Category: self-experimentation

How Wonderful is Lipitor? (continued)

Seth Roberts5 Comments

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.

Potti: The Final Act

Seth Roberts1 Comment

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.Â

Effect of Flaxseed Oil on Arithmetic

Seth Roberts6 Comments

After I moved to China in September, I was surprised that my arithmetic speed went down. (That is, I got faster.) I had lowered it from about 630 msec/problem to 600 msec/problem by eating lots of butter. I had no idea how to lower it further. I didn’t deliberately change my diet in China but it was quite different. I kept some things the same: the amount and brand of butter/day, the amount and brand of flaxseed oil/day.

I failed to figure out why I had gotten faster. I reduced the amount of flaxseed oil from 3 T (tablespoons) per day to 2 T per day. It made no difference. (In the beginning of my interest in flaxseed oil, change from 2 T/day to 3 T/day had made a difference.) Perhaps because of the butter.

Surprised that the change from 3 T/day to 2 T/day hadn’t made a difference, I went down to 1 T/day for two weeks, then back to 2 T/day. Both changes made a difference:

Each point is a separate test. Each test had 32 arithmetic problems (e.g., 3+4, 11-3). In the beginning of the data shown in the figure I tested myself once per day. After 12 days I started doing two tests/day, one right after the other. I was curious about the repeatability of the numbers; it wasn’t hard; it was a way to get better measurements. Averaging over the tests for each day to get one value per day, combining the 19 2-T/day (before) days and the 11 2-T/day (after) days, and comparing the combination to the final 7 1-T/day days, t (38) = 6.5. If you’re not familiar with t values, t = 2 is a barely reliable difference, t = 4 is a very clear difference.

This is more evidence that flaxseed oil improves brain function. It interests me because it implies the optimum dose is close to 2 T/day. It cost about $20 and took 1 person-month. In contrast, the DHA-Alzheimer’s study I mentioned two days ago cost about $1 million and took about 7000 person-months. And used (a) a cruder something-versus-nothing comparison, b) a less-sensitive between-subjects comparison, and (c) a more ethically-problematic placebo-controlled design.

Dangerous Acne Medicine

Seth Roberts9 Comments

Treatment of acne with isotretinoin is associated with suicide attempts, according to a new study. A puzzle is that suicide attempts started to rise before the treatment started. They sharply declined to baseline after treatment stopped.

Acne is an good target for self-experimentation because it is easy to measure and is surely related to diet. My discovery of the value of self-experimentation happened with acne: I discovered that of the two drugs my dermatologist had prescribed, one (benzoyl peroxide) worked, the other (tetracycline) didn’t. I had believed the opposite, that tetracycline worked and benzoyl peroxide didn’t work.

Why Small Change = Big Deal (revised)

Seth Roberts10 Comments

Last week a journalist asked me why the 5% improvement in arithmetic speed produced by butter was important. In an earlier post I said I’d given a poor answer. A few days later I figured out what I should have said. The article was delayed, it turned out, so there was time to use my new strategy. I answered the question like this:

I was excited by this discovery because it was so big and unexpected. Someone once found a correlation between IQ and reaction time. The higher your IQ, the faster your reaction time. I don’t know what the exact function was but a decrease of 30 milliseconds might correspond to 10 more IQ points. I felt a little bit smarter. It was so unexpected because hardly anyone was going around saying butter is good for you — and thousands of people were saying it is bad for you. The only ones saying butter is good for you were the followers of Weston Price, and they had almost no evidence for what they were saying. Compared to their evidence, my evidence was crystal clear. Among mainstream nutritionists, butter is universally scorned. Yet my data suggested exactly the opposite — that it had a large amount of an important nutrient I wasn’t getting enough of. If mainstream nutrition advice could be so wrong, it would have big implications for what we eat. Maybe other things we are constantly told about what to eat are also wrong.

I discovered this big effect of butter by substituting butter for pork fat. So the reason butter was so helpful wasn’t anything as simple as animal fat is food for us. I ate plenty of animal fat before I started eating lots of butter. The reason was something more specific.

Madame Bovary and Self-Experimentation

Seth Roberts4 Comments

Someone asked Lydia Davis: Why another translation of Madame Bovary? She replied:

In the case of a book that appeared more than 150 years ago, like Madame Bovary, and that is an important landmark in the history of the novel, there is room for plenty of different English versions. For example, 1) the first editions of the original text may have been faulty, and over the years one or more corrected editions have been published, so that the earliest English translations no longer match the most accurate original; 2) the earliest translators (as was the case with the Muirs rendering Kafka) may have felt they needed to inflict subtle or not so subtle alterations on the style and even the content of the original so as to make it more acceptable to the Anglophone audience; with the passing of time, we come to deem this something of a betrayal and ask for a more faithful version. 3) Earlier versions may simply not be as good in other respects as they could be—let another translator have a try.

This reminds me of my three-part answer to the question a journalist asked me: why it mattered that butter improved my arithmetic speed by 5%.

Just as I disliked my answer, I disliked Davis’s answer. It’s hypothetical (“may have been faulty”, “may have felt”, “may not be as good as they could be”). It’s flat and obvious (earlier versions may have room for improvement). It’s irrelevant (bad translation of Kafka does not justify new translation of Flaubert).

I had trouble figuring out a better answer to what I was asked, but I could instantly say what Davis should have written: The story of how she decided to do a new translation. (“I began to think about doing a new translation when . . . “) That would have been a lot more emotion-laden and not hypothetical, obvious, or irrelevant.

As soon as I thought what Davis should have said, I could see what I should have said. I should have answered the journalist’s question like this: Why does 5% matter? Let me tell you why I was so excited by this. . . .Â

Via Marginal Revolution.

The C.I.A. and Self-Experimentation

Seth Roberts1 Comment

I learned of The Human Factor: Inside the CIA’s Dysfunctional Intelligence Culture by Ishmael Jones (a pseudonym) from an interview on the New Yorker website. This comment by the author interested me:

Once the C.I.A. became a place to get rich, effective operations ended. Today, more than ninety per cent of C.I.A. employees live and work entirely within the United States, in violation of the C.I.A.’s founding charter [to supply only foreign intelligence].

I could say much the same about science: Once it became a place to get rich (or at least get large grants), effective science became a lot less common. A great deal of science is done by drug companies. They pay a lot. Some of their scientists are surely brilliant but their talents are wasted by the need to find solutions that will be highly profitable. My self-experimentation found solutions that cost nothing and make far more intellectual sense. I was able to do something that didn’t produce a lot of publications because it wasn’t my job.

Many skills make good full-time jobs. Science doesn’t. There is too much pressure for short-term results. Without short-term results, you may lose your job or your grant. (Or, in China, most of your income.) Nor is science a good source of status. If you want your science to provide your status, you will be under great pressure to conform. Yet for practically all scientists, it’s their full-time job and their main source of status. This may not make it impossible for them to do good work but I suspect it comes close to doing so. My self-experimentation was effective not only because it was fast and cheap (per experiment) but also because I could be slow (per publication) and do something low-status.

Periodontitis and Omega-3

Seth Roberts6 Comments

A few years ago, after I started taking about 3 tablespoons/day of flaxseed oil, my dentist told me my gums were much healthier. They were less red, more pink. Friends and blog readers who took flaxseed oil in similar amounts noticed the same thing. Tyler Cowen’s gums improved so much he no longer needed gum surgery.

An epidemiological study in the November Journal of the American Dietetic Association reports correlations between omega-3 intake and periodontitis (an extreme form of inflamed gums). The more omega-3, the less periodontitis. I’m sure that sufficient omega-3 intake cures periodontitis so this study has methodological interest for me. One interesting point is that the study reached a correct conclusion — contrary to the nihilism of John Ioannidis. Another is that the correlations were weak. The risk of periodontitis was only 20% lower in the group (quintile?) with the highest omega-3 intake. Although there were 9000 subjects, there was no significant correlation with linolenic acid, the form of omega-3 found in flaxseed oil.

Thanks to Sean Curley.

Walnuts: Brain Food?

Seth Roberts20 Comments

At a Mr. Lee’s restaurant (a Chinese chain), I started chatting with a girl sitting near me. I told her I was a psychology professor. “You know what people are thinking,” she said. I lamely said, no, I study what foods make the brain work best.

“I don’t know the English word for it,” she said. She drew a walnut. Good for your brain, her parents had told her. I was astonished. When I got to China, my arithmetic scores mysteriously improved. I had expected them to get worse, if anything. I tried to duplicate my American diet in Beijing but it is hard to duplicate the flaxseed oil. (Chinese flaxseed oil is worthless. I can bring it from America but not easily, and it’s impossible to keep it cold the whole way.) I had tested various explanations of the improvement but none held up.

I was starting to believe the reason for the improvement was walnuts. I have two servings/day of yogurt, each time with walnuts. I ate a lot of yogurt with walnuts in Berkeley, too; this was not a dramatic change. But maybe I eat more walnuts in China, and maybe the walnuts have more omega-3. Maybe the walnuts are fresher. In Berkeley I put ground flaxseed in my yogurt (in addition to walnuts), without obvious improvement. Walnuts are lower in omega-3 than flaxseeds.

A Chinese friend of mine had told me the same thing — that her parents had said that walnuts are good for the brain. This is a common Chinese belief, mingled with the curious idea that they are good for the brain because they look like a brain. The Wikipedia entry for walnut, which includes its use in Chinese medicine, says nothing about improving brain function. This long article about the benefits of walnuts doesn’t connect them directly with better brain function. It does say they are considered “brain food” because of high omega-3 content and links to a page that says 1/4 cup of walnuts (25 g) has 2.3 g of omega-3. I am now consuming 2 tablespoons/day of flaxseed oil, which contains 14 g of omega-3. I have sometimes consumed 3 or 4 tablespoons/day (with 21 or 28 g omega-3). You can see why 2 g doesn’t impress me, especially when added to 14 g. I thought I was getting the optimal amount of omega-3 from flaxseed oil. Adding a small amount to the optimal amount shouldn’t have a noticeable effect. This article says walnuts are brain food because of their lecithin content. Lecithin is used to make acetylcholine, a neurotransmitter.

Miraculously I can gather better evidence by myself, in a month, than all the evidence I’ve found. I simply vary how much walnuts I eat and see what happens to my arithmetic score. The experiment is worth doing because of the common Chinese belief and my puzzlingly good scores. Maybe walnuts help a brain that is already getting plenty of omega-3. Maybe not.