovascular health—apart from its role in blood clotting. Calcium deposits in the walls of blood vessels can lead to “arterial calcification,” which contributes to hardening of the arteries. The body needs vitamin K to make “matrix Gla protein,” or MGP, and animal studies suggest that MGP helps direct calcium to bone instead of to arteries.

In one animal study, researchers found that both vitamin K1 and K2 reduced arterial calcification by about 50 percent.¹¹ The Rotterdam Heart Study, one of the first large-scale population-based studies that looked at the connection between K2 and heart disease, found that subjects who consumed the largest amounts of vitamin K2 in their diet experienced a 57 percent reduction in death from heart disease compared to people who consumed the least amount. They also had less calcium buildup in the aorta.

Some physicians, such as cardiologist Stephen Sinatra, M.D., recommend 150 mcg of the MK-7 form of vitamin K to prevent or reverse arterial calcification. Vitamin K might also protect against varicose veins, based on a study that found low MGP (and thus low vitamin K) activity was related to the formation of varicose veins.¹²

Blood sugar

The newest frontier for vitamin K may be in preventing or reversing type 2 diabetes. In August 2007, researchers from Columbia University in New York City reported their discovery that the bone protein osteocalcin also functions as a hormone. Osteocalcin regulates the number of insulin-producing cells in the pancreas, the secretion of insulin, sensitivity to insulin, and the size of fat cells.¹³ Of course, vitamin K is needed to make osteocalcin.

Other research also supports the role of vitamin K, through osteocalcin, in maintaining normal blood sugar levels. Studies of young men in Japan found that low vitamin K levels were associated with poor insulin function, one of the signs of prediabetes. Vitamin K2 supplements improved insulin function in response to a glucose-tolerance test.¹⁴

A further link between glucose tolerance and vitamin K was identified earlier this year by researchers at Tufts University in Boston. The researchers investigated the relationship between vitamin K1 intake and glucose tolerance in 2,719 men and women. Higher intake of vitamin K1 was associated with better glucose tolerance and insulin sensitivity after glucose-tolerance tests.¹⁵

Cancer

Some research suggests that vitamin K may help reduce the risk of cancer. An eight-year study of eating habits found that men who consumed the most vitamin K2 from food had a 63 percent lower risk of developing prostate cancer. Vitamin K1 did not provide similar protection.

The most dramatic study found that vitamin K2 significantly reduced the risk of developing liver cancer. Japanese researchers treated 21 women with viral liver cirrhosis, giving them 45 mg of vitamin K2 daily for eight years. Vitamin K had two significant benefits. First, it reduced bone loss in the women, compared with a group of 19 women who did not take vitamin K supplements. Second, only two of the 21 women receiving vitamin K developed liver cancer. In contrast, almost half of the women not taking vitamin K supplements developed liver cancer.¹⁶

Cognitive Function

New research suggests that vitamin K insufficiency is connected to cognitive decline in older individuals.¹⁷ In the study, 800 older adults with an average age of 75 and living in Tokyo, were given a comprehensive geriatric health examination. The evaluation consisted of a Mini Mental State Examination (MMSE) to assess cognitive function and a blood test to measure levels of undercarboxylated osteocalcin (ucOC), with higher levels of this protein indicating greater vitamin K insufficiency. Researchers then evaluated the relationship between cognitive function and vitamin K status, finding that as levels of ucOC increased or vitamin K insufficiency worsened, so too did the likelihood of cognitive impairment. More specifically, individuals with the highest levels of ucOC had an increased prevalence of worse scores on the MMSE, particularly in the areas of orientation, calculation, and language.

Skin Health

Vitamin K may also benefit the skin, both when taken internally and when applied topically. Because of vitamin K’s role in coagulation, it is often recommended internally and topically to reduce bruising. Vitamin K may also support healthy skin in people with psoriasis and atopic dermatitis since it is involved in inflammation modulation.^{18 19} Finally, topical vitamin K has been shown to improve the healing of wounds and bruising.^{20 21 22 23} In research it has been shown to work well topically with vitamins A, C, and D, and caffeine.

Newborn Health

Vitamin K2 is deemed essential for infants and pregnant and breastfeeding moms. After birth, babies’ vitamin K stores are low, and since human milk is relatively poor in this nutrient, breast-fed infants are at particular risk of a bleeding disorder called “vitamin K deficiency bleeding.” Vitamin K2 (in the form of MK-7) has a documented history of safe and effective use. The research indicates that it’s “an ideal choice for supplementation by pregnant and nursing women and children, in both healthy subjects and in those suffering from various malabsorption and health disorders.”²⁴

Interactions Between Coumadin and Vitamin K

Doctors frequently prescribe Coumadin and other blood-thinning drugs to people who have had a heart attack or stroke or have had an artificial heart valve inserted. More than 2 million people in the United States currently take Coumadin, and more than 300,000 new prescriptions are written for the drug each year, according to a pharmaceutical industry report. Coumadin and related anti-coagulant drugs interfere with vitamin K to reduce the risk of blood clots. By doing so, however, Coumadin reduces carboxylation of osteocalcin and MGP.

Because of how Coumadin affects vitamin K and osteocalcin, the drug increases the risk of bone fractures.^{25 26} It also increases calcification of the arteries and could potentially increase the risk of diabetes. Moreover, physicians typically ask patients taking Coumadin to minimize their intake of vitamin K-containing foods and to avoid vitamin K supplements.

Is there a compromise? In a recent study, published in the Journal of Thrombosis and Haemostasis, researchers gave vitamin K1 supplements (100 mcg daily) to patients and also increased their Coumadin dosage. They found that vitamin K levels were actually more stable and predictable with the supplements, so the drug dose could also remain consistent.²⁷

This is very important: If you take Coumadin, ask your physician if he can prescribe an anti-coagulant that does not interfere with vitamin K activity. If he cannot switch you to another anti-coagulant drug (that does not target vitamin K), ask him if you can safely take a low-dose (100 mcg) vitamin K supplement. If you are taking anti-coagulants, do not take vitamin K without your doctor’s approval.

So, How Much Vitamin K Should You Take?

You can maintain optimal intake of vitamin K through diet or supplements—or both. Many different types of vegetables are rich sources of vitamin K1, including kale, collards, spinach, Brussels sprouts, broccoli, scallions, asparagus, dark green lettuce, endive, and sauerkraut.²⁴ But the American diet is almost entirely devoid of the foods that are the best sources of vitamin K2, like organ meats, fermented foods, pasture-raised eggs, and butter from grassfed cows. It is also important to note that trans fats and vegetable oils inhibit vitamin K2’s action in the body (so do common statin drugs and warfarin).²⁹

If you opt for supplements, decide on whether your objective is general health maintenance or part of a more aggressive prevention or self-care regimen. Large amounts of vitamin K1—about 1,000 mcg (1 milligram) daily—do seem to reduce the risk of osteoporosis. But Vitamin K2, at daily doses of 5 mg (5,000 mcg), may do a better job at preventing osteoporosis and fracture.

Meanwhile, taking 45 mg daily of the MK-4 form of vitamin K2 is very effective in reversing osteoporosis. Note: Be sure to consult a physician if you are considering taking such high amounts of MK-4. Finally, although human studies on the MK-7 form of vitamin K2 are currently limited, modest amounts—150 mcg daily—may also help strengthen bones and prevent arterial calcification.

References

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