This article came out recently online at Medscape.com –– and I believe many will be interested in the advances being made concerning our understanding of Vitamin K nutrition, and bone and cardiac health.
DwN
Vitamin K2 Steps into the Spotlight for Bone and Heart Health
John Watson; Reviewed by: Anya Romanowski, MS, RD
DISCLOSURES
October 10, 2018
Read Comments Below
Since its discovery nearly 90 years ago, vitamin K has enjoyed the uncomplicated status of an essential nutrient, respected but somewhat overlooked. Guidelines advised that we get our daily recommended intake of vitamin K (120 µg for men and 90 µg for women[1]), but most likely made no mention that it exists in two variants, K1 and K2.
Beginning in the 21st century, however, researchers started closely scrutinizing the structural differences between K1 and K2, which before had been considered largely irrelevant.[2] Their work has indicated that K2 may deserve special consideration as a treatment for osteoporosis and cardiovascular disease.
How Do Vitamins K1 and K2 Differ?
The umbrella term “vitamin K” actually describes a family of fat-soluble compounds. The body has limited ability to store the vitamin and amounts are rapidly depleted without regular dietary intake.
Vitamin K1, also known as phylloquinone, is primarily found in green leafy vegetables. K1 accounts for approximately 90% of daily vitamin K consumption in the United States.[3]
Vitamin K2, also known as menaquinone (MK), is primarily bacterial in origin. K2 is mostly encountered in fermented foods, meats, and dairy products.[4] It is further subgrouped based on the length of its side chains, from MK-4 to MK-13.[4,5] For example, meat products typically include the MK-4 variants, whereas the traditional Japanese vegetarian dish natto, made from fermented soybeans, contains MK-7, which provides the highest known vitamin K activity. K2 can also be produced by the human gut’s microbiome, though the absorption and transport of K2 produced in this manner is less understood.[1]
K2 comes to us primarily through products derived from animals, who can synthesize it from the K1 they ingest from eating grass. As agricultural practices have shifted animals away from grassy pastures toward grains, K2 levels have decreased.[2] Because K2 is usually present in only modest amounts, and even less so in low-fat and lean animal products, many Western diets are inadequate providers of a nutrient researchers consider increasingly important.
What Are K2’s Proposed Benefits?
Although K2’s effect has been studied across a variety of conditions, including cancer and arthritis, to date the strongest evidence exists to support its use in osteoporosis and cardiovascular health.[5]
Bone Health
Vitamin K’s bone-building reputation is well earned, as it is necessary for activating proteins secreted by osteoblasts.[2] K2 draws calcium into the bone matrix and can inhibit bone resorption when administered with vitamin D3.[2] The MK-7 form of vitamin K2 has proven particularly adept in this process.[6]
Supplemental K2 has been associated with significant reductions (approximately 25%-80%) in fracture risk when used alone or combined with vitamin D and calcium,[7,8] as well as with maintenance of bone density in osteoporotic patients.[9,10] K1 supplementation has shown comparatively less benefit for such outcomes.[11]
A 2017 systematic literature review recommended considering K2 alongside vitamin D and calcium as an adjunct osteoporosis treatment “rivaling bisphosphonate therapy without toxicity.”[11]
Cardiovascular Disease
K2 activates matrix Gla protein (MGP), which keeps calcium deposits from forming on vessel walls. Research has shown that adequate K2 intake generally frees up calcium for its more beneficial roles, whereas K2 deficiencies will lead to a buildup of calcifications.[5]
This simple cause-and-effect relationship was on display in the 2004 prospective population-based Rotterdam Study, which included 4,807 individuals with no history of myocardial infarction.[12] After following the cohort for up to 7 years, researchers reported that high K2 intake led to significant risk reductions in coronary heart disease, all-cause mortality, and severe aortic calcification when compared with those with the lowest K2 intake. In comparison, K1 intake had no discernible protective benefits.
A cohort study of over 16,000 women free of cardiovascular disease also reported a strong correlation between increased K2 intake and reduced coronary events, but not for K1.[13]
Remaining Questions
Supplemental K2 is now standard care for treating osteoporosis in Japan, and has been gaining attention in Western cultures as well.[11] Although the promising results described above merit enthusiasm, important questions remain regarding its use.
Studies comparing relatively lower doses of MK-7 supplementation with placebo in early menopausal[14] and post-menopausal women[15] produced conflicting results, with the former experiencing no differences in bone loss at 1 year but the latter seeing less age-related decline in bone content and density at the femoral neck and lumbar spine at 3 years. This raises questions regarding the optimal dose range of K2 for various populations, the duration of follow-up needed to determine its effect, and whether supplements can provide nutrient levels as adequate as dietary intake.
There have been several reports of elevated risk for cardiovascular disease among older adults and postmenopausal women taking calcium supplements.[16,17,18,19,20,21] However, this link has been questioned by other recent studies,[22,23] with clinical guidelines[23,24] suggesting that any risk can be mitigated if calcium supplements are taken within tolerable ranges (eg, not above the range of 2000-2500 mg/d). As this link continues to be investigated, the possible role of K2 supplements in counterbalancing any such risk is highly worthy of a robust clinical analysis.
Certain varieties of K2 supplements, such as MK-7, have also been shown to interfere with anticoagulation therapy, whereas others like MK-4 carry no risk for hyper-coagulation even at relatively high doses.[11] Physician awareness of the different properties of various K2 supplements is therefore crucial in patients taking anticoagulation therapy.
Although the evidence on K2 is preliminary and sometimes contradictory, there is nonetheless valid reason to be excited about the potential of this modest intervention. If nothing else, this collection of studies indicates that, although vitamin K remains essential, it is in no way monolithic.
COMMENTS
Karen Ahmad | Registered Nurse (RN) 1 hour ago
Several years ago I read that the “new” digital mammography actually did a decent job of visualizing calcium deposits in the aorta and coronary arteries. I made some effort to see if someone (? cardiologist ? Radiologist) might be able look at my digital mammography ….but no one seemed to know much about it. In that some time has passed now and more of these digital studies are now being done, it would be nice to see a study on the use of digital mammography to screen for vascular calcium deposits.
Dr. William Blanchet | Internal Medicine 23 minutes ago
The presence of arterial calcium on mammography is associated with a significant increased risk of coronary events. The presence of calcification on mammography should be an indication for doing coronary calcium imaging.
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Caroline Levy | Medical Student 1 hour ago
As a health consultant I see the benefit in both and both should be in our diet. Now, at 80 I have no osteoporosis, no heart problems, very good teeth, good muscles, etc., etc. Had a full physical 3 months ago and everything great. Variety is also essential in good health, but cutting back on wheat and sugary products, boxed cereals, is essential in the USA, as nobody’s body is made to survive on poor but sickening foods. Fermented foods are very good but most today do not have the time to do at home and locating these foods is somewhat difficult. We are made physically to eat a variety of foods for good health. I have noted some doctors do not allow K2 at all for some heart patients but I believe they also do not known much about real nutrition as it is not one of their studies.
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Barbara Banfield | Registered Nurse (RN) 2 hours ago
I have been taking a high dose K2 supplement (5 mg MK-4) along with Vit D3 for about 5 years now. My fingernails became much stronger and my tooth enamel became superslick and shiny. “Watch spots” of weakening enamel on my teeth also cleared up and I have had no cavities since starting the K2. Occasionally I run out of the K2 and do not buy more for a few weeks. During these times, I quickly notice my fingenails becoming softer.
As a post menopausal woman on prednisone for an auto immune condition with a higher risk for osteoporosis, my bones are slightly osteopenic, but holding steady per DEXA scans. After caring for patients who had mandibulectomies for osteonecrosis, I will never take a bisphosphinate, so this is a godsend.
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Dr. Justin Baldwin | Internal Medicine 2 hours ago
Nice to see this article. I hope Medscape will increase its coverage of nutritional and other research oriented toward prevention.
Dr. Luis Todd | Internal Medicine 3 hours ago
If you are taking clopidigrel, it’s still Indicated??
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Dr. William Blanchet | Internal Medicine 21 minutes ago
If you are taking anti-platelet drugs, you probably have vascular disease and should be on K2 — unless you have a coagulopathy.
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Dr. Paolo Bini | Rheumatology 5 hours ago
In my practice i was always struck by chest xrays from older patients with osteoporosis showing translucent spine bones and very radiopaque aortic and other vessel diffuse calcifications; I did wonder that *calcium moved from bone to vessels *. This paper on vit.K2 phisiology may explain the reason: due to nutritional deficit of vit K2, there is loss of function in Preventing parietal calcium deposition in vessels, and loss of function in promoting matrix calcium deposition in bones. It would be interesting to ascertain if such a radiologic pattern could substitute for blood measurement in diagnosing vit K2 deficiency (although clearly at a late stage of disease).
Kerre Willsher | Registered Nurse (RN) 7 hours ago
Have any studies been done on bone health to compare populations since Vitamin K2 commenced to be routinely given to neonates?
Vit K2 has been routinely given to neonates in Australia since the 1960s. I was a midwife.
––Kerre Willsher, Whyalla, South Australia
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Bao-Anh Nguyen-Khoa | Pharmacist Oct 16, 2018
Please note that population-based studies, such as Rotterdam, cannot demonstrate a cause-effect relationship, as stated by the author.
George MacDonald RN | Registered Nurse (RN) 1 hour ago
True, but neither can watching people jump out of airplanes without parachutes.
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Mark Seaman | Other Healthcare Provider Oct 14, 2018
The article is generally excellent. It does mention that certain varieties of K2 supplements, such as MK-7, have been shown to interfere with anticoagulation therapy. I believe that is a positive. I’m on warfarin and use a daily K2 MK-7 pill to stabilise my INR. The K2 overwhelms the variation in Vit K intake in my diet and consequently I can remain in the right INR range (2-3) about 99% of the time.
Mary Beth Horst | Nurse Practitioner (NP) 4 hours ago
@Mark Seaman Thank you for sharing this, I have believed for years that we should not restrict patients from foods that contain either K1 or K2, but rather have them eat or supplement these consistently and adjust warfarin dose accordingly. How crazy is it that we tell patients they can’t eat greens?
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Lisa Abermoske | Pharmacist 2 hours ago
@Mary Beth Horst — where I practice (Madison, WI) the common practice is always to counsel patients to eat consistent amounts of leafy dark greens, cranberry juice, or other forms of Vit K – never to avoid. That would be extreme I would think.
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Dr. Catherine Rice | Anesthesiology 2 hours ago
I test my INR daily and adjust my dose of Coumadin accordingly. Buy an INR test device and eat what you want.
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Dr. JOSÉ RAYMOND HERRERA | Endocrinology, Metabolism Oct 12, 2018
It has to be stressed that Vit K1 and Vit K2 are completely different animals and the studies should not mix them up. Also, it looks like the «French paradox» is more related to fermented and strong cheese (rich in MK-9) than to the traditional mediterranean diet (olive oil, tomatoes, red wine), which is not bad though but apparently better with those cheeses.
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Dr. Joseph Turcillo | Internal Medicine Oct 12, 2018
Excellent information! Keep it coming! Thank you. J Turcillo MD FACP