Stacking up the claims against the research

In animal studies, calorie restriction does increase autophagy. And in humans, chronic calorie restriction without malnutrition can have a powerful anti-inflammatory effect.

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But, just because something works in animals, doesn’t mean it works in humans. And just because there is an effect from calorie restriction, doesn’t mean a more extreme form of fasting will enhance the effect. Calorie restriction and intermittent fasting typically involve reducing energy intake by about 20 per cent, not removing nutrients altogether.

“[Prolonged fasting is] a completely different metabolic and physiological state,” says Professor Luigi Fontana, director of the Healthy Longevity Research Group at the University of Sydney.

Of fasting, he says: “There’s a lot of wishful thinking and inaccurate conclusions. News and socials are loaded with partial truths and misinformation.”

Now, researchers are interested in better understanding the effects.

Surprising findings

For a new study, published in Molecular Metabolism, Fontana and his team sought to test the biological effects of prolonged fasting (defined as four or more days) with the hypothesis that it would reduce markers of inflammation.

Twenty volunteers were examined before, during and after a water-only fast, and contrary to the hypothesis, the researchers found prolonged fasting led to increased inflammation and a prothrombotic environment, which can increase the likelihood of blood clots in at-risk people.

The effects were transient and participants returned to normal when they began eating again.

“I don’t understand why the body is reacting that way,” Fontana says.

He speculates that it may be the result of lipolysis, which is the metabolic process of breaking down triglycerides into free fatty acids and glycerol to fuel the body during fasting or intense exercise. He says that perhaps during this process the liver is being flooded with excess fat or the toxins stored in the fat, leading to inflammation.

It may also be due to a stress response. “Indeed, we see a huge increase in cortisol,” says Fontana. “The body perceives fasting as a stressful condition.”

For people with a high risk of thrombosis or unstable plaque, Fontana says: “Even a bout of inflammation and prothrombosis could potentially lead to a major event.”

Associate Professor Tim Sargeant, a cell biologist at the South Australian Health and Medical Research Institute who was not involved with this study, was surprised by the findings.

“In popular culture, fasting is seen as a way to reduce something like this,” Sargeant says. “I think what Luigi has shown is that an intervention of this magnitude is more complex than what people realise.”

In January, 34-year-old athlete Lachlan Clancy completed a three-day water fast in which he consumed nothing but four litres of water a day.

Clancy, inspired by Gary Brecka’s podcasts on water fasting, did it as a mental challenge and to activate a gut reset. There is some evidence that fasting triggers changes in the gut microbiome, but those changes don’t last.

He also hoped it would kickstart autophagy: “For me, longevity is quite a big one.”

This was the second time he had done such a fast, and by day three, he says, he felt energised and clear. He would not, however, fast several weeks before a Hyrox fitness competition as he did this time: “I didn’t quite appreciate the stress it puts on your body.”

Water fasting: A complex reality

Royal Australian College of General Practitioners obesity management chair Dr Terri-Lynne South says the biological changes of fasting are intriguing and may hold promising health benefits.

“In practice, fasting interventions are often short-term, and the biological changes they induce typically revert to baseline once regular eating patterns are resumed,” she says.

South advises medical supervision for anyone considering a prolonged fast, reminding that risks increase in likelihood and severity with the duration of a fast.

“Ensuring safety and adherence can also become more challenging as fasting periods lengthen,” she says.

For his part, Fontana says he isn’t against fasting. “I’m agnostic,” he says, adding that if researchers can prove it increases autophagy, then there will be a demonstrable benefit.

“The message is, be careful” he says. “Fasting is not for everyone. It does cause a pro-inflammatory, prothrombotic response.”

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