Where it all starts…
The only reason you could ever feel bad about life is when *something*, somewhere, is static. This is always physical first...
How would a person be unable to handle a stressor if they had all of the resources to handle it?
Something must be impairing energy production...
If someone is *technically* getting all of the resources that they need, yet still experiencing issues, then it simply becomes an issue of conversion, or digestion.
Better yet, metabolism...
Anywhere that energy is static, flow must be restored. After this everything will regulate itself. I have yet to talk to someone who has anxiety or depression who hasn't been dealing with some sort of impairment of energy at some certain point...
Physical digestion is no different than mental digestion, for this reason. When we have a physical impairment of energy, we fixate mentally. Things are static in our body and static in our mind, trying to preserve our limited resources.
Physical Manifestation
Under stress, cells are usually overexcited and de-energized. This is because we aren't producing enough energy to maintain structure, or properly metabolize what's moving through our system. Everything that we consume has an effect in either promoting energy, or impairing energy…
This can be what we consume as food, watch, listen to, think about, places we spend time, etc. Each part of the environment affects us on a physical→mental→spiritual level.
For example, a stressful environment will put a person into fight or flight, depleting their energetic resources, causing them to synthesize the protective stress hormones.
Also, under stress, a person will naturally hyperventilate, in an effort to make oxygen available.
Hyperventilation creates an imbalance between oxygen and carbon dioxide1, which is, actually the substance that allows oxygen to be delivered to cells effectively. (more on carbon dioxide here)
This graphic I adapted, (credit to Danny Roddy) does an amazing job to show the cascade of stress towards nitric oxide synthesis. I think this is vital to understand cognitive disorders… which are really just energy disorders...
Stress also diverts blood flow away from the less vital systems, such as the digestive, and reproductive systems, and towards the more essential organs for survival, such as the brain and heart. Nitric oxide can serve as a as an emergency vasodilator, but if chronically elevated, can impair energy and kill cells.2
“The basic control of blood flow in the brain is the result of the relaxation of the wall of blood vessels in the presence of carbon dioxide, which is produced in proportion to the rate at which oxygen and glucose are being metabolically combined by active cells. In the inability of cells to produce CO2 at a normal rate, nitric oxide synthesis in blood vessels can cause them to dilate. The mechanism of relaxation by NO is very different, however, involving the inhibition of mitochondrial energy production (Barron, et al., 2001).3 Situations that favor the production and retention of larger amounts of carbon dioxide in the tissues are likely to reduce the basic “tone” of the parasympathetic nervous system, and there is less need for additional vasodilation.” -Ray Peat4
Both serotonin, and nitric oxide serve as emergency mediators that lower energy requirements under stress in a effort to preserve resources.
The only problem with this is that when less energy is being produced, this makes an organism turn inward… This is a sort of hibernation, or protection from harmful circumstances...
Now do you see why having these hormones elevated chronically is an issue?
For example, when the digestive system becomes stagnant, endotoxin builds up; more serotonin & nitric oxide are synthesized to promote transit through gut, but this is through inflammation.5
All of this damages blood vessels, allowing leakage of toxins into bloodstream...6 This causes a whole host of inflammatory reactions, impair energy production EVEN further, and causes more harmful cognitive effects. Most notably being brain fog.
If you aren't producing energy in abundance.. You WILL NOT face life with the proper capacity.
You "don't feel like enough", because you literally aren't enough! You are deficient in energetic resources!
You feel numb and depressed because your body is trying to protect you from your circumstances! It's trying to say that you DON’T HAVE ENOUGH RESOURCES!
Cortisol and adrenaline are obviously elevated in times of stress. This is to to keep the metabolic rate high (except they oppose thyroid), and when they stay elevated, this is when major deterioration occurs, and I shouldn't need to convince anyone of this.
Cortisol is catabolic, and breaks down muscle into energy. This is why ensuring abundant caloric intake (especially from carbohydrate) under stress is essential to prevent the body from breaking down it's tissues into energy. (which also feeds this whole vicious cycle of stress)
Now I understand this may not seem exactly interrelated to anxiety and depression yet, but I'm about to explain...
Cortisol activates aromatase which synthesizes estrogen...7
High estrogen is reliably associated with emotional instability8, and as many of us may know... high estrogen is NOT just bad for males, but for females as well.
“Estrogen is just one of the intrinsic excitatory substances, which are produced by stress, and which participate in self-stimulating loops. Ammonia and nitric oxide are two of the most pervasive endogenous excitants and toxins. NO [nitric oxide] is emerging as an important endogenously-derived neurotoxin” (Dawson and Dawson, 1995).9 -Ray Peat
Estrogen directly opposes the youth associated hormone, progesterone; a hormone of vitality, and longevity that opposes stress. Alloprenenolone, which is a downstream metabolite of progesterone, is known to be a powerful mood regulator, and promoter of GABA.10
Inhibiting the synthesis of estrogen with natural aromatase inhibiting foods such as orange juice, grapefruit, marmalade (all rich in naringinin, an aromatase inhibiting substance) and parsley (rich in apigenin, another aromatase inhibiting substance) can help to lower estrogen.
Well cooked white button mushrooms, aspirin, and coffee can help to inhibit aromatase as well.
Insoluble fiber such as carrots can also help to bind and detoxify excess estrogen. Combatting PUFA and estrogen with vitamin E and progesterone can also be useful.
An issue of excitation.
One of the most commonly overlooked but vitally important aspects of cognitive disorders is overexcitation at a cellular level...
This comes from a lack of inhibitory substances. As mentioned earlier, estrogen and the other stress hormones are excitatory. Glutamate is excititory as well, and high glutamate directly correlates with low GABA, which is calming. (also correlates with low dopamine)
Glutamate can be synthesized from ammonia, breaking down protein into energy (stress or when protein intake is too high) and from inflammatory amino acid consumption, most notably, tryptophan.
Constantine wrote an amazing blog here, explaining glutamate and GABA, I’d recommend reading.
Essentially, when estrogen is high, and thyroid is low, magnesium and vitamin B6 are lost quickly.
This prevents tryptophan from being converted into niacin, and instead it easily gets converted into the inflammatory and neurotoxic quinolinic acid.
Also, most notably, glutamate is unable to be converted into GABA. With excess glutamate and low GABA, dopamine will almost undoubtedly be low.
Under stress, when cells lose structure, they take up calcium, which is another part of the excitatory process, lowering energy production.
This is a clear part in cell death.
“All cell death is characterized by an increase of intracellular calcium….” “Increase of cytoplasmic free calcium may therefore be called ‘the final common path’ of cell disease and cell death. Aging as a background of diseases is also characterized by an increase of intracellular calcium. Diseases typically associated with aging include hypertension, arteriosclerosis, diabetes mellitus and dementia.” -Fujita, 1991 -Ray Peat11
EMF also opens up the calcium channels and plays a role as a chronic stressor that can cause overexcitation, and deplete energy.12
Eating calcium in the diet such as in milk, cheese, ice cream, or consuming a calcium carbonate supplement can help to prevent the influx of calcium inside the cells. (calcium channel blockers and keeping parathyroid hormone low can help too, see end of page)
Maintaining adequate resources under stress, allows the body to continue to produce energy properly. Essentially, the goal is to clear whatever roadblocks are preventing the flow of energy…
Interventions
Support digestion.
anything to improve bowel movements (to prevent fermentation of bacteria, and keep endotoxin low)
easily digestible foods (to keep transit time quick)
natural laxatives and detoxifiers (magnesium, cascara sagrada, coffee enema, carrot, aloe vera juice, etc.)
Lower cortisol.
meditation and breathing exercises (ex. 4-7-8, bag breathing, Buteyko) aspirin, cascara sagrada (emodin), cyproheptadine, progesterone, pregnenolone.
Lower estrogen.
aromatase inhibiting foods (orange juice, grapefruit, marmalade, parsley, white button mushrooms)
oppose with (aspirin, coffee, vitamin e, progesterone, carrot salad)
More on estrogen here.
https://x.com/natelawrence_/status/1741280139462267170?s=46
Increase carbon dioxide.
provides oxygen to the cells for proper function and order creation (read my thread on carbon dioxide here)
Increase GABA. (lowers glutamate and helps increase dopamine)
magnesium, gelatin (glycine), l-theanine, taurine, vitamin B6, pregnenolone, progesterone
Increase dopamine.
coffee, vitamin K (or other quinones), mucana pruriens, phenylalanine, phenibut, adamantane, metergoline, tianeptine, lisuride, bromocriptine, etc.
Keep inflammation low.
minimize tryptophan, methionine, and cysteine, eat gelatin
aspirin, ginger root, methylene blue
This could be an entire post in itself so all I'm going to say is anything that promotes energy, physically or mentally, will likely lower inflammation.
Lower nitric oxide.
keep carbon dioxide high, methylene blue, niacinamide, aspirin, coffee, thiamine, baking soda, vitamin K, progesterone, thyroid, etc.
Regulate calcium and parathyroid hormone.
consume more calcium (dairy, well cooked greens mineral broth, calcium carbonate, mineral water)
prevent the influx of calcium (magnesium, cyproheptadine)
vitamin D and K
Improve thyroid function.
all of these things help to improve thyroid, but mainly ensuring adequate protein, carbohydrate, micronutrients, like B-vitamins, calcium, magnesium, sodium, potassium, zinc, copper, selenium, and considering supplemental thyroid hormone, pregnenolone, progesterone can be useful.
"The cistern contains, the fountain overflows." -Willam Blake
https://pubmed.ncbi.nlm.nih.gov/10693382/ Gilbert C. Hyperventilation and the body. Accid Emerg Nurs. 1999 Jul;7(3):130-40. doi: 10.1016/s0965-2302(99)80072-1. PMID: 10693382.
https://pubmed.ncbi.nlm.nih.gov/10320672/ Murphy MP. Nitric oxide and cell death. Biochim Biophys Acta. 1999 May 5;1411(2-3):401-14. doi: 10.1016/s0005-2728(99)00029-8. PMID: 10320672.
https://pubmed.ncbi.nlm.nih.gov/8562443/ Dawson VL, Dawson TM. Physiological and toxicological actions of nitric oxide in the central nervous system. Adv Pharmacol. 1995;34:323-42. doi: 10.1016/s1054-3589(08)61095-9. PMID: 8562443.
https://raypeat.com/articles/articles/dark-side-of-stress-learned-helplessness.shtml Peat R. The dark side of stress (learned helplessness)
https://doi.org/10.1093/jcag/gwad020 Jensine A Grondin, BSc., MSc , Waliul I Khan, MBBS, PhD, FRCPath, CAGF, Emerging Roles of Gut Serotonin in Regulation of Immune Response, Microbiota Composition and Intestinal Inflammation, Journal of the Canadian Association of Gastroenterology, 2023;, gwad020
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413787/ Császár N, Bókkon I. Gut Serotonin as a General Membrane Permeability Regulator. Curr Neuropharmacol. 2022;20(2):269-271. doi: 10.2174/1570159X19666210921100542. PMID: 34548000; PMCID: PMC9413787.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004350/ Durán WN, Beuve AV, Sánchez FA. Nitric oxide, S-nitrosation, and endothelial permeability. IUBMB Life. 2013 Oct;65(10):819-26. doi: 10.1002/iub.1204. Epub 2013 Sep 17. PMID: 24078390; PMCID: PMC4004350. “These observations bring back the suggestion that the key regulator of S-nitrosation of endothelial AJ proteins is eNOS, an enzyme whose activity is exquisitely regulated by a number of factors, and whose location (via agonist-induced translocation) in the cytosol is fundamental for the onset of hyperpermeability responses.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469458/ Appleton J. The Gut-Brain Axis: Influence of Microbiota on Mood and Mental Health. Integr Med (Encinitas). 2018 Aug;17(4):28-32. PMID: 31043907; PMCID: PMC6469458.
https://pubmed.ncbi.nlm.nih.gov/23384445/ Foster JA, McVey Neufeld KA. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013 May;36(5):305-12. doi: 10.1016/j.tins.2013.01.005. Epub 2013 Feb 4. PMID: 23384445.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330700/ Litvinova L, Atochin DN, Fattakhov N, Vasilenko M, Zatolokin P, Kirienkova E. Nitric oxide and mitochondria in metabolic syndrome. Front Physiol. 2015 Feb 17;6:20. doi: 10.3389/fphys.2015.00020. PMID: 25741283; PMCID: PMC4330700.
https://www.nature.com/articles/1301530 Newhouse, P., Dumas, J., Hancur-Bucci, C. et al. Estrogen Administration Negatively Alters Mood Following Monoaminergic Depletion and Psychosocial Stress in Postmenopausal Women. Neuropsychopharmacol 33, 1514–1527 (2008).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951843/ Shansky RM, Hamo C, Hof PR, Lou W, McEwen BS, Morrison JH. Estrogen promotes stress sensitivity in a prefrontal cortex-amygdala pathway. Cereb Cortex. 2010 Nov;20(11):2560-7. doi: 10.1093/cercor/bhq003. Epub 2010 Feb 5. PMID: 20139149; PMCID: PMC2951843.
https://doi.org/10.1016/B978-0-12-801028-0.00235-X Kazuyoshi Tsutsui, Shogo Haraguchi, Subchapter 96C - Allopregnanolone, Editor(s): Yoshio Takei, Hironori Ando, Kazuyoshi Tsutsui, Handbook of Hormones, Academic Press, 2016, Pages 544-e96C-3, ISBN 9780128010280,
https://academic.oup.com/endo/article/153/4/2012/2424116 Wangsheng Wang and others, Cortisol Induces Aromatase Expression in Human Placental Syncytiotrophoblasts Through the cAMP/Sp1 Pathway, Endocrinology, Volume 153, Issue 4, 1 April 2012, Pages 2012–2022
https://raypeat.com/articles/articles/alzheimers2.shtml Peat R. The problem of Alzheimer's disease as a clue to immortality - Part 2 2006
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