Wednesday, November 12, 2008

Can Vitamin K2 Reverse Arterial Calcification?

It certainly can in rats. In April 2007, Dr. Cees Vermeer and his group published a paper on the effect of vitamin K on arterial calcification (the accumulation of calcium in the arteries). As I mentioned two posts ago, arterial calcification is tightly associated with the risk of heart attack and death. Warfarin-treated rats are an established model of arterial calcification. Warfarin also causes calcification in humans. The drug is a "blood thinner" that inhibits vitamin K recycling, and inhibits the conversion of vitamin K1 (phylloquinone) to K2 MK-4 (menaquinone-4). This latter property turns out to be the critical one in the calcification process.

Rats are able to convert vitamin K1 to K2 MK-4, whereas humans don't seem to convert well. Conversion efficiency varies between species.
Dr. Vermeer's group treated rats with warfarin for 6 weeks, during which they developed extensive arterial calcification. They also received vitamin K1 to keep their blood clotting properly. At 6 weeks, the warfarin-treated rats were broken up into several groups:
  • One continued on the warfarin and K1 diet
  • One was placed on a diet containing a normal amount of K1 (no warfarin)
  • One was placed on a high K1 diet (no warfarin)
  • The last was placed on a high K2 MK-4 diet (no warfarin)
After 6 more weeks, the first two groups developed even more calcification, while the third and fourth groups lost about 40% of their arterial calcium. The high vitamin K groups also saw a decrease in cell death in the artery wall, a decrease in uncarboxylated (inactive) MGP, and an increase in arterial elasticity. They also measured the vitamin K content of aortas from each group. The group that received the 12-week warfarin treatment had a huge amount of K1 accumulation in the aorta, but no K2 MK-4. This is expected because warfarin inhibits the conversion of K1 to K2 MK-4. It's notable that when conversion to K2 was blocked, K1 alone was totally ineffective at activating MGP and preventing calcification.

In the group fed high K1 but no warfarin, there was about three times more K2 MK-4 in the aortas than K1, suggesting that they had converted it effectively and that vascular tissue selectively accumulates K2 MK-4. A high K1 intake was required for this effect, however, since the normal K1 diet did not reverse calcification. The rats fed high K2 MK-4 had only K2 MK-4 in their aortas, as expected.


What does this mean for us? K2 MK-4 appears to be the form of vitamin K that arteries prefer (although not enough is known about the longer menaquinones, such as MK-7, to rule out a possible effect). Humans don't seem to be very good at making the conversion from K1 to K2 MK-4 (at normal intakes; there are suggestions that at artificially large doses we can do it). That means we need to ensure an adequate K2 MK-4 intake to prevent or reverse arterial calcification; eating K1-rich greens won't cut it. It's worth noting that the amounts of K1 and K2 used in the paper were very large, far beyond what is obtainable through food. But the regression took only 6 weeks, so it's possible that a smaller amount of K2 MK-4 over a longer period could have the same effect in humans.

K2 MK-4 (and perhaps other menaquinones like MK-7) may turn out to be an effective treatment for arterial calcification and cardiovascular disease in general. It's
extremely effective at preventing osteoporosis-related fractures in humans. That's a highly significant fact. Osteoporosis and arterial calcification often come hand-in-hand. Thus, they are not a result of insufficient or excessive calcium, but of a failure to use the available calcium effectively. In the warfarin-treated rats described above, the serum (blood) calcium concentration was the same in all groups. Osteoporosis and arterial calcification are two sides of the same coin, and the fact that one can be addressed with K2 MK-4 means that the other may be as well.

Both osteoporosis and arterial calcification may turn out to be symptoms of vitamin K2 deficiency, resulting from the modern fear of animal fats and organs, and the deterioration of traditional animal husbandry practices. So eat your pastured dairy, organs, fish roe and shellfish! And if you have arterial calcification, as judged by a
heart scan, you may want to consider supplementing with additional K2 MK-4 (also called menaquinone-4 and menatetrenone).

The osteoporosis studies were done with 45 milligrams per day, which was well tolerated but seems excessive to me. Smaller doses were not tested. From the limited information available on the K2 content of foods, 1 milligram of K2 MK-4 per day seems like the upper limit of what you can get from food. That's about 40 times more than the average person eats. Anything more and you're outside your body's operating parameters. Make sure you're getting adequate vitamin D3 and A if you supplement with K2. Vitamin D3 in particular
increases the secretion of MGP, so the two work in concert.

34 comments:

scott said...

I supplement daily with D3 and near daily with A from fish liver oil and after reading this blog have started taking a Carlson 5mg K2 capsule once a week, which approximates a normal daily dose.

Given that K2 is fat soluble, am I correct in thinking that the once/week dose stays in my system and is used by the body as needed? Or is a more steady dosing scheme needed? Preferred, probably, but needed is the question.

Have to balance convenience, availability of K2-rich foods, etc. I know there are drops, but not as convenient to use as the capsule.

Great blog...I see stuff here that I dont' see anywhere else. Thanks.

Scott

Debs said...

The osteoporosis stuff is interesting. The more I read about K2 and bone health, the more I think all the emphasis put on calcium for osteoporosis prevention has been misplaced, and that K2 is much more important. My 60-something year old mother takes calcium (with D3), but I've been slipping her grass-fed butter too.

Aaron said...

"Make sure you're getting adequate vitamin D3 and A if you supplement with K2." What is adequate amounts of D3 and A. And can one get enough vitamin A from dietary sources? If not, should one supplement with Beta carotene? I have read that too much vitamin A leads to vitaminosis A (aptly named condition).

Stephan said...

Hi Scott,

MK-4 lasts about 8 hours in serum after ingestion. It also has another tissue pool that turns over more slowly. Not much is known about this pool. I think once a week is fine as long as you're getting some K2 in your diet otherwise.

Debs,

Absolutely. Osteoporosis is not caused by insufficient calcium! In the U.S., we have a very high calcium intake and also high osteoporosis rates.

Aaron,

See my post on vitamin D for the adequate amount. Beta-carotene is not a great source of vitamin A. Your body only converts around 10% of it to actual vitamin A, but on the nutrition label it will list it as if it will all be converted. So you can divide the percentage by 10. "Vitaminosis A" is BS. The problem is vitamin A will exacerbate a vitamin D deficiency, so except for extreme doses, vitamin A toxicity is really vitamin D deficiency. The optimum is still a relatively high intake of both. The Weston Price foundation recommends 10,000 IU vitamin A per day. If you take that as an isolated supplement, make sure to balance it with D. Or better yet, take cod liver oil which naturally contains both.

Anna said...

Stephan,

Have you been following the apparent conflict lately between what Dr. Cannell of the Vitamin D Council says (don't take Cod Liver Oil, take Vit D) with what you and Chris Masterjohn (& the WAPF) says about taking Vit A & D?

While I like the Vit D Council's advice most of the time, I'm inclined to think they might be blinded by their devotion to D at this point, and not seeing the forest for the trees when it comes to how these player work together. If you have any comments or different interpretation, do tell.

Stephan said...

Hi Anna,

Yes, there have been a few high-profile doctors speaking out about vitamin A toxicity. I've read what Dr. Cannell has to say, and I've read what the WAPF foundation has to say, and here's what I think in a nutshell: the WAPF is right.

Sally Fallon has always advocated a diet high in vitamin A (along with D and K2), because it's what Price found in healthy populations throughout the world. She often uses fuzzy logic, but she tends to be right anyway because her framework is correct (do what has worked in the past).

Chris Masterjohn published an article a while back that's the most in-depth review of the evidence I've ever seen. When you look critically at the massive amount of data on the subject, it supports the idea that the optimum is a high intake of both A and D, but the worst is high A and low D (which is really what Dr. Cannell and others are seeing). Here's Chris Masterjohn's article, if you have a minute and want to wonk out:

http://www.westonaprice.org/basicnutrition/vitamina-osteo.html

I may write about this since so many people have brought it up.

dgpenn2ca said...

There is no need for dietary K2, because it is made by intestinal bacteria in our guts. Populations with relatively low k2 intake, such as Japanese and Chinese have much lower coronary calcification than Europeans or Americans with higher intakes.

Anna said...

"There is no need for dietary K2, because it is made by intestinal bacteria in our guts."

My first thought is that a variety of GI problems afflict large numbers of North Americans and Europeans, so it's likely that they don't have a healthy gut bacteria population anyway, and can't count on enough K2 from that source.

Plus, so many people take antibiotics, which greatly lowers gut bacteria populations.

Look at the "healthy" sales of processed probiotic food products, such as Activia, in both North America and Europe. The sterile industrial food supply doesn't maintain a healthy gut colony, so artificial means to support the GI function are too often pursued.

Stephan said...

dgpenn2ca,

Actually, it has been shown beyond reasonable doubt that intestinal menaquinones do not contribute to our dietary needs. Rats can use intestinal menaquinones, but only because they practice coprophagy (turd eating).

The Japanese have a higher intake of menaquinones than Americans.

Micawber said...

The Japanese have a higher intake of menaquinones than Americans.

Stephen, is that primarily because of Natto consumption?

Personally, I'd love to hear your take on the vit A/D controversy; as well your take on Dr. Marshall's work on the potential for immune suppression via Vit D/fish oil.

Stephan said...

Micawber,

Yes, they get MK-7 from natto but they also get menaquinones from fish and fish roe. Eating insects is also traditional in some parts of Japan.

If all our animal food were traditionally raised in the US, we would have a much higher menaquinone intake.

I think I'm going to write a post about the vitamin A controversy, since so many people have brought it up.

As far as vitamin D and immune suppression, I'd have to look into it more. I'm superficially familiar with the Marshall protocol, and highly skeptical of it. But I'm not familiar enough to make a judgment at this point. I do know that their simplistic claims that vit D suppresses the immune system are false. It may suppress certain parts of it, but it definitely activates others. What's the optimum? Probably what we evolved with: high serum D. I've also heard people associated with the Marshall protocol say inane things like vitamin D deficiency doesn't cause rickets. I don't know how widespread that belief is within that community, but it definitely taints my view of them. I'm open to their basic idea, that persistent infections play a role in chronic disease.

Blood said...

"What's the optimum? Probably what we evolved with: high serum D."

Only if you're interested in living to be 50 to 60. If you want to live to be 100+, then you'll have to be smarter than evolution.

Anna said...

Blood,

Not sure I want to live to be 100, but I'm not too worried about living past 50 or 60 if I can avoid trauma or have emergency medical care available. A simple accident that we can take care of in any emergency room in the US could have meant the end for a paleolithic human.

Average life expectancy wasn't much above 30 ya for all of human existence, until the 20th century, yet of course, there were plenty of people who exceeded that age. There's not much reason to assume that even though average life expectancy of paleo humans was low due to high infant mortality, lack of modern medical care for trauma and infection, and predators, paleo humans weren't capable of living as long as we do. We have essentially the same physiology and they didn't have a polluted environment.

Stephan said...

I think it's worth noting that maximum lifespan in healthy non-industrial people was similar to ours today, with a 100-year-old for every few hundred people. That's based on the available data from the Inuit and Kitavans. The Inuit and Kitavans also had 25%+ of their population over 60 years old. They were mostly dying of injury and infectious disease. Subtract those causes of death, and they would likely outlive us.

Blood said...

The general point I was making was that if you're trying to live to be a healthy 100+, then you'll have to outwit evolution, and you can't do this by simply matching your diet to that of our distant ancestors.

Marshall's work is a good example of the problem: It conflicts with what we know about ancient diets and sun exposure, but he may be right with respect to living to be 100+ (i.e., those pesky, unseen infections may be killing us off, with D as an accomplice).

Another example is the effect of AGEs on long-term health. Low-carb, cooked foods are loaded with AGEs, yet that's what our ancestors were consuming. Again, we will need to be more clever than that to reach 100+.

Evolution simply doesn't care if we reach 100+. In fact, it has an interest in killing us off long before that, since death is required to evolve the species to compete with other species. (Or at least that was true until we learned to directly manipulate genes.)

Aaron said...

Quoting blood: "The general point I was making was that if you're trying to live to be a healthy 100+, then..."

Many of us who contribute to this blog are trying to live healthy right now, and until our term is up.

"Evolution simply doesn't care if we reach 100+. In fact, it has an interest in killing us off long before that"

It is incorrect to view evolutionary forces teleologically.

"since death is required to evolve the species to compete with other species."

What is required for evolution by natural selection are three things:

1. Traits (measurable characteristics of an individual) are heritable from parent to offspring.
2. Traits vary among individuals in a population.
3. Some variants of a trait are better than others within a given environment.

Species evolution, a large focus of Darwin's seminal first book on the subject, is actually quite difficult to track both in the wild and in the lab, though some good efforts have produced moderate results (e.g., Jerry Hirsch's fruit fly studies).

But death has never been listed as a requirement for species-level evolution (except in the Malthusian rule about how population growth is constrained by the growth of our food supply). But again, that is among individuals (or groups) in a population, not inter-specific.

Blood said...

"But death has never been listed as a requirement for species-level evolution (except in the Malthusian rule about how population growth is constrained by the growth of our food supply)."

Given limited resources, death certainly is a requirement for evolution! The point is that there are reasons why we die when we do (versus the lifetime of other creatures), and that these reasons are tied to evolutionary forces, which may not be intersted in (are working against) having you live to be 100+.

And whenever the argument is made that we should just go back to eating and living like our distant ancestors (minus some trauma and infections), then you'll be stuck with their life expectancies, which I have no interest in being stuck with.

(And these are not "teleological" arguments. It's just shorthand to view "evolution" as a player in your destiny, but its actions are, of course, impersonal and without intention or purpose.)

Anna said...

Then why did average human life expectancy not go up very much at all from paleolithic times until the 20th century, when hygiene (including things as basic as doctors washing their hands), public sanitation campaigns, underground sewer systems and improved refuse disposal, and some dramatic developments in medical science (such as pharmaceuticals) dropped infant mortality and overall mortality rates dramatically?

10,000 years of consuming foods of agriculture didn't seem to make much of a dent in average life expectancy compared to stone age humans, in fact, some nutrition status indicators worsened, like height and dental decay.

KKCorey said...

It is suspected that bone marrow is a K2 source as well. I have a friend who grew up in Hong Kong who said that growing up she had bone marrow soup every day.
Kathy

westie said...

I have a question about K1. In this review paper: "Lipids (2007) 42:821–825" hydrogenation of K1 (phylloquinone)results in dihydro-K1 which is not converted to K2. Could this (partly) explain the undesirable health effects of hydrogenated plant oils?

Stephan said...

Hi Westie,

We don't seem to be very good at converting K1 to K2 to begin with; other animals are better at it. But who knows, having odd K metabolites in vegetable oil could be part of the problem. Partially hydrogenated fats are bad enough on their own that they don't require anything else to explain their health effects, though.

Wendy said...

I started taking MK-7 about a year ago. I was told by my chiropractor that I had calcification in my abdominal aorta (at a very young age of 43). I had a CT scan (neck to pelvis) 3 mos. ago that stated my abdominal aorta was "unremarkable" as well as an ultrasound of my abdominal aorta a month ago that didn't find any plaques.

I also eat a large bowl of dark leafy greens every day.

Stephan Guyenet said...

Wendy,

Cool, but... how confident was your chiropractor of the initial diagnosis? That's not exactly something they're trained to diagnose.

Kurt G. Harris MD said...

Wendy

Your chiropractor was no doubt looking at a plain xray and seeing what looked like calcification. On a film obtained in a chiropraactic office, it could easily look like there is somethiing there that is not.

Trust the CT scan. Aortic calcification big enough to see on a plain film would be very rare in a 43 year old.

Kurt G. Harris MD said...

Wendy

Your chiropractor was no doubt looking at a plain xray and seeing what looked like calcification. On a film obtained in a chiropractic office, it could easily look like there is somethiing there that is not.

Trust the CT scan. Aortic calcification big enough to see on a plain film would be very rare in a 43 year old.

Kurt G. Harris MD said...

Wendy

Your chiropractor was no doubt looking at a plain xray and seeing what looked like calcification. On a film obtained in a chiropractic office, it could easily look like there is somethiing there that is not.

Trust the CT scan. Aortic calcification big enough to see on a plain film would be very rare in a 43 year old.

Joshua said...

@ Stephan:

Depending on where the chiropractor went to school, there can be a varying level of focus on diagnosis in the curriculum, including identifying soft-tissue abnormalities that happen to show up on film. (side note: I feel this falls outside of the practice of chiropractic, and will most definitely refer out instead of trying to make my own diagnosis once I am in practice)

Another possibility is that, without knowing the exact diction the doctor used, s/he was trying to say something along the lines of "there is something here that may be aortic calcification."

@ Dr. Harris:

She should definitely trust the CT scan as you said, for both the fact that it is more precise, and also because it gives a more recent picture of where she is at now, instead of a 2D x-ray taken a year ago. However, the presence of a clear CT does not preclude the possibility of having aortic calcification 9 months prior.

Without knowing the case history of Wendy, I feel that it is fuzzy at best to make assumptions that she conforms to the epidemiology of the general population. I understand that it is the best guess without further information, but would rather reserve my opinion on the veracity of the diagnosis until I had further information.

@ Wendy:

Another variable besides the amount of vitamin K you consume is the chiropractic care itself, especially if you either started care for the first time, or changed chiropractors, at the time these x-rays were taken. As Stephan referred to in a previous post (small intestine-brain stem-liver neurological control via the vagus nerve), the nervous system, especially the brain stem, controls the other systems of the body. Removing interference to the nervous system, be it due to compressive, tensile, or torsional force by the soft tissue surrounding the nervous system, or due to insufficient blood flow to the nervous tissue because of sympathetic interruption, can cause a remarkable improvement in the presentation of symptoms, especially with an improvement in nutrition and living conditions like Stephen suggests. The synergy between better instructions for the tissue cells from the nervous system and better building blocks from an improved diet can encourage the expression of homeostasis within the body to a much greater degree than either can on its own. The time frame of 9 months between the x-ray and the CT also gave time for your body to make changes. This is why a truly principled chiropractor will focus on clearing out interference to the nervous system and letting the body heal itself, rather than focus on treating symptoms like back pain, atherosclerosis, or cancer.

Emla said...

Stephan,

Have you seen the new study out of Europe that found a genetic link to Vitamin A deficiency????

http://www.sciencedaily.com/releases/2009/11/091118072051.htm

Nearly half of all the women in the UK have a genetic variation which reduces their ability to produce sufficient amounts of Vitamin A from beta-carotene.



.

lostinchina said...

Hello all

I am an American guy living in China for the last 8 plus years. I got a CT Heart scan... wow... dang "StarGate" machine... and that dye... they never done a "big guy" so I had to buy an extra jug of dye. Man, that dye rushed through my body like a wild ghost... yikes, and stopped dead center of my butt... what a sensation!...however, one that I would not invite again. They dumped the entire load of dye all at once... and it bore down the right side of my heart unchallenged but little went to the left. They offered a re-do but I said "uh-uh". So they "did their best" to tweak the info and several hours rendered a batch of "re-contrasted" images that cast a set well calcified coronary paths. Creeps me out. I am sure some of you know what I mean. SO I went home and started reading. This fellow here, Stephen Guyenet... this kind of person is not so common. Bright, curious mind and a devotion to science... only ask for donations and leads no one into any form of disadvantageous arrangement... THANKS Stephen!
Now I have got to get out of China to Hong Kong and buy K2, D3, A and other supplements. Since K2 worked well on rats, I am in luck! So, I trust they may work well, as, by Chinese astrology, I was born in the year of the rat... ha-ha... so the K2 should be my salvation!
I wonder about that CT heart scan... wonder if all that over exposure was made accurate. Hope they over shot and I am not as bad as they thought...

Later all

Don

ADAMANDIA said...

as a greek american i know we must all eat better.....vitamin k is important....broccoli has it...my mother had to avoid these foods due to coumadin she was on for 10yrs along with hydroxyurea....which killed her with tumors in her liver....so please take this seriously....we ancient greeks lived long lives to age 110yrs....we ate raw foods and cooked foods...a little of everything organic!...please eat organic...eat fresh eat garlic raw choppe dnot that bottld stuff and eat sauted onions and other roots and bulbs that are healthy...but remembe--ginger is for flatulence...and this wil help with increased fiber....i take vti 4 20,000 iu...and vd3 400iu..and vit k ..not usre dosagfe as i eat veggies and fish and fish roe/caviar..with my sushi..what is natto??..thank u....my mom was 82 at her death --3 months after her birhtday..she did not have to die if the doctors had only told us to watch for tumors every 6 months...wwe had gr8 health ins so that was malpractic on their part!! as far as i am concerned..so demand the truth in all things !!i have met so many who dont do their jobs well as doctors and i am frustrated by them here in massachusetts of all states!!

Spunk said...

here is idea for living to 100..
"Jeanne Calment lived to be 122-the world's longest lived woman.
When she was 120, Jeanne said to a reporter, “I have only one wrinkle… and I’m sitting on it.”

She was there when they built the Eiffel tower. And she met Vincent van Gogh when she was 14. What an amazing life.

She had no signs of dementia, and rode a bike past the age of 100.

When researchers looked into what she might have been doing or eating that made her live so long, they found something unusual: Olive oil.

Jeanne said she used to spread it all over all her food all the time. She even used it to keep her skin healthy.

As it turns out, there’s a reason olive oil worked so well for Jeanne Calment.

Olive oil has a powerhouse anti-aging ingredient called tyrosol. Almost no one has ever heard of it, but tyrosol is also one of the strongest antioxidants we have. It can get rid of free radicals 10 times better than green tea, and twice as well as CoQ10.1

Tyrosol can also shut down aging in your cells. Tyrosol turns on a group of longevity genes called “forkhead box” genes, or FOXOs.

Scientists have known for a long time that cells which multiply rapidly – like white blood cells – protect themselves from free-radical attacks by using antioxidants.

But there are a lot of other cells in your body that don’t multiply very fast, and don’t have antioxidant protection. So how were they surviving free-radical attacks?

What they discovered was that FOXO genes were doing the work.

FOXOs were shutting down the aging of these cells when under attack, and directly increasing amounts of the body’s “master antioxidant,” superoxide dismutase (SOD).2

FOXO genes were extending life in those cells… and tyrosol turns on FOXO genes.

Tyrosol has also been found to protect cells of the central nervous system from dying after exposure to toxins like glutamate (MSG and artificial sweeteners). And because it’s neuroprotective, tyrosol is being studied as a beneficial treatment for Alzheimer's, Parkinson's and other diseases.3

I take all forms of K.

KAYUMOCHI said...

Then why did average human life expectancy not go up very much at all from paleolithic times until the 20th century

++++++++++++++++++

The Industrial Age added 25-30 years to all our lives because no longer do we work ourselves to death nor freeze in the winter.

John Berry said...

It sounds interesting. K2 and bone health, all this emphasis put on calcium for osteoporosis prevention has been misplaced, and that K2 is much more important.

patricia ann Sage said...

I take Calcium with Vitamin K2.

Vitamin K2 helps direct calcium to the bones and teeth(where it belongs), keeping the calcium from attaching itself to the arteries.

Natural sources are Natto, egg yolk, butter...problem is I don't like the cholesterol in egg yolk and butter and I don't like the taste of Natto.

I found this online and order it online as well http://tinyurl.com/q8fjc93
It is made in USA; head office is in California. That's why delivery and handling is free in USA. Delivery took about 3 to 7 days. It has Omega 3+ as well as CoQ10 and Vitamin K2 and it is Extended release(long-term effect).