Calcium – Alone or with Only Vitamin D – May Increase Risk of Dementia in Older Women Who Have Had a Stroke
According to a study just published in Neurology (August 2016), older women who have had a stroke or have other signs of cerebrovascular disease* may have an increased risk for dementia if taking supplements providing only calcium or calcium plus only vitamin D.
*Cerebrovascular disease is blood vessel disease affecting the arteries that supply oxygen to the brain. The most common cerebrovascular diseases are:
- Transient ischemic attacks (TIA, a kind of mini-stroke after which blood flow is quickly restored, so TIAs do not cause lasting damage)
- Ischemic stroke (when a clot blocks a blood vessel in the brain)
- Hemorrhagic stroke (when blood leaks out of blood vessels directly into or around the brain)
Any of these interruptions of oxygen supply to the brain can result in vascular dementia – dementia caused by a disruption in blood vessel function that impairs the supply of blood to the brain.
Hypertension (high blood pressure) is considered the most important contributing cause to vascular dementia because high blood pressure damages the lining of the blood vessels, and the repair process can result in narrowed, calcified blood vessels – especially if vitamin K2 is not available to activate matrix Gla protein, which (when activated) prevents calcium from depositing in our blood vessels.
The study just published in Neurology involved 700 dementia-free Swedish women between the ages of 70 and 92 who were followed for 5 years. (More specifically, 4 were born in 1908, 27 in 1914, 137 in 1918, 193 in 1922, and 339 in 1930). At the beginning of the study, a CT brain scan was performed in 447 participants, and all participants were evaluated for memory and thinking skills. Unfortunately, no CT scans were done at the end of the study, but participants’ memory and thinking skills were again tested.
When the study began, 54 of the 700 women had already experienced a stroke, and 98 were taking calcium supplements. During the study, 54 additional women had strokes, and 59 developed dementia. Among the 447 women who had CT scans at the start of the study, 71% were found to have lesions in their brains’ white matter (lesions are a marker for cerebrovascular disease). (71% of 447 = 317 women, far more than the 98 who took calcium supplements.)
White matter is the communications system in the brain; it’s composed of axons, which are long projections from the main body of each brain cell (aka, neuron) that carry nerve impulses between them. So, white matter lesions disrupt brain cell communication and thus brain functioning. Lesions in white matter tissue indicate the occurrence of mini-strokes (TIA) or some other problem that is impeding blood flow within the brain.
When the researchers analyzed the data, they found that supplemental calcium alone or taken with vitamin D increased risk of dementia, but only in women who have cerebrovascular disease.
- Women with a history of stroke who took supplements had a nearly 7 times increased risk of developing dementia than women with a history of stroke who did not take calcium supplements.
- Women with white matter lesions who took supplements were 3 times as likely to develop dementia as women who had white matter lesions and did not take supplements.
- Women without a history of stroke or without white matter lesions had no increased risk of dementia when taking calcium supplements alone or with vitamin D.
In the concluding section of the Neurology paper, the authors present a number of limitations to their research:
- The data they used was extracted from a decade-old observational study, which was not focused on calcium and was not designed to assess calcium intake.
- Their new analysis of the data collected in the observational study on 700 women included just 98 who took calcium supplements, and only 14 of them had or later developed dementia — and that’s all we know about them:
- “We [the study authors] had no information on the women’s dietary intake of calcium, blood levels of calcium, or calcium use.” (In other words, the researchers were completely clueless as to the amount of calcium in the women’s typical diet, the dose of supplemental calcium each woman was taking or how often a calcium supplement was taken. They don’t know how much calcium the 98 study participants who were taking a calcium supplement were taking—and in particular how much the 14 elderly women who developed dementia during the study took – and whether they took calcium once a week, or a few times a week for one month, or for one year, or daily during the 5-year study. Obviously, if the women did not consistently take a calcium supplement, the likelihood of its contributing to dementia would be negligible.
- “Information on duration of drug use or dosage regimen was unavailable, but the average recommended daily dose of calcium supplements in Sweden is 1,000 mg.” Since the study authors had no information as to what these 98 women’s supplemental calcium dose was, how long or how often they were taking calcium supplements, or what their dietary intake of calcium was, the researchers “assumed” the typical supplement dose was 1,000 mg because that’s the RDI in Sweden. And that seems strange – very few calcium supplements provide the entire RDI because it is assumed around 400 mg of calcium will be present in the average person’s diet. This is why AlgaeCal Plus provides, from 4 types of plant-derived calcium, 720 mg in a full day’s 4 capsule dose, not the full RDI of 1,200 mg/day.
- And finally, CT scans were run on 447 of the 700 women only at the beginning of the study, but we don’t know how many of these 447 were also in the group of 98 taking calcium supplements, nor if any of the 14 women who developed dementia during the study were among those who had a CT scan run. And no CT scans were performed at the end of the study, so the researchers were not able to assess the effect of calcium supplements – if any — on changes in the women’s white matter lesions or silent strokes.
By the time I got to this point in the study authors’ comments about the limitations of their “analysis” of the data, I was ready to toss this paper into the recycle bin. But, where your health is concerned, it’s always best to err on the side of caution.
Should you be concerned?
YES — if you have high blood pressure, have had a TIA or stroke, and are taking a calcium supplement that provides only calcium or calcium plus vitamin D, but no vitamin K2.
You do not want to stop taking supplemental calcium – enough supplemental calcium to bring your total daily intake from both your diet and supplements to 1,200 mg per day.
Calcium deficiency definitely contributes to osteoporosis, which is one of the reasons the RDI (recommended daily intake) for calcium in the U.S. is 1,200 mg per day for men and women age 50 or older.1 Getting this recommended amount through diet alone is difficult, especially as we age because our ability to effectively digest our food and absorb the nutrients it contains lessens. So, supplemental calcium is widely recommended.
Unfortunately, few physicians are aware of the current research clearly showing that the human body’s healthful use of calcium requires not just vitamin D, which help us absorb calcium, but vitamin K2, which activates the proteins that put calcium into our bones (a protein called osteocalcin) and keep it out of our soft tissues, which include our brains, arteries, hearts and kidneys (a protein called matrix Gla protein).
So, supplements containing only calcium or, potentially even worse, calcium plus just vitamin D are what are typically recommended. The calcium + vitamin D supplement is even more likely to cause harm because vitamin D will result in more calcium being absorbed into the bloodstream, but the vitamin K2-dependent proteins, which are required to put that calcium where we want it and prevent it from depositing where we don’t, will not be working. And that can increase your risk for a heart attack as well as cerebrovascular disease, e.g., a TIA or a stroke, and the development of white matter lesions, and eventually, dementia.
In the last few years, two large meta-analyses of studies looking at the effects of calcium alone or with just vitamin D have been published reporting increased incidence of precisely the problems that would be expected to happen. Both were authored by the same Australian research group led by Mark Bolland.
The first paper, published in the British Medical Journal in 2010, claimed supplemental calcium and vitamin D increase risk for heart attack and stroke.2 This paper was followed, in 2011, by another that used data from the Women’s Health Initiative Study to claim that taking calcium and vitamin D could slightly increase risk for a heart attack.3
These papers got a lot of press and continue to be cited as gospel in the medical research literature.
Since 2010, Bolland et al., have really been on a roll. Their next target appears to be vitamin D. In 2014, Bolland et al. published a paper claiming that vitamin D supplements do not lower risk of mortality.4 This paper came out shortly after a large meta-analysis that included 73 cohort studies (849,412 participants) and 22 randomized controlled trials (vitamin D given alone compared to placebo or no treatment; 30,716 participants) found “Supplementation with vitamin D3 significantly reduces overall mortality among older adults.”5
However, before recommending widespread supplementation, the researchers of this meta-analysis thought further investigations were required to establish the optimal dose of vitamin D, and whether vitamin D3, the natural form of vitamin D in animals, or D2, a form found in some plants and the form synthesized in the lab, aka the pharmaceutical version, should be used.
When the research was analyzed comparing the effects of vitamin D2 to vitamin D3, vitamin D3 was shown to significantly decrease risk of mortality (by 9% overall), while vitamin D2 (the synthetic, pharmaceutical version) had little effect.6 In their paper, Bolland et al., of course, combined the D2 and D3 data, effectively averaging out the beneficial effects of D3. A good try, but knowing what they did, we will not be fooled!
Bolland et al’s latest, anti-supplement salvo, claiming that vitamin D supplements do not prevent falls, came out in June 2016 in response to a paper published in April 2016 that included a review of the research on vitamin D and recommended its use along with calcium and exercise for the prevention of falls in elders. Once again, the data used by Bolland et al. to assert that vitamin D does not help prevent falls was drawn from studies many of which used vitamin D2 and none of which used vitamin K2.7-8
The problem with the conclusions drawn in all the Bolland et al. papers – and this latest paper in Neurology suggesting that calcium supplements increase risk for dementia — is that all are based upon ignoring a key fact of human physiology: healthful absorption and use of calcium requires both vitamin D and vitamin K2
It’s really a shame that, instead of attacking supplemental calcium and vitamin D, Bolland’s team is not using their research findings to underscore the essential nature of the partnership among calcium, vitamin D3 and vitamin K2 — because this is exactly what their papers – and the paper in Neurology — underscore and what the current research shows.
Vitamin K2’s protective effects on the vasculature have been confirmed in many human studies
Following is a very small sampling of recent human studies confirming vitamin K2’s highly protective effects on our blood vessels:
One of the first large human studies to demonstrate vitamin K2’s beneficial effects on the vasculature was the Rotterdam study, whose results were published in 2004 in the Journal of Nutrition.
The Rotterdam study involved 4,807 healthy men and women, aged 55 years or older, and looked at the relationship between dietary intake of vitamin K and aortic calcification, heart disease, and all-cause mortality.
The aorta is the main artery in the human body. It originates from the left ventricle of the heart, extends down to the abdomen, then splits into two smaller arteries (the common iliac arteries), which extend down into the legs. The aorta is responsible for sending oxygenated, nutrient-rich blood to all parts of your body through the systemic circulation. You can see why calcification of your aorta is extremely harmful to your health.
In the Rotterdam study, dietary intake of vitamin K2 as low as 32 mcg per day, with no intake of vitamin K1, was associated with a 50% reduction in death from cardiovascular issues related to arterial calcification and a 25% reduction in all-cause mortality.9
In 2007, a double-blind, randomized clinical trial investigated the effects of supplemental K2 in the form of MK-7 over a 3-year period in a group of 244 postmenopausal Dutch women. A daily dose of 180 mcg was enough to improve bone mineral density, bone strength, and cardiovascular health as measured by ultrasound and pulse-wave velocity, which are recognized as standard measurements for cardiovascular health.10-15
Also in 2009, the results of a large study involving 16,000 healthy women aged 49 to 70 years, who were participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and were followed for 8 years, confirmed K2’s protective effect on the vasculature. A high intake of natural vitamin K2 in the form of MK-7, 8 or 9 (but not either menatrenone, which is synthetic MK-4, or vitamin K1, which is found in leafy greens and vegetable oils) was associated with protection against cardiovascular events.
More about EPIC: EPIC is the largest study of diet, nutrition and disease ever undertaken. More than half a million healthy adults, mostly aged 35–70 years, enrolled in 23 centers in ten European countries: Denmark (11%), France (14%), Germany (10%), Greece (5%), Italy (9%), The Netherlands (8%), Norway (7%), Spain (8%), Sweden (10%) and the United Kingdom (17%). The study began in 1993, and data collection and analysis are ongoing.
For every 10 mcg of dietary vitamin K2 consumed in the form of one of the long-chain menaquinones (i.e., MK-7, 8 or 9), risk of coronary heart disease (heart disease caused by calcification of the coronary arteries, which deliver blood to the heart) was reduced by 9%.
In the western diet, MK-7, 8 and 9 are found in tiny amounts free range eggs and certain cheeses. For the full discussion of food sources of K2 in the form of the long chain menaquinones, please listen to my Vitamin K videos. A day’s dose of AlgaeCal Plus delivers 100 mcg of MK-7.16
Another study of 564 postmenopausal women published in 2009 further confirmed that intake of vitamin K2 was associated with decreased coronary calcification, whereas intake of vitamin K1 was not.17
I mention these earlier papers to let you know that the medical community has known about vitamin K2’s effects on the vasculature for well over a decade. Since 2010, 69 further papers, 21 of which were the results of human studies, have been published in the peer-reviewed medical literature confirming the essential role vitamin K2 plays in ensuring calcium is deposited in bone and prevented from depositing in our blood vessels, kidneys and brains.
A few highlights from the latest of these:
K2 helps prevent vascular calcification in patients with advanced chronic kidney disease
Recognition of K2’s importance in preventing vascular calcification has resulted in it use in a number of studies of people with chronic kidney disease. Calcification of the delicate blood vessels in the kidneys is a major factor in the progression of kidney disease and in the kidneys’ loss of function.
When vitamin K2 was given along with vitamin D to a group of patients with chronic kidney disease (stages 3 to 5) who also had:
- A lower estimated glomerular filtration rate (eGFR) at baseline (and were therefore at even higher risk of atherosclerosis progression), and
- Lower hemoglobin levels, which indicates more extensive damage to the kidneys, the patients benefited significantly.
Patients receiving combined treatment with vitamins K2 + D3, compared to those given vitamin D alone, had significantly less increase in common-carotid artery intima-media thickness (a marker of the degree of arterial narrowing) just after 270 days (9 months) of treatment.18-19
K2 lessens arterial stiffness in postmenopausal women
The effect of vitamin K2 (MK-7 given in a dose of 180 mcg per day) on arterial stiffness was investigated in a 3-year, double-blind, placebo-controlled trial involving 244 postmenopausal women. Study participants were given either a placebo (124 women) or MK-7 (120 women). Arterial stiffness (an indicator of calcification of the blood vessels) did not decrease in the women given placebo, but significantly decreased in all the women receiving K2, and decreased the most in those women whose arterial stiffness scores were the highest (worst) when the study began.20
K2 quickly increases blood levels of active matrix Gla protein
Eighty individuals aged 70 years or older (average age was 77) who already had vascular disease were randomly assigned to receive either K2 (MK-7 at a dose of 100 mcg) or a placebo for 6 months, despite the fact that a number of studies have now shown that major clinical benefits are not seen until at least 9 months and are much more likely to be evident after 2-3 years.
Nonetheless, in subjects given K2, levels of inactive matrix Gla protein dropped significantly, indicating that much more of this vitamin K-dependent protein, which prevents calcium from depositing in blood vessels when activated by vitamin K2, was at work. In addition, a small improvement was also noted in pulse wave velocity, an indicator of blood vessel flexibility and health.21
Results of a study published July 2016 in the journal, Atherosclerosis, show high intake of vitamin K2, but not K1, lowers risk of peripheral arterial disease* even in people with high blood pressure.22
*Peripheral artery disease (PAD) is a narrowing of the arteries other than those that supply the heart or the brain and most commonly affects the legs, but when narrowing of the blood vessels is occurring in the legs, it is also highly likely to be occurring elsewhere in the body. When arterial narrowing occurs in the brain, it’s called cerebrovascular disease and contributes to dementia; when it occurs in the heart, it’s called coronary artery disease and increases risk of heart attack and stroke. In PAD, the classic symptom is leg pain when walking which resolves with rest; the medical term for this is intermittent claudication. PAD is associated with increased risk of coronary artery disease or stroke, and may be present without clinical symptoms. Up to 50% of cases of PAD are without symptoms.23-2
In the study just published in Atherosclerosis, which involved 36,629 participants over 12.1 years of follow-up, K2 intake of just 33 micrograms per day or higher reduced risk of PAD by 41%!26
KEY FACT: Your brain, heart and legs are all connected via your vasculature.
A few of the ways through which K2 promotes healthy bones AND healthy blood vessels
Vitamin K2 stimulates bone formation by:
- Promoting the production of osteoblasts (the cells that build new bone).
- Activating osteocalcin, the vitamin K2 dependent protein that pulls calcium into bone.
- Increasing a number of key markers of bone formation (including alkaline phosphatase, insulin-like growth factor-1, & growth differentiation factor-15).
- Increasing levels of stanniocalcin 2, a hormone that is secreted when calcium levels rise too high in the blood and inhibits calcium’s absorption from the intestines and its reabsorption from the kidneys – until blood levels of calcium drop.
- Keeping osteoblasts active for longer by reducing the production of two proteins (Fas and Bax) involved in osteoblast cell death.
- Decreasing osteoclast production by decreasing the production of RANKL (receptor activator of nuclear factor kappa-B ligand) and increasing the production of OPG (osteoprotegerin). When RANKL binds to RANK, this sets off the production of osteoclasts. OPG, which looks a lot like RANK, serves as a decoy molecule and lowers osteoclast production since, when RANKL binds to OPG, it does not trigger osteoclast production.
Vitamin K2 prevents blood vessel calcification by:
- Activating matrix Gla protein and Gla rich protein, both of which prevent calcium from depositing in the walls of our blood vessels
- Increasing growth arrest-specific gene 6, another protein activated by K2 that has numerous protective effects on vascular smooth muscle cells, which are the cells the make up the lining of our blood vessels
- Inhibiting vascular smooth muscle cells from changing into osteoblasts, which they do when the blood vessel wall is damaged and no K2 is around to prevent it27-28
Obviously, an adequate supply of vitamin K2 is needed to protect the health of the blood vessels supplying your brain and heart. Not having enough K2 will prevent the healthful use of calcium in your body. Specifically, insufficient K2 will promote both the loss of calcium from your bones and the calcification of your blood vessels.29
The percentage of individuals with vitamin K deficiency increases with age for a number of reasons including:
- A decline in our consumption of vitamin K rich leafy greens and
- Because of modern manufacturing processes, in which the vitamin K1 in vegetable oils, the leading source of vitamin K in the western diet, is converted into a form with virtually no vitamin K activity.
In the modern world, even a well-balanced diet is not likely to provide sufficient vitamin K to activate either osteocalcin or matrix Gla protein adequately.30
Add to this the fact that supplementation with calcium alone or with vitamin D increases our need for vitamin K2, and it becomes obvious that also supplementing with vitamin K2 is a requirement for healthy bones and blood vessels.31-33
To sum up: 34-45
- To have healthy bones, we certainly have to have calcium.
- And to be able to effectively absorb calcium, we have to have vitamin D.
- And to be able to put that calcium into our bones and keep it out of our blood vessels, kidneys and brains, we have to have vitamin K2.
- Your body is intelligently designed! Supplying your body with calcium alone or with vitamin D does not cause strokes, heart attacks or dementia – when you are also providing vitamin K2.
- Not providing your body with enough vitamin K2 results in impaired calcium deposition in bone (and increased likelihood of calcified arteries, heart attack, stroke and dementia) because neither osteocalcin, which puts calcium in bone, nor matrix-Gla protein, which keeps calcium out of soft tissues, can be activated.
- By striking the right balance in intake of calcium, D3 and K2, we can support bone building and, at the same time, prevent the calcification of our blood vessels, which promotes high blood pressure, heart attacks, strokes, and cerebrovascular disease/dementia.
What to do if you have any form of cerebrovascular disease
Even if you are already taking some vitamin K2 – and it should be at least 100 mcg of K2 in the form of MK-7, which is far more effective than the MK-4 form — if you have cerebrovascular disease, you need to have your vitamin K2 status checked. Having any type of vascular disease is strongly suggestive of vitamin K2 insufficiency.
It’s easy to check your vitamin K2 status. The lab test you want to ask your doctor to have run for you requires only a simple blood draw, and your blood will be checked for its content of uncarboxylated osteocalcin (unOC). This is the inactive form of osteocalcin, the protein that, when turned on by vitamin K2, pulls calcium out of your bloodstream and into your bones. If you have high levels of unOC, you don’t have enough K2 available to activate it – or the other vitamin K-dependent protein so critical for your vascular health, matrix Gla protein.
And you must be getting the vitamin D3 you need to enable you to absorb the calcium you consume, whether from food or supplements, from your intestines. Without vitamin D3 available, we absorb only 10-15% of the calcium we consume. Most people require at least 2,000 IU of vitamin D3 daily to maintain adequate levels of 25(OH)D, the form in which vitamin D circulates in the bloodstream. Optimal levels of 25(OH)D are in the range of 50-80 ng/mL.
Why you want to take AlgaeCal, a plant-based calcium supplement
In the Neurology paper, the lead researcher on this study, Silke Kern, MD, PhD, University of Gothenburg, Gothenburg, Sweden, noted that calcium from food affects the body differently than calcium from supplements and appears to be safe or even protective against vascular problems. Why might this be?
Because food contains a lot more than just calcium. For example, cheese, if made from the milk of grass-fed cows, contains a bit of vitamin K2. Calcium-containing greens, like spinach, deliver a hefty amount of vitamin K1, and when we have extra K1 available, it can be converted into K2 by friendly bacteria in our intestines. Plus, spinach, and other greens, are also good sources of magnesium, which balances calcium’s activities, relaxes our blood vessels, and along with K2, helps protect against high blood pressure.
AlgaeCal Plus is effective in building bone because, just like calcium-rich foods, AlgaeCal Plus contains a lot more than just calcium:
Your daily 4 capsules of AlgaeCal Plus (2 capsules AM and 2 capsules PM) will provide your bones—and your blood vessels—with:
- 4 types of plant-derived calcium – each 2 capsules deliver 360 mg of calcium for a total of 720 mg per day.
- Vitamin D3 – 800 IU per 2 capsule serving for a total of 1,600 IU per day.
- Vitamin K2 (MK-7) – 50 mcg per 2 capsule serving for a total of 100 mcg per day.
- Magnesium – 175 mg per 2 capsule serving for a total of 360 mg per day (the correct ratio of half as much magnesium as calcium).
- Boron – 1.5 mg per 2 capsules, so 3 mg per day (the amount shown in the research to help build bone).
- Vitamin C – 25 mg per 2 capsules (an essential ingredient in the formation of osteoid, the cartilage-like material into which osteoblasts deposit calcium).
- And all of the other essential bone supporting minerals naturally found in the sea plant, Lithothamnion superpositum (or Algas Calcareas as the locals call it); copper, manganese, silicon, nickel, selenium, strontium, phosphorus, potassium, vanadium, and zinc.
So, don’t forego your calcium and vitamin D supplements, your bones need them! Just be sure to also take vitamin K2 to ensure calcium’s healthful use in your body. If you’re taking AlgaeCal Plus, you’re covered.
I hope this information has helped you get a better understanding of why vitamin K2 is crucial. Let me know your thoughts in the comments below!
- Bolland MJ, Avenell A, Baron JA, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010 Jul 29;341:c3691. doi: 10.1136/bmj.c3691. PMID: 20671013
- Bolland MJ, Grey A, Avenell A, et al. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ. 2011 Apr 19;342:d2040. doi: 10.1136/bmj.d2040. PMID: 21505219
- Bolland MJ, Grey A, Reid IR. Vitamin D supplements do not reduce mortality risk. BMJ. 2014 Apr 29;348:g2860. doi: 10.1136/bmj.g2860 PMID: 24780291
- Chowdhury R, Kunutsor S, Vitezova A, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014 Apr 1;348:g1903. doi: 10.1136/bmj.g1903. PMID: 24690623
- Fletcher RH. Review: vitamin D3 supplementation may reduce mortality in adults; vitamin D2 does not. Ann Intern Med. 2014 Jul 15;161(2):JC5. doi: 10.7326/0003-4819-161-2-201407150-02005. PMID: 25023271
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- Bolland MJ, Grey A, Reid IR. Vitamin D supplements do not prevent falls. BMJ. 2016 Jun 1;353:i3005. doi: 10.1136/bmj.i3005. PMID: 27250717
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- Bruno RM, Bianchini E, Faita F, Taddei S, Ghiadoni L. Intima media thickness, pulse wave velocity, and flow mediated dilation. Cardiovasc Ultrasound. 2014;12:34.
- http://www.cardiovascularultrasound.com/content/12/1/34. Published August 23, 2014. Accessed November 26, 2014.
- Stoner L, Young JM, Fryer S. Assessments of arterial stiffness and endothelial function using pulse wave analysis. Int J Vasc Med. 2012(2012):903107.
- http://www.hindawi.com/journals/ijvm/2012/903107/. Published March 2, 2012. Accessed November 26, 2014.
- American Society of Echocardiography. Ultrasound FAQ’s. See My Heart Web site. http://www.seemyheart.org/ultrasound-faqs/. Accessed November 26, 2014.
- Gast GC, de Roos NM, Sluijs I, et al. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis. 2009;19(7):504-510.
- Beulens JW, Bots ML, Atsma F, et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2009;203(2):489-493.
- Kurnatowska I, Grzelak P, Masajtis-Zagajewska A, et al. Effect of vitamin K2 on progression of atherosclerosis and vascular calcification in nondialyzed patients with chronic kidney disease stages 3-5. Pol Arch Med Wewn. 2015;125(9):631-40. Epub 2015 Jul 15. PMID: 26176325
- Stompór T, Winiarska A.Vitamin K in chronic kidney disease: time for a (hint of) hope? Pol Arch Med Wewn. 2015;125(9):618-9. PMID: 26406579
- Knapen MH, Braam LA, Drummen NE, et al. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost. 2015 May;113(5):1135-44. doi: 10.1160/TH14-08-0675. Epub 2015 Feb 19. PMID: 25694037
- Fulton RL, McMurdo ME, Hill A, et al. Effect of Vitamin K on Vascular Health and Physical Function in Older People with Vascular Disease–A Randomised Controlled Trial.J Nutr Health Aging. 2016 Mar;20(3):325-33. doi: 10.1007/s12603-015-0619-4.PMID: 26892582
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