A new study was performed by scientists to explore the impact of intermittent fasting on the human body. The study was conducted by Washington University, Mater Salutis Hospital and University of Palermo, Johns Hopkins, and University of Sydney in collaboration with others. The study was a randomised control trial monitoring the various metabolic markers over a period of time in the sample population.
Introduction
Obesity is a major public health challenge which has become a greater challenge since the pandemic. Calorie restriction along with adequate nutrients intake, resulting in weight loss has shown improvement in cardiovascular performance in individuals. Inflammation and insulin sensitivity have also improved due to calorie restriction.
Intermittent fasting is a currently popular approach to calorie restriction. It involves not eating for decided intervals in hours or days. Intermittent fasting has been shown to improve several pathways of metabolic ageing such as mTOR and autophagy. It has also been found to improve metabolic health in rodents and humans. However, the results have been inconsistent in human studies.
Study Protocol
The randomised control trial was designed to determine if any beneficial metabolic effects were observed from sustained weight loss by intermittent fasting in individuals who are overweight without any chronic medical conditions. The individuals were divided into two groups. One group ate a normal western diet followed by intermittent fasting for 6 months. The other group followed intermittent fasting for the full 12 months. Intermittent fasting (IF) involved consuming only raw or cooked non-starchy vegetables on the fasting days. Depending on their body mass index (BMI), people followed a two or three non-continuous days per week routine. The study examined inflammatory factors, insulin sensitivity, glucose tolerance, body composition, cortisol concentration and other health markers in the body.
Observations
The following results were obtained from the randomised trial.
Intermittent fasting reduces body fat and weight significantly
Consistent IF decreases body fat, waist circumference, fat in trunks, body weight and BMI and lean mass. This was observed in all groups following intermittent fasting.
Intermittent fasting reduce leptin and increases adiponectin
Leptin is a hormone indicative of the amount of energy stored in fat tissues. It decreased in the IF sample. Adiponectin, a hormone found to improve insulin sensitivity, showed higher levels in blood in people.
Intermittent fasting did not improve levels of inflammation markers
To assess the effects of IF on inflammation in the body, various markers of acute inflammation (e.g. C reactive protein) and chronic inflammation (e.g. cytokines, cortisol) were measured. There was no significant reduction in the inflammatory markers in the study group. Hence this confirmed previously observed results that the positive anti-inflammatory effects of calorie restriction seen in rodents did not seem to occur in humans.
Intermittent fasting and weight loss effect on insulin sensitivity
As body fat increases, it causes increased insulin resistance leading to raised insulin levels. Long-term raised insulin in blood is responsible for diabetes, cancer, accelerated ageing and other morbidities. The study found some improvement in insulin sensitivity in the study group, however, the positive benefit of weight loss on insulin sensitivity seemed to be reversed on going back to a Western protein rich diet.
Multifactorial changes due to intermittent fasting
IF was found to improve lifespan and health in rodents. This was seen as transcription changes improving regulation of anti-ageing processes such as autophagy, mitophagy, and response to free radicals. In humans, various factors were considered and compared to assess its effects in this study. To assess the effect on molecular health, gene profiling of colon tissue of individuals was done. Blood plasma profiling was also done. These factors were correlated with other indicators such as waist size, BMI and Insulin index.
Effects of intermittent fasting on lifespan extension pathways
m-TOR autophagy and ciliary growth pathways are established pathways which enable lifespan extension. This has been demonstrated in several dietary, pharmacogenetic and genetic studies. This study found a non-linear correlation between calorie restriction and positive regulation of these pathways in reversal of ageing.
Discussion
The study, being a randomised controlled trial, was able to eliminate selection bias. The molecular and metabolic phenotypic analysis also made it a robust study. However, the number of clinical participants was small.
In spite of that, some clinically important data was collected which raises hope for the potential of intermittent fasting as a practical way of slowing ageing and improving metabolic health.
Author: Joydev Bhattacharjee
Reference
When a calorie is not a calorie: metabolic and molecular effects of intermittent fasting in humans; exploratory outcomes of a randomized clinical trial – Luigi Fontana et al - Aging Biology 2022
