Vitamin K and myeloma

Premise: my interest in most vitamins, except for vitamin D and (occasionally) a few others, has always been marginal. I also do not take a multivitamin or any individual vitamins.

 

Recently, though, I happened upon a Japanese study on vitamin K and myeloma: http://tinyurl.com/4tg824. I had already read about vitamin K on Don’s “Myeloma Hope” blog. But what this particular study revealed was news to me. As follows:

 

Vitamin K inhibits the growth of myeloma cells.

 

Before taking a look at the study, though, what is vitamin K, and can we obtain it from our diet? It’s a fat-soluble vitamin known as the “clotting” vitamin (the “K” in fact derives from the German word Koagulation), because our blood would not clot without it. (Note: warfarin, or Coumadin, is a vitamin-K antagonist because it inhibits coagulation.)

 

There is a lot of helpful but very technical information on the Linus Pauling Institute website: http://tinyurl.com/33dlfy

 

A few observations. Vitamin K is essential for the health of our bones. One of the consequences of vitamin K deficiency is, in fact, a reduction in osteoblast, i.e. bone-building, activity (see the LP Institute’s “Disease Prevention” section). And, surprise surprise!, I read that vitamin K deficiencies frequently occur in multiple myeloma patients. Hah.

 

Our bodies are unable to store vitamin K for long periods of time or in large amounts, which is why it is crucial to eat foods that contain it (unless you are taking warfarin). Vitamin K is present in cabbage, kale, broccoli, cauliflower, spinach and leafy vegetables in general. A partial vitamin K food list can be found on the LP Institute website (scroll down to “Sources”).

 

Interesting excerpt: To consume the amount of vitamin K associated with a decreased risk of hip fracture in the Framingham Heart Study (about 250 mcg/day), an individual would need to eat a little more than 1/2 cup of chopped broccoli or a large salad of mixed greens every day. Well, that’s not too difficult!

 

An excellent source of information on vitamin K is the World’s Healthiest Foods: http://tinyurl.com/ewrbe It tells us how vitamin K works and clearly explains the difference between the three different forms of vitamin K: Vitamin K1, phylloquinone, is the plant form of this nutrient. Vitamin K2, menaquinone, is produced from K1 by the bacteria in animal and human intestines. Vitamin K3, menadione, is a synthetic version. The one that is of interest to us myeloma folks, as we will see in a second, is vitamin K2, found mainly in eggs, liver (bleah!), some cheeses and fermented foods. This page also provides a long list of foods high in vitamin K. Very, very useful!

 

Okay, let’s go back now to the Japanese study that I mentioned at the beginning of the post. It examines the effect of vitamin K2 (aha!) specifically on myeloma cells. Previous studies showed that vitamin K2 can kill cell lines derived from patients with myelodysplastic syndrome (MDS) and acute leukemia, as well as freshly isolated leukemic cells.

 

An excerpt from the study’s Discussion: VK2 may be a good candidate therapeutic agent for myeloma patients since it caused growth inhibition, induced apoptosis via the mitochondrial pathway, activated apoptosis-inducing p38 MAPK,37-39 and generated reactive oxygen species.

 

Another important result was that vitamin K2 and dexamethasone were found to work synergistically against myeloma cells. And, by the way, the study mentions our old enemy, Bcl-x. When exposed to vitamin K2, Bcl-x was reduced. Hah!

 

Before filling up on vitamin K2, though, we should know that high doses could cause adverse effects such as thromboembolic events. This is of particular clinical relevance, because it is now recognized that thalidomide leads to increased rates of thromboembolic events in MM patients, especially when used in combination with other anti-myeloma agents (e.g., dexamethasone or alkylators). Therefore, if VK2 were to be used clinically as one of the therapeutic agents, it would have to be started at a low dose and with meticulous care to avoid thrombotic events.

 

Final considerations. The researchers point out that these were in vitro experiments done at high-dose concentrations for short periods. The long-term effects of vitamin K2 are not known. However, they add, supplementation with vitamin K2 might be useful in the treatment of elderly patients or patients who are unable to undergo harsh conventional treatments.

 

I will not take a vitamin K supplement, but I will print the WHF chart of vitamin K food sources and hang it up in my kitchen…just to make sure now and again that my vitamin K intake is adequate. I am so glad I did this bit of research today!

4 Comments

  1. Hi Margaret:

    I don’t really know what all this means but it seemed to be relevant to the feverfew and Vit. K discussion. Although this research discusses Vit. K-3 instead of Vit K-2. Don’t know the difference, over my head.
    I knew I had read something about Vit.K and feverfew acting similarly and thought I had read it here. But I got some of my saved research out and found what I was looking for in the Denver Naturopathic newsletter dated June 29,2005.
    http://www.denvernaturopathic.com/news/feverfew.html
    Its kind of a long article but interesting quotes are:
    A Singapore study in 2004, looked at Feverfew’s effects on the biochemistry of colon cancer cells and found …an action parallel to K-3 and Vit. C…which induced a unique form of cell death called autoschizis. Like K-3 , feverfew appears to deplete glutathione in the cancer cells and causes cell death while leaving healthy cells unaffected. Also the effect of feverfew on cancer cells is stopped by N-acetyl-cysteine (NAC), a nutritional supplement that increases glutathione levels. A paper from 2003 , the effect of feverfew on leukemia cells describles as atypical apoptosis, similar to what the Vit. K researchers describe.

    Its easy to look up which supplements increase the glutathione levels. I know my milk thistle does. And I stopped some others like selenium, I think because of this. I think folic acid might be another. All very good supplements unless there is a specific reason not to take, like watching the glutathione level. I’m like you I wouldn’t take Vit.k supplement, just try to add to my diet. Actually, the more I read, the less vitamins and supplements I take, much more focused now on certain ones and definately will continue with the curcumin after reading your lab results.

    After writing this I’m not sure what I’m trying to say, except it seemed in some way related to the discussion.

    This same article speaks to Feverfew being well tolerated at 4g. without toxicity, but also did not provide detectable plasma concentrations and that there was need of a purer parthenolide for higher doses. Your comments posted on Oct. 2, 07, mentions study update regarding the water soluble analog of parthenolide/feverfew is DMAPT which has 70% bioavailability. I am assuming that DMAPT is not available to the public as a supplement?? A quick search and I did not find.
    Just my brain spurt of the day. You have a way of digesting it all and re wording in a more understandable way.

  2. There is a review article, http://tinyurl.com/7lsw26 published in the October issue of Nutrition Reviews titled “Update on the role of vitamin K in skeletal health”. There is less than definitive correlations between Vitamin K1 and bone health, but as quoted “There are few reports of associations between MK-4 intake and skeletal health, primarily due to the limited food composition data available for this form of vitamin K. However, reports from Japan indicate that consumption of natto, fermented soybeans rich in MK-7, is associated with higher bone mineral density; this was found both in a population study and in a smaller study of premenopausal women (n = 117) with a VDR polymorphism that renders them prone to bone loss.”

    Vitamin K1 is as you indicated is a coagulation protagonist and supplementation should be discussed with your doctor if you are on an anticoagulant. Unfortunately “Warfarin prevents the activation of MGP and Gas-6, and in animals, induces vascular calcification.” ( http://tinyurl.com/8uvtl9 )

    Vitamin K2 on the other hand although important in the coagulation cascade does not appear to be a strong Warfarin antagonist. In fact “These results indicate that the pharmacological dose of vitamin K2 prevents both the progression of atherosclerosis and the coagulative tendency by reducing the total-cholesterol, lipid peroxidation and factor X activity in plasma, and the ester-cholesterol deposition in the aorta in hypercholesterolemic rabbits.” ( http://tinyurl.com/94u795 ) That along with “Numerous peer-reviewed studies have shown that vitamin K2 – given either as the synthetic form MK-4 (a short-chain version called menatetrenone) at a dosage of 45 mg/day, or as the natural form, MK-7 (a long-chain menaquinone derived from natto) at a dosage of 45 mcg/day – is a highly effective activator of osteocalcin, the Gla-containing protein integral to calcium deposition in bone. This body of research conclusively demonstrates that vitamin K2 not only lessens fracture incidence and improves bone density but also, via the carboxylation of another Gla protein (matrix Gla protein), inhibits arterial calcification.” ( http://tinyurl.com/8nfb7x )

    “A number of cell experiments have shown that vitamin K2 has powerful anti-carcinogenic properties that may make it useful in preventing or treating cancer in humans.” ( http://tinyurl.com/9dvnwk http://tinyurl.com/8xaj2p http://tinyurl.com/76ech8 …)

    So in short there is little evidence that Vitamin K2 intake is problematic. My doctor highly recommended it at sub-clinical levels.

  3. Margaret-

    I believe that vitamin supplementation is a function of what kind of condition your body is in. In other words, since I have undergone lots of chemo, radiation and a sct, I supplement more. This includes curcumin, of course, fish oil, vit d, etc.

    I would not recommend the extensive supplementation that I do unless the person had undergone the damage of conventional therapies. I wish that I had read about antioxidant therapy during my cancer treatments.

    http://beating-myeloma.org/search/node/antioxidants+during+chemo

    David Emerson
    http://beating-myeloma.org/

  4. Thanks, Linda and LPC, I will look more closely at the info you provided asap. It’s hard, ok almost impossible!, to be productive during the holiday season, not that Stefano and I are doing much (he has my cold and cough now…poor sweetie)…but still…

    Vitamin K3 is a synthetic form of vitamin K, AND there are problems (side effects, as I recall) connected with it. I don’t recall any details right now, but I read about them while doing research for this post. For more info on vitamin K, click on the World’s Healthiest Foods link.

    You are right, Linda, DMAPT is not available to us. In fact, the Phase I DMAPT clinical trial hasn’t even begun yet. Very frustrating. Eh!

    Margaret

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