Vitamin K antagonists

[pjoshea13]

This is a response to a warning that someone gave in a recent thread:

"Be careful about taking Vitamin K. The following study suggests that long-term use of a Vitamin K ANTAGONIST may DECREASE the risk of prostate cancer by 17%:

journals.lww.com/md-journal...

"Based on that, I would be wary of increasing Vitamin K intake."

....

The coagulation cascade is quite complex and involves many factors - see list after my signature.

If you want to be amused/bemused for 5 minutes, here is a video that claims to be: "Coagulation Cascade SIMPLEST EXPLANATION !!"

youtube.com/watch?v=LVYmV5m...(Not working as expected?)

The point is, one can interfere with coagulation at many points in the cascade.

Warfarin (Coumadin) is the classic vitamin K antagonist. Why antagonize vitamin K?

"Warfarin decreases blood clotting by blocking an enzyme called vitamin K epoxide reductase that reactivates vitamin K1. Without sufficient active vitamin K1, clotting factors II, VII, IX, and X have decreased clotting ability."

As you can see, Warfarin creates a vitamin K deficiency in order to prolong clotting time. Vitamin K is never the reason someone is on Warfarin. People ask: "Will I get a clot if I take too much vitamin K?" Does spinach come with a warning?

What are the consequences of vitamin K antagonist use?

[1a] Osteoporosis.

[1b] Arterial calcification.

"Long-term warfarin therapy may be associated with bone mineral loss and vascular calcification in 60-80 year old hypertensive patients."

ncbi.nlm.nih.gov/pubmed/266...

[3] A bleed out on the way to the ER, following a serious accident involving blood loss (carry the antidote at all times - vitamin K)

medpagetoday.com/emergencym...

For those with the misfortune to be on a vitamin K antagonist, vitamin K deficiency is the norm.

Everyone else should avoid insufficiency, since that will lead to osteoporosis & arterial calcification.

Is there particular benefit for those with PCa?

"Our results suggest an inverse association between the intake of menaquinones, but not that of phylloquinone, and prostate cancer." i.e. use vitamin K2.

ncbi.nlm.nih.gov/pubmed/184...

...

The study cited in the other thread states:

"This meta-analysis indicates that VKAs use may be associated with a decreased risk of prostate cancer, especially in long-term users."

It's possible, but one has to be crazy to want to go on Warfarin. And the protection would be due to clot inhibition - not vitamin K restriction. One could simply cut out all sources of the vitamin from the diet, of course. Let me know if that affects your PSA.

That meta-analysis was from last month. There was another one just 3 months earlier:

"In conclusion, we did not observe a reduced risk of prostate cancer associated with VKA use in this nationwide study and, taken together with previous study findings, a major protective effect of VKAs against prostate cancer seems unlikely."

ncbi.nlm.nih.gov/pubmed/302...

In a Danish study from 2016:

"This study, which included a larger number of PCa cases with warfarin exposure than previous studies, does not support previous notions of decreased risk of PCa among warfarin users."

ncbi.nlm.nih.gov/pubmed/276...

An Italian study from 2011:

"These results support the hypothesis that anticoagulation might have a protective effect on cancer development, especially prostate cancer."

ncbi.nlm.nih.gov/pubmed/211...

Choose the studies you like!

...

The PCa benefit of coagulation inhibitors - not specifically VKAs - is that they may prevent metastasis, rather than incidence. But in population with a low rate of screening, that may appear as a drop in incidence.

-Patrick

Coagulation factors and related substances

Number and/or nameFunctionAssociated genetic disorders

I (fibrinogen)Forms clot (fibrin)Congenital afibrinogenemia, Familial renal amyloidosis

II (prothrombin)Its active form (IIa) activates I, V, X, VII, VIII, XI, XIII, protein C, plateletsProthrombin G20210A, Thrombophilia

III (tissue factor or tissue thromboplastin )Co-factor of VIIa (formerly known as factor III)

IV CalciumRequired for coagulation factors to bind to phospholipid (formerly known as factor IV)

V (proaccelerin, labile factor)Co-factor of X with which it forms the prothrombinase complexActivated protein C resistance

VIUnassigned – old name of Factor Va

VII (stable factor, proconvertin)Activates IX, Xcongenital factor VII deficiency

VIII (Antihemophilic factor A)Co-factor of IX with which it forms the tenase complexHaemophilia A

IX (Antihemophilic factor B or Christmas factor)Activates X: forms tenase complex with factor VIIIHaemophilia B

X (Stuart-Prower factor)Activates II: forms prothrombinase complex with factor VCongenital Factor X deficiency

XI (plasma thromboplastin antecedent)Activates IXHaemophilia C

XII (Hageman factor)Activates factor XI, VII and prekallikreinHereditary angioedema type III

XIII (fibrin-stabilizing factor)Crosslinks fibrinCongenital Factor XIIIa/b deficiency

von Willebrand factorBinds to VIII, mediates platelet adhesionvon Willebrand disease

prekallikrein (Fletcher factor)Activates XII and prekallikrein; cleaves HMWKPrekallikrein/Fletcher Factor deficiency

high-molecular-weight kininogen (HMWK) (Fitzgerald factor)Supports reciprocal activation of XII, XI, and prekallikreinKininogen deficiency

fibronectinMediates cell adhesionGlomerulopathy with fibronectin deposits

antithrombin IIIInhibits IIa, Xa, and other proteasesAntithrombin III deficiency

heparin cofactor IIInhibits IIa, cofactor for heparin and dermatan sulfate ("minor antithrombin")Heparin cofactor II deficiency

protein CInactivates Va and VIIIaProtein C deficiency

protein SCofactor for activated protein C (APC, inactive when bound to C4b-binding protein)Protein S deficiency

protein ZMediates thrombin adhesion to phospholipids and stimulates degradation of factor X by ZPIProtein Z deficiency

Protein Z-related protease inhibitor (ZPI)Degrades factors X (in presence of protein Z) and XI (independently)

plasminogenConverts to plasmin, lyses fibrin and other proteinsPlasminogen deficiency, type I (ligneous conjunctivitis)

alpha 2-antiplasminInhibits plasminAntiplasmin deficiency

tissue plasminogen activator (tPA)Activates plasminogenFamilial hyperfibrinolysis and thrombophilia

urokinaseActivates plasminogenQuebec platelet disorder

plasminogen activator inhibitor-1 (PAI1)Inactivates tPA & urokinase (endothelial PAI)Plasminogen activator inhibitor-1 deficiency

plasminogen activator inhibitor-2 (PAI2)Inactivates tPA & urokinase (placental PAI)

cancer procoagulantPathological factor X activator linked to thrombosis in cancer

en.wikipedia.org/wiki/Coagu...

i

[JimVanHorn]

I'll go through this several times to understand, but thank you for this detailed explanation.

[Kuanyin]

A number of years ago my wife saw a cardiologist. She had had a vascular CT scan that revealed abnormal calcium deposits in her arteries ( the scan is no longer covered by Medicare). So we went to see the cardiologist. When asked what she could do to reduce or get rid of the calcium, he curtly answered “nothing”. I did some research and found one of the first studies of Vitamin K and reduction of calcium deposits done by Dutch researchers. I made a copy of the paper and sent it to her cardiologist. He pooh-poohed the results, telling us it would not work and was a waste of money. This guy was a fairly well-known cardiologist, at least in our area. I actually got into an argument with him asking him what exactly was wrong with the methodology of and conclusions drawn in the study. I had already pissed him off when I had asked if we could call him by his first name. His reply was that Mrs. C. did not spend all of that money putting her son through medical school only to be called by____. In any case, both my wife and I have been taking Vitamin K for years to reduce vascular calcium. I, too, have vascular calcium deposits that don't appear abnormal for my age.

[pjoshea13 in reply to Kuanyin]

My wife had the start of osteoporosis in her early 50's.

She later started using the LEF product & by her late 50's bone density was that of a young woman.

I had only been taking K a couple of years when I had a calcium scan. Very inexpensive, but not covered by insurance. No calcification in two arteries & only minor in the other two.

When my wife was 65, she had the scan - zero calcification in all four. Her doctor said it was unheard of in a woman of her age.

I keep meaning to repeat my scan, just to verify that the minor calcification has now cleared.

-Patrick

[j-o-h-n in reply to Kuanyin]

What a self centered arrogant a-hole of a doctor. So his mommy had to pay his way through medical school? Ohhh that poor little baby... Probably got him out of the draft too... My Cardia bleeds for him....

Send him my regards....

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 01/05/2019 12:47 PM EST

[Sculler]

Very interesting, my husband is on Coumadin for 1 year he got multiple blood clot to lungs after prostate surgery. Dec 2017.

It can be hard at times to control his blood INR levels. He is about to start Lupron then radiation for reoccurring prostate cancer. We are worried about the drug interaction. We have tried to get him off the Coumadin but Doc says cancer changes the blood and they won’t let him off.

Anyone have any experience with Lupron and Coumadin?

Thank you again ,you all have been helpful on our journey with PC.

[pjoshea13 in reply to Sculler]

I hated being on Warfarin. Mostly, I hated having to stop vitamin K.

It took forever for my INR to be in the "therapeutic range". Meanwhile, I had to inject Lovenox at double the dose for 6 weeks. When INR was finally behaving, I made the mistake of having wine with lunch before one test. INR was way out or range, so I was back to 3 visits to the "Coumadin Clinic" that week.

After 3 months, one DVT had cleared, but the other hadn't. Nevertheless, my doctor allowed me to stop using Warfarin & to start nattokinase. I monitored the situation via D-dimer & have been doing so for about 5 years.

-Patrick

[Sculler in reply to pjoshea13]

Hi Patrick

Thank you for your story ,it gave my husband some hope.

husband did lovonox too. It was a rough 4 months to clear lungs. He was 55 when he had surgery, he gets depressed thinking he has to be on Coumadin for life .

We have thought of trying nattokinase, what brand do you use? I’ve read consistency in nattokinase is the key.

Right now he goes every 2 weeks for D-dimer . Did you monitor it every week to start?

Right now my husband takes 12.5 Mg of Coumadin daily.

Kaiser in CA wants nothing to do with natural medicine.

We are thinking of going outside of Kaiser and getting help with a naturopathic dr.

Thanks again

Becca

[pjoshea13 in reply to Sculler]

Hi Becca,

I used Nattozyme for about 5 years:

swansonvitamins.com/nutrico...

The company seems to have stopped suppliers from offering the very steep discounts I once enjoyed. My maintenance dose is 6 caps / day, so it is expensive.

At the beginning of last year I switched to Doctor's Best:

swansonvitamins.com/doctors...

Much more affordable, & my D-dimer remains close to zero.

...

I had an active DVT when I first switched from Warfarin. I had no idea how much nattokinase to take. I started with 6 caps in the morning & 6 at night. Within days, I could feel my calf getting hot in the same place as when my 2 DVTs were diagnosed. So I doubled the dose & the hot feeling eased off & went away in a few days.

I didn't test D-dimer immediately, since nattokinase will elevate it while it is breaking down a clot.

Anyway, I know that Nattozyme is effective when starting out with a clot.

I have only used Doctor's Best for maintenance.

Best, -Patrick

[cesanon]

Patrick,

At first glance I think I read your post wrong.

So what you are saying that while Vitamin k might in theory be contra-indicated for prostate cancer, perhaps, at least in moderation it might be overall helpful. Especially in our demographic where our risk of coronary problems and mortality is so high.

So what do you think is a reasonable prophalactic dose range for Vitamin k?

Do you think taking a pill every other day is a rational dosing strategy, or because of a half life effect that might generate some kind of yo yo effect?

[pjoshea13 in reply to cesanon]

For those on Vitamin K antagonists, vitamin K supplements must be avoided. IMO, everyone else should be taking K2.

This has worked very well for my wife & I:

lef.org

-Patrick

[cesanon in reply to pjoshea13]

Patrick for dosing what do you think about taking left.org

Super K, Advanced K2 Complex,

Https://lifeextension.com/Vitamins-...

Once every other day?

See:

Modelling of vitamin K half-life in patients

Https://ncbi.nlm.nih.gov/m/pubmed/2...

[pjoshea13 in reply to cesanon]

"The MK-7 stays available in your body up to 48 hours":

lifeextension.com/Vitamins-...

-Patrick

[PhilipSZacarias]

Hello Tall_Allen, I am blown away by the mini dissertation and I appreciate the time you took to respond. It appears that only on this forum can we have important technical exchanges (unfortunately, never from our doctors...so far). I knew the clotting process was complex but after watching the YouTube video you recommended I was bemused more than ever by the complexity of how the clotting process evolved to be so complex (comparable to the complexity of the immune system). I am taking a mixture of K1 and K2 (Life Extension Super K) for the primary purpose of maintaining bone health according to the information that I have been able to obtain (sorry, I don't have my references as well organized as yours). My PSA started to rise slowly after docetaxel and then again after SBRT (Note: I have been on ADT since early 2016). Starting mid 2017 the PSA has slowly declined from 0.2+ to 0.1 ng/ml when I started taking diindolylmethane (DIM) and glucoraphinin (sulforaphanin precursor). I have been taking VK since October 2017. It should be noted that I am also taking aspirin and many phytochemicals that have anti-platelet or anticoagulant effects - there may complex interactions that will be difficult or impossible to sort out. As I mentioned previously, I will delve into the VK issue in greater depth. Again, appreciate the discussion as well as comments from other members. Regards, Phil

[j-o-h-n]

Does Kellogg's Special K cereal count?

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 01/06/2019 1:22 AM EST

[ARIES29 in reply to j-o-h-n]

Ha Ha Ha, that blew me away J-O-H-N

[j-o-h-n in reply to ARIES29]

Well Thank you... I try... I try....

BTW That's the cutest kid I ever saw... Is she for sale?... They're so nice when they're small but a real PITA when they're teenagers....

Good Luck, Good Health and Good Humor.

j-o-h-n Sunday 01/06/2019 6:07 PM EST

[ARIES29 in reply to j-o-h-n]

She is my very reason for living now j-0-h-n & a bit older & a handful.

Keep up the humour in the midst of this terrible disease & despair that people have when they first hear the word cancer.