Peat diet and the risk of Vitamin A toxicity, fatty liver
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In scrapie and many other degenerative diseases (the amyloidoses), proteins condense into fibrils that tend to keep enlarging, with a variety of very harmful effects. The condensation of the “amyloid” proteins is sensitive to temperature, and a slight increase in the disorder of the water can induce functional proteins to change their conformation so that they spontaneously associate into fibrous masses. In the absence of sufficient carbon dioxide, all proteins are susceptible to structural alteration by the addition of sugars and fats and aldehydes, especially under conditions that favor lipid peroxidation.
The amyloidoses affect different tissues in different ways, but when they occur in the brain, they produce progressive loss of function, with the type of protein forming the fibrils determining the nature of the functional loss. The protein which carries thyroid hormone and vitamin A, transthyretin, can produce nerve and brain amyloid disease, but it can also protect against other amyloid brain diseases; in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and the “prion diseases” (scrapie, kuru, CJD, BSE, etc.) amyloid particles are formed by different proteins. The transthyretin protein which is binding small molecules resists condensation into the amyloid fibrils, but without its normal vitamin A and thyroid hormone, it can create toxic fibrils. (Raghu, et al., 2002.)Serum amyloid A, which can increase 1000-fold under the influence of proinflammatory cytokines, resulting from irradiation, stress, trauma, or infection, is an activator of phospholipase A2 (PLA2), which releases fatty acids. Some of the neurodegenerative states, including amyloid-prion diseases, involve activated PLA2, as well as increases in the toxic breakdown products of the polyunsaturated fatty acids, such as 4-hydroxynonenal. The quantity of PUFA in the tissues strongly determines the susceptibility of the tissue to injury by radiation and other stresses. But a diet rich in PUFA will produce brain damage even without exceptional stressors, when there aren’t enough antioxidants, such as vitamin E and selenium, in the diet.
Amyloidosis has traditionally been thought of as a condition involving deposits mainly in blood vessels, kidneys, joints and skin and in extracellular spaces in the brain, and the fact that the “amyloid” stained in a certain way led to the idea that it was a single protein. But as more proteins--currently about 20--were identified in amyloid deposits, it was gradually realized that the deposits can be identified inside cells of many different tissues, before the larger, very visible, extracellular deposits are formed.
There is evidence of a steady increase in the death rate from amyloidosis. It kills women at a younger age than men, often at the age of 50 or 60.
Serum amyloid P is called “the female protein” in hamsters, because of its association with estrogen; castrated (or estrogen treated) males also produce large amounts of it, and its excess is associated with the deposition of amyloid (Coe and Ross, 1985). It can bind other amyloid proteins together, accelerating the formation of fibrils, but this function is probably just a variation of a normal function in immunity, tissue repair, and development.
Estrogen increases the inflammation-associated substances such as IL-6, C-reactive protein, and amyloid, and liberates fatty acids, especially the unstable polyunsaturated fatty acids. It also increases fibrinogen and decreases albumin, increasing the leakiness of capillaries. The decrease of albumin increases the concentration of free fatty acids and tryptophan, which would normally be bound to albumin.
In the U.S. and Europe, livestock are fed large amounts of high-protein feeds, and currently these typically contain fish meal and soybeans. The estrogenic materials in soybeans increase the animals’ tendency toward inflammation (with increased serum amyloid).
Officially, BSE appeared because cows were fed slaughter-house waste containing tissues of sheep that had died of scrapie. Scrapie was a nerve disease of sheep, first reported in Iceland in the 18th century. When I was studying the digestive system and nutrition of horses, I learned that it was common for horses in Norway to be fed dried fish during the winter. This abundant food was probably used for sheep, as well as for horses. The extra protein provided by fish meal is still important for sheep in areas where pastures are limited, but it has now become common to use it to increase productivity and growth throughout the lamb, beef, and dairy industries, as well as in most lab chows fed to experimental animals, such as the hamsters used for testing the infectivity of the diseased tissues.
Increased dietary polyunsaturated fatty acids (PUFA) suppress the activity of the ruminal bacteria which are responsible for the hydrogenation-detoxication of PUFA in the animal’s diet. This allows the unstable fats, 98% of which are normally destroyed, to pass into the animals’ tissues and milk.
The polyunsaturated fats in fish are very unstable, and when they get past the bacterial saturases (biohydrogenases) in the rumen that normally protect ruminants from lipid peroxidation, they are likely to cause their toxic effects more quickly than in humans, whose antioxidant systems are highly developed. The toxic effects of polyunsaturated fats involve altered (immunogenic) protein structure, decreased energy metabolism, and many inflammatory effects produced by the prostaglandin-like substances. Marine fish are now so generally polluted with dioxin, that in Japan there is a clear association between the amount of fish in a person’s diet (their body content of EPA and DHA) and the amount of dioxin in their body.
Radiation and many kinds of poisoning cause early peroxidation of those highly unsaturated fats, and the breakdown products accelerate the changes in the folding and chelating behavior of proteins. The accumulation of altered proteins is associated with the degenerative diseases. The role of toxic metals in brain inflammation is well established (e.g., aluminum, lead, mercury: Campbell, et al., 2004; Dave, et al., 1994; Ronnback and Hansson, 1992).
The “prion hypothesis” has the value of weakening the fanaticism of the DNA-genetics doctrine, but it has some problems. There are now several examples in which other degenerative diseases have been transmitted by procedures similar to those used to test the scrapie agent. (e.g., Goudsmit, et al., 1980; Xing, et al., 2001; Cui, et al., 2002.) Experimental controls haven’t been adequate to distinguish between the pure prion and its associated impurities. Gajdusek burned a sample of the infective hamster brain to ash, and found that it still retained “infectivity.” He argued that there was a mineral template that transmitted the toxic conformation to normal proteins. Others have demonstrated that the active structure of the infective agent is maintained by a carbohydrate scaffolding, or that the infectivity is destroyed by the frequency of ultraviolet light that destroys the active lipid of bacterial endotoxin, lipopolysaccharide.
But simply injuring the brain or other organ (by injecting anything) will sometimes activate a series of reactions similar to those seen in aging and the amyloidoses. When a slight trauma leads to a prolonged or expanding disturbance of structure and function, the process isn’t essentially different from transmitting a condition to another individual. The problem is being “transmitted” from the initial injury, recruiting new cells, and passing the disturbed state on to daughter cells in a disturbed form of regeneration. Keloids, hypertrophic scars, are analogous to the dementias in their overgrowth of connective tissue cells: In the aging or injured brain, the glial cells (mainly astrocytes) proliferate, in reparative processes that sometimes become exaggerated and harmful.
When tissue phospholipids contain large amounts of polyunsaturated fatty acids, large amounts of prostaglandins are immediately formed by any injury, including low doses of ionizing radiation. The liberated free fatty acids have many other effects, including the formation of highly reactive aldehydes, which modify DNA, proteins, and other cell components.
Animals which are “deficient” in the polyunsaturated fatty acids have a great resistance to a variety of inflammatory challenges. Their tissues appear to be poor allergens or antigens, since they can be easily grafted onto other animals without rejection. Something related to this can probably be seen in the data of human liver transplants. Women’s livers are subjected to more lipid peroxidation than men’s, because of the effects of estrogen (increasing growth hormone and free fatty acids, and selectively mobilizing the polyunsaturated fatty acids and increasing their oxidation). Liver transplants from middle-aged female donors fail much more often (40 to 45%) than livers from male donors (22 to 25%), and other organs show the same effect. The autoimmune diseases are several times as common in women as in men, suggesting that some tissues become relatively incompatible with their own body, after prolonged exposure to the unstable fatty acids. If we consider the healthy function of the immune system to be the removal or correction of injured tissue, it’s reasonable to view the random interactions of oxidized fats with proteins as exactly the sort of thing our immune system takes care of.
The serum amyloids A and P and the closely related lipoproteins are considered to be important parts of our “innate immunity,” operating in a more general way than the familiar system of specific acquired immunities.
The amyloids and lipoproteins are powerfully responsive to bacterial endotoxin, LPS, and their structural feature that binds it, the “pleated sheet” structure, appears to also be what allows the amyloids to form amorphous deposits and fibrils under some circumstances. Our innate immune system is perfectly competent for handling our normal stress-induced exposures to bacterial endotoxin, but as we accumulate the unstable fats, each exposure to endotoxin creates additional inflammatory stress by liberating stored fats. The brain has a very high concentration of complex fats, and is highly susceptible to the effects of lipid peroxidative stress, which become progressively worse as the unstable fats accumulate during aging.
More than 60 years ago, a vitamin E deficiency was known to cause a brain disease, sometimes associated with sterility and muscular dystrophy. The symptoms of the brain disease were similar to those of “mad cow disease,” and the condition is now usually called “crazy chick disease.” Veterinarians are usually taught that it is caused by a selenium deficiency, but it is actually the result of an excess of PUFA in the diet, and is exacerbated by increased iron or other oxidants, and prevented by increased vitamin E, selenium, or substitution of saturated fats for the unsaturated.
The modification of proteins’ structure by glycosylation is involved in the development of the toxic form of the “prionic” protein, as well as in all the degenerative processes of aging. Until the ability to use sugar is impaired, cells produce enough carbon dioxide to protect proteins against random glycation, but with each exposure to free polyunsaturated fatty acids, the ability to use glucose is damaged. In the dementias, the brain has a greatly reduced ability to use glucose.
One of estrogen’s central effects is to shift metabolism away from the oxidation of glucose, decreasing carbon dioxide production. There is a much higher incidence of Alzheimer’s disease in women, and estrogen exposure exacerbates all of the changes that lead to it, such as shifts in nerve transmitters, increased vascular leakiness, and the increased production of the acute phase proteins.
Everything that is known about the “always fatal” prionic diseases, the diseases of disturbed protein folding, suggests that they can be avoided and even reversed by systematically reversing the processes that amplify inflammation.
People who take aspirin, drink coffee, and use tobacco, have a much lower incidence of Alzheimer’s disease than people who don’t use those things. Caffeine inhibits brain phospholipase, making it neuroprotective in a wide spectrum of conditions. In recent tests, aspirin has been found to prevent the misfolding of the prion protein, and even to reverse the misfolded beta sheet conformation, restoring it to the harmless normal conformation. Nicotine might have a similar effect, preventing deposition of amyloid fibrils and disrupting those already formed (Ono, et al., 2002). Vitamin E, aspirin, progesterone, and nicotine also inhibit phospholipase, which contributes to their antiinflammatory action. Each of the amyloid-forming proteins probably has molecules that interfere with its toxic accumulation.
Thyroid hormone, vitamins A and E, niacinamide (to inhibit systemic lipolysis), magnesium, calcium, progesterone, sugar, saturated fats, and gelatin all contribute in basic ways to prevention of the inflammatory states that eventually lead to the amyloid diseases. The scarcity of degenerative brain disease in high altitude populations is consistent with a protective role for carbon dioxide.
https://raypeat.com/articles/aging/madcow.shtml...................
Studies involving doxycycline and TUDCA
**The combined doxycycline and TUDCA treatment in lowering TTR deposits was tested in different animal models of FAP. In one study, it was found that the two drugs have a synergistic effect and work by lowering both fibrillar and non-fibrillar deposits. The results of this study, published in the Journal of Translational Medicine, indicate that doxycycline acts as a fibril disruptor in vitro and works by removing TTR amyloid deposits. TUDCA works by lowering the amount of deposited non-fibrillar TTR.These positive results led to the investigation of the effect of doxycycline plus TUDCA in patients with transthyretin amyloidosis, or ATTR amyloidosis, of which FAP is a subtype.
The results of a Phase 2, open-label study of doxycycline (100 mg twice daily) plus TUDCA (250 mg three times a day), published in the journal Amyloid, indicated that the combination of the two compounds stabilized the disease in patients. The treatment was well tolerated and halted the progression of heart disease as well as neuropathy in patients for at least one year.**
https://fapnewstoday.com/doxycycline-and-taurodesoxycholic-acid-tudca/ -
@CO3 Vitamin A seems to increase iodine usage and it's entirely possible that increased vitamin A requires increased iodine. Populations that eat lots of sweet potatoes tend to get high iodine as well (and they also live extremely long lives)
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Lots of nutrients work inefficiently when there is exesses of estrogen and PUFA and eating higher amounts of fiber is a good way to detox estrogen freeing up the liver to help rid the body of PUFAs. More than likely by eating the higher amounts of fiber this detox is happening leading to better usage of these nutrients like A and copper which seems to follow estrogen too. This is one of the reason Peat recommends the carrot salad, mushrooms, bamboo shoots or even oat or wheat bran.
It's weird to think people underestimate the potency of estrogen and pufa as they increase each others effects on the body especially people who know about Ray Peat. If Androgens are low these issues are much worse as there is no defence against this. Looking from a macro perspective is sometimes best as it can be easy to get lost down a road of reduction
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This is a topic for the retard forum. Why does it have to get dragged into here too? Do you really have to discuss 'vitamin is toxic' in the place that was created (partially) in reaction to the absurd outgrowth of that idea and legion of fools following it?
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@TexugoDoMel, when we think that they've dodged toxins and escaped misfortune because their sweet potatoes are purple and low in macabrotenoids, the same detective reappears to add that polyphenols are toxins too. I'm not making this up.
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@Amazoniac rabbit holes galore. makes for many shades and tints between red and blue pilling. how nice. in itself a new field of science is born to supplant virology and quantum physics.
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@GreekDemiGod said in Peat diet and the risk of Vitamin A toxicity, fatty liver:
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greekdemigod u are just as retarded as the people at raypeat forum /thread
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@raypneat blocked and reported. Get out.
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@GreekDemiGod serotonic behavior
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@Hando-Jin @GreekDemiGod can't think and will believe anything charlie says on that forum, also "what is the best idealabs combo?" hurr durrr
