Intermittent Fasting Versus Calorie Restriction: Which Method Reaps Greatest Rewards?

What is calorie restriction (CR) as a diet plan versus intermittent fasting? The basic premise of CR is that a person consumes no more than a certain number of total calories in any give day but not below a level that would lead to malnutrition, nor to a restriction in essential nutrients. Conversely, intermittent fasting does not necessarily limit total calorie intake, these diets restrict when and how often an individual consumes food.

The potential benefits of CR were originally identified in non-mammalian organisms such as fruit flies (Drosophila melanogaster) and a particular round worm, a nematode (Caenorhabditis elegans). In these organisms CR resulted in significant life extension, hence the potential benefits to this type of diet in humans. However, as yet the longevity benefits of CR have not been as robust as in the non-mammalian organisms. Numerous experiments in laboratory mammals have suggested that CR does indeed contribute to significant health benefits.

The term "intermittent fasting" can potentially be used to describe many different types of dieting but in the clinical setting this type of dieting generally refers to three main forms. These three forms are alternate day fasting (ADF), time-restricted eating (TRE; or time-restricted feeding, TRF) and the 5:2 diet.

Alternate day fasting, as the name implies, involves eating one day and fasting the next, repeating over and over. In some examples of ADF diets the fasting day involves only the consumption of water, referred to as a zero calorie alternate day. There are some versions of ADF that involve consuming calories on the fast day but only up to 25% of caloric need. This latter version of ADF is referred to as modified alternate day fasting. Evidence has shown that individuals who consume this 25% or less calorie restriction all at once or throughout the day with no differences in weight loss. Therefore, the method of choice is often whichever works best for the individual. On the days of eating in the ADF diet there are no caloric restrictions.

The distinction of the time restricted eating (TRE) diet plan is that individuals are restricted to eating at specific times during the day. The eating time frame is usually four to eight hours with the remaining time spent drinking only water or zero calorie fluids. In most successful forms of the TRE consuming calories is restricted to be accomplished prior to 4pm to 6pm.

It is important to point out that although studies in mice and rats are excellent measures of health implications in humans there are limitations. Nonetheless, numerous diet-based studies performed in mice show equivalent benefits in humans in side-by-side statistical comparisons.

A recent study published in the prestigious journal, Cell Metabolism, has found that calorie restriction (CR) reaps superior benefits, related to health and longevity, when compared to time restricted fasting (TRF) or ad libitum eating (meaning as much or as often as desired):

Prolonged fasting times reap greater geroprotective effects when combined with caloric restriction in adult female mice

Of significance to humans and dieting, this study found that older females on a TRE (TRF) diet were hyperphagic, meaning they ate more during the periods when food was provided, and they did not maintain body weight efficiently. In addition the CR diet provided protective benefits at the level of cancer and the severity of inflammatory diseases in the lungs.

The older mice in this study were 60 weeks old which is the equivalent of around 47 to 50 years of age for a human and the study was carried out over a period of 80 weeks which would be through the equivalent of a human of 105 years of age.

When the metabolic profiles of the CR versus TRF mice were compared there were statistically significant differences. The mice on the CR diet had increased serum levels of bile acids, dicarboxylic acids, saturate and unsaturated fatty acids, and acylcarnitines which are lipids that are associated with the expression and activity of energy-related metabolic pathways. Conversely, the TRF mice showed increased serum levels of glycerophospholipids, monoacylglycerols, and ceramides, classes of lipids associated with a decrease in insulin sensitivity. Comparisons of additional physiological and metabolic signatures showed a differential and beneficial systemic impact of CR compared to TRF.

TAKE HOME: The benefits of consuming the proper amount of calories as well as the composition of those calories has been well documented in numerous randomized controlled trials (RCT) in humans. Correlation of data obtained in mice, with respect to calorie restriction and intermittent fasting is of significant utility in the context of human health and longevity and this most recent work strongly indicates that reduced caloric intake is superior to diets that consist of various forms of intermittent fasting.

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