All Hail The Chondrion!

MightyChon “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.

“The influence of thyroid hormone (T(3)) on respiration is partly mediated via its effect on the cytochrome c oxidase…enzyme, a multi-subunit complex within the mitochondrial respiratory chain.”

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.

“…expression of cytochrome c in isolated mitochondria was reduced after treatment with…linoleic acid…polyunsaturated linoleic acid induces apoptosis and mitochondrial dysfunction…”

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.”

“Under the influence of PRL [prolactin] anaerobic glucose metabolism was stimulated by 40.5% and oxidative phosphorylation was inhibited…”

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.

“…oestrogen exposure is known to cause weight gain, primarily through thyroid inhibition and modulation of the hypothalamus…”

“Glucocorticoid levels were elevated in response to both stressors…exposure to a relatively acute stressful event immediately and persistently enhances serum estradiol…”

“…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.

“In the absence of peripheral serotonin, steatohepatitis was associated with significantly less hepatocellular damage, inflammatory infiltrates, lipid peroxidation, and mitochondrial injury…”

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.”

“A major product of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), is highly cytotoxic…Exposure of mitochondria to…HNE caused rapid declines in…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.

“…high plasma FFA [free fatty acids] itself, whether it may be exogenous or endogenous, may impair the oxidative phosphorylation of the mitochondria…”

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 essential sites for steroid hormone biosynthesis…Mitochondria…contain the…enzyme system converts cholesterol to pregnenolone…serves as the chronic regulator of steroidogenesis…”

“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.

See more here

Long-term exposure of INS-1 rat insulinoma cells to linoleic acid and glucose in vitro affects cell viability and function through mitochondrial-mediated pathways.

Polyunsaturated fatty acids mobilize intracellular Ca2+ in NT2 human teratocarcinoma cells by causing release of Ca2+ from mitochondria.

Arachidonic acid and docosahexaenoic acid supplemented to an essential fatty acid-deficient diet alters the response to endotoxin in rats.

Arachidonic acid as a possible modulator of estrogen, progestin, androgen, and glucocorticoid receptors in the central and peripheral tissues.

Acrolein inhibits respiration in isolated brain mitochondria.

Inhibition of NADH-linked mitochondrial respiration by 4-hydroxy-2-nonenal.

Chronic cellular hypoxia as the prime cause of cancer: what is the de-oxygenating role of adulterated and improper ratios of polyunsaturated fatty acids when incorporated into cell membranes?

Effect of methylene blue on estrogen-receptor activity.

Partial inhibition of fatty acid oxidation increases regional contractile power and efficiency during demand-induced ischemia

Influence of prolactin on metabolism and energy production in perfused corpus luteum bearing bovine ovaries.

Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways

Direct effects of prolactin on corticosterone release by zona fasciculata-reticularis cells from male rats.

Effect of high plasma free fatty acids on the free radical formation of myocardial mitochondria isolated from ischemic dog hearts.

Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways.

Elevated lactate suppresses neuronal firing in vivo and inhibits glucose metabolism in hippocampal slice cultures.

Steroid hormone synthesis in mitochondria.

Circulating dehydroepiandrosterone-sulphate decreases even with a slight change in oestradiol.

Vitamin K2 Is a Mitochondrial Electron Carrier That Rescues Pink1 Deficiency

The effects of fat deficiency upon enzyme activity in the rat.

Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress

Taurine as a constituent of mitochondrial tRNAs: new insights into the functions of taurine and human mitochondrial diseases

Increased stress reactivity is associated with reduced hippocampal activity and neuronal integrity along with changes in energy metabolism.

Acetazolamide treatment prevents in vitro endotoxin-stimulated tumor necrosis factor release in mouse macrophages.

THYROID-HORMONE EFFECTS ON STEROID-HORMONE METABOLISM

Tissue-specific regulation of cytochrome c oxidase subunit expression by thyroid hormone.

Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids

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.

Cancer as a mitochondrial metabolic disease

Methylene blue improves mitochondrial respiration and decreases oxidative stress in a substrate-dependent manner in diabetic rat hearts.

Thyroid hormones and mitochondria.

The Estrogen Hypothesis of Obesity

NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation

Transcutaneous Application of Carbon Dioxide (CO2) Induces Mitochondrial Apoptosis in Human Malignant Fibrous Histiocytoma In Vivo

Severe mitochondrial damage associated with low-dose radiation sensitivity in ATM- and NBS1-deficient cells.

The role of dopamine in methylene blue-mediated inhibition of estradiol benzoate-induced anterior pituitary hyperplasia in rats.

Mitochondria and the economy of stress (mal)adaptation.

Glycine metabolism in skeletal muscle: implications for metabolic homeostasis

Serotonin-induced decrease in brain ATP, stimulation of brain anaerobic glycolysis and elevation of plasma hemoglobin; the protective action of calmodulin antagonists.

Lactate stress test in the diagnosis of mitochondrial myopathy.

Iron induces hepatocytes death via MAPK activation and mitochondria-dependent apoptotic pathway: beneficial role of glycine.

Decreased Cytochrome c Oxidase IV Expression Reduces Steroidogenesis.

NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice.

Effects of Caffeine on Metabolism and Mitochondria Biogenesis in Rhabdomyosarcoma Cells Compared with 2,4-Dinitrophenol

Phosphorylation processes mediate rapid changes of brain aromatase activity.

Induction of PGE2 by estradiol mediates developmental masculinization of sex behavior.

The neuroprotective effects of progesterone on traumatic brain injury: current status and future prospects

Effects of neurosteroids on the human corticotropin-releasing hormone gene.

Low-dose ionizing radiation rapidly affects mitochondrial and synaptic signaling pathways in murine hippocampus and cortex.

CoEnzyme Q10 and riboflavin: the mitochondrial connection.

11β-HSD1 reduces metabolic efficacy and adiponectin synthesis in hypertrophic adipocytes.

Ketone body utilization drives tumor growth and metastasis

Human mitochondrial diseases caused by lack of taurine modification in mitochondrial tRNAs.

Stress-induced change of mitochondria membrane potential regulated by genomic and non-genomic GR signaling: a possible mechanism for hippocampus atrophy in PTSD.

Rapid and reversible inhibition of brain aromatase activity.

Lipidomic analysis for carbonyl species derived from fish oil using liquid chromatography-tandem mass spectrometry.

The regulation of adenohypophyseal prolactin secretion: effect of triiodothyronine and methylene blue on estrogenized rat adenohypophysis.

Free fatty acids as inducers and regulators of uncoupling of oxidative phosphorylation in liver mitochondria with participation of ADP/ATP- and aspartate/glutamate-antiporter.

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease

Pre-adaptation, adaptation and de-adaptation to high altitude in humans: hormonal and biochemical changes at sea level.

Biphasic Dose Response in Low Level Light Therapy

Inhibition of cardiac mitochondrial respiration by salicylic acid and acetylsalicylate.

Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro.

Cancer metabolism: fatty acid oxidation in the limelight

Treatment with dehydroepiandrosterone (DHEA) stimulates oxidative energy metabolism in the liver mitochondria from developing rats.

Effects of aromatase inhibition and androgen activity on serotonin and behavior in male macaques.

In vitro effects of nicotine on mitochondrial respiration and superoxide anion generation.

Hormonal basis of male and female androgenic alopecia: clinical relevance.

Medical treatment with thiamine, coenzyme Q, vitamins E and C, and carnitine improved obstructive sleep apnea in an adult case of Leigh disease.

Protection against neurodegeneration with low-dose methylene blue and near-infrared light

The ω6-fatty acid, arachidonic acid, regulates the conversion of white to brite adipocyte through a prostaglandin/calcium mediated pathway

The oxidative stress and the mitochondrial dysfunction caused by endotoxemia are prevented by alpha-lipoic acid.

Heated and humidified CO2 pneumoperitoneum inhibits tumour cell proliferation, migration and invasion in colon cancer

Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects

The nitric oxide hypothesis of aging.

Influence of thyroid hormone on androgen metabolism in peripuberal rat Sertoli cells.

Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness

Acute exercise causes mitochondrial DNA deletion in rat skeletal muscle.

A role for taurine in mitochondrial function

Acrolein, a product of lipid peroxidation, inhibits glucose and glutamate uptake in primary neuronal cultures.

Carcinoid myopathy and treatment with cyproheptadine (Periactin)

Regulation of human metabolism by hypoxia-inducible factor

Endotoxin-induced mitochondrial damage correlates with impaired respiratory activity.

Etiology and therapeutic approach to elevated lactate

Lactic acidosis induced by metformin: incidence, management and prevention.

Age-Dependent Decrease of Mitochondrial Complex II Activity in Human Skin Fibroblasts.

Metabolic features of chronic fatigue syndrome

Palmitate-induced Activation of Mitochondrial Metabolism Promotes Oxidative Stress and Apoptosis in H4IIEC3 Rat Hepatocytes

A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle.

Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia.

HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells.

Progesterone induces neuroprotection following reperfusion-promoted mitochondrial dysfunction after focal cerebral ischemia in rats

The Involvement of Secondary Neuronal Damage in the Development of Neuropsychiatric Disorders Following Brain Insults

Mitochondria are required for pro‐ageing features of the senescent phenotype

Serotonin mediates oxidative stress and mitochondrial toxicity in a murine model of nonalcoholic steatohepatitis.

UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness

Hormone studies in females with androgenic hairloss.

Norepinephrine stimulates testosterone aromatization and inhibits 5 alpha reduction via beta-adrenoceptors in rat pineal gland.

Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria

Mitochondrial stress-induced p53 attenuates HIF-1α activity by physical association and enhanced ubiquitination

Iron Potentiates Acetaminophen-Induced Oxidative Stress and Mitochondrial Dysfunction in Cultured Mouse Hepatocytes

Thiamine deficiency induces oxidative stress in brain mitochondria of Mus musculus.

Restoring oxidant signaling suppresses pro-arthritogenic T-cell effector functions in rheumatoid arthritis

Improvement of mitochondrial NAD(+)/FAD(+)-linked state-3 respiration by caffeine attenuates quinolinic acid induced motor impairment in rats: implications in Huntington’s disease.

Inhibition of SIRT1 deacetylase suppresses estrogen receptor signaling

Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome

Stimulation of respiration by methylene blue in rat liver mitochondria.

Acute stress persistently enhances estrogen levels in the female rat.

Twenty‐eight days of exposure to 3454 m increases mitochondrial volume density in human skeletal muscle

Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase.

Light Effect on Water Viscosity: Implication for ATP Biosynthesis

Exogenous taurine attenuates mitochondrial oxidative stress and endoplasmic reticulum stress in rat cardiomyocytes

Mitochondria II: Methylene Blue

Biological Effects of Low Level Laser Therapy

Statins affect skeletal muscle performance: evidence for disturbances in energy metabolism

Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression

Caffeine and Caffeic Acid Inhibit Growth and Modify Estrogen Receptor and Insulin-like Growth Factor I Receptor Levels in Human Breast Cancer

Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer*

Metabolic features of chronic fatigue syndrome

#sugarsaves
#pufaispoison
#raypeat

Image: m.imgur.com/account/skylamoonsock/albums

You may also like...

x
Please "like" us:Already liked? You can close this