Seth's Blog

In response to my previous post about Lipitor, someone named Brian commented:

I recently stopped taking Zocor [a statin, like Lipitor, and the most prescribed anti-cholesterol drug]. I started taking it at the same time I started using a CPAP machine to treat sleep apnea. While my sleep was more restful, I remained fatigued. After a year of Zocor, I was diagnosed with ADHD. Following this diagnosis, I tried a string of medications — adderall, stratera, and ritalin. I even became depressed and was put on an SSRI. My memory and mental prowess faded and became extremely spotty at best. I would use IQ apps on my iPhone to measure my mental prowess — and usually scored in the 75-100 range! (Prior to Zocor, similar computerized IQ tests would yield answers from the 130s to the 170s.) . . .

So I quit taking Zocor. (Initially, I tried using COQ10 to moderate the effects, but it proved ineffective.) . . . My mind is back, as are my computerized IQ scores. I no longer arbitrarily stop talking in the middle of sentences after losing my train of thought.

Apparently Zocor caused serious mental problems. Is this rare or common? Common. Here is an article about it. The idea that statins have bad mental effects is old. At first it was dismissed. Here is one dismissal:

The issue of low serum cholesterol and depression was directly examined in three randomized, placebo controlled trials of statins in which indices of depression were measured in all the participants—a total of 7400 people taking active treatment and 2400 taking placebo. Depression was no more common among those taking active treatment.

Apparently these three large randomized placebo-controlled trials got the wrong answer. Curious.

Perhaps statins cause mental impairment in everyone. Everyone’s brain uses cholesterol. If you are going to start or stop taking a statin (such as Zocor or Lipitor) and would like to learn how the drug affects/affected your mental function, please contact me. I am interested in helping you do that.

In the top 15 most prescribed drugs, Lipitor (#7) was the only non-generic. The profits are large, the benefits small and plausibly outweighed by the costs. There is great room for improvement in determination of how much Lipitor and other statins impair mental function.

John Cassidy, a staff writer at The New Yorker, understands clearly the poor judgment of economics professors. In How Markets Fail he said the Nobel Prize in Economics has made things worse, because it has often been given for worthless work. Outside of economics, however, he can write this:

That such a smart well-informed non-party-liner can believe Lipitor is wonderful shows Orwell was right: with enough repetition, people can be convinced war = peace. Here is the truth about Lipitor:

Statin therapy is extremely efficient in lowering cholesterol numbers, but unfortunately not without adverse effects on the body. To prevent a first heart attack, for every life that is saved – 1% over 10 years of use – statins cause an equal number of adverse deaths due to accidents, infection, suicide and cancer — 1% over 10 years’ use and significantly greater levels of serious side effects and suffering. . . . In a study to see the effects of raising the Lipitor levels from 10 to 80 mg (more sales) on patients, those taking 80 mg had increased liver problems, that is the rate of raised liver enzymes was six times higher than those given 10 mg of Lipitor. Even though the total deaths due to CVD in the 80 mg group was fewer (126) than in the 10 mg group (155), the total deaths due to other causes was higher in the 80 mg (158) than the 10 mg (127) group. There was no difference in the overall mortality rate.

Lipitor, the miracle drug. Taken by millions at a cost of billions. This is what happens when you — such as those in charge of health care — have little understanding of a problem: You aren’t good at solving it.

Cardiologists believe that high cholesterol causes heart attacks. Their depth of understanding was illustrated by the cardiologist at my Quantified Self talk about butter who said that the Framingham study showed that diet caused heart attacks (no, it found new correlations between heart disease and “risk factors” such as cholesterol — see also this) and that the recent reduction in heart attacks is evidence of our improved understanding (e.g., the science behind Lipitor). That a thousand other things changed over the same time period he apparently hadn’t considered. He simply couldn’t defend — at least then — his core belief that butter was bad. A cardiologist! How many thousands of people has he told to eat less butter?

Cassidy’s article about the harm done by the financial industry, from which that quote was taken, is excellent.

You can find statements like the following in a hundred places:

Both fish and flax are good sources of omega-3. Flaxseed oil is less expensive, which can be an important consideration. The main difference is that flaxseed oil contains only alpha-linoleic acid (ALA), which is the parent compound from which other omega-3 fatty acids are derived. This leaves it to your body to do the conversion to the other forms it needs, eicosapentaonoic acid (EPA) and docosahexaenoic acid (DHA). The problem is that the conversion is not always that efficient, and the body often uses the ALA for extra energy, leaving less for conversion to the other types. The body uses various enzymes to convert ALA to other omega-3s, and the process is not very efficient, especially as one gets older. Estimates of the rate of conversion range from 5% to 25%. In order to make sufficient amounts of EPA and DHA, one needs to consume 5-6 times more ALA than if one relies on fish oil alone. Fish oil, on the other hand, contains the other forms and delivers them directly to your body with no conversion necessary.

It isn’t that simple. Here are three things I rarely see mentioned:

1. The conversion rate is not fixed. It depends on the amount of the conversion enzyme, which increases with ALA exposure. The body makes the enzymes it needs and doesn’t make the enzymes it doesn’t need. You don’t have enzymes to digest food you don’t eat — but if you start to eat them you will build up the enzymes. The measurements of ALA conversion rate I have seen measured the conversion rate without giving the subjects extensive exposure to ALA before the test. (Measurements of glycemic index have the same problem.) They should be considered lower bounds of what would happen with long exposure.

2.  Time release is good not bad. When you take a dose of flax oil, its ALA is converted to DHA and EPA, which takes time, thus smoothing out the supply versus time function. If you take a dose of fish oil, the brain receives a sudden burst of DHA and EPA. It is likely that a smoother supply is better.

3. ALA (omega-3) conversion blocks AA (omega-6) conversion. Omega-3 fatty acids and omega-6 fatty acids are almost identical. The enzyme that converts short-chain omega-3 to long-chain omega-3 also converts short-chain omega-6 to long-chain omega-6. Long-chain omega-6 probably has bad effects in your brain, at least in large amounts, because it displaces long-chain omega-3. For industrial reasons, our diets are high in short-chain omega-6. Having ALA in your system, which flax oil provides but fish oil does not, slows down the conversion of short-chain omega-6 to long-chain omega-6 by occupying the conversion enzymes.

Thanks to Gary Skaleski.

Dr. Amil Potti has resigned from Duke. The clinical trials based on his (faked) research have been stopped. Duke has not exactly covered itself with glory. The two statisticians who first noticed a problem:

In November 2009, we identified and reported the exact problems now cited for retracting the paper…. Given that Duke knew of these problems, why were (Potti’s) clinical trials reopened in January 2010?”

And:

Experts say that Nevins ["who supported his collaborator Potti through four years of controversy over reliability of their findings"] has admitted that the clinical trials that followed the laboratory research — more accurately described as experiments with human beings — harmed patients. Up until this moment, Duke has steadfastly denied this; and in a Halloween statement, Duke affirmed “we do not believe that patients were endangered.”

Recall that the case against Potti attracted notice only when it was discovered he wrongly said he had won a Rhodes Fellowship. Giving new meaning to the devil is in the details. 

Ann Beattie, a great writer, has a new book out called The New Yorker Stories. I loved her early stories. Her first story in The New Yorker (1974) was “A Platonic Relationship“. I still remember this:

When he did have a beer he would take one bottle from the case and put it in the refrigerator and wait for it to get cold, and then drink it. . . . One night Sam asked her if she would like a beer. . . . He went to his room and took out a bottle and put it in the refrigerator. “It will be cold in a while,” he said quietly.

Last night I put a Diet Coke in the freezer. It will be cold in a while, I thought, remembering this passage.

Alas, I haven’t liked her work over the last 20 years as much, although I am looking forward to reading Walks With Men, her latest novel.