Think fast

Can fasting be good for you? Two studies reveal how it changes the body

Here’s why the eating pattern can result in health benefits.

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Researchers studying calorie restriction and intermittent fasting agree that how we eat — or don’t eat — can affect our longevity.

Among those same researchers, however, is debate over which practice is actually responsible for the well-documented health benefits.

Studies, mostly in animals, have linked molecular, metabolic, and antiaging benefits to both calorie restriction and intermittent fasting. But it’s difficult to parse exactly why scientists are observing this, mainly because of the inherent nature of this work.

For example, calorie restriction studies in rodents typically have the animals eat once per day, rapidly consuming their food. This unintentionally results in fasting — which is more defined as an eating pattern that revolves around meal timing.

However, two recent studies both argue fasting is responsible for these help benefits more so than calorie restriction.

Scientists led by researchers from the University of Wisconsin wanted to parse the differing effects of fasting and calorie restriction. A study published Monday in Nature Metabolism found that when mice were on a specific type of fasting diet, it resulted in the most health benefits.

A different study, published last week in Nature Metabolism found that similar benefits could be achieved through a diet that “mimicked” fasting.

Valter Longo, director of the University of Southern California’s Longevity Institute and lead author of the second study, tells Inverse these conclusions are in line with the way research has been moving.

“Just reducing calories has been studied for 100 years,” Longo says, “but it’s never really gone anywhere because it doesn’t lead to too many benefits.”

What you need to know first — Intermittent fasting is less about what you eat than when you eat. There are a variety of different options, but people who practice intermittent fasting often do it one of three ways.

  • The 16:8 schedule (16 hours of fasting, then a set window of 8 hours for food and drink)
  • The 5:2 (eating normally for 5 days, fasting or eating very few calories for 2)
  • Alternate-day fasting, or periodic fasting with occasional consecutive fasting periods

Calorie restriction (CR) is more about what you eat than when. When someone is on a calorie-restricted diet, they eat fewer calories than they typically would, while still getting all the nutrients they need throughout the day.

Researchers led by scientists from the University of Wisconsin wanted to determine which diet yielded more health benefits in mice.

How the discovery was made— The scientists put three groups of male mice on different diets, all of which reduced their daily calorie intake by 30 percent for 16 weeks. Each group had different access to their food:

  • Group 1 had unlimited access to their food
  • Group 2 received food in three equal meals spaced over a 12 hour period
  • Group 3 was trained to rapidly eat all the food at once, which resulted in them fasting for the rest of the day.

Mice receiving a normal diet tailored to rodents without calorie restriction acted as controls.

What they found — The researchers found fasting was necessary for “insulin sensitivity” which the researchers explain is “a key physiological hallmark” for calorie restriction in mammals. They also found fasting increased fatty acid oxidation and reduced age-related frailty.

Further, the researchers found that “fasting improves glucose tolerance and insulin sensitivity, reduces adiposity and increases fatty acid oxidation,” all of which have been linked to health benefits and longevity. While calorie restriction was inherent in the study design, it was the fasting that spurred the positive changes.

While the authors note humans are not mice and more research needs to be done, they also say this suggests fasting is responsible for many of the health benefits often associated with calorie-restricted diets.

One of the challenges with translating those results to humans, says Longo, who didn’t work on the study but describes it as “elegant,” is that humans have a much harder time only eating once per day than rodents in a lab who are forced to only eat once per day.

That’s why Longo wanted to study the effect of a fasting-mimicking diet to see if the known benefits of fasting could be achieved in a way humans were more likely to adhere to.

What is a fasting-mimicking diet?— In contrast to a calorie-restricted diet, which simply reduces the number of calories consumed, a fasting-mimicking diet, Longo explains, is much more carefully calibrated.

A fasting-mimicking diet (FMD) is a low-calorie, low-sugar, low-protein diet with high, good fats. This diet is administered for four to five days and “mimics” the conditions the body experiences when fasting. In 2017, Longo published a study suggesting people who followed an FDM diet for five days per month for three months of an otherwise unrestricted diet could reverse many of the negative health effects of that largely unhealthy diet.

In his most recent study, published last week in Nature Metabolism, Longo wanted to see the effect of a monthly FMD over a longer period of time.

What they discovered — For five days a month over the course of two years, Longo and his colleagues administered an FMD diet to female mice. For the approximately 25 days the mice were not on the FMD diet, they were fed a high fat, high-calorie diet (HFCD).

The researchers found that five days of an FMD diet inhibited the obesity that would have resulted from the HFCD. It did so, the researchers explain, by “reducing the accumulation of visceral and subcutaneous fat without causing loss of lean body mass.”

Longo and colleagues also found the FMD cycles increased “cardiac vascularity and function and resistance to cardiotoxins” while protecting against high cholesterol levels and benefiting insulin and glucose tolerance.

These promising results, Longo says, suggest following this eating pattern can result in many of the health benefits typically seen in fasting studies. Furthermore, people are more likely to actually adhere to it.

“If you fast every day for 21 hours, yes, you might get lots of benefits,” Longo says, “but you’re going to get a compliance of probably less than 1 percent.”

Taken together, the two studies make a case for forms of fasting over just following a calorie-restricted diet. This is especially true for the FMD study: A monthly 5-day course of FMD may result in the same health benefits one would get from fasting, without the associated malnutrition or rates of non-compliance.

While forms of fasting do appear capable of stimulating advantages, it’s also a way of eating that comes with psychological risks. Before you change the way you eat, you should talk to your doctor first.

Abstract: Calorie restriction (CR) promotes healthy aging in diverse species. Recently, it has been shown that fasting for a portion of each day has metabolic benefits and promotes lifespan. These findings complicate the interpretation of rodent CR studies, in which animals typically eat only once per day and rapidly consume their food, which collaterally imposes fasting. Here we show that a prolonged fast is necessary for key metabolic, molecular and geroprotective effects of a CR diet. Using a series of feeding regimens, we dissect the effects of calories and fasting, and proceed to demonstrate that fasting alone recapitulates many of the physiological and molecular effects of CR. Our results shed new light on how both when and how much we eat regulate metabolic health and longevity, and demonstrate that daily prolonged fasting, and not solely reduced caloric intake, is likely responsible for the metabolic and geroprotective benefits of a CR diet.
Abstract: Diet-induced obesity is a major risk factor for metabolic syndrome, diabetes and cardiovascular disease. Here, we show that a 5-d fasting-mimicking diet (FMD), administered every 4 weeks for a period of 2 years, ameliorates the detrimental changes caused by consumption of a high-fat, high-calorie diet (HFCD) in female mice. We demonstrate that monthly FMD cycles inhibit HFCD-mediated obesity by reducing the accumulation of visceral and subcutaneous fat without causing loss of lean body mass. FMD cycles increase cardiac vascularity and function and resistance to cardiotoxins, prevent HFCD-dependent hyperglycaemia, hypercholesterolaemia and hyperleptinaemia and ameliorate impaired glucose and insulin tolerance. The effect of monthly FMD cycles on gene expression associated with mitochondrial metabolism and biogenesis in adipocytes and the sustained ketogenesis in HFCD-fed mice indicate a role for fat cell reprogramming in obesity prevention. These effects of an FMD on adiposity and cardiac ageing could explain the protection from HFCD-dependent early mortality.
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