Vitamin K is an under-rated vitamin that may need to be taken in tablet form daily.
This is a personal theory, based on personal experience of a progressively disabling medical condition, and coupled with a close study of over 200 research papers to date. I believe that every human being should take a daily supplement of vitamin K.
The theory is evidence-based.
After several attempts at starting this post, I’ve decided that the chronological narrative of my own recent events might be the best approach. I can then elaborate in detail if anyone shows any interest in certain aspects of the topic. I now have quite a list of clinical signs and behavioural changes I would be checking off with patients if I were a GP, and if anyone is interested.
In a nutshell, I was progressively and insidiously losing the use of my legs, ankles and feet over decades to the point where I had inquired of my GP about amputation of my feet and replacement with artificial limbs. The response was an absence of support for this and an assurance that amputated stumps would be more of a problem than my current situation. I already had bilateral knee replacements. My left ankle had been the subject of a couple of accidents over the years with the result that my right ankle was supporting most of my weight. During 2013 (Age 82 in July), the right ankle began to progressively seize up like a rusty hinge and a large osteophyte began to develop on the medial side of the navicular and talus bones. By December 2013, I was getting around with the aid of crutches and felt that I would be in a wheelchair within 12 months. In May 2014, I sought arthrodesis of the right ankle, believing that a club foot would be an improvement on an arthritic ankle for a while.
Protocol required ultrasounds of my leg arteries to ensure healing from the operation. Surprisingly, this revealed massive, advanced atherosclerosis with varying degrees of stenosis from the lower aorta down to the dorsal pedal arteries, widespread calcification of arteries and probable occlusions of both left and right anterior and posterior tibial arteries, and the left peroneal artery. An Xray of the right ankle revealed osteoarthritis of the navicular/calcaneo joint, widespread osteopenia of most bones, and a 25 mm osteophytic protrusion on the medial aspect of the navicular and talus bones. Such a condition in a cart horse would have been diagnosed as ‘bone spavin’ and I would have been shot. One aspect of the left ankle X-ray was a visible 12 cm-long white line of calcification of the left tibial artery.
A few years earlier, I had asked my GP about the possibility of peripheral arterial disease (PAD) when I’d experienced a ‘dull’ feeling in my lower right calf region, while walking (really a slow hobble) around the block. The standard clinical test then for PAD was to palpate the dorsal pedal artery, which he performed. He opined that the circulation was not a problem; the words ‘diabetic neuropathy’ followed as a diagnosis. I received exactly the same clinical test and a ‘diabetic neuropathy’ response when I made a routine visit to a cardiologist a week later. Both were quite positive in their responses, so I passively accepted the confirmed opinion. I concluded that both must have attended the same cardiovascular lectures as undergrads. Though I must admit that I had a lingering doubt about the diagnosis because my resting blood glucose concentration had never exceeded 8 mmol/L since taking metformin.
While waiting for the vascular surgeon’s next appointment to read the artery ultrasounds, I consulted Dr Google Scholar for information on arteriosclerosis – because of the extensive calcification visible on the left ankle X-ray and the radiologist’s report of extensive calcification shown in the Doppler Ultrasounds.
The first research paper I opened was one by Seyama et al (1999; http://medcontent.metapress.com/content ... 484254404/
) who reported that high doses of vitamin K2 (50,000 µg/kg) and vitamin E (40 mg/kg body weight) injected into rats would prevent experimentally-induced deposition of calcium and inorganic phosphorus in the aorta and the elastin fraction. High doses of vitamin D2 and an atherogenic diet were used for the inductions. (A very interesting side experiment in this particular research project was that in vitro, both vitamin K2 and vitamin E displayed lipid-radicle [oxygen] scavenging activity; this suggests that both are ‘anti-oxidants’; I’ve inserted that here for my own reminder; please DO NOT comment; it’s a totally new subject). The doses of both vitamins were grossly in excess of the human recommended daily requirements of 1 µg/kg/day and 14-15 mg/day of vitamin K and E respectively. This experimental production of arteriosclerosis was also successfully reproduced in rats by feeding high doses of vitamin D to 49-day-old rats and warfarin at 1 mg/kg/ day to 22-day-old rats by Price et al (2001; http://atvb.ahajournals.org/content/21/10/1610.short
Yet the first paper did raise the possibility of vitamins K and E of being useful in the prevention of arteriosclerosis. I had been taking vitamin E, but not vitamin K, supplements intermittently for some years. My first question to the vascular surgeon was whether calcium chelation therapy had been tried to remove soft-tissue calcium. He replied to the effect that it had been tried extensively but that the long-term results had not been promising. My next question as to whether vitamin K had been trialled against arteriosclerosis was answered with the response “I’ve never heard of it.”
So I left it there with the vascular surgeon and foot orthopaedic surgeon and decide to try self-administered vitamin K as a conservative measure.
My only memory recall of vitamin K at that time was that it was a blood coagulant and that there was a disease of cattle in the USA called ‘Sweet Clover Disease’ in which cattle bled to death because of a chemical in Sweet Clover called dicoumarol that interfered with the role that vitamin K played in the formation of prothrombin. It was the investigation of the biochemistry of this disease that eventually led to the development of warfarin as a prophylactic medication in human beings prone to the effects of blood clots within the vasculature. And in line with the vascular surgeon’s response that he’d never heard of vitamin K with respect to arteriosclerosis, there appeared to be a medical bias against anything that might ‘thicken’ the blood. Blood ‘thinners’ are currently prescribed for atherosclerotic conditions (strokes, anginas, peripheral arterial disease) in the form of drugs such as Aspirin, Warfarin, Pradaxa, Elequis, Xarelto, Plavix, Prasugrel, Brilinta, Cilostazol and Aggrenox.
A mass of research since the 1990s has broadened our knowledge of the functions of vitamin K. There is now evidence that it’s a co-factor in the production of at least two anti-coagulation proteins – proteins C and S. So that it should be regarded more as a blood-clotting regulator than a coagulator.
And possibly more importantly, it has a vital role in one stage of the deposition of calcium into bone as a co-factor in the gamma carboxylation of glutamic acid during the formation of matrix-gla-protein. From my personal point of view, it also has a vital role in the prevention of calcium-deposition in soft tissues, particularly the endothelium of arteries, ligaments and tendons.
There is one available standard review on vitamin K that is updated every few years by the Linus Pauling Institute (http://lpi.oregonstate.edu/mic/vitamins/vitamin-K#ref33
). It’s worth a read to get a relatively recent overview of our understanding of vitamin K. Another interesting article is one put out by the Weston Price Foundation. If you remember the book called Nutrition and Physical Degeneration by Weston Price in 1931, you will recall that he postulated the existence of “a new vitamin-like activator” that played an influential role in the utilization of minerals, protection from tooth decay, growth and development, reproduction, protection against heart disease and the function of the brain”. His successors make the claim that vitamin K is Activator X on this site - http://www.westonaprice.org/health-topi ... d/#summary
The following are some of the more pertinent articles to consider when deciding whether to take vitamin K tablets daily at some time in life.
We are born with a negligible amount of vitamin K (Zipursky 1996; https://scholar.google.com.au/scholar?q ... _sdt=0%2C5
) and human milk contains little; studies by Canfield et al (1990; http://link.springer.com/article/10.1007/BF02537985
) indicated that K1 is measurable only in digit quantities per mL, and that there is no vitamin K2. Conly and Stein (1992; http://europepmc.org/abstract/med/1492156
) reviewed the literature and concluded that human beings are dependent on dietary sources and gut flora for vitamin K requirements. Yet hundreds of studies over the last 20 years are suggesting that vitamin K may be one of the most essential substances required to delay or prevent the progression of many debilitating conditions of the aged.
Since 1935 when a Danish scientist, Henrik Dam, identified a substance he termed ‘koagulationvitamin’ in wheat-germ oil, that prevented fatal internal haemorrhages in chicks, we have tended to regard vitamin K as a blood-coagulation substance (http://www.nature.com/nature/journal/v1 ... 5652b0.pdf
). It has subsequently been established as a necessary co-factor for the production of clotting factors II, VII, IX, and X in humans, but since the 1960s, it has also been identified as a co-factor in the production of at least two anti-clotting substances – Proteins C and S. As I said earlier, perhaps vitamin K should be recognised more as a blood-clotting regulator than a coagulator. Proteins C and S have been shown to play a role in the health and permeability of vascular endothelium. Wikipedia has an excellent review of the role of Protein C on this website - https://en.wikipedia.org/wiki/Protein_C ... seegers-10
Vitamin K is now being researched in connection with osteoporosis, atherosclerosis, osteoarthritis, and even Alzheimer’s disease. In my particular case, the links betwen vitamin K deficiency and atherosclerosis with osteoarthritis were of interest. For example Neogi et al (2006; http://onlinelibrary.wiley.com/doi/10.1 ... 21735/full
) concluded that there was a significant association between low plasma phylloquinone concentrations and increased prevalence of osteoarthritis manifestations in the hand and knee. Later, the editor of the journal Rheumatology (2007; http://rheumatology.oxfordjournals.org/ ... 1763.short
) claimed that “There is mounting evidence that vascular pathology plays a role in the initiation and/or progression of the major disease of joints: osteoarthritis (OA). Potential mechanisms are: episodically reduced blood flow through the small vessels in the subchondral bone at the ends of long bones, and related to this, reduced interstitial fluid flow in subchondral bone. Blood flow may be reduced by venous occlusion and stasis or by the development of microemboli in the subchondral vessels.” Obviously, if this is so, then stenosis and occlusion of major blood vessels would not only lead to this osteoarthritic effect, but many other side effects as well.
All of the above suggest that our biochemical requirements for vitamin K appear to be extensive.
By 2012, Theuwissen et al (http://advances.nutrition.org/content/3/2/166.full
) claimed, in the introduction to a paper, that seventeen vitamin K–dependent proteins had been identified and that several were involved in regulating soft-tissue calcification. In the same paper, they concluded that there was no such thing as healthy human subjects with fully carboxylated-extra-hepatic Gla proteins and that western diets contained insufficient vitamin K to meet the requirements of healthy bone and vascular wall. This was a reinforcement to some extent of the opinion of Shearer & Newman (2008; https://scholar.google.com.au/scholar?q ... _sdt=0%2C5
) who stated that data on the bioavailability of the various forms of vitamin K is limited, and that although the absorption of pure vitamin K1 is 80%, the absorption from foods such as spinach is only 4-17% of that absorbed from tablets because of its tight binding to chloroplasts.
Research such as the following suggested that maybe a therapeutic dose should include both vitamin K1 (phylloquinone) and vitamin K2 (menaquinone). Thijssen and Drittij-Reijnders (1994;http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN72_03%2FS0007114594000449a.pdf&code=b1ed2e69097bf75191802b67ab63f032 ) demonstrated that phylloquinone supplements in rats could be converted to menaquinone MK-4 in tissues, but the concentrations of either form varied between tissues. Liver, heart, bone and cartilaginous tissues had high K1 but brain had low concentrations whereas K2 was low in plasma and liver, but much higher in pancreas, salivary gland and sternum. In 1996 (http://journals.cambridge.org/action/di ... 4596000153
) the same two authors performed post-mortem analyses on human tissues and found phylloquinone in all tissues examined and menaquinone-4 in most tissues with more in brain and kidney and less in other tissues. In fact, Joline et al (2013; http://journals.cambridge.org/action/di ... 4513001013
) reviewed the literature on vitamin K metabolism, and concluded that K1 and K2 may have different physiological roles and that therapeutic medication may require both.
In addition, the author could not find any research indicating that vitamin K2 could be converted to vitamin K1 as required, so decided to use both forms. This decision to use both was further reinforced by findings such as those of Beulens et al (2009); http://www.sciencedirect.com/science/ar ... 5008005078
) who studied the association between diets of vitamin Ks and coronary heart disease, and found that high menaquinone but probably not phylloquinone were associated with low coronary events.
I first had to decide on the dose to use. The US Department of Health and Human Services (https://ods.od.nih.gov/factsheets/Vitam ... fessional/
) recommends 120 micrograms vitamin K daily for adult human males (updated April 2016). You will note that under the Heading “Am I Getting Enough Vitamin K?”, this site states that vitamin K deficiency is very rare – and this is contrary to the research of Shearer and Newman above. After considering these references, I regarded 120 micrograms as a ‘ball-park’ minimum dose. All reports suggested that a toxic dose of vitamins K1 and K2 had never been determined, that massive doses over short periods had not produced any side effects (one exception was a synthetic form of vitamin K called menadione and known as vitamin K3, which does not appear to be in production any longer). Borowitz et al (2002; http://journals.lww.com/jpgn/Fulltext/2 ... ric.4.aspx
) reviewed the literature on the nutritional requirements of adults with cystic fibrosis and concluded that those being treated with antibiotics for any reason may be taking insufficient vitamin K replacement therapy at 5000 micrograms four times a week. I did have personal reservations about using relatively high doses because of the possibility of other metabolites being thrown out of balance. A dose of 180 micrograms of the MK7 version of vitamin K2 for 3 years was trialled by Knapen et al (2013; http://link.springer.com/article/10.100 ... 013-2325-6
). They found “significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favourably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae” in healthy post-menapausal women. (It may be pertinent here to mention that vitamin K2 comes in a number of forms with differing numbers of methyl radicles in side chains. For example MK4 has 4 methyl radicles, MK7 has 7 and MK9 has 9. MK4 has been researched more than MK7; there is some evidence that MK7 may be slightly more active and may persist for longer in the body.)
The Linus Pauling Institute review cited a number of trials in which doses as high as 15,000 and 45,000 micrograms were used daily for up to 3 years without any great therapeutic or prophylactic usefulness. This raises the possibility that although there were no side effects of any kind, too high a dose may be non-productive for reasons unknown.
Considering all of the above information, I decided arbitrarily on 500 micrograms daily of both vitamin K1 (phylloquinone) orally and 500 micrograms of a sublingual tablet containing the MK4 version of vitamin K2 (menaquinone). This was in addition to other vitamin and mineral supplements that had been taken for years. Magnesium had been taken most days, vitamin E every few days, plus occasional B vitamins and zinc. There is a possibility that the subsequent surprisingly successful results could have been due to ‘priming’ by some of these other supplements.
Regular supplementation was commenced in late July 2014, some weeks after the first arterial ultrasounds. Multiple scans were taken of all of the main arterial pathways and branches from the lower aorta to the dorsal pedal artery. The following gives a rough guideline to normal and abnormal tracings.
Bearing in mind that the above is a rough guide only, the first three of the following tracings demonstrate the changes that occurred in three of the most proximal arteries between the original tracings in July 2014 and those after 15 months of supplementation in October 2015, while the fourth showed no change in the dorsal pedal artery.
The first 3 tracings demonstrate a marked improvement in blood flow. Note the clean baselines with an absence of ‘damping’ in the 2015 tracings. The fourth pair, of the dorsal pedal arteries at the end of the main arterial flow demonstrated no change. In general, there was noticeable improvement from the lower abdominal aorta to the knees, but no significant improvement in the main arteries below the knees.
I believe that no study anywhere else has shown such a marked reduction of stenosis following therapeutic supplementation of any kind.
The interesting part about the radiologist’s reports is that even after a third set of ultrasound tracings in October 2016, the arteries that showed occlusions in 2014 still showed occlusions, and those with severe stenosis at the same time still showed no improvement. Yet clinical improvement was marked.
Of note, the 2014 tracing reported “dense atherosclerotic calcifications”. The 2015 and 2016 reports mention “dense calcific plaque” in the occluded arteries of the calf areas. Unfortunately, this is not clear-cut evidence of a reversal of calcification.
Clinically, however there has been slow and steady change in mobility. I had a habit of recording my daily exercise regimes while checking blood pressures. ‘Walking’ was becoming a sort of flat-footed plod with clenched toes in an effort to take weight off the insteps. Plantar dermal padding was thin and pressure was felt on most joints. Uneven ground was avoided because it caused pain in joints with minimal cartilage cover.
Up till July 2013, between one and four ‘walks’ were undertaken a week around the shortest local block of 1.8 km (1.1 miles), at which time it became too painful and replaced by 15 to 20 minutes daily on an exercise bike. That was the daily exercise for the next 12 months.
Within three weeks of commencing supplementation on July 30 2014, there was a slight noticeable improvement in that instead of plodding on clenched feet in an effort to minimise weight-bearing on the tender feet, a few steps were taken with slightly extended feet. Some weight was taken on the heels with a slight tendency to do so with the ball of the foot (I’m aware now that in normal walking, pressure is taken on the heel first and is taken along to the balls of the feet and toes in a rolling-type action). Within the next three months, occasional attempts were made at walking as well as the regular exercise-bike riding eg 400 metres one day, 800 and 1200 metres a week later, then 1.8 km two weeks later and 1.8 km three weeks after that.
By late October 2014, the realisation that some new articular cartilage may be forming and that too much walking may result in too much wear and tear, the author rationalised that limited distances with maximum cardio-vascular-respiratory effort would be sensible. (I noted that Biv mentioned that he adopted this same principle at one stage of life because of leg problems). Since then, walks have been undertaken up a triple hill with a rise of 42 metres over a road length of 300 metres on week days when it is not raining. A three-hour session at the gym on Saturdays and a day of rest on Sundays completes the week (as well as working on box air-conditioners and water coolers up to four days a week).
The feet were no longer cold at night and after a hot shower the skin was visibly pink with noticeable blue veins. A capillary-refill test time (3.5 s) could be performed for the first time for years. Clenching of the feet resulted in a lesser degree of a feeling of ‘crinkling cardboard’ in the soles; it’s difficult to describe the sensation, but the soles of the feet felt abnormal when clenched. Dermal padding has gradually been returning and I can walk with shoes and orthotics on almost any surface now.
Visible proof of osteoarthritis is provided by the attached image of the right foot taken in October 2016. That swelling is a 25 mm high osteophyte and remains as proof of osteoarthritis.
Additional evidence of improvement in mobility was the ability to go shopping with my wife again instead of preferring to remain in car. The shopping trolley was no longer used as a ‘walker’, but was pushed independently, and the house furniture was no longer leaned on while walking about for balance or to take weight off the feet and ankles (referred to by my wife as ‘furniture-walking). By July 2016, I was able to push a loaded wheelbarrow again for the first time for six or more years.
This degree of improvement in locomotion has been, and still is occurring, in spite of the fact that the right and left leg anterior and posterior tibial arteries are occluded. The probability is that blood is being supplied by a collateral circulation in the calf areas.
Apart from an improvement in mobility, my minor bouts of angina at the commencement of exercise have ceased. In fact I can now exert myself in gym sets to the max without any angina (I have a stent in the right descending coronary artery and a pacemaker). My chronic obstructive pulmonary disorder is less of a problem. My urine micro-albumin concentration has decreased significantly. The osteoarthritis in the left wrist has improved to the point where I can use heavier weights on the barbell for biceps curls. My lower calf muscles are largely atrophied from lack of circulation, but have improved to the point where I can stand upright with eyes covered without losing balance for longer periods. My back pains first thing in the morning have disappeared.
In a sort of proviso discussion/conclusion, I have to emphasise that vitamin K was the only NEW supplement I’d taken since July 2014 till April 2015. I cannot rule out the possibility that it needed maybe some of the other supplements I’d been using at the time – eg magnesium, vitamin E, occasional vitamins B1 & B6, vitamin B12, zinc or fish oil or glucosamine to work synergistically with vitamin K. I was aware that a cascade of biochemical events was going to be needed to reverse the osteoarthritis that may have occurred as a result of primary atherosclerosis. My research suggests that many supplements have been shown to improve (at least temporarily) the adverse effects of osteoarthritis statistically in clinical trials – eg fish oil (omega 3 fatty acid), chondroitin, dimethyl sulphone, boron, manganese, hyaluronic acid. In theory folic acid and vitamin B12 also needed to be present to ensure enough DNA health to provide stem cells as essential precursors for new chondrocytes and osteocytes to deposit new cartilage and bone. At this stage I have to confess that I did not take the vitamin K religiously daily every day. As a fat-soluble vitamin, it was obvious that it would be stored in fat and persist in the body for more than 24 hours. My records show that I took both forms every day for the first four months, then missed the odd day or two after I’d decided I should have had a satisfactory body supply. I regarded it as a supplement.
No significant other changes were made in lifestyle, diet or medications
The only possibly significant change in supplement use, months after I was showing improvement in mobility, was that I commenced taking folinic acid supplement (800 micrograms daily) in April 2015. The reason for taking the folinic acid was firstly that, among my other co-morbidities, I’d been anaemic for years with a red cell count of 4 million per microliter or less. Specialist medical consultations produced no answers and it was regarded as just geriatric anaemia. I had tried folic acid and the usual haematinics without any effect. I came across an article (http://custommedicine.com.au/health-art ... olic-acid/
) stating that some people have deficiency of an MTHFR gene that converts folic acid into folinic acid before it becomes metabolically active. I used the rationale that if a gene deficiency can prevent this conversion, why not old age?
The second reason was that I realised, as stated above that I needed healthy DNA for stem cells, chondroblasts and osteoblasts if I was going to get any healthy regeneration of devitalised tissues. Folic acid and vitamin B12 are essential (http://www.jhrr.org/article.asp?issn=23 ... st=Mahmood
), I began to take vitamin B12 more regularly as well. An interesting side effect since taking the folinic acid and B12 is that almost every Saturday I’ve been going to the gym I’ve been doing a personal best effort or two in the sense of using heavier weights or an increased number of ‘reps’ in sets. My blood count had gone up to 4.6 million per microlitre.
Although my mobility is now satisfactory for all normal daily functions, including walking to and from public transport, I feel there is room for another 20 or 30% improvement. My general health is great. It’s slightly humorous that my GP does not wish to know about the vitamin K, but at my last annual check-up he expressed surprise at the reversal of so many of my blood profile parameters and simply advised me to continue doing whatever I was doing.