Effect of Vitamin D3 on My Sleep

I have blogged many times about biohacker Tara Grant’s discovery that she slept much better if she took Vitamin D3 in the morning rather than later. Many people reported similar experiences, with a few exceptions. Lots of professional research has studied Vitamin D3 but the researchers appear to have no idea of this effect. They don’t control the time of day that subjects take D3 and don’t measure sleep. If the time of day of Vitamin D3 makes a big difference, measuring Vitamin D3 status via blood levels makes no sense. Quite likely other benefits of Vitamin D3 require taking it at the right time of day. Taking Vitamin D3 at a bad time of day could easily produce the same blood level as taking it at a good time of day.

I too had no idea of the effect that Grant discovered. I had taken Vitamin D3 several times — never in the morning — but after noticing no change stopped. I tested Grant’s discovery by taking Vitamin D3 at 8 or 9 am. First, taking it at 8 am, I gradually increased the dose from 2000 IU to 8000 IU. Then I shifted the time to 9 am. The experiment ended earlier than I would have liked because I had to fly to San Francisco.

When I woke up in the morning I rated how rested I felt on a 0-100 scale, where 0 = not rested at all and 100 = completely rested. I’d been using this scale for years. Here are the results (means and standard errors):

Vitamin D3 had a clear effect, but the necessary dose was more than 2000 IU. If Vitamin D3 acts like sunlight, you might think that taking it in the morning would make me wake up earlier. Here are the results for the time I woke up:

There was no clear effect of dosage on when I got up. Shifting the time from 8 am to 9 am may have had an effect (I wish I had 3 more days at 9 am).

Many people have reported that taking Vitamin D3 in the morning gave them more energy during the day. I usually take a nap in the early afternoon so I measured its effect on the length of those naps:

Maybe my naps were shorter with 6000 and 8000 IU at 8 am. It’s interesting that 4000 IU seemed to be enough to improve how rested how I felt but not enough to shorten my naps.

What do these results add to what we already know? First, the large-enough dose was more than 2000 IU. (A $22 million study of Vitamin D3 is using a dose of 2000 IU.) The dose needed to get more afternoon energy may be more than 4000 IU. Second, careful experimentation and records helped, even though many people found the effect so large it was easy to notice without doing anything special. For example, these results suggest the minimum dose you need to get the effect. Three, these support the value of supplements. Many people say it is better to get necessary nutrients from food rather than supplements. However, supplements allow much better control of dosage and timing and these results suggest that small changes in both can matter. I cannot imagine this effect being discovered with Vitamin D3 in food.

Assorted Links

Thanks to Alex Chernavsky.

What Motivates Scientists? Evidence From Cancer Research

A friend of mine who worked in a biology lab said the grad students and post-docs joked about the clinical-relevance statements included at the end of papers and grant proposals: how the research would help cure cancer, retard aging, and so on. It was nonsense, they knew, but had to be included to help funding agencies justify their spending.

Principal investigators never say such things. Are they wiser than grad students and post-docs? Fortunately for the rest of us, actions speak louder than words. An action — actually, a lack of action — that suggests that P.I.’s know their research has little connection to curing cancer, etc., is 50 years of widespread indifference by cancer researchers to the possibility that their research uses a mislabeled cell line. For example, you think you are studying breast cancer cells but you are actually studying melanoma cells. A recent WSJ article says that the problem was brought to the attention of cancer researchers in 1966 but they have been “slow” to do anything about it:

University of Washington scientist Stanley Gartler warned about the practice [of using mislabelled cells] in 1966. He had developed a pioneering technique using genetic markers that would distinguish one person’s cells from another. Using the process, he tested 20 of the most widely used cancer cell lines of the era. He found 18 of the lines weren’t unique: They were Ms. Lacks’ cervical cancer. . . . A decade after publication of his findings Gartler attended a conference and introduced himself to a scientist. Dr. Gartler recalled the man told him, “‘I heard your talk on contamination. I didn’t believe what you said then and I don’t believe what you said now.’ “

What he meant was: I ignored what you said. Yet it costs only $200 to check your cell line. Fifty-plus years later, mislabeled cell lines remain a big problem. “Cell repositories in the U.S., U.K., Germany and Japan have estimated that 18% to 36% of cancer cell lines are incorrectly identified,” says the article. This indicates considerable indifference to the possibility of mislabeling.

If you truly wanted to cure breast cancer, would you spend $200 (out of a grant that might be $100,000/year) to make sure you were using a relevant cell line? Of course. If you were trying to cure your daughter’s breast cancer or your mother’s melanoma, would you make absolutely sure you were using the most relevant cell line? Of course. I conclude that a large fraction of cancer researchers care little about the practical value of their research.

I believe that one reason my personal science found new solutions to common problems (obesity, insomnia, etc.) is that my overwhelming goal was to find something of practical value. I wasn’t trying to publish papers, impress my colleagues, renew a grant, win awards, and so on. No doubt many cancer researchers want to cure cancer. But this 50-year-and-not-over chapter in the history of their field suggests that many of them have other more powerful motivations that conflict with curing cancer.

Thanks to Hal Pashler. Hal’s work on “ voodoo neuroscience” is another instance where the guilty parties, I believe, knew they might be doing something wrong but didn’t care.

Assorted Links

Thanks to David Cramer and Nadalal.

Science in Action: Unexplained Changes in Brain Speed

This is me a few days ago. I did a choice reaction time task many times. Each dot is a session with enough trials to supply 32 correct answers.The y axis is in “percentile” units, meaning speed relative to recent performance. If my speed was at the average of recent performance, the percentile would be 50, for example. Higher percentiles = better performance = faster (shorter reaction time). Each point is a mean; the vertical bars are standard errors. The dotted line is the median of the means.

The graph shows that Friday afternoon I was suddenly unusually slow. After dinner, I returned to normal. A change from 60%ile to 20%ile to 60%ile resembles an IQ change from 105 to 87 to 105 (an 18-point change).

At the same time accuracy was roughly constant:

Because accuracy was roughly constant, the change in speed was not due to a shift on a speed-accuracy tradeoff function.

There are two puzzles here. 1. Why were my scores low Friday afternoon? 2. Why did they recover after dinner? On Friday I didn’t feel well. As a result, I didn’t eat much. Maybe my blood sugar was lower than usual. I usually eat 30 g butter twice/day. On Friday I didn’t have any. At dinner I did have moderate amounts of pork fat (but not butter) and sugar (in lemon citron tea). Friday 6 pm I had a cup of black tea. Although I haven’t noticed effects of tea on these scores, there’s a first time for everything.

Here is a clue to what makes my brain work well (= fast), I conclude. Butter causes sudden improvement, I have found; which makes it plausible that lack of butter (and other animal fat) could cause sudden degradation. Another possibility was that my blood sugar was low Friday afternoon. (I didn’t think of this at the time, and didn’t measure it.) I’m surprised that something as important as brain function would be as fragile as these results imply. When various nutrient deficiencies are studied with conventional measures, it generally takes weeks or months without the nutrient for the bad effects to become apparent. It takes many weeks without Vitamin C to get scurvy, for example.

These results raise the intriguing possibility that everyone has sudden ups and downs in brain function and that these ups and downs can be detected at high signal/noise ratios. If so, we can use these ups and downs to learn how to make our brains work well. These results also imply — because my choice reaction time test required only a laptop — that anyone can detect them, study them, and learn what causes them. No experts needed. What a change that would be.

 

Fermented Foods Improve Irritable Bowel Syndrome

It’s hard to get scurvy. If you eat anything resembling an ordinary diet you won’t get it. The existence of scurvy, produced by extreme conditions, led to the discovery of Vitamin C. From the case of scurvy and Vitamin C we learned — well, most people learned — that some diseases are clues to what we need to eat to be healthy.

There is no lab test for irritable bowel syndrome (IBS). It is diagnosed if you have “abdominal pain or discomfort in association with frequent diarrhea or constipation,” says Wikipedia, and a dozen other things (colon cancer, lactose intolerance, celiac disease and so on) can be ruled out. It is common. In the United States, one study found that 14% of those surveyed had it. Surveys in other countries produce even higher values — the United States is not a hotspot. “It is one of the most common diseases diagnosed by doctors,” says an NIH webpage.

What is it telling us? According to the NIH webpage, “medications are an important part of relieving symptoms.” Those medications include anti-depressants. If you treat the problem with drugs, you completely ignore the possibility that a digestive problem is due to eating the wrong food. You might think that would be obvious — but no. Of course, people with IBS are less interested in taking medicine so they often believe they are “intolerant” to various foods. But they have a hard time figuring out what those foods are, and their problems persist. The Wikipedia section about causes is a monument either to the ignorance of medical school professors or Wikipedia contributors:

The cause of IBS is unknown, but several hypotheses have been proposed. The risk of developing IBS increases sixfold after acute gastrointestinal infection. Post-infection, further risk factors are young age, prolonged fever, anxiety, and depression.Publications suggesting the role of brain-gut “axis” appeared in the 1990s, such as the study “Brain-gut response to stress and cholinergic stimulation in IBS” published in the Journal of Clinical Gastroenterology in 1993. A 1997 study published in Gut magazine suggested that IBS was associated with a “derailing of the brain-gut axis.” Psychological factors may be important in the etiology of IBS.

That’s all. Nothing about eating the wrong food. And people wonder what to do about the cost of health care! My suggestion: get rid of everyone (especially medical school professors) too blind or biased to consider that a digestive problem may caused by the wrong food.

Fortunately not everyone is rushing to treat IBS sufferers with drugs. In an obscure journal called Molecular Medical Reports, an open-access article recently appeared about diet and IBS (“Diet and effects of diet management on quality of life and symptoms in patients with irritable bowel syndrome”). The authors are from Norway, which makes the sanity more understandable. The article looks at the effect of dietary advice on IBS symptoms. It compares three groups of patients (IBS patients given dietary advice, IBS patients not given dietary advice, and people without IBS). Patients with IBS eat quite differently than everyone else (for example, they eat less dairy, thinking they might be lactose intolerant), but they are still bad off.

The main point of the article is that the dietary advice was helpful. IBS patients given the advice two years before the study were better off than IBS patients not given the advice, although even those given the advice were considerably worse than normal. Looking at the difference between the diets of the two IBS groups, the better-off group ate a lot more probiotic dairy:

The guided IBS patients reported a consumption of sour milk products containing probiotics almost twice as often as the unguided IBS patients and one and a half times that of the controls. The products used were supplemented with Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5 and Bifidobacterium Bb-12. Patients with IBS were found to have fewer Lactobacillus spp. and Bifdobacterium spp. in their intestinal flora than healthy individuals (44). These bacteria have been shown to bind to epithelial cells and inhibit pathogen binding, and to enhance barrier function (46). Furthermore, these bacteria do not produce gas on fermenting carbohydrates, an effect which would be amplified as they also inhibit Clostridia spp. (46). A number of studies have shown an improvement in flatulence and abdominal distension with a reduction in the composite IBS symptom score, following probiotic intake (45,46) [emphasis added]

It is highly unlikely that we need to eat sour milk products containing probiotics to be healthy — such products are new in evolutionary history. But it is entirely possible that we need to eat plenty of microbe-laden (e.g., fermented) food to be healthy, as I have said countless times on this blog. The big improvement in IBS symptoms produced by probiotics supports my belief that we need to eat plenty of fermented foods to be healthy. (The Wikipedia entry about IBS mentions probiotics and yogurt, but not fermented foods.) Maybe IBS, like scurvy, is a clue to something really important.

Thanks to Melissa McEwen.

 

Nick Winter’s Big Success with Percentile Feedback

I have posted several times about using what I call percentile feedback to boost productivity. Percentile feedback means comparing your current performance to your previous performance using a percentile. If the current performance is in the middle of your previous performances, the percentile is 50, for example. Percentile feedback is easy to understand (scores above 50 are better than average) and is sensitive to small improvements — so even small improvements are rewarded. My implementation had three other helpful features: 1. It adjusted for the time I woke up to make different days more comparable. 2. It measured efficiency (time working/time available) to further improve comparability across days. 3. It was graphical. I made a graph of efficiency throughout the current day versus previous days. It greatly increased how much I worked every day.

I love it and wish I had it for everything I measure. Unlike so many feedback systems, it is realistic and encouraging. I found it worked extremely well — to my surprise, actually. It’s not so surprising I would think of it because it vaguely resembles an animal-learning procedure. (Animal learning is my area of expertise within psychology.)

Nick Winter, one of the developers of Skritter (which I use), recently started to use it. He gave a much-too-short QS talk about it in Pittsburgh a month ago. I asked him about his experience. He is as enthusiastic as I am. He wrote:

The percentile feedback has been a huge success–I’m getting way more done than I ever did, and I’m much better at prioritizing toward my main project. Seeing the graph going in real time has been much better at making me aware of what I need to do to hit high targets each day. I will do a full writeup on this, and on my self experiments, when I finish this iOS app and stop focusing so much on work. The short teaser goes something like this:
Phase 0: just tracking normal work at end of day in a Google Doc, average 2 hours a day on iOS development
Phase 1: tracking normal work and iOS dev separately in the Google Doc, average 4 hours a day on iOS development
Phase 2: using Beeminder to have better graphing and goal incentive for iOS dev, average 5 hours a day
Phase 3: first three weeks of using percentile feedback, average 6.4 hours a day
Phase 4: second three weeks of using percentile feedback, deciding to really push it based on the positive feedback from my metrics (more productivity, more happiness), average 9.4 hours a day
So now I’m getting close to averaging 70 hours of focused iOS dev a week and it feels great. In a normal work place, “time spent working” != “productivity”, but for me they’re very similar as long as my energy is good, which it almost always is now.
The surprising insight is that changing the way that I measured my work performance–from spreadsheet, to better spreadsheet, to graph, to better graph–has had such a huge impact. I have been working on maximizing work productivity for four years, ever since starting the startup, but in the last six months I’ve become radically more effective. I love the percentile feedback graph design!

You can see his implementation on his homepage.

Coconut Oil Cures Foot Fungus

About ten years ago my doctor pointed to a thin white line on my foot: That’s fungus, he said. Huh. He prescribed an antifungal medicine, previously available only by prescription, that had recently become over-the-counter (OTC). I tried several OTC remedies from my drugstore. None worked. According to the directions, they were to be applied twice per day. My doctor said the reason for the failure was that I hadn’t precisely followed the directions. This reminded me of a doctor who said that fat people know what to do about being fat (eat less) and simply fail to do it.

Years later I discovered that socks matter. With a much larger number of socks, my foot fungus got much better. Apparently the fungus died if it didn’t come in contact with my foot within a week or so. (I had it only on one foot.) With a large number of socks, my foot fungus never got really bad. But it did not entirely go away.

I discovered that tea tree oil works. When my foot fungus got noticeable I would put on some tea tree oil and it would get better.

In January I went back to Berkeley for a month. Without doing anything, my foot fungus seemed to vanish. Apparently being away from my apartment for 4 months was enough to get rid of the fungus. When I returned to Beijing in February, the fungus returned within a day or two. The shape of a particularly bad spot matched exactly where a plastic sandal touched the upper part of my foot. A sandal I’d worn in the shower to prevent foot fungus.

All this is to show how little I know about foot fungus in spite of having it for years.

In November (3 months ago) a reader of this blog named Chuck Currie wrote me:

Sometime in the spring I noticed that I was getting what looked like a rash around the large toe of my right foot. It began spreading, first under and between my toes and then across the top and then under my foot. There was a definite line with little bumps that showed it progression. And, it itched really bad – like bad athlete’s foot.

In July I was prescribed Nystatin and Triamcinolone Acetonide cream. [I tried this — Seth] I was told to put it on twice a day, which I did. Because I wear flip flops all summer, I didn’t need to cover it. The cream did not work at all. It actually seemed to make it worse.

I have been interested in coconut oil since going paleo, even though I can’t eat it, or coconut milk – they really upset my stomach. I was reading an article on coconut oil that mentioned its anti-fungal properties and I remembered reading this before. So I thought I would give it a try on my foot.

After showering, I cover my foot with coconut oil, place a plastic bag over my foot (the kind you put produce in) to keep it from being wiped off and then place a sock over the bag to hold it on. I leave it on for two or three hours and then take everything off and lightly wipe my foot with a paper towel and go to bed.

I do this three or four nights a week and have been doing it for three months. I knew immediately that it was doing something. My foot became very warm, almost like it was on fire, the first time I did this. It didn’t have this effect the second time. My fungus/rash started to retreat. My skin would dry out and flake off between sessions, like I was using an exfoliate.

Then I noticed that my [toenail fungus] started to clear up and I could see the nail growing from the cuticle on my big toe was clear, not yellow and thick. By now the line has progressed two thirds of the way up my toe. At this rate, it should be completely clear in another couple of months.

I still get small flare ups of the rash/fungus on my foot, but it has almost completely cleared up. You can still see where it had been. The skin is dryer and lighter in color than the rest of the foot.

I think if I had done this every night the progress would have been faster. I’m now starting to put a small amount of coconut oil on the top of my foot in the morning and letting it air out for a while before putting on my socks and shoes. When the fungus was on the bottom of my foot this was not possible, but now that it only seems to be on the top, this works and I think this will speed up the process. The best thing is there are no bad effects. I use extra virgin, cold pressed, unprocessed coconut oil. My understanding is that heat processed coconut oil does not have the same anti-fungal properties.

Pretty convincing, huh? In Berkeley I bought Whole Foods house brand coconut oil (cold-pressed). Edible was cheaper than non-edible. In Beijing, after my foot fungus had gotten quite noticeable, I started to use it. At bedtime, I rub it all over my foot, put my foot in a thin plastic bag, and put on a sock. When I get up, I take off the sock and the plastic bag.

After doing this once, my foot was much better. After five applications, I couldn’t detect any fungus. Application is pleasant (without trying, I don’t miss a night) and, as Chuck says, obviously safe — I could eat what I am spreading on my foot. It costs a few dollars/month. Tea tree oil works, too, but it wasn’t easy to spread all over my foot, wasn’t pleasant to apply, wasn’t edible, and cost $15/tiny bottle. On the internet you can find many home remedies, such as soaking your feet in apple cider vinegar. Apparently they work. This is much easier.

If you try this, please tell me your experience, whether it works or not.

Personal Science and Varieties of DIY

How does personal science (using science to solve a problem yourself rather than paying experts to solve it) compare to other sorts of DIY?

Here’s an example of personal science. When I became an assistant professor, I started to wake up too early in the morning. I didn’t consider seeing a doctor about it for several reasons: 1. Minor problem. Unpleasant but not painful. 2. Doctors usually prescribe drugs. I didn’t want to take a drug. 3. Sleep researchers, based on my reading of the sleep literature, had almost no idea what caused early awakening. They would have said it was due a bad phase shift of your circadian rhythm. They often used the term circadian phase disorder but never used the term circadian amplitude disorder — apparently they didn’t realize that such a thing was possible. I decided to try to solve the problem myself — an instance of DIY. Except that, if I made any progress, that would be better than what the experts could provide, which I considered worthless.

There are thousands of instances of DIY, from fixing your car yourself to sewing your own clothes to word processing. Here is one dimension of DIY:

1. Quality of the final product. Better, equal, or worse to what you would get from professionals. Richard Bernstein’s introduction of home blood glucose testing led him to much better control of his blood glucose levels than his doctors had managed. Same as my situation: DIY produced acceptable results, the experts did not.

In contrast to Bernstein, who reduced his blood glucose variability within months, it took me years to improve my sleep. That is another dimension:

2. Time needed. Personal science, compared to other DIY, is orders of magnitude slower.

Here are some more dimensions:

3. Training needed. I don’t know how much training personal science requires. On the face of it, not much. I had acne in high school. I could done self-experimentation at that point. It just didn’t occur to me. On the other hand, I think effective personal science requires wise narrowing of the possibilities that you test. For most health problems, you can find dozens of proposed remedies. How wise you need to be, I don’t know.

4. Commercialization. Some forms of DIY are entirely the creation of businesses — cheap cameras, home perms, IKEA, etc. Bernstein’s work happened because of a new product that required only a drop of blood. The company that made it wanted doctors to do DIY: measure blood glucose levels in their office (fast) rather than having the measurement made in a lab (slow). When I started to study my sleep, no business was involved. Now, of course, companies like Zeo and the makers of FitBit want users to do personal science.

5. Price. My sleep research cost nothing, which in the DIY world is unusual. The term DIY is almost entirely a commercial category: Certain books and goods are sold to help you DIY.

6. Customization possible. Some kinds of DIY give you the tools to build one thing (e.g., IKEA, home perms). Other kinds (e.g., Home Depot, word processing) give you the tools to build a huge range of things. This dimension is variation in how close what you buy is to the finished product (Ikea = very close, word processing = very far). Personal science allows huge customization. It can adjust to any biology (e.g., your genome) and environment (your living conditions).

7. Benefit to society. If I or anyone else can find new ways to sleep better — especially safe cheap easy ways — and these solutions can be spread, there is great benefit to society, by comparison to DIY that allows non-professionals to reproduce what a professional would create (e.g, IKEA).

You might say that personal science isn’t really DIY because, compared to other DIY, (a) it is much slower and (b) the potential benefit to society is much greater. But those features are due to the nature of science. Any form of DIY has unique elements.

My mental picture of DIY is that there are two sides, producers and consumers, and in many domains (health, car maintenance, word processing, etc.) they creep toward each other in the sense that what producers can make slowly increases and what consumers are capable of slowly increases. When they meet, DIY begins. In some cases, the business has done most of the changing; the DIY is very easy (e.g., Ikea). In other cases, the consumer has changed a lot (literacy — not easy to acquire). Either way, the new DIY causes professionals who provided that service or good for a living to lose business.

One Doctor’s View of Personal Science (more)

A few weeks ago I blogged about a leukemia doctor’s disapproval of self-experimentation (“you won’t learn anything and others won’t learn from it, either”). What I wrote was reposted at The Health Care Blog, where it elicited this comment (by “rbar”):

Sigh. Mr Roberts did it again, he simply does not (want to) understand that anecdotal evidence is of little value (let me give you an example: I self experiment with traffic signals; I noted that I can considerable cut down on travel times when ignoring red lights and stop signs; there are no drawbacks whatsoever, no one get hurts, and even my gas mileage/carbon footprint got better) .

Individuals who have similar questions as Mr. Roberts should look up the following key words, because they may understand why controlled studies are far superior to anecdotal evidence:
-placebo effect
-regression to the mean
-misattribution error [apparently rbar means error in determining the cause of a change]-self limited conditions/natural fluctuation of chronic conditions
-and in terms of drawbacks of experimentation: primum non nocere, and also the fact that anecdotal evidence adds relatively little to humanity’s knowledge base

Does all that mean that patients should not be well informed, active and making suggestions to their treating physicians? Of course absolutely not. Being knowledgeable about one’s condition is different from self experimentation. Is that intellectually challenging?

One reply to this comment said we should be aggregating data across patients. “I believe Mr. Roberts is alluding to the power of aggregating real-world data across patients to generate insights into what may and may not work, not to giving undue weight to any single anecdotal case.” No, I was looking at it from the point of view of the self-experimenting patient. If you have a health problem, and you can measure it often (daily, weekly) you can find out what works faster than your doctor — often much faster. You can test many more possible solutions. This is what Richard Bernstein taught the whole world of diabetes, starting in the 1960s, when he pioneered home blood glucose testing. Apparently rbar also objects to that.

Rbar’s comment is dismissive (“Sigh”, “Is that intellectually challenging?”) and partly obscure (“ignoring stop signs and stoplights” — huh?). Because patients who self-experiment may make “misattribution errors” they shouldn’t self-experiment? That’s like saying because people may make reasoning errors they shouldn’t reason.

The true meaning of rbar’s comment may be hidden in his statement that it’s okay for patients to “make suggestions to their treating physician.” Which shows who he thinks should be boss in the doctor-patient relationship. When a patient self-experiments, the doctor is no longer boss. Maybe rbar is a doctor. Maybe he feels threatened by self-experimentation. If so, I hope he’s right.

More A later reply to rbar put it well: ” Your list of possible pitfalls . . . is similar to lists I remember seeing back in graduate school in various research handbooks. I do not see how you go from the fact that these effects and errors are possible to the conclusion that the whole endeavor isn’t worthwhile.”