Fasting for renewal and rejuvenation

Fasting stimulates autophagy, mitophagy, stem cell production, detoxification, mitochondrial biogenesis, neurogenesis, and neuroplasticity. Fasting also down-regulates muscle catabolism and up-regulates growth hormones to preserve muscle tissue. Because all of these are crucial for health and youthfulness, but tend to decrease rapidly with age, regular fasting is by far the most effective way to naturally slow down ageing and prolong health.

Autophagy means self-eating but refers to the breaking down and removal of damaged tissues, cells, and cellular component to reuse the molecules of which they are made to build new, healthy cells and tissues.

Mitophagy is the same but for mitochondria. Those damaged and dysfunctional are broken down into their constituents to be made available for rebuilding new ones, which is called mitochondrial biogenesis. Fasting is the most effective way to stimulate autophagy and mitophagy primarily through activation of a special enzyme, Adenosine Monophosphate-activated Protein Kinase, or AMPK for short. Fasting also increases production of nerve growth factor that stimulates the growth of new brain cells, no matter how old you are.

Stem cells have as their main purpose to repair tissues. Stem cell activity is highest in embryos and babies, and steadily decreases with age. Stem cell regeneration is strongly stimulated by fasting, but it’s uniquely related to the burning of fat for fuel, and not to the fasting itself. We know this because genetically switching off fat-burning in fasting mice stops stem cell production.

Detoxification takes place through the release of toxins from tissues. Biological survival mechanisms have evolved to sequester into fat cells chemicals and heavy metals from the bloodstream, and isolate them from damaging more sensitive and biologically active tissued and organs in the rest of the body. When fat cells split open to release the energy stored in the fatty acids they stockpile, these toxins are released into circulation for elimination.

Neurogenesis refers to the making of new neurons (brain cells), and neuroplasticity refers to the creation of new synaptic connections and nerve flux pathways in the neural network of the brain. This is without a doubt one of the most remarkable benefits of fasting.

brain-bright

(Image credits here)

All of these biological mechanisms have deep evolutionary roots. We know this because they are common to the most complex (and thus most recent), and to much simpler (and thus much older) organisms. It is most likely in these deep evolutionary roots that the remarkable healing power of fasting comes from.

Autophagy, mitophagy, stem cells, and ketones

Fasting stimulates the breakdown dysfunctional proteins and cellular components, the preservation of active muscle tissue, and the rebuilding of new proteins and cells upon refeeding. (Read here an excellent article by Dr Jason Fung on the up-regulation of muscle preservation during fasting.) The acute stress of vigorous exercise, especially of strenuous resistance training, stimulates autophagy in much the same way as fasting does. Both stimulate mitochondrial biogenesis. Does this sound inconsequential to you? It really isn’t.

First, the accumulation of damaged cells and cellular debris can be equated to senescence. And senescence can be equated to death. Or rather, the accumulation of death in the body. Death, in this sense, is not really binary, it’s not like one moment we are alive, and the next we’re dead. It’s much more like we accumulate, over time, dead and dysfunctional cells, dead and dysfunctional mitochondria, dead and dysfunctional organelles. Little by little they accumulate, but there’s a threshold. There’s a point beyond which no more death can be accumulated inside the body. And when that threshold is reached, life can no longer be sustained. This is when we die. We call this ageing. The slowing down of things, the loss of energy, the loss of vitality, the loss of strength and flexibility, and the loss of mental acuity and intelligence. But it is, in reality, nothing other than the gradual the loss of life through the gradual accumulation of death.

Second, mitochondria are the source of all the energy that is produced and made available to the body. The mitochondria in the cells produce ATP (adenosine triphosphate), the energy currency for all cellular operations and transactions. And no matter how you look at it, every last little bit of energy that is needed to do anything at all comes from these mitochondria in the cells throughout the body. A tiny drop or increase in energy production in the mitochondria would result in a massive effect on your strength, speed, endurance, resilience, but also concentration and sharpness of mind. Why?

Because there are around 30 trillion cells, and most have between 1000 and 2500 mitochondria each. That makes tens of thousands of trillions of mitochondria. The average cell uses 10 billion units of ATP per day, which means an average adult needs about 3 x 10^25 units of ATP per day. Now you can imagine what happens if the ATP production per mitochondria drops or increases by a tiny fraction, say of just a thousandth of a percent. Because there are so many mitochondria, the magnitude of the effect would be enormous.

Do you remember the “blues and greens” that Jeremy Renner and the other agents carried in little aluminum cases around their necks in the Hollywood film The Bourne Legacy? Remember how much they enhanced both physical and mental performance? This is what these little pills’ main purpose was: to increase mitochondrial energy production efficiency.

We don’t usually think about it in this way, but we should. Doing so, we would understand how important it is to support the body in cleansing and clearing out damaged tissues and cellular components so that they don’t accumulate. And we would also understand how important it is to support the body in rebuilding new, healthy cells and mitochondria to maintain optimal function for as long as possible.

Stem cells everywhere in the body appear to love fat-burning. Because fasting triggers fat-burning in basically every cell of the body, it also triggers an explosion in stem cells activity. It is this explosion of stem cell activity that powerfully stimulates tissue repair and regeneration throughout the body’s tissues.

Ketones are produced in the liver by transforming free fatty acids into beta hydroxy butyrate and acetoacetate through beta-oxidation. Ketones are the preferred fuel for the brain and heart, because burning ketones to generate energy (ATP) produces much fewer reactive oxygen species (free radicals), and thereby significantly reduces oxidative damage to the muscle cells in the heart and the neurons in the brain. Isn’t that so amazing?

The relationship between nutritional ketosis and fasting is simple: the brain is one of if not the most crucial organ because it regulates and coordinates almost everything that happens in the body; the metabolic activity of the brain can be fuelled by glucose or ketones; as blood glucose concentration drops and thus becomes less abundant, ketone production in the liver increases to ensure an adequate supply of fuel to the brain. Glucose levels naturally drop within a few hours, even after a carbohydrate-rich meal, due to the action of insulin. Fasting lowers and maintains low blood glucose levels over significantly longer periods of time. Therefore, in general, the longer the fast, the more ketones are produced, and the more are in circulation in the bloodstream.

Burning ketones for fuel stimulates the production, within cells, of antioxidants like superoxide dismutase (that transforms the superoxide radical into molecular oxygen and hydrogen peroxide), and catalase (that breaks down peroxide). Both the superoxide radical and the hydrogen peroxide molecule can cause many types of cellular damage if not neutralised or broken down as early as possible. So, the more ketones available, the more cellular superoxide dismutase produced, and the less cellular damage from free radical damage sustained. Isn’t this amazing?

Ketones also stimulate the production of adenine dinucleotide phosphate (NADPH) and NAD coenzyme that recharge antioxidants like glutathione, ubiquinol, and vitamin C to a functional state. Major functions of NADPH include recharging antioxidants; providing electrons for the synthesis of fatty acid steroids, proteins, and DNA; and acting as the substrate for NADPH oxidase (NOX) which plays a key role in immune function. 

MCT oil and caprylic acid, both derived from coconut oil, are directly and easily converted to fuel and ketones by the liver to fuel brain and heart, and that will therefore bring your lucidity and clarity of mind and thinking. For this reason, they are excellent supplements to take in the morning and during the first part of the day, but should be avoided in the evening because they can lead to hyper-alertness and interfere with a restful sleep. MCT oil shouldn’t be used in case of liver disease.

Nutritional ketosis improves insulin sensitivity, stimulates fat loss, improves mental clarity, reduces risk of cancer, and increases longevity. It reduces cellular damage and inflammation through much lower free-radical and inflammatory cytokine production.  And it also increases cellular and tissue repair by stepping up autophagy, mitophagy, and stem cell activation. All of these benefits are consequences, direct and indirect, of sustained low glucose and low insulin levels, and of the derivation of cellular energy from fats and ketones rather than from glucose. In short, nutritional ketosis is amazingly—actually almost supernaturally—good for you.

Toxins and Detoxification

We are all exposed to many toxic chemicals. No matter where we live, and no matter what we do: mold toxins; heavy metals like Hg, As, Pb, Cd from air, water, and food; arsenic (As) from pressure-treated wood, electronics, herbicides; lead (Pb) from gasoline, water pipes, paints; cadmium (Cd) from fertilizers; copper (Cu) as a by-product of many industrial processes that builds up in soil and water; pesticides and herbicides like glyphosate; PAH (polycyclic aromatic hydrocarbons) produced from the combustion of fossil fuels; BPA (bisphenol A) and phtalates used to make plastics; dioxins and dioxin-like (PCBs) from industrial chemical processes; heterocyclic amines from grilling at high heat; hexane, a neurotoxic chemical used to extract more oil from nuts and seeds (including coconut). The list goes on and on.

These are in the soil, in the food, in the water, and in the air. They are also in the soaps, shampoos, creams, makeup, and the countless number of chemical cleaning agents manufactured and sold the world over that we use in our homes. Obviously, the more of them you avoid direct exposure to the better. Consuming toxin-free food as much as possible, and using the simplest and most natural household and personal care products is an essential first step. But if embryos, as protected as one could ever be deep in a mother’s wombs and behind several layers of protective membranes and mechanisms, are known to accumulate toxins, then what about us?

Most of these chemical toxins are fat-soluble. The biochemical processes that have evolved to transport and isolate environmental toxins, whatever they may be, into fat cells is a remarkable survival mechanism that has without a doubt played an important part in allowing living organisms to evolve over the past 3.5 billion years into increasingly more complex plants and animals. However, the Industrial Revolution led to an explosion of human-made chemicals into the environment the pace of which has never ceased to increase.

Did you know that strawberries contain a fibre called fisetin that help remove and eliminate senescent cells from the body, which is essential for prolonging health? But did you know that they are also some of the most chemically contaminated foods together with spinach, nectarines, apples, grapes, peaches, cherries, pears, tomatoes, celery, potatoes, bell peppers? Among the least contaminated are avocados, sweet corn, pineapple, cabbage, onions, sweat peas, papaya, asparagus, mangos, eggplant, honeydew, kiwi, cantaloupe, cauliflower, and broccoli.

In the past four decades only, more than 85 thousand different chemicals have been released into the environment. And the amount has only increased with time. One of, if not the most dangerous is Monsanto’s infamously well-known glyphosate because it is the most heavily used broad-spectrum herbicide of all time: from 1974 to 2016, soils, waters, plants, and animals have absorbed 1.8 million tons in the US alone, and 9.4 million tons worldwide.

Since 1974 in the U.S., over 1.6 billion kilograms of glyphosate active ingredient have been applied, or 19 % of estimated global use of glyphosate (8.6 billion kilograms). Globally, glyphosate use has risen almost 15-fold since so-called “Roundup Ready,” genetically engineered glyphosate-tolerant crops were introduced in 1996. Two-thirds of the total volume of glyphosate applied in the U.S. from 1974 to 2014 has been sprayed in just the last 10 years. The corresponding share globally is 72 %. In 2014, farmers sprayed enough glyphosate to apply ~1.0 kg/ha (0.8 pound/ acre) on every hectare of U.S.-cultivated cropland and nearly 0.53 kg/ha (0.47 pounds/acre) on all cropland worldwide. (Environmental Sciences Europe, 2016, 28:3)

Our fat cells are the body’s chemical storage facility. The more of them there are, the more chemicals can be stored. The less body fat there is, the less chemicals are stored. And if your storage unit is full, then no matter how hard you try, you won’t be able to add another piece of furniture. This is also true for the body’s chemical storage capacity.  This is both good and bad, but for different reasons.

More storage allows the organism to survive and function even in the face of significant chemical contamination. But the more chemicals are stored in the body’s fatty tissues, the more the organism as a whole becomes contaminated, and the less able it becomes to function optimally. A large dose of chemical exposure, say from a chemical leak, would require a large fat storage capacity in order to prevent overwhelming the rest of the body’s organs and systems. In such circumstances, someone with more body fat would be better off than someone with less.

But for most of us, this kind of acute exposure from a chemical accident in our near vicinity is not much of a concern. Moreover, you shouldn’t imagine that because chemical toxins are stockpiled in fat cells to minimise exposure in other tissues that they have no effect. Does burying radioactive waste makes it innocuous? It makes it a lot less dangerous and damaging, that’s for sure. But only in the short term, and to some extent, because the radioactive wastes leak out into the soil and the ground water.

The same is true for the chemicals stored in our fat cells. The storing of them protects us from the major toxic effects of direct and large scale exposures, but there is some leaking of these toxins out into the system, especially over time, and as our storage tanks get full. In general, therefore, this is what we should be concerned about: the low-grade chronic exposure and its long-term effects. And the less fat storage, the less chronic exposure there will be.

Fasting regularly and smartly, is the best way to both clear out the storage tanks, and  shrink the overall storage capacity for chemical toxins, thus minimising the amount of leaking taking place on a day-to-day basis. So, here’s what we need to know about this:

The more access to fat stores for fuel, the more toxins are mobilised and released from the tissues. This is what we stimulate in the most efficient manner when we fast, because the body needs to sustain all of its cellular processes by burning fat for fuel. But fat loss releases toxins in bloodstream. And this is good because toxins are mobilised.  Detoxification, however, must be supported in order for the toxins to be excreted. Otherwise they are released into circulation and can be very damaging. It is for this reason that water fasting is in general not a great idea: it releases too many toxins too quickly, and offers no mechanisms for bindings and eliminating them.

Once toxins are liberated, they must be bound to something in order to be eliminated. To be liberated, toxins are first made water soluble by the addition of a hydroxy (OH) radical. This is essential for elimination, but it makes the toxin more reactive. In a second stage, the now water-soluble but reactive toxin, is conjugated by the addition of a methyl, sulfur, or acetyl group, or else of an amino acid like glycine or glutathionine, in order to be made less reactive. After this, it is transported out of the cell to be eliminated through urine, sweat, or stools.

The detoxification process is supported by facilitating urination (drinking more); facilitating passive sweating (sauna, near-IR is best); eating cruciferous vegetables (broccoli, cauliflower, cabbage, Brussel sprouts, and kale); and supplementing with toxin binders (activated charcoal, chlorella, chitosan, psyllium husks, and citrus pectin). Actually, fat regain following fat loss, something which is very common, is almost certainly a protective mechanism to sequester the toxins that were released but not eliminated. And sweating has to be passive, because exercise suppresses detoxification: the system can be either in fight-or-flight or in rest-and-repair mode; exercise is associated with the former.  

Effective detoxification depends on healthy intestinal function. A compromised gut lining allows toxins from the foods or process of digestion to enter the bloodstream. This leads to chronic inflammation and a chronically triggered immune system that eventually results in autoimmune conditions. Fasting reduces gut permeability by enhancing integrity of gut lining: it induces a metabolic switch to fat-burning in the intestinal stem cells that significantly enhances their function, and promotes the healing of the junction between gut lining cells, as well as gut flora diversity.

Resistant starches are good because they feed the gut bacteria, and do not break down into glucose. They are found in under-ripe bananas, papayas, and mangos. Most notable is that if rice is cooked with coconut oil, allowed to cool for 12 hours, and reheated, it will increase in resistant starch by a factor of 10! This reduces calories that would be absorbed from the starch going to glucose by 60%! This simple preparation of the rice turns it from a damaging high-sugar food to avoid, into a beneficial prebiotic. Quite amazing, isn’t it?

How to fast: first steps

Now, before going any further, you should not fast if you are underweight or malnourished; pregnant or breastfeeding; or if you have excessively high uric acid levels. Fasting while underweight or malnourished will exacerbate the negative consequences of the malnourishment. Fasting while pregnant or breastfeeding will release toxins that could potentially be highly detrimental to the baby. And because fasting naturally increase uric acid levels due to the process of cellular cleaning, it could, if starting from an already excessively high concentration, be damaging to the organism. Otherwise, fasting will in general be very beneficial.

First, because fasting strongly influences the regulation of the circadian rhythm, and because one of the most important functions of sleep is to clean out the brain from the byproducts and wastes of its metabolic activity during the waking hours, we should never eat during the night, and always allow at the very least three but preferably four to five hours from our last bite to the time we go to bed. This is necessary to set the conditions for a deep, restorative sleep that keeps our brain in good shape. This is true independently of everything else. So, you can start doing this right away without even having to do any prolonged fasting.

Second, in order to avoid a negative impact on your mental and physical performance during the fast, the body should be adapted to using fat for fuel before you start fasting. You will feel shitty otherwise. I have written two articles that relate to this: Keto-adaptation for optimal physical performance and The crux of intermittent fasting. You should read both. It’s important to understand the biochemical and physiological foundations of why we do things in a particular way. Otherwise, we will lack the intellectual understanding on which depends our ability to make informed choices, but also out resolve to see them through.

Third, in order to have a smooth transition to longer fasting periods, you need to increase your fasting window gradually: to gradually increase the time between your last bite in the evening, and your first bite the next day. Let’s say your sleeping schedule is near optimal, sleeping from 22:00-23:00 to 7:00-8:00. Let’s also assume that you make sure you leave 4 hours before going to bed so that you have your last bite of food around 18:00. Everyone should fast for at least 12 hours. That’s the minimum to aim for, and it requires very little effort.

It would be much better to fast for at least 14 hours, in which case you would wait until 9:00 before having any food. A 16-hour fast would bring you to 11:00 for a late breakfast or early lunch. An 18-hour fast would have you eating lunch at 13:00. And a 20-hour fast means you would be having your first meal around 15:00. Take as long as you need to gradually go from the minimum of 12 hours to at least 16, 18, or even 20 hours.

When you can do this, you will know for sure that your metabolism is well fat-adapted, that your liver is producing ketones efficiently to nourish your brain during fasting periods, that the coarsest detoxification has to a great extent taken place during those weeks or months you have been adapting to longer fasting periods, and that you are now ready to extend your fasts to 24 or 36 hours once in a while, or as much as a couple of times a week. It is far more beneficial on the long term to fast for shorter periods of time every day, then it is to fast for a longer time less frequently. Because each time we fast and then refeed, we activate and benefit from the health-promoting and youth-enhancing mechanisms of the body.

Eating protein activates the mTOR (mammalian or mechanistic target of rapamycin) pathway, which is a powerful catabolic (tissue breakdown) that raises blood sugar levels. Hence, in general, we should keep protein intake to the optimal minimum for our needs. That’s something like this:

  • Young: 1g/kg of lean body mass per day
  • Older: 1.2g/kg of lean mass per day
  • Athletes: 1.5g/kg of lean mass per day

It’s important to remember that beyond the minimum optimal amount, protein intake should be adapted to level of activity: more activity means more protein, and less activity means less protein. Once you are well fat-adapted—after about 8 weeks on a very low carbohydrate diet—you should make a point of having a high fruit and/or starch day once a week. This will ensure that you maintain metabolic flexibility and a perky insulin response. Long term nutritional ketosis can lead to a sluggish insulin response, higher-than-optimal glucose levels and thus glycation, and otherwise unwanted biochemical and hormonal adaptations, which will prevent fat-loss and promote muscle breakdown. Variety stimulates metabolic flexibility.

But make sure it’s clear to you what this means: it means staying in nutritional ketosis for at least 5 days per week. And having a high-carb day means having between 100 and 150 g of sugar/starch from fruit, sweet potatoes, or rice. You should also make that high-carb day a low-fat day. In addition, digestion quality must remain your top priority. This means having your fruit or starches on their own as much as possible, and avoiding combining them with a lot of protein, which will compromise the digestion of both.

How to fast: specifics of keto-fasting

Very importantly, clearance of damaged cells and cellular debris or damaged organelles takes place during fasting, but rebuilding of organelles, cells, and tissues, most notably liver rejuvenation, occurs during refeeding.

Ketofasting following Dr Joseph Mercola’s method is partial fasting lasting ideally around 24 to 36 hours and up to 48 hours. It starts after the last meal of the day, extending over the course of the day following that, either ending with a meal 24 hours later; extending through a second night and ending at the start of the next day for the 36 hour fast; or extending 48 hours to latter part of the day. We saw why water-fasting is not something most of us should be doing in this day and age, and why it’s important to support the detoxification process while fasting. This requires some inputs: it requires protein (amino acids), mitochondrial support, and toxin binders.

The notion of breaking a fast is often taken as binary: we are either fasting or we are not. To some extent this is true. But in many ways it is not. It depends a lot on what it is that we ingest. The essential point is that the benefits of fasting come from maintaining very low blood sugar levels, remaining in nutritional ketosis, and therefore keeping the body in a cleanse-detoxify-repair mode.

Hence, there is a big difference between ingesting a teaspoon of coconut oil or a teaspoon of honey: both provide some calories, but the former supplies only fatty acids that actually promote nutritional ketosis, while the later supplies only simple carbohydrates that will immediately raise blood sugar levels and suppress ketosis, albeit temporarily, and more or less, depending on several other factors defining the body’s metabolic state and efficiency. So, in this regard, it’s better to think of fasting as grey rather than strictly black and white. Naturally, it’s really not an issue to have cucumber and celery with salt, for example.

Protein intake, needed to support the detoxifications processes, should be about half of your daily requirement, for example, 45 g instead of 90 g for 60 kg of lean body mass exercising 3-4 per week. During fasting, protein should not be branched-chain amino acids (BCAAs) nor animal protein rich in BCAAs, because they activate the mTOR pathway that inhibits autophagy. The rest of the calories should be from fat to reach 300-600 kcal from coconut oil, MCT oil, or caprylic acid. Even small amounts of 85% chocolate for which each 10 g square provides 5.3 g of fat, 0.8 g of protein, and 1.5 g of sugar, amounting to 62 kCal of which 48 are from fat, 3.2 from protein, and 6 kCal are from sugar. These are all considered supplemental levels.

In fact, because the purpose of eating protein is to supply amino acids in support of basic functions and detoxification, it is most effective to replace protein intake by an amino acid supplement. And because converstion of protein to amino acids is at most 1/3 efficient, meaning that the highest quality animal protein (e.g., beef) will yield at most 1/3 of its amino acid contents once digested, we can replace 45 g of protein by 15 g of amino acids. Splitting this intake into 4 doses of 4 g each makes for a good rhythm of taking these every couple of hours over 8 hours or so. And they can be taken together with the chlorella and spirulina supplements as well as the phospholipids.

Even though exercising suppresses hunger due to the increase of stress hormones, unfortunately, it also suppresses detoxification. For this reason, you shouldn’t do strenuous exercise on fasting days. Focus on rest and repair.

Supplements to support autophagy and toxin elimination include:

  • Ubiquinol 100-150 mg twice to support mitochondrial energy production, regulate gene expression of processes related to inflammation, growth, and cellular detoxification.
  • Phosphatidylcholine and broad spectrum phospholipid to support rebuilding and thereby eliminating chemicals from cell membranes, especially in the brain.
  • Probiotics (not dairy-based) to help rebuild/balance gut flora if digestion is suboptimal. Keep in mind that the natural flora of the gut is adapted and adapts according to food and drink intake, as well as to the daily rhythms.
  • Bitters to support the liver in cleansing and elimination (e.g., Dr Shade’s Liver Sauce by Quicksilver Scientific; Swedish Bitters by Flora or by Maria Treben; herbs like Gentian, Dandelion, Goldenrod, Myrrh.)
  • Binders to support elimination of toxins, all to be taken on an empty stomach to not interfere for nutrient absorption in the gut:
    • Psyllium husks (1 tbs 1-2 times/day) stirred into a large glass of water—binds to stuff in gut to eliminate in stools;
    • Charcoal capsules (3 caps 1-2 times/day)—binds and removes pathogenic bacteria, Pb, Hg, and excess Fe;
    • Chitosan (2-3 g)—binds and removes heavy metals and radionucleotides;
    • Modified citrus pectin (5 g 1-3 times/day)—binds and removes dead/weak cells;
    • Chlorella—binds and removes Hg, but also provides a balanced plant protein.

Refeeding is as important as fasting, because this is when the rebuilding takes place. It is very important to remember that. Unless you are overweight and carrying around a lot of energy reserves in the form of extra body fat, intermittent fasting is not a matter of replacing three meals with only one. You need to provide the body with all the energy, macro and micro nutrients it needs to thrive. This remains true under all circumstances. Therefore, you need to make sure to not fall into the trap of eating 1/3 of what you normally would, and grow thinner and  thinner with time. That is not the point, and is obviously not sustainable in the long term. You need to provide the bodymind all the nutrition and calories it needs. The key is that this is true on average: If you don’t eat for extended periods of time, you naturally need to eat more when you do.

Concluding remarks

As time goes on and as our technological means of detailed investigations at the cellular level improve, we discover more and more amazing health-enhancing mechanisms through which fasting acts on the organism to make it stronger, more resilient, more functional, and more youthful.

But beyond all the super cool details about the mechanisms by which fasting works its magic on our body and brain, the essential message here is that fasting is really good for us. It’s in fact so good that it’s amazing. And considering that it can stimulate the growth of new mitochondria and even new brain cells, we could even say that it’s miraculously good for us.

Having understood that it is the combination of the fasting period and the refeeding that follows which makes the magic happen, the natural question is how can we maximise this. And the answer is quite simple: we fast and refeed frequently. We fast long enough to activate the health-enhancing cleansing, detoxification, and preservation mechanisms and pathways, and refeed with the most nutrient dense and nutritious foods to maximise the efficiency and effectiveness of the rebuilding and renewal mechanisms and processes.

Once well keto-adapted, and after a period of gradual adaptation to longer fasts, it becomes very easy, and even natural, to fast daily from 18:00 to 12:00 or even 14:00. It even becomes easy and natural to eat two small meals or a single large meal just once a day. In this way, we can get the benefits of fasting and refeeding every single day. Of course, longer fasts of 2, 3, or 4 days will go deeper in stimulating the cleansing, preservation, and repair potential of the fast. But the longer the fast, the more difficult it grows to maintain, and the less frequently it can be done because the rebuilding in between fasts must also be longer. After all, our daily requirements for calories and nutrients is what it is, and although we can easily postpone providing the organism what it needs to function optimally for some time, everything it needs must eventually nevertheless be provided.

This is therefore what I do. A daily fast of about 16 to 20, and usually 18 hours. Once or twice a week a full day’s fast with a single large meal, but typically one small meal around 14 and one larger one around 17 or 18. A comprehensive daily supplement programme; bitters over extended periods a couple of times a year; binders like psyllium husks semi regularly according to need based on quality of bowel movements, and smell of underarm sweat; maximum hydration and alkalisation of body fluids during the fast; and most fundamentally, maximum nutrition at refeeding. Maximum nutrition and nutrient density from plant foods, and maximum nutrition and nutrient density from animal foods. And the final note I’d like to leave you with is this:

The process of ageing is the process of dying. And this process of ageing and dying is a very slow and gradual process of accumulating dead and dysfunctional cells, mitochondria, organelles, and tissues. As these accumulate, we age and die. The faster they accumulate, the faster we age and die. The more we have accumulated, the closer we are to the end, to the threshold beyond which the organism cannot sustain its activity. Fasting—and this is the single most essential benefit of fasting—is by far the most effective way to slow down, minimise, prevent this continuous accumulation of death, and instead promote and stimulate cleansing, renewal, and rejuvenation within this organism that we call our bodymind.

I hope all of what we saw here together will help you enhance your health, and improve the quality of your life.

 

This article is inspired by and primarily based on KetoFast by Dr. Joseph Mercola.

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Is it possible to make universal recommendations about health?

Focus these days tends to be on individuality. Especially in this age of genetic testing. The fact is, however, that ahead of individual differences, we are all human. Not only that, but as far as we know today, with the latest studies of mitochondrial gene evolution and transmission, we are all descendants of the same group of homo sapiens from the south western coast of Africa. Hence the question: can we make universal recommendations?

Imagine we could examine every human being on the planet, and assess organ function. For example, examine function of the kidneys, liver, pancreas, gall bladder, stomach, small intestine, and large intestine. Would we find differences in how these are working from one person to another? Of course we would! That’s obvious. But does that have to do with inherent individual differences, or does it have to do with acquired differences that have developed over time for a range of different reasons? What if we were to ask this question instead: is there a difference, from one person to another, in how these organs are meant to work, a difference in how these organs should be working?

If that were the question, we would most certainly agree, together with probably all anatomists and physiologists, that all of these organs, and the rest of the internal organs of our organism, are meant to work in the same way. That all these organs, no matter in which person they happen to be, and no matter how they are currently working, are nevertheless meant to work in precisely the same way to perform precisely the same functions. And this not only in humans, but also in most animals with whom we share these fundamental anatomical and physiological characteristics. This naturally points not to individual differences but to inherent similarities as the fundamentally essential.

It is however quite easy to understand why there is so much emphasis on individuality. Aren’t we all unique and different? Aren’t we all so special in this uniqueness? Don’t we all have to learn to listen to our inner voice and pursue what we need to feel fulfilled in our own unique way? And how cool it is to be able to know our genetic profile, our own, completely unique, personal, and individual genetic profile? How special does it make us feel to know that there isn’t a single other person that has the same genetic profile as us?

What if everyone was brought to believe that each type of cancer is different, not superficially but fundamentally, and that in addition, each type is expressed differently in each individual because of the different interactions with their unique genetic makeup? That it is necessary to treat each individual cancer and each individual person with a drug that is genetically tailored just for them in their particular situation? What if we were brought to believe that this was the case for most illnesses and chronic diseases: that what is needed are specific drugs for specific conditions that are genetically tailored to each person? What endless possibilities! What awesome growth potential! What amazing investment opportunities! And what astronomical potential for returns on investments!

Contrast this with a position holding that cancer is a metabolic disease, and that no matter what kind it is, fundamentally cancer is always caused by a mitochondrial dysfunction that leads to excessive fermentation of glucose for fueling accelerated reproduction and a cellular activity that has become undifferentiated, and that therefore, all cancers can be prevented and even reversed by effectively starving the cancer cells of fuel by maintaining very low glucose and very low insulin levels in the bloodstream to ensure that healthy cells derive their energy from fatty acids and ketones, while the weakened and dysfunctional cancer cells starve and die. What growth potential? What investment opportunities? What returns on investments?

Contrast this with a position holding that all chronic diseases are also rooted in metabolic dysfunctions, and arise, simply and naturally, in a rather predictable manner, from things like chronic dehydration, chronic dysfunctions in digestion, absorption, and elimination, chronic nutritional deficiencies, biochemical imbalances, accumulation of metabolic acids and wastes, and result from all the consequences brought on by these dysfunctions and imbalances over years and decades that grow in severity in time until we are really quite sick, but all of them very simply prevented and treated with proper self care, hydration, and nutrition. Again we can ask, what growth potential, what investment opportunities, what returns on investments?

Whatever your personal inclination about any of this, it’s definitely something to keep in mind when evaluating statements concerning the general applicability versus the individual tailoring of treatments for ailments and approaches to health.

My position is simple:

  • as living organisms and complex animals, all humans are basically the same in anatomy and physiology;
  • there are obvious differences from one person to another that must be taken into account when considering each person individually; but
  • on the whole similarities are many and fundamental, while differences are fewer and generally superficial.

This is not to say that differences can be dismissed or even overlooked. Of course not. There are important differences in the expression of fundamental genes like the MTHRF gene that regulates methylation in the body, and which hence directly affects the body’s biochemistry and state of health. Similarly, there are important differences in response to sunlight and vitamin D metabolism from one person to another, even people from the same general gene pool. But these are nevertheless superficial compared to the totally fundamental considerations of how cells, organs, systems, and hormones work.

With all of this in mind, let’s come to the main point: what recommendations I would make with confidence to any adult not suffering from a major disorder, younger or older, weaker or stronger, more fragile or more robust, knowing that these recommendations would in no way be harmful, and would instead be helpful to improve health. They are presented in order of importance.

  1. Drink plenty of water and eat plenty of unrefined salt with meals. This is essential for proper hydration on which every cell relies, and proper kidney function on which the organism as a whole relies.
  2. Get at least 8 hours of quality sleep per night, on a regular schedule, somewhere between 21:00 and 8:00 the next day. Nothing is more important for health than sleep, and there is no way in which we can make up for a lack of it.
  3. Practice intermittent fasting. Nothing offers a more effective way to cleanse, repair, heal, and optimise cells, tissues, organs and metabolic function than fasting.
  4. Eat only nutrient dense whole foods. Ideally organic and pasture raised, focusing on high quality animal protein and fats, and micronutrient dense plant foods, avoiding all processed carbohydrates, lectins from grains and nightshades, and any foods to which you may be intolerant (e.g., dairy, eggs, nuts, etc).
  5. Take vitamins A, D3, and K2. These are fundamentally important fat-soluble vitamins, essential for healthy gene expression, calcium metabolism, healthy bones and teeth, and healthy arteries and soft tissues throughout the body.
  6. Take baking soda. Start the day with half to three quarters of a teaspoon of baking soda dissolved in a large glass of water on a completely empty stomach. This is the easiest way to supply the most important alkaline compound used by the body, and offset the acid load and potential accumulation in tissues of metabolic acids.
  7. Take iodine. This is essential for healthy thyroid, mammary, and glandular function in general. But iodine is needed in every cell, and basically everyone is iodine deficient. Unless you live by the sea and eat fish and seafood regularly, you need extra iodine (either in pills or by eating sea vegetables).
  8. Take magnesium. This mineral is also needed by all cells, but especially muscle cells that need and use up magnesium in order to relax, and our soils are globally deficient in it. Thus, naturally, so are we. Contraction of muscle requires calcium, which is quite abundant in our diet; relaxation requires magnesium, which is, on the contrary, rather scare in our food supply.
  9. Practice resistance training. Focus on large compound exercises like the deadlift, squat, benchpress, and standing overhead press. There is no way more effective to maintain a strong and healthy balanced musculature, nervous system, skeletal structure, and hormonal system than whole body exertion through complex lifts with sufficient resistance.
  10. Find purpose and fulfillment in your life. This is fundamental. Without a sense of purpose we feel useless, unneeded, unwanted. Without a sense of fulfillment from what we do, we feel hollow, empty, worthless. It is therefore essential to find and to actively seek to maintain a strong sense of purpose, and a feeling of fulfillment in life. Do not take this lightly. Look into it and find it.

Here you have it: ten simple recommendations for a healthy life. And, from the perspective presented here, ten universal recommendations for any adult without a major disorder requiring specific considerations, which are sure to not cause harm, and instead sure to bring about improvements and benefits to metabolic, hormonal, muscular, skeletal, and physiological functions of the organism as a whole. Therefore, in conclusion, I would say that yes, it is possible to make universal recommendations about health.

 

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Stop the bleeding and heal the tissues

This is a healing programme for someone who has had chronic haemorrhoids and bleeding for a long time. Following an operation that was supposed to resolve the problem, the situation worsened, the bleeding increased, and consequently, they now have haematologic issues. The situation could quickly become critical.

Good morning,

In all likelihood, the cause of all the blood-related problems is the colon dysfunction, hemorrhoids, and most importantly the bleeding from the anus. This needs to be corrected before things get much worse. The basic strategy is to minimise bowel movements until the colon and anus have healed, and maximise the speed of healing and nutrient density specific to blood building. 

Eat no fibres

To allow the colon and anus to heal, we need to stop stressing their tissues, which means less bowel movements. This will be done by eating only animal foods and zero plant fibres. In your case, this means animal flesh, fat, and organ meat only (no eggs or dairy products). No matter what anybody you may talk to thinks about it, this is a perfectly healthy way to eat that eliminates all low density nutrient food sources, and is in fact used very successfully to treat and heal serious autoimmune conditions that do not respond to other kinds of treatments. It provides an extremely nutritious diet because all animal foods are concentrated sources of proteins and protein-bound nutrients, fats and fat-soluble nutrients, that are all easy to absorb and digest because the gut is free of intervening fibres that slow down or prevent absorption, and contain none of the natural toxins found in all plants to a greater or lesser extent. You can read many testimonials, some truly amazing, on Zero Carb Zen.

It is important to keep in mind that while protein is used for tissue building and repair, it is fat that is used for cellular energy production. Hence, you need to have plenty of fat and salt with your meals. You should have always have liberal amounts of the highest quality grass fed butter, extra virgin organic coconut oil, extra virgin olive oil, and unrefined sea salt.

Build blood with liver and chlorophyll

There is nothing more effective at building blood than liver from the animal food world and chlorophyll from the plant food world. So, you will have both. Liver should be grass fed veal liver, as it is one of the most nutritious. But other animal livers including chicken are also good. It is very interesting to note that chlorophyll is really like plant blood because it has the same structure as haemoglobin with the only difference being that its central component is Mg instead of Fe for haemoglobin.

I think that in order to accelerate healing, you should have liver every day, but in small amounts, like 50 g. The chlorophyll you will have with water. You can either have it more concentrated (in a single glass of water) and have it 2-3 times per day, or you can have it more diluted and have it over longer periods. The taste might be any issue, so you can see what works best for you. Also, you need to be cautious to not take too much as this will cause loose stools. You need to increase your intake gradually. Naturally, all zero-to-very-low sugar green juices are also excellent to have as much as you want. You should always add a little olive oil to your green juices to increase absorption of nutrients.

Supplements: Chlorophyll

Accelerate healing with amino acids and proteolytic enzymes

To maximize the speed of healing you will take amino acids that, as a supplement, are almost 100% absorbed without any inefficiencies related to compromised digestion. The first place they will be used it for tissue repair. Proteolytic enzyme are the specialised proteins that actually perform the breakdown of damaged tissue, as well as the repair and rebuilding of tissues throughout the body.

They should both always be taken on an empty stomach and at least one hour before eating anything. They can be taken several times a day, so I suggest 3-4 times, taking 3-5 amino acid tablets and 3 proteolytic enzyme capsules each time, first thing in the morning, one hour before the midday meal, one hour before the evening meal, and before bed. Vitamin A is also essential for tissue repair, but liver is one of the richest sources of it, so you don’t need to take extra.

Supplements: Amino acids and proteolytic enzymes

Moisturise skin with oil

The last thing is to help the tissue of the anus from the outside by putting some olive oil with a small amount of essential oils of lavender and geranium. The proportion is 3 drops of each essential oil for 30 ml of oil. Dip your finger only once in the small oil container, and moisturise the skin around the anus. Do this a few times per day, and always before and after a bowel movement.

Following these recommendations, you should see improvements very soon, but as is always the case, healing time is proportional to the time over which disease and damage has persisted. So, be consistent and patient.

 

Thank you to all our patrons, and in particular to Eric Peters, Toni, and Bostjan Erzen, for their continued support. Become a proud sponsor of healthfully.net and join our patrons today!

Your gallbladder and why it’s important

Yesterday I had a video coaching session with one of my patrons, and the last thing we talked about was the gall bladder. They recently had an ultrasound done to check out the insides of the abdomen—obviously to make sure everything looks good. The kidneys looked good, the liver had a small benign lump of 1–2 mm  in size (angioma sounds so much more serious), and the gall bladder had a bunch of little stones. I asked what the doctor recommended.

“There’s nothing to worry about. Let’s check again in half a year.” That was it. Nothing more. So, they asked me if there was anything that could be done to help in some way.

What do you think? Is there not always something that can be done to help—to help the body cleanse itself, repair itself, heal itself, improve its physiological and metabolic functions?

We’ll take the time to study and explore the liver and its functions in greater detail later—the liver is a lot more complex. The gall bladder is quite simple, and so, I just wanted to share with you what I explained yesterday, and at the same time, take the opportunity to expand a little on that.

First the Anatomy

Looking at the abdomen from the bottom of the sternum (the bone between the pectorals) to below the hips, after having removed the skin and layers of muscle, cut out the front part of the ribs, and changed the appearance to make it cartoon-like, without any blood, veins, arteries, or nerves, and thus not so shocking to look at, we would see something like this:

abdomen-front-labels

Digestive system: front view with labels

The large, dark red organ that is the liver sits at the very top of the abdomen with its largest lobe located on the right side of the body. On the left, below the liver’s smaller left lobe, is the stomach that curves back towards the middle where it connects to the small intestine (duodenum). The gallbladder—the small dark green pouch—is nestled between the bottom of the liver’s right lobe and the first part of the duodenum. Below the stomach, sweeping across the abdomen from one side of the body to the other is the transverse part of the large intestine (colon). The entire lower portion of the abdomen is filled with the longest segment of the intestines.

If we zoom in on the upper abdomen,

upper-abdomen-front-nolabels

Upper digestive system: close up front view

and then hide the liver,

upper-abdomen-front-noLiver-nolabels

Upper digestive system: close up front view without liver to show bile ducts

we see all of the little green ducts embedded into the liver whose function it is carry the bile from the different parts of the organ to the main bile duct and gallbladder.

Taking a look at the same part of the abdomen from the back,

upper-abdomen-back-top-labels

Upper digestive system: close up back view with labels

we see how the gallbladder sits between the liver and duodenum, and how the main bile duct sweeps down behind the pancreas to connect to the main pancreatic duct such that the bile from the liver and gallbladder can be injected into the small intestine together with the enzymes, insulin, glucagon, and bicarbonate from the pancreas. We also see from this side the dark red, bean shaped, right and left kidneys, and the yellow adrenal glands sitting on top of them.

And then the physiology

Why do we need bile and what does it do? Why is there a gallbladder? And what is bile anyway?

Bile is 97% water, 0.7% bile salts (sodium and potassium), 0.5% cholesterol, fatty acids, and lecithin, 0.2% bilirubin, and a tiny bit of inorganic salts. In human adults the liver produces 400–800 ml of bile per day (Wikipedia).

The liver produces bile continuously but slowly. When we eat, depending on how much fat there is in the meal, the digestive system may need quite a bit of bile to handle the fat that was just ingested. Hence the need for storage and thus the function of the gallbladder.

The purpose of bile is to emulsify fat. Emulsifying means making into tiny droplets that can mix into another liquid to form a smooth homogeneous solution. For example, a bit of mustard works very well to emulsify the oil and vinegar that would otherwise not mix into a smooth creamy vinaigrette. After emulsification, fat droplets are typically 15–30 microns in size.

We need bile to emulsify the fats that we eat so that the pancreatic enzyme lipase can then break these triglycerides down into monoglycerides and free fatty acids. This is done in the small intestine where the bile and enzymes are secreted from the pancreas with the bicarbonate solution. This in turn allows the fat to be transported through the intestinal wall before being reassembled into triglycerides and absorbed into the lymphatic system. Without bile, fat could not be absorbed. It would go straight through the gut and be excreted undigested.

Why would stones form in the gallbladder? Is there a way to prevent the formation of gallstones? And what actually are these gallstones?

Gallstones are basically little hard lumps of cholesterol. One of the functions of the gallbladder is to concentrate the bile which comes in quite diluted, as we saw earlier, being 97% water. But when the concentration grows too high, then cholesterol precipitates out and forms little lumps. These are what we call gallstones.

Given that we know that stones form out of precipitated cholesterol when the concentration of the bile is too high in the gallbladder, it is simply logical that if the concentration can be kept low enough, below the threshold at which cholesterol will precipitate, then no stones would form. But why does the concentration of bile grow to the point of precipitation?

Let’s ask another question: what happens if we don’t eat much fat? The liver produces bile continuously, between 400 and 800 ml per day. This bile is stored into the gallbladder until it is needed after a meal in which fat was ingested. If we don’t eat much fat in a meal, then, naturally, not much bile will be needed, and most of the available bile will therefore remain in the gallbladder. Because the liver continues to produce it, the gallbladder needs to make room for it, and thus concentrate its contents further.

So, what happens if we never eat very much fat, and if actually, every meal is a relatively low fat meal? Well, what happens in a pool of water if the water does not flow out, and is by this not renewed by fresh water? Stagnation. In the case of the pool of water, we all know what happens: it grows dirty, then thick, then greenish, then totally filled with lumpy green gelatinous stuff. In the case of the gallbladder, we can imagine that something analogous takes place, and that the lumps of cholesterol are like the lumps of green gelatinous stuff in the water.

The solution is simple: eat plenty of fat on a regular basis. This way, the gallbladder can empty itself out regularly, and the bile does not stagnate, grow more concentrated, and eventually lumpy with gallstones.

Your gallbladder and why it’s important

Here’s what we learned:

The gallbladder sits between the right lobe of the liver and the first part of the small intestine. It stores and concentrates bile which is mostly water with small amounts of salts, bilirubin, lecithin, and cholesterol. The liver produces bile continuously in the amount of 400 to 800 ml per day.

The function of bile is to emulsify the fat we eat to make it absorbable. Without bile, fat just go through and gets excreted undigested. The same is therefore true for all fat-soluble minerals and vitamins, including some of the most important of them all, the crucial vitamins A, D, E, and K2.

If we don’t eat fat, there’s no need for bile. If we don’t eat much fat for a long time, the bile will get more and more concentrated. Eventually, the concentration will be high enough for cholesterol to precipitate out of the bile and form little lumps. These lumps of cholesterol are called gallstones.

Imagine that this continues for years and even decades, following a good “heart-healthy” low-fat diet. What do you think will eventually happen based on what we’ve just discussed? More stagnation, more highly concentrated bile, more gallstones, and then at one point, this whole thing explodes into acute infection, acute inflammation, excruciating pain, and emergency surgery to remove the infected gallbladder.

And then what? I’ll you finish this exercise in deductive reasoning which you now have all the necessary background to complete.

 

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Why every undigested protein is an allergen

We come out of our mother’s womb, and we are very soon thereafter given a bottle to suckle on. In the bottle there’s a powdered ‘infant formula’ mixed with water, or milk, or both. “The most commonly used infant formulas contain purified cow’s milk whey and casein as a protein source, a blend of vegetable oils as a fat source, lactose as a carbohydrate source, a vitamin-mineral mix, and other ingredients depending on the manufacturer” (source: Wikipedia). The water is municipal tap water with residues of agricultural and industrial chemicals, of prescription drugs of various kinds, fluoride that suppresses the immune system and makes the bones and teeth brittle, and chlorine that kills the bacteria and destroys the flora of the gut. The milk is most likely UHT, which stands for ultra high temperature pasteurised, cow’s milk from cows that have never set food outside, have never eaten a blade of grass, have only ever eaten soy, oats, and corn, and have their whole lives received antibiotics preventatively to lower the probability infection due to the fact that they are sick and immunosuppressed from the living conditions they are subjected to. How’s that for a start?

We start teething and we are given ‘teething cookies’ to nibble on. Cookies, like Gerber’s classic arrowroot cookie, made wheat and arrowroot flours, dairy proteins and solids, vegetable oils, sugars, and other stuff like stabilisers, preservatives, texture and flavour enhancers, and some added vitamins and minerals, of course.

We don’t need to have teeth to have ice cream. In fact, parents are encouraged to give cold things like ice cream teething infants to soothe their gums aching from the teeth pushing through them. And we love it, of course! We’re still far from being able to speak, but we eagerly await the next spoonful, which, if delayed too long, makes us impatient, and soon angry enough to cry out and let our parents know we want more.

Naturally, we never make a fuss when we are fed apple sauce, or pear sauce, or pureed bananas, peaches, or apricots, nor when we are are given mixes like banana-strawberry, or strawberry-kiwi, or even apple-carrot-parsnips. We also like sweet potatoes, squash, and even regular mashed potatoes with our pureed meals. But the green things like mashed pees or broccoli, that we like less—quite a lot less.

We always start the day with orange juice. In fact, this is so much a part of our upbringing that we can’t even imagine a morning with having orange juice. And as soon as we can chew, our breakfast is made of those delicious, sweet and crunchy cereals served in a big bowl of milk. This is another part of our upbringing that is so much a part of us that we  often consider it a normal part of life, and can’t imagine a life with it.

We snack on cookies, on muffins, on granola bars, and particularly like the chocolate covered ones. We snack on chips, crunchy and salty—on Doritos, Pringles, and all sorts of different kinds of chips—and we love them too. We love our regular home pasta dinners, our pizza dinners, our hot dogs, our burgers, our fries. When we’re hungry in the afternoon, we make ourselves those delicious peanut butter and raspberry jam sandwiches on ultra moist slices of white bread, and they’re so good we have a hard time to stop eating them one after another. And what about our Nutella, that amazing chocolate spread we can never have enough of? We really could eat the whole jar if we didn’t force ourselves to stop. It’s so delicious we even eat it by the spoonful when we don’t feel like having bread with it. And they tell us it’s good for us, that’s a good source of nutritious milk and hazelnuts. Wow! How great!

We get sick pretty often as school children, but not more than anyone else, about ten times a year or so. Our parents seem to get colds less often than we do, only about 4 or five times per year. Sometimes it’s worse than others, and we are given antibiotics. We take them because our parents give them to us. And they give them to us because our family doctor tells them to. We get loose stools for a while, and we don’t understand why. After some time, things kind of get back to normal.

We go on like this for years. Actually, usually for at least two or three decades. Everything we do destroys our gut flora. All the foods, the chemicals, the drugs, destroy the essential health-promoting bacteria and the balance between the different varieties that are meant to populate the gut, and at the same time promote the overgrowth of specific kinds of pathogenic bacteria and yeasts that take over our gut.

All the foods we eat are loaded with lectins that damage the lining of our gut, making it thinner, less functional, less protective, and more vulnerable to further damage. This damaged gut with its damaged lining and damaged glycocalyx becomes leaky. Not only do we not digest food properly, not only do we not absorb nutrients properly, not only do we not excrete wastes properly, but all sorts of stuff starts leaking from our gut into our blood. And possibly the worst thing that can happen is to have a leak into our bloodstream of undigested proteins.

The reason is that undigested proteins in the blood trigger the immune system that responds to them as allergens. As this is the result of a degenerative process, and is therefore a chronic condition that grows more severe with time, the dysfunction eventually manifests itself into auto-immune disease conditions. Those ‘incurable’ disease conditions on which modern conventional medicine has given up. This is how serious it is.

Proteins from out food are not meant to enter the bloodstream—ever. So much so that the kidneys will completely clog themselves up trying to remove proteins from the bloodstream to the point of kidney failure. Proteins are meant to be broken down into the much smaller units of which they are made called amino acids. And breaking down proteins into amino acids is meant to be done by the stomach before entering the intestines. Hence, having not fully broken down proteins in the gut can only really happen if they haven’t been broken down while they were in the stomach. Clearly, it isn’t therefore only the gut that is dysfunctional and damaged: the stomach must also be dysfunctional in some way to allow these undigested proteins to pass into the intestines in the first place.

We have previously looked in detail at the process of digestion in Understanding digestion. The essence of what we need to know is that the stomach has specialised cells whose purpose is to secrete hydrochloric acid to break down proteins; that acid is produced when these cells detect the presence of protein in the stomach; that as proteins are broken down, the pH rises and the stomach secretes more acid to keep the pH low in order to continue breaking down the protein; that when the pH stays low for a few hours or so, this signals that all the proteins have been properly broken down, and that the chyme (the processed contents of the stomach) can be transferred to the small intestine; and that at which point the stomach valve opens, the acidic chyme moves through, and the pancreas injects into the small intestines a concentrated solution of bicarbonate to neutralise the acid which would otherwise damage the lining of the intestines. This is how it’s supposed to work.

But if there isn’t enough bicarbonate in the system, the pancreas cannot do this properly. If there isn’t enough water, the pancreas cannot do this properly. If the stomach doesn’t produce enough acid, the proteins are not broken down properly. And if the acid producing cells of the stomach are not regularly exposed to high concentrations of hydrochloric acid, they lose their ability to produce it. This happens when little or no concentrated sources of protein are eaten, like when we are vegetarian or vegan for a long time. But it also happens when the lining of the stomach, which is supposed to be protected by a thick layer of mucus while digesting protein, is instead exposed to and damaged by its own hydrochloric acid. This happens when there isn’t enough water to make that protective layer of mucus, and it is why we should drink water before meals.

So, here’s what we get: not enough water or bicarbonate—loss of acid-neutralising function of pancreas, and damage to intestines; not enough protein in the diet—loss of acid production ability, and undigested proteins; not enough water—damage of stomach lining, loss of acid production ability, and undigested proteins; undigested proteins—chronic immune response to circulating allergens and autoimmune disease conditions. This is compounded with the damage that results from exposure to chemicals and antibiotics, from the overload of sugars and starches, and from the destruction of the cells lining the gut by the lectins in our diet.

The end result is, as expected, precisely what we observe: a population where basically everyone has, to some extent, compromised digestion, and therefore, a population where everyone is, to some extent, sick. Because we don’t know any of this, because we don’t know how food affects the body, because we don’t know how the organs of the body function, because we don’t now how digestion works, and because nobody else around us knows any of it either, we believe everything is normal and everything is just fine, just as it should be, just as it always has been. But the truth is that it isn’t.

What’s actually hard to believe is how simple the solution is: 1) avoid as much as possible exposure to chemicals and antibiotics, and adopt measures to systematically help the systems of the body cope with and recover from the exposure we cannot entirely avoid; 2) avoid as much as possible the overload of sugars and starches, and focus on animal protein and fats from free range animals, and green vegetables. This will automatically lead to a nutrient-dense, whole foods diet that also minimises exposure to gut-damaging lectins; 3) drink plenty of clean water to ensure good hydration, especially with enough time to replenish the stomach’s and pancreas’s reserves before meals, and take a little extra bicarbonate on an empty stomach with your first glass of water in the morning to maintain a good alkaline buffer and balance.

 

This strategy is so simple, and yet it is both preventative and curative. The extent to which we need to be strict depends on the extent of the damage from which we need to recover. And as it true for everything, it’s far easier to prevent damage than to recover from it. That’s obvious but it’s good to remind ourselves of it when our motivation weakens or strength of will falters. The amazing news is that, as shown by doctors Terry Wahls and Steven Gundry who specialise in the treatment of autoimmune disease conditions, recovery from even the most severe cases is virtually guaranteed and only a matter of consistency, patience, and time. I hope this is enough of a motivation for you. Enough of a motivation to at least start to make the effort to regain and then preserve the health of your gut and digestive system—the system on which everything about your health depends.

Oh, and breakfast? Just skip it and have your first meal at lunchtime. Breakfast is not, as we have been told over and over again, the most important meal of the day. It’s actually the most important meal of the day to skip. We’ll get back to this point some other time.

 

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Every undigested protein is an allergen

If someone asked you what you thought was the most fundamental, the most essential, the most important health challenge that we face as modern human beings living in industrialised countries, what would you tell them?

Take a moment. Shift your gaze away from this text, and think about it.

When we read or hear something about health and nutrition in the news, on websites, on blogs, on social media, or even in books, the information we encounter is almost always biased and directed  in some way. It is also always restricted in scope. In fact, it is usually very restricted in scope. All this is perfectly natural and expected: whenever we sit down to write, it is usually about something in particular, something specific, some topic we want to address or explore. It’s hard to think of circumstances where this would not be the case.

Moreover, basically everybody who writes anything, does so in order to be read, and therefore naturally attempts to appeal as much as possible to their readership, both in content and in style. But maybe the most influential factor is that we have grown accustomed to information packets, to bite-size bullets of information: quick-to-read, quick-to-scroll-through, and quick-to-either-share-or-forget. And this has above everything else shaped the way information is being presented by all those people out there trying to appeal to more readers. Little can be done to counter this tendency. It’s just how it is at this time.

As a consequence, for all these reasons, we are—the whole world is—migrating away from the mindset that encourages inquiry into the global, the general, the underlying aspects of things. Instead, we are migrating towards an evermore concentrated, focused, laser-beam approach to basically everything. This is true in all fields of study and inquiry to some extent. In matters of nutrition, it is particularly noticeable, and the reason is surely at least in part because we tend to be at the same time very interested and highly sensitive to advice about what we should or should not eat. We take such advice very personally, and often react strongly to it.

Our relationship to food is very deep because it is so constant and continuous, so intimately related to our survival. This relationship starts when we come out of our mother’s womb, and persists throughout each day, every day of our life, until this life of ours itself comes to an end. What in addition makes this relationship so close and so intense is that if we don’t drink or eat, usually even for a few hours, we get headaches and stomach aches, we get light headed, weak, and unable to concentrate and function, we get grumpy and irritable. It is very clear and naturally understandable that we therefore tend to be—that we are—very sensitive to advice about what to eat, but immensely more so to advice about what not to eat, especially if we happen to eat those foods about which the advice is given.

Hence the movement to superficial, non-contentious, bite size bullets of information: ‘blueberries are excellent: they are low in sugar and full of antioxidants’; ‘avocados are amazing: they are not only full of healthy fats but they are also alkalising’; ‘hydrogenated vegetable oils are very bad: they are full of toxic trans fatty acids.’

But what about the essential, the fundamental, the underlying aspects of things?

You have had more than a few minutes to think about it. What would you say, then, to this question of what is most fundamental to the health, to what constitutes the most fundamental health challenge we face? I would say it’s digestion.

Digestion is where everything about us begins and ends. It is in and through the digestive system that we absorb all the nutrients from our food and excrete all solid wastes. It is through the digestive system that we absorb all the constituents of everything that we call body, and excrete all that is toxic, be it produced from the environment or from within through healthy digestive and metabolic processes. Do you find this sufficient to illustrate why digestion is so fundamental? For me it is. But we can go a lot further.

Evolutionary considerations, arguments, and observational evidence, are always useful, and usually very powerful in guiding clear thinking about matters of health. One of the main questions that has and continues to preoccupy evolutionary biologists is that of the growth of the human brain. In this, one of the most compelling ideas put forward to explain its evolutionary history is called The Expensive Tissue Hypothesis. I plan to, in the future, devote much more time to it. But I must refer to it here because of its relevance to digestion.

The Expensive Tissue Hypothesis is based on the fact that there is a strict minimum to the amount of calories any animal requires to survive, the observation that the brain is the most metabolically expensive organ in the body, and the conclusion that it would be very hard for any large complex animal to sustain two systems as energetically expensive as the brain. Because the gut is the second most metabolically expensive, and because both the brain and gut together account for a disproportionately large fraction of the body’s caloric needs, an increase in the size of the brain would necessarily be at the expense of that of the gut, and vice versa. It simply would not be possible to sustain both a large brain and a large gut. And thus, the growth of the brain would have to be accompanied by a shrinking of the digestive system. This is what is observed.

However, it is important to emphasize that it is the shrinking of the digestive system that allowed for the growth of the brain; not the growth of the brain that precipitated the shrinking of the gut. The growth of the brain would only be possible with a surpluss of calories for it to growth and have its increased activity sustained. It is even more important to emphasize that this evolution was the unintended consequence of a shift from a high-fibre, nutrient-poor, plant-based diet, to one consisting mainly of low-fibre, nutrient-rich, animal-based foods.

Number two Silverback Mountain Gorilla (Gorilla gorilla beringei) of Kwitonda Group, Akarevuro, Virunga Mountains, Rwanda

Male mountain gorilla of the berengei berengei subspecies of eastern gorillas in Ruanda (Source: Time). As you can see from the chest muscle definition, this adult male’s bodyfat is low. The huge bulging belly that is apparent when they are seated and relaxed is the consequence of having it hold the very long gut required to process each day approximately 20 kg of fibrous roots, leaves, and stocks of the plants they eat.

It is very interesting—and it is surely related to this evolutionary history—that the gut has by far the largest number of nerve endings, second only to the central nervous system. Moreover, unlike other organs and systems of the body, all of which are entirely controlled by the brain, it is the only one with directive nervous signalling to the brain. Because of this, it is the only organ with a direct influence on the brain. Thus, besides the physical implications, some of which we’ll explore soon, it is quite literally the case that a happy gut means a happy brain. And conversely, a sad, unhappy, depressed brain is very likely to be caused by a dysfunctional gut.

It is a sick, dysfunctional, damaged gut that is the primary characteristic underlying states of disease. This is why I would say that it is a sick, dysfunctional, damaged gut that is the most fundamental health challenge we face today as modern human beings.

I know this might leave you hanging. Especially because we have not yet made any reference to the title. But I promise, we’ll pick up from here next time.

 

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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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