Vitamin K2 and Warfarin

[Lynlw]

That was also my short answer, Lyn. But I think I assumed they continued the Coumadin dosing of the non-control rates (even groups 2, 3, & 4). Your contrary reading may be right. I'm not sure it affects the "bottom line", except that (I think) my way it's about overcoming the ingoing effects of Coumadin, and your way it's about reversing the past effects.

That's why I was asking for a link to the study.
I "think" they would have mentioned "+ coumadin" for groups 2, 3, 4, since they mentioned "standard diet" each time. IF they were able to not only prevent more calcification but also able to reverse the past effects while the rat was still taking same amount of coumadin, I would think that would make a big difference compared to adding high dose Vit K but not having to overcome also taking Coumadin.

 

[Lynlw]

Here is the link

http://www.lmreview.com/articles/view/vitamin-d-and-vitamin-k-team-up-to-lower-cvd-risk-part-II/

Putting all the techno mumbo jumbo aside, my root question is simple; foe a person taking coumadin, would taking 45mcg of K2 help prevent calcium build-up in arteries and valves.

Even with open heart surgery and all the meds that come with it, I feel strongly a patient can reach a relatively high level of health with the right lifestyle. If coumadin does indeed contribute to calcium deposits in the wrong places, and contributes to weak bones, then I want to do what I can to stop it. All I am suggesting is a collective input to help one another.

Todd, i don't know if this helps answer your basic question

here is the 'rat" study

http://bloodjournal.hematologylibrary.org/cgi/content/full/109/7/2823
Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats

"To induce vascular calcification, rats (n = 30) received a diet containing warfarin (3 mg/g food) and vitamin K1 (1.5 mg/g food; the minimal dose required for rats is 0.5 µg/g food), according to the method described earlier by our group.25 These animals are designated as the W&K group. Control rats (n = 18) received no warfarin and a normal dose of vitamin K1 (5 µg/g food; this is equivalent to the vitamin K amount in normal standard rat food). From the control group, 6 rats where killed at the start of the experiment to measure the baseline calcium content of the abdominal aorta and left carotid artery. After 6 weeks of treatment, 6 control rats and 6 W&K rats were killed to monitor the effect of treatment. The remaining rats in the W&K group (n = 24) were subdivided into 4 groups of 6 rats for another 6-week treatment. One group continued the W&K diet, whereas warfarin was discontinued in the remaining 3 groups: one group received normal vitamin K1 (5 µg/g food), one group received high vitamin K1 (100 µg/g food; the dietary vitamin K requirements for rats are 0.5 µg/g food to maintain normal blood clotting), and the last group received high vitamin K2 (menaquinone-4, 100 µg/g food). In addition, the remaining 6 control rats continued their diet for another 6 weeks "

I "believe" the reason they stopped the Coumadin for the 3 groups, was they weren't really interested in Coumadin and Vit K, they just used the Coumadin to cause the vascular calcification, so they could see what effect the different levels of Vit k1 and high dose K2 would have on the calcification.

From the intro

"The rat arterial calcification model, as developed by Price et al20 and used by others,21,25,29 has thus far only looked at the development of arterial calcification. The aim of the present study was to use the rat arterial calcification model to investigate whether maximal MGP activity, ascertained by high–vitamin K intake, may stop the progression or even induce a reversal of warfarin-induced arterial calcification and the associated decrease in arterial distensibility"

Also for the Rotterdam study mentioned above (hooks post #13) that showed the benefit with just 45mcg of K2 a day

“The effect of K1 and the conversion rate of K1 to K2 was due to the extremely high dose of K vitamins used in this model,” said Schurgers. “This would be probably less in a normal diet, even with supplemental K1. In contrast, the Rotterdam study showed a significant protective benefit with Natural Vitamin K2 at just 45mcg per day, whereas K1 had no correlation at all"

Here is a link to the Abstract http://www.ncbi.nlm.nih.gov/pubmed/15514282

Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.

heres the fulltext http://jn.nutrition.org/content/134/11/3100.long

I'm not sure if it helps with your question tho, since they studied the general population and their diets and not people on Coumadin, for their study. So if their study showed 45 mcg a day lowerred their risks, I don't know what effect Coumadin would have on it, since it blocks the Vit K from doing its job. Most likely someone on Coumadin would need more than the 45 a day.
Also IF you increased your levels of Vit K2, most likely you would have to increase your Coumadin to keep your INR in range so it MIGHT be a catch 22 type of thing.

 

[hook]

You bring up the million dollar question. Will increased K2 require increased Coumadin, and will that increase in Coumadin cancel out all actions of the K2. The catch 22 if you will

From what I can simplify, the Coumadin does its work in the liver where Vit K1 activates the proteins that work on blood coagulation. I have read in a couple other articles that the K2s structure has a much longer half life, and is metabolized into the body in other places other than the liver. With that said, it may be possible an added dose of K2 may be able to do its job for the body, even if a little extra Coumadin is required.

I have a home INR tester, and have a small surplus of strips. I am going to start 45mcg of K2 and test every other day for two weeks to gather results. If this causes only minor changes in INR I will try the 90mcg. If I am able tolerate this with only minor increases in Coumadin, I will make this part of my regiment just to play it safe. I don't eat many greens, so this could be my primary source of K that we have all learned we need to maintain our levels. In a few years they will determine I was either wasting my money, or that I may have helped stop a deadly progression of calcification. We will see

 

[Lynlw]

You bring up the million dollar question. Will increased K2 require increased Coumadin, and will that increase in Coumadin cancel out all actions of the K2. The catch 22 if you will

From what I can simplify, the Coumadin does its work in the liver where Vit K1 activates the proteins that work on blood coagulation. I have read in a couple other articles that the K2s structure has a much longer half life, and is metabolized into the body in other places other than the liver. With that said, it may be possible an added dose of K2 may be able to do its job for the body, even if a little extra Coumadin is required.

I have a home INR tester, and have a small surplus of strips. I am going to start 45mcg of K2 and test every other day for two weeks to gather results. If this causes only minor changes in INR I will try the 90mcg. If I am able tolerate this with only minor increases in Coumadin, I will make this part of my regiment just to play it safe. I don't eat many greens, so this could be my primary source of K that we have all learned we need to maintain our levels. In a few years they will determine I was either wasting my money, or that I may have helped stop a deadly progression of calcification. We will see

But Coumadin Blocks/ inhibits vit K (1- K2) from doing its job anywhere NOT just the liver. Coumadin inhibits vitamin K(1 and 2) from activating the Vit K dependent proteins (like Matrix Gla Protein) to do their jobs (coagulation, protect from calcification etc)

There are tons of articles about coumadin + Vit K but this is easy http://cjasn.asnjournals.org/content/3/5/1504.full
Vitamin K-dependent proteins (VKDPs) require carboxylation to become biologically active. Although the coagulant factors are the most well-known VKDPs, there are many others with important physiologic roles. Matrix Gla Protein (MGP) and Growth Arrest Specific Gene 6 (Gas-6) are two particularly important VKDPs, and their roles in vascular biology are just beginning to be understood. Both function to protect the vasculature; MGP prevents vascular calcification and Gas-6 affects vascular smooth muscle cell apoptosis and movement. Unlike the coagulant factors, which undergo hepatic carboxylation, MGP and Gas-6 are carboxylated within the vasculature. This peripheral carboxylation process is distinct from hepatic carboxylation, yet both are inhibited by warfarin administration. Warfarin prevents the activation of MGP and Gas-6, and in animals, induces vascular calcification. The relationship of warfarin to vascular calcification in humans is not fully known, yet observational data suggest an association...
The most well-known vitamin K-dependent proteins (VKDPs) are the coagulant factors II,VII, IX, and X. Produced by the liver, they are converted into their biologically active forms by the carboxylation of glutamic acid residues, a process requiring vitamin K as a cofactor. By interfering with this carboxylation process, warfarin has become the mainstay of anticoagulant therapy. However, beyond these coagulant factors, there are other VKDPs with widespread physiologic activities. Recent studies have focused on two particularly important VKDPs, Matrix Gla protein (MGP) and Growth Arrest Specific gene 6 (Gas-6) protein. These proteins have many diverse biologic functions, yet with the recognition that they are produced by vascular smooth muscle cells, their roles in vascular biology are being increasingly explored. MGP functions primarily as a vascular calcification inhibitor. Gas-6 affects vascular smooth muscle cell movement and apoptosis. Together, these proteins constitute a new mechanism of local vascular regulation, where the blood vessel defends itself against injury and participates in self-repair. A failure of these local mechanisms might be an important first step in a cascade of events culminating in vascular calcification, and supports the notion that vascular calcification is an active, regulated process.

To become biologically active, both MGP and Gas-6 undergo carboxylation, a process that occurs at the blood vessel level. Like hepatic carboxylation, this peripheral carboxylation is inhibited by the administration of warfarin, yet whereas warfarin's anticoagulant effect is well known, its effect on the vasculature is less certain.

 

[normofthenorth]

Todd, I think that's a great plan, given what I've gleaned from those studies. I think K1 is more involved in INR, and Warfarin interferes with both "even-handedly", so you should end up with more K2 (and its metabolites) in your blood, the same INR, and a slightly increased ACT dose.

Those of us who have been trying to quantify and clarify the risks of ACT here haven't even mentioned this one, though it's important to the choices people make. (If you choose a mech. valve because you never, ever want another OHS, but the ACT means that you need a multiple bypass 10 years later, then you blew it!) ... But your approach may well reduce that risk to normal levels -- or even lower, if you end up with better K2 levels than the population as a whole. (Now I wonder why nobody's thought of this and acted on it before!)

 

[Bina]

I'm not ready to put the total blame on Coumadin for my bone loss and Osteoporosis....My doc discovered that I had
stopped drinking milk and gone through menopause a couple of years before he asked me to go for a Bone Mineral
Density scan. He suggested I take Actonel and calcium supplements, but the rest of my diet is healthy and varied,
so no fooling around with Vit K2 or K1 for me.

 

[normofthenorth]

If I can't ditch the Warfarin in a couple of weeks, as planned/hoped, I'll be looking to buy some Vit. K2, and join Todd/hook in the experiment.

 

[hook]

Todd, I think that's a great plan, given what I've gleaned from those studies. I think K1 is more involved in INR, and Warfarin interferes with both "even-handedly", so you should end up with more K2 (and its metabolites) in your blood, the same INR, and a slightly increased ACT dose.

Those of us who have been trying to quantify and clarify the risks of ACT here haven't even mentioned this one, though it's important to the choices people make. (If you choose a mech. valve because you never, ever want another OHS, but the ACT means that you need a multiple bypass 10 years later, then you blew it!) ... But your approach may well reduce that risk to normal levels -- or even lower, if you end up with better K2 levels than the population as a whole. (Now I wonder why nobody's thought of this and acted on it before!)

I love your take on it, and you said what I have been thinking. Lyn, I appreciate your information as well. As it seems K2 protien conversions will be affected in all parts of the body; the next question to be answered is how much of of this action is shut down, and can some of the K2 get past the enemy lines and do the job. It is obvious that more work needs to be done on this.

 

[Lynlw]

You should check out the clinical trials. to see what they are using what amounts etc. Also since K2 isn't really 1 vitamin, but a few different ones M-7 M4... each that seem to work on different protiens for different functions, so deciding which to take would probably make a difference. There are quite a few studies being done, if you search Vitamin K or K2 They might give you an idea where to start and IF you really are interested ideas of what to blood tests to ask about to see if you even need Vit K2 or if your gut is making enough.

Here's one as an example http://clinicaltrials.gov/ct2/show/NCT01194778?term=vitamin+K2&rank=1
Of course for most of the trials being on Coumadin or other K antagonists exclude you, but reading the different trials will give you ideas of what they are doing. from the trial I linked above (that is completed )

"Vitamin K is a group name for a number of compounds: K1 is present in chloroplasts in green vegetables, K2 is of microbial origin. Lactic bacteria produce a mixture of higher menaquinones, including menaquinone-7, menaquinone-8, and menaquinone-9. Nothing is known yet about the efficacy of bacterial K2 vitamins for in vivo K function (carboxylation of essential proteins). Therefore, this study was undertaken to study effects of different dosages of bacterial vitamin K2 on carboxylation of extrahepatic proteins.
down lower it says
Further study details as provided by Maastricht University Medical Center:


Primary Outcome Measures:
The concentration of the circulating biochemical markers matrix-Gla protein and osteocalcin. Both proteins will be measured in their active form (carboxylated form) and their inactive form (undercarboxylated form). [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
The main purpose of the study is to investigate the efficacy of different dosages bacterial vitamin K2 and vitamin K1 on carboxylation degree of the vitamin K-dependent proteins osteocalcin and matrix-gla protein.

Secondary Outcome Measures:
the number or type of bacteria in the stool [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
The second purpose of the study is to monitor whether the increased vitamin K intake will change the composition of the intestinal flora, as measured from the collected stools. Vitamin K, notably K2 is produced by a number of colonic bacteria and our principal is interested to learn whether the intake of extra vitamin K will affect the number or type of bacteria in the stool.

then under the desciption of the different arms of the trial
Detailed Description:
Vitamin K is a group name for a number of compounds: K1 is present in chloroplasts in green vegetables, K2 is of microbial origin. Lactic bacteria produce a mixture of higher menaquinones, including menaquinone-7, menaquinone-8, and menaquinone-9. Higher menaquinones not only have very long half-life times (over 3 days rather than 1 hour for vitamin K1); K2 vitamins are also transported to extra hepatic tissues such as bone and vessel wall whereas K1 is preferentially transported to the liver. Nothing is known yet about the efficacy of bacterial K2 vitamins for in vivo K function (carboxylation of essential proteins). This study describes a dose-response experiment for different dosages of bacterial K2 which are compared with one selected dose of K1 and placebo. The efficacy is concluded from the carboxylation of the bone Gla-protein osteocalcin and of the vascular Gla-protein matrix-Gla protein (MGP

IMO IF I were on coumadin and wanted to experiment with my own body, I probably wouldn't start at the higher doses, but the lower ones incase it does drop your INR quickly. it would be kind of sad to risk a stroke to "hopefully" prevent needing a CABG a decade or so from now. Or at least talk to my doctors and get their thoughts.

IF you search the trials for coumadin and Vitamn K, there are quite a few, http://clinicaltrials.gov/ct2/home

 

[hook]

I need the Vit K2 book for dummies.:eek2:

 

[Lily]

Since this thread is partly in regard to Vitamin K, I'll toss this little bit of info in, though it doesn't fit exactly. We picked up an amoxicillin RX the other day and the pharmacist included an information sheet with it, with info I don't recall reading before, and this is part of what it said:

Taking this medication may cause the following mineral depletion: BIOTIN FORTE; INOSITOL ORAL; LACTOBACILLUS ORAL (LACTINEX); VITAMIN B1 ORAL (THIAMINE); VITAMIN B2 ORAL (RIBOFLAVIN); VITAMIN B3 ORAL (NICOTINAMIDE); VITAMIN B6 ORAL (PYRIDOXINE); VITAMIN B12 ORAL; PHYTONADIONE-VIT K1 ORAL (MEPHYTON); VITAMIN K.

 

[hook]

That fits, since K2 is produced in the gut by native and ingested bacteria; that is our homegrown source. The amoxicillin kills the good bugs. I guess it is safe to say the antibiotics can raise INR if taken long enough.

 

[Lynlw]

That fits, since K2 is produced in the gut by native and ingested bacteria; that is our homegrown source. The amoxicillin kills the good bugs. I guess it is safe to say the antibiotics can raise INR if taken long enough.

that Probably part of the reason why Antibiotics can mess up INRs...
BTW I rememberred reading that people taking boost, ensure type products having trouble raisng their INR, so I looked to see how much Vitmani K was in them.. Boost has Vitamin K 32 mcg 40 %DV

 

[hook]

I have looked for vit K free whole food multi vitamins, and they are expensive. Even though I am taking the K2 as my little project, I would rather eat mt K1 vitamins.

I home test tomorrow, I will post the results.

 

[normofthenorth]

I don't get "I would rather eat mt K1 vitamins", Todd. You'd rather eat no K1 in your pills? Don't forget that the studies have shown that it's apparently easier to stabilize INR WITH some K(1) supplementation, than with none. It does mean you have to increase your ACT dose to compensate, of course. I'm not sure if your K2 will show up in your INR readings or not, since it doesn't seem to be much involved in clotting. . .

 

[Bina]

FWIW....it is next to impossible to completely omit vit K from the diet. It is in oils, desserts, fruits, breads,
veggies, etc. and we easily consume our RDA of this vitamin. The docs just freak out if we overload on
the HIGH K items and throw our INR into a dive. This has never been a problem for me and I continue to
enjoy my broccoli 4 times weekly.

 

[hook]

I don't get "I would rather eat mt K1 vitamins", Todd. You'd rather eat no K1 in your pills? Don't forget that the studies have shown that it's apparently easier to stabilize INR WITH some K(1) supplementation, than with none. It does mean you have to increase your ACT dose to compensate, of course. I'm not sure if your K2 will show up in your INR readings or not, since it doesn't seem to be much involved in clotting. . .

All I meant was I would rather eat a few salads every week rather than take K1 in a pill.

 

[hook]

I started the K2 last week 45mcg. Considering how much Coumadin I am on, there was little or no change in my INR so far.

Since my surgery last May, I have noticed I get a lot of tater build-up on my lower teath near my salivary glands. I have to scrape this every other week with a dental tool to keep it clean. Tarter is caused by minerals (calcium being one of the main ones) that build up on the teeth, and petrified bacterial colonies that adhere to that build up. There may be no connection, but I have no build-up since I started the K2. just an observation

 

[drivetopless]

drivetopless........
If you enjoy your salads and had one a day when you had stabalized your INR, why not go back to enjoying your salads rather than taking a supplement? Too bad they were so 'out of date' with INR stabalization in the hospital and denied you salads. Must have been very frustrating for you.

Sending you best wishes for no more bumps.......

I'm doing both (daily salad and a multivitamin with a small amt of Vit K (30mg). The idea is that by taking a vitamin wiht a small amt of Vit K, if you miss some veggies you still have a small amt of daily Vit K to normalize your system. Don't know if this is based on scientific fact or just anecdotal, but I'm giving it a try. Last INR was 2.9 so it seems to be working!

Thanks JKM

 

[hook]

I'm doing both (daily salad and a multivitamin with a small amt of Vit K (30mg). The idea is that by taking a vitamin wiht a small amt of Vit K, if you miss some veggies you still have a small amt of daily Vit K to normalize your system. Don't know if this is based on scientific fact or just anecdotal, but I'm giving it a try. Last INR was 2.9 so it seems to be working!

Thanks JKM

Very logical approach. I like it.