Friday, July 27, 2012

The Benefits of High Cholesterol

The Benefits of High Cholesterol

By Uffe Ravnskov, MD, PhD
People with high cholesterol live the longest. This statement seems so incredible that it takes a long time to clear one´s brainwashed mind to fully understand its importance. Yet the fact that people with high cholesterol live the longest emerges clearly from many scientific papers. Consider the finding of Dr. Harlan Krumholz of the Department of Cardiovascular Medicine at Yale University, who reported in 1994 that old people with low cholesterol died twice as often from a heart attack as did old people with a high cholesterol.1 Supporters of the cholesterol campaign consistently ignore his observation, or consider it as a rare exception, produced by chance among a huge number of studies finding the opposite.

But it is not an exception; there are now a large number of findings that contradict the lipid hypothesis. To be more specific, most studies of old people have shown that high cholesterol is not a risk factor for coronary heart disease. This was the result of my search in the Medline database for studies addressing that question.2Eleven studies of old people came up with that result, and a further seven studies found that high cholesterol did not predict all-cause mortality either.

Now consider that more than 90 % of all cardiovascular disease is seen in people above age 60 also and that almost all studies have found that high cholesterol is not a risk factor for women.2 This means that high cholesterol is only a risk factor for less than 5 % of those who die from a heart attack.

But there is more comfort for those who have high cholesterol; six of the studies found that total mortality was inversely associated with either total or LDL-cholesterol, or both. This means that it is actually much better to have high than to have low cholesterol if you want to live to be very old.

High Cholesterol Protects Against Infection

Many studies have found that low cholesterol is in certain respects worse than high cholesterol. For instance, in 19 large studies of more than 68,000 deaths, reviewed by Professor David R. Jacobs and his co-workers from the Division of Epidemiology at the University of Minnesota, low cholesterol predicted an increased risk of dying from gastrointestinal and respiratory diseases.3

Most gastrointestinal and respiratory diseases have an infectious origin. Therefore, a relevant question is whether it is the infection that lowers cholesterol or the low cholesterol that predisposes to infection? To answer this question Professor Jacobs and his group, together with Dr. Carlos Iribarren, followed more than 100,000 healthy individuals in the San Francisco area for fifteen years. At the end of the study those who had low cholesterol at the start of the study had more often been admitted to the hospital because of an infectious disease.4,5 This finding cannot be explained away with the argument that the infection had caused cholesterol to go down, because how could low cholesterol, recorded when these people were without any evidence of infection, be caused by a disease they had not yet encountered? Isn´t it more likely that low cholesterol in some way made them more vulnerable to infection, or that high cholesterol protected those who did not become infected? Much evidence exists to support that interpretation.

Low Cholesterol and HIV/AIDS

Young, unmarried men with a previous sexually transmitted disease or liver disease run a much greater risk of becoming infected with HIV virus than other people. The Minnesota researchers, now led by Dr. Ami Claxton, followed such individuals for 7-8 years. After having excluded those who became HIV-positive during the first four years, they ended up with a group of 2446 men. At the end of the study, 140 of these people tested positive for HIV; those who had low cholesterol at the beginning of the study were twice as likely to test postitive for HIV compared with those with the highest cholesterol.6

Similar results come from a study of the MRFIT screenees, including more than 300,000 young and middle-aged men, which found that 16 years after the first cholesterol analysis the number of men whose cholesterol was lower than 160 and who had died from AIDS was four times higher than the number of men who had died from AIDS with a cholesterol above 240.7

Cholesterol and Chronic Heart Failure

Heart disease may lead to a weakening of the heart muscle. A weak heart means that less blood and therefore less oxygen is delivered to the arteries. To compensate for the decreased power, the heart beat goes up, but in severe heart failure this is not sufficient. Patients with severe heart failure become short of breath because too little oxygen is delivered to the tissues, the pressure in their veins increases because the heart cannot deliver the blood away from the heart with sufficient power, and they become edematous, meaning that fluid accumulates in the legs and in serious cases also in the lungs and other parts of the body. This condition is called congestive or chronic heart failure.

There are many indications that bacteria or other microorganisms play an important role in chronic heart failure. For instance, patients with severe chronic heart failure have high levels of endotoxin and various types of cytokines in their blood. Endotoxin, also named lipopolysaccharide, is the most toxic substance produced by Gram-negative bacteria such as Escherichia coli, Klebsiella, Salmonella, Serratia and Pseudomonas. Cytokines are hormones secreted by white blood cells in their battle with microorganisms; high levels of cytokines in the blood indicate that inflammatory processes are going on somewhere in the body.

The role of infections in chronic heart failure has been studied by Dr. Mathias Rauchhaus and his team at the Medical Department, Martin-Luther-University in Halle, Germany (Universitätsklinik und Poliklinik für Innere Medizin III, Martin-Luther-Universität, Halle). They found that the strongest predictor of death for patients with chronic heart failure was the concentration of cytokines in the blood, in particular in patients with heart failure due to coronary heart disease.8 To explain their finding they suggested that bacteria from the gut may more easily penetrate into the tissues when the pressure in the abdominal veins is increased because of heart failure. In accordance with this theory, they found more endotoxin in the blood of patients with congestive heart failure and edema than in patients with non-congestive heart failure without edema, and endotoxin concentrations decreased significantly when the heart’s function was improved by medical treatment.9

A simple way to test the functional state of the immune system is to inject antigens from microorganisms that most people have been exposed to, under the skin. If the immune system is normal, an induration (hard spot) will appear about 48 hours later at the place of the injection. If the induration is very small, with a diameter of less than a few millimeters, this indicates the presence of “anergy,” a reduction in or failure of response to recognize antigens. In accordance, anergy has been found associated with an increased risk of infection and mortality in healthy elderly individuals, in surgical patients and in heart transplant patients.10

Dr. Donna Vredevoe and her group from the School of Nursery and the School of Medicine, University of California at Los Angeles tested more than 200 patients with severe heart failure with five different antigens and followed them for twelve months. The cause of heart failure was coronary heart disease in half of them and other types of heart disease (such as congenital or infectious valvular heart disease, various cardiomyopathies and endocarditis) in the rest. Almost half of all the patients were anergic, and those who were anergic and had coronary heart disease had a much higher mortality than the rest.10

Now to the salient point: to their surprise the researchers found that mortality was higher, not only in the patients with anergy, but also in the patients with the lowest lipid values, including total cholesterol, LDL-cholesterol and HDL-cholesterol as well as triglycerides.

The latter finding was confirmed by Dr. Rauchhaus, this time in co-operation with researchers at several German and British university hospitals. They found that the risk of dying for patients with chronic heart failure was strongly and inversely associated with total cholesterol, LDL-cholesterol and also triglycerides; those with high lipid values lived much longer than those with low values.11,12

Other researchers have made similar observations. The largest study has been performed by Professor Gregg C. Fonorow and his team at the UCLA Department of Medicine and Cardiomyopathy Center in Los Angeles.13 The study, led by Dr. Tamara Horwich, included more than a thousand patients with severe heart failure. After five years 62 percent of the patients with cholesterol below 129 mg/l had died, but only half as many of the patients with cholesterol above 223 mg/l.

When proponents of the cholesterol hypothesis are confronted with findings showing a bad outcome associated with low cholesterol—and there are many such observations—they usually argue that severely ill patients are often malnourished, and malnourishment is therefore said to cause low cholesterol. However, the mortality of the patients in this study was independent of their degree of nourishment; low cholesterol predicted early mortality whether the patients were malnourished or not.

Smith-Lemli-Opitz Syndrome

As discussed in The Cholesterol Myths (see sidebar), much evidence supports the theory that people born with very high cholesterol, so-called familial hypercholesterolemia, are protected against infection. But if inborn high cholesterol protects against infections, inborn low cholesterol should have the opposite effect. Indeed, this seems to be true.

Children with the Smith-Lemli-Opitz syndrome have very low cholesterol because the enzyme that is necessary for the last step in the body’s synthesis of cholesterol does not function properly. Most children with this syndrome are either stillborn or they die early because of serious malformations of the central nervous system. Those who survive are imbecile, they have extremely low cholesterol and suffer from frequent and severe infections. However, if their diet is supplemented with pure cholesterol or extra eggs, their cholesterol goes up and their bouts of infection become less serious and less frequent.14

Laboratory Evidence

Laboratory studies are crucial for learning more about the mechanisms by which the lipids exert their protective function. One of the first to study this phenomenon was Dr Sucharit Bhakdi from the Institute of Medical Microbiology, University of Giessen (Institut für Medizinsche Mikrobiologie, Justus-Liebig-Universität Gießen), Germany along with his team of researchers from various institutions in Germany and Denmark.15

Staphylococcus aureus α-toxin is the most toxic substance produced by strains of the disease-promoting bacteria called staphylococci. It is able to destroy a wide variety of human cells, including red blood cells. For instance, if minute amounts of the toxin are added to a test tube with red blood cells dissolved in 0.9 percent saline, the blood is hemolyzed, that is the membranes of the red blood cells burst and hemoglobin from the interior of the red blood cells leaks out into the solvent. Dr. Bhakdi and his team mixed purified α-toxin with human serum (the fluid in which the blood cells reside) and saw that 90 percent of its hemolyzing effect disappeared. By various complicated methods they identified the protective substance as LDL, the carrier of the so-called bad cholesterol. In accordance, no hemolysis occurred when they mixed α-toxin with purified human LDL, whereas HDL or other plasma constituents were ineffective in this respect.

Dr. Willy Flegel and his co-workers at the Department of Transfusion Medicine, University of Ulm, and the Institute of Immunology and Genetics at the German Cancer Research Center in Heidelberg, Germany (DRK-Blutspendezentrale und Abteilung für Transfusionsmedizin, Universität Ulm, und Deutsches Krebsforschungszentrum, Heidelberg) studied endotoxin in another way.16 As mentioned, one of the effects of endotoxin is that white blood cells are stimulated to produce cytokines. The German researchers found that the cytokine-stimulating effect of endotoxin on the white blood cells disappeared almost completely if the endotoxin was mixed with human serum for 24 hours before they added the white blood cells to the test tubes. In a subsequent study17 they found that purified LDL from patients with familial hypercholesterolemia had the same inhibitory effect as the serum.

LDL may not only bind and inactivate dangerous bacterial toxins; it seems to have a direct beneficial influence on the immune system also, possibly explaining the observed relationship between low cholesterol and various chronic diseases. This was the starting point for a study by Professor Matthew Muldoon and his team at the University of Pittsburgh, Pennsylvania. They studied healthy young and middle-aged men and found that the total number of white blood cells and the number of various types of white blood cells were significantly lower in the men with LDL-cholesterol below 160 mg/dl (mean 88.3 mg/l),than in men with LDL-cholesterol above 160 mg/l (mean 185.5 mg/l).18 The researchers cautiously concluded that there were immune system differences between men with low and high cholesterol, but that it was too early to state whether these differences had any importance for human health. Now, seven years later with many of the results discussed here, we are allowed to state that the immune-supporting properties of LDL-cholesterol do indeed play an important role in human health.

Animal Experiments

The immune systems in various mammals including human beings have many similarities. Therefore, it is interesting to see what experiments with rats and mice can tell us. Professor Kenneth Feingold at the Department of Medicine, University of California, San Francisco, and his group have published several interesting results from such research. In one of them they lowered LDL-cholesterol in rats by giving them either a drug that prevents the liver from secreting lipoproteins, or a drug that increases their disappearance. In both models, injection of endotoxin was followed by a much higher mortality in the low-cholesterol rats compared with normal rats. The high mortality was not due to the drugs because, if the drug-treated animals were injected with lipoproteins just before the injection of endotoxin, their mortality was reduced to normal.19

Dr. Mihai Netea and his team from the Departments of Internal and Nuclear Medicine at the University Hospital in Nijmegen, The Netherlands, injected purified endotoxin into normal mice, and into mice with familial hypercholesterolemia that had LDL-cholesterol four times higher than normal. Whereas all normal mice died, they had to inject eight times as much endotoxin to kill the mice with familial hypercholesterolemia. In another experiment they injected live bacteria and found that twice as many mice with familial hypercholesterolemia survived compared with normal mice.20

Other Protecting Lipids

As seen from the above, many of the roles played by LDL-cholesterol are shared by HDL. This should not be too surprising considering that high HDL-cholesterol is associated with cardiovascular health and longevity. But there is more.

Triglycerides, molecules consisting of three fatty acids linked to glycerol, are insoluble in water and are therefore carried through the blood inside lipoproteins, just as cholesterol. All lipoproteins carry triglycerides, but most of them are carried by a lipoprotein named VLDL (very low-density lipoprotein) and by chylomicrons, a mixture of emulsified triglycerides appearing in large amounts after a fat-rich meal, particularly in the blood that flows from the gut to the liver.

For many years it has been known that sepsis, a life-threatening condition caused by bacterial growth in the blood, is associated with a high level of triglycerides. The serious symptoms of sepsis are due to endotoxin, most often produced by gut bacteria. In a number of studies, Professor Hobart W. Harris at the Surgical Research Laboratory at San Francisco General Hospital and his team found that solutions rich in triglycerides but with practically no cholesterol were able to protect experimental animals from the toxic effects of endotoxin and they concluded that the high level of triglycerides seen in sepsis is a normal immune response to infection.21 Usually the bacteria responsible for sepsis come from the gut. It is therefore fortunate that the blood draining the gut is especially rich in triglycerides.


So far, animal experiments have confirmed the hypothesis that high cholesterol protects against infection, at least against infections caused by bacteria. In a similar experiment using injections of Candida albicans, a common fungus, Dr. Netea and his team found that mice with familial hypercholesterolemia died more easily than normal mice.22 Serious infections caused by Candida albicans are rare in normal human beings; however, they are mainly seen in patients treated with immunosuppressive drugs, but the finding shows that we need more knowledge in this area. However, the many findings mentioned above indicate that the protective effects of the blood lipids against infections in human beings seem to be greater than any possible adverse effects.

Cholesterol as a Risk Factor

Most studies of young and middle-aged men have found high cholesterol to be a risk factor for coronary heart disease, seemingly a contradiction to the idea that high cholesterol is protective. Why is high cholesterol a risk factor in young and middle-aged men? A likely explanation is that men of that age are often in the midst of their professional career. High cholesterol may therefore reflect mental stress, a well-known cause of high cholesterol and also a risk factor for heart disease. Again, high cholesterol is not necessarily the direct cause but may only be a marker. High cholesterol in young and middle-aged men could, for instance, reflect the body’s need for more cholesterol because cholesterol is the building material of many stress hormones. Any possible protective effect of high cholesterol may therefore be counteracted by the negative influence of a stressful life on the vascular system.

Response to Injury

In 1976 one of the most promising theories about the cause of atherosclerosis was the Response-to-Injury Hypothesis, presented by Russell Ross, a professor of pathology, and John Glomset, a professor of biochemistry and medicine at the Medical School, University of Washington in Seattle.23,24 They suggested that atherosclerosis is the consequence of an inflammatory process, where the first step is a localized injury to the thin layer of cells lining the inside of the arteries, the intima. The injury causes inflammation and the raised plaques that form are simply healing lesions.

Their idea is not new. In 1911, two American pathologists from the Pathological Laboratories, University of Pittsburgh, Pennsylvania, Oskar Klotz and M.F. Manning, published a summary of their studies of the human arteries and concluded that “there is every indication that the production of tissue in the intima is the result of a direct irritation of that tissue by the presence of infection or toxins or the stimulation by the products of a primary degeneration in that layer.”25 Other researchers have presented similar theories.26

Researchers have proposed many potential causes of vascular injury, including mechanical stress, exposure to tobacco fumes, high LDL-cholesterol, oxidized cholesterol, homocysteine, the metabolic consequences of diabetes, iron overload, copper deficiency, deficiencies of vitamins A and D, consumption of trans fatty acids, microorganisms and many more. With one exception, there is evidence to support roles for all of these factors, but the degree to which each of them participates remains uncertain. The exception is of course LDL-cholesterol. Much research allows us to exclude high LDL-cholesterol from the list. Whether we look directly with the naked eye at the inside of the arteries at autopsy, or we do it indirectly in living people using x-rays, ultrasound or electron beams, no association worth mentioning has ever been found between the amount of lipid in the blood and the degree of atherosclerosis in the arteries. Also, whether cholesterol goes up or down, by itself or due to medical intervention, the changes of cholesterol have never been followed by parallel changes in the atherosclerotic plaques; there is no dose-response. Proponents of the cholesterol campaign often claim that the trials indeed have found dose-response, but here they refer to calculations between the mean changes of the different trials with the outcome of the whole treatment group. However, true dose-response demands that the individual changes of the putative causal factor are followed by parallel, individual changes of the disease outcome, and this has never occurred in the trials where researchers have calculated true dose-response.

A detailed discussion of the many factors accused of harming the arterial endothelium is beyond the scope of this article. However, the protective role of the blood lipids against infections obviously demands a closer look at the alleged role of one of the alleged causes, the microorganisms.

Is Atherosclerosis an Infectious Disease?

For many years scientists have suspected that viruses and bacteria, in particular cytomegalovirus and Chlamydia pneumonia (also named TWAR bacteria) participate in the development of atherosclerosis. Research within this area has exploded during the last decade and by January 2004, at least 200 reviews of the issue have been published in medical journals. Due to the widespread preoccupation with cholesterol and other lipids, there has been little general interest in the subject, however, and few doctors know much about it. Here I shall mention some of the most interesting findings.26

Electron microscopy, immunofluorescence microscopy and other advanced techniques have allowed us to detect microorganisms and their DNA in the atherosclerotic lesions in a large proportion of patients. Bacterial toxins and cytokines, hormones secreted by the white blood cells during infections, are seen more often in the blood from patients with recent heart disease and stroke, in particular during and after an acute cardiovascular event, and some of them are strong predictors of cardiovascular disease. The same is valid for bacterial and viral antibodies, and a protein secreted by the liver during infections, named C-reactive protein (CRP), is a much stronger risk factor for coronary heart disease than cholesterol.

Clinical evidence also supports this theory. During the weeks preceding an acute cardiovascular attack many patients have had a bacterial or viral infection. For instance, Dr. Armin J. Grau from the Department of Neurology at the University of Heidelberg and his team asked 166 patients with acute stroke, 166 patients hospitalized for other neurological diseases and 166 healthy individuals matched individually for age and sex about recent infectious disease. Within the first week before the stroke, 37 of the stroke patients, but only 14 of the control individuals had had an infectious disease. In half of the patients the infection was of bacterial origin, in the other half of viral origin.27

Similar observations have been made by many others, for patients with acute myocardial infarction (heart attack). For instance, Dr. Kimmo J. Mattila at the Department of Medicine, Helsinki University Hospital, Finland, found that 11 of 40 male patients with an acute heart attack before age 50 had an influenza-like infection with fever within 36 hours prior to admittance to hospital, but only 4 out of 41 patients with chronic coronary disease (such as recurrent angina or pervious myocardial infarction) and 4 out of 40 control individuals without chronic disease randomly selected from the general population.28

Attempts have been made to prevent cardiovascular disease by treatment with antibiotics. In five trials treatment of patients with coronary heart disease using azithromyzin or roxithromyzin, antibiotics that are effective against Chlamydiapneumonia,yielded successful results; a total of 104 cardiovascular events occurred among the 412 non-treated patients, but only 61 events among the 410 patients in the treatment groups.28a-e In one further trial a significant decreased progression of atherosclerosis in the carotid arteries occurred with antibiotic treatment.28f However, in four other trials,30a-d one of which included more than 7000 patients,28d antibiotic treatment had no significant effect.

The reason for these inconsistent results may be that the treatment was too short (in one of the trials treatment lasted only five days). Also, Chlamydia pneumonia, the TWAR bacteria, can only propagate inside human cells and when located in white blood cells they are resistant to antibiotics.31

Treatment may also have been ineffective because the antibiotics used have no effect on viruses. In this connection it is interesting to mention a controlled trial performed by Dr. Enrique Gurfinkel and his team from Fundación Favaloro in Buenos Aires, Argentina.32 They vaccinated half of 301 patients with coronary heart disease against influenza, a viral disease. After six months 8 percent of the control patients had died, but only 2 percent of the vaccinated patients. It is worth mentioning that this effect was much better than that achieved by any statin trial, and in a much shorter time.

Does High Cholesterol Protect Against Cardiovascular Disease?

Apparently, microorganisms play a role in cardiovascular disease. They may be one of the factors that start the process by injuring the arterial endothelium. A secondary role may be inferred from the association between acute cardiovascular disease and infection. The infectious agent may preferably become located in parts of the arterial walls that have been previously damaged by other agents, initiating local coagulation and the creation of a thrombus (clot) and in this way cause obstruction of the blood flow. But if so, high cholesterol may protect against cardiovascular disease instead of being the cause!

In any case, the diet-heart idea, with its demonizing of high cholesterol, is obviously in conflict with the idea that high cholesterol protects against infections. Both ideas cannot be true. Let me summarize the many facts that conflict with the idea that high cholesterol is bad.

If high cholesterol were the most important cause of atherosclerosis, people with high cholesterol should be more atherosclerotic than people with low cholesterol. But as you know by now this is very far from the truth.

If high cholesterol were the most important cause of atherosclerosis, lowering of cholesterol should influence the atherosclerotic process in proportion to the degree of its lowering.

But as you know by now, this does not happen.

If high cholesterol were the most important cause of cardiovascular disease, it should be a risk factor in all populations, in both sexes, at all ages, in all disease categories, and for both heart disease and stroke. But as you know by now, this is not the case

I have only two arguments for the idea that high cholesterol is good for the blood vessels, but in contrast to the arguments claiming the opposite they are very strong. The first one stems from the statin trials. If high cholesterol were the most important cause of cardiovascular disease, the greatest effect of statin treatment should have been seen in patients with the highest cholesterol, and in patients whose cholesterol was lowered the most. Lack of dose-response cannot be attributed to the knowledge that the statins have other effects on plaque stabilization, as this would not have masked the effect of cholesterol-lowering considering the pronounced lowering that was achieved. On the contrary, if a drug that effectively lowers the concentration of a molecule assumed to be harmful to the cardiovascular system and at the same time exerts several beneficial effects on the same system, a pronounced dose-response should be seen.

On the other hand, if high cholesterol has a protective function, as suggested, its lowering would counterbalance the beneficial effects of the statins and thus work against a dose-response, which would be more in accord with the results from the various trials.

I have already mentioned my second argument, but it can’t be said too often: High cholesterol is associated with longevity in old people. It is difficult to explain away the fact that during the period of life in which most cardiovascular disease occurs and from which most people die (and most of us die from cardiovascular disease), high cholesterol occurs most often in people with the lowest mortality. How is it possible that high cholesterol is harmful to the artery walls and causes fatal coronary heart disease, the commonest cause of death, if those whose cholesterol is the highest, live longer than those whose cholesterol is low?

To the public and the scientific community I say, “Wake up!”

1. Krumholz HM and others. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. Journal of the American Medical Association 272, 1335-1340, 1990.
2. Ravnskov U. High cholesterol may protect against infections and atherosclerosis.Quarterly Journal of Medicine 96, 927-934, 2003.
3. Jacobs D and others. Report of the conference on low blood cholesterol: Mortality associations. Circulation 86, 1046–1060, 1992.
4. Iribarren C and others. Serum total cholesterol and risk of hospitalization, and death from respiratory disease. International Journal of Epidemiology 26, 1191–1202, 1997.
5. Iribarren C and others. Cohort study of serum total cholesterol and in-hospital incidence of infectious diseases. Epidemiology and Infection 121, 335–347, 1998.
6. Claxton AJ and others. Association between serum total cholesterol and HIV infection in a high-risk cohort of young men. Journal of acquired immune deficiency syndromes and human retrovirology 17, 51–57, 1998.
7. Neaton JD, Wentworth DN. Low serum cholesterol and risk of death from AIDS.AIDS 11, 929–930, 1997.
8. Rauchhaus M and others. Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation 102, 3060-3067, 2000.
9. Niebauer J and others. Endotoxin and immune activation in chronic heart failure.Lancet 353, 1838-1842, 1999.
10. Vredevoe DL and others. Skin test anergy in advanced heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy. American Journal of Cardiology 82, 323-328, 1998.
11. Rauchhaus M, Coats AJ, Anker SD. The endotoxin-lipoprotein hypothesis.Lancet 356, 930–933, 2000.
12. Rauchhaus M and others. The relationship between cholesterol and survival in patients with chronic heart failure. Journal of the American College of Cardiology 42, 1933-1940, 2003.
13. Horwich TB and others. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. Journal of Cardiac Failure 8, 216-224, 2002.
14. Elias ER and others. Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS). American Journal of Medical Genetics 68, 305–310, 1997.
15. Bhakdi S and others. Binding and partial inactivation of Staphylococcus aureus a-toxin by human plasma low density lipoprotein. Journal of Biological Chemistry258, 5899-5904, 1983.
16. Flegel WA and others. Inhibition of endotoxin-induced activation of human monocytes by human lipoproteins. Infection and Immunity 57, 2237-2245, 1989.
17. Weinstock CW and others. Low density lipoproteins inhibit endotoxin activation of monocytes. Arteriosclerosis and Thrombosis 12, 341-347, 1992.
18. Muldoon MF and others. Immune system differences in men with hypo- or hypercholesterolemia. Clinical Immunology and Immunopathology 84, 145-149, 1997.
19. Feingold KR and others. Role for circulating lipoproteins in protection from endotoxin toxicity. Infection and Immunity 63, 2041-2046, 1995.
20. Netea MG and others. Low-density lipoprotein receptor-deficient mice are protected against lethal endotoxemia and severe gram-negative infections. Journal of Clinical Investigation 97, 1366-1372, 1996.
21. Harris HW, Gosnell JE, Kumwenda ZL. The lipemia of sepsis: triglyceride-rich lipoproteins as agents of innate immunity. Journal of Endotoxin Research 6, 421-430, 2001.
22. Netea MG and others. Hyperlipoproteinemia enhances susceptibility to acute disseminated Candida albicans infection in low-density-lipoprotein-receptor-deficient mice. Infection and Immunity 65, 2663-2667, 1997.
23. Ross R, Glomset JA. The pathogenesis of atherosclerosis. New England Journal of Medicine 295, 369-377, 1976.
24. Ross R. The pathogenesis of atherosclerosis and update. New England Journal of Medicine 314, 488-500, 1986.
25. Klotz O, Manning MF. Fatty streaks in the intima of arteries. Journal of Pathology and Bacteriology. 16, 211-220, 1911.
26. At least 200 reviews about the role of infections in atherosclerosis and cardiovascular disease have been published; here are a few of them: a) Grayston JT, Kuo CC, Campbell LA, Benditt EP. Chlamydia pneumoniae strain TWAR and atherosclerosis. European Heart Journal Suppl K, 66-71, 1993. b) Melnick JL, Adam E, Debakey ME. Cytomegalovirus and atherosclerosis. European Heart Journal Suppl K, 30-38, 1993. c) Nicholson AC, Hajjar DP. Herpesviruses in atherosclerosis and thrombosis. Etiologic agents or ubiquitous bystanders? Arteriosclerosis Thrombosis and Vascular Biology 18, 339-348, 1998. d) Ismail A, Khosravi H, Olson H. The role of infection in atherosclerosis and coronary artery disease. A new therapeutic target. Heart Disease 1, 233-240, 1999. e) Kuvin JT, Kimmelstiel MD. Infectious causes of atherosclerosis. f.) Kalayoglu MV, Libby P, Byrne GI. Chlamydia pneumoniaas an emerging risk factor in cardiovascular disease. Journal of the American Medical Association 288, 2724-2731, 2002.
27. Grau AJ and others. Recent bacterial and viral infection is a risk factor for cerebrovascular ischemia. Neurology 50, 196-203, 1998.
28. Mattila KJ. Viral and bacterial infections in patients with acute myocardial infarction. Journal of Internal Medicine 225, 293-296, 1989.
29. The successful trials: a) Gurfinkel E. Lancet 350, 404-407, 1997. b) Gupta S and others. Circulation 96, 404-407, 1997. c) Muhlestein JB and others. Circulation 102, 1755-1760, 2000. d) Stone AFM and others. Circulation 106, 1219-1223, 2002. e) Wiesli P and others. Circulation 105, 2646-2652, 2002. f) Sander D and others. Circulation 106, 2428-2433, 2002.
30. The unsuccessful trials: a) Anderson JL and others. Circulation 99, 1540-1547, 1999. b) Leowattana W and others. Journal of the Medical Association of Thailand 84 (Suppl 3), S669-S675, 2001. c) Cercek B and others. Lancet 361, 809-813, 2003. d) O’Connor CM and others. Journal of the American Medical Association. 290, 1459-1466, 2003.
31. Gieffers J and others. Chlamydia pneumoniae infection in circulating human monocytes is refractory to antibiotic treatment. Circulation 104, 351-356, 2001
32. Gurfinkel EP and others. Circulation 105, 2143-2147, 2002.
About the Author
Dr. Ravnskov is the author of The Cholesterol Myths and chairman of The International Network of Cholesterol Skeptics (thincs.org).
Read the complete article here.

Doctors criticise plans for cholesterol screening in children

Doctors criticise plans for cholesterol screening in children

Back in November 2011, a panel of experts assembled by the National Heart, Lung and Blood Institute (NHLBI) in the US published recommendations regarding cholesterol screening in children. The panel recommended that all children aged 9-11 should be screened, and that more targeted testing (in those deemed to be at high risk) should be used in 2-8 year-olds and 12-16 year olds.

These recommendations risk making millions of American children into patients with their diagnosis of ‘dyslipidemia’ (disordered blood fat levels). Many may end up on cholesterol-reducing medication, of course, which is not without risk. And what evidence is there that this strategy will reap dividends in the long term?

The problems inherent in the NHLBI panel recommendations were made plain this week in an on-line article penned by three doctor-researchers at the University of California in San Francisco which appeared on-line in the journal Pediatrics [1]. In the piece, the authors draw our attention to the fact that the guidelines are simply a matter of opinion, albeit supposedly ‘expert’ opinion. The fact of the matter is that there has been no proper study which assesses the benefits (or otherwise) of screening children or the recommendations that may come out of this screening.

Not only this, but there has been simply no effort to quantify the costs of such an endeavour. So, in addition to not knowing whether the proposed strategy would even work, we have no idea what it would cost and are therefore unable to determine if it offers value for money (and if that money might be better spent elsewhere).

The authors of the article also draw our attention to the fact that there were significant financial conflicts of interest to be found in the NHLBI panel. The website sciencedaily.com reports here that:
The authors [of the article] note that the panel chair and all members who drafted the lipid screening recommendations disclosed an “extensive assortment of financial relationships with companies making lipid lowering drugs and lipid testing instruments.”  
Some of those relevant relationships include paid consultancies or advisory board memberships with pharmaceuticals that produce cholesterol-lowering drugs such as Merck, Pfizer, Astra Zeneca, Bristol-Myers Squibb, Roche and Sankyo.

“The panel states that they reviewed and graded the evidence objectively,” said Newman [Thomas Newman – one of the authors of the article]. “But a recent Institute of Medicine report recommends that experts with conflicts of interest either be excluded from guideline panels, or, if their expertise is considered essential, should have non-voting, non-leadership, minority roles.”

Evidence is needed to estimate health benefits, risks and costs of these proposed interventions, and experts without conflicts of interest are needed to help synthesize it, according to Newman. He said that “these recommendations fall so far short of this ideal that we hope they will trigger a re-examination of the process by which they were produced.”
Pediatrics also published on-line this week a rebuttal to this article co-written by several of the panel members, including its chairman Dr Stephen Daniels [2]. Here Dr Daniels (who has worked as a consultant or advisory board member for several cholesterol drug manufacturers including Abbott Laboratories, Merck and Schering-Plough) is quoted as saying that he feels industry ties did not influence the debate among panel members. He can say what he likes, but common sense suggests otherwise, as does the distinct lack of rigour in the panel’s recommendations.

In the linked article, the NHLBI’s acting director and the person who convened the panel, Dr Susan Shurin, tells us that there are few qualified specialists which have no industry relationships. This perhaps goes to show just how the effective the industry can be in sewing up an area and ensuring it gets the ‘expert’ opinion it wants.

“We got the best people in the country to do this,” Dr Shurin is quoted as saying. What a shame the ‘best people’ come with so many of conflicts of interest attached, and that their recommendations are set to convert millions of kids into patients despite there being simply no good evidence that this will benefit them or society in general.

1. Newman TB, et al. Overly Aggressive New Guidelines for Lipid Screening in Children: Evidence of a Broken Process. Pediatrics Published online July 23, 2012(
2. McCrindle BW, et al. Guidelines for Lipid Screening in Children and Adolescents: Bringing Evidence to the Debate. Pediatrics Published online July 23, 2012
Read the complete article here.

Thursday, July 26, 2012

Prescription drugs kill 6200% more Americans than homicidal shootings

Prescription drugs kill 6200% more Americans than homicidal shootings

In the aftermath of the Aurora, Colorado Batman movie theater shooting, President Obama chimed in on the gun control debate yesterday, saying, "Every day, the number of young people we lose to violence is about the same as the number of people we lost in that movie theater. For every Columbine or Virginia Tech, there are dozens gunned down on the streets of Chicago or Atlanta..." (http://www.washingtontimes.com/news/2012/jul/25/obama-calls-measures-...)

What he didn't say, however, is that every day 290 people are killed by FDA-approved prescription drugs, and that's the conservative number published by the Journal of the American Medical Association.

As no one seems to believe these numbers are real, I'll quote the source: The Journal of the American Medical Association (JAMA) Vol 284, No 4, July 26th 2000, authored by Dr Barbara Starfield, MD, MPH, of the Johns Hopkins School of Hygiene and Public Health.

That study, which is twelve years old -- and drug deaths have risen considerably since then -- documents 106,000 deaths per year from the "adverse effects" of FDA-approved prescription medications.

To reach this number from outbreaks of violent shootings, you'd have to see an Aurora Colorado Batman movie massacre take place every HOUR of every day, 365 days a year.

If a massacre of people using slugs of lead is bad, why is a massacre of people using deadly chemicals perfectly acceptable?

A medical massacre that dwarfs the number of deaths from shootings

No one in Washington talks about prescription drug deaths. There are no sobbing victims shown on the evening news. This "chemical massacre" happens quietly, behind closed doors. Yet to achieve this level of mass death in the world of plane crashes, for example, you'd have to see a jumbo jet airliner crashing into the ground once a day, every day of the year.

But that's only the beginning of the mass death caused by modern medicine, where greed-driven doctors are routinely bribed by the drug giants (http://www.naturalnews.com/036510_doctors_bribes_drug_companies.html) and thereby make the "Joker" James Holmes look like a boy scout by comparison. As NaturalNews previously revealed, just one company -- GlaxoSmithKline -- had a bribery network of 49,000 doctors who received financial kickbacks to prescribe more Glaxo pharmaceuticals to patients.

According to the report Death by Medicine, by Drs. Gary Null, Carolyn Dean, Martin Feldman, Debora Rasio and Dorothy Smith, the medical establishment kills 783,936 people in the United States every year. (http://www.lef.org/magazine/mag2004/mar2004_awsi_death_02.htm)

Those deaths include:

• 106,000 Americans killed from drug side effects
• 115,000 Americans killed from bedsores
• 98,000 Americans killed from medical error
• 88,000 Americans killed from infections
• 32,000 Americans killed from surgery
• 37,000 Americans killed from unnecessary procedures

... and so on. See the source link, above, for the rest of the numbers.

The bottom line total comes to 783,936 deaths every year from "conventional" medicine (drugs and surgery medicine).

You are 6200% more likely to be killed by your doctor than by a shooter

According to the CDC's numbers from 2007, the total number of homicide shooting deaths in the United States each year is roughly 12,600 (Xu, Jiaquan; Kenneth D. Kochanek, Sherry L. Murphy, Betzaida Tejada-Vera (2010-05-20). "Deaths: Final Data for 2007" (PDF). National Vital Statistics Reports (CDC) 58(19): 11.)

This means that your risk of being killed by your doctor is 62 times higher than the risk of being killed by a shooter. Put another way, that's a 6200% higher risk.

It seems that before we even think about the issue of gun control, we need a national debate on DOCTOR control.

After all, when doctors inadvertently kill people by prescribing deadly chemotherapy cocktails or deadly prescription drugs, they don't even get arrested for it! But they do get financial kickbacks, exotic vacations paid by drug companies, free travel, free meals and other perks of being a Big Pharma sellout. Plus, they're free to go on killing other people, over and over again. While doctors obviously don't intend to kill people, they nonetheless keep doing so as long as they get their bribes, kickbacks and perks. (http://www.naturalnews.com/036417_Glaxo_Merck_fraud.html)

If Obama really wanted to protect Americans from being killed, he'd call for restrictions on the prescribing of deadly pharmaceuticals. But don't hold your breath on that one, because when it comes to actually protecting the American people from medical massacres, or GMOs, or toxic fluoride in the water supply, the real Joker is Obama himself.

Watch the YouTube video.

Learn more: http://www.naturalnews.com/036599_gun_control_prescription_drugs_deaths.html#ixzz21lMuOOpQ

Saturday, July 21, 2012

Three more studies that should make you skeptical of mainstream health advice - Kresser

caution signFor the last 50 years mainstream medical “authorities” have been hammering it into our heads that high cholesterol levels are dangerous and low cholesterol levels are desirable; that eating saturated fat is bad for us; and that a low-fat, high carbohydrate diet is healthy and helps people lose weight.

If you’re a new reader, you might be surprised to learn that there’s very little evidence to support these recommendations and plenty of evidence that contradicts them. Long ago I learned that if I wanted to live a long, healthy life it was in my best interest to ignore the dietary advice of the medical mainstream. And of course that’s why I started this blog – to share this information with all of you so you can make educated, and informed choices about your health.

Lately I’ve been encouraged by the number of studies being published that undermine the anti-fat, anti-cholesterol dogma we’ve been brainwashed with for so long. This is good news.

The bad news is that paradigm shifts do not happen overnight. It took half a century for researchers and doctors to convince people that eating toxic, highly processed, nasty-tasting vegetable oils was somehow better for them than eating traditional animal fats like butter and lard; that eating dry bagels, boneless-skinless chicken breast and salad with fat-free dressing was a path to good health; and that the best way to lose weight was to eat a highly unnatural diet high in processed, refined carbohydrates and low in fat.

So I don’t expect these ideas to disappear anytime soon, in spite of the solid evidence being published that contradicts them. It’s going to take time. But my sense is that it will take less time to convince people that eating traditional, nutrient-dense, whole foods that have been minimally processed is better for them than eating what the industrial food conglomerates have been selling us.
Here are the three studies.

The first is yet another study that associates low cholesterol with an increase in the risk of death (total mortality). It showed increased death rates in hospitalized patients with low cholesterol levels.

CONCLUSIONS: In our cohort, lower LDL-cholesterol at admission was associated with decreased 3-year survival in patients with NSTEMI.
This shouldn’t be a surprise. There’s already plenty of evidence suggesting low cholesterol increases the risk of death – as well as contributing to other conditions such as cancer and depression. For more on this see my previous article Cholesterol Doesn’t Cause Heart Disease.

The second study shows (once again) that cutting carbs is the best way to lose weight and fight obesity.

No surprise here either. Countless studies, trials and reviews have demonstrated that low-carb diets are superior for weight loss, managing diabetes and preventing many of the other modern diseases which plague us. How long will it take until doctors and the media get the message? For more on one such recent review, see Low-carb Diet Best for Weight Loss.

The last study I want to share with you was performed by a Swedish PhD student. It demonstrates that children who eat saturated fat and full-cream dairy products are healthier than those who do not.

Conclusions: BMI correlated strongly to fat mass and leptin was the best marker of overweight and fat mass in 8-year-olds. Food choice was similar to that at 4 years of age. An intake of fat fish once a week was associated with higher serum concentrations of n-3 fatty acids. Saturated fat and intake of full fat milk were inversely associated with BMI. Serum phospholipid fatty acids were associated with bone mineralisation. The results for metabolic markers may provide preliminary reference intervals in healthy children.
If you’re surprised by this, read my recent post Have Some Butter with Your Veggies as well as Whole Fat Milk: Benefits for Moms and Kids.

Friday, July 20, 2012

The Polypill has never been proven to benefit anyone - Briffa

It’s easy to fall for the polypill hype, but the reality is this medication has never been proven to benefit anyone

There’s been a ton of press over the last couple of days regarding a study of what is termed the ‘polypill’ – a combination medication conceived more than a decade ago with, supposedly, the prevention of heart disease and stroke in mind. The original ‘formulation’ combined blood pressure- and cholesterol-lowering medications, along with aspirin and vitamin B12. From time to time in the scientific literature we have seen studies which purport to support the idea of polypill taking for disease prevention. And the latest of these was published this week. Here, in short, is the study design and what it showed. After that, I’ll offer my own interpretation of the data.

This latest study tested the impact of a polypill comprising the following drugs:
  • amlodipine (blood pressure lowering medication) – 2.5 mg
  • losartan (blood pressure lowering medication) – 25 mg
  • hydrochlorothiazide (blood pressure lowering medication) – 12.5 mg
  • simvastatin (a statin) – 40 mg
The medication was given for 12 weeks to men and women aged 50 and over. At another time, they took a placebo for 12 weeks. In this sense, individuals acted as their own ‘controls’ in this study.

Individuals were selected for the study on the basis of two criteria:
  1. They needed to be currently taking at least one of the medications in the polypill
  2. They needed to be aged 50 or over
The impact on blood pressure and cholesterol levels was assessed. The polypill did bring significant reductions here. The authors estimate from the degree of reductions here that heart disease and stroke would be reduced by 72 and 64 per cent respectively. Impressive numbers. There’s talk of this extending life by a decade or more.

But here’s the thing: this study simply can’t be used to judge whether the polypill prevent cardiovascular disease and delays death. These ideas are based on speculation based on the idea that lowering blood pressure and cholesterol translates into significant benefits for health. Yet, as I explored most recently here and here, blood pressure and statin medications are generally very ineffective for the purposes of disease prevention and preventing death. Most people who take these drugs just won’t benefit.

This is particularly the case when individuals are deemed to be at low risk of cardiovascular disease. Normally, medication is prescribed on the basis of, say, blood pressure or cholesterol levels. But not in this study: here people were selected on the basis of age, irrespective of perceived risk. Of course it’s possible that some might benefit from the polypill, but it’s also likely that many more will not.

And of course the drugs in the polypill are not without risk. Any one of these medications on its own might cause problems, but the risk is magnified when medication are taken in combination. The design of the study (individuals had to be on at least one of the drugs in the polypill prior to the study) essentially preselects for individuals who, compared to members of the general population, are more likely to tolerate the medication being tested. So, risk of side-effects in the study population would be generally lower than we would expect to see in real life.

But, all of this is a diversion from the main point that we simply cannot predict the value of a drug on its impact on so-called ‘surrogate markers’ such as blood pressure and cholesterol. I mean, who would have predicted that ezetimibe, a potent cholesterol-lowerer, would never be shown to have benefits for health, or that the drug torcetrapib (which lowers ‘bad’ cholesterol and raises ‘good’ cholesterol) happens to increase the risk of people dying?

If we want to know how effective the polypill is, we need to test its impact on health. What impact does the polypill have on risk of heart disease, stroke and overall risk of death? We just don’t know because this latest study does not tell us. There are four previous polypill studies in the literature, and none of them look at these critically important ‘end points’ or ‘outcomes’ either.

The lead author of the latest study is David Wald, son of Professor Sir Nicholas Wald, co-inventor of the polypill. Professor Wald and a colleague (Professor Malcom Law) hold a polypill patent. I suspect they have at least some desire to cash in on their invention. But if they want to do that, why not test the polypill in a way which does not lead to wild speculation but cool hard facts? Perhaps if the polypill was properly studied we’d get to see that, like so many drugs, the ‘expected’ benefits fail to materialise. Maybe it’s better to keep the dream alive with a string of studies and articles that allow rampant speculation and uber-enthusiasm but simply fail to tell us what we really need to know.

1. Wald DS, et al (2012) Randomized Polypill Crossover Trial in People Aged 50 and Over. PLoS ONE 7(7): e41297. doi:10.1371/journal.pone.0041297
Please read the complete article here.
Sept 8, 2014 -  An FDA advisory committee looks at a new cardiovascular polypill about which FDA staff expressed serious reservations

Thursday, July 19, 2012

Harvard To Be Tried for Research Fraud


Harvard To Be Tried for Research Fraud

The US Court of Appeals, 1st Circuit has overturned a summary judgement by a lower court ordering a whistleblower lawsuit filed by Dr. Kenneth Jones against Harvard Medical School, its teaching hospitals, Brigham and Women’s and Massachusetts General Hospital, and Dr. Marilyn Albert (Principal Investigator) and Dr. Ronald Killiany to proceed to trial.
The case involves the largest Alzheimer’s disease [AD] research grants awarded by the National Institutes of Health (from 1980 through 2007) for a large project aimed at identifying early physical signs of Alzheimer’s by scanning certain regions of the brain with MRIs.

Dr. Jones was the chief statistician for the NIH grant. He blew the whistle after realizing that measurements used to demonstrate the reliability of the study had been secretly altered. Without these alterations, Dr. Jones explained, there was no statistical significance to the major findings of the study. When he insisted that the altered measurements be subjected to an independent reliability study, and that the manipulated results could not be presented as part of a $15 million federal grant extension application, he was terminated and his career came to an end.

The allegations in the suit concern multiple research fraud: data manipulation, significant deviations from the protocol, altered and re-traced MRI scans. To get positive results, Dr. Jones alleges, Dr. Killiany “fraudulently altered the MRI study data prior to 1998 to produce false results of a statistically significant correlation between conversion to AD and volume of the EC [entorhinal cortex].”

He further alleged that Dr. Albert and Dr. Killiany violated federal regulations (43 CFR 50.103(c)(3) by making false statements in the NIH grant application: Statements that “were predicated on falsified data that the defendants, knowing of this falsity, failed to take corrective action or disavow the data.”

In overturning the lower court and ordering the case to proceed to trial, the Court of Appeals cited the lower court failure to consider substantial evidence of research fraud, and failed to consider relevant testimony from three expert witnesses presented by Dr. Jones:
“A statistician who confirmed that the alterations were responsible for the statistical significance of the study results, a medical researcher who identified that the altered results could not be justified and were changed to establish a predetermined outcome, and a third expert who confirmed that NIH would not have funded the study had the falsity of the data been revealed during the application process and that Harvard failed to adequately investigate allegations of research fraud.”
The Court of Appeals decision states:
“the essential dispute is about whether Killiany falsified scientific data by intentionally exaggerating the re-measurements of the EC to cause proof of a particular scientific hypothesis to emerge from the data, and whether statements made in the Application about having used blinded, reliable methods to produce those results were true.”
Michael D. Kohn, one of the lead attorneys for Dr. Jones said:
“This is a major breakthrough holding universities accountable for the integrity of reported research results. Fraud committed in order to obtain NIH funding not only robs taxpayers, but also sets back long-term medical research goals. The facts of this case indicate that the report of false data misdirected research efforts at other institutions.”
This case also underscores an inconvenient truth about the financial stakes that drive clinical trials. Those who are persuaded to serve as human subjects “for the good of humanity” and “to help medical progress” believe in the integrity and high mindedness of medical researchers–especially those at premier academic institutions. That trust, however, is all too often misplaced. Vulnerable human subjects are being shamelessly exploited in invalid, most often commercially driven experiments.

Indeed, the rationale behind the Harvard brain scanning experiment was to justify early interventions.
Another example is Eli Lilly’s Alzeheimer’s imaging detection test (Amyvid) launched last month.
Inasmuch as no effective, safe treatment for Alzheimer’s exists, and ALL such screening tests have been demonstrably inaccurate and inconsistent, such an “early intervention” approach in clinical practice is unethical and controversial.

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Read the complete article here.

NEJM editor: “No longer possible to believe much of clinical research published”

NEJM editor: “No longer possible to believe much of clinical research published”

Harvard Medical School’s Dr. Marcia Angell is the author of The Truth About the Drug Companies: How They Deceive Us and What to Do About It. But more to the point, she’s also the former Editor-in-Chief at the New England Journal of Medicine, arguably one of the most respected medical journals on earth. But after reading her article in the New York Review of Books called Drug Companies & Doctors: A Story of Corruption, one wonders if any medical journal on earth is worth anybody’s respect anymore.

“It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of The New England Journal of Medicine.”

Dr. Angell cites the case of Dr. Joseph L. Biederman, professor of psychiatry at Harvard Medical School and chief of pediatric psychopharmacology at Harvard’s Massachusetts General Hospital. She explains:

“Thanks largely to him, children as young as two years old are now being diagnosed with bipolar disorder and treated with a cocktail of powerful drugs, many of which were not approved by the Food and Drug Administration (FDA) for that purpose, and none of which were approved for children below ten years of age.”

Biederman’s own studies of the drugs he advocates to treat childhood bipolar disorder were, as The New York Times summarized the opinions of its expert sources, “so small and loosely designed that they were largely inconclusive.”

In June 2009, an American senate investigation revealed that drug companies, including those that make drugs he advocates for childhood bipolar disorder, had paid Biederman $1.6 million in “consulting” and “speaking” fees between 2000 and 2007.

“Two of Biederman’s colleagues received similar amounts. After the revelation, the president of the Massachusetts General Hospital and the chairman of its physician organization sent a letter to the hospital’s physicians expressing not shock over the enormity of the conflicts of interest, but sympathy for the beneficiaries: “We know this is an incredibly painful time for these doctors and their families, and our hearts go out to them.”

Biederman’s failure to disclose his Big Pharma payments to his employers ar Harvard (as is required for all Harvard employees) has been under investigation* for the past two years by Harvard Medical School, in as journalist Alison Bass describes this: “what must be the longest investigation in that school’s history”).

Dr. Angell’s article contains bombshell after bombshell, all gleaned during her tenure as NEJM editor. For example, on the subject of doctors who are bought and paid for by Big Pharma, she writes:

“No one knows the total amount provided by drug companies to physicians, but I estimate from the annual reports of the top 9 U.S.-based drug companies that it comes to tens of billions of dollars a year in North America alone.By such means, the pharmaceutical industry has gained enormous control over how doctors evaluate and use its own products. Its extensive ties to physicians, particularly senior faculty at prestigious medical schools, affect the results of research, the way medicine is practiced, and even the definition of what constitutes a disease.”

Revelations like this from medical profession insiders cast serious doubt on more than what’s printed on the pages of these medical journals.

Your physician reads these journals, treatment decisions are changed, care is affected, drugs are prescribed – all based on Big Pharma-funded medical ghostwriter-prepared journal articles from physicians who fraudulently claim to be the study authors. Then you walk out of your doctor’s office with a prescription for a drug that may or may not kill you, based on treatment protocols written by doctors like Biederman who are on the take from Big Pharma.

A very recent example of the sad reality over at the once-prestigious New England Journal of Medicine is their decision to publish a drug company-funded review article. This review attempts to discredit emerging research suggesting that many years of using Merck’s Fosamax or Procter & Gamble’s Actonel (both osteoporosis drugs in a class called bisphosphonates) could actually result in more leg bone fractures.

Not surprisingly, drug manufacturers of bisphosphonates are fighting back ferociously against this emerging (independent) research. A Merck-funded review paper published in the NEJM on March 24, 2010 concludes:

“The occurrence of fracture of the subtrochantericor diaphyseal femur was very rare, even among women who had been treated with bisphosphonates for as long as 10 years.”

Sounds promising for Big Pharma. But if you look very, very closely, the article’s fine print confesses:
“The study was underpowered for definitive conclusions.”
You might justifiably ask yourself why a medical journal would stoop to publishing a meaningless scientific paper that the paper’s own authors admit lacks any conclusion. Even more troubling than a journal article that was itself bought and paid for by Merck, is the conflict of interest disclosure list at the bottom of this NEJM article. It reads like a Who’s Who of Big Pharma.

Of the 12 study authors listed in the NEJM article, at least three are full-time employees of Merck or Novartis. Each one of the other nine admit owning equity interests in or receiving cash, travel expenses, or “consulting and lecture fees” from companies including Merck, Novartis, Amgen, Roche Nycomed, Procter & Gamble, AstraZeneca, GlaxoSmithKline, Medtronics, Nastech, Nestle, Fonterra Brands, OnoPharma, Osteologix, Pfizer, Eli Lilly, Sanofi-Aventis, Tethys, Unilever,Unipath, Inverness Medical, Ortho Clinical Diagnostics, OSIProsidion, or Takeda.
Why is the New England Journal of Medicine or any other credible medical journal accepting for publication articles submitted by paid employees of pharmaceutical companies?

As a cardiac patient, I’m gobsmacked by what appears to be this systemic corruption of not only medical journals who continue to publish what they clearly know is tainted research linked to drug marketing, but of the very doctors whom patients trust to look out for us. Since my heart attack in 2008, I take a fistful of cardiac meds every day, and I have no clue which of them were prescribed for me based on flawed research or tainted medical journal articles funded by the very companies that make my drugs.

And worse, neither do my doctors.

Happily, there are other decent physicians out there who, like Dr. Angell, are just as outraged as she is. Her targets are not just guilty of unethical conflict of interest – they are criminals who should be charged with endangering our health while padding their wallets.

Read Dr. Angell’s article from the New York Review of Books, called Drug Companies & Doctors: A Story of Corruption.

* NEWS UPDATE: “Massachusetts General Hospital Discloses Sanctions against Three Psychiatrists for Violating Ethics Guidelines”, July 1, 2011: The Boston Business Journal said today that three psychiatrists have been sanctioned for failing to adequately report seven-figure payments they received from drug companies.

Drs. Joseph Biederman, Thomas Spencer and Timothy Wilens disclosed the disciplinary actions against them in a note to colleagues. According to a copy of the note made public upon request by the hospital, the three doctors:

• must refrain from all industry-sponsored outside activities” for one year

• for two years after the ban ends, must obtain permission from Mass. General and Harvard Medical School before engaging in any industry-sponsored, paid outside activities and then must report back afterward

• must undergo certain training

• face delays before being considered for “promotion or advancement.”

The three doctors have been under the political microscope since June 2008 when Senator Charles Grassley, R-Iowa, began investigating conflicts of interest involving clinicians. Biederman and Wilens have since admitted to accepting $1.6 million from drug companies whose drugs they were promoting; Spencer took $1 million.

Senator Grassley said, according to an online version of the Congressional record:

“These three Harvard doctors are some of the top psychiatrists in the country, and their research is some of the most important in the field. They have also taken millions of dollars from the drug companies.”
See also:
Read the complete article here.

Monday, July 16, 2012

Statins for pregnant women and kids? - Kresser

One of my favorite researchers, Chris Masterjohn, has just launched a new blog called “The Daily Lipid” where he writes about fats, cholesterol and health. Chris is pursuing a Ph.D. in Molecular and Cell Biology and is one of the most knowledgeable contemporary writers on cardiovascular health that I’m aware of. With his permission, I am cross-posting the first two articles on his blog – which you should definitely consider adding to your blogroll!
pregnant woman

Statins for pregnant women?

Statin manufacturers, the sycophantic researchers they pay, and the shameless hucksters who sell them are always up to no good, but their recent attempts to market them to pregnant women are simply horrifying.

According to a recent news article published in Mail online, researchers from liverpool believe that taking statins during pregnancy might help women avoid caesarean sections by promoting more robust uterine contraction. They hope to begin human trials in three to five years.

Somehow, the author of this article failed to react with the shock and horror appropriate to the situation — which should be the same shock and horror with which we would react to the suggestion that pregnant women should take thalidomide to avoid morning sickness.

Back in 2004, a report in the New England Journal of Medicine showed that the use of statins in the first trimester of pregnancy was associated with birth defects, especially severe central nervous system defects and limb deformities. In fact, 20 out of 52 women exposed to statins gave birth to offspring with such defects, which represents a birth defect rate of 38 percent, nearly 20 times the background rate of birth defects!

Even before this report was published, researchers already knew that statins caused birth defects in animal experiments, and the FDA already required the drugs to carry a label warning pregnant women to stay away from them. The article linked to above stated the following:

“FDA took this action because it was recognized that fetal cholesterol synthesis was essential for development, and because animals given statins during pregnancy had offspring with a variety of birth defects,” [one of the study's authors] said.

Less than a year later, Merck and Johnson & Johnson jointly asked the FDA for permission to market an over-the-counter statin. One of the concerns about the proposal was the risk to pregnant women. USA Today reported:

The FDA classifies Mevacor and other statins as pregnancy category X, which means they are not supposed to be taken by pregnant women. Not only have category X drugs been linked to fetal abnormalities in animal or human studies, but the FDA also has declared that the benefits of taking them do not outweigh potential risks.

According to the same article, Merck made a disturbing admission:

“Of course, there will be women who take it off-label,” acknowledges Merck executive Edwin Hemwall, referring to the use of non-prescription Mevacor by women under 55.

And what could prompt women to use statins during pregnancy against recommendations? Certainly a news article declaring that statins might prevent the need for caesarean sections and their associated complications could prompt some women to do so.

So what ground-breaking research made these Liverpool researchers so confident that taking drugs associated with twenty times the normal rate of major birth defects during pregnancy might be a good idea that they put out a press release declaring this confidence to the public before any trials were even under way?

Well, according to the article:

Tests have already shown that raising levels of cholesterol interferes with womb tissue’s ability to contract.

 Really. Raising levels of cholesterol. You might wonder how they accomplished that. Did they use cholesterol-raising drugs? I don’t know of any drugs that do that. Did they use egg yolks, or the dreaded dietary villain — gasp — saturated fats?

No, the story is quite different.

The apparent basis for this ridiculous statin cheerleading is a 2004 study published by researchers from the University of Liverpool in the American Journal of Physiology — Cell Physiology entitled “Increased cholesterol decreases uterine activity: functional effects of cholesterol alteration in pregnant rat myometrium.”

Rather than feeding anything to pregnant women or pregnant rats, the researchers took pregnant rats and killed them. So the first thing we can say is that statins might help you deliver a baby if your doctor kills you first.

Then they extracted the uterine tissue and either extracted cholesterol from it with a chemical solvent called methyl beta-cyclodextrin, or enriched it either with cholesterol mixed with this solvent or with LDL (which they didn’t measure for oxidation prior to use). Then they added drugs to induce contraction under either cholesterol-depleted or cholesterol-enriched conditions, and found that contraction was greater under cholesterol-depleted conditions.

So now we know that — wait, what is it we know?

Well, quite clearly, we don’t know anything that we can have any confidence has any physiological relevance at all. That is, except the fact that statins cause birth defects in animals, and they increase the rate of birth defects in humans by nearly twenty times, primarily by causing severe defects of the central nervous system and limb deformities.

To add to that, we also know that the vast majority of humans conceived with Smith-Lemli-Opitz Syndrome (SLOS), a genetic inability to synthesize enough cholesterol, die of spontaneous abortion in the first 16 weeks of gestation. Those who live long enough to be born suffer from mental retardation, autism, facial and skeletal malformations, visual dysfunctions and failure to thrive.
Statins for pregnant women? I don’t think so.
Article written by Chris Masterjohn

Statins for 8-year old children?

child with drug
The American Academy of Pediatrics recently announced new recommendations for giving cholesterol-lowering drugs to children as young as eight years old. They also recommend giving low-fat milk to infants as young as one year old.

The New York Times published several articles on this, first announcing the recommendation the day the academy made it, then describing the backlash of saner doctors and other members of the public against it, and finally editorializing that while they were first “appalled” at the recommendation, after reading the report they were more dismayed at the state of our children’s health.

Concerning this frightful state of children’s health, the Times reported the following:

“We are in an epidemic,” said Dr. Jatinder Bhatia, a member of the academy’s nutrition committee who is a professor and chief of neonatology at the Medical College of Georgia in Augusta. “The risk of giving statins at a lower age is less than the benefit you’re going to get out of it.”

Dr. Bhatia said that although there was not “a whole lot” of data on pediatric use of cholesterol-lowering drugs, recent research showed that the drugs were generally safe for children.

An epidemic of what? High cholesterol? Not according to the academy’s report, which states that cholesterol levels in children declined between 1966 and 1994 and stayed the same between 1994 and 2000.

No, we are in an epidemic of obesity. As the Times reported:

But proponents say there is growing evidence that the first signs of heart disease show up in childhood, and with 30 percent of the nation’s children overweight or obese, many doctors fear that a rash of early heart attacks and diabetes is on the horizon as these children grow up.

Is there any evidence that statins lead to weight loss? If there is, I am not aware of it.

The point is immaterial, because the academy doesn’t claim to have any evidence for its position in the first place. For example, its report states the following:

Also, data supporting a particular level of childhood cholesterol that predicts risk of adult CVD do not exist, which makes the prospect of a firm evidence-based recommendation for cholesterol screening for children elusive.

 And further down:

It is difficult to develop an evidence-based approach for the specific age at which pharmacologic treatment should be implemented. . . . It is not known whether there is an age at which development of the atherosclerotic process is accelerated.

In other words, they don’t know what level of cholesterol is risky and at what age it starts posing a risk, but they will nevertheless assume that there is some level that does start to pose a risk at some age and they will thus have to make a guess just what that level and what that age is.

The report discusses evidence that the “metabolic syndrome” and the “recent epidemic of childhood obesity” are tied to the risk of diabetes and heart disease and evidence that even modest weight loss at a level of five to seven percent is sufficient to prevent diabetes. Yet somehow instead of making a recommendation about how to more effectively lose weight the authors derive from this data a much less logical but much more profitable conclusion that 8-year-olds should be put on statins.

As to the recommendation to feed infants low-fat milk, the Times reported the following:

The academy also now recommends giving children low-fat milk after 12 months if a doctor is concerned about future weight problems. Although children need fat for brain development, the group says that because children often consume so much fat, low-fat milk is now appropriate.

This is rather remarkable, because the academy attributed the drop in childhood cholesterol levels to the successes of the anti-fat, anti-cholesterol campaign that began in the 1950s. But now children no longer need milkfat because they are getting plenty of fat. Well which is it? Are they getting more fat now or less fat?

Of course milkfat is also a source of choline, along with liver and egg yolks, which is essential to brain development.

But even this misses the point. Cholesterol is essential to brain development!

One of the first articles I added to my section on the functions of cholesterol was an article entitled “Learning, Your Memory, and Cholesterol.” It discusses the evidence uncovered eight years ago that cholesterol is the limiting factor for the formation of synapses, which are the connections between neurons that allow learning and memory to take place.

Lowering brain levels of cholesterol can be detrimental at any age beacause of this, but the consequences for children — whose brains are still developing at a much more rapid rate — could be much more dire.

No doubt, most researchers and medical doctors mean well and are honestly trying to help our children. But surely someone in these drug companies must know that cholesterol is necessary for brain development, and that cholesterol-lowering drugs reduce mental performance in adults. Surely they must know that if we raise our next generation of children on statins during the critical periods of brain development, we may raise a whole generation with compromised intelligence.

And if that’s the case, are they trying to dumb us down? Sometimes it seems like that’s the case.
Article written by Chris Masterjohn
Read the complete article here.