The Longevity Diet: Discover the New Science Behind Stem Cell Activation and Regeneration to Slow Aging, Fight Disease, and Optimize Weight

Overall score

Scientific accuracy

Reference accuracy

Healthfulness

How hard would it be to apply the book's advice? Fairly difficult

Book published in 2018

Published by Avery - Penguin Books

First Edition, Hardcover

Review posted February 13, 2019

Primary reviewer: Hilary Bethancourt

Peer reviewer: Seth Yoder

Table of contents

1. Introduction
2. Scientific accuracy
3. Reference accuracy
4. Healthfulness
5. Most unusual claim
6. Other
7. Conclusion
8. Updates

TLD focuses heavily on the importance of limiting total protein intake. But the referenced studies suggest that associations between protein and risk of diabetes and cardiovascular, cancer, or all-cause mortality are observed with animal protein but not plant-based protein. Overall, the relationship between high protein diets and markers of cardiovascular disease or glycemic control are highly inconsistent, and associations may only be observable at higher levels of animal protein consumption or in connection with separate unhealthy dietary and lifestyle behaviors (see further explanation of claim 2 below).

Finally, with regard the recommended FMD, research does suggest that regular intermittent day-long and multiple-day periods of fasting can help with weight loss and improve health markers. The proprietary FMD promoted in the book was designed with the goal of achieving the benefits of fasting without having to feel completely deprived of food or suffer some of the tradeoffs of long-term caloric restriction (e.g., downregulated immune function, longer wound healing, and cold intolerance). Nonetheless, the few human studies testing the effects of the FMD on health markers are a little underwhelming and are unable to speak to the long-term health advantage of regularly implementing the FMD (see further explanation of claim 3 below).

Overall, TLD points to a decent but limited body of research in yeast, mice, and humans that suggest that the recommended low-protein, low-sugar, low-refined grain, whole plant-based Longevity Diet plus regular FMD cycles could result in health improvements, at least among individuals that A) currently follow a standard American, “Western,” or industrialized diet, B) are overweight or obese, or C) have existing diabetes or cardiovascular disease or are at risk for those conditions. Nonetheless, the evidence does not support the need to limit plant-based protein, nor do they convincingly support a need to completely eliminate all meat, dairy, and eggs. There is good reason to believe that periodic bouts of very low caloric intake could reduce markers of cardiometabolic health risk. Yet we lack long-term data in humans to show that the periodic FMD recommended by TLD would add an appreciable benefit above and beyond a continuous moderate calorie, whole foods, plant rich diet and healthy lifestyle for preventing disease and extending healthspan.

Claim 1

The optimal diet for preventing and managing aging-related diseases and promoting longevity is one that is primarily plant-based (with the exception of fish) and very low in sugar, protein, and saturated fat.

Supporting quote(s) and page number(s)

Page 47: “When you look at the multidisciplinary studies, you realize that the high-protein, high-saturated fat, and low-carb diet is one of the worst for your health. Populations with record longevity do not eat this way…”

Page 59: “Aim for a diet that is close to 100 percent plant- and fish-based, limiting fish consumption to two or three portions a week and avoiding fish with high mercury content.”

Page 84: “[W]hereas the correct levels of proteins, unsaturated fats, and carbohydrates are beneficial, excess levels of proteins, saturated fats, and sugars can accelerate aging and damage the human body.”

Pages 71-72: “Areas of the world known to have the highest prevalence of centenarians – Okinawa, Japan; Loma Linda, California; small towns in Calabria and Sardinia, Italy; and in Costa Rica and Greece – all share diets that are (1) mostly plant-based with lots of nuts and some fish; (2) low in proteins, sugars, and saturated fats; and (3) high in complex carbohydrates coming from beans and other plant-based foods.”

Page 80: “It turns out that although she ate eggs and meat in her old age [living to 117], Emma’s diet was probably much more plant-based, with lots of rice and minestrone, for many decades of her life.”

Page 82: “Sardinia…is an area of record longevity validated by demographers. The Sardinians eat a diet that is…mostly plant-based, with bean, whole-grain breads, and lots of vegetables. Because of high local production, they also consume pecorino, the high omega-3 cheese made from ewe’s milk.”

Page 163: “Data from studies of centenarians show that extreme longevity has little to do with the Mediterranean diet per se. It is instead associated with specific ingredients and how heavily they are featured in diets common to the Mediterranean, Okinawa, Loma Linda, and Costa Rica…the Mediterranean diet appears to be a very good choice, but…the Longevity Diet, which includes the periodic FMD outlined in chapters 4 and 6, has the potential to be much more beneficial.”

Criterion 1.1. How well is the claim supported by current evidence?

3 out of 4

This claim received a score of 3, indicating that it is moderately supported by current evidence.

The existing evidence fairly consistently draws a picture of there being a health benefit from eating more whole, plant-based foods (e.g., whole grains, legumes, nuts and seeds, and fruits and vegetables) and from reducing intake of refined grains and added sugars. Indeed, many studies have led to conclusions that segments of the global population that follow meatless diets or Mediterranean-type diets (containing large amounts of whole plant-based foods and low to moderate meat and dairy) often have lower disease and mortality risk.

The problem is that observational research is often unable to isolate the effects of omitting meat or animal products from other health-promoting dietary and lifestyle behaviors (e.g., eating more fruits and vegetables and dietary fiber, engaging in physical activity, refraining from smoking, etc.) that often correlate with voluntarily choosing to omit all or specific animal products from the diet. Variation in those accompanying dietary and lifestyle behaviors may help explain why vegetarians and vegans do not consistently have lower mortality rates than omnivores. Randomized controlled trials have not convincingly isolated the health effects of omitting animal products from the diet either, as dietary interventions often incorporate multiple dietary changes at once, such as eliminating meat consumption along with reducing fat intake, restricting processed foods, moderating total calories, and increasing fruit and vegetable consumption.

It is true that processed red meat tends to be associated with cardiovascular- and metabolic-related diseases and mortality. Such associations are not always observed with unprocessed red meat, however, and poultry is generally not associated with disease or mortality risk in epidemiological studies. Again, it can be difficult to interpret the findings of these studies, as individuals that tend to eat more processed meat or red meat may be generally consuming a diet containing more processed foods, added sugars, and total calories. Interestingly, some dietary intervention studies have suggested that consumption of lean meat and fish in the context of a diet that is otherwise mostly vegetables, whole fruit, nuts, and seeds (void of all processed foods and added sugars) may lead to greater improvements in metabolic and cardiovascular health measures than following a Mediterranean diet or other commonly recommended diets.

Beyond meat, there is limited evidence of some milk products being associated with mortality risk, but most studies suggest that dairy consumption (particularly fermented dairy, like yogurt) is either not related to health outcomes or may be beneficial. Consumption of eggs may be ill-advised for people with type 2 diabetes, but eggs are otherwise not typically associated with poor health outcomes in the general population.

In sum, the evidence strongly suggests that replacing foods high in refined grains and added sugars with whole, minimally processed, fiber-rich plant-based foods will likely benefit health and longevity. However, we lack evidence demonstrating a detrimental effect of including moderate amounts of lean meat, fermented dairy, or eggs in an otherwise healthy, whole foods, plant-rich diet. Thus, the claim that omission of all meat, dairy, and eggs is a crucial part of a health- and longevity-promoting diet is not strongly or consistently supported by the existing evidence.

Criterion 1.2. Are the references cited in the book to support the claim convincing?

2 out of 4

The book’s references received a score of 2, indicating that they are weakly convincing.

The studies cited in TLD to support the need to refrain from eating animal products do conclude that consumption of animal protein is detrimental to health. However, there are some caveats to many of the studies. For example, one cited article reported higher risk of cardiovascular mortality in relation to consumption of animal protein but only among individuals with at least one other lifestyle risk factor (e.g., smoking, heavy alcohol intake, overweight or obesity, and physical inactivity). Also, this study found no increase in cancer-related deaths or all-cause mortality in relation to higher animal protein intake. Similarly, another study suggested that animal protein may increase risk of dying from cancer and cardiovascular disease; yet those classified as consuming “high animal protein” also consumed more processed meats and sugar-sweetened beverages and were more likely to smoke. So the study may not have isolated the health effects of animal products. A third cited study reported that risk of diabetes was higher among people who ate more animal protein. However, on closer examination, it appeared that consumption of red and processed meat intake accounted for most of the association between animal protein intake and diabetes risk.

The most frequently cited study is one that analyzed survey data from the National Health and Nutrition Survey (NHANES) III and reported an association between animal protein and overall and cancer-related mortality among adults aged 50-65 but not among adults >65 years old. TLD points to this study to support the allowance of eggs and dairy only after the age of 65. The problem with this conclusion is that if one assumes that what 50- to 65-year-olds reported eating on a single 24-hour recall was representative of their usual diet up until death, then that same assumption must hold for the adults in the >65 age group. If we keep that assumption constant, then we must conclude that the adults in the >65 category were also in the “high protein” intake group when they were younger.

Intriguingly, a separate study not cited in TLD used food frequency questionnaire (rather than 24-hour recall) data from a broader age range of adults in that same NHANES III cohort and found no association between meat consumption (whether looking at red or white meat) and cancer-related, cardiovascular-related or all-cause mortality. While food frequency questionnaire data is notoriously imprecise, it may in this case be a better measure of usual diet than a single 24-hour recall.

Apart from these observational studies, TLD references one large intervention trial suggesting reduced incidence of cardiovascular events (e.g., myocardial infarction, stroke) among study participants instructed to consume a Mediterranean diet with healthy fats (in the form of olive oil or nuts) as opposed to a “healthy low-fat diet.” This study was retracted after the publication of TLD; a reanalysis of the data revealed similar findings but no differences in overall mortality risk, and there continue to be concerns about how this study was conducted.

Finally, TLD discusses the diets and lifestyles of populations in Okinawa, Japan; several small Italian villages; and Loma Linda, California (where there is a large vegetarian Seventh Day Adventist community). Studies among Okinawans and Seventh Day Adventists have reported exceptional health and longevity combined with low intake of meat among those populations. Yet these studies, as well as the book’s anecdotal accounts of centenarians from small Italian villages and claims that their diets were “probably much more plant-based, with lots of rice and minestrone, for many decades” (pg 80) provide only very limited support for the need to eliminate animal products from the diet. It is important to consider that, when we compare the proportions of centenarians across different populations, we need to account for differences in population age structure, in- and out-migration, and birth rates. A baby boom in the 1900s, for instance, contributes to the large proportion of elderly in Japan. Similarly, populations like the small Italian villages described in TLD are going to have a higher proportion of centenarians if much of the young population tends to migrate out to bigger cities.

Most centenarians of today will have grown up consuming less meat and fewer animal products because they were born before the global nutrition transition – the period during which major changes in food production, transportation technologies, and industrial farming practices made meat and animal products, as well as refined carbohydrates, added sugars, and edible oils, more affordable and consistently accessible. Thus, it would be very unlikely to observe any centenarians that grew up eating tons of meat, as that was not the norm for most populations 100 years ago. This means that we lack an appropriate comparison group or counterfactual. Perhaps in some hunter-gatherer populations we might have observed more regular meat consumption 100 years ago, but such groups face a high infectious disease burden that typically prevents the survival to very old ages. It is nonetheless worth noting that, even at older ages, there is evidence that some hunter-gatherers and hunter-horticulturalists alive today have extremely low risk of developing aging-related diseases, like heart disease, despite including meat in their diets.

Criterion 1.3. How well does the strength of the claim line up with the strength of the evidence?

3 out of 4

The claim received a score of 3, indicating that the claim is slightly overstated.

Despite the issues raised above, the existing data suggest that a plant-based, pescatarian-type diet focused on whole, minimally processed foods is a healthy dietary choice that may (particularly for anyone following a standard American/”Western”/industrialized diet) reduce the risk of cardiovascular disease, diabetes, and cancer. However, some of the claims and the strength of the evidence are at times overstated given the lack of data demonstrating that the Longevity Diet would be superior to any other diet that similarly omits refined grains and added sugars and emphasizes whole plant-based foods but also includes moderate amounts of dairy, eggs, poultry, organ meats, and even unprocessed red meat.

Overall (average) score for claim 1

2.7 out of 4

Claim 2

High protein intake is associated with aging, disease, and premature mortality.

Supporting quote(s) and page number(s)

Page 33: “[S]ugars and proteins (amino acids) affect genes and pathways widely recognized to accelerate aging…”

Page 47: “When you look at the multidisciplinary studies, you realize that the high-protein, high-saturated-fat, and low-carb diet is one of the worst for your health.”

Page 57: “High protein intake…causes the activation of the growth hormone receptor, which in turn increases the levels of insulin and insulin-like growth factor 1 (IGF-1), whose altered concentrations are associated with diabetes and cancer, respectively. Proteins and certain amino acids derived from them, including leucine, can activate TOR-S6K, a set of genes that accelerate aging.”

Page 57: “By reducing calorie intake, particularly reducing calories from proteins and sugars, you can decrease the activities of the growth hormone receptor, and thus of the TOR-S6K and PKA genes known to accelerate aging.”

Page 58: “We are starting to accept that a high-sugar diet is unhealthy. Unfortunately, many are turning to proteins, and in some cases bad fats, as replacements for sugar. Instead they should be turning to healthier complex carbohydrates and good fats.”

Page 66: “We know that proteins (amino acids) consistently accelerate aging in most organisms, including yeast, flies, and mice. We also know that IGF-1 and TOR-S6K, both of which are increased or activated by protein intake, are central promotors of aging and age-related diseases in mice.”

Page 67: “[O]ur epidemiological study of six thousand Americans suggested that consuming a high-protein diet is associated with increased levels of the pro-aging growth factor IGF-1, a 75 percent increased risk of overall mortality, and a three-to-fourfold increased risk in cancer mortality compared with consuming the low-protein and plant-based diet recommended here.”

Page 68: “Because we know that protein consumption is the key regulator of IGF-1 levels and that animal-protein intake is usually associated with intake of saturated fats, these studies bolster the case for a link between cancer, diabetes, and high protein and saturated fat intake.”

Pages 78-79: “Because the younger generation has adopted a more modern diet, we speculated that transitioning to a higher-protein diet with more animal-based ingredients – which many centenarians did in their eighties and nineties – may contribute to their extreme longevity. In other words, maintaining a high-vegetable, low-protein diet for the first seventy or eighty years of life, and later switching to a diet richer in proteins but also animal-based foods like eggs, chicken, milk, and certain cheeses, may have slowed down aging and optimized the health of the Molochio centenarians.”

Pages 145-146: “As for a high-fat, low-carbohydrate diet, while it’s true that in most cases this regimen will result in weight loss, a significant portion of that loss comes from water and muscle. In addition, the high-fat and high-protein diet, in the long run, is the worst of all possible regimens both in terms of overall mortality and the incidence of cancer or death from cancer.”

Page 149:  “Because proteins are the major regulators of the growth hormone gene…high protein intake may promote diabetes in part by increasing the activity of growth hormone and the growth factor IGF-1, associated at high levels with multiple diseases.”

Page 166: “As we and others have shown, people with high vegetable-based protein intake normally have lower or much lower overall protein intake, suggesting that the lower incidence of disease may be caused by both the beneficial effects of plant-based foods and the lower overall protein intake, compared with people eating high levels of animal-based foods.”

Criterion 1.1. How well is the claim supported by current evidence?

2 out of 4

This claim received a score of 2, indicating that it is weakly supported by current evidence.

TLD recommends restricting total dietary protein to 0.31-0.36 grams per pound of body weight. This amount of protein is in line with what the Food and Nutrition Board recommends, and it comes to about 40-47 grams per day for someone weighing about 130 pounds or 60-70 grams per day for someone weight 200-220 pounds. However, even strict vegetarians from a large cohort of North American Seventh Day Adventists, known for their exceptional longevity, may consume more protein than that on a daily basis.

TLD supports the claim to lower protein intake by describing how protein raises insulin-like growth factor 1 (IGF-1), a hormone that plays an important role in cellular growth. Some research suggests that protein restriction may lower IGF-1 more than overall caloric restriction. However, the research generally suggests that dairy proteins, but not necessarily other animal proteins, are the main animal proteins associated with IGF-1. This may explain why vegetarians do not necessarily have lower IGF-1 than meat-eaters, though vegans do. IGF-1 appears to be associated with increased incidence of some cancers, though associations are generally described as modest. The association between IGF-1 and risk of type 2 diabetes, on the other hand, has not been consistently demonstrated; in fact, administration of IGF-1 may improve glycemic control in insulin resistant patients. Also, evidence suggests that there is a U-shaped relationship between IGF-1 and cardiovascular disease, with both very high but also very low levels of IGF-1 being associated with greater risk of cardiovascular events. A U-shaped relationship has also been found with IGF-1 and all-cause mortality and even cancer mortality.

It is worth pointing out that IGF-1 is not all bad either. In older ages, IGF-1 may be important for maintaining cognitive function, muscle mass, and bone density. Hence, we do not necessarily want IGF-1 levels that are too low.

Some research has suggested that protein restriction may account for some of the health benefits of caloric restriction, at least those observed in animal models. However, animal studies do not always report a benefit of protein restriction, and some researchers argue that protein restriction offers no benefit beyond those observed with caloric reduction. Moreover, it may not be the restriction of all amino acids but rather specific amino acids (e.g., methionine) that is the important longevity-promoting factor, though we lack the data in humans to demonstrate the benefits of restricting any particular amino acid on lifespan and healthspan. In general, plant–based proteins have not been linked with disease, cancer progression, or mortality.

Overall, even if there is a benefit to moderating protein intake and prioritizing plant protein over animal protein, the evidence does not provide conclusive support that total protein needs to be restricted to the degree suggested by TLD. More research is needed to understand the effects of different sources of protein in an otherwise healthy, whole foods, moderate calorie diet.

Criterion 1.2. Are the references cited in the book to support the claim convincing?

2 out of 4

The book’s references received a score of 2, indicating that they are moderately convincing.

The study frequently cited in TLD to support the claim to minimize protein found that animal protein intake, but not necessarily plant-protein intake, was associated with cancer-related and all-cause mortality. This study did not convincingly demonstrate that total protein intake needs to be restricted. The other referenced observational studies in human populations similarly find no association between plant-protein consumption and disease risk, and even the relationships between animal protein and disease or mortality may be accounted for by other correlated lifestyle risk factors or may depend on the source of the animal protein (e.g., processed meat versus unprocessed meats versus dairy or eggs).

The animal studies cited in TLD are a bit more convincing than the human studies. For example, one study demonstrated that cancer incidence and progression was greater in mice fed higher protein diets than mice fed ultra low protein (~4% of calories) diets. Yet, the low protein diets did not entirely prevent cancer incidence; 80-90% of mice fed a 4-7% protein diet (compared with 100% of mice on a high protein diet) still eventually developed cancer following the transplantation of tumor cells. Also, though low-protein diets slowed tumor growth, they did not prevent tumors from progressing. However, a major portion of the protein fed to mice in this and another referenced study was casein, a milk-derived protein. Thus, these findings in mice may be due the tendency of dairy (relative to other animal proteins) to cause increases in insulin and IGF–1. Only in one experiment was soy protein was also show to be related to higher IGF-1 in mice.

In sum, the cited research does not demonstrate that all plant proteins, or even that all animal proteins, increase IGF-1 and disease or mortality risk humans.

Criterion 1.3. How well does the strength of the claim line up with the strength of the evidence?

1 out of 4

The claim received a score of 1, indicating that the claim is substantially overstated.

The claim that total protein needs to be minimized to prevent disease and promote healthy aging appears to be overstated given that the literature does not generally find associations between plant-proteins and poor health outcomes, and the associations between animal proteins and disease risk were in some studies explained by other lifestyle risk factors or by only specific animal-based foods. Further research is needed to support the low threshold for total protein recommended in TLD.

Overall (average) score for claim 2

1.7 out of 4

Claim 3

A periodic (2-12 times/year) 5-day fasting-mimicking diet (FMD), especially when combined with the Longevity Diet, can (more effectively than chronic caloric restriction) extend healthy lifespan and prevent or even reverse chronic aging-related diseases.

Supporting quote(s) and page number(s)

Page xiv: “Combining these two elements [the Longevity Diet and the FMD], I have discovered, can protect, regenerate, and rejuvenate the body to keep us young and healthy longer. This is achieved in part by turning back the biological aging clock, which means that these diets can be adopted by relatively young people to help delay aging and prevent disease, and also by older individuals to help them return to a more youthful state.”

Pages 58-59: “We know that chronic and extreme diets – diets that restrict calories by 20 percent or more and are maintained for long periods or permanently – can negatively affect necessary processes, including wound healing, immune response, and cold-temperature tolerance…The rest of this book is on how to obtain the remarkable beneficial effects of calorie restriction without the negative ones.”

Pages 99-100: “The fasting itself destroys many damaged cells, and damaged components inside the cells but it activates stem cells. Once the mice begin eating again, these stem cells become part of a program to regenerate the organ or system, with the newly regenerated cells bearing characteristics of younger, more functional cells.”

Page 102: “[The FMD was designed to] provide sufficient calories to be safe outside of a clinic [but to be] equally effective as fasting, if not more so.”

Pages 102-103:  “The FMD, as demonstrated in our animal studies, treats aging and promotes healthy longevity using the following processes: switching cells to a protected anti-aging mode; promoting autophagy (self-eating of parts of the cell) and replacing damaged cell components with newly generated functional ones; killing damaged cells in many organs and systems and replacing them with newly regenerated cells from activated stem cells; shifting the body into an abdominal/visceral fat-burning mode, which continues after returning to a normal diet (probably due to epigenetic changes, which are modifications of the DNA and proteins that bind DNA).”

Page 105: “In fact, both in humans and mice, we detected a transient elevation of circulating stem cells in the blood during FMD, which may be responsible for the regeneration and rejuvenation occurring in multiple systems. By feeding people a very specific diet that tricks the organism into a starvation mode, most organs and systems eliminate unnecessary components (proteins, mitochondria, etc.) but also kill off many cells.”

Page 108: “The major advantage of the FMD approach – compared with drug interventions and stem cell-based therapies – is that it awakens a highly coordinated response that is already built into the body but that has fallen dormant because of our steady and constant consumption of food.” “At present, FMD represents perhaps the safest and most potent way to reverse many age- and diet-related problems by fixing or replacing, and thereby rejuvenating, cells, systems, and organs in a natural way.”

Page 109: “FMD cycles promote the regeneration of pancreatic cells to restore insulin production [in mice with type 1 and type 2 diabetes].”

Page 124: “Permanent therapeutic effects are achieved only through the combination of fasting and chemotherapy.”

Page 147: “[F]or some patients with type 2 diabetes and the great majority of prediabetic patients, the combination of the dietary interventions described above could lead to a cure. I’m not saying everyone would be cured or that it’s easy for diabetes patients to execute this plan. But the mouse and human data indicated that some and potentially many patients who follow the chronic dietary changes outlined in the first part of this chapter or the periodic FMD, and preferable both, could eventually be free of type 2 diabetes, the most common type, especially if the treatment is started right after the initial diagnosis, when the pancreas is still functioning well.”

Criterion 1.1. How well is the claim supported by current evidence?

3 out of 4

This claim received a score of 3, indicating that it is moderately supported by current evidence.

For a period of time, continuous caloric restriction (~30% reduction in calories) was thought to have the potential to extend lifespan and reduce chronic disease risk. However, further research revealed a number of side effects of chronic deprivation, including reductions in fertility, muscle mass, and immune function; increased cold intolerance and susceptibility to infections; and chronic hunger. Moreover, some studies suggested that caloric restriction may not necessarily be superior to a healthy diet in the promotion of health and longevity.

More recently, a number of studies have suggested that intermittent fasting (very low or no food intake 1 to 3 days a week) or alternate day fasting (very low or no food intake every other day) might have the potential to reduce fat mass and improve health markers as much or more than continuous caloric restriction but without the side effects. The fasting-mimicking diet (FMD) is unique in that it recommends a consecutive 5-day period of restricting calories to such a degree that the body purportedly responds as though it is in a fasted state. TLD argues that this period of time is necessary to induce or heighten the process of cellular repair and regeneration.

It is no surprise that reducing food intake for even a short period of time would result in acute reductions in weight, blood cholesterol, and blood sugar. But what are the long-term benefits of multiple-day periods of food restriction practiced intermittently throughout the year? Does compensatory feeding during non-fasting periods negate the acute benefits of fasting, or are there lasting effects even despite any compensation in food intake after fasting? Much of the research on this topic (many papers on which Dr. Longo is a coauthor) has been conducted with yeast or rodents, but it suggests that multiple consecutive days of water only or very low calorie diets has more dramatic effects than continuous caloric restriction on lowering IGF-1 and growth hormone thought to promote cancer growth, and fasting may have some very promising effects on improving the efficacy of chemotherapy in cancer treatment and reduce its toxic effects on healthy cells.

In humans, the data on the health effects multiple-day fasting is much more limited. Notably, because the prescribed FMD is a novel and proprietary intervention, there is no research on its health effects outside of what Dr. Longo and his research team have published (reviewed in the next subsection). Therefore, the lack of research on the long-term effects of the FMD in humans and the lack of research from different research teams contributed to this section not receiving full points.

Criterion 1.2. Are the references cited in the book to support the claim convincing?

3 out of 4

The book’s references received a score of 3, indicating that they are moderately convincing.

Only the rodent studies referenced in TLD provided strong data in support of the FMD. Various experiments in mice suggested that several cycles of the FMD may have the potential to:

1)   Lower IGF-1 and protect against chemotherapy-induced immunosuppression and aging-related immune function decline;

2)   Reduce cancer incidence, delay its onset and slow its progression;

3)   Reduce the toxic side effects of chemotherapy

4)   Extend 75% and median (but not maximum) survival;

5)   Improve beta cell function, thereby improving insulin sensitivity and promoting glucose homeostasis;

6)   Improve cognitive performance; and

7)   Reduce symptoms of multiple sclerosis.

It should be noted, however, that the FMD did not prevent cancer altogether. In one experiment, ~40% of mice intermittently fed the FMD diet developed cancer compared with ~70% of mice that consistently consumed their normal diet. In another experiment in which mice were implanted with breast cancer cells, ~70% of mice put on the intermittent FMD regimen developed cancer compared with 100% of mice that were not put on the FMD regimen. Also, the tumors that developed in mice still grew despite being put on the FMD regimen; they just grew at a slower rate.

With regard to the “reversal” of multiple sclerosis symptoms described in TLD, this was observed in only 20% of mice put on the intermittent FMD regimen.

With regard to the life-extending benefits of the FMD, mice were not breaking any longevity records, but a greater proportion of the mice put on the intermittent FMD regimen were living longer. However, at older ages, bouts of the FMD may have been detrimental to longevity.

Also, it is not clear whether the FMD cycles have lasting benefits. The mice in these studies were shown to compensate for the caloric restriction in FMD periods by eating more during the unrestricted periods; this resulted in a similar amount of food intake overall in the mice that were and were not given the intermittent FMD diet. Importantly, blood sugar, insulin, and IGF-1 levels of mice returned to baseline levels within 7 days after resuming the normal diet.

The studies in humans were less convincing. Only a few studies have explored the health effects of periodic FMD cycling in humans, and they have been limited to a three-month period. TLD describes one pilot study with 19 participants and a larger study with 82 participants (the book describes this study as having 100 participants but only 82 completed the study). In these studies, participants were randomized to either continue their usual diet or engage in one 5-day FMD cycle per month for three months, returning to their usual diet in between cycles. These studies observed greater decreases in body weight and IGF-1 among participants that engaged in monthly FMD cycles. Significant decreases in trunk fat and waist circumference relative to the control group were observed in the larger study only. Significant drops in blood sugar and C-reactive protein, a marker of inflammation, in the FMD group relative to the control group were observed only in the pilot study. The reductions in total and LDL cholesterol, triglycerides, and C-reactive protein, were not significant relative to the control group in the larger study.

Nonetheless, the book reports that remarkable changes in health markers were observed on the FMD because it focuses only on changes that occurred within the group of participants that completed three cycles of the FMD intervention and on just the participants that started out with higher levels of blood sugar, triglycerides, blood cholesterol, and C-reactive protein. These are very misleading and biased ways to present study results. Without comparing changes in health markers to those of a control group, we cannot conclude that the changes observed in response to the FMD are greater than the natural variation we see day-to-day even in the absence of a substantial dietary change. Also, by looking only among those with high baseline blood sugar and cholesterol levels, we cannot rule out “regression to the mean,” the well-documented fact that anyone starting out with higher levels of cholesterol and blood sugar is more likely to experience a reduction in those measures by chance alone than someone who starts out in normal ranges. We also do not know how long these effects on health measures last; more research is needed to explore how many weeks or months any benefits of the FMD cycles will persist.

TLD also promotes the FMD as a regimen with the potential to prevent or help in efforts to treat cancer, autoimmune issues, and Alzheimer’s disease. However, the data supporting these claims are more limited than the data on cardiovascular and metabolic health measures.

In the chapter on diet and cancer, there is mention of ten case reports of reductions in self-reported side-effects from chemotherapy when received in a fasted state; no citation was provided for these case-reports. There is also mention of two small studies conducted among cancer patients that suggested that fasting around the period of chemotherapy is tolerable and may reduce DNA damage caused by chemotherapy. One of these studies reported that fasting patients experienced no reduction in blood sugar, and TLD mentions that high blood sugar may be associated with adverse health outcomes in cancer patients. That study did, however, report a reduction in insulin and IGF-1 in relation to fasting.

With regard to autoimmune conditions, TLD referenced one pilot study with 60 relapsing-remitting multiple sclerosis patients (48 of whom completed the study) that suggested that a single 7-day FMD cycle followed by six months on Mediterranean diet may at least temporarily reduce white blood cell count and lymphocyte count and improve subjective measures of quality of life. However, many similar benefits were also observed among patients randomized to a ketogenic diet (high fat, ultra-low carbohydrate diet). Greater benefits may have been observed in the FMD group if they had implemented monthly FMD cycles, but clearly more research in this area is needed.

No human studies are cited that demonstrate the potential of FMD to prevent or help treat Alzheimer’s disease in humans, though other studies are cited suggesting that overall healthy diet rich in omega-3 fatty acids and certain vitamins may be beneficial.

Finally, a piece that is missing from this literature is a description of how Dr. Longo and his team designed and came up with the specific proprietary FMD regimen that they recommend. For example, how was it determined what level of calories and what proportion of macronutrients would be appropriate to produce health effects that mimic those of a complete fast from food?

Criterion 1.3. How well does the strength of the claim line up with the strength of the evidence?

2 out of 4

The claim received a score of 2, indicating that the claim is moderately overstated.

The cyclical FMD regimen has potential to reduce risk factors for aging-related diseases, such as helping to reduce blood cholesterol, blood sugar, body weight, and inflammation. Nonetheless, given the limited research with humans, particularly limited research looking at the long-term effects of the FMD, this book is perhaps promising a bit more than it should, or doing so a bit prematurely. Readers are reminded about the limited research and are advised to only undertake the FMD under supervision of a healthcare professional. Nevertheless, some of the alleged benefits of the FMD are sensationalized, and it might be easy to come away from reading this book feeling that the FMD is a panacea for everything. While the FMD protocol has promise, there is no guarantee that it will prevent or reverse the health conditions readers may be wishing to prevent or reverse. Moreover, it is unclear how the FMD stacks up against other fasting regimens or whether it offers a substantial boost to health beyond continuously following a healthy, whole foods, moderate calorie diet and engaging in other healthy lifestyle patterns. More research is needed comparing the short- and long-term effects of a healthy diet with and without the inclusion of the FMD protocol, and, perhaps, testing different variations of the FMD (different levels of calories and macronutrient intake).

Overall (average) score for claim 3

2.7 out of 4

Overall (average) score for scientific accuracy

2.3 out of 4

Reference 1

Reference

Chapter 4, Reference #15: de Koning L, Fung TT, Liao X, et al. Low-carbohydrate diet scores and risk of type 2 diabetes in men. Am J Clin Nutr 2011; 93(4): 844-50.

Associated quote(s) and page number(s)

Page 68: “A similar study of forty thousand men suggests that a low-carb, high animal-protein diet is associated with a twofold increase in diabetes, a finding also consistent with our discovery in the six-thousand person-protein study.”

[Note that the de Koning et al. reference is for the “study of forty thousand men”. The “six-thousand-person protein study” is the Levine et al. 2014 discussed previously and again below]

Criterion 2.1. Does the reference support the claim?

3 out of 4

This reference received a score of 3, indicating that it offers moderate support for the claim with the caveats that it appears to be low-carbohydrate, high protein diets that are specifically high in red and processed meats that are associated with the highest relative diabetes risk, particularly for individuals with a high body mass index. The cited “twofold” difference is comparing the fifth to the first quintiles (the highest to the lowest extremes) of a dietary score that ranked people by degrees of animal protein and fat intake relative to carbohydrate intake. That “twofold” difference turned into only a 37% increase in diabetes risk when the authors accounted for body mass index. Moreover, that association was no longer significant once the authors adjusted for red and processed meat intake, suggesting that it was not all animal protein but rather specific animal protein foods (e.g., processed meat) that accounted for this relationship. Finally, individuals in this study who consumed more animal protein were also less physically active and more likely to smoke and drink more alcohol, and consumed lower fruit, vegetables, and legumes. These other factors may have also contributed to their higher risk of diabetes.

Reference 2

Reference

Chapter 2, Reference #5: Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, et al. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med 2011; 3(70): 70ra13.

Associated quote(s) and page number(s)

Pages 28-29: “It would take another six years for our data on genes activated by sugars to get published, along with the discovery of pro-aging genes activated by amino acids and proteins [different citation here]. Eight more years passed before different laboratories would confirm these data experimentally in mice, and another ten years before my own lab provided initial evidence that similar genes and pathways may protect humans against age-related diseases…”[4] “After five years of working together, we published our findings concluding that there was a major decrease in the incidence of cancer and diabetes in subjects with Laron syndrome, despite poor diet (consuming large quantities of fried food) and unhealthy lifestyle choices (smoking, drinking, etc.)” [5]

[Note that references 4 and 5 are for the same article.].

Criterion 2.1. Does the reference support the claim?

4 out of 4

This reference received a score of 4, indicating that it offers strong support for the claim. It is worth noting, however, that the deficiencies of growth hormone and low levels of IGF-1 that appear to protect individuals with Laron’s syndrome against some aging related diseases (e.g., cancer and diabetes) do not appear to be protective against all aging related diseases. The proportions of death caused by cardiovascular disease were similar among those with and without growth hormone deficiencies.

Reference 3

Reference

Chapter 8, Reference #8: Levine ME, Suarez JA, Brandhorst S, et al. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab 2014; 19(3): 407-17.

Associated quote(s) and page number(s)

Page 146: “Those results [from the de Koning study reviewed above] are consistent with our 2014 study of six thousand people in the United States indicating increased diabetes risk in those with the highest protein intake, although the small population size limited the significance of our results.”

Note that this article is also referenced in other parts of the book:

Pages 66-67, Chapter 4, Reference 9: “In our recent study, we showed that simply by lowering protein intake in mice, we can reduce the incidence of melanoma and breast cancer.”

Page 67, Chapter 4, Reference 12: “[O]ur epidemiological study of six thousand Americans suggested that consuming a high-protein diet is associated with increased levels of the pro-aging growth factor IGF-1, a 75-percent increased risk of overall mortality, and a three- to fourfold increased risk in cancer mortality compared with consuming the low-protein and plant-based diet recommended here.”

Page 79, Chapter 4, Reference 22: “This explanation [of centenarians consuming a high-vegetable, low-protein diet earlier in life and switching to a diet richer in proteins later in life when younger generations were adopting a more modern diet] is consistent with our discovery that low-protein intake is associated with extended longevity and a major reduction in cancer in people age sixty-five and younger, but not those above sixty-six.”

Criterion 2.1. Does the reference support the claim?

3 out of 4

This reference received a score of 3, indicating that it offers moderate support for the claims with which it is associated. However, there are some nuances worth pointing out:

1) Given the ridiculously large confidence intervals for the estimate of increased diabetes risk in relation to protein intake (due to a very low number of diabetes-related deaths in their sample), these results should be interpreted with caution.

2) Cancer incidence was reduced in mice on low-protein diets, but by only 10-20%.

3) The “75-percent increased risk of overall mortality” in relation to high protein intake was barely statistically significant and was reduced to a non-significant 18% increase when the researchers adjusted for calories from animal protein (suggesting that it is not total protein but animal protein specifically that accounted for these associations).

4) The suggestion that high-protein diets are associated with reduced longevity and increased cancer risk only before the age of 65 rides on the assumption that individuals in the 65+ year-old group only began consuming more protein after the age of 65. But how do we know that they were not consuming higher amounts of protein for many years before the age of 65 and yet did not suffer any noticeable consequences with regard to cause-specific and overall mortality?

Reference 4

Reference

Chapter 3, Reference #1: Fontana L, Kennedy BK, Longo VD, Seals D, Melov S. Medical research: treat ageing. Nature News 2014; 511(7510): 405-7.

Associated quote(s) and page number(s)

Page 37: “We are so used to associating death with cancer, heart disease, or another illness that the concept of ‘dying healthy’ seems alien. But this is the promise of the ‘longevity revolution.’”

Criterion 2.1. Does the reference support the claim?

4 out of 4

This reference received a score of 4, indicating that it offers strong support for the claim. The references is a brief commentary article. It discusses the projected increase in individuals over the age of 60 and highlights some of the research that has looked at the beneficial effects of caloric restriction and protein restriction on lifespan and markers of inflammation, oxidative damage, diabetes, heart disease, cancer, and neurodegeneration – mostly all research in mice. The article is calling attention to the lack of cross-talk among scientists, clinicians, laboratory researchers, gerontologists and calls attention to the inadequate funding going into studying interventions that could potentially extend healthspan, the need for more human trials with suitable endpoints and more animal studies that are designed to “better mimic human aging.”

Reference 5

Reference

Chapter 7, Reference #5: Weiser MA, Cabanillas ME, Konopleva M, et al. Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen. Cancer 2004; 100(6): 1179-85.

Associated quote(s) and page number(s)

Page 125: “[H]igh glucose levels in combination with chemotherapy in patients are associated with an increased risk of developing infections and with higher death rates when compared with patients with normal blood glucose.”

Criterion 2.1. Does the reference support the claim?

4 out of 4

This reference received a score of 4, indicating that it offers strong support for the claim.  This study provides some evidence that high blood glucose, even in the absence of a prolonged history of elevated blood sugar, might influence survival and remission rates from cancer. This study with patients receiving chemotherapy treatment for acute lymphocytic leukemia found that those with signs of hyperglycemia (defined as having at least two random glucose measurements above 200 mg/dL) within the first 30 days of treatment had shorter median remission and survival durations and increased risk of infection compared with those deemed as having normal glucose levels.

Reference 6

Reference

Chapter 10, Reference #6: Ross GW, Abbott RD, Petrovitch H, et al. Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 2000; 283(20): 2674-9.

Associated quote(s) and page number(s)

Page 184: “The role of coffee in health and longevity has been controversial. Although earlier studies included coffee as a risk factor for a variety of age-related diseases, including cancer and heart disease, later more carful studies indicate that moderate coffee consumption may in fact protect against diseases including Parkinson’s, type 2 diabetes, and liver diseases. A few studies suggest that coffee may also protect against Alzheimer’s. Researchers at the University of South Carolina reviewed studies published between 1966 and 2014 assessing the relationship between coffee consumption and dementias. They examined eleven studies of a total of 29,000 participants. Overall coffee drinkers and non-coffee drinkers showed no difference in their risk of developing dementia. However, the group with the highest coffee consumption had an approximately 30 percent reduction in the risk of developing Alzheimer’s disease. It is possible that drinking three or four cups of coffee a day may protect against Alzheimer’s, as it was shown to protect against Parkinson’s.”

Criterion 2.1. Does the reference support the claim?

3 out of 4

This reference received a score of 4, indicating that it offers moderate support for the claim. The article does show a protective effect of coffee against Parkinson’s disease when comparing men who drank >28 oz/day with those who did not consume coffee. There was no apparent benefit of lower amounts of coffee consumption. This article does not speak directly to the effects of coffee on Alzheimer’s disease.

Side note: there is no citation provided for the preceding sentence describing “30 percent reduction in the risk of developing Alzheimer’s disease” among individuals drinking higher amounts of coffee.

Reference 7

Reference

Chapter 10, Reference #5: Sofi F, Abbate R, Gensini GF, Casini A. Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. Am J Clin Nutr 2010; 92(5): 1189-96.

Associated quote(s) and page number(s)

Pages 183-184: “[A]n analysis of many studies on the Mediterranean diet and neurodegenerative diseases concluded that adherence to the Mediterranean diet only decreases the risk of neurodegenerative diseases by 13 percent [reference 5]. Thus, in order to optimize brain health and delay or prevent Alzheimer’s onset, I recommend the Longevity Diet plus additional nutrients including olive oil and nuts…Though the efficacy of this diet in the prevention of dementia has not been demonstrated yet, it has a higher potential for significant impact since it represents a stricter version of the Mediterranean diet and includes many additional nutrients of reported benefit.”

Criterion 2.1. Does the reference support the claim?

3 out of 4

This reference received a score of 3, indicating that it offers moderate support for the claim. The 13 percent reduction in neurodegenerative diseases reported in the referenced meta-analysis of five data sources is in relation to a 2-point increase in adherence to a Mediterranean-type diet (measured using a 0-9 point scoring system). Hence, it is not comparing adherence vs non-adherence to a Mediterranean diet but rather varying degrees of inclusion of fruits, vegetables, nuts, whole grains, etc. that count toward more points on the scoring system. Nonetheless, the article does support the suggestion that a strict form of the Mediterranean diet might have a beneficial effect on the prevention of dementia. However, the claim insinuates that the Longevity Diet might have an even greater effect on the prevention of dementia, and this article cannot provide support for that.

Reference 8

Reference

Chapter 10, Reference #9: Morris MC, Tangney CC. Dietary fat composition and dementia risk. Neurobiol Aging 2014; 35 Suppl 2: S59-64.

Associated quote(s) and page number(s)

Page 186: “In studies conducted at the Chicago Health and Aging Project, consumption of saturated and trans fatty of saturated and trans fatty acids was associated with an increased risk of [Alzheimer’s Disease][a different study cited here]. These findings support adoption of the Longevity Diet, which is nearly free of the saturated fats and trans fats found in high quantities in animal derived foods (especially red meat, butter, cheese, whole milk, pork, and candy) [the Morris and Tangney study cited here].”

Criterion 2.1. Does the reference support the claim?

3 out of 4

This reference received a score of 3, indicating that it offers moderate support for the claim. The article is a review article that discusses some observational studies that have suggested that there might be an association between hypercholesterolemia (high blood cholesterol levels) and risk of developing dementia. It also cites some animal studies suggesting that feeding dogs and mice diets high in saturated fats may lead to disfunction of the blood brain barrier, decreased cognitive performance, and increased learning errors. The epidemiological research discussed in this article suggests that the relationship between fatty acids and risk of dementia is mixed but may point to an increased risk of cognitive decline associated with diets higher in saturated fats.

What is confusing is that this article appears to better support the preceding sentence. It seems ill-placed in the sentence describing the animal foods high in saturated fats and high fats.

 

Reference 9

Reference

Chapter 9, Reference #3: Mattison JA, Roth GS, Beasley TM, et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 2012; 489(7415): 318-21.

Associated quote(s) and page number(s)

Page 162: “In contrast to the Wisconsin study, the NIA study, led by Rafael de Cabo, found no apparent difference in the cause of death between control and CR [calorically restricted] groups. Both groups showed similar distribution of cardiovascular disease, amyloidosis, neoplasia, and general health deterioration [reference #3]. The difference between these two decades-long studies on diet in monkeys underscores the importance of diet composition in addition to limiting calories. In the NIA study, the control group received a healthy diet in which proteins were derived mainly from plant-based sources, including wheat, corn, soybean, and alfalfa, plus fish…the animals were fed only twice a day, and their portions were adjusted for the age and body weight of each individual monkey.”

Criterion 2.1. Does the reference support the claim?

4 out of 4

This reference received a score of 4, indicating that it offers strong support for the claim. Further explanation not necessary here.

Reference 10

Reference

Chapter 10, Reference #7.a: Fernando WM, Martins IJ, Goozee KG, Brennan CS, Jayasena V, Martins RN. The role of dietary coconut for the prevention and treatment of Alzheimer’s disease: potential mechanisms of action. Br J Nutr 2015; 114(1): 1-14.

Chapter 10, Reference #7.b: Hu Yang I, De la Rubia Orti JE, Selvi Sabater P, et al. Coconut oil: Non-alternative drug treatment against Alzheimer’s disease. Nutr Hosp 2015; 32(6): 2822-7.

Associated quote(s) and page number(s)

Page 185: “In a study of patients with Alzheimer’s disease, consumption of 40 milliliters (1.5 fluid ounces) per day of extra virgin coconut oil resulted in an improvement in cognitive status. This finding is consistent with other studies suggesting medium chain fatty acids protect against dementia. While coconut oil’s protective role must be confirmed in large clinical studies, the published data indicates it may improve cognition in Alzheimer’s disease patients.”

Criterion 2.1. Does the reference support the claim?

4 out of 4

This citation actually refers to two separate articles, but together they receive a score of 4 indicating that they offer strong support for the claim.

The first is a review article that provides a theoretical background framing the hypothesis that coconut oil and MCT oils may have some benefit on cognitive health, but it does not in itself support the claim that simply supplementing with 40 mL/day of coconut oil will have a substantial on either the prevention or treatment of Alzheimer’s.

The second article was a trial that tested the effects of 40 mL/day of coconut oil for 21 days on the cognitive performance of 44 patients with Alzheimer’s disease. The group of 22 patients that received the coconut oil had a statistically significant increase in cognitive test scores, while the control group did not experience a significant increase. The researchers did not compare the change in the coconut oil group to the change in the control group; they only looked at changes within each group. The difference in cognitive test scores appear to be substantially greater in the treatment group than in the control group, but they should have done a statistical test to confirm that.

Overall, these two references are in line with the claim, especially since it includes the statement that larger trials are needed to confirm what the limited body of literature suggest might be a beneficial effect of coconut oil.

Overall (average) score for reference accuracy

3.5 out of 4

Despite limited research to support some of the claims, the Longevity Diet program still stands as a comprehensive regimen that incorporates many key components of diet and lifestyle habits that have been demonstrated to help prevent, manage, and reverse aging-related degenerative diseases. Even though the existing research is unable to isolate the health effects of any single dietary factor, it is quite clear that the combination of a healthy diet (specifically one that is moderate in calories, high in antioxidant-rich plant foods and healthy fats, and low in sugar and processed or refined foods), time-restricted feeding (eating with a 12-hour window or less), exercise, and a healthy lifestyle (avoiding smoking, excessive drinking, etc.) will increase the likelihood of living a long, healthy life and maintaining physical and cognitive capacities. The Longevity Dietary program encompasses all of these components. The addition of periodic fasting or the proprietary FMD program has the potential to further improve cardiometabolic health markers, though the long-term effects of cyclical fasting periods on health outcomes have yet to be demonstrated in humans.It is another question, however, as to whether this diet will necessarily prolong life and reduce the wear and tear of continuing to live and breathe in the modern world. While the Longevity Diet is certainly comprehensive, it is still important to remember that even the best diet and exercise regimen cannot reverse the detrimental effects of chronic stress, environmental pollution, sleep deprivation, or genetic or epigenetic conditions that might make us more susceptible to certain ailments. There is also a substantial variability in how a person might respond to a given diet, depending on their genetics, early childhood and intrauterine environments, gut microbiome, and other lifestyle and environmental factors. Thus, while I rank this diet high in terms of healthfulness, it is important to understand that it is no panacea. As indicated by both the mice and human studies cited in TLD, there is never 100% improvement among those put on a low-protein plant-based diet or FMD intervention. Some individuals may find more help in following a distinct dietary regimen that differs in macronutrient or food composition. Nonetheless, the Longevity Diet is, overall, a great improvement over many conventional diets consumed in modern, industrialized contexts. Importantly, the advice to limit daily eating hours and practice regular bouts of reduced caloric intake is advice that could be implemented into any dietary plan, regardless of its composition.

Summary of the health-related intervention promoted in the book

The key steps of this intervention are:

1)   Follow a primarily plant-based diet supplemented with 2-3 servings/week of fish (and small amounts of eggs and/or goat milk products if >65 years old).

2)   Keep protein intake to 0.31-0.36 grams per pound of body weight per day (adding an additional 5-10 grams of protein/day if >65 years old).

3)   Fat intake should come from olive oil, nuts and seeds, and fish, avoiding saturated, hydrogenated, and trans fats. Supplementing with 40 mL/day of coconut oil is recommended for anyone at high risk for dementia.

4)   Carbohydrates should come from whole grains, legumes, and vegetables, limiting intake of sugar, pasta, rice, breads, fruit, and fruit juices. [though rice, different pastas, and different breads all show up in the meal plans]

5)   Choose a variety of foods that will supply different nutrients; take a multivitamin 2-3 times/week to help assure you meet recommended vitamin and mineral intake.

6)   Prioritize foods eaten by your grandparents; consider avoiding foods that would not have been consumed by your recent (last ~400 years) ancestors.

7)   Eat two meals plus a low-sugar snack (consuming more frequently only if elderly and/or if weight or muscle mass is too low).

8)   Eat within a 12-hour window or less, avoiding eating within 3-4 hours of going to sleep.

9)   Periodically (2-12 times/year) engage in a 5-day cycle of the calorically-restricted, low-protein fasting-mimicking diet (FMD). Do this until the age of 60-70. Avoid the FMD if frail or undernourished.

Condition targeted by the book, if applicable

Aging and aging-related diseases or conditions, including obesity, cardiovascular diseases, type 2 diabetes, cancer, dementia, and autoimmune or inflammatory conditions.

Apparent target audience of the book

Anyone wanting to lose or manage their weight, improve their health, prevent or manage chronic diseases, and live a longer, healthier life.

Criterion 3.1. Is the intervention likely to improve the target condition?

4 out of 4

The Longevity Diet program received a score of 4, indicating that it is likely to greatly improve many of the health conditions it aims to target, at least among individuals currently consuming standard industrialized diets (i.e., diets containing large amounts of processed and refined grains, added sugars, fried foods, and very little whole, fiber- and antioxidant-rich plant-based foods).

Vegetarian or vegan dietary interventions may (though not always) promote cardiovascular and metabolic health by helping to reduce body weight and improve in blood cholesterol levels, glycemic control. However, many trials involving vegan or vegetarian dietary interventions have involved low-fat versions of these diets, which the Longevity Diet is not. Interventions involving Mediterranean-type dietary patterns, which likewise involve an increase in whole plant-based foods but do not restrict fats or fully eliminate animal products, show similar (and similarly inconsistent) promise with regard to improvements in cardiovascular and metabolic health.

Though observational studies have suggested that adherence to a vegetarian or vegan diet may be associated with slight reductions in cancer incidence (but not necessarily in cancer mortality), we lack evidence from clinical trials showing a clear benefit of such diets over other diets for cancer prevention. Similarly, adherence to a Mediterranean Diet pattern has been associated with reduced cancer incidence and mortality, which may be attributable to the consumption of fiber- and antioxidant-rich fruits and vegetables other plant-based foods, as well as fish intake. Again, we lack evidence from randomized-controlled trials showing that plant-based diets will be more effective than other dietary regimens for preventing cancer, but there is good reason to hypothesize that the Longevity Diet program, particularly when combined with period fasting, may help prevent, delay, or slow the progression of cancer relative to many standard, industrialized diets.

Given some suggestion that Mediterranean diet interventions may also help prevent cognitive decline, we might hope that the Longevity Diet, particularly when combined with fats from nuts, olive oil, and coconut oil, may offer some protection against cognitive decline. Yet again, we need more long-term clinical trials to confirm this.

Finally, evidence that plant-based diets may help to reduce markers of inflammation offer hope that this program may also provide some relief from autoimmune and/or inflammatory conditions associated with aging, diet, and lifestyle.

In sum, the clearest benefit of the Longevity Diet protocol will probably be observed in markers of cardiovascular and metabolic health. It is less clear that this diet will necessarily prevent cancer, dementia, or autoimmune conditions. Yet, given that there is little reason to believe that this diet would cause or aggravate such conditions, it seems like a reasonable dietary approach to try in effort to reduce disease risk overall.

Criterion 3.2. Is the intervention likely to improve general health in the target audience?

4 out of 4

The Longevity Diet program received a score of 4, indicating that it is likely to greatly improve general health, at least for anyone currently consuming a a standard American, industrialized, or “Western” diet. Given the high and growing prevalence of overweight, obesity, and metabolic disorders and the fact that cardiovascular diseases at the top of the list of leading causes of death worldwide, the advice of this book is relevant for the general population. Even for individuals not currently suffering from any chronic aging-related diseases, following a diet that includes ample whole plant-based foods and limits sugars and refined grains, particularly when combined with the recommendations to limit eating windows and meal frequency, could help prevent the onset of health complications later in life. These recommendations are supported by observational studies on the long-term health benefits of vegetarian/vegan and Mediterranean diets. The research also supports the notion that time-restricted feeding and avoiding late-night eating or finishing the last meal earlier in the day, could provide a health benefit irrespective of dietary changes.

Criterion 3.3. Does the diet portion of the intervention promote an adequate nutrient intake for general health in the target audience?

4 out of 4

The Longevity Diet received a score of 4, indicating that it is likely substantially more than nutritionally adequate most standard “Western” or industrialized diets. Given its emphasis on whole grains, legumes, vegetables, and fruit, it should easily lead to the consumption of recommended amounts of fiber and health-promoting phytochemicals. Though protein intake is restricted, the recommended amounts still meet the estimated average requirements. Though the dietary plan limits most animal products, the allowance of fish should help provide essential fatty acids and other nutrients (e.g., Vitamins B12 and D, calcium, and zinc) that might otherwise be lacking or not found in as readily bioavailable forms in a completely plant-based diet. To help readers identify foods they should incorporate into their diet to meet nutrient needs, the book includes tables with examples of foods rich in vitamins A, B12, C, D, E; calcium; magnesium; iron; and omega-3. Strangely there is no table indicating good sources for zinc, which could be lacking in an otherwise vegetarian or vegan diet.

Still, it will be important, as with any diet, for adherents to make sure that they eat a large enough variety of different plant-based foods from the tables provided in the book and consume the recommended amounts of fish each week in order to better ensure adequate intake of all vitamins, minerals, and essential fatty acids. Additionally, different individuals may need to adjust intakes of some foods, macronutrients, or total calories if they are more physically active or are expending more energy or losing nutrients for other reasons (e.g., pregnancy, lactation, illness).

Overall (average) score for healthfulness

4 out of 4