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Where is the evidence -- real evidence -- that vitamin K2 is so important?

by (1317)
Updated September 16, 2014 at 7:58 PM
Created November 22, 2012 at 8:58 AM

Thanks largely to the Weston Price Foundation and all its adherents, we never stop hearing about vitamin K2.

My efforts to find the actual evidence to support a benefit of K2 over, say, other variants of the vitamin (such as K1) turn up very little, however.

I am happy to be enlightened, though. Can anybody show me solid evidence from RCTs, epidemiology or anything clinically validated that K2 is worth specifically seeking out?

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10919 · November 23, 2012 at 2:25 PM

And I don't think you hit a nerve because we're doubting k-2's importance. You hit a nerve because it seems so ludicrous that someone would be doubtin k-2 at this point in the game. It is no accident that humans are so inexplicably attracted to foods rich in this nutrient like foie gras and caviar. The craving for it is ingrained in our taste buds. No doubt some people are better at making k-2 in their intestines from k-1 than other but with most people's messed up gut biomes and increases needs during pregnancy, it may be more important than you think. Just needs more research.

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10919 · November 23, 2012 at 2:16 PM

U = I (sorry typing on a phone.)

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10919 · November 23, 2012 at 2:15 PM

The Japanese seem pretty convinced of its importance. N=1 isn't science but when I'm taking lots of k-2 inthe mk-4 form from food and supplementation I wake up with completely plaque free teeth, regardless of my carb intake for the day. I'm convinced from the evidence I've read and from my own personal experience that it's important. Unfortunately it was only recognized as a separate vitamin in 1997 so it doesn't have the half a century of research vitamin D and A have. U can't imagine anything that is so critical to neonate health is unimportant but feel free to ignore it in your diet

121a16aded2bed8dca492d3c9662ef4c
1317 · November 23, 2012 at 1:25 PM

I'm comparing it to the standard of evidence for other nutrients, like vitamin D -- there's much better, more expansive evidence there, probably because it has been studied more. But even in the realm of vitamin D, people make outrageous claims that simply aren't supported by that evidence, like arguing that the optimal serum 25(OH)D level is between 50-80 ng/mL. I tried for a long time to find the basis for those assertion, and turned up nothing. It is speculation, nothing more, and it might even be dangerous advice. We don't know.

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1317 · November 23, 2012 at 12:32 PM

I said I hadn't found anything valid, and was prepared to be corrected. What I got, though, was stuff I'd seen before, and I'm sorry, but I am not convinced. Note that I am not saying that vitamin K isn't important, I'm questioning the assertion that K2 has some special magic that K1 doesn't. There have been very few comparisons of the two, the doses of K2 used in the few trials that have been done are enormous, far beyond what even the best nourished person could expect to get from diet, and to my knowledge, nobody has tried doses of K1 that large.

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10984 · November 22, 2012 at 9:58 PM

Mkay, there are also clinical studies in human adults included showing significant increases in bmd and a published book that describes the specific mechanisms whereby k2 facilitates the transfer of calcium into the bones instead of soft tissues. I just don't understand how this is at all controversial.. Maybe if you referenced some studies and critiqued them but no, you act like there's nothing valid out there. If I was in front of a computer I'd cite a wall of studies that met your criterium. Until then, critique this, clinical and in women. http://www.scicompdf.se/osteolis/gast_2008.pdf

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10919 · November 22, 2012 at 9:45 PM

http://wholehealthsource.blogspot.com/2009/01/vitamin-k2-and-cranial-development.html This is also an interesting writeup about what warfarin (a drug that blocks vitamin K) does to rat pup's cranial development.

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10919 · November 22, 2012 at 9:42 PM

http://www.ncbi.nlm.nih.gov/pubmed/2592801 this is interesting too. Again... nutrients that respond so dramatically and quickly in lactating women tend to be the most important ones.

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10919 · November 22, 2012 at 9:41 PM

The fact that it rises quickly in breast-milk in response to k-1 much like ALA to DHA is also a good sign. Most nutrients are fairly consistent in breastmilk but for some reason those fat soluable activators and and long chain fatty acids rise when one gets more in the diet which indicates that it's incredibly important to growing brains and bodies. http://www.ncbi.nlm.nih.gov/pubmed/12064330

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10919 · November 22, 2012 at 9:37 PM

To me, any vitamin or nutrient that is found abundantly in brain tissue and other vital organs is probably pretty important.

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10919 · November 22, 2012 at 9:36 PM

To me, any vitamin or nutrient that is found abundantly in brain tissue is probably pretty important.

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1317 · November 22, 2012 at 8:58 PM

You know, this was a legitimate question. If I had been satisfied with the results of five minutes of research, I wouldn't have asked the question in the first place. Your list contains duplicates, mouse studies, and three trials, all of which have serious methodological flaws. One paper was from a journal published by Thorne Research, which manufactures K2! The Rotterdam study is the only one of sufficient size to be really interesting, and yet even it is weak, since it relied on food frequency questionnaires.

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1317 · November 22, 2012 at 8:37 PM

11180916 This is by the same authors as 15320745, and wasn't blinded either. Moreover, the K2 dosage used was massive - 45 mg/d.

121a16aded2bed8dca492d3c9662ef4c
1317 · November 22, 2012 at 8:37 PM

15771560 This appeared in the Alternative Medicine Review, which is published by Thorne Research. Guess what they sell?

121a16aded2bed8dca492d3c9662ef4c
1317 · November 22, 2012 at 8:37 PM

10750556 I have seen this one already. It was an open-label trial. Weak.

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1317 · November 22, 2012 at 8:36 PM

15320745 is a speculative, mechanistic analysis. Even the abstract includes the statement, "No randomized well-controlled prospective studies conducted on a sufficiently large number of patients have been reported yet, therefore, further studies are needed to confirm the efficacy of vitamin K2 in the treatment of osteoporosis." Considering this comes from a research group in Japan, where K2 is actually used in the treatment of osteoporosis, that's saying something.

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1317 · November 22, 2012 at 8:36 PM

15320745 is a speculative, mechanistic analysis. Even the abstract includes the statement, "No randomized well-controlled prospective studies conducted on a sufficiently large number of patients have been reported yet, therefore, further studies are needed to confirm the efficacy of vitamin K2 in the treatment of osteoporosis." Considering this comes from a research group in Japan, where K2 is actually used in the treatment of osteoporosis, that's saying something. 10750556 I have seen this one already. It was an open-label trial. Weak.

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1317 · November 22, 2012 at 7:38 PM

@wildwabbit: Thanks for the kind words.

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2387 · November 22, 2012 at 2:39 PM

You are a real lazy SOB if you complain like this but can't find the references as point out below. Even the WAPF stuff has references in it.

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10919 · November 22, 2012 at 9:53 AM

A quick search on Google scholar of vitamin k-2 will give you lots of results. There are studies where k-2 greatly improved diabetes, osteoporosis, etc. Do some research. I am by no means a science scholar and I was able to get dozens of hits with just one search.

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4 Answers

Cb9a270955e2c277a02c4a4b5dad10b5
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10984 · November 22, 2012 at 10:31 AM

Just 3-4 days ago I posted a question "where do you get your k2? Where I cited 3 ncbi pages showing decreased rates of chd and increased bone mineral density in under 1 year with calcium and D showing negligible results in that same study. There are really a lot of studies on the subject on either google or google scholar. http://paleohacks.com/questions/161814/where-do-you-get-your-k2#axzz2CwhId9Iz

http://www.ncbi.nlm.nih.gov/pubmed/15320745

http://www.ncbi.nlm.nih.gov/pubmed/10750566

http://www.ncbi.nlm.nih.gov/pubmed/15771560

http://www.ncbi.nlm.nih.gov/pubmed/11180916

http://www.ncbi.nlm.nih.gov/pubmed/20850029

http://www.ncbi.nlm.nih.gov/pubmed/15514282

http://onlinelibrary.wiley.com/doi/10.1359/jbmr.2000.15.3.515/full

http://europepmc.org/abstract/MED/15320745/reload=0;jsessionid=m7C0IB6AaGtJ761Jbz9A.10

http://europepmc.org/abstract/MED/7895417

http://europepmc.org/abstract/MED/9177427

http://jama.jamanetwork.com/article.aspx?articleid=199121

http://www.jbc.org/content/278/45/43919.short

http://onlinelibrary.wiley.com/doi/10.1002/hep.20260/full

http://onlinelibrary.wiley.com/doi/10.1002/cncr.21667/full

Took 5 minutes to find.. lol.

http://www.amazon.com/Vitamin-K2-Calcium-Paradox-Little-Known/dp/1118065727/ref=sr_1_1?ie=UTF8&qid=1353581591&sr=8-1&keywords=vitamin+k2+book

This book was on the Today Show I believe and has 5/5 stars on Amazon, it might be able to help you if you don't want to read through all the individual studies yourself.

121a16aded2bed8dca492d3c9662ef4c
1317 · November 23, 2012 at 1:25 PM

I'm comparing it to the standard of evidence for other nutrients, like vitamin D -- there's much better, more expansive evidence there, probably because it has been studied more. But even in the realm of vitamin D, people make outrageous claims that simply aren't supported by that evidence, like arguing that the optimal serum 25(OH)D level is between 50-80 ng/mL. I tried for a long time to find the basis for those assertion, and turned up nothing. It is speculation, nothing more, and it might even be dangerous advice. We don't know.

121a16aded2bed8dca492d3c9662ef4c
1317 · November 23, 2012 at 12:32 PM

I said I hadn't found anything valid, and was prepared to be corrected. What I got, though, was stuff I'd seen before, and I'm sorry, but I am not convinced. Note that I am not saying that vitamin K isn't important, I'm questioning the assertion that K2 has some special magic that K1 doesn't. There have been very few comparisons of the two, the doses of K2 used in the few trials that have been done are enormous, far beyond what even the best nourished person could expect to get from diet, and to my knowledge, nobody has tried doses of K1 that large.

Cb9a270955e2c277a02c4a4b5dad10b5
10984 · November 22, 2012 at 9:58 PM

Mkay, there are also clinical studies in human adults included showing significant increases in bmd and a published book that describes the specific mechanisms whereby k2 facilitates the transfer of calcium into the bones instead of soft tissues. I just don't understand how this is at all controversial.. Maybe if you referenced some studies and critiqued them but no, you act like there's nothing valid out there. If I was in front of a computer I'd cite a wall of studies that met your criterium. Until then, critique this, clinical and in women. http://www.scicompdf.se/osteolis/gast_2008.pdf

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10919 · November 22, 2012 at 9:45 PM

http://wholehealthsource.blogspot.com/2009/01/vitamin-k2-and-cranial-development.html This is also an interesting writeup about what warfarin (a drug that blocks vitamin K) does to rat pup's cranial development.

1da74185531d6d4c7182fb9ee417f97f
10919 · November 22, 2012 at 9:42 PM

http://www.ncbi.nlm.nih.gov/pubmed/2592801 this is interesting too. Again... nutrients that respond so dramatically and quickly in lactating women tend to be the most important ones.

1da74185531d6d4c7182fb9ee417f97f
10919 · November 22, 2012 at 9:41 PM

The fact that it rises quickly in breast-milk in response to k-1 much like ALA to DHA is also a good sign. Most nutrients are fairly consistent in breastmilk but for some reason those fat soluable activators and and long chain fatty acids rise when one gets more in the diet which indicates that it's incredibly important to growing brains and bodies. http://www.ncbi.nlm.nih.gov/pubmed/12064330

1da74185531d6d4c7182fb9ee417f97f
10919 · November 22, 2012 at 9:37 PM

To me, any vitamin or nutrient that is found abundantly in brain tissue and other vital organs is probably pretty important.

1da74185531d6d4c7182fb9ee417f97f
10919 · November 22, 2012 at 9:36 PM

To me, any vitamin or nutrient that is found abundantly in brain tissue is probably pretty important.

121a16aded2bed8dca492d3c9662ef4c
1317 · November 22, 2012 at 8:58 PM

You know, this was a legitimate question. If I had been satisfied with the results of five minutes of research, I wouldn't have asked the question in the first place. Your list contains duplicates, mouse studies, and three trials, all of which have serious methodological flaws. One paper was from a journal published by Thorne Research, which manufactures K2! The Rotterdam study is the only one of sufficient size to be really interesting, and yet even it is weak, since it relied on food frequency questionnaires.

121a16aded2bed8dca492d3c9662ef4c
1317 · November 22, 2012 at 8:37 PM

11180916 This is by the same authors as 15320745, and wasn't blinded either. Moreover, the K2 dosage used was massive - 45 mg/d.

121a16aded2bed8dca492d3c9662ef4c
1317 · November 22, 2012 at 8:37 PM

15771560 This appeared in the Alternative Medicine Review, which is published by Thorne Research. Guess what they sell?

121a16aded2bed8dca492d3c9662ef4c
1317 · November 22, 2012 at 8:37 PM

10750556 I have seen this one already. It was an open-label trial. Weak.

121a16aded2bed8dca492d3c9662ef4c
1317 · November 22, 2012 at 8:36 PM

15320745 is a speculative, mechanistic analysis. Even the abstract includes the statement, "No randomized well-controlled prospective studies conducted on a sufficiently large number of patients have been reported yet, therefore, further studies are needed to confirm the efficacy of vitamin K2 in the treatment of osteoporosis." Considering this comes from a research group in Japan, where K2 is actually used in the treatment of osteoporosis, that's saying something.

121a16aded2bed8dca492d3c9662ef4c
1317 · November 22, 2012 at 8:36 PM

15320745 is a speculative, mechanistic analysis. Even the abstract includes the statement, "No randomized well-controlled prospective studies conducted on a sufficiently large number of patients have been reported yet, therefore, further studies are needed to confirm the efficacy of vitamin K2 in the treatment of osteoporosis." Considering this comes from a research group in Japan, where K2 is actually used in the treatment of osteoporosis, that's saying something. 10750556 I have seen this one already. It was an open-label trial. Weak.

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25467 · November 22, 2012 at 2:15 PM

Yadav VK, Ryu JH, Suda N, et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 2008;135: 825-837.

GASTROENTEROLOGY 2011;141:439-442

http://care.diabetesjournals.org/content/34/9/e147.full

Shea MK, Booth SL, Gundberg CM, Peterson JW, Waddell C, Dawson-Hughes B, Saltzman E: Adulthood obesity is positively associated with adipose tissue concentrations of vitamin K and inversely associated with circulating indicators of vitamin K status in men and women.

J Nutr. 2010 May;140(5):1029-34

PMID: 17145139 [PubMed - indexed for MEDLINE]

Wu S, Liao AP, Xia Y, Li YC, Li JD, Sartor RB, Sun J: Vitamin D Receptor Negatively Regulates Bacterial-Stimulated NF-{kappa}B Activity in Intestine. Am J Pathol. 2010 Jun 21

http://www.ncbi.nlm.nih.gov/pubmed/16942519

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12642 · November 22, 2012 at 5:57 PM

I asked a question recently about vitamin K2 benefiting insulin sensitivity. There is some evidence listed in the answers:

http://paleohacks.com/questions/160891/could-vitamin-k-improve-insulin-resistance

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1317 · November 23, 2012 at 1:45 PM

Clearly, I touched a nerve here. If anybody felt personally attacked by my question, I apologise.

I said I hadn't found anything valid, and was prepared to be corrected. What I got, though, was stuff I'd seen before, and I'm sorry, but I am not convinced. Note that I am not saying that vitamin K isn't important, I'm questioning the assertion that K2 has some special magic that K1 doesn't. There have been very few comparisons of the two; the doses of K2 used in the few trials that have been done are enormous, far beyond what even the best nourished person could expect to get from diet, and to my knowledge, nobody has tried doses of K1 that large.

I'm comparing it to the standard of evidence for other nutrients, like vitamin D -- there's much better, more expansive evidence there, probably because it has been studied more. But even in the realm of vitamin D, people make outrageous claims that simply aren't supported by that evidence, such as arguing that the optimal serum 25(OH)D level is between 50-80 ng/mL. I tried for a long time to find the basis for those assertions, and turned up nothing. It is speculation, nothing more, and it might even be dangerous advice. We don't know.

Let's be honest, though -- who's pounding the K2 drum loudest? The Weston Price Foundation, whose official position on raw milk is hardly uncontroversial. The reason I asked the question is that the people who write for WAP are not actually doing any research of their own. They're analysts and essayists. They read papers, and write opinions and speculation based on what they read.

That is, for sure, an important part of science, since you can't study anything without a hypothesis, but it is not, on its own, science. People read these articles, say, "hmn, sounds right!" and make choices based on that, including spending big bucks on supplements. Does that sound like a good idea?

Price's book is often cited and gets many people on to real food, but it suffers from exactly the same methodological weaknesses. It reads like an ethnography and makes connections which are plausible but fails on the rigorous testing. I want to believe this stuff, but if I am expected to, I have to be able to verify the claims myself. With the material provided by WAP, that is not possible. I have to take Price's word for it.

In any event, I question any importance ascribed to a nutrient that would require the continued consumption of dairy products into adulthood. That doesn't wash - 70% of humanity is lactose intolerant. Are they all K2 deficient? Or is adequate K1 enough? What's the answer? We don't know one way or the other, because the evidence isn't there - yet.

Last point: people often confuse basic research -- like this -- with clinical or epidemiological studies. Basic research can tell us how substances and cells behave in certain, specific circumstances, but it is absolutely useless when trying to predict how diet will impact health. If you've ever tried to model a biological system, even a simple one, you know that this is so incredibly difficult that one wonders why anybody would bother trying. This is why intervention trials, preferably blinded and with large sample sizes, are so important. Population studies that use clinical markers are next. Studies that rely on food frequency questionnaires (like the Rotterdam study) are notoriously unreliable. How many people can remember what they ate last week, let alone last year? At the risk of whipping a dead horse... correlation is not causation.

I had hoped that somebody knew of something that I may have missed. The nice thing about science, though, is that our understanding changes all the time. Right now, as I said -- I'm not convinced. I'll change my opinion tomorrow, though, if somebody shows me enough evidence of the kind I've already described.

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10919 · November 23, 2012 at 2:25 PM

And I don't think you hit a nerve because we're doubting k-2's importance. You hit a nerve because it seems so ludicrous that someone would be doubtin k-2 at this point in the game. It is no accident that humans are so inexplicably attracted to foods rich in this nutrient like foie gras and caviar. The craving for it is ingrained in our taste buds. No doubt some people are better at making k-2 in their intestines from k-1 than other but with most people's messed up gut biomes and increases needs during pregnancy, it may be more important than you think. Just needs more research.

1da74185531d6d4c7182fb9ee417f97f
10919 · November 23, 2012 at 2:16 PM

U = I (sorry typing on a phone.)

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10919 · November 23, 2012 at 2:15 PM

The Japanese seem pretty convinced of its importance. N=1 isn't science but when I'm taking lots of k-2 inthe mk-4 form from food and supplementation I wake up with completely plaque free teeth, regardless of my carb intake for the day. I'm convinced from the evidence I've read and from my own personal experience that it's important. Unfortunately it was only recognized as a separate vitamin in 1997 so it doesn't have the half a century of research vitamin D and A have. U can't imagine anything that is so critical to neonate health is unimportant but feel free to ignore it in your diet

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