Skepticism about science and medicine

In search of disinterested science

Archive for March, 2013

STATINS are VERY BAD for you, especially FOR YOUR MUSCLES

Posted by Henry Bauer on 2013/03/29

There is no convincing evidence that what is currently regarded as “high cholesterol” is harmful; rather, cholesterol is actually good for you  at levels (200-260) that current practices seek to lower.

Lip service is paid by official agencies and by drug advertisements to using diet and exercise as the first way to lower cholesterol. In practice, innumerable people are taking statins to that end.
That end can be quite literal, because statins can kill you. Bayer’s statin, Baycol, did kill at least 800 people before it was very belatedly withdrawn from the market:
“Bayer had their statin (cerivastatin, Baycol) approved in June 1997. Within 4 months, Bayer knew that it could cause rhabdomyolysis — muscle wasting and death. But this risk was not noted in the drug’s package insert for another year-and-a-half, and the drug was withdrawn only in August 2001 . . . after some hundreds of acknowledged deaths” and perhaps 100,000 or even more actual deaths.

All statins do much the same sort of thing. Drugs are called statins because they do that sort of thing. All statins have the same type of “side” effects, albeit not to the same degree; and of course dosage also matters.
I am perpetually astonished that anyone would take these drugs after learning about their “side” effects. For instance, one of the daddies of them all, Lipitor, “can cause serious side effects. These side effects have happened only to a small number of people. Your doctor can monitor you for them. These side effects usually go away if your dose is lowered or LIPITOR is stopped [emphases added]”.

Note how this official Lipitor website tries to downplay the risks while guarding against law suits by revealing the essential facts. The admission that the side effects can be serious — “fatal” would however be more accurate — is followed by something like a lie about numbers of people affected, and the doubtfully true insinuation that the side effects can be reversed, and the nice-sounding but meaningless and misleading notion that one’s doctor can “monitor” for them.

The term “side” effect is in itself altogether misleading. Chemicals do what they do irrespective of what we might want them to do or not to do. “Side” effects are just as real as the desired effect. Drugs are supposed to be approved only if they are safe as well as effective, in other words that the “side” effects are not dangerous enough as to outweigh their possible benefits. Lowering cholesterol has not been shown to be of benefit. Therefore any undesirable “side” effects are too many and too much.

But let’s continue with Lipitor’s listing of its “side” effects.
“These serious side effects include:
Muscle problems. . . . weakness, tenderness, or pain that happen without a good reason, especially if you also have a fever or feel more tired than usual. This may be an early sign of a rare muscle problem [emphasis added]”.
Yet “In clinical studies, patients reported the following common side effects . . . . Muscle and joint pain” [emphasis added] and right at the very bottom of the page, “Common side effects are diarrhea, upset stomach, muscle and joint pain, and changes in some blood tests” [emphases added].
In other words, Lipitor doing unpleasant things to muscles is anything but rare.

The CYA* rationale for the manner in which the manufacturer describes Lipitor’s “side” effects is illustrated also by
Call your doctor right away if:
You have muscle problems like weakness, tenderness, or pain that happen without a good reason, especially if you also have a fever or feel more tired than usual”.
How on earth is one to judge whether there’s no good reason? How many of us would not feel embarrassed to “ask our doctor” because we feel weaker and more tired than we might like? With a fever, of course one expects to feel weak and tired. And what does “right away” even mean in this context? Do you feel weaker or more tired “than usual” all of a sudden?
Anyway, it’s one thing to call our doctor “right away”, but getting through is a different matter. The clinic where my (excellent, cautious, exceptionally reasonable and forthcoming) doctor works has one of those robotic phone-answering systems whose first words are, “If this is an emergency, call the hospital”.

Muscle problems are not “side” effects of statins, they are direct effects of statins.
When official statements describe statins as well tolerated, what they mean is that the typical weakness induced by statins can be lived with by many people for varying lengths of time.
But since “high” or “bad” cholesterol is not harmful, why deliberately induce any muscle pain or weakness at all?

The claimed benefits from using statins and lowering cholesterol are based on clinical trials paid for by the manufacturers of statins. Those clinical trials are not be trusted, for a large number of reasons, including that they need be no longer than 6 months and that only two successful trials need be submitted to the Food and Drug Administration — no matter how many unsuccessful trials there had also been!
A comprehensive critique explaining why not to rely on clinical trials in general has been given by Ben Goldacre (MD and Guardian columnist) in Bad Pharma.  Perhaps the most direct proof that these trials are typically biased is that almost every trial concludes that the drug made by the particular sponsor of the trial is not only safe and effective but also better than its competitors. It’s rather like that fictional place (Lake Wobegon) where all the children are above average: All prescription drugs are superior to all the others, if you were to believe the clinical trials.

Even then, those typically biased clinical trials have not shown appreciable benefit for statins. A review of data on 5 common statins showed that they produced an average reduction of mortality risk of only 0.27% per year (Joel Kaufmann, Malignant Medical Myths, pp. 88-90). The risk of non-fatal heart attacks was reduced by only 0.037%, whereas Bufferin reduced that risk by 0.11%, three times better (Kaufmann p. 93).
Those numbers are reductions in absolute risk of all-cause mortality, which is the most meaningful for human patients. It’s not much good to reduce one’s risk of heart disease by, say 50%, if the drug we take increases our risk of death by an equivalent amount; death would come just as soon without treatment, just more expensively. But drug companies invariably report reductions in relative risk, not absolute risk. So trials with pravastatin claim a risk reduction of 22% (relative, compared to controls) when the absolute reduction is only 0.2 – 0.5% (Kaufmann, p. 89).
The very small risk reduction by statins is nowadays ascribed by many researchers to an anti-inflammatory action rather than lowering of cholesterol; but anti-inflammatory action weaker than that of Bufferin, which is cheaper and much safer.

A very general axiom nowadays should be: If you really need to take a drug, take the one that has been on the market for the longest time and has been used by the largest number of people. The newer a drug is, the more likely that it will be withdrawn soon after having been first approved (Dogmatism  in Science and Medicine, Table 5, p. 240 and associated text).

Not only have trials shown that statins are of negligible benefit, the risk of damaging “side” effects is greater at higher doses, another illustration that the “side” effects are just as direct and immediate as the desired effect. Less obviously, “side” effects are also greater when certain other drugs are being taken at the same time; a significant factor since so many people are taking so many prescription and other drugs.

This blog is already long enough. A later posting will explain why the “side” effects invariably accompany the cholesterol-lowering, and how the drug companies have deliberately avoided telling statin users of things to do to lessen the impact of the common “side” effects.

_______________________________________________

*   CYA = Avoid being sued, also known as “cover your arse”

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Cholesterol is good for you

Posted by Henry Bauer on 2013/03/25

That’s why the body makes it. (For a somewhat biased encomium to the benefits of cholesterol, have a look at cholesterol-and-health.com.)

The medical-science literature does not support the conventional wisdom about cholesterol. It’s a myth that
——    high cholesterol causes heart disease
——    lowering your cholesterol will lengthen your life
——    cholesterol blocks arteries
——    high-fat foods raise blood cholesterol and cause heart disease.

Just as with blood pressure, current medical practices concerning cholesterol are not based on good evidence, indeed they run contrary to the best evidence. And again just as with blood pressure, a few popular writings as well as the medical-science literature have been pointing that out for a decade or two or three.

Data from the World Health Organization (The WHO MONICA Project) shows that there is no correlation at all between mortality from heart disease and cholesterol levels:

CholesterolHeartDisease

How then did the mistaken view come about, that “high” cholesterol makes for heart disease?

Just as with blood pressure: Through misinterpretation of statistical data, in particular making the mistake of treating correlation as causation, taking symptoms as the actual cause of illness, and failing to take certain variables into account when looking for correlations.

All this and more was set out in great detail a dozen years ago by Uffe Ravnskov (for what it’s worth, he had earned both an M.D. and Ph.D.) in The Cholesterol Myths: Exposing the Fallacy that Saturated Fat and Cholesterol Cause Heart Disease (New Trends Publishing, 2000). There is a great deal of pertinent information at Ravsnkov’s website. Nearly a hundred doctors and scientists  endorse his heretical views about cholesterol. A comprehensive and critical review of Ravnskov’s book  finds its main points to be sound: “Despite its flaws, The Cholesterol Myths is a very important book. It convincingly demonstrates that there is something seriously wrong with the mainstream theory of heart disease. It . . . makes a compelling case against the use of cholesterol-lowering drugs”. Ravnskov has also discussed in detail  what the causes of heart disease might be.

Graphs like the one shown above can be misleading. Lack of correlation across whole national populations may hide quite different relationships in smaller groups. To determine whether cholesterol levels actually correlate with heart disease, one ought to eliminate all other variables; for instance one might look at males of a certain age and ethnicity with similar lifestyles including diets — individuals who differ only in cholesterol level. Such studies are impossible, because the number of possibly influential variables is too great, but this train of thought shows that one should gather information from as many different studies with different groups as possible. Here are a couple that concur in finding “high” cholesterol innocent.

Among Japanese being treated with a statin, mortality was lowest with total cholesterol at 240-259, and mortality increased markedly when cholesterol was lower than about 180; it increased less markedly with cholesterol levels above about 260.
Even more contrary to the conventional view: “Bad” cholesterol (LDL) between about 120 and 200 made for the lowest mortality, and mortality increased perceptibly when LDL was lower than about 120 and was much higher with LDL below about 80 or above about 200.

MortalityCholesterolKaufmann96

The Framingham (Massachusetts, USA) Heart Study is widely respected because it has monitored cohorts for more than 60 years. As with the Japanese data, the Framingham data indicate that heart disease is not apparent at cholesterol levels lower than about 260:

FraminghamCVDcholesterol

These cites are just a tiny sample of data in the scientific-medical literature contradicting the popularly disseminated view that high cholesterol is bad and that the lower it is, the better. As mentioned in an earlier post, “The Institute of Medicine Report, Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease (2010), finds that none of the commonly used biomarkers is a valid measure of the illness it supposedly tracks. . . . None of the commonly used biomarkers for heart disease are valid indicators of heart disease: . . . not overall cholesterol or LDL (“bad” cholesterol) or HDL (“good” cholesterol) — all those are statistically correlated with cardiovascular disease and mortality, but none of them are correlated 100% with those and none of them is indicated to be a cause of heart disease or a contributor to heart disease” [emphasis added].
Therefore one should not be surprised that lowering cholesterol has not been shown to be of benefit: “There are no valid data on the effectiveness . . . [of] statins” (Järvinen et al., British Medical Journal, 342 [2011] doi: 10.1136/bmj.d2175).

The more one compares the scientific medical literature with what is disseminated by such official agencies as the National Institutes of Health or the Centers for Disease Control & Prevention, the more one finds that the public is being dangerously misled. Definitions of disease and recommendations for treatment run contrary to what the soundest research studies indicate.

Those of us who are not professional researchers are rightly hesitant to question what the experts and their organizations tell us. However, it is worth bearing in mind that experts specialize, to an increasing degree as science progresses, and any given expert knows more and more about less and less, as the saying goes. Researchers seeking vaccines against HIV, for example, don’t concern themselves with the epidemiology of HIV or of AIDS and are therefore unaware that HIV is not correlated with AIDS and is therefore not the cause of AIDS (see The Origin, Persistence and Failings of HIV/AIDS Theory).
Since the experts don’t see the forest, only bits of individual trees, and since their institutions disseminate conclusions and assertions for bureaucratic self-promotion and without independent review, a commonsense approach can serve us well when considering how much credence to give to official pronouncements.
In the case of cholesterol, one might ask, are there other cases where a substance that the body needs, makes, and uses has been implicated in causing disease?
Since the body manufactures cholesterol, there exist feedback mechanisms regulating the process. There could only be too much cholesterol if that regulating system had gone out of whack. What evidence is there that this is the case with levels of cholesterol in the range 200-260, which are associated with the lowest mortality from heart disease?
Since cholesterol is being continually manufactured and used, what evidence is there that the level in blood at any given time is even a meaningful measure of cholesterol-associated reactions and phenomena?
Where is the evidence of benefit from reducing levels in that range of 200-260 to the current aim of 200 or less? Similarly with LDL.
And anyway, why should all individuals be treated to bring their individual characteristics to some population average?

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Placebo

Posted by Henry Bauer on 2013/03/22

In recent years there’s been increasing interest in the mechanism and applications of placebos. Well worth reading is  The Placebo Response: How You Can Release the Body’s Inner Pharmacy for Better Health (by Howard and Daralyn Brody, Harper, 2000).

Here’s an interesting tidbit from the  New Scientist (22 March 2013, issue 2908):

“Placebos for sale
PLACEBOS are now available to the general public ‘”for the first time ever’. . . . ‘Although used in virtually every drug trial this is the first time that these powerful agents have been available on demand.’ They can be purchased online from APlacebo.com of Chelmsford, UK, a company set up “to promote the safe and effective use of placebos”. . . . prices starting at just £5 for the ‘revolutionary’ SMS (text) placebo. A kit for the homeopathic placebo costs £14.99 and comes with instructions on how to dilute it. . . The site also tackles the question: “But I know it’s a placebo – will it still work?” The answer is an emphatic “YES!”, backed by links to yet more prestigious journals reporting exactly this effect.”

The Placebo Response offers some insights into this apparent paradox.

In any case, placebos are far safer than prescription drugs.

 

 

 

 

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“Hypertension”: An illness that isn’t illness

Posted by Henry Bauer on 2013/03/16

The most irrational and people-damaging use of a biomarker  (see “Everyone is sick?”)  is probably that perfectly normal levels of blood pressure are labeled “hypertension”.

Here’s how I came to learn that.
I haven’t had routine annual physical exams for many years and had paid no attention to what my blood pressure (BP) might be. Then one morning I woke to find my left side numb and partly inoperative. Fortunately this turned out to be the most minor of strokes, which had no lasting disabling effect. But when the ambulance had come that morning to take me to the hospital, my BP had been at a level that greatly alarmed everyone — over 200! (systolic).

Some little while later I visited a periodontist for “root lengthening” surgery, recommended by my dentist to possibly save a tooth. I’ve long resisted any periodontal work, and was very unhappy to be there. The nurse took my BP and immediately rushed to get the periodontist: I was reading over 190!
I knew about “white coat” syndrome, universally acknowledged by doctors and others: BP is always high when one first visits a doctor because of a certain degree of apprehension.
Since I knew that I definitely and badly wanted not to be there, I tried to explain that >190 only reflected temporary emotion. But the periodontist — to my enormous relief! — decided that he couldn’t do surgery under these circumstances, and advised me to see my physician as soon as possible.

We happened to have at home a wrist-fastened BP measuring device that we had used while caring for a parent, so for several weeks I monitored my BP many times throughout the day. That was surprising and informative. For one thing, this device — like all BP measuring machines — gives instructions to rest for 15 minutes before measuring BP, which of course is not done when one goes to the doctor’s office. At any rate, my BP at reasonable rest is anywhere between 120 and 160. It varies markedly over time, by several units or even a couple of tens of units within 10 or 15 minutes.
(I checked the accuracy of the wrist monitor on several occasions against more conventional upper-arm devices. The wrist machine tends to read a bit higher than those but is not far off.)

One evening I had been sitting for more than an hour, engrossed in an exciting TV movie. I hadn’t measured BP for some time, so reached for the machine and had a look. A bit over 200!
After the vicarious excitement of the movie wore off, I was soon back to about 160.
On another occasion my BP went down from 174 to 140 within minutes.

These experiences led me to read up on BP, and to discover that current practices are irrational to the n-th degree. Not only that our BP is routinely measured when we arrive at the doctor’s office, typically in a state of apprehension if not outright fear or panic: much worse is that the very definition of hypertension makes no sense; and that even if it did, there is no evidence that hypertension causes illness or constitutes a illness.

The first datum everyone should know, but apparently doesn’t, is that BP increases with age. Not because one is getting ill, just because one is getting older.
The second bit of information that everyone should know — but evidently doesn’t — is that the official definition of hypertension takes no account of the normal, natural increase of BP with age.
A third datum that doesn’t ever seem to be talked about is that all physiological characteristics vary over quite a range among different yet healthy individuals. What is optimal for one person might not be so for another.

Duane Graveline  is a physician (MD) who worked in the space program and for more than two decades in private practice. His reading of the research literature as well as his own experience made him realize that current practices relating to BP are irrational and harmful.
BP increases naturally with age. A former traditional rule-of-thumb was that normal systolic BP equals one’s age plus 100. Since I was about 80 when I had my minor stroke and my visit at the periodontist, pressures within 10% or so of 180 should not have alarmed anyone.
Graveline also describes how stress, mental perhaps even more than physical, can raise BP very much. During their training, Graveline and his fellow budding flight surgeons held their hand for one minute in melted ice: that physical stress caused the BP of these healthy 25-year-olds to rise to an average of 235/135 (systolic/diastolic).
A mental test involved simply subtracting 7 sequentially from 100, as rapidly as possible. This raised their average BP to 245/140.

If medical practices were evidence-based — a common mantra nowadays — then no one would ever be diagnosed as having hypertension unless their BP, measured after 15 minutes of quiet rest and in absence of mental stress, were frequently and significantly in excess of their age plus 100.
By contrast, nowadays hypertension is defined without regard to age, and anyone above 140/90 is said to have hypertension and to be a candidate for treatment, typically with drugs. The consequence is that, according to the Institute of Medicine (Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease, 2010), about one-third of American adults including 75–80% of seniors have hypertension — even though none of them may have any feeling of being ill. I suggest that this is absurd. And it is more than absurd, it is dangerous to administer drugs to be taken lifelong that are intended to counteract the normal age-related increase in pressure. In fact, half a century ago when diuretics were first being marketed to reduce blood pressure, many cardiologists disapproved, calling it a dangerous experiment and pointing out that increasing pressure with age might well be a compensation for the decreased flexibility of arteries, so that more pressure is needed to ensure that enough blood reaches the extremities as well as all organs (Jeremy Greene, Prescribing by Numbers: Drugs and the Definition of Disease, Johns Hopkins University Press, 2007, p. 53).

Here is a diagram that illustrates the silly present state of affairs:

BPageSystolic

Several data sets on variations of BP with age all agree roughly with what’s shown in this graph. Some also show ranges of what’s normal, typically 10% or so below or above the population average.  I haven’t found specifics, though, for how far away from the average an individual may be without any symptoms of illness.

Some of the official statements seem as though written by people ignorant of the natural increase in BP with age, for example from the National Institutes of Health:
Hypertension
“Normal blood pressure is . . . lower than 120/80 mmHg most of the time.
High blood pressure (hypertension) is . . . 140/90 mmHg or above most of the time.
If . . . 120/80 or higher, but below 140/90, it is called pre-hypertension.
If you have pre-hypertension, you are more likely to develop high blood pressure.”

Of course you are: All you have to do is live a bit longer.

According to current official declarations, almost everyone has heart disease:

HeartFailureDefinition

Note that “mild” (Class I) HEART FAILURE has no symptoms at all!

Further more, a review of all available data showed that no benefit results from “treating” BP in people with “mild hypertension”, systolic 140-159 and diastolic 90-99 (Jeanne Lenzer, “Cochrane review finds no proved benefit in drug treatment for patients with mild hypertension”, British Medical Journal, 345 [2012] :e5511).
I have no scientific data as to how many people with those numbers are currently being treated for hypertension, but anecdotes suggest that it is more than a few.

The data in the medical science literature give no warrant
for defining hypertension without taking into account
the normal increase of BP with age.
There is no warrant for defining hypertension as other than
markedly above the average for a particular age.
Since the quantitative characteristics of things like BP
vary quite widely among individuals,
there is no warrant for seeking to bring
everyone’s numbers to the same population average.
There is no warrant for believing that the lower BP is, the better.
For instance, the data showed that
for individuals with CVD and diabetes,
BP lower than 140 was actually bad for health.
Current practice is to administer BP-lowering medications
to perfectly healthy people, particularly older ones,
without proven benefit
and with the likelihood of deleterious side effects,
given that the medications are to be taken for life.

This is NOT evidence-based medicine,
it is medical (mal)practice AGAINST THE EVIDENCE.

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Everyone is sick?

Posted by Henry Bauer on 2013/03/13

I might well have titled this post not “Everyone is sick” but “The ‘health-care’ business is sick and sickening”. Healthy people are being told that they are ill, and they are being treated as though they were ill: they are fed physiologically powerful substances that are toxic to various degrees as well as doubtfully beneficial.

There are two interconnected reasons for this:
Natural conditions, particularly those associated with aging (Seeking Immortality? Challenging the drug-based medical paradigm), are pronounced to be sub-optimal (“unhealthy”, “an illness”) and capable of being improved (“treated”, even “cured”).
Illness is judged not by felt or observable symptoms but by biomarkers: things measured by instruments and presumed to reflect some state of ill health, for example blood pressure.

Biomarkers have proliferated as research turns up more and more physiological variables that can be measured. Perhaps the earliest to come into general use was blood pressure. Jeremy Greene has described in fascinating detail the story (beginning in the late 1950s) of measuring blood pressure and thereupon defining and treating hypertension. Shortly thereafter came blood-sugar measuring and the defining and treating of diabetes. Not long after that, measuring cholesterol levels and seeking ways to lower them (Prescribing by Numbers: Drugs and the Definition of Disease, Johns Hopkins University Press, 2007).

The general presumption is that “high” blood pressure, hypertension, is harmful; that it is itself — or at least causes — cardiovascular disease (CVD); that lowering high blood pressure is beneficial to health.
Similarly, it is presumed that elevated levels of blood sugar indicate a tendency to diabetes, and that this can be staved off or even reversed by lowering blood-sugar levels, and that this improves health and potential life-span.
Again, it is presumed that high levels of cholesterol indicate a tendency for plaques to form inside the arteries, and that it is beneficial to health to lower cholesterol levels in the blood.

We are so accustomed to this line of thinking that it may seem remarkable to discover that the evidence in favor of these presumptions is slim to none, and that practices based on those presumptions may be causing harm rather than aiding health. Nevertheless, that’s what the evidence is.

The Institute of Medicine Report, Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease (IOM 2010), finds that none of the commonly used biomarkers is a valid measure of the illness it supposedly tracks. As to subsequent treatment, Järvinen et al. have pointed out that “There are no valid data on the effectiveness . . . [of] statins, antihypertensives, and bisphosphanates” (the last, e.g. Fosamax, are prescribed against osteoporosis) — British Medical Journal, 342 (2011) doi: 10.1136/bmj.d2175.
That last quote is surely an astonishing assertion, given that innumerable individuals are being fed statins and blood-pressure drugs and bisphosphanates not because they feel ill in any way but purely on the basis of levels of biomarkers (bone density in the case of bisphosphanates).

That Institute of Medicine Report can be downloaded free at the National Academies Press website, or purchased as a volume of some 336 pages (ISBN 978-0-309-15129-0; ed. Christine M. Micheel & John R. Ball; 2010). The provenance seems as authoritative as one can get, since it was prepared for the Committee on Qualification of Biomarkers and Surrogate Endpoints in Chronic Disease; Board on Health Care Services; Board on Health Sciences Policy; Food and Nutrition Board, under the auspices of the Institute of Medicine, a division of the National Academies, “Advisers to the Nation on Science, Engineering, and Medicine”.
Possibly to demonstrate expertise and authority, the Report is not welcoming to readers, especially lay readers; it is virtually unreadable: unfocused, repetitive, altogether badly organized, replete with jargon. The conclusions of greatest interest to potential patients are neither concisely nor clearly stated; they are best divined by thinking about the implications of the various sets of Recommendations. For example:

“Recommendation 5:
5a. Congress should strengthen the FDA’s [Food and Drug Administration] authority to request and enforce postmarket surveillance across drugs, devices, and biologics when approvals are initially based on putative surrogate endpoint data.
5b. Congress should grant the FDA authority to request studies and sufficient authority to act on the results of studies on consumer understanding of claims on foods and supplements.”

What 5a refers to is that drugs and devices are approved on the basis of inadequate trials, so that safety and efficacy could be discovered only after sufficiently large numbers of patients have been exposed to them, but there is no system for monitoring actual performance of drugs and devices once they have been approved. Congress legislated that drug companies must pay the FDA the costs of evaluating requests for initial approval of drugs, but Congress also forbade the FDA from using those funds to monitor performance of the drugs after they have gone into general use. So the possibly fatal “side” effects of drugs become known to the FDA and the public more or less as a matter of chance. There are many examples where knowledge of harm, and later withdrawal off drugs, came only years after some unknown number of individuals had suffered damage, sometimes death. Thus Bayer had their statin (cerivastatin, Baycol) approved in June 1997. Within 4 months, Bayer knew that it could cause rhabdomyolysis — muscle wasting and death. But this risk was not noted in the drug’s package insert for another year-and-a-half, and the drug was withdrawn only in August 2001 (IOM 2010: 205-6), after some hundreds of acknowledged deaths and as many as 100,000 estimated or possible deaths.

What 5b means is that the Food and Drug Administration cannot presently safeguard consumers against unwarranted health claims on food packaging, in some part because the validity of the claims is not known. FDA doesn’t have the resources to do the needed studies itself, and has to rely on the product manufacturers for information.

“Recommendation 6:
6a. The U.S. Department of Health and Human Services should facilitate a coordinated, department-wide effort to encourage the collection and sharing of data about biomarkers for all uses, including drugs, biologics, devices, and foods.
6b. The FDA in coordination with other federal agencies should build needed data infrastructure and surveillance systems to handle the information necessary to gain sufficient understanding of the effects of biomarker use.”

In other words: Even though biomarkers are used universally as measures of health and illness and general physiological status and action, it is not known whether these practices are valid.

In fact, they are known to be NOT valid when employed in the manner most relevant to patients. IOM 2010 points out that biomarkers are used in several ways, for example as an initial screening for potentially useful drugs. Biomarkers are known to be associated in some way with certain conditions, so if a potential medication has no effect on a pertinent biomarker, then it is highly unlikely to be of use in treating that condition. There is nothing to criticize about such a use, nor about research on biomarkers. What does matter profoundly is when a biomarker is used to diagnose illness and treatment is based on that biomarker.

All that’s generally known about biomarkers is that they are associated in some way, correlated, with some physiological condition. For example, people with higher blood pressure have a higher mortality. But as with all statistical associations, this does not demonstrate cause and effect, it does not demonstrate that high blood pressure causes earlier death. It might be that there is some underlying factor that causes both higher mortality and higher blood pressure. In fact there is: increasing age brings both higher blood pressure and higher mortality.

Burrowing into IOM 2010 reveals that none of the commonly used biomarkers are valid for diagnosis of the condition that they are in practice used to diagnose. For example:
The size of cancer tumors is not a measure of how far the disease has advanced or what the prognosis is.
None of the commonly used biomarkers for heart disease are valid indicators of heart disease: not C-reactive protein, not troponin, not overall cholesterol or LDL (“bad” cholesterol) or HDL (“good” cholesterol) — all those are statistically correlated with cardiovascular disease and mortality, but none of them are correlated 100% with those and none of them is indicated to be a cause of heart disease or a contributor to heart disease.

In common parlance, biomarkers are often referred to as “risk factors”. Risk factors are nothing more than statistical correlations, they are not actual risks or causes of disease. Thus for CVD, the traditional risk factors are “smoking, hyperlipidemia, high blood pressure, and diabetes mellitus” (IOM 2101: 142), but those have not been shown to be causally related to CVD. For pertinent comparison: Smoking was shown to be a cause of lung cancer not because of the statistical correlation between smoking and lung cancer but only after animals forced to inhale tobacco smoke were found to develop lung cancer. No such direct test of CVD biomarkers is available.

Drugs administered to treat “hypertension” and “high” cholesterol
have not been proven to be of benefit
in preventing heart disease or to decrease mortality.

Similarly with other biomarkers and treatment based on them.

That is concluded and stated in the most authoritative official literature.

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