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MK4 or MK7, Which is Better for Bones?

Article at-a-glance:

  • MK4 and MK7 are two forms of vitamin K2 commonly found in dietary supplements.
  • Both are naturally occurring, and both have health benefits.
  • But only MK4 has been shown to promote healthy bone density and maintain strong bones. 
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By Dr. John Neustadt

MK4 and MK7 are two forms of vitamin K2 commonly found in dietary supplements. Both are naturally occurring, and both have health benefits. But which one is better? When should you take one instead of the other? This article answers these questions so you can make the best possible decision for your health. 

What’s in a name? 

Vitamin K is not a single nutrient. It’s a category that includes many different types of vitamin K. Vitamin K1 is found in green leafy vegetables and is also called phylloquinone. In fact, the “phyllo-“ in phylloquinone is Greek for “leaf,” which indicates the part of the plant in which the nutrient is found in the highest concentrations. The “-quinone” part of the word indicates the type of molecule, which in the case of quinones is an organic compound abundantly found in nature. 

Another category of vitamin K nutrients is vitamin K2. This contains MK4 and MK7. Each of these molecules contains a side chain, like a tail, of carbon atoms. The number in the name of each type of vitamin K2 indicates how many carbon atoms there are in the sidechain or tail. For example, MK4 contains a four-carbon tail, and MK7 contains a seven-carbon tail. This is important because in biochemistry if you change one atom, you can change the activity of the nutrient. For vitamin K2, the tail length changes the potential health benefits of each molecule.

Where they’re found

While both naturally occur, MK4 and MK7 are not produced by all organisms. Bacteria produce MK7. It is not naturally produced in your body.1 Humans and other mammals only produce the MK4 form of the nutrient. Because MK7 is only produced by bacteria, it’s only found in fermented food, such as a Japanese fermented soybean dish called natto. In contrast, because mammals, including humans, produce MK4, MK4 is found in dairy products and meat.2  

The predominant form of vitamin K2 found in the body is MK4. In fact, your biochemistry converts all forms of vitamin K, including vitamin K1 and MK7, to MK4.3 Only the MK4 form of vitamin K2 accumulates in your body. It’s in the breasts, thyroid, ovaries, salivary glands, skin, pancreas, spleen, testes, intestines, brain, kidneys, and bone.4-6 This suggests that MK4 is the biologically active form of vitamin K2 with wide-ranging health benefits.7  

Bioavailability

Bioavailability is a chemistry and research term that describes how well a substance is absorbed. In the case of vitamin K, all forms of vitamin K are absorbed through the small intestines.8  

Since they are fat-soluble, having some fat present helps increase their absorption. This is the same for all fat-soluble nutrients, including vitamins A, D, and E. That is why it’s often recommended to consume these nutrients with meals since some fat should be present. 

One small study compared the bioavailability of MK4 and MK7 and concluded that MK7 is more bioavailable. In this study, MK4 and MK7 were given to healthy Japanese women. A single dose of 420 micrograms (mcg) of MK4 or MK7 was given in the morning with breakfast. Their blood was then tested for both nutrients to see if they had been absorbed. They then gave them smaller doses of the nutrients, 70 mcg each, for seven days and ran the same blood test. In this study, the blood level of MK7 but not MK4 was detected on all blood tests.9

However, this study is misleading in several important respects. First, it’s crucial to understand that a bioavailability study is a laboratory study. It doesn’t give us any information about whether or not a substance is active in the body, if it has any health benefits, or if any potential benefits are better than something else. We need to look at clinical trial results, which I discuss below. 

Second, clinical trials with MK4 typically give 45 mg/day, which is more than 1000 times higher than what was used in the bioavailability study. However, even at one-third of that dose—15 mg—MK4 is absorbed and detected in the blood. A bioavailability study of MK4 given as a single dose of 15 milligrams (mg) with a meal detected MK4 in the volunteers’ blood.10  

Had the bioavailability study compared MK4 and MK7 and given volunteers the amount of MK4 used in clinical trials, their results surely would have been different and more applicable in the real world. 

Half-Life

Another comment I often hear is that MK7 has a longer half-life; therefore, it’s better than MK4. The half-life of a substance is how long it takes the body to eliminate 50% of it. This is a standard measurement in pharmacology and biochemistry. 

Indeed, the half-life of MK7 is longer than that of MK4. One study that evaluated the half-life of MK7 gave a single dose of 1000 mcg (1 mg) of MK7 to 15 volunteers. The highest plasma (the liquid portion of blood) concentration of MK7 was detected after four hours. The time it took for 50% of the MK7 to be eliminated in this study was 68 hours, which approximates a previous study that showed a half-life of three days.11, 12   

In comparison to MK7, MK4 is eliminated from the plasma faster. One study gave a single dose of 15 mg of MK4 with a meal. The blood concentration of MK4 peaked after two to six hours. The time for the body to eliminate 50% of the MK4 in this study was about two hours.6  

Companies marketing their MK7 products say that MK7 is better than MK4 because it has a longer half-life. This means that people only need to take MK7 once a day, while people taking MK4 need to take it multiple times a day. 

But when considering the half-life, it’s important to ask whether or not this translates into superior health benefits. The short answer is that it doesn’t matter how long something lasts in the body if it hasn’t been shown to promote health in the areas you need it most. The half-life is a laboratory value and does not indicate whether something actually helps you. To know that, we need to look at the clinical trials. 

Bone Density

A bone density test measures the amount of minerals in bone. How do MK4 and MK7 stack up when it comes to supporting healthy bone mineral density (BMD)? 

MK4

A search on May 4, 2022, for clinical trials that used “menatetrenone” (the technical, chemical name of MK4) returned 48 studies. When the results were limited to studies that evaluated bone mineral density, Pubmed showed 24 clinical trials. The studies overwhelmingly found that MK4 (45 mg/day) significantly promoted healthy bone density. A small study published in 2017 evaluated the effect of MK4 on bone density in 16 volunteers taking epilepsy medication, which reduces bone density. In those volunteers taking MK4, bone density improved 5% after six months and 9% after twelve months.13 

A larger, multicenter, randomized, double-blinded, controlled clinical trial with 213 volunteers saw bone density increase by 1.2% in the lumbar spine and 2.7% in the hip after twelve months. The study participants were all postmenopausal women with a mean age of 64 years old. The results were so impressive that the researchers concluded that MK4 “was well tolerated and safe” and that MK4 “is an effective and safe choice.”14

A third study that evaluated MK4 (45 mg/day) alone and with vitamin D in 172 women with a mean age of 52 concluded that taking the two together for two years increased bone density by 5%. In contrast, taking MK4 alone in this study only increased density by 0.14%.15

MK7

In contrast to MK4, a search on May 4, 2022, of the National Library of Medicine’s Pubmed database for “MK7” and “bone mineral density” clinical trials only returned four studies. Expanding the search to “menaquinone-7,” another name for MK7, only increased the number of studies to seven, and most of the seven were the same as the original four results.  The studies show that MK7 does not boost bone density.

A 2010 randomized, double-blind, placebo-controlled clinical trial evaluated the bone-building effects of 360 mcg/day of MK7 compared to placebo in 334 postmenopausal women ages 50-60 years old. The study lasted one year, with bone density tests given before starting and after 12 months. After a year of supplementing with MK7, there was no difference in the amount of bone lost in the hips or any other site between those taking MK7 and the women taking the placebo. The authors concluded that MK7 “did not influence bone loss rates.”16

A 2013 clinical trial gave 180 micrograms (mcg) of MK7 or placebo daily to 244 postmenopausal women for three years. A bone density test was given before starting the study, then yearly after that. MK7 did not stop or reverse bone loss. In fact, the researchers wrote, “BMD of the total hip steadily decreased during the 3-year study period in both…groups with no significant differences between the groups.” In the spine, after adjusting for age and body mass index (BMI), there was no statistically significant difference in bone density between those taking MK7 and those taking the placebo. The bottom line of this study is that MK7 did not maintain or increase bone density.17

A more recent study published in 2021 evaluated the effects of a higher dose of MK7 in a three-year, randomized, placebo-controlled clinical trial. The study enrolled 142 postmenopausal women, with a mean age of 67 years old. The volunteers received either 375 mcg of MK7 or a placebo each day. Both groups also took 1520 IU of vitamin D3 and 800 mg of calcium daily. Unfortunately, the researchers did not specify which type of calcium was used. All the women had bone density tests before starting the study, then at three months, six months, one year, two years, and three years later. The results showed no benefit from taking MK7. In the spine, the women taking MK7 had just as much bone loss as those taking placebo. But in the hips, those taking MK7 experienced significantly more bone loss than those taking the placebo.18

Bone Strength

While most people, including doctors, equate bone mineral density with bone strength, they are different. A bone density result is a number on a test and only measures the mineral content of bone. But bone is a complex tissue and is more than simply a bunch of minerals stuck together. In addition to minerals, the bone contains about 200 different proteins, including collagen.19 Bone density represents the quantity of bone, but bone collagen creates the bone strength and quality.20    

In fact, we’ve known since the 1990s that a bone density test predicts less than half of people who will break a bone. And in 2008, a study determined that a bone mineral density (BMD) test only predicts that 44% of women and 21% of men will break a bone.21

Therefore, when evaluating whether MK4 or MK7 maintains strong bones, it’s important to ask the question, “Do they maintain strong bones as indicated by fewer fractures in clinical trials?” The short answer is that only MK4 has been shown to maintain strong bones. 

Let’s take a closer look. 

MK4 

Five clinical trials examined fractures in MK4 clinical trials. Additionally, three peer-reviewed, published research reviews pooled data from all clinical trials on MK4 to see if the results still showed benefit when larger data sets were evaluated. Overwhelmingly, the results show that MK4 maintains strong bones, as indicated by fewer fractures in clinical trials. 

One meta-analysis of clinical trials published in 2006 concluded that MK4 (45 mg daily) maintains strong bones, as indicated by fewer fractures in clinical trial volunteers. This study has been criticized because three clinical trials “were found to be problematic or retracted” after publication.22 This means that we could only draw conclusions from the data if the meta-analysis had removed those three clinical trials from its original analysis. 

Fortunately, Dr. Cockayne and his team did just that in their original paper. In Table 3 of their study, they analyzed the pooled data without those three problematic clinical trials. Even when those three clinical trials were omitted, the researchers concluded that the volunteers taking MK4 (45 mg/day) had a statistically significant 60% fewer vertebral fractures and 76% fewer nonvertebral fractures than those not taking MK4.23

Another meta-analysis published in 2015 reviewed data from 19 randomized, controlled clinical trials involving 6,759 volunteers and reached the same conclusion–MK4 (45 mg/day in divided doses) maintains strong bones as indicated by reducing fractures in clinical trials.24

Finally, two more recent systematic reviews and meta-analyses published in 2022 confirmed the earlier research. One of these studies pooled data from 10 randomized, controlled clinical trials with 5,413 women ages 45-81. The data showed that MK4 maintains strong bones, as indicated by 62% fewer fractures in volunteers.25 The other evaluated 20 clinical trials with 3,950 volunteers and concluded that MK4 (45 mg/day) maintains strong bones as indicated by 58% fewer fractures in volunteers.26

MK7

There is not much to write about MK7 and bone strength because there aren’t any studies that have evaluated fractures as the endpoint in clinical trials. Therefore, whether MK7 maintains strong bones is only theoretical at this point. Perhaps future research will show benefits, but for now, only MK4 has been shown to maintain strong bones, as indicated by fewer vertebral and nonvertebral fractures. 

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References

 

1Barbara W, Magali C. IntechOpen; 2017:Ch. 4.

2Vermeer C, Braam L. 2001;19(4):201-206.

3Sato T, Inaba N, Yamashita T. 2020;12(4).

4Shearer MJ, Okano T. 2018;38:127-151. 

5Shearer MJ, Newman P. 2014;55(3):345-62.

6Konishi T, Baba S, Sone H. 1973;21(1):220-4.

7Popa DS, Bigman G, Rusu ME. 2021;10(4).

8Louka ML, Fawzy AM, Naiem AM, et al. 2017;629:108-116.

9Sato T, Schurgers LJ, Uenishi K. 2012;11:93.

10 Uematsu T, Nagashima S, Niwa M, et al. 1996;85(9):1012-1016.

11Schurgers LJ, Teunissen KJ, Hamulyák K, et al. 2007;109(8):3279-83.

12Schurgers LJ, Vermeer C. 2000;30(6):298-307.

13Kodama Y. 2017;39(10):846-850.

14 Jiang Y, Zhang ZL, Zhang ZL, et al. 2014;9:121-7.

15Ushiroyama T, Ikeda A, Ueki M. 2002;41(3):211-221.

16Emaus N, Gjesdal CG, Almås B, et al. 2010;21(10):1731-40.

17Knapen MHJ, Drummen NE, Smit E, et al. 2013;24(9):2499-2507.

18Rønn SH, Harsløf T, Oei L, et al. 2021;32(1):185-191.

19Sroga GE, Vashishth D. 2012;10(2):141-50.

20Viguet-Carrin S, Garnero P, Delmas PD. 2006;17(3):319-36. 

21Liu H, Paige NM, Goldzweig CL. 2008;148(9):685-701. 

22Torgerson DJ. 2018;178(6):863-864. 

23Cockayne S, Adamson J, Lanham-New S, et al. 2006;166(12):1256-1261. 

24Huang ZB, Wan SL, Lu YJ, et al. 2015;26(3):1175-1186. 

25Ma ML, Ma ZJ, He YL, et al. 2022;10:979649. 

26Salma, Ahmad SS, Karim S, et al. 2022;10(5):1048.

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