Ray Peat - The Generality of Adaptogens

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References Peat, R. (1991). The Generality of Adaptogens. Townsend Letter for Doctors & Patients, (100), 930. Retrieved from EBSCOhost. The Generality of Adaptogens There are far more sensory nerves entering the brain, than motor nerves leaving the brain. Generalization and judgment intervene between the complexity of sensation and the coherence of behavior. Encountering an infinite world, we marshall our resources for an adequate response. For me, this sensory domination of the brain is an i
   ReferencesPeat, R. (1991). The Generality of Adaptogens. Townsend Letter for Doctors & Patients , (100),930. Retrieved from EBSCO host  . The Generality of Adaptogens There are far more sensory nerves entering the brain, than motor nerves leaving the brain.Generalization and judgment intervene between the complexity of sensation and the coherence of behavior. Encountering an infinite world, we marshall our resources for an adequate response.For me, this sensory domination of the brain is an important metaphor that offers some insightinto other systems, because it suggests that interesting events of integration might be happening above the easily observable mechanical behavior of a particular system that we are trying tounderstand.To bring generality to the understanding of cellular resistance, we should look for events thatcommonly occur during successful or unsuccessful responses to stressors of various types.Several years ago, someone found that a final common pathway of cellular death was theabsorption by the cell of a large amount of calcium, when the cells were injured in a variety of ways. Working with the stressed heart, F.Z. Meerson spoke of the calcium triad, suggestingthat there are ways to interrupt the progress of cellular death even after it has started. Calciumactivates proteinases, phospholipasis, ATP-ases, contraction and oxidative peroxidation, anduncouples oxidative phosphorylation, so that numerous drugs can interfere with various aspectsof the cellular death process after it has begun. Knowing that calcium is a normal activator of muscle contraction and other normal processes, we can consider the normal physiologicalcontrols over calcium, as places where a little extra support might keep our cells safely awayfrom the final common pathway of cell death.In different situations, we can see different components of a terminal process. For example,iron tends to accumulate with age, and areas of calcification in soft tissue typically show ironassociated with the calcium. (This association is probably both physicochemical andpathophysiological.) Vitamin E is protective against the lipid peroxidation induced by iron,[ 1]as well as that stimulated by calcium. Mice killed by a variety of methods show a high level of histamine in their tissues, suggesting that histamine might be involved in a terminal pathway on either the organismic or the cellular level. Histamine can stimulate the entry of calcium intocells.[ 2]On the organismic level there are hormonal changes that accelerate the progress into a terminal state, and several of these are closely associated with the metabolism of calcium(cortisol, prolactin, and estrogen). Others are associated with the suppression of thyroid function.Adaptogens are chemicals which increase an organism's ability to resist stress without sufferingcumulative damage. This is a useful definition, since it excludes the glucocorticoids, whichpromote adaptation and short term resistance to stress, but do so at the expense of the organism'sfuture reserves. Every aspect of our normal resistance that precedes our resort to cortisol can  suggest possible classes of adaptogenic substances to strengthen those functions. The avoidance,binding, and detoxifying functions are all part of adaptation, but the most important aspect of adaptation is the ability to maintain a high level of tissue energy, and the stabilization of respiratory energy production is needed for that. Besides the oxidative production of energy, weneed to prevent the wasteful expenditure of energy, and this requires the ability to raisethresholds to stimulation. (We can see both of these processes working in the adaptation of ahealthy child to a serious infection: having a fever, and sleeping.)As soon as something interferes with the oxidative production of energy (not having enoughoxygen, for example, as when running) we adapt biochemically first by increasing theconsumption of glucose for glycolytic energy production. This increased consumption of glucosetends to lower the concentration of glucose in the blood, and this (or various other signals, suchas pain or fear, that are associated with the need for more glucose) causes the secretion of adrenalin, which can mobilize glucose from the liver's glycogen stores. If the glucose stores aredepleted, the body resorts to the secretion of cortisol, to provide glucose (and other material) bycannibalizing protein from tissues which are momentarily less essential.Both adrenalin and ACTH mobilize fat from storage. Stress-mobilized fatty acids contribute tothe increased lipid-peroxidation seen during stress, and they also tend to damage mitochondria.The large increase in the death rate from asthma in the last decade or two is now believed[*] tobe the result of cardiovascular damage caused by the common use of inhalants containingcatecholamines. Isoproteron01, a commonly used bronchodilator, causes mitochondrial damage,which can be prevented by blocking the carnitine-dependent oxidation of fatty acids. Sincecarnitine is required for the oxidation of long-chain fatty acids, its analog-betaines (whichinterfere with its transport of fatty acids into the mitochondria) protect against the damage thatnormally results from stress-induced (or catecholamine-induced) fatty acid oxidation. Sincesaturated fats protect against the cardiac necrosis produced by corn oil, I think it is probablylipid-peroxidation resulting from rapid oxidation of unsaturated fats which causes the heartdamage in both catecholamine damage[ 3]and corn-oil toxicity. Vitamin E, coconut oil, and the carnitine antagonists (betaine derivatives) are adaptogens that protect respiration by directlydecreasing lipid-peroxidation.Uncompensated stress or injury is a complex process, so it shouldn't be suprising that adaptogenshave a broad spectrum of beneficial biological effects, but it is precisely the breadth of vitaminE's effect that have made many physicians reluctant to use it, because they are trained to think interms of lock and key specificity in pharmacology. The same reaction can be expected fromdrug-dominated medicine, as results with other adaptogens are published. For example, a Sovietadaptogen of the betaine class which is used as a feed-additive for animals, has been reported:to induce interferon and protect against influenza virus,to protect the brain against hypoxia, to promote healing of wounds, burns, and sores,to activate immune responses,to promote cell division in thymus and spleen,  to restore contractility to hypoxic heart tissue,to increase the contractile capacity of the heart by increasing ATP concentration,to prevent decrease of ATP levels under various conditions,to reduce isoproteronol or catecholamine-induced myocardial injury,to protect the heart against fatty diets,to promote methylation of chromatin proteins,to promote reparative and replicative DNA synthesis,to increase translation of nucleic acids (protein synthesis),to stimulate the rate of growth in chickens,to have very low toxicity, andto be suitable for use in treating a wide variety of cardiovascular diseases, such as cardiacinsufficiency, myocarditis, cardiosclerosis, ischemic heart disease, and arrhythmias of varyingetiology, and to have long-lasting positive inotropic effect, and cardiac-dilating activity.[Literature search by P. Hockstaff.]Since the substance seems to be a natural plant growth regulator, and to be cheap to produce, it isprobably going to meet serious resistance from the drug industry/FDA monopolists, though themeat industry is likely to eventually find that it replaces many of the toxic chemicals that arenow used.The adaptogens of Eleutherococcus and ginseng are already in wide use. It is assumed that theirsteroidal components support the functions of our own protective steroids. These functions(normally adequately sustained by our endogenous steroids) are probably catatoxic, anti-catabolic, anti-inflammatory, and osmoregulatory. Since there is so much talk about catabolic oranabolic steroids, it's important to say something about the anti-catabolic aspect of the protectiveor adaptogenic steroids.On a time scale longer than that of the immediate stress experience, preventing cumulativedamage is just as important as blocking the immediate injury process. Since cortisol, which islife-saving on the short time scale, is a major cause of cumulative damage to the organism, it isimportant to investigate things which will limit its chronic catabolic effect.Although testosterone is very catabolic for the thymus gland, it is anabolic for muscle, and thereis some evidence that it is directly competitive with cortisol, which is catabolic for muscle. Whenradioactive testosterone was injected into a person, the experimenters were surprised to find thatits main concentration was in the heart muscle, rather than in the skeletal muscle. This high  concentration of testosterone in the heart muscle suggests that an antagonistic relationshipbetween testosterone and cortisol is responsible for the ability of the heart to retain its proteinwhile starvation or stress is causing protein to be removed from skin muscle, thymus, and othertissues, under cortisol's influence. Such an anti-catabolic effect must be especially importantduring the years of growth, so the youth-associated steroids (prenenolone, progesterone, DHEA)probably serve in this way, while being available for conversion into the more specifichormones. Plant steroids such as those in ginseng, having some structural similarity to thenormal protective hormones, would serve as adaptogens by making up for a reduced amount of those normal youth-associated substances.Filatov found that stressed tissues of both plants and animals produce protective and stimulatingsubstances, which can be extracted for medical use. He identified succinic acid as a componentof his extracts. Szent-Gyorgyi found that succinic acid stimulates respiration, which mightexplain why it promotes synthesis of pregnenolone and related steroids. It and fumaric acid arenow considered to be adaptogens. Since succinic acid safely chelates toxic heavy metals out of mitochondria, it might also safely carry copper into the mitochondria. Succinic acid is alsoclosely associated with GABA metabolism (gamma-amino butyric acid is converted to succinicsemialdehyde in a transamination reaction), and so is probably complementary to the GABAanalogs GHB (gamma-hydroxy butyrate) and its lactone (which has anti-viral activity). GABAanalogs are now one of the most actively studied classes of adaptogens. GABA has a wide rangeof stress-blocking actions, including neural inhibition, progesterone promotion, and blood sugarregulation.The local anesthetics, which generally have a broad range of effects, are an important class of adaptogens. Procaine has been found to normalize almost every system studied.[ 4]Doses far too small to have an anesthetic effect have clear biological effects. Lidocaine is used to prevent heartarrhythmia, and acts partly by preventing excessive calcium uptake by the cells. The atropinefamily of drugs is structurally similar to the local anesthetics, and also have a long history of use in treating sickness and stress. Most of these chemicals have anti-histamine actions that areprobably relevant to their value as adaptogens. These chemicals can protect microcirculationagainst spasms produced by exhaustion or overstimulation. Light can also have this effect.[ 5]  Promotion of synthesis and stabilization of the detoxifying enzymes is another function of someadaptogens. The catatoxic steroids do this, but since they also have an immediate protectiveeffect (that could hardly involve the production of new enzymes), they probably have othermechanisms of action, such as improving the capacity for binding toxins of proteins such asalbumin. Since even cholesterol has catatoxic action, I often advise people to eat more eggs for avariety of problems. The egg lipids (including phospholipids and cholesterol) enter the blood inmicroscopic particles, called chylomicrons. Synthetic liposomes are a pharmaceutical fad,promoted for their ability to transport various drugs, but the liposomes themselves (made fromegg phosphatidylcholine and cholesterol) have anti-inflammatory and anti-bacterial actions.( Anti-inflammatory action of liposomes, V.M. Kreys, et al., Vestnik Akademii MeditsinskikhNauk no. 6 June 1990, pages 44-47.) I think we have to include dietary eggs in our list of adaptogens.
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