Michael Carlston, M.D. - Family Practice & Complementary Medicine

Carlston, M.D.
Family Practice and Complementary Medicine

www.carlstonmd.com

November 17, 2008

Dear Patients,

Long ago, maybe it was even back in medical school, I learned to brace myself when an upset child was quiet for a long time because that lengthy silent inhalation was the preparation for a loud, unhappy cry. The longer the period of quiet inhalation, the louder and longer the inevitable outburst to follow. My silence since the media splash a week ago Sunday has been filled with a similar gathering of my own energies for the reaction you will find below. Many of you have also asked about the studies supposedly proving that vitamins did not reduce cancer risk. I don’t want to overwhelm you with research so look for that next time. Suffice it to say that it was another example of conclusions contradicting the study data.

Best
Michael Carlston, MD
www.carlstonmd.com

Statins, Inflammation, Vascular Disease and Thinking Clearly
Fans May Prevent Sudden Infant Death Syndrome
GERD Drugs and Osteoporosis
Environmental Arsenic and Diabetes

Statins, Inflammation, Vascular Disease and Thinking Clearly
A new study showed that healthy patients, with normal cholesterol levels, but one elevated blood marker for inflammation, had a lowered rate of vascular events (heart attack and stroke) if they took the study drug (Crestor). The study was funded by the manufacturer of Crestor and conducted by an individual holding the rights to the blood test used in the study, found the drug and the test both impressively useful. Can you detect the skepticism in that depiction?

In 2004, Astra-Zeneca’s rosuvastatin (aka Crestor) was the subject of an FDA Public Health Advisory < http://www.fda.gov/CDER/Drug/advisory/crestor.htm >. The FDA then refused to ban Crestor despite a strong drive by consumer advocacy groups. The problem was that studies showed that the drug was worse than the average statin, apparently causing even higher rates of muscle, liver and kidney damage (2- 8 times higher likelihood per Tufts study Click here ). Initially the increased incidence of adverse effects was attributed to the high doses of the drug in common usage, however dosage turned out not to account for the disparity. The FDA chose not to ban the drug, claiming, despite this evidence, that Crestor was not significantly worse than any other approved statin. The controversy had obvious financial repercussions for the company.

The excitement over this study is quite surprising for a number of reasons. One reason is that those writing about the study seem to have forgotten the questions about Crestor. Another matter is that the effect was much more modest than you could think reading these articles. Given the low risk of vascular disease among the people in the study, 220 people would have to take Crestor every day for 2 years to prevent ONE heart attack. The researchers did not control for all known risk factors, also tarnishing their conclusions. The cost of preventing even one heart attack would be quite high.

Another, subtler, problem with this study is that Astra-Zeneca recruited 1,300 medical centers in 26 countries to find 18,000 subjects. That means that, on average, each center enrolled 14 – 15 subjects in the study. This makes the data suspect because of the extremely high likelihood of technical problems collecting the data. When a company designs a trial like this, those of us with extensive experience at analyzing studies recognize that there is only one reason for this “super study” design and that is for the company to promote it’s drug. As many countries require that drugs sold with their borders must have some research also conducted within the country’s borders, the fact that this study included no less than 26 countries is another indication of the company’s intent.

Nearly glossed over in the discussions of this study, is the fact that the healthy people taking the drug had a significantly increase risk of developing diabetes. This has been seen before with other statin drugs. Unfortunately the study was stopped prematurely, limiting our ability to interpret the findings and quite possibly obscuring long-term ill effects.

As many of you know, I am quite concerned about the bad effects of inflammation on nearly every known disease process including heart attack and stroke. There are many dietary and lifestyle factors that promote or reduce inflammation. In the early 1990’s, when I underwent my postgraduate research training at UCSF, one of our faculty was highly critical of the effects of cholesterol-lowering drugs. He liked the statins because they are strongly anti-inflammatory but he also disliked them due to the short term and long term health risks he saw in research data, including cancer.

In addition to making my anti-inflammatory recommendations (more on that later) for over a decade I routinely measured the test they used in this study (high sensitivity C Reactive Protein HS-CRP). I stopped testing for it so often when evidence accumulated that it was not a very good indicator of risk and my own clinical experience confirmed that. I never saw even one patient with an elevated HS-CRP suffer a heart attack. Also many insurance companies did not like paying for the blood test. While I still believe that combating inflammation is very important, HS-CRP may not be a good way to measure that or quite possibly HS-CRP elevations are not so strongly predictive for any one individual. Much like my surprise at seeing such a seemingly positive on a medication immersed in a long-standing cloud of poor results, this positive finding on a measure (HS-CRP) that has been falling from favor was surprising.

A reasonable recommendation to prescribe any medication, known to produce serious adverse effects, to healthy people for years demands a very high level of proof. Making a rare event even rarer is very difficult to conclusively prove and even more difficult to justify when there are known risks involved. Medical faculty at Harvard and Stanford went on record criticizing this trial, the overreaching conclusions and prescribing recommendations of the authors.

The smartest approach is to do you already know should do, and for many reasons. There are numerous means of reducing the amount of inflammation in your body without destroying your liver, kidneys or muscles. In addition, these measures are good for you in other ways, often fun and cost little if anything. Exercise is a powerful anti-inflammatory and proven to lower your HS-CRP. Healthy oils, like olive oil, fish oil, and the oil in tree nuts lower inflammation, as do veggies. Frying damages oils and increases the CRP measure of inflammation. Obesity raises inflammation, as does stress and too little sleep. Other studies have shown that Vitamin C and E each reduce HS-CRP more than did Crestor in this trial.

There is a pattern of eating we have come to call the Mediterranean diet because it is common to so many peoples around the Mediterranean. This diet is the classic “anti-inflammatory” diet, shown to be better for weight control, blood pressure, heart disease, cancer and many other health problems than the classic US government food pyramid approach. The Mediterranean diet consists of relatively small amounts of meat, high consumption of fish, monounsaturated oils (especially olive) lots of fruits and veggies with high fiber also derived from moderate consumption of whole grains. Researchers, following 1.5 million people for 3-18 years, learned that those who adhered to the Mediterranean diet even slightly better than others (2 points on a scale of 0-9) had a 9% lower death rate from all causes. Breaking it down by disease they found the following reductions 13% for Alzheimers and Parkinson’s, 9% for cancer and 9% for cardiovascular disease.

The Nurses Health Study (77,000 + female US nurses) provided a confirmation of the benefits of healthy (ie anti-inflammatory) lifestyle. Over 24 years, nurses who were overweight, smoked cigarettes, exercised very little, ate poorly and drank too much (or no) alcohol were EIGHT times as likely to die from heart disease, three times as likely to die from cancer and over four times as likely to die for any reason compared to other nurses in the study.

Although only tangentially related, I should tell you about another recent study of Crestor used by patients with heart disease. In this case the heart disease in question was heart failure. In a four year long study comparing Crestor with fish oil or placebo, investigators found that the fish oil significantly reduced the death rate but Crestor did not. There have been other studies showing an increased death rate among patients with heart failure using statin drugs.

Fans May Prevent Sudden Infant Death Syndrome
Several years ago we learned that placing infants on their backs to sleep greatly reduced the risk of sudden infant death syndrome (SIDS). Although the habit of placing infants on their stomachs had been a long-established practice, promoted by physicians, and there was some initial resistance from confused parents, the change was successfully, effectively and relatively rapidly implemented. The prevailing theory as to the reason this intervention is successful centers around the neurologic and hormonal impacts of keeping the face warm and the simple physical impediment to breathing when your face is buried in a soft bed or pillow.

Confirming the wisdom of the “Back to Sleep” approach, investigators reviewed records of SIDS deaths compared to closely matched nonSIDS children. They found significantly increased risk of SIDS associated with sleeping on stomach or side, sharing a bed with a nonparent and smokers in the home. An unanticipated finding, which makes a good deal of sense in view of our understanding of the principles behind the “Back to Sleep” approach, they learned that having a fan running in the bedroom dramatically lowered the risk of SIDS deaths. This needs further study but there is little risk to running a fan in an infant’s bedroom.

GERD Drugs and Osteoporosis
A study of 63,000 older Canadians provided further evidence of the ill effects of one class of drugs used to treat gastro-esophageal reflux. Individuals using proton pump inhibitors (Aciphex, Nexium, Prilosec, Prevacid, Protonix) for more than 7 years were twice as likely to suffer an osteoporotic fracture of the spine, wrist or hip than controls. Looking specifically at hip fractures, the increased risk was evident by 5 years with 60% increased risk. However by 7 years, the risk rose dramatically – 4.5 times that of people not using the drugs. This is another reason why I push so hard to get patients off these medications.

Environmental Arsenic and Diabetes
Many years ago I learned a great deal about arsenic exposure. News broke that millions of people on the Indian subcontinent were exposed to toxic levels of arsenic in their drinking water. Prior to that Sonoma County residents were alerted to high levels of arsenic in local well water, including the water supply on the idyllic rural campus of the school my children attended. Given the development of Sonoma County, it was dismaying but not terribly surprising that no governmental organization had a registry of wells. Consequently our public health agency had no way to identify which of us were at risk because we were using wells highly likely to be contaminated with dangerous levels of inorganic arsenic.

Just now I threw in the word “inorganic” because it is important in this discussion. Arsenic is also found in living animals, especially seafood. Inorganic arsenic is highly toxic. Organic arsenic, the kind of arsenic found in seafood, is not.

One of the many ill effects of inorganic arsenic is that it interferes with your body’s response to insulin. Insensitivity to insulin is the defining characteristic of noninsulin dependent (ie Type 2) diabetes. That is the most common form of diabetes, appearing on a practically epidemic scale. While that rising incidence of Type 2 diabetes is significantly fueled by our epidemic of obesity, investigators decided to look at the influence of arsenic as well. They found no influence from organic arsenic but those individuals with the highest blood levels of inorganic arsenic were four times more likely to have Type 2 diabetes than those with the lowest levels.

If you use well water, make certain to get it tested periodically (once a year?) for a broad range of contaminants including arsenic.

top

Archives