Intermittent Fasting for Longevity: The Science Behind the Hype

Intermittent Fasting for Longevity: The Science Behind the Hype

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According to the International Food Information Council’s 2020 Food and Health Survey, you most likely know someone who is practicing intermittent fasting. The survey of 1,000 adult Americans found that one in ten were putting down the fork during specified periods of time, making it America’s most popular “diet.” 

It’s no surprise that the diet has charmed so many Americans. Intermittent fasting is the preferred diet of celebrities, from Kourtney Kardashian to Twitter CEO Jack Dorsey, and is reportedly a staple of Silicon Valley culture. Fox News reported that it’s “hailed by trainers [and] doctors as [an] easy weight loss program that works.” 

Of course, interest in intermittent fasting came from somewhere. From popular longevity books like James Clement’s The Switch to longevity experts like David Sinclair, Valter Longo, and Rhonda Patrick, intermittent fasting is a life-extension darling for scientists and celebrities alike.

Intermittent fasting for longevity: the science behind the hype

With all the hype, one must ask: What’s the science behind the fasting trend? What does it have to do with human life extension? And how can you get started with it if it’s right for you? 

This article aims to use the latest research to answer those questions, but first, let’s define exactly what we’re talking about. 

What is intermittent fasting for longevity?

Intermittent fasting, often shortened to “IF,” is cyclical, purposeful fasting. It’s not a “diet” so much as an eating pattern. 

Some people choose to do multi-day fasts every once in a while, while others skip a meal or two every day. Intermittent fasting does not place emphasis on calories or macros—vegans, Keto enthusiasts, and diets between the extremes all have their IF practitioners. 

The most common forms of intermittent fasting are:

  • Overnight fasting: Fast for twelve hours a day. For example, stop eating at 8:00 PM and resume eating in the morning at 8:00 AM.
  • 5:2: Made popular by The FastDiet, the 5:2 method involves eating a normal amount for five days of the week, and then eating 500 to 600 calories each day for the remaining two. 
  • Eat-Stop-Eat: Eat normally most days of the week, but completely fast for one or two 24-hour periods. 
  • Alternate-day fasting: Rotate eating normally and fasting (or restricting yourself to 500 to 600 calories) every other day (this is the method used in the famous 1957 Spanish nursing home study showing lower all-cause mortality for fasters). 
  • 16/8: Eat for eight to ten hours a day and fast for the rest. I suspect that this is the most common form of intermittent fasting, as, for many, it simply involves skipping breakfast. 
  • OMAD: OMAD, an acronym for One Meal a Day, is exactly what it sounds like: skip eating for the day until it’s time for your One Meal (which is typically at the same time each day). No snacking!

The science behind intermittent fasting

A quick search on PubMed revealed that 678 studies that include the exact phrase “intermittent fasting” have been published since 2011. A majority of them focus on weight loss

The weight loss makes sense. When you reduce the number of meals consumed, you also tend to reduce the number of calories that you eat

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But that’s not where intermittent fasting is particularly interesting. Instead, it may be that insulin regulation is the real benefit to intermittent fasting. 

Intermittent fasting and insulin regulation

When humans eat, our gut uses enzymes in our stomach to turn food into molecules in our bloodstream. The most common molecules in food are macronutrients: carbohydrates, proteins, and fats. Carbohydrates are converted into sugar. Sugar molecules called “glucose” are the major energy source for our cells. For example, if you go for a swim, muscle cells release chemical energy from glucose to power your strokes. As Dr. Monique Tello writes for Harvard’s Health Blog:

If our cells don’t use [all the available glucose], we store it in our fat cells as, well, fat. But sugar can only enter our cells with insulin, a hormone made in the pancreas. Insulin brings sugar into the fat cells and keeps it there. Between meals, as long as we don’t snack, our insulin levels will go down and our fat cells can then release their stored sugar, to be used as energy. We lose weight if we let our insulin levels go down. The entire idea of IF is to allow the insulin levels to go down far enough and for long enough that we burn off our fat.

This system is called the Carbohydrate-Insulin Model of Obesity

Intermittent fasting has been shown to reduce insulin levels, which, again, may contribute to weight control. 

Intermittent fasting and autophagy

Autophagy is another area where intermittent fasting may benefit its practitioners. Autophagy, I imagine, is way more interesting for spanners, because it’s more directly related to life extension. 

Autophagy—from Greek, “auto” meaning “self” and “phagy” meaning “to eat, devour”—is the process in which a cell consumes the parts of itself that are malfunctioning. The most well-studied form of autophagy is macroautophagy, which “delivers cytoplasmic material to lysosomes via the double-membraned autophagosome.” That’s a whole lot of jargon, so let’s simplify it. Mark’s Daily Apple likens autophagy to “cellular pruning” and Cedars-Sinai calls it cellular “recycling.” The idea is the body destroys what isn’t working to make way for new, healthy cells.

Intermittent fasting and life extension may have to do with cell autophagy
Source: Nature

Autophagy is essential to human health and is particularly critical to studying human longevity. For example, studies have shown that autophagy dysregulation is associated with:

  • Cardiovascular diseases: “Growing evidence suggests that autophagy plays a role in age-related and disease states of the cardiovascular system, and it may even be effective in preventing or treating cardiovascular disease.”
  • Alzheimer’s Disease: “There is substantial evidence that dysregulation of autophagy occurs in both AD animal models and AD patients.”
  • Muscle loss: “Altogether, these studies indicate that reduced autophagic capacity to degrade damaged contractile proteins and dysfunctional organelles likely contributes to age-related decline in myofiber function and muscle strength in mice and humans.”

While digging through the research, I was surprised to find that intermittent fasting is a possible, but not definitive, way to induce autophagy in humans. Most research has been done on animals, and those studies have been able to establish correlation, but not necessarily causality. A 2018 review of the literature concludes, “Both fasting and [caloric restriction] have a role in the upregulation of autophagy, the evidence overwhelmingly suggesting that autophagy is induced in a wide variety of tissues and organs in response to food deprivation.”

What in particular isn’t clear is just how long you have to fast to achieve autophagy. Autophagy is a naturally occurring process in humans regardless of if they’re fasting or not, so it’s difficult to control for. And as one 2017 article published in the International Journal of Molecular Sciences underscored, “Presently, there is no established method to measure autophagic flux in humans; therefore, it remains practically impossible to monitor autophagy properly in humans. Static analyses with the limitations stated above are often misleading, or can provide only suggestive results at best.”

For people interested in intermittent fasting, that presents a problem. How long do you need to fast to induce heightened autophagy? The Cut reports in their interview with nephrologist Jason Fung: “‘your body will take the oldest, junkiest proteins and burn them for energy,’ which happens ‘probably in the later stages of a long fast — somewhere around 20 to 24 hours, is my guess, and it probably maxes out somewhere around 32 hours, again is my best guess.’”

Will intermittent fasting help you live longer?

Maybe. Benefits associated with caloric restriction, insulin regulation, and autophagy suggest the answer is “yes,” with the most promising research being about the latter of the three. If cellular autophagy is protective against age-related diseases, then pursuing it seems to be a good use of your time. 

And there have been some animal studies with promising findings. 

For example, fruit flies subjected to two days fed and five days fasted over the course of a month “showed a significant reduction in age-related pathologies and improved gut barrier function” and lived substantially longer than the control. Mice fed every other day in another study lived, on average, 12% longer than mice fed every day, largely due to the delay of cancerous diseases. Another study testing mice found that a bi-monthly fasting-mimicking diet “started at middle age extended longevity, lowered visceral fat, reduced cancer incidence and skin lesions, rejuvenated the immune system, and retarded bone mineral density loss,” suggesting that intermittent fasting may extend healthspan as well.  

With that said, intermittent fasting isn’t for everyone. For some, it could even be harmful.

The science that conflicts with intermittent fasting for life extension

Autophagy research isn’t quite there yet

Because autophagy is so difficult to measure, especially in humans, studies on autophagy are often “contradictory, incomplete, or subject to alternative interpretation, leading to controversial and possibly incorrect conclusions.” While autophagy is the leading reason why intermittent fasting may extend life, it’s important to understand that there are few established knowns about the cellular process itself. Fasting is theorized to induce autophagy, but no one knows the right “dose” to achieve healthy autophagy… if there is such a thing. 

You’ll notice that I didn’t mention “cancer” in the list of things that autophagy can help with. That’s because autophagy is hardly a discerning process. A 2020 article in Frontiers in Oncology calls autophagy a “double-edged sword.” The authors write, “Early in tumorigenesis, autophagy is a tumor suppressor via degradation of potentially oncogenic molecules. However, in advanced stages, autophagy promotes the survival of tumor cells by ameliorating stress in the microenvironment.” 

In other words, autophagy may prevent tumor growth. Great! But if you already have cancer, it may incentivize that tumor to become more aggressive. While fasting is often touted as a supplement to chemotherapy, the reality is not at all so simple. 

Autophagy can also limit cutaneous wound healing

It’s important to note that most studies on autophagy in humans are acute. While there are some long-term studies on the effect of intermittent fasting on humans, those studies have trouble establishing causality. For example, in one study from Utah, researchers asked 2,001 patients undergoing cardiac catheterization a series of lifestyle questions, including whether or not they intermittently fasted. They followed up five years later and found that the intermittent fasters had lower rates of mortality. But something muddied the study: all subjects were Latter-day Saints. Their gauge of intermittent fasting was whether or not they fasted the first Sunday of every month. Was it the intermittent fasting that led them to live longer, or their heightened religiosity—especially when practicing a religion with healthier habits than the general population? 

Researchers concluded, “While the study does not show that fasting is the causal effect for better survival, these real-world outcomes in a large population do suggest that fasting may be having an effect and urge continued study of the behavior.” [Emphasis added].

Again, there’s nothing definitive here. 

Intermittent fasting can affect your brain and lead to lethargy

According to a review published in Sports Medicine in 2015, researchers observed that “Systemic inflammation can also occur in intermittent fasting through the maintenance of neurotrophic support for hippocampal neurons, which are part of a major brain structure involved in spatial learning” in athletes. In other words, intermittent fasting can make its practitioners feel disoriented and cause brain inflammation. While bodily inflammation reportedly goes down in the rest of the body with intermittent fasting, this is certainly an area that demands more research. 

Another study in the journal Nature and Science of Sleep found that current research on intermittent fasting may also negatively affect REM sleep. The authors write, “Several researchers have demonstrated a reduction in the proportion of rapid eye movement stage sleep as the significant alteration in sleep architecture during fasting.” In other words, intermittent fasting may disrupt your sleep cycle, which, in turn, may shorten your life

Intermittent fasting can be hard to stick to and may cause disordered eating

One underreported problem with intermittent fasting research is the study participation dropout rate. In one 2019 review, researchers found that participants in intermittent fasting studies dropped out at a rate as high as 40%, explicitly citing the difficulty of the diet pattern itself for the reason why. 

For many prone to eating disorders, intermittent fasting may not be a good fit. One five-year study in adolescent girls found that “fasting generally showed stronger and more consistent predictive relations to future onset of recurrent binge eating and threshold/subthreshold bulimia nervosa over 1- to 5-year follow-up relative to dietary restraint.” (I’ll add that dieticians and doctors almost universally agree intermittent fasting is probably not the best idea for children.) Another study that looked at intermittent fasting in male rats found that, “More [time] restricted access [to food] promoted greater binge-like intake and fat accumulation, whereas longer access promoted evidence of greater food reward tolerance.” 

In other words, food can become a little too special if it’s not regularly available, leading to disordered eating patterns. 

Some animal studies show neutral results

Some mice studies don't necessarily demonstrate life extension from intermittent fasting.
Source: Wikipedia

While there are many studies that show extended lifespans and healthspans in animal subjects due to intermittent fasting regimens, some findings are less than exciting. For example, one of the studies that showed extended lifespans in mice found that their overall healthspans—or time spent without disability—were unaffected. Another study that proved beneficial to male mice had “little positive effect in females.” More research is certainly needed. 

Who should avoid intermittent fasting? Who is it best for? How can you get started with IF?

 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 it dangerous, or if you’re pregnant.  

Experts warn that intermittent fasting may not be for you if… 

  • You are underweight
  • You are under 18 years old
  • You need to take medication with food

Women should also note that intermittent fasting may affect fertility, result in menstrual abnormalities, and reduce glucose tolerance. Current intermittent fasting conventions recommend that women should not fast for longer than 14 hours, but I have had difficulty finding the source of that recommendation (if you know which study that this recommendation originally comes from, let me know!). 

All that said, intermittent fasting is not necessarily a bad approach to longevity. Researchers are enthusiastic about its possibilities, and more research may prove that it’s one of the best ways to live longer. I personally think that intermittent fasting, like so many other spanning protocols, should be gauged body to body until more causal, long-term research is established. 

Seeing as most relevant studies on intermittent fasting and longevity used alternate-day fasting, my personal take is that that seems the method with the most evidence to be effective for longevity. That doesn’t mean that it’s The Best Form of Intermittent Fasting, but it does mean that it’s the chosen method for researchers. 

My experience with fasting is this: start slow. I started by simply giving myself a firm ending time for food for the day and I did that for a full month until my body got used to it. I then delayed breakfast, which I normally had at 7:30 AM, to 10:00 AM. And then I pushed breakfast back to noon. Tweak as your body adjusts—for example, one meal a day was too difficult on my body (to the point of amenorrhea), but others swear by it. There’s also research that shows that starting and ending your fast earlier in the day may be beneficial, but that kind of eating pattern (skipping dinner) can prove to be antisocial. Figure out what works for you and stick to it. 

Do you practice intermittent fasting for longevity?

Intermittent fasting is popular. Is it something that you’ve tried? Why or why not? Has it worked for you? 

Let your fellow longevity lovers know in the comments below! 


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  12. Chia-Cheng KIng

    I am a 95 years old man, have been doing 16:8 fasting for over 8 years.
    I don’t eat any food after 8PM to noon next day.
    I eat vegetables and fruits every day . eat fish, shrimp, tofu, nuts, seeds.
    I drink lots of fluid every day. I don’t eat meat and milk and soda.
    I am very healthy. I live alone. take care of myself. I drive, I shop, I cook.
    I take care of my yard and my fruit trees and flowers.
    Hope more people will do the same thing to live a long and healthy life.

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