Does the Type of Fat in Your Diet Affect Your Brain?

Here’s how a Ph.D. student at UC San Francisco doing research on neural stem cells answered that question:

If dietary fat affected the brain in a significant way, we would know about it. It would have been discovered. Which isn’t to say it doesn’t affect it in a trivial way. Not just an acute action — like if you drink a small amount of alcohol or the effect of a sugar high. I mean the long-term functioning.

Why?

Because a lot of people would have tested it. Fat gets a lot of money. It’s a crowded area of research. People try to exploit it. It’s an area with a lot of public interest. It’s very popular to study anything related to fat. Also anything related to the brain. People are worried that they will lose their mind as they age. If there was something significant found it would have been a big story all over the New York Times.

She was very sure of this, it seemed to me.

My main posts about omega-3.

Interview about Self-Experimentation (part 2 of 2)

8. How do you verify your results?

Repetition — first by me, later by others.

9. It seems your whole life is nothing but a self-experiment – how can your friends handle this?

Well, I spend a few hours in the morning differently than anyone else. I go to sleep earlier and wake up earlier than most people around me. And I eat less than most people. I like to think I make up for it by being in a better mood.

10. How do your colleagues react to your self-experiments?

Most of them think self-experimentation is a mistake, a waste of time. A few think it is creative and important.

11. Your most recent research is dealing with the effects of omega-3 on dental health. What is this research exactly about?

It’s not about dental health – that effect (omega-3 improved my gums) was an accident. It’s about the effects of omega-3 on my brain. I am varying the omega-3 in my diet in various ways and measuring how well my brain works in various ways. I began this research when I discovered that swallowing flaxseed oil capsules improved my balance. I was surprised but the effect makes sense: balance is controlled by the brain and the brain is more than half fat. Maybe you need the right fats in your diet if you want your brain to work as well as possible.

12. How did you get the idea of searching for the relation between omega-3 and dental health?

See answer to previous question.

13. How did you get the idea of taking oil to lose weight?

It was a three-step process. Step 1: I came up with a new theory of weight control. Step 2: I accidentally lost my appetite during a trip to Paris. I guessed that the cause was the unfamiliar sugar-sweetened soft drinks I’d been drinking because of the heat. This led me to discover that drinking small amounts of sugar water cause a lot of weight loss. Step 3: A friend pointed out that my theory predicted that flavorless oil should be just as effective as sugar water.

14. Are you going to search for a medical explanation for the effects of omega-3 fats?

No. Just convincing most people that there are effects is hard enough. It will also take a long time to learn how to maximize the effects. For example, what oils are best? How much oil is best? Other people are in a better position than me to try to explain the effects. But I don’t think it is terribly mysterious or surprising that dietary omega-3 should improve brain function: the brain is more than half fat. Surely the type of fat matters. My discovery is how big and fast the effect is. That’s not obvious.

15. When you consider your work as a whole, what is the most important result of your scientific research via self-experimentation?

Discovery of the effect of morning faces on mood. I believe depression is a deficiency disease, caused by too little exposure to morning faces. (See this paper for details.) No doubt that sounds very odd — even odder than the Shangri-La Diet — but consider this. In a wonderful book called The Good Women of China, the author, a Chinese radio host named Xinran Xue, wrote about her travels all over China to learn how different women lived. The last chapter is about visiting an extremely poor and backward community called Shouting Hill where an egg is a luxury and each women has multiple husbands because two or three girls are traded for a wife. She comes back to the radio station and tells her colleagues what she has seen. One of them asks, “Are they happy?” Another says, “Don’t be ridiculous, how could they be happy?” Because they were so poor — very poor even by Chinese standards. Xue answered:

I said to Mengxing that, out of the hundreds of Chinese women I had spoken to over nearly ten years of broadcasting and journalism, the women of Shouting Hill were the only ones to tell me they were happy.

It is pretty clear they saw plenty of faces in the morning.

Omega-3 and Cognitive Decline

It’s the golden age of omega-3 research. The February 2007 issue of the A merican Journal of Clinical Nutrition, perhaps the most prestigious nutrition journal, had two articles on the topic, the March issue seven (including four letters to the editor). The April issue has three (two research articles and an editorial), all on omega-3 and cognitive decline with age.

One was from Holland. Data were collected in 1990 and 1995 on 200-odd men, who were 70-89 in 1990. Those who ate fish had less cognitive decline from 1990 to 1995 than those who didn’t eat fish. A virtue of this paper is that the main results are shown graphically — a most basic point that AJCN papers usually get wrong.

The other study was done in Minneapolis. It looked at cognitive decline in about 2000 elderly men and women over a similar time period as the first study. Rather than asking subjects what they ate, this study measured blood levels of various fats. They did not find a reliable correlation between omega-3 levels and cognitive decline when considering all subjects but did find reliable (negative) correlations in subgroup analyses.

Both studies have selection problems. The first study looked at a small fraction of all the men in the study (total n = about 900) selected because of better health. I would have liked to see the results from the rest of the men. The second study did not correct for the vast number of significance tests done.

Both studies support — the second one quite weakly — the idea that omega-3s prevent cognitive decline. The main thing I notice is how difficult the research is. Data published 12 years after collection? Two thousand people studied twice, five years apart, with results barely different from noise?

Omega-3 and Dental Health (part 2 of 2)

I looked at my gums this morning. I had never seen them so pink (that is, non-red). They looked just like the picture of healthy gums at the dentist. As I explained yesterday, my gums are in good shape because I am drinking 4 tablespoons/day of flaxseed oil, which contains a lot of omega-3.

Meta-analyses of the effects of omega-3 have had trouble finding an effect. A meta-analysis about mood found a barely-reliable effect and concluded “the evidence available provides little support for the use of n–3 PUFAs to improve depressed mood.” (They should have said “ a little support.”) A meta-analysis about heart disease concluded “Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.” The effect on total mortality was close to significant and there was evidence of heterogeneity (i.e., studies varied) so their results were not completely negative, as the authors noted in response to comments. The effect is just weak, apparently.

In other words, after combining many experiments, each experiment with dozens or hundreds of subjects, meta-analyses can barely see an effect of omega-3. Yet I found a perfectly clear effect with one subject? An effect I wasn’t even looking for? That seems discrepant, and worth trying to explain.

My explanation is this: What I had in my favor and all those other studies did not were the benefits of self-experimentation. In particular,

1. The effect on balance was so clear that I used it to find the best dose. I found that 3 tablespoons/day was better than 2 tablespoons/day and even at 3 T/day there was an effect of time of day. So I went to 4 T/day. It seemed no better than 3/T day, so I stopped there. Conventional studies have not been able to do anything like this.

2. The effect on balance was so clear that I could use it for quality control. If I happened to buy a bad bottle of flaxseed oil I would have noticed — the results would not have been consistent, starting from when I started the new bottle. (I have gone through about six bottles.) Previous studies have had little or no quality control. If half their omega-3 went bad, they would have had no way of knowing.

3. I was strongly motivated to take the flaxseed oil. I know it is beneficial. This is not the case in any double-blind experiment when treatment is compared to placebo. In such experiments, every subject has reason to doubt that taking the pill will make a difference.

4. Dosage in nutrition, as in these mood and heart disease studies, has been built around avoiding failure — for example, what dose will avoid heart disease? Whereas I was looking for the optimum. My brain does not fail in any obvious way if I don’t have enough omega-3; it just functions worse. The amounts needed to avoid obvious failure are probably (a) different for different parts of the body and (b) less than optimal. For example, the amount of omega-3 needed to avoid dementia may be 1 T/day whereas the amount needed to avoid heart disease may be 2 T/day. The optimal amount, the amount needed for best performance, is likely to be greater than all of these failure thresholds. It is a better target.

Something else in my favor, not related to self-experimentation is that I studied the effect of omega-3 on my balance — how long before I lost my balance, a measure that can have many values. In contrast, most omega-3 research has involved binary measures like mortality or heart attacks. Someone either dies or does not die, for example. Binary measures tell you less than many-valued measures.

Given these advantages, it makes sense that I could find a much clearer effect.

Omega-3 and Dental Health (part 1 of 2)

Today I had my teeth cleaned and was told my gums were in excellent shape, better than ever before. They were less inflamed than usual. “What causes inflammation?” I asked. “Tartar,” I was told. I haven’t changed my cleaning habits. The only thing I have deliberately changed since my last cleaning is how much flaxseed oil I drink. At the time of my previous cleaning I was drinking about 1 tablespoon/day; now I drink 4 tablespoons/day. The person who commented about my gums doesn’t know about my omega-3 intake.

Omega-3 is believed to be anti-inflammatory, so it is quite plausible that the change in my omega-3 intake is what improved my gums. There have been a few studies of omega-3 and gum inflammation but none found impressive results. Weston Price emphasized that dental health and overall health go together. Lots of research connects gum disease and heart disease. The importance of omega-3s was first realized because of their effect on heart disease.

This research means better gums is very good news — for which I thank SLD-forum posters, who sparked my interest in omega-3.

Omega-3 and Mood Disorders

I subscribe to the Arbor Clinical Nutrition Updates. It is a nice way to slowly learn more about recent nutrition research. A partial subscription is free. Last week’s topic was omega-3 and mood disorders. The update summarized three articles:

1. Appleton KM. et al. Effects of n–3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials. Am J Clin Nutr 2006;84:1308 –16. This meta-analysis of 12 clinical trials found that omega-3 fats significantly reduced depression.

2. Frangou S. et al. Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Br J Psychiatry. 2006 Jan;188:46-50. This experiment found that an omega-3 fat helped persons with bipolar disorder.

3. Hallahan B. et al. Omega-3 fatty acid supplementation in patients with recurrent self-harm: Single-centre double-blind randomised controlled trial. Br J Psychiatry. 2007 Feb;190:118-122. This experiment found that omega-3 fats reduced a depression score.

I recently reviewed an article for the American Journal of Clinical Nutrition that found that omega-3 fats did not reduce depression scores. Unfortunately the article was not accepted for publication. I hope it gets published somewhere else.

Science in Action: Omega-3 (old data re-analysed)

A few months ago I did a little experiment to test my belief that omega-3 was affecting my balance. I replaced fats high in omega-3 (flaxseed oil and walnut oil) with a fat low in omega-3 (sesame oil). Here is a new analysis of the data:

walnut oil and flaxseed oil versus sesame oil

The raw data are the same. The new analysis differs from the earlier analysis in two ways: 1. How the number for each day is computed. The old analysis dropped the first 5 trials and took the mean of the rest. The new analysis fits a regression line to balance as a function of trial to estimate an effect of trial and subtract it, then takes a mean of all the trials. 2. Allowance for improvement. The new analysis, as the graph shows, fits a slope to all the data. The improvement over days is subtracted from each day’s score before the two conditions are compared.

The old analysis gave t = 4.1 (p = very tiny). The new one gives t = 6.3 (p = very very tiny). Big improvement!

Directory of my omega-3 posts.

Science in Action: Omega-3 (what’s the best dose?)

With a better understanding of how to measure balance, I looked again at my data about the effects of flaxseed oil. Here is a new, improved comparison of 2 tablespoons/day and 3 tablespoons/day:

2 vs 3 tablespoons/day

Very clear difference: one-tailed p = .004.

Here is a messy comparison between 3 and 4 tablespoons/day:

3 vs 4 tablespoons/day

I compared 3 tablespoons/day at 2 different times with 4 tablespoons/day divided between those 2 times. I didn’t want to take 4 tablespoons at one time and I wanted to have at least 2 tablespoons in the evening because of the sleep benefits. The graph shows that 4 tablespoons/day has about the same effect as 3.

The big picture: Earlier data convinced me there is probably an effect. Before doing more subtle, convincing, publishable experiments, I have been trying to make the effect as large as possible. For two reasons: 1. To make the effect as clear as possible. 2. To have the most beneficial possible baseline (a baseline to which I will return many times). I foresee doing an experimental design like this: baseline (n days), something else 1 (n days), baseline (n days), something else 2 (n days), baseline (n days), something else 3, and so on. During those many baseline days I want the effect to be as strong as possible.

Science in Action: Omega-3 (measurement improvement)

I’ve learned a few things. As some of you may know, I’ve been measuring my balance by standing on a board that is balanced on a tiny platform (a pipe plug) — pictures here. Now and then the board would slip off the platform. I supposed this was a failure of balance but I wasn’t sure, especially if it happened as soon as I stood on it. So I got another board into which my brother-in-law kindly drilled the perfect-size hole so that the plug will never slip:

New board (with hole for plug)

To see if this made a difference I did an experiment with a design I have never used before but that I really like: ABABABAB… (one day per condition). In other words, Monday I tested my balance with the old board, Tuesday with the new board, Wednesday with the old board, Thursday with the new board, etc. Simple, efficient, well-balanced. Here are the results:

new board vs. old board

The red line is fit to the red points, the blue line to the blue points. The two lines are constrained to have the same slope.

Well, that’s clear. I expected my balance to be better with the new board, actually.

Speaking of the unexpected, I made another measurement improvement that truly surprises me — the surprise is that I never did it before. When I looked at my early balance data (the first 10 or so days of data) I saw that my balance improved for the first 5 trials and was roughly constant after that. Each session was 20 trials so I dropped (excluded) the first 5 trials from my analyses — considering them “warm-up” trials. I took the mean of the last 15 trials. That seemed very reasonable and I thought nothing of it.

Recently I asked again how performance changes over a session. The answer was a bit different: I found that performance improved for the first 10 trials. Now there are 30 trials in a session, so dropping the first 10 of them seemed okay. And that’s what I did.

But then I looked at how variability changed over a session. I expected the earliest trials to be more variable than the rest but the data didn’t show that. Variability was pretty constant from the first trials to the last. Hmm. Maybe I am losing valuable information by not including those early trials in my averages. It occurred to me: why not allow for the warmup effect by modelling it, rather than by excluding it? (Modelling it meaning estimating it and then subtracting it.) I did that, and then I looked at the size of the standard errors of the means (standard errors based on the residuals from the fit) for the most recent 40 days — essentially, the error in measurement. Here is what I found. Median standard errors:

First 10 trials (out of 30) excluded: 0.073
First 5 trials excluded: 0.064
First trial excluded: 0.061
No trials excluded: 0.059

My eyes opened wide when I saw these numbers. Oh my god! I was throwing away so much! A reduction in error from 0.073 to 0.059 — that’s 20% better.

Science in Action: Omega-3 (time of day effect)

Flaxseed oil seems to have detectable effects within hours. For example, I increased the dose in the evening and my balance was better the next morning. To get some sense of the time course of the effect, I varied the time of day that I took the flaxseed. I usually took it around 10 pm; I tried 10 am instead. I continued to test my balance around 7 am.

Here are the results from an ABA experiment.

Taking 3 tablespoons at 10 am produced better results than taking the same amount at 10 pm. I fit lines with equal slope to both the A (10 pm) and B (10 am) treatments, as the graph shows. The two lines had different intercepts, p < .05.

Although 10 am produces better balance, it produces worse sleep — more evidence that the sleep improvement and the balance improvement are due to different mechanisms. I want both improvements, so I am going to split my dose — half in the morning, half in the evening.

Of course, the fact that time of day of flaxseed oil matters is more reason to think that presence/absence of flaxseed oil matters. It is very hard to explain these results in terms of expectations: I had no reason to expect one time to be better than the other.