Science is complicated. Simple concepts that appear at first to be obviously true or untrue usually turn out to be more nuanced than we thought. Newtonian physics was taken as “the truth” until we learned in the 20th century that it didn’t apply on cosmological or subatomic scales. Medicine and human physiology are more complicated than most people realize or want to believe. A case in point is the recent realization that vitamin K is not a single chemical compound, but a whole family of them, and that vitamin K2 has unique properties that vitamin K1 lacks.
Recently, there has been some interesting preclinical research on K2 that warrants further study to tease out its implications for human health, diet, and supplementation. There has also been a lot of hype that warrants taking its claims not with a grain but with a large bolus of salt. According to Canadian naturopath Kate Rhéaume-Bleue, author of Vitamin K2 and the Calcium Paradox:
- It could save your life
- It is missing from the modern diet
- It is the most important anti-aging nutrient for fighting wrinkles, Alzheimer’s, heart disease, osteoporosis and more
- It promotes straight, cavity-free teeth
- It is needed to get the benefits from calcium and vitamin D supplements; without it, those nutrients will increase the risk of heart attack and stroke
- It is the only vitamin known to prevent and reverse atherosclerosis
The old adage is still true: if something sounds too good to be true, it probably is. There is only weak evidence behind these strong claims.
A brief review of vitamins
The first vitamin was discovered in 1912 when Dr. Kasimierz Funk found that the disease beriberi occurred in people who ate polished, processed white rice but not in those who ate brown rice. He isolated the responsible factor, thiamine, and called it a “vital amine.” A growing alphabet of vitamin discoveries followed, from A through K. Later, some of them had to be re-classified. The former vitamin F is now known as essential fatty acids, G and H are the B vitamins riboflavin and biotin, and J is choline, no longer considered to be a vitamin. The B vitamins are numbered 1 to 12; B4, 8, 10 and 11 are missing because they were found not to be essential nutrients.
Vitamin supplementation for deficient patients and vulnerable populations is one of the triumphs of scientific medicine, but supplements for healthy people have a poor track record. A parade of studies over the last decade has shown an absence of benefit or even harm in ingesting extra vitamins in pill form, as discussed in many posts on SBM (for example, see Should I Take a Multivitamin?, Vitamins and Mortality, and More evidence that routine multivitamin use should be avoided).
Vitamin K is a group of fat-soluble compounds essential for blood coagulation and calcium binding in bone and other tissues. Vitamin K1, phylloquinone, is important for coagulation and vitamin K2 (menaquinone) is more important for calcium metabolism. We get most of our vitamin K from diet; K1 is abundant in leafy vegetables. We get K2 from animal sources, and the bacteria in our intestines synthesize a small amount. There are several types of menaquinone, including MK-4 from animals and MK-7 from bacteria, with somewhat different properties. Available supplements may contain MK-4 or MK-7, and the smelly, slimy, fermented soybean Japanese breakfast food natto contains large amounts of MK-7 but is seldom acceptable to the American palate. One supplement, menadione or K3, is known to be toxic to the liver and is no longer used.
In a recent SBM article, Clay Jones explained the need for routine vitamin K injections in newborns. Vitamin K is present in many foods, and deficiency is thought to be uncommon in adults. Patients taking the anticoagulant warfarin are advised to limit the vitamin K in their diet, and vitamin K is used as an antidote to reverse the anticoagulant effect in patients with an overdose.
Evidence for the benefits of K2
Does K2 deficiency cause heart disease? The population-based Rotterdam study found an inverse correlation between dietary K2 intake and atherosclerosis, coronary heart disease, and all-cause mortality. A cross-sectional study of post-menopausal women found a reduced risk of coronary calcification (not actual cardiac events) in those with higher dietary intakes of K2.
Rhéaume-Bleue reports on a lot of K2 studies, but they are mostly in vitro and animal studies, with a few epidemiologic studies in humans that found correlations (which we know don’t necessarily imply causation). She marshals a lot of preclinical evidence, but makes claims based on speculation and reasoning that go beyond the actual evidence. No reliable clinical studies have been done to test whether supplementation of K2 would have any meaningful effects on disease progression or health outcomes in humans.
The reliable source The Natural Medicines Comprehensive Database, disagrees with Rhéaume-Bleue. They found there was “insufficient evidence to rate” the use of vitamin K for coronary heart disease. They made this determination after reviewing all the available published evidence. They noted that it was likely safe, with few adverse effects, but that it could interact with various drugs and supplements, and with lab tests, and could lead to complications in patients with liver disease or on hemodialysis. They found little evidence to support increasing the currently recommended vitamin K intake for the population.
The calcium paradox
Rhéaume-Bleue explains the calcium paradox: we take calcium supplements to prevent osteoporosis, but that doesn’t actually do much to prevent fractures, and it increases the risk of coronary heart disease. She envisions calcium supplements as killing us by causing calcium deposition in our arteries, and K2 as effectively preventing that deposition and of removing existing calcifications. She tells us that if 1,000 women take calcium supplements for 5 years, it will prevent 3 fractures but will cause 6 heart attacks or strokes. There are indeed studies indicating cardiovascular risk from calcium supplements, but the risk is not dose-dependent and does not occur with dietary calcium. This 2013 review showed that the evidence for cardiac risk is varied and the benefits of supplementation exceed the risks. And this 2014 meta-analysis of randomized controlled trials concluded that:
current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increase coronary heart disease or all-cause mortality risk in elderly women.
She seems to think that it is a buildup of calcium that causes artery-clogging atherosclerotic plaques, but calcium deposition is really only a secondary phenomenon occurring mainly in advanced lesions. Coronary heart disease is not a feature of hypercalcemia, and although CT heart scans are done to measure coronary calcium scores, they are not recommended for general screening. Not all plaques contain calcium; the larger ones are more likely to contain it, but smaller plaques with no calcium are the ones that are more likely to rupture.
Vitamin D is taken along with calcium supplements to improve the body’s ability to use the calcium, but K2 is essential for vitamin D to work. She highlights the importance of interactions between nutrients in the case of D, K2, and calcium, but doesn’t seem to consider the possibility that K2 supplementation might cause unforeseen harmful interactions between nutrients. There are many examples of vitamin supplements having adverse effects on heart disease and other conditions. Vitamin K and K2 appear to be safe, but the safety of K2 supplementation needs to be better tested before supplementation can be widely recommended.
She says if you have osteoporosis or heart disease, vitamin K2 deficiency is “a given,” and you are probably deficient if you have any of a whole list of other conditions, including diabetes, cancer, wrinkles, varicose veins, dental cavities, kidney disease, or a narrow, crowded dental arch. She says adolescence and menopause are times when vitamin K2 deficiency is even more likely. She says that bone density and arterial calcification vary cyclically with the seasons, showing “humans’ delicate interconnectedness to the sun and earth.” Essentially, she thinks everyone is deficient in K2, mainly because our cows and chickens are no longer grass-fed. Most of these claims are just speculation on her part. They may or may not be true; they need to be tested.
She makes a good point that older studies may have produced misleading results because they looked at vitamin K rather than at K2. Now that we are aware of K2, we need to re-assess the evidence with new eyes.
She marshals an impressive array of references in the endnotes for much of what she says, but then she makes statements like this without any citations:
Research now confirms that vitamin K2 is the single most important nutritional factor in preventing and even reversing arterial blockages. Indeed, ensuring adequate vitamin K2 intake might be the most important thing you can do to extend your life.
I must remain skeptical of those claims until I see some supporting evidence.
The references she provides for other claims don’t really support the claims. For instance, she says “vitamin K2 also helps restore arterial flexibility once the calcium has been removed.” She cites a study titled “Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats.” That’s nice to know if you are a warfarin-treated rat that has developed elastocalcinosis; but it tested vitamin K rather than K2, and it doesn’t necessarily translate to a benefit in humans. Anyway, elastocalcinosis is not the same as atherosclerosis.
She says things that are demonstrably not true, for instance that high doses of the statin drug Crestor “carry crippling side effects for most people.” (They do cause side effects, but only in a minority of users, and the side effects are not always crippling.) She idolizes Weston Price, a man who has been called “the patron saint of crank dentistry” and who is criticized on Quackwatch. Price travelled around the world making uncontrolled observations of native peoples and drawing unwarranted conclusions about nutrition. He saw physical perfection in those who ate a traditional diet, and thought that after women switched to a Western diet, their children had poor jaw development, needed orthodontia, and had pointy teeth, an atavism harking back to the canines of our primate ancestors. She claims that he figured out the health consequences of K2 deficiency without being able to identify the cause, which he called factor X. Among other things, he blamed increasing C-section rates on nutritional deficiencies. She describes how Price stopped drilling and filling cavities, and healed them with a combination of vitamins. But she isn’t willing to follow Price that far; she doesn’t advocate giving up dental care.
We are just starting to learn about vitamin K2, and I intend to watch developments with great interest. But I subscribe to what Druin Burch called “Medicine’s Beautiful Idea,” the idea that even the most reasonable-sounding theories must be properly tested. Rhéaume-Bleue’s claims have not been properly tested, and promoting them in a popular book is jumping the gun. I’m willing to believe that K2 deficiency might be widespread and harmful, but I’m not willing to believe for sure that it is until I see better evidence. And I don’t think telling everyone to take K2 supplements is justified at this point.
This article was originally published in the Science-Based Medicine Blog.