Life, the Universe, and Everything

This past spring I adopted a diet resembling Dave Asprey’s. After about 5 weeks on it, I took a fancy blood test (trying to optimize things such as my vitamin D levels, Omega-6/Omega-3 ratio, etc). When I finally got the results back, I was shocked to find that the most important results involved my cholesterol levels.

Six years earlier my cholesterol had been good enough that I hadn’t had any reason to pay attention to it. But this May it was 369, with an LDL of 208, and an amazingly good HDL of 108.

If I’d been unlucky enough to get those results from Kaiser, I’d have felt helpless for quite a while. But the WellnessFX report also mentioned that my ApoE Genotype is 3/4. When I got around to researching the implications of that, I figured out that the ApoE4 gene can contribute to some unusual reactions to fat, and that a few people with a copy of it had reported skyrocketing cholesterol in response to a diet of paleo foods plus much coconut and grass-fed butter.

So I cut back on my fat intake, and figured out how to test how my diet affects my cholesterol. I’ve been using CardioChek about once a week. It’s unreliable (about 50 mg/dL too low, judging by my two comparisons with Kaiser). And I’ve only been getting total cholesterol numbers. I could get better info by also measuring HDL with it and subtracting that from the total to get the number that I really want to reduce. But that would require getting a second blood sample, and I barely have enough patience to take one good sample (I often end up with too little blood and need to start over).

With all the uncertainty about the accuracy of those numbers and the time delay between altering my fat intake and when my cholesterol levels showed my response, I wasn’t too optimistic about getting clear results. But the first ways I quantified the evidence gave correlations of 0.540 or 0.418 using 12 or 13 data points (the first of those excludes an implausibly low reading the first time I used it). That’s using an exponential moving average of my saturated fat intake that roughly corresponds to the past week. Other averages of my saturated fat intake have produced somewhat similar results.

My saturated fat consumption ranged 23.5 to 53 grams per day for that data, and the cholesterol levels at the high end of the range are something like 30-50 mg/dL higher than the low end.

So I see a clear and moderately strong connection.

My limited attempts to analyze subclasses of saturated fat have been inconclusive.

Now, how good or bad is the combination of very healthy HDL and disturbingly high LDL?

There are a variety of algorithms to estimate my risk based on my cholesterol levels. Some weight LDL heavily and say I ought to be concerned about the higher readings. Others weight HDL more, and say I’m unusually healthy. The TC/HDL criterion says I have improved with each of the tests I’ve taken [excluding the home tests that only measured TC].

Without strong evidence about which algorithm is more reliable, I’m disposed to keep my cholesterol somewhat close to normal levels.

What about the evidence that societies with high coconut consumption are healthy? That could mean that high cholesterol with ApoE4 is a healthy sign – the body sees lots of rich food, and decides it devote more resources than normal to reducing inflammation. Or it might mean that ApoE4 genes got selected out of those populations.

It looks like coconuts have been eaten for the longest time in islands of the west Pacific, with the Philippines currently having the highest consumption for a sizable country, and high consumption extending west to India.

According to this study the ApoE4 prevalence in countries from the Philippines to India (including China, which presumably hasn’t had much dietary coconut in the north) ranges from 6 to 10 percent, as opposed to 17 percent in the US (which is about average). (This paper(paywalled) has some different-looking numbers on a not very readable map.)

So it looks like there has been enough selection against ApoE4 in those areas that I shouldn’t feel safe eating lots of coconut fat. But I suspect that there are other relevant genes which make it hard to generalize to everyone with an ApoE4 gene.

Eating Insects

In my quest for a diet that more closely resembles what we evolved to eat, I tried eating some insects.

Fluker’s Gourmet Canned Mealworms are ok, but the taste isn’t memorable. The texture is interesting, but hardly a reason to eat them again. They’re sold as pet food, and labeled not for human consumption. That might mean too much bacteria, but cooking should kill those. Could they have pesticides? Maybe, but insects are usually what pesticides kill, so it would be odd to use pesticides to grow them.

I tried some insects from Hotflix, which markets them as candy. All seem to be coated with varying amounts of sugar. The “chocolate covered insects” are mostly packaging, and have an ingredient list that includes hydrogenated oil but no chocolate. The various flavors of Larvets are better – mostly insect with only a small amount of sugar, spices, and artificial flavor or color. The spices make them taste fairly good, but the price per gram makes them too expensive to be a reasonable source of significant nutrition, and the artificial additives make me consider them less safe to eat than the bugs sold as pet food.

It seems like there ought to be a way to get affordable healthy nutrition from insects, and I’ll keep looking occasionally, but we probably need more demand for economies of scale to make that practical.

Omega-6 Revisited

I’ve researched omega-6 some more and the evidence that it is harmful is much less clear than I previously thought.

There’s some evidence that omega-6/omega-3 ratios above some threshold (between 2.5 and 4?) are harmful, but also arguments against focusing on the ratio:

This paper reviews a variety of studies that, in the aggregate, suggest that the ratio is, both on theoretical and evidential grounds, of little value. Metrics that include the n-3 FAs alone, especially eicosapentaenoic and docosahexaenoic acids, appear to hold the greatest promise.

While omega-6 can be converted into proinflammatory molecules, it also has antiinflammatory properties.

in observational studies, higher omega-6 PUFA consumption was associated with unaltered or lower levels of inflammatory markers

in 1 study in Israel,39 where 25% of the population consumes >12% of energy as omega-6 PUFA, an inverse association was found between adipose LA [Linoleic acid] and acute myocardial infarction after controlling for other omega-6 PUFAs.

This meta-analysis seems to be the most rigorous analysis:

They looked for

all RCT that increased PUFA and reported relevant CHD outcomes

For non-fatal myocardial infarction (MI)+CHD death, the pooled risk reduction for mixed n-3/n-6 PUFA diets was 22 % (risk ratio (RR) 0·78; 95 % CI 0·65, 0·93) compared to an increased risk of 13 % for n-6 specific PUFA diets (RR 1·13; 95 % CI 0·84, 1·53).

They found 7 randomized trials that raised omega-6 levels and provided a tolerable amount of info about other fats. Three that had apparently low dietary omega-3 showed that higher omega-6 combined with lower trans-fats produced more heart disease/death (i.e. above some high omega-6/omega-3 ratio, omega-6 can cause more harm than trans-fats), while four where the higher omega-6 was combined with arguably adequate omega-3 and lower trans-fats had less heart disease/death with that combination (i.e. omega-6 might have helped or might have caused harm that was small compared to trans-fats).

From another paper:

High intakes of linoleic acid were not associated with excess risk of AMI [acute myocardial infarction]

arachidonic acid, the long chain n?6 derivative of linoleic acid, was positively associated with AMI

(Arachidonic acid is found mainly in eggs, meat, and seafood).

Other sources suggest arachidonic acid is safe, mentioning studies of biomarkers that show no harm from arachidonic acid, but biomarkers are less convincing than actual disease. There are some reports that ratio of arachidonic acid to eicosapentaenoic acid (AA:EPA) in blood plasma is a useful measure of cardiovascular problems.

In my previous post I expressed doubts about high omega-3 diets, but this paper on hunter-gatherer diets gives the following estimates for fat intake:

  • Omega-3 9.6g/day
  • Omega-6 14.2g/day
  • Saturated 18g/day
  • Monunsaturated 44.3g/day

I don’t know how typical this is of our ancestors, but at least it’s likely within the range of diets that we’re adapted to. This suggests it’s hard to get too much omega-3 or too much fat from seafood (I’d get too much protein if I ate much more than 2 pounds of salmon, but not too much of any type of fat). It also suggests that it’s reasonable to aim for high enough omega-3 that I can’t easily get an omega-6/omega-3 ratio that is high enough to be of much concern.

More from that paper:

Compiled ethnographic studies of 229 hunter-gatherer societies, as well as quantitative studies of hunter-gatherers have demonstrated that animal foods contributed slightly more than half (55-65%) of the daily energy, whereas plant foods would have made up the remainder (35-45%) of the average daily caloric intake. Of the energy obtained from animal foods, historically-studied hunter-gatherers typically derived half of their energy from aquatic animals and the other half from terrestrial animals. Animal food intake would have also been constrained by the physiologic protein ceiling, which has been shown to occur between 30 to 41% of total energy.

There is an increasing body of evidence that suggests high protein diets may improve blood lipid profiles and thereby lessen the risk for cardiovascular disease (CVD).

[I plan to check this evidence later.]

At a cryonics social event yesterday Keith Henson mentioned a mysterious cosmic event in 774 or 775 which appears drastic enough that if it were to repeat today it would likely destroy all technology in orbit, and possibly enough planetary electronics to cause major problems. People are wondering why it apparently didn’t wipe out the ozone layer.

Attempts to find historical records of observed anomalies from that time have so far only produced a few vague hints.

Omega-6

In early April I started measuring my diet fairly carefully (using CRON-O-Meter). It is a somewhat tedious project, but it has has shown me that I’m getting too much Omega-6.

Most of the discussion I’d previously noticed implied that I should improve my Omega-6/Omega-3 ratio by consuming more Omega-3.

But after finding Dave Asprey’s website and hearing him at the Personalized Life Extension Conference, his framing of the issue as Omega-6 poisoning led me to look more carefully at my Omega-6 consumption, and is one of the reasons I tried CRON-O-Meter.

There are conflicting opinions about what ratio people ought to aim for, but those who advocate a ratio close to 1:1 seem to have a good theory (resemblance to hunter-gatherer diets), while I suspect those who advocate much higher Omega-6 levels either assume it’s hopeless to convince many people to achieve a ratio anywhere near 1:1 or have motives unrelated to Omega-fats for pushing oils with a high Omega-6 to Omega-3 ratio.

So my guess is that I should aim for a ratio less than 2:1, and be concerned if my ratio exceeds 3:1.

Even with fairly drastic changes to my diet (virtually eliminating canola oil and olive oil, and cutting back on my peanut addiction by an order of magnitude), I still find that it takes careful thought to keep my daily Omega-6 consumption below 10 grams.

I could in principle take a dozen or more fish oil pills to offset the Omega-6, but the safety of taking over 6 grams of Omega-3 per day seems unknown.

So I am working on switching to foods that have fat that’s very low in Omega-6, mainly coconut oil and butter from grass-fed cows (Kerrygold is the widely available brand).

That mostly doesn’t require eating food that’s less tasty (Kerrygold butter tastes better than most other fats), but it reduces the variety of foods I can eat. It rules out what I used to consider ordinary amounts of most nuts, and many processed foods (Trader Joes’ eggplant and red pepper spreads looked like a convenient way to get veggies until I quantified the effect of the sunflower oil that is the fourth ingredient in each).

I’ll try to post some of my best recipes in a few months.

For more references, see this pubmed entry and Wikipedia.

I have always been somewhat sensitive to noisy environments, and over the past few years his has seemed like an increasing obstacle to my social life (possibly because I’ve become more ambitious rather than more sensitive).

A few months ago I tried Auditory Integration Training (AIT), which consists of listening to music CDs with strange noises added. I don’t understand it very well, but part of what it does is train my brain to equalize the sensitivity in each ear at a particular frequency.

About halfway through the program I noticed a clear improvement in my ability to handle noise levels in a typical restaurant or subway. That improvement has persisted for several months. I think I was previously using a lot of mental energy to filter out background noise, especially when trying to hold a conversation.

AIT is expensive and has a somewhat poor reputation. My impression is that it is only appropriate for a small number of people who suffer from auditory overload. But I felt the auditory overload was enough of a problem for me to be worth trying what might well be a placebo (and I can’t be confident that it was more than a placebo, but placebos are sometimes better than nothing). I suspect that whatever scientific tests that have been done on AIT looked at symptoms that are only loosely related to auditory overload. And it wouldn’t be easy to design good measures of the auditory overload that it seems to help with.

I recommend AIT to people who have unusual sensitivity to noise levels that most people can handle, but I also recommend skepticism about the broader claims that have been made about AIT.

Update on 2014-02-14: my sensitivity to noise has fluctuated a good deal since then without any clear improvement, and it’s quite possible that the improvement I felt while using AIT was an ordinary change unrelated to AIT.

Book review: The Beginning of Infinity by David Deutsch.

This is an ambitious book centered around the nature of explanation, why it has been an important part of science (misunderstood by many who think of science as merely prediction), and why it is important for the future of the universe.

He provides good insights on jump during the Enlightenment to thinking in universals (e.g. laws of nature that apply to a potentially infinite scope). But he overstates some of its implications. He seems confident that greater-than-human intelligences will view his concept of “universal explainers” as the category that identifies which beings have the rights of people. I find this about as convincing as attempts to find a specific time when a fetus acquires the rights of personhood. I can imagine AIs deciding that humans fail often enough at universalizing their thought to be less than a person, or that they will decide that monkeys are on a trajectory toward the same kind of universality.

He neglects to mention some interesting evidence of the spread of universal thinking – James Flynn’s explanation of the Flynn Effect documents that low IQ cultures don’t use the abstract thought that we sometimes take for granted, and describes IQ increases as an escape from concrete thinking.

Deutsch has a number of interesting complaints about people who attempt science but are confused about the philosophy of science, such as people who imagine that measuring heritability of a trait tells us something important without further inquiry – he notes that being enslaved was heritable in 1860, but that was useless for telling us how to change slavery.

He has interesting explanations for why anthropic arguments, the simulation argument, and the doomsday argument are weaker in a spatially infinite universe. But I was disappointed that he didn’t provide good references for his claim that the universe is infinite – a claim which I gather is controversial and hasn’t gotten as much attention as it deserves.

He sometimes gets carried away with his ambition and seems to forget his rule that explanations should be hard to vary in order to make it hard to fool ourselves.

He focuses on the beauty of flowers in an attempt to convince us that beauty is partially objective. But he doesn’t describe this objective beauty in a way that would make it hard to alter to fit whatever evidence he wants it to fit. I see an obvious alternative explanation for humans finding flowers beautiful – they indicate where fruit will be.

He argues that creativity evolved to help people find better ways of faithfully transmitting knowledge (understanding someone can require creative interpretation of the knowledge that they are imperfectly expressing). That might be true, but I can easily create other explanations that fit the evidence he’s trying to explain, such as that creativity enabled people to make better choices about when to seek a new home.

He imagines that he has a simple way to demonstrate that hunter-gatherer societies could not have lived in a golden age (the lack of growth of their knowledge):

Since static societies cannot exist without effectively extinguishing the growth of knowledge, they cannot allow their members much opportunity to pursue happiness.

But that requires implausible assumptions such as that happiness depends more on the pursuit of knowledge than availability of sex. And it’s not clear that hunter-gatherer societies were stable – they may have been just a few mistakes away from extinction, and accumulating knowledge faster than any previous species had. (I think Deutsch lives in a better society than hunter-gatherers, but it would take a complex argument to show that the average person today does).

But I generally enjoyed his arguments even when I thought they were wrong.

See also the review in the New York Times.

The Personalized Life Extension Conference 2012 presented lots of ideas, with occasionally some science to back them up.

A lot of the advice backed up by the best science won’t be followed. In spite of the title of Brian Delaney’s Calorie Restriction talk, he didn’t have a solution to the problem of feeling hungry. When Max Peto reminded us of the dangers of sitting, the percentage of people who remained seated only dropped from maybe 97 to 95. There were vendors pushing food that had higher than optimal sugar content, and I think at least one pusher had some success.

I’ve been cutting back drastically on my vitamin/supplement consumption, and Stephen Spindler’s talk (arguing that most apparently good results in other animals were due to supplements inducing calorie restriction) has me thinking about cutting back farther to just fish oil and vitamin D.

The telomere guys still haven’t come up with a good theory for why evolution didn’t do the apparently easy thing and make some telomerase available to non stem cells, so I’m still assuming there’s some tradeoff such as cancer.

The most interesting talk was by David Asprey, describing an “upgraded paleo” diet – high fat, with careful attention to the quality of the fat. He has more ideas than he has time to communicate them.

Unfortunately he seems too busy throwing out new opinions to document the evidence behind them (or maybe the evidence is hiding somewhere on his poorly organized website). But in most cases he has a plausible paleo-like theory, and I’m generally confident they’d be little worse than a placebo, so I’m trying some of them.

At the moment that involves consuming more of some paleo-like foods that I’d already been starting to add to my diet. Grass-fed (Kerrygold) butter is possibly the most important, and coconut products are also rather high on the list. The butter tastes better than my dim recollection of butter from malnourished grain-fed cows. Coconut milk works well as a substitute for milk in dishes such as chowder and cream of onion soup.

Josh Whiton had an intriguing idea about trying to get the benefits of calorie restriction via a very low protein diet once or twice a week (with a paleo-like diet the rest of the time).

Book review: Inside Jokes – Using Humor to Reverse-Engineer the Mind, by Matthew M. Hurley, Daniel C. Dennett and Reginald B. Adams, Jr.

This book has the best explanation I’ve seen so far of why we experience humor. The simplistic summary is that it is a reward for detecting certain kinds of false assumptions. And after it initially evolved it has been adapted to additional purposes (signaling one’s wit), and exploited by professional comedians in the way that emotions which reward reproductive functions are exploited by pornography.

Some of the details of which false beliefs qualify as a source of humor and how diagnosing them to be false qualifies as a source of humor seem arbitrary enough that the theory falls well short of the kind of insight that tempts me to say “that’s obvious, why didn’t I think of that?”. And a few details seem suspicious – the claims that people are averse to being tickled and that one sensation tickling creates is that of being attacked don’t seem consistent with my experience.

They provide some clues about the precursors of humor in other species (including laughter, which apparently originated independently from humor as a “false alarm” signal), and give some hints about why the greater complexity of the human mind triggered a more complex version of humor than the poorly understood versions that probably exist in some other species.

The book has some entertaining sections, but the parts that dissect individual jokes are rather tedious. Also, don’t expect this book to be of much help at generating new and better humor – it does a good job of clarifying how to ruin a joke, but it also explains why we should expect creating good jokes to be hard.

Protein

A protein rich diet may make us more alert and help us lose weight.

The reaction of Hypothalamic orexin/hypocretin neurons to amino acids (especially nonessential amino acids) appears to be a mechanism for this effect.

Poultry products appear to be one of the better ways to get nonessential amino acids.

I’ve been trying to increase the protein in my diet for the past four months (in response to weaker evidence than I’ve linked to here), and have found that animal sources have been the easiest way to do that (I’ve mainly increased my egg and meat consumption). I think I’ve found it slightly easier to avoid gaining weight. I think I’ve also been more alert, but I don’t think the increase in alertness coincided too closely with the increase in protein consumption.