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 hear a great deal of half-baked vermin disguised as health “facts” or “advice” about what they describe to be the happy hormone, serotonin. Much of this vermin originates from the medical-scientific-industrial establishment and is indirectly kept relevant by their cronies in the media.
Even going by their own pseudo-logic, if serotonin is the happy hormone that makes people pro-social as it is often alleged and oxytocin is the love hormone that makes people feel close and connected to people near and dear to them, shouldn’t these two hormones work in a mutually-reinforcing relationship?
Only that they don’t. Serotonin and oxytocin work reciprocally, where elevated levels of one reduces the levels of another (Mottolese, Raphaelle et al. PNAS. 2014).
What’s more? The authors of the same study cite other studies looking at hormonal cross-talk which shows the serotonin-oxytocin relationship is not much unlike its relationship with other stress hormones, cortisol-oxytocin (Tops, Mattie et al. Psychophysiology. 2007) and estrogen-oxytocin (McCarthy, MM et al. Physiology & Behaviour. 1996), only reinforcing the status of serotonin as a cardinal stress hormone.
So then, we must start thinking.. if the effects of a stress hormone is found to be desirable (or even beneficial) towards one’s social life, is it not possible then that the environments in which stress hormones adapt one to is also stressful? This is akin to saying, “because a man with a life vest stuck around his neck stays alive in the water, the life vest tethered around the neck is the most optimal state.” Common sense and a little analytical inquiry presents us with the notion that it is not and that the pathological state is actually having the life vest permanently tethered to you.. or a state of high serotonin, however more appropriate it may be towards survival in a pathological society. In light of this realisation, we must remind ourselves not to redefine morality altogether on the grounds of life outcomes, as we do with utilitarian thinking.
Furthermore, we must also wonder then, why is a stress state i.e. one of high serotonin, touted to be a healthy state which, when examined within a broader systems context, turns out to be essentially no different that other cardinal signals of distress in the body.
Stressful situations re-orient the priorities of biological systems away from growth towards self-preservation. By doing so, they suppress oxytocin which is involved in deeper understanding, trust and love for one another. Because in times of distress, one has to focus his mental resources on how to get by and keep himself above the water, not on giving love to others. One can quickly see then that any stressful activity, stressful environments and even stressful conditions brought on by the diet (high PUFAs, starch tend to do this) also modulate behaviour and thought in ways we could have never considered.
So what then is serotonin’s role besides mediating our sleep-wake cycle in conjunction with melatonin?
Energy homeostasis, plain and simple, just like all other stress hormones (Donovan, Michael H et al. Frontiers in Neuroscience. 2013). Within the CNS, serotonin mediates a number of inhibitory and maintenance functions. It makes you seek out to comfort and familiarity while encouraging complicit social behaviour, all necessary survival behaviours in desperate times or when the organism is too weak for the challenges of its environment. In peripheral tissue, serotonin works together with other stress hormones like estrogen (Rybaczyk, Leszek A et al. BMC Women’s Health. 2005) to promote survival of the organism. Your adrenal stress hormone, cortisol, a glucocorticoid, is a homeostatic factor in blood glucose and energy metabolism, just like serotonin. Serotonin and cortisol work together to induce insulin resistance of skeletal tissue, mobile fatty acids and improve its uptake and utilisation in times of stress (tissue catabolism).
So all the stress hormones (cortisol, estrogen, serotonin and histamine).. are all really just energy homeostatic factors?
Yes. Unlike dopaminergic pathways, which are highly concentrated within the frontal lobe and moreover, within the prefrontal cortex, serotonergic pathways extend mostly into the reptilian centres of the brain. In this regard, serotonin can be thought of as a more “basic” or primordial regulator of behaviour, cognition and bodily functions (metabolism, temperature, etc.) in response to environmental and social factors that evolved much further back, before we even differentiated into homo erectus. The serotonergic system is therefore more “bodily” than “cerebral”. From crustaceans to primates and all other mammals in-between, we find that members of a tribe that sit higher up on the pecking order or social strata have higher serotonin. Even in humans, serotonin seems to be associated quite unmistakably with the inhibitory behaviour observed in high-status or high-responsibility positions. Or in other words, serotonin within the CNS seems to be responsible for many of the inhibitions brough on by social commitments and obligations, which is a “stress” or inhibitory state and not a “relaxed” or uninhibited state of mind. All stress hormones, in other words, find the right balance between survival and growth for the organism, in its environment.
Much like how stressful conditions at childhood hinders normal growth causing stunting, serotonin, like cortisol and other signals of stress, prepares the body for survival and “getting by” with what’s available. Many of the behaviours related to depression such as apathy are driven by these cardinal stress signals. For instance, thyroid insufficiency causes elevated estrogen activity. This causes estrogenic agonists like cortisol, serotonin and histamine to also go un-checked, now without the antagonism of active thyroid hormone, T3. (Recall that thyroid hormone is rate-limiting in catecholamine synthesis.). Therefore, women with endometriosis almost always have sub-clinical or clinical hypothyroidism, which brings with it elevated cortisol, serotonin and histamine, predisposing them to immunosuppression, depression, allergies, weight gain and other metabolic disorders. This state of altered serotonergic neurotransmission by estrogen, low thyroid and other stress signals predisposes such women to disordered feeding habits since serotonin agonises many of our ‘long-term’ satiety hormones like leptin, a hormone made by fat cells that relays how much energy you are carrying as stored fat to the brain. When serotonin neurotransmission is increased by means of stimulants, reducing synaptic serotonin, the release of ghrelin, an appetite-stimulating hormone, in fasted states is reduced. Leptin also works backwards to influence the CNS’s serotonergic system, increasing serotonin turnover and thereby lowering synaptic serotonin by inhibiting the production of nitric oxide (NO), another pro-inflammatory mediator (Calapai, Gioacchino et al. The Journal of Clinical Investigation. 1999). In light of this, we see that a well-nourished state i.e. of carrying sufficient fat reserves is an anti-inflammatory signal or “non-stress” state, which makes sense considering that being famished would put your body into a stress state, increasing serotonin by the missing checks-and-balances of leptin on NO and serotonin. In fact, anything that sufficiently reduces inflammation such as an NSAID (aspirin) automatically upregulates dopamine production while lowering serotonin by increasing its turnover (Bentley-Hewitt, K L et al. Scientific Reports. 2020 and Rangasamy, Suresh B et al. Journal of Neuroimmune Pharmacology. 2019).
Naudon, Laurent et al. (Brain Research. 2002) showed that long-term treatment with SSRIs (fluoxetine, brand name Prozac) results in a similar downregulation of serotonin transporters (increasing synaptic serotonin and serotonergic neurotransmission) to learned helplessness in an experiment meant to make the animals helpless. When subject to chronic stress, organisms learn to “cope” with them by suppressing their humane tendencies that would make them respond adversely to such environmental challenges. For a more layman’s example, someone who goes through heartbreak several times naturally becomes desensitized to the feelings of “falling in love” or feeling intimacy with someone special. This desensitization to the feelings of romantic love is a desperate adaptation and far from a healthy state. It would be terribly short-sighted and absurd then to proclaim that the one who feels nothing is better off than the one who feels profoundly. Depression then can be thought of as a stress state, or an adaptation to which, making you less proactive, apathetic and indifferent to all things where acting on your inclinations can prove catastrophic.
More recently, a meta-analysis by Wang, Ling et al. (BMC Psychiatry. 2016) showed lower expression of serotonin receptors within the brains of depressed patients. While it is tempting to interpret this as a need for more serotonin to simply try and offset the effects of low receptor binding, this is not ‘fixing the cause’ as in the majority of depressions, levels of synaptic serotonin and serotonergic neurotransmission are already increased (Andrews, Paul W et al. Neuroscience & Biobehavioral Reviews. 2015). Besides, treatment with anti-depressants does not seem to improve receptor binding (Sargent, P A et al. Archives of General Psychiatry. 2000 and Moses-Kolko, Eydie L et al. Synapse. 2007). What’s happening then is control of receptor binding by other related systems, such as underactive thyroid and dopamine system (Lee, Minkyung et al. Synapse. 2015), which then causes the ‘pile up’ of serotonin we see at the synapse, while other stress signals like cortisol downregulate the receptors (López, J F et al. Biological Psychiatry. 1998), also contributing to this ‘pile up’. Histamine (Flik, Gunnar et al. Journal of Molecular Neuroscience. 2015) and estrogens (Paredes, Stephania et al. International Journal of Molecular Sciences. 2019) also have this effect. Acutely, as with injury and inflammation, estrogen increases synaptic serotonin (increasing its synthesis within the CNS while reducing its reuptake and metabolism). Chronically, as with gender differences (i.e. female gender), estrogen increases serotonin transporter expression as a way to curtail the serotonergic effects of estrogen. Paredes, Stephania et al. reported a staggering nine-fold increase in tryptophan hydroxylase activity by estrogen, the enzyme involved in serotonin synthesis. Unlike stress signals, de-stress signals like oxytocin instead upregulate these serotonin receptors as shown by Mottolese, Raphaelle et al. to reduce synaptic serotonin. A state of high serotonin can therefore be categorised as a pathological state. The pathology of many depressions shares similar mechanisms with that of SSRIs, a downregulation of serotonin receptors and/or lower expression of serotonin transporters (lower reuptake) followed by an increase in synaptic serotonin available for neurotransmission.
From Paredes, Stephania et al., estrogen, which Dr. Ray Peat calls the “shock hormone”, has a pronounced effect on the brain’s serotonin system, increasing its synthesis by transcriptionally upregulating tryptophan hydroxylase and preventing its reuptake by downregulating its transporters. This increases synaptic serotonin, similar to depression and other stress states. However, a negative feedback mechanism exists at the pre-synaptic neuron to prevent excess synaptic serotonin by means of autoreceptors. Estrogen downregulates these autoreceptors effectively inhibiting this negative feedback on serotonin production and release. Estrogen simultaneously inhibits MAO, an enzyme involved in serotonin metabolism to 5-HIAA, the primary metabolite of serotonin. Levels of 5-HIAA are often measured in cerebrospinal fluid as a shrewd indicator of serotonin turnover within the brain. The varying levels of estrogen throughout the menstrual cycle could then explain the mood swings, irritability and depressions reported by women. Estrogen is at its peak both before ovulation and nearing the end of the luteal phase, before menstruation, explaining the “pre-menstrual” in pre-menstrual syndrome (PMS).
All inflammatory activities, which are indicated at the grassroots by an activation of AP-1 and NF-kappa B, transcription factors that copy inflammatory genes from your DNA helping with cytokine production, diminish MAO activity, a common point of contact with estrogen (Liu, Christina H et al. Journal of Biomedical Science. 2016). Cortisol has a similar inhibitive effect on MAO (Soliman, Alexandra et al. The Journal of Neuroscience. 2012). This shows us that many of the anti-depressants prescribed for increasing serotonin (MAO inhibitors, SSRIs) are really just estrogenic “stressors”, like paracetamol, which Dr. Peat calls a “designer estrogen” which also has been shown to increase serotonin (Maharaj, Himant et al. Metabolic Brain Disease. 2004). Aspirin instead works against paracetamol’s effects on brain neurotransmitters to increase serotonin turnover. This explains the anti-depressant and anti-anxiety effects observed in aspirin users (Ketterer, M W et al. Journal of Psychosomatic Research. 1996), by upregulating tyrosine hydroxylase involved in dopamine synthesis (Rangasamy, Suresh B et al. Journal of Neuroimmune Pharmacology. 2019). When rats have their ovaries removed, their dopamine transporters are downregulated, allowing for high synaptic dopamine, while dopamine receptors were upregulated (Chavez, Carolina et al. Brain Research. 2010). This high dopamine state was reversed by re-administering estrogen. Dr. Peat rightfully says, “if we think biologically, starting with the role of serotonin as a damage-induced inflammatory mediator, we can speculate that an infinite number of irritating substances will be “serotonin reuptake inhibitors.”” The reuptake inhibition or MAO inhibition are simply high-level manifestations of a long cascade of low-level inflammatory events.
When serotonin receptors are downregulated elsewhere in the body, the severity of reactions to a stressor reduces (Kritas, S K et al. Journal of Biological Regulators and Homeostatic Agents. 2014). Other stressors like estrogens either facilitate the acute-phase reaction (mast cell degranulation, higher PUFA metabolism by aromatase whose lipid derivatives (PGE2) increases mast cell proliferation) or buffer the chronic-phase reaction i.e. long-term coping to injury or stress (Kim, Jae Gon et al. Experimental & Molecular Medicine. 2018). This is why estrogenic drugs like paracetamol (Harnagea-Theophilus, Eugenia et al. Toxicology Letters. 1999 and Harnagea-Theophilus, Eugenia et al. Toxicology and Applied Pharmacology. 1999) are effective at reducing the perception of pain or reactions to chronic and unavoidable stress, acting as a sort of adaptogen to serotonin and other stressors. The role of CNS’s serotonin receptors in the pathology of depression then becomes apparent. Downregulating receptors during stressful conditions (lack of stimulation i.e. low dopamine activity, lack of human contact, elevated levels of the stress hormones histamine, cortisol and estrogen) serves as a way to cope with the chronically unavoidable conditions in depressive patients. It tells of a state of stress, whereby the body is adapting to conditions of chronic and unavoidable stress by means of making itself less receptive to serotonin, a stress signal, which is now being produced in abundance unlike under normal physiological conditions.
Any efficacy of antidepressant medication is related, not to the increase of serotonergic neurotransmissions as purported, but rather from a further inhibition of the serotonergic system. Patients who receive positive therapeutic outcomes from antidepressant medication have downregulated serotonin receptors (Stahl, S. Psychopharmacology Bulletin. 1994). Older tricyclic antidepressants and benzodiazepines used for the treatment of general anxiety and depression downregulated serotonin receptors, leading the authors to conclude that a downregulation of serotonin receptors may be responsible for the clinical responses of antidepressants (Stahl, S M et al. Clinical Neuropharmacology. 1993). More modern antidepressant medication like SSRIs are no different in their mechanisms of action. It’s not the inhibition of serotonin reuptake and “increased serotonin” that cures depression but rather the negative feedback via the pre-synaptic serotonin autoreceptors which results in a subsequent inhibition of serotonin release and neurotransmission (Celada, Pau et al. Journal of Psychiatry & Neuroscience. 2004). As the authors note, SSRIs “rapidly block serotonin (5-HT) reuptake, yet the onset of their therapeutic action requires weeks of treatment.” This fact alone invalidates the alleged serotonin deficiency hypothesis as any drug that rapidly increases serotonin must readily alleviate symptoms of depression. Instead, the efficacy of SSRIs are improved, as the authors note, to the antagonism of serotonin receptors similar to its downregulation (Gray, J A, and B L Roth. Brain Research Bulletin. 2001).
Consistent with our understanding of serotonin as a stress signal, we find in these studies that 5-HT release is paralleled by a release of related stress mediators like pituitary (ACTH and prolactin) and adrenal stress hormones (cortisol). Dopamine, on the other hand, opposes prolactin. Serotonin precursors like tryptophan also have indirect inflammatory effects by stimulating prolactin (Price, L H et al. The Journal of Clinical Psychiatry. 1990). Since tryptophan is a central component of our muscle proteins, more tryptophan is liberated during catabolic (stressful) conditions. More dopamine undergoes converted to ACTH within the hypothalamus during stress states whereby the hypothalamic dopamine:ACTH ratio then becomes a good indicator of CNS stress.
This state of altered serotonergic neurotransmission is essentially no different from what PUFAs and their lipid derivatives (prostaglandins, leukotrienes, etc.) do, mimicking a stress state within the CNS (Gopaldas, Manesh et al. Journal of Affective Disorders. 2019). This is why an anti-leukotriene like montelukast works like an anti-depressant (Sun, Yu et al. BMC Pharmacology and Toxicology. 2016), by alleviating the antagonisms of inflammatory lipid derivatives on the dopaminergic system. The same anti-leukotriene also works to antagonise serotonin in peripheral tissue, helping alleviate many of the effects of serotonin such as bronchoconstriction (in case of asthma), fluid retention (in hypothyroid patients), etc. Serotonin in peripheral tissue behaves no differently, working in a self-reinforcing cycle with PUFA by increasing the production of lipid derivatives of PUFAs (PGE2), suggesting serotonin and PUFA go hand-in-hand (Ménard, G et al. Clinical and Experimental Immunology. 2007).
This adaptation in behaviour to conditions of chronic and unavoidable stress by SSRIs is essentially no different from lobotomies. These barbaric surgical procedures involved severing connections within the frontal lobe (also the center of higher reasoning and thought) as a way to “destroy the human” in terminally ill patients, and others deemed too ill to be remediated or integrated back into society. Many patients were then reported to showing no signs of distress. Remember that dopaminergic pathways are highly concentrated in the prefrontal cortex. This tells us something about the role of dopamine (and that of the prefrontal cortex) in growth and differentiation of the individual. Modern SSRIs are not much unlike these barbaric procedures, opting instead for a more non-invasive means of suppressing dopaminergic activity, effectively zombifying people, leaving them unable to tell what about their life is going wrong and equally unable and moreover unwilling to do anything about it.
Many on serotonergic drugs (SSRIs) report diminished levels of arousal and interest in place of better social outcomes. A whole 64.5 percent of the long-term users report feeling “emotionally numb” (Cartwright, Claire et al. Patient Prefer Adherence. 2016) and in most cases, SSRIs are no better than placebos in treating depression (Lacasse, Jeffrey R et al. PLOS Medicine. 2005). The same authors also jokingly remark on the post hoc reasoning used by SSRI proponents that “the fact that aspirin cures headaches does not prove that headaches are due to low levels of aspirin in the brain.” Other researchers also raise concerns to how SSRIs are no different from depression itself on their effects on serotonin neurotransmission, whereby increasing synaptic serotonin, as we’d already seen, will only make one more susceptible to depression (Kirsch, Irving. Zeitschrift fur Psychologie. 2014). The whole “serotonin hypothesis”, as we can see, has gotten the whole thing laughably backwards, reflecting a poor understanding of the brain’s serotonergic system and moreover of serotonin’s fundamental role in our pathology and physiology.
In many of the studies on the CNS’s serotonin, only the hippocampal serotonergic system is analysed. This is also our most insightful way of looking at serotonin (or any other hormone really) by illuminating how it directly modulates our stress mechanism as it pertains to adapting the organism to environmental challenges. The hippocampal serotonergic system (or 5-HT1A system) handles the more autonomic responses to adversity, not much unlike the modulative effects of adrenal stress hormones on your limbic system (HPA axis) or the adipocyte-hypothalamic axis mediated by leptin which prevents overeating and expectedly, there’s a lot of cross-talk between these related systems. The autonomic stress responses are largely outside of our control and work closely with the rest of the body to maintain energy homeostasis. They are fundamentally geared for survival of the organism. The cortical serotonergic system (or 5-HT2A system via its influences on the glutamate system) on the other hand handles more deliberative or “active” coping to adversity (Carhart-Harris, RL et al. Journal of Psychopharmacology. 2017). The active coping of the cortical serotonergic system is instead not caused by serotonin itself but instead mediated by the dopamine and glutamate system, the latter of which is neurotropic (Ansah, Twum A et al. Frontiers in Systems Neuroscience. 2011 and Dantsuji, Masanori et al. The Journal of Physiology. 2019). In light of understanding how the CNS’s serotonergic system is altered by stress i.e. increases of synaptic or “available” serotonin, we can conclude that serotonin is a stress signal that prepares one for adversity – for a time of famine, for social collapse or environmental disaster – promoting many of the behaviours associated with stress both on a more unconscious (or autonomic) and conscious (or somatic) level. This translates to disordered eating, paving the way for obesity, as the body prepares for a winter that’s never coming. This can also cause more closed-ended and rigid thinking, or should I say survivalist thinking?
In studies where serotonin synthesis is reduced more generally by means of acute tryptophan depletion, a reliable means of reducing serotonin synthesis within the CNS, cognitive rigidity is negatively affected (Evers, E A et al. Current Medicinal Chemistry. 2007) and anti-social and other pathological (narcissism, psychopathy, etc.) tendencies increase (Sadeh, Naomi et al. Journal of Abnormal Psychology. 2010). When the serum tryptophan/LNAA ratio is increased and the tyrosine/LNAA ratio (a precursor to dopamine) depressed by means of dietary manipulations (high-carbohydrate, low-protein breakfast option), it results in more harsher punishments of non-compliant behaviour in an Ultimatum Game (Strang, Sabrina et al. PNAS. 2017). Ultimatum Games are commonly used in economical experiments to examine the nature of association between two people i.e. whether they are coming together and cooperating with an utilitarian (self-maximising, opportunistic) or humanistic (mutually-maximising, consequentialist) mindset.
The findings from Sadeh, Naomi et al. are most insightful about the fundamental role of serotonin in regulating social behaviour. Polymorphisms of the serotonin transporter promoter gene (5-HTTLPR) were studied against measures of anti-sociability like narcissism and a lack of negative affect (remorse, etc.). The long/long allotype expresses more serotonin transporters (5-HTT), which moves serotonin from the synapse back into the pre-synaptic neuron, reducing available serotonin for neurotransmission. The long/long allotype or the low serotonin allotype showed the greatest dependence on socioeconomic status (SES), whereby lower SES (which models conditions at childhood and access to opportunities) translated to the greatest anti-sociability while higher SES produced the lowest anti-sociability of all allotypes.
This tells us of a very critical role of serotonin, that serotonin is a stress adaptogen that evolved as a adaptation to chronic and unavoidable evolutionary stress. The S/S allotype was simply an adaptation to an agricultural mode of subsistence. The hypothesis based on dual inheritance or gene-culture co-evolution has it that “lower levels of relational openness (i.e. lesser inclinations to meet new people) and 5-HTTLPR s allele co-evolved under the environmental pressure of high pathogen prevalence.” (Kashima, E S et al. Culture and Brain. 2021). Previous studies cited by the authors have made out countries with a greater prevalence of the L/L allotype to have higher relational mobility, which Wikipedia defines as “a sociological variable that represents how much freedom individuals have to choose which persons to have relationships with, including friendships, working relationships, and romantic partnerships in a given society.” Societies with low relational mobility, therefore, “have less flexible interpersonal networks.” Serotonin on a behavioural front is responsible for in-group sociability, an adaptation to stressful evolutionary conditions – wars, famines and pandemics which came part and parcel of agriculture (Thomson, Robert et al. Proceedings of the National Academy of Sciences of the United States of America. 2018). High in-group sociability is also a hallmark of authoritarian personality disorder, characterised by a displacement of anger and aggression onto the out-group. In many ways, one could say that high serotonin is indicative of an ancestral subsistence on agriculture.
Intolerance of ambiguity is the mark of an authoritarian personality.
Theodor Adorno
In the Trier Social Stress Test, the S/S allotype shows the most acute stress response (Caspi, A et al. Science. 2003), suggesting high synaptic serotonin from lower transporter expression and function results in a more pronounced reaction to stress. It’s almost as if high synaptic serotonin is tell-tale of an “apprehensive” mental state whereby one is actively looking out and all geared up, ready to put up a fight at a moment’s notice. The L/L or the low serotonin allotype is most common in European populations over Asians, who are more likely to express S/S or the high serotonin allotype (Goldman, Noreen et al. Depression and Anxiety. 2010), an adaptation to an agricultural mode of subsistence. This also neatly explains away why Asian cultures generally tend to embody many of the high serotonin traits, of risk aversion, high power distance (authoritarianism) and restraint, all behaviours motivated be fear when the organism is to weak for the challenges of its environment, living in apprehension of being cast out of the tribe, ostracized or judged (Way, B M et al. Biological Psychiatry. 2010). SSRIs mimic the effects of carrying a shorter allele on your 5-HTTLPR gene, by inhibiting the action of serotonin transporters to prevent reuptake into the pre-synaptic neuron, only predisposing one to more depression. Expectedly, the S/S or high serotonin allotype is associated with increased depression and suicide risk.
The buck doesn’t stop there. Higher levels of synaptic serotonin or higher serotonergic neurotransmission causes anxiety (Jennings, Katie A et al. The Journal of Neuroscience. 2006). The authors show that when brain serotonin levels are reduced along with subsequent serotonergic neurotransmission by means of genetically engineering mice to overexpress serotonin transporters (analogous to humans expressing the L/L allotype of promoter gene), they exhibited lower anxiety in tests subjecting them to novel environments. The authors confirmed causality by showing whole tissue levels of serotonin and synaptic serotonin levels were indeed diminished in the genetically modified mice. They also showed that these beneficial changes to the serotonergic system can be reversed by means of an SSRI (paroxetine).
If high serotonin is all bad, causing lower cognitive flexibility, anxiety, depression and suicide risk, how would it translate in the real world or as many proponents of SSRIs say, help one function better in society? At what cost does this function come at? Or what at least seems to be driving this functioning?
Countless studies have shown the S/S or high serotonin allotype to be associated positively with social outcomes or professional success and negatively with pro-social tendencies in everyone from wrestlers at the top of their field (Butovskaya, P R et al. Mol Gen Mikrobiol Virusol. 2015) to synchronised female swimmers (Maliuchenko, N V et al. Zh Vyssh Nerv Deiat Im I P Pavlova. 2007 and Sysoeva, Olga V et al. International Journal of Psychophysiology. 2009) to the Estonian Children Personality Behaviour and Health Study (Harro, Jaanus et al. Biological Psychology. 2009) to a cohort of Swedish adults (Rahman, Md Shafiqur et al. Psychiatry Research. 2017) to volunteers from Szczecin, Poland (Samochowiec, Jerzy et al. Neuropsychobiology. 2004) and others (Sen, Srijan et al. Biological Psychiatry. 2004). The same studies also looked at personality traits expressed in these high serotonin individuals to find that serotonin activity was negatively correlated with openness (measured on the Five-Factor Inventory), a dimension of personality that models curiosity, intellect and attitudes towards novelty (i.e. willingness to explore and try out new things) and neuroticism, a dimension that models negative emotions and a propensity for which. The studies were however mixed on the other dimensions with Harro, Jaanus et al. showing serotonin correlating negatively with agreeableness, a dimension of personality that model sociability and friendliness, and also conscientiousness whereas Butovskaya, P R et al. show a positive correlation with conscientiousness. In all cases, serotonin was associated with indirect hostility (measured on the Buss-Durkee Hostility Inventory) such as of passively aggressive tendencies (or social aggression). Indirect hostility or aggression is defined by the Encyclopedia of Evolutionary Psychological Science as “behavior[s] intended to harm others, particularly others’ social position and self-esteem, through circuitous means.. Indirect aggression is exemplified by behaviors such as gossiping behind back, spreading rumors, social exclusion, slandering remarks, etc.” Hmm.. so society’s top dogs are indeed a bunch of toxic bitches.
While the overwhelming amount of data collected were from European populations, there was one very recent study looking at Asian (Japanese) populations that instead showed L/L or low serotonin allotype to be associated with greater anxiety (Tanahashi, Shunsuke et al. Neuropsychobiology. 2021). I found this outlier very intriguing for it further goes to re-affirm serotonin’s status as a “social compliance” hormone since high serotonin allows you fit in to and function with ease in more high serotonin culture (collectivist, risk aversive, high PDI and restraint). Expectedly, this study reported that “a significant interaction effect was found between openness to experience and comorbid depression”, suggesting that the L/L or low serotonin allotype, associated with higher openness, struggles to fit into the high serotonin Japanese society, which as Goldman, Noreen et al. showed, is largely populated by S/S carriers.
Moving away from the Five-Factor Inventor, serotonin’s more fundamental role in determining personality comes to light when we examine something Nardi, Bernardo et al. call personal meaning organisation (PMO) in their post-rationalist worldview. Post-rationalism here is a rebuttal to the limits of rationalism, which dictates what can be “known” or “proven” when looked at through that paradigm. They propose a dichotomy between inward and outward personal meaning organisations. This is where an individual derives his “meaning” from i.e. what it is that they value, seek out to or wish to create in their lives. I think this provides valuable insights into how a high serotonin person thinks and perceives the world, not to mention what they value in themselves and others. Broadly speaking, a person can then be said to either have an inward or outward organisation of personality. The authors make no reductionistic attempts such as of distinctions or categorisations as with other models of personality. An introvert could just as easily have an outward PMO if their values and value system are more tribe-centric, regardless of how inclined they might be to socialising with others. This is not much unlike an extrinsic form of motivation. An extrinsically motivated individual will naturally structure their ambitions around what is rewarded by their society. Equally, they will value the same qualities in others around them, placing it on a higher moral pedestal.
A S/S or high serotonin allotype predicted an outward PMO while the L allele carriers had more inwardly organised personalities (Nardi, Bernardo et al. PLoSOne. 2013). It’s important to remind ourselves that we speak of systems of meaning here, not of introversion or extroversion as with the more traditional models of personality. Similarly, in other tests subjecting children to selective attention tasks, the the high serotonin children had greater event-related potentials on an EEG, suggesting greater task-related attention and a more externalised locus of processing consistent with an outwardly organised personality (Isbell, Elif and Neville, Helen J. Developmental Cognitive Neuroscience. 2016).
When looked at under an EEG, S/S and L/L allotypes show different brain activation patterns. The S/S or high serotonin allotype shows a skew towards the right-frontal hemisphere in affective processing while the skew is in the opposite direction with L/L carriers (Christou, Antonios I et al. Development and Psychopathology. 2016). This left-frontal skew is associated with approach motivation, a form of affective (or emotional) processing exemplified by the “expression and experience of anger, jealousy, desire, and joy” whereas the right-frontal skew goes with withdrawal motivation, exemplified by the “expression and experience of some forms of sadness, crying, and depressed mood” (Angus, D J and Harmon-Jones, E. Recent Developments in Neuroscience Research on Human Motivation. 2016). Withdrawal and approach motivation govern how we process our external reality, whether we view it with hostility or acceptance. The left prefrontal cortex is associated with a system that processes appetitive stimuli while the right prefrontal cortex processes aversive stimuli, all that the organism fears or feels threatened by (Spielberg, Jeffrey M et al. Social and Personality Psychology Compass. 2008). The high serotonin allotypes expectedly showed greater withdrawal motivation consistent with their anti-social tendencies established earlier.
What’s more? When looked at within a bigger picture of genetic adaptations to stressful evolutionary condition (i.e. to an agricultural mode of subsistence), we find that other polymorphisms in genes that govern things like BDNF expression, a neurotrophic factor that facilitates the growth and differentiation of neurons to create neuroplasticity, influence how one perceives the world (Christou, Antonios I et al. Frontiers in Behavioral Neuroscience. 2015). Those carried the Met or the low neuroplasticity allele on their Val66Met polymorphic region of their BDNF gene displayed negative affectivity as in a “vigilance–avoidance pattern of visual scanning” in a test subjecting them to facial expressions over those carrying the Val or high neuroplasticity allele. The S/S or high serotonin allotype of 5-HTTLPR displayed similar negative affectivity, avoiding eye contact with the faces.
The case against serotonin becomes evident. It is a stress hormone. High serotonin activity is an adaptation to evolutionary stress – war, famine and pandemic – brought on by an agricultural mode of subsistence. And serotonin is anything but the “happy hormone”. And the poorer the strength and capacities of the organism (low intellect, low neuroplasticity and adaptability, etc.), the greater the degree of apprehension to its environment.
Mrazek, Alissa J et al. (Culture and Brain. 2013) showed that cultural tightness, a measure of social norm compliance and penalties for deviant behaviour, is associated positively with higher frequency of S alleles or higher synaptic serotonin. “A desire for dominance” is observed in these cultures as a review by Chen, Hao et al. recently showed (Journal of Experimental Social Psychology. 2021). According to the authors, “culture tightness triggers a desire for physical formidability (being big and muscular), and interpersonal dominance.”
This speaks of a very telling reality, that social success is driven, not by any of the “good” or pro-social qualities that is so endlessly advertised to us, by religion, society and the very people at the top, or necessarily by intellect or anything cerebral for that matter, modelled by the openness trait of the Five-Factor Inventory, but rather by the vert quality of anti-sociability. This encourages behaviours motivated by a need for dominance to give way to vanity and exploitation of others. This is not much unlike a boy who grows up to become exceptionally talented at pick-pocketing thanks to his prudent upbringing. It would be terribly short-sighted then to proclaim this state of functioning as a pick-pocketer and all of the predispositions that enable it to somehow reflect the best of his potential. In reality, this state is merely a desperate adaptation to unavoidable stress, one where other traits or functions had to be traded. More foolish would it be to place the subtle art of pick-pocketing as the non-negotiable standard to attain and live by. As established already at the beginning of this post, serotonin is a stress hormone that adapts you to a stressful (or inhumane) society that simply does not facilitate the realisation of human potential.
This is why many women on anti-depressants report earning promotions and doing better in the workplace. When primates are given the same drugs, they rapidly climb up the social hierarchy and go on to oppress others below them. Or at least that’s what Dr. Julie Holland, a specialist of psychopharmacology thinks. She asks in her book Moody Bitches: The Truth About the Drugs You’re Taking, the Sleep You’re Missing, the Sex You’re Not Having, and What’s Really Making You Crazy, “SSRIs augment social dominance behaviors, elevating an animal’s status in the hierarchy. So they may well help women get along, and even get ahead, in the workplace, but at what cost?”
Alison Beard, who specialises in organisational behaviour writes for Harvard Business Review, “People who express certain genes in the dopamine system tend to be curious, creative, spontaneous, energetic, and mentally flexible. They are risk-takers and seek novelty. People who have high serotonin activity (or who take SSRI antidepressants) are more sociable, more eager to belong. They’re quite traditional in their values and less inclined toward exploration.” She continues about the validity of her findings, “I did two fMRI studies—one with young couples, the other with older couples. The subjects answered my questionnaire and then went into the scanner. It turned out that people who scored high on my scale measuring the traits linked with the dopamine system showed a lot of activity in dopamine pathways of their brains. Those who scored high on my serotonin scale had increased activity in an area linked with “social norm conformity.””
All the sick and sickly instinctively strive after a herd organization.. the strong are as naturally inclined to separate as the weak are to congregate.
Friedrich Nietzsche
What this presents us with is societies built on obedience and respect and not understanding and trust for one another. Because we must remember that trust and understanding are higher states of mind, not possible when one is stressed and only looking out only for themselves. Such a low-trust society is conducive to the ambitions of the ruling elite for it perpetuates their system. When the people do not trust each other and are not able to come together meaningfully, in a way that satisfies each others needs, they will cease to need a system, to depend on. You wouldn’t be going to the cops or the hospital if you cultural institutions hadn’t already failed you. In the same way, a low-trust society has to depend on “leaders” to guide the flock and prevent internal conflicts. The moral criteria also shifts to one of conformity. The people that walk in file behind their leaders now scorn and look down upon anyone who fails to do so. Non-conformity is seen as a crime in itself because it fails to uphold and perpetuate the status quo they so endlessly depend on now to conduct their own lives.
Oxytocin, or the love hormone, encourages humane relationships instead of the utilitarian relationships of serotonin.
People may appear to get along fine in utilitarian relationships by falling in line with social conventions but there is a profound lack of any understanding, let alone appreciation for one another, for ‘who’ they are and not for ‘what’ they are within some transactional economy. Utilitarian thinking values people upon socially-constructed notions of worth such as rank, reputation and status, where everyone is merely looking out to see “what they can get” i.e. maximising. We can quickly see why such a society would be beneficial to the ruling class for these people will also be the most ardent defenders of their offices.
The “anti”-social people in such a system are the people who are humanistic (altruistic, want understanding and want to build relationships out of trust) and not utilitarian. Trust also requires that people don’t just play pretend and express authentically, which doesn’t sit well with pathological types (which constitutes the majority of a low-trust society) whose only achievement is learning to play by an unspoken rulebook of social conduct from an early age, using said conventions opportunistically at every turn in their lives. Asking them to be authentic then almost feels like an insult to them and the personas they have had to so carefully sculpt and maintain for the better part of their lives, in order to remain functional in their societies. I’ve seen a great many people take offence with this humanistic approach.
The anti-socials in a high-trust society would be the utilitarians, much like humanists in a low-trust society who go looking after deeper understanding and trust, only for it to be misconstrued as a form of anti-sociability. Social morality is therefore relative. The most dominant tribe sets the moral code. In a low-trust society full of pathological and pretentious characters, the one who doesn’t play pretend, speaks honestly and acts sincerely is the troublemaker. Such a person is readily scapegoated within an utilitarian status quo, like a narcissistic family for example.
I’ll sign off this post with this ode to love from my fave Twitch all-rounder, Fareeha:
While I don’t think I will have the time to completely lay out my premises and prior understanding, I will try my best shot at summarising these absurdly broad and complex ideas that will pave the way for my later arguments.
All naturally-ordered systems, biological systems included, respond and adapt to their environment as a means to survive within said environment. A cell or any biological system really, responds to stressful conditions by re-orienting its priorities away from growth and differentiation towards self-preservation and survival. A way to look at this is to think of growth and differentiation as activities of abundance. Since these activities carries with them risks, it would be preferable to do them in times of safety and abundance. Likewise, when biological cells are threatened, they move their priorities away from growth to survival, looking out how to get by while incurring the least possible damage.
Abundance and scarcity necessitate different paradigms of existence – and thinking. When you are flourishing, you can take risks, try out new things, go explore and be whatever you want to be for the night. When you are barely keeping your head above the water, however, you are apprehensive to risks which includes doing anything even slightly out of the ordinary, out of the familiar and out of your comfort zone. As we will examine in later paragraphs, many of these mechanisms that underpin personality is also common to larger biology.
Studying endocrinology then gives us a valuable sneak peek into what our cells are doing and how they’re talking among themselves. Cells release several messengers or hormones as a way to let other cells and tissue know what’s up – either within themselves or with their environment. When stressed, cells release the four cardinal stress hormones – estrogen, cortisol, serotonin and histamine. Go over any literature on leaky gut, Celiac’s disease or IBS and you will find that an irritated gut liberates more serotonin. The case with asthma and liver injury is no different. When you look at allergies (a case of Th2 dominance), you will find that the helper cells are releasing low-level (belonging to adaptive immune system) hormone mediators such as IL-6 which ultimately results in the high-level release of histamine (by the innate immune system). Histamine, cortisol, estrogen and serotonin all work in a tight, self-reinforcing loop. For instance, when you’re stressed out, you are more likely to suffer an allergic reaction because glucocorticoids moves T-cell differentiation towards a Th2 bias while increasing the expression of aromatase. Estrogen has affinity for the H1 receptor and they work in a self-reinforcing cycle with histamine. Estrogen also degranulates mast cells, increasing histamine, which alongside other monoamines like serotonin, further drives up estrogen production via increased aromatase expression in stressed-out cells. Aromatase (which really is just a P450 monoxygenase) also naturally drives up the production of lipid derivatives of arachidonic acid, including various excitatory prostaglandins which stimulates the HPA axis causing more cortisol to be released while simultaneously also causing negative emotions by their interactions with receptors in the endocannabinoid system. Estrogens also directly antagonise the pro-metabolic signalling of androgens like progesterone, reducing the rate of mitochondrial respiration. Low ATP increases solubility of proteins, causing protein misfolding and dysfunction, allowing extra-cellular protein aggregates to be taken up as ‘seeds’ for prion disease. All stress states, put simply, brings down cellular resilience to stress by lowering rate of respiration, directly or indirectly. Ugh.. I could go on about the inter-relatedness of everything but I will cut it short for the sake of keeping this post relevant.
These four cardinal stress hormones produce many of the same effects both in the body and within the CNS. Under stressful conditions, such as learned helplessness, serotonin is released within the CNS. When animals (and humans alike) are repeatedly subject to debilitating conditions such as negative reinforcement (i.e. punishment), they develop an inhibited personality by means of high serotonin activity. Debilitating conditions may be anything where one has no control over the outcome of the situation such as when an authoritarian supervisor scorns and threatens to call your parents in for a redressal or when a parent physically assaults you, leaving you with no say over the situation. Serotonin gears the mind towards self-preservation, increasing tendencies that would benefit your survival such as of selfishness and collectivism. Many of the signs and symptoms of an authoritarian personality are caused by the effects of high serotonergic and low dopaminergic activity.
Serotonin is responsible for the inhibitions of learned helplessness similar to anti-depressants (Naudon, Laurent et al. Brain Research 2002). Many people in society have learned that they are fundamentally helpless against their tyrannical rulers, government mandates and economy and so, they hardly try to overcome these debilitating conditions. This makes people outwardly “fine” with whatever they’re subject to. This however, must not be interpreted as a healthy state as in modern (behavioural) psychiatry.
Many of the modern dogmas surrounding SSRIs, a type of drug that mimics a stress state within your CNS to inhibit the reuptake of serotonin, were the making of the FDA’s concerted efforts to outlaw psychedelics and psychedelic culture in the 60s as part of the larger “war on drugs”. A lot of these psychedelics like LSD were powerful dopamine agonists. They powerfully inhibited serotonin within the CNS, thereby opening up the brain, quite literally, allowing for new growth and differentiation. Those who felt stuck or felt like they had reached an impasse with life often benefitted from psychedelic therapy since it helped break down many of the inhibitions of serotonin (ego, respect and adherence to social convention, fear of social judgement and ostracization, commitment to social or institutional obligations, the conditionings of past traumas like learned helplessness, etc). You could see how such an intervention would then be against the ruling class’s interests bringing justification to why the FDA, along with their cronies at the pharmaceutical industry, would want to collude so hard to move dopaminergic substances into an almost taboo-like status. Traditional tricyclic antidepressants before the 60s targeted the dopaminergic pathways, much like the anti-leukotriene montelukast, which simultaneously relieves many of the effects of serotonin on the body such as histamine intolerance and bronchoconstriction while improving dopaminergic activity in the brain. This is why anti-serotonin agents work so well with asthma – and most other inflammatory conditions.
It would seem absurd to then expect serotonin to magically start behaving differently (within the CNS) from its observed role in all other places as an inflammatory mediator. Serotonin is also produced by the mast cells, which are part of your high-level or innate immune system. When you start looking at it through systems thinking, you are quickly able to weed out any potential falsehoods and other exaggerations that have been taken out of context. When you look at serotonin and the cross-talk between all other hormones and between the various systems of the body, we quickly hone in onto a cardinal role for serotonin, as one of mediating inflammation, a signal of distress so to speak. Within the brain, serotonin causes inhibitive behaviour, suppressing many of the systemic causes of mental illness, which then conveniently gets interpreted through the behaviourist lens as disease resolution.
Now why am I telling you all this? Because it’s going to help us understand why certain environments, with its own unique social and cultural pressures, select certain phenotypes of people. By understanding how dopamine (involved in growth activities like creation, self-expression, learning and play) and oxytocin (involved in understanding for others or empathy, trust and good intent) are antagonised by many of the cardinal stress signals within the body, we can see how stressful childhood conditions and other factors such as those prevalent in third-world countries select for certain types of individuals, those who are particularly resilient, apathetic and closed-ended in thinking.
The contrast between dopamine and serotonin dominant personalities is captured by the dandelion-orchid child theory of Thomas Boyce. Dr. Boyce, through practical analogy, explains how dandelions are resilient. They can grow anywhere and flourish with little in the way of care. Orchids are the exact opposite. They require tender and nourishing care to flourish. The life trajectories of orchids is most sensitive to conditions at childhood and later life. Dandelions can be thought of as serotonin dominant types, who feel little i.e. have low sensitivity which makes them very immune to the conditions of the outside world. They are risk-aversive and closed-ended, choosing the safest and most treaded path, aiming for integration into the collective. While this severely limits their scope for individual development, they are happy for the social perks a life of complacency brings. Dopamine dominant types on the other hand have a strong drive for self-expression and to seek out experiences in accordance with one’s inclinations. This in itself makes them terribly anti-authoritarian. They are the last people to walk in file, take and execute orders or suck up to the elders for the sake of it. For this reason, they are also the most cerebral of the types.
As an anecdotal case study, I’d like to talk about my home town and state of Tamil Nadu in India. The culture here is fairly conservative, satisfying many of the criteria for a ‘restraint’ culture by Hofstede’s dimensions. These include high power distance (PDI) which is marked by an almost unquestioning respect for authority, risk-aversive or uncertainty avoidance marked by a general contempt for anything outside of the ordinary such as for people who dress differently, look different and so forth. Tamil culture, from my experience, is also a low indulgence culture, where explorative, open-ended activities are frowned upon. The culture, like most agrarian and Asian cultures, glorifies self-sacrifice and repression of basic human drives such as of expression and play (growth activities mediated by dopamine), replacing them with respect and duty (mediated by serotonin). Naturally, the most socially successful types that take root and prosper within such a society are a special kind of what I can only call zombies, who don’t feel much, think much. Anyone with any measurable bent of sophistication or sensitivity will quickly find themselves in a debilitating situation, which either will force upon them a condition of learned helplessness, where they learn to repress and regulate their humanity as a desperate means to survive or resort to other extreme escapisms of drugs, suicide, etc. Because with the kind of nutrition and conditions you have here, optimal human development simply isn’t possible, in the same way an arid patch of land only gives birth to weeds and creepers. Only a more fertile environment may nurture beautiful orchids, gardens or farms.
Highly restraint cultures, regulated social environments and authoritative instruction and parenting all pave the way for inhibited growth and differentiation within the CNS. Without differentiation, there is less difference between people, as with when the brain is prevented from seeking out to experiences it sees fit for its developmental needs. Systems can only evolve in response to variety and stimulation. People then turn out to be more or less the same as this ambiguous-looking mush, having no discerning features to them. No character, thoughts or anything of their own choosing.
Since serotonin is inherently a stress signal, it mediates a number of whole-body processes that can be spotted quite easily. Serotonin, for one, slows the rate of mitochondrial respiration and encourages water retention. Authoritarians, therefore, tend to have puffier faces, may be prone to swollen feet and also feel cold often, preferring warmer days. Serotonin is also associated with reduced verbal fluency and poorer psychomotor ability. On a personality front, they may be rigid and argumentative about their beliefs, passively aggressive and non-assertive, closed-ended, loyal to the in-group and overly calculating automatically considering other people to be untrustworthy – all adaptations to being weak or impotent themselves. Stress, as we had already discussed, modifies behaviour in a way that maximises survival. They may also have thyroid insufficiency.
The thyroid is the master regulator of metabolic processes within the body, basically serving as the switch between abundance and scarcity programming. This is why all the stress hormones show some cross-talk with thyroid hormone production and signalling. SSRIs, which are believed to increase serotonin at the synapse, are also known to cause thyroid insufficiency and weight gain. Dopaminergic drugs (amphetamine cocktails like Adderall and other stimulants) prescribed for ADHD have the exact opposite effect, of causing weight loss by improving thyroid function. The rate of metabolism governs things like steroid hormone synthesis which is rate-limiting in myelination and brain development. Like I tell people, always find someone who loves coffee and pro-metabolic foods to sit down to have a chat with, because these are often going to be the most intellectually-endowed people you are going to find. After all the ectomorph (or cerebrotonic) body type is also called the thyroid body type. As its name suggests, cerebrotonic types are highly introspective and peace-loving, or cerebral. Only a body (and mind) that feels safe in its environment is going to be receptive to all acts of learning, exploration and play.
High serotonin (or prudent) diets and environments gear the body for survival. For instance, we know that PUFAs and starch-centric diets are highly serotonergic while SFAs, protein and sugar-centric are dopaminergic (by its modulative effects on serum tryptophan/LNAA, glucocorticoid induction and thyroid hormone production and signalling), opposing serotonin both in the body and CNS. We can quickly work towards a ‘theory of everything’ as it pertains to diet and culture of a peoples. People on prudent diets send signals of scarcity to their body, which suppresses thyroid and dopamine production, both responsible for growth and to maintain a certain level of proactive-ness with the environment, rendering them passively aggressive and apathetic. After all, of the behaviours one would expect to see from a creature that feels threatened can be attributed to serotonin — being defensive, low trust, thinking ill of everyone, being overly calculating, etc. This creates a culture that in-turn selects for serotonergic traits in its people by means of selection pressures, co-evolving a peoples and their culture in one big self-reinforcing loop.
Therefore, in light of everything we’ve seen, we find that the people who are healthy i.e. optimal minds and bodies are also the ones to find themselves in a debilitating position in such societies, becoming unhealthy in a rebound effect, much in the same way a very potent firework must produce the most destructive effect if inappropriately ignited. The same firework which, when ignited appropriately, in the right place and time, would otherwise have produced an engaging spectacle. A very potent drug, administered improperly, should produce the worst effects over a placebo. Anything with potency (think of high thyroid, dopamine, low serotonin) will also react the most adversely to environments over something with no potency at all (low thyroid, dopamine and high serotonin). Where the more unhealthy (or impotent) creature will be able to remain indifferent to its environment, the more healthy (or potent) creature is going to succumb to his own stress. I think this is why we find a disproportionate amount of highly gifted children (high neurological development) to acquire allergies, autoimmunity and other forms of immune overexcitibilities, not to mention being diagnosed with ADHD and other hyperactive disorders. The creature of greatness is then left with one devastating option. Become less sensitive and receptive to his environment i.e. to become less intelligent as a way to thrive in sub-optimal environments.. or alternatively, find a better environment.
Here’s something I wrote, contrasting the life experiences of someone with a sensitive nervous system that is also highly receptive to its environment (high dopaminergic activity morphing into ADHD/Asperger’s in rigid and understimulating social environments) against those of the larger population.
I was born hyperactive. My hyperactive nervous system makes me easily stressed out. I have a shorter but more sharper attention span. My hyperactive nervous system predisposes me to allergies and makes me extremely sensitive to environmental triggers. (I opened the window this evening to let some fresh air in and I smelt a little bit of incense being burnt somewhere and it gave me a terrible allergy. Now I am unable to even eat properly let alone do any other work.)
They call people like us orchid children. People like you and most others are dandelions.
Dandelions are resilient plants. They grow in a wide range of conditions. They will bloom anywhere.
Orchids are sensitive plants. They only bloom when the conditions are right. But when they do, they catch everyone’s attention. They leave their mark. But when they don’t, they fare worser than dandelions.
Where most people can get ‘get with it’, I cannot.
Where most people can eat any food they get, I will get sick.
Where most people can just talk to anybody and feel content, I cannot.
While it is impossible to prove psychological distress to people, you can show them bloodwork as proof of how your body is responding more aggressively to these triggers. You can show inflammation markers, for instance.
Most orchids accumulate a lot of trauma from growing up in these inhospitable conditions.
My hyperactive nervous system which is easily stressed out is also my strength. My acute stress response allows me to remain vigilint. It allows me to respond to situations as they may come in a effective manner.
Orchids for this reason respond optimally in unpredictable environments where any situation must be dealt with in a timely and appropriate manner. [Basically the jungle, an airline cockpit, etc..]
Dandelions on the other hand have a duller stress response. They respond optimally in predictable environments that come without surprises. [Basically school, office, college, etc.]
Orchids become stressed out in environments where they have to maintain a certain amount of focus for a long time. They are prone to zoning out, distractions and boredom.
Dandelions become stressed out in environments where they have to focus intensely on a task that came by without prior notice. They are prone to feeling overwhelmed and as if their discipline (i.e. their usual effective way of working through the task) is falling apart.
My hyperactivity allows me to concentrate fiercely on a task I feel most passionately towards. For those short stretches of time, nothing else can deter me. I am immovable. I am able to use my whole brain, bringing in insights from every corner, making connections that no one could’ve seen.
Orchids naturally take a high-risk/effort, high-return strategy. They are most productive working in short bursts with lots of leisure and time to tend to other distractions in-between. [Working as a pilot, freelancer, journalist, etc.]
Dandelions take a low-risk/effort, low-return strategy. They are most productive working with a schedule and routine with fixed times for work and leisure. [Corporate 9-5 job, security guard, lawyer, government employee, etc.]
Orchids want open-ended goals that gives them the freedom to explore, incorporate their own ideas and prespectives and enjoy the process. They take in rewards intrinsically.
Dandelions want well-defined goals to feel motivated. They want to know what constitutes an achievement so they can work steadfastly towards it to feel accomplished. They take in rewards extrinsically.
Orchids want looser deadlines to allow them enough time to enjoy the process. They want to revel and lose themselves in whatever they do, becoming one with it, to synergize with their highest self.
Dandelions want rigid deadlines to allow them enough time to enjoy what they had worked for. They want to know when they can get that vacation in Bali or retirement package they’d been hoping for.
For these reasons, dandelion children will have a ‘get with it’ attitude to life where orchids will feel suffocated, demotivated to do anything since the rewards they can be given under such a system don’t bring them any fulfilment.
There are polarising anecdotes on LCHF type diets, the keto diet being the most extreme of which. There are people on one end of the spectrum, including myself, who consider keto a life saver and spit in the face of doctors and other practitioners whose first instinct is to pick up a prescription pad without any deeper understanding of how the body works. Then there are people who are vehemently opposed to this type of eating for its contentious attitude towards the dietary guidelines and other recommendations from health authorities. But both parties are equally justified in what they say and have experienced. Saying otherwise would be cruel and invalidating to what they have felt. So why are carbohydrates so unique? When I eat rice, I get heart palpitations and cannot go to sleep. It makes me light headed and gives me a racing heart the likes of which I never experience eating a fat-based meal. When my grandmother eats rice, she feels relaxed and sleepy and swears by it as the go-to for regulating mood and appetite.
The underlying point of departure is quite simple from what I think it is. It all boils down to inflammation.
You see, when you are sick i.e. have allergies, are stressed out or are living in an incompatible environment, whether it is a social environment that doesn’t let you do what you are wired for or whether it is sensitivities to certain pollutants, noises, etc. it causes systemic inflammation and allergic responses within your immune system which is also the end manifestation of all types of un-health.
When the body is inflamed or sickly i.e. fighting against the environment, there are some key changes in carbohydrate and lipid metabolism that takes place. Generally, when the body is sick, it prefers to oxidise fats over carbohydrate. This is seen quite evidently in lipid markers of the sickly. Meta-analyses have repeatedly made out patients with infectious diseases, whether acute or chronic like psoriasis or HIV, to have elevated triglycerides and triglyceride-rich lipoproteins and depressed HDL. This pattern of dyslipidaemia is associated with inflammation or being sickly.
The underlying logic governing this system might be related to the biochemical changes that oxidising fatty acids vs. glucose brings. It has been shown that when the brain or the heart is sickly i.e. when you have a neurodegenerative disease or have cardiomyopathy, there is impaired glucose uptake and utilisation. Instead, these vital organs in their desperate and ailing times prefer to oxidise fatty acids and ketones. Studies have shown ketone therapy improves recovery and so forth. In the brain, ketone body metabolism is known to express BDNF, a necessary neurotropic factor for brain development and recovery from a major traumatic event, increase endogenous cholesterol synthesis to support myelination, improve the reducing environment of the cell by reducing antioxidant requirements and redox states of vital co-factors involved in cellular respiration like NAD+ and so forth. A shift towards glucose utilisation in the heart, which is predominantly configured to derive its ATP from fatty acid oxidation as evidenced by its high carnitine reserves, reduces cardiac output via falling ATP levels and other fast-acting energy substrates (phosphocreatine), starting a vicious cycle of hypertrophying cardiac muscle to meet the required cardiac load. Many of the therapeutic effects of exercise can be derived from a fasting or low-carb protocol since the underlying mechanisms of action involve increased fatty acid mobilisation and oxidation which consequentially, brings about a host of beneficial changes in cardiac metabolism. So running on fats and ketones means healing for the body. An ailing body does not want to be fed rice or other starchy foods, no matter how great these foods might be for someone who is healthy.
I suffered from allergic rhinitis for the better part of my life. And I remember every day when I would eat my lunch, I would feel lightheaded and get a racing heart. The carbohydrate rich meals where making me feel terrible. They were causing hyperglycaemia because my body wasn’t willing to use the glucose. In other words, an inflamed body is least sensitive to the effects of insulin.
Mechanisms of inflammatory insulin resistance. (Ajay Chawla, 2010 Annual Review of Pathology Mechanisms of Disease)
Elevated free circulating fatty acids are signature of an inflammatory response. An ailing body prefers to use fat as the preferred energy source. This is seen in observational studies where people who are sickly, regardless of diet i.e. the amount of fats or carbohydrate they might be consuming, show elevated levels of circulating free fatty acids along with all of the hormones to support their mobilisation and utilisation in peripheral tissue. This metabolic configuration is behind the “sickness behaviour” observed in people with colds or infections, who prefer going without food, losing much of their appetite.
Any inflammatory responses is also then conversely a stress response since stress hormones are required to mobilise free fatty acids. This is seen in studies where levels of cortisol, glucagon and growth hormone are elevated in SARS-CoV-2 patients. This type of metabolic configuration is typical of a keto diet or fasting regimen where cortisol is used to mobilise fat stores and kick-start hepatic gluconeogenesis while growth hormone prevents muscle catabolism and also facilitates protein quality control systems (autophagy) to create cellular efficiencies that would allow the cells to thrive with what little they have. Growth hormone isn’t just called the “fountain of youth” for no reason where many of the signs of declining health we develop with age are attributed to falling growth hormone secretion. A fasting or low-carb protocol can breath new life into you, quite literally. So anyways, this endocrinological signature of inflammation or infection, which is also mediated by inflammation, configures the body to oxidise fats, spare and re-route glucose and to heal itself at the cellular level. This healing process occurs in two-stages, often at once. Foremost, the cell tries to minimize any additional damage to itself i.e. by choosing to oxidise fuels that produce less ROS (which equals less mitochondrial dysfunction or allows better use of dysfunctional mitochondrion), spares more NAD+ (which improves the reducing environment of the cell equalling to better antioxidant recycling, less oxidative stress, etc.), reduces oxygen requirement (such as in the case of ischaemic heart disease) and also by choosing fuels that facilitates the inflammatory process itself allowing itself to recover (helping with the production of pro-inflammatory signalling molecules and so forth).
Secondly, the cell tries to create the necessary efficiencies necessary to let the cell run more effectively with less resources, which helps reduce ROS generation going forward. Mitophagy, a form of macroautophagy, gets rid of dysfunctional mitochondrion, basically putting it in “bag” and throwing it into the lysosome for digestion where its constituent amino acids can be extracted to build back better. (And no, that wasn’t political.) Dysfunctional proteins slows down cellular processes, creates inefficiencies in how resources are utilised, generating more wastes. (I speak mainly of mitochondrial dysfunction because I have good reason to believe it is at the root of all pathologies. Biological energy or ATP supports all secondary processes within the cell, including processes the cell was specialised to do. For a tardy example, when the mitochondrion of the endothelial cells lining our arteries dysfunction, there is impaired NO production and consequently, poor maintenance of the vascular tone which sets the stage for cardiovascular diseases.) For example, a prion or misfolded protein is quite toxic to the cell as they transmutate their shape to otherwise healthy proteins. (Sounds like something out of a sci-fi, right?) Autophagy gets rid of prions, which modern medicine is only starting to recognise as a therapeutic intervention for neurodegenerative disease. As you can see, these free fatty acids serve an important role where they help mediate the inflammatory response necessary for fighting disease and recovery. The Randle cycle then dictates that less glucose oxidation take place along with impaired insulin sensitivity since fatty acid oxidation selectively inhibits glucose oxidation via inhibition of malonyl-CoA and its rate-limiting effects on carnitine acyltransferase (required for LCFA access to mitochondrial beta-oxidation enzymes), acting in-tandem with hormones (like glucocorticoids which reduce insulin sensitivity in peripheral tissue) and inflammatory pathways (NF-kappa B) activation by cytokines.
While sensitivity to insulin is variably controlled by homeostatic factors in blood glucose like glucocorticoids and even your circadian rhythm (melatonin), a pathological state of chronic insulin resistance is caused by two main factors: a bad lifestyle or diet OR chronic inflammation from an underlying dissonance between body and environment.
(High intelligence: A risk factor for psychological and physiological overexcitabilities, Karpinski, R.I et al. Intelligence)
I have discussed in my other posts about the hyper brain-hyper body hypothesis which explains how people with sensitive nervous systems i.e. higher IQs are more susceptible to develop allergies, hyperactivity, and present with over-reactive immune systems. This is consistent with the law of reciprocity in nature and within natural systems. (More on the hermetic principles in another post.) If a system is specialised to be exceptionally good at one thing, it must be exceptionally bad at something else. A ‘type A’ manager who is exceptionally good at delivering results in fast-paced environments must also be exceptionally bad at handling and regulating his own emotions, being prone to irrational outbursts and tantrums when things don’t go his way. A person who loves deeply must also hurt deeply than someone who is capable of neither.
Much in the same way, a nervous system that is sensitive and highly receptive to its environment i.e., highly observant and intuitive, must also be so much more sensitive to all of its adversaries, whether it’s noise, environmental toxins or other experiences that upsets the homeostasis of the bodily processes, where someone less intellectually-endowed is able to just push through, unfazed. A highly sensitive nervous system might experience a more disproportionate reaction to a trigger, whether a loud noise or exposure to a common pollutant, than someone who isn’t so sensitive. Their bodies might produce more pro-inflammatory signalling molecules and cortisol to the same stressor, bringing about systemic changes in the homeostatic balance of bodily processes, which over due course of time, can develop into pathologies. In other words, a nervous system that is sensitive to the environment is indiscriminately sensitive to everything the environment has to offer, not just the “positives”. Feeding carbohydrate to a body that is already ailing and sickly is going to cause uncomfortable hyperglycaemia which, over due course of time, can result in pathologies such as T2 diabetes or insulin resistance. Our reductionistic scientific approach then finds it convenient to say anxiety or depressive disorders increase the risk for diabetes rather than to address or let alone acknowledge the systemic root causes.
@glucosegoddess shares some very interesting blood glucose experiments on her Instagram. Here are post-prandial blood glucose levels for two kids, Jessie and Luna, who eat the same quantity and serving of cookies and ice cream.
Jessie is probably very stressed out. Likely born with a sensitive nervous system in an environment where she is unable to express herself and live her truest self or fighting an ongoing infection or illness. In either case, Jessie’s inflammation markers are probably elevated along with markers of insulin resistance (elevated serum triglycerides, free fatty acids). Further studies using fMRI could show how Jessie’s organs are preferring to use fatty acids and ketones, which explains why sickly people mobilise such large amounts of fat i.e. present with high circulating free fatty acids. For the next 2 hours, Jessie experiences all of the symptoms of hyperglycaemia – lightheadedness, moodiness, irritability. Because let’s remember the brain as an organ requires blood glucose to be maintained within a narrow optimal range where it can function optimally. She also succumbs to greater damage from glucose, such as glycation-related damages to her blood vessels and proteins. Jessie and Luna, while eating more or less of the same foods, handle them very differently.
So what I’ve realised after all these months of keto and even eating carbs every now and then is that your body is most equipped to use glucose when it’s healthy. I was on the keto for over 7 months and I had never felt better in my life. Until then, I battled daily allergies, waking up sneezing a few dozen times with a runny nose, was constantly inflamed and had a very limited ability to tolerate stress, naturally. With keto, I had no allergies, no depression and just better health overall. My heart palpitations were better managed and my brain was sharper and clearer than ever. However, on the downside, I did find it harder to gain muscle, experienced some hair fall and found other ‘tertiary’ bodily functions such as libido to be depressed. After all, these ‘secondary’ or ‘tertiary’ functions are intertwined with anabolism i.e. growth as they do not only serve to keep you alive.
Over the past week, I had a good amount of white rice every day. I made sure my glycogen reserves were mostly depleted before each meal so as to control for the insulin-sensitizing effects of which. On the first day, I was able to tolerate the carbs rather well. I had absolutely no signs or symptoms of hyperglycaemia. I was happy, but only somewhat because this ran counter to my past experiences with consuming such large doses of carbohydrate. So I ran the same experiment another day, this time without much fasting or exercise. My glycogen reserves were surely not depleted this time. I had been snacking the night before as well. Again, no signs of hyperglycaemia. This was new. I felt much more relaxed than usual since exogenous carbohydrate was helping bring down my stress hormones which perhaps would have otherwise found themselves busy mobilising fatty acids and facilitating gluconeogenesis. This went on for a few days until today where I had left home for the first time in a while. I experienced some allergic symptoms from the fragrances used in a certain hand sanitizer I was forced to use by my paranoid parent, props to the ongoing and never-ending Coronavirus pandemic. I also find myself irritated by the VOCs (volatile organic compounds) in the car which are endocrine-disrupting in themselves. This is why I prefer open spaces and hesitate to shower frequently or put on synthetic fragrances which makes me allergic and inflamed. I know this because I listen to my body and I feel best on those days I avoid all contact with synthetic fragrances, including the ones found in bathing soaps and shower gels. So to cut to the chase, I was inflamed and the usual carbohydrate-dense meal, which previously had caused no adverse effects, suddenly gave me a racing heart, palpitations, irritability and other uncomfortable symptoms. So was it the rice.. or was it my body’s metabolic configuration due to an ongoing upset by toxin exposure?
I think this is an often overlooked aspect of our discussion on diabetes, dyslipidaemias, obesity, fatty liver and other diseases of affluence that it is not always the source that aggravates the condition that is also the cause of it. Yes, carbohydrate consumption is positively correlated with all of those pathologies and I have seen it, both anecdotally and on a population-level thanks to my very vegetarian upbringing in India where a grain-based, carbohydrate-rich diet provides much of the daily calories for the population. It is rather the context in which carbohydrate is consumed that matters. Consuming carbohydrate in the context of inflammation-induced insulin resistance or a pathological insulin resistance, brought on by years of overfeeding and energy surplus, is going to be deleterious to your health.
Feeding unhealthy people carbohydrate will push them down a slippery slope of more unhealth as you deny their stressed out organs of their preferred fuel, namely fatty acids and ketones, while also burdening their metabolism with more glucose than it is configured to utilise. This will most certainly cause weight gain, diabetes, dyslipidaemia and fatty liver due to a metabolism that is configured by the immune system to heal and not grow. With exposure to inflammatory substances and mediators at an all-time high, the need for a “low-carb reset” is the need of the hour to give their body the time it needs to heal without entrapping it in a vicious cycle of low-grade inflammation and un-health.
On a sidenote, inflammation-induced insulin resistance as a pathogenetic pathway to our diseases of affluence is being increasingly noted in a variety of contexts. One review even blamed paediatric vaccine schedules and the indiscriminate use of adjuvants therein, used to kick-start an immune response in the immunocompromised, to the rising prevalence of obesity and diabetes in children. Adjuvants sometimes increase inflammation several-fold more than your immune system normally would during exposure to the actual pathogen. However, with exposure to pathogens, you get “sickness behaviour”, something you don’t observe with vaccinations. Adjuvants are used in hopes that provoking an aggressive immune response at the local site of injection will synergize the antibody production. While this is effective for the immunocompromised and elderly, poisoning the rest of us with otherwise healthy and vigilant immune systems with adjuvants is needless and excessive where the risks far outweigh the benefits. “Thimerosal-containing Hepatitis B Vaccine Exposure is Highly Associated with Childhood Obesity: A Case-control Study Using the Vaccine Safety Datalink” by Geier, David A et al. in the 2016 North American Journal of Medical Sciences shows a clear causative role of childhood vaccination in obesity in later life. The underlying mechanism? Post-vaccination inflammatory syndrome in the context of a high-carbohydrate diet.
A stressed out body undoubtedly has no time to grow. Fats and ketones are the way to heal and rejuvenate your body. Carbs, on the other hand, are good for maintenance and growth. Carbohydrates (along with adequate dietary protein) help activate several pathways related to growth and proliferation while also helping with the production of growth factors and anabolic hormones like IGF-1, androgens and thyroid hormone. Insulin release from carbohydrate feeding catalyses the conversion of HGH to IGF in the liver and T4 to T3. All this creates an overall anabolic environment in your body to facilitate growth activities. T3 for instance helps with cholesterol clearance where low levels of T3, either from extreme or prolonged stress (i.e. catabolism) such as starvation or a long-term keto, have been shown to cause hypercholesterolemia. This is because LDL is a disease-fighting agent that helps curb virulence. Studies show that people with familial hypercholesterolemia have less infectious mortality in countries where the infectious burden is high. With a little bit of systems analysis, we can then see how almost everything in the body is invariably inter-connected and that nothing ever happens arbitrarily for its own sake.
So the next time someone is able to stay lean eating a lot of rice, remember it’s probably just how their immune systems are working. If you have overexcitibilities or other sensitivities, allergies, feel sick or tired all the time or are generally stressed out by the world around you, you are better off giving your body the fuel that it needs to heal and rejuvenate itself before you feed it carbs for growth.
In allegory, understand that growth is not possible for all people in the same environment. Much like how some flowers bloom in some soils or climatic conditions while other wither away and die no matter the amount of care given, not all people can take root and prosper in our societies that is founded on the ideals of compliance to a singular set of standards, expectations and behaviours. Naturally, some people are going to not grow and rather be stuck in a loop of barely thriving against the odds while others will experience unchecked growth when the odds work in their favour. If your genes, IQ and so forth do not accommodate the local environment, you will be inflamed and naturally, in a healing mode rather than a growth mode. During this time, you need to facilitate what your body is already trying so hard to do on its own with the appropriate nutritional provisions.
Unlike the more cardinal flavours of sweet and sour, umami reserves a special place for its unusualness. Unlike the more traditional flavours, which either indicate a presence of electrolytes or the presence of energy, umami acts more like a sensor for protein in food. I have reason to believe that a craving for umami foods – stir frys, woks, ramen, you name it – could indicate a protein deficiency.
A serious zinc deficiency in children often manifests in a craving for chalk and plaster. I knew someone who was diagnosed with an “eating disorder” for craving chalk when in actuality, they really just needed more minerals in the diet. The very idiotic medical establishment then recommended her to a psychiatrist for an ED. It is then obvious that the body has a sophisticated mechanism of sensing nutritional status to create the right cravings that would satisfy them. This is how I like to think of cravings, as something that motivates you to seek out foods that would fill the gaps in your nutritional status. If you were missing out on something, your body will make you crave it. It’s not always a matter of willpower or personal preference.
*totally relevant rant begins*
Our society which likes to make people responsible for their own misery, so as to conceal the systemic root causes of people’s suffering which risks unearthing some very inconvenient truths about the way our social structures function, makes them more helplessly miserable when in reality, they were just mishandled by an incompetent healthcare system. Making people take responsibility for their dietary choices conceals the root causes of their poor health and the systemic abuse they face from a profit-driven healthcare and food industry that sells them misleading dietary guidelines and pesudo-foods (breakfast cereal).
Feed a man artificial sweeteners and he will experience hypoglycaemia some two hours later which will make him need more food. It was not his personal choice to have hypoglycaemia. It was the food that set the initial conditions for hypoglycaemia and subsequent sugar cravings to occur. It would be short-sighted then to shame such a person for what is believed to be their lack of willpower, demanding that they ‘man up’ and take personal responsibility for their sugar cravings. Such is the predicament of an utterly incompetent, short-sighted and simple-minded society that lacks that intellectualism to critically analyse and understand intimately objective reality.
*end rant*
The umami sensation is created by sensing certain peptides and free amino acids in food. Receptors on your tongue, a modified form of mGluR4 found elsewhere in your body, senses and relays the presence of amino acids (glutamic acid) in food. A certain salt of this amino acid is used widely used as a quick-and-tardy means of achieving the umami flavour without any of the hassle of preparing them. You may know this salt as monosodium glutamate (MSG). We also know that the umami flavour can be enhanced or brought out in non-umami foods by means of fermentation as microbial action breaks down complex proteins into more bioavailable peptides. The proteases in microbes may also liberate more glutamate from these peptides, increasing the amount of free glutamate that can interact with its corresponding receptors on your tongue. *cues soy sauce*
So why MSG? I think the main reasons why MSG is so widely used by the processed food industry is to make up for a lack of protein. You see, carbs are cheap. Protein and (healthy) fats are expensive. Nobody is going to serve you a dish with a lot of meat and butter in them. While these latter ingredients are healthy, they are also expensive to produce and maintain i.e. highly perishable. So to make otherwise low-protein dishes palatable, MSG is added. This creates an instant meaty flavour, reminiscent of the missing protein. This fuels unhealthy eating patterns and subsequent obesity. On the one hand, you are signalling to your brain that you are eating a protein-enriched meal by the sensation of umami but on the other you are only getting a very small portion of the protein your brain had hoped for. You end up sending conflicting signals to your brain and body.
This is an overlooked aspect of our discussion surrounding obesity and healthy eating. We need to remind ourselves that the processed food industry is spending considerable effort to engineer our food, to make it hyper-palatable. It is exploiting our evolutionary programming to seek out protein-rich foods to sell you foods that contain none of it. This creates a vicious cycle of low-satiation and hunger, which makes you crave even more umami foods in a desperate attempt to nourish your body with the protein it needs.
So the next time you find yourself craving some East Asian food, go get some beef instead. Now there’s your real umami 😉
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. 🙂
This is why all vegetables in in more plant-based cultures are finely chopped and sautéed in oil in a fairly high heat to break down these polymers. The oil acts as a carrier for fat-soluble vitamins. This has the effect of sweetening up the vegetable since polymers are broken down into constituent simple sugars like glucose which we can taste. However, this isn’t nutritionally superior to fermentation which introduces new nutrients. Nor is this healthy since a lot of times, the oils used in high-heat sautéing are unsaturated and readily undergo lipid peroxidation, introducing damaging free radicals into the body. This can also oxidise the fat-soluble vitamins in a chain reaction. Not to mention the act of cooking destroys many water-soluble vitamins like those of the B-complex and vitamin C.
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 am not the most avid gamer but I do spend a fair amount of my time playing videogames. That being said, it’s only because I spend almost no time watching TV, movies or other forms of passive media. Videogames, to me, is a very unique media in the fact that it’s not only interactive, requiring your active participation to move things along, but it also is perhaps the only media that doubles as an expressive medium. You most certainly don’t see people streaming their late night Netflix binges from their couch but you see people stream their Minecraft universe or a Counter Strike strategy. Put simply, videogames provides this sandbox for you to express yourself in, sans the limitations of physical world (or the moral limitations of the social world), much like you would dance or do taekwondo. There’s just something you learn about yourself, you repressions and all, by driving over a bunch of inappropriately outfitted pedestrians in GTA that you cannot do in therapy (lol). It’s not uncommon to find many gamers also having dabbled in music, the fine arts among other things. An example of which would be streamers like Fareeha, who routinely stream their piano improvs alongside Overwatch gameplay.
Moving children and young adults away from TV into the rich world of videogames, in my opinion, would be a massive win as far as the average IQ of this population goes. Most of us don’t get a whole lot of intellectual stimulation in our social lives, whether school, jobs or even popular recreation activities like going to a pub for drinks. Much of social life is very repetitive, lacking any variety in the duties performed. Jobs are mostly clerical. It’s not very cerebral. So is social interaction with other people, especially if you are someone with an above-average IQ. Most people are only capable of talking in simple platitudes and common sense. There is not much intellectual rigour. Now I don’t want people making this reductionistic argument that social interactions are instead about emotions because let’s be honest, most people’s idea of emotionality is being dramatic and petty. It’s not like you’re gathering around to read Edgar Allan Poe or listen to some Chopin or present a literary critique of Hermann Hesse. Most people aren’t so empathetic either. They are only playing by an unspoken rulebook of social conduct so they can all get along fine to the ends of maintaining social order. If people truly had deeper understand for each other, for their motives and intentions, they wouldn’t feel so threatened when somebody strayed outside the file of acceptable convention. Think about bachelorette parties Much of “networking” amounts at best to gossip. Much of corporate etiquette is to maintain a status quo, where much of the days duties revolves around propping up each others egos and managing other people, not actually creating anything of value. (A famer is creating something of value, that which we need to nourish our bodies. An artist is creating something of value, that which nourishes our soul, that inspires new thinking and develops and maintains morale of the people. An engineer tinkering away at his workstation in his garage is creating something of value, that which makes our lives easier. A corporate coolie and the whole spectrum of service-based jobs on the other hand, only serve to maintain a status quo way of doing things, a modus operandi if you will, and to sustain the powers vested in them.) On the other hand, 3 hours spent in a flight simulator game like Prepar3D can vastly improve your spatial reasoning abilities, or the same spent in DOTA could help you build team strategy and coordination in very diverse and dynamic situations or an FPS game like Valorant or Rainbow Six could develop your mechanistic abilities and dexterity, keeping all of these cognitive faculties stimulated.
Screen grab from a recent sunset departure out of London Heathrow.Games like Control develop aesthetic and emotional sensitivity, by presenting such varied stimuli that you could not find in the physical world.Valorant is FPS with a facelift, moving its art style away from the realism of military warfare to one of creative play, with sci-fi abilities and unique environments.Not to mention videogames allow you to socialise with people of your neurotribe, especially if you are born with certain predispositions (or a personality) that leaves you sharing no common grounds with those around you. Here’s me and my girlfriend messing around in electrical (lol), creating intimacy in a long-distance relationship.
Anyways, going back to the premise of my post, I have made some careful observations about people and society from playing a lot of Valorant late into the nights, on weekdays especially. To cut to the case, I’ve found that players at night on the local server (so they’re all on the same time zone) tend to be more intuitive, intelligent and sensitive. There’s less aggression or toxicity, more empathy and deeper understanding for each other. A more remarkable finding is that night time players are far less utilitarian in their moral reasoning. During the day, the average player is a short-sighted loudmouth who can only think one or two steps in either direction. He lacks any higher intelligence or intuition. He is angered easily, only reads situations at the symptomatic level and forms friendships out of utilitarian needs. He is an ego-centric thinker and cannot entertain ideas in the abstract, but only as they relate to him or his needs. The last point, about utilitarian friendships, is especially relevant for people like me, who are above-average intelligent and tend to have seek more deeper connections with people, on grounds of shared aesthetic sensibility, philosophies or thinking. The utilitarian, on the other hand, has no such aesthetic needs. They are content as long as everybody is able to just get the task at hand done, even if they cannot stand each other. This is why utilitarian relationships enforce strict boundaries and entertain ‘busyness’ since there is no higher synergy between the parties and without this ‘busyness’, there would be no reason for them to remain together, or simply even get along.
Why am I telling you all this? Or moreover, what broader implications does this have?
I think this is where we put on our thinking hats and start to view the problem in its abstract. This phenomenon of more sensitive and intuitive plays propping up in the servers at night tells us a lot about what larger society values – and rewards. This is because most of society’s activities are conducted during the day. If the most refined and sophisticated minds are out at night, it tells us that these types aren’t doing much during the day. They certainly cannot be rising at 7 AM while playing their last game at as late as 5 AM. So is it then safe to say the 7 AM crowd you see out on the streets, on the bus to work or at the local café don’t have their share of these night time players? I think so.
Now why could this be happening? Why are more intuitive and esoteric peoples choosing to stay up at night playing videogames when they could be, say, doing something more tangible during the day?
While it is most certainly easy to write off their late night gaming as stemming from personal vices such as laziness or tardiness. But it is not the case. As with most things in our social phenomenon, there exists a complex dynamic between the individual and his society that ultimately goes to shape his responses or adaptations to which. One isn’t simply born lazy. They become lazy (or unambitious) when they don’t feel rewarded for what they do most naturally. Otherwise, the task becomes a chore. But even chores can be rewarding, if the rewards justify the effort put into them. For a lot of people, merely functioning in this society demands a lot of their effort. Take for example, introverts. Their nervous systems are highly sensitive. This predisposes them to psychological and physiological overexcitabilities. Now if a task that others can do with ease, without experiencing much distress, is not rewarded fairly, the introvert will feel no motivation to do it again. In other words, we see that there must the rewards must exist in proportion to the effort. And the amount of effort one may have sacrifice varies wildly depending on their innate predispositions (or personality), as with the example of introverts I just gave.
So what’s happing at the end of the day is that many esoteric types don’t feel as though the effort they have to expend to merely remain functional in society – to hold jobs, to attend classes and so forth – is ever justified by its rewards. The cost to me then is greater than the compensation. This makes the task not worthwhile. What this ultimately manifests as is this laziness we see with highly gifted individuals, whose gifts are more generalised and creative than narrow and applied.
The day time players, who feel motivated to wake up, go out and make things happen, are only motivated to do so because their natural proclivities are accommodated by this society. They find themselves at home in our social activities. As for the night time players, their proclivities don’t serve them well in society, regardless of the extents of effort. This forces them to withdraw into environments, such as those offered in videogames, they they instead find more rewarding. Here, they feel as though they can attain mastery and be good at something and to feel good about themselves, something they could never get from participating in society.
I’ve always been of the opinion that platforms like Quora and TED cater to a marginally above-average population in intellect confirm their prejudices. A circle-jerk so to speak. An echo chamber for the (pseudo-)intellectual elite who have managed to convince the community of their alleged superiority over others. But I still thought I’d give it a fair shot, because on forums like Reddit, most people wouldn’t have the attention span to sit through a 3000-word reading of a well-reasoned argument, often choosing to go after the most impactful one-line mic drop-style responses. I find that counterproductive. But it’s still got its place and purpose, being significantly more open to new perspectives and ideas than the more dogmatic elitists over at Quora. It’s funny because you find just about the most snobby, arrogant and closed-minded people at the upper echelons within the site. Quora then, in what would seem like a self-reinforcing cycle, helps perpetuate their half-baked opinions far and wide on its site.
There seems to exist only two types of characters who thrive long-term on this platform. The pseudos who masquerade as these all-perfect, all-knowing Nietzscheans who for one, can’t put down their silly egos and think straight and their spineless army of yes men. Without these men, who they’d recruited into their army, their reign sure wouldn’t exist. Anyone who openly challenges or expresses their distaste with the ruling class are censored and silenced by force, without justification.
I wouldn’t say I’m surprised the least bit, I expected this going into Quora. I’d read plenty of accounts from other users who had their answers deleted, without explanation. Any appeals to the moderation team were fruitless. How can you expect justice when your accusers are incapable of reasoning. This is expected with pseudo-intellectualism, where your entire sense of intellectual superiority rides on your fragile ego that’s convinced itself that’s its better for doing some things better than others, by earning those titles. And when these titles are blatantly disregarded and an inconvenient truth is being uncovered, the perpetrators are forcefully silenced, all without reason.
Quora is just this – insecure egos hiding behind everything from their stupid test scores, college degrees and even Myers-Briggs type. Most of these people couldn’t reason, so they justify the half-baked vermin they spew upon those socially-respected achievements, which again, can only awe the normies who cannot think for themselves.
Which also brings me to my problem with the modern scientific community, this short-sighted tendency to put down and ostracize opinions that don’t agree with an existing body of research. Need I remind these pseudos that all widely-accepted theories today were once a ridiculous hypothesis on what was then believed to be a crazy man’s board. Is it my fault that your phoney brains cannot tolerate ambiguity to the level where it can impartially sift through things for once without clinging onto the first confirmation of your prejudice in a laughable case of anchoring bias? This is where compulsive fact-checking is going to take us – ideological policing. And we see this shift well underway on social media sites. Any uncomfortable or culturally-inappropriate opinions, that are inconvenient to the interests of the ruling class are shunned, the person behind the argument attacked. Most well-reasoned theories never see the light of day this way, not because they’re of inherently less worth as the elite would want you to believe, but rather because it was never given a fair chance to prove its mark. This is precisely what we see with modern medicine that continually puts down approaches at holistic healing because they refuse to perform a concerted evaluation into its efficacy. It’s like how the medical community outlawed research on psychedelics in the 60s, using the lack of evidence, to paint their opponents unfairly.
The ruling class don’t want to reason, they chose to hide behind titles. They then find feeble-minded men who will buy into those titles without posing a challenge, or brainwash them into believing those titles actually mean something. This is how the “science” community works today. You are promoted and called a good researcher when you align your interests with the those of the ruling class, who will then grant you elevated privileges to conducting your sketchy “research” on the condition that you stick to your promises. They cleverly set up incentives so good men leave out of frustration when their honest work doesn’t translate to tangible returns, in the form of institutional appraisal or better funding.
With Valentine’s day (ugh, I know right?) inching closer by day, my interest in this weirdly confusing phenomenon of love has been reinstated. I have always found myself awed by the many ways love presents itself at various psychological and physiological levels in people who allege to be experiencing it. Without much of an introduction, I want to get down to business with these questions that I think are relevant to uncovering the mysteries of romantic love as exemplified by the countless break-up songs of American pop star, Taylor Swift (more ugh, I know but I will make a pass for the synth-pop Goddess, Carly Rae Jepsen – at least her love songs are generously clad with 80s-inspired synth sounds).
if everything is motivated by sex, why love?
A popular theory in neuroscience about the workings of the reptilian brain goes on to state that the fundamental impetus to all our Earthly endeavors is our collective desire to procreate. Approaching from an evolutionary standpoint, this seems only plausible because how else is this species going to sustain itself if it weren’t for horny men wanting to furnish every woman in a ten mile radius with their priced seed? The drive to procreate is deeply-imbibed into the sub-conscious of every healthy male – but is this also perhaps what motivates men to perform great feats of architecture, engineering and art? Is this some sort of symbolic expression of sexual dominance on the part of men? Continue reading “The Wildly Perplexing Phenomenon of Romantic Love”→
Stoicism, to me, is far from being the pursuit of happiness. It is instead self-sufficiency attained by absolving the emotional imperative in life through an extensive and rational evaluation of oneself, which neither brings happiness nor sadness. It is equanimity.
In my previous post about coping strategies for emotional suffering and trauma, I had postulated that being narcissistic is one excellent and fool-proof way – and this was back when my knowledge in this wonderful Hellenistic school was at its infancy. Now that I can safely regard myself as a practicing Stoic, how did I tie that in with my past subscription to narcissism? The form of narcissism I’d advocated had its premises not in the reluctance to uphold virtue, in holding an ignorant and over-inflated ego but rather in the autonomy from society. Most people are evolutionary conditioned to predicate their social, economic and life decisions upon the repercussions it might have on one’s social standing. Women are particularly susceptible to this sort of social behavior. Men are too, but only to a lesser degree. Narcissism, in the context of social autonomy, refers to the individual’s ability to operate autonomously, or without the influence, from the many dictates of society. This lack of social autonomy is regarded in my philosophy as a massive hindrance to self-actualization and personal enlightenment.
chronic overthinking 