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Topic: VITAMIN K2 combined with Vitamin D3 IMPROVES bone density

Forum: Bone Health and Bone Loss —

Talk with others about bone density, osteopenia and osteoporosis, and ways to keep your bones strong

Posted on: Dec 24, 2015 09:16PM - edited Oct 31, 2019 09:16AM by macb04

macb04 wrote:

Something I never see mentioned, which was never mentioned to me even when I saw an orthopedic specialist after breaking my foot, was that Vitamin K2 deficiency along with Vitamin D3 deficiency increases the risk of fractures.

Just look at the following research about it. Vitamin K2 works SYNERGISTICICALLY with Vitamin D3 to move Calcium out of blood vessels and soft tissue spaces into bones. Without enough Vitamin K2 it is very hard to get the Calcium into your bones. Not only that, but Vitamin K2 is important in lowering risks of Atherosclerosis and Coronary Heart Disease. This should be a major health article, but you don't hear a word about it. Guess it might cut into the pricey, revenue generating big bucks the pharmaceutical industry gets with the Bisphosphonates

http://www.ncbi.nlm.nih.gov/pubmed/14529146

http://www.medscape.com/viewarticle/509074_4

http://www.lifeextension.com/magazine/2008/3/Protecting-Bone-And-Arterial-Health-With-Vitamin-K2/Page-01

http://link.springer.com/article/10.1007/s00223-012-9571-z

http://smilinsuepubs.com/vitamin-k2-inhibits-deadly-breast-cancer-growth/

http://articles.mercola.com/sites/articles/archive/2012/05/16/vitamins-d-and-k2-reduce-osteoporosis.aspx

http://jeffreydachmd.com/2014/10/vitamin-k/

Vitamin K2 is not the same as Vitamin K 1, which is involved in blood clotting. There are a number of studies out of Japan where it is used in combination with Vitamin D3 for prevention and treatment of osteoporosis/osteomalacia. The research is using MK 4 and MK 7 types of Vitamin K2. MK4 is found in animal products like Gouda, Edam and Brie Cheeses. MK 7 is found in Natto, a weird Japanese food made from fermented Soy beans.

No Vitamin K2 supplements unless approved by your doctor if taking Blood Thinners.

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Mar 20, 2016 11:59PM macb04 wrote:

Naturalpartners.com

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Mar 21, 2016 01:33AM marijen wrote:

I don't think we have natural partners here, it's $34 for .07 fl oz at Amazon. Does that sound right? How many drops and how long does it last

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Mar 21, 2016 09:15AM Italychick wrote:

I take this one. I got my vitamin d level to 98 using it, and I don't think it is $34. A bottle lasts a long time



Lumpectomy 1/27/15, TCH chemo, Finished chemo 5/27/15, rest of treatments 2/17/16 Dx IDC
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Mar 21, 2016 10:09AM marijen wrote:

my Vitacost has this but not a mulsion. Are these the right ingredients Italychick your d3 is about $18+


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Mar 21, 2016 11:09AM zogo wrote:

ItalyChick, that product is just a D3, not with the K2.

As for the versions of K2, I can't remember where I read it or even what the reason is, but I only take the MK-7 not the MK-4.

Does anyone have input on that?

~Jane~ "Most obstacles melt away when we make up our minds to walk boldly through them" ......"You'll never know how strong you are until being strong is your only option"
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Mar 21, 2016 11:33AM marijen wrote:

The reason I picked the Vitacost mix was because I read somewhere a long tine ago that both are needed.

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Mar 21, 2016 11:36AM marijen wrote:

From macb04 life extension link:

Intervention—the Evidence

Since it was first discovered in 1929, vitamin K has been best been known for its crucial role in the blood-clotting process. Since that time, scientists have uncovered compelling evidence that vitamin K plays an equally important role in bone health.

The majority of vitamin K research to date has focused on vitamin K1, the dominant dietary form of vitamin K that occurs in green, leafy vegetables. Yet it appears that vitamin K2, which occurs in organ meats, egg yolks, and dairy products, is a more important inducer of bone mineralization in human osteoblasts (bone-building cells) than vitamin K1.4

Vitamin K2 Protects Against Coronary Heart Disease

The Japanese long ago recognized the power of vitamin K2 to maintain or restore bone health. In certain regions of Japan, a staple dish called natto or fermented soybean, frequently eaten several times a week, is uniquely rich in vitamin K2. Recent scientific examination has pinpointed vitamin K2, and in particular vitamin K2 as menaquinone-7 (MK-7), as the active ingredient in this popular eastern Japanese dish, as having a supportive effect on bone quality during osteoporosis treatment.5

People living in the Japanese regions where this dish is eaten have several-fold greater blood levels of vitamin K2 (MK-7), accompanied by less osteoporosis and bone fractures.6

These findings are supported by clinical trials, in which vitamin K2 has been shown to successfully reduce the incidence of bone fractures. A two-year Japanese study found that vitamin K2 (MK-4) reduced the incidence of vertebral (spine) fractures by 52% in 120 patients with osteoporosis, compared with patients who did not receive this nutrient.7 The high dose used in this trial—as with most studies examining vitamin K2's effect on bone density—was 45 mg/day, a prescription dose used in Japan to treat osteoporosis that is unavailable in the US. As you will read later, lower doses of K2 found in dietary supplements appear to also provide significant benefits.

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Mar 21, 2016 04:53PM Italychick wrote:

Yes, I know the supplement I posted is D3 only, I take the K2 separately. I'm pretty psycho about making sure I do K2 with my D3. I focus more on the MK-4 form.

Sorry, I got lost in the thread and wasn't sure if people were looking for a D3 supplement or a D3/K2 combined supplement.

The K2 supplements I take are:

Complementary Prescriptions ultra k2 (mk4) 15 mg
Superior Source k2 (mk7) 100mcg

Not a cheap combo. Eek, I hate looking at what I actually pay for these supplements.

Lumpectomy 1/27/15, TCH chemo, Finished chemo 5/27/15, rest of treatments 2/17/16 Dx IDC
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Mar 21, 2016 05:05PM muska wrote:

I am only taking D3 at 4,000 units a day, no calcium or K2 or any other supplements. My pre-AI bone density test was two years ago and it showed some osteopenia. I am not taking any calcium because of history of kidney stones, apparently the science is not clear on what calcium supplementation does to my type of stones, so my MO and I decided to wait and see. I exercise more than I ever did before diagnosis. My moment of truth will be in April when I will have a second bone density test. I will keep you posted. I consider this an experiment of sort.Happy

Dx at 54 Dx 5/9/2013, DCIS/IDC, Right, <1cm, Stage IIIA, Grade 3, 7/11 nodes, ER+/PR+, HER2- (FISH) Surgery 6/12/2013 Mastectomy: Left, Right; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Dx 6/13/2013, LCIS, Both breasts Chemotherapy 7/24/2013 AC + T (Taxol) Surgery 2/19/2014 Reconstruction (left); Reconstruction (right) Hormonal Therapy 3/11/2014 Arimidex (anastrozole) Radiation Therapy 3/22/2014 Breast, Lymph nodes, Bone
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Mar 21, 2016 06:09PM - edited Jun 9, 2016 07:34AM by marijen

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Mar 21, 2016 09:40PM macb04 wrote:

Muska, have you looked at the Vitamin K2 research I posted at the start of this thread? If you already had a diagnosis of Osteopenia, I would worry about covering all the bone health bases, and K2 has such good research on the physiology of bone building, with no real downsides to it. Weight bearing exercise is of course crucial, but can't ignore the balancing act of Vitamin D3 working in concert with Vitamin K2 to Usher the Calcium into bones and out of blood vessels/soft tissue spaces, reducing risks of Osteoporosis and Coronary Heart Disease. Vitamin K2 usage is a win/win on a number of levels.

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Mar 22, 2016 10:15AM macb04 wrote:

Oh, it is online, Natural Partners.com. Or try Emerson Ecologics online. Good online source forhigh quality supplements. That is where I order from, Vitamin D3 /K2, Thorne Meriva Curcumin, and other things like Biogest for Digestive support as Ihave gallstones.

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Mar 22, 2016 05:43PM LovingIsLiving wrote:

I've been taking K2 100mcg (MK7) with no side effects. My oncologist confirmed that it doesn't interact with aspirin or tamoxifen. I'm going to up my vitamin D to 2000IU, and I added magnesium of 500mg along with 1000mg calcium. I still doubt whether I need some kind of bone strengthener, but my doctor said they might not even work and the benefits don't outweigh the side effects for me. I hope all of this works, because these supplements are not cheap!

"The Lord is my light and my salvation; whom shall I fear? The Lord is the strength of my life; of whom shall I be afraid?" (Psalms 27:1). The stats below are mine. ♥ My brother lost his fight against breast cancer on Feb 27, 2017 ♥ Dx 10/1/2015, DCIS/IDC, Left, 2cm, Stage IIB, Grade 2, 1/22 nodes, ER+/PR+, HER2- Surgery 11/10/2015 Lymph node removal: Left; Mastectomy: Left Hormonal Therapy 12/28/2015 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
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Mar 22, 2016 05:48PM - edited Jun 9, 2016 07:35AM by marijen

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Mar 22, 2016 06:34PM Italychick wrote:

Okay, thank you!

Lumpectomy 1/27/15, TCH chemo, Finished chemo 5/27/15, rest of treatments 2/17/16 Dx IDC
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Mar 25, 2016 03:11PM patoo wrote:

Mine is by MaxX Labs, combo Vit D3 (2000 IU) and Vit K2 (15 mcg). Only other ingredient is Olive Oil. I take one drop morning and one evening together with my Calcium.

"for we live by faith, not by sight" - 2 Corinthians 5:7 Dx 10/24/2008, ILC, 1cm, Stage IB, Grade 1, 0/5 nodes, ER+/PR+, HER2- Hormonal Therapy 2/12/2009 Arimidex (anastrozole) Radiation Therapy 4/2/2009 Breast Surgery Lumpectomy: Right; Lymph node removal: Right, Sentinel
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Oct 14, 2016 09:50PM marijen wrote:

Could Calcium Supplements Be Bad for You?

New research shows that people who take calcium supplements are more likely to have calcified coronary arteries; dietary calcium is protective.

Terry GraedonOctober 13, 2016

People who take calcium supplements are more likely to end up with calcium in their arteries. That is the conclusion from a new study that took 10 years to complete.

The Multi-Ethnic Study of Atherosclerosis:

More than 5,000 people between 45 and 84 years old participated in the Multi-Ethnic Study of Atherosclerosis (MESA) over the course of 10 years. They filled out questionnaires about their dietary habits and supplement use. Coronary artery scans were performed to detect calcification. About half of the participants had a second scan at the end of the study.

More Calcium from the Diet, Less from Calcium Supplements:

The researchers found that those who got the most calcium had the cleanest arteries–unless it was coming from calcium supplements. In that case, they had the most calcification.

Calcium and Atherosclerosis:

Atherosclerosis is the medical term for hardened arteries. But, you may wonder, doesn't that have to do with plaque in the arteries? Well, yes it does. Even though doctors have focused most sharply on cholesterol in arterial plaque, these lesions actually contain more calcium than cholesterol. It is the calcium that makes plaque-laden arteries "hard."

When coronary arteries become calcified, people are more likely to develop heart disease. This study confirms the results of other research implicating calcium supplements in the development of hardened arteries. You can read what we wrote about some previous studies here and here. You may also want to read what else we have written about these findings from the MESA study.

Journal of the American Heart Association, October 11, 2016

What About Strong Bones?

Most of the people taking calcium supplements are doing so because they believe this will prevent bone loss and protect them from fracture. If only that were the case!

While a certain amount of calcium is essential so that young people can develop healthy bones and older people can maintain bone strength, it turns out that excess calcium from supplements is not associated with stronger bones that don't break. A meta-analysis of 59 studies found that people taking calcium had very modest increases in bone mineral density, one way to measure bone strength (BMJ, Sept. 29, 2015). These gains did not last beyond a year or two, however. The researchers concluded: "for most individuals concerned about their bone density, increasing calcium intake is unlikely to be beneficial."

The Take-Home Message:

The bottom line is complicated in theory, but (luckily) simpler in practice. To benefit both your heart and your bones, be sure to exercise every day. That gives your bones the resistance they need to stay strong, and it keeps your heart pumping and your blood vessels in shape.

Also, eat a varied diet with lots of vegetables and nuts, along with some dairy products if you tolerate them. You can get adequate calcium from almonds, beans, broccoli, bok choy, corn tortillas, kale, mustard greens, spinach and Swiss chard. Tofu is a good source, too. If you are not vegetarian, add canned salmon and sardines, with the bones.

Either the Mediterranean diet or the DASH diet will make all this easier. If you'd like to learn more about these dietary approaches, you might want to read our book, The People's Pharmacy Quick & Handy Home Remedy. It describes how to follow these diets. You might also want to listen to our Show 752: Bone Vitality, in which we discuss how to strengthen bones through diet rather than through calcium supplements.

Vitamin D is also needed for strong bones and healthy arteries. You can learn more about vitamin D supplements and the British recommendation that all adults take them here

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Mar 6, 2017 08:49AM windingshores wrote:

K2 seems to be made from natto, which is sourced from soy. Is it safe for those on hormonal therapy?

Dx 2/2015, DCIS/ILC/IDC, Right, 1cm, Stage IA, Grade 3, 0/3 nodes, ER+/PR+, HER2- (FISH) Surgery Lymph node removal; Mastectomy: Right Surgery Mastectomy: Left; Prophylactic mastectomy: Left Hormonal Therapy
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Mar 6, 2017 01:02PM Hopeful82014 wrote:

Good question, WS. Even if phytoestrogens aren't an issue, I would be concerned whether the soy is GMO and what chemicals are used both in cultivation and processing. :(


Dx IDC
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Mar 6, 2017 01:53PM zogo wrote:

I use Jarrow K2 MK-7. It is non-GMO.

The MK-4 is synthetic, while MK-7 is from fermentation. The MK-7 will also stay in the blood at therapuetic levels longer.

You should be careful on dosage if you are on blood thinners or coumadin however.


~Jane~ "Most obstacles melt away when we make up our minds to walk boldly through them" ......"You'll never know how strong you are until being strong is your only option"
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Mar 6, 2017 05:22PM Hopeful82014 wrote:

Thanks, zogo :)

Dx IDC
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Jul 18, 2017 08:48PM - edited Jul 18, 2017 09:21PM by macb04

Here is a cool study about Vitamin K2 being of help for people with Rheumatoid Arthritis.

http://vitamink2.org/menaquinone-7-novel-pharmacological-therapy-treatment-rheumatoid-arthritis-clinical-study-abdel-rahman-ms-et-al/


Menaquinone-7 as a novel pharmacological therapy in the treatment of rheumatoid arthritis: A clinical study (Abdel Rahman MS, et al.)


  • There is no known toxicity associated with high doses of menaquinones (vitamin K2). Individuals taking anticoagulant medications, such as warfarin (coumarins) should consult their doctor before taking vitamin K2. Unlike the other fat-soluble vitamins, vitamin K is not stored in any significant quantity in the liver; therefore toxic level is not a described problem. All data available at this time demonstrate that vitamin K has no adverse effects in healthy subjects. Animal models involving rats, if generalizable to humans, show that MK-7 is well-tolerated.
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Sep 4, 2017 11:58PM Chenning wrote:

Hi there,

I see this thread is from last year but I'm hoping someone will still see my questions.

I'm taking arimidex and have been having lots of bone pain. Which I've learned is common. I've read about the k2, d3 and magnesium should help with this. My original dexa scan was good before I started the AI, but I'm concerned by the way my bones feel that the AI might be doing some damage.

I'm not sure when to take supplements? Is it best to take in morning, evening, with food, without food? Should they be taken all 3 together? Also, I've been taking magnesium oxide 250mg which I had no trouble with but now that I've started k2, I'm having to use restroom way more than I did before. I see that MG oil or spray has been used by some how do you use it?

I also take zinc, coQ10, fish oil, cranberry, biotin, turmeric and vit C, plus a baby aspirin. I feel like I take way too many pills.

My legs and hands tend to swell a lot and my hair is thinning which I think is because of the AI. Anyone else have these issues and find a solution?

Thanks for your response in advance!!

Regards,

Chri


Dx 10/7/2014, IDC, Right, 2cm, Stage IIB, Grade 2, 2/17 nodes, ER+/PR+, HER2- Surgery 11/24/2014 Lymph node removal: Right, Sentinel, Underarm/Axillary; Mastectomy: Right; Prophylactic mastectomy: Left; Reconstruction (left): Tissue expander placement; Reconstruction (right): Tissue expander placement Chemotherapy 1/14/2015 AC + T (Taxol) Hormonal Therapy 7/10/2015 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone) Radiation Therapy Whole-breast: Breast
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Sep 5, 2017 12:20AM Peregrinelady wrote:

Just a caution from my own experience. Best not to take vitamin K if you are taking Tamoxifen. I read that it helped with absorption of vit D, so I took it after 2nd stage of reconstruction. Ended up with a DVT that went to my lungs. I was on warfarin for a year. I also had a narrowed iliac vein, so may have happened anyway, but I am sure the K didn't help.
Dx 4/24/2015, IDC, Left, 2cm, Stage IIB, Grade 2, 1/2 nodes, ER+/PR+, HER2- Surgery 5/18/2015 Mastectomy: Left Hormonal Therapy 6/1/2015 Liquid tamoxifen (Soltamox) Surgery 4/19/2016 Mastectomy: Right; Prophylactic ovary removal; Reconstruction (left): DIEP flap; Reconstruction (right): DIEP flap Hormonal Therapy 8/1/2016 Arimidex (anastrozole) Hormonal Therapy 7/20/2020 Femara (letrozole)
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Sep 5, 2017 12:53AM macb04 wrote:

Peregrinelady, don't mix up Vitamin K1, (which is involved in the normal blood clotting response, it is given to newborns for that very reason) and Vitamin K2. Tamoxifen is known to cause blood clots, all by itself. Sorry to hear you had a Pulmonary Thromboembolism, but if you took only tamoxifen, as you can see, all by itself it causes a large number of blood clots.

CHENNING, I will get back to your question tomorrow. It's late here and have to get to bed, because I get up early tomorrow for work.

Tamoxifen Blood Clots

This medication increases the risk of developing a blood clot, which most frequently occurs in the calves, and can travel from there to the lungs. Blood clots can also cause a stroke. Women at higher risk for developing blood clots include those with a family history of blood clots, heavy smokers, those who have an inactive lifestyle, older women, and those with other predisposing medical problems. Women with any one of these risk factors may want to consider another therapy that does not have this side effect.

Being immobile increased the risk of a blood clot. You should stop taking this medication 3 days prior to and during any prolonged immobilization (hospitalization or bed rest). When traveling, be sure to get up and move around frequently to reduce the risk of a clot.

Signs of a blood clot in the leg may include any of the following: leg pain, warmth, swelling of one leg more than the other. Signs of a blood clot in the lung could include: fever, shortness of breath that comes on very quickly, racing heart, chest pain (that tends to be worse when you take a deep breath). Signs of a stroke include: numbness or weakness on one side of the body, trouble talking, confusion or mental status changes. If you have any of these signs or symptoms of blood clots, you will need to be seen immediately so that you can be treated. Blood thinners can be given. Call your doctor or nurse.

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Sep 5, 2017 01:06AM ChiSandy wrote:

Most of us here taking D3 & K2 are doing so to strengthen or protect bones weakened by AIs. Tamoxifen strengthens bones (as does the other SERM Raloxifene), therefore no K2 supplementation is necessary. Since the K vitamins promote clotting (which is why when we’re on blood thinners to prevent DVTs after joint replacement surgery we have to avoid green tea and limit dark green leafy veggies), and Tamoxifen’s most common serious side effect is clot formation, the combination of Tamox. & K2 could be deadly. Peregrinelady was lucky that her DVT wasn’t a fatal PE.

Chenning, if it makes you feel better, here is what I have to take daily: morning & evening—snort of Nasacort, artificial tears, calcium citrate (with added magnesium & D3), GTF chromium (to help me handle carbs) and arthritis formula acetaminophen. Morning: CoQ10, krill oil, D3, K2, low-dose aspirin, Feosol (combination heme & non-heme iron pill for anemia) & Vit C to absorb it, B complex, bupropion (for depression), and olmesartan HCTZ for hypertension. Bedtime: Colace (thank you, iron!), fiber gummies, multivite gummies, biotin, Zantac (had been on a PPI till I had to start taking iron), melatonin, Xanax to help with sleep, Magnesium (to help prevent nighttime foot cramps). Zyrtec for allergies, Pazeo (antihistamine eye drop), letrozole, montelukast (asthma), and rosuvastatin.

And that’s just if I’m healthy. If I’ve strained a muscle I ditch the Xanax in favor of baclofen; if I have a bacterial infection, whatever abx I’m prescribed; if severe laryngitis before a singing engagement (or intractable wheezing), a Medrol steroid dose-pack. Before a workout, going out in the cold air or bedtime during hay fever season, a couple hits off a Ventolin inhaler. So as pillheads go, you’re strictly minor-league compared to me.

Every night I portion out my meds into two shot glasses. Packing meds before a trip can take me over an hour!

Diagnosed at 64 on routine annual mammo, no lump. OncotypeDX 16. I cried because I had no shoes...but then again, I won’t get blisters.... Dx 9/9/2015, IDC, Right, 1cm, Stage IA, Grade 2, 0/4 nodes, ER+/PR+, HER2- (IHC) Surgery 9/23/2015 Lumpectomy: Right Radiation Therapy 11/2/2015 3DCRT: Breast Hormonal Therapy 12/31/2015 Femara (letrozole)
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Sep 5, 2017 01:21AM Peregrinelady wrote:

Believe me, I know how lucky I am that my PE wasn't fatal, especially after waiting 2 hrs. in the ER. It took my plastic surgeon calling twice to get them to ultrasound my leg. Btw, I had no calf pain at all. The clot was in my thigh, perhaps because I had May-Thurner syndrome, where the iliac vein is narrowed. I read about K2 here and had no idea that it contributes to blood clotting, but I will never know if the clot would have happened anyway. I was on a daily baby aspirin before the surgery so it may have prevented the clot previously. I am much more careful about supplementation now.
Dx 4/24/2015, IDC, Left, 2cm, Stage IIB, Grade 2, 1/2 nodes, ER+/PR+, HER2- Surgery 5/18/2015 Mastectomy: Left Hormonal Therapy 6/1/2015 Liquid tamoxifen (Soltamox) Surgery 4/19/2016 Mastectomy: Right; Prophylactic ovary removal; Reconstruction (left): DIEP flap; Reconstruction (right): DIEP flap Hormonal Therapy 8/1/2016 Arimidex (anastrozole) Hormonal Therapy 7/20/2020 Femara (letrozole)
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Sep 5, 2017 10:54PM macb04 wrote:

ChiSandy, did you forget that Coronary Artery Disease is the NUMBER # 1 KILLER OF WOMEN???

Also, PeregrineLady, Vitamin K2 (Menaquinone) is NOT, I repeat, NOT the same as Vitamin K1 (Phylloquinone). At normal physiologic doses of Vitamin K2, it DOES NOT have effects on blood clotting. Please stop saying something highly inaccurate without doing the research.

Also, here is food for thought from a long term follow-up of fractures in Danish women who used Tamoxifen, actually had MORE fractures versus those who did not take tamoxifen. Increased BMD( Bone Mineral Density) does not always correlate with increased bone STRENGTH.

There is also emerging research on Vitamin K2 and risks of Breast Cancer. Explain to me again why its a bad idea to take Vitamin K2 ?

  • to protect my bones, and reduce risks of Osteoporitic Fractures
  • reduce my risks of Coronary Artery Disease (Number 1 Killer of Women)

reduce risks of several types of cancers including Breast, Liver, Colon, Lung

Well suit yourselves, I am plan to keep taking Vitamin D3 and Vitamin K2.

The mechanisms of vitamin K2-induced apoptosis of myeloma cells.Tsujioka T1, Miura Y, Otsuki T, Nishimura Y, Hyodoh F, Wada H, Sugihara T.
Growth inhibitory effects of vitamin K2 on colon cancer cell lines via different types of cell death including autophagy and apoptosis.

Kawakita H1, Tsuchida A, Miyazawa K, Naito M, Shigoka M, Kyo B, Enomoto M, Wada T, Katsumata K, Ohyashiki K, Itoh M, Tomoda A, Aoki T.

Real-time cell analysis of the inhibitory effect of vitamin K2 on adhesion and proliferation of breast cancer cells.

Kiely M1, Hodgins SJ2, Merrigan BA3, Tormey S4, Kiely PA1, O'Connor EM5.

Author information Abstract

Breast cancer is the most prevalent cancer type worldwide. Continued efforts to improve treatment strategies for patients with breast cancer will be instrumental in reducing the death rates associated with this disease. In particular, the triple-negative breast cancer subtype of breast cancer has no targeted therapy available so it is essential to continue to work on any potential therapies. Vitamin K (VK) is known for its essential role in the clotting cascade. The antitumor properties of VK derivatives have been reported in both hepatocellular carcinoma and glioblastoma. Our hypothesis was that menaquinone-4, the most common form of vitamin K2 (VK2), is an effective anticancer agent against breast cancer cell types. In this study, we used a novel impedance-based live cell monitoring platform (xCELLigence) to determine the effects of VK derivatives on the triple-negative breast cancer cell line, MDA-MB-231, and the HER2+ breast cancer cell line, MDA-MB-453. Cells were treated with varying concentrations of menaquinone-4 (VK2) previously reported to have an antiproliferative effect on human glioblastoma cells. After initial testing, these concentrations were adjusted to 100, 125, and 150 μmol/L. A significant dose-dependent, growth inhibitory effect was found when cells were treated at these concentrations. These effects were seen in both adhesion and proliferation phases and show a dramatic reduction in cell growth. Additional analysis of MDA-MB-231 cells treated with VK2 (100 μmol/L) in combination with a low-glucose nutrient media showed a further decrease in adhesion and viability. This is the first study of its kind showing the real-time effects of VK derivatives on breast cancer cells and suggests that dietary factors may be an important consideration for patients.

Vitamin K2-derived compounds induce growth inhibition in radioresistant cancer cells.

Amalia H1, Sasaki R, Suzuki Y, Demizu Y, Bito T, Nishimura H, Okamoto Y, Yoshida K, Miyawaki D, Kawabe T, Mizushina Y, Sugimura K.

Author information Abstract

A strategy to overcome radioresistance in cancer treatment has been expected. To evaluate the strategy, appropriate experimental models are needed. Radioresistant tumour models were originally established from human colon cancer cells, and we evaluated their molecular basis. Next, the growth inhibitory effects of newly synthesized vitamin K2 (VK2)-related compounds were tested. Here, we showed that these novel compounds have growth inhibitory effects not only on cancer cells of various origins, but also on radioresistant cells, through the generation of reactive oxygen species (ROS). Human colon, lung, and breast cancer cell lines were used for testing the growth inhibitory activities of several chemical compounds. Radioresistant tumour models were established by fractionated radiation exposure. Irradiated cells were selected by a single cell cloning method, and their sensitivity to ionizing radiation was evaluated by a colony-forming assay. The VK2 derivatives (named MQ-1, MQ-2, and MQ-3) were chemically synthesized. To evaluate the generation of ROS, flow cytometer analyses were performed. A radioresistant tumour model was established from the HCT116 human colon cancer cell line. The radioresistant cells from HCT116 also showed resistance to cisplatin. In the radioresistant cells, NF-κB was highly activated. MQ-1, MQ-2, and MQ-3 showed greater growth inhibitory activities than VK2 not only in various cancer cells but also in radioresistant cells through the generation of ROS. In conclusion, a radioresistant tumour model was originally established from colon cancer cell lines through NF-κB activation, and it could be a useful tool for evaluating anti-tumour agents. Newly synthesized VK2 derivatives (MQ-1, MQ-2 and MQ-3) seemed to be potential anti-tumour agents in various cancers and radioresistant cancers. The efficacy of those compounds was related to the generation of ROS. These findings together might pave the way for the treatment of radioresistant or recurrent cancers.

PMID:
21063145


Femoral fractures in postmenopausal breast cancer patients treated with adjuvant tamoxifen.

Kristensen B1, Ejlertsen B, Mouridsen HT, Andersen KW, Lauritzen JB.

Author information Abstract

The anti-estrogen tamoxifen is the prevalent endocrine treatment in postmenopausal breast cancer patients. However, nothing is known about the long-term effects of the drug on the skeleton as assessed by the occurrence of fractures. We investigated the occurrence of fractures of the femur in patients from a Danish Breast Cancer Cooperative Group (DBCG) trial initiated in 1977 by a linkage of data from the Danish National Registry of Patients with data from the DBCG registry. 1716 postmenopausal women with high-risk breast cancer were randomized to local radiotherapy with or without tamoxifen, 30 mg daily for 1 year. Fifty-one patients in the control group had one femoral fracture and 64 tamoxifen treated patients had one femoral fracture. Eleven patients in the control group had one trochanteric fracture compared to 27 patients in the tamoxifen group (logrank = 5.28. P = 0.022; hazard ratio = 2.12, 95% CL 1.12, 4.01). The results could not be explained by a longer survival in the tamoxifen group nor by bone metastases with pathological fractures. In conclusion, our study suggests that tamoxifen does not seem to offer protection against fractures in old age and may even increase the risk of fractures at particular sites. This hypothesis needs to be disproved or confirmed in other trials.

PMID:
8877012


Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women.

Powles TJ1, Hickish T, Kanis JA, Tidy A, Ashley S.

Author information Abstract PURPOSE:

Tamoxifen is an effective treatment for metastatic and primary breast cancer and is now being evaluated as a chemoprevention agent in healthy women. Any long-term effects on estrogen-sensitive tissues such as bonemay have important therapeutic implications.

METHODS:

We measured bone mineral density (BMD) in the lumbar spine and hip using dual-energy x-ray absorptiometry (DXA) in premenopausal and postmenopausal healthy women who participated in our placebo-controlled tamoxifen chemoprevention of breast cancer trial.

RESULTS:

BMD data are now available from 179 women for this analysis. In premenopausal women, BMD decreased progressively in the lumbar spine (P < .001) and in the hip (P < .05) for women on tamoxifen, but not those on placebo. The mean annual loss in lumbar BMD per year over the 3-year study period in tamoxifen-treated compliant women who remained premenopausal throughout the study period was 1.44% (1.88% calculated on an intent-to-treat basis) compared with a small gain of 0.24% per annum for women on placebo (P < .001). Tamoxifen had the opposite effect in postmenopausal women. The mean annual increase in BMD for women on tamoxifen was 1.17% in the spine (P < .005) and 1.71% in the hip (P < .001) compared with a noninsignificant loss for women on placebo.

CONCLUSION:

These results indicate that tamoxifen treatment is associated with a significant loss of BMD in premenopausal women, whereas it prevents bone loss in postmenopausal women. These adverse and beneficial effects of tamoxifen should be considered in the assessment of the therapeutic benefits for both the adjuvant treatment and the chemoprevention of breast cancer.


Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects.

Theuwissen E1, Cranenburg EC, Knapen MH, Magdeleyns EJ, Teunissen KJ, Schurgers LJ, Smit E, Vermeer C.

Author information Abstract

Vitamin K is required for the carboxylation of Gla-proteins in the liver (coagulation factors) and extra-hepatic tissues, such as bone (osteocalcin, OC), and arterial wall (matrix Gla-protein, MGP). Although the coagulation factors are essentially fully carboxylated under normal conditions, 10-40 % of OC and MGP remains undercarboxylated. We were therefore interested to study the dose-response effects of extra intake of menaquinones on the carboxylation of the extra-hepatic Gla-proteins. A total of forty-two healthy Dutch men and women aged between 18 and 45 years were randomised into seven groups to receive: placebo capsules or menaquinone-7 (MK-7) capsules at a daily dose of 10, 20, 45, 90, 180 or 360 μg. Circulating uncarboxylated OC (ucOC), carboxylated OC (cOC) and desphospho-uncarboxylated MGP were measured by ELISA. The ucOC:cOC ratio was calculated from circulating ucOC and cOC values. Endogenous thrombin potential and peak height were determined by calibrated automated thrombography. To increase the statistical power, we collapsed the treatment groups into three dosage groups: placebo, low-dose supplementation (doses below RDA, Commission Directive 2008/100/EC), and high-dose supplementation (doses around RDA, Commission Directive 2008/100/EC). MK-7 supplementation at doses in the order of the RDA (Commission Directive 2008/100/EC) increased the carboxylation of circulating OC and MGP. No adverse effects on thrombin generation were observed. Extra MK-7 intake at nutritional doses around the RDA (Commission Directive 2008/100/EC) improved the carboxylation of the extra-hepatic vitamin K-dependent proteins. Whether this improvement contributes to public health, i.e. increasing the protection against age-related diseases needs further investigation in specifically designed intervention trials.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00483431.

A high menaquinone intake reduces the incidence of coronary heart disease.

Gast GC1, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT.

Author information Abstract BACKGROUND AND AIM:

Vitamin K dependent proteins have been demonstrated to inhibit vascular calcification. Data on the effect of vitamin K intake on coronary heart disease (CHD) risk, however, are scarce. To examine the relationship between dietary vitamins K(1) and K(2) intake, and its subtypes, and the incidence of CHD.

METHODS AND RESULTS:

We used data from the Prospect-EPIC cohort consisting of 16,057 women, enrolled between 1993 and 1997 and aged 49-70 years, who were free of cardiovascular diseases at baseline. Intake of vitamin K and other nutrients was estimated with a food frequency questionnaire. Multivariate Cox proportional hazards models were used to analyse the data. After a mean+/-SD follow-up of 8.1+/-1.6 years, we identified 480 incident cases of CHD. Mean vitamin K(1) intake was 211.7+/-100.3 microg/d and vitamin K(2) intake was 29.1+/-12.8 microg/d. After adjustment for traditional risk factors and dietary factors, we observed an inverse association between vitamin K(2) and risk of CHD with a Hazard Ratio (HR) of 0.91 [95% CI 0.85-1.00] per 10 microg/d vitamin K(2) intake. This association was mainly due to vitamin K(2) subtypes MK-7, MK-8 and MK-9. Vitamin K(1) intake was not significantly related to CHD.

CONCLUSIONS:

A high intake of menoquinones, especially MK-7, MK-8 and MK-9, could protect against CHD. However, more research is necessary to define optimal intake levels of vitamin K intake for the prevention of CHD.

PMID:
19179058
DOI:
10.1016/j.numecd.2008.10.004
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Sep 6, 2017 08:00AM zogo wrote:

Thank you for the valuable information macb! I take my D3 and K2 MK-7 daily (along with a handful of other supplements).

Do be aware that if on coumadin, the dose of K2 needs to be lower (per Kate Rheaume-Bleue "Vitamin K2 and The Calcium Paradox"). But, you are correct in saying that it is completely different than K1.


~Jane~ "Most obstacles melt away when we make up our minds to walk boldly through them" ......"You'll never know how strong you are until being strong is your only option"
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Sep 6, 2017 08:20PM macb04 wrote:

Hi Zogo, I just love that book. It is really well written, and has extensive references.

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