First high-carb-low-fat day after 8 years on a low-carb-high-fat diet

A little taste of what’s to come from the results of my experiment with continuous glucose monitoring: this roller coaster ride is what most people experience every day. What was on the menu: melon, raspberries, watermelon, (nap), coconut water, tomato salad, fresh corn, a little ‘financier aux pistaches’, and finally, popcorn to finish off the day. Can you guess when I ate? Pretty obvious, isn’t it?

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He walks in, puts his apple on the edge of the counter, says hello, and walks into the stall. When he sees the water moving, he hesitates because in this moment he understands that I was just there. He doesn’t want to offend me by going to the other stall, but he’s uncomfortable with the idea of using this one immediately after someone else did, and that person happens to be still there. The strange thing, though, is that there is no evidence of any kind: no visual evidence and no smell. It’s traceless.

I reassure him by saying, in a jolly manner, that it is perfectly clean because I just wiped the seat with a damp paper towel (as I always do before and after). As I’m walking out I add, in an even jollier tone: “and there’s no smell either; imagine that!”

This is the shortest post I’ve ever published. I will, in the future, publish a detailed explanation of every aspect of what this means and implies. But I want the main point to be utterly clear:

Your stools should be of perfect texture: not hard and dry, not soft and sticky; they should come out easily and without effort: no pushing, no squeezing and no waiting around; they should have a light smell that diffuses in a matter of seconds after flushing; and they should not require much wiping: once or twice at the most, and ideally no wiping at all, something that can be seen from a clean paper after the first wipe.

When your stools are like this every time or almost every time you go to the bathroom, you know that the digestive system is clean and is working well. This is foundational for optimal health. And I mean: without this, there can be no optimal health.

Living healthy to 160 – insulin and the genetics of longevity

Of the most remarkable discoveries of the last 15 years, discoveries that might well turn out to be the most remarkable of the 21st century, are those of the telomere—a little tail at the end of our DNA whose length tells us how long we have left to live, and of the enzyme telomerase—the specialised protein whose job it is to try to repair the telomeres so that the cells (and we) can live longer and, from an evolutionary perspective, increase the probability that we’ll have more babies. This and other research into the biology of ageing and the details relating to the transcription of DNA, and the expression or suppression of genes is truly amazingly fascinating. I will turn to this in time, but think it would be jumping the gun to do so now.

What is definitely one of the most remarkable discoveries of the 20th century pertains to the hormone insulin. I am not, however, here referring to the fact that its discovery revolutionised medicine by allowing the saving of countless diabetics from highly premature and painful deaths, usually preceded by torturous amputations of their feet or legs and all the of the horror and misery brought on by these seemingly barbaric and radically extreme measures. (And don’t for one second imagine that such amputations are a thing of the past: I know for a fact—heard directly from the mouth of a practicing orthopaedic surgeon—that amputations are the reality of his everyday, performing sometimes two in a single day.) I’m not either, at least this time, talking about insulin as the master metabolic hormone that regulates the storage into cells of nutrients circulating in the bloodstream. What I am referring to as one of the 20th century’s greatest discoveries in regards to insulin is that of its role in regulating the rate of ageing.

Something that is almost as remarkable is that we hardly ever hear or read about this. For me, that’s really strange. But whatever, I’m not going to hypothesise and speculate to come up with an explanation for why this is. Insulin as regulator of the rate of ageing is what we’ll look at in this article.

Why do mice live two years but bats fifty? Why do rats live three years, but squirrels fifteen. Why do some tortoises live hundreds of year? Why do the smallest dogs, like Chihuahuas, live about twenty years, while the largest, like Great Danes, live five to seven years only? And why do we, humans, live around 80 years, rarely making it to 90, and very rarely to 100 years of age? It is this line of questioning that triggered in the late 80’s and early 90’s a geneticist working in evolutionary biology to hypothesise, for the first time, that ageing could be genetically regulated, at least to a certain extent.

It was the discovery and subsequent realisation in evolutionary biology at that time, that a large number of fundamental cellular processes and mechanisms regulated by a variety of genetic expressions were common to widely different organisms. The realisation was that because all animal life must necessarily share a common ancestor, it is not only logical that the most fundamental functions of cells and especially of how genes express themselves under the influence of hormones essential for life could be the same, but that it should be, to a great extent, expected to be that way. And even though these considerations may seem obvious in retrospect, the fact is that there was only one person with this knowledge, asking these questions, and having the means to do something about seeking an answer to some. Cynthia Kenyon, Professor at UCSF, was this person.

The subject was quick to choose: the tine worm that Kenyon had already been studying for years, C. elegans, was perfect because it is simple but nonetheless a complex animal, and because it has a short natural lifespan of about 30 days. The first step was clearly defined: find at least one long-lived individual. What seems very surprising from our current vantage point it that she couldn’t readily find one: she couldn’t convince anyone to join with her in this endeavour. Everyone was at that time convinced that ageing was something that just happened: things just wore out and deteriorated with use and with time; nothing to do with genes. But how could this be if different species—some very physically similar—are witnessed to have such widely different lifespans? It just had to be genetic at some level, Kenyon thought. Eventually, after a few years of asking around and searching, she found a young PhD student that was up to it, and set out to find a long-lived mutant.

A number of months down the road a long-lived mutant was found and immediately identified as a ‘DAF-2 mutant’. This mutation made the DAF-2 gene—a gene responsible for the function of two kinds of hormone receptors on a cell’s membrane—less active. The next step was to artificially create a population of DAF-2 mutants and see how long they live, statistically speaking, compared to normal C. elegans. It was found that the genetically ‘damaged’ worms, the ones for which they had turned down the expression of the DAF-2 gene, lived twice as long: starting with exactly the same number of worms, it took 70 days for the last one of the mutants to die compared to 30 days in the normal population.

But an additional observation was made: the curve that traced the fraction of worms remaining was stretched by a factor of two from about the start of adulthood for the mutants. They had the same relatively short childhood but then for the remainder of their lives, for every day in the life of the normal worms, the mutants would live two days. The most impressive was that they were really half their chronologically equally aged cousins in all respects: external appearance, level of activity and reproduction.

To make your appreciate this point as much as you should, this observation with respect to not just the lifespan but notably the healthspan of C. elegans would translate in human terms in someone being 80 years old but looking and acting like a 40 year old in the sense that nobody could tell that they were not 40, let alone 80 years old. Just like Aragon in the The Lord of the Rings. This person would be like a 40 year old at 80, like a 60 year old at 120, and like an 80 year old person coming to the end of their life by the time they were 160! Can you even imagine that? Hard isn’t it. But this is exactly what Kenyon and her team were looking at in these experiments with these little worms.

Now they wanted to understand the effect of the DAF-2 gene, or rather, understand the effect of suppressing its expression in the DNA of each cell’s nucleus at different developmental stages. If it was turned off completely, the worms would die: clearly, DAF-2 expression, at least in C. elegans, is essential for life. If it was suppressed immediately after birth (hatching), the little worms would enter the Dauer state in which they don’t eat, don’t grow, don’t reproduce, and basically don’t move either: they just sit and wait. Wait for what? For better times!

This Dauer state is a remarkable evolutionary adaptation seem in some species that allows the individual to survive during periods of severe environmental stress such as lack of food or water, but also high UV radiation or chemical exposure, for example, for long periods of time with respect to their normal lifespan in a very efficient kind of metabolic, physiological and reproductive hibernation. What’s really cool is that inducing worms out of the Dauer state, no matter how long they’ve been in it, they begin to live normally again, moving and eating, but also reproducing. So, in the Dauer state C. elegans literally stops ageing altogether and waits, suspending metabolic activities and physiological functions until conditions for reproduction and life become adequate once again.


Taken from Worms live longer when they stop eating  (

If DAF-2 expression was turned back up to normal, then they moved out of Dauer and resumed their development stages equivalent to childhood, teenage-hood, and then adulthood, but didn’t live any longer as adults. Finally, suppressing DAF-2 expression at the onset of adulthood resulted in the extended lifespan as originally observed. The conclusion was therefore clear: DAF-2 expression is essential for life and necessary for normal and healthy growth and development in immature individuals from birth until they reach maturity, and suppressing DAF-2 expression was only effective at extending both lifespan and healthspan in mature individuals.Going further, they now wanted to understand how DAF-2 suppression actually worked to extent healthspan: what were the actual mechanisms that made the worms live longer when DAF-2 expression was turned down. For this, Kenyon’s team needed to look at all of C. elegans’s 20000 genes and figure out how they affect each other. (Note that this is also more or less how many genes we have, but C. elegans has only 3 chromosomes and is also hermaphrodite.) The sequencing of the worm’s genome was done in 1998, and what was found after analysis was very interesting:

The DAF-2 gene activate a phosphorylation chain that attaches phosphate groups onto the DAF-16 transcription factor. In normal individuals the DAF-2 gene is expressed normally, the phosphorylation chain works unimpeded, and the DAF-16 transcription factor is inactivated. In the mutants, the DAF-2 gene expression is suppressed, and as a consequence, the DAF-16 transcription factor is not inactivated and instead accumulates in the nucleus. There, DAF-16 encodes what Kenyon’s team showed to be the genetic key to health and longevity they were looking for from the start of this now decade long pursuit: the FOXO gene.

What does FOXO do? It promotes the expression of other genes, at least four other genes: one responsible for manufacturing antioxidants to neutralise free radicals the largest amount of which are produced by the mitochondria as they make energy for the cell, a second responsible for manufacturing ‘chaperons’ whose role as specialised proteins is to transport other proteins and in particular to bring damaged ones to the cell’s garbage collector and recycling facility to promote the replacement of those damaged proteins by new and well-functioning ones; a third responsible for manufacturing antimicrobial molecules that increase the cell’s resistance to bacterial and viral invaders; and the fourth that improves metabolic functions and in particular fat transport (reduce) and utilisation (increase).

It is these four genetically regulated cellular protection and repair mechanisms, the cumulative combined effects of all these increased expressions of antioxidants, chaperons, antimicrobials and metabolic efficiency—all of them at the cellular level—that allow the lucky DAF-2 suppressed mutants to live twice as long twice as healthy. Remarkable!

Now that all the cards about how the long-lived mutants actually live twice as long as expected under normal conditions are laid on the table, and that there is only one detail I left out of the story up to this point, tell me: can you guess what are the two sister hormones to which the cell’s sensitivity through the activity of its receptors for them are controlled by the DAF-2 gene? It’s a trick question because I told you half the answer in the introduction: The DAF-2 gene encodes the hormone receptors for both insulin and the primary form of insuline-like growth factor IGF-1. Surprised? It isn’t surprising, really. In fact, it all makes perfect sense:

Insulin and IGF-1 promote growth; nutrient absorption and cellular growth and reproduction are essential for life and thus common to all living organisms, including the more primitive of them like yeasts; growth in immature individuals is fundamental for health and for ensuring they reach maturity; but growth in adults, in mature individuals, just means ageing, and the more insulin and IGF-1 there is, the faster the rate of cellular damage and deterioration, the more genetic mutations from errors in transcription, the more pronounced the deterioration of the brain and the heart, of the arteries and the veins, of the muscles, the bones and the joints, and obviously, the faster the rate of ageing. Because what is ageing if it is not the word we use to describe the sum total, the multiple negative consequences, the end result of all of these deteriorations in these vital organs and systems but also everywhere else throughout the organism, all of it starting at the cellular level, in the nucleus of every cell.

About the necessity of insulin for normal growth, you should definitely not think that these observations impliy we should stimulate insulin secretion in the young in order to ensure proper growth. Totally not! The body knows exactly when and how much insulin is needed at any given time. In fact, any additional stimulation of insulin promoted by eating simple and starchy carbs actually deregulates the proper balance of hormones that the body is trying to maintain. This deregulation from a sugar laden diet in children is the very reason for many wide spread health problems in our youth most important of which is childhood obesity and the metabolic and physiological stresses this brings on. So, leave it to mother nature to know how to regulate the concentration of insulin in the bloodstream. Do not disrupt the delicate biochemical balance by ingesting refined carbohydrates: it’s the last thing anyone needs for good health and long life.

The first results were so interesting that several other groups joined in this research into the genetics of ageing. Not as much as one would think, but at least a handful of other groups began to apply and expand the techniques to other species. Unsurprisingly, the same effects, although with different magnitudes, were seen in these very different species, from an evolutionary standpoint: fruit flies and mice. In addition, the connection was made with lifespan-extending experiments using calorie-restriction, which have also been carried out on mice and other animals (we’ll look into this another time). And beyond the work around DAF-2, DAF-16 and FOXO, Kenyon’s group investigated other ways to influence lifespan and found two more.

The first was by disabling some of the little worm’s sensory neurones of which there are very few, making it easy to test and determine the influence they have separately and in combinations. They tested smell and taste neurones, found that disabling some would extend lifespan while disabling others didn’t. They also found that disabling different combinations of smell and taste neurones could have nulling effects. The second was playing with the TOR gene expression. For now, however, we will leave it at that.

As the fact that it is rare and relatively hard to come by this work without actually looking for it, there is something else I find very hard to comprehend. In Kenyon’s various lectures on this work, there is usually a mention of the biotech company she founded called Elixir Pharmaceuticals and how they aim to find one or more drugs that can suppress DAF-2 expression in humans without causing negative side-effects in order to extend lifespan and healthspan as was done in C. elegans with genetic manipulation. That’s fine, and does make sense to a certain extent, especially if we can find not chemical drugs but natural plant-derived compounds that have this effect on us.

The thing that doesn’t make sense and that is hard to understand from the naive perspective of the honest scientist looking for the simplest possible solution to a problem of inferring something we don’t know from information that relates to what we want to know: in this case this mean the simplest way to make the best use of this information and apply what we have learnt from these two and half decades of research in a way that we know would be beneficial in promoting a longer and healthier lifespan in humans without risks through the introduction of foreign substances in our body. Because they haven’t, here I offer my attempt to do this.

We have, thanks to Kenyon and others, understood in great detail how lifespan in complex organisms can be, to a great extent, genetically regulated, and which genes, transcription factors and mechanisms are involved in the process of regulating the rate of ageing in conjunction with the propensity for developing age-related degenerative diseases. In the final analysis, the main players are the DAF-2 gene that tunes up or down the sensitivity of insulin and IGF-1 receptors, the DAF-16 transcription factor that encodes the FOXO gene but is made inactive by the expression of DAF-2, and the star FOXO longevity gene that promotes the expression other genes responsible for stimulating the cell’s most powerful protection and repair mechanisms.

We have, from many decades of research on calorie-restriction and fasting in animals including humans (and which we’ll explore elsewhere), understood that this is an extremely effective way to extent both lifespan and healthspan and basically eliminate the occurrence of age-related degenerative diseases by greatly increase resistance to health disorders of all kinds. Some key observations on calorie-restricted animals include their very low blood levels of sugar, insulin and IGF-1, high metabolic efficiency and ability to utilise fat demonstrated by low blood levels of triglycerides, and their remarkably younger appearance with increased energy and activity levels.

And finally, we have, from more than a century of observations and research, concluded that diabetics, whose condition is characterised by very high levels of blood glucose, insulin and triglycerides, are plagued by a several-fold increase in rates of cancer, stroke, heart disease, kidney disease, arthritis, Alzheimer’s and dementia, basically all the age-related degenerative diseases known to us, and in addition, also a several fold increase in their rate of ageing based on the spectrum of blood markers used for this purpose, their appearance, but also on the length of their telomeres.

Is it not, therefore, obvious from these observations that high blood sugar, high insulin and high triglycerides are hallmarks of accelerated ageing and a propensity for degenerative diseases, while low blood sugar, low insulin and low triglycerides are instead necessarily related to extended lifespan, extended healthspan and increased resistance to all disease conditions including those categorised as degenerative, and this, independently of the actual mechanisms involved?

Is it not, therefore, plausible from these observations that the genetic mechanisms relating to the function of the DAF-2 gene, DAF-16 transcription factor and FOXO gene in conferring to the DAF-2 mutants twice as long a life can, in fact, be activated and enhanced epigenetically by creating an environment in the organism that is conducive to it: simply by keeping blood sugar, insulin and triglycerides as low as possible? In other words, isn’t it plausible from these observations that by manipulating the biochemistry to ensure that blood sugar, insulin and triglycerides are throughout the day and night as low as possible depending on the organisms requirements, that this will actually translate into the activation of the FOXO gene to enhance protection and repair at the cellular level and thus extend lifespan and healthspan?

And what is, not only the easiest and simplest, but also the most effective way to do this? It is to eliminate insulin-stimulating carbohydrates—sugars and starches—from the diet completely. This, within 24-48 hours, will allow sugar levels to drop to a functional minimum. The low blood sugar will allow the pancreas to reduce production and insulin levels to drop bit by bit. Lowered insulin will eventually allow the cells to start using the fat circulating in the blood, and in time, increase in efficiency, thereby dropping triglyceride levels lower and lower.

Why is it you think that Kenyon never mentions this anywhere? Do you think that this has simply not occurred to her? I honestly don’t know. But if there is a single thing to remember it is this: insulin is necessary for life; in the immature individual, insulin regulates growth; in the mature individual, insulin regulates the rate of ageing and the propensity for degenerative diseases. Hence, if you are a mature individual, and by this I mean full grown, and if you want to live long and healthy, the very first thing you need to do is to keep the concentration of insulin circulating in your blood as low as possible. Everything else that we can do to extend healthspan and lifespan is secondary to this.

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Two short fat-loss tales

– You look like you’ve lost some weight.
– Yes, I have! I’ve lost 12 kg in 4 months. You remember, a year ago, I told you I would do my own diet, and I did!
– That’s great, congratulations!
– You know what I did? I stopped eating junk. I didn’t do anything else. I stopped eating chocolate bars and candy; cakes, cookies and ice cream; chips and fried foods, and that’s it. I eat everything: anything that is a whole food, and I do have bread and potatoes, rice and pasta, as well as cheese and fruit. I didn’t do anything crazy or radical, I just eliminated junk food from my diet.
– That’s really good. I’m happy for you. Keep it up!

This is how went a short conversation I had recently with a colleague who, a couple of years ago, was one of the 25 people who attended the talk I gave at ESAC: Water, sugar, protein and fat. It could be (I’d like to imagine) that the talk was like a little seed in her mind that was what eventually grew into enough of a motivation to start what she had been doing for a few months already, making her feel really great about it, as anyone would, of course. And I’m really happy for her, and also very happy to possibly having been a little positive influence somewhere along the line.

Another colleague stopped by my office in the spring to ask about the fitness club (a club to encourage people to exercise by subsidising part of the monthly membership to a great sports club close to where we work for which I was president for several years until a month ago or so). He mentioned in passing that he wanted to start doing sports in order to lose weight. Naturally, I immediately said that exercising wasn’t really the key to fat-loss. He was surprised, as most people are when they hear this. Being interested and inquisitive about this point (he works as a scientist, after all), I gave him a 10-minute summary of the biochemistry of fat loss, and he left very motivated to start on his fat-loss programme.

About one month later we crossed paths on the main road in front of the canteen. He looked much thinner: he actually looked quite trim considering that as little as four weeks before he not only looked but was definitely quite chubby.

– Things are going well, I see! You look like you’ve lost a lot of weight already.
– Yes, I’ve lost 10 kg. Now, after the first four weeks, I’ve started to eat carbs again, but I’m eating 1500 calories and exercising every day. I started eating some complex carbs because I need energy.

I masked my internal cringing, and just said “well, you are much leaner than you were. Good job and keep it up!” But I thought: What in the world!?! How did he come to think like this after I explained to him how fat loss works, and which he seemed to understand? The thing is, he did cut out all carbs for four weeks—there’s no way in the world he would have lost this much fat any other way—but for whatever reason, he now thought he should start again because he was exercising every day and therefore “needed energy”. He really didn’t understand the most important points I had tried to relate in that chat we had in my office. I am, in any case, very happy for him as well, because it is always better to be leaner than fatter, especially considering that a lot of the excess fat accumulating in our abdominal cavity is stuffed in between and all around our vital and digestive organs, putting constant pressure on everything in there, and that’s really bad.

Now, I would like to think that all of you readers of this blog already know what I want to point out and explain in regards to these two short fat-loss tales. Whether you do or not, I thought it was a good occasion to review the essentials of fat-loss in a quick and focused but more informal style than in other articles I have written. You are more than welcome to take a few minutes and try to guess what I’m about to explain about these two cases before moving your eye gaze down onto the first line of the next paragraph.

Why did the first colleague I talked about lose so much weight? Is it because she started exercising? No. She never exercised and still doesn’t. Is it because she starved herself on a low-calorie diet Weight Watchers style? No. She hasn’t been hungry because she hasn’t tried to eat a lot less, and has three meals a day without paying close attention to how much and is certainly not counting calories. Is it even because she stopped eating “junk food”? No, it’s not. The reason why she has lost this weight seemingly so easily is only because she markedly decreased the amount of sugar she ate, which immediately translated in lower blood sugar levels throughout the day and night, which in turn translated into lower insulin levels also throughout the day and night. As insulin drops, fat-burning starts.

Will she continue to lose her fat reserves indefinitely at this rate until there are none left? No, she won’t: fat utilisation, and therefore fat-loss rate, is inversely proportional to insulin levels. So, the lower the blood sugar, the lower the insulin, and the lower the insulin, the faster the fat-loss rate. Because she still eats sugar in the form of starches, the sugar/insulin concentration will only sometimes drop low enough for fat-burning to start, and will not drop very low and stay there to allow the metabolism to fully adapt and settle into a stable and more or less constant fat-burning mode. She will remain in intermittent fat-burning and sugar-burning. Because her fat reserves are at this stage still very large (from the organism’s perspective they are still effectively infinite), the relatively lower blood sugar for periods of several hours will prompt the body to continue to let go of these excessive fat reserves relatively easily until a steady state is reached and fat-loss stops. At that point she will still have plenty of excess body fat, but will be unable to lose any more without dropping insulin levels lower.

Of course, eliminating junk food—mostly commercial sweets and fried stuff—and feeding ourselves with actual food, no matter what it is, makes a huge difference. This is definitely the very first step in any change of diet towards better health. That’s obviously not something worth debating or even discussing. The point is that no matter what the changes in the diet, the biochemistry of fat loss is always the same, and it is the same for everyone. Everything is about insulin for the very simple reason that it is insulin that shuttles nutrients from the bloodstream into cells. This is true for sugar, protein and fat. But insulin is released by the pancreas primarily in response to the presence of sugar in the blood (but also in the absence of stress hormones which block insulin’s action to retain the sugar in circulation as long as the “potential threat” remains). The gist of it is: high insulin—nutrient storage, low insulin—nutrient release; high insulin—fat storage, low insulin—fat-burning.

What about the second colleague exercising and eating only 1500 calories that include starches and some fruit? He will continue to lose fat until the body determines that the bulk of the really excessive fat reserves have been spent, and then will stop. This will happen probably somewhere around 20% body-fat for guys and 30% for women, but will depend on age, exercise level, food, etc. So, he will get lean enough to appear slim, feel light, and also feel pretty good about himself every time someone compliments him on his figure. The more serious problem for him is that exercise, and especially the aerobic exercise like running that he is does to “burn more calories”, breaks down muscle quite quickly but it is not rebuilt.

The low calorie intake places the metabolism in calorie-deficit given that an average man needs about 1500 calories just for basic metabolic functions. This means that all additional calorie requirements have to come from somewhere other than the food that is eaten. Ideally, of course, these would come from fat reserves of which there are plenty; that’s the idea of the low-calorie dieter. But this will and can only happen if insulin levels are at rock bottom: I mean 1–3 units. Otherwise, the body will cannibalise its muscles because it can most easily get the easiest-burning cellular fuel it needs by converting protein into glucose. And the result? Over time he’ll lose most of his muscle, will retain that 15-20% fat, and will inevitably acquire the skinny-fat look. You know what I mean: the look of a slow, 40-50 year-old long-distance runner on a typical high-carb “runner’s diet” who looks skinny but giggly, with barely any visible muscle and no definition at all: muscle tissue broken down and not rebuilt; fat reserves not used because insulin is too high.

Had you guessed all that? Do you now understand how to burn fat without hunger and without losing muscle? Drop sugar levels, drop insulin levels: lose the fat reserves, keep the muscle. Eat fibrous veggies, lots of unprocessed fats and enough clean protein; don’t eat any sugar or starch. Very simple.

And here’s a teaser for a future series: if you want to build muscle and maximally slow down ageing, you will—in addition to this kind of shift in diet—also start lifting weights: squats and dead lifts, bench press and overhead standing press, bent-over rows, dips and pull-ups; and the heavier and more strenuous the better!

But if you’ve never done any of that, don’t go out and start lifting as much as you can right away because you’ll hurt yourself: you have to start slow, and have impeccable form and technique before starting to put on more weight. However, the fact is that there is really nothing more effective than heavy weight lifting to correct metabolic imbalances, postural problems, muscle and joint weaknesses; to burn fat, build muscle, and increase bone density; and totally rejuvenate the body and restore a incredibly youthful hormonal profile. The most amazing thing is that this is true for men and women of any age. I hope to find the time and write about this in the not-so-distant future.

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One of Hitler’s most devastating gifts to humankind

The Third Reich, under its Fuhrer’s rule from 1933 to 1945, but especially during the second world war, was in more ways than those most obvious to us, masterfully devastating in the scope and effects that would have its scientific research programmes.

One of the branches in which laboured a great deal of keen scientific minds was that of biological warfare with the use of poisonous chemical agents. What could be the most effective means to impede, disable, neutralise or completely remove someone’s abilities to fight or even resist? It would be to sever the connection between the central nervous system and a vital organ: pretty simple and definitely very effective.

German determination, dedication, focus, methodology and efficiency is well recognised and highly appreciated all over the world. This is true today as it was then, and if in this day and age it means to us more in terms of German technology—great industrial machinery and equipment, great cars, great appliances, great electronics—together with the fact that, on the world’s stage, we can trust their government’s word and commitment to seeing things through unwaveringly to the end, it certainly would have had a different connotation to the millions who suffered under the Germans during the great war, be it directly or indirectly. Regardless of these considerations, however, these qualities of determination, dedication, focus and efficiency are excellent qualities, well established in German culture and society, and obviously foundational in making the country a powerful and stable industrial and political leader.

It was to be expected that those scientists tasked to identify, develop and refine the biological and chemical technologies necessary to accomplish their intended function of quickly, silently and as effectively as possible disable the human target without as much as a single drop of blood being shed in the process, was indeed accomplished, and masterfully so. The result was chemical agents that were called ‘nerve gas’.

Nerve gas worked exactly as it was intended: it broke the biochemical connection between the brain and the heart. More specifically, it inhibited the enzyme cholinesterase whose critical function is to break down excesses of the neurotransmitter acetylcholine that enacts the brain’s messaging to the heart in order to avoid overstimulation. Acetylcholine is there to trigger the firing of neurons that control heart and bowel function. It sits in the synapses, the gap between neurons, and does this. The mechanism to ensure that there is enough but not excessive acetylcholine nerve stimulation, is the enzyme-depended breakdown of any surplus acetylcholine. Without optimal function of the enzyme cholinesterase, acetylcholine accumulates between neutrons and induces overstimulation, which can quite effectively bring the heart to a stop without bloodshed, without pain, without any noise, and without any drama: just quickly and effectively.

How does nerve gas work today? Precisely in the same way it did in 1945. It was recognised early on in this research that most, and maybe all animals, no matter how large or small, share if not identical, very similar biochemical and hormonal pathways, especially in terms of nervous system function. Can you see where this is leading?

The technological developments during the era of the second world war were tremendous: the planes, the cars and trucks, the tanks,  the guns, the bombs, and all the physics and engineering, the chemistry and the biochemistry involved. It really was revolutionary in regards to the power available at our fingertips to do whatever we could imagine or whatever was needed to make things simpler, easier, more efficient. What came of all this was global, widespread use of large , complex machinery and global, widespread use of chemical for anything and everything we could think of.

The shift from traditional family farming, which since it began 10000 years ago was always done on really very small scales, and naturally with the largest workable and sustainable variety of plant species being grown together, to the modern ways that could best accommodate the limitations imposed by using great big machines instead of our hands to tend the fields, gave way to huge monocultures, which in turn, gave way to huge problems with insects attracted to these particular species of plants being grown without the natural balancing effects of competing or antagonistic insects attracted to different plants growing side by side in the small space of the family garden.

Just follow this impeccable human logic: nerve gas kills humans by blocking the action of the enzyme cholinesterase required to regulate the amount of stimulation triggered by the neurotransmitter acetylcholine that controls heart function by adjusting neuron firing and breakdown rate; all higher animals, including insects, have similar functioning nervous systems because we all evolved from the same primitive ancestors whose most essential function were controlled by their nervous system, whatever form it took; we want to cultivate huge fields of monocultures because it is efficient in producing large quantities of food without much time or labour by using large machines to take care of these field; unfortunately, large monocultures attract disproportionally large numbers of the same kinds of pests that then have free reigns over the plants cultivated because they have no other insects to compete against; insects are affected in similar ways as we are by nerve gas, but because they are much smaller, because we are so much larger and stronger than they are, they would be lethally affected by small quantities of nerve gas while we would not, or at least not very much.

It’s perfect! Amazing! We spray diluted nerve gas on our large mono-cultured crops, kill all these awfully annoying insects that are trying to eat our food, and then simply collect everything intact and in perfect condition. This is the magic of industrial chemistry. What do we call this diluted nerve gas, these chemical agents? Pesticides, of course. Very popular right from the start, but incredibly more popular today than 70 years ago.

In fact, pesticides are more than 30 times more popular today than they were in 1945. Every year we dump more than four billion pounds of pesticides on the soil of the Earth. Four billion pounds worldwide, and one quarter of this—one billion pounds—is used in the US alone!

As can be expected from our amazing human ingenuity, cleverness, tenacity and industriousness, there are now tens of thousands of different kind of ‘nerve gases’ with different purposes, different functions, different effects and different potencies. We are so darn good, so clever at improving things, making them longer lasting, more effective, more targeted, more concentrated, and naturally… more lethal.

The obviousness of the truth is painful and so we look away: all pesticides are neurotoxic because this is how they function to kill pests. But since we are also a pest of sorts, they are neurotoxic to us in the same way as they are to those insects we want to get rid of. As a result, we are killing the insects, and we are killing ourselves. Moreover, we are doing it better and better each year and with every passing day. That’s the long and short of it. Sorry to be the bearer of such bad news.

Yes, we can eat our own home-grown stuff, and exclusively organic and pasture raised food—I do and have been for the last 18 years since graduating from McGill in the spring of 1996. But pesticides are in the rivers, oceans and water tables, as well as in the air, the clouds and the rain. And this, in ever-increasing concentrations. What we can do is try to protect ourselves as best we can by minimising our ingestion of and exposure to such poisons by all the means available to us, integrate continuous detoxification practices in our daily life, and do whatever we can to shift the balance of policymaking towards the support of small scale organic farming and away from the industrial monoculture model pervading over so much of the planet. Maybe the trends will change, and maybe sooner rather than later, but it’s hard to tell.

With the opportunity and truly great privilege we have to be alive and able to look back onto the past, and consider anew the circumstances, events and developments that took or might have taken place with a fresh perspective encompassing a multitude of informative elements available to us now but that were not at the time, I believe that nobody could have foreseen that the chemical technology of biological warfare agents developed during the second world war in Germany would become so incredibly popular as to pervade the entire planet to the extent of reaching virtually all ecosystems from the poles to the equator, up and down and all around to the most isolated and distant. And although seldom recognised as such, it is this, one could argue, that has had the most important and pervasive negative impact on humankind, one of the most devastating consequences of Hitler’s lethally poisonous legacy: the gift of pesticides.

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Essential blood test reference sheet

No matter how healthy we feel, and how healthy we think or we believe we are, if we are serious about health, we have to have a quantitative approach. To measure the concentration of various biochemical species in the blood is the best way to “take a look inside” with minimal intrusion. And with a complete set of tests, we can gain a fuller picture of what’s happening now, what is in progress, and what might be waiting to happen.

An issue that is definitely problematic is that whenever we get a blood test, as rudimentary or extensive as it may be, the reference range for each marker is based on the average from the typically sickly population of the country or region where we get the blood test, and incredible as this may seem, there are sometimes very important differences in these references. However, it should be clear that independently of our genetic background and tendencies, and independently of what we need to be in perfect health at a given stage or during a specific period of our life, there are some markers that are far more important or have far greater diagnostic power than others, and that there are optimal values for each one of these biochemical markers.

As you may already know, I am an astrophysicist, and my research work relates to developing advanced statistical analysis methods for treating data and extracting as much information from them as possible. This, for now, applied to topics in observational astrophysics. I really enjoy working with data, with optimal analysis methods and novel statistical treatments. As you also have most probably understood, it is through this hard, no-nonsense, scientific approach of the thorough physical data scientist that I strive to understanding how the bodymind works and what it needs to do it perfectly on all levels and for as long as possible.

This is why I have compiled and typeset this blood test reference sheet, the likes of which I have not encountered, which is intended to both keep track and guide you to optimise all essential biochemical markers—an optimisation without which we cannot possible achieve and maintain perfect health. I hope you find it useful, and you are naturally welcome to share it with those you know or think will appreciate or benefit from it. Your comments and questions are also welcome. It will be updated whenever I come across something that should be included or modified.

Here is my essentialBloodTestReferenceSheet (click to view and download the PDF), and this is a Google spreadsheet version of it (courtesy of my colleague Ivan) that you can “save as” to your own Google docs and add a column each time you get a blood test to keep track of your results.

The crux of intermittent fasting

It is less than futile, in fact, it is outright nonsensical, to argue in favour of or promote an explanation that is in contradiction with observational evidence. What is required is to find, or at least try to find, a sound and well-founded explanation. And not just for some of the observations, but for each individual observation, as well as for the entire ensemble of observations. This is what we should do.

Fasting means not eating; everyone knows that. The meaning of the word has been loosened to include not consuming appreciable amounts of calories, as in doing a green juice fast, for example, but which should instead rightly be called a cleanse. The expression intermittent fasting implies a cycle of some kind, and is used to mean not eating for periods of 16, 18, 24 or 48 hours, but on a regular basis, like every week or even every day.

Fasting has been known and recognised for its often quasi-miraculous curative effects for thousands of years. Indeed, it is possible to find accounts of individuals recovering from just about any ailment and disease imaginable simply from fasting long enough. It seems, however, that fasting as a healing modality, has, over the past couple of centuries, steadily grown less popular in the medical profession and, as a consequence, also in the general population.

A resurgence of scientific interest over the last decades in the benefits of fasting for treating various degenerative conditions like arthritis and cancer, but also for extending healthy lifespan about which I will write at one point in the future, has brought it back into the spotlight, especially in circles of optimal health enthusiasts, which includes some gym go-ers and body builders interested not so much in optimal health, but mostly in losing fat and gaining muscle.

Therefore, there has been quite a few people trying out or adopting intermittent fasting for periods of a few weeks to a few months, or even longer, but reading things here and there shows that they have had varying success given their initial motivations, whatever those might have been.

Ori Hofmekler was one of the first to popularise the idea of intermittent fasting with his book The Warrior Diet. He has continued to write and to encourage intermittent fasting for a wide range of benefits, especially in regards to the goal of improving body composition, as one of his last titles expresses perfectly: Maximum Muscle, Minimum Fat. Dr Hertoghe, the world famous endocrinologist and anti-ageing specialist, as well as Mark Sisson (Primal Blueprint) have also been vocal and influential proponents of intermittent fasting for a while. More recently, Dr Mercola did several interviews with Hofmekler, and wrote a few articles on the topic, sharing his experience and enthusiasm for the health and fitness benefits intermittent fasting can bring. These are just some of the well known players that I know of and respect in the natural health community, that have endorsed and promoted this kind of cyclical fasting.

Naturally, as is the case for almost any topic we can think of, there are opposing opinions and, in fact, bashing of intermittent fasting as a means to improve health and body composition, especially in the popular fitness and gym culture. And, as is also the case for almost any topic we can think of, contradictory views and opinions are usually caused by misunderstanding or at least incomplete understanding of the elements involved, and in particular the more subtle ones.

On the one hand, we have the proponents claiming that we can very effectively get much healthier, with much improved energy levels, mood, digestion, and natural detoxification and excretion of metabolic acids; normalise and recover the optimal balance of specific hormones, and eventually, of the entire hormonal system; over time lose all excess body fat reserve, increase flexibility and hasten recovery, better preserve our precious muscle tissue and build more very efficiently. And these are just some of the claimed (but also documented) benefits of intermittent fasting.

On the other hand, the nay-sayers and bashers report that these claims are more than just false, they are, in fact, often the exact opposite of what they have found or seen for themselves or in others coming to them for help and expert advice. Reports of feeling really terrible, with massive headaches, bad digestion, awfully low energy levels, and thus, obviously, very bad and destructive moods; loss of some fat but also, over time, of lots or maybe even most of their muscle tissue; extreme hunger, with frightening ravenousness when evening mealtime comes around, leading to monstrous, uncontrolled and uncontrollable overeating without discrimination of food kinds or quality, and over time, showing obvious signs that can be identified as those associated with eating disorders.

How is it possible to have research, studies and documented cases—plenty of documented cases—that provide observational evidence—proof, if you prefer—that support the claims of both of these camps? How can we observe and actually measure such profoundly different consequences in different people that are supposed to follow comparable diets, consequences that are diametrically opposed to one another. In other words, observational evidence that appears to be completely and totally contradictory?

A simple approach, the one espoused by many, maybe most, of the intermittent fasting bashers, is to just say that proponents are wrong and imagining things, letting themselves be fooled by the hype, but actually blind to the reality of the detrimental consequences of practicing cyclical fasting.

For me, the only satisfactory approach is the one that seeks to explain all the observations, to reconcile all the observational evidence, and make sense of the entire ensemble of information available through a physiology and biochemistry based explanation that is complete. I also think it is fair to say that there are more better informed proponents than there are opponents, but this is not obviously the case, and I would thus not bet much on this claim.

Here it is, the crux of the matter, the one single crucial element needed to understand and explain the wide spectrum of apparently contradictory observations that is overlooked because it is misunderstood: The body’s response to intermittent fasting is entirely dependent upon the state of one’s metabolism, and everything about it hinges on the physiology of nutritional ketosis. 

In fact, the vast majority of the benefits of intermittent fasting are those derived from nutritional ketosis but heightened by the fasted state, and therefore, can only become manifest if the fasting individual is keto-adapted and remains in nutritional ketosis most of the time.

You might be thinking: what in the world is nutritional ketosis, and where’s the explanation for the contradictory observations? Nutritional ketosis is the metabolic state in which the liver manufactures ketone bodies from fat to provide fuel for the brain cells that can only use glucose or ketones for their energy needs. This only happens if and when circulation insulin levels are low, and when blood glucose stays below 80-90 mg/dL for a period of 24-48 hours. The reason is fat will not be burned for fuel is there is plenty of glucose in the blood, and in order to burn fat, insulin must be low.

This metabolic state is induced either by fasting—this is the quickest but also most extreme way to do it, or by eliminating insulin-stimulating carbohydrates (sugars and starches) from the diet—this is by far the easier and obviously much more sustainable way to do it. The longer it is maintained, the better adapted the metabolism becomes. But before ketones are produced to fuel the brain, the body goes through metabolic changes to which it tries to adapt as best it can. The most important but also most severe of them all, is the fundamental shift from using glucose as the primary fuel, not just for the brain, but for all cellular energy needs in the body, to using fats, both from body fat reserves and from food.

The bane of our time is global, chronically elevated insulin levels. Hyper-insulinemia, as it is technically called, sits squarely as one of the root cause of all the diseases of civilisation that kill most (90%) of us today, more or less uniformly across the planet. What does this have to do with our considerations of intermittent fasting? It has everything to do with it: insulin is the master hormone that orchestrates the metabolism in what relates to storage and usage of macronutrient (carbs, fats and proteins) at the cellular level.

Chronically elevated insulin always and inevitably leads to insulin resistance. Insulin resistance means that cells do not respond to insulin as they should, and require ever increasing concentrations of insulin in order to move glucose into the cell. And ever increasing concentrations of insulin means ever increasing inability to use fat as fuel of cells, with particular difficulty in unlocking and tapping into the usually greatly overabundant reserves of body fat.

What is truly remarkable is that insulin resistance, even if it has been developing and growing steadily with each passing day and with each high carb meal or snack over our entire lifetime, it can be reversed in weeks when insulin-stimuating carbs are eliminated from the diet: 48 hours to enter nutritional ketosis; one week for water retention release, initial intestinal detox and basic adaptation to fat-burning; four weeks for functional keto-adaptation; and 8 weeks for complete keto-adpatation.

Eliminating insulin-stimulating carbs eliminates the need for insulin secretion by the pancreas. Therefore, both glucose and insulin concentrations steadily decrease with time, and eventually fat-burning and ketone production kicks in, marking the first step in the transition of the metabolism from sugar-burning to fat-burning, which is what we referred to as keto-adaptation.

There is a catch though: before fat-burning and ketone production begins, the metabolism of the insulin resistant individual will go through withdrawal from its sugar addiction. First, sugar levels start to drop. After a number of hours, 3 to 4 hours say, blood sugar is too low to supply enough fast-burning glucose to cells for their metabolic activities. Because insulin remains high, and because the body is highly insulin resistant, as we said, it is not possible to use fat from the body’s fat stores. Therefore, it is the liver that comes to the rescue and begins to convert its stores of glycogen into glucose and pumping that into the bloodstream to provide cellular fuel.

Within a few hours, however, the glycogen in the liver is depleted, and blood sugar drops once again, and lower still. Because the body remains unable to tap into its fat reserves due to the state of insulin resistance, it has, at this point, no choice but to turn to muscle tissue, from which it is far easier to breakdown protein and manufacture glucose than it is to start burning fat. And thus, the muscles are eaten away in order to provide the glucose to all of the multitude of insulin resistant (sugar-addicted) cells throughout.

We now come to the final analysis of our observational evidence in regards to intermittent fasting, and consider two scenarios that can explain, as it rightly should, the ensemble of observations in its entirety, and thus clarify and reconcile the apparent contradictions that are seen, and which lead to serious confusion about the issue, even, and maybe especially, among our health, fitness and bodybuilding experts.

Scenario 1: We take a perfectly keto-adapted person whose been eating a diet devoid of insulin-stimulating carbs for a long time, and who therefore always has very low glucose and insulin levels, and as a consequence, exquisite insulin-sensitivity. What happens if they stop eating? Nothing special, really. Their body is always using fat and ketones to supply all healthy body and brain cells with their metabolic energy needs. So, if there is no fat that is provided through the digestive system, then it is taken, without any trouble or noticeable changes in energy levels or concentration, from the body’s fat reserves that are always plentiful, even in the leanest among us with single digit body fat, because 1 gram provides 9 calories, which means that we need only about 200 g for a whole day of normal activities, and have at least 5 kg at any given time (8.5% fat on 63 kg, like me).

Moreover, if we exercise during the fast, there is no noticeable difference because at low intensity, cellular energy needs are taken care of by fat which is continuously released from the fat stores into the bloodstream, while at higher intensity the glycogen stored in the muscle cells themselves, can be used in the form of quick burning glucose together with additional supply from the liver than converts its stores of glycogen if need be (if stress hormones are secreted).

So, biking and working out with weights, for example, is perfectly fine and actually feels great. Even more interesting is the fact that stimulating the muscular system by exercising while fasting triggers the release of various hormones in addition to growth hormone for which there is nothing more effective than fasting, whose purpose is primarily to preserve those physiologically important muscle tissues as essential for functional survival, while breaking down to recycle the proteins of other tissues which are not required like lumps, tumours, and scar tissue. And this means that the hormonal environment created by exercise under fasting conditions is conducive to both preserving and building more muscle, all the while also expediting and maximising fat-burning. And this is what is observed.

Hunger is present at times, but is certainly far from being problematic. There are no headaches, no stomach pains, no sleepiness, no scattered mental discursiveness, no problems concentrating or working. Sitting down to eat the evening’s nutrient-dense, enzyme-rich and high fat meal with adequate amounts of protein for tissue repair and muscle building, is nourishing, perfectly satisfying, and well digested throughout the evening and night. No over-eating, no cravings, no psychological disturbances, no problems at all. A picture of perfect metabolic efficiency.

Scenario 2: We take an average but pretty active person from the general population who eats a standard diet with plenty of insulin-stimulating carbs, both simple and complex in the form of pasta, rice, whole grain bread, etc (70% of calories), and who therefore always has high blood glucose and insulin levels, and as a consequence, pretty strong insulin resistance. What happens if they stop eating? We saw this earlier: blood glucose drops, but not insulin; the liver starts to pump out glucose to pick up the slack, and runs out after about 3-5 hours; sugar drops once more, but not really the insulin; since fat stores cannot be tapped into, muscle tissue is broken down to manufacture glucose; longer period of fasting means more muscle breakdown.

If we exercise gently, things are fine at first because we can tap into the glycogen stored in the muscles, but will soon get much worse because we increase the energy demands, but continue to be unable to use body fat stores, and therefore increase the rate at which muscle tissue is broken down, especially if we do weights and high intensity training.

Low intensity aerobic exercise depletes glycogen from the muscles and when it runs out, we feel exhausted, completely flat out. (This is the same as hitting “the wall” in long distance events, and only occurs because the body cannot readily tap into its fat stores: a well keto-adapted athlete never really hits any such walls!) Far worse is high intensity exercise, which causes more intense and faster muscle breakdown, the higher the intensity, the more muscle breakdown.

Waking up in the morning after a night’s sleep (and unconscious fast), we are starving, dearly longing for the bread, the jams, the cereals, the orange juice, the waffles, the maple syrup, and everything else we can imagine, but we hold out and go to work. Every hour is excruciating, terrible headache, hunger pains throughout the abdominal cavity, when these subside, we are falling asleep, with a complete inability to concentrate on anything at all. We feel like shit.

By the time evening rolls around, we are so ravenous we would eat a horse. So we sit down and eat, and eat, and eat everything we can get our hands on: pizza, pasta with sauce and cheese, garlic bread with butter, steak and potatoes or french fries, and then desert, sweets, oh man, we waited all day to eat, and now we can eat anything and everything we want, because tomorrow we’ll be starving again for the whole day. We get up in the morning, and the whole cycle starts over again.

Over time we kind of get used to it, but because we don’t understand the most essential element of the whole thing—nurturing nutritional ketosis—we remain just as insulin-resistant, every day we feel shitty, every night we eat like a pig, and throughout the whole time, more or less, we break down muscle, and our insulin resistance prevents appreciable fat loss. After doing this for a while and seeing the detrimental effects of this regime, we go seek help from a fitness expert. They tell us that this intermittent fasting thing is a load of shit, and as them, grow instantly convinced that all the stuff people say about the benefits it can bring for optimal health and improved body composition is also a load of shit: if it didn’t work for me, then it simply cannot work for anyone.

Unfortunately, neither we nor the fitness expert understands enough physiology, biochemistry and endocrinology to be able to make sense of these conflicting and contradicting accounts, personal experiences, and observations reported in the scientific literature, and just settle into this view that it really is a load of BS, and that it might work a little, sometimes, on some people, but not on others, and no matter what, it always leads to pathological states of mind, if not full fledged eating disorders.

It is my hope, however, that you are now able to see how these very observations, as conflicting, contradictory, and certainly quite puzzling as they may seem at first, can be explained and reconciled marvellously well in light of a better understanding of the basic principles of energy metabolism, and of the remarkable but unfortunately almost universally misunderstood state of nutritional ketosis, that most medical professionals mistake for the pathological condition of diabetic ketoacidosis, (but that’s for another time).

Finally, in closing, I have a confession to make: I have been experimenting with intermittent fasting in one form or another for many years now. I never eat anything before midday, and on most days until about 14:00, which makes it an approximately 18-hour fast from 20:00 the night before. Once in a while, on weekends, I fast until noon, and then go do weight training. On those days, I usually eat for the first time around 17:30, and make that my single meal of the day. On some days I eat a large lunch and dinner to increase my overall calorie and protein intake. I usually workout 3 times a week, and usually in the late afternoon-early evening.

I have not experienced loss of muscle since I dropped the insulin-stimulating carbs from my diet in 2007. Both muscle tone and strength is maintained very well even after long periods without resistance training. I have, however, never made a particular effort to gain muscle mass. This year, I would like to see how much muscle I can put on, and will thus put the science to the test for myself. If you are interested, don’t worry, I’ll keep you posted. If you’re not, then that’s fine too. But if there is a single thing you must remember from what I wrote, it is this: you can only really benefit from intermittent fasting when you are keto-adapted, and remain in a state of nutritional ketosis the majority of the time. Otherwise potential benefits are lost, and the practice can become rather detrimental.


How long do you think these hunters hunt each day? Do you think they have a big breakfast before going, or a large lunch while they are out? How long do you think they are out before they settle back around the fire in their village to have their main meal of the day? And what do you think they will eat when they do return with their catch of the day?

(This article was written after reading this article by Dani Shugart on T-Nation sent to me by a friend who knew I would have some remarks to make, and probably some clarifications to bring to it.)