While reading up on vitamin K2 recently, I’ve noticed a number of connections that have me wondering if one of the culprits behind several widely occurring neurological diseases might be a relative scarcity of this vitamin in many people’s diets. Unfortunately, there is little research yet on using vitamin K2 to treat neurological conditions in humans. What research exists shows that vitamin K and particular the K2 MK4 form are capable of protecting brain cells in vitro from certain types of damage that could be connected to many neurological diseases. There is also a much larger research base showing that vitamin K2 helps prevent cardiovascular system damage. As the brain is a major user of blood flow, it is relatively obvious that improvements in blood flow could improve brain function. Thus vitamin K2 could offer a multifaceted protection mechanisms for the brain against some of the driving factors suspected to be involved in neurodegenerative diseases.
Vitamin K: Not Just A Single Vitamin
Vitamin K is one of the more poorly understood and under-appreciated vitamins. There are three known major forms: K1, K2, and K3. Of these, K1 and K2 are naturally occurring and K3 is synthetic.
Among the K2 form, there are multiple variations. The most commonly researched ones are MK4 (an abbreviation for menaquinone-4 that is also known as menatetronone) and MK7 (an abbreviation for menaquinone-7). MK4 is more commonly produced in animals and MK7 (along with some others such as MK5 to MK14) are made by bacteria. Many animals can convert vitamin K1 to K2 MK4. Humans can do this also, but not as efficiently.
Vitamin K3 is synthetic. Perhaps not coincidentally, it is the only K form found to be toxic to humans.
Historically much of the research on vitamin K focused on the K1 form found predominantly in plants. But in recent years, researchers have started to understand that the K2 forms produced in animals and by bacteria may function very differently in the human body. In general, they have found that K1 seems to be widely dispersed throughout the body and to be necessary for proper blood clotting function. Of obvious concern might be that too much vitamin K1 could produce too much clotting. In general, this is not true as vitamin K1 activates clotting proteins via a chemical process known as carboxylation but does not actually create the clotting proteins. But people taking warfarin, a dangerous and overused anticoagulation drug, are often advised to avoid or severely limit their vitamin K intake because warfarin’s function in the body is to interfere with vitamin K carboxylation in order to reduce the blood’s ability to clot.
Vitamin K1 does not provide the benefits of vitamin K2. That is part of why there are an increasing number of supplements that feature some form of vitamin K2 and an increasing number of advocates of diets (such as the “paleo diet” and the dietary recommendations of Dr. Terry Wahls) that incorporate sources of K2. While these diets differ and you can see their vocal adherents engaging in nasty fights over some of the differences, in general they advocate getting K2 from animal food sources. Foods with relatively high K2 include liver, fermented cheeses, and pastured dairy products. Natto is a plant source for K2, but I think most Westerners will not like it much based upon the couple of times I have tried it.
Indeed some of the biggest “cheerleaders” for vitamin K2 are Paleo Diet bloggers such as Richard Nikoley of Free the Animal who wrote about Dutch study on cardiovascular disease risk being reduced by what is probably K2 in cheese:
Well, here, let me give you a hint: other than natto — which I doubt is consumed by post-menopausal Dutch women in great quantity, if at all — the chief dietary source of the longer chain K2 vitamins is hard & soft fermented cheeses (high in “artery clogging” saturated fats). Now do you get it? These researchers may have unwittingly done us a big favor, because if it turns out that long-chain K2s are actually causal for massive (9% per 10 micrograms) reduction coronary heart disease, then they will have shown that those who eat the most “artery clogging” cheese have less clogged arteries.
Nikoley, along with many others in the paleo diet community, have long advocated the position that dietary fat by itself does not cause cardiovascular disease and generally blame high-carb diets low in nutrients as being a significant cause. The study speculates the benefits were from K2 MK7, MK8, and MK9 forms found in cheese and dairy products, whereas previous papers on K2 association with reduced cardiovascular disease risk mostly talk about K2 MK4. It is quite possible that longer K2 forms (MK5 to MK14) have somewhat different benefits or biochemical actions than MK4 and therefore it would be unsurprising if there are benefits more than one type.
The following video discusses K2 sources and its use as a preventive and treatment approach for osteoporosis and atheroscelosis. It also briefly mentions some of the findings regarding K2 in brain and mitochondrial health:
Vitamin K2 is more concentrated in certain organs such as the pancreas, salivary glands, brain, and some regions of the heart. K2 is strongly involved at keeping calcium in the bones where it belongs instead of allowing it to drive calcification of arteries and other soft tissues such as the kidney. K2 MK4 is rapidly absorbed used by tissues and mostly disappears from blood circulation in a matter of a few hours, whereas MK7 in human blood circulation lasts a day or longer. MK4 and MK7 are both being investigated as treatments for osteoporosis, atherosclerosis, and heart diseases involving calcification such as aortic sclerosis and stenosis and atrial fibrillation. Asian health agencies have approved various MK4 and MK7 based products for treatment and prevention of osteoporosis.
Weston Price’s “Activator X” is Vitamin K2 MK4
Dentist and nutritional researcher Weston Price in the 1920s and 1930s identified a compound he called “Activator X” that he used to treat variety of health problems. He wrote about his nutritional research on health conditions in his work Nutrition and Physical Degeneration: A Comparison of Primitive and Modern Diets and Their Effects and applied it to his own patients. Decades later, as the scientific understanding of vitamin K increased, it was discovered that vitamin K2 MK4 is the mysterious “Activator X” compound. In On the Trail of the Elusive X-Factor: A Sixty-Two-Year-Old Mystery Finally Solved , Chris Masterjohn mentions how Weston Price was able to use butter oil rich in Activator X to treat a four year old child suffering from dental caries (cavities), a broken leg, and seizures:
Price also administered the butter oil concentrate to a four-year-old who suffered from rampant tooth decay, a fractured leg and seizures. A dessert spoonful of the butter oil served over whole wheat gruel with whole milk once before bed and five times over the course of the following day immediately resolved his seizures. Rapid healing of his fracture and dental caries followed soon after. The fact that these three symptoms appeared together and resolved following the same treatment suggests a common cause for each of them. Sixty years later, modern research is now elucidating the essential role that vitamin K2 plays not only in the dental and skeletal systems, but in the nervous system as well. This strongly suggests it was the key unidentified factor in Price’s protocol.
Butter oil likely contains many other fat soluble nutrients in addition to vitamin K2 MK4, but based upon today’s understanding it is likely that the physiological effects in this particular case were related to the MK4 more than other components.
Regions of the brain containing myelin also have more K2 MK4 and it is the most common form of vitamin K in the brain:
Reports published in the past decade confirm the presence of VK in brain homogenates in concentrations that generally reflect intake (18–21). Interestingly, although VK is present in the forms of K1 and menaquinone-4 (MK-4) in the majority of extrahepatic tissues, in the brain VK is present predominantly as MK-4. Explanations for this tissue-specific vitamer profile are not yet available but could suggest a unique role for MK-4 in the brain (22,23).
That paper mentions how K2 is involved in the brain’s production of sphingolipids which include sulfatides. Sphingolipids and sulfatides appear to be markedly lower in autopsies of Alzheimer’s patients. Animals unable to make sulfatides due to enzymatic deficiencies have lower activity levels, weak legs, and seizures. This mixture of information hints that vitamin K2 may be far more important to the brain than widely understood, and the newer studies on K2 preventing oxidative death of oligodendrocytes and neurons hint at this, too.
Thus it’s possible that a dental and nutrition researcher working in the early 20th century managed to uncover a nutrient important for brain health that nearly a century later is still very poorly understood and researched. This may be because there is little financial incentive to pharmaceutical corporations to do the research. Vitamin K2 cannot be patented and so therefore it will never be possible for them to make heaps of money by selling it as a curative agent, even if it turns out to be highly effective with long-term consumption. Hence it may be up to individuals, progressive doctors, and universities to start experimenting with K2 to see just how important and useful it may be to improving human health.
Vitamin K2 Can Boost Mitochondrial ATP Production
Mitochondrial dysfunction is a common feature of several neurological diseases. In May 2012, researchers in Belgium published a paper showing that fruit flies with a genetic mutation known as PINK1 have energy production problems that can be reversed via the addition of vitamin K2. The fruit flies with this mutation are unable to fly, that is until vitamin K2 is added that improved ATP production in the mitochondria. PINK1 is a known genetic mutation in some people with Parkinson’s Disease, one of the conditions known to have mitochondrial dysfunction as a culprit. Although there are no studies that say vitamin K2 supplementation will work wonders in patients with Parkinson’s Disease, the vitamin is quite safe for virtually everybody except for people taking anticoagulation medications such as Coumadin (warfarin).
Vitamin K1 and K2 MK4 Protect Oligodendrocytes, Neurons, and Myelin
Previous research has shown that vitamin K2 can block injury to oligodendrocytes that produce the myelin sheathing protecting nerve bundles in the brain. It appears to be highly effective at blocking certain kinds of oxidative damage to these cells.
A 2003 paper discussed that vitamins K1 and K2 MK4 inhibit death of oligodendrocytes in culture (i.e., experimental outside of a living person) when the supply of the antioxidant glutathione is disrupted. The authors noted that warfarin did not appear to interfere with this protective mechanism and that it does not appear to be related to any kind of carboxylation process related to the blood clotting and calcium distribution control effects usually associated with vitamin K. They also found that K1 and K2 MK4 protected both oligodendrocytes and neurons from death by glutamate toxicity which can also cause low glutathione levels. They tried K3 (the synthetic) in some of their experiments and found it did not have the same protective effects and appeared toxic at higher concentrations. They also found that pretreatment of cells with K2 MK4, but not with K1, was sufficient to avoid cell death. Their paper mentions periventricular leukomalacia and cerebral palsy occurring in infants and how they are believed to be connected to hypoxia (low oxygen) or ischemia (interruption of blood flow) that would produce conditions such as glutathione deficiency and elevated glutamate levels.
Some of these same researchers followed up with a 2009 paper on further exploring the oxidative protection of oligodendrocytes from vitamin K that found K1 and MK4 could prevent cell death from exposure to high levels of arachidonic acid metabolism involving 12-LOX which could be a common problem related dietary omega 6 fats consumed far in excess of omega 3 fats. Note that although arachidonic acid gets a bad rap in many circles, there are studies showing that supplementation using it that have shown benefits for developing fetuses and those benefits improve further with added omega 3 DHA intake. The key, as with so many things, is probably balance — in this case balance between omega 6 and omega 3 fat intake combined with other nutrients that help encourage omega 6 fats to be turned into anti-inflammatory compounds.
Alzheimer’s Correlates with Bone and Cardiovascular Degradation
A number of studies have demonstrated that Alzheimer’s patients have lower vitamin K, lower bone mass and density, and elevated rates of atherosclerosis. Some of the researches speculate that their findings simply reflect generally poor nutrition in many Alzheimer’s patients. Others speculate that the brain regions first damaged by Alzheimer’s may have significant influence over bone maintenance. But another explanation, one that I personally consider to be worth a lot more investigation, is that inadequate vitamin K2 supplies lead to accelerated bone loss, worsened atherosclerosis and cardiovascular calcification, and damage to brain cells that are being exposed to oxidative compounds against which vitamin K has been shown to have protective effect.
Japanese researchers published a study in 2005 showing that vitamin K1 deficiency may cause incomplete carboxylation of osteocalcin in Alzheimer’s patients. The speculated that general malnutrition may be part of the cause for Alzheimer’s.
A 2008 study in Canada found that early-stage Alzheimer’s patients have lower vitamin K intake than control subjects.
A 2009 study examining bone density, brain structure, and cognitive function found that early-stage Alzheimer’s patients have lower bone mineral density, smaller brain volume, and worse cognitive function than a control group. The authors suspect that a common mechanism is contributing to the bone loss and Alzheimer’s symptoms of smaller brains and worse brain function. They specifically looked at vitamin D and calcium supplements and common osteoporosis drugs and did not find a connection. They note they did not actually test vitamin D blood levels but relied upon participant reports of supplement usage.
Then a 2010 follow-up study by the researches in the 2009 study look at the brain’s hypothalamus and bone loss in Alzheimer’s patients. They showed that hypothalamus volume corresponds with bone mineral density. From that they speculate that damage to the hypothalamus may impair bone regeneration.
Japanese researchers in 2011 showed they could reduce bone fractures in Alzheimer’s patients using K2 MK4 (menatetrenone or menaquinone-4) using in part three doses of K2 MK4 per day at 15 mg per dose. They observed vitamin D deficiencies in these patients, but did nothing to correct them. It looks like that is because they cite they already showed in a previous study in 2005 that they could use ergocalciferol (vitamin D2, inferior in action to vitamin D3) to lower hip fractures in Alzheimer’s patients.
From a review of studies mentioned in PubMed, it appears Japan is probably at the leading edge of therapeutic research on vitamin K in Alzheimer’s patients yet the Japanese are still focused on bone fractures and not on cognitive function. Thus it appears very little work has been done on vitamin K activity in the brain, a view that is confirmed by a 2012 overview paper by a Guylaine Ferland of University of Montreal on vitamin K in the nervous system that mentions:
The role of vitamin K in the nervous system has been somewhat neglected compared with other physiological systems despite the fact that this nutrient was identified some 40 y ago as essential for the synthesis of sphingolipids. Present in high concentrations in brain cell membranes, sphingolipids are now known to possess important cell signaling functions in addition to their structural role. In the past 20 y, additional support for vitamin K functions in the nervous system has come from the discovery and characterization of vitamin K-dependent proteins that are now known to play key roles in the central and peripheral nervous systems.
The same writer also published a second overview paper citing possible involvement of vitamin K dependent proteins and specifically K2 MK4 in neurodegenerative diseases such as Alzheimer’s. He was also involved in showing that low vitamin K1 intake in rats results in old age cognitive impairments and another paper that showed the main form of vitamin K in the brain is MK4 and it is concentrated in regions with higher myelin content.
Could Vitamin K Help Multiple Sclerosis Patients?
It is well known that myelin is damaged in multiple sclerosis patients. MRI scans showing white areas indicating myelin damage are among the most common diagnostic tools for determining a patient has MS. As Life Extension explains in its article on multiple sclerosis:
Pathology of Disease Progression
Multiple sclerosis (MS) is an immuno-inflammatory disease in which immune cells enter the central nervous system (CNS) and destroy the myelin sheath. Immune cells, which become activated through complex mechanisms migrate into the CNS, and attack the myelin sheath. The resultant demyelination is thought to be carried out by T lymphocytes, B lymphocytes, and macrophages, three primary classes of immune cells, which are routinely found in MS lesions (Noseworthy 2000).
Loss of myelin followed by subsequent lack of neural communication and neuronal death is accepted as the primary cause of disability in MS patients (Dutta 2007). Axonal transection, or the severing of axons, occurs under conditions of both acute and chronic demyelination (Trapp 1998; Bjartmar 2000; Lovas 2000).
Remyelination is the process by which demyelinated axons are naturally re-wrapped with myelin, restoring nerve conduction and functionality (Smith 1979). This phenomenon is the result of oligodendrocytes repairing the damage to the myelin sheath that occurs during an episode of increased disease activity. However, as the disease progresses over years (usually decades) the oligodendrocytes begin to lose their ability to repair the damage, and symptoms become progressively worse and episodes more frequent due to remyelination failure. In addition to developing therapies that slow MS disease progression, many laboratories are developing novel therapeutics that aim to promote remyelination and reverse existing CNS damage.
In addition to immune-mediated loss of myelin, another characteristic feature of MS is inflammation caused by a class of white blood cells called T cells (Compston 2002, Friese 2006). Some of the damage in the CNS is directly carried out by two subpopulations of T lymphocytes called T helper 1 and T helper 17 which produce pro-inflammatory factors (Goverman 2009). Recent studies have identified that chemical mediators, interleukin-23 (IL-23) and granulocyte macrophage colony-stimulating factor (GM-CSF), contribute to the autoimmune characteristics of these T cells. Data suggests that absence of these pro-inflammatory signals was sufficient to prevent inflammation in the brain (El-Behi 2011). This suggests that therapeutic strategies directed at blocking the production of inflammatory mediators could be effective for treating MS.
When the immune system attacks myelin and oligodendrocytes, it is likely they are using at least some oxidative attack mechanisms like they would use on actual pathogens. So it is possible that boosting the ability of oligodendrocytes to resist oxidative damage might be enough to help more of them survive and keep replenishing the myelin sheathing. So far I have not found any research that has looked in depth at a possible connection between vitamin K and multiple sclerosis. Hopefully the recent papers on the protective effects of vitamin K in the brain will motivate some further investigation.
Get More Vitamin K2 In Your Diet
It may be decades before vitamin K function in the brain is widely understood. However, as vitamin K is readily available in foods and supplements you could start trying to boost your intake now as the vitamin is quite safe except in patients using warfarin or other drugs opposing vitamin K. I’d encourage them to be looking to find alternatives as such drugs are unreliable given dietary variation and dangerous given how important vitamin K has been amply shown to be in bone and cardiovascular health.
For the most part, mainstream diet and nutrition discussion focuses almost exclusively on vitamin K1 that you find primarily in plant based foods. However, studies show humans have trouble absorbing more than 200 mcg of vitamin K1 from diet or more than 1000 mcg from supplements per day and K1 to K2 conversion is not very efficient. So you should be looking for foods and supplements that offer vitamin K2, particularly the MK4 and probably also the MK7 forms that are the most researched so far. Paleo diet advocates would have you getting these largely from animal meats and organs such as liver. Cheese, diary products and eggs may also be good sources particularly if they are from grass-fed animals as grain-fed cows and chickens have lower vitamin K levels. Natto (a type of Japanese fermented soy) is one of the few vegetarian-friendly sources for K2, but the taste is certainly not widely appealing.
Several of the paleo diet and Weston Price fans are big on butter oil products as sources of vitamin K2. However, few if any of these have much consistency in their levels of vitamin K2. So I’d have to advocate doing what you can to improve your diet to include vitamin K2 sources such as K2 rich foods and butter oil while also ensuring you get at least a reasonable minimum amount each day via a supplement with a known quantity of K1 and K2 forms.
The Life Extension Super Booster with Advanced K2 Complex product is a reasonably good choice as it offers 1000 mcg of K1, 1000 mcg of K2 MK4, and 100 mcg of K2 MK7 along with other useful nutrients such as mixed tocopherol vitamin E. If you want to focus just on the vitamin K, they also have a product Super K with Advanced K2 Complex which leaves out most of the other nutrients and bumps the number of softgels per bottle from 60 to 90.
If you’re looking for higher levels of K2 MK4 as supplements, 15 mg capsules are currently the largest ones I was able to find. Vitamin Research Products Ultra K2 is such a product. Japanese studies of up to 45 mg per day (three doses of 15 mg each) show it is safe for most people, the main exceptions being those on warfarin as mentioned previously. There is also an intermediate dosage product ”Carlson Labs Vitamin K2 5 mg”that offers twice the number of capsules for about the same price, making it more affordable to take the rapidly utilized MK4 with each meal.
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