• Amy Loughman

Intermittent fasting - will your microbes be happier for it?

This week I was asked to provide some background information on intermittent fasting for a science show on the ABC, Australia's public broadcaster. It has been a couple of years since I have looked into this, so I have jumped back into the literature to find out where the evidence is now.

Here's what I learnt.


1. There are various kinds of intermittent fasting

Intermittent fasting includes alternate day fasting (skipping a whole day of eating), time-restricted eating (fasting for a period of every day, such as the 16:8 model) and religious fasts such as Ramadan. A popular recent adaptation is the 5:2 diet which has moderate caloric restriction on two days per week (25-30% of normal recommended caloric intake).

2. Fasting (of various kinds) makes animals healthier

Animal studies have shown that fasting can induce improvements across many indicators of health including metabolic function, reduced inflammation, lipid metabolism, insulin sensitivity and increased production of brain-derived neurotrophic factor.


In mice, fasting in the form of time-restricted eating can reduce the detrimental impact of an obesogenic diet, including the several of the progression of metabolic diseases.


3. The microbiome might be involved (quelle surprise!)

The microbiome is known to have a circadian rhythm, influenced by both dark/light cycles and the timing of food intake. Obesity dampens the circadian rhythms of the microbiome, and at least in mice, time-restricted eating can restore them. By the way, jet lag and shift work changes the microbiome, and promotes glucose intolerance. So there is an intimate relationship with the timing of our eating and activity, the microbiome, and metabolic health.


4. There is more evidence in metabolically unhealthy than healthy people

There are approximately 30 studies of intermittent fasting in people, almost all in fewer than 100 participants. Most of these were done in people with pre-existing conditions such as diabetes or obesity.


Meta-analysis of effects on lipid profiles (Meng et al., 2020, see below), showed that both intermittent fasting and energy restriction diets improved total and LDL cholesterol. However when you scour the forest plot to understand the effects in otherwise healthy individuals (as I was, for a healthy family member who has hereditary high cholesterol), only one of 4 studies shows a convincing effect. Energy restriction diets may be more effective, but probably not appealing if you're of normal weight since weight-loss is likely.


A relatively large human study published in JAMA Internal Medicine showed that a 16:8 protocol was no better than traditional 3-meal-per-day eating for weight-loss.


5. We couldn't recommend it on the basis of brain outcomes just yet...

I saw one study showing some improvement of diabetes-induced cognitive impairment following intermittent fasting, but not much else - at least in humans.


6. Tolerability and feasibility are important considerations

One major consideration when comparing human and animal studies is the controlled, and often extreme nature of fasting in animal studies. Far more than is likely to be well-tolerated and sustainable for the average person, or even one with spectacular will power.


The concept has strong theoretical and pre-clinical support. But is it feasible as a public health recommendation? I suppose many people make arguably greater sacrifices to improve health or reduce disease. But unless there is strong motivation and robust clinical evidence for a particular condition, I don't think we could recommend it on a large scale just yet.


TL;DR

There is great promise in the health promoting potential of various forms of fasting. Certainly animal studies show positive effects on metabolic health, neurobiology and longevity.


There is much less clinical evidence, and human studies are generally shorter and less well-controlled than animals studies. Limited evidence so far suggests the potential for reduced caloric consumption and decreased bodyweight in humans. We don't yet know why.


Fasting has and continues to form, an important part of many cultural and religious practices. This suggests that a) it has a place in the broader eating practices of humans and b) people older and wiser than myself in generations gone by have found it beneficial for body or mind. In combination with the emerging evidence, I therefore conclude that intermittent fasting is likely to be healthful, and this may be in part due to a positive impact on the gut microbiome.


Too short; give me more

Frank, J., Gupta, A., Osadchiy, V. and Mayer, E.A., 2021. Brain–Gut–Microbiome Interactions and Intermittent Fasting in Obesity. Nutrients, 13(2), p.584.


Meng, H., Zhu, L., Kord-Varkaneh, H., Santos, H.O., Tinsley, G.M. and Fu, P., 2020. Effects of intermittent fasting and energy-restricted diets on lipid profile: a systematic review and meta-analysis. Nutrition, 77, p.110801.

Vancouver


Lee JH, Verma N, Thakkar N, Yeung C, Sung HK. Intermittent fasting: physiological implications on outcomes in mice and men. Physiology. 2020 May 1;35(3):185-95.


Patterson, R.E. and Sears, D.D., 2017. Metabolic effects of intermittent fasting. Annual review of nutrition, 37.

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