A blood pH below 7.4. [1]
Adrenaline, besides leading to increased production of cortisol, is lipolytic, releasing the fatty acids which, if they are polyunsaturated, inhibit the production and transport of thyroid hormone, and also interfere directly with the respiratory functions of the mitochondria.
Adrenaline decreases the conversion to T4 to T3, and increases the formation of the antagonistic reverse T3.
Adrenalin mobilizes fat from storage, and the free fatty acids create a chronic problem involving 1) blocked ATP production, 2) activation of the protein kinase C system (increasing tension in blood vessels), 3) inhibition of thyroid function with its energetic, hormonal, and tissue-structure consequences, 4) availability of fats for prostaglandin synthesis, and 5) possibly a direct effect on clot dissolving, besides the PAI-1 (plasminogen activator inhibitor) effect seen in diabetes.
Age pigment is the brown material that forms spots on aging skin, and that accumulates in the lens of the eye forming cataracts, and in blood vessels causing hardening of the arteries, and in the heart and brain and other organs, causing their functions to deteriorate with age. It is made up of oxidized unsaturated oils with iron.
Albumin, besides maintaining blood volume and preventing edema, serves to protect respiration, by binding free fatty acids. Estrogen blocks the liver's ability to produce albumin, and increases the level of circulating free fatty acids.The decrease of albumin increases the concentration of free fatty acids and tryptophan, which would normally be bound to albumin.
Amyloid is the old term for the "starchy" appearing (including the way it stains) proteins seen in various diseases, and in the brain in Alzheimer's disease. [2]
Anemic means lacking blood, in the sense of not having enough red blood cells or hemoglobin. It is possible to have too much iron in the blood while being anemic. Anemia in itself doesn't imply that there is nutritional need for iron.[3]
Vitamin E and vitamin C are known as antioxidants, because they stop the harmful free-radical chain reactions which often involve oxygen, but they do not inhibit normal oxidation processes in cells. "Chain breaker" would be a more suitable term. It is often the deficiency of oxygen which unleashes the dangerous free-radical processes. Many substances can function as antioxidants/chain breakers: thyroxine, uric acid, biliverdin, selenium, iodine, vitamin A, sodium, magnesium, and lithium, and a variety of enzymes. Saturated fats work with antioxidants to block the spread of free-radical chain reactions. [3]
Aldosterone causes less sodium to be lost in the urine and sweat, but it achieves that at the expense of the increased loss of potassium, magnesium, and probably calcium.
Aldosterone secretion increases during the night, and its rise is greater in depressed and stressed people. It inhibits energy metabolism, increases insulin resistance, and increases the formation of proinflammatory substances in fat cells. During aging, salt restriction can produce an exaggerated nocturnal rise in aldosterone.
A pH of the blood above 7.4.[1]
Carbon dioxide (or acidity) displaces oxygen from hemoglobin.[1]
"Cancer metabolism" or stress metabolism typically involves an excess of the adaptive hormones, resulting from an imbalance of the demands made on the organism and the resources available to the organism. Excessive stimulation depletes glucose and produces lactic acid, and causes cortisol to increase, causing a shift to the consumption of fat and protein rather than glucose. Increased cortisol activates the Randle effect (the inhibition of glucose oxidation by free fatty acids), accelerates the breakdown of protein into amino acids, and activates the enzyme fatty acid synthase, which produces fatty acids from amino acids and pyruvate, to be oxidized in a "futile cycle," producing heat, and increasing the liberation of ammonia from the amino acids. Ammonia suppresses respiratory, and stimulates glycolytic, activity. [4]
Carbon dioxide, produced in the cells, releases oxygen into the tissues, relaxes blood vessels, prevents edema, eliminates ammonia, and increases the efficiency of oxidative metabolism.
The presence of carbon dioxide is an indicator of proper mitochondrial respiratory functioning.
In every type of tissue, it is the failure to oxidize glucose that produces oxidative stress and cellular damage.
In animals, cholesterol is the basic sterol molecule, which is massively converted into other substances, including the steroid hormones. Thyroid hormone and vitamin A are required for this conversion.
HDL and LDL are often called "good cholesterol" (High Density Lipoproteins) and "bad cholesterol" (Low Density Lipoproteins) because of a slight association between their ratio and heart disease, but in fact the ratio that suggests freedom from heart disease suggests susceptibility to cancer. LDL ("bad") is extremely good because it is used as the source for producing progesterone and DHEA.
Cortisol, for example, inhibits the conversion of T4 to T3, which is responsible for the respiratory production of energy and carbon dioxide.
Excessive serotonin and estrogen cause a relatively uncontrolled production of cortisol. A vicious circle of inflammatory mediators and amino acid imbalance can result.
Crabtree effect, observed originally in yeast, refers to the inhibition of respiration in the presence of glucose. This occurs in cancers (e.g., Miralpeix, et al., 1990) and in rapidly proliferating normal cells (e.g., Guppy, et al., 1993). [4]
The cytochromes are "pigments," in the same sense that they contain the colored "heme" group that gives hemoglobin its color. P450 means "protein that absorbs light at a wavelength of 450. The scc means "side-chain cleaving," which refers to the removal of the 6 carbon atoms that distinguish cholesterol from pregnenolone. Other Cyt P450 enzymes are important for their detoxifying oxidizing action, and some of these are involved in brain metabolism.[2]
Known as the youth hormone, is very similar to progesterone, but is present in both men and women at very high levels. It can be turned into either estrogen or testosterone.
*reference above image
Bacteria and plants produce a variety of lipids that serve some purposes analogous to our cholesterol phospholipids. Some of the common intestinal bacteria produce a molecule containing amino sugars and fatty acids (lipopolysaccharide, LPS), that's called endotoxin. The "endo" root distinguishes it from the "exotoxins" secreted by some bacteria, because the endotoxin is a structural part of the bacterium, that protects the bacteria against some of the exotoxins produced by other microorganisms. Normally, our intestine and liver destroy most of the LPS endotoxin before it reaches the general circulation. The bile acids, a major end product of cholesterol, have detergent action in the intestine that usually keeps endotoxin in solution, away from the absorptive surfaces of the intestine. If the flow of bile is obstructed, endtoxin is allowed to enter the system. Estrogen can inhibit the flow of bile. A mucus lining is part of the protective barrier, but the microscopic integrity of the intestinal cells themselves finally regulated the passage of materials into the blood and lymphatic vessels.
Stress and shock tend to increase our absorption of bacterial endotoxin from the intestine, and endotoxin causes the release of serotonin from platelets in the blood.
Chronic constipation, and anxiety which decreases blood circulation in the intestine, can increase the liver's exposure to endotoxin.
Antibiotics, for example, lower endotoxin formation in the intestine, protect against the induction by endotoxin of serotonin, histamine, estrogen, and cortisol.
EFA are, according to the textbooks, linoleic acid and linolenic acid, and they are supposed to have the status of "vitamins," which must be taken in the diet to make life possible. However, we are able to synthesize our own unsaturated fats when we don't eat the "EFA," so they are not "essential." The term thus appears to be a misnomer.[5]
If we named hormones according to their place of origin, as Selye suggested, we could call estrogen folliculin (as Selye did because it is produced abundantly in the ovarian follicle), or adipin, because it is sometimes produced in fat cells. But it can be produced by many cells when they are under stress, and it seems to be normal for some to be produced in the testicle.
Estrogen is the hormone for beginnings, a sort of biochemical eraser which can eliminate recently recorded information, restoring the underlying primitive capacity for growth. When we are threatened, by injury or aging, we need the capacity for renewal of ce
Estrogen steals oxygen from mitochondria, shifting patterns of growth and adaptation.
It has recently been demonstrated that estrogen stimulates the adrenal glands, independently of the pituitary's ACTH. This can increase the production of androgens, leading to hirsutism, and other male traits, including anabolic effects.
When the body doesn't have enough glucose, free fatty acids are released from the tissues, and their oxidation blocks the oxidation of glucose even when it becomes available from the breakdown of protein caused by cortisol, which is released during glucose deprivation.
Free radicals are reactive molecular fragments that occur even in healthy cells, and can damage the cell. When unsaturated oils are exposed to free radicals they can create chain reactions of free radicals that spread the damage in the cell, and contribute to the cell's aging.[5]
Glial means "glue-like," and glial cells are mostly spidery-shaped cells that used to be thought of as just connective, supportive cells in the brain.[2]
The attachment of a sugar to a protein.[6]
The conversion of glucose to lactic acid, providing some usable energy, but many times less than oxidation provides. Lactic acid, produced by splitting glucose to pyruvic acid followed by its reduction, is associated with calcium uptake and nitric oxide production, depletes energy, contributing to cell death.
...The presence of oxygen normally restrains glycolysis so that glucose is converted to carbon dioxide instead of lactic acid.
A point made by O. Warburg and A. Szent-Gyorgyi and others is that there is an important difference between the energy provided by glycolysis and that provided by mitochondrial respiration. They felt that glycolysis was a more primitive form of energy production, and supported only primitive function and cell division, while the more efficient respiration supported cell differentiation and complex functioning.
Aerobic glycolysis is the conversion of glucose to lactic acid even in the presence of oxygen. The presence of oxygen normally restrains glycolysis so that glucose is converted to carbon dioxide instead of lactic acid.
Anaerobic glycolysis is the increased conversion of glucose to lactic acid when the supply of oxygen isn't sufficient, which is a normal event during intense muscle action.[4]
Oxygen displaces carbon dioxide from hemoglobin, in proportion to its partial (specific) pressure. [1]
Insoluble in water, a nonpolar oil-like molecule that repels water.[7]
The presence of too much ammonia in the blood.[7]
The reduced production of lactic acid at a given work rate at high altitude. Muscle work efficiency may be 50% greater at high altitude. ATP wastage is decreased.[1]
Lactic acid and carbon dioxide have opposing effects. Intense exercise damages cells in ways that cumulatively impair metabolism. There is clear evidence that glycolysis, producing lactic acid from glucose, has toxic effects, suppressing respiration and killing cells. Within five minutes, exercise lowers the activity of enzymes that oxidize glucose. Diabetes, Alzheimer's disease, and general aging involve increased lactic acid production and accumulated metabolic (mitochondrial) damage.
The presence of lactic acid in the blood.[1]
The liberation of free fatty acids from triglycerides, the neutral form in which fats are stored, bound to glycerine.[6]
The metabolic rate is very closely related to thyroid hormone function, but defining it and measuring it have to be done with awareness of its complexity.
"Basal” body temperature is influenced by many things besides thyroid. The resting heart rate helps to interpret the temperature. In a cool environment, the temperature of the extremities is sometimes a better indicator than the oral or eardrum temperature.
The “basal” metabolic rate, especially if the rate of carbon dioxide production is measured, is very useful. The amount of water and calories disposed of in a day can give a rough idea of the metabolic rate.
Or pineal hormone: the pineal gland in the brain responds to an absence of light (or to any stress which increases the adrenalin systems) by secreting a hormone called melatonin, which lightens the skin, makes the brain sluggish, turns off thyroid and progesterone production, and suppresses immunity and fertility.
The structure inside the cell in which energy is produced by respiration is called the mitochondria.
The vitality of the mitochondria, their capacity for oxidative energy production, is influenced by nutrition and hormones. In healthy people, mitochondria work efficiently at almost any altitude, but people with damaged or poorly regulated mitochondria are extremely susceptible to stress and hyperventilation. Progesterone, testosterone, and thyroid (T3 and T2) are protective of normal mitochondrial function, by both local and systemic effects.
Mitochondria (the "thread-like bodies") are the structures in cells which produce most of our metabolic energy by respiration, in response to the thyroid hormones.[2]
Refers to a mucoprotein, a protein which contains some carbohydrate. A glycoprotein; usually not intended as a precise term.[2]
Myelin is a multilayered enclosure of the axons (the long processes) of nerve cells, composed of proteins and complex lipids, including cholesterol. The layered material is a flat, thin extension of the cytoplasm of the oligodendroglial cells.[2]
Nicotinamide adenine dinucleotide, and its reduced form are coenzymes for many oxidation and reduction reactions in cells.[7]
Oligodendrocytes are one of the kinds of glial (or neuroglial) cells, and structurally they are unusual in having sheet-like, rather than just thread-like processes; they have a sensitivity ("receptors") to stress and valium, and produce pregnenolone when activated. Under the influence of thyroid hormone, they wrap themselves in thin layers around the conductive parts of nerve cells, leaving a multilayered "myelin" coating. Their absorption of thyroid hormone is promoted by butyrate, an anti-stress substance found in butter and coconut oil.[2]
Oxidation refers to the combination of a substance with oxygen. This can be beneficial, as in normal respiration that produces energy, or harmful, as in rancidity, irradiation, or stress reactions. [3]
Polyunsaturated fats (PUFAs) are fatty acids with many double carbon bonds (double bonds link four electrons, versus the usual two). PUFAs contain double bonds because they lack several hydrogen atoms. This is why they are referred to as “unsaturated.” Remember from the last chapter that saturated fatty acids have only single bonds and are fully “saturated” with hydrogen atoms. Double bonds, although stronger, are more reactive to oxygen than single bonds, making them unstable and susceptible to oxidative stress.
Oxidative stress occurs within the body when oxygen reacts with food to create energy (metabolism) and produces by-products called free radicals. (Free radicals are molecules that have an unpaired electron in the outer shell and are looking to “gain or lose” an electron.) Since PUFAs are unstable, once they are exposed to oxygen, free radicals are created. These free radicals “steal” electrons from other molecules, creating more unstable molecules. Over time, this creates a chain reaction of free radical damage that can cause accelerated aging, hormone imbalance, cancer, and immune disorders. Yikes![9]
When an oil is saturated that means that the molecule has all the hydrogen atoms it can hold. Unsaturation means that some hydrogen atoms have been removed, and this opens the structure of the molecule in a way that makes it susceptible to attack by free radicals.
In good health, especially in children, the stress hormones are produced only in the amount needed, because of negative feedback from the free saturated fatty acids, which inhibit the production of adrenalin and adrenal steroids, and eating protein and carbohydrate will quickly end the stress. But when the fat stores contain mainly PUFA, the free fatty acids in the serum will be mostly linoleic acid and arachidonic acid, and smaller amounts of other unsaturated fatty acids. These PUFA stimulate the stress hormones, ACTH, cortisol, adrenaline, glucagon, and prolactin, which increase lipolysis, producing more fatty acids in a vicious circle. In the relative absence of PUFA, the stress reaction is self-limiting, but under the influence of PUFA, the stress response becomes self-amplifying.
The parathyroid hormone (PTH) is an important regulator of calcium metabolism. If dietary calcium isn't sufficient, causing blood calcium to decrease, the PTH increases, and removes calcium from bones to maintain a normal amount in the blood. PTH has many other effects, contributing to inflammation, calcification of soft tissues, and decreased respiratory energy production.
The normal response of cells to restrain glycolysis in the presence of adequate oxygen.[4]
Persorption refers to a process in which relatively large particles pass through the intact wall of the intestine and enter the blood or lymphatic vessels. It can be demonstrated easily, but food regulators prefer to act as though it didn't exist.[8]
The pituitary gland sits at the base of the brain, where it receives signals from the brain, and secretes hormones that regulate the production of various other hormones and secretions.
Removing the pituitary gland (or its equivalent) and providing thyroid hormone, he found that animals lacking the pituitary lived much longer than intact animals, and maintained a high metabolic rate. Making extracts of pituitary glands, he found a fraction (closely related to prolactin and growth hormone) that suppressed tissue oxygen consumption, and accelerated the degenerative changes of aging.
To produce pregnenolone, thyroid, vitamin A, and cholesterol have to be delivered to the mitochondria in the right proportion and sufficient quantity. Normally, stress is balanced by increased synthesis of pregnenolone, which improves the ability to cope with stress. Lipid peroxidation, resulting from the accumulation of unsaturated fatty acids, iron, and energy deficiency, damages the mitochondrias' ability to produce pregnenolone. When pregnenolone is inadequate, cortisol is over-produced. When progesterone is deficient, estrogen's effect is largely unopposed. When both thyroid and progesterone are deficient, even fat cells synthesize estrogen.
Progesterone is the main female hormone, and is a protective hormone during pregnancy, but it is also important in men since it is a general brain regulating and protective hormone.
Progesterone, because of its normal anesthetic function (which prevents the pain of childbirth when its level is adequate), directly quiets nerves, and in this way suppresses many of the excitotoxic processes. It has direct effects on mitochondria, promoting energy production, and it facilitates thyroid hormone functions in various ways. It promotes the elimination of estrogen from tissues, and is a "diuretic" in several benign ways, that are compatible with maintenance of blood volume.
Progesterone is an anti-androgen and blocks testosterone's effects.
*Reference above image
Prolactin is a hormone secreted by the pituitary gland during pregnancy, and during stress. It promotes milk production, removes calcium from the bones, and inhibits progesterone formation.
Arachidonic acid stimulates prolactin secretion, and prolactin acts on the thyroid gland to decrease its activity, and on other tissues to increase their glycolysis (with lactate production), while decreasing oxidative metabolism
Rancidity of oils occurs when they are exposed to oxygen, in the body just as in the bottle. Harmful free radicals are formed, and oxygen is used up.
Respiration refers to the absorption of oxygen by cells, which releases energy.[3]
Monosaccharide -- a simple sugar; examples, glucose, fructose, ribose, galactose (galactose is also called cerebrose, brain sugar).
Disaccharide -- two monosaccharides bound together; examples, sucrose, lactose, maltose.
Oligosaccharide -- a short chain of monosaccharides, including disaccharides and slightly longer chains.
Polysaccharide -- example, starch, cellulose, glycogen.
Just friction, or scratching or stretching the intestine is enough to cause it to release serotonin into the bloodstream. Serotonin increases the permeability of the intestine and blood vessels, and so is likely to be a major cause of the absorption of endotoxin (and other harmful material) during intestinal irritation or stress. The biological meaning of serotonin might be very different without endotoxin, but that hasn't been investigated.
In the brain, serotonin regulates circulation and mitochondrial function, temperature, respiration and appetite, alertness and learning, secretion of prolactin, growth hormones and stress hormones, and participates in the most complex biochemical webs.
The simple availability of oxygen, and the ability to use it, are regulated by carbon dioxide and serotonin, which act in opposite directions. Carbon dioxide inhibits the release of serotonin. Carbon dioxide and serotonin are regulated most importantly by thyroid function.
Serotonin is a mediator of inflammation that suppresses metabolism, disturbs blood pressure, and promotes clotting, so it would be a Manichean-seeming misfortune if it was also essential to have lots of it to experience euphoria. But in reality a state of 'serotonergia' is a state of torpor, discomfort, and depression, rather than a state of alert pleasure.
Creation of steroids, usually referring to the conversion of cholesterol to hormones.[2]
Testosterone is the main male hormone, though it is present in females too.
Progesterone, testosterone, and thyroid (T3 and T2) are protective of normal mitochondrial function, by both local and systemic effects.
Testosterone and progesterone are estrogen antagonists that inhibit carbonic anhydrase.
The inhibition of the oxidation of glucose by an excess of fatty acids. This lowers metabolic efficiency. Estrogen promotes this effect.
The thymus gland is important for growth and fertility, but it is now considered to be an important regulator of the immune system. As the gland shrinks with aging, the incidence of "autoimmune diseases" increases possibly because the regulatory functions of the gland have been lost.
The thymus gland is extremely sensitive to stress, and atrophies quicker under the influence of cortisone or the sex steroids, but it can also regenerate under the influence of thyroid and progesterone (and under some circumstances, probably DHEA) or just good nutrition. Chronic atrophy of the thymus produces immunological weakness. Infectious diseases, then, are not so difference from the degenerative diseases, since the failure of biological energy, and the resulting stress response, can be responsible for both classes of sickness. Even radiation damage, which seems like a fairly exotic problem in comparison to infections and aging, is ameliorated by things like thyroxin, which increases energy production.
Cells of the thymus are sensitive to glucose deprivation, and even in the presence of glucose, cortisol prevents them from using glucose, causing them to take up fatty acids. The thymic cells die easily when exposed either to excess cortisol, or deficient glucose. The polyunsaturated fatty acids linoleate, arachidonate, and eicosapentaenoic, are especially toxic to thymic cells by preventing their inactivation of cortisol, increasing its action.
Thyroid hormone is necessary for respiration on the cellular level, and makes possible all higher biological functions. Without the metabolic efficiency, which is promoted by thyroid hormone, life couldn’t get much beyond the single-cell stage.
Without adequate thyroid, we become sluggish, clumsy, cold, anemic, and subject to infections, heart disease, headaches, cancer, and many other diseases, and seem to be prematurely aged, because none of our tissues can function normally.
TSH itself can produce lipolysis, raising the level of circulating free fatty acids. This suggests that a high level of TSH could sometimes contribute to functional hypothyroidism, because of the antimetabolic effects of the unsaturated fatty acids
In cellular respiration, oxidation of "fuel" in the mitochondrion is coupled to the phosphorylation of ADP, forming ATP.
Uncouplers are chemicals that allow oxidation to proceed without producing the usual amount of ATP.[7]
When an oil is saturated, that means that the molecule has all the hydrogen atoms it can hold. Unsaturation means that some hydrogen atoms have been removed, and this opens the structure of the molecule in a way that makes it susceptible to attack by free radicals.[5]
Water near surfaces, especially hydrophobic surfaces, that is physically and chemically different from ordinary water.[7]
"Warburg Effect" refers to Otto Warburg's observation that cancer cells produce lactic acid even in the presence of adequate oxygen. Cancer cells don't "live on glucose," since they are highly adapted to survive on protein and fats.[4]