Bayesian Investor Blog

Book review: Outlive: The Science and Art of Longevity, by Peter Attia.

This year’s book on aging focuses mostly on healthspan rather than lifespan, in an effort to combat the tendency of people in the developed world to have a wasted decade around age 80.

Attia calls his approach Medicine 3.0. He wants people to pay a lot more attention to their lifestyle starting a couple of decades before problems such as diabetes and Alzheimer’s create obvious impacts.

He complains about Medicine 2.0 (i.e. mainstream medicine) treating disease as a binary phenomenon. There’s lots of evidence suggesting that age-related diseases develop slowly over periods of more than a decade.

He’s not aiming to cure aging. He aims to enjoy life until age 100 or 120.

According to Gordon (2016), nearly all the reduction in mortality since 1900 was due to fewer deaths from the top 8 infectious diseases. The world has done a poor job with non-infectious diseases.

That leads Attia to focus on diseases of civilization, especially the Four Horsemen: cancer, heart disease, metabolic dysfunction, and neurodegeneration.

Compared to Functional Medicine

I’ll classify Attia’s approach as halfway in between conventional medicine and Functional Medicine.

Attia focuses on categories of disease that cause the most impairment in older people, whereas Functional Medicine focuses more on whatever has been most neglected by Medicine 2.0.

Both Attia and Functional Medicine demand that patients be more informed and medically literate than does Medicine 2.0, and that they take more tests.

Functional Medicine has been concerned about overuse of statins, and has been less concerned about high cholesterol than most doctors. Bredesen has recommended keeping total cholesterol above 150. I presume this is due to correlational evidence linking low cholesterol with cognitive problems.

In contrast, Attia comes close to advocating statins in the water supply. He wants unusually low ApoB and LDL levels (i.e. LDL below 20 if possible!). I got my LDL down to 46 this summer, and the corresponding total cholesterol of 126 worried me enough to cut my statin dose in half.

The book doesn’t provide good evidence for the benefits of unusually low cholesterol levels, but I tracked down a pair of Attia blog posts that explain his reasoning. I now feel confused.

I tracked down a pro-statin paper that Attia likes: A Long-term Benefit Approach vs Standard Risk-Based Approaches for Statin Eligibility in Primary Prevention (blog summary here). Again, I feel confused.

The paper says that we get a very different view of whether to prescribe statins if we use a 30-year risk window than if we use the standard 10-year window. Doesn’t the strong dependence on an arbitrary number suggest that there’s something wrong with using an n-year risk window?

Cancer

Attia recommends more frequent colonoscopies than almost anyone currently gets.

Screening for Colorectal Cancer (2021) says that colonoscopy is correlated with a 68% reduction in colorectal cancer death. Some of that is presumably due to a real benefit from early treatment of cancer. Some of that is presumably due to something else related to those patients being more conscientious or wealthier.

How does that likely-overstated 68% reduction compare to the more rigorously measured 9% to 22% reduction from fecal occult blood tests?

We have an additional data point from RCTs of sigmoidoscopy, which resembles a colonoscopy enough that it ought to provide some hints about colonoscopy benefits. Those RCTs show a 26% reduction in colorectal cancer mortality. That amounts to “10 to 17 fewer CRC deaths per 100,000 person-years” at the cost of 0.7 serious harms per 10,000 sigmoidoscopies.

Colonoscopy seems likely to detect roughly twice as many cancers as sigmoidoscopy, but it creates 25 times as many serious harms. I think that adds up to a net advantage for colonoscopy, but it’s not strong enough to make me eager.

Functional Medicine would likely warn us that Attia underestimates the harm to our gut microbiome due to the cleansing needed for colonoscopy. Attia might also underestimate the subtle costs of sedation (but I see some reasons to think those concerns are minor for colonoscopy). Most likely those are both smaller issues than the cancer risk, but I’m concerned that Attia doesn’t mention them.

My current guess is that Attia has reached the correct conclusion, but is a bit overconfident about the evidence. See this Attia blog post for more detailed analysis than the book provides. I’m still procrastinating any decision about whether to get a colonoscopy. I’m leaning toward asking my doctor why he hasn’t recommended it, and getting an opinion from my Functional Medicine provider.

Exercise

Health-related sources that I’ve read before this book either focused on getting us to do whatever form of exercise we could most easily persuade ourselves to do, or failed to convince me that they were based on evidence of increased healthspan. As a consequence, I developed reliable routines to get at least 1500 calories per week of exercise, but put little thought into optimizing beyond that.

Attia persuaded me to put more thought into exercise. He knows more about longevity than the other exercise fanatics that I’ve come across, and more about exercise than any other health nut that I’ve encountered.

I’m going to take up rucking, working my way up to hiking with a 50 pound pack.

I’m gone to measure my heart rate while doing strenuous hikes, and aim to spend more time in “zone 2”, which looks like it requires keeping my heart rate between 105 and 125.

Finally, I’ll do something to increase my VO2 max. The most practical way to work on that seems to be to quantify my zone 2 pace, then do 4-minute intervals of hiking at 133% of that pace.

Diet

Attia’s nutrition advice is to mostly figure out what diet fits best with the specifics of your body. He rants against people who claim that nutrition research is good enough to justify encouraging everyone to eat or avoid specific categories of foods.

Then he somewhat violates that advice by advocating a very high protein diet. He superficially sounds like the opposite of protein restriction advocate Valter Longo.

However, if you look closely, you’ll see that their advice is almost compatible. Longo only advocates protein restriction for people under 65. Attia indicates that the importance of consuming more protein increases with age. Attia’s advice is for patients who presumably follow his exercise advice, which likely increases the optimal protein levels.

Anyone who worries a lot about protein should remember the Tukisenta, whose diet is allegedly 94.6% carbs (from sweet potatoes), leaving slightly more than 5% for protein. They appear to be fairly healthy.

I continue to believe that problems with dietary protein are almost entirely due to something other than consuming the wrong amount. My main concern is the glycine/methionine ratio. Attia likes whey protein. Whey protein’s low glycine/methionine ratio seems inappropriate for older patients unless it’s balanced by plant protein, collagen, or bone broth.

How Much of the Book is Correct?

Most of the book seems fairly solid. His claims tend to be more cautious than most bestselling health books.

His Medicine 3.0 is hardly revolutionary at the level of scientific research. The main reason his advice hasn’t (yet?) been adopted is that it’s inconvenient for patients, and doesn’t fit the habits and skills of most doctors.

I am mildly dissatisfied at how few references he provides to back up his claims.

Closing Thoughts

The book is a bit more technical than I expect from a bestseller.

Something seems not quite right with his one of his reasons for intervening in diseases decades before they become serious. The length of time that it takes for problems to develop does not tell me much about how quickly those problems can be reversed.

There’s a moderate amount of anecdotal evidence that diabetes and Alzheimer’s can sometimes be reversed much faster than they develop. The limiting factor there seems to be willingness to make lifestyle changes. With cardiovascular disease and cancer, I’m more confused by the evidence.

Starting too early is a safer way to err than starting too late. I’m close enough to the age where I’d expect problems that it isn’t taking strong evidence to get me to follow most of Attia’s advice here. But I’m guided more by the argument that the relevant diseases are not binary conditions. Early stages of metabolic disease and muscle weakness are plausibly causing enough subtle problems that his advice is worth following, even for people who will otherwise avoid diagnosable disease.

The book contains a surprising and well-written chapter on emotional health. I can’t figure out how to summarize that chapter.

If you’re reading three books about personal health, Outlive ought to be one of them. If you’re only reading one, my current top picks are Bredesen’s The End of Alzheimer’s if you’re focused on age-related disease, or Kresser’s Paleo Cure for optimizing health before age 50.