Bottom line:

• Regular moderate exercise reduces the chances of your getting ill

• Extreme exercise can multiply the chances of your succumbing to an infectious disease as much as sixfold.

The trouble with these sorts of epidemiological studies is that we are dealing with two distinct groups of people, those who engage in extreme exercise and those who exercise moderately. Perhaps there is something in the makeup of people who go in for extreme sports that makes them more susceptible to infection. Perhaps even if they were to change their exercise pattern they would still be more vulnerable to infection than people whose natural inclination is to exercise moderately.

Professor Jeffrey Woods works with mice rather than humans. Working with mice has the advantage that it is possible for him to decide which mice exercise and how hard they exercise. The mice have no say in the matter.

In 2004 Professor Woods found that sedentary mice are most vulnerable to the affects of infection but mice that exercised moderately did better on average than mice that were forced to engage in extreme exercise. Since Professor Woods’ mice had no say in their exercise regime it cannot be the something in the makeup of the mouse that caused the extreme exercise group to become vulnerable to infection. It could only be the extreme exercise itself.

Now Professor Woods has gone a step further. In a recent paper in Exercise and Sports Science Reviews titled Exercise and Respiratory Tract Viral Infections Professor Woods and his team identify the mechanism that cause extreme exercisers to become more susceptible to respiratory tract infection. And thereby hangs a fascinating tale.

When a bacterium, virus or some other pathogen enters your body your immune system mounts a furious all-out assault on the “invasion site”. We experience this as inflammation. The animation below shows what happens.

So far so cool. But at some point the initial inflammatory response needs to be turned off. If it persists it can cause problems. It is now believed that a number of diseases including arthritis, cardiovascular disease and cancer can result from persistent inflammation.

The inflammatory response is mediated by T-helper cells. It turns out that there are two distinct types of T helper cells called Th1 and Th2. The Th1 cells start the inflammation going and the Th2 cells damp it down.

Th1 cells are the “on” switch

Th2 cells are the “off” switch

It turns out that moderate exercise suppresses the Th1 response a little and bolsters the Th2 response. This results in a gentler immune response than sedentary animals experience.

But extreme exercise suppresses the Th1 response too much. The inflammation dies down before it has destroyed the invading virus.

Vitamin E is a powerful antioxidant which means it neutralises the free radicals that cause cell and tissue damage. In addition your body needs vitamin E to make the red blood cells that enable blood to transport oxygen.

Your body needs vitamin E. Fortunately it is readily available. You can buy the stuff in 50 Kg (110 lb) drums from Nutrakey Industries in China. While you’re about it why not stock up on a 25 Kg (55 lb) drum of vitamin C from the same supplier?

OK, maybe I am being a little facetious. But if vitamin E is such good stuff would it do any harm to pop a few vitamin E pills just to make sure you’re getting enough?

Excess Vitamin E may lead you to an early Grave

The answer is a definite “yes”. An analysis of available data by Edgar R. Miller and other published in Annals of Internal Medicine, 4 January 2005 | Volume 142 Issue 1 | Pages 37-46 suggests that high vitamin E consumption provides no discernible health benefits and may cause premature death.

Too many Antioxidants diminish the Benefits of Exercise

It gets worse. You’re working out regularly at the gym. You know that hard exercise speeds up metabolism which causes the production of large quantities of free radicals. You protect yourself by taking supplements containing antioxidants – specifically vitamins C and E. You’re got yourself covered. Right?

Wrong?

Too many antioxidants actually diminish the benefits of exercise. This is the surprise finding of Michael Ristow and others published in Proceedings of the National Academy of Sciences, 31 March 2009.

A Reality Check – Those important Micronutrients.

Here is a reality check. Antioxidants such as vitamins C and E belong to a class of chemicals called micronutrients. They are called micronutrients because you need them in small quantities.

A healthy body needs a whole cocktail of micronutrients. Not all micronutrients have been identified. Even among those that have been identified, we do not know all their precise roles. Most importantly, we do not know how the different micronutrients interact. Some micronutrients may be ineffective, perhaps even harmful, unless taken in combination with others. When it comes to micronutrients the cocktail is greater than the sum of the parts.

Maybe one day we shall have a better understanding of the micronutrient cocktail. Combined with an analysis of your genome it may be possible to give you a micronutrient pill precisely tailored to your needs; a pill that delivers all the micronutrients you need in jusy the right quantities.

That day is not yet. Today in 2009, for most people, the only way you can be certain of getting a full micronutrient cocktail with the right dosages is to eat fruits and vegetables. Anyone who tells you otherwise is either lying or does not understand the issues.

If your doctor has diagnosed a deficiency in some micronutrient and has prescribed supplements then take them. Otherwise flush the supplements down the toilet and plan on eating at least 5 different fruits and vegetables daily.

In simple terms free radicals are molecules, ions or even some individual atoms that are hungry for electrons. They steal electrons from wherever they can find them. Free radicals are bad news because they can steal electrons from the vital molecules inside your cell thus disrupting the functioning of those cells. Free radicals have been shown to be involved in a variety of serious afflictions from cancer to premature aging. Free radicals are also involved in heart disease. They react with LDL particles stuck in the arterial wall causing inflammation and the immune response that leads to the formation of atheromous plaque.

The process of stealing electrons is called oxidation. Too much oxidation causes oxidative stress.

Your body produces free radicals in the normal course of metabolism. When you exercise hard your metabolism speeds up and you produce free radicals in greater abundance. The harder you exercise the more free radicals your body produces.

Antioxidants to the rescue

Do not conclude from this that you should throw away those running shoes and lead a life of indolence. What you need is a regular supply of antioxidants. Antioxidants react with free radicals and make them safe.

The best known antioxidants are vitamins C and E. Many people take these in the form of supplements. Don’t! I shall explain why you should avoid vitamin pills in a subsequent post.

You need a Cocktail of Antioxidants

There is no “magic bullet” antioxidant that will protect you from free radicals anywhere and everywhere. Our bodies seem to need a cocktail of antioxidants to provide in-depth defence of every part of the cell against the depredations of free radicals. Cocktails of antioxidants are freely and cheaply available in fruit, vegetables, green tea, coffee and red wine.

Here is a list of some of the better known antioxidants and where you can get them.

Overall pomegranates may deliver the most powerful cocktail of antioxidants. makes a delicious and refreshing drink.

Conclusion

You need a cocktail of antioxidants to control the free radicals that are a by product of normal metabolism. We do not yet know all the ingredients of the cocktail but we know where to get it. Eat a variety of fruits and vegetables and you’ll get all the antioxidants you need.

Rely on vitamin pills and supplements instead of fruits and vegetables and you may be missing out on some vital ingredients in the cocktail.

Let me start by saying where I agree with Dr. Maldonado.

In his New Yorker article and in subsequent articles and follow-ups Dr. Gawande extols the virtues of the Mayo Clinic model of health care. While I think much can be learned from the Mayo Clinic I do not think this model can be replicated across the United States. Dr. Maldonado has stated the reasons in his essay and I shall not repeat them here.

Dr Maldonado rightly points out that most doctors are highly skilled, hard working and want to do what is best for their patients. That has been my experience. The reality is that doctors work longer hours, endure greater stress and receive less financial reward than most other professionals. I doubt any doctor has ever come close to matching the almost half a billion dollar bonus erstwhile Lehman Brothers CEO Richard Fuld received for instituting polices that sent his bank belly-up.

However Dr. Maldonado fails to come to grips with the thrust of Dr. Gawande’s essay which is that Medicare enrolees in McAllen are subject to unnecessary procedures to the point where, on balance, the risk outweighs the benefits. Furthermore, it is not only Dr. Gawande who is making this claim. To quote Elliot Fisher again:

“…Gawande appears as the translator of what we’ve all known for a long time.”

That is, the medical establishment has known for a long time that some doctors subject patients to unnecessary procedures.

Surely Dr. Maldonado is not suggesting that doctors should supplement their incomes by performing unneeded procedures. But if he is not suggesting that then what is he suggesting?

Dr. Maldonado also fails to deal with the very real conflicts of interest, not to mention kickbacks, that Dr. Gawande’s essay revealed. Surely it cannot be right that a primary care doctor has a financial stake in a hospital to which he refers patients.

It would not surprise me if you’ve never heard of the town of McAllen in Texas, USA. Neither had I until a week ago. McAllen is located in Hidalgo County which has the lowest household income of any county in the US. McAllen is the largest city in what may be the poorest county in the United States.

Here’s what makes McAllen special. It may have the most dysfunctional group of medical professionals in the first world.

ABOUT US MEDICARE?

Let me explain. In broad terms, US Medicare funds healthcare for people over 65 or people under 65 who are disabled. Almost every American over age 65 is enrolled in some sort of Medicare plan.

Medicare “‘Part A” covers hospital stays. Medicare “Part B” covers almost everything else except for drugs.

THE COST OF US MEDICARE

How expensive is Medicare? To put it another way, how much does Medicare disburse per enrolee?

According to the Dartmouth Atlas of Health Care the 2006 cost per enrolee for Medicare Parts A and B was $8,300. Since over 42 million Americans are covered by Medicare the total cost is of the order of $350 billion.

The average of $8,300 hides wide variations. In Texas the 2006 average per enrolee is $7,900 in El Paso and a whopping $14,800 in McAllen.

WHY DO MEDICARE COSTS DIFFER BETWEEN REGIONS?

The demographics of El Paso and McAllen are similar. Why is there such a wide disparity between two towns in the same state? Why is the El Paso average slightly below the national average while the McAllen average is nearly 80% above the national average?

DOCTOR ATUL GAWANDE’S NEW YORKER ESSAY

That is the subject of a New Yorker essay, “THE COST CONUNDRUM”, by Atul Gawande. If you want to know what Barack Obama and his advisers are reading about health care, read Dr. Gawande’s essay.

SOME SALIENT FACTS

• McAllen was not always the most expensive Medicare city in the US. Back in 1992 Medicare disbursements per enrolee in McAllen were close to the national average.

• El Paso and McAllen have similar demographics. There is no obvious reason why McAllen should be almost twice as expensive as El Paso.

• The Medicare enrolled population of McAllen is not noticeably sicker than in El Paso. If anything the rate of cardiovascular disease among Medicare enrolees in McAllen is slightly lower than the comparable rate in El Paso.

• In terms of outcomes it is hard to spot any benefits Medicare enrolees in McAllen enjoy for the additional $7,000 that is spent on their health. If anything Medicare enrolees in lower-cost El Paso may actually be doing better than their counterparts in high cost McAllen.

• Medicare ranks hospitals according to the quality of care they deliver. On average the five largest hospitals in McAllen ranked below El Paso’s.

• The cost difference cannot be attributed to prescribing practices because drugs are not covered by Medicare Parts A and B. Whatever the reason for the cost differences between McAllen and El Paso, it has nothing to do with the pharmaceutical companies.

HIGH MEDICARE COSTS IN MCALLEN HAVE NOTHING TO DO WITH MISLEADING ADVERTISING BY PHARMACEUTICAL COMPANIES

I want to emphasise the last point. High Medicare costs in McAllen have nothing to do with deceptive advertising by the pharmaceutical industry. Whatever differences exist must be due to differences in the needs of patients in McAllen as compared to patients in El Paso, or due to differences in the way doctors in McAllen practise medicine, or both.

DOCTOR GAWANDE ASKS MCALLEN DOCTORS WHY THEIR TOWN IS SO EXPENSIVE

Dr Gawande asked doctors in McAllen why they thought their town was so expensive. Some excerpts from Dr. Gawande’s essay:

“Come on,” the … surgeon finally said. “We all know these arguments are bullshit. There is overutilization here, pure and simple.” Doctors, he said, were racking up charges with extra tests, services, and procedures.

The surgeon came to McAllen in the mid-nineties, and since then, he said, “the way to practice medicine has changed completely. Before, it was about how to do a good job. Now it is about ‘How much will you benefit?’ ” (Emphasis added)

Here we have a doctor flatly stating that his colleagues are motivated more by personal financial reward than by doing what is best for their patients. This has more than mere financial consequences, serious as these may be.

TO CATHETERISE OR NOT

From Dr. Gawande’s essay:

I gave the doctors around the table a scenario. A forty-year-old woman comes in with chest pain after a fight with her husband. An EKG is normal. The chest pain goes away. She has no family history of heart disease. What did McAllen doctors do fifteen years ago?

Send her home, they said. Maybe get a stress test to confirm that there’s no issue, but even that might be overkill.

And today? Today, the cardiologist said, she would get a stress test, an echocardiogram, a mobile Holter monitor, and maybe even a cardiac catheterization.

“Oh, she’s definitely getting a cath,” the internist said, laughing grimly. (Emphasis added)

WHAT IS “A CATH”?

In a procedure known as cardiac catheterisation a thin tube is inserted into an artery or vein, usually the femoral artery in the groin. From there it is advanced under X-ray guidance to the coronary arteries or into the chambers of the heart. It is used to measure blood pressure in the heart as well as the heart’s pumping capacity. Catheterisation may also be used to take real time pictures of the heart and arteries or to perform a heart biopsy.

It is a tribute to the skills of cardiac surgeons and to the progress of surgical techniques that this highly invasive procedure is relatively low risk. Appropriately used it saves lives.

However the key word is “relatively”. It is not risk free. According to Medline the risks of catheterisation include heart attack and stroke. It is definitely not a procedure to be used without carefully considering whether the potential benefits really do outweigh the risks. “She’s definitely getting a cath…” does not bode well for Medicare patients in McAllen.

BROAD COMPARISONS BETWEEN MCALLEN AND EL PASO

Excerpts:

“Between 2001 and 2005, critically ill Medicare patients received almost fifty per cent more specialist visits in McAllen than in El Paso, and were two-thirds more likely to see ten or more specialists in a six-month period. In 2005 and 2006, patients in McAllen received twenty per cent more abdominal ultrasounds, thirty per cent more bone-density studies, sixty per cent more stress tests with echocardiography, two hundred per cent more nerve-conduction studies to diagnose carpal-tunnel syndrome, and five hundred and fifty per cent more urine-flow studies to diagnose prostate troubles. They received one-fifth to two-thirds more gallbladder operations, knee replacements, breast biopsies, and bladder scopes. They also received two to three times as many pacemakers, implantable defibrillators, cardiac-bypass operations, carotid endarterectomies, and coronary-artery stents. And Medicare paid for five times as many home-nurse visits….”

Remember none of this increased use in medical resources seems to have resulted in improved outcomes for Medicare enrolees in McAllen. If anything the reverse is true.

THE LESS IS MORE RULE

Yet more excerpts:

“…Rochester, Minnesota, where the Mayo Clinic dominates the scene, has fantastically high levels of technological capability and quality, but its Medicare spending is in the lowest fifteen per cent of the country—$6,688 per enrollee in 2006, which is eight thousand dollars less than the figure for McAllen. Two economists working at Dartmouth, Katherine Baicker and Amitabh Chandra, found that the more money Medicare spent per person in a given state the lower that state’s quality ranking tended to be. In fact, the four states with the highest levels of spending—Louisiana, Texas, California, and Florida—were near the bottom of the national rankings on the quality of patient care.

“In a 2003 study, another Dartmouth team, led by the internist Elliott Fisher, examined the treatment received by a million elderly Americans diagnosed with colon or rectal cancer, a hip fracture, or a heart attack. They found that patients in higher-spending regions received sixty per cent more care than elsewhere. They got more frequent tests and procedures, more visits with specialists, and more frequent admission to hospitals. Yet they did no better than other patients, whether this was measured in terms of survival, their ability to function, or satisfaction with the care they received. If anything, they seemed to do worse.”

In other words when it comes to health care the rule seem to be that, up to a point, less is more.

WHY IS LESS MORE?

Obviously “less is more” applies only up to a point. I am not suggesting we can improve health outcomes by reducing medical expenditure to zero!

I am saying that beyond a certain point, and where that point is reached will always remain a matter of clinical judgement that will vary from patient to patient, more becomes self-defeating. No procedure and no medication is risk free and beyond some point the risks start outweighing the benefits to the patient.

Perhaps in McAllen and other regions where Medicare costs are high the local medical communities have passed the point where risks to the patient outweigh the benefits. And perhaps they have been motivated more by the desire to maximise their revenues than by considering what is best for their patients.

THE DOCTORS OF MCALLEN RESPOND

The doctors of McAllen have not taken Dr. Gawande’s assertions lying down. In a media release they assert that McAllen’s Medicare expenditures are high because McAllen doctor’s see patients who are sicker than most and who require longer hospital stays because of their poor living conditions.

That may be. It does not explain why the “less is more” rule seems to apply in other states or why the Mayo clinic, perhaps the world’s finest, seems able to provide top quality care at such relatively low cost.

THE MOST OUTRAGEOUS REVELATION IN DOCTOR GAWANDE’S ESSAY - KICKBACKS

Perhaps the most outrageous revelation in Dr. Gawande’s essay is the fact that some doctor’s demand kickbacks. Another excerpt:

“…I spoke to a marketing rep for a McAllen home-health agency….Her job is to persuade doctors to use her agency rather than others. …She described how, a decade or so ago, a few early agencies began rewarding doctors who ordered home visits with more than trinkets: they provided tickets to professional sporting events, jewelry, and other gifts. That set the tone. Other agencies jumped in. Some began paying doctors a supplemental salary, as “medical directors,” for steering business in their direction. Doctors came to expect a share of the revenue stream.

“Agencies that want to compete on quality struggle to remain in business, the rep said. Doctors have asked her for a medical-director salary of four or five thousand dollars a month in return for sending her business. One asked a colleague of hers for private-school tuition for his child; another wanted sex.

“I explained the rules and regulations and the anti-kickback law, and told them no,” she said of her dealings with such doctors. “Does it hurt my business?” She paused. “I’m O.K. working only with ethical physicians,” she finally said.”

Doctors taking kickbacks should have their licences to practise medicine yanked. For life.

THE MOST DAMNING INDICTMENT OF THE AMERICAN MEDICAL ESTABLISHMENT

A leading journal, Health Affairs, organised a round table discussion on Dr. Gawande’s essay and related topics. Here is what one of the participants, Elliott Fisher, Director of Health Policy Research at Dartmouth’s Center for the Evaluative Clinical Sciences, had to say:

“…he [Gawande] was able to tell plausible stories that are consistent with lots of what we’ve found in our research. He made it easily understandable to a lay audience that the differences in practice aren’t about differences in patient need, and that they can be driven — sometimes quite powerfully — by both the payment system and how local physicians decide to practice.”

And:

“…Gawande appears as the translator of what we’ve all known for a long time.” (Emphasis added)

In other words, according to a distinguished member of the American medical establishment, Dr. Gawande’s essay is old news!

And that may be the most damning indictment of the American medical establishment.

DO THE SAME PROBLEMS EXIST IN AUSTRALIA?

I do not know but I am going to try and find out. I am drafting a letter to send to the minister of health and to the health spokespersons for the Liberal and Green parties.

Recall that JUPITER is an acronym for “Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin.” The JUPITER trials were intended to justify the use of a class of cholesterol lowering medications known as statins on apparently healthy patients who had:

• Normal cholesterol levels (They did not need cholesterol lowering medication)
• Elevated levels of c-reactive protein (CRP) indicating the prevalence of inflammation

The purpose of the trial was to determine whether such patients could benefit from the inflammation fighting properties of statins. The actual statin used in the study was Rosuvastatin marketed by AstraZeneca as Crestor. I discussed the JUPITER trials in a previous post .

JUPITER epitomises what is wrong with the current medical paradigm

JUPITER epitomises everything that is wrong with the contemporary medical paradigm. To see why let’s take a look at the characteristics of the patients who participated in the JUPITER trials.

• They are a rather hefty lot. Three quarters of them are overweight (body mass index greater than 25) or downright obese (BMI greater than 30).
• About 15% of them are smokers! Using statins to combat heart disease in a smoker is like trying to fight a bush fire with a water pistol. You may as well not bother.
• The blood pressure of the participants tends to be on the high side and over 40% suffer from metabolic syndrome. Metabolic syndrome is a common consequence of an unhealthy lifestyle.

In short, the trial participants are an unhealthy lot. This is not surprising. Elevated CRP levels are most often associated with being overweight or obese, smoking and lack of exercise.

Let’s be clear on something. Not everyone who has elevated CRP levels leads an unhealthy lifestyle and not everyone who leads an unhealthy lifestyle has elevated CRP levels. However unhealthy lifestyles and elevated CRP levels are often associated. Judging by what we know of the trial participants it is fair to assume that many eat too much of the wrong kinds of food and do not get enough exercise.

Now we see why the very idea behind the JUPITER trials is flawed. We already know that certain lifestyle changes can both reduce CRP levels and reduce the risk of cardiovascular disease. Here is the good news:

• Lifestyle changes can reduce the risk of cardiovascular disease
• Lifestyle changes do not carry any of the risks associated with taking statins. (See here and here).
• As we have seen, taking Rosuvastatin is associated with an increased risk of type 2 diabetes. Lifestyle changes can actually reduce the risk of type 2 diabetes.
• Far from impairing brain function lifestyle changes can enhance brain function.

In subsequent posts I shall be presenting evidence for all the claims I am making about the benefits of suitable lifestyle changes.

It is likely that, as a therapy, lifestyle changes – a healthy diet and regular exercise - are in every way superior to medicating apparently healthy people with statins.

So what’s the downside to lifestyle changes? Why are we even bothering with statins?

We already know the answer. It is easier to pop a pill than to change your lifestyle. I write this without in any way meaning to disparage people who find it hard to change their eating and exercise habits. I can attest from personal experience how hard it is. But it is possible. In later posts I shall be describing evidence based strategies for effecting healthy lifestyle changes.

Will doctors change their clinical practice as a consequence of the JUPITER study?

Let us return to the JUPITER study. The editors of the New England Journal of Medicine which published the results of the JUPITER study ask readers, mainly doctors, whether it will change their practice. You can see how readers responded here. In response to the question “Do you believe, on the basis of the JUPITER trial results, that the therapeutic use of statins in apparently healthy adults should be changed?” 48% of readers answered “yes” and 52% “no.”

Note that if 48% of clinicians start prescribing more statins as a result of the JUPITER study AstraZeneca will recover the cost of financing the trials many times over. For them it will prove to have been a highly profitable investment.

What should the doctor tell the patient?

What should a doctor say to a somewhat portly 60 year old sedentary patient with elevated CRP levels?

It seems to me an honest doctor would have to say something along the following lines.

I’ve conducted a test that shows you have an inflammation in your body. That raises the risk of your getting cardiovascular disease. In other words, you are at increased risk of suffering either a heart attack or a stroke. One out of every 74 people with your condition suffers a heart attack or stroke every year.

I can prescribe this pill. You will have to take it for the rest of your life. If you take the pill it reduces the probability of your getting cardiovascular disease by 0.59% per year.

On the other hand you have a 1.17%chance per year of getting type 2 diabetes if you do not take the pill. If you choose to take the pill it increases the odds of your getting type 2 by 0.28% per year. Type 2 diabetes is a serious illness which itself carries an increased risk of cardiovascular disease as well as dementia.

One of the risks associated with taking the pill is damage to your muscles. Taking the pill may also cause your brain to function below par.

Alternatively you could try TLC.

TLC stands for THERAPEUTIC LIFESTYLE CHANGES. lt That means you change your eating drinking and smoking habits, get serious about losing weight and exercise for at least half and hour a day at least five days a week.

TLC is usually even better at averting the risk of cardiovascular disease than the pill. It also reduces the risk of getting type 2 diabetes and enhances brain function.

The downside of TLC is that most people can’t bring it off.

Which do you, Mr. Patient, want to try?

An alternative to the JUPITER study

Here is what I would have liked to see. Instead of two groups we needed four groups as follows:

• A placebo group
• A Rosuvastatin group
• A group that received lifestyle counselling and a placebo
• A group that received a combination of lifestyle counselling and Rosuvastatin.

The last group is necessary because there could be a synergistic interaction between statin therapy and TLC in which the benefits clearly outweigh the risks.

Such a study really would have thrown up which is the most effective therapy.

In a nutshell

The JUPITER study illustrates that medicating some apparently healthy people with statins brings about small benefits at the cost of not insignificant risks. The alternative of a “TLC” was not included in the study. TLC carries no risks and probably greater benefits.

JUPITER was hyped in a totally misleading fashion. The risks were understated. The benefits were overstated by using relative instead of absolute risk reduction. A relative risk reduction of almost 50% sounds much better than an absolute risk reduction of 0.59%.

In a nutshell that is what is wrong with the current medical paradigm.

What Paul Ridker has to say.

In fairness to the JUPITER study’s principle researcher, Dr. Paul Ridker, he emphasises that lifestyle changes should precede statin therapy. Here is what he said in a recent interview:

“…the first step is not a statin; the first step is diet, exercise, smoking cessation and getting into a good preventive program.“

In my previous post I analysed the results of the JUPITER drug trials. I demonstrated that, for the participants, the benefits of taking Rosuvastatin (Crestor) were slight while the risks were far from negligible.

I shall now explain how this translates into a difference of opinion with Healthy Skepticism. However, first, a general comment.

Most Australian doctors are dedicated to doing the best for their patients. I have never encountered a doctor in Australia who prescribes medication in a cavalier fashion. What follows is not an attack on doctors generally or on any one doctor.

It is however an attack on what might be called the “Medical Establishment.” I believe the leaders of the medical profession have let their members down badly.

Let us return to the JUPITER trials. Suppose you read TIME magazine’s puff piece on the benefits of statins generally and Crestor in particular. Not realising that TIME employs scientifically illiterate journalists to write about medical matters you truly believe that the JUPITER trials were one of the 10 top medical breakthroughs of 2008.

What do you do?

You go and have your CRP levels checked to see whether there is any sign of inflammation. If it turns out that your CRP levels are elevated you start dosing yourself with 20mg of Crestor per day for the rest of your life.

You need a prescription to buy statins

Except that if you live in Australia, the UK, the US or most industrially advanced countries you can do nothing of the sort. You cannot walk into a pharmacy and buy Crestor or any other statin over the counter. First you need a prescription from a doctor. A pharmacist who sold you a statin without a valid prescription would be breaking the law.

Why do you need a doctor’s prescription to buy certain drugs?

Why is that? Why is there all this bureaucratic “red tape” about buying a heart medication? It’s not as if you can get high on Crestor. DUI means driving under the influence of alcohol, not Crestor. There is no record of Crestor crazed motorists wreaking havoc on our roads.

Crestor is safer than alcohol. A 20mg dose of Crestor probably does you less harm than the average cheeseburger with fries. Given the mysterious growth in nut allergies you are probably safer giving a stranger a Crestor pill than a peanut.

Alcohol, cheeseburgers with or without fries and peanuts are all freely available. So for that matter are cigarettes. Why restrict the sale of Crestor and not cigarettes? You may get ill from second-hand cigarette smoke but people can pop Crestor pills in your presence without harming you one iota.

Governments restrict the sale of Crestor and other medications because they believe, or purport to believe, that a medically untrained person cannot take such decisions on their own. We need a skilled professional to tell us what medication to take. That is why we grant doctors a monopoly of the prescription pad.

Doctors value their monopoly of the prescription pad

Make no mistake, doctors value this monopoly as is demonstrated by the Australian Medical Association’s strong objections to allowing “nurse practitioners” to prescribe.

I agree with the Australian Medical Association

Now I happen to agree with the Australian Medical Association. I think highly trained professionals should keep a monopoly of the prescription pad. I do not think that nurses have the scientific training that will enable them to keep up with the ever accelerating advances in biology. And I shudder to think what would happen if we ever allowed pharmaceutical companies to sell their products directly to the public.

We need doctors to guard us against misleading pharmaceutical advertising

Fact is, we need trained doctors to guard us against being misled by pharmaceutical company advertising.

What does the Healthy Skepticism website say?

Now consider the following quotes from the Healthy Skepticism website:

“Companies would not spend such massive amounts on promotion if it were not effective at influencing prescribing. …”

“Promotion influences prescribing much more than most health professionals realise…”

“Many advertisements and statements from pharmaceutical representatives are misleading…”

“Reliance on promotional information may endanger lives and expose prescribers to the risk of litigation…”

“Thirteen observational studies have found that exposure to pharmaceutical promotion and doctors positive attitudes towards pharmaceutical promotion both correlate with harmful use of pharmaceuticals….”

This is tantamount to whining:

“Oh poor little us. Those nasty people in the pharmaceutical companies keep bombarding us with misleading promotions and we keep believing them.”

Does this sound as if the leaders of the medical profession are behaving like worthy custodians of the prescription pad?

Here is a quote from the Healthy Skepticism website concerning the JUPITER trials.

“So there you have it. A possibly unethical trial with marginal results gets trumpeted in the media as showing “wide benefit” (New York Times). Based on the laudatory quotes coming from the leaders of the American College of Cardiology, this off-label use of statins will quickly find its way into clinical practice guidelines and drug compendia. Within a few years, health care payers will be forking over billions more dollars to the statin drug makers in the name of preventing heart disease.” (Emphases added)

This “off-label use of statins”will only “find its way into clinical practice guidelines” if the leaders of the medical establishment allow that to happen. The pharmaceutical companies may attempt to persuade but they cannot compel the profession to adopt clinical practice guidelines.

The nub of my philosophical difference - who is to blame?

And here is the nub of my philosophical difference with Healthy Skepticism. The blame for inappropriate prescribing does not lie with the pharmaceutical industry or “the system.” Nor does it lie with most doctors.

The blame lies squarely with the leaders of the medical profession’s professional bodies. They have shamelessly abdicated their responsibility to ensure that their members have access to high quality, unbiased continuing professional education; professional education that is free from the taint of pharmaceutical company promotions.

I said that we need doctors to guard us from “Big Pharma’s” misleading advertising. More than 2,000 years ago the Roman poet, Juvenal asked:

Quis custodiet ipsos custodes? (Who shall guard the guardians themselves?)

In the case of the medical profession this can only be the leaders of the doctors’ professional bodies. If they fail to “guard the guardians” the vacuum will be filled by pharmaceutical companies and snake oil salesmen.

Not an attack on doctors generally

I want to repeat that this is not an attack on doctors generally. Most doctors really do have the best interests of their patients at heart.

Healthy Skepticism still part of the solution

Flawed as I believe it to be, Healthy Skepticism is part of the solution, not part of the problem.

I am afraid that I must respectfully differ with Dr. Mansfield. I do have a philosophical difference or, at any rate, a difference of opinion, with Healthy Skepticism. Rather than argue in the abstract I shall use a “case study” to illustrate our differences. To be specific I shall analyse the much hyped JUPITER study on the use of the cholesterol lowering drug, Rosuvastatin. AstraZeneca markets Rosuvastatin as “Crestor.”

One of the top 10 medical breakthroughs of 2008?

The TIME Magazine website contains a segment called The Top 10 Everything of 2008. The segment lists what TIME’s editors believe are the top 10 stories of 2008 for various news categories.

One of the “top 10″ categories is the top 10 medical breakthroughs of 2008. The alleged medical breakthrough that caught my attention appears second on the list. It is called Inflammation vs. Cholesterol.

Statins, cardiovascular disease and inflammation

Recall that high LDL-C levels often portend a heart attack. However it turns out that only about half of all heart attack victims have elevated LDL-C levels. The rest have “normal” LDL-C levels. Further, many people with elevated LDL-C levels never suffer a heart attack.

What accounts for the difference? Why do some people with apparently healthy LDL-C levels get heart attacks and why do many people with elevated LDL-C levels never suffer any sort of cardio-vascular problem?

The difference may be inflammation. Inflammation plays a role in both the formation of atheromatic plaque and in the rupture of the plaque cap that leads to the formation of blood clots. Could it be that it is the combination of elevated LDL-C levels and inflammation that leads to heart attacks? Could it be that inflammation is the root cause of heart attacks in people who have what appear to be healthy LDL-C levels?

A widely used class of cholesterol lowering drugs known as statins also have anti-inflammatory properties. In addition to reducing LDL-C levels they combat inflammation rather like aspirin and Panadol. Is it possible that it is the combination of LDL-C and inflammation reduction that make statins allegedly so effective in protecting people against heart attacks?

Testing for inflammation

But how do we know whether inflammation is present?

Just as there is a test to determine LDL-C levels there is a test to determine whether inflammation is present in the body. The test has the unfortunate acronym of hs-CRP which stands for high-sensitivity C-Reactive Protein.

The liver produces elevated levels of C-reactive protein when inflammation is present in the body. The hs-CRP test measures the level of C-reactive protein in the blood.

The JUPITER trials

And this brings us to the JUPITER trials.

JUPITER stands for “Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin.” Rosuvastatin is a statin, a cholesterol lowering drug, marketed by AstraZeneca under the name “Rosuvastatin”. JUPITER was intended to test the theory that Rosuvastatin could reduce the incidence of heart attacks and other cardiovascular diseases such as stroke among people with elevated CRP levels and normal LDL-C levels. AstraZeneca, Merck, Novartis and other pharmaceutical companies financed the JUPITER trials. Dr. Paul Ridker, the principal researcher, is joint patent-holder, along with Brigham and Women’s Hospital, of the hs-CRP assay used to determine CRP levels. The results of the JUPITER trial were published in the New England Journal of Medicine in November 2008.

The results created a sensation – especially among scientifically illiterate journalists. As TIME Magazine put it:

“…Ridker’s recent research, published in the New England Journal of Medicine, showed that when people with normal cholesterol and high levels of CRP… took statins, their CRP levels plummeted and their heart attack risk fell 54%.”

Well that’s fantastic! Heart attacks are a leading cause of death and disability in all industrialised countries. Isn’t it wonderful to have a drug that can cut the risk by more than half? No wonder the editors of TIME considered JUPITER one of the top 10 medical breakthroughs of 2008.

Does reality match the hype?

Let’s take a closer look at the JUPITER results and see whether the reality matches the hype.

17,802 people in 26 countries participated in the study. They were assigned randomly to a placebo group and to a group that received 20mg of Rosuvastatin daily. Both groups were monitored for the onset of cardiovascular diseases – called “primary endpoints” in the study. The primary end points of interest were:

• Myocardial infarction - ie heart attack
• stroke
• Arterial revascularization - for example, bypass surgery
• Hospitalisation for unstable angina.
• Death from cardiovascular disease. Cardiovascular disease is any disease involving the heart or blood vessels.

If significantly fewer members of the Rosuvastatin group suffered a “primary end point” as compared to the placebo group then it is reasonable to say that Rosuvastatin has some prophylactic value.

In plain English, did taking Rosuvastatin protect the participants against the onset of a cardiovascular condition such as heart disease or stroke? Did those who took Rosuvastatin have to undergo fewer bypass surgeries? Did fewer of the Rosuvastatin group die as a result of cardiovascular disease?

A cursory reading of the JUPITER trial results appears to bear out the prophylactic value of taking Rosuvastatin. The incidence of “primary end points” in the Rosuvastatin group was just slightly more than half that of the incidence in the placebo group.

In plain language, participants in the Rosuvastatin group were much less likely to be afflicted with cardiovascular disease than those on the placebo group. The actual reduction in the likelihood of getting a cardiovascular condition was a whopping 44%. Who wouldn’t want to cut their risk of getting a cardiovascular condition by 44%?

The results were considered so positive that the trial was cut short because it was felt unethical to deprive the placebo group of the benefits of Rosuvastatin. No wonder the editors of TIME magazine included the results of the JUPITER trails in their list of top 10 medical breakthroughs of 2008.

Well, maybe.

A closer look at the results of the JUPITER trials

Let’s take a closer look at the results. Below I’ve set out the first line of the table of results in what I hope is a more understandable form.

There were 8,901 patients in each group. 142 patients in the Rosuvastatin group experienced the onset of cardiovascular disease compared to 251 in the placebo group. So far so simple.

The next line is a little trickier. The trial ran for five years but not all patients were enrolled for the full term. Line 3 shows the likelihood of a patient getting cardiovascular disease per year.

What line 3 shows is that 0.77% of the patients in the Rosuvastatin group and 1.36% of the patients in the placebo group experienced the onset of cardiovascular disease.

Here is another way of understanding line 3. Taking Rosuvastatin reduced the likelihood of getting a cardiovascular condition by 0.59%. (1.36 – 0.77) per year. A 0.59% reduction sounds less dramatic than a 44% reduction. What happened to the 44%?

Well 0.59% is 44% of 1.36%. The percentage of those getting cardiovascular conditions dropped 44% (from 1.36% to 0.77%) per year.

The difference between relative risk and absolute risk

Here we see the difference between relative risk and absolute risk. The relative risk dropped 44%. But, since the risk per year of getting a cardiovascular condition was low for both groups, the absolute effect is quite small.

How many people to we need to treat to avert just one instance of cardiovascular disease?

Here is yet another way of understanding line 3.

0 .59% of 170 = 1 (approximately)

So you needed to treat 170 people with Rosuvastatin to avert a single incident of cardiovascular disease per year. In any one year only one participant in 170 benefited from taking Rosuvastatin. This is considerably less dramatic than saying you’ve cut the risk almost in half.

Of course the risks of getting a cardiovascular condition mount up over the years. The norm is to look at the risk reduction over a five year period. How many people do you have to treat with Rosuvastatin in order to avert just one onset of a cardiovascular condition?

According to the authors the answer is 25. 25 people have to pop pills for 5 years in order to avert one of them getting a cardiovascular condition.

The risks associated with statins

Cost aside, this might not matter if taking a statin was risk free. But it isn’t. Far from it. As reported in the study, 270 people in the Rosuvastatin group got type 2 diabetes versus only 216 in the placebo group. A very rough “back of the envelope” calculation indicates that this represents an increase in absolute risk of approximately 0.28% per year - about half the reduction in absolute risk of getting a cardiovascular condition.

Extrapolating we have the following result. If 50 people take Rusuvastatin for five years we can expect to prevent 2 cases of cardiovascular disease at the cost of one extra case of type 2 diabetes. Type 2 diabetes is a serious condition. It is itself associated with increased risk of cardiovascular disease and dementia. Had the trial continued the complications resulting from the additional cases of type 2 diabetes may well have tilted the balance against Rosuvastatin.

However diabetes is not the only risk facing patients who take statins. As Dr. Beatrice Golomb of the University of California, San Diego School of Medicine has documented, the adverse effects of taking statins range from muscle problems to cognitive disorders which is medicalese for “statins can effect your brain.”

Yeon-Kyun Shin, professor of biophysics at the Iowa State University has shown how statins may lessen brain function by inhibiting the brain’s ability to manufacture the cholesterol it needs. Professor Shin’s research will appear in Proceedings of the National Academy of Sciences, a leading peer reviewed scientific journal.

Are the benefits worth the risks?

All medical treatment is trade-off between benefits and risks. I have no doubt that there are many instances in which the benefits of statin treatment outweigh the risks. However, in the case of the people who participated in the JUPITER trails, the benefits appear to be slight. It takes 25 people popping pills for 5 years to avert one instance of cardiovascular disease. The risks are far from negligible.

Do the risks really outweigh the benefits?

Is there a better way?

Here is a more pertinent question. Are there better ways of averting the onset of cardiovascular disease than popping statins – ways that do not carry the risks inherent in statin usage? There are and I shall be discussing them in future posts.

In my next post I examine the position that Healthy Skepticism takes on these issues and explain why we have a difference of opinion.

Healthy Skepticism does have a comment on the JUPITER trials. You can read it here.

Keep watching this space.

The Mayo Clinic does an exceptional job of educating the public about health issues. I recommend you make their website your first port of call whenever you want to research a medical issue.

The Mayo Clinic also publishes a number of excellent books and DVDs which are available from the Mayo Clinic book store. I especially commend Fitness for everybody.

However, let’s take a reality check. Most of us rely on doctors – either our own GP or a specialist to whom we have been referred by our GP – for health advice. We do not generally take advice on health from a website no matter how excellent its content.

How good is the advice we get from our doctors?

In the twenty-first century biology is the most rapidly advancing of all the sciences. Many of these advances have implications for medical practice. Doctors have to work hard to keep abreast of advances in medicine. If our doctors fail to master new knowledge their advice becomes devalued.

Do they? Do doctors keep themselves current? And, if they do, how?

It is not realistic to expect a busy practitioner to keep up with all the developments in medicine on her own. Doctors, and this applies especially to GPs, rely on their professional associations to help keep abreast of the latest developments.

And herein lies the problem. Allowing the pharmaceutical industry to play a major role in the ongoing education of doctors inevitably distorts the message doctors get when they attend conferences or read up on the latest news releases. Doctors get to hear more about the latest wonder drug and less about best practice for preventing illness in the first place.

To understand how all-pervasive is the role of the pharmaceutical industry in ongoing medical education consider these quotes made by Dr. Jon Jureidini of “Healthy Skepticism” on a recent Health Report broadcast on the Australian Broadcasting Corporation’s Radio National station:

“Well the extent [of pharmaceutical company involvement in doctor education] is enormous; I mean there’s hardly any medical education that doesn’t have at least a presence of the pharmaceutical industry in it….”

“…it [pharmaceutical company involvement] works on many levels, I mean first the companies actually just give money to support the funding of the conference and supposedly once they’ve given that money it’s up to the conference organisers how they spend it. They also pay a lot of money to have exhibition space at conferences. A lot of the registrants at a conference are drug company staff so the ones who come to man exhibition booths have to pay registration. There’s a unknown amount of doctors who have their registration paid by the pharmaceutical industry. There are symposia run at conferences which are not actually part of the core scientific program but are advertised in the program and are given space and time to operate.”

Has your doctor told you about this wonder drug?

Let me further illustrate the point by quoting from a Mayo Clinic publication. This particular publication describes a wonder drug that will:

“…help prevent illness and disease – including cancer. It will help you lose excess weight and keep it off. It will slow the aging process making you look and feel younger than your years. It will give you energy and increase your self-esteem. It will reduce stress, fight depression and anxiety, and put you in a better mood. It will make you stronger and healthier. It will improve your posture, your flexibility, your balance and your endurance. It will help you sleep better.”

According to the authors of the Mayo Clinic publication this drug:

“…doesn’t cost a penny and …you can take it several times a day or just once a day and still see results. In fact you’ll start seeing results within two weeks of your first dose.”

This drug really exists. Has your doctor told you about it? If not, why not?

I suggest it is because most doctors are simply not trained to think that way and that part of the reason is that the pharmaceutical industry has been allowed to exercise undue influence on the way doctors are educated.

If you want to know more about the wonder drug the Mayo Clinic is punting keep following developments on this website or contact the Mayo Clinic.

In my previous post, The Heart Attack Process (1) I included a link to a video that illustrates how most heart attacks occur. As I pointed out, the video was the product of AstraZeneca, a pharmaceutical company.

AstraZeneca did not produce the video out of the goodness of their collective heart. It is a promotional video which, so the makers hope, will contribute to the bottom line. The video ends with a segment in which viewers are urged to take their medication as directed by their doctors. Clearly the management of AstraZeneca hope that medication will be Crestor, AstraZeneca’s cholesterol reduction medication.

Judging by the comments that accompanied the video, some of those who viewed it are medical students. One viewer put it this way:

“Explains it all!!
all 3 lectures im revising , 5 mins of this just explains it even better. top vid thank u sooo much. “

I think it safe to say that this is one student who now has a positive image of AstraZeneca. If he or she is a future doctor the video may make her more receptive to other AstraZeneca promotions.

So why include an advertising video in a non-commercial website? To put it another way, why would I give AstraZeneca free publicity?

When I started searching Youtube for videos depicting the mechanism behind most heart attacks I expected to find something produced by the American Heart Association or one of the leading university medical schools. I had hoped I might find something produced by the Mayo Clinic.

I found nothing of the sort. The best, the most scientifically accurate, video I found was the AstraZeneca video. As far as it goes the video reflects what we know about the process of atheromous plaque formation and the dangers of plaque rupture.

In short I chose to link to the AstraZeneca video because nothing better was available.

I want to make that clear. I have no quarrel with AstraZeneca. As a commercial enterprise they have every right to produce a promotional video. Unlike many promotional videos I have seen this one, as far as it goes, is scientifically accurate.

But it is a sad commentary on the medical profession that they leave the education of the public to a pharmaceutical company because, as it happens, there are problems with the video. It does not go far enough.

I shall return to the topic of how the medical profession has de facto outsourced certain aspects of the education of doctors to the pharmaceutical industry and the consequences that flow from this. Drug company sponsoships was the topic of a recent edition of the Australian Broadcasting Corporation’s “Health Report” program. The program featured an interview with Dr Jon Jureidini of Healthy Skepticism

I have a philosophical difference with Healthy Skepticism. I think it wrong to depict the pharmaceutical industry as the great villain. The nub of the problem is that the medical profession has abdicated its responsibility to educate both to its members and the general public.

In my next post I shall discuss some of the things the AstraZeneca video leaves out.