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.

international_dairy_week_banner

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.  If you think it could be useful to others, please Like and Share it.

On the origin of cancer cells – part 2

Fifty years of intense research had passed from the year he received his doctorate in chemistry in 1906 to the year when On the Origin of Cancer Cells was published in 1956. The uniquely exceptional scientist that was Professor Otto Warburg was nominated for the Nobel Prize by his scientific peers a total of 46 times between 1923 and 1931, with 13 of these nominations in that last year. And in 1931, he was awarded the Nobel Prize for his seminal work on the essential role of iron in the biochemistry of cellular respiration published in 1928, and more generally for his work on the aerobic and anaerobic metabolic processes in cells. He was also, in that year, made director of the Kaiser Wilhelm Institute for Cell Physiology in Berlin (renamed Max Planck Society in 1948), and he maintained not only his post but also his scientific activity until his death in 1970 at the age of 86.

otto-warburg-old-highresfaceshot

In fact, in 1969, just months before his passing, he published with one of his long-standing collaborators Dean Burk who translated the text (as he did for the 1956 paper), a revised and additionally prefaced version of the lecture he gave at the meeting of Novel Laureates at Lake Constance, Germany, in 1966 entitled The Prime Cause and Prevention of Cancer. The tone of this lecture, both for the first part of 1966 and the second of 1969, transpires frustration and even anger at the general lack of notice and acceptance of the crucial elements of the physiology of cancer cells that he had studied, understood, elucidated and clearly described in his publications over the course of more than 60 years of research.

Attempting to formulate a well-rounded and balanced explanation would require a lot of time and effort, not to mention a lot more words. But it is evident that then as now, financial interests have generally always been among the strongest driving forces both in research and in developing applications based on the understanding derived from this research. Hence, it is more than clear that eliminating the use of chemicals in all agricultural and industrial processes, stopping the consumption of simple and starchy carbohydrates and refined foods, and supplementing with iron, niacinamide and enzymes in general like Warburg recommended and did as a means to prevent and treat cancer is not only not at all lucrative, but it is highly financially detrimental to all chemical-based agricultural and industrial activities. I believe this is a most important part of the explanation, as it is for so many things.

What Warburg understood

Warburg had slowly, carefully, cautiously, diligently, painstakingly carried out experiment after experiment, trial after trial, studying every last detail of every aspect of the experimental process. He explained the cell’s most vital function, that of respiration, using oxygen to burn glucose or fats and produce energy, with a particular focus on the critical role of iron as a ‘respiratory enzyme’ carrying the oxygen molecule. He explained that the glucose molecule was ‘fermented’ (that it underwent glycolysis) in the cytosol of the cell, split into pyruvate molecules and fermented to lactic acid, and that this produced a small amount of adenosine triphosphate (ATP) without the need or use of oxygen. This process is termed anaerobic fermentation.

He explained that this process could either stop there, or be extended further by the pyruvate being taken up into mitochondria of the cell, and with the use of much oxygen, almost magically produce a lot more ATP without needing any additional glucose, but going through a series of steps and transformations relying primarily on clever recycling and reusing mechanisms of the niacin (B3) based molecule NAD (which stands for Nicotinamide Adenine Dinucleotide) within the mitochondria.

The ATP-generating process taking place inside the mitochondria was eventually described in detail by one of Warburg’s students, Krebs, who was awarded a Nobel Prize in 1953, and to which his name was given as the Krebs cycle also known as the citric acid cycle, as everyone who has studied some biology has heard (even if you never quite understood was this stuff was all about). Note that the Krebs cycle produces only 2 molecules of ATP, just as glycolysis does, and that it is what is called the electron transport chain, also taking place inside the mitochondria and using plenty of oxygen, that produces the bulk of the ATP with a potential of an additional 34 molecules, using products of the Krebs cycle, and in particular the 10 molecules of NADH.

Warburg was motivated to understand at the most fundamental level what was the difference between healthy cells and cancer cells. Naturally, as cancer was already a devastating disease in the 1930’s, he wasn’t the only scientist working and leading researchers in the study of the mysteries of cancer. He was, however, one of the most talented, dedicated and productive, together with the group of scientists he led at the Kaiser Wilhelm Institute and those with whom he collaborated.

The first major step was made in showing that tumours fermented glucose much more intensely than healthy tissues that normally hardly do so at all. This fact—that tumours ferment a lot more glucose than healthy mature tissues even in the presence of oxygen—is known as the Warburg Effect and is universally studied in physiology, medicine and oncology (cancer-ology). This fact is so fundamental to cancer metabolism as well as cancer research that it is the basis of the PET scan imaging technique in which radioactively labelled glucose is used to make detailed images of active tumours and their tendrils in our tissues. The reason why it works is that cancer cells take up glucose from the bloodstream far more efficiently than normal cells.

What is unfortunate but not surprising given how myopic scientists and we all in general tend to be, is that this has been consistently overlooked as being a critical aspect of the genesis of cancer, as Warburg’s research implied, and instead has been interpreted as a consequence of the dysfunctional cellular metabolism of these mutated cells that is unrelated to the actual development of the cancer.

This is pretty absurd. After all, if cancer cells derive a substantial fraction of their energy from fermenting sugar, wouldn’t the absence of sufficient glucose naturally halt the growth and proliferation, and thus the development of tumours? And even more fundamentally, because glucose can only be transported inside the cell by the action of insulin, and it is, in fact, to insulin—not glucose per se—that cancer cells are incredibly more sensitive than healthy cells, wouldn’t an important drop in circulating insulin levels be detrimental or even lethal to cancer cells? Of course it would! They would be starved of the only fuel they can use, and as a consequence, eventually become incapable of sustaining their activity.

How was this measured?

The way it was done was to measure oxygen consumption and lactic acid production either with plenty of oxygen or without any, for tumours and different tissues under physiological conditions of pH and temperature. This is the perfect trick because fermentation outside the mitochondria does not require any oxygen, whereas energy production by glucose oxidation inside the mitochondria depends entirely on the presence of ample amounts of oxygen, In fact, even a minute drop in oxygen concentration will negatively affect mitochondrial ATP production. Cancer cells don’t care much if there is oxygen or not: they don’t use much and therefore don’t depend on it. They ferment glucose anaerobically no matter what because this is the only way they can generate enough energy to survive.

It was understood a number of years later that tumours are rather heterogenous both in terms of the types of cells and tissues they are derived from, and in the concentration of cancer cells: tumours can grow extremely fast or extremely slowly; they can have a large proportion of cancer cells in relation to normal cells or a small one; and since different specialised tissues require different conditions and function differently, it is an obvious consequence that tumours developing in different tissues will have different characteristics.

Hence, the next step necessitated the isolation of cancer cells in order to avoid the problem of dealing with heterogeneous mixtures of cancer and healthy cells cohabiting in a solid tumour. It was this that Warburg presented in the 1956 paper, and what a difference this would make! These are his opening paragraphs:

Our principal experimental object for the measurement of the metabolism of cancer cells is today no longer the tumour but the ascites cancer cells living free in the abdominal cavity, which are almost pure cultures of cancer cells with which one can work quantitatively as in chemical analysis. Formerly, it could be said of tumours, with their varying cancer cell content, that they ferret more strongly the more cancer cells they contain, but today we can determine the absolute fermentation values of the cancer cells and find such high values that we come very close to the fermentation values of wildly proliferating Torula yeasts.

What was formerly only qualitative has now become quantitative. What was formerly only probable has now become certain. The ear in which the fermentation of cancer cells or its importance could be disputed is over, and no one today can doubt that we understand the origin of cancer cells if we know how their large fermentation originates, or, to express it more fully, if we know how the damaged respiration and the excessive fermentation of the cancer cells originate.

This was the programme that in the end led to the discovery that cancer cells produced 2-3 times (that’s 200-300%) more lactic acid than the most solid tumours. This meant that even those most solid tumours must have been composed of only about 1/3 active cancer cells, and thus 2/3 normal and inactive cancer cells.

This is necessary because cancer cells cannot do the things needed for the tumour to survive and grow, like making new blood vessels for example; only healthy cells can carry out such specialised activities. The wildly fermenting and proliferating cancer cells are dependent on healthy cells in the tissue where they are growing in order to survive. This makes good sense given that cancer cells gradually devolve, generation after generation, losing their function, their specialisation and their differentiated nature, and eventually cannot do much of anything but ferment glucose and replicate. For this reason, they rely on the healthy cells to maintain a viable environment for them.

Oxygen is crucial

Recall a key observation that was made in comparing the metabolic activity of cancer cells to normal cells: as the cell transitions from functioning normally and deriving virtually 100% of its energy needs by burning glucose (or fat) with oxygen inside the mitochondria, towards the defective cancerous cellular metabolism characterised by fermenting glucose without oxygen outside the mitochondria, they derive progressively more energy from fermentation and less from oxidation, independently of the amount of oxygen available.

You see, if oxygen in the cell drops, then ATP concentration drops because the mitochondria need the oxygen to make ATP. Immediately, fermentation outside the mitochondria will begin or increase in order to make up the energy deficit. This is normal and happens in all healthy cells whenever this situation occurs. However, the drop in available oxygen will also trigger heart rate and breathing to increase in order to make more available. This will very quickly correct the problem, allowing the cell to stop fermenting and return to the much preferred condition of generating ATP though oxidation in the little power plants that are the mitochondria. Once again, this is perfectly normal and happens in healthy, well-functioning cells every time we exercise.

Those cultured cells with which they were working did not have the support of the entire organism that we have, exquisitely fine tuned and orchestrated by countless specialised hormones, sensor cells, worker enzymes, etc., to react instantly to any kind of chance of condition. As oxygen concentration dropped, fermentation increased. But if oxygen levels weren’t replenished quickly enough, the damage to cellular respiration was found to be irreversible. Now, fermentation continued no matter if oxygen levels were raised to saturation following the period of hypoxia.

Not only did fermentation continue under oxygen saturation, but it increased over time. This is what was meant by irreversible in terms of the damage to respiration sustained by the period of deficient oxygen levels, and this is what showed very clearly how a cell can transition and devolve from normal and healthy to cancerous. The same observations were made irrespective of the means that were used to damage respiration: arsenic, urethane, hydrogen sulphide and its derivatives, hydrocyanic acid, methylcholanthrene and whatever else, whether oxygen was deficient or prevented from reaching the cell by a respiratory poison, the result was irreversible damage that always eventually resulted in cancer cells if the damage wasn’t too severe, because otherwise the cell would not survive at all.

The unavoidable consequence of this was immediately understood: it is the cumulative effect of chronic exposure to small amounts of carcinogenic respiratory poisons or low-oxygen that causes and leads to cancer within our tissues. Very unfortunately for us, the number, spread and quantity of such carcinogens grows with each passing day. Is it any wonder then, that cancer rates are soaring? That it is a modern plague in our highly industrialised, pesti-cised, herbi-cised, fungus-ised and globally chemi-cised countries?

Measuring cancer cell metabolism

Quantitative measures of cellular activity and metabolism of ascites cancer cells were done keeping the cells in their natural medium, ascites serum, that was ‘adjusted’ physiologically once they were removed from the abdominal cavity. Adjusted how? By adding glucose to feed them, but also bicarbonate to neutralise the lactic acid, because the fermentation rate was so strong that without the bicarbonate the pH would drop too quickly and too drastically, causing fermentation to be brought to a standstill and soon after the cells to die.

Under physiological conditions of pH and temperature, in units of cubic mm for 1 mg of tissue (dry weight) per hour at 38 C, they found the following:

  • Oxygen consumption: 5 to 10,
  • Lactic acid production with oxygen saturation: 25 to 35, and
  • Lactic acid production without oxygen: 50 to 70.

Warburg and colleagues estimated that in anaerobic glucose fermentation, one mole of ATP was produced for every one mole of lactic acid. In contrast, even though the exact details were not yet known, measurements indicated that in cellular respiration, 7 moles of ATP could be produced for every mole of oxygen that was consumed. Based on these estimates, they compared ATP production form fermentation and oxidation in different types of cells.

Healthy liver and kidney cells showed identical metabolic values, consuming 15 cubic mm of oxygen per mg per hour, and in the absence of it, producing only 1 cubic mm of lactic acid. This means these cells were very poor at fermenting glucose; they could basically only derive energy from oxidation within the mitochondria. And this was made even more apparent by comparing, as they did, the amount of ATP that can be derived from fermentation or from oxidation. Using the 1:1 ratio of lactic acid to ATP under fermentation, and the 1:7 ratio of oxygen to ATP under oxidation, they found that these healthy liver and kidney cells could derive 105 (that’s 15 x 7) moles of ATP from oxidation versus only 1 from fermentation. As a fraction of the total, this is 105/106 or 99.1% from the normal mechanism reliant on the Krebs cycle and electron transport chain inside the mitochondria.

Next they looked at very young embryonic cells and found equal oxygen consumption of 15 cubic mm, but with a significantly greater—25 times greater—production of lactic acid when oxygen supply was cut. What this means is that these embryonic cells were much better adapted to surviving in anaerobic conditions without oxygen. This is quite natural given that the less evolved the cell, the more primitive and less specialised or differentiated, and therefore the closer to simpler cellular forms like yeasts. Doing the same as above in translating this metabolic function to compare the amount of ATP derived from either anaerobic or aerobic usage of glucose, we find that the same amount of 105 cubic mm of ATP from respiration, but in this case 25 moles of ATP from fermentation. And so, in this case the fraction is 105/130 or 80.8%, compared to the above 99.1% in normal liver and kidney cells.

The difference between these numbers and those calculated for the ascites cancer cells was large: they consumed less than half the oxygen, 7 cubic mm, but produced a whopping 60 cubic mm of lactic acid. That was 60 times more than the healthy mature liver/kidney cells! Here, ATP derived from respiration was therefore 49 (7 x 7) compared to 60 from fermentation. Hence, the fraction of the total that could be derived from oxidation was a mere 49/109 or 45%, implying that more than half the energy requirements could be derived from fermentation. This is how these quantitative measurements on the metabolism of healthy and cancer cells were done, and the result was indeed a remarkable finding.

What these results explained

So many things were understood or clarified through his efforts across these five long decades of intense research, and now with these latest results we understood different cell types have different propensity to become cancerous based solely on the cell’s inherent propensity towards fermentation: the higher the amount of ATP that could be derived from anaerobic fermentation, the easier it would be for the cell to become cancerous, and also the faster the tumour would grow.

The unfortunate but unavoidable implication is that embryos whose cells are all immature and therefore more primitive and naturally prone to greater fermentation, are the most susceptible to sustain damage to respiration whether from periods of low oxygen (think asthmatic mothers) or from exposure to respiratory poisons (think anything from pesticides, herbicides, food preservatives, to just supermarket household ‘cleaning’ and skin ‘care’ products, synthetic perfumes or substances they contain, and on and on…). Here again we can ask: is it any wonder that infantile cancer rates are also on a sharp rise?

We understand, for exactly the same reasoning, why cancer tumours in different tissues grow at different rates under the same physiological conditions, and easily explain why the increase in fermentation is gradual, requiring many cell divisions after the initial injury. As we know very well, it typically takes decades for adults to develop large cancer tumours that cause enough of an effect to get us to the hospital before it is diagnosed as such. Also, we know that tumours in or near the brain can develop and grow very quickly—within a year or two—whereas for the prostate they typically take an entire lifetime, sometimes completely unbeknownst to the host whose quality of life is not affected noticeably.

It was also understood why radiation therapy was generally effective at reducing the size of solid tumours by killing those already weakened and energy deficient cancer cells through a final blow to their injured and struggling mitochondria. By the same token, however, radiation will also always damage mitochondria of healthy cells, and thus set them on their way towards the process of devolution into dysfunctional fermenting cancer cells that the injury to respiration brings about.

And imagine this: 52 years following the publication of this landmark paper and a whole three quarters of a century after Warburg’s discovery of the fermentation of tumour cells even in the presence of oxygen, was published in the journal Nature a paper entitled The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. In this paper the authors describe how they were able to manipulate the expression of this enzyme in cancer cells, and doing so, decrease fermentation while increasing oxidation of glucose.

This enzyme, pyruvate kinase, is expressed in mammals in four different flavours (isoforms): L is expressed in liver cells, R in red blood cells, M1 is by far the most dominant and is expressed in most adult tissues, and M2, a variant of M1, is expressed during embryonic development. As it turns out, and as reported by two other groups of researchers in 2005 (refs 2 and 7 in the 2008 Nature paper), tumour tissues exclusively express the embryonic M2 form of pyruvate kinase.

Expressing these results as simply as we can, the situation appears to be as follows: once a glucose molecule enters the cell through one of the insulin-mediated entry ports, it is in the cytosol. There, through a series of 10 enzyme-mediated steps, it is split in two molecules of pyruvate. This requires 2 ATP but produces 4 ATP molecules; hence there is a net production of 2 ATP. At this stage pyruvate can either be converted to lactate which then turns to lactic acid, or to acetyl-CoA which is then transported to the mitochondria to enter the Krebs cycle and the electron transport chain. This transformation of pyruvate is performed by the enzyme that is the subject of these scientists’ investigation, pyruvate kinase. It would seem that the M1 form, the one that is active in healthy cells, takes pyruvate into acetyl-CoA and into the mitochondria, whereas the M2 form, the one that is expressed in embryos and cancer cells, takes it into lactic acid.

By some clever genetic manipulation, working with tumours in rats, they were able to switch off M2 expression and switch on M1 expression in cancer cells, and measured a decrease in lactic acid production and an increase in oxygen consumption that was associated with ATP production in the mitochondria through oxidative phosphorylation. This is the remarkable result that made the paper worthy of a publication in Nature magazine. And it is indeed amazing! This is why they write in the first paragraph that based on their research, the defect is not with the mitochondria as Warburg thought, but rather it is with the expression of the enzyme pyruvate kinase that goes from the healthy M1 to the embryonic M2 form. Why or how this happens is unknown.

This is indeed very encouraging! Just the idea of being able to force the expression of the healthy M1 and suppress the cancerous M2 form of pyruvate kinase is really amazing and has very important potential implications for cancer prevention and treatment. And this even if we don’t really yet know why or how it happens. But tell me, have you ever heard of this more than critically important result in cancer research on the news? Do you think your doctor has? Or his oncologist colleagues that cut, poison and burn cancer patients day in and day out?

Our basic cancer-fighting strategy?

What can we gather from this work that can help us not just understand Warburg’s research and his remarkable contribution to humanity though it, but also avoid cancer in this world where more than 1/3 of people currently succumb to it and where cancer rates keep rising every year?

Naturally, we want to minimise as much as possible our exposure to all manufactured chemicals, especially those confirmed as carcinogenic. We are all exposed to a greater or lesser extent through our being immersed in the environment in which we live, but we can go a long way by eating the cleanest, most natural and unprocessed food possible, drinking the cleanest water possible, using only natural cleaning and skin care products, and using regular or daily detoxification strategies such as taking sodium bicarbonate and magnesium chloride baths one to three times a week, drinking psyllium husks in water to cleanse the colon, and supplementing with iodine, chlorella and spirulina daily to flush out chlorine, fluorine, bromine and heavy metals like lead, mercury and arsenic on a continuous basis. These are, in a way, the simplest and easiest preventative measures we can take to reduce as much as we can our exposure to external sources of potentially carcinogenic and otherwise dangerous substances, as well as do what we can to flush them out to prevent accumulation in our tissues.

In consideration of the two fundamental characteristics of cancer cells—that they rely on glucose fermentation, and that they live and thrive in a milieu that his highly acidic and deprived of oxygen—it is just common sense to conclude that doing the opposite of what they need and prefer would be a good strategy. Doing the opposite means minimising glucose availability and especially insulin that is ultimately the agent responsible for transporting the glucose into the cell; remember that this is why cancer cells typically have 10 times the number of insulin receptors on their surface than normal cells. Doing the opposite also means preventing the accumulation of metabolic acids in their subsequent storage in tissues, preventing latent tissue acidosis, and ensuring a plentiful oxygen supply from a highly alkalising drinks, foods and lifestyle.

The first can be achieved by eliminating all simple and starchy carbohydrates, refined or not. Blood glucose levels will drop, and insulin levels will follow suit. This will shift the metabolism towards relying on fat as the primary source of cellular fuel throughout the day and night, day after day. The cool thing is that healthy cells function much more efficiently by burning fatty acids in the sense that they derive a lot more energy than they can do from burning glucose, even if the later is easier and enzymatically simpler: it is, after all, common to all living organisms, including the most primitive. The important difference is that all evolved and highly specialised animal cells can use fat, whereas primitive or devolved cancer cells simply cannot.

The second can be achieved by keeping the body hydrated and alkaline by drinking and eating to promote the alkalisation of the digestive tract, the blood, the other fluids of the body, and thus the tissues throughout: alkaline water and pressed lemon water, highly alkaline and alkalising freshly cold pressed green vegetables both juiced and whole, and magnesium chloride and sodium bicarbonate baths. Eating plenty of unrefined sea salt is also of the utmost importance in this. These are among the most important and effective means to first pull out and eliminate stored acids from the tissues and body, and then maintain alkalinity.

The only caveat is that digestion of concentrated protein in animal food, for example, require an acidic stomach for complete breakdown and digestion. Therefore,we should not combine alkalising water, lemon water or green juice when eating protein because this will cause poor digestion and absorption. Also, because protein is very important but also highly acid-forming, it is essential to not have excessive amounts, especially in a single serving, because this will cause excessive acidification and toxicity. Restrict your servings of animal protein to about 30-50 grams per serving, and try to restrict that to one main meal in the latter part of the day (afternoon or evening).

Pretty simple, aren’t they, these two strategies that we can draw from what we have learnt about cancer up to now. We will further explore cancer metabolism, prevention and treatment in the future, looking at methods that have been and continue to be successfully used to treat cancer patients and bring them back to health, as well as important nutrients and supplements with powerful cancer-fighting and health-promoting properties. But the fact is that these two basic points that address the most fundamental characteristics of cancer cells to ensure, on the one hand, that those that do emerge one way or another cannot sustain themselves or grow due to the lack of enough glucose and insulin for their needs, and on the other, cannot readily develop from being pushed towards fermentation because the environment of the body is everywhere alkaline and oxygen rich, are probably the most effective and important measures to grasp and apply in order to remain optimally healthy and cancer-free for as long as we are alive.

In closing

Before closing I want to briefly highlight that the vast majority of effective natural cancer healing treatments are based to a greater or lesser extent on the understanding of cancer as I have presented it in this and the previous article on the subject. However, there is a truly wide range of successful treatments that are used out there in various specialised cancer treatment centres. One important point to make in regards to the consumption of simple sugars from sweet root vegetables such as carrots and beets or fruit is that several treatment protocols include these and in sometimes large quantities still with great success in overcoming cancers of various kinds. This shows us that there is definitely more to preventing and treating cancer than just eliminating simple sugars.

There is lot of tremendously interesting material to explore about cancer, a disease that has been an important cause of suffering for at least a century. A lot of this exploration will be of historical research, experiments and discoveries that either have escaped the attention of the masses and medical establishment, or been actively suppressed by various agencies and individuals intent on nurturing as substantial population of ailing people for the purpose of profiting from the treatments they would require.

As awful as this may seem, it is unfortunately the sad truth. And even more unfortunately, this is not only historical as in the case of this well documented 1921 action plan by the US government, FDA and AMA for an influenza vaccination campaign to quickly and effectively spread disease across the country and greatly stimulate the need for medical attention and case as a means to generate profits from the associated expenses, but this continues to this day. The essential conclusion to draw from this is that it is we who must care for ourselves, our children, our family members, and our friends. And to do this, it is again we who must first learn and then teach our children and each other how to best do it. This is what I strive to do and what I strive to share with you.

If you think this article could be useful to others, please ‘Like’ and ‘Share’ it.

On the origin of cancer cells – part 1

On February 24 1956 was published in the journal Science a remarkable and exceptional paper by an equally remarkable and exceptional scientist. The paper was entitled On the Origin of Cancer Cells, and the author was the winner of the 1931 Nobel prize for Physiology or Medicine, Professor Otto Warburg.

otto-warburg-old-highresfaceshot

Professor Otto Heinrich Warburg (1883-1970)

After more than 50 years of research on cellular respiration, metabolism and physiology, Warburg had identified, understood, demonstrated and now explained the mechanisms by which cancer cells develop, survive, spread and proliferate, and what, at the most fundamental level, distinguishes them from normal cells.

It is my intention to relate the essence of these results, together with the necessary background, as clearly as it is possible for me to do with the hope that you will remember it well. This is without any doubt one of the most important and far-reaching results of medical science in its entirety. Such is the importance of this work, that it may well be the most important bit of medical science I will ever write about and that you will ever read about. But although this is so, it can be stated in a single sentence.

The truth about the origin of cancer is that despite the numerous carcinogenic agents, those identified as such and those still unknown, and despite the numberless forms and tissues in which cancer can manifest itself, there is only one fundamental cause of cancer at the cellular level: injury to respiration by damage to mitochondria.

Biological energy

The mitochondria, independent micro-organisms with their own metabolic and reproductive systems living symbiotically with the other organelles inside the cell, could be considered as the most important of the organelles because it is the mitochondria that normally produce the energy (in the form of adenosine triphosphate or ATP) on which each cell, and therefore also the entire organism, rely for function and survival.

Each cell must produce the energy it needs to sustain its activity and maintain its structure, and each cell cares only about itself: it knows only what it must do and what it needs in order to keep itself alive in the best possible condition and health that it can manage through continual adaptation. The way it knows anything else outside of itself is by sensing its environment, its immediate surroundings, through the various sensors (biochemical receptors) and doorways (ionic channels) in its walls (the cell’s outer double-layered membrane).

Cells can produce energy using glucose (from carbohydrates), amino acids (from protein) or fatty acids (from fat). By far the most effective way to do it is through burning fatty acids. This produces the most energy and no acidic byproducts. This is therefore a normal cell’s preferred fuel.

There are two intervening factors, however, that make it rather rare for humans to function primarily on energy derived from fat. And although this is true today, it wasn’t for the bulk of our evolutionary history during which all species of homo must have derived most, and probably often even all, of their energy from fat. The first and most important of these factors is that today, we tend to get most of our calories from carbohydrates.

Because it is easier for cells to breakdown and use the much smaller and simpler glucose molecules than it is to use the longer and more complex fatty acids, while there is enough glucose in the bloodstream, it will always be used preferentially, and eventually almost exclusively, as the cells grow insulin-resistant and become unable to use fatty acids almost completely. In such a metabolic state, because protein can relatively easily be converted into glucose, this is what the body does when it runs out of glucose, because, from the lack of practice, it cannot access the fat stores. Therefore, due to insulin resistance, fat just keeps accumulating, stock piled in ever larger and distended fat cells throughout the body, and never used to make energy for the now struggling, energy-starved cells.

The second factor is strictly physiological, and relates to the fact that it takes longer to oxidise fat than to oxidise glucose, and even for glucose, it takes about 100 times longer to oxidise inside the mitochondria than it does to process it anaerobically (without oxygen) in the protoplasm, the general space within the cell, outside the mitochondria. For this reason, in circumstances where the cell needs ATP quickly (in lifting weights or sprinting, for example), it will need to use this super fast energy production mechanism in addition to the slower oxidation in the mitochondria, with proportions that depends on the energy demand.

All ATP production using glucose begins with its breakdown into something called pyruvate. This is called glycolysis (or substrate level phosphorylation). It takes place whether there is oxygen available or not, and does not involve the mitochondria because it takes place in the protoplasm. Glycolysis involves 10 steps each of which requires the action of specialised worker proteins (respiratory enzymes). From this process the cell derives two molecules of ATP. Pyruvate is the main product, but the process also leads to the production of lactic acid and hydrogen ions.

At this point, the pyruvate can be carried to the mitochondria where through a much lengthier and vastly different process (oxidative phosphorylation), which in this case relies on an ample supply of oxygen, the mitochondria can produce up to an additional 34 ATP molecules (this is the case in aerobic yeasts), for a total of 36 counting the first two from glycolysis.

In practice, factoring in some metabolic inefficiencies in the process, the result is probably somewhere around 28-30 molecules of ATP for our cells. This is nonetheless a lot of energy—15 times more than from glycolysis alone—that can be derived from a single molecule of glucose. Bear in mind, however, that gram for gram, fat can produce six times more energy than glucose, raising the total to around 200 molecules of ATP, and this without producing acidic byproducts.

Aside on the use of words and names as symbols

Before going any further, I want to bring your attention to something important, generally unrecognised, but essential to our understanding and perception of the world and everything we come into contact with. It is language, complex language, symbolic language, that allowed a small subgroup of Homo Sapiens to first distinguish themselves from all other animals and also from all other species of Homo, and then spread across the continents and come to dominate almost every ecosystem on the planet.

The more language is refined and the more thorough is its mastery, the more complex cognitive processes become and the more subtleties of understanding can be both expressed and discerned. There is a major problem, however, that comes about in every language-using person, and this is that the symbol used to refer to something, the word, is unconsciously taken to be the same as the object to which it refers. Furthermore, not only is the object treated as an entity on its own, a thing that does not depend on anything else to be what it is (which, of course, it does), but the word also becomes a thing unrelated to other words that are different in appearance and sound.

This is a serious problem for understanding complex processes. And it is particularly relevant in this discussion here. We must remember that even if we are talking about all sorts of different things like glucose, amino acids, fats, pyruvate, enzymes, mitochondria, organelles, and on and on, that these are all words, symbols that we use to identify molecules and little beings like mitochondria that do not possess language, and further, that do not care at all what we call them.

It is best to view this whole business of processes at the cellular level as a ceaseless dance where atoms mostly of carbon, hydrogen, oxygen and nitrogen with a few others here and there, combine into molecules that are manipulated by proteins into other molecules, sometimes simpler and sometimes more complex, the change sometimes being unidirectional and sometimes a reversible state change going back and forth, everything depending everywhere on the characteristics of the environment, the stage, in which this dance is taking place. And that all of this takes place totally unaffected and independently from any of the names we have for any of its characters and dancers.

So don’t be fooled by the words and names in thinking that because the names are so different they are referring to inherently different things. This is not so. Words and names are just words and names. We use them to express ourselves, but must not be moved to believe that they are referring to entities having a life of their own, interacting in a world of things where every thing bounces against every other thing. This is just wrong, and it is highly misleading: clearly misleading in the realm of cellular biology, which is our immediate concern in this article, but also misleading in our everyday, which should definitely be of concern.

Back to cellular respiration

Cellular respiration (oxidation in the mitochondria) requires oxygen. If for any reason there is not enough, the cell uses a backup method to sustain its energy needs. This happens when the energy demand is so great that the cell cannot wait for the mitochondria to produce the additional ATP (as mentioned above under extreme exertion), but also if there is simply a lack of oxygen for any other reason, whether it is acute, like from exposure to a large enough amount of a respiratory (mitochondrial) poison or during an asthma attack, or chronic, like when we spend our days in an office building with recycled air where levels of oxygen are lower and carbon dioxide higher than they should ideally be, but not quite enough to become a problem noticeable by a critical number of people. In such cases, instead of being brought to the mitochondria, the pyruvate can be used as the oxidative agent by the respiratory enzymes to ferment the lactic acid, and recondition the NAD so that it can engage again in the breakdown of another molecule of glucose into pyruvate. (We’ll come back to the details of this another time.)

Essential to remember is that for a normal cell this is the solution of last resort when there is not enough oxygen, and that animal tissues suffer serious damage when deprived of oxygen for an extended time, where ‘extended’ here is on the timescale of cellular processes, which for us is very short—on the order of minutes.

Anyone who has done all out sprints with high resistance on a bike, or bench pressed a heavy weight to muscular failure, knows the feeling associated with the muscles being unable to respond to the load. This is because the cells are starved of oxygen and overloaded with acid. Under extreme exertion, lactic acid fermentation for ATP production dominates from about 10 to 30 seconds, and muscular failure follows within 30 to 60 seconds.

Struggling to survive

As we’ve seen, there are two major differences between these processes of using glucose for energy production. The first is that for one molecule of glucose, complete oxidation produces around thirty molecules of ATP, whereas glycolysis or fermentation produces only two. The second is that oxidation occurs inside the mitochondria, whereas fermentation, sustained by respiration enzymes, takes place outside the mitochondria. Therefore, it is both the quantity and quality of the energy that is degraded.

Also as we’ve seen, a normal cell under normal circumstances sustains itself—both in function and structure—by relying on the energy produced by the mitochondria, whether by oxidation of glucose (pyruvate) or fatty acids, and only ever use fermentation for energy balance adjustments in exceptional circumstances. If, however, for any reason at all, even a small number of the mitochondria in the cell get damaged, a serious problem arises because the injury makes the cell incapable of producing the energy it needs for proper function, maintenance and repair.

If the damage is severe, the cell will die, and will, if things are running relatively smoothly, be broken down, cleaned up, excreted and replaced by a new one that will take its place. If the damage to the mitochondria is not so severe, the cell will not die, but will be crippled in its energy-producing capacity, the mitochondria will not be able to produce all of the ATP the cell needs, and this will force it to use fermentation to top up its energy requirements.

Unfortunately, the injury to the mitochondria’s genetic code will not only be passed down from the damaged parent to the next generation, but will lead to an irreversible degradation of mitochondrial function with each transcription and reproduction into each successive generation of these vital organelles. With each generation, the mitochondrial function is degraded further and the energy deficit grows.

As a consequence, the growing energy deficit is compensated by increasing ATP production from fermentation. But the energy from fermentation is not just less plentiful, it is also of a much lesser quality compared to that resulting from proper aerobic respiration involving the mitochondria, and it simply cannot maintain the structure and function of the cell. Thus, the cell degrades. Everything about the cell degrades as it struggles for survival.

The evolution in the ratio of energy produced by respiration to that produced by fermentation, initiated by the damage to the mitochondria and driven by the cell’s striving to maintain energy balance, is in fact a devolution from a finely tuned energy production system of a highly refined and specialised cellular structure and function, to a primitive energy producing mechanism and a coarse and severely degraded cellular structure and function akin to what we see in yeasts and fungi.

The birth of a cancer cell

Degradation and devolution continue until fermentation energy is enough to fully compensate the loss of respiration. It is at this point that we witness the emergence of a cancer cell. And it is now a perfectly functional and healthy cancer cell that has lost enough of its original characteristics, both structural and functional, to begin a programme of its own, intended to increase as much as possible survival probability in its new and partially self-generated environment that should ideally be high in glucose—as high as possible, low in oxygen—this is preferred but not critical, and highly acidic—cellular pH as low as 6 or even less and extracellular pH potentially significantly lower.

Although these terms, birth and emergence, are powerful and very useful in conveying a vivid imagery of a developing process that eventually reaches and overcomes a critical threshold as it is the case here, it is not really a birth or an emergence as much as it is a metamorphosis, gradual and typically very slow, taking place over decades if not over most of a person’s lifetime, with a continual and intimate dependence on the biochemical makeup of the environment surrounding the cell, and surrounding each and every cell throughout the body, from hair, scalp and skin, to fingers, fingernails, toes and toenails, from mouth to colon, from brain to liver, from breast to uterus, from throat to prostate, and from and to everything else that constitutes the entire human organism inside and out.

Over this long struggle for survival, because this is truly what it is, the cell is at first forced to generate supplemental energy from fermentation to make up the small difference that the slightly damaged mitochondria cannot. This increases the level of acid inside the cell. Because every enzyme-mediated biochemical process that takes place—and that indeed has to take place—is sensitively pH-dependent, all are instantaneously affected negatively by this acidification and drop in pH.

Moreover, increased acid translates directly into lack of oxygen, which further stresses the mitochondria, making their oxidation of glucose and fatty acids more difficult and less efficient. This in turn leads to a further degradation of the mitochondria, cell structure and function, an increased reliance on fermentation energy, a rise in acid levels, and a drop in oxygen availability: clearly a vicious cycle—a very vicious cycle.

Because ATP production is so much less efficient through fermentation than through respiration, the cell needs much greater amounts of glucose. This forces it to develop a greater sensitivity to it, which forces the formation of more insulin receptors because it is insulin that carries the glucose through the cell wall. And it is, in fact, the case that cancer cells typically have about ten time more insulin receptors than normal cells, and that this makes them ten times more capable of grabbing hold of circulating glucose to sustain themselves. But again, remember that this is yet another adaptation in a struggle for survival without which the cell would die.

Questions, questions and more questions

There is quite a lot more that needs to be addressed and explained. General questions like: How did Warburg figure all this stuff out? And what else did he discover? Specific questions like: Are cancer cells weaker or stronger, more fragile or more resilient? What is it that fundamentally distinguishes them from normal cells? And why does it sometimes take an entire lifetime but at other times just a few years to grow a cancerous tumour? Epidemiological questions like: Why is cancer spreading? Why does it appear more and more in young people? And why does it tend to not only develop but intensify with each generation along family lines? Finally, from all of this detailed information and knowledge, wouldn’t we like to know if there is something to do to prevent or cure cancer? Wouldn’t we like to know what that is: what we can do to prevent and cure it? Of course! That’s our main goal, isn’t it?

We will look at all of these issues and more together, but now I can’t help wonder if the following question, this multi-billion dollar question, might have popped up in your mind while you were reading, as it did for me when I read Warburg’s paper: If he, and by extension, we, as the community of thinking human beings, had understood, explained and demonstrated how cancer arises and then develops in 1956 already, why is it that today, almost 60 years later, cancer rates continue to rise every year, cancer cases appear in people at an increasingly younger age every year, and cancer claims the lives of more people every year than it has ever done? How can this be, and why is it so? Hasn’t anybody else looked at his research and reproduced the results? Haven’t we got today much better instruments and technical means of verifying everything he presented throughout his long career? Don’t worry. We’ll definitely look at that too.

If you think this article could be useful to others, please ‘Like’ and ‘Share’ it.