I came down with a terrible case of vaccine-induced Serotonin Syndrome. After all, a great many of SARS-CoV-2’s symptomatic presentations closely resemble one of Serotonin Syndrome. The thrombocytopenia and blood clotting, the pulmonary hypertension and anaphylactic shock.
A screengrab from a video presentation by Farid Jalali, MD who discusses the pathological increase in tissue and circulating levels of serotonin with a corresponding decrease in platelet-bound serotonin.
Platelets and mast cells hold the majority of the body’s circulating serotonin. When activated by certain cytokines, they release their pathogenic serotonin, causing aggregation of platelets. The decrease in platelets activates the body’s coagulation systems to maintain hemodynamics. This causes blood clots to form.
Earlier, it was shown with dengue that serotonin derived from mast cells were responsible for infectious mortality (Masri, Mohamad Fadhli Bin et al. Blood. 2019). Mast cell-derived serotonin, the authors say, induces thrombocytopenia (low platelet counts verified by hemogram) by acting upon the 5-HT2A receptor mainly[1].
I had received my first dose of the Covaxin vaccine, an inactivated, whole virion vaccine this October. Since then, I’d suffered a range of very disturbing and rather irrelevant symptoms ranging from tremors, sharp pains, shortness of breath, dizzy spells, depersonalisation, abdominal bloating and severe allergies the likes of which I had never experienced in years. All these symptoms would only get worse whenever would I exert myself. My heart palpitations would occur uncontrollably to even the slightest triggers. Exerting myself also gave me this weird sense of tightness all over my body, a general sense of numbness and tingling all throughout my body (platelet hyper-reactivity maybe?). But that wasn’t even the worst of it. It all culminated one morning when I’d woken up with a swollen face, disoriented, with a blurry vision and unable to balance myself[2].
My parents were around thankfully at the time to take me to a family doctor. He was an ENT specialist so he examined my nasal passages and throat with an endoscope. He diagnosed me with allergic rhinitis. He simply wrote off my nervous symptoms as “vascular headache”, putting me on some beta-blockers and migraine medication. I was prescribed some anti-histamines for the allergies. Like most specialised ant-humans of our industrial society, they lack any meaningful integrative knowledge to pin-point the root cause of all issues.
The medicine only helped dull out the symptoms of my ongoing allergies. It made no difference whatsoever to all of the other symptoms. I was still unable to exercise or do anything, living in constant apprehension of feeling like shit afterwards. My facial swelling and heaviness persisted, coming on and off. I also noticed that I was bruising more easily and developed a weird “pressure sore” on my forearm, or at least that’s what another doctor called it.
I finally feel like my old self today. My usual feelings returned. As I leaned in to sip on my cup of coffee, I felt the usual euphoria. I felt in the moment, present and not like I was observing my reality through a third person. I felt light, energetic, playful and care-free. I didn’t feel the numbness or general heaviness. I felt free to do whatever.
What brought this on? Cyproheptadine.
I was trying out cyproheptadine after learning of its incredible and very broad-ranging anti-inflammatory effects. I had some numbness relief from aspirin but it didn’t cure my tremors or the swelling. Coffee seems to make it worse (perhaps by activating the renin-angiotensin system). I tried drinking hypertonic salt solutions which only provided minimal improvements, if any.
I already knew at this time about the blood clotting issues with vaccines but I could’ve never guessed the underlying role of serotonin. Platelets weren’t the problem. It was serotonin — in the same way mast cells do not cause allergies as much as their histamine contents do. I didn’t need aspirin. I needed an anti-serotonin drug.
While I’d been toying with cyproheptadine in very small doses of 1-4 mg/day which noticeably improved my facial swelling and general malaise, it went back to square one when I took some antibiotics along with it. I was trying to improve my Serotonin Syndrome by targeting a large source of the body’s serotonin, the gut. The gram-negative bacteria produce lipopolysaccharides or endotoxin which is a big contributor to serotonin production. Given my persistent bloating, I had reason to suspect an outgrowth of certain endotoxin-producing bacteria. I’d also been taking sodium bicarbonate and considering acetazolamine since they improve osmotic regulation via oxidative metabolism (biocarbonate production and inhibiting its conversion to CO2) instead of NO, which is a direct route to serotonin. The biggest improvement came with the suggested dosing for Serotonin Syndrome, which is 12-16 mg/day. The next day I woke up a new man. I had thought the vaccine had screwed me up for good since its symptoms stayed with me on and off for a good 2 months. My face felt light and at ease, my tummy not bloated at all. What sorcery was I seeing here, I wondered.
Cyproheptadine antagonises a number of serotonin receptors, including the 5-HT2A and 2B which causes edema (water retention), blood clotting and depressions. Cyproheptadine also powerfully antagonises H1. Post-synaptic 5-HT2B signalling, a G-protein coupled receptor, for instance involves AC activation which forms cyclic AMP (a stress-adaptive pathway via protein kinase A that prevents apoptosis by mitochondrial biogenesis), increased Ca++ uptake (to cause excitation) and activation of phospholipase A2 (to liberate polyunsaturated fatty acids from cell membrane phospholipids to produce prostaglandins, leukotrienes, etc.). All this is prototypical of stress signalling within the cell, any eukaryotic cell basically. Since biogenesis and other proliferative activities involves transcription and translation of genes, the cell shifts metabolism away from the high ROS-generating oxidative metabolism (known as oxidative phosphorylation) to the low ROS-generating glycolysis within the cytoplasm. This is a metabolic phenotype of cancer cells (Warburg effect) since cancer loves to proliferate. Keeping ROS low is fundamental to preventing DNA damage during the rather short cell cycle. Serotonin signalling in the brain’s hypothalamus produces stress hormones like prolactin and ACTH which then causes a peripheral stress response by inducting glucocorticoids. Dopamine (and its precursors like tyrosine) opposes all stress hormones while serotonin (and tryptophan) encourages stress signalling on an endocrine level. All stress hormones unequivocally moves cellular respiration away from oxidative metabolism in the mitochondrion.
I felt rather warm after this high-dose cyproheptadine, a feeling I’ve only experienced after aspirin and eating high-fructose fruit. Salicylates like aspirin also inhibit the serotonin pathway (NO production) by uncoupling mitochondrial respiration from ATP synthase. This increases bicarbonate production, which alleviates the need for NO-mediated osmotic regulation.
Perhaps the antibiotics only really backfired because destroying gram-negative bacteria released bacterial debris and endotoxins (duh!). But it works towards the greater good since a large source of this problematic serotonin would be gone by the end of this antibiotic course. Until then, I’ll hold onto cyproheptadine[3] for dear life.
Cyproheptadine also alleviated my heart palpitations as 5-HT2B antagonism inhibits proliferation of cardiac valve fibroblasts. Serotonin causes remodelling of the heart valves in the same way angiotensin II, the primary pro-inflammatory peptide of the renin-angiotensin system causes cardiac remodelling like hypertrophies. A cardiologist I was taken to sometime in school commented that one of my valves were “twisted” while putting me on an indefinite course of beta-blockers. As always, it never addressed the true root causes of the issue. Upon further research, I was brough to realise that a poor diet (a high-carbohydrate, grain and starch-centric diet elevates tryptophan) might have caused gradual deterioration of my heart, made worse by other stressors.
Cyproheptadine also cured my brain fog and depersonalisation which I had suffered since day 1 of vaccination. Since depressions and delirium are caused by excess CNS serotonin, cyproheptadine behaves like an anti-depressant too, restoring healthy cognition. I felt more “present” and “in my body”, like I was indeed here and not merely observing myself. I felt more eager to do things and not so apathetic. My depersonalisation started sometime in middle school from a chronically stressful (abusive and authoritative treatment at school and home) and under-stimulating lifestyle. While it got better with dietary modifications, it made a comeback for the first time in years props to the wonderful jab.
Likewise, my abdominal bloating also went way which, like IBS, is caused by excess liberation of serotonin. Fiber and other abrasive material increases gut serotonin release. Gas and fermentation, which causes mechanical stresses in the gut walls, also liberates serotonin.
By keeping serotonin receptors blocked for the duration of the initial antibody response and the immune-mediated platelet activation, I should be able to prevent its inflammatory signalling. Cyproheptadine treatment may be weaned off once platelet morphology and function returns to normal. Reducing inflammatory activities also fundamentally increases carbohydrate tolerance (insulin sensitivity), as discussed in my previous posts, which works in a virtuous cycle to create healthy metabolism to bring about cascades of anti-inflammatory signalling.
Cyproheptadine, losartan and methylene blue work to stop SARS-CoV-2 pathology on a very fundamental level.
Unlike ACE inhibitors, losartan merely blocks the signalling of angiotensin II without affecting the downstream metabolism of angiotensin II to angiotensin-(1-7) by ACE2. Losartan merely holds off the inflammatory signalling of angiotensin II, buying the body more leeway to process angiotensin and bradykinin. This prevents pulmonary hypertension and vascular pathologies from either contracting the virus or vaccine since all vaccines generate anti-idiotypic antibodies (ACE2 antibodies) to anti-spike protein antibodies, a form of auto-immunity. This imbalances ACE/ACE2, causing the increased ACE activity to cause vascular inflammation (dysfunction of the endothelium). The anti-idiotypic antibodies can be thought of as the “clean up crew” that form immune complexes (which are inflammatory in itself) with existing anti-spike protein antibodies, removing them from circulation.
Methylene blue is a potent redox state balancer. It acts as a sort of electron buffer, donating and accepting electrons, allowing electrons to go where they need to go. Despite being the standard treatment for shock, methylene blue finds itself off-label use as a cellular rejuvenator like high-dose niacinamide or CoQ-10. This in itself so profoundly improves oxidative metabolism, building up cellular efficiencies, allowing the body to come out of whatever upset, going back to physiologic functioning.
Quinine, hydroxychloroquine and other anti-virals stop the inflammatory signalling by SARS-CoV-2 by antagonising toll-like receptors, stopping interferon production. But I wouldn’t recommend them since they are “specific” to treating the disease while cyproheptadine, losartan and methylene blue work on a more fundamental level, potentiating the body’s own anti-inflammatory activities while providing additional and more generalised protection.
Footnotes:
A low metabolism from inactivated ChREBP and SREBPs can also predispose one to carrying an excess amount of mast cells. These transcription factors are central to metabolism along with PPARs, which determine the cell cycle. Estrogen causes proliferation of mast cells. When cells are inflamed i.e. either by endogenous sources of stress or exogenous sources (such as PUFAs), the expression of gene related to oxidative metabolism is suppressed. PUFAs suppress ChREBP and SREBP, as do most pro-inflammatory cytokines, prostaglandins, leukotrienes, oxLDL contents, among other things. Since the cell membranes are made of phospholipids the presence of unsaturated fats, in eukaryotic cells, is interpreted as a state of oxidative damage, causing stress-adaptive gene expressions (PPAR, PGC-1alpha activation, ChREBP and SREBPs inactivation), causing proliferative activities while impairing oxidative metabolism. This increases the risk for cancer, causes insulin resistance of cells (by downregulating pyruvate kinase via ChREBP suppression), moving energy expenditure away from all higher, protective functions of the cells (impaired steroidogenesis from StAR downregulation via SREBPs suppression). This skews the ratio of androgens:estrogens, which could be a key determinant of metabolic rate and mitochondrial oxidative capacity.
Like most things we hear from mainstream medical establishment, Parkinson’s disease is anything but an excess of CNS dopamine. Parkinson’s however, is an extreme manifestation of peripheral Serotonin Syndrome. All of the signs and symptoms of Parkinson’s line up neatly with what I had experienced from my vaccine-induced Serotonin Syndrome — tightness of muscles, loss of co-ordination or balance, apathy, depression, tremors, etc.
Like anything that opposes cytoplasmic glycolysis, cyproheptadine has strong anti-cancer effects. This thread from Ray Peat Forum cites a lot of these studies. Aspirin has also been shown to have anti-cancer properties, again by opposing the metabolic phenotype of cancer cells. Saturated fats also have strong anti-cancer properties by inhibiting cAMP/PKA signalling cascade while unsaturated fats encourage this metabolic phenotype in cells, making the body more hospitable for tumours.
We’ve probably all heard the adage, the pillars of health are physical activity, rest and healthy eating habits. But does this always hold?
From my experience and from my understanding, the answer to that would be a ‘no’.
Diet and nutrition is what fundamentally determines our ability to exercise and reap its benefits.
To even metabolise energy and transport oxygen, you need B vitamins and iron. If you are deficient in one or more B-complex vitamins or an important mineral like iron, you are going to find it harder to exercise, or enjoy it.
To even reduce your blood pressure, a benefit of intense physical activity, you need an amino acid, arginine, which is a precursor to nitric oxide. Nitric oxide helps vasodilation. Arginine deficiency = inadequate vasodilation. As simple as that.
To even relax, you need two things. A healthy electrolyte balance so your muscles can contract and function normally and secondly, nutritional adequacy to support inhibitory neurotransmitter synthesis and signalling. A choline deficiency here, which is quite prevalent even in the first-world thanks to shady corporate interests writing the dietary guidelines, can seriously impact your parasympathetic tone and your ability to sustain a normal and healthy heart rhythm following exercise. Healthy electrolyte balance between sodium, potassium and magnesium, in that order, if often hard to sustain even if you were getting enough in your diet but were inadequate in other nutrients such as vitamin D, which is an important modulator of the renin-angiotensin-aldosterone system (RAAS). The RAAS is a complex system, consisting of several glands, their secretions (hormones) and organs (kidneys) that controls everything from BP, vascular tone and function as well as electrolyte levels in the body.
In fact, even the metabolic state you are in profoundly affects your ability to relax as for instance, being in ketosis encourages the biosynthesis of GABA, an inhibitory neurotransmitter than raises the seizure threshold, since ketone body metabolism utilises the glutamate pathway.
It is therefore important to understand biochemistry well enough, from the basics, not to mentions the cobwebs of factors from genetics to environment, if you wish to have a meaningful opinion on nutrition and health.
The same applies to sleep and recovery. To even relax and remain in sleep, you need to maintain these underlying homeostatic factors. From personal experience, I was able to rid myself of panic disorder and disordered sleeping by going on a high fat (mainly saturated and omega-3 enriched) diet. I also supplement with vitamin D3 orally once a week to maintain serum 25-hydroxy(vitamin D) levels around 60 ng/mL. Believe it or not, vitamin D has also helped me build and retain muscle far more easily, lost an additional 2-3 kgs without doing much which really goes to show its importance in muscle health and regulating metabolism.
I think it should be sufficiently clear at this point that whole-body wellness is really downstream of nutritional adequacy and metabolic health. You can exercise all you want and still feel like shit. You can socialise and spend as much time around other people and still feel agitated and irritated. You can sleep 12 hours a day and still experience depressive symptoms and dysregulated moods.
So where does whole-body wellness begin? At the cell, unsurprisingly.
Healthy cells = health organs = healthy body.
Any metabolic disturbances inside the cell ultimately manifests as sickness.
Let’s take diabetes for instance. What does diabetes, fatty lives, dyslipidaemia and obesity all share in common at the cellular level? Chronic AMP-k deactivation.
AMP-activated kinase or AMP-k is a master regulator of cellular energy homeostasis. It senses the ATP/AMP ratio (which ideally should be greater than 100 for the cell to function). If the AMP levels rises, such as during exercise, fasting and other stress states, AMP-k translocates the glucose transporter protein, namely GLUT4 as expressed in skeletal tissue, to the cell surface. This increases the sensitivity of the cell to insulin, the body’s primary anabolic hormone which, as people already know, is important in diabetes. APM-k activation, put simply, increases insulin sensitivity which reduces the amount of insulin needed to clear glucose from circulation. Less insulin = less load on pancreas = reduced risk of beta-cell atrophy = reduced risk of type 2 diabetes. Simple as that.
When one truly understands biochemistry from the bottom-up, you start to realise all of our modern diseases of affluence have very simple cellular causes.
Ugh.. I could go on but I have to cut it short to the chase.
A good diet, to me, is one that creates metabolic health and nutritional adequacy. In this light, a lot of ‘fad’ diets simply aren’t healthy, even if they are shown to be healthy for certain reasons in specialised and narrow settings. In fact, the majority of nutrition research is designed and done using the same paradigms of reductionist thinking that helps you understand phenomenon in the physical science. But guess what, nutrition, health and wellness are whole-body concerns that are better addressed through systems thinking.
I always cringe when some reactionary empiricist comes running at me with a new paper to justify his coffee habit. “Look Shrey, drinking 2-3 cups of coffee daily in this RCT with n=490 reduced liver fat and inflammation markers!” But at the same time, we have studies that show that poor metabolisers of caffeine, which really is a pesticide made by plants to dissuade predators from consuming its seeds by creating a bitter taste when consumed, have an increased risk of adverse cardiovascular events following coffee consumption. So here, the context really matters. Are you drinking coffee as someone of Caucasian descent (fast metabolisers) or Asian descent (slow metabolisers)? Are you drinking coffee in the context of first-world nutritional adequacy, enough anabolic and high-quality animal protein that helps you biosynthesize the necessary enzymes required to process said caffeine in coffee or are you struggling to barely meet your protein needs? These contexts matters. In the right context, anything can be ‘medicinal’, even dog shit can be proven to cure cancer if you study it in the right context. But that is no excuse to get everyone on dog shit, right? You just need to be smart enough to understand whole systems, which is a HUGE PROBLEM in modern academic which almost exclusively is an erudite club of reductionist thinkers.
Anyways, coming back to my point.
I think diet and nutrition aren’t so much the pillars to good health as they are the foundation upon which all health may take form.
So if diet is the foundation, what are the structures or pillars of health?
I think foremost is a nurturing and safe environment. If you don’t feel safe where you work or live or spend a considerable amount of your time daily, you will end up with a dysregulated nervous system. You need to feel safe, accepted and important where you are, doing what you do. Now this in itself is so hard to get or establish. While it is no guarantee that society or the people around you are going to see your gifts or value you or let you do something of your own inclinations, what you can do is seek romantic relationships early in your life. And this is quite an achievement in itself, finding true and great love. And it’s nothing like the fairytale of ‘love at first sight’ painted by children’s stories and Hollywood. (I think these false expectations are a prime cause of unhappiness in relationships, where people never seem to find what they want because often times, what they want is just what they have been programmed to want and doesn’t serve their own, best interests.) The reason why I emphasize romantic relationships of all is because they serve many of the most fundamental needs for a human, from physical (safety, comfort, etc.) to psychological (intimacy, etc.) needs. You cannot get all of these from a friend. But you could do everything you can with a friend and more with a good lover.
But what about diet? What should ideally go into a good diet to make this all work? And what’s a good lifestyle?
Let me present to you..
Shrey’s legendary ‘big brain and big balls’ diet plan UwU:
You may flexibly design and use your own recipes involving foods from the following categories, in the presented order:
Always choose foods from higher up in the list, when and where they are available. If not, move further down the list. The first three categories of foods are nutritionally complete in themselves. So you wouldn’t be missing out any any major nutrient groups consuming nothing but beef or cheese in a day, although not ideal.
Red meat is perhaps the only nutritionally complete food category, not to mention the most compatible, for a monogastric mammal such as ourselves. All ruminant animals up-cycle nutrients from plants into biologically-active forms that our bodies can absorb and assimilate. Ruminants can covert the vitamin K from grass to vitamin K2, the form that is most beneficial for our bodies. They can synthesize nutrients like several B vitamins in the rumen and for this reason, contain all of the nutrients that would otherwise be impossible to obtain directly from plants. They also provide the right synergy of nutrients alongside each other. Like milk, for example, contains calcium and vitamin K2/D3, which helps transport calcium into bone. You do not get calcium from any other plant source in this synergy.
The further up the food chain you go, the more variety and density of nutrients you get. I cringe when vegetarians say, “why do you need to eat animals if animals can get their nutrients from plants? After all, the strongest and biggest animals are herbivores.” They are. because they have very different digestive systems that uses living matter, namely microbes that live in symbiotic relationships with their host, to process and synthesize new compounds from their feed. Ruminants are, in other words, creating their own nutrient supply through a metabolically intensive and elaborate process called enteric fermentation.
Humans, on the other hand, cannot convert our nutrients or access nutrients from plants as easily within our digestive systems. We are monogastric and have putrefactive stomachs. Ruminants have fermentative stomachs where all of the nutrition the animal absorbs into its body was either manipulated or made by microbes. This means even the most herbivorous of animals are, in reality, are living off other living creatures, whether unicellular or multicellular. For instance, precursors to bioactive nutrients like carotenoids, ALA or vitamin K have to be acted upon my microbes or enzymes before they can become tangible nutrients that our bodily processes can access and utilise. We also cannot synthesize many of the long-chain fatty acids in adequate amounts from short-chain precursors because our elongases and desaturases involved in polyunsaturated fatty acid metabolism are nowhere as effective. This predisposes monogastric animals with a tendency to bioaccumulate dietary fats in their original form. Modern feeding practices, as a result, produces higher omega-6:3 ratio* in tissue of pork and chicken, both of which monogastric, while producing much less omega-6:3 in the tissue of beef, a ruminant, even when the feed’s fatty acid profile is maintained.
Fermentation produces many important nutrients that our bodies need since microbes (and larger multicellular organisms) share many of the same biochemical apparatuses that make our own cells tick. What this means is that consuming animal cells provides all of the necessary co-factors, antioxidants and nutrients, the right balance and combination of which, that ultimately helps nourish our own cells. Many powerful cytoplasmic and mitochondrial antioxidants like glutathione, coenzyme Q-10, which is a co-factor in the electron transport chain, are found abundantly and exclusively in animal foods. Plants contain nutrients for plant functions and animals contains nutrients for animal functions, put simply. A nutrient is nothing but a co-factor, precursor or some other metabolically important compound that participates in our cellular activities. Vitamin K, for example, is just a fancy term for a co-factor in our carboxylation cycle which helps us synthesize proteins involved in blood-clotting. Vitamin B12 and amino acids like methionine are co-factors in our methylation cycle, to supply the necessary methyl groups to the methyltransferase enzymes that keeps our DNA, lipids among other things methylated.
Many important B vitamins like niacinamide are found in meat and fermented veggies but not in the fresh veggies themselves, which only contains the precursor of which called niacin. It’s our bodies that then have to convert niacin to niacinamide. In other words, our bodies have to spend its own nutrient reserves and enzymatic apparatus to render these nutrients active. This process of nutrient activation or conversion is naturally confounded on prior nutritional status and health. So using plants as your primary source of nutrients while you are already depleted of other supporting nutrients that would help you make use of nutrients in plants only perpetuates a vicious cycle of malnourishment. Because when you eat fermented veggies, you are also consuming the microbes and any of their secretions within them, the nutrients they have hoarded so to speak. And niacinamide is the biologically relevant form of B3 that our life-giving enzymes like NAD+, which catalyses over 400 other enzymatic processes within the body, is built from. Ruminants also do this, which is why we must take a hint from nature, whereby they digest the microbes itself in a separate chamber of their stomachs called the abomasum. This way, they opportunistically employ microbes, first to nourish themselves and multiply in numbers, and then eating them itself itself to gain any nutrients they might have processed and hoarded, maximising the benefits for the host.
When you eat some metabolically-intensive animal or plant tissue, like the heart muscle of an animal or the leaves of a plant, you get all of the important nutrients that helps your own cells function. However, plants don’t use the same metabolic processes our cells do and therefore lacks the right synergy or variety of nutrients that balances and enables our own bodily processes. For example, a plant makes its own energy through a process called photosynthesis. This process utilises many nutrients. For instance, magnesium is a central component of the chlorophyll complex. The excitation energy from chlorophyll that is inducted from photons is transmitted via carotenoids such as lutein and zeaxanthin. These carotenoids also function as passive antioxidants as they can donate electrons. (In biochemistry lingo, any electron donator is an antioxidant.) Our own cells use a very different biochemistry to function. So while eating spinach will provide you with magnesium and carotenoids, it lacks the other life-giving nutrients and in the right combination or synergy of which that animal cells more readily provide on top of everything you could get from directly consuming plant life.
The electron transport system in plant life is dissimilar to our own mitochondrial electron system, which uses a different set of co-factors to make the magic happen. In contrast, the metabolically-intensive tissue of an animal, such as the heart or working muscles of the limbs, provide all of the necessary co-factors in our own cellular respiration (B vitamins) with all of the antioxidants to go with it.
The phytochemicals or other compounds found in plant life also disrupt many of our own cellular processes. Phytosterols, for instance, cause cholesterol malabsorption and metabolism. Several other phytochemical selectively inhibit cellular pathways, protein synthesis (as a way to kill pests) as well as deactivating enzymes or depleting the nutrient reserves in our bodies. Tannins in green tea for instance can deactivate catalase, an antioxidant enzyme found abundantly in our liver. It also deactivates enzymes like β-glucosidase involved in the digestion or hydrolysis of plant proteins or non-starch polysaccharides. This is also why plant proteins are harder to digest since, after all, the plant, as a living thing, doesn’t want to be eaten. Unlike the ‘fight or flight’ of the animal kingdom, the kind of warfare plants engage in with predators is more chemical than physical. The majority of pesticides we consume, as a result, are of a natural origin than synthetic. Not to mentions the whole array of both heat-sensitive and heat-resistant anti-nutrients which cause mineral malabsorption and carbohydrate-binding proteins like lectins that cause autoimmunity by forming glyosidic bonds with our glycoproteins. You also get a whole array of digestive enzyme inhibitors in the seeds of plants that are specifically meant to make it harder for your gastric secretions to break them down. Legumes are especially guarded with protease inhibitors which makes your stomach more acidic since proteases work best in low-pH environments. Protein digestion requires an acidic medium after all and deactivating the proteases only makes it harder on your stomach.
It is therefore no doubt that plants contain some of the compounds found in our own bodies, like with plant protein, which can contain all of the essential amino acids we require when combined properly (grains + legumes are quite complete). But the question of whether they are accessible to us in their immediate form is dependent on the architecture of the digestive system. In other words, plants do contain nutrients for us, but processing them to the appropriate composition yields a lot more wastes that needlessly load our filtration systems without having the intended nutritional effect on our bodies.
Looking at plant vs. animal protein for a quick case study, we find that the composition of amino acids in plants results in greater losses to deamination and oxidation, since they do not occur in the right synergy required to support protein synthesis in animals. Deamination of excess amino acids when they come lacking of other synergistic amino acids, results in greater nitrogenous wastes such as urea, making plant protein more deleterious on the kidneys. In simple terms, when nutrients are used ‘as is’, there is less waste generated. Our bodies have more in common with a cow than a cucumber and therefore, less wastes are generated in the process of digesting, accessing and assimilating the nutrients found in beef.
Fermentation gets rid of a number of these anti-nutrients, from phytates to lectins and even gluten, breaking them down via microbial enzymes before they even encounter our digestive systems. They perform many of the chores required to bring out the nutrients, so to speak, from relatively inaccessible sources through processes such as cleaving, hydrolysis, etc.
The way to think of ruminant digestion as a multi-layered stomach with progressively increasing pH. Unlike our highly acidic stomachs that are designed to immediately digest bioavailable protein, herbivores use their rumen’s microbiome, much like the sauerkraut that offers nutritional benefits beyond that of fresh cabbage, to build the necessary profile of nutrients that suits animal life before digesting them, much like humans, in their more acidic chambers. Anytime you encounter an acidic environment as far as digestive systems go, you can safely assume that it was meant for protein digestion since proteases work best in a low pH environment. No living matter can survive beyond this point and all fermentation is effectively stopped here, much like the yeast that eventually dies out after the ale has fermented.
In very simple terms, all nutrients for monogastric animals are best obtained from an animal or from something involving animal cells, namely fermentation.
Minerals also are best absorbed into our system when they are packaged into carriers. For example, mineral supplements like Shilajit show superior bioavailability of minerals because fulvic acid’s molecular structure acts as sort of carrier, creating these mineral complexes that are easily absorbed. It is also for this reason that vegetarians, who get most of their iron from non-complex sources to consume vitamin C along with iron because vitamin C provides the necessary carrier for free, non-heme bound iron. So it’s important to consider if a mineral is absorbed in its free form or as a complex, bound to some protein or other organic acids.
Unlike ruminant animals, humans are best nourished by directly consuming other ruminants OR doing the process of fermentation outside our bodies. Fermenting wheat, for example, brings down its gluten and lectin content significantly. These are two known gut irritants and anti-nutrients that makes it harder for our body to access other nutrients in wheat. Secondly, some proteins are broken down by microbial enzymes which makes them all the more easier to digest and assimilate into our bodies.
Fresh vegetables or whole plants (seeds and leaves mainly) are full of toxins and anti-nutrients that can cause serious gastrointestinal troubles (IBS, gut-wall permeability, etc.). Any kind of plant is best eaten processed, fermented to render it more appropriate for our digestive systems. Here, the digestion begins outside the body, long before you put it in your mouth where you are essentially performing what a cow’s rumen does with it’s low pH environment.
Let’s do a case study with sauerkraut, due to its popularity and since we have a name for it. Virtually any vegetable can be fermented or pickled, not just cabbages. Fermented spinach and other green leafy vegetables can be excellent sources of vitamin K2 in a vegetarian diet!
Sauerkraut, which translates in German to sour cabbage, is a popular fermented vegetable dish made by finely chopping fresh cabbage leaves and grinding them into a brine solution. This step ensures the microbes can access as much of the vegetable by increasing surface area. This can be viewed as an analog to rumination, where the animal chews up grasses and processes them in a low pH rumen, where microbes can thrive. This vegetable in brine is then left to sit around at room temperate for a few days to weeks to achieve the desired palatability. After fermentation, the vegetable in brine solution is moved to cold storage, traditionally cellars but the most accessible form of cold storage today for most people is a fridge. The cold temperate is used to arrest the fermentation process. In the cow, this step is achieved by moving the digested mass into a low pH environment for final digestion.
Why is this so nutritionally superior you may ask? Foremost, we must familiarise ourselves with the anatomy of a plant cell. It has a cell wall made of polymers of carbohydrate, unlike the easily digestible phospholipids that makes up animal cells, which to animals lacking cellulase is indigestible. This in itself renders most of the nutrients within plants inaccessible. Secondly, the nutrients in plants are not packaged in a way that facilitates their absorption into our system. All of the fat-soluble nutrients (A, D, E and K) need fat for their absorption. Neither carrots nor cabbage contains any measurable amount of fat. This makes it virtually impossible for our bodies to tap into the nutrients within them. However, fermentation breaks down cellulose into its monomers and monomers into short-chain fatty acids. These short-chain fatty acids are the ruminant’s main energy source, not glucose. Fermentation thus introduces fat into an otherwise fat-free vegetable while rendering the nutrients more accessible since that stubborn cell wall is now mostly weakened or gone. Yay! Fresh vegetables, when eaten with minimal processing, are only a good way to fill yourselves up cheapy. But then again, so is cardboard, which is also high in fiber and low in calories, which means it is good for weight loss. 🙂
Lacto-fermentation is the most beneficial fermentation strategy. Vinegar and other kinds of acidic fermentation doesn’t allow the a microbiome to form and thrive. Fermentation improves the accessibility of nutrients from foods that would otherwise not be optimal in the diet of a monogastric mammal like ourselves.
Obtaining all of our nutrients or nutrients in sizable, appreciable amounts directly from plants is really a myth, which is why red meat from ruminant, grass-eating animals takes the top spot for all-round wellness on my diet. They are well-rounded nutritionally, have all of the essential fats and proteins, the right combination and relative quantities of which, with the necessary vitamins and minerals, in more sizable quantities than you would otherwise get from plants. There are also a plethora of nutrients only obtained from animal products like choline, creatine, carnosine and a whole bunch of peptides, enzymes and fats (like CLA) that are not fully acknowledged or understood by mainstream science. So if we were to use a ‘wager argument’ here, your best bet is to eat animal-sourced foods mainly because this way, regardless of where nutrition stands on its progress, you will have everything needed for health.
For all these reasons, an ideal diet should, whenever possible, be structured around animal-sourced foods with microbially-manipulated plant foods as a fall back.
Not only are fermented foods more nutritious than the OG, they are also more palatable or delicious without cooking or any other processing. You can serve cabbage raw after fermentation as sauerkraut but you could never eat the same cabbage raw. Even if you did, it wouldn’t be significantly nutritional to you, a human.
Moving along to the side dishes I’d presented, I think fruits are naturally the best when in season for the following reasons. One, they are naturally low in any sort of toxin, whether oxalates, phytates, tannins (the skin of apples and some fruit contains some amount of tannins), etc. Secondly, consumption of fruit is consistent with our evolutionarily past where, for the greatest amount of time, we roamed as hunter-gatherers. All of the vegetables, grains and legumes we consume today were only introduced in the diet within the past 10,000 years or so, which on an evolutionary scale, is a short period of time. While some populations are developing adaptations to this novel dietary habit, such as in India, where fatty acid desaturase expression in the liver is improving (FADS1/2 genes), a lot of populations and people still cannot survive on a plant-based diet. Fatty acid desaturases are a family of enzymes that help metabolise short-chain fatty acids in plants to long-chain, animal forms so that our bodies can use it. We are also evolving many other adaptation, mainly involving carbohydrate and lipid metabolism, such as with polymorphisms in APOE gene. ApoE2 expressing brains have been shown to work best on glucose, showing the lowest fatty acid and ketone uptake. E4 allotype carriers instead show the best fatty acid uptake and the worst glucose uptake. This shows that our brains, perhaps also the most important organ, is adapting to use a very different fuel from what it was used to during our paleolithic past.
Recovering from that tangent, fruits also provide a healthy amount of simple sugars to fuel your metabolism. Glucose is oxidised at the highest priority, only after alcohols, and are therefore associated with greater thermogenesis. Enjoying some alcohol or a fruit juice perhaps can help bring up your body temperature, giving you a short burst of fast-acting energy. In the context of a sedentary lifestyle however, both alcohols and carbohydrate predispose one to metabolic disorder since oxidative energy from these macronutrients cannot be stored in their original form. Only fat is stored as fat. All other energetic macros have to be converted to fat, which in itself, is a damaging process. Since alcohols and carbs are fast-acting, they are also stored as fast-acting fat, namely visceral fat and intrahepatic and intramuscular fat. These fat reserves are far more easy to access for energy than subcutaneous fat, which is your standard belly fat. Fat is stored subcutaneously for long-term storage and as insulation. These fast-acting fats, if left un-oxidised, causes insulin resistance since the cells have a lot of local energy sitting around and don’t need any more energy from circulation. They also cause fatty organs as these intracellular fats build up, causing the organs to swell up from the outside and changing their texture with fatty liver the most common example of which since almost everybody these days is on a high-carbohydrate diet. Burning through these local energy stores, by keeping your insulin levels low either through a low-carb diet or fasting or a combination of the two, along with exercise, can help rapidly deplete these local energy stores, allowing them cells to become sensitive to insulin again. Insulin is the body’s primary anabolic hormone, whose function is to inhibit lipase and the subsequent breakdown of triglycerides to free fatty acids and glycerol. Insulinogenic diets, namely high-carb or high-(lean)protein diets, especially when not supplemented with adequate exercise, can make it hard to burn fat.
A little understand of the biochemistry of fuel selection helps us understand why carbs, mainly simple carbs, can be healthful when used in the right combination with other foods. This is where I must interject the Randle fatty acid-glucose cycle, which neatly lays out how cells modulate their response to insulin, the anabolic hormone that commands fat storage (synthesis of new fats and re-esterification of any dietary fats) and glucose uptake, both states of energy deprivation inside the cell or energy surplus outside the cell. Since glucose is hard to store long-term, whose storage form, glycogen, is also a short-term reservoir of energy, glucose is preferentially oxidised whenever available, pushing all fats into storage while also synthesizing any new fats (mainly palmitic acid, which is a major product of hepatic de-novo lipogenesis) from any excess energy that cannot be oxidised at the moment. However, in the absence of glucose, when the body is running on fat, it choses to spare as much glucose for the brain where it is most needed. During periods of extreme carbohydrate restriction such as starvation, the liver makes as much as 70g of glucose per day through a somewhat inefficient process known as gluconeogenesis. This pathway is also enabled during stress states, such as intense exercise or even psychological stress. This is why blood glucose levels rise during stress since the glucocorticoids and other adrenal stress hormones command glycogen breakdown and if glycogen is not available, then gluconeogenesis. The same hormones that mediate the stress response and production and release of glucose also simultaneously induce transient insulin resistance in skeletal tissue to amplify this glucose-sparing effect of fatty acid oxidation. This creates a situation where fuel selection during times of abundance i.e. when fed is controlled by oxidative priority of the macronutrients (alcohols > glucose > fats) or by the fuel currently being oxidised during fasted states. The simple logic governing this system is to maintain an uninterrupted supply of glucose for the brain, which cannot completely run on fats.
This is why eating breakfast is super unhealthy as cortisol and glucocorticoid levels are naturally elevated in a diurnal cycle during the mornings. This serves to wake us up, serving as our body’s own alarm clock. Eating in this stress state will almost certainly dysregulate your carbohydrate metabolism, causing hyperglycaemia which has the potential to cause moodiness and cravings later in the day. Our diurnal endocrinology gives us the best pointers towards an appropriate meal time, which for most people, is during the late afternoons around 2 PM, assuming you woke up with the sun, for this is the time when your body is most sensitive to the effects of insulin, helping mitigate the amount of substrates in the liver that might be converted to fat (via de novo lipogenesis).
In the same way, eating fat when you are preferentially oxidising glucose, either during a period of stress or following a meal high in carbohydrate, is most certainly going to cause that fat to be sent straight to the bunk.
Ugh.. so much of what we are sold as “healthy” lifestyle habits are really motivated by commercial interests, not in the interest of public health (pfft.. obviously).
Another possible logic behind this system is basing fuel selection around its storage potential. Alcohols, for instance, can be oxidised for energy, not much unlike carbs and fats. The catch, however, is in the subtle fact that alcohols cannot be stored in the body, in its original form, as alcohol. In other words, any oxidative energy from alcohol must be promptly oxidised if they body isn’t to go into a state of metabolic toxicity. Metabolic toxicity can then be thought of as a state where the body is overfed oxidative energy beyond its capacity to store them, in its original form, forcing the body into a dysfunctional state of storing or utilising energy. Now you get a situation where you are producing excess substrates in the liver for de novo lipogenesis, causing unhealthy fat accumulation. Such ‘high-priority’ (or fast-acting) fuels exert a high thermogenesis, meaning they make the metabolism run harder which sometimes gets misinterpreted as a desirable effect when in reality, you’re straining your body into burning off an inappropriate fuel.
But wait.. if excesses of carbs (beyond our glycogen storage capacity) and any amount of alcohol (which cannot be stored at all) can cause unhealthy fat storage, what’s the deal with dietary fat? Doesn’t fat go straight to storage as fat? The answer to that would be an unequivocal ‘yes’ but the metabolic effects of exogenous fat and endogenous fat formed via DNL are very different, not to mention they are stored differently. Foremost, the fatty acid profile of hepatic DNL is very different, with a large amount of palmitic acid, which is the main product of all fatty acid synthesis. (A biopsy into your adipose tissue will often reveal more about your lifestyle and dietary habits than your weight.) Palmitic acid is sensed by cells as a state of over-feeding and metabolic dysfunction, inducing controlled cell death or apoptosis as an adaptation to metabolic stress. Since palmitic acid is the major product of DNL, a symptom of over-feeding, palmitic acid is sensed within cells via malonyl-CoA. The inhibition of acetyl-CoA-carboxylase by palmitic acid depletes cytoplasmic malonyl-CoA levels. This, if you may recollect from our discussion on the Randle mechanism of insulin resistance, encourages fatty acid oxidation and discourages fatty acid synthesis, or re-esterification. In this way, malonyl-CoA acts as a sort of master fuel source selector for the cell. Glucose oxidation activates acetyl-CoA-carboxylase, which substitutes a carboxyl group in place of the acetyl group on coenzyme A (CoA), increasing cytoplasmic malonyl-CoA. This reduces the available acetyl pool, forcing the cell to scavenge acetyl from LCFAceyl-CoA instead via fatty acid synthase. Palmitic acid, therefore, encourages fatty acid beta-oxidation by inhibiting the conversion of acetyl-CoA to malonyl-CoA, which works to prevent the re-esterification of any fats. This is your body’s way of preventing metabolic toxicity from excess DNL. If you recall from our discussion on catabolic states, we find that palmitic acid uptake into the cell induces many of the same mechanisms, of enhanced fatty acid oxidation which more or less produces the same glucose-sparing effect.
Any palmitic acid, whether obtained through exogenous dietary intake or produced as a product of DNL, under normal metabolic conditions, are desaturated and elongated at the delta-9 position to prevent a fatty acid imbalance, desaturating them to palmitoleic acid or elongating them to stearic acid, a C18 fat. A cabal of elongase and desaturase enzymes work closely to maintain the optimal fatty acid composition within the body since they serve, not just as a source of oxidative energy, but as structural components of cells and hormones. An optimal balance of SFAs to UFAs maintains cell membrane integrity. Palmitic acids, for instance, comprise up to 20-30 percent of all SFAs in the body, finding themselves important structural use in the phospholipids of our cell membrane.
Secondly, the way the body accumulates fats from fast-acting (alcohols and carbs) differently from slow-acting (fats), with varied effects on the body’s metabolic functioning. Any fat made from fast-acting fuels, like alcohols and carbs, are stored viscerally (in-between organs) and intrahepatically or intramuscularly (within organs and skeletal tissue). While this is desirable on a wagyu steak, where it is interpreted as marbling, it’s not good for you (or the animal). This type of local fat accumulation makes cells resistant to the effects of insulin, predisposing one to more metabolic dysfunction in a vicious cycle should they continue overfeeding their body of oxidative energy from fast-acting macronutrients. This is because the body like to store any excesses of oxidative energy from fast-acting fuels in more accessible storage compartments. Subcutaneous fat, which some of you might have heard is healthy is moderate amounts as they insulate and protect your body from blunt force trauma, is also the least accessible form of fat. This is why you have people complain of belly fat as “arrogant” as it’s usually the least preferred by the body to burn. Unhealthy, or insulin antagonising fat, also known as visceral and intrahepatic fats are also the easiest to burn. They’re stored locally for a reason, to provide a rapid backup of energy. When you go into a state of ketosis, your intrahepatically stored fats will be the livers first preference for oxidation, into acetyl-CoA, from where they may be either converted to ketones or glucose.
Thirdly, the metabolic pathways of converting excesses of oxidative energy from other macronutrients to fat is more damaging than storing dietary fat, as is. Unlike dietary fat, which is transported from the intestinal walls via chylomicrons to adipose tissue, endogenously produced fats, namely DNL is largely stored locally, in the tissue that it was made. Hepatic DNL directly affects intrahepatic triglyceride levels. Pathologically, this is known as fatty liver syndrome. Fats made through DNL in skeletal tissue, for instance, are stored intramuscularly. This is because fat synthesized locally all over the body cannot be transported backwards to adipose tissue, the target for long-term storage. Hepatic DNL also directly influences hepatic VLDL export, predisposing one to dyslipidaemias of triglyceride-rich lipoproteins and triglycerides itself. Viscerally stored fat is also ‘leaky’, meaning it spills out triglycerides into circulation, unlike the more long-term subcutaneously stored fat. In an insulin desensitised body, where organs and skeletal tissue already have a lot of locally stored energy, indicated by chronic AMP-k deactivation, these triglyceride-rich lipoproteins have no use and they are bound to stay in circulation for longer. This allows plasma lipid transfer proteins like CETP to act on them, increasing the atherogenic potential of Apo B particles while simultaneously depressing the formation of Apo A1 particles. The tendency of an insulin resistant body to become hyperglycaemic works catastrophically with increased VLDL output, to further slow down the metabolism of triglycerides from triglyceride-rich lipoproteins. Elevated triglycerides and lowered HDL concentrations on a blood test will almost certainly guarantee the presence of unhealthy viscerally stored fat.
In simple terms, not all body fat is created alike. Fats stored in different parts of the body exert varied influences on your overall carbohydrate + lipid metabolism.
Wagyu cows are often fed alcohol and a grain-based diet, both of which fast-acting fuels that dispose the animal to unhealthy (insulin desensitizing) fat accumulation. They feed the animals beer and grains so your steaks can look like this.
Notice the fat spillage, from subcutaneous storage compartments to within the skeletal tissue. This kind of fat is there for a reason, to be accessed most readily for energy, since they are located closest to metabolically-intensive tissue. The only two strategies to access this fat is to either deprive one of all energy or to deprive one of fast-acting fuels, namely alcohols and excess carbs, also known as fasting and low-carb (LCHF) diets.
This is where we must take a hint from animal husbandry since they often hold pointers to how feeding practices and macronutrient composition of diet directly translates to body composition and metabolic functioning of the animal.
Fasting offers a short-term intervention with lifestyle to improve carbohydrate metabolism via improving insulin sensitivity while LCHF diets offer us a more long-term intervention with diet. Fat-enriched diets discourage the storage of intrahepatic and other viscerally storied fat, improving body fat distribution. LCHF diets also train your liver to burn fats through epigenetic epigenetic modifications in transcription factors SREBP-1c and ChREBP, both of which are activated by insulin and glucose respectively. These genes are involved in hepatic lipid metabolism. SREBP, for instance, governs the expression of enzymes involved in DNL. Replacing calories from fast-acting fuels in the diet, that are either burnt promptly or converted to fat, with calories from slow-acting fuels like fats encourages the lipolytic pathway, providing a sort of insurance against unhealthy fat accumulation, moving hepatic lipid metabolism away from fatty acid re-esterification towards fatty acid oxidation.
The last point I wish to address pertains to lifestyle. This pertains to methods of balancing your stress response by using acute stress to aid deeper relaxation. But before I put words in your mouth, let me ask you for a quick moment. When have you felt most relaxed? Following a stressful but rewarding situation or when you had nothing good to do, bored out of your mind? I bet most people’s answers would point us in the direction of post-stress relaxation. And this most certainly is true. You need to experience stress in order to relax. And moreover, stress invigorates the body, delivers nutrients to important organs, and keeps your metabolism running optimally. But aren’t we told stress is bad and de-stressing is what’s important? Well, this is where we must introduce our old friend, context. In the context of chronic stress i.e. stress that is unresolving, the physiological effects of stress can be very damaging. When the same stress response is acute and followed by meaningful resolution, it becomes very healthy and almost necessary for life. If humans experienced no stress, we would have nothing to get us off our asses and moving, to find food, shelter and new grounds. Stress, put simply, is the invigorating force that drives us. And it is for this reason that we make the highest amount of our stress hormone, cortisol, first thing in the morning or whenever you it is that you wake up.
Speaking of the diurnal activity of cortisol, which belongs to a class of hormones called glucocorticoids, let’s take some time out here to address the importance of understanding the endocrinology of carbohydrate and lipid metabolism itself as there exist many common points of contact between these glucose homeostatic factors and overall health. As you all probably know, insulin aids in the clearance of glucose into skeletal tissue and glucagon liberates glucose from glycogen reserves. These hormones work reciprocally. They are the two basic homeostatic factors in blood glucose. But why are we so single-mindedly focused on blood glucose to understand the broader endocrinology of broader health? Well, that’s because as we had already discussed with the mechanisms of fuel selection, the body’s only metabolic priority is to maintain blood glucose levels within an optimal range for the brain, which can neither store energy nor oxidise other fuels. This is the logic that drives the whole system.
What this means for broader health is that your glucose homeostatic factors, namely your pancreatic and adrenal hormones mainly, work round the clock to maintain a steady supply of glucose for the brain, while flexibly inducing insulin resistance in less metabolically-important tissue to create the necessary glucose-sparing effect. What most people don’t know beyond this point is how this ties beautifully into our immune system function and the very health of our cells i.e. by modulating cellular protein quality control systems (proteostasis).
The adrenal glucocorticoids we talked about which mediates the body’s catabolic response in tandem with pancreatic glucagon (and also pituitary epinephrine), are responsible for elevating and maintaining blood glucose levels in the absence of exogenous glucose. These hormones, if you may re-collect from psychology 101, are also stress hormones. They mediate the body’s response to ‘flight or fight (or freeze)’. What this then clearly shows is that catabolic states are also stress states whereas anabolic states are relaxed states. This again makes sense within our broader understanding of our evolutionary programming to ‘feed and breed’. The parasympathetic nervous system is stimulated during digestion of food. The parasympathetic tone is associated with the release of gastric juices and the contractions of smooth muscle fibers along the GI tract. This is also the part of your autonomic nervous system that handles bodily relaxation, in everything from vasodilation and blood pressure, heart rate, etc. Simultaneously, the pituitary also releases LH which incentivises sexual behaviour in both males and females by liberating testosterone form the leydig cells of the testes in males and estrogen in females. All this fits in squarely with the fundamental logic driving the system i.e. to ‘feed and breed’.
Now that we have established that periods of carbohydrate-deprivation, such as fasting or low-carb diets, are stressful for the body, we must then think about what this stress response is, on a more abstract level. While specialists in different disciplines will give you varying and contradicting answers, the fundamental purpose of a response of any biological system to stress is to adapt. Nothing more, nothing less. Stress is good. Stress is strengthening, as long as it occurs within a hormetic range.
Introduce, hormesis.
All biological systems, from single cells to whole bodies, respond bi-phasically to stress. Stress, put simply, is anything that that upset the homeostasis of the cellular systems. We discussed AMP-k, which maintains energy homeostasis within the cell. So exercise or calorie restriction upsets this balance which AMP-k, as an energy sensor, seeks to correct. These are, in system engineering terms, feedback networks.
Understanding hormesis in itself so fundamentally challenges the definition of health put forth by our medical establishment. Unlike its definition of health as the absence of disease i.e. the symptoms of which or the reduction of ‘risk’ factors, good health is rather a state of resistance to disease. This is achieved by keeping bodily systems in a state of homeostasis, which creates the necessary head room or wiggle room, so to speak, to becomes less sensitive to the effects of stress.
In the context of carbohydrate metabolism, the catabolic state achieved through carbohydrate-restriction puts the body in a state of eustress, or hormetic stress. The very hormones that mediate the catabolic response also simultaneously exert their appropriate influence on other bodily systems. Glucocorticoids, for example, shuts down the immune system by inhibiting NF-kappa B and COX, the same enzyme that is targeted by NSAIDs to stop inflammation. In other words, stress i.e. cortisol is immunosuppressive, which is a good thing, when balanced. Inhibiting NF-kappa B halts the production of signalling molecules used by your immune system to command inflammation. These include eicosanoids, cytokines, among others. This is why LCHF diets almost universally lower inflammation markers. But inflammation isn’t always bad either. You need inflammation to achieve adaptive immunity. Your body inflames for a reason i.e. to fix a problem. Therefore, the focus shouldn’t be so much as to suppress inflammation when it spirals out of control but rather to calibrate the body’s immunological signature i.e. whether it tends to over inflame or under inflame to stress. Fasting and LCHF diets can recalibrate this response by foremost inhibiting the production of inflammatory signalling molecules (perhaps from a poor n-6:n-3 PUFA ratio), providing the necessary therapeutic counter-balances.
Under anabolism, mTOR (a sensor of mainly branched-chain amino acids) kick-starts protein synthesis and NF-kappa B commands DNA transcription and cell division, whose inhibition can be life-extending and also offer us a way to starve cancerous cells by inducing programmed cell death. In other words, anabolism is marked by increased cell growth and proliferation. Anabolism is therefore necessary, or you wouldn’t even exist. The need of the hour however, is balance which is what people are sorely lacking when they eat high-carbohydrate meals three times a day, keeping their body for the better part of the day in an anabolic state. This keeps the immune system in a hyper-aroused state, more willing to inflame than deflame. Eating quality protein-rich meals instead, which really is what your anabolic response should be mediated by for healthy body-building, and eating less frequently i.e. one or two large meals allows your metabolism to cycle between catabolic and anabolic states.
Catabolism is marked by a deactivated mTOR and activated AMP-k, both of which are sensors of amino acid and energy sufficiency i.e. the vital components for your cells to sustain itself. This deactivation of mTOR signals amino acid deficiency to the rest of the cell. One of it’s key activities is to activate another pathway called ULK1 which is your cell’s master autophagy switch. Autophagy is a part of a very complex system that maintains the quality of the cellular proteome. ULK1 activation then kick-starts house-keeping activities within the cell, the most fundamental component of your body from where all diseases really take root. Entire organelles are wrapped and transported to the lysosome where they are digested should they have become too dysfunctional. This salvages their constituent amino acids to build back better through a process called macroautphagy. It’s like how you would break down a sand castle if it has become too disfigured. The sand, which can be thought of as the amino acids, is essentially the same. It’s just that the structures build from them that have become dysfunctional. Microautophagy takes care of dysfunctional enzymes as well as other cellular debris such as prions and even viral spike proteins. After all, there are useful nutrients in pathogens too! Other proteins may perform re-folding of proteins such as the heat-shock proteins, owing to their function to prevent denaturation as protein folding becomes compromised by heat.
Glucocorticoids also starts house-keeping activities outside the cell, in the liver, where they activate cytochrome P450 enzymes. These are detoxification enzymes that catalyse redox reactions of fat-soluble toxins, converting them into polar, water-soluble metabolites for easy excretion. Other enzymes like glutathione, act as antioxidants** to these redox reactions since redoxes are inherently stressful for the cell since they yield reactive species of oxygen. Any detoxification effort therefore, produces oxidative stress.
In simple terms, catabolism = stress and stress = improved adaptations to stress.
Autophagy improves enzyme health and the function of organelles. This creates many cellular efficiencies that enables you body to work with less. Detoxification rectifies many hormonal imbalances and rids the body of its own metabolites (waste products) that improves signalling. For instance, glucocorticoid-induced CYP1A2 activity (an enzyme belonging to the cytochrome P450 superfamily) in the liver metabolises sterols and other steroid hormones. Estrogens, which are one such steroids, are an androgen antagonist meaning that regardless of testosterone levels, estrogen can block its signalling. When you have estradiol, an estrogen, docked into its receptor while a testosterone is also docked into its respect receptor, you create confusing signalling within the cells. Estrogens are somewhat anabolic as they encourage fat accumulation, which is why women tend to gain weight more easily and low testosterone levels have been correlated with obesity in men. Metabolites of estrogen also command cell proliferation. During a fast, your body needs to liberate as much energy and therefore, a conflicting signal to accumulate fat is counter-productive to this end. It would then make sense why estrogens are metabolised more rapidly in the absence of carbohydrate via glucocorticoid induction.
So while fasting doesn’t exactly increase testosterone levels, which is mediated via LH as a response to feeding, it certainly improves the efficacy of the hormone in the body. And this is what I meant by stress adaptation. The body learns to work better when it is subject to stress, much in the same way you become better at financial planning when you receive a salary cut (lol). So eventually when you receive a bonus, you are already equipped with the know-how on how to spend it wisely, having weeded out many unnecessary expenses.
PS I know that I am not citing anything. I would be happy to if this post gains traction and more people demand sources for their own research or as proof for my claims here. As of now, you may refer to my Quora answers on these topics to find the required literature.
*omega-6:3 ratio of your diet determines the signature of your inflammatory responses. Too much omega-6 and your immune system will tend towards inflammation, or over-inflame. Too much omega-3 (which rarely ever happens thanks to our grain-based agrarian diets) predisposes you to under-inflammation. Both of these states are bad. What your body needs is balance. The inflammatory response, mediated by the prostaglandins made from metabolising long-chain derivatives of omega-6/3 via COX among other signalling molecules, regulate a number of inflammatory responses all over the body. PGE2 for instance, the prostaglandin associated with omega-6 fats, causes constriction of blood vessels, a process known as vasoconstriction and PAF (platelet-activating factor) activation which causes blood-clotting which, in extreme cases, can be fatal. Prostaglandins belong to a broad group of immunologically important hormones called eicosanoids and sit alongside the cytokines such as the interleukins most people tend to be familiar with due to their established status as inflammation markers as well as other important messengers that command inflammation all throughout your body.
It is important to know that inflammation, in itself, is necessary for life. Several important events, such as the formation of T cells and adaptive immunity to viruses, for instance, happens only through inflammatory pathways such as the type I interferon system. Interferons are another type of signalling molecules belonging to the eicosanoid family. This is why taking NSAIDs, which are really just COX inhibitors, are a very bad following vaccination or an infection because it pulls the brakes on this very inflammatory response necessary to develop immunity, only temporarily relieving you of the symptoms of which. COX inhibitors stops the downstream metabolism of inflammatory agents in the body to its associated signalling molecules. The meaningful solution then isn’t to forcefully pull the brakes at the last moment, once shit has hit the fan and causes a shitstorm (or a cytokine storm, literally), but to prevent the runaway train in the first place by balancing your inflammatory responses using the right ratio of omega-6:3 in the diet. A ratio less than 4 and greater than 1 is desirable.
What we see again here, as with our discussion on stress, is that inflammation is necessary for any meaningful resolution i.e. the production of immunoglobins or anti-bodies, for example.
**antioxidants production is governed by Nrf2. This pathway acts as a sort of sensor of ROS in the cell.
Once again, we find that oxidative stress is necessary for the production of antioxidants. In other words, a stress is needed to meaningfully de-stress.
I felt compelled to jot down my inner monologues on the collective shadow. How it forms, why it exists and how it affects others in society.
According to the psychoanalytic theory of Carl Jung, what we repress as part of our social persona becomes our shadow. Our persona is the role we take up to remain functional and in good standing with our societies — to fit into its social hierarchies, to maintain appropriate social conduct and to be “good” citizens. The shadow then is all that has been deemed apprehensible by our societies that we have learned to repress from an early age. These include some very natural inclinations and tendencies such as of curiosity. Unlike individuation, where one exists in their wholeness, playing a persona severely inhibits all individual development leaving people in a repressed mess of child-like emotions. This is why society’s most functional members are also the most psychologically infantile. It’s relatively uncommon to not find CEOs, managers or other big stakeholders not suffering one form or the other of what I like to call the ‘high maintenance syndrome’. They always need to be right. They have a strong ego drive that measures, processes and comprehends the world as it relates to them, and not in its entirety, also called the utilitarian mindset. This turns everybody around them into diaper sniffers, walking on eggshells to prevent upsetting them. They have, in other words, child-like emotions and god-like egos. This is why I say capitalism and social hierarchies (of power) puts just about the most incompetent breed of people at the top. Not because that’s how the system might have originally worked but rather by the action of those who desire success or are motivated rather well to succeed. This is the fatal flaw of success, that the people who desire to be the ‘first’ or be the ‘best’ aren’t often the best at what they do because ‘winning’ is an extrinsic drive while all other meaningful attempts at being good at something i.e. through understanding, appreciation and creativity are intrinsically motivated. I’ll save more on this for another post.
When people collectively aspire to ‘fit in’ to their societies, they begin repressing more or less the same traits that their societies find apprehensible. This is what gives birth to the collective shadow. This collective shadow is every iconoclast’s worst nightmare. Because should you dare to colour outside the lines of acceptable behaviour, however slightly more idiosyncratic you may be, you will attract the collective hatred and maltreatment of the people.
Allow me to demonstrate this with a case study:
A child in kindergarten who curiously turns away from the blackboard to look at a plane fly overhead, tending to this novel stimulus, is scorned at and punished by his teacher. He therefore learns that curiosity i.e. the quality of tending to one’s own inclinations in a free-flowing and uninhibited manner to further one’s understanding of the environment is inherently a vice. Over due course of his early childhood, he learns to repress this impetus to explore, to seek out novel experiences because it is immoral, as demonstrated by the actions of his moral authorities, which in this case, are his teachers and parents.
Now when this child grows up into an adult and encounters someone, either an adult or a child, engaging in the same sort of behaviour he was once penalised for, he will feel irritated by it. He may mistreat this person for he feels as though they deserve it by being a ‘bad’ person. They feel justified and self-righteous in doing so.
What we see here is that what you repress, you give control over you. By choosing to repress his curiosity, a once curious child grew up to be irritated by expressions of curiosity in other children (and adults). He hates what he was denied.
The collective shadow manifests in much the same way. When a society of citizens in good standing, with their local religion or moral code, grow up repressing what is considered bad, they grow to be irrationally irritated, without explanation, by those very qualities in others.
This leads to a number of maladaptations in later life, from seeking the company of the similarly adapted so they may never have to come face to face with the forces operating within their own psyche. This way, they may not inadvertently irritate each other’s shadow and bring out unexplained disdain for each other. This repression cultivates a subconscious distrust or hatred of innocence, good intent and other child-like ways that they themselves had to forego in order to reach a place of eminence within society.
The most forthright employee will quickly land himself in hot waters by not knowing how to conduct himself appropriately (or play pretend) around his superiors, oblivious to the power dynamics operating in hidden sight. The most creative artist pursuing his own aesthetic sensibility will never land a record deal, unable to churn out a fairly formulaic track that the labels would want to sign to capitalise on an already existing market. It can be seen that to be successful, one needs to repress authenticity, a drive for which children are naturally born with. The pretentious successful population will then hate the authentic individual.
This causes them to act out in all sorts of irrational ways to those they feel irritated by, those who display many of the traits repressed into their collective shadow. Since this motivation for this behaviour takes root from within subconscious, they can never consciously acknowledge what it is they might be doing. Those who are have chosen a noble path in life, having chosen to transcend above this herd morality, are often dealt with harshly. They attract the distrust and disdain of people everywhere they do. This opens them up to maltreatment as their cronies are instead reserved preferential treatment, all the while being oblivious to the monster within.
What makes the phenomenon of the collective shadow so uniquely dangerous is its capacity to systemically deny justice to authentic individuals. This happens when those who are tasked with enforcing justice are again, repressing more or less the same traits in their shadow that makes them again hate you for no apparent reason, unless of course, they are intellectually endowed enough to be able to examine their own subconscious imperatives. This creates a vicious cycle of mistreatment (and oppression) of authentic individuals.
I think it is then no coincidence that some of society’s most functional and high-ranking members also seem to take the greatest offence with honesty, playfulness, curiosity and good intent – all qualities of born humans. They frequently assume malice where there is none by projecting what they would have done themselves when presented with such a situation. This is why I think examining a society’s most functional members gives us valuable insight into its moral priorities. Does this society care more about turning out well-educated citizenry or a merely ‘useful’ workforce who will upkeep the status quo? Hm..
This is why I stand opposed to the pseudo-morality of Christianity and other Abrahamic religions because it preaches wrongly that humans are born ‘bad’ and they transition to being ‘good’ by virtue of repression. What foolishness! Dishonesty is learned. Lying is learned in a society that teaches you can live far easily doing these things. There would be no incentive for a child to lie if honesty was rewarded in the first place. It’s only because our society had become so unhinged from reality, having created a system so hostile to anyone who speaks their mind that we have liars.
chronic overthinking 