Health for life

If you read my last post about cholesterol-lowering drugs, then you understand some of the problems that can arise from their use.  Statins can produce some nasty side effects.  But side effects aside, statins save lives right?  I mean, doctors prescribe them to just about everyone, they must be effective.  Not quite... the story is not as simple as it may seem.

When looking at the statin drug clinical trials, its important to keep a few things in mind.  Firstly, and most importantly... total mortality is more important than heart disease mortality.  If a drug prevents you from dying of heart disease but doesnt affect your chances of dying in general, then that drug is not worth taking.  Whats most important is whether or not the drug will extend your life.  Secondly, you must consider that different groups of people may respond differently to the drug.  Women, middle-aged men, the elderly, and those with preexisting heart disease may all respond differently to treatment. 

Id like to begin by talking about women... both because I like women, and because they dont respond well to statins.  Although many statin studies notoriously neglect to reveal the all-cause death data for women, there are a few studies that do.  Check out the Scandinavian Simvastatin Survivial Study (4S), which was one of the most positive trials to date.  The big pharma folks must have been partying it up when this one came out.  This was a secondary prevention trial, meaning that participants all had pre-existing heart disease (previous heart attack or angina).  For future erence, a primary prevention trial would be an experiment in which the participants did not have pre-existing heart disease.  So, half of them took simvastatin and half of them took a placebo.  The results were great across the board: heart attack numbers were reduced, along with deaths from heart disease and all-cause mortality.  But there was one group that clearly didnt benefit:  women.  Over the duration of the 5.4 years of the trial, 27 (6.6%) of the women taking the statin died, while only 25 (6%) of the women taking the placebo died.  So despite the rest of the data, which was very supportive of statins, there was actually a slight increased risk of death in women from taking the statin.  As youll soon see, this finding is consistent throughout all of the statin trials, yet it is completely ignored by mainstream medicine.  These drugs simply dont work for women.


Now, men are a bit of a different story.  Its important to split men up into two distinct groups:  those with diagnosed heart disease (previous heart attack or angina), and those without diagnosed heart disease.  In those without heart disease, statins appear to be largely ineffective.  Both the University of British Columbia and Dr. Graham Jackson in the UK have published review articles looking at many of the primary prevention statin trials.  These were both reviews of the existing research, and they did not pick and choose studies that would support one side or the other.  Heres a key statistic from the UBC paper:  "71 primary prevention patients with cardiovascular risk factors have to be treated with a statin for 3 to 5 years to prevent one myocardial infarction or stroke."  And heres one from Dr. Jacksons study:  "Long term use of statins for primary prevention of heart disease produced a 1% greater risk of death over ten years versus placebo when the result of all the big controlled trials reported before 2000 were combined."  Although both studies showed reduction of cardiovascular deaths in those taking statins, overall deaths were either the same or higher.  Oh, and they also found zero effect on cardiovascular deaths in women.  Sounds like statins arent so effective in those without pre-existing heart disease. 

And Ive got more.  In 2005, a study called ASCOT-LLA, which studied Lipitor on high blood pressure patients, was stopped early due to the supposed "massive" reduction in cardiovascular deaths experienced by the Lipitor group.  The researchers considered the benefits so great that it was unethical to continue to deprive the placebo group of proper treatment. This study is considered to be one of those landmark trials that proved once and for all the life-saving benefits of statins.  Well, lets look at the data... youll have to click to enlarge it.



In that first set of data, Id like to draw your attention to the "all-cause mortality" graph in the bottom right.  See that vertical line there that Ive drawn in?  Thats a little trick I learned from Dr. Malcolm Kendrick in his book The Great Cholesterol Con.  The reason that line is drawn in there is because the trial ended at 3.3 years.  The graphs, however, show data until 3.5 years.  If you look closely at the graph, at 3.3 years there is almost no difference between the Lipitor group and the control group, but for the last 0.2 years of the study, the two lines begin to suddenly separate.  WTF mate?  How does one acquire data for a study after the study has ended?  Something seems fishy to me...  tampering of evidence perhaps?  No way to know for sure, but I can say with certainty that there was no reason to shut down this study early.  Theres virtually no difference in the all-cause mortality data.  Oh, and that second graph... thats showing the effectiveness of Lipitor on cardiovascular mortality (note: NOT all-cause mortality).  Notice women in this trial had an increased risk of dying from heart disease on the drug.

To sum up the statin drug data, heres a convenient table copied again from Dr. Malcolm Kendrick:


You can see here that the 4S trial, which I discussed earlier, was overall very supportive of statin use.  This trial was purely a secondary prevention trial.  And I must admit that statins do appear to save lives in men with previous heart disease.  But that is the ONLY group for which they save lives.  Purely primary prevention trials, like EXCEL, actually showed in increase in all-cause death on statins.  And then there are trials like WOSCOPS, which was a mix of primary and secondary prevention, and those trials typically yield results somewhere in the middle of the extremes.  Even in the most positive statin data for those with pre-existing heart disease, however, the results are really underwhelming.  You would think that with all the hype surrounding these supposed "life-saving" drugs, the data would be a little stronger.  Even if you do have pre-existing heart disease, and are a man, you can only expect about a 3% reduction in the chance of dying over the next several years.  That is just unimpressive to me.

So despite the relentless pushing of these drugs by big pharmaceutical companies, mainstream doctors, and my Anatomy and Physiology professor, caul examination of the data shows a surprising lack of evidence to support their use.  Statins decrease the risk of dying of heart disease; thats good.  But they dont decrease the risk of dying overall in the majority of the population; thats bad.  So then, if heart disease deaths are decreasing but overall deaths are not, statins must be increasing the risk that youll die of something other than heart disease.  Im even going to go as far as to say that they cause these non-cardiovascular-related deaths. Unfortunately, most studies fail to specify exactly what these non-cardiovascular deaths are, but take a look at my previous post for an idea.  If youre a woman, statins wont even reduce your risk for heart disease, and they actually increase your risk of dying overall.  The only population for which statins can save lives is men with pre-existing heart disease, which is less than 5% of the population.  If youre one of those people, take your statin if youre so inclined.  But if youre anyone else, especially a woman, you are barking up the wrong tree.

This isnt going to surprise anyone: Diabetes is getting more costly to treat, both for individuals, and for the nation as a whole.

A study last month in the Archives of Internal Medicine reported that drug costs for type 2 diabetes just about doubled in the six short years between 2001 and 2007 (from $6.7 billion in 2001 to $12.5 billion in 2007).¹

The costs are increasing because more people are being diagnosed with diabetes, and because the cocktail of drugs patients are being prescribed is getting more complex. In 1994, 82% of patients were being treated with just one diabetes drug. In 2007, only 47% received one diabetes drug.

The cost of the drugs is rising too. The average price of a diabetes-related prescription rose from $56 in 2001 to $76 in 2007. Keep in mind, thats $76 per prescription and by 2007 more people were being written more than one prescription. (Those are averages. Many drugs are more costly, e.g. a one-month supply of Januvia is going for $181 at Drugstore.com.)

This study just looked at drug costs. According to Merck spokeswoman Amy Rose, drug costs represent less than one-fifth of the total public health costs of diabetes. The bulk of costs, more than 80%, were due to hospitalizations and outpatient care - areas of treatment that are also experiencing price increases.

Theres an alternative, but according to Dr. Stuart Weiss, an endocrinologist at New York University Medical Center, its not being embraced:²

"Diet and exercise is the best thing we can do for our diabetic patients, but they are not very comfortable accepting diet and exercise as the treatment for diabetes."

"There is no medication that cant be overwhelmed by a bad diet."

The findings in this report beg the question:²

"Are these changes going to lead to overall significant improvement in the outcomes that matter to patients and their doctors?"
- G. Caleb Alexander MD, lead author and associate professor of medicine at the University of Chicago

The jury is still out on that.
________
¹ National Trends in Treatment of Type 2 Diabetes Mellitus, 1994-2007, Archives of Internal Medicine

² Cost of Diabetes Care Has Doubled, Washington Post, October, 2008

In recent years, the prescription of statin drugs to reduce cholesterol has soared through the roof.  Youve heard of them:  Lipitor (atorvastatin), Crestor (rosuvastatin), Zocor (simvastatin), and the like. The supposed benefits of these drugs, as your doctor will tell you, is that theyll reduce your cholesterol levels, hence lowering your risk of heart disease.  Im sure you all know by now how I feel about lowering cholesterol levels (see this)... but thats beside the point in todays discussion.  I will just say that statin drugs effectiveness may have been a bit overstated.  Today, though, Id like to focus on the dangers, or side effects, one may encounter in taking statins.

First, just a little information about how statin drugs work in the body.  Their main function is to block an enzyme called HMG CoA Reductase.  This is one of the enzymes that is involved in making cholesterol in the liver.  So through blocking this pathway, the drug has inhibited the bodys ability to make cholesterol molecules.  As a result, your blood cholesterol level goes down, your doctor is happy, and youre happy.  Weve finally won the battle against cholesterol!  Yeah... except cholesterol is needed in the body for all sorts of vital processes, like hormone production, vitamin D synthesis, cell membrane structure, and brain function, just to name a few.  Hopefully by the end of this, youll realize how ridiculous it is to think that blocking an important biochemical pathway like this one is a good idea.





Meet Dr. Duane Graveline.  Dr. Graveline is a family doctor with a high cholesterol level, who began taking statins several years ago.  Shortly after starting on statins, he suffered a serious and disturbing loss of memory, so he stopped taking the drug.  He had no further problems for a year while off statins, so his doctor persuaded him to begin taking them again.  That high cholesterol needed to be treated.  Shortly after returning to the meds, Dr. Graveline experienced a much worse episode of memory loss, during which he regressed into his teenage years, unable to recall his training as a doctor at all.  After getting off the statins, though, his memory returned again.  Interesting huh?  Well Dr. Graveline decided to tell his story by publishing a letter on a website called Peoples Pharmacy.  Almost immediately, he was flooded with letters from hundreds of other statin-takers who had experienced a similar problem.  Clearly, something about these drugs was causing serious impairment in the brain.

On a related note, there has been consistent data since the 1960s showing that people taking cholesterol-lowering drugs tend to die more frequently from violent deaths, such as car accidents, suicides, and shootings.  This information has largely been disregarded for lack of a plausible explanation.

But how about this... 25% of the cholesterol in the body is concentrated in the brain.  Until recently, we didnt understand the reason why, but new research by Dr. Frank Pfrieger shows that cholesterol is absolutely essential to neuronal communication in the brain.  Cholesterol is so important, in fact, that without it the brain would be almost entirely useless.  So, now we have a very plausible mechanism to explain the mysterious amnesia experienced by Dr. Graveline and others.  That also may explain the increase in car accidents; lapses in brain function lead to mistakes on the road.  Low cholesterol, not necessarily as a result of statins, has also been shown to lead to reduced serotonin levels in the brain.  Low serotonin is one of the key brain abnormalities involved in depression, and it has been linked to increased violence and aggression as well.  Heres an example of a study that linked low cholesterol levels to increases in school suspensions and expulsions.  According to the researchers, "the results of the current study are consistent with the majority of previous studies examining the associations between low cholesterol and various forms of aggression in adults."  Looks like its no accident that those with low cholesterol are more likely to be suicidal or violent.  Still think blocking pathways is a good idea?  Read on.

As I mentioned before, statin drugs act on the enzyme HMG CoA Reductase, inhibiting its action.  While this prevents cholesterol synthesis, it also prevents synthesis of another important molecule that shares the same biochemical pathway.  This molecule is known as coenzyme Q10 (CoQ10).  This vital substance is found in every cell in the body, and in particularly high concentrations in high-energy cells such as muscles, especially the muscle cells of the heart.  CoQ10 is an important part of ATP synthesis, meaning that it is needed for your body to turn food into useable energy.  If cells run out of ATP, they die... so yes, CoQ10 is seriously important.  Which cells did I say had the highest concentrations of CoQ10?  Ohh yes, cardiac muscle cells!  And what will happen if your cardiac muscle cells run out of CoQ10, along with ATP?  Heart failure.  Thats right, the medication that is supposed to be protecting your heart can cause heart failure.  Incidentally, while heart disease rates have actually been on the decline in America, there has been a recent sharp increase in congestive heart failure.  Theres no evidence to prove statins are causing this recent phenomenon, but its certainly an interesting coincidence.

You know, every time I write one of these blogs, I try my best to be as concise as possible so that I dont end up with something so long that nobody wants to read it.  But, here I am again with another research-paper-length post.  Anyway, in conclusion here, Id like to reiterate the problems with blocking the pathway that makes cholesterol.  Cholesterol is an important molecule with a number of vital functions in the body, not the least of which is to allow the brain to function.  Without it, the brain is useless.  Think about that (with your brain) next time you take your statin drug.  And dont forget about that whole car accidents, suicide, violence thing.  Low cholesterol levels, resulting from statins or not, increase your risk for depression.  Also, blocking the cholesterol pathway prevents CoQ10 production, which is vital to every cell in the body, especially heart cells.  Without it, youre at risk for heart failure (the irony kills me).

The take-home lesson:  While taking a statin drug will make your cholesterol numbers look better, at least in your doctors eyes, there are serious problems with inhibiting cholesterol synthesis.  Cholesterol is far more important throughout the body than most people give it credit for.  And while it may be a risk factor for heart disease in certain populations, it is not the true cause... where is the logic in treating the innocent risk factor??  Its clear to me that the path to health does not lie in working against your bodys natural mechanisms; we need cholesterol, not statins.