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Ironically, we’re kicking off our two-month-long content series about eating and nutrition with two articles about not eating. Today we’re diving into caloric restriction for longevity, and next week we’ll look at intermittent fasting.

Caloric restriction is the kind of thing that critics of life extension like to hold up and say, “See? Spanners are so extreme they’ll even starve themselves to try and attain immortality.”

But calorie restriction isn’t at all the same thing as starving yourself.

If you starve yourself for too long, you’ll die: don’t starve yourself to try and live longer. Severe caloric restricted diets can lead to a decrease in bone density and lean body mass. Anorexia has one of the highest mortality rates of any mental disorder. That’s not what we’re talking about today. 

Instead, caloric restriction (“CR” for all you hip kids) is lowering the amount of calories you consume by a set amount (10%-30% of a calculated baseline, usually—we’ll get into the science of why below) while ensuring the necessary amount of essential nutrients in your diet, and keeping to this calorie restricted diet forever.

caloric restriction for longevity

It’s not starving yourself, but it may not be all that fun either.

Longevity expert Dr. David Sinclair, in Lifespan, his 2019 anti-aging book, wryly observed, “If calorie restriction doesn’t make you live longer, it will certainly make you feel that way.”

“If calorie restriction doesn’t make you live longer, it will certainly make you feel that way.”

But, in fact, there’s some pretty compelling scientific evidence that you can eat less and live longer. Caloric restriction (or drugs and regimens that mimic caloric restriction) has almost a century of research behind it.

In this calorie restriction guide, we’ll touch on some of the key scientific studies for and against CR as a longevity tool, as well as look at how to safely do CR if you decide it’s something you’re interested in trying.

Spoiler alert: I don't personally intend to practice a calorie restriction diet after my research for this piece, but I am quite interested in the prospect of periodic multi-day fasts to accomplish many of the same benefits of caloric restriction without having to permanently reduce my food intake. So stay tuned for next week's article on fasting, and sign up below to get an email when it comes out!
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What is caloric restriction?

Caloric restriction is basically what it says on the tin: a practice where you restrict the total number of daily calories you eat by a set amount, indefinitely.

It was all the rage in the 1990s and early 2000s based on tons of promising animal studies (which we’ll cover below). The movement was so popular that it even spawned the CR Society International, which still has some informative and active life extension forums with lots of helpful, knowledgeable members.

Since then, several more animal and human studies have substantiated the basic claims of calorie restriction: that lowering the total number of calories you eat every day can have positive, health-promoting effects and even possibly extend total healthy lifespan.

Scientists aren’t yet in full agreement about just how caloric restriction does this. And there are some important caveats to the research and some risks and negative side-effects to caloric restriction. Still, on the whole, there’s a huge tome of scientific studies to back up caloric restriction as a life-extension intervention.

So let’s dig into the nerdy stuff!

The science in favor: caloric restriction benefits

Caloric restriction is one of the (if not the) most-studied anti-aging interventions, especially in animals, with research going back over 100 years. Not every study has found universally positive results, but many have.

Since there are SO many caloric restriction studies out there, this roundup will just be an overview of some of the most interesting and foundational ones, and not a comprehensive review.

Animal studies of caloric restriction

As we mentioned in our very first article on human life extension:

The longevity-promoting effects of moderate starvation have been known as far back as 1914, when a study showed that caloric restriction in mice inhibited tumor growth, while in 1935 a different study showed that caloric restriction increased average rat lifespan from 483 days to 894 days. In humans, that would be the equivalent of getting an extra seven decades of life. 

calorie restriction and tumors in mice
An illustration from the 1914 study showing caloric restriction slows tumor growth in mice. Source.

Decades of additional animal studies followed, with life extension from calorie restriction being shown in organisms as varied as yeast, fruit flies, dogs (a 1.8 year median lifespan extension: recently relevant to me with our new puppy), mice (even old mice), and worms.

And for most of these species, not only was lifespan increased, but dietary restriction also resulted in better health generally, including healthier immune systems and improved resistance to chronic diseases like cancer, diabetes, and cardiovascular disease.

In fact, a 2014 review noted:

“Not only calorie restricted rodents lived longer than the ad libitum fed counterparts, but a significant part of them (about 30%) died without any apparent pathology, raising the striking possibility that aging is not necessarily tightly linked with costly pathologies.” [Emphasis added].

Get that?

Caloric restriction led to such healthy animals that they died without any visible chronic disease whatsoever. This is the holy grail of what’s called “compressed morbidity.” Instead of becoming afflicted with all sorts of age-related ailments for the last decades of your life, you remain healthy and mobile and active up to almost the day you die.

Even if CR didn’t end up extending lifespan, the extra healthy years you might get at the end of your life still sounds like a pretty good deal. I’d rather have that than lay in a hospital bed or sit in a wheelchair all day through my 80s and 90s.

More recent animal research on dietary restriction found that a 40% reduction in daily calories led to a 30% increase in median lifespan of female mice, while also slowing the epigenetic clock associated with biological age.

And, last but not least, some very important studies in primates—the closest animals to humans—have shown mixed, but still fairly positive results for caloric restriction and longevity.

The caloric restriction monkey studies

The first study, done by the University of Maryland, followed 117 rhesus monkeys (88 males, 21 females) from January 1977 to July 2001 (almost 25 years). Eight of the males were on calorie restricted diets while the rest were on unrestricted, or ad libitum, diets.

Rhesus monkeys share about 93% of their DNA with humans, and are fairly long-lived for primates, averaging around 25-30 years, making them ideal for testing if caloric restriction might work in humans as it does in less complex species like yeast and roundworms.

The University of Maryland study found, “The age at median survival in the [ad libitum group] was approximately 25 years compared with 32 years in the [dietary restricted group]… These results suggest that dietary restriction leads to an increased average age of death in primates, associated with the prevention of hyperinsulinemia and the mitigation of age-related disease.”

monkeys calorie restriction
Monkeys on a calorie-restricted diet lived longer than those fed an unrestricted diet.

Interestingly, rather than a blanket percent reduction in calories for the dietary restricted group of male monkeys, the study “calorically titrated on an individual monkey basis to maintain a goal weight of 10 to 11 kg, the weight of normal lean adult monkeys,” adjusting up or down based on weekly weigh-ins.

The next two primate studies also tested caloric restriction on rhesus monkeys over long periods of time. One was started in 1987 by the National Institute on Aging (NIA), and the other in 1989 by the Wisconsin National Primate Research Center (WNPRC).

Both studies followed the monkeys for 20+ years and tracked all sorts of health indicators, as well as disease incidence and death.

In the NIA study, the calorically restricted monkeys didn’t live any longer than the controls. However, researchers recorded  a whole host of additional health benefits from CR. For instance, “Old-onset CR was beneficial on several measures of metabolic health and overall function” including lower cholesterol and fasting glucose, while measures of inflammation and immune response were all better in monkeys who started caloric restriction at an early age.

Additionally, chronic disease incidence (like diabetes and cardiovascular disease) was lower in the calorically restricted group (though not at a significant level) and, “The incidence of cancer was markedly improved in young-onset CR monkeys… in fact, neoplasia has not been identified in any monkey from this group.”

So the NIA study indicates caloric restriction may compress morbidity and make your sunset years healthier, though not necessarily longer.

But the WNPRC study had much more positive findings.

The Wisconsin researchers found that a 30% calorically restricted diet (introduced 10% at a time over three months rather than all-at-once) “lowered the incidence of aging-related deaths… Of the original 76 animals, 37% (14/38) of the control animals died of age-related causes compared to only 13% (5/38) of the CR group.”

The Wisconsin study reported similar positive health effects for the calorically restricted monkeys as the NIA study: “Further, CR delayed the onset of age-associated pathologies. Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy.”

Both health benefits and life extension were sex independent for both studies, meaning both male and female monkeys saw the positive effects of caloric restriction.

calorically restricted monkeys
The monkey on the left and the monkey on the right are the exact same age. Can you tell which one is on a caloric restriction diet?

So what explains the difference in results between the WNPRC and NIA studies? How could one find incredible longevity benefits to caloric restriction while the other found no effect?

A couple papers have been published trying to explain the discrepancy, and one of the most compelling explanations I read, published in Nature in 2017, concluded that all the NIA monkeys, both the control and the CR group, were actually calorically restricted:

“All males and females from the NIA old-onset groups consumed fewer calories than their counterpart controls from [WNPRC], instead both control and CR were closely aligned with food intake values of [WNPRC] CR. Importantly, the median survival estimates for old-onset males were very high, similar to what has been reported previously as the 90th percentile for this species (∼35 years of age). Six of the original 20 monkeys have lived beyond 40 years of age, the previous maximal lifespan recorded, and one old-onset CR male monkey is currently 43 years old, which is a longevity record for this species.”

In other words, the study that supposedly showed no longevity benefits to caloric restriction in monkeys managed to set the world record for lifespan in a monkey of that species. 

The NIA paper admitted this may a possible explanation as well:

“Another important difference in study design was that the NIA study control monkeys were not truly fed ad libitum, unlike the WNPRC study. The regulated portioning of food for the NIA control monkeys may be a slight restriction and thus, largely prevented obesity. It has been reported that 10% CR increased lifespan in rats compared to ad libitum, even more than 25 and 40% CR. The NIA control monkeys may experience survival benefits from this slight restriction.”

Human studies of caloric restriction

Of course, the billion-dollar question with regard to animal studies of anti-aging treatments is: Will it translate to humans?

It’s hard to do a direct study on the longevity effects of caloric restriction in humans. Humans live a lot longer than even rhesus monkeys and you can’t (ethically) lock them up and carefully control everything they eat each day. That said, there are still some ways to study caloric restriction and human lifespan, accidentally.

For instance, you could look at populations of people who, for geographic or historical reasons, naturally eat a calorically restricted diet and see how that affects their lifespan.

In 1978 Japanese researcher Yasuo Kagawa did just that and found that Okinawans “were found to have the lowest total energy, sugar and salt, and the smallest physique, but had healthy longevity and the highest centenarian rate.”

The Okinawan diet is naturally calorically restricted compared to mainland Japan and Okinawans live 4-5% longer than mainland Japanese (who already live longer than most of the rest of the world).

Another accidental way to study caloric restriction in humans is to set up a science experiment to see if eight people can live in a closed environment similar to the space habitat featured in The Martian for two years. Then, when their crops fail like Matt Damon’s did, don’t give them any extra food and make them survive on just 1,700 calories a day while requiring them to do heavy physical activity.

And, in fact, that’s exactly what happened between 1991 and 1993 in the Biosphere 2 experiment.

biosphere 2 caloric restriction experiment
Ok, maybe a little fancier than Matt Damon’s Martian habitat.

But surprisingly, what the researchers discovered (since all the participants were closely medically monitored) was, “With regard to the health of humans on such a diet, we observed that despite the selective restriction in calories and marked weight loss, all crew members remained in excellent health and sustained a high level of physical and mental activity throughout the entire 2 years.”

Markers of health like blood pressure, blood sugar levels, and cholesterol levels, all improved for the people inside the biosphere.

And then there are the voluntary human calorie restriction studies.

Remember those lovely folks from the CR Society International? In the early 2000s, several of them allowed a researcher from Washington University in St Louis to study them and their low-calorie diets, and the result was several different papers showing the impact of caloric restriction on various key health biomarkers.

For instance, they found that CR Society members practicing caloric restriction (eating between 1,112-1,958 kcal/day) had a lower risk for atherosclerosis and 40% less plaque formation in their arteries than controls on a normal diet (eating 1,976-3,537 kcal/day). Diastolic function was improved, and resting heart rate and heart rate variability were better for CR practitioners compared to controls.

Additionally, a six-month, randomized controlled trial of caloric restriction in 48 men and women from 2006 found that two biomarkers of aging, fasting insulin level and body temperature, were impacted positively by CR.

Finally, the largest randomized controlled trial of caloric restriction in humans just recently published results in 2019 and the findings are largely promising. The study, called CALERIE (for “Comprehensive Assessment of Long term Effects of Reducing Intake of Energy”), ran over two years and followed 218 healthy, non-obese men and women on either a calorie restriction diet, or a normal “ad libitum” diet.

The individuals on a calorie restriction diet reduced calories by an average of 11.9%. Researchers concluded, “2 years of moderate calorie restriction significantly reduced multiple cardiometabolic risk factors in young, non-obese adults” including better readings for cholesterol, blood pressure, insulin sensitivity, and measures of inflammation like C-reactive protein.

All seems like kind of a slam dunk, right?

Well, hold up.

The science against: caloric restriction risks

As with any dietary intervention, and especially with one as counter-intuitive and apparently extreme as long-term caloric restriction, there are risks.

The first risk is that caloric restriction can do the opposite of what we want it to.

Despite the reams of studies referenced above, there are other studies that have shown caloric restriction can actually shorten lifespan in some organisms and under some conditions, including in certain kinds of mice.

caloric restriction risks in mice
Some CR mice did worse than their ad libitum fed counterparts. Source.

The second risk is that it’s difficult to implement caloric restriction correctly. As we noted in our article on why nutrition is so confusing, humans are horrible at tracking their calories. And if you fail to maintain adequate levels of nutrients while going on a calorie-reduced diet, you can get all kinds of problems caused by nutrient deficiencies, including fatigue and weakness, memory loss, dementia, and even death.

In the famous Minnesota Starvation Experiment in 1944, subjects were put on a deliberately poor starvation diet (low in protein and in fruits and vegetables) and experienced increases in depression, severe emotional distress, and declines in cognitive and sexual functioning. During the re-feeding period, one guy even cut off three of his fingers with an axe (although even then, half of the subjects who survived to age 80 lived eight years longer than expected for men born at the same time).

Even if you do caloric restriction perfectly, some research suggests it can still lead to negative side-effects like poor bone health and density, a weakened immune response, menstrual irregularities in women, and worse wound healing.

Additionally, many CR practitioners report increased sensitivity to cold, and several studies show a decrease in libido and fertility in animal models and in humans, as well as muscle loss in both.

And if you attempt an aggressive low-calorie diet for a while but “fall off the wagon” and later go back to a higher calorie intake, you could be worse off than before. Your body’s metabolism decreases on the lower calorie diet, but isn’t as quick to increase again once you’re off it, leading to weight gain and other potential health issues. This seems especially true for adolescents attempting extremely restricted diets.

Another caveat to consider, which we’ll cover in more detail in our discussion of intermittent fasting next week, is that caloric restriction may not actually be what’s responsible for the beneficial results we see from caloric restriction studies. Some research suggests meal timing and duration is what causes the longevity extension from CR, especially since many animal studies limited caloric intake by limiting the feeding window of the animals. Other studies conclude that restricting specific nutrients like protein or components of protein like methionine, not restricting total calories, has the same beneficial impact.

Finally, it could be that the positive findings in animals are simply an artifact of the terrible laboratory diets researchers normally feed them and that any reduction in this unhealthy diet will have positive effects on lab animals. That’s what this 2018 paper argues happened in the NIA and WNPRC monkey studies, concluding, “[T]hese results are better explained by a lifespan decrease in the control group because of a bad diet and/or overfeeding, rather than by a real lifespan increase in calorie-restricted animals.”

If that’s the case, there may not be much of a benefit for otherwise fit individuals currently following a healthy diet to engage in caloric restriction.

How does caloric restriction increase lifespan?

Assuming calorie restriction does work to increase longevity, we still don’t really understand how.

Partly, this is because we also don’t even really understand why we age. Any explanation for how caloric restriction makes us live longer has to fit into one of the many different aging theories out there.

But partly this is because the body is so complicated that there are many possible explanations for how reduced calorie intake could extend lifespan, some of the leading contenders include:

  • Eating less slows down our metabolic processes, so if you hold to the oxidative damage theory of aging, our body produces fewer free radicals that would otherwise be tearing up our insides and causing lasting cellular damage associated with aging.
  • When our body senses it’s not getting as much food as it needs, it starts using autophagy (“self eating”) to convert damaged proteins and parts of cells into the energy it would normally get from food. This clearing up of old damaged elements helps to keep cells healthy and functioning longer.
  • Some scientists, like Harvard’s Dr. David Sinclair, hold that the body has two main states: a “growth” state or pathway, and a “survival” pathway. When the growth pathway is active, and the body is getting lots of calories, cellular growth machinery like mTOR is only focused on building and growing, and any accumulated DNA damage or things like misfolded proteins are simply ignored. But when the survival pathway is activated by, say, caloric restriction mimicking the body being in a famine, the growth machinery is shut down, and the repair machinery is activated. This machinery includes enzymes called sirtuins that help repair DNA damage, and autophagosomes that help eat and clean up damaged organelles in cells thus maintaining health and delaying aging.

It may be the case as well that all of the above theories are true, and it’s some mix of each that actually contributes to the lifespan extension we see with caloric restriction.

How do I start a calorie restriction diet?

 First off, don’t start any diet intervention without first consulting your doctor, especially if you may have health conditions (like genetic nutrient deficiencies) or comorbidities that could make caloric restriction dangerous, or if you’re pregnant. 

The NIA does not recommend caloric restriction diets in humans since they don’t feel comfortable with the amount of scientific evidence yet.

But if you decide to start a calorie restriction diet, you can use some of these guidelines and tools to make it easier.

So long as you restrict the total calories while maintaining necessary nutrients it may not matter if you’re eating a vegan, keto, Mediterranean, or other diet. For instance, all three of the monkey studies reference above used different diets and still showed positive health results.

Additionally, results from the studies cited above seem to hold consistent across sex and age range. There may be downsides to starting too early in life, but the NIA monkey study found possible cancer-protective effects as well when started early, so your call.

There are lots and lots of great guides to starting a caloric restriction diet online, even including books written by members of the CR Society, and they all seem to recommend some combination of the below steps:

  1. Track your biomarkers: Get a baseline of your current health markers through blood tests and other measurements before you start any health routine change, and track any changes over time to make sure you’re staying within safe ranges.
  2. Use a calculator to estimate how many calories to eat/cut: Animal studies showed health benefits for anywhere between 10%-40% calorie reduction, though the biggest human trial (CALERIE) showed that just an 11%-12% reduction in calories had beneficial results, so you may not even need to cut that much. But it’s important to note that many of these percent reductions were calculated from what an already lean individual would need to eat to maintain their weight, so if you’re currently overweight, you may need to reduce your calories further than 11%-12% to see the same benefit. Several free online calculators exist to help you estimate how many calories to cut based on your total daily energy expenditure (TDEE), including: 
    1. https://www.scientificpsychic.com/health/cron1.html
    2. https://cronometer.com/
    3. https://www.niddk.nih.gov/health-information/weight-management/body-weight-planner.
    4. https://www.nal.usda.gov/fnic/calculators-and-counters
  3. Ensure adequate nutrition: Don’t be like the guy who cut off three of his fingers with an axe because he was on a 45% calorie deficit and not eating sufficient fruits and vegetables. It’s important when cutting calories that you still keep all the essential nutrients in your diet. The USDA maintains a good calculator for estimating how much of each essential macro and micro-nutrient you need to consume:
    1. https://www.nal.usda.gov/fnic/dri-calculator/
  4. Track your calories: In order to know what to cut, you need to know what you’re actually consuming, so before starting a low calorie diet, track how many calories you’re currently eating for a couple weeks. There are tons of free calorie-tracking apps out there, including the above-mentioned https://cronometer.com/.
  5. Start Slowly: In almost all the studies I went through, both animals and humans introduced caloric restriction over an extended period of time, not all at once. For instance, the WNPRC monkey study reduced calories by 10% a month for three months to get to the target 30% that they then stuck to for the rest of the trial. It may be dangerous to try to restrict calories too quickly, so most online guides recommend starting at 5% reduction or less for a few weeks or months before increasing the calorie cutting in slow stages.

How many calories do you eat in a day?

Are you currently practicing or have you practiced a calorie-restricted diet? What has your experience been? I’d love to hear from you in the comments!

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4 Comments

  1. Norma Lake Castillo

    I think that the concept of calorie restriction and its effects on longevity is much more complicated than has been investigated so far. The idea of maintaining adequate nutrition, for example, is not one universally accepted diet — different foods have different effects on health and so the same caloric restriction of a meat based diet versus a plant based diet might be expected to have differing effects on healthspan and lifespan. One must also consider the importance of the gut and other microbiomes (skin, mouth etc) to human health and longevity, and those bacterial constituents (whose DNA is at least 10 fold greater than our total human DNA) have nutritional requirements for fibre and complex carbohydrates to produce factors essential for our health:proper immune function for example. Since meat does not provide fibre, since saturated fat leads to inflammaging etcetc , since diets affect hormones that regulate so many processes,etc it will not be a straight forward reducing number of calories, but WHICH food or supplement calories, and how much of them are absorbed (since eating combinations of foods can change individual absorptions). So to me it is not surprising that the field and conclusions are conflicting and not reproducible and that what happens in worms or mice is difficult to understand when some of the complexities are unknown and even more difficult to show as relevant to humans. And then there is the diversity of humans…..

    1. J.P.

      All great points, and it should be noted that the Okinawan diet includes a lot of complex carbs high in fiber like purple sweet potatoes. That said, in animal studies at least, there seemed to be some benefit to CR regardless of the diet. Could you get even more benefit by combining CR with a healthier diet? Probably, but you should still see some health benefits almost no matter what diet you’re on.

  2. sulo

    Could it be essentially summed up that benefits are not in CR per say, but rather in maintaining healthy body composition and biomarkers?

    Because if you reduce your calories by 20% now, then you lose weight to a point where such CR is no longer CR but just maintenance calories. If you would always stay in 20% caloric deficit, you would end up dead pretty quickly.
    So in this sense, calling it caloric restriction may make it sound too scary for some people because what is essentially is, is just getting enough nutrients to maintain healthy body composition and biomarkers. Which sometimes may require increasing calories when physical demands increase too.

    For this reason I found that monitoring 1. How you feel 2. Essential biomarkers predictive of diseases in long term, are more important than tracking calories or food because that is going to change based on demands that are being put on your body.

    However, I found that doing intermitted fasting seems to help me lose weight faster even when I keep calories same, but this comes at a price: by eating too much food in too short feeding window I create gut problems with digestion and absorption of nutrients and if I don’t eat all that food in that short amount of time I have only two other options, either eat less to a point of starvation and malnutrition or to restrict my physical activity to a point where I do completely nothing all day. Neither are optimal.

    Everything has some negative side effects and consequences, for this reason I think that hedging my bets is most wise and listen to my body and switch between different modalities based on my body’s needs until I stop feeling like they are beneficial by tracking how I feel and how my biomarkers are progressing. Different times will require different tools, sometimes it is being carnivore, sometimes vegan, sometimes fasting or restricting calories and sometimes bulking up and being in surplus. This seems to be lowest risk method to me.

    1. J.P.

      Not a bad way to look at it, though I’m thinking caloric restriction, on a molecular level, likely has some effects beyond just maintaining a healthy body weight, like activating autophagy and apoptosis of senescent cells more frequently. But I do think there’s some scientific backing for what you suggest about mixing things up a bit, especially around different energy demands. I’ve also heard this more generally around things like supplementation (e.g. have off weeks where you don’t take any supplements etc.). The mTOR vs. autophagy debate would also suggest this, where there are times you want to activate mTOR and other times you want to activate AMPK to kickstart autophagy.

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