Vitamin K2: Part One

In the past year and a half, vitamin K2 has been the second most common topic, after oxalate, that I’ve received questions about.

Vitamin K2 is relevant to vegan diets because the only plant food that has an appreciable amount is natto, a fermented soy product that most of us don’t eat and which has a taste many people don’t care for.

Until recently, mainstream science has considered K2 to be unnecessary both because people can get the same benefits from K1 (which is found in leafy greens) and because K2 is made by common intestinal bacteria. But then research came out at the end of the 00’s suggesting that K2 might have benefits.

K2 is now being used to promote eating animal products such as in the article Vitamin K2: A Little Known Nutrient Can Make a Big Difference in Heart and Bone Health, by Aglaée Jacob, MS, RD, CDE in Today’s Dietitian (June 2013). Jacob promotes animal products to prevent heart disease because of the vitamin K2.

As an aside, I’m not sure if this is Today’s Dietitian’s position on saturated fat and animal products, but it’s not the only article they have run in which Jacob jettisons the idea that saturated fat causes heart disease (see also Coconut Oil – Learn More About This Superfood That Contains Healthful Saturated Fats).

My plan is to review the studies on K2 more closely to try to figure out to what extent, if any, vegans are setting themselves up for heart disease, osteoporosis, or other diseases by not having an intake of vitamin K2.

A quick refresher on the forms of vitamin K:

– Phylloquinone is vitamin K1 and found primarily in plant foods, especially leafy greens.

– Menaquinone (forms MK4 through MK10) is vitamin K2. It is found in animal tissues and made by bacteria.

More background info can be found in the article vitamin K at VeganHealth.org.

The first study I’ll review is from one of the two Dutch cohorts of the European Prospective Investigation Into Cancer (EPIC). It was published in 2009 (1). They followed over 16,000 women for an average of 8 years.

The researchers did a fairly rigorous job in measuring vitamin K intake which ranged from 1 – 128 µg, with an average of 29 µg.

They found that every 10 µg increase in vitamin K2 intake was associated with an decreased risk of heart disease but the finding was of only borderline statistical significance (.92, .85 – 1.00). Interestingly, even though they divided the group into quartiles of vitamin K2 intake, they did not report on the relative risk between the different quartiles.

In contrast, intake of vitamin K1 was not associated with risk of heart disease.

Unlike Aglaée Jacob, the authors caution against getting vitamin K2 through typical animal foods:

“Thus, although our findings may have important practical implications on [cardiovascular disease] prevention, it is important to mention that in order to increase the intake of vitamin K2, increasing the portion vitamin K2 rich foods in daily life might not be a good idea. Vitamin K2 might be, for instance more relevant in the form of a supplement or in low-fat dairy. More research into this is necessary.”

I’m skeptical that their findings have important practical implications for cardiovascular disease prevention, but I’ll be reviewing other papers in the days ahead to find out more.

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References

1. 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. | link

37 Responses to “Vitamin K2: Part One”

  1. menne Says:

    This is a good updated article. You will also find references to recent publications and studies. http://menaq7.com/uploads/Nutracos_Maresz.pdf.

    I have been eating MK-7 for 18 months now. I have (as a part of my job) read a lot about it and are hopeful that it really can be beneficial, especially if you are on a non diary/meat diet. I have tried to eat Natto, but it is not that pleasant.

  2. Silvia Says:

    Very interesting! I was just reading about this as well, and I never heard of it before. I’m not so thorough that I study the original literature, as you do, but based on Wikipedia and various other websites I think I read that the Dutch scientists are recommending doses of 50-200 micrograms per day, ideally at least 150. In supplemental form. Also in Wikipedia on the page about Vitamin K (but not on the separate wiki page for vitamin K2) there is a table based on their research. It can be seen that the only animal food that could provide such doses is liver, which hardly anyone still eats these days… the other foods are way too high in calories and fat and actually still very low in K2 so they won’t help to even get close to 100 micrograms… But natto is so rich that even 10 grams a day would provide adequate k2 and it’s cheaper than most brands of supplements. I’m going to try if I can swallow it whole or something (it seems very unappealing…)

  3. Marion Says:

    Jack,
    Natto is admittedly an acquired taste but I have been eating it for about 30 years mixed with Japanese mustard, soy, and green onions. You can put it in a sandwich, mix into rice, and roll into sushi. I think it’s the texture that turns most people off, but even my German 92 year old Grandmother liked it
    It’s not so bad :)

  4. Dan Says:

    Hi Jack,

    I very much look forward to reading your analysis of K2. When I looked into this issue a while back, I found that most of the interventional trials on K2 and osteoporosis were done in Japanese populations, and we know there are major ethnic differences in osteoporotic risk. K2 could be a stick with which non-vegetarians beat vegans and vegetarians, or it could be one of the vitamins that vegans are prone to be deficient in.

    I had a completely unrelated question. I noticed that most store-bought hummus contains soybean oil. In your post on omega-3’s, you’ve mentioned that veg*ns should try to limit their consumption of omega-6 rich oils, because the linoleic acid inhibits conversion of ALA to DHA and EPA. “Do not prepare food with oils high in omega-6 such as corn, soy, safflower, sunflower, most vegetable oil blends (typically labeled “vegetable oil”) and sesame oil. Instead, use low omega-6 oils like olive, avocado, peanut, or canola. Only cook canola under low heat and for short periods.”

    Does that mean one should try to make one’s own hummus and/or avoid processed foods that are rich in omega-6 oils? What do you think?

  5. Larry Says:

    Hi Jack, really glad you have been doing research on this subject. I’ve been wondering about this for years. I receive the Life Extension magazine, it is for free, I don’t agree with much of it since they basically push supplements, however, lately they have been featuring articles on K2 and claim that most everyone lacks the nutrient. I have searched for Natto for years at the Co-Op and other places but nobody carries it here. Since Tempeh is cultured, do you think it may contain k2? thanks, Larry

  6. Jack Norris RD Says:

    Larry,

    I’ve never seen anyone say that tempeh has K2, only the opposite, but I haven’t seen any studies that have actually tested tempeh for K2 and couldn’t find any on PubMed.

  7. Jack Norris RD Says:

    Dan,

    If you are supplementing with DHA then you definitely don’t need to worry about omega-6s much. If you aren’t supplementing (and I realize this changes from day to day with you :), then minimizing omega-6s is more important, but if the oil in your hummus is the only significant source I doubt it’s much to worry about.

  8. Silvia Says:

    Tempeh is not cultured with a bacteria but with a mould. It is specifically the bacteria strain that is used in natto which creates the K2 as far as I’ve understood it. That’s why it happens to be the only non-animal food (so far!) that contains it. Although sauerkraut seems to contain a small amount as well. It would be great if there is more research so we know exactly which strains of bacteria/moulds create k2 when fermenting (which) plant foods. :-)

  9. Dan Says:

    Thanks, Jack. (I’ve only had one supplement holiday from DHA since going vegan.) Having said that, I have been deliberating on whether to stop my DHA after this pack runs out because of the cost and difficulty of getting my hands on vegan DHA.

    I was more concerned about that trial I sent you from BMJ, which showed that patients who supplemented with safflower oil (to reduce their saturated fat) had a higher risk of mortality, cardiovascular death and coronary death, than patients in the control group. The authors believe this is due to the omega-6 linoleic acid. “Sydney Diet Heart Trial”.

    Hummus is far from the only omega-6 oil in my diet – they are ubiquitous and in everything (nuts, seeds, condiments, dressings, tofurkey sausages, etc). Some people say that intake of omega-6 should be minimal, no more than twice as much as omega-3 (so the overall ratio is 2:1). Others say it’s not that important. Which camp are you in?

  10. Marion Says:

    Larry,
    If there is a Japanese or Asian market near you check the frozen section. I have never seen Natto in a health food store or a coop. But when I lived in San Francisco I got in Japantown and here in NJ it is found in every Asian market

  11. Jack Norris RD Says:

    Dan,

    I was speaking in reference to the omega-6 in your hummus inhibiting the conversion of ALA to EPA and DHA, not in regards to the effects of omega-6s on heart disease. You would know more about that than I do because I don’t keep up on the research. I would want to see a consistent finding across more than just one study before I got too worried about it.

  12. Jon Says:

    Jack, the form of k2 found in natto is not mk4 and it does not help the bones. You, unfortunately, NEED the animal derived mk4 for bone health. I am vegan, but I’m just telling you what is true.

  13. Corrin Radd Says:

    Anyone who enjoys strong flavors will likely enjoy natto–stir in a bit of soy sauce and green onion and eat it with rice. I find it to be delicious, and the mucilaginous texture doesn’t bother me at all (though i can see why it might for some people). Look for it in the refrigerated section of your Asian market in little styrofoam three or four packs.

  14. Jack Norris RD Says:

    Jon,

    Can you cite any research to back that up?

  15. Nadine Says:

    I’ve started to take vegan vitamin K2 pills occasionally last year. I basically go through a bottle in 2 months and then wait a bit and buy it again. It’s inexpensive and I personally don’t want to risk my bone health, especially if there’s any question that vegans may not get enough K2. If there’s evidence that it’s a total waste of time/money/effort, I am open to that, but like DHA, I’d rather play it safe.

  16. Dan Says:

    Jack – here’s the paper. As I recall, you were not very impressed by it. Many vegans seem to be scared about omega-6’s, believing them to be pro-inflammatory and atherogenic.

    Nadine – sometimes supplements have unintended consequences, and this has been seen in large clinical human trials with vitamin E, vitamin A, beta carotene, magnesium, folic acid, etc. I, personally, would not take a supplement unless it has actually been shown to do something, rather than just take it because of a doubt in my mind that it may work for something I may be deficient in which may be important for bone health.

    http://www.bmj.com/content/346/bmj.e8707

    [Dan – I replaced the abstract with the link to keep the comments on this thread manageable.]

  17. Jack Norris RD Says:

    Dan,

    I’m guessing it’s because the findings were barely significant (and not significant in terms of their meta-analysis) with very wide confidence intervals.

  18. Dan Says:

    Jack,

    >> I’m guessing it’s because the findings were barely significant (and not significant in terms of their meta-analysis) with very wide confidence intervals.

    You are right on the money but the statistical trends are definitely there for the meta-analysis. Certainly, judging from the meta-analysis in Figures 3-4, replacing SFA with n-6FA does not yield any benefit in terms of preventing cardiovascular disease or all cause mortality – the meta-analysis appears to exclude this. And then since SFA is clearly harmful in the evidence base, the question is why reducing SFA and replacing it with n-6FA does not show any benefit. A logical supposition would be that if you replace one atherogenic or harmful dietary factor with another atherogenic or harmful dietary factor, then you come out with no benefit (or worse). So I would say that these data do not exculpate n-6FA by a long shot, and since they are randomized, they are the best data we have on the long-term effects of n-6FA on cardiovascular health. At a minimum they call for caution when it comes to long-term n-6FA use.

  19. menne Says:

    Regarding Jons statement that only MK-4 if beneficial against Osteoperosis: The latest studies tells another story. Please check this article http://www.ncbi.nlm.nih.gov/pubmed/23525894. MK-7 is making big difference with low doses (180µg).

    MK-7 converts to MK-4 in the body. The problem with MK-4 as a supplement is the short half-life. MK-4 has 1,5 hours compared to MK-7, that has 72 hours.

    The latest scientific research shows that MK-7 is far more potent than MK-4. Natto contains MK-7 NOT mk-4. (http://www.nutraingredients-usa.com/Research/Vitamin-K2-Study-unlocks-which-forms-have-higher-bioavailability).

    This is new research, a few years back it was commonly believed that MK-4 was better.

  20. Jack Norris RD Says:

    Dan,

    It sounds like I need to read that full paper. It’s in the queue.

  21. Dan Says:

    $100 (USD) to your beautiful organization (Vegan Outreach) and the amazing work you all do to prevent animal suffering and raise the public’s consciousness…THANK YOU!

  22. Jack Norris RD Says:

    Thanks so much, Dan!

  23. Ayla Says:

    Thank you so much for taking on this topic! I’m really curious what else you’re going to find.

  24. TL Says:

    Hi Jack:

    From the abstract :

    “Mean vitamin K(1) intake was 211.7+/-100.3 microg/d and vitamin K(2) intake was 29.1+/-12.8 microg/d”.

    I’ve been tracking my eating with your excellent Peacounter, and my average vitamin K intake is 730 mcg per day. ( I eat leafy greens, usually kale or collards, almost every day.)

    Two thoughts:

    1) was there enough variation among the groups and sufficiently high doses of K1 in the highest intake group to detect an effect?

    2) ” After adjustment for traditional risk factors and dietary factors. . .”

    It seems to me (an I’m not a nutritionist) that K1 intact is co-linear with green leafy vegetable intake. Is it statistically possibly to detect an effect of K1 intact after factoring out green leafy vegetable intake?

    (Sorry, I don’t have access to the full article, just looking at the abstract.)

  25. Jack Norris RD Says:

    From a reader:

    If possible, I’d be glad to see any comments about whether K2 might increase the risk of blood clots in a person who already has some elevated risk. From a brief look at Wikipedia and a linked-to abstract, it looks like K2 (unlike K1) does not much influence blood clotting, but if you wished to include comments on the issue in your Part 2, you’d have at least one interested reader.

  26. Sayward Rebhal Says:

    Looking forward to reading your thorough review of this topic, Jack. I’ve been supplementing on and off with K2 for a few years. I discovered it when I went through a big “know they enemy” phase and spent about 6 months completely immersed in WAPF/Weston Price literature. They call vitamin K2 “the X factor” and claim it’s the essential nutrient that keeps bones and teeth healthy, strong, and (in children) well developed. I didn’t see a downside so I’ve been supplementing my son on and off since he started solids.

    There is a lot of anecdotal evidence on the internet regarding vegans and vegetarians (especially raw folks) having teeth issues, and Ive wondered if K2 isn’t part of the problem. (If there is actually a problem at all, which there very well might not be)

    I’m excited to see more research on the subject, regardless. Thanks for always staying on the cutting edge!

  27. Jay Howard Says:

    Hi Jack,

    Japanese researchers found that people in Eastern Japan who eat natto frequently have less incidents of bone fractures, in other words, less osteoporosis. Here’s a link to the research:

    http://www.ncbi.nlm.nih.gov/pubmed/11369171

  28. Daniel Says:

    I saw a bottle of pills on a friends desk, it was Vitamin K2 from a brand, ProNordic. I checked them out, but I was hoping someone could give me a review/recommendation for a good brand. thanks http://www.pronordick2.com

  29. Silvia Says:

    Daniel, I live in the Netherlands and the cheapest one that I could find (comparing the price per microgram vitamin K2, not the price per bottle or something) was from an American brand called Now. Of course I have no clue how many other good brands there may be in the US and whether they are actually available cheaper for you…

  30. Jay Howard Says:

    Hi Daniel,

    I took a look at the ProNordic brand via the link you provided. I personally don’t like to take things when the manufacturer doesn’t tell you what the source is. I take Nature’s Plus, which is made from organic natto. In addition, the NordicPro capsules are made from gelatin, which is an animal product. The Nature’s Plus are vegan. If that isn’t enough, the Nature’s Plus come to less than half the price.

  31. menne Says:

    Pronordic sell a synthetic that has a high ratio of cis molecules. They say it is 100 % trans molecules, but that is simply not true (they overload their formula with 105 %. Then they sat its 100 % trans, but it is still about 4 % cis and 1 % unkown. E-mail them and ask them what studies they have made on their molecule. They will state that they have made “comparison studies” in India. I would go for the K2 brand that has actually done studies of K2 in humans. I don’t know if I can post the brand name, I don’t want to brake any rules here. But google human studies made on K2. It’s a big difference between K2 and K2.

  32. Dan Says:

    I am not certain of the benefits of taking Vitamin K2 for bone health. Here is what UpToDate says on this topic:

    “Vitamin K – Exogenous vitamin K is required for the carboxylation of osteocalcin, which in turn allows osteocalcin to bind to hydroxyapatite mineral. A vitamin K2 preparation (menatetrenone) is widely used for the treatment of osteoporosis in Japan.

    Observational data suggest that low vitamin K consumption or impaired vitamin K status may be associated with an increased risk of fracture in older men and women [56,57]. (See “Vitamin K, gamma carboxyglutamic acid, and the function of coagulation and other proteins”.)

    Clinical trial data suggest that vitamin K supplementation may reduce bone loss and fracture risk [58]. This was best illustrated in a meta-analysis of 13 trials of oral vitamin K (phytonadione and menaquinone) supplementation for bone loss and fracture prevention [59]. Both supplements increased bone mineral density. Seven trials reported fracture data; all were in Japanese patients (primarily postmenopausal women with osteoporosis) and used menaquinone. Significant reductions were seen for vertebral, hip, and all non-vertebral fractures (odds ratio 0.40, 0.23, and 0.19, respectively, with 95% CI of 0.25-0.65, 0.12-0.47, and 0.11-0.35, respectively).

    This report should be interpreted with some caution as fracture data are available only in Japanese women, who may have significant dietary differences from other populations. In addition, the magnitude of the fracture risk reductions seems unlikely, as it was far greater than what is seen for other proven therapies, such as bisphosphonates. Furthermore, in subsequent randomized trials in healthy, older, predominantly Caucasian men and women receiving calcium and vitamin D supplements, vitamin K (200, 500, or 1000 micrograms phylloquinone daily or 45 mg menatetrenone daily) did not have any effect on BMD [60-62]. Based upon the available data, we, therefore, do not recommend routine vitamin K supplementation for the maintenance of skeletal health or the prevention of fractures in high-risk individuals.”

    Jack – any comments?

  33. Jack Norris RD Says:

    Dan,

    It sounds good to me. I’ve never reviewed the research on it. I was planning to as part of my vitamin K2 series.

  34. M Butterflies Katz Says:

    So, I’ve read about K2 lately. And not only natto, but kombucha, fresh raw sauerkraut, kefir using plant milk, kimchi – have K2 (and probiotics and possibly real B12). So I’m recommending vegans include these foods/beverages in their diet. So I got some kombucha and then I read online that it is linked with cancer. One bottle of kombucha drink that I bought in the states said 20% B12 on the label. What is your take on these foods and their K2 food-sourced content? And are they good foods/drinks to consume on other levels beside their K2 content?

  35. Jack Norris RD Says:

    Butterflies,

    Unless it’s fortified, you shouldn’t rely on these foods for B12. I don’t know about the K2 content of these foods.

  36. Micki Jacobs Says:

    The topic of vitamin K2 is the interesting area where vegan/carnivore intersect: fermented foods are made via bacteria and you are therefore eating ‘critters’ – only you can’t see them! Eating a live fermented food (the recommended way because of the benefits of bacterial gene transfer with gut bacteria), means you ARE eating animals. And really important animals, to boot.
    Many of the references above are missing the whole picture of menaquinones. Yes, specific health issues have been pretty well correlated with menaquinones (bone health, CVD risk, cancer risk, AD risk, etc) – but supportive RCT trials are probably years away – but when one looks at the mechanisms and the various components of how vitamin K2 works, a more holistic picture emerges.
    Menaquinones are important for electron transfer, for suppressing inflammation (they counteract ROS effects), for calcium regulation, and many other roles.
    They are impaired in their actions via many common drugs (statins, bisphosphonates, NSAIDs, and I also think SSRIs) 1 and also via dihydrophylloquinone, marked by trans fatty acids made when high vitamin K1 oils are hydrogenated (canola and soy, both GM and therefore way too represented in our foods). No good single reference to show how awful dihydrophylloquinone is because this substance is from the powerful food industry – just search it, put together what you find, and be amazed.
    Currently, our ‘experts on vitamin K’ (e.g. vitamin K lab at Tufts) think that banning trans fats from food will solve dihydrophylloquinone, but the manipulations of labels will likely prevent this. Crisco is zero trans fats.
    American research is hobbled by the fact that we think vitamin K is vitamin K1, a lovely nutrient found in many wonderful foods, but rather insipid when compared to long chain vitamin K2. Our US dietary guidelines are based on K1. We are flummoxed by vitamin K2 and consider it an ‘also ran’ nutrient/hormone. 2,3
    BTW, vitamin K2 IS a hormone: it binds SXR.
    The best info on K2 is from countries other than America (in general) and it is difficult for our dogmatic dieticians to get their heads around the idea that real cheese, for example, is a good food since we have been equally flummoxed by fats, calories, etc. Artisan cheese scares the crap out of many because we are so industrialized and we have lost so very many traditional foods. Sauerkraut has K2 of long chain forms, just not much, but sauerkraut is a great food. Natto has a lot of MK-7, but also a little MK-8 and a very little K1.
    The life of long chain menaquinones in our bodies is much longer than K1 or MK-4, both of which have short lives.
    All the longest lived and healthiest cultures have vitamin K sufficiency, often from fermented foods.
    Campbell’s Chinese rural peasants ferment their cabbage – he missed this entirely. They ferment other things, too. This is why they are so healthy, nothing to do with animal consumption at all. They eat animals they can’t see.
    Many Asian cultures eat insects. They are very high in long chain menaquinones.
    Termites are HUGE sources, for example.
    All the Blue Zones eat lots of long chain menaquinones with the exception of Adventists in southern California, but an absolute TON of K1 can convert into MK-4 and meet needs, which they do consume.
    Offal or organ meats are consumed in many Blue Zone countries. Cheeses are normal in these countries. All these foods are high in long chain menaquinones.
    In order to understand vitamin K2, look to UBIAD1 (also called TERE1), Gprc6a, the mevalonate pathway (where MK-4 is biosynthesized along with cholesterol and CoQ10), NFkB.
    As long as a culture is truly nutritionally replete, they can flourish. Americans have lost dietary long chain K2, they block its conversion in tissues throughout the body (high in brain, beta cells of pancreas, kidneys, muscles, etc) via drugs and industrialized foods, and we desperately need it back!
    1 http://www.asbmr.org/Meetings/AnnualMeeting/AbstractDetail.aspx?aid=c2b01dc2-a02d-4e1c-88dd-f8f83332ebe7
    Statins and Bisphosphonates Inhibit Menaquinone-4 Biosynthesis in Bone

    2 http://advances.nutrition.org/content/3/2/182.full
    Vitamin K Nutrition, Metabolism, and Requirements: Current Concepts and Future Research

    3 http://onlinelibrary.wiley.com/doi/10.1002/mnfr.201300683/abstract
    Vitamin K metabolism: Current knowledge and future research

  37. Berit Says:

    ProNordic’s vitamin K2

    We have been waiting to respond to the previous comments about our product until this was official. The source of our product has been approved by the Australian government agency TGA, the Therapeutics Goods Administration, for inclusion in their registry. Other sources have tried to achieve this status but have failed. The purpose of this agency is to evaluate therapeutic products based on quality, safety and performance. Being included on the list is a requirement for sales in Australia and export from Australia.

    For those who question the source of ProNordic’s MK-7, it is organically derived from essential oils – free from any bacterial elements, GMO’s, soy or any other fermented medium. The Australian registry requires K2 be from a non-fermented source.

    This listing also means that vitamin K2, MK-7 will now be available for the first time to those living in Australia.

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