Health Comments

Does preventive care save money - part 2

2008-07-31T21:47:58Z

A few months ago I commented on an article in the New England Journal of Medicine that questioned the cost-effectiveness of disease prevention (1). The article had the rather astonishing title "Does prevention save money?". It turned out the authors had a rather peculiar idea of prevention. They weren′t thinking of healthy eating, physical activity, smoking cessation, stress reduction etc. Instead, their main interest lay in the cost-effective use of medical diagnostics to catch diseases at their most treatable stages.

There is nothing wrong with medical tests to detect problems as early as possible, but this obviously does nothing to prevent these problems from occurring in the first place. Many of today's health problems are avoidable lifestyle diseases — think of obesity and its consequences — and one would have thought that this fact wasn′t lost on medical doctors.

Of course prevention pays, and a recent report from the Trust for America′s Health makes this very clear (2). The paper, titled "Healthier America: Investments in disease prevention yields significant savings, stronger communities", presents a detailed analysis of the kinds of savings that can be realized by relatively modest investments in practical measures:

"This study … examines how much the country could save in health care costs if we invested more in disease prevention, specifically by funding proven community-based programs that result in increased levels of physical activity, improved nutrition (both quality and quantity of food), and a reduction in smoking and other tobacco use rates." (2)

The authors based their estimated changes in disease risks, program costs and savings in treatment costs on published studies that focused on:

prevention programs that do not require medical treatment,
programs that target communities rather than individuals, and
evidence-based programs that have been shown to reduce disease through improving physical activity and preventing smoking and other tobacco use in communities.

From these studies the authors concluded that an investment of $10 per person per year in proven community-based prevention programs could yield net savings in U.S. health care costs of

more than $2.8 billion annually in 1 to 2 years,
more than $16 billion annually within 5 years, and
nearly $18 billion annually in 10 to 20 years.

The authors emphasize that they consider these cost savings conservative estimates. It would require 5% reductions in type 2 diabetes, high blood pressure, heart and kidney disease, and stroke, and 2.5% reductions in the incidence of some forms of cancer, chronic obstructive pulmonary disease, and arthritis. These estimates assume that any achieved improvements in health are sustained. They do not include likely savings on such factors as nursing home care, reductions in worker disability (i.e. increases in productivity), or decreases in other diseases. It would also spare millions of people unnecessary suffering.

"The nation′s economic future demands we find ways to reduce health care costs. Preventing people from getting sick is one of the most important ways we can drive costs down." (2)

And this undoubtedly holds true for other countries as well.

Sources

Cohen JT, Neumann PJ, Weinstein MC. Does preventive care save money? Health econmics and the presidential candidates. N Engl J Med 2008;358(7):661-663. [Full Text]
Levi J et al. Healthier America: Investments in disease prevention yields significant savings, stronger communities. Trust for America′s Health. July 2008. [Full Text]

Study finds little difference between low-fat, low-carb and Mediterranean weight loss diets

2008-07-23T13:56:04Z

The July 17, 2008 issue of the New England Journal of Medicine published the results of the Dietary Intervention Randomized Control Trial (DIRECT) study comparing the effects of low-carb, Mediterranean, and low-fat diets on weight loss (1). Predictably, this paper elicited a flurry of commentaries. You can find some of the headlines, and Tom Venuto′s take on the study, on his BURN THE FAT blog (2).

Trial details

A total of 322 participants (mean age 52 years, 86% men) enrolled in the two year trial. All were either moderately obese (BMI > 27), had type 2 diabetes or suffered from coronary heart disease. They were randomly assigned to follow one of three dietary protocols:

A low-fat calorie-restricted diet. Daily target energy intakes were 1800 and 1500 kcal for men and women, respectively, with at most 30% of calories from fat and one third of that from saturated fat. The participants were advised to eat low-fat grains, vegetables, fruits and legumes.
A Mediterranean diet, restricted to the same daily calorie limits, with no more than 35% of calories from fat. This diet was rich in vegetables, poultry and fish replaced red meat, and olive oil and nuts were the major sources of added fat.
A low-carb diet. This group aimed for a daily carbohydrate intake of no more than 120g. There were no restrictions on total calories, protein or fat.

The two year study was about as well controlled as it is possible with a dietary intervention. It was carried out at an Israeli research centre with an on-site medical clinic. All participants were employees at that centre, and all ate their main meal of the day at the centre′s cafeteria. The cafeteria staff was advised by a dietitian, and suitable dishes were prepared for each of the three diet groups. In addition, a dietitian met with each group 18 times for 90 minute sessions. Total daily food and calorie intakes were estimated from food questionnaires.

Results

Of the 322 original participants, 272 completed the trial: 90.4% in the low-fat, 85.3% in the Mediterranean, and 78% in the low-carb group. The following weight-related changes were observed:

Among all participants completing the trial, the mean weight losses were 3.3 kg in the low-fat, 4.6 kg in the Mediterranean and 5.5 kg in the low-carb group.
Among the women, the mean weight losses were 0.1 kg for the low-fat group, 6.2 kg for the Mediterranean diet group, and 2.4 kg for the low-carb group.
The decreases in BMI were 1.0 in the low-fat group, and 1.5 in the other two goups.
Average waist sizes decreased by 2.8 cm in the low-fat group, 3.5 cm in the Mediterranean diet group, and 3.8 cm in the low-carb group.
Levels of circulating leptin (a reflection of body fat) decreased significantly in all diet groups.

Changes in biomarkers:

The greatest average drop in blood pressure, 5.5/2.2 mm Hg, was observed in the Mediterranean group.
The greatest average increase in HDL levels, 8.4 mg/dL or 0.22 mmol/L, occurred in the low-carb group. LDL levels remained unchanged in all three groups.
The level of high-sensitivity C-reactive protein decreased significantly only in the Mediterranean (21%) and low-carb (29%) groups.
Among diabetic subjects, only the Mediterranean diet group had a decrease in fasting glucose levels. There was no corresponding change in non-diabetic subjects.
Fasting insulin levels dropped in all three groups, and in diabetics as well as in non-diabetics.
Among diabetics, glycated hemoglobin levels (a measure of blood glucose levels) dropped significantly only in the low-carb group.

Maximum weight loss was reached after about six months, followed by a partial rebound and a plateau. On the other hand, biomarkers like HDL, C-reactive protein and fasting insulin levels continued to improve throughout the two year trial period. As the authors point out, a healthy diet has benefits beyond weight loss.

Conclusions

Here is how the authors summarize the results of their clinical trial:

"Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate diet) and on glycemic control (with the Mediterranean diet) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions." (1).

I don′t see any great difference between the outcomes of the three dietary protocols. This might be partly due to common calorie limits in the low-fat and Mediterranean diet groups. I suspect though that the food intakes in the three groups weren′t quite as different as the investigators believed — true low-fat and low-carb diets are difficult to follow.

Low-fat diets are tasteless — just compare low-fat to regular cheese. They are almost by definition high-carb diets, and excess glucose is simply converted to saturated fatty acids. If you don′t eat fat, you make it from the extra carbs you eat! With a low-fat diet you deprive yourself for nothing.

Low-carb diets, on the other hand, are difficult to follow because so many of our dietary staples are starchy foods — bread, pasta, rice, potatoes, breakfast cereals (not to mention desserts). It′s hard to devise meal plans that don′t contain any of these foods. In any event, low-carb eating doesn′t even make sense. Our brains and muscles need glucose, and glucose is the only fuel that red blood cells can use. We need carbohydrates, but of the low-glycemic variety.

If this study proved anything, it is that real food — the Mediterranean eating plan — works just as well as diet fads like low-fat and low-carb schemes.

References

Shai I et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med 2008;359(3):229-241. [Full Text]
Tom Venuto. What the new "low carb" study REALLY says. [Blog]

Eight drugs doctors would never take

2008-07-16T20:27:18Z

Would doctors take the medications they prescribe to their patients? Not necessarily, if a recent article in Men′s Health is any indication (1). A number of physicians were asked which drugs they themselves would refuse to take. Here is their list:

Asthma drug Advair
Diabetes drug Avandia
Pain reliever Celebrex (a relative of the infamous Voixx)
Antibiotic Ketek
Heartburn medication Prilosec
Heartburn medication Nexium
Eye drops Visine Original
Decongestant Pseudoephedrin

The doctors questioned also suggested alternative treatments. Unfortunately, all they could come up with were other drugs! You can find their recommendations in the original article (1).

I first came across this list on Dr. Mercola′s site (2). Here is the beginning of his commentary:

"Seemingly positive and helpful articles like these really highlight how pervasive the conventional drug culture is. Although these drugs are exposed as being dangerous and best avoided at all costs, the writer failed miserably in providing ′healthier′ alternatives; in all cases but two, merely citing alternative drug treatments …" (2)

Actually it was the doctors who failed miserably; the writer just quoted the doctors′ recommendations. Mercola then goes on to comment on three of the drugs on this list — the asthma, diabetes and heartburn / acid reflux medications — and suggests non-pharmaceutical alternatives. I′ll restrict my own comments to Avandia.

In May of 2007 the U.S. Food and Drug Administration (FDA) issued a safety alert on Avandia (3):

"The U.S. Food and Drug Administration (FDA) is aware of a potential safety issue related to Avandia (rosiglitazone), a drug approved to treat type 2 diabetes …" (3)

The agency goes on to say that safety data from some controlled clinical trials showed a potential increase in the risk of heart attacks, but other data provided contradictory evidence. The agency then issues this warning to patients on Avandia:

"Patients who are taking Avandia, especially those who are known to have underlying heart disease or who are at high risk of heart attack should talk to their doctor about this new information as they evaluate the available treatment options for their type 2 diabetes." (3)

Why didn′t the FDA just mandate the removal of the drug from the market?

"FDA′s analyses are ongoing. FDA has not confirmed the clinical significance of the reported increased risk in the context of other studies. Pending questions include whether the other approved treatment from the same class of drugs, pioglitazone, has less, the same or greater risks. Furthermore, there is inherent risk associated with switching patients with diabetes from one treatment to another even in the absence of specific risks associated with particular treatments. For these reasons, FDA is not asking GlaxoSmithKline, the drug′s sponsor, to take any specific action at this time." (3)

If changing treatments poses such a significant health risk, why advise patients to talk to their doctors about their available treatment options, i.e. about switching drugs? And exactly what was the information available to the agency that made it so difficult for them to make a decision?

"Recently, the manufacturer of Avandia (GlaxoSmithKline) provided FDA with a pooled analysis (meta analysis) of 42 randomized, controlled clinical trials in which Avandia was compared to either placebo or other anti-diabetic therapies in patients with type 2 diabetes. The pooled analysis suggested that patients receiving short-term (most studies were 6 months duration) treatment with Avandia may have a 30-40 percent greater risk of heart attack and other heart-related adverse events than patients treated with placebo or other anti-diabetic therapy. These data, if confirmed, would be of significant concern since patients with diabetes are already at an increased risk of heart disease." (3)

Of significant concern? Can you imagine a natural health product remaining on the market with a rap sheet like that. Does the pharmaceutical industry control the FDA, or what?

The sad thing about all of this is that type 2 diabetes is considered a life style disease that is both preventable and reversible. The American Diabetes Association readily admits this:

"People with diabetes have the same nutritional needs as anyone else. Along with exercise and medications (insulin or oral diabetic pills), nutrition is important for good diabetes control. By eating well-balanced meals in the correct amounts, you can keep your blood glucose levels as close to normal (non-diabetic level) as possible." [emphasis added] (4)

Pharmaceutical intervention shouldn′t even be necessary in type 2 diabetes. Yet the drug peddling continues, with the active participation of the medical establishment.

Sources:

Morgan Lord. 8 Drugs doctors would never take. If they don't use these medications, why should you? Men's Health June 22, 2008. [Full Text]
Dr. Mercola. 8 Drugs doctors would never take. Mercola.com July 10, 2008. [Full Text]
FDA issues safety alert on Avandia, May 21, 2007. [Full Text]
Nutrition & Recipes. American Diabetes Association. [Quote]

Pharma tricks - Harvard psychiatrists for sale

2008-07-18T19:16:55Z

In my last post (Pharma tricks - "key opnion leaders") I commented on an article in the British Medical Journal (1) about pharmaceutical companies hiring leading medical specialists to front for them. The fact that this article appeared in a major medical journal shows that doctors are getting concerned about the undue influence of the pharmaceutical industry on medical practice. The general public should be even more concerned, since we are the guinea pigs. Unfortunately, too many people are unaware of this cosy arrangement between the pharmaceutical industry and the medical establishment.

Just how substantial pharmaceutical "consulting fees" can be was revealed in a June 8, 2008 article in the NY Times (2). The report concerned a group of Harvard child psychiatrists, two of whom were paid at least $1.6 million and the third at least $1 million, from 2000 to 2007. What prompted this exposé was the fact that none of these prominent medical doctors declared their outside incomes to Harvard as required by university conflict-of-interest rules. Lying about their nice fat cheques from drug makers also violated the conflict-of-interest rules of the U.S. National Institutes of Health (NIH) which partially funded their work.

These facts came to light as the result of a U.S. Congressional investigation into the relationship between the pharmaceutical idustry and the medical establishment. Drug companies have replaced the U.S. federal government as the major source of research funding, and law makers have become concerned about the undue influence of industry money on the integrity of medical research.

Obviously, both the drug companies and the medical doctors participating in this scam want to keep this financial arrangement quiet. The whole purpose of this subterfuge is to give the appearance of scientific objectivity, which is obviously out the window once the scale of these payments becomes known. Drug makers cannot hide their involvement in clinical trials; they sponsor these trials, and it is their drugs that are tested. However, the amount of money that is paid to outside researchers speaks volumes about the credibility of the results. Compensation for time spent is one thing, and apparently annual outside revenues of less than $10,000 dollars needn't be reported to universities. But one simply has to believe that payments of a million dollars or more over a period of seven years buy a good deal more than just time.

What did drug money buy in this case? Apparently it bought a whole new pharmaceutical market. These Harvard researchers "discovered" that a large number of children and adolescents suffer from dipolar disorder, a mood problem formerly thought to be confined to adults. They promoted the aggressive diagnosis and treatment of this condition with anti-psychotic drugs. Conveniently, it wasn't even necessary to develop new drugs — anti-schizophrenic drugs are prescribed for this newly discovered disease.

The result of all this was a huge increase in diagnoses and prescriptions for this condition. According to the same NY Times article, "Some 500,000 children and teenagers were given at least one prescription for an antipsychotic in 2007, including 20,500 under 6 years of age, according to Medco Health Solutions, a pharmacy benefit manager." (2)

Not all researchers agree with the Harvard trio on childhood dipolar disorder. Some consider the clinical studies "proving" the condition poorly designed and the results inconclusive. The biggest problem in this field is the fact that assessment of symptoms is subjective; it is difficult to prove the diagnosis or to disprove the success of pharmaceutical intervention. What better "health" field could you find if you wanted to invent a disease to make money?

"The price we pay for these kinds of revelations is credibility, and we just can't afford to lose any more of that in this field", another researcher is quotes as saying. "In the area of child psychiatry in particular, we know much less than we should, and we desperately need research that is not influenced by industry money." (2)

How credible are the findings of researchers who lie about their financial links to the drug companies sponsoring their studies? And it is unlikely that problems of this sort are restriced to the field of child psychiatry. So much for "evidence-based" medicine.

Sources:

Key opinion leaders: independent experts or drug representatives in disguise? R. Moynihan. Brit Med J 2008;336:1402-1403. [Full Text]
Researchers fail to reveal full drug pay. Gardiner Harris and Benedict Carey. NY Times June 8, 2008. [Full Text]

Pharma tricks - "key opinion leaders"

2008-07-18T19:17:42Z

What on earth are key opinion leaders (KOLs)? In the world of medicine they are influential doctors who help pharmaceutical companies sell drugs (1,2). Drug companies realized that doctors don′t like to be ″educated″ by drug reps, but will listen to their medical colleagues. So they set out to recruit leading specialists to pitch their drugs — for a handsome fee of course. This seems to be a worldwide phenomenon.

″[Key opinion leaders] can influence thousands of prescribers and hence prescriptions through their research, lectures, publications and their participation on advisory boards, committees, educational boards, professional societies and guideline/consensus document development.″(2)

Typically KOLs lecture at company-sponsored events, using company-supplied material and saying what the companies want them to say. KOLs are also referred to as thought leaders; this presumably makes the medical doctors in their audience thought followers, not exactly reassuring if you are a patient.

How can pharmaceutical companies be sure that they′re getting their money′s worth from any given KOL? Drug companies actually have access to prescription records, incredible as it may sound. They routinely track prescriptions before and after every presentations, i.e. they can calculate their return on investment in their KOL to the Dollar; KOLs that don′t live up to expectations get dumped. Those that ″perform″ get paid quite handsomely. Typical fees might be $3000 per lecture, $200 per hour for participating in clinical trial, etc (2).

Sometimes a disgruntled drug rep quits and spills the beans. These former pharma employees make it very clear that drug companies consider KOLs sales people. But you don′t even have to listen to former sales reps; it all happens in broad daylight. In fact, the KOL practice has even spawned a niche business sector. Enter "key opinion leader management" in a search engine to see what I mean. There are actually central databases of opinion leaders, showing their return on investment (2).

What is wrong with all this?

Pharmaceutical companies will do anything to maximize profits, whether their drugs benefit patients or not. Their own pronouncements will be perceived as self-serving — drug companies have little credibility left. By persuading prominent doctors to front for them, their sales pitches appear to be objective presentations by independent experts. And this practice does seem to influence prescribing physicians, to the detriment of their patients.

It is bad enough that continuing medical education courses can be turned into pitch fests. At least the physicians in the audience know that these events are put on, and the speakers paid, by pharmaceutical companies. One would therefore hope that they take what they are told with a grain of salt.

But how are doctors to know which medical articles published by prominent physicians are trustworthy? The companies sponsoring the studies have the power to decide what gets published, and they are not above fudging results. Worse still, the supposed authors may not even have been involved in ″their″ studies, but were simply paid to put their names on publications (yes, this happens!).

It seems though that the ultimate use that pharmaceutical companies can make of KOLs is to get them on advisory boards and committees, where they can influence policies and standards of medical treatment that favour the firms they represent and the pharmaceutical industry in general.

What is the solution?

Medical doctors are now required to declare all sources of funding and potential conflicts of interest in their publications. This is of course a step in the right direction, but one wonders if one gets the whole truth. It is certainly not in Big Pharma′s interest to disclose their financial dealings, since it defeats the purpose of working with KOLs, whose principal asset is after all their perceived integrity.

I would think that patients′ best protection is to know as much as they can about health matters. Our health has to be our own concern, not something to be managed by doctors with pharmaceutical products.

Key opinion leaders — the best integrity money can rent!

Souces:

Doctors for pharma. Physician ″opinion leaders″ — helping or hurting medicine? The Scientist Community June 20, 2008
Key opinion leaders: independent experts or drug representatives in disguise? R. Moynihan. Brit Med J 2008;336:1402-1403.

Hypertension and ASA

2008-07-18T19:18:29Z

Are you taking ASA (aspirin) to lower your blood pressure? If you do, take it before going to bed!

People with pre-hypertension (<140/90 mm Hg) taking 100 mg ASA per day showed statistically significant drops in both systolic and diastolic blood pressure (-5.4/-3.4 mm Hg), but only if they took the medication before going to bed. (1). There was no blood pressure change when ASA was taken in the morning. Pre-hypertension is a risk factor for cardiovascular disease.

The same researchers had earlier found the same pattern in patients with mild hypertension (2). Only ASA taken before going to bed resulted in blood pressure drops (-4.9/-3.5 mm Hg). Blood pressure varied throughout the day, but after evening ASA administration it remained consistently lower all day, compared to pre-treatment values.

It isn't known why taking aspirin is more effective at night. One possible explanation is better absorption by the gastrointestinal tract at night. ASA taken before going to bed may also slow the production of hormones and other substances that may cause clotting, many of which are produced by the body at rest. (1)

This drop in blood pressure at night only holds true for low doses of ASA. The much larger amounts taken for anti-inflammatory effects (500 mg/day or more) may actually increase the blood pressure, even if the medication is taken at night. However, even there it is still better to take ASA before going to bed. Doses of 1300 mg of ASA at night resulted in 37% fewer gastric hemorrhagic lesions, i.e. even large doses of ASA are better tolerated at night. (2)

Sources

Aspirin at bedtime lowers blood pressure. HealthDay News May 14, 2008.
Hermida RC et al. Administration time-dependent effects of aspirin on blood pressure in untreated hypertensive patients. Hypertension 2003;41:1259-1267.

Trouble at the FDA

2008-07-18T19:19:08Z

Two recent articles in the New England Journal of Medicine dealt with problems at the U.S. Food and Drug Administration (FDA), particularly the lack of public confidence in the agency and the need for reform (1,2). The FDA oversees 25% of the U.S. consumer economy, from food to cosmetics, drugs and medical devices. (2)

"Public opinion polls show that confidence in the FDA fell from 80% in the 1970s to 36% in 2006 - ratings usually reserved for tobacco companies and used-car dealers." (2).

The authors specifically mention the Vioxx scandal, the heparin contamination, and a recent decision by the U.S. Supreme Court concerning medical devices:

"[The Supreme Court] ruled in February that FDA approval of a medical device precluded lawsuits brought by patients against the manufacturer over adverse events in state courts. ... [This leaves] patients without recourse if the FDA has certified that a medical device is generally safe and effective. In effect, FDA approval is now a shield protecting a manufacturer from subsequent claims - a role the agency undoubtedly never intended to play. A similar case, involving drugs, will be argued before the Court this fall." (2)

Problems with adulterated drugs, like the heparin affair, are blamed on the fact that today 80% of all active pharmaceutical ingredients (APIs), i.e. starting materials for drugs, are imported from factories with questionable safety standards, primarily in China and India. The heparin contamination, for example, was traced to a Chinese supplier. The FDA monitors foreign manufacturers of APIs, but doesn't have the resources to do a thorough job.

The authors go on to point out that it is the FDA's mandate to inspect producers of both drugs and chemicals used to manufacture drugs, in order to certify that plants meet the current Good Manufacturing Practice (GMP) standards. This includes the inspection of factories abroad. One author then goes on to say that:

"... It is inappropriate and unrealistic to expect the FDA to ensure the integrity of every manufacturer's entire supply chain. If a manufacturer chooses to save money by purchasing raw material from China, then it must bear the additional costs of zealous quality control and oversight in a country with a very limited regulatory system and a fluid commercial structure. ... U.S. taxpayers shouldn't have to pay to send inspectors to every factory in China to allow industry to obtain cheaper and largely unregulated products there." (2).

The authors rightly point out that the adulteration of drugs cannot be prevented solely by regulatory agencies. It has to be the responsibility of the manufacturer, with the FDA providing the regulatory framework. To rectify the situation, the authors call for holding manufacturers responsible for the safety of their products, and for increased funding for the FDA:

"The public's health is at stake, and the time for adequate funding of the FDA is now." (2).

It may well be that the FDA is underfunded, but the key to food and drug safety is surely to hold manufacturers responsible for what they sell. Given Merck's behaviour in the Vioxx affair, it is unlikely that Big Pharma will act responsibly without the threat of lawsuits. The recent decision by the U.S. Supreme Court concerning medical devices has obviously lessened even that threat, although a case involving drugs has yet to be decided. Even the threat of lawsuits doesn't seem much of a deterrent though. Settlements of class action suits in the billions still leave the richest pharmaceutical companies with net profits from selling products that harm. The financial, if unethical, bottom line is that lawsuits are just part of doing business.

This leaves regulatory oversight, which brings us back to Americans' low opinion of the FDA. This low opinion has little to do with the agency's lack of funding, and throwing money at the problem isn't going to restore public confidence. The problem is simply the public's perception that the agency is controlled and corrupted by the very industry it is supposed to oversee.

Sources

Schweitzer SO. Trying times at the FDA - The challenge of ensuring the safety of imported pharmaceuticals. N Engl J Med 2008;358:1773-1777.
Wood AJJ. Playing "Kick the FDA" - Risk-free to players but hazardous to public health. N Engl J Med 2008;358:1774-1775.

Does preventive care save money?

2008-07-31T21:49:42Z

The February 14, 2008 issue of the New England Journal of Medicine ran an article with the astonishing title "Does preventive care save money?" (1). That analysis was prompted, according to the authors, by the health care campaign promises made by various U.S. presidential candidates.

The very question - whether preventive care saves money - seems astonishing enough. But prevention surely isn't just about money. I'd rather not get sick in the first place, even if "curing" me wouldn't cost any more than preventing my disease. Medical treatment is one of the leading causes of death, and I'll take my chances with prevention.

The authors do concede that prevention might just do some good:

"Indeed, some evidence does suggest that there are opportunities to save money and improve health through prevention."

But then they go on to say:

"Although some preventive measures do save money, the vast majority reviewed in the health economics literature do not."

What on earth are these authors talking about? When one reads further one discovers that they aren't discussing what you or I would consider prevention at all. The article is primarily about early diagnosis to detect malignancies in their most treatable stages. In other words, the authors' interest is restricted to medical interventions. Only one sentence in the article pays lip service to genuine disease prevention, and then it's back to medicine:

"Preventable causes of death, such as tobacco smoking, poor diet and physical inactivity, and misuse of alcohol have been estimated to be responsible for 900,000 deaths annually - nearly 40% of total yearly mortality in the United States."

It turns out that the cost of preventive medical interventions actually isn't all that different from the cost of treating diseases. The reason for this, the authors point out, is that too many unnecessary diagnostic tests are performed. For screening to be cost-effective, it should only target populations at high risk for a given disease. The authors' prescription for achieving better health results:

"Conduct careful analysis to identify evidence-based opportunities for more efficient delivery of health care - whether prevention or treatment - and then restructure the system to create incentives that encourage the appropriate delivery of efficient intervention."

I can't help thinking that the authors of this paper are as naive as the presidential candidates with their proposed solutions to the "health" care crisis. What kinds of incentive can you create for service providers by cutting back on spending?

Why is U.S. "health" care so expensive? Because providing it is so lucrative. The more "services" can be provided, even if they are totally ineffective, the more enormous the profits for the service providers. Vested interests will fight any expenditure reductions on preventive interventions tooth and nail.

In fact, an enormous amount of money is spent by the "health" care industry on preventing prevention. Big Pharma has no intention of giving up their customers without a fight. They are spending huge sums of money to influence legislators, regulatory agencies, and medical professionals. Supplement manufacturers cannot make perfectly well-supported health claims, and compounding pharmacies are prevented from supplying bio-identical hormones, to give just two examples of the nefarious influence of the pharmaceutical industry. I would think that the providers of diagnostic services will also fight any cost-effectiveness measures, i.e. any reductions in their profits.

The solution to the "health" care crisis won't come from the medical establishment or from Big Pharma. Our best hope to be healthy is to be informed and proactive. We do need medical care for certain problems, but our health is our own responsibility.

Sources

Cohen JT, Neumann PJ, Weinstein MC. Does preventive care save money? Health econmics and the presidential candidates. N Engl J Med 2008;358(7):661-663. [Full Text]

The Simpleology blogging course

2008-07-18T19:20:47Z

Well, I finally got around to checking out Mark Joyner's blogging course, and I must say that it is an excellent introduction to the subject. Mark teaches you what your blog needs to have, how to drive traffic to your blog, and how to make money with it. Here are some of the things you'll learn:

Creating your blog

Why your blog needs to focus on a specific topic, and why you need to choose a topic that interests you.
Why it is important to develop a list of keywords for your chosen niche and use them in your titles and your text, and how to develop such a list.
Why quality is all-important, and why you need to post regularly to your blog.

Drivng traffic to your blog

Why the right keywords and incoming links from quality blogs are vital for traffic generation.
How well-chosen keywords and regular postings increase your chances that you are "spidered" by search engines.
How you can submit your blog to search engines.
Why you should alert your readers to other blogs that you find relevant and interesting, and how this gets you inbound links and a higher ranking.
Why you should participate in forums related to your niche.
Why you should turn your posts into articles and give them away for free.

Making money with your blog

How you can earn advertising revenues with programs such as AdSense.
How you can join affiliate programs with major companies, such as Amazon.com, ClickBank etc and earn commissions.
How you can earn money as a professional blogger.

There are also a couple of topics that I would have liked to see discussed in more detail. For example, for some purposes it is better to use a website; for others a blog might be more appropriate. That topic could have been treated in more detail. Secondly, there are traffic-generating tools that work for blogs but not for website. That subject too might have been worth a separate lesson.

But these are mere quibbles. The bottom line is that this is an excellent introductory blogging course. Follow Mark's guidelines and you will end up with a first-rate blog. I for one am going to use this course as a blueprint for improving my own.

Free blogging course available from Mark Joyner for a limited time

2007-12-20T20:32:23Z

I'm evaluating a multi-media course on blogging from the folks at Simpleology. For a while, they're letting you snag it for free if you post about it on your blog.

It covers:

The best blogging techniques.
How to get traffic to your blog.
How to turn your blog into money.

I'll let you know what I think once I've had a chance to check it out. Meanwhile, go grab yours while it's still free.

Lipoproteins - the cast of characters

2008-07-18T19:27:03Z

The following material is largely taken from references (1) and (2).

Our bodies make essentially three types of lipoproteins: chylomicrons, very low density lipoproteins (VLDLs), and high density lipoproteins (HDLs or "good cholesterol"). As these particles unload their lipid cargo, the chylomicrons change into chylomicron remnants, and the VLDLs become VLDL remnants, also known as intermediate density lipoproteins (IDLs), some of which eventually turn into low density lipoproteins (LDLs or "bad cholesterol").

Lipids are less dense than the proteins on the particle surfaces, the so-called apolipoproteins. The size of the lipid load therefore determines the particle density. Chylomicrons carry the largest lipid load and are the least dense. The names of the rest of the lipoproteins reflect their relative lipid loads and densities.

Chylomicrons

Chylomicrons are assembled in the cells of the small intestine and carry dietary lipids to the tissues. As they pass through the capillaries, they discharge their cargo of triglycerides (TGs), but not their cholesteryl esters. The TG-depleted particles, called chylomicron remnants, are rapidly taken up whole by liver cells and dismantled. Some of the dietary cholesterol is used for bile acid synthesis.

Three proteins control the fate of chylomicrons. The defining apolipoprotein is apo B48. HDLs provide two additional freely exchangeable proteins, apo C-II and apo E. These proteins control the discharge of the triglycerides and the uptake of the lipoprotein remnants by the liver.

Apo C-II binds to the enzyme lipoprotein lipase (LPL) bound to capillary walls and serves as LPL cofactor in the hydrolysis of TGs to free fatty acids (FFAs) and glycerol. The free fatty acids cross the capillary walls and most are taken up by the tissues. Any leftover FFAs bind to albumin and eventually return to the liver.

As long as apo C-II is present, it prevents the uptake of the chylomicron particle by the liver. The transfer of apo C-II back to an HDL particle exposes apo E and permits its binding to an hepatic apo E receptor, followed by endocytosis of the complete lipoprotein.

VLDLs (very low density lipoproteins)

VLDLs are assembled in the liver and carry lipids from the liver to the tissues. These may be lipids synthesized by the liver or returned to the liver by remnants of other VLDLs or chylomicrons, or albumin-bound free fatty acids.

Like chylomicrons, VLDLs initially unload their TG cargo and become TG-depleted remnants, called intermediate density lipoproteins (IDLs). However, unlike chylomicron remnants, VLDL remnants can turn into a new type of lipoprotein - LDLs.

The defining protein of VLDLs is apo B-100. In addition, VLDLs also get apo C-II and apo E from HDLs; these apolipoproteins play the same roles here as they do on chylomicrons. Apo C-II is the lipoprotein lipase cofactor required for TG hydrolysis and release of free fatty acids. In addition, it blocks the premature elimination of VLDLs.

The IDLs have discharged most of their triglycerides and essentially carry only cholesteryl esters. They have also lost their apo C-IIs. If they keep their apo Es, they bind to apo E receptors and are taken up by the liver. If they lose their apo E apoproteins as well, they can no longer bind to apo E receptors and remain in circulation. This new type of particle is called LDL.

LDLs (low density lipoproteins)

LDLs deliver cholesterol from the liver to the tissues. This cholesterol load is made up of molecules synthesized by the liver, dietary cholesterol delivered to the liver via chylomicrons, and cholestryl esters transferred in plasma from HDLs. These LDLs rich in cholesteryl esters only carry one type of apolipoprotein, namely apo B100.

Most tissues are able to synthesize all the cholesterol they need and do not rely on the liver or on dietary sources. However, growing tissues and organs synthesizing steroidal hormones require large amounts of cholesterol. Cells in those tissues display LDL receptors on their plasma membranes; the number of LDL receptors is related to a cell's need for cholesterol. When an LDL particle binds to an LDL receptor via the apo B100 protein, the whole lipoprotein is taken up by the cell.

Liver cells also express LDL receptors, and LDL particles that weren't taken up by extra-hepatic tissues are removed in this way.

HDLs (high density lipoproteins)

HDLs are synthesized in the liver and, to a lesser extent, the small intestine. They have two functions. First, HDLs are involved in triglyceride transport by supplying apo C-II and apo E proteins to TG-carrying lipoproteins. Secondly, they collect excess cholesterol from tissues and transfer it either to cholesterol-hungry cells for use or to the liver for disposal.

HDLs are excreted empty or in a lipid-poor form, in which state they are collapsed disk-shaped bags. Apo A-I is the defining apo protein of HDLs. It is their only apolipoprotein at the initial stage, and it is present throughout the life cycle of an HDL particle. It binds to hepatic HDL receptors and serves as cofactor for lecithin:cholesterol acyltransferase (LCAT).

Excess cholesterol mainly comes from cellular debris, including damaged lipoproteins, taken up by macrophages and incorporated into their plasma membranes. Lipoproteins can suffer oxidative damage to the lipid or protein components. In addition, elevated blood glucose levels can damage the apolipoproteins by glycating lysyl residues. Damaged lipoproteins are disfunctional and are quickly eliminated by macrophages.

The uptake of cholesterol by HDLs requires the conversion to cholesteryl esters. which is catalyzed by the HDL-bound enzyme lecithin:cholesterol acyltransferase (LCAT). As its name implies, the source of the fatty acid used to esterify cholesterol is the lecithin part of a phospholipid.

The collection and disposal of surplus cholesterol is called reverse cholesterol transport (RCT). Reverse cholesterol transport can occur directly or indirectly.

In the direct route the HDLs themselves deliver the cholesterol to the target cells. Either they bind to a so-called scavenger receptor class B type I (SR-BI) and transfer only their cholesterol load, or the HDL particle binds via apo A-I to an hepatic HDL receptor and is taken up whole and dismantled.

In the indirect route the HDLs transfer cholesterol to VLDLs, many of which become LDLs. The LDL apo B-100 binds to an LDL receptor on a cell that need cholesterol; the cell then takes up the whole lipoprotein.

The transfer of cholesteryl esters between HDLs and VLDLs is catalyzed by the plasma enzyme cholesteryl ester transfer protein (CETP).

To summarize, both chylomicrons and VLDLs deliver their triglyceride cargo directly to their destination cells in muscle and adipose tissue. The transport and delivery of cholesterol is a different matter. Dietary cholesterol ends up in the liver via endocytosis of the chylomicron particles. The liver controls the cholesterol export via VLDLs and the elimination of any excess via bile formation.

Only LDLs have the necessary apolipoprotein, apo B100, for binding to LDL receptors and delivering cholesterol to cells that need it. Only HDLs can salvage excess cholesterol and recycle it via LDLs. Cholesterol distribution is essentially controlled by HDLs and LDLs.

Cholesterol is clearly more than just a risk factor for atherosclerosis. It is a vital substance, an important component of cell and lipoprotein membranes, and the starting material for the synthesis of all steroidal hormones. Its distribution is carefully orchestrated by the interplay of lipoproteins and enzymes.

Sources

Harper's Biochemistry, 25th Edition, Appleton & Lange 2000
Nutritional Biochemistry, 2nd Edition, Tom Brody, Academic Press 1999

Lipoproteins – an overview

2007-10-22T15:43:27Z

In my last post “Can vitamin C prevent cardiovascular disease?” I alluded to the role of lipoproteins in covering lesions on blood vessel walls and in the development of atherosclerosis. In this and the next few posts I want to talk about the structures and functions of lipoproteins in some detail, before getting back to cardiovascular disease.

What are lipoproteins? They are particles that transport lipids to and from the tissues.

Lipids are fatty acids and their glycerol esters, cholesterol and its fatty acid esters, and the lipid-soluble vitamin families A, D, E and K. Lipids are hydrophobic, i.e. water-insoluble, and special water-miscible particles are required to shuttle them through the bloodstream to the cells that need them. Free fatty acids travel non-covalently bound to the protein albumin. The rest of the lipids are transported in lipoproteins.

The basic structure of lipoproteins is best explained by comparison to cells. The contents of a cell are enclosed by a plasma membrane called a lipid bilayer. The two layers consist of phospholipids and unesterified cholesterol (plus proteins, which we’ll get to in a moment). The hydrophobic ends of the lipids in the two layers point toward each other, and the hydrophilic ends face the inside and outside of the cell, respectively. Both the inside and outside surfaces are hydrophilic, i.e. cells are water-miscible enclosures for hydrophilic content.

Of course the lipid bilayer is only the enclosure. Proteins on the cell surface and in the plasma membrane are needed to control entry of nutrients and exit of waste, for signaling purposes etc. It is the protein components of the plasma membrane that distinguish different cell types.

What happens if you eliminate the inner shell of the lipid bilayer? What is left is a container that is still hydrophilic on the outside, but the inner surface consists of the now exposed hydrophobic ends of the phospholipids and cholesterol molecules. In other words, we now have a water-miscible container for hydrophobic content - for lipids. A particle enclosed by a monolayer membrane is called a micelle, and it is the basic structure of lipoprotein particles.

Again, proteins have to be added to this structure to direct these particles to their destinations and to load and unload their lipid cargo.

In future posts we’ll look at
· The different types of lipoproteins and their functions,
· The surface proteins that determine the behaviour of these lipoproteins, and
· The enzymes that are needed to make the whole system work

To be continued…

Can vitamin C prevent cardiovascular disease?

2008-07-18T19:31:50Z

In a recent issue of his newsletter, Dr. Mercola talked about a theory of cardiovascular disease (CVD) and its treatment propounded by Linus Pauling and Matthias Rath(1). And, yes, vitamin C (ascorbate) plays a leading role in their solution, as you might expect from Pauling. Their theory and treatment claims are bold and sweeping:

"Ascorbate deficiency is the precondition and common denominator of human CVD. Ascorbate deficiency is the result of the inability of man to synthesize ascorbate endogenously in combination with insufficient dietary intake. The invariable morphological consequences of chronic ascorbate deficiency in the vascular wall are the loosening of the connective tissue and the loss of the endothelial barrier function.
Thus human CVD is a form of pre-scurvy."(1)

The authors made it clear though that their claim to a cure for CVD was as yet only an unproven theory:

"Clinical confirmation of this theory should largely abolish CVD as a cause for mortality in this generation and future generations of mankind."(1)

The loosening of the connective tissue and the loss of the endothelial barrier function in the vascular wall referred to by the authors are the result of the impairment of collagen synthesis. For collagen to fulfill its structural role, the protein has to self-associate to form a triple-helical structure. This self-association can occur only if specific proline residues on the collagen protein are oxidized to hydroxyprolines.(2)

The active site of the enzyme catalyzing the conversion to hydroxyproline contains iron, which must be kept in the reduced (divalent, ferrous) state. It is the role of the antioxidant ascorbate to reverse any iron oxidation that may occur. Unchecked oxidation deactivates the enzyme, i.e. a lack of ascorbate leads to defective collagen synthesis.(2)

So what has all this got to do with cardiovascular disease?

The structural integrity of the arteries depends on the collagen fibers wrapped around them. Impaired collagen synthesis therefore leads to damaged blood vessels and to potentially fatal hemorrhages. The body deals with this threat by depositing lipoproteins at the sites of lesions in the blood vessel walls.

While these lipoprotein deposits are effective at plugging the leaks, they can obviously create problems of their own. If this defense mechanism overshoots its target, cardiovascular disease results. Excessive plaque formation narrows and hardens the arteries (atherosclerosis). Pieces of plaque may break loose and block the narrowed coronary and cerebral arteries, leading to heart attacks and strokes.

In other words, the solution (lipoprotein deposits) can be as problematic as the problem it is meant to solve (arterial structural impairment). The essence of Pauling and Rath's proposed solution is to prevent the need for arterial repairs by supplying the body with enough ascorbate to ensure proper collagen synthesis.

The theory sounds perfectly convincing, IF defective collagen synthesis due to ascorbate deficiency is the sole, or at least the major, cause of arterial lesions.

But is it?

Sources

A Unified Theory of Human Cardiovascular Disease Leading the Way to the Abolition of This Disease as a Cause for Human Mortality.
Matthias Rath M.D. and Linus Pauling Ph.D
J. Ortho Med., 1992; 7:5-15
Nutritional Biochemistry, 2nd Edition, Tom Brody, Academic Press 1999.

American healthcare funding - part 2

2008-08-01T11:37:02Z

I don't know if "Sicko" stimulated the debate over the future of healthcare in the U.S., or if the film simply made me more aware of the ongoing debate.

In any event, I just watched former Massachusetts Governor Michael Dukakis' video editorial on Medscape General Medicine 9(3) 2007, "Getting Control of Health Costs - For Real". Dukakis certainly doesn't have any illusions about market solutions to healthcare costs. Here is an excerpt of what he had to say on the subject:

"Virtually all of these proposals [for healthcare reform] are coming from people who tell us that if only we can create a healthcare 'market' and people can shop around for their healthcare, all will be well. The fact of the matter is that the market doesn't work in healthcare. It never has and it never will -- for reasons that should be obvious to anybody who has taken the time to study the subject."

Why doesn't the "market" work in this case? Here are some of the reasons I can think of.

First, most people aren't qualified to make medical decisions; they have to leave healthcare decisions to experts. A largely uninformed public is no market force and no match for the powerful special interests in the healthcare field.

Secondly, every dollar spent on healthcare is a dollar made by healthcare providers. These healthcare providers obviously intend to keep it that way, whether their products and services are useful or not.

Lastly, and I think most importantly, the big players in the healthcare field, especially pharmaceutical companies, have no intention of permitting a free market. Why leave purchasing decisions to consumers, if the companies have the money and power to manipulate legislators and regulatory agencies, take over medical education, and bribe and intimidate individual doctors to ensure that their products and services are the only conceivable, the only legal treatment options.

The individual is clearly powerless in this matter. One might wonder though why insurance companies and large employers accept the status quo. I don't know the answer, but I suspect that the insurance companies make money by dumping expensive clients, and that companies pass their employee insurance costs on to their customers. Of course passing these costs on to their customers isn't so easy once you lost your competitive edge, as U.S. car manufacturers have found out.

Sicko and American healthcare funding

2007-09-14T19:58:43Z

I didn't see Michael Moore's film Sicko, but I found some of the reactions to it rather interesting, particularly Dr. Hyman's response on his blog www.ultrametabolism.com/blog/ and Jon Herring's article "Don't Take Health Advice From a "Sicko" on Early To Rise.

Herring concurs with Dr. Hyman's statement that "If we improve a broken system just by reorganizing how it is paid for, we still have a broken system." This may be so, but it also true that if one improves a broken system just by optimizing medical care, one still has a broken system because that medical care has to be paid for, and getting seriously ill now can bankrupt you.

There are clearly two separate issues here, namely how to optimize medical care and how to pay for that care.

Unfortunately, there are limits to what optimizing medical care can do to reduce costs. Most chronic illnesses are considered lifestyle diseases. Your doctor can't quit smoking for you, get you off the couch, make you eat right, or manage your stress for you. When the inevitable problems arise, bills will have to be paid regardless of the state of the medical system.

There is something amusing about the Americans belief that the market - capitalism, free enterprise, call it what you want - is the solution to all problems. How can private companies provide coverage at a profit for patients whose lives may depend on the best and most expensive medical treatment available? You already know the answer - it's the system you've got now, with some people uninsured and others losing coverage or being bankrupted by co-payments.

The bottom line is that other industrialized countries achieve better health for less, and they all have a publicly funded system of medical care.

Chondroitin and osteoarthritis

2008-02-22T20:53:36Z

The other day I came across an opinion piece by freelance medical reporter Dan Hurley, entitled "Evidence-Based Standards Should Apply to Dietary Supplements, Too".

They should indeed. I certainly wouldn't want to waste my money on unproven, useless and potentially dangerous products. But how evidence-based is allopathic medicine?

Evidence-based medicine - Hurley tells us - is the rallying cry of a generation of physicians. Thankfully, Big Pharma readily obliges with seminars at all-expenses-paid weekend retreats and drug reps bringing gifts, uh, drug information right to the doctors' offices. Apparently, drug companies preferentially recruit former college cheerleaders for these jobs. I couldn't imagine why.

Nowadays, most clinical drug trials are carried out by pharmaceutical companies. Interestingly, the results of drug trials funded by Big Pharma are always more favourable than independent trials. But then of course drug companies aren't above fudging data, as the Vioxx scandal showed.

In addition, drugs are frequently prescribed for off-label applications. In other words, there is no clinical support for many drug uses whatsoever. So much for evidence-based medicine.

Hurley goes on to claim that evidence-based reviews found supplements and herbals to be either ineffective or outright harmful. He claims for instance that trials supported by the National Center for Complementary and Alternative Medicine have concluded that glucosamine-chondroitin does not relieve arthritic pain.

If you want a medical doctor's take on this, I suggest that you visit drtheo.com, the website of Jason Theodosakis, M.D., and read his Review of the NIH Glucosamine and Chondroitin Arthritis Intervention Trial (Gait).

The evidence for potential harmfulness, meanwhile, - Hurley goes on to say - grows ever stronger. Since 1983, he informs us, the American Association of Poison Control Centers has tallied more than 1.6 million reports related to the use of supplements, including 251,799 serious enough to require hospitalization. Mercifully he spares us the death toll from this tragedy.

I vaguely recall reading about thirty to forty deaths per year from side effects due to "natural remedies", but over 100,000 deaths per year from "properly" described pharmaceutical drugs. Interesting use of the word "properly", don't you think.

Makes you wonder what planet this Dan Hurley comes from.

Welcome to my Blog

2007-09-16T21:26:47Z

Once or twice a week I intend to post comments or short articles on matters related to health and nutrition. I might be talking about subjects like weight control, the glycemic index, nutritional deficiencies, supplementation, metabolic typing, skin care, news from mainstream medicine, or any number of other health-related topics.

Do we really need yet another health blog? There is certainly plenty of useful health information out there already. Unfortunately you'll also find a considerable amount of misinformation, questionable claims and just plain nonsense. You have undoubtedly seen health gurus contradict one another and probably wondered which side made sense; they couldn't very well both be right.

So what can I contribute and why would you want to read what I write? Well, I have a science background and should certainly be able to tell which health claims make sense and which don't, and which arguments are based on sound scientific evidence.

Obviously you need to take everything you read on health matters with a large grain of salt, including the posts on this blog. So don't hesitate to let me know when you disagree with me or have something useful to add. I'd much rather use your input to correct my mistakes and provide solid information for my readers than insist on being right and risk losing them.