Understanding the role of vitamin K-dependent proteins in vascular calcification

What if the process of arterial calcification was regulated from within the cells of the blood vessels, and that it had nothing directly to do with what you ate and what circulated in the bloodstream because calcification takes place not anywhere near the surface but inside the blood vessel wall?

What if the process of arterial calcification was actually a process by which muscle is transformed into bone, a process by which vascular smooth muscle cells transform themselves into bone cells which then actually build bone tissue within the blood vessel wall?

And what if apoptosis preceded calcification, what if cell death was what triggered the process of calcification, and it was the apoptotic bodies of dead vascular smooth muscle cells within the blood vessel wall that served as the nodes around which calcium crystals formed?

Would you not find this shocking? Find it incredible that any of these could be true, let alone all of them? It’s entirely not at all what we’ve been told by “health experts” and “health authorities” for more than half a century!

All of these statements are hard to believe. It is especially unbelievable that muscle cells can change into bone-building cells, and begin to grow bone tissue within the artery wall. It sounds surreal, kind of like science fiction. But it isn’t. All of it is true. All of this has been observed.

Interesting, you may think, but what does any of this have to do vitamin K? Everything! It has everything to do with vitamin K.

How clever we are

The sophistication and precision of biochemical reactions and processes in animals and humans are mind blowing. Understanding how they work is a wonderfully noble endeavour that is certainly very fulfilling in its own right. In some cases though, it can be a matter of life and death. And in the case of the processes related to and regulated by vitamin K dependent proteins it definitely is.

This is not an exaggeration to push you to read on. It’s a statement of fact. And you’ll see how this is true by the time we finish. I believe it is essential, for each one of us to understand the details of how things in our body work and how they are related and connected in order to appreciate their significance and their importance.

We are so clever. We can figure out such complicated things when we put our minds to it. Things like complex biochemical pathways, or long chains of enzymatic reactions that, one step at a time, transform molecules from one form into another. And it is this kind of cleverness that has enabled us to develop the hundreds of different types of medications we can find today in drug stores.

We have designed medications to address basically every symptom we can think of. If it’s a symptom we’ve had, it’s most likely a symptom that many others have or have had. And if many have the same or a similar symptom, we can be sure that at least one pharmaceutical company will have made a drug for it.

Warfarin was developed in the 1950s to prevent or at least suppress coagulation, and in so doing help prevent or at least reduce the number of strokes and heart attacks. Because so many people either suffer from, are susceptible to, or are at risk of cardiovascular disease, many people take warfarin.

And what I mean by many in this case is between 20 and 30 million prescriptions per year in the United States alone. The number went up to 35 million in 2010 and dropped back to 20 million in 2015. That’s a lot of warfarin pills! You can see the stats here (http://clincalc.com/DrugStats/Drugs/Warfarin). Warfarin is in the top 50 drugs. It’s 42nd down the list. Just below aspirin at 39, insulin at 36, and ibuprofen at 34, as you can see here (http://clincalc.com/DrugStats/Top200Drugs.aspx).

Surely close to every household in the western world will have somewhere in a bathroom cupboard or drawer a bottle of aspirin or ibuprofen. Given how close to warfarin they are in popularity of usage, there’s clearly no need to even say that this anti-coagulant drug is in broad and widespread use.

Isn’t this great, though? Millions of people at risk of having blood clots that would possibly cause them a stroke or heart attack, protected by taking a little warfarin every day? Yes, I suppose in some ways, it is, if these people are actually at risk. But, unfortunately, with a drug like that, we can be pretty sure that most are taking it preventatively, as in, just in case. And this is a problem.

Warfarin works by disrupting the process that leads to the activation of coagulation factors. The blood’s ability to form clots quickly is one of its most vital functions, because without it we would just bleed to death from a flesh wound. Evolutionarily, we simply would not have made it to here without this protection mechanism that ensured that when we were wounded, the blood would immediately thicken to stop it bleeding out of our body by forming clots at the surface of the open wound as fast as possible. The special proteins responsible for regulating coagulation are vitamin K-dependent proteins (VKDPs).

It has taken a long time to understand, first of all, that there wasn’t just vitamin K, but in fact two different kinds of vitamin K. It is also true that it has taken a long time to identify the major vitamin K-dependent proteins and figure out how they work. We are talking about 40 years from the 1950s to the 1990s. So, you really shouldn’t be surprised if you haven’t read or heard about this before.

But today, a lot has been understood through in vitro and in vivo observations, trials and studies both in animal models and in humans. And even though we will inevitably continue to deepen our understanding of the subtleties of the molecular mechanisms, the species, and the interactions involved in the life of cells and proteins in how they affect the state of our blood vessels and organs, this is a sketch of the picture we have at this stage.

Vitamin K dependent proteins

There are about twenty identified VKDPs belonging to two classes: hepatic—those produced by the liver, and extra-hepatic—those produced in other tissues. Those from the first class are the most well-known and well-studied. They are the coagulation factors (II, VII, IX, and X) manufactured by the liver and activated within it before being pushed into the bloodstream and circulated throughout the body to maintain a healthy coagulation response in case it is ever needed. These are the ones targeted by warfarin. Naturally, since that drug has been around since the 1950s, the role and function of these vitamin-K dependent coagulation factors have also been known at least since that time.

The second class is less known and less studied but has—luckily for us—gained much more attention in the last two decades. It includes three very important proteins whose functions are essential in maintaining healthy blood vessels. But unlike the coagulation factors produced in the liver, these proteins are instead produced by the vascular smooth muscle cells and activated there locally in the vasculature. These vascular health factors, we call them that in analogy to but to distinguish them from the coagulation factors, were identified much more recently in the 1980s and 1990s. All are proteins that contain gamma-carboxyglutamic acid abbreviated Gla.

Some important ones for us here are osteocalcin, for which it took 30 years to be identified as an inhibitor of calcification when it was discovered in vitro to prevent the precipitation of crystals in a supersaturated calcium solution. This means that without it, calcium crystals would have inevitably formed spontaneously in the solution. Osteocalcin is also called bone Gla protein. Growth arrest specific protein 6 is involved in the regulation of cell proliferation, and seems to inhibit premature cell death. And the most important one in relation to soft tissue calcification, matrix Gla protein abbreviated MGP.

Matrix Gla protein was originally isolated from bone, but it has been found to be expressed in several other tissues including kidney, lung, heart, and—most critically—vascular smooth muscle cells or VSMCs. It is now known to be the most potent inhibitor of calcification of blood vessels, and even though the liver does produce and secrete MGP into the bloodstream, only the MGP produced in the vasculature inhibits calcification.

Besides being produced in different tissues, another important difference between the two classes of VKDPs is that the liver-produced coagulation factors are phylloquinone—or vitamin K1-dependent, whereas the vascular smooth muscle cell-produced proteins are menaquinone—or vitamin K2-dependent. In light of the fact that it is rather hard to find vitamin K1 insufficiency with a diet that contains at least some green plant foods, while the exact opposite is true for vitamin K2 of which the western diet is practically devoid, this difference is highly significant.

Both vitamin K1 and K2 are absorbed in the second and third portions of the small intestine, the jejunum and ileum, K1 is delivered to the liver, whereas K2 is transported via LDL and HDL to other organs. K1 is mainly found in the liver, whereas K2 is preferentially stored in peripheral tissues, with the highest levels in the brain, aorta, pancreas, and fat tissues. This obviously attests to the importance of these essential vitamins.

While vitamin K1 and K2 are really two different vitamins with different functions, transport mechanisms, and distribution in the tissues, and while there are several differences between the vitamin K1-dependent and the vitamin K2-dependent proteins, these have one essential thing in common. This is, as their name says, that they are vitamin K-dependent. What this means is that all these proteins share the same enzymatic chain of activation—whether it mediated by K1 or K2—that transforms them into their biologically active form, the form they need to have in order to do the things they are meant to do.

All VKDPs must be carboxylated in order to be activated. The process is complicated and not yet completely understood. We know that it is targeted to the glutamic acid (Glu) residues on the protein that must be made into gamma-carboxylglutamic acid (Gla). We also know that the process is mediated by the enzyme gamma-glutanyl carboxylase (GGC), and that vitamin K is the main co-factor that enables the enzyme to perform the activation. In the end, the process leads to the addition of a carbon dioxide molecule to the gamma-carbon of Glu, which transforms it into Gla. However, it is the reduced form of vitamin K that is required.

Vitamin K, whether it is the plant-based phylloquinone (K1) or the animal-based menaquinone (K2), enters the body through the diet in its non-reduced form. Reduction involves the addition of hydrogen in molecular form, H2, to make KH2. Transformations of this kind are generally always done by enzymes, and so is this one. In this case the enzyme is vitamin K epoxide reductase (VKOR). Its action is essential because it is the reduced form KH2 that acts as the co-factor in the process of carboxylation.

The energy released by the oxidation of KH2 drives the addition of the carboxyl group unto the glutamic acid residues. But the oxidised form of vitamin K, KO, can subsequently be reduced again to KH2. Thus vitamin K is first reduced, then oxidised to help push the carboxyl group unto the glutamic residue, and then reduced once more to start the whole cycle again. This cycle is called the vitamin K epoxide reductase or VKOR cycle.

For this class of proteins, the VKDPs, activation through carboxylation means for them to acquire the structure and properties needed to bind calcium in order to transport it. You may recall from a previous chapter in the story of vitamin K2, matrix Gla protein generally transports calcium out of soft tissues in order to prevent calcification, and bone Gla protein generally transports it into bones and teeth to prevent osteopenia, osteoporosis, and tooth decay.

The big red flag

Now you understand why it is that when, in our remarkable cleverness, we understood that the main coagulation factors depended on the action of these enzymes to be activated and rendered functional, we naturally concluded that the best way to prevent clot formation would be to prevent coagulation, and that this could be achieved by blocking these enzymes from doing what they are intended to in a healthy organism. This is precisely what warfarin does.

And it does it well. Otherwise it wouldn’t have become as commonly used as it is. And we can be certain it has saved a lot of people much of the pain and possibly life-threatening conditions that a blood clot could have caused them. The problem is that the vascular health factors so critical for maintaining healthy blood vessels, depend on the same enzymes for activation as do the coagulation factors. Preventing the carboxylation of coagulation factors, prevents, in exactly the same way, the carboxylation of the vascular health factors.

This was only understood to be a major problem relatively recently. We first had to understand that there isn’t just one kind of vitamin K, but that there are two, and that they are very different in their functions. We had to understand that both vitamin K1 and vitamin K2-dependent proteins rely on the same enzymes to get activated. We had to understand the carboxylation process by which they are activated. And we had to understand that MGP, BGP, and Gas 6 are vitamin K-dependent proteins, that they are specifically vitamin K2-dependent, how they are activated, what they actually do in our veins and arteries, and what happens if they can’t do what they are designed to do.

A major red flag about anticoagulants and warfarin came up from what was seen in mice. The first part of the study was with MGP-knockout mice, (mice in which the MGP-encoding gene was deactivated). They were observed to have stunted growth from the premature calcification of the epiphysis—the part at the end of bones and at the junction with the cartilage of the joint which allows the bone to grow longer. As as soon as the epiphysis calcifies, longitudinal growth stops. But this was the least severe of the problems that were observed.

The MGP-knockout mice very quickly developed severe arterial calcification, and died highly prematurely, within 6 to 8 weeks, of strokes, heart attacks, and rupture of the aorta. Normal lab mice live 2 to 3 years and some even up to 4 years. So, in the least extreme case, a MGP-knockout mouse dying from aortic rupture at 2 months instead of living a relatively short normal life of only 2 years, would be equivalent for a human that would normally live to the age of 72 to die at the age of 6!

Here is what severe coronary calcification looks like in humans:

severe_coronary_calcification

Severe coronary calcification in a patient with end-stage renal disease. We can see that these blood vessels are basically filled with bone tissue that appears bright white. (https://www.bmj.com/content/362/bmj.k3887)

It was also observed that although the liver did produce and release MGP into the bloodstream, it had no effect on the arteries. Only the tissue-specific, locally-produced MGP within the vascular smooth muscle cells was able to inhibit calcification.

To check these conclusions, a similar study was done on normal mice that were given vitamin K1 to ensure proper liver function and healthy coagulation, and warfarin to block all extra-hepatic MGP action in tissues. The result? Stunted growth, pervasive arterial calcification, and premature death from stroke, heart attack, and aortic rupture.

The conclusions were solid: matrix Gla protein is the organism’s primary protection against soft tissue and arterial calcification; liver MGP has no protective effect on arteries, and only VSMCs-produced MGP can inhibit calcification in the arteries; both vitamin K deficiency and disruptions of the action of the enzymes that activate MGP cause extensive soft tissue calcification; and only vitamin K2, not vitamin K1, can inhibit warfarin-induced calcification.

Going further

When this was understood, more attention began to be paid to matrix Gla protein. Many other details were elucidated through further investigations. It was found that MGP is an 84-amino acid protein with five Gla residues. That all of these Gla residues are produced by gamma-carboxylation, which is mediated by the enzyme gamma-carboxylase that requires vitamin K2 as a cofactor, and that until now, the only known function of Gla residues is to bind calcium ions and crystals (calcium apatite). It was discovered that the concentration of calcium and phosphate in extracellular fluids is high enough to trigger and sustain growth of crystals, but that MGP and BGP prevent this from happening. That MGP is required by VSMCs to maintain their elastic and contractile nature. And not just that.

MGP actually inhibits the transformation of VSMCs into bone cells by antagonising the action of Bone Morphogenic Protein 2 (BMP2). It turns out that the muscle cells of the blood vessels have in them the potential to either stay smooth elastic contractile muscle cells, or turn into osteoblast-like bone building cells. BMP2 triggers that osteogenetic gene expression in the VSMCs: it tells muscle cells of the blood vessels to transform into bone-building cells.  And as if this wasn’t enough, BMP2 also induces apoptosis: it tells blood vessel muscle cells to commit suicide, which is certainly to help in the process given that once dead, they can be used as seeds for calcium crystal formation, and thus promote a faster and more efficient calcification.

What induces expression of BMP2 in cells? Probably several things that we haven’t yet identified. But for now we know that BMP2 is stimulated by oxidative stress, chronic inflammation, and high blood sugar levels. The good news is that MGP protects against all of these effects by antagonising BMP2. So if there is enough MGP and enough vitamin K2, if there are no disruptions to the action of the vitamin K dependent enzymes by anticoagulants like warfarin, and if oxidative stress, inflammation, and blood sugar are kept low, then there is protection against calcification of the arteries and other soft tissues like the liver, kidneys, and heart.

Recap

Here we have it. We have now understood the role of vitamin K dependent proteins in vascular calcification. And although it was a little long and maybe somewhat arduous, all the details are clear. It is complicated. I won’t deny that. But I have strived to make it all as accessible as I could without diluting the mechanisms of action and relationship between the different players. Let’s recap to make sure you are left with the essential elements in mind.

Vitamin K dependent proteins can either be vitamin K1 or vitamin K2 dependent. The dependence comes from the fact that vitamin K is required to activate the protein. This activation is the carboxylation in which a carbon dioxide is added to the glutamic acid residues along the protein. Carboxylation is mediated by carboxylase (GGC) that requires the reduced form of vitamin K in order to oxidise it and get the energy to push the carbon dioxide molecule onto the glutamic acid residue. Vitamin K is reduced by reductase (VKOR) which can do it over and over again in what is called the VKOR cycle.

Vitamin K1 dependent proteins are mostly liver based coagulation factors. Vitamin K2 dependent proteins are mostly outside the liver and generally involved in inhibiting soft tissue calcification. The most important calcification-inhibiting VKDP is matrix Gla (MGP), which performs a wide range of tasks to maintain elastic, flexible, calcium-free blood vessel walls.

Calcification is triggered by the death of vascular smooth muscle cells. These dead muscle cells act at seeds for calcium apatite crystals to form. VSMCs can be induced to become osteoblast bone-building like cells that then go on to stimulate the growth of bone tissue within the artery walls. This process is stimulated by bone morphogenic protein 2 (BMP2), which is expressed under conditions of oxidative stress, inflammation, and hyperglycaemia.

To prevent and reverse calcification the most important is to provide a good supply of vitamin K2 through diet and supplementation. Because it is essential in the activation of Gla proteins but only through its role in the VKOR cycle, the amount of K2 is the rate limiting factor. Hence more is better than less, and excess will simply remain unused but will not cause harm.

Naturally, matrix Gla protein needs to be available. Cells of tissues where calcification occurs (kidney, liver, heart, and blood vessels) secrete MGP. An interesting evolutionary self-protection adaptation mechanism. And here’s another: the amount of MGP that is produced by a cell depends on at least two factors that have been identified. One is the amount of calcium; the other is the amount of vitamin D3. In both cases, the more there is, the more MGP is produced.

So, vitamin D3 has the role of making calcium available but at the same time stimulates the production of MGP in order for the calcium to be available to the bones and not to the soft tissues. But for this, it relies on vitamin K2. This is why vitamin D3 without vitamin K2 leads to calcification: because MGP and BGP remain inactive and incapable of binding to the calcium ions to move them into bones and out of tissues. On the other hand, plenty of vitamin K2 would indeed activate the available MGP, but without enough vitamin D3 there might not be enough MGP to confer proper protection against calcification. This is a perfect example of the complementarity of action and function in essential micronutrients. There are certainly many more, but this one is particularly remarkable.

Final thoughts

I want to close on a final consideration. It is so easy and seems so natural for us to think in terms of this and that, good and bad, for and against, that our tendency is to look at everything in these terms. This is also true when we look at biochemical processes like the ones we have described and explored here. We naturally lean towards looking at the calcification inhibiting mechanisms as protective, and those that promote calcification and apoptosis as destructive.

But the reality is that cells, proteins, and enzymes don’t behave in these terms, they don’t think in these terms simply because they don’t think. They react biochemically to what they are exposed to, to the molecules and chemical messengers they encounter, to the quality of the liquids in which they bathe, to the characteristics of the environment in which they live, microsecond after microsecond, without any forethought or concern for the microsecond that will follow. The only guiding principle that can be used to lead us to understand why things happen the way they do is evolutionary adaptation to survive.

Having recognised this, we immediately see that the mechanisms that promote apoptosis of VSMCs, their subsequent transformation to osteoblast-like cells, and the growth of bone tissue within the artery walls that we refer to as arterial calcification, can only be a protection mechanism. A mechanism to protect the tissues and cells from the damaging effects of exposure to free radicals, inflammatory molecules, and glucose. Because, as we have seen, the process is reversible, it would be perfectly natural to undergo periods of calcification followed by periods during which the bone tissue is broken down and removed from our arteries and other soft tissues and organs when the circumstances allow it. Actually, we should say when the circumstances dictate it, because no matter what happens, it is always the circumstances—the environment—that dictate what is to happen.

What we can do, with the knowledge of what we have understood, is make choices about what we eat and drink, when and how much we eat, and how we live, sleep, and exercise. Choices that will shape or reshape, define or redefine the makeup of this internal environment of the body to always move us in the direction of optimal biochemistry, optimal physiology, optimal metabolism, and optimal health.

Everything that we explore together is always about just this. But sometimes the corrective action requires effort, sometimes even a lot of effort. In this case, however, it is as simple as can be, because it only requires us to supplement with vitamin K2 and possibly also D3. Of course, the last thing we want is a lifestyle that promotes the expression of BMP2 and the growth of bone tissue within our arteries. But supplementing with K2 and D3 together will in general bring only benefits. I know it was a very long-winded way to get to this, but now you understand why. That was—and is—the whole point of this blog, after all. I hope you enjoyed reading.

 

The information in this article comes primarily from the following papers: Molecular Mechanisms Mediating Vascular Calcification by Proudfoot and Shanahan (2006); Vitamin K-dependent Proteins, Warfarin, and Vascular Calcification by Danziger (2008); The Role of Vitamin K in Soft Tissue Calcification by Theuwissen, Smit, and Vermeer (2012).

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Reversing calcification and the miracle of vitamin K2

Vitamin K2 is the only known substance that can stop and reverse soft tissue calcification.

If you didn’t stop at the end of that sentence to say Wow to yourself, you should keep reading.

Soft tissue calcification is one of the most serious health problems we face as individuals, as modern societies, and, on a global scale, as a species.  Cardiovascular disease—which leads to heart attacks and strokes, and accounts for nearly half of all deaths in industrialised countries—is a disease of soft tissue calcification: the calcification of our arteries.

Arthritis, of which basically everyone past the age of 40 suffers, and increasingly more with time and with age, is a disease of soft tissue calcification.  It is caused by the calcification of the cartilage in the joints:  the joints of the knees, but also of the shoulders; the joints of the hips, but also of the wrists; the joints of the elbows, but also of the feet and the toes; the cartilage between the vertebrae of the neck and the spine all the way down the back, but also of the hands and of the fingers.

Soft tissue calcification also causes kidney stones and kidney disease.  How many people above the age of 60 don’t have kidney problems?  Hardly any.  And how many young men and women in their 20s and 30s already have kidney stones and kidney dysfunction?  More and more every year.

Every one of the processes generally associated with ageing, from heart disease and stroke, to Alzheimer’s and dementia, to arthritis and kidney disease, to stiffness in the joints and muscles, but also to the wrinkling of the skin, is intimately linked to soft tissue calcification.

And now, let me repeat the sentence with which we opened:  Vitamin K2 is the only known substance that can stop and reverse soft tissue calcification.  It is really remarkable.

Maybe you didn’t know about calcification.  And so, maybe you are wondering why it is such a major and widespread problem, why it affects everyone no matter where we are or what we do.  It’s a good question.  But because we know that only vitamin K2 can prevent this from happening, we already have our answer:  soft tissue calcification is a major and widespread problem because our intake of vitamin K2 is inadequate to provide protection from calcification.

Naturally, the next question is why?  Why is our intake of vitamin K2 so inadequate?  If it is such a crucial essential nutrient, we would surely not be here as a species if intake had always been so inadequate.  Looking at things the other way around, if we are so dependent on adequate K2 intake for staying healthy, this must necessarily mean that we evolved having plenty of it in our food supply.  What’s so different now?

To answer this question with some level of detail—meaning with an explanation more extensive than just saying that it’s industrialisation that stripped our food supply of vitamin K2 as it has for all the essential nutrients to a greater or lesser extent—we have to understand what K2 is, how it’s made, and where it’s found in food.

The short answer is that K2 is found in the fat of pastured animals that graze on fresh green grass, and produced from vitamin K1 by certain kinds of bacteria in their gut.

The longer answer is that vitamin K2 is a family of compounds called menaquinones, ranging from MK-4 to MK-13 depending on their molecular structure.  These compounds are derived from the plant analog, the sister compound, vitamin K1, called phylloquinone, and found in chlorophyll-rich plant foods.  Phylloquinone is consumed by the pastured animal, it makes its way into their intestines, and there it is transformed by the bacteria of the animal’s intestinal flora.  The resulting menaquinone is then stored in the fat cells of the animal as well as in the fat of their milk if they are milk-producing.  Consuming these animal fats in which vitamin K2 has been concentrated will provide this precious essential micronutrient.

If the grazing animal does not feed on green grass, they get no vitamin K1.  If they get no vitamin K1, their gut flora is not only compromised and negatively altered with respect to what it should be if they were consuming the grass they have evolved eating, but it produces no vitamin K2.  If their gut flora produces no vitamin K2, their fat and milk will contain no vitamin K2, and neither their offspring nor any person consuming products derived from the animal will get any vitamin K2.  Hence, no grass feeding, no vitamin K2 in the animal’s fat.

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It is most natural that grass-eating animals should be grazing on fresh green grass in open pastures.  And yet, it is rather rare.  But without green grass, there is no vitamin K1.  And without vitamin K1 there can be no vitamin K2.

Maybe you’ve already thought ahead, and wondered since it is bacteria that produces vitamin K2 from vitamin K1 in the guts of grazing animals, can’t we make vitamin K2 without the need for grass-fed animals to do it for us?  Yes, it is possible.  Fermented vegetables and dairy products like cheese can also contain vitamin K2.  In fact, in the case of cheese, there is a lot more in the finished hard cheese than in the milk used to make it.  The amount varies widely because it depends on the kind of bacteria.  For dairy products, hard cheeses like Gouda have the most, and for plant foods, even if fermented veggies have a little, the Japanese fermented soybean snack natto is the ultimate source of K2.

As we all know, pastured meat and dairy is not easy to come by in our modern world.  It’s actually quite hard to find.  Our supermarkets and food stores are flooded with industrially produced meat and dairy from animals that have never seen a blade of grass—grass-grazing animals living their entire lives indoors, in stalls, fed and fattened exclusively on grains, corn, and soybeans.  This is how we have stripped our food supply of vitamin K2, and this is why is this a modern phenomenon—most of our grand-parents were still eating pastured meats and animal foods.

And if this wasn’t enough of a blow to vitamin K2 status, trans-fats, which are formed when vegetable oils are hydrogenated to be made saturated and stable (for long shelf life), and which most of us consume in great quantities, contain a K2 analog called DHP (dihydrophylloquinone) that displaces the little K2 that might has found its way into our diet.

It is for all these reasons that soft tissue calcification is so widespread.  And you have at this point what you need to know in order to first stop the process by which your soft tissues are getting increasingly calcified, and then, in time, to remove the accumulated calcium from these tissues.  It’s simple: healthy grass-fed animals produce yellow butter, yellow yolks, and yellowish fat;  you need to eat plenty of pastured animal foods, making sure you eat the fat in which vitamin K2 is concentrated, and, to be sure you have enough to reverse the already present calcification, take K2 supplements.  And this might be enough for you.

If it is, you can head to your browser to find and order some K2 supplements (I currently get mine, it’s a 500 mcg per tablet, from Phoenix Nutrition).  Also, we need to know that the two main forms of K2 are MK-4 (with four double bonds) and MK-7 (with seven).  The first is the one generally found in animal fats that haven’t been fermented, while the second is the product of bacterial fermentation.  Hence, meat and butter contain mostly MK-4, whereas natto, sauerkraut, and cheese contain mostly MK-7.

There is an important difference between these two forms of K2 in terms of their effects inside the body which has to do with their half-life, not in the sense of radioactivity, but in the sense of duration of biological activity in the body.  MK-4 will be in circulation at therapeutic doses for a number of hours, while MK-7 remains in circulation between 24 and 48 hours.  Therefore, to be safe, we need to eat grass fed meat and butter, and take MK-7 supplements (I take 1000 mcg), always after a meal with plenty of fat to maximize absorption.

If you are curious to find out more, if you want to know how menaquinone does this, how vitamin K2 does its miracles inside the body, then we need to take a closer look at the biochemistry of calcium metabolism.

There are three proteins found in bone matrix that undergo gamma-carboxylation via Vitamin K-dependent enzymes: matrix-gla-protein (MGP) (Price et al., 1983), osteocalcin (bone gla-protein, BGP) (Price et al., 1976), both of which are made by bone cells, and protein S (made primarily in the liver but also made by osteogenic cells) (Maillard et al., 1992) (Table V).  The presence of di-carboxylic glutamyl (gla) residues confers calcium-binding properties to these proteins.

MGP is found in many connective tissues and is highly expressed in cartilage.  It appears that the physiological role of MGP is to act as an inhibitor of mineral deposition.  MGP-deficient mice develop calcification in extraskeletal sites such as in the aorta (Luo et al., 1997).  Interestingly, the vascular calcification proceeds via transition of vascular smooth muscle cells into chondrocytes, which subsequently hypertrophy (El-Maadawy et al., 2003).  In humans, mutations in MGP have been also been associated with excessive cartilage calcification (Keutel syndrome, OMIM 245150).

Whereas MGP is broadly expressed, osteocalcin is somewhat bone specific, although messenger RNA (mRNA) has been found in platelets and megakaryocytes (Thiede et al., 1994).  Osteocalcin-deficient mice are reported to have increased bone mineral density compared with normal (Ducy et al., 1996).  In human bone, it is concentrated in osteocytes, and its release may be a signal in the bone-turnover cascade (Kasai et al., 1994).  Osteocalcin measurements in serum have proved valuable as a marker of bone turnover in metabolic disease states.  Interestingly, it has been recently suggested that osteocalcin also acts as a hormone that influences energy metabolism by regulating insulin secretion, beta-cell proliferation, and serum triglyceride (Lee et al., 2007).

These are the first three paragraphs of the chapter Noncollagenous Bone Matrix Proteins in Principles of Bone Biology (3rd ed.) which I found it on the web when I was searching for more info on the biochemical action of menaquinone.

And now, here is my simple explanation of how things work:

The players are the fat-soluble vitamins A, D, and K2;  three special proteins called osteocalcin, matrix gla protein, and protein S;  and an enzyme called vitamin K-dependent carboxylase.

First, vitamin D makes calcium available by allowing its absorption from the intestines into the bloodstream.  This is vital for life and health.  You know that severe vitamin D deficiency is extremely dangerous and develops into the disease that deforms bones called rickets.  Milder forms of vitamin D deficiency are much harder to detect without a blood test, but can and do lead to a huge spectrum of disorders and health problems.  However, without vitamin K2, ample or even just adequate levels of vitamin D will inevitably lead to increased soft tissue calcification.

Vitamins A and D make bone-building cells (osteoblasts) and teeth-building cells (odontoblasts) produce osteocalcin (also known as bone gla protein or BGP) and matrix gla protein (or MGP).  This is key because it is these proteins that will transport the calcium.

Vitamin K2, through the action of the vitamin K-dependent carboxylase enzyme, activates bone and matrix gla proteins by changing their molecular structure which then allows them to bind and transport calcium.

Once activated, bone gla protein brings calcium (and other minerals) into the bones;  and matrix gla protein takes calcium out of the soft tissues like smooth muscle cells of arteries, but also organs, cartilage, skeletal muscles, and skin.  Without this K2-dependent activation, BGP and MGP remain inactive, and the calcium accumulates in soft tissues all over the body.

What completes the act, is that vitamin K2 activates protein S which oversees and helps the immune system clear out the stuff of arterial plaques that remains once the calcium making the plaques structurally stable has been taken out.  And, amazingly, protein S does this without triggering a large inflammatory response.

Even though it is quite straight forward when explained in this way, this understanding of vitamin K2 and its action in the body is really quite recent: in the last 20 years or so.  For one thing, it was only 10 years ago that Chris Masterjohn solved the 60-year old mystery of Weston A. Price’s X-Factor, correctly identifying it for the first time as vitamin K2. (You can read that for yourself here.)  And although some laboratory studies and experiments on vitamin K were done several decades ago, the majority are from the last 10 years (take a look at the references in Masterjohn’s paper.)

We’ll stop here for now.  But we’ll come back to vitamin K2 because there are so many other amazing things it does for our health.

This article was inspired by Dr. Kate Rheaume-Bleue’s book entitled Vitamin K2 and the Calcium Paradox.

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A simple 10-step arthritis treatment plan

What are the most important things we can do to stop and reverse the degeneration, and alleviate the stiffness and pain of arthritis? You can be sure that no matter how bad things are, there are many things that will help, and they don’t involve pharmaceuticals.

We looked in some detail at how to treat arthritis in Treating Arthritis I and II, and have at least one of our readers, an artist, Catherine Bath, who has been able to alleviate a great deal of her stiffness and pain, and recover a good amount of mobility and ease of movement by following the various recommendations we made there and throughout this blog.

Here, prompted by a request from a good friend who needs it, we present a simple treatment plan with the most important elements, and just the essential details needed to understand why the interventions are useful, and how to put them into practice right away.

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Illustration of painful, inflamed, arthritic joints. (Image taken from Everyday Health)

1. Hydrate and alkalise

This is the most important point of all. Without it nothing will work, really. Every joint works thanks to the cartilage that allows the bones to move within it without rubbing against one another. Arthritis is always characterised by the degradation of this cartilage and the pain associated with the inflammation caused by the bones not moving properly or rubbing inside the joints. Cartilage is water (85% by weight) held together in a matrix made mostly of collagen, and chronic dehydration is the first cause of cartilage breakdown (details in Your Body’s Many Cries for Water).

Metabolic acids (mostly uric acid) can only be excreted efficiently by the kidneys when there is an excess of both water in which to dilute the acid, and salt to help carry it out in the urine. Without excess water, the kidneys will prioritise retaining as much of it as they can. Without excess salt, the uric acid will be recycled instead of being excreted in order to to maintain the concentration gradient in the medulla of the kidney that ensures its ability to reabsorb as much water as possible. Chronic dehydration and avoidance of salt, coupled with the drinking of acidic liquids and eating of acid-forming foods inevitably leads to chronic acidosis.

To maintain the pH of the blood at 7.365 in spite of the continuous flow of acids into it from the muscles and digestive system, two main coping strategies are available: 1) The body’s main acid buffering mechanism using the reserves of alkalising minerals stored in the bones and teeth to counterbalance the acid load. If you don’t quite understand the implication here, this means erosion of the bones and teeth to put into the blood some of the alkalising calcium, phosphate and magnesium as acid-buffering minerals. 2) The crystallisation of the uric acid to pull it out of circulation, but then storing it into tissues, of which the joints, regrettably for arthritis sufferers, seem to be used preferentially, even though all tissues can be used for this to a certain extent.

The strategy is simple: drink alkaline water (either naturally so, or made to be with pH drops) on an empty stomach, and allow at least 30 minutes before eating. Aim for 3 litres per day. One litre before each meal, drank over a period of one to two hours, is a simple rule of thumb and easy schedule to remember. And aim for 2 full teaspoons of unrefined salt with your meals.

2. Magnesium chloride and sodium bicarbonate baths

Magnesium is at the very top of the list of supplements for anyone in any circumstance. We explored and explained why in Why you should start taking magnesium today.

Transdermal magnesium and bicarbonate therapy is the best way to simultaneously replenish magnesium stores in the cells, while alkalising the tissues directly by transdermal absorption of magnesium and sodium bicarbonate. If you have a bath tub, do this once or twice per week, or more if you can or need it. Add two cups of each magnesium chloride and baking soda, and soak for 45 to 60 minutes.

I also recommend that in addition to this—but crucially if you don’t have a bath—you take magnesium supplements. I take a fat-bound magnesium supplement called L-Threonate. Another alternative is the amino acid-bound supplement called magnesium glycinate (using glycine). Both of these form maximise absorption. Take it with meals.

3. Silicic acid, collagen, hyaluronic acid, and proteolytic enzymes

An essential constituent of hair, skin, and cartilage. Absorption is poor and slow. This means you need to take small amounts every day for long periods of time. Every morning, first thing, with your first glass of water. You will need to do this in cycles of three months on, three month off. I take Silicea, a concentrated water-soluble silicic acid gel by the German brand Huebner.

Collagen and hyaluronic acid will help greatly in rebuilding the damaged cartilage. Look for type II collagen for better absorption. Now Foods has good products at good prices. Also, glucosamine, chondroitin, MSM have all been shown to be useful for joints.

Proteolytic enzymes are responsible for breaking down, building, and repairing tissues. They can be amazing in accelerating a healing process, no matter what it is. Therefore, this is an essential supplement to take in treating arthritis.

4. Vitamin D3 and K2

These are the two vitamins that control and regulate the availability and deposition of calcium. Vitamin D3 makes it available, and vitamin K2 directs it to the bones and teeth.  Lots of vitamin D3 without K2 will lead to calcification with calcium being deposited all over the place in the arteries and soft tissues. Lots of K2 without D3 will lead to a depletion of available calcium in the bloodstream because it will be stored away in the bones and teeth. K2 is also used to decalcify soft tissues by pulling out and redirecting the deposited calcium from the tissues to the bones.

Vitamin D deficiency is universal in the west, and so is vitamin K2 deficiency. Arthritis sufferers need large doses of both for extended periods of time (at least a year). I recommend taking a combo supplement containing both in an optimal ratio, and take as many capsules as needed to bring vitamin D intake to 20 000 – 50 000 IU per day with breakfast and lunch. For years I took DaVinci’s ADK combo, which I think is one of the best. Now I take Life Extension’s D and K combo, without vitamin A, because its presence dampens the activity of vitamin D3. However, vitamin A promotes the healing of tissues. You can take both, alternating between the two.

Another of our readers who had his entire adult life an arthritic wrist that caused him pain and trouble whenever he used his hand for anything at all, followed my suggestion of taking 50 000 IU of vitamin D3 per day, together with the appropriate amount of vitamin K2 to match in the D3 intake, for six months. Within the first month, he found incredible improvement, something he had never been able to achieve using all the methods and drugs that had been proposed to him by MDs. After three months, his wrist was completely healed. He continued for the entire 6 months just to be sure, and now, his painful, debilitating, arthritic wrist that he was living with for more than 20 years, is a thing of past, a bad memory.

5. Vitamin C

Whole food vitamin C is essential for healing and keeping tissues and cells healthy. And there is definitely a difference between whole food C and ascorbic acid. We discussed this in Vitamin C is not vitamin C. This is not specific to arthritis, but everyone with arthritis should be loading up on it. I take The Synergy Company’s Pure Radiance C. You should take at least three capsules, but better 6 capsules per day, split evenly with each meal.

6. Turmeric extract

Turmeric is one of if not the most powerful natural anti-inflammatory. And inflammation is a hallmark of arthritis. You should take an extract that concentrates the curcuminoids, but you should also think of making yourself hot turmeric drinks, adding as much turmeric to your soups and curries as the flavours and combinations of foods will allow. It always needs to be taken with a lot of fat to maximise assimilation.

7. Food

Naturally, you will have guessed that my recommendations for food are the same as always, but even more important in this case when we are trying to bring inflammation as low as possible, and maximise healing:

  • no simple or starchy carbs because they cause inflammation, tissue damage, and metabolic disorder, except for berries once in a while;
  • unlimited unprocessed saturated fats from coconut oil, butter, and animal sources;
  • enough high quality protein from healthy animals including organ meats, especially liver; and
  • as many green veggies as you like, especially leafy like spinach, kale and lettuces, watery like cucumbers, fibrous like celery and broccoli.
  • Avocados are fantastic to eat as often as you want. Walnuts and hazelnuts are excellent health-promoting nuts (either roasted, or raw and soaked, subsequently dehydrated or not).

8. Sunshine, fresh Air, exercise and sauna

Go out in the sun, go for long hike, expose your skin, breath deeply, run up the hills, work your muscles at the gym if you can, go to Pilates and yoga classes, do lots of stretching whenever you can, and go to the sauna when you can. Make sure you stay 15 minutes to get really hot and for the heat to penetrate into the tissues and joints.

9. Iodine

Iodine is the universal medicine. Everyone needs it, and everyone should be supplementing with it. You can read for yourself why in Orthoiodosupplementation. Start at 12.5 mg and work your way up to 50 mg per day. Increment by 12.5 mg each week. Take the supplements on weekdays and give the kidneys a break on weekends. I take Iodoral, and recommend that. Using the generic Lugol’s solution is as good but less convenient.

10. Melatonin and good sleep

Good sleep is absolutely essential for repair and healing. Make sure you get plenty every day. Melatonin has, in addition to its effects in helping you sleep, many other amazingly health-promoting effects that we will explore in another article sometime soon, I hope.

Last words

Are there more supplements you can take? Of course there are. I personally take all of the above and several others. I wanted to stick to the things which I believe most essential. If I were to recommend additional supplements, I would say to take

  • omega-3’s, which are useful for lowering inflammation, as well as tissue healing and repair. I take Life Extension’s Mega EPA/DHA. Don’t take more than the recommended dose. Omega-3’s are very easily oxidised, and should always be taken in very small quantities.
  • Niacin in the form of niacinamide is also a universally useful supplement because it provides molecular building blocks needed by every single cell to produce energy. I take 500-1000 mg/day, but you could take 3000 mg (1000 mg with each meal). Niacin supplements will also do wonders for your mood (see No more bipolar disorder?).
  • Ubiquinol, the active form of Co-enzyme Q10, is also essential in cellular energy. I would recommend at least 50 mg per day, but more (like 100 or even 200 mg) would probably be better.
  • Vitamin B12 is crucially important for health. And the older we get, the more critical it becomes. I get an injection of 5 mg every month, and recommend that for everyone (see B12: your life depends on it).

Keep in mind that the timescale for improvements is long: on the scale of months. If you think that is too slow, ask yourself how old you are, and how long it took to get to the state you’re in. Now, with the answers in mind, remind yourself to be patient. You need to be determined to get better, consistent with your new regimen, and patient. But I assure you that you will get better. And please, keep me posted on your progress.

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You have cancer, and there’s lots you can do

Everybody knows that cancer rates are rising everywhere and every year. Everybody also knows that the words, “You have cancer. I am sorry.”, fall upon us like a death sentence. Everybody knows this, because we see it all around us, everywhere we look, and we hear about it every day, everywhere we turn.

If a doctor has, indeed, said these words to us, then we are probably scared, probably very scared. We know that basically everyone we have ever heard of who were diagnosed with cancer, died. Sometimes they died really quickly, like, within a few weeks. Sometimes they died within a few months. Sometimes it wasn’t so quick. Maybe it took a year of two, or three, or even five. They went through rounds of chemo. They were on sick leave at home for months on end. They sometimes appeared to recover at some point, maybe a bit, for a little while, but in the end, they died. And they died of cancer.

We also know that not even the most famous and richest people, like Steve Jobs, for example, can escape this kiss of death that the diagnosis of cancer delivers. Wealth and power are irrelevant when it comes to our prognosis as cancer patients: it is always bad. Of course, how bad it is depends on the kind of cancer, but why is it that so many different people, in so many different places, die of cancer every day?

I won’t venture into formulating an answer to this question, and I won’t dwell on cancer survival statistics. I don’t think it’s useful for us right now. I want to hurry and move to the good news. And the good news is that there many things you can do to help your body rid itself of cancer, which is usually the result of a long-standing disease process that has evolved over a lifetime, and has finally manifested itself in this way. This presentation of the question at hand is definitely not exhaustive, nor attempting to be. But this is what I consider to be some of the essential elements.

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White blood cells (shown in blue) attacking cancer cells (shown in red).

 

Understanding cancer

To understand cancer, we have to understand the origin of cancer cells. Cells become cancerous due to a defect in energy production, a mitochondrial dysfunction, an inability to manufacture enough ATP (adenosine triphosphate) through oxidation of glucose or fatty acids to sustain the cell’s functions. This forces the cell to fall back on anaerobic (without oxygen) fermentation of glucose to supplement the deficient energy production from the dysfunctional or reduced number of mitochondria. Fermentation produces an increase in lactic acid in and around the cell. This decreases the availability of oxygen to the mitochondria, which further impedes their ability to produce ATP through oxidation of nutrients, and creates a negative feedback loop that pushes towards further mitochondrial stress and dysfunction, less oxidation, more fermentation, more acid, and less available oxygen.

Because energy production through fermentation is so very inefficient, the cell needs far more glucose, and naturally develops more insulin receptors in order to be ever more sensitive to, and able to capture circulating glucose more effectively. Cancer cells often have 10 times more insulin receptors than healthy cells. What should be clear is that it doesn’t matter where the cancer is, and it doesn’t matter how it evolved, whether it was due to a gradual evolution from an environment too high in glucose, lacking in oxygen, and saturated with acid, or whether it was due to exposure to a toxin or mitochondrial poison, of which there are many and increasingly more in our environment. In the final analysis, this is how cancer cells become how they are, and this is how they survive.

As to their multiplication and proliferation from a single or small group of microscopic cells to large macroscopic tumours in one spot or all over the place, this can be understood by considering that the cell that is devolving from its normal function to that of cell whose only function is to ferment glucose at the fastest possible rate, loses, little by little, the ability to do whatever it was doing before, by losing the ability to produce ATP that can be used by its different specialised parts and constituents to perform their specialised functions, the cell becomes less and less specialised, less and less differentiated and therefore more and more general and more and more primitive, to the point where the essential ability of the cell to destroy itself, when something in its workings has gone wrong, is lost. Having lost this safeguard, the primitive, the undifferentiated, but also necessarily abnormal and weakened cell, just ferments and multiplies, limited only by its ability to fuel itself and sustain this most basic activity of survival without other purpose but this survival in and of itself.

Removing cancer

Having recognised and understood this, the strategy by which we can help the body rid itself of the cancer cells, and regain its healthy physiological functions becomes clear. We have to 1) do all we can to cut off the source of fuel to the cancer cells, 2) clear out the accumulated acids and transform the acidic environment into one that is alkaline and oxygen-rich, 3) help restore the cells’ mechanism of apoptosis—their ability to self-destruct, and 4) do everything else we can to further weaken and destroy cancer cells by means that simultaneously strengthen healthy cells. It’s a simple strategy that is also simple to put into practice, as we will see in a moment.

1) Starve the cancer cells

The first point is to cut off the fuel to the cancer cells. The source of fuel is glucose, because cancer cells can only ferment and cannot oxidise, and the way the glucose is supplied to the cell is by the action of insulin that moves it across the cell membrane. Therefore, what has to be done to is minimise the availability of glucose, and, more important still, minimise the availability of insulin to shuttle the glucose into the cells. The lower the glucose, the less potential fuel there will be. The lower the insulin, the less glucose will actually be able to enter cells. There is no real lower limit. Without ingesting any carbohydrates, the body maintains and regulates blood sugar according to the stress levels and kinds of activities we engage in, independently of how low insulin levels are. And so, the focus should be to have the lowest possible insulin levels naturally.

The fastest way to lower blood sugar, but especially insulin, is to fast, to stop eating altogether, and just drink water and herbal tea, remembering to eat enough salt to match the water intake. The second best way of doing this is in form very similar, but turns out to be much easier to do, is also a kind of water fasting, but with the addition of fat from coconut oil and butter, melted in the herbal teas. Both of these forms of fasting will most effectively deprive the body of anything that can easily be made into glucose, and of anything that will stimulate the secretion of insulin, thereby will allow glucose to drop as low as possible, but more importantly, insulin to drop and stay at an absolute minimum, and therefore most effectively starving cancer cells, no matter where they are in the body and bodily fluids, in the tissues and organs. The first form of the classic water fast is harder, but many people do it without hesitation nor difficulty. The second form is much easier, and may even be more effective in inducing a deep state of ketosis given the additional intake of medium chain fatty acids.

We can easily imagine doing such a fat “fast” for days, or even weeks, depending on the severity of the situation, our resolve to suffocate and starve the cancer cells as quickly as possible, and, of course, the state and circumstances in which we find ourselves. In addition, we can do this as much as possible on any given day, independently of what else we eat. The more fat and the less carbohydrate we ingest, the lower the insulin and the more effective the anti-cancer healing protocol will be.

The third option is to eat and drink to keep insulin levels as low as possible. Here again, because fat is the macronutrient that stimulates the least secretion of insulin, truly minimal, it should be the main source of calories. Simple carbohydrates and starches are most insulinogenic, and protein is about half as insulinogenic as are carbs. Indigestible fibre does not stimulate insulin. Therefore, in the extreme, we would eat only fat, pure fat. The best ones being the most natural and least processed, most saturated and least unsaturated: coconut fat, butter, animal fat and, the best of the vegetable oils, cold pressed olive oil.

It’s important to understand the difference between having low blood sugar, and having low insulin levels. The first is like the amount of food in the kitchens of the restaurant, the second is like the waiter bringing it to the table. It is far, far more important in our efforts to stop the supply to cancer cells that we keep insulin levels as low as possible, than it is to try to keep glucose levels low. And to push the point further, it doesn’t really matter what the amount of glucose actually is, because as long as insulin is low, it will not be brought into the cell, into the cancer cells. The reason I emphasise this is because lack of sleep, emotional or psychological stress, intense physical exercise will all raise blood sugar levels temporarily, in some instances, to high levels. But as long as insulin is as low as it can be, the sugar will not be readily transported into the cells.

Naturally, we cannot have zero insulin, because we would die: our cells would literally starve to death, no matter how much we ate. Babies with a genetic defect that makes their pancreas not able to produce insulin always died of emancipation before the discovery and subsequent commercialisation of insulin as medicine. Similarly, if at any point in a child’s or adult person’s life, insulin stops being produced, incredible weakness and emancipation will follow, before it is tested and identified as the cause of their problem, hopefully in time before permanent damage ensues. Therefore, there is always some insulin in circulation, and therefore, sugar will eventually make its way into at least some cancer cells. This is why it is important to keep it as low as we possibly can naturally, and this is how we can appreciate the essential difference between the effects of high glucose and high insulin.

In a less extreme form than the fat-fast, we maintain low sugar and low insulin by getting and deriving most of our energy from fat. Eating cucumber or celery with almond butter or tahini, for example, or a green leafy salad with lots of olive oil, walnuts, and avocado, provides basically all calories from the fat, given that cucumber, celery and lettuce greens, are basically just water and indigestible fibre, while almond butter and tahini are 80\% fat by calories, and walnuts are 84\%. So is coconut milk, for example, at nearly 90\%, and dark 85\% chocolate, at 84\% fat based on calories. Focusing on feeding the body with these kinds of healthful, high-fat foods, will nourish, stimulate healing, and keep insulin and glucose levels as low as we can without either water fasting, or consuming only fat.

2) Alkalise to remove and excrete accumulated acids

The second point is just as important as the first, because it is the environment in which the cells live that actually has the most direct effect on their function. We have looked at the importance of achieving and maintaining an alkaline environment in the body in several other places. The essence is excellent hydration with alkaline water (pH>8) combined with the intake of proportional amounts of unrefined salt to promote the release of acids from the tissues, and its excretion through the urine by the kidneys. Without proper hydration, the cells will retain the acid with the little water they have to hold on to. Without proper amounts of salt, the kidneys will also retain the acid in order to maintain the concentration gradient that allows the nephron to function when it re-absorbs water.

Naturally, alkaline water will work infinitely more effectively. But the most important detail is the controlled balance between water and salt intake, and what we want is a lot of water and a lot of salt. We cannot take in large amounts of salt water without getting loose stools. So, it has to be smoothly distributed throughout the day, except in the morning, when we get up, because we are dehydrated, and need to drink about 1 litre of water over the course of one to two hours, before we start taking salt.

If you buy mineral or spring water, find the one that has the highest pH value. It should be greater than at least 8. If you have a water filter at home, then add alkalising drops to it before drinking it. I use Dr. Young’s PuripHy drops.

As acidity decreases, and the environment becomes more alkaline, oxygen will flow more freely, and become more available to mitochondria for oxidising fatty acids in producing energy. Remember that cancer cells do not use oxygen, and cannot use fatty acids to fuel themselves, whereas normal, healthy cells, not only can, but function much more efficiently on fat rather than glucose as their primary fuel. Adding chlorophyll and fresh juice of green vegetables to the alkaline water is an excellent way to further boost alkalisation, neutralisation, and elimination of accumulated metabolic acids. Unlike the first step, which is to lower insulin and glucose levels, and that can be done, to a great extent, literally overnight under fasting conditions, alkalising to eliminate accumulated acids is something that takes time. But in both cases, what matters most is consistency. Hour by hour, and day after day, the body will do what it needs to do as best is can, and improve in these functions with time.

Beyond this fundamental necessity to hydrate with alkaline water throughout the day, and day after day, the most therapeutic way to alkalise the tissues, and detoxify the body, is by taking medicinal baths in which we add two cups of sodium bicarbonate (baking soda), and two cups of magnesium chloride (nigari), or magnesium sulphate (epsom salts), if nigari is not available. This is easy, relaxing, extremely medicinal, and very effective in neutralising and eliminating acids and toxins from the body. In fighting cancer, you should be soaking in this kind of hot bath for 45-60 minutes three times per week. The benefits of this ultra simple trans-dermal therapy with sodium bicarbonate and magnesium are incredible. You can read a lot more about this from the baking soda, magnesium and iodine doctor, Dr Sircus.

3) Restore cellular self-destruct function

The third line of action is also essential, and it only requires you to take a few key supplements. The most important of these in the fight agains cancer is iodine, because of its fundamental role both in the structure and architecture of cells, but also in the regulation of apoptosis, the process by which a damaged cell will self-destruct when things have gone wrong somewhere. The importance of iodine cannot be overemphasised. And in healing cancer, or any serious disease condition, we will want to take high doses daily. Doses of at least 50 mg, but preferably 100 mg.

However, because of its very strong detoxification effects, as it pushes out all accumulated toxic halogens out of the cells to replace these by iodine in its proper place, we must work up to these high doses gradually, starting with 12.5 mg, and increasing the dosage as quickly as possible given the body’s response to it. Some people , maybe most, will experience headaches and possible nausea when starting on iodine. This is perfectly normal. The stronger the reaction, the more indicative of the body’s level of toxicity. Therefore, you should always view this as something good, in that toxins are being excreted out of your cells. It is important to support the detoxification process by taking chlorella and spirulina, probiotics and psyllium husks every day as well, while always drinking a lot of alkaline water with added chlorophyll for extra cleansing, if possible.

What I take and consider to be the best supplement is Iodoral by Optimox. Optimox recommends taking the iodine on an empty stomach for faster absorption, but it can also be taken with food for slower and possibly better assimilation. In addition, although iodine can easily be taken on an empty stomach, the co-factors, which include B vitamins, are much better taken with food to avoid potential nausea or queasiness. Moreover, taking it with food will slow down the absorption, and thereby decrease the negative sensations from the detoxification effects. The only thing is that iodine, given its stimulation of thyroid function, will energise the body. Therefore, it should be taken before midday. I take it either first thing in the morning or at lunch (or both).

You can read about the importance and functions of iodine in the following three books: Iodine, Why You Need It, Why You Can’t Live Without It by Dr. Brownstein; What Doctors Fail to Tell You About Iodine and Your Thyroid by Dr. Thompson; and The iodine crisis: what you don’t know about iodine can wreck your life by L. Farrow. There are also many web resources and highly informative forums about iodine and cancer. You can search for the words iodine and cancer to see for yourself.

Other fundamentally important micronutrients are vitamins B12 and D, both of which are needed for proper cellular function, and DNA transcription and replication, because of their roles in the nucleus of cells, activating and de-activating, switching on and off genes, to ensure everything in the cell works as it should. For best and fastest results—and that’s definitely what we need in our fighting cancer—B12 should be injected weekly in the amount of 1 mg, and in the form of methylcobalamin. (For optimal health in normal circumstances, it can be injected once a month in the amount of 5 mg.) Vitamin D should be taken with its sister vitamins, A and K2, for synergistic effects and biochemical balance in their functions. Each of these have complimentary roles, and should generally be taken together, unless there is a reason not to. You can read these two articles published by Chris Masterjohn from the Weston A. Price Foundation to learn why and how: On the trail of the elusive X-factor: a sixty two year old mystery finally solved, and Update on vitamins A and D.

It is by supporting proper cellular function, especially in the nucleus, with iodine, B12 and D, that cells will regain, little by little, the ability to recognise that they are damaged and need to self-destruct. There will always be millions or even billions of cells involved in the disease process we call cancer, but they will be distributed along a wide spectrum of dysfunction, from having very mildly impaired mitochondrial function from a light oxygen deficit cause by a little too much acid in the environment surrounding the cell, to full cancer cells that derive 100% of their energy needs from anaerobic fermentation without using any oxygen at all, and thriving in extremely acidic conditions.

Hence, many cells will die from being starved of glucose, because that’s the only fuel they can use; many cells will recover enough of their normal regulatory mechanisms to know its time to self-destruct; and many cells will actually regain their healthy function, repair their damaged parts, and replace their dysfunctional mitochondria with new ones. Nothing is ever black and white when it comes to cells and cellular function. Instead, everything is grey. But it is a million different shades of grey.

4) Do everything else that can help

The fact is that there are many, many more things you can do. Many therapies, many treatments, many supplements and herbal formulas, that have all proved highly effective against cancer. There are so many that many books have been written about them: About Raymond Rife, you can read The Cancer Cure That Worked by Barry Lynes; about Gaston Naessens, you can read The Persecution and Trial of Gaston Naessens: The True Story of the Efforts to Suppress an Alternative Treatment for Cancer, AIDS, and Other Immunologically Based Diseases by Christopher Bird; about Rene Caisse and the Essiac tonic, you can read Essiac: The Secrets of Rene Caisse’s Herbal Pharmacy; about Johanna Budwig, you can read Cancer – The Problem and the Solution; and the list goes on. There are websites devoted to these people and their approach to cancer, and this is just a few of them that I know about. One book that compiles a lot, maybe most, of the information on non-toxic treatments for cancer, is Ty Bollinger’s Cancer: Step Outside the Box.

Maybe you find it hard to believe that our governmental and medical authorities would have gone—and continue to this day—to go through such extreme measures in order to suppress treatments that work so effectively to help and heal people of their illnesses and of cancer, without negative side effects, and at very low costs. But this is a simple fact. And it is quite easy to understand if we consider that anyone, or any institution, that has commercial investments and interests in a particular endeavour, will go to great lengths to maintain and strengthen, as much as they can and for as long as they can, the conditions that make them successful. There’s nothing more to it than that. Let’s look at a few of those therapies and supplements which are easy to implement, and highly effective against cancer: hyperthermia, flax seed oil, enzymes, and turmeric.

Hyperthermia, or heat therapy, is a very well studied and effective therapy against cancer, both preventatively and curatively. The idea or principle is very simple: healthy cells can withstand high temperatures without damage. The reason why this is so, and why we know it for sure, is that the body produces fevers as a defence mechanism to destroy invading viruses and bacteria that, unlike our own cells, cannot withstand the heat. Similarly, cancer, and other compromised and damaged cells, are unable to cope with high heat. Hence, it was hypothesised, tested, verified and demonstrated that hyperthermia is really very effective at destroying cancer, while simultaneously cleansing and strengthening healthy cells and tissues. Infrared saunas are ideal in heating the tissues more deeply, but any sauna, steam room, or even bath that induces hyperthermia by raising the temperature in the body, will help kill cancer cells, cleanse, and restore health.

Enzyme therapy has also been used for many decades in the treatment of cancer patients extremely successfully. The late Nicolas Gonzalez who passed away last year, was its most recent champion, following in the footsteps of his mentor, Dr William Kelley. The treatment protocols are more complicated, and are always highly individualised, but the main element is the supplementation with large doses of enzymes, combined with the colon cleansing to eliminate the dead tumour tissues from the body. Large quantities of fresh vegetable juice are also often included in his recommendations. You can read about it here: http://www.dr-gonzalez.com/index.htm, but whether you decide to throw yourself completely into it or not, I strongly recommend taking proteolytic enzymes three times per day, always on an empty stomach at least 30 minutes before eating, and support cleansing by taking a colon cleanser before going to bed. This site, http://www.losethebackpain.com, has good quality enzymes and cleansing supplements that we’ve used, but you can also do your own research.

Flax seed oil, organic and cold pressed, combined with fresh organic quark or cottage cheese is, based on Johanna Budwig’s extensive, lifelong research, as well as practical clinical experience with patients, is another one of the most effective and simple cancer treatments. And although the biochemistry of it, and biochemical pathways through which the cancer is weakened and destroyed may be complicated, the implementation is very easy and simple, costs very little, and cannot in any way bring about harm, unless one is severely allergic to milk proteins (in which case the dairy can be replaced with another source of protein that will work as the carrier). Here is a good article that has links to other excellent articles about this: https://www.cancertutor.com/make_budwig/

Turmeric, an ancient, bright yellow, Indian spice, which is a powder made from drying the ginger-like root that is turmeric, is one of the most researched natural substances in modern times, and is surely one of the most powerful natural anti-cancer supplements. Since it has tons of wide-ranging health benefits, and carries no risks at all, it’s clear that everyone can benefit from it. You can read about it from Mercola here. You should take it three times per day, but with your meals, because the more fat there is in the gut, the better the absorption will be, as is true for most antioxidants, vitamins, and minerals.

I feel it is important to emphasise the point just made about the risk-free nature of supplementing with turmeric, because it is a crucial point that applies to everything we have discussed here, and everything we have discussed in all the natural healing protocols and nutritional approaches we have presented in the past. Food-based nutritional healing is, in general, risk-free, because it doesn’t involve ingestion of or exposure to toxic substances, and instead involves correcting deficiencies, boosting nutritional status, and optimising the biochemical and hormonal environment of the body in order to promote healing.

Of course, we can object by referring to examples of people dying from drinking too much water too quickly. But we are not talking about such extremes. Nonetheless, we could, for example, eat coconut oil or butter all day, and other than the possible nausea from taking in so much fat, you wouldn’t get anything more than loose stools. Moreover, the body’s own hormonal responses would naturally prevent overconsumption through a feeling of extreme satiety that would basically make it impossible to willingly eat more.

Another example is that of using baking soda or iodine. So simple, and yet so powerful, they stand as the perfect examples of the benign nature but extreme effectiveness of natural healing. We find written in the most recent edition of the Manual for the Medical Management of Radiological Casualties of the US Military Medical Operations, Armed Forces Radiobiology Research Institute, that sodium bicarbonate will “prevent deposition of uranium carbonate complexes in the renal tubules”, and that we should, “within 4 hours of exposure, administer potassium iodide (KI) to block uptake of radioactive iodine by the thyroid”, because they are the best known ways to protect the kidneys and thyroid from being destroyed by the radioactive elements that would—without the use of sodium bicarbonate and potassium iodide—migrate to these organs and destroy them.

But why wait for a chemical spill or a nuclear power station meltdown in order to rid the body of accumulated chemicals and toxins, and to replenish every cell with a plentiful supply of iodine to ensure that all cells and all glands function at their best, now and every day? We don’t have to wait. The same goes for turmeric, for enzymes, for B12, for A-D-K2, for hydration, for alkalisation, for minimal glucose and minimal insulin loads, for maximum nutrition and maximum health. Why don’t we start doing this preventatively right now?

Summary and Wrap up

Maybe you know all of this stuff already, or maybe you don’t and you are blown away and overwhelmed by the amount of information and range of topics we have covered. Maybe you are reading this because you are interested and curious to learn and be as well-informed as you can about health topics, or maybe you are desperately looking for relevant information that can help you or a loved one. No matter in which camp you find yourself, here is the summary and wrap up I can offer to bring all of what we have discussed down to a simple set of recommendations that anyone faced with a diagnosis of cancer, and fearful of, or skeptical about, or doubtful that the current standard of care in the cancer industry will help them, can understand and follow, knowing that none of these food choices, supplements, and therapies will bring them harm in any way, and that all will only do good, regardless how dire or hopeless their situation may appear to be.

  • Keep low insulin levels, as low as possible, by not having insulin-stimulating carbohydrates, and by keeping protein intake reasonably low. Focus on consuming natural, unprocessed fats as much as possible to supply the largest proportion of your daily calories. Consider a water or a tea-with-fat fast for a few days when it is suitable, or even as an intermittent fasting strategy on a daily basis. Consider also doing a green juice “fast” (only green vegetables) with added fat from blending in melted coconut oil or milk.
  • Drink alkaline water, always on an empty stomach, considering the day as divided between hydration periods, and feeding and digestion periods. The first hydration period is from the time you get up until you have your first meal. It is good to extend that period if you can to allow plenty of time for proper hydration after a long night of dehydration, with at least 1 to 1.5 litres over a period of at least 2 hours. Drink slowly to improve absorption and not pee everything out. Always allow 30 minutes without drinking before meals, and 2-3 hours after meals, depending on their size. The cycles of hydration and feeding during the day (for 3 meals) should be as follows: drink, wait, eat, wait, drink, wait, eat, wait, drink, wait, eat. For only two meals, which I recommend, then periods of drinking are extended and allow for even better hydration, cleaning of the blood, and better digestion.
  • Take iodine supplements with the co-factors and with food to maximise absorption and effectiveness. Start with 12.5 mg per day, and work your way up to 100 mg. Do this as quickly as your body allows you to. Take the iodine every weekday, and stop on weekends; five days on, two days off. (My wife and I take 50 mg per day.)
  • Take hot baths with sodium bicarbonate and magnesium chloride (or sulphate; 2 cups of each). Soak for 40 to 60 minutes. Do this three times per week. Always take your baths on an empty stomach, and drink at least one litre of alkaline water during the length of the bath. (Once per week is what I aim for as preventative medicine.)
  • Get B12 injections of methylcobalamin, 1 mg on a weekly basis. (My wife and I get a 5 mg injection once per month.)
  • Take proteolytic enzymes and Essiac tonic three times per day, always on an empty stomach, always at least 30 minutes before meals. (We take it once, first thing in the morning.)
  • Take turmeric and turmeric extract, as well as A-D-K2 with every meal or fatty snack, three times per day during recovery. (Once daily in normal circumstances.)
  • Take infrared or regular saunas, every day if possible, or even in the morning and at night if you have or decide to buy your own little sauna. I would definitely do this given how effective hyperthermia is at destroying cancer cells.
  • Eat Budwig cream.
  • Eat and drink greens.
  • Spend time outdoors, as much time as you can, moving, breathing fresh air, exposing your skin to the sunlight.
  • Keep low stress levels, as low as possible. Take tulsi, ashwagandha, and HTP-5 to keep stress hormone levels low, and mood high.
  • Take probiotics, chlorella and spirulina in the morning, and a colon cleansing supplement before bed.
  • Sleep well, long restful nights. Melatonin is very useful for this, and has many additional health benefits.

Cancer is very easy to prevent, but somewhat harder to dislodge once it has taken hold somewhere within the body. But no matter what type of cancer, how localised or generalised it is, or at what stage it finds itself, there is always hope. Hope of getting better and more comfortable, and hope for a complete recovery.

We have to remember that cancer cells are degenerate and weak. By making the environment as health-promoting to normally functioning cells, and simultaneously as hostile as possible to cancer cells, they will perish and be cleared out from the body as the waste that they are. The body heals itself, often miraculously quickly, when impediments are removed, and the elements needed for healing are provided. With all my heart, I hope this can help you and your loved ones.

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