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標 題: Cholesterol(I): Diet vs. Blood 膽固醇 (I)：飲食與血液
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英文版
http://neuro.ohbi.net/med/#cholesterol
http://neuro.ohbi.net/med/cholesterol/diet_cholesterol.pdf
http://neuro.ohbi.net/med/cholesterol/diet_cholesterol.php
Cholesterol(I): Diet vs. Blood
(膽固醇 (I)：飲食與血液)
Part of the secret of success in life is to eat what you like and let the
food fight it out inside.
－ Mark Twain (1835 -- 1910)
It is generally believed that taking food high in cholesterol content will
increase the cholesterol level in blood. The "dietary cholesterol is blood
cholesterol" hypothesis is the current basis for dietary recommendation, yet
very few consider whether this is justified. On reviewing the evidence and
the physiology of metabolism, this hypothesis cannot be supported in a
normal person. There is little, if any, connection between dietary
cholesterol and blood cholesterol in normal people. The de facto connection
between diet and blood cholesterol is not as simple as the hypothesis
suggests. It is time to point out that the emperor wears no clothes.
There is much evidence that food cholesterol has no significant
relation with blood cholesterol. For example, eggs are well known for their
high cholesterol content in the yolk: A yolk contains about 210 mg to 280 mg
cholesterol. There is evidence that eating eggs not only will not raise, but
lower the blood cholesterol level. Dr. Ravnskov once used himself as a human
guinea pig to find out how egg consumption influenced his own blood
cholesterol. His usual egg consumption was one or two eggs per day. His
cholesterol value at the start of the experiment was 278 mg/dl. On day one,
he ate one egg; on day two, four eggs; on day three, six eggs; and on days
four to nine, eight eggs per day. The data from his experiment showed that
instead of going up, his cholesterol went down a little to 246 mg/dl
(Ravnskov, 2000). And, this is not an exception. People eating more than
four eggs per week were found to have significantly lower mean serum
cholesterol than those eating one or fewer eggs per week (Kerver, et al.,
2000, as cited in Hasler, 2000).
Not only are these small studies showing no correlation, there are
also big studies supporting that eating eggs does not increase blood
cholesterol level. One very large scale longitudinal community study is the
Framingham Heart Study. Since 1948 and still ongoing, the famous Framingham
Heart Study is a longitudinal study of generations of residents in
Framingham, Massachusetts. Under the direction of the National Heart
Institute (now known as the National Heart Lung and Blood Institute, NHLBI)
of America, this study was designed to investigate the risk factors for
heart disease. In 1961, a high blood cholesterol level was found to be a
risk factor in coronary heart disease through this study. However, on
reviewing the original material of this study on the blood cholesterol
distribution curve of each of the 912 subjects and their estimated egg
consumption, it is concluded that "within the range of egg intake of this
population, differences in egg consumption were unrelated to blood
cholesterol level" (Dawber, Nickerson, Brand, & Pool, 1982, p. 617).
Not just eggs, our diet actually has little to do with our blood
cholesterol. In another large scale community study, the Tecmseh Study at
Tecmseh, Michigan, 24-hour dietary recall interviews were conducted among
957 men and 1,082 women. It was concluded that cholesterol levels are
"unrelated to quality, quantity, or proportions of diet consumed" in the
24-hour recall period (Nichols, Ravenscroft, Lamphiear, & Ostrander, 1976,
p. 1384).
Meta-analysis is a combination of many studies with same subjects.
From a meta-analysis of 224 published studies between 1966 and 1994 on 8,143
subjects in 366 independent groups (Howell, McNamara, Tosca, Smith, &
Gaines, 1997), Dr. McNamara concluded that the "restriction of foods rich in
dietary cholesterol is now proven to have little -- if any scientific
justification" (Food Safety Network, 1997, Para 12).
Dr. Ancel Keys, dubbed "Mr. Cholesterol," is the very patriarch
who, for the first time, postulated the correlation between coronary heart
disease and high blood cholesterol levels in the 1950s (Center for Disease
Control Morbidity and Mortality Weekly Report, 1999). Who else would be more
worth quoting? "There's no connection whatsoever between cholesterol in food
and cholesterol in blood. None. And we've known that all along. Cholesterol
in the diet doesn't matter at all unless you happen to be a chicken or a
rabbit" (Keys, 1997, as cited in Egg Nutrition Center, 1997, p. 1; Kendrick,
2002, p. 1; Food Safety Network, 1997, Para 7).
And I am not alone; Health Canada is with me. Quite different from
the Dietary Guidelines for Healthy American Adults advocated by American
Heart Association (AHA) which "recommends < 300 mg/d[ay] on average’’
(Krauss, Eckel, Howard, Appel, Daniels, Deckelbaum, et al., 2001, p. 136),
Canada's Food Guidelines for Healthy Eating (Office of Nutrition Policy and
Promotion, 2002) produced by Health Canada, has never specified an upper
limit for daily dietary cholesterol, because Health Canada believes that
rather than dietary cholesterol, there are other factors more powerful to
determine the cholesterol levels in blood (McDonald, 2004).
To quote from “Fats and Cholesterol” by the Department of Nutrition,
Harvard School of Public Health,
Scientific studies have shown that there is only a weak relationship between
the amount of cholesterol a person consumes and their blood cholesterol
levels or risk for heart disease. For some people with high cholesterol,
reducing the amount of cholesterol in the diet has a small but helpful
impact on blood cholesterol levels. For others, the amount of cholesterol
eaten has little impact on the amount of cholesterol circulating in the
blood (Fats and cholesterol, 2004, p. 4)
It should be noted that a hypothesis or scientific statement is
quite different from a competition between two sports teams where the team
that gets the highest score wins. If a scientific hypothesis is sound, it
must agree with all observations. Even one observation not supporting a
hypothesis is enough to disprove it. Thus, scientists claiming that
"increase dietary cholesterol will increase blood cholesterol (in normal
population)" should be ready to modify their statement even if there is only
one person (in normal population) that does not show increased blood
cholesterol level despite a diet high in cholesterol.
Then, why does ingesting cholesterol not raise the blood
cholesterol level? This can be made understandable through examining
cholesterol metabolism. First, the amount of dietary cholesterol, when
comparing to endogenous cholesterol, is insignificant. The secreted bile
contains one to two grams of cholesterol everyday (Guyton, 1991), equivalent
to eight to ten eggs. Although dietary cholesterol does contribute, for
example, 300 mg a day according to Dietary Guidelines for Healthy American
Adults, the majority of cholesterol delivered to the intestine is derived
from bile. Thus, restricting diet cholesterol from 300 mg to even 0 mg, when
compared to the bile cholesterol, is not significant at all.
Furthermore, the absorption of intestinal cholesterol is variable
and limited. Cholesterol is insoluble in water. It has to form micelles with
bile salts and phospholipids before it can be absorbed. So, the bile salt
availability may influence the absorption. Moreover, instead of passive
diffusion, absorption of cholesterol involves receptors and channels
(Niemann-Pick type C1 Like 1 Protein: NPC1L1) on intestinal cells and the
absorption process requires energy to do active transportation. Even when
cholesterol is present in the intestine cell wall channel, the intestine
cell still may reject it (by ATP-binding cassette, sub-family G, member 5:
ABCG5, and member 8: ABCG8) (Cohen, 2004). The cholesterol absorption is
determined by availability of these absorption devices, and there are
personal and genetic variations, and many other inhibiting or enhancing
factors may be involved.
Second, our body has a self-control system for cholesterol
synthesis. To maintain a rather constant plasma cholesterol level when
cholesterol is ingested, the rising concentration of cholesterol inhibits
the most essential enzyme for endogenous synthesis of cholesterol,
3-hydroxy-3-methylglutaryl CoA reductase (HMGR), thus providing an intrinsic
feedback control system to regulate cholesterol synthesis. As a result, the
plasma cholesterol level usually does not fluctuate upward or downward more
than 15 per cent, though the response of individuals differs markedly
(Guyton, 1991).
The absorbed cholesterol has four possible fates once it reaches
the liver: mostly, up to more than 80 per cent is converted into bile acids;
tenth as much bile acids is directly secreted as cholesterol into bile
juice; it can be esterified -- became cholesterol esters -- and stored
locally in liver cells; or it can be packaged into very low density
lipoprotein (VLDL) and secreted into blood. After secreted into blood, at
peripheral vascular endothelium surface, VLDL is changed into VLDL remnants.
Half of VLDL remnants are removed by the liver cell with LDL receptors
(LDLR), and the remainder mature into LDL. An estimated 70 per cent of
circulating LDL is also cleared by the liver cells with LDLR by binding
their apolipoprotein part, apo B-100, to the receptors (Rader, Cohen, &
Hobbs, 2003). Thus, after all these understandings, how can the diet affect
cholesterol levels, (which is less than one-seventh of total intestine
cholesterol which is absorbed variably,) influence the blood LDL level,
after less than ten per cent of the absorbed cholesterol being transformed
into VLDL, after half of the VLDL being converted into LDL at peripheral
sites, and after most of the LDL being then removed from blood into liver
cells?
Then, how did scientists conclude that "food high in cholesterol
content will increase the (total and bad) cholesterol level in blood?" They
were probably misled by Familial Hypercholesterolemia and other hereditary
diseases characterized by high blood cholesterol which responds to
cholesterol intake. People with familial hypercholesterolemia must have been
encountered in the studies of 1950s, for there is a frequency of one
hypercholesterolemia in every 200 to 500 persons (Marks, Wonderling,
Thorogood, Lambert, Humphries, & Neil, 2000; Lansberg, Tuzgol, Ree,
Defesche, & Kastelein, 2000), and they did not know much about these
diseases at that time. Familial hypercholesterolemia and many other
indistinguishable clinical hypercholesterolemias are caused by a variety of
genes that affects receptors, enzymes, or proteins at various levels of
cholesterol metabolism. Researchers in the 1950s did not exclude these
hypercholesterol persons from the normal population; they just thought
hypercholesterolemia is a feature of the normal population. Thus, a
conclusion based on the most significant findings of those with genetic
hypercholesterolemia, when extrapolated to a "normal" population, can be
false. So, average data obtained from mixed populations of normal and
pathological values should not be used to advise the normal majority of that
population (Reiser, 1978).
But, why is the media today still advocating the correlation
between dietary and blood cholesterol? The answer might lie in who has the
resources to buy media time. There are profits in food and pharmaceutical
industries if there is a need for low cholesterol food or
cholesterol-lowering drugs. The more people believe that it will make them
healthy, the more profit these industries may make. Surely these industries
have resources to utilize the media. Moreover, many researchers receiving
funds from these industries, might do research in a certain direction; at
least the unwelcome research is less supported. Most importantly, there are
advocators that do not differentiate between genetic hypercholesterolemia
and normal people. And most people, including health care providers, just
blindly follow the messages they heard. It is true that a
cholesterol-restricted diet or even cholesterol-lowering medications might
be helpful for those who have hereditary hypercholesterolemia, including but
not limited to Familial Hypercholesterolemia. But, for a normal people,
dietary cholesterol is harmless.
From the results of diet-blood cholesterol studies, small and big,
from the attitude of many leading persons and institutes involving in
cholesterol-studies, including Harvard and Health Canada, from the current
knowledge of physiology and metabolism of cholesterol, and from the possible
mistakes in history and biases of profiting groups, we can now comprehend in
depth how and why diet cholesterol has little impact on blood cholesterol
level, and understand why it was and is still reported the other way. As
Ravnskov states, "if you want to know something you must look at all the
premises yourself, listen to all the arguments yourself, and then decide for
yourself what seems to be the most likely answer. You may be easily led
astray if you ask the authorities to do this work for you" (Ravnskov, 2000,
epilogue).
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