All Hail The Chondrion!
“The vitality of the mitochondria, their capacity for oxidative energy production, is influenced by nutrition and hormones…people with damaged or poorly regulated mitochondria are extremely susceptible to stress and hyperventilation.” – Ray Peat PhD
When the ‘big picture’ of human physiology is observed through a genuinely holistic lens – an honest approach to biological systems and interactions – many degenerative conditions and related symptoms, can start to make sense as well as become more predictable.
Mitochondria, which exist within cells, can be understood as being responsible for a large amount of cellular energy production.
The things that foster healthy thyroid function and metabolism, also impact upon the condition and performance of mitochondria, and vice versa. Sugar is not an exception.
Chronic stress – as well as starvation and malnutrition – interferes with mitochondrial energy production. This promotes the release of stress substances which can then cause further interference with energy systems, eventually leading to a downward spiral in metabolic health.
“…by supplying the majority of cellular energy, mitochondria contribute to the organism’s overall adaptive capacity…mitochondria participate in the processing of subcellular stress signals. A given stressor does not directly determine the magnitude or nature of the resulting physiological response, because stress signals are processed, or “interpreted” by the integrated action of the brain and other systems…”
When stress and insufficient fuel cause glycogen stores to be depleted, the body responds by mobilizing increasing amounts of fat into the blood stream, as an alternative form of energy.
If fatty acids released into circulation under conditions of stress are polyunsaturated, this can cause chronic interference with, and damage to, mitochondrial energy system function.
“In a variety of disorders, overaccumulation of lipid in nonadipose tissues, including the heart, skeletal muscle, kidney, and liver, is associated with deterioration of normal organ function, and is accompanied by excessive plasma and cellular levels of free fatty acids (FA). Increased concentrations of FA may lead to defects in mitochondrial function found in diverse diseases.”
Polyunsaturated fatty acids (PUFA) directly (and indirectly) suppress thyroid function, and proper thyroid performance is required for the mitochondria to be able to produce energy in a more optimal, less stressful manner.
The enzyme cytochrome c oxidase, is fundamental to mitochondrial energy production, and thyroid hormone directly impacts upon its availability.
Stress in general interferes with mitochondrial energy function, and the release of PUFA into circulation during stress inhibits cytochrome c oxidase activity, and limits energy production potential.
When more sugar is consumed than is able to be used for energy (or stored as glycogen), excess is converted largely into the saturated fats, in particular palmitic acid, the most common saturated fatty acid.
Palmitic acid is a powerful promoter of mitochondrial energy production, as well as protecting against the damaging and stressful effects of PUFA. This is further explanation as to why excess sugar consumption (combined with some other important nutrients) can be a safe way to promote metabolism and reduce stress and disease.
“Since mitochondria require oxygen to carry out oxidative phosphorylation, increased oxygen consumption is a direct measure of increased mitochondrial metabolism. Palmitate-treated cells exhibited a 2-fold increase in oxygen consumption rate…”
Some excess sugar is converted into the omega-9 unsaturated fats, however these fats – unlike the omega-3 and omega-6 PUFA – have been demonstrated to be genuinely anti-inflammatory, as well as not damaging mitochondria.
PUFA inhibits and slows digestion, promoting bacterial growth. This leads to an increase in levels of bacterial toxins – endotoxin – in the intestine, with greater amounts passing through to the liver, and then into circulation in the main system.
Endotoxin acts as a promoter of stress, and (particularly in combination with PUFA) encourages the production of inflammatory substances – including estrogen, serotonin, lactate and nitric oxide – which inhibit mitochondrial function.
“Nitric oxide (NO) and its derivatives inhibit mitochondrial respiration by a variety of means…Nanomolar concentrations of NO immediately, specifically and reversibly inhibit cytochrome oxidase…Higher concentrations of NO and its derivatives (peroxynitrite, nitrogen dioxide or nitrosothiols) can cause irreversible inhibition of the respiratory chain…”
“Feeding an EFAD [essential fatty acid-deficient] diet reduces baseline inflammation and inflammatory response to endotoxin…and added AA [arachidonic acid] + DHA [docosahexaenoic acid] modifies this response…”
Stress, endotoxin and an underactive thyroid, promote the release of cortisol and prolactin which also suppress mitochondrial energy production, directing the cell away from efficient metabolism of glucose, towards a stress induced (low carbon dioxide production) hyperventilation state.
“Mitochondrial function is significantly impaired during acute sepsis…mitochondrial functional impairment may contribute to the pathogenesis of altered oxygen metabolism in systemic organs during sepsis.”
“…cortisol-induced changes of the mitochondrial membrane potential can result in the release of cytochrome c from the mitochondria to the cytoplasm where the cytochrome c promotes of the action of caspases which leads to apoptosis.”
Carbon dioxide (CO2) produced by mitochondria, is a by-product of a properly functioning metabolism. CO2 helps to protect against stress, inflammation and the promotion of degenerative disease, including cancer.
“…we demonstrate that transcutaneous application of CO2 to human MFH [malignant fibrous histiocytoma] cells…increased the number of mitochondria, and led to mitochondrial-induced apoptosis…we…observed a similar effect on human breast cancer cells in vivo…our transcutaneous CO2 therapy may have an antitumoral effect on various human malignancies.”
When thyroid function is inhibited by stress, estrogen levels tend to rise, and estrogen interferes with mitochondria in a number of ways. PUFA and estrogen synergise to enhance inflammatory disease promoting potential.
“…effect of the unsaturated fatty acids on brain…estrogen receptors is unique…The dose-dependent potentiation by arachidonate was found in the brain estrogen receptors, in contrast with the dose-dependent inhibition on the progestin receptors”
When stress is high – and when large amounts of PUFA are stored in the body – it isn’t so important what occurs first (hypoglycemia, high serotonin or estrogen, bacterial issues etc) – the potential exists for any and all of these symptoms to promote any or all of the others.
Consumption of PUFA (including fish oil) directly inhibits mitochondrial function. Excessive exercise, chronic hyperventilation, or simply carbohydrate restriction, can all promote the release of polyunsaturated free fatty acids out of storage in tissue.
“Lipid peroxidation is elevated in…neurodegenerative diseases…Acrolein [breakdown product of fish oil]…is a major cytotoxic product of lipid peroxidation…Mitochondrial abnormalities are implicated in…neurodegenerative disorders…acrolein is a potent inhibitor of brain mitochondrial respiration.”
Whether consumed or released, this can promote the substances of stress (cortisol, adrenalin, endotoxin, estrogen, serotonin, nitric oxide etc.) worsening symptoms of disease, including disorders of mood.
In a similar way, ongoing emotional stress can directly suppress digestion and metabolism, and cause the release of the same stress substances, creating a similar end result.
Generally speaking, the effectiveness of the mitochondria is dependent upon a balance between the provision of energy and the degree of exposure to stress.
“Brain function appears to be particularly sensitive to the modulatory effect of mitochondria. Both the central and peripheral nervous systems are preferentially affected in patients with systemic mitochondrial diseases…Our study demonstrates how mitochondria can shape the major stress–response pathways, thereby recalibrating the multisystemic response to psychological stress…”
Even though the stress hormones – released when energy is deficient – are part of a defensive, survival mechanism, when very high or chronically raised they can damage energy systems, and (particularly in the presence of excessive amounts of PUFA), can help to feed a vicious circle of metabolic suppression.
Interference with mitochondrial energy system function, reduces the conversion of cholesterol into the anti-aging protective hormones – pregnenolone, progesterone and dhea – placing the balance more in favour of stress, inflammation, hyperventilation and further energy production inefficiency.
“Mitochondria are very susceptible to any insult, due to their critical role in energy metabolism… large set of experimental evidence strongly supports the neuroprotective role of the steroid hormone progesterone (P4) in many CNS [central nervous system] injury models…finding sheds light on the mitochondrial protective and anti-apoptotic role of P4 that can be utilized therapeutically in stroke injury…”
Sugar is required to provide energy for optimal mitochondrial performance, and for protection from rising levels of stress hormones and inflammatory mediators.
Sugar promotes thyroid function and lowers cortisol and adrenalin. Cortisol and adrenalin promote the release of PUFA into circulation. PUFA interferes with thyroid hormone and causes a chronic inability to use sugar for oxidative energy production.
“Mitochondrial dysfunction in hypertrophic adipocytes can reduce adiponectin synthesis…increased 11β-HSD1 [also known as cortisone reductase…reduces cortisone to the active hormone cortisol] expression contributes to reduced mitochondrial respiration and adiponectin synthesis in hypertrophic adipocytes.”
Interference with energy systems leads to more stress which causes levels of the stress hormones, cortisol, adrenalin, estrogen, serotonin etc. to rise. Serotonin and estrogen damage mitochondria. Mitochondrial interference promotes stress and inflammation, which promotes the release of nitric oxide. Stress interferes with the production of the anti-estrogen anti-serotonin hormone progesterone.
“5-HT [serotonin] has an inhibitory effect on mitochondrial respiration, causing brain ATP depletion. It causes excitotoxic death of nerve cells, which involves both limitations of energy production and increased cellular activation. Levels of both of these neurotransmitters were found to be elevated…and were attenuated by P4 [progesterone] treatment. P4 is known to possess specific anti-5-HT actions…”
Nitric oxide directly suppresses energy metabolism, increasing serotonin and estrogen and the release of PUFA into the blood. PUFA causes more damage to mitochondria, inhibiting thyroid activity, increasing stress and the need for sugar. Methylene blue is highly protective against a number of the stress substances which interfere with mitochondria.
“Mitochondrial dysfunction and oxidative stress are thought to be key aberrations that lead to cellular senescence and aging. MB [methylene blue] may be useful to delay mitochondrial dysfunction with aging and the decrease in complex IV in Alzheimer disease.”
Sugar is important for the production of cholesterol and equally important in the conversion of cholesterol into the hormones – pregnenolone and progesterone – which support thyroid function and the mitochondria. Thyroid hormone and mitochondrial energy systems are involved in the production of pregnenolone and progesterone, potentially creating a dilemma.
“PROG [progesterone] can reduce lipid peroxidation…PROG limits neuronal apoptosis by stabilizing the mitochondria…PROG has neuroprotective…anti-inflammatory, anti-excitotoxicity, anti-lipid peroxidation and anti-apoptotic properties and so on…”
Stress uses sugar inefficiently, promoting lactic acid production in the place of carbon dioxide. Lactic acid suppresses energy production, further damaging mitochondria, and on and on it goes.
“Glucose is well accepted as the major fuel for neuronal activity…Lactate suppressed glucose oxidation…data suggest that alteration of redox ratio underlies the suppression of neural discharge and glucose metabolism by lactate.”
It sounds so fragile, and yet it can be so resilient and robust. Even though the system can seem to self destruct, it does not want to fail. Sometimes all that it takes is a break in the chain of stress, long enough to enable redirection. Sugar is one of the things that make all the difference.
A diet minus the polyunsaturated fats, avoiding iron and other heavy metals, limiting difficult to digest grains, beans and legumes, and including sufficient protein from milk, cheese or gelatin, and plenty of fuel from sweet ripe fruits, fruit juice, honey and white sugar, is one approach to minimizing damage from chronic stress and hyperventilation, helping to support mitochondrial respiration and metabolic function.
Some other things which might be able to benefit mitochondrial performance include vitamin K, methylene blue combined with red light, exposure to daylight, niacinamide, taurine, thiamine, thyroid hormone supplementation, glycine, cyproheptadine, riboflavin, coenzyme Q10, caffeine, pregnenolone, DHEA, aspirin, nicotine, activated charcoal, selenium, raw carrot, coconut oil, regular bag breathing as well as just having a good time.
Sugar restriction, polyunsaturated fats, iron and other heavy metals, radiation including low dose x-rays and environmental estrogens are some of the most damaging things.
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Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.