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標 題: Cholesterol (II): The Misguided War 膽固醇(II): 誤導的戰爭
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英文版
http://neuro.ohbi.net/med/#cholesterol
http://neuro.ohbi.net/med/cholesterol/cholesterol_the_misguided_war.pdf
http://neuro.ohbi.net/med/cholesterol/cholesterol_the_misguided_war.php
Cholesterol (II): The Misguided War
(膽固醇 (II)：誤導的戰爭)
An atheroma is an unhealthy tissue growth which develops within the
walls of arteries over time in a process called ahterosclerosis. The
atheroma plaque may progresively narrow the lumen (thrombosis) or suddenly
rupture into the lumen causing distal embolization. In certain important and
vulnerable areas like the heart and the brain, either thrombosis or
embolization will result in dysfunction and lead to coronary heart disease
(CHD) and stroke, end eventually death. The atheroma contains white blood
cells, red blood cells, platelets, calcium, and cholesterol, among many
other blood components. The real mechanism of atherogenesis is not yet
clearly understood.
Yet, it is generally believed that "bad" cholesterol, or
low-density lipoprotein (LDL), causes the atheroma plaque, which eventually
resulting in coronary heart disease (CHD), and death. Since the
atherogenesis is a slow process, high LDL at younger age is also believed to
predict an increased risk of CHT at later age. This "cholesterol-heart
hypothesis" or "LDL-CHD hypothesis" is the current basis for the treatment
of high cholesterol level in blood. Hence, to ensure a healthy life, people
are advised to check their blood cholesterol level regularly. The American
Heart Association (AHA) advises, "Everyone age 20 and older should have
their cholesterol measured at least once every 5 years" (2004). The aim is
to keep their blood cholesterol levels in the optimal ranges, less than 100
mg/dL for LDL and less than 200 mg/dL for total cholesterol. If a person's
LDL or total cholesterol concentration remains high, various advice is given
including diet, for example restrict diet cholesterol, living measures, for
example lose weight, exercise, and quit smoking, and finally, the
cholesterol-lowering drugs. The LDL causes the atherosclerosis is the
premise for the current treatment. And the "lower cholesterol the better" is
the guide of current treatment (Pasternak, 2002). However, it is unjustified
to say that LDL causes the atheroma plaque. The truth is that there is no
such a thing as bad cholesterol because neither LDL nor total cholesterol
causes the atheroma.
Cholesterol is absolutely essential for human life. Cholesterol
plays an important role in biosynthesis of steroid hormone, bile acid, and
vitamin D. It is also an essential component of cell membranes; it
stabilizes the cell membranes, and is a component of some receptors on the
cell membranes. Cholesterol acts as an antioxidant (Cranton & Frackelton,
1984) that reduces oxygen damage to cell membranes. As an antioxidant,
cholesterol protects us against free radical damage that leads to many
diseases and cancers. Cholesterol also functions as a detoxicant,
anti-inflammatory, and protective agent in the human body. Cholesterol is
also needed for proper function of serotonin receptors in the brain. The
surprising truth is that cholesterol is not a bad substance to be avoided at
all but rather an important biochemical essential for human health. If
cholesterol is depleted, such as when on cholesterol-lowering medications,
people will suffer from depression, suicide, and violent behavior (Hawthon,
Cowen, Owens, Bond, & Elliott, 1993; Ainiyet, & Rybakowski, 1996).
Cholesterol actually helps protect people from cancer, maintains memory and
well-being, and aids longevity (Graveline, 2004).
First of all, let us assume that there is an association between
LDL and CHD, and find out how this association works? First, the association
between LDL and CHD works only on men, not on women (Hulley, Walsh, &
Newman, 1992). There was no association with women older than forty-seven or
younger than forty. Second, even in men, the association does not work on
the elder men. There was no increased overall mortality with either a high
or low serum cholesterol level among men over forty-seven years of age
(Hulley, Walsh, & Newman, 1992; Krumholz, Seeman, Merrill, Mendes de Leon,
Vaccarino, Silverman et al, 1994; Criqui, & Golomb, 2004). So, if there is
an association between LDL and CHD, it exists only in a limited portion of
human beings: only males younger than fifty --- about one quarter of the
population. But the cholesterol level in the other three quarters of the
population actually does have another assication, surprisingly a reversed
one, or a protective association: "high total cholesterol concentrations are
associated with longevity owing to lower mortality from cancer and
infection" (Weverling-Rijnsburger, Blauw, Lagaay, Knook, Meinders, &
Westendorp, 1997, p. 1119; Gillman, Cupples, Millen, Ellison, & Wolf, 1997).
So, if high LDL predicts or causes the future CHD, how could it become
protective after they turn fifty, and why does LDL not cause CHD in women of
any age?
As is known, the white blood cell count is found increased when the
body is experiencing a bacterial infection, for white blood cells are the
major defense mechanism against bacteria. There might be even a linear
correlation that the severer the infection, the higher the
white-blood-cell-count. For sure it is wrong to say that white blood cells
are the cause of the infection. And treatment aiming at reducing the white
blood cells is definitely on the wrong target. But there might also be
another association that actually has no clear relationship. For example,
the houses price of Vancouver has been increasing for years. At the mean
time, the population of polar bears has steadily declines. Even if these two
were statistically significantly correlated, there is not a significant
association, not to mention that the association is causal. Similarly, even
if when LDL is found associated with atheroma plaque or CHD, it does not
automatically become the cause. It might well be a consequence, a victim, a
witness, a hero, an indicator of something else, or nothing at all.
Then, let us see how significant the association is. Almost every
study finds no connection between blood cholesterol and the degree of
atherosclerosis; those who had a high cholesterol level died as frequently
from atherosclerosis as those who had low cholesterol level (Paterson,
Armstrong, Armstrong, 1963). This non-relationship was found woorldwide
(Cabin, & Roberts, 1982; Marek, Jaegermann, & Ciba, 1962), although a
correlation was exceptionally reported in the famous Framingham study and
became the key milestone in the cholesterol-heart hypothesis: Serum
cholesterol 1, 5, and 9 years antemortem all correlated positively with the
degree of luminal insufficiency in men, while in women only cholesterol 9
years before death correlated significantly. ... Only age was an independent
significant correlate of the extent of coronary atherosclerosis in women For
men, coronary atherosclerotic involvement was independently correlated with
only the serum cholesterol and measures of obesity were the major predictors
of heart size (Feinleib, Kannel, Tedeschi, Landau, & Garrison, 1979)
But the correlation coefficient between cholesterol and atherosclerosis is
only 0.36. The correlation coefficient is a statistic concept used to
determine the statistic significance of a correlation. It is a measure of
how well trends in the predicted values follow trends in past actual values,
or how well the predicted values from a forecast model "fit" with the
real-life data. If there is no relationship between the predicted values and
the actual values the correlation coefficient is 0 or very low (the
predicted values are no better than random numbers). As the strength of the
relationship between the predicted values and actual values increases, so
does the correlation coefficient. A perfect fit gives a coefficient of 1.0.
Thus, given a value between 0 and 1, the higher the correlation coefficient,
the stronger the correlation. Usually it requires 0.45 or higher to predict
a possible relationship. A correlation coefficient value of 0.36 indicates a
desperately weak relationship, if any.
Next let us assume that LDL should cause CHD, and ratiocinate
accordingly. Cholesterol flows in blood vessels, that is, in arteries,
veins, and capillaries. First rationcination: if cholesterol were the cause
of atherosclerosis, then, cholesterol might cause atherosclerosis in
arteries, veins and capillaries, especially vines, given that the vain have
slower blood-flow, less turbulance, and lower presser than arteries so that
cholesterol has more time contacting with the venous wall and hence should
be more ready to precipitate on them. But atherosclerosis only presents in
arteries, not in vein or cappilaries. Yet, if a segment of vein is grafted
between arteries, as in bypass surgery, the venous graft is soon
arterialized and become atherosclerotic. Thus, rather than on the
cholesterol, the cause of atherosclerosis is the vessels -- the artery.
Why are arteries so susceptible to atherosclerosis? The arteries, with their
higher blood pressure, faster blood flows, turbulent flows at bifurcations,
and all the oxidation pressure and free radicals in the oxygenated blod, are
prone to injury. As a component of cell membrane and antioxidant,
cholesterol tries to repair the injured arterial walls. If there is low
cholesterol in blood, the atheroma will still be formed, however, only with
less cholesterol. Thus, cholesterol is not causing the damage on arterial
wall; cholesterol is only being deposited on arterial wall where damage has
already occurred (McCully, & McCully, 1999). In this sense, cholesterol
correlates with atheroma as a repairperson, like firefighters protecting
against the fire, or white blood cells killing the invading bacteria.
Cholesterol is not the cause of the atheroma, but is actually protecting
against the arterial wall damage. And there is evidence that vitamin Bs can
prevent arteriosclerosis lesions from getting worse (Peterson, & Spence,
1998), because the vitamins prevent arterial wall from damages.
Second ratiocination: if high cholesterol cause CHD, then people
with high cholesterol would significantly suffer or die from more severe CHD
than people with lower cholesterol. People with Familial
Hypercholesterolemia, a genetic disease, are characterized by a high
cholesterol level in their blood. Tracing large pedigree in Netherlands back
to a single pair of ancestors in the nineteenth century, a study examined
250 members of pedigree twenty years and older with 0.5 probability of
carrying a mutation for Familial Hypercholesterolemia (Sijbrands,
Westendorp, Defesche, Meier, Smelt, & Kastelein, 2001). About forty per cent
of the untreated patients with Familial Hypercholesterolemia reached a
normal life span. Their standardized mortality ratio was similar to normal
population. They did not suffer or die from more severe CHD than normal
people. The normal mortality pattern of people with high cholesterol
suggests that cholesterol or LDL does not "cause," or more precisely, has no
correlation at all with, CHD.
Third rationcination: if cholesterol should causes CHD, then people
with a similar cholesterol level will have similar CHD prevalence. In a
study, 11,900 Japanese males, between 45 to 69 years old, living in Japan,
Hawaii, and California, were checked for cholesterol which showed a
Japan-Hawaii-California gradient. At each cholesterol level, the greater
prevalence of CHD in California persisted (Marmot, Syme, Kagan, Kato, Cohen,
Belsky, 1975; Marmot, Syme, 1976). The prevalence of CHD did not correlate
with the cholesterol level. It other words, people with similar cholesterol
level do not suffer a similar frequency of CHD. This suggests that the
cholesterol does not relate with CHD.
We do not take the firefighter as the cause of the fire. Nor do we
think that white blood cells cause the infection. So why should we take
cholesterol as enemy, ignoring all its essentiality, and eliminating it when
we see it working hard to repair our arteries? Twenty-five years ago, it was
recognized that, all well-controlled trials of cholesterol-reducing diets
and drugs have failed to reduce coronary (CHD) mortality and morbidity.
Nevertheless, commercial, professional, and even government-sponsored
propaganda continues. It can be comprehended that promoting the cocept of
"bad cholestrol" is beneficial to certain industries -- food, drug, and
health-care providers. The worse people think their cholesterol is, the more
these industries might profit. Professor Sir John M. McMichael advocated,
"[o]fficial medical endorsement of these cholesterol reducing measures
should be withdrawn" (McMichael, 1979, p. 173). He said,
All published efforts to help by drug or dietary reduction of blood
cholesterol have uniformly and convincingly failed. ... [W]e need a fresh
approach to the problem at scientific level and should avoid further public
speculation and confusion by repeated propaganda through the media until we
have clarified our own professional minds and shaken off what most critical
doctors are likely to regard as an untenable hypothesis of causation
(McMichael, p. 175).
And this approach is ignored in the commercial, professional, and
government-sponsored propaganda today.
(Neuro 黃學仁 March 29, 2005)
Reference
Ainiyet, J., & Rybakowski, J. (1996). Low concentration level of total serum
cholesterol as a risk factor for suicidal and aggressive behavior. Psychiatr
Poland, 30, 499-509.
American Heart Association. (2004). What Are Healthy Levels of Cholesterol.
Retrieved March 21, 2005, from American Heart Association Web site:
http://www.americanheart.org/presenter.jhtml?identifier=183
Cabin, H. S., Roberts, W. C. (1982). Relation of serum total cholesterol and
triglyceride levels to the amount and extent of coronary arterial narrowing
by atherosclerotic plaque in coronary heart disease: Quantitative analysis
of 2,037 five mm segments of 160 major epicardial coronary arteries in 40
necropsy patients. American Journal of Medicine, 73, 227-234.
Cranton, E. M., & Frackelton, J. P. (1984). Free radical pathology in
age-associated diseases: Treatment with EDTA chelation, nutrition and
antioxidants. Journal of Holistic Medicine, 6, 6-37.
Criqui, M. H., & Golomb, B. A. (2004). Low and lowered cholesterol and total
mortality. Journal of the American College of Cardiology, 44, 1009-1010.
Feinleib, M., Kannel, W. B., Tedeschi, C. G., Landau, T. K., Garrison, R. J.
(1979). The relation of antemortem characteristics to cardiovascular
findings at necropsy: The Framingham Study. Atherosclerosis. 34 145-157.
Gillman, M. W., Cupples, L. A., Millen, B. E., Ellison, R. C., & Wolf, P. A.
(1997). Inverse association of dietary fat with development of ischemic
stroke in men. Journal of American Medical Association, 278, 2145-2150.
Graveline, D. (2004). Lipitor, thief of memory: Statin drugs and the
misguided war on cholesterol. Haverford, PA: Infinity.
Groves, B. (April 11, 2004). Retrieved March 20, 2005, from Part 7: So where
does that leave heart disease? of Second Opinion Web site:
http://www.second-opinions.co.uk/cholesterol myth 7.html
Hawthon, K., Cowen, P., Owens, D., Bond, A., & Elliott, M. (1993). Low serum
cholesterol and suicide. British Journal of Psychiatry, 162, 818-825.
Hulley, S. B., Walsh, J. M., & Newman, T. B. (1992). Health policy on blood
cholesterol: Time to change directions. Circulation, 86, 1026-1029.
Krumholz, H. M., Seeman, T. E., Merrill, S. S., Mendes de Leon, C. F.,
Vaccarino, V., Silverman, D. I., et al. (1994). Lack of association between
cholesterol and coronary heart disease mortality and morbidity and all-cause
mortality in persons older than 70 years. Journal of American Medical
Association, 272, 1335-1340.
Marek, Z., Jaegermann, K., & Ciba, T. (1962). Atherosclerosis and levels of
serum cholesterol in postmortem investigations. American Heart Journal, 63,
768-774.
Marmot, M. G., Syme, S. L., Kagan, A., Kato, H., Cohen, J. B., Belsky, J.
(1975). Epidemiologic studies of coronary heart disease and stroke in
Japanese men living in Japan, Hawaii and California: Prevalence of coronary
and hypertensive heart disease and associated risk factors. American Journal
of Epidemiology, 102, 514-525.
Marmot, M. G., Syme, S. L. (1976). Acculturation and coronary heart disease
in Japanese-Americans. American Journal of Epidemiology, 104, 225-247.
McCully, K., & McCully, M. (1999). The heart revolution: The B vitamin
breakthrough that lowers homocysteine, cuts your risk of heart disease, and
protects your health. New York: Harper Collins Publisher.
McCully, K. S. (1993). Chemical pathology of homocysteine: I: Atherogenesis.
Annals of Clinical and Laboratory Science, 23, 477-493.
McMichael J. (1979). Fats and atheroma: An inquest. British Medical Journal,
20, 173-175.
Navab, M., Ananthramaiah, G. M., Reddy, S. T., Van Lenten, B. J., Ansell, B.
J., Fonarow, G. C., et al. (2004). The oxidation hypothesis of
atherogenesis: The role of oxidized phospholipids and HDL. Lipid Research,
45, 993-1007.
Paterson, J. C., Armstrong, R., Armstrong, E. C. (1963). Serum lipid levels
and the severity of coronary and cerebral atherosclerosis in adequately
nourished men, 60 to 69 years of age. Circulation, 27, 229-236.
Peterson, J. C., & Spence, J. D. (1998). Vitamins and progression of
atherosclerosis in hyper-homocyst(e)inaemia. Lancet, 351, 263.
Richard, C. P. (2002). The ALLHAT lipid lowering trial: Less is less.
Journal of American Medical Association, 288, 3042-3044.
Sijbrands, E. J. G., Westendorp, R. G. J., Defesche, J. C., de Meier, P. H.
E. M., Smelt, A. H. M., Kastelein, J. J. P. (2001). Mortality over two
centuries in large pedigree with familial hypercholesterolaemia: Family tree
mortality study. British Medical Journal, 322, 1019-1023.
Weverling-Rijnsburger, A. W., Blauw, G. J., Lagaay, A. M., Knook, D. L.,
Meinders, A. E., Westendorp, R. G. (1997). Total cholesterol and risk of
mortality in the oldest old. Lancet, 350, 1119-1123.