Overall score
Scientific accuracy
Reference accuracy
Healthfulness
How hard would it be to apply the book's advice? Fairly easy
Outlive: The Science and Art of Longevity by Peter Attia, MD, examines how to extend both lifespan and healthspan through individualized, evidence-based approaches. Although the book discusses things like exercise, sleep, and mental health, our review focuses on the nutritional aspects of the book.
Key Points from Our Review
- The book's claims are generally supported by scientific evidence, for example, the recommendation to avoid eating excess calories.
- The advice to eat a higher-protein diet and avoid glucose spikes isn’t as strongly supported by evidence, but is still reasonably well-supported.
- The book tends to cite references accurately.
- The book’s dietary advice aligns with commonly recommended healthy eating patterns and is likely to provide some health benefits.
- The advice in the book would probably be fairly easy to follow, as it isn’t overly restrictive.
Bottom Line
Outlive offers light guidance on nutrition that is generally evidence-based.
Book published in 2023
Published by Harmony Books
First Edition, Hardcover
Review posted December 8, 2024
Primary reviewer: Seth Yoder
Peer reviewer: Matthew Carpenter
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Table of contents
Introduction
Red Pen Reviews chose to write a review for Outlive: The Science and Art of Longevity by Peter Attia for a couple of reasons. The first and most important is that it was fully funded in our last funding drive, which guaranteed a review of the book. Secondly, it has received significant attention since its publication last year, so we feel a review would be useful to the public. Lastly, longevity research and information on healthspan have been of increasing relevance as populations age all over the world.
Outlive was a particularly challenging text to review. One reason is that we decided to limit the scope of the review to the parts of the book that focused solely on nutrition. This left only about two chapters that were relevant. Another challenge was that, while the text focuses on describing some of the nutrition research as it relates to health and longevity, it contains few explicit dietary recommendations. In fact, the text downplays the role of nutrition to some degree. Some examples are on page 48:
I won’t be telling you to eat this, not that, or prescribing a specific diet that everyone should follow, and I’m definitely not taking sides in the pointless, never-ending diet wars pitting low carb versus paleo versus vegan, and so on. We will avoid such religious discussions in favor of biochemical evidence.
Page 215:
Providing very granular exercise, dietary, or lifestyle advice requires individual feedback and iteration, something I can’t safely or accurately accomplish in a book.
Page 348:
I have one final piece of advice. Stop overthinking nutrition so much. Put the book down. Go outside and exercise.
Because Outlive is not primarily about nutrition and doesn’t take a strong or detailed stance on nutrition, our review method is a limited lens through which to examine the book. Please keep that in mind when reading this review.
Scientific Accuracy
This section examines three central claims from Outlive , evaluating how well they align with current scientific evidence. The claims focus on calorie intake, protein intake, and blood glucose management. Overall, the book’s claims have a reasonably strong scientific foundation, scoring an average of 3.3 out of 4 for scientific accuracy.
The first claim we reviewed was Outlive’s argument about the importance of avoiding excess calorie intake. We found it is strongly supported by current scientific evidence. Outlive doesn’t really advocate for a particular means of reducing caloric intake (or keeping calories in energy balance). The text discusses three broad ways to “diet” or ways to restrict calories: calorie restriction, dietary restriction, and time restriction. Calorie restriction is defined in the text as “eating less in total, but without attention to what is being eaten or when it’s being eaten.” Dietary restriction is defined in the text as “eating less of some particular element(s) within the diet (e.g., meat, sugar, fats).” And time restriction is defined as “restricting eating to certain times, up to and including multiday fasting.” At any rate, whichever way one chooses to avoid consuming too many calories, we think it will yield health benefits.
The second and third claims we reviewed from the book received slightly lower scores, but scores that still indicated the claims were at least moderately supported by evidence. The reason for the lower scores in the other two claims is the disparity between clinical trial evidence and observational evidence. For those claims (high protein intake being critical as we age and avoiding glucose spikes) there is strong evidence from observational studies, but the evidence becomes weaker when looking at data from clinical trials on the same subject. The contrast of the two scientific approaches is discussed in Chapter 14.
Claim 1
To maintain metabolic health and reduce the risk of chronic diseases, it’s essential to avoid consuming more calories than your body can utilize or store safely.
Supporting quote(s) and page number(s)
Page 311: “[I]t should be obvious by now that many of the problems we want to address or avoid stem from consuming calories in excess of what we can use or safely store.”
Page 347: “The bad news is that most Americans are not metabolically healthy, so they need to pay attention to nutrition. In most cases, addressing the problem means reducing overall energy intake—cutting calories—but in a way that is sustainable for the individual person.”
Page 311: “How many calories you consume has a huge impact on everything else we’re talking about in this book.”
Page 48: “The best science out there says that what you eat matters, but the first-order term is how much you eat: how many calories you take into your body.”
Criterion 1.1. How well is the claim supported by current evidence?
4 out of 4
This claim received a score of 4 out of 4, meaning that the claim is strongly supported by current evidence.
Although some popular nutrition books do not accept the principle of energy balance, it is a widely accepted principle within the mainstream scientific community. If you consistently consume more calories (energy intake) than your body expends through physical activity and basic metabolic functions (energy expenditure), this will lead to weight gain. A positive energy balance over a long enough time period can lead to overweight and obesity.
There is strong evidence that obesity plays a role in the development of type 2 diabetes. The mechanism behind this is thought to be that accumulation of excess fat, particularly in the abdominal area, leads to adipose tissue dysfunction and inflammation. The chronic inflammation disrupts insulin signaling pathways, causing insulin resistance and ultimately leading to type 2 diabetes. Although diabetes is not the only disease: the same inflammation can also contribute to metabolic syndrome.
Overweight and obesity have long been linked to alterations of serum lipids which contribute to poorer health outcomes, an increased risk of chronic disease, and mortality. Outlive notes on page 93 that some obese people can be metabolically healthy while some normal-weight people can be metabolically unhealthy. However, even metabolically healthy obese individuals are at higher risk for adverse events than their normal weight counterparts, according to a 2013 systematic review. A more recent review article makes the argument that while some people with obesity appear metabolically healthy, this is often a transitional state to increased metabolic dysfunction.
A 2016 systematic review and meta-analysis of 230 cohort studies demonstrated that overweight and obesity was associated with increased risk of mortality from any cause. The analysis also demonstrated that those who are underweight also face an increased risk of mortality. The lowest mortality risk was observed in the BMI range between 20-25. A similar systematic review and meta-analysis was published in 2024 that only included 82 cohort studies and came to a slightly different conclusion: that a BMI in the range of 25-30 (typically classified as overweight) had the lowest mortality risk compared to other ranges.
However, there is also a phenomenon in the literature known as the “obesity paradox” which is a term for the observation that individuals with obesity may have slightly better prognosis compared to their normal weight counterparts when diagnosed with a chronic disease. Although much has been written about this supposed paradox, some researchers claim that it’s not much of a paradox at all, but more of the limitations of observational studies.
So that is the evidence correlating obesity with disease and longevity. What about caloric restriction for the same outcomes? In chapter 5, the text discusses some of the rodent studies that demonstrate caloric restriction (or prolonged fasting) increases lifespan. However, it doesn’t appear to be true for all the species for which studies are available. In fact, a 2012 meta-analysis of animal studies suggests that longevity is more closely linked to protein intake than general caloric restriction.
Humans are not as easy to study as animals, but there was a large randomized controlled trial examining the effects of sustained caloric restriction in humans, called the CALERIE trial (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy). Participants ranged from normal weight to slightly overweight and were randomized into a 25% reduction in calories or a control diet. Several publications have resulted from the study, and according to the data, moderate calorie restriction for two years resulted in a reduction of cardiometabolic risk factors, including: improved cholesterol, blood pressure, insulin sensitivity, and a shift in lipoproteins from atherogenic to lipid transporting. Other publications from this trial have identified a reduction in oxidative stress and metabolic slowing.
Overall (average) score for claim 1
4 out of 4
Claim 2
Protein is an essential macronutrient for building and maintaining muscle mass, which is crucial for overall health, especially as we age and lose muscle mass more easily.
Supporting quote(s) and page number(s)
Page 17: “One macronutrient, in particular, demands more of our attention than
most people realize: not carbs, not fat, but protein becomes critically important as we age.”
Page 332: “There is some evidence that older people might require more protein because of the anabolic resistance that develops with age—that is, their greater difficulty in gaining muscle.”
Page 295: “The correlation between poor metabolic health and being overnourished
and undermuscled is very high. Hence, for a majority of patients the goal is to
reduce energy intake while adding lean mass. This means we need to find
ways to get them to consume fewer calories while also increasing their protein
intake […]”
Page 330: “Why is protein so important? One clue lies in the name, which is derived from the Greek word proteios, meaning ‘primary.’ Protein and amino acids are the essential building blocks of life. Without them, we simply cannot build or maintain the lean muscle mass that we need. As we saw in chapter 11, this is absolutely critical to our strategy, because the older we get, the more easily we lose muscle, and the more difficult it becomes to rebuild it.”
Criterion 1.1. How well is the claim supported by current evidence?
3 out of 4
This claim received a score of 3 out of 4, meaning that the claim is moderately supported by current evidence. Age-related sarcopenia is complex and involves mitochondrial dysfunction, oxidative stress, chronic inflammation, an imbalance with protein synthesis and degradation, stem cell dysfunction, and hormonal changes.
The importance of dietary protein for muscle protein synthesis and maintenance is well-documented in nutrition science. Major reviews have consistently shown that adequate protein intake is crucial for maintaining muscle mass and function, particularly in aging populations. While the RDA for protein in younger adults is 0.8g/kg of body weight, research suggests that older adults may benefit from consuming up to 1.5g/kg of body weight daily to maintain muscle mass and function. However, this research is somewhat mixed.
A 2009 Cochrane Review found that protein supplementation reduced mortality in elderly people at risk of malnutrition, but showed no mortality benefit in well-nourished elderly individuals. The review found no improvements in physical function measures, including walking speed, distance, hand-grip strength, leg strength, mobility, or hip fracture recovery. However, malnourished elderly patients with COPD did show improved lung function with protein supplementation.
A 2022 systematic review of controlled trials with healthy adults indicates a small increase in lower body strength and lean body mass with increased protein intake, but only among younger adults participating in resistance training and with an intake that is double that of the current recommended dietary allowance for protein (which is 0.8g per kg of body weight). The authors state that “[e]ffects on bench press strength, handgrip strength, and improved performance in physical tests in healthy adults seem to be trivial.”
On the other hand, observational studies tell a different story. The data from cross-sectional studies and cohorts have more favorable data toward protein intake. A 2022 meta-analysis of elderly adults indicated that protein intake was associated with better physical performance, including faster walking speed, greater lower-limb and isometric handgrip strength, and better balance. An analysis of four cohort studies in North America and Europe found similar results: protein intake was associated with a slower decline in physical function.
It seems that at minimum protein needs to be consumed in combination with some sort of resistance exercise to be effective, particularly with older populations. Resistance exercise stimulates muscle protein synthesis, and consuming adequate protein is necessary for muscle repair and growth.
Overall (average) score for claim 2
3 out of 4
Claim 3
Focus on a diet that minimizes blood glucose spikes to safeguard long-term health and organ function.
Supporting quote(s) and page number(s)
Page 347: “We also have to focus on eliminating those types of foods that raise blood glucose too much, but in a way that also does not compromise protein intake and lean body mass.”
Page 242: “Chronic blood glucose elevations damage organs from our heart to our brain to our kidneys and nearly everything in between—even contributing to erectile dysfunction in men.”
Page 322: “[T]here is also evidence suggesting that repeated blood glucose spikes, and the accompanying rise(s) in insulin, may have negative consequences in and of themselves.”
Criterion 1.1. How well is the claim supported by current evidence?
3 out of 4
This claim received a score of 3 out of 4, meaning that it is moderately supported by current evidence. The mechanism behind blood glucose spikes and organ and tissue function is complicated, but it seems that glucose variability (i.e. glucose spikes) cause damage by increasing oxidative stress and inflammation, endothelial dysfunction, and advanced glycation end products (AGEs).
To discuss some of the evidence around this, it may be helpful to define some terms. Glycemic response refers to how quickly and how high a food raises blood glucose levels. Different foods have varying glycemic responses. Some foods can cause a rapid and sharp increase in blood glucose, while other foods raise blood glucose more slowly and gradually.
The glycemic index is a term for a system that ranks food based on their glycemic response. Foods can then be assigned a value and categorized as having a high, medium or low glycemic index based on how much and for how long a standard amount of food raises blood glucose. The glycemic load is a measurement that accounts for both the glycemic index and the amount of available carbohydrate in a food. The glycemic load will also be a numerical value that can help when evaluating how foods affect blood glucose levels.
With that out of the way, a 2019 meta-analysis of prospective cohort studies investigating the link between the dietary glycemic index and glycemic load and the risk of developing type 2 diabetes. The authors concluded that diets with a high glycemic index or glycemic load were strongly associated with development of type 2 diabetes. A similar association was found in the PURE study that included 127,594 people from 20 countries.
A 2014 review of observational studies on the topic indicated that high glycemic load diets increased risk of coronary heart disease, though this was observed in women and not men. Analysis of ten large cohorts found that regularly eating foods with a high glycemic index were associated with increased risks of type 2 diabetes, heart disease, certain cancers, and slightly higher all-cause mortality.
An interesting cohort not included in the above reviews is the Whitehall II study. This was a study that observed a cohort of British civil servants for many years. One publication after 33 years indicated that those with difficulty clearing glucose from their blood were at an increased risk of death from: all causes, cardiovascular disease, stroke, respiratory disease, but not cancer.
In contrast, a Cochrane review of randomized controlled trials notes that, while there are randomized trials that examine glycemic diets and risk factors for cardiovascular disease (blood pressure, cholesterol, etc.), none of the trials measured actual mortality from cardiovascular disease or cardiovascular events. Since that Cochrane review was published, a 2021 systematic review of controlled trials in people with diabetes concludes that a low glycemic dietary patterns result in slightly lower levels of HbA1c and small improvements with other biomarkers of cardiovascular disease risk, such as blood lipids, body weight, blood pressure, and inflammation.
A 2013 review article states that epidemiological evidence suggests that elevated glucose after a meal “contribute(s) to an approximately threefold increase in the risk of developing coronary heart disease or a CV event.” However, the review also states that the RCT’s are less clear, with a range of findings, such as the NAVIGATOR and HEART2D trials, that found no impact of a glucose lowering drug on a range of outcomes. That said, a more recent meta analysis suggested glucose-lowering drugs are useful at reducing the risk of major acute cardiovascular events.
While existing evidence generally supports the importance of minimizing blood glucose spikes for long-term health, further research is needed to clarify the impact on health.
Overall (average) score for claim 3
3 out of 4
Overall (average) score for scientific accuracy
3.3 out of 4
Reference Accuracy
Outlive tends to cite references accurately, receiving an overall reference accuracy score of 3.0 out of 4.0. This indicates that most of the references we checked support the claims made in the book.
Some minor issues were identified, such as a discrepancy between a claim about the impact of protein consumption on muscle loss and the actual findings of the cited study. Additionally, one reference used to support a claim about satiety resulting from dietary fat was found to suggest the opposite.
Despite these minor inaccuracies, we judge the book’s overall reference accuracy to be strong.
Reference 1
Reference
Chapter 14, reference 3. Bao Y et al. Association of nut consumption with total and cause-specific mortality. N Engl J Med. 2013 Nov 21;369(21):2001-11
Associated quote(s) and page number(s)
Page 297: “Even at face value, the ‘associations’ that nutritional epidemiologists come up with are often absurd: Will eating twelve hazelnuts every day really add two years to my lifespan, as one study suggested? I wish.”
Criterion 2.1. Does the reference support the claim?
1 out of 4
The cited study is an examination of two prominent cohort studies: the Nurses’ Health Study and the Health Professionals Follow-up Study. It reports that people who consumed nuts frequently (seven or more times per week) had a 20% lower death rate compared to those who didn’t. The study does not mention lifespans, does not provide data on the average lifespan of participants in different nut consumption groups, nor does it account for other factors that influence lifespan. It is unclear how one is able to translate a 20% reduced risk of mortality into specific years of added life. The only source of an explicit mention of a two year increase in lifespan is from a 2015 blog post that also links to the Bao report.
The text does provide a footnote that more accurately describes the study results: “According to a 2013 study by Bao et al., people who ate a dozen hazelnuts per day reduced their chances of dying in the next thirty years by 20 percent. (No word on the exact mechanism behind this miraculous outcome.)” However, the study does not mention specifically 12 hazelnuts. In fact, the only mention of hazelnuts in the main study or the supplementary material is in the Introduction where another study is mentioned that involves the Mediterranean Diet. Bao et al mention that one component of the Mediterranean Diet “was supplementation with walnuts, hazelnuts, or almonds […]” Additionally, the parenthetical remark about mechanisms is discussed in the Introduction as well and other studies examining the potential mechanisms are cited.
So although a specific claim is not made in Outlive that uses the Bao report as supporting evidence, the report is used to create a straw man argument that Outlive characterizes as absurd and then rebuts (with the statement “I wish”) without providing any other evidence.
Perhaps when initially writing Outlive the author had mentioned this study along with the blogpost as part of a broader discussion on how epidemiological results get misconstrued by the media, and perhaps the context got 86’d in the editing process. But in any case, the study cited does not support the text.
Reference 2
Reference
Associated quote(s) and page number(s)
Page 299: “For comparison’s sake, someone who smokes cigarettes is at more like 1,000 to 2,500 percent (ten to twenty-five times) increased risk of lung cancer, depending on the population being studied..”
Criterion 2.1. Does the reference support the claim?
4 out of 4
This reference received a score of 4 out of 4, meaning that it strongly supports the claim. Outlive actually cites several studies to support the lung cancer and smoking correlation; the above study is the first on the list. The cited study is an analysis of several case control studies. According to the study, the odds ratio for developing lung cancer by male current smokers compared to male never smokers is 23.6, which corresponds to a roughly 2,260 percent increase in risk. This is in line with the range provided by Outive.
Reference 3
Reference
Chapter 14, reference 10. Ejima K et al. Observational research rigour alone does not justify causal inference. Eur J Clin Invest. 2016 Dec;46(12):985-993. doi: 10.1111/eci.12681. Epub 2016 Oct 28. PMID: 27711975; PMCID: PMC5118066.
Associated quote(s) and page number(s)
Page 300-301: “A few years ago, a scientist and statistician named David Allison ran an elegant experiment that illustrates how epidemiological methods can lead us astray, even in the most tightly controlled research model possible: laboratory mice, which are genetically identical and housed in identical conditions. Allison created a randomized experiment using these mice, similar to the caloric restriction experiments we discussed in chapter 5. He split them into three groups, differing only in the quantity of food they were given: a low calorie group, a medium-calorie group, and a high-calorie, ad libitum group of animals who were allowed to eat as much as they wanted. The low-calorie mice were found to live the longest, followed by medium-calorie mice, and the high-calorie mice lived the shortest, on average. This was the expected result that had been well established in many previous studies.
But then Allison did something very clever. He looked more closely at the high-calorie group, the mice with no maximum limit on food intake, and analyzed this group separately, as its own nonrandomized epidemiological cohort. Within this group, Allison found that some mice chose to eat more than others—and that these hungrier mice actually lived longer than the high calorie mice who chose to eat less. This was exactly the opposite of the result found in the larger, more reliable, and more widely repeated randomized trial.
There was a simple explanation for this: the mice that were strongest and healthiest had the largest appetites, and thus they ate more. Because they were healthiest to begin with, they also lived the longest. But if all we had to go on was Allison’s epidemiological analysis of this particular subgroup, and not the larger and better-designed clinical trial, we might conclude that eating more calories causes all mice to live longer, which we are pretty certain is not the case.”
Criterion 2.1. Does the reference support the claim?
2 out of 4
This reference received a score of 2 out of 4, meaning that it weakly supports the claim. This study is presented in Outlive as part of a larger argument made about the weakness of epidemiology. The description of the study is a reasonably accurate representation of what happened. However, the conclusion drawn (the mice that were strongest and healthiest had the largest appetites) is not really supported by the study. The authors offer the possibility that some mice might have undiagnosed diseases which would affect their appetite and cause them to die sooner than other mice. However, the actual cause of differing results remains ambiguous, as the specific cause was not investigated. So ironically, the Outlive text is doing what the research paper is cautioning against: drawing a causal conclusion without proper evidence.
Reference 4
Reference
Chapter 15, reference 3. Mattison JA et al. Nature. 2012 Sep 13;489(7415):318-21. doi: 10.1038/nature11432. PMID: 22932268; PMCID: PMC3832985.
Associated quote(s) and page number(s)
Page 313: After describing a study in rhesus monkeys that demonstrated caloric restriction led to a longer lifespan, a similar study is described with differing results. “Three years later, in August 2012, another monkey study made the front page of the Times, but with a markedly different headline: ‘Severe Diet Doesn’t Prolong Life,’ the paper declared grimly, adding, ‘At Least in Monkeys.’ This study, also begun in the 1980s, was conducted under the auspices of the National Institute on Aging, one of the National Institutes of Health, and the study design was nearly identical to the Wisconsin study, with one group of monkeys being fed about 25 to 30 percent less than the other. Yet the NIH researchers found that their calorically restricted monkeys had not lived longer than the controls. There was no statistically significant difference in the lifespans of the two groups. From a headline writer’s point of view, caloric restriction had not ‘worked.’”
Criterion 2.1. Does the reference support the claim?
4 out of 4
This reference received a score of 4 out of 4, meaning that it strongly supports the claim. Outlive adequately summarizes the study and results.
Reference 5
Reference
Chapter 15, reference 6. Cordain L et al. The paradoxical nature of hunter-gatherer diets: meat-based, yet non-atherogenic. Eur J Clin Nutr. 2002 Mar;56 Suppl 1:S42-52. doi: 10.1038/sj.ejcn.1601353. PMID: 11965522.
Associated quote(s) and page number(s)
Page 317: (In the context of a discussion on dietary restriction) “The hard part is figuring out what foods to eliminate or restrict. This wasn’t an issue for our ancestors. There is ample evidence to suggest that they were opportunistic omnivores, out of necessity. They ate anything and everything they could get their hands on: lots of plants, lots of starch, animal protein whenever they could, honey and berries whenever possible. They also seemed to be, at least on the basis of the study of the few remaining hunter-gatherer societies, very metabolically healthy.”
Criterion 2.1. Does the reference support the claim?
3 out of 4
This reference received a score of 3 out of 4, meaning that it moderately supports the claim. The cited paper is a 2002 paper that reviews 13 other studies published on hunter-gatherer diets. It focuses mainly on cardiovascular health, discussing the beneficial lipid profiles (i.e. cholesterol and triglycerides) of the study populations. Outlive also cites another reference to support this claim: a 2018 review focusing on hunter-gatherers and their low prevalence of obesity. Interestingly, both papers offer somewhat contrasting data on the diets of hunter-gatherers (animal-based vs plant-based and high carbohydrate vs. low carbohydrate). Nevertheless, both make the case that the hunter-gatherer type diet is healthier than a diet consumed in an industrialized society, at least as it relates to obesity and cardiovascular health.
Overall, the claim that hunter-gatherers were “very metabolically healthy” is not fully supported by the evidence presented in the two studies. While the studies do show that hunter-gatherers had low rates of cardiovascular disease and obesity, they also highlight the lack of research on other metabolic diseases, such as diabetes and nonalcoholic fatty liver disease.
Reference 6
Reference
Associated quote(s) and page number(s)
Page 325: (As part of a discussion on glucose monitoring) “Another study in 2019 looked at the degree of variation in subjects’ blood glucose levels and found that the people in the highest quartile of glucose variability had a 2.67 times greater risk of mortality than those in the lowest (most stable) quartile. From these studies, it seems quite clear that we want to lower average blood glucose and reduce the amount of variability from day to day and hour to hour.”
Criterion 2.1. Does the reference support the claim?
4 out of 4
This reference received a score of 4 out of 4, meaning that it strongly supports the claim. The cited study is a post-hoc analysis of data from a prospective cohort study examining the link between antihypertensive treatments and heart disease among participants with hypertension. Although one thing worth noting is that the 2.67 times greater risk of mortality figure was calculated after diabetics were removed from the analysis. When diabetics and non-diabetics are included the risk is 2.22. Nevertheless, the study does show a positive association between glucose variability and mortality risk.
Reference 7
Reference
Associated quote(s) and page number(s)
Page 324: “Multiple studies suggest that the more protein we consume, in general, the better. A large prospective study called the Healthy Aging and Body Composition Study, with more than two thousand elderly subjects, found that those who ate the most protein (about 18 percent of caloric intake) kept more of their lean body mass over three years than those in the lowest quintile of protein consumption (10 percent of calories). The difference was significant: the low-protein group lost 40 percent more muscle than the high-protein group.”
Criterion 2.1. Does the reference support the claim?
3 out of 4
This reference received a score of 3 out of 4, meaning that it moderately supports the claim. The cited study is a post-hoc analysis of data from a prospective cohort study using a food frequency questionnaire to estimate protein intake among the elderly participants. The results found that participants in the highest quintile of protein intake (approximately 18% of caloric intake) lost 40% less lean mass over three years than those in the lowest quintile (11.2% of caloric intake). However, there is a difference in stating that the high protein group lost 40% less lean mass than the low protein group and stating (as described in Outlive) that the low protein group lost 40% more muscle than the high protein group.
The statement that the high protein group lost “40% less muscle” refers to a relative difference. If the high protein group lost 60 grams of muscle mass, and the low protein group lost 100 grams, then 40% less muscle loss would mean the high protein group lost 60% of what the low protein group lost.
Saying that the low protein group lost 40% more muscle would suggest that the low protein group lost only 40% more than what the high protein group lost. However, this would not capture the same magnitude of difference.
Reference 8
Reference
Associated quote(s) and page number(s)
Page 335: “On a practical level, dietary fat also tends to leave one feeling more satiated than many types of carbohydrates, especially when combined with protein.”
Criterion 2.1. Does the reference support the claim?
2 out of 4
This reference received a score of 2 out of 4, meaning that it weakly supports the claim. The cited did not directly compare the satiating effects of dietary fat and carbohydrates. The authors investigated the effects of a low-carbohydrate, high-protein, high-fat diet on body weight, energy intake, and various metabolic parameters in obese patients with type 2 diabetes. Participants were restricted in their carbohydrate intake but not in their protein and fat intake. However, the authors noted that “[a]lthough patients had free access to all noncarbohydrate food items, they increased their protein and fat intakes very little.”
The study found that participants on the low-carbohydrate diet spontaneously reduced their energy intake and lost weight. However, the authors did not specifically investigate the role of dietary fat in appetite regulation. They suggested that the reduced energy intake might be due to the lack of diet variety and palatability or changes in humoral satiety factors such as insulin and leptin.
In addition to the above citation, Outlive also cites a 1995 paper titled “A Satiety Index of Common Foods” that actually suggests the opposite of what Outlive claims here. In that paper, potatoes had the highest satiety score, while the authors state “Increasing fat content was associated with a lower SI score whereas increasing protein, fibre and water contents were associated with higher SI scores.”
A third citation is included in support of this claim, which is a chapter in an academic textbook. It paints a more nuanced relationship between fat and satiety, concluding “Is dietary fat satiating? Within a controlled environment, yes, fats do have an effect on satiety […]” However, the author also states that in free-living individuals the answer is more complicated.
The part of Outlive’s claim about dietary fat being especially satiating when combined with protein is not supported in any of these cited sources.
Reference 9
Reference
Chapter 15, reference 33. Bagherniya M et al. The effect of fasting or calorie restriction on autophagy induction: A review of the literature. Ageing Res Rev. 2018 Nov;47:183-197. doi: 10.1016/j.arr.2018.08.004. Epub 2018 Aug 30. PMID: 30172870.
Associated quote(s) and page number(s)
Page 341: (In the context of a discussion on fasting) “At the same time, lack of nutrients accelerates autophagy, the cellular ‘recycling’ process that helps our cells become more resilient […]”
Criterion 2.1. Does the reference support the claim?
4 out of 4
This reference received a score of 4 out of 4, meaning that it strongly supports the claim. The cited source is a review article that does support the idea that nutrient deprivation, such as fasting or calorie restriction, can accelerate autophagy. The authors state that “fasting and CR [calorie restriction] are the most potent non-genetic autophagy stimulators.” They also provide evidence that autophagy is induced in various tissues and organs in response to food deprivation.
Reference 10
Reference
Chapter 15, reference 34. Gross DN, van den Heuvel AP, Birnbaum MJ. The role of FoxO in the regulation of metabolism. Oncogene. 2008 Apr 7;27(16):2320-36. doi: 10.1038/onc.2008.25. PMID: 18391974.
Associated quote(s) and page number(s)
Page 341: “[Fasting] activates FOXO, the cellular repair genes that may help centenarians live so long.”
Criterion 2.1. Does the reference support the claim?
4 out of 4
This reference received a score of 4 out of 4, meaning that it strongly supports the claim. It is a review article that examines the role of FoxO in the regulation of metabolism. The article does support the idea that fasting can activate FoxO transcription factors. However, it might be worth noting that FoxO is not an actual gene, but a transcription factor: a protein that helps regulate gene expression.
Overall (average) score for reference accuracy
3.0 out of 4
Healthfulness
Like we mentioned above in the introduction, Outlive does not provide much in the way of explicit health advice or dietary recommendations. In fact, the book explicitly mentions avoiding dietary recommendations. However, there are a few suggestions in the book that we can examine. For example, the book does state that you should limit alcohol consumption to fewer than seven drinks per week and no more than two on any given day.
There are also the suggestions that were mentioned in the Scientific Accuracy section of this review: avoiding excess calories, consuming adequate protein, and avoiding a diet that will produce blood glucose spikes after a meal. This last one seems particularly important because several pages are devoted to utilizing a continuous glucose monitoring device to collect real time data on blood glucose with the goal of minimizing glucose and insulin spikes.
The book also does not take a firm stand on low-carb versus low-fat diets, but does state that monounsaturated fat consumption should be prioritized over polyunsaturated fats, while saturated fats should be limited to 15-20% of overall fat intake.
Overall, the recommendations in the book come down to fairly standard dietary advice that will likely provide a general improvement to health. However, any longevity benefit from this diet would likely be due to reducing the risk of chronic disease and not because the diet influenced something more esoteric, like telomere length.
Based on our assessment of the explicit dietary advice given in the book, Outlive scored 3 out of 4 in all of our Healthfulness criteria, meaning the recommendations are likely to result in health improvements and are more than nutritionally adequate.
Summary of the health-related intervention promoted in the book
The dietary advice in Outlive involves fairly common recommendations, such as reducing calorie intake to achieve energy balance, limiting alcohol and saturated fat, reducing or eliminating sugar-sweetened beverages, and consuming an adequate amount of protein.
Condition targeted by the book, if applicable
The goal of Outlive is to improve general health to increase longevity.
Apparent target audience of the book
The implicit target audience are adults wanting to live a longer, healthier life.
Criterion 3.1. Is the intervention likely to improve the target condition?
3 out of 4
The intervention received a score of 3 out of 4, meaning that it is likely to moderately improve health and promote longevity.
This is not a clearly defined dietary pattern with a history of study behind it like a vegan diet, Mediterranean Diet, the DASH diet, or the Atkins diet.
If one were to try to align it with a more studied dietary pattern, it could align with the Mediterranean diet or the DASH diet, both of which promote caloric balance, emphasize protein intake, limit alcohol, and limit saturated fats in favor of unsaturated fats from olive oil, nuts, and fish. Although the DASH diet is not mentioned in the book, Outlive does mention the Mediterranean Diet a few times and in a favorable light. Page 337 mentions an eating pattern similar to what you might find in a Mediterranean Diet:
Putting all these changes into practice typically means eating more olive oil and avocados and nuts, cutting back on […] things like butter and lard, and reducing the omega-6-rich corn, soybean, and sunflower oils—while also looking for ways to increase high-omega-3 marine PUFAs from sources such as salmon and anchovies.
As readers may already be aware, the DASH Diet and Mediterranean Diet both have a body of evidence that supports their beneficial health effects, and there is also some evidence that indicates they help to promote longevity as well.
However, since the advice in Outlive is not very extensive, trying to equate it to a more thoroughly-researched dietary pattern may be misleading. We can attempt an examination of individual components of some of the recommendations, which might be a better fit to evaluate the health effects.
For example, one cohort in the Netherlands indicated that those who had the greatest chance of living longest consumed between 5-15 grams of alcohol per day. This is consistent with about 0.3-1 standard drinks per day. Excess alcohol consumption is (perhaps obviously) strongly associated with health risks, such as increased risks of cardiovascular disease, cancer, and mortality.
One recommendation in Outlive that is somewhat outside the norm is protein intake. Page 332 includes the statement that “The ideal amount can vary from person to person, but the data suggest that for active people with normal kidney function, one gram per pound of body weight per day (or 2.2 g/kg/day) is a good place to start—nearly triple the minimal recommendation [RDA].” As evidence this review article on optimal protein intake for the elderly is cited; but the study actually says that 1.2-2.0 is what experts recommend, with the authors of the article generally finding that 1.2-1.5g/kg/day is optimal. This is consistent with other studies that review the literature on protein intake for the elderly. Additionally, this 2017 meta-analysis examining protein intake and resistance training states that “Protein supplementation beyond a total daily protein intake of ~1.6 g/kg/day during RET provided no further benefit on gains in muscle mass or strength.”
Criterion 3.2. Is the intervention likely to improve general health in the target audience?
3 out of 4
The intervention received a score of 3 out of 4, meaning that it’s likely to moderately improve general health.
Reducing sugar-sweetened beverages, consuming an adequate amount of calories without consuming enough to promote weight gain, consuming more unsaturated fats and reducing saturated fats, and consuming a moderate to high protein diet will likely improve health in most people, especially relative to a traditional American diet. However, Outlive makes little mention of foods such as leafy green vegetables, whole grains, legumes, and pulses – all of which have demonstrated health benefits. There is also little promotion of fresh fruits, with the exception of a parenthetical remark on page 347 that suggests eating fruit instead of drinking fruit juices.
Criterion 3.3. Does the diet portion of the intervention promote an adequate nutrient intake for general health in the target audience?
3 out of 4
The diet received a score of 3 out of 4, meaning that it’s likely more than nutritionally adequate. Levels of macronutrients are likely adequate, as well as essential vitamins and minerals. However, because there is little mention of the cruciferous vegetables, fresh fruits, and whole grains in the text, the food pattern promoted in the book might lack polyphenols and bioactive compounds that likely reduce chronic diseases and have anti-inflammatory properties.
Overall (average) score for healthfulness
3 out of 4
Most unusual claim
Chapter 7 states: “The various treatment guidelines specify target ranges for LDL-C, typically 100 mg/dL for patients at normal risk, or 70 mg/dL for high-risk individuals. In my view, this is still far too high. Simply put, I think you can’t lower apoB and LDL-C too much, provided there are no side effects from treatment. You want it as low as possible.” Levels varying between 10 and 30 mg/dL are suggested as LDL-C targets, with statins recommended as a means of helping to achieve this goal. This is unusual since, as mentioned above, these targets are dramatically below what is recommended by most institutions.
As evidence for this, Outlive cites an article by cardiology researcher Peter Libby: “As Peter Libby, one of the leading authorities on cardiovascular disease, and colleagues wrote in Nature Reviews in 2019, ‘Atherosclerosis probably would not occur [emphasis mine] in the absence of LDL-C concentrations in excess of physiological needs (on the order of 10 to 20 mg/dL).’” (italics and brackets are from Outlive) The book mistakenly sources this quote from a 2021 Nature article by Libby, but the quote actually appears in a 2019 Nature Reviews Disease Primers article.
How much evidence is available to support this atypical LDL-C target? There is some evidence in the scientific literature that supports this. Research shows that people born with PCSK9 mutations have naturally very low LDL-C levels (below 58 mg/dL) throughout their lives and face significantly lower cardiovascular risks. Researchers have developed medications that block PCSK9 to reduce LDL-C levels. The FOURIER-OLE trial found that lowering LDL-C to very low levels (below 20 mg/dL) was both safe and effective at preventing cardiovascular events. Similarly, the GLAGOV trial showed that combining these medications with statins lowered LDL-C to an average of 36.6 mg/dL and helped slow the progression of atherosclerosis. It should be noted that these trials examined people with elevated cardiovascular risk.
So although current guidelines generally recommend LDL-C targets of <70 mg/dL for high-risk patients and <100 mg/dL for those at moderate risk, emerging evidence suggests that further lowering LDL-C levels, potentially even below 20 mg/dL, may provide additional benefits for some high-risk individuals.
Other
Red Pen Reviews director Stephan Guyenet recused himself from substantive involvement in this review. This is due to personal contacts with Outlive author Peter Attia, and an appearance on Attia’s podcast in 2022 in which they discussed Red Pen Reviews extensively. Stephan copy-edited the review but did not edit it for content.
Conclusion
Outlive discusses nutrition’s impact on health and aging. The book suggests that dietary needs vary among individuals, focusing on metabolic health and calorie management. While some recommendations differ from standard guidelines, the book provides generally well-supported perspectives on using nutrition to support long-term health. Its emphasis on personalized approaches rather than strict diet rules may be helpful for readers interested in understanding how food choices affect their health and for being fairly easy to follow.