When I had started to study vitamin K, I had some confusion about the efficacy of the two most studied forms of vitamin K2. MK-7 has longer self-life and more bioavailability and also marketed more but lesser presence in tissues. That means your body better absorbs MK7 and also it stays in your body for a longer period than MK-4. On the other hand, MK-4 has shorter self-life but has more presence than MK-7 in tissues of critical organs. You will find as go through the article. That indicates MK-4 as more important. Both forms have pros and cons. Although there is no major head to head study available for finding MK-4 VS MK-7: which form of vitamin K2 supplement should you take? I have made an effort to find out from available data.
Vitamin K has emerged as an X factor vitamin mostly as vitamin K2. And the sad thing is that we have limited resources of K2 in the present world. Vitamin K2 has many crucial roles in human health. You can go through our earlier articles:
Vitamin K2-A crucial vitamin for benefits of heart and bone health
Vitamin K2 for healthy brain and nervous system, prevent kidney stones, cancer, beauty and more…
Food sources database for vitamin K2
Why you need to give special importance for vitamin K2 in the present environment.
Vitamin K group consists of two primary vitamers phylloquinone(K1) and menaquinone(MK). And the third vitamin K3 or menadione may be toxic due to interference with the function of glutathione. In the human body, Vitamin K2 shows higher biological activity than K1. (1)
Vitamin K2 is also called menaquinone or MK and the number in MK denotes the number of isoprenoid residues in their side chains. MK-4 and MK-7 are the two most studied forms of vitamin K2. Can your body convert MK-7 to MK-4 or vice versa? We lack data. Now go to the part to be discussed.
MK-4 VS MK-7: which form of vitamin K2 supplement should you take?
MK-4 or Menaquinone-4
Pros of MK-4
Mammalian cells naturally synthesize MK-4 from food containing vitamin K1. MK-4 was recovered from most of the tissues. Liver stores vitamin K1 and long-chain forms of vitamin K2. (1) In addition to the liver, vitamin K is found in the bone, brain, heart, testis, kidney, pancreas and salivary glands mainly as MK-4. The higher menaquinones, MK-6-11, were recovered in the liver samples (n 6), trace amount of MK-6-9 were found in some of the heart and pancreas samples. The results show that in man there are tissue-specific, vitamin-K distribution patterns.(2,3)
As the main vitamin K present in the brain MK-4 participates in the nervous system through its involvement in sphingolipid metabolism, a class of lipids widely present in brain cell membranes.
Deterioration of sphingolipid metabolism causes cognitive decline and neurodegenerative diseases, such as Alzheimer’s disease. Also MK-4 has anti-inflammatory activity as well as offers protection against oxidative stress. (4)
In a small experiment on 15 pregnant women, researchers found vitamin K1 and menaquinones (MK-4, MK-6, and MK-7) were found in placentas and maternal plasma. The observers had not found MK-7 in the plasma umbilical cord after supplementation of MK-7 through food. But K1 and MK-4 were found in umbilical cord plasma. (5) That indicates baby in mother’s womb can benefited from by dietary intake of MK-4 by the mother. Mother’s milk also contains MK-4 derived from dietary phylloquinone or vitamin K1. (6)
Cons of MK-4
One problem with the MK-4 supplement is that it not from grass-fed diary-like butter, cheese, pastured egg or grass feed animal meat source. Rather in general MK-4 supplement is from synthetic source as usual. Hence such MK-4 may have low bioavailability. In a small study on healthy women, researchers found that MK-4 did not contribute to the vitamin K status as measured by serum vitamin K levels. On the other hand MK7 intake significantly increases serum MK-7 levels. (7)
MK-4 has a shorter half-life. Circulation removes the majority of vitamin K1 and MK-4 within 24 hr of ingestion. (8)
However as normal having more tissue presence MK-4 may rapidly be taken up by tissues as removed quickly from the bloodstream.
MK-7 or Menaquinone-7
Pros of MK-7
MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels. MK-7 however significantly increases serum MK-7 levels. (7)
While circulation removes majority MK-4 within 24 hr of ingestion but MK-7 last for longer period and doesn’t appear to be completely removed from circulation after 72-96 hr. (8) MK-7 appears to offer benefits over MK-4 in terms of lower dosing and single daily dosing instead of multiple doses. (9)
Cons of MK-7
MK-7 has lesser presence in tissue. MK-7 has none or negligible presence in brain tissue. Researchers had not found MK-7 in the plasma umbilical cord of pregnant women after supplementation of MK-7 through food. (5)
MK-7 may not be always in natural form. Both MK may undergo extensive fermentation, purification, extraction, and precipitation that can affect bioavailability.
To see further we can go to some studies.
What had researches found?
Vitamins K2, especially MK-4, promotes bone formation by stimulating the differentiation of the osteoblast, regulating the mineralization of the extracellular matrix, upregulating the expression of the bone marker genes, and inhibiting the osteoclastogenesis. (1) MK-4 also used to treat osteoporosis even with synthetic form menatetrenone. (10)
A randomized clinical intervention study among 325 postmenopausal women receiving either placebo or 45 mg/day of MK-4 as menatetrenone during three years found K2 helps maintaining bone strength. (11) Other studies also showed the therapeutic properties of MK-4 in osteoporosis. (12)
In a study in healthy Japanese who consumed natto high in MK-7, carboxylated osteocalcin were significantly increased which is an important factor for bone health. (13)
A study on 244 postmenopausal women who took supplements with 180 mcg of vitamin K2, as MK-7, for 3 years daily had prevented age-related bone loss. (14)
For bone health, apart from calcium you also need vitamin d for circulating calcium. Read more about vitamin D deficiency linked with chronic fatigue and body aches and safe upper limit and also food sources.
Data from prospect-EPIC cohort consisting of 16,057 women aged 49-70 years MK-7, MK-8 and MK-9 but not K1 inversely relates with coronary heart disease. (15)In a double-blind randomized clinical trial concluded long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having high arterial stiffness. (16)
High blood sugar or diabetes, obesity emerged as major risk factors for heart disease. Also, read how both types of sugar can kill your health, make you overweight, shorten your lifespan, damage your skin, increases cholesterol level, changes LDL pattern, damages the kidney and more. Apart from that also creates cravings to eat more.
How glucose from simple carbohydrates can kill your health.
What happens to your body when you consume more fruit sugar?
Heart disease is an inflammatory disease with the oxidation of cholesterol. In modern days chronic inflammation is the key driver in the development of chronic diseases. Read more about
Lesser-known foods and factors that cause inflammation you need to take control
13 powerful anti-inflammatory foods but lesser-known to protect your health.
Also, read our articles in heart disease archives.
Vitamin K2 and Brain Health
We have mentioned that MK-4 involves in sphingolipid metabolism in brain cells. MK-4 the main vitamin K present in the brain cells has anti-inflammatory activity and also offers protection against oxidative stress. Research data suggest that vitamin K has the potential to influence psychomotor behavior and cognition. (17)
MK-4 has been recommended as an agent for the treatment of RA either alone or in combination with standard RA therapy. Kate Rhéaume-Bleue author of Vitamin K2 And The Calcium Paradox performed a study with administration of MK-7 (100 µg/d) to Eighty-four RA both male and female an average age 47 years for 3 months. She observed MK-7 treated group showed a marked decrease in RA biochemical markers. (9)
These are just as few examples. Being tissue specific both of them can exert their effects in different ways.
Learning of vitamin K is just in the initial stage. Different types of vitamin K vary in their biological activities. This is triggered by the discrepancies in enzyme affinity and tissue distribution. Different sub types of vitamin K2 also differ in the levels of bio-activity and enzyme affinity. (1) Therefore it is wiser to have both forms rather than a particular form. Pastured raised non cross breed antibiotic-free Australian emu oil, gouda cheese are some good source of MK-4. Japanese natto has rich source of MK-7. You may try natto product from good source. MK-7 has two chemical isomers as Transform and CIS form. Trans form is found in nature but CIS for is not. So CIS form may act differently. Therefore in MK-7 supplements it is better to have lesser CIS form. Apart from these also try to include enough greens in your menu.
The daily dosage of MK
Daily dosages are not updated in many places. Based on research findings the dosages are as below. These researches basically had aimed for the prevention of osteoporosis.
MK-4 daily dosage
Fifteen healthy males aged 25 as average participated in a non-placebo-controlled dose-examination study. And they received MK-4 daily for 5 weeks. This preliminary graded-dose study suggested that MK-4 at 600 mcg/day or more is likely to be important in terms of vitamin K requirements for bone health.(18)
Menaquinone-4 (MK-4) administered at a dosage of 45 mg/day has been used for the treatment of osteoporosis in Japan. A study aimed to examine the long-term effects of comparative low dose 1.5 mg (1500 mcg) daily supplementation of MK-4 in healthy postmenopausal women aged 50-65 years. The study was designed as a randomized, double-blind, placebo-controlled trial. The results of the study suggest that low-dose MK-4 supplementation for 6-12 months improved bone quality without any substantial adverse effects.(19)
MK-7 daily dosage
For MK-7 research suggests daily intake as ≥100 mcg for bone health for adult. (20)
Vitamin K2 works better with vitamin D. To know more about vitamin D, best form, daily dosage, safety limit, etc you can go through this link.
Other minerals go well with vitamin K2 includes calcium, magnesium, zinc. For daily dose for child, safety measures you can go to our previous article.
Disclaimer: Information provided here are generalized information for
educational purpose only, not intended to provide one to one health
consultation or replace practice of a qualified practitioner. Different
people may have different health condition and may have different reaction
to the same food. Hence it has been advised to consult with health care
provider before application of any of above guidelines.
Source and References:
1. Solmaz Akbari and Amir Alireza Rasouli-Ghahroudi,Vitamin K and Bone
Metabolism: A Review of the Latest Evidence in Preclinical Studies,Biomed
Res Int. 2018; 2018: 4629383
2.Komai M, Shirakawa H.,[Vitamin K metabolism. Menaquinone-4 (MK-4)
formation from ingested VK analogues and its potent relation to bone
function],Clin Calcium. 2007 Nov;17(11):1663-72
3.Thijssen HH, Drittij-Reijnders MJ.,Vitamin K status in human tissues:
tissue-specific accumulation of phylloquinone and menaquinone-4,Br J Nutr.
4.Ferland G.,Vitamin K and brain function,Semin Thromb Hemost. 2013
5.Hiraike H, Kimura M, Itokawa Y.,Distribution of K vitamins (phylloquinone
and menaquinones) in human placenta and maternal and umbilical cord plasma,
Am J Obstet Gynecol. 1988 Mar;158(3 Pt 1):564-9
6.Thijssen HH, Drittij MJ, Vermeer C, Schoffelen E.,Menaquinone-4 in breast
milk is derived from dietary phylloquinone,Br J Nutr. 2002 Mar;87(3):219-26
7.Toshiro Sato, Leon J Schurgers, and Kazuhiro Uenishi,Comparison of
menaquinone-4 and menaquinone-7 bioavailability in healthy women,Nutr J.
2012; 11: 93
8.Beulens JW, Booth SL, van den Heuvel EG, Stoecklin E, Baka A, Vermeer
C.,The role of menaquinones (vitamin K₂) in human health,
Br J Nutr. 2013 Oct;110(8):1357-68
9.Kate Rhéaume-Bleue, Choosing the Right Vitamin K2: Menaquinone-4 vs
Menaquinone-7-Clinical considerations of different forms of vitamin K2 ,
Natural Medicine Journal,October 2015 Vol. 7 Issue 10
10.Iwamoto J, Takeda T, Sato Y.,Menatetrenone (vitamin K2) and bone quality
in the treatment of postmenopausal osteoporosis,Nutr Rev. 2006
11.M. H. J. Knapen, L. J. Schurgers, and C. Vermeer,Vitamin K2
supplementation improves hip bone geometry and bone strength indices in
postmenopausal women,Osteoporos Int. 2007 Jul; 18(7): 963–972
12.Jun Iwamoto,Vitamin K2 Therapy for Postmenopausal Osteoporosis,
Nutrients. 2014 May; 6(5): 1971–1980
13.Tsukamoto Y, Ichise H, Kakuda H, Yamaguchi M.,Intake of fermented
soybean (natto) increases circulating vitamin K2 (menaquinone-7) and
gamma-carboxylated osteocalcin concentration in normal individuals,
J Bone Miner Metab. 2000;18(4):216-22.
14.Knapen, Marjo, Drummen, Nadja, Smit, E, Vermeer, Cees,Theuwissen, Elke,
Three-year low-dose menaquinone-7 supplementation helps decrease bone loss
in healthy postmenopausal women, Osteoporos Int. 2013 Sep;24(9):2499-507.
doi: 10.1007/s00198-013-2325-6. Epub 2013 Mar 23.
15.Gast GC, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM,
Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT., A high menaquinone
intake reduces the incidence of coronary heart disease,
Nutr Metab Cardiovasc Dis. 2009 Sep;19(7):504-10
16.Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C.,
Menaquinone-7 supplementation improves arterial stiffness in healthy
postmenopausal women. A double-blind randomised clinical trial,
Thromb Haemost. 2015 May;113(5):1135-44
17.Ferland G, Vitamin K, an emerging nutrient in brain function,
Biofactors. 2012 Mar-Apr;38(2):151-7.
18.Eriko Nakamura,Mami Aoki, Fumiko Watanabe and Ayako Kamimura,
Low-dose menaquinone-4 improves γ-carboxylation of osteocalcin in young
males: a non-placebo-controlled dose–response study,Nutrition Journal 2014
19.Koitaya N, Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, Gando
Y, Miyachi M, Aoki M, Komatsu M, Watanabe F, Morishita K, Ishimi Y.,
Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone
metabolism and prevents forearm bone loss in postmenopausal Japanese
women,J Bone Miner Metab. 2014 Mar;32(2):142-50
20. Inaba N, Sato T, Yamashita T.,Low-Dose Daily Intake of Vitamin K(2)
(Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind,
Randomized Controlled Trials,J Nutr Sci Vitaminol (Tokyo). 2015;61(6):471-
Vitamin K is a fat soluble vitamin, is it? How much is oral bioavailability? Has anyone worked to make a small molecule activator of VDR? That would be interesting given so many important biological effects of Vitamin K.
Vitamin K and D both are fat soluble. Natural sources have better bioavailability. Due to less food source MK-4 supplement from synthetic source. Menatetrenone form of MK-4 is used for osteoporosis. Australian emu oil is a good source of MK-4 as natural source. My previous article I have listed a food source database. http://holistichealthnlife.com/best-vitamin-k2-food-sources-are-you-getting-enough/ In mk-7 usually Lesser CIS form indicates better bioavailability. In supplement it may not be labeled always. When asked usually manufacturer or supplier give the answer, if they avoid that can be considered as good.
VDR relates to vitamin D. The perception on vitamin D was changed after finding vitamin D receptor (VDR) and the vitamin D activating enzyme 1-α-hydroxylase are expressed in many cell types. Active for vitamin D as activated by enzyme bind with VDR (Vitamin D receptor) present in cells and involves in regulation of gene expression. So vitamin D also called hormone
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