Ray Peat on Cholesterol

 The Connection Between Hypothyroidism and Arteriosclerosis

“Several researchers showed in the 1930s and 1940s that hypothyroidism causes arteriosclerosis and that thyroid supplementation corrects it. In people whose thyroid was removed, serum cholesterol increased while their metabolic rate slowed, and when they were given dried thyroid to normalize their metabolic rate, their serum cholesterol immediately normalized accordingly.”

September 2018 – Ray Peat's Newsletter

The Role of Cholesterol in Progesterone Production

“The rising cholesterol had a protective function. For example, when the amount of cholesterol flowing into an ovarian artery was increased, the amount of progesterone flowing out of an ovarian vein increased proportionally, as the raw material was converted into the product.”

September 2018 – Ray Peat's Newsletter

The Popularity of the Lipid Bilayer Cytoplasmic Membrane

“In the 1960s, the lipid bilayer of the cytoplasmic membrane was a real hype, and the physical properties of cholesterol and saturated fatty acids were popularly used to explain everything in terms of membrane fluidity. (Between January 1964 and the present, PubMed lists more than 37,000 entries on the lipid bilayer.)”

September 2018 – Ray Peat's Newsletter

Cell Stiffness and Degenerative Changes Unrelated to Cholesterol

“The actual physical stiffness of whole cells and their environment is very important. For example, excitotoxicity (Fang et al., 2014) and other forms of energy deficiency stiffen cells, and persistent energy deficiency as well as inflammation lead to degenerative changes—such as tissue calcification, fibrosis, and invasive, disorganized cell movement. These stress-induced stiffenings of the cell substance and matrix have nothing directly to do with the local amount of cholesterol.”

September 2018 – Ray Peat's Newsletter

The Role of Cholesterol in the Flexibility of Red Blood Cells

“When the cholesterol content of red blood cells is experimentally reduced, they become stiffer, and restoring the normal cholesterol level restores their flexibility.”

September 2018 – Ray Peat's Newsletter

Comparative Cholesterol Content in Fat and Muscle Tissue

“In the body, fat tissue with a high fat content has a significantly lower cholesterol level than muscle tissue. This is partly because muscles produce more cholesterol than fat tissue, but also because the structural proteins of the cells have a high affinity for cholesterol. As a result, fat and proteins are mutually soluble.”

September 2018 – Ray Peat's Newsletter

Composition of Protoplasm and Cholesterol as a Lubricant

"I believe it is correct to view the protoplasm as a complex type of solution of proteins, water, cholesterol, and other lipids, nucleic acids, ATP, as well as smaller amounts of other substances, with a viscosity that changes when small changes in dissolved substances shift the balance of cohesive forces. Due to its molecular shape and hydrophobicity, cholesterol acts both as a lubricant and a stabilizer of this complex system. It reduces cell stiffness by increasing the mobility of proteins."

September 2018 – Ray Peat's Newsletter

Paradox of the Lipid Bilayer Membrane Doctrine

"The fact that cholesterol strengthens cells and protects them from breaking down under stress obviously has nothing to do with a lipid bilayer membrane. This membrane doctrine has paradoxically made it seem that the loss of cholesterol makes cells stiffer while simultaneously weakening them. Gilbert Ling has pointed out the numerous paradoxes faced by proponents of the lipid boundary membrane for 65 years, yet the membrane doctrine still prevails."

September 2018 – Ray Peat's Newsletter

Discovery of Oxidation Contamination in Commercial Cholesterol

"About 40 years ago, someone noticed that the commercial cholesterol used for research purposes was contaminated by oxidation and that pure cholesterol did not produce the same toxic effects."

September 2018 – Ray Peat's Newsletter

Composition of Foam Cells and Impact on Cholesterol Regulation

"The foam cells found in atherosclerotic plaques contain cholesterol esters, especially cholesteryl eicosapentaenoate, cholesteryl docosahexaenoate, cholesteryl arachidonate, cholesteryl linoleate, and cholesteryl oleate. The oxidation of these fatty acids produces acrolein and related compounds that block the cells' ability to regulate cholesterol."

September 2018 – Ray Peat's Newsletter

PUFA and the Impairment of Cholesterol's Normal Functions

"In combination with unstable polyunsaturated fatty acids, cholesterol cannot perform its normal functions. The unstable polyunsaturated fatty acids inactivate the corrective (ABCA) protein that removes the damaged form of cholesterol."

September 2018 – Ray Peat's Newsletter

Cholesterol in the Young and Aging Brain

"The healthy young brain contains a very large amount of cholesterol, almost exclusively in pure, non-esterified or free form – more than 99.5%, according to Orth and Bellosta (2012, citing Bjorkhem and Meaney, 2004). The aging, degenerating brain contains an increasing amount of esterified cholesterol."

September 2018 – Ray Peat's Newsletter

Carcinogenic Nature of PUFA and Pharmaceutical Industry Interest

"While there remains significant reluctance to acknowledge the carcinogenic nature of PUFA, findings like these have prompted the pharmaceutical industry to consider using their ACAT inhibitors (which block the attachment of PUFA to cholesterol) for cancer treatment."

September 2018 – Ray Peat's Newsletter

Conversion of Cholesterol into a Toxin by PUFA

"Polyunsaturated fatty acids transform cholesterol by binding with normally protective cholesterol into a kind of toxin, a disorganizing factor that leads to neurodegeneration, arteriosclerosis, cataracts, chronic kidney disease, and cancer."

September 2018 – Ray Peat's Newsletter

Liver Response to a Deficiency of Polyunsaturated Fatty Acids

"When the diet lacks polyunsaturated fatty acids, the liver synthesizes saturated fatty acids and exports its cholesterol mainly combined with palmitate, which does not promote lipid peroxidation, or in the non-esterified, free form."

September 2018 – Ray Peat's Newsletter

Reversing Liver Degeneration through Diet

"A lifelong accumulation of PUFA gradually impairs the liver's protective functions, but these functions can be gradually restored by supplying carbohydrates and saturated fats without polyunsaturated fatty acids, along with some of the factors depleted along with free cholesterol, especially pregnenolone and progesterone."

September 2018 – Ray Peat's Newsletter

Progesterone Therapy for Male Infertility and Sports-Related Infertility

"Progesterone is the precursor (after acetate and cholesterol) for all other steroid hormones and can therefore also be used in men. It (or its precursor pregnenolone) has been used for prostatitis, arthritis, and male infertility. Large amounts would likely suppress LH and reduce testosterone synthesis, but a smaller amount (especially in older men) seems to increase sperm count and motility. In male and female athletes who become infertile, it appears to be the appropriate therapy, usually combined with thyroid hormones."

Nutrition For Women

Cholesterol from Diet and Liver Cholesterol Production

"Since a healthy liver produces cholesterol to compensate for a deficiency in the diet, avoiding cholesterol-rich foods does not necessarily lead to lower blood cholesterol levels."

Nutrition For Women

Influence of Vitamin C on Cholesterol and Related Nutrients

"Vitamin C lowers blood cholesterol levels according to current knowledge. Eggs are rich in cholesterol but also contain lecithin, which apparently makes cholesterol usable or at least less harmful. Niacin and vitamin E also help regulate cholesterol. High insulin levels, caused by sugar consumption, seem to play an important role in cholesterol damaging blood vessels."

Nutrition For Women

Connection between high cholesterol, hypothyroidism, and heart attacks

"High cholesterol usually indicates low thyroid function. When thyroid function is reduced, cholesterol is not efficiently converted into progesterone. The actual cause of heart attacks seems to be hypothyroidism and its effects, including a loss of magnesium."

Nutrition For Women

Eggs and their protective role against cholesterol deposits

"Eggs may actively protect against the formation of cholesterol deposits for several reasons. One of the men who discovered insulin, Best, later showed that choline (a component of lecithin) can prevent fatty degeneration of the liver."

Nutrition For Women

Comparison of the effects of margarine and butter on cardiovascular disease

"Animal studies show that margarine causes more cardiovascular disease than butter or cholesterol."

Nutrition For Women

Effect of thyroid hormones on metabolic rate and body temperature

"In the 1930s, it was known that thyroid hormones increase metabolic rate and raise body temperature. Since serum cholesterol decreased in proportion to the increased metabolic rate caused by thyroid supplementation, it was proposed to use cholesterol measurement to diagnose hypothyroidism."

November 2020 – Ray Peat's Newsletter

Aging skin, progesterone, and vitamin D

"It has been known for several decades that the production of progesterone and DHEA steadily decreases with age, and in recent years it has been found that aged skin produces only about half as much vitamin D as young skin when exposed to sunlight. Old skin contains about half as much cholesterol as young skin, so it is not surprising that the substances derived from it are also reduced."

November 2018 – Ray Peat's Newsletter

Cholesterol content and appearance of aged skin

"The characteristic dullness of aged skin is the result of an accumulation of layers of dead cells on the surface. While the living, underlying skin cells contain significantly less cholesterol than normal, the inert cells show an increased amount of cholesterol sulfate. When the free cholesterol content in the skin is experimentally increased, the skin regains its ability to shed the dead surface cells. Conversely, when it is experimentally decreased, for example by a statin, the skin takes on the structure and appearance of aged skin. Aging seems to be a state of cholesterol deficiency."

November 2018 – Ray Peat's Newsletter

Low Cholesterol and Effects on Mental Health

"Low serum cholesterol has been linked to depression, suicide, violence, and increased cancer mortality. Since statins enter the brain and inhibit cholesterol synthesis there, reduced mitochondrial function is undoubtedly a factor in the mental side effects they can cause."

November 2018 – Ray Peat's Newsletter

Synergy of Cholesterol and Progesterone

"The functions of cholesterol resemble those of progesterone in many ways. In the pregnant uterus, for example, the relaxing effect of progesterone is supported by cholesterol (Smith et al., 2005). In the brain, nerve excitation by glutamic acid is controlled by a uptake protein that binds this neurotransmitter, and the function of this protein depends on cholesterol; a reduction in cholesterol prolongs nerve excitation."

November 2018 – Ray Peat's Newsletter

Interaction of the Cell Nucleus with Cholesterol and Lipids

"Within the cell nucleus is a highly organized substance, the nuclear matrix, which closely interacts with the rest of the cytoskeleton and allows DNA to be expressed according to the cell's needs and in response to its environment. Cholesterol and other lipids are essential for the specific, highly organized interactions between DNA and the rest of the cell apparatus."

November 2018 – Ray Peat's Newsletter

The Role of Cholesterol in Maintaining Stem Cells

"Cholesterol is involved in maintaining stem cells and controlling their maturation into functional cells. A cholesterol chelator, cyclodextrin, which affects cellular cholesterol, causes cardiac stem cells to mature into functional heart muscle cells: β-CD exerted its effect by increasing free intracellular cholesterol."

November 2018 – Ray Peat's Newsletter

Excitatory Signal Transmission and Cholesterol in the Brain

"Excitatory signal transmission appears to contribute to the loss of cholesterol in the brain during aging; the amount of cholesterol in synapses decreases with age (Sodero et al., 2011). Although excitatory (glutamatergic) stimulation lowers cholesterol in the brain, environmental enrichment (meaningful experiences) increases it (Levi et al., 2005) and also reverses the age-related decline of cholesterol-derived neurosteroids."

November 2018 – Ray Peat's Newsletter

Accumulation of cholesterol esters and neurodegeneration

"In the brain, the accumulation of cholesterol esters (at the expense of free cholesterol) increases with age and contributes to neurodegeneration. Interventions that separate cholesterol from fatty acids have a neuroprotective effect in a worm model of Parkinson's disease."

November 2018 – Ray Peat's Newsletter

Lipofuscin formation from polyunsaturated fatty acids

"The age pigment lipofuscin is formed by the oxidation of polyunsaturated lipids. The polyunsaturated fatty acids that accumulate with age have been known for about 80 years as the main source of this material. These fatty acids inhibit cholesterol synthesis."

November 2018 – Ray Peat's Newsletter

Increase in cholesterol ester concentration with age

"At birth, the concentration of cholesterol esters is very low, and this proportion remains low until about age 20, when growth slows. After age 20, cholesterol esters accumulate at about five times the rate of cholesterol accumulation. After age 40, cholesterol esters become the main component of the lipids in blood vessels."

November 2018 – Ray Peat's Newsletter

Stress-induced increase in serum cholesterol as an adaptive response

"The stress-induced increase in serum cholesterol is an important protective adaptation."

November 2018 – Ray Peat's Newsletter

Methods to reduce the formation of cholesterol esters

"In addition to avoiding polyunsaturated fatty acids (n-3 and n-6) in the diet to reduce the formation of cholesterol esters and slow the age-related decline in cholesterol synthesis, supplementation with progesterone is another way to reduce ester formation (Synouri-Vrettakou and Mitropoulos, 1983; Miller and Melnykovych, 1984; Jeng and Klem, 1984; Mulas et al., 2011; Anchisi et al., 2012). Lidocaine is another inhibitor of cholesterol ester formation (Bell, 1981; Bell et al., 1982), which is likely useful in certain degenerative diseases."

November 2018 – Ray Peat's Newsletter

The role of cholesterol in neurosteroid production

"Cholesterol is the precursor of pregnenolone, progesterone, and other neurosteroids, and its own properties include stabilizing effects similar to those of progesterone."

May 2019 – Ray Peat's Newsletter

Cholesterol after birth and mental health

"Several studies have found a connection between lower cholesterol levels after birth and symptoms of anxiety and depression."

May 2019 – Ray Peat's Newsletter

Progesterone After Birth and Brain Health

"With insufficient cholesterol, the normally high progesterone concentration after birth likely cannot be maintained, and instead of brain regeneration, the various proinflammatory effects of serotonin and estrogen predominate, resulting in depression, joint pain, anxiety, and brain edema."

May 2019 – Ray Peat's Newsletter

Conversion of Animal Cholesterol into Steroids and the Role of the Thyroid

"In animals, cholesterol is the fundamental sterol molecule extensively converted into other substances, including steroid hormones. This conversion requires thyroid hormones and vitamin A."

Generative Energy Restoring The Wholeness Of Life

Historical Evidence of Thyroid Deficiency in the USA

"Many researchers found (before the late 1940s) that about 40% of people in the USA showed signs of insufficient thyroid function (low oxygen consumption and high serum cholesterol) and benefited from taking a thyroid preparation."

Generative Energy Restoring The Wholeness Of Life

Mitochondrial Damage Affects Hormone Production and Energy

"Since protective hormones depend on the mitochondria's ability to convert cholesterol into pregnenolone, it is clear that mitochondrial damage impairs our supply of protective hormones while energy production fails. This forces the body to shift toward atrophy-promoting stress hormones, including cortisol."

Generative Energy Restoring The Wholeness Of Life

The Role of Thyroid Hormones in Cholesterol Conversion

"Thyroid hormones tend to lower cholesterol levels by converting it into pregnenolone and other steroids."

Email Response by Ray Peat

Reevaluating the Role of Cholesterol in Heart Disease

"Given the clear and well-defined toxicity of adrenaline and free fatty acids, the role of cholesterol in heart disease begins to appear more epiphenomenal."

June 1992 – Ray Peat's Newsletter

The Role of Blood Cholesterol in Immune Function and Allergies

"Both low and high concentrations of blood cholesterol are associated with immune defects. Most people I have spoken to who have multiple severe allergies have very low cholesterol levels, while hypothyroid individuals who are very susceptible to infections usually have high cholesterol levels."

December 1992 – Ray Peat's Newsletter

Effects of Endotoxins on Mitochondrial Respiration and Pregnenolone

"Bacterial endotoxins inhibit mitochondrial respiration, and this respiration is required for the intramitochondrial conversion of cholesterol into pregnenolone."

August–September 1992 – Ray Peat's Newsletter

Mitochondrial damage and impaired pregnenolone production

"If the mitochondria are damaged, the protective steroid pregnenolone (which is formed in the mitochondria from cholesterol) cannot be produced."

January 1991 – Ray Peat's Newsletter

Promoting protective hormones with succinic acid and atropine

"Protective hormones can be used directly, or their synthesis can be promoted by using succinic acid, thyroid hormones, vitamin A, and atropine-like drugs, as well as by maintaining an adequate cholesterol level."

January 1991 – Ray Peat's Newsletter

Unsaturated oils, cholesterol, and increased cancer mortality

"It was noted decades ago that unsaturated oils lower cholesterol levels. However, studies showed that adding polyunsaturated oils to the diet did not prevent deaths from heart disease but increased cancer mortality."

April 1991 – Ray Peat's Newsletter

Influence of cholesterol on the production of protective hormones

"The highest concentration of cholesterol in the body is found in the brain. The cholesterol level in the blood strongly influences the production of protective hormones like progesterone."

October 1990 – Ray Peat's Newsletter

Positive feedback systems with progesterone and thyroid hormones

"The presence of some positive feedback systems (self-stimulation) shows, however, that our basic structure is oriented in an expansive, upward direction. Progesterone (and its precursors pregnenolone and cholesterol) as well as thyroid hormones are involved in some of the important positive feedback systems affecting energy production, stress resistance, and brain growth."

October 1990 – Ray Peat's Newsletter

Cholesterol conversion in the mitochondria and effects on hormones

"Within the mitochondria, a cytochrome P-450 converts cholesterol into pregnenolone. The loss of both energy and steroid hormones would have far-reaching consequences."

January 1989 – Ray Peat's Newsletter

The role of thyroid hormones in estrogen breakdown and progesterone production

"While thyroid hormones promote the breakdown of estrogen, they are also indispensable for the production of progesterone. Vitamin A (together with cholesterol) is consumed at a high rate by the corpus luteum when sufficient thyroid hormone is present."

January 1988 – Ray Peat's Newsletter
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