Cholesterol, longevity, intelligence, and health.

[Guest guest]

http://raypeat.com/articles/articles/cholesterol-longevity.shtml

 

Cholesterol, longevity,

intelligence, and health.

. The biological meaning of cholesterol is just starting to

be explored.

. Everything that doctors know about cholesterol is

wrong.

. New information about cholesterol is clarifying important

issues in physiology and pathology.

by Ray Peat

Medical magazines and television stations like to propagate

the idea that cholesterol is bad stuff, and as a result, that

cliche is known to almost every American. Recent journal

articles have promoted the idea that " the lower the serum

cholesterol is, the better " it is for the health of the

patient.

The theory that heart disease is " caused by cholesterol "

has

gone through several stages, and most recently the use of the

" statin " drugs has revived it in a radical way. One

consistent

theme for fifty years has been that people should eat more

polyunsaturated fat and less saturated fat, to lower their

cholesterol, and to avoid butter, cream, eggs, and " red

meat, "

because they contain both saturated fat and cholesterol.

Often, medical attention is focused on the fats in the

atheroma, rather than on the whole disease process, including

clotting factors, vascular spasms, heart rhythm, viscosity of

the blood, deposition of calcium and iron in blood vessels,

and the whole process of inflammation, including the reactions

to absorbed bowel toxins.

Almost 100 years ago, some experiments in Russia showed that

feeding rabbits cholesterol caused them to develop

atherosclerosis, but subsequent experiments showed that

rabbits are unusual in responding that way to cholesterol, and

that even rabbits don't develop atherosclerosis from

cholesterol if they are given a supplement of thyroid

(Friedland, 1933). By 1936, it was clear that

hypercholesterolemia in humans and other animals was caused by

hypothyroidism, and that hypothyroidism caused many diseases

to develop, including cardiovascular disease and cancer. There

was already more reason at that time to think that the

increased cholesterol was a protective adaptation than to

think that it was maladaptive.

The strange idea that cholesterol causes atherosclerosis was

revived in the 1950s when the vegetable oil industry learned

that their polyunsaturated oils lowered serum cholesterol.

(Many other toxins lower cholesterol, but that is never

mentioned.) The industry began advertising their oils as

" heart protective, " and they enlisted some

influential

organizations to help in their advertising: The American

Dietetic Association, the American Heart Association, the US

Dept. of Agriculture and FDA, and the AMA. Besides the early

rabbit research, which didn't make their case against

cholesterol and might actually have had implications harmful

to their argument (since Anitschkow had used vegetable oil as

solvent for his cholesterol feedings), the oil industry helped

to create and promote a large amount of fraudulent and

unscientific work.

The death rate from heart disease in the United States began

increasing early in the twentieth century, and it reached its

peak from about 1950 to 1975, and then began declining. During

the decades in which the death rate was rising, consumption of

animal fat was decreasing, and the use of vegetable oil was

increasing. In the southern European countries that have been

said to show that eating very little animal fat prevents heart

disease, the trends after the second world war have been the

opposite -- they have been eating more animal fat without an

increase in heart disease.

The correspondence between heart disease and consumption of

saturated fat and cholesterol is little more than advertising

copy. If people were looking for the actual causes of heart

disease, they would consider the factors that changed in the

US during the time that heart disease mortality was

increasing. Both increases in harmful factors, and decreases

in protective factors would have to be considered.

The consumption of manufactured foods, pollution of air and

water, the use of lead in gasoline, cigarette smoking,

increased medicalization and use of drugs, psychosocial and

socioeconomic stress, and increased exposure to radiation --

medical, military, and industrial -- would be obvious things

to consider, along with decreased intake of some protective

nutrients, such as selenium, magnesium, and vitamins.

 

But those harmful factors all had their defenders: Who defends

socioeconomic stress? All of the social institutions

that

fail to alleviate it. In 1847, Rudolph Virchow was sent to

Poland to study the health situation there, and when he

returned, the highly regarded anatomist, physiologist and

pathologist announced that the Poles wouldn't have a health

problem if the government would stop oppressing them, and

institute economic reforms to alleviate their poverty. The

reforms weren't made, and Virchow lost his job. Other harmful

factors, such as seed oils, degraded foods, and radiation,

have specific, very well organized and powerful lobbies to

defend them.

Despite the growing knowledge about the dangers of

polyunsaturated fats, many medical articles are still

advocating the " official " heart protective diet

(e.g.,

" ... diets using nonhydrogenated unsaturated fats as the

predominant form of dietary fat, " Hu and Willet, 2002).

 

Some dogs alertly look at the thing a person is pointing at,

other dogs just sniff the pointing finger. The publicists who

disregard the complete nutritional and ecological situation,

to focus on cholesterol and fat in the diet, are like the

finger sniffers.

Recent articles in the medical and lipids journals are

praising the 1950 work of J. W. Gofman, and the 1914 rabbit

studies of N. N. Anitschkow, as the research that revealed

cholesterol to be the cause of heart disease. Anitschkow and

his co-workers, however, understood that their experiment

hadn't explained human heart disease, and John Gofman, about

50 years after publishing his work on the lipoproteins, has

done some large studies that could be crucial in disproving

the doctrine that has become almost a national religion.

He has shown that mortality from both heart disease and cancer

corresponds very closely to the population's exposure to

medical services, and specifically to medical radiation.

During the peak years of heart disease mortality, medical

x-rays gave very large doses of radiation with each exposure,

and the population was also exposed to radioactive fallout

from atomic bomb testing (explosions from 1945 to 1963

produced a peak of heavy fallout that persisted through the

'sixties and into the 'seventies).

Around 1971, someone noticed that the commercial cholesterol

being used in feeding experiments was oxidized, that is, it

wasn't really cholesterol. Comparing carefully prepared,

unoxidized cholesterol with the oxidized degraded material, it

was found that dietary cholesterol wasn't necessarily

atherogenic (Vine, et al., 1998).

Dietitians often recommend eating poached salmon, rather than

" red meat, " to lower cholesterol. Experimenters have

measured

the toxic oxidized cholesterol in different foods prepared in

a variety of ways. Steaming salmon produced several times as

much oxidized cholesterol as frying it, because of the longer

cooking time that allowed the polyunsaturated fatty acids to

break down, producing toxins such as acrolein and free

radicals that oxidize the cholesterol and other components of

the fish. The toxic cholesterol content of the steamed salmon

was much higher than that of beef cooked at a high temperature.

 

When oxidized polyunsaturated oils, such as corn oil or

linoleic acid, are added to food, they appear in the blood

lipids, where they accelerate the formation of cholesterol

deposits in arteries (Staprans, et al., 1994, 1996).

Stress accelerates the oxidation of the polyunsaturated fatty

acids in the body, so people who consume unsaturated vegetable

oils and fish will have some oxidized cholesterol in their

tissues. The constant turnover of cholesterol in the tissues

tends to lower the proportion of the toxic oxidized

degradation products of cholesterol, but in hypothyroidism,

the use of cholesterol is slowed, allowing the toxic forms to

accumulate.

Many antioxidant nutrients act like a thyroid supplement did

in the 1934 rabbit experiments, preventing atherosclerosis

even when extra toxic cholesterol is given to the animals.

People who eat seafood get much more selenium in their diet

than people who eat nothing from the sea, and selenium is one

of the extremely protective nutrients that prevent

atherosclerosis in animal experiments with excess cholesterol.

 

It is well established that several antioxidant nutrients are

protective factors in heart disease. The medical establishment

has expended a great amount of money and time in the last 60

years fighting the use of vitamin E or selenium for treating

or preventing heart disease, though many physicians now take

vitamin E themselves. But people who study free radical

chemistry recognize that polyunsaturated fats are highly

susceptible to oxidation, and that saturated fats tend to slow

their degradation, acting to some extent as antioxidants.

Several experiments and observations have shown that

cholesterol itself can protect against damaging oxidation of

polyunsaturated fats, protecting DNA and other vital

components of the cell. A consistent program to prevent the

oxidation of cholesterol would have to include all of the

vitamins and minerals that are involved in antioxidant

defense, avoidance of nutrients that exacerbate the

destructive oxidations, and an effort to normalize the

hormones and other factors, such as carbon dioxide, that have

protective effects against free radical oxidation. A low level

of cholesterol might increase susceptibility to the oxidants.

 

The steroids in general, especially those produced in large

amounts, progesterone and DHEA, are important parts of the

antioxidant defenses. Cholesterol, either that produced

internally by the cell, or taken in from the blood stream, is

the precursor for all the steroids in the body. Several of the

major steroid hormones are antiinflammatory, and cholesterol

itself is antiinflammatory. (Mikko, et al., 2002; Kreines, et

al., 1990). Cholesterol also protects against radiation

damage, and many forms of toxin (saponins, cobra venom,

chloroform -- W.G. MacCallum, A Text-book of Pathology, 1937,

Saunders Co.; many more recent studies show that it protects

blood cells against hemolysis -- breakdown of red blood cells

-- caused by heat and other harmful agents; e.g., Dumas, et

al., 2002, Velardi, et al., 1991). Cholesterol, vitamin E,

progesterone, and vitamin D are considered to be

" structural

antioxidants, " that prevent oxidation partly by

stabilizing

molecular structures. One of the basic functions of

cholesterol seems to be the stabilization of mitochondria,

preventing their destruction by stress. Serious stress lowers

ATP, magnesium, and carbon dioxide. When ATP and intracellular

magnesium are decreased, cholesterol synthesis increases.

 

During stress, free fatty acids are released from the tissues,

and circulating in the bloodstream they are highly susceptible

to oxidation. They contribute to the formation of the age

pigment, lipofuscin, which is an oxygen-wasting substance

that's found in the atheroma plaques in the damaged blood

vessels. Iron and calcium accumulation adds to the tissue

damage.

The hemolysis which is promoted by polyunsaturated fats and an

imbalance of antioxidants and oxidants, releases iron and heme

into the blood stream. The incidence of atherosclerosis is

increased when the body iron stores are high (Kiechl, et al.,

1997), probably because of its role in lipid peroxidation and

lipofuscin formation.

Especially when the lining of the blood vessel is too

permeable, because of the influence of polyunsaturated fats,

prostaglandins, estrogen, etc., the heme and iron will enter

the endothelial cells, where the iron will catalyze the

formation of free radicals, and the heme will be broken down

by the enzyme heme oxygenase, into biliverdin, iron, and

carbon monoxide, which can contribute to the oxidative stress

of the cells. Carbon monoxide makes the blood vessel lining

more permeable, allowing fats and fibrinogen to enter the

cells (Allen, et al., 1988).

Although cholesterol is protective against oxidative and

cytolytic damage, the chronic free radical exposure will

oxidize it. During the low cholesterol turnover of

hypothyroidism, the oxidized variants of cholesterol will

accumulate, so cholesterol loses its protective functions.

 

When the metabolic pathways of the steroid hormones were being

worked out, an experimenter perfused an isolated ovary with

blood. When the amount of cholesterol in the blood pumped into

the ovary was increased, the amount of progesterone in the

blood leaving the ovary increased proportionately. In the

healthy organism, cholesterol is constantly being synthesized,

and constantly converted into steroid hormones, and, in the

liver, into the bile salts that are secreted to emulsify fats

in the intestine. Thyroid hormone and vitamin A are used in

the process of converting cholesterol into pregnenolone, the

immediate precursor of progesterone and DHEA. Anything that

interfered with these processes would be disastrous for the

organism. The supply of cholesterol, thyroid and vitamin A

must always be adequate for the production of steroid hormones

and bile salts. When stress suppresses thyroid activity,

increased cholesterol probably compensates to some extent by

permitting more progesterone to be synthesized.

In very young people, the metabolic rate is very high, and the

rapid conversion of cholesterol into pregnenolone, DHEA, and

progesterone usually keeps the level of cholesterol in the

blood low. In the 1930s, a rise in the concentration of

cholesterol was considered to be one of the most reliable ways

to diagnose hypothyroidism (1936 Yearbook of Neurology,

Psychiatry, and Endocrinology, E.L. Sevringhaus, editor,

Chicago, p. 533). With aging, the metabolic rate declines, and

the increase of cholesterol with aging is probably a

spontaneous regulatory process, supporting the synthesis of

the protective steroids, especially the neurosteroids in the

brain and retina.

Many people refer to the structural importance of cholesterol

for " membranes, " and often imply that the membranes are

just

at the surface of the cell (the plasma membrane). But in fact

cholesterol is found in the nucleus in the chromosomes, bound

to DNA and in the nuclear matrix that governs the activation

of genes, and in the mitotic spindle, which regulates

separation of the chromosomes during cell division: without

sufficient cholesterol, cells divide irregularly, producing

aneuploid daughter cells (i.e., they have an abnormal number

of chromosomes). Aneuploidy is now coming to be recognized as

an essential feature of cancer cells. A significant amount of

cholesterol was recently discovered to bind to hemoglobin,

suggesting that it will be found in association with many

other types of protein, when it occurs to anyone to look for

it. Osmotic regulation, which is closely involved in cell

division and other functions, appears to require cholesterol

synthesis.

Around 1985, a big study in Hungary showed that lowering

cholesterol with drugs caused a huge increase in the cancer

death rate. Hundreds of publications appeared in the U.S.

saying that wasn't possible, because low cholesterol is good,

the lower the better. The extreme increase in cancer mortality

in the Hungarian study was probably the result of the drug

that was commonly used at that time to lower cholesterol, but

the pattern of mortality in that study was approximately the

same pattern seen in any group with very low cholesterol. In

the last 20 years, there have been many studies showing that

lowering cholesterol increases mortality, especially from

cancer and suicide, and that people with naturally low

cholesterol are more likely to die from cancer, suicide,

trauma, and infections than people with normal or higher than

average cholesterol.

The increased mortality from accidents and suicide when

cholesterol is lowered is reminiscent of the problems seen in

progesterone deficiency, and it's very likely that a

deficiency of the neurosteroids accounts for it. A deficiency

of progesterone and other neurosteroids (the steroids

synthesized by the nerves themselves) causes depression of

mood and impaired learning ability, among other neurological

changes. As was the case with cancer, the pharmaceutical

industry continues to deny that their anticholesterol drugs

cause suicide, depression, and dementia, but there is a large

amount of evidence from human as well as animal studies

showing that mood and intelligence are depressed by lowering

cholesterol. Simply injecting cholesterol into animals can

improve their learning ability. In the Framingham heart study

of 1894 people extending over a period of about 20 years,

people with cholesterol naturally in the " desirable "

range,

below 200 mg.%, scored lower on " verbal fluency,

attention/concentration, abstract reasoning, and a composite

score measuring multiple cognitive domains " than those

with

higher cholesterol (Elias, et al., 2005).

After the age of fifty, low cholesterol is clearly associated

with an increased risk of dying from a variety of causes. A

study of old women indicated that a cholesterol level of 270

mg. per 100 ml. was associated with the best longevity

(Forette, et al., 1989). " Mortality was lowest at serum

cholesterol 7.0 mmol/l [=270.6 mg%], 5.2 times higher than the

minimum at serum cholesterol 4.0 mmol/l, and only 1.8 times

higher when cholesterol concentration was 8.8 mmol/l. This

relation held true irrespective of age, even when blood

pressure, body weight, history of myocardial infarction,

creatinine clearance, and plasma proteins were taken into

account. "

The next step in studies of this sort should be to see how the

combination of extra thyroid with adequate cholesterol

influences longevity. The rising cholesterol that commonly

occurs with aging is probably only partial compensation for

declining thyroid function, and by optimizing all of the

protective factors, radical changes in the aging process may

be possible.

In the flatworm C. elegans, which is now a very popular animal

for testing aging theories, because its genes and cells have

been thoroughly " mapped, " it was recently found that

adding a

gene that simply allows it to synthesize cholesterol, rather

than depending on food for its sterols, increased its life

span by as much as 131% (Lee, et al., 2005). That would be

like increasing the human lifespan to about 175 years. These

worms are also more resistant than normal to radiation and

heat stress.

The cells of the thymus are extremely sensitive to radiation

and other stressors, and their enrichment with cholesterol

inhibits lipid peroxidation, DNA degradation, and death in

response to radiation (Posokhov, et al., 1992).

Many high altitude regions of the world have high levels of

background radiation, from minerals as well as cosmic rays, so

it has been dogmatically believed that mortality from cancer

and heart disease would increase with altitude, but the

reverse is true. Because oxygen at lower pressure displaces

less carbon dioxide from the blood, the body is able to retain

more carbon dioxide at high altitude. Carbon dioxide protects

against free radicals, and also helps to deliver oxygen to

tissues, to maintain efficient energy production, and to

prevent cellular stress. One study found 18 times higher

incidence of hypertension in low altitude populations than in

high altitude people (Fiori, et al., 2000). For many years,

these principles have been applied in treating atherosclerosis

and other degenerative diseases, in high altitude health

resorts. Even a short period of hypoxic treatment can improve

the body's ability to eliminate atherogenic lipid peroxides,

possibly by improving the stress-resistant functions of the

liver (Meerson, et al., 1988; Aleshin, et al., 1993; Kitaev,

et al., 1999).

I think editors of medical journals generally see themselves

as the purveyors of enlightenment, i.e., as the pushers of the

stylish and prestigious doctrines. (Selectivity of evidence to

serve the received doctrine is the commonest form of

scientific dishonesty.) But because their mental framework is

culturally narrow, they sometimes publish things which later

could turn out to be embarrassing (if inconsistency could

embarrass such types).

The recent discovery that the size of the LDL particle is a

predominant factor in the development of atherosclerosis is

one of those things that the editors and medical professors

should find embarrassing.

Smaller lipoprotein particles have a greater surface area

exposed to the oxidative factors in the serum, and so are more

rapidly degraded into toxic substances. People with larger LDL

particles are remarkably resistant to heart disease, and the

drug companies are looking for a way to turn their

lipoproteins into products. But the conditions that govern the

size of the LDL particles are physically and chemically

reasonable, and are causing confusion among the doctinaire.

 

There have been several studies in India showing that

consumption of butter and ghee is associated with a low

incidence of heart disease; for example, according to one

study, people in the north eat 19 times more fat (mostly

butter and ghee) than in the south, yet the incidence of heart

disease is seven times higher in the south. A study in Sweden

found that the fatty acids in milk products are associated

with larger LDL particles (Sjogren, et al., 2004).

In a 35 day study, when butter (20% of the calories) was

compared to various kinds of margarine (with more trans fatty

acids) in a similar quantity, the LDL particles were bigger on

the butter diet (Mauger, et al., 2003). But in a study of the

habitual diet of 414 people, large LDL particles were found to

be correlated with increased intake of protein, animal fat,

and trans fatty acids (Kim and Campos, 2003).

In a study of the effect of dietary cholesterol on the

atherogenicity of the blood lipids, 52 people were given

either an egg diet (with 640 mg. of extra cholesterol per day)

or a placebo diet for 30 days. Those whose LDL increased the

most on the high cholesterol diet had the largest LDL particle

size (Herron, et al., 2004). They concluded that " these

data

indicate that the consumption of a high-cholesterol diet does

not negatively influence the atherogenicity of the LDL

particle. " A similar study in Mexico found that " Intake

of 2

eggs/d results in the maintenance of LDL:HDL and in the

generation of a less atherogenic LDL in this population of

Mexican children " (Ballesteros, et al., 2004).

The estrogen industry tried to get into the heart disease

business several times over the last half century, and they

are still trying, but the issue of estrogen's harmful effects

on LDL particle size is getting some attention. Estrogen

clearly decreases the size of the LDL particles (Campos, et

al., 1997). The LDL particles also get smaller at menopause,

and in polycystic ovary syndrome, and in preeclamptic

pregnancies, all of which involve a low ratio of progesterone

to estrogen. But there are still journals publishing claims

that estrogen will protect against heart disease, by reducing

the atherogenic response in increasingly mysterious ways.

Occasionally, people have argued not only that estrogen is the

factor that protects women against heart attacks, but that

androgens predispose men to heart disease. One of their

arguments has been that androgens lower HDL, the " good "

form

of cholesterol. However, there are many studies that show that

testosterone and DHEA (Arad, et al., 1989) are protective

against atherosclerosis. The LDL particle size is increased by

androgens, and postprandial triglyceridemia is decreased

(Hislop, et al., 2001).

The studies in the 1930s that showed the protective effects of

thyroid hormone against atherosclerosis and heart disease have

sometimes been interpreted to mean that the thyroid is

protective because it lowers the cholesterol, but since

cholesterol is protective, rather than harmful, something else

explains the protective effect. Ever since the time of

Virchow, who called atherosclerosis arteritis deformans, the

inflammatory nature of the problem has been clear to those who

aren't crazed by the anticholesterol cult. We are all subject

to a variable degree of inflammatory stimulation from the

endotoxin absorbed from the intestine, but a healthy liver

normally prevents it from reaching the general circulation,

and produces a variety of protective factors. The HDL

lipoprotein is one of these, which protects against

inflammation by binding bacterial endotoxins that have reached

the bloodstream. (Things that increase absorption of endotoxin

-- exercise, estrogen, ethanol -- cause HDL to rise.)

Chylomicrons and VLDL also absorb, bind, and help to eliminate

endotoxins. All sorts of stress and malnutrition increase the

tendency of endotoxin to leak into the bloodstream. Thyroid

hormone, by increasing the turnover of cholesterol and its

conversion into the protective steroids, is a major factor in

keeping the inflammatory processes under control.

In hypothyroidism, the pituitary secretes more TSH to activate

the thyroid gland, but TSH itself has a variety of

pro-inflammatory actions. The C-reactive protein (CRP), which

is recognized as a factor contributing to atherosclerosis, is

increased in association with TSH. CRP activates mast cells,

which are found in the atheroma plaques, to produce a variety

of pro-inflammatory substances, including histamine.

The belief that cells are controlled by a plasma membrane, and

that cholesterol's main function is to participate in that

membrane, has led to a culture that treats cholesterol

physiology with little curiosity. A different perspective on

the cell starts with a recognition of the lipophilic nature of

the structural proteins (not " membrane proteins, " but

things

like cytoskeleton-cytoplasmic ground substance, spindle,

centrosome-centrioles, nuclear matrix, etc.), with which

lipids interact. Modifying an extremely complex system, the

living substance, cholesterol participates in complexity, and

must be investigated with subtlety. I suspect that the

physiological meaning of cholesterol has to do with movement,

stability, differentiation, memory, and sensitivity of the

parts of the cells, that is, with everything physiological.

 

The functions of cholesterol parallel the functions of other

sterols in plants and other types of organism. Its functions

have been refined and extended with the development of other

steroids, such as progesterone, as biological requirements

have evolved, but cholesterol is still at the center of this

system. To deliberately interfere with its synthesis, as

contemporary medicine does, reveals a terrible arrogance.

Many participants in the cholesterol-lowering cult believe

that they have succeeded in hijacking our science culture, but

when the patents on another generation of their drugs have

expired, the cult could begin to fade away.

 

REFERENCES

Biochim Biophys Acta. 1996 Sep 13;1297(1):77-82. Effect of

cholesterol on rhodopsin stability in disk membranes. Albert

AD, Boesze-Battaglia K, Paw Z, Watts A, Epand RM.

J Hepatol. 2003 May;38(5):623-8. A possible role of

cholesterol-sphingomyelin/phosphatidylcholine in nuclear

matrix during rat liver regeneration. Albi E, Cataldi S, Rossi

G, Magni MV. " In nuclear matrix, cholesterol and

sphingomyelin

are respectively five and three times higher than those

present in chromatin; the amount of phosphatidylcholine, which

it is enriched in saturated fatty acids, is lower, thus

indicating a less fluid structure. " " The nuclear matrix

lipids

are independent from chromatin lipids; the ratio

cholesterol-sphingomyelin/phosphatidylcholine is higher and,

as a consequence, nuclear matrix is less fluid in relation to

DNA synthesis, suggesting a specific role of nuclear matrix as

a structure involved in DNA duplication. "

Gynecol Endocrinol. 1997 Aug;11(4):281-8. Impact of combined

hormone replacement therapy on serum lipid metabolism: new

aspects. Alexandersen P, Haarbo J, Christiansen C.

J Vasc Surg. 1988 Jan;7(1):139-52. The effect of cigarette

smoke, nicotine, and carbon monoxide on the permeability of

the arterial wall. Allen DR, Browse NL, Rutt DL, Butler L,

Fletcher C.

Ziegler's Beitrage, 1913, lvi, 379; 1914, lvii, 201.

Anitschkow, N.N.

Arteriosclerosis. 1989 Mar-Apr;9(2):159-66.

Dehydroepiandrosterone feeding prevents aortic fatty streak

formation and cholesterol accumulation in cholesterol-fed

rabbit. Arad Y, Badimon JJ, Badimon L, Hembree WC, Ginsberg HN.

 

Fiziol Zh Im I M Sechenova. 1995 Feb;81(2):47-52. [The unknown

physiological role of carbon dioxide] Baev VI, Vasil'eva IV,

L'vov SN, Shugalei IV.

Am J Clin Nutr. 2004 Oct;80(4):855-61. Dietary cholesterol

does not increase biomarkers for chronic disease in a

pediatric population from northern Mexico. Ballesteros MN,

Cabrera RM, Saucedo Mdel S, Fernandez ML.

Atherosclerosis. 2002 Jun;162(2):425-32. Changes in LDL size

and HDL concentration in normal and preeclamptic pregnancies.

Belo L, Caslake M, Gaffney D, Santos-Silva A, Pereira-Leite L,

Quintanilha A, Rebelo I.

J Clin Pharmacol. 1980 Aug-Sep;20(8-9):487-99. Biochemical and

histological effects of intermittent carbon monoxide exposure

in cynomolgus monkeys (Macaca fascicularis) in relation to

atherosclerosis. Bing RJ, Sarma JS, Weishaar R, Rackl A,

Pawlik G.

Physiol Behav. 2004 Sep 30;82(4):703-11. Hypercholesterolemic

diet applied to rat dams protects their offspring against

cognitive deficits. Simulated neonatal anoxia model. Bohr I.

 

Kardiologiia. 1980 Aug;20(8):48-52. [Molecular mechanisms of

the action of antioxidants in treating cardiovascular

diseases] Burlakova EB.

J Clin Endocrinol Metab. 1997 Dec;82(12):3955-63. Effect of

estrogen on very low density lipoprotein and low density

lipoprotein subclass metabolism in postmenopausal women.

Campos H, Walsh BW, Judge H, Sacks FM. Department of

Nutrition, Harvard School of Public Health, Boston,

Massachusetts 02115, USA. hphac

" Estrogen decreases low density lipoprotein (LDL)

particle

size, and smaller LDL particles are associated with coronary

atherosclerosis. "

J Cell Mol Med. 2002 Oct-Dec;6(4):583-92. Blood histamine is

associated with coronary artery disease, cardiac events and

severity of inflammation and atherosclerosis. Clejan S, Japa

S, Clemetson C, Hasabnis SS, David O, Talano JV.

J Biol Chem. 2003 Sep 5;278(36):33928-35. Epub 2003 Jun 23.

Cholesterol impairs the adenine nucleotide

translocator-mediated mitochondrial permeability transition

through altered membrane fluidity. Colell A, Garcia-Ruiz C,

Lluis JM, Coll O, Mari M, Fernandez-Checa JC.

FEBS Lett. 2004 Feb 27;560(1-3):63-8. Mitochondrial

permeability transition induced by reactive oxygen species is

independent of cholesterol-regulated membrane fluidity. Colell

A, Garcia-Ruiz C, Mari M, Fernandez-Checa JC.

J Mal Vasc. 1996;21(3):181-4. [Effect of cholesterol on the

cellular deformability and osmotic fragility of erythrocytes]

Dumas D, Didelon J, Humbert JC, Gigout T, Rasia RJ, Stoltz JF.

 

Psychosom Med. 2005 Jan-Feb;67(1):24-30. Serum cholesterol and

cognitive performance in the framingham heart study. Elias PK,

Elias MF, D'Agostino RB, Sullivan LM, Wolf PA.

J Neurochem. 2002 Jan;80(1):178-90. Cholesterol-dependent

modulation of dendrite outgrowth and microtubule stability in

cultured neurons. Fan QW, Yu W, Gong JS, Zou K, Sawamura N,

Senda T, Yanagisawa K, Michikawa M.

Nutrition. 2003 Jun;19(6):531-5. In vitro effects of selenite

and mercuric chloride on liver thiobarbituric acid-reactive

substances and non-protein thiols from rats: influences of

dietary cholesterol and polyunsaturated and saturated fatty

acids. Farina M, Soares FA, Feoli A, Roehring C, Brusque AM,

Rotta L, Perry ML, Souza DO, Rocha JB.

Sheng Li Ke Xue Jin Zhan. 1999 Jan;30(1):23-8. [Relationship

between oxysterols and atherosclerosis] [Article in Chinese]

Feng ZH, Cheng S.

Exp Cell Res. 2004 Oct 15;300(1):109-20. Cholesterol is

essential for mitosis progression and its deficiency induces

polyploid cell formation. Fernandez C, Lobo Md Mdel V,

Gomez-Coronado D, Lasuncion MA.

Biochemistry. 1994 Apr 5;33(13):4065-71. A role for

cholesterol as a structural effector of the nicotinic

acetylcholine receptor. Fernandez-Ballester G, Castresana J,

Fernandez AM, Arrondo JL, Ferragut JA, Gonzalez-Ros JM.

Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1567-71.

Memory-enhancing effects in male mice of pregnenolone and

steroids metabolically derived from it. Flood JF, Morley JE,

Roberts E.

Lancet. 1989 Apr 22;1(8643):868-70. Cholesterol as risk factor

for mortality in elderly women. Forette B, Tortrat D, Wolmark

Y.

Biochem Biophys Res Commun. 2003 Jan 31;301(1):212-7. The

canine mast cell activation via CRP. Fujimoto T, Sato Y,

Sasaki N, Teshima R, Hanaoka K, Kitani S.

J Neurooncol. 1999 Jan;41(2):175-80. Serum cholesterol in

cerebral malignancies. Grieb P, Ryba MS, Jagielski J,

Gackowski W, Paczkowski P, Chrapusta SJ.

Atherosclerosis. 2001 Dec;159(2):425-32. Effects of androgen

manipulation on postprandial triglyceridaemia, low-density

lipoprotein particle size and lipoprotein(a) in men. Hislop

MS, St Clair Gibson A, Lambert MI, Noakes TD, Marais AD.

JAMA, 2002;288:2569-2578. Optimal Diets for Prevention of

Coronary Heart Disease Hu FB; Willett WC.

Obstet Gynecol. 1999 Apr;93(4):566-70. Small low-density

lipoprotein particles in women with natural or surgically

induced menopause. Ikenoue N, Wakatsuki A, Okatani Y.

FEBS Lett. 2000 May 12;473(2):249-53. Detection of

lipofuscin-like fluorophore in oxidized human low-density

lipoprotein. 4-hydroxy-2-nonenal as a potential source of

fluorescent chromophore. Itakura K, Oya-Ito T, Osawa T, Yamada

S, Toyokuni S, Shibata N, Kobayashi M, Uchida K.

Indian J Exp Biol. 2001 Aug;39(8):793-7. Selenium

supplementation protects from high fat diet-induced

atherogenesis in rats: role of mitogen stimulated lymphocytes

and macrophage NO production. Kang BP, Mehta U, Bansal MP.

" Similarly, NO levels with LPS+ and LPS- macrophages also

found to be higher in HFD fed group and decreased in group

III. These studies reveal the protective role of selenium in

HFD-induced atherogenic process. "

Circulation. 1997 Nov 18;96(10):3300-7. Body iron stores and

the risk of carotid atherosclerosis: prospective results from

the Bruneck study. Kiechl S, Willeit J, Egger G, Poewe W,

Oberhollenzer F.

Metabolism. 2003 Jun;52(6):693-8. Intake of trans fatty acids

and low-density lipoprotein size in a Costa Rican population.

Kim MK, Campos H.

Z Ernahrungswiss. 1994 Jun;33(2):146-58. The effects of

dietary oils on the fatty acid composition and osmotic

fragility of rat erythrocytes. Kirchgessner M, Stangl GI,

Reichlmayr-Lais AM, Eder K.

Atherosclerosis. 1991 Jan;86(1):85-90. Do antioxidants and

polyunsaturated fatty acids have a combined association with

coronary atherosclerosis? Kok FJ, van Poppel G, Melse J,

Verheul E, Schouten EG, Kruyssen DH, Hofman A. " ... high

PUFA

levels, when insufficiently protected by antioxidants against

peroxidation, may indicate a higher risk of

atherosclerosis. "

Vestn Akad Med Nauk SSSR. 1990;(6):44-7. [Anti-inflammatory

effects of liposomes] Kreines VM, Mel'nikova VM, Margolin IaM,

Mel'iantseva LP, Gladshtein AI, Andriasian BA.

Biochem Biophys Res Commun. 2005 Mar 25;328(4):929-36.

Cholesterol-producing transgenic Caenorhabditis elegans lives

longer due to newly acquired enhanced stress resistance. Lee

EY, Shim YH, Chitwood DJ, Hwang SB, Lee J, Paik YK.

Eur Urol. 1993;23(4):490-501. Influence of cholesterol

derivatives on cytoskeletal organization of human carcinoma

cells. Ludes B, Schmit AC, Cremel G, Lambert AM, Hubert P,

Jacqmin D, Bollack C, Staedel C.

Am J Clin Nutr. 1997 Nov;66(5):1240-9. Effect of

cholesterol-rich diets with and without added vitamins E and C

on the severity of atherosclerosis in rabbits. Mahfouz MM,

Kawano H, Kummerow FA.

Am J Clin Nutr. 2003 Sep;78(3):370-5. Effect of different

forms of dietary hydrogenated fats on LDL particle size.

Mauger JF, Lichtenstein AH, Ausman LM, Jalbert SM, Jauhiainen

M, Ehnholm C, Lamarche B.

Nestle Nutr Workshop Ser Clin Perform Programme.

2004;(9):69-75. Mechanisms of insulin-induced alterations in

metabolism during critical illness. Mesotten D, Van den Berghe

G.

J Clin Endocrinol Metab. 2004 Jan;89(1):219-26. Contribution

of circulating lipids to the improved outcome of critical

illness by glycemic control with intensive insulin therapy.

Mesotten D, Swinnen JV, Vanderhoydonc F, Wouters PJ, Van den

Berghe G.

J Neurochem. 1999 Jun;72(6):2278-85. Inhibition of cholesterol

production but not of nonsterol isoprenoid products induces

neuronal cell death. Michikawa M, Yanagisawa K.

BMC Immunology 2002, 3:13. Decreased inducibility of TNF

expression in lipid-loaded macrophages, Ares MP, Stollenwerk

M, Olsson A, Kallin B, Jovinge S, Nilsson J.

Am J Med. 2000 May;108(7):538-46. Effects of lovastatin on

cognitive function and psychological well-being. Muldoon MF,

Barger SD, Ryan CM, Flory JD, Lehoczky JP, Matthews KA, Manuck

SB.

Clin Biochem. 2004 Jan;37(1):22-6. Cholesterol bound to

hemoglobin in normal human erythrocytes: a new form of

cholesterol in circulation? Nikolic M, Stanic D,

Antonijevic

N, Niketic V.

Integr Physiol Behav Sci. 2000 Apr-Jun;35(2):120-31. Blocking

cholesterol synthesis impairs acquisition of the classically

conditioned eyeblink response. O'Brien WT, Xu G, Tint GS,

Salen G, Servatius RJ.

Free Radic Biol Med. 1995 Oct;19(4):511-6. Cholesterol

protects the phospholipid bilayer from oxidative damage.

Parasassi T, Giusti AM, Raimondi M, Ravagnan G, Sapora O,

Gratton E.

Clin Chim Acta. 1988 Dec 30;178(3):271-82. Increase of

erythrocyte resistance to hemolysis and modification of

membrane lipids induced by hemodialysis. Peuchant E, Salles C,

Vallot C, Wone C, Jensen R.

Biull Eksp Biol Med. 1992 Feb;113(2):136-8. [Modification of

radiation sensitivity of lymphocytes of the rat thymus gland

using cholesterol-enriched autoliposomes] Posokhov VS,

Rozenberg OA, Khanson KP.

J Clin Invest. 1993 Nov;92(5):2386-93. Involvement of the

tyrosinase gene in the deposition of cardiac lipofuscin in

mice. Association with aortic fatty streak development. Qiao

JH, Welch CL, Xie PZ, Fishbein MC, Lusis AJ.

Mol Nutr Food Res. 2005 Mar;49(3):274-84. Coffee consumption

and human health - beneficial or detrimental? - Mechanisms for

effects of coffee consumption on different risk factors for

cardiovascular disease and type 2 diabetes mellitus. Ranheim

T, Halvorsen B. [Coffee increases cholesterol in blood, and is

antioxidant.]

Chem Phys Lipids. 2000 Apr;105(2):121-34. Damage to liposomal

lipids: protection by antioxidants and cholesterol-mediated

dehydration. Samuni AM, Lipman A, Barenholz Y.

Behav Neurosci. 2003 Dec;117(6):1220-32. Cholesterol modifies

classical conditioning of the rabbit (Oryctolagus cuniculus)

nictitating membrane response. Schreurs BG, Smith-Bell CA,

Lochhead J, Sparks DL.

J Nutr. 2002 Jul;132(7):1879-85. A ketogenic diet favorably

affects serum biomarkers for cardiovascular disease in

normal-weight men. Sharman MJ, Kraemer WJ, Love DM, Avery NG,

Gomez AL, Scheett TP, Volek JS.

J Nutr. 2004 Jul;134(7):1729-35. Milk-derived fatty acids are

associated with a more favorable LDL particle size

distribution in healthy men. Sjogren P, Rosell M,

Skoglund-Andersson C, Zdravkovic S, Vessby B, de Faire U,

Hamsten A, Hellenius ML, Fisher RM.

Arterioscler Thromb Vasc Biol. 1996 Apr;16(4):533-8. Oxidized

lipids in the diet accelerate the development of fatty streaks

in cholesterol-fed rabbits. Staprans I, Rapp JH, Pan XM,

Hardman DA, Feingold KR.

Arterioscler Thromb. 1994 Dec;14(12):1900-5. Oxidized lipids

in the diet are a source of oxidized lipid in chylomicrons of

human serum. Staprans I, Rapp JH, Pan XM, Kim KY, Feingold KR.

 

Free Radic Biol Med. 2005 Mar 15;38(6):687-97. The powerhouse

takes control of the cell: Is the mitochondrial permeability

transition a viable therapeutic target against neuronal

dysfunction and death? Stavrovskaya IG, Kristal BS.

Am J Epidemiol. 1988 Dec;128(6):1276-88. Heart disease

mortality among bridge and tunnel officers exposed to carbon

monoxide. Stern FB, Halperin WE, Hornung RW, Ringenburg VL,

McCammon CS.

Biokhimiia. 1988 Sep;53(9):1449-54. [Composition of DNA-bound

lipids in the regenerating rat liver] Struchkov VA,

Strazhevskaia NB.

J Exp Clin Cancer Res. 2004 Jun;23(2):233-40. Reduced

low-density-lipoprotein cholesterol causing low serum

cholesterol levels in gastrointestinal cancer: a case control

study. Tomiki Y, Suda S, Tanaka M, Okuzawa A, Matsuda M,

Ishibiki Y, Sakamoto K, Kamano T, Tsurumaru M, Watanabe Y.

 

Neurosci Res. 2000 Apr;36(4):261-73. Novel brain function:

biosynthesis and actions of neurosteroids in neurons. Tsutsui

K, Ukena K, Usui M, Sakamoto H, Takase M.

J. Experimental Medicine 67:111, 1938. The role of the thyroid

in the regulation of the cholesterol of rabbits. Turner KB,

Present CH, Didwell, DH.

Endocr J. 2005 Feb;52(1):89-94. Subclinical Hypothyroidism may

be Associated with Elevated High-sensitive C-Reactive Protein

(Low Grade Inflammation) and Fasting Hyperinsulinemia. Tuzcu

A, Bahceci M, Gokalp D, Tuzun Y, Gunes K.

Patol Fiziol Eksp Ter. 1988 Jul-Aug;(4):27-9. [Effect of

emotional-pain stress on the level of lipids and

esterification of cholesterol in the blood of rats] [Article

in Russian] Tverdokhlib VP, Ozerova IN, Tvorogova MG, Olfer'ev

AM, Meerson FZ.

Int J Biochem Cell Biol. 1998 Feb;30(2):209-15. The decrease

of liver LDL receptor mRNA during fasting is related to the

decrease in serum T3. van der Wal AM, Bakker O, Wiersinga WM.

 

Lancet. 2005 Jan 1;365(9453):53-9. Protection of hepatocyte

mitochondrial ultrastructure and function by strict blood

glucose control with insulin in critically ill patients.

Vanhorebeek I, De Vos R, Mesotten D, Wouters PJ, De

Wolf-Peeters C, Van den Berghe G.

Gastroenterology. 1991 Aug;101(2):457-64. Cell type-dependent

effect of phospholipid and cholesterol on bile salt

cytotoxicity. Velardi AL, Groen AK, Elferink RP, van der Meer

R, Palasciano G, Tytgat GN.

J Lipid Res. 1998 Oct;39(10):1995-2004. Dietary oxysterols are

incorporated in plasma triglyceride-rich lipoproteins,

increase their susceptibility to oxidation and increase aortic

cholesterol concentration of rabbits. Vine DF, Mamo CL, Beilin

LJ, Mori TA, Croft KD.

Arkh Patol. 1971;33(6):51-5. [Changes in the arterial wall in

rabbits following their prolonged ingestion of native and

oxidized fat (a non-cholesterol model of arteriosclerosis)]

Voskresenskii ON, Vitt VV.

Obstet Gynecol. 1998 Feb;91(2):234-40. Estrogen-induced small

low-density lipoprotein particles in postmenopausal women.

Wakatsuki A, Ikenoue N, Sagara Y.

J Psychosom Res. 1995 Jul;39(5):549-62. Cholesterol and

psychological well-being. Wardle J.

Metabolism. 1998 Jul;47(7):878-82. Relationship between

abnormal cholesterol synthesis and retarded learning in rats.

Xu G, Servatius RJ, Shefer S, Tint GS, O'Brien WT, Batta AK,

Salen G.

Zhonghua Gan Zang Bing Za Zhi. 2002 Apr;10(2):129-31.

[Relationship between plasma carbon monoxide and blood-brain

barrier permeability in cirrhotic rats] [Article in Chinese]

Yang S, Wang J, He B, Fang G, Fu R, Chen X.

Am J Clin Nutr. 2004 Aug;80(2):291-8. Serum cholesterol

concentrations are associated with visuomotor speed in men:

findings from the third National Health and Nutrition

Examination Survey, 1988-1994. Zhang J, Muldoon MF, McKeown RE.

 

Aging Clin Exp Res. 2004 Dec;16(6):472-5. Combined measurement

of serum albumin and high-density lipoprotein cholesterol

strongly predicts mortality in frail older nursing-home

residents. Zuliani G, Volpatol S, Romagnoni F, Soattin L,

Bollini C, Leoci V, Fellin R

 

 

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