Self-experiment for vitamin K2 and anticoagulant medication

After a mechanical cardiac valve implantation, a blood thinner medication is needed against the risk of thrombosis. I have used for it Syncumar (acenokumarol) tablets as vitamin K1 agonist (which also agonist of K2). However, enough vitamin K2 is also needed for blocking arteriosclerosis and other civilization illnesses on the ground of the osteoporosis. These illnesses speeding up aging, lower the quality of life, and reduced the chances of the long-term survival. In a self-experiment I could balanced (at around INR=3,0) the synchronous effect of vitamin K2 and the surplus of Syncumar.

I found in my self-experiment, that at the beginning 90 μg/day (or more) vitamin K2 could balance on a shorter time the surplus of 1 mg/days Syncumar (when instead of 2.5 mg Syncumar Mite I take 3.5 mg). Then, on a longer time a Syncumar surplus of 0.75 mg could be balanced by a relatively little quantity of a vitamin K2, first by 32.14μg of Vitaking Natto, and then 22.5μg of Doctor's Best (NattoPharm) MenaQ7. Therefore, there seems to be an accumulation effect of the fat-soluble vitamin K2 on a longer distance. This experience is in accordance with which was found in VitaK research institute. The results of the 1. phase of my self-experiment are illustrated by the Figure 1.

Figure 1. (can be enlarged by a click on it)

The details, together  further data until last controll (nowdays), of my self experiment are shown by Table 1a and 1b.

 Table 1a. (can be enlarged by a click on it)

Table 1b. (can be enlarged by a click on it)

Unfortunately, my chronic bronchitis (COPD) existing since decades has an acute exacerbation. The long-acting anti cholinergic bronchodilator tiotropium (Spiriva) and a β2 agonist (Formoterol) inhalation powders were prescribed and a weekly long steroid pulse therapy was applied (by Medrol which is a corticosteroid hormone [Methylprednisolone]).

Then occurred even bigger problem. An allergic, bilateral diffuse, interstitial hypersensitive lung tissue inflammation with an acute pulmonary circulation decompensation. Against these an intensive steroid therapy was applied with diuretic Furosemide and antibiotic treatment, which were INR-increasing medicines. For compensation of these I did not reduce Syncumar value, but increased the K2-vitamin (the hospital it entrusted the treatment of anticoagulation to me). INR values obtained were not bad, despite of the unusual medicines (and a diarrhoea lasting several days). After that 2 capsules (90μg/day) vitamin K2 have been applied.

It turned out under my hospitalization by X-ray CT, that there are atherosclerotic lesions in the coronary of my heart and plaques in the aorta (and also a 1,4x1 centimeter wall thrombus in the aorta arc).

Note for the change at 2014.01.24: During (because of) antibiotic treatment I fortunately could duplicate the Vitamin K2 intake, instead of decreasing the Syncumar portion too much. Previously this was not possible without increasing the Syncumar intake into a very high range (with the hazard of many bad side effects).


Note for the change at 2014.01.28: During (because of) cortikosterioid Medrol treatment  I could again duplicate the Vitamin K2 intake, instead of decreasing the Syncumar. Details at the and of the description.

Note for the change at 2014.04.24: After a decreasig trend, INR is too low! For the future I shall increase the portion of Syncumar, as shown in the last row by the plan for the following time.

Last updated at 08.11.2014 .  
No copyright. All results described here can be used freely. Any reference will be appreciated.

CONTENTS
The accumulation of the fat-soluble vitamin K2
Guidelines for taking the blood thinning medicament and the Vitamin 2 together
Conclusions of VitaK & CARIM
High Vitamin K2 activity of menaquinone-7
MenaQ7 and OAC treatment

Dr. Kate: “Vitamin K2: Friend or Foe of Blood-Thinning Medications?
   I thank Dr. Kate very much for notice me (in July 29, 2013) about this problem
Details of COPD exacerbation and hypersensitive pneumony
Atherosclerosis in my coronary and aorte
References-----------------------------------------------------------

The accumulation of the fat-soluble vitamin K2

The accumulation effect of the fat-soluble vitamin K2 at longer distance of time, SIMILAR to the case of CoQ10 Ubiquinol which is one of the most powerful fat-soluble antioxidants with a general guideline: start supplementing with 200-300 mg per day for the first 2–3 weeks. After that, 100 mg per day is a good amount to maintain optimal Q10 Ubiquinol levels, as shown in Figure 2.

Figure 2. (can be enlarged by a click on it)

http://ubiquinol.org/supplement-info

  

Guidelines for taking the blood thinning medicament and the Vitamin 2 together 

For taking the blood thinning medicament and the vitamin 2 together general guidelines, based on my experiment, could be as follows:

1.) Stabilize your INR~3 (±10-20%) for at least 1-2 months.

2.) Take a small (10-45 μg) amount of vitamin K2.

3.) Within one week control your INR to see the INR change/decrease and your sensitivity to vitamin K2.

4.) If everything is all right INR~3 (±10-20%), then duplicate amount of vitamin K2.

5.) Within one week control your INR to see the its change/decrease.

…..and so on, until INR<~2,5.

After that you can choose between the increased intake of blood thinner or decrease the amount of vitamin K2 to continue this try and error type adjusting.

Notice1:

The most important is, to understand the effect on INR change of both vitamin K2 and blood thinning to adjust their quantity at about INR~3 (±10%).

Notice2:

To see and compensate the possible accumulation effect of the fat-soluble K2, do not break off the weekly INR measurement until the INR~3 (±10-15%) is for at least 1-2 months.

Notice3: From the literature in different formulations:

·    Talk to your doctor about how natto might affect your lab test results if you are taking Warfarin.

·    If you take a blood thinner like COUMADIN® (WARFARIN), which works by inhibiting the effect of vitamin K, the use of a vitamin K supplement should be discussed with your doctor before you begin taking it, as changes in blood thinning may occur.

·    A point of concern is however the potential interference of K vitamins with long-term oral anticoagulant treatment. Individuals taking anticoagulant medications, such as warfarin (coumarins) should consult their doctor before taking.

Conclusions of VitaK & CARIM

Surprisingly, the conclusion of the common research of VitaK & CARIM in 2013 was to avoid MK-7 supplements needs to be avoided in patients receiving VKA therapy, as can be seen as follows (Source: http://www.ncbi.nlm.nih.gov/pubmed/23530987):

"J Thromb Haemost. 2013 Jun;11(6):1085-92. doi: 10.1111/jth.12203.

Effect of low-dose supplements of menaquinone-7 (vitamin K2 ) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers.

Theuwissen E, Teunissen KJ, Spronk HM, Hamulyák K, Ten Cate H, Shearer MJ, Vermeer C, Schurgers LJ.

Abstract

BACKGROUND AND OBJECTIVE:

Despite the worldwide use of vitamin K antagonists (VKAs), there is limited knowledge of the influence of dietary vitamin K on anticoagulation control. In view of the increasing nutraceutical availability of menaquinone-7 (MK-7; vitamin K2 ) and its promotion for bone and cardiovascular health, it is important to determine the posology for the interference of supplemental MK-7 with VKA therapy.

PATIENTS:

Eighteen healthy men and women were anticoagulated for 4 weeks with acenocoumarol, and 15 of them attained a target International Normalized Ratio (INR) of 2.0. In the six subsequent weeks, subjects were given increasing doses of MK-7 (10, 20 and 45 μg day(-1) ) while continuing acenocoumarol treatment at established individual doses.

RESULTS:

Apart from the INR, acenocoumarol treatment significantly increased the levels of uncarboxylated factor II (ucFII), uncarboxylated osteocalcin (ucOC), and desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP), and decreased endogenous thrombin generation (ETP). A daily intake of 45 μg of MK-7 significantly decreased the group mean values of both the INR and ucFII by ~ 40%. Daily intakes of 10 and 20 μg of MK-7 were independently judged by two hematologists to cause a clinically relevant lowering of the INR in at least 40% and 60% of subjects, respectively, and to significantly increase ETP by ~ 20% and ~ 30%, respectively. Circulating ucOC and dp-ucMGP were not affected by MK-7 intake.

CONCLUSIONS:

MK-7 supplementation at doses as low as 10 μg (lower than the usual retail dose of 45 μg) significantly influenced anticoagulation sensitivity in some individuals. Hence, the use of MK-7 supplements needs to be avoided in patients receiving VKA therapy."

MenaQ7 and OAC treatment

According to the new version of page "MenaQ7 and OAC treatment", the conclusion is: "the present insights are that the target window for anticoagulation can be maintained with greater accuracy from high levels of vitamin K intake than from low levels", as can be seen as follows:

MenaQ7 and OAC treatment

Source: http://menaq7.com/index.php?page=menaq7-and-oac-treatment

Oral anticoagulants (also known as coumarin-derivatives) act as antagonists of vitamin K. Therefore, dietary vitamin K counteracts the activity of these coumarins, which is the reason why patients on oral anticoagulant therapy need to be kept in a delicate balance: their natural vitamin K intake should be counteracted partly by a carefully calculated dose of coumarin. The problem is that the therapeutic window is narrow: if the dose of coumarin is too high the patient will bleed, if it is too low there is risk of thrombosis. This problem is encountered at all levels of vitamin K intake, but in general we see that the lower the dietary vitamin K intake, the wider the day-to-day fluctuations are and the more difficult it is to maintain the patient in the target window.

Everyone ingests vitamin K all the time. It is very hard to find food items completely devoid of vitamin K and yet our total vitamin K intake is so low that most non-supplemented individuals are sub-clinically vitamin K deficient. Only few foods contain relatively high concentrations of vitamin K: green vegetables like spinach, broccoli or Brussels sprouts provide 100 micrograms of K1 per 100 grams of product. Cheese, curd cheese, eel and flatfish provide between 30 and 60 micrograms K2 per 100 grams of product. Because of the very limited number of foods rich in vitamin K, typical daily vitamin K intake shows considerable variation. For patients on coumarin treatment this means that their level of anticoagulation (INR-value) shows substantial day-to-day variation, and frequent control of the anticoagulant level is needed.

VitaK has conducted studies that have attempted to identify how MenaQ7 consumption levels affect oral anticoagulation. In these studies we have used healthy volunteers who received a vitamin K-restricted diet combined with a low dose of acenocoumarol with a target INR value of 2.0. This is the most sensitive human model that can be designed, and very prone to fluctuating vitamin K intake.

The results presented below showed that, for patients receiving oral anticoagulant treatment, it should be recommended that they do not take MK-7 supplements without consulting their medical doctor. For patients with unstable INR values it may be helpful, on the other hand, to combine a high dose of oral anticoagulant medication with a fixed daily dose of MK-7 (Stafford et al, Blood 2007;109:3607).

Studies confirming the influence of Vitamin K on anticoagulant treatment:

• In an early dose-response study among anticoagulated human volunteers, it was found that the daily intake of 150 μg/day of vitamin K1 significantly affected the INR value (Schurgers et al, Blood 2004;104:2682-2689).
• In a subsequent study comparing the potencies of K1 and MK-7 it was found that MK-7 was at least three-fold more potent than K1, which led to the following conclusion: Hematologists need to be aware that relatively low doses of MK-7 may have a larger impact on the stability of oral anticoagulation than vitamin K1. Obviously, a large study in patients on oral anticoagulant treatment is needed to demonstrate the safety of even low doses of MK-7 in this population. Until that time, it was proposed to use an upper safety limit for intake of 50 μg/d for long-chain menaquinones (including MK-7) in patients on oral anticoagulant treatment (Schurgers et al, Blood 2007;109:3279-3283).
• In May 2013, a larger study was published, showing that if measured at group level, a daily intake of 45 μg/day of MK-7 does not lead to a statistically significant decrease of the INR value, but that 10-20% of the population belongs to the “quick responders,” i.e. that they even show effects on their INR value at 10 μg/day (Theuwissen et al, J. Thromb. Haemostas 2013, epub).

 For patients on oral anticoagulants it is important to maintain a regular lifestyle and to avoid wide day-to-day variations in their dietary pattern. It benefits their INR stability if their vitamin K intake is relatively constant, with daily consumption of the same (or routine) amounts of green vegetables, cheese and other vitamin K-containing products, including supplements and fortified foods. (NB: also other factors like alcohol consumption and other medication should be kept constant since they influence the rate at which the coumarins are metabolized in the liver). The present insights are that the target window for anticoagulation can be maintained with greater accuracy from high levels of vitamin K intake than from low levels."

 

Dr. Kate: “Vitamin K2: Friend or Foe of Blood-Thinning Medications?

I think, the situation is very well the described (in 2011) by dr. Kate Rhéaume-Bleue in her book “Vitamin K2 and the Calcium Paradox. How a Little-Known Vitamin Could Save Your Life”. Thanks be to god. It would be worth wile to translate her book into Hungarian, too.

Figure 3. (can be enlarged by a click on it)

In the chapter entitled “Vitamin K2: Friend or Foe of Blood-Thinning Medications?” of dr. Kate's book could be found what shows the text picture 3.

Text picture 3 (can be enlarged by a click on it)

Intermezzo by an operation

Table 4 (can be enlarged by a click on it)

It was surprising, that after the inguinal hernia operation (on 13 May, 2014) the Syncumar need grew very much (from 3,0 onto 4,5 mg/day, under 1,5 month). Before the operation already appeared a decreasing trend for Syncumar need. The reasons and the solution of the problem were not solved before the operation.

Then I have changed Doctor’s Best MenaQ7 into Dr. Chen's Vitamin K2 (MK-7) which is much cheaper an have good quality, too. Table 4 show, that Dr. Chen's Vitamin K2 (MK-7) is also suitable to get ideal INR values (between 2,8-3,3). Then with Syncumar of 3,5 mg/day, INR became too low. Intake again Syncumar of 4mg/day, INR become higher, than ideal (but not very much). However, its was change too large. Then the portion of Vitamin K2 was doubled and the INR value became quite good, in spite of the fact that I had stopped the Formoterol and Budesonid inhalation, too. Then I decided, that about 2 weeks long I shall change nothing. I try to stabilize the present situation.

Atherosclerosis in my coronary and aorte

As shown in Figure 4 (according to Herbert C. Stary pathologist professor’s classification), the arterial calcification and plaque development is a very slow process, starting typically in later childhood due to an accumulation of white blood cells in the walls of the arteries. According to Milton E. Alvis cardiologist, no symptoms occur for decades, though arteries get stiffer. Most events are without symptoms (despite tissue damage). When symptoms finally do occur, they are commonly of sudden onset due to plaque rupture.

Figure 4. (can be enlarged by a click on it)

I hope that the relatively stable equilibrium state of my arteriosclerosis remains for a long time yet. May help, that meanwhile I lost bodyweight 6 kg weight (from 90 kg which was to much compared to 175 cm of my height).

I am considering, that instead of Syncumar, if it is possible, I take another anticoagulants [like Eliquis® (apixaban), Pradaxa® (dabigatran) és Xarelto® (rivaroxaban)] which might make possible taking more Vitamin K2 to achieve a regression of my arteriosclerosis in my coronaries and aorta.

Then high HDL serum cholesterol values would be necessary to attain the wrong LDL cholesterol (and his plaques) deposited and to sweep it out (to resolve and to remove) from the arteries!

References

1.) K-vitamin család áttekintése.

  http://sebtiben.blogspot.hu/2013/07/k-vitamin-csalad-attekintese.html

2.) Sebestyén Tibor: K2 vitamin szedése vérhígító kezelés mellett. http://sebtiben.blogspot.hu/2013/07/k2-vitamin-szedese-verhigito-kezeles.html

3.) Szendi Gábor: Az életmentő K-vitamin. (2013. márc.)

  http://www.tenyek-tevhitek.hu/eletmento-k-vitamin.htm

4.) Dr. Kate Rhéaume-Bleue: Vitamin K2: Friend or Foe of Blood-Thinning Medications? A chapter in: Vitamin K2 and the Calcium Paradox: How a Little-Known Vitamin Could Save Your Life. http://www.goodreads.com/book/show/13277614-vitamin-k2-and-the-calcium-paradox

4.) Leon J Schurgers, Martin J Shearer, Karly Hamulyak, Elisabeth Stoecklin and Cees Vermeer (2004): Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose response relationships in healthy subjects. http://bloodjournal.hematologylibrary.org/content/early/2004/07/01/blood-2004-04-1525.full.pdf

6.) Nattopharma ASA (Norway): MenaQ7 and OAC treatment. http://menaq7.com/index.php?page=menaq7-and-oac-treatment.

7.) NattoPharma ASA: http://news.cision.com/nattopharma-asa

8.) About NattoPharma and MenaQ7®: http://news.cision.com/nattopharma-asa/about/

9.) Theuwissen E, Teunissen KJ, Spronk HM, Hamulyák K, Ten Cate H, Shearer MJ, Vermeer C, Schurgers LJ [VitaK & Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands]: Effect of low-dose supplements of menaquinone-7 (vitamin K2 ) on the stability of oral anticoagulant treatment: dose-response relationship in healthy volunteers. J Thromb Haemost. 2013 Jun;11(6):1085-92. http://www.ncbi.nlm.nih.gov/pubmed/23530987

10.) Dr. Milton E. Alvis Jr. (MD Cardiologist in San Antonio, TX): HealthTap:
https://edc2.healthtap.com/ht-staging/user_answer/avatars/771223/large/Arterial_Disease_Natural_History__with_comments.jpeg?1386604594 .

11.) Herbert C. Stary (MD, Professor of Pathology): Natural History and Histological Classification of Atherosclerotic Lesions. Arterioscler Thromb Vasc Biol.. 2000; 20:1177-1178. http://atvb.ahajournals.org/content/20/5/1177.long.