Outlive: A Critical Review

Outlive: The Science & Art of Longevity by Peter Attia (with Bill Gifford1) gives Attia’s prescription on how to live longer and stay healthy into old age. In this post, I critically review some of the book’s scientific claims that stood out to me.

This is not a comprehensive review. I didn’t review assertions that I was pretty sure were true (ex: VO2 max improves longevity), or that were hard for me to evaluate (ex: the mechanics of how LDL cholesterol functions in the body), or that I didn’t care about (ex: sleep deprivation impairs one’s ability to identify facial expressions).

First, some general notes:

  • I have no expertise on any of the subjects in this post. I evaluated claims by doing shallow readings of relevant scientific literature, especially meta-analyses.
  • There is a spectrum between two ways of being wrong: “pop science book pushes a flashy attention-grabbing thesis with little regard for truth” to “careful truth-seeking author isn’t infallible”. Outlive makes it 75% of the way to the latter.
  • If I wrote a book that covered this many entirely different scientific fields, I would get a lot more things wrong than Outlive did. (I probably get a lot of things wrong in this post.)
  • When making my assessments, I give numeric credences and also use terms such as “true” and “likely true”. The numbers give my all-things-considered subjective credences, and the qualitative terms give my interpretation of the strength of the empirical evidence. For example, if the scientific evidence suggests that a claim is 75% likely and I understand the evidence well, then I rate the claim as “likely true”. If I only read the abstract of a single meta-analysis, and the abstract unequivocally supports the claim but I’m only 75% sure that the meta-analysis can be trusted, then I rate it as “true”. Both claims receive a 75% credence.

Now let’s have a look at some claims from Outlive, broken down into four categories: disease, exercise, nutrition, and sleep.

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Protein Quality Calculator

Last updated 2024-09-06 to add more content.

You may know that complete proteins are good because they contain every essential amino acid. But you might not know that that’s not the full story.

Take wheat. Wheat is a complete protein—it contains all nine essential amino acids. But it has a problem. Wheat only contains 27mg of lysine (an essential amino acid) per gram of protein, whereas the Food and Agriculture Organization recommends 48mg of lysine per gram. To make full use of a gram of protein, your body needs to get those 48mg. It doesn’t matter that wheat has lots of other essential amino acids. Once your body uses up all the lysine, it can’t make good use of the other amino acids in wheat protein.

You can evaluate the protein quality of a food using the Digestible Indispensable Amino Acid Score (DIAAS). This score determines the quality of a source of protein based on which essential amino acid will run out first, adjusted for digestibility. A score of 100 means the protein has plenty of every essential amino acid.

Sometimes you can improve the protein quality of your food by mixing different ingredients. Wheat has a DIAAS of 57 because it only has 57% as much lysine per gram as your body needs. Peas have a score of 82 because they don’t have enough methionine + cysteine. But peas have 131% of the lysine requirement, and wheat has 149% of methionine + cysteine, so mix them together and they cover for each other’s weaknesses. A 50/50 mixture of wheat and pea protein has a DIAAS of 94.

With this calculator, you can determine the DIAAS for mixtures of different protein sources.

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A 401(k) Sometimes Isn't Worth It

You don’t always save money by putting your investments into a 401(k).

When you invest money inside a 401(k), you don’t have to pay taxes on any returns earned by your investments. But you also have to pay a fee to your 401(k) provider.

  • If you buy and hold index funds in a taxable account, you don’t have to pay any capital gains tax on price increases until you sell.
  • In a 401(k), the annual fee adds up every year and may eventually exceed the tax savings.

So the taxes cap out at the capital gains tax rate (15% or 20% depending on your tax bracket),1 whereas the expenses of a 401(k) continue to accumulate.

However, in a taxable account, you do still have to pay taxes on dividends (and bond payouts) every year, and those taxes might cost you more than the 401(k) fees.2

Below is a calculator to determine how many years before the 401(k) fees exceed the tax savings, if ever.

employer matching (%)
total investment return including dividends (nominal) (%)
dividend yield (%)
401(k) fee (%)
capital gains tax rate (%)
income tax rate today (%)
income tax rate in retirement (%)

A 401(k) falls behind a taxable account after:

This calculator assumes you buy index funds and hold them forever. If you trade stocks within a taxable account, you have to pay taxes every time you make a trade.

Something else to consider: If you quit your job, your old employer’s 401(k) provider will let you roll your 401(k) into an IRA. You don’t have to pay any fees on an IRA.3 So even if the 401(k) fees exceed the tax benefits after (say) 30 years, that’s not a problem if you expect to quit your job after less than 30 years. Realistically, few people stay at one job for so long that the 401(k) fees exceed the tax savings.

(If you change jobs, usually you can roll your old 401(k) into your new 401(k), but I wouldn’t do that because it means you have to keep paying 401(k) fees. It’s almost always better to roll your old 401(k) into an IRA.)

Notes

  1. The capital gains tax will always be less than 15%/20% of your account value (depending on which tax bracket you’re in), but it converges on 15%/20% as the value approaches infinity.

    Example: If you invest $100 in an index fund and you sell when the price reaches $101, you have to pay 20% of $1 (assuming you’re in the 20% tax bracket), which is only 0.2% of the total value. If you sell when the price reaches $1 million, you have to pay 20% of $999,900, which is 19.998% of the total value. 

  2. H/T Ben Kuhn for raising this possibility. I’m sure someone somewhere had considered it before him, but I’ve never seen anyone else bring it up, and standard financial advice ignores it. 

  3. Other than ETF/mutual fund fees, but you have to pay those no matter what. 

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Continuing My Caffeine Self-Experiment

I did another caffeine experiment on myself. This time I tested if I could have caffeine 4 days a week without getting habituated.

Last time, when I took caffeine 3 days a week, I didn’t get habituated but the results were weird. This time, with the more frequent dose, I still didn’t get habituated, and the results were weird again!

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What's the Healthiest Body Composition?

Last time, I found that the healthiest BMI range for all-cause mortality is 20–22. But BMI doesn’t tell the whole story. Most obviously, it doesn’t account for body fat vs. lean mass. All else equal, you’d rather have more muscle1 and less fat.

So what’s the healthiest combination of lean mass + fat mass?

I’m not going to answer that question because I can’t. Instead, I will explain why I can’t, and then give a rough guess at the answer.

Scientists have been measuring and collecting data on BMI for decades. You can find plenty of giant BMI studies with three million participants in various countries.

We have much sparser data on body fat. Scientists didn’t start collecting data on body fat until the last few decades. And body fat is harder to measure—we have various methods for estimating body fat, but they’re all more complicated than calculating BMI.

I managed to scrounge together some studies on body fat and mortality. My best guess: the average woman should aim for a BMI of 21 with 20% body fat, and the average man a BMI of 21 with 10% body fat. (Subject to individual variation due to genetics and whatnot.)

Trans men should probably target the same body fat % as cis men, and likewise for trans women and cis women, because hormone therapy alters body fat distribution (Spanos et al. (2020)2).

The evidence weakly suggests that there is no lower bound on healthy fat mass, and no upper bound on healthy lean mass. We have so little mortality data on extremely lean + muscular people that we can’t say how healthy they are.

A more in-depth analysis would look at a variety of health indicators (blood pressure, HDL cholesterol, etc.) and use that to predict mortality. I didn’t do that, I just looked at mortality data.

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Caffeine Cycling Self-Experiment

Last updated 2024-07-26 to clarify wording.

Confidence: Likely.

I conducted an experiment on myself to see if I would develop a tolerance to caffeine from taking it three days a week. The results suggest that I didn’t. Caffeine had just as big an effect at the end of my four-week trial as it did at the beginning.

This outcome is statistically significant (p = 0.016), but the data show a weird pattern: caffeine’s effectiveness went up over time instead of staying flat. I don’t know how to explain that, which makes me suspicious of the experiment’s findings.

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Does Caffeine Stop Working?

Last updated 2024-09-02.

Confidence: Likely.

If you take caffeine every day, does it stop working? If it keeps working, how much of its effect does it retain?

There are many studies on this question, but most of them have severe methodological limitations. I read all the good studies (on humans) I could find. Here’s my interpretation of the literature:

  • Caffeine almost certainly loses some but not all of its effect when you take it every day.
  • In expectation, caffeine retains 1/2 of its benefit, but this figure has a wide credence interval.
  • The studies on cognitive benefits all have some methodological issues so they might not generalize.
  • There are two studies on exercise benefits with strong methodology, but they have small sample sizes.
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Avoiding Caffeine Tolerance

Summary

Caffeine improves cognition1 and exercise performance2. But if you take caffeine every day, over time it becomes less effective.

What if instead of taking caffeine every day, you only take it intermittently—say, once every 3 days? How often can most people take caffeine without developing a tolerance?

The scientific literature on this question is sparse. Here’s what I found:

  1. Experiments on rats found that rats who took caffeine every other day did not develop a tolerance. There are no experiments on humans. There are no experiments that use other intermittent dosing frequencies (such as once every 3 days).

  2. Internet forum users report that they can take caffeine on average once every 3 days without developing a tolerance. But there’s a lot of variation between individuals.

This post will cover:

  1. The motivation for intermittent dosing

  2. A review of the experimental research on the effect of taking caffeine intermittently (TLDR: there’s almost no experimental research)

  3. A review of self-reports from the online nootropics community

  4. Intermittent dosing vs. taking caffeine every day

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Should Patient Philanthropists Invest Differently?

TLDR: No.

Confidence: Somewhat likely.

Summary

Some philanthropists discount the future much less than normal people. For philanthropists with low discount rates, does this change how they invest their money? Can they do anything to take advantage of other investors’ high time discounting?

We can answer this question in two different ways.

Should low-discount philanthropists invest differently in theory? No. [More]

Should low-discount philanthropists invest differently in practice? The real world differs from the standard theoretical approach in a few ways. These differences suggest that low-discount philanthropists should favor risky and illiquid investments slightly more than high-discount investors do. But the difference is too small to matter in practice. [More]

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