What are the effects of calorie restriction in men?

Animal studies show that calorie restriction, or eating fewer calories, generally results in increased longevity and a lower incidence of chronic diseases like cancer. Researchers are conducting studies to find out if such effects exist in humans. Here are the lessons from a recent study.

The CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) clinical trial is the first controlled study of calorie restriction in healthy humans. She has delivered several lessons, comparing in certain cases the effects of calorie restriction alone and those of calorie restriction accompanied by physical exercise.

Calorie restriction beneficial for immunity and inflammation

For the purposes of a study published in February 2022, researchers first established baseline calorie intake among more than 200 participants. The researchers then asked a portion of these participants to reduce their calorie intake by 14% while the others continued to eat as usual. The health effects of calorie restriction were evaluated over the next two years.

The researchers particularly examined the effects on inflammation and immunity. The thymus is a gland found in the thorax; it is the site of the production of T lymphocytes, a type of white blood cell of the immune system. The thymus ages more quickly than other organs; it gradually becomes loaded with fat. Thus, around the age of 40, 70% of the thymus is no longer functional, which means not only that it produces fewer T lymphocytes, but that these cells are less effective in fighting infections. But the researchers found that the thymuses of calorie-restricted participants had less fat and greater functional volume after two years of calorie restriction, meaning they produced more T cells than at the start of the study. The volunteers who did not restrict their calories, however, experienced no change. “The fact that this organ can be rejuvenated is, in my opinion, astounding because there is very little evidence that this is the case in humans“, comments Dr Vishwa Deep Dixit, lead author of the study. “That this is possible is very exciting..”

Researchers also looked at body fat because it is the site of an important immune system. There are several types of immune cells in fat that, when aberrantly activated, become a source of inflammation. “We found remarkable changes in adipose tissue gene expression after one year that were maintained until the second year“, says Dr. Dixit. “This revealed unique targets mimicking calorie restriction that can improve the metabolic and anti-inflammatory response in humans.”

The researchers notably identified the PLA2G7 gene – which codes for an enzyme, platelet activating factor acetyl hydrolase or Lp-PLA2. Several studies suggest that Lp-PLA2 may contribute to atherosclerosis and certain cancers, such as prostate cancer. It is an enzyme produced by immune cells called macrophages. To find out if the PLA2G7 gene is at the origin of Some of the effects observed with calorie restriction, researchers reduced the expression of this gene in mice: it produced benefits similar to those observed with calorie restriction in humans. Specifically, the thymus glands of these mice were functional for longer, the mice were protected from diet-induced weight gain and age-related inflammation. This is because the PLA2G7 gene targets a specific mechanism of inflammation called the NLRP3 inflammasome, which is involved in many inflammatory processes. Decreasing PLA2G7 expression protected aged mice from inflammation. “These results demonstrate that PLA2G7 is one of the drivers of the effects of calorie restrictionsaid Dixit, which can point us to potential targets that could improve immune function, reduce inflammation, and even improve healthy lifespan.”

Calorie restriction (with physical exercise) significantly loses weight, reduces cardiovascular risk, protects DNA

In a branch of the CALERIE study, researchers recruited 36 volunteers whom they divided into three groups (2). The former received a daily caloric intake reduced by 25%, the latter received a caloric intake reduced by only 12.5% ​​but at the same time had to practice physical activity increasing their expenditure by 12.5%. The last group served as a control group. At the end of 6 months of follow-up, the weight loss was similar in the two groups of volunteers who saw their body weight decrease by approximately 10%.

The researchers sought to monitor markers of cardiovascular risk in volunteers who restricted calories alone and in those who practiced a less severe reduction accompanied by exercise. Result: volunteers in the restriction only and restriction plus exercise groups showed a drop in trglyceride levels, a reduction in diastolic blood pressure and an increase in the level of “good” HDL cholesterol. The researchers estimate the overall reduction in the risk of developing cardiovascular disease at 29% for the calorie restriction group and 38% for the calorie restriction plus sport group.

To compare the effects of calorie restriction and physical exercise on the oxidation of DNA (support of the genetic code) and RNA, Doctor Luigi Fontana, specialist in work on calorie restriction and his colleagues recruited 18 men and women. (3) The volunteers were divided into two groups, one reduced their calorie intake by 20%, the other having increased their expenditure by 20% thanks to exercise. The energy deficit was similar in both groups of volunteers. The researchers then measured the damage produced by oxidative stress on DNA and RNA. Result: for DNA, oxidative damage decreased by 48.5% for the calorie restriction group and by 49.6% for the physical exercise group. Same observation for RNA: 35.7% less damage with calorie restriction and 52.1% with physical activity. The researchers conclude that these two methods give similar results in terms of protecting DNA and RNA.

Furthermore, animal studies have found that physical exercise has the same beneficial effects on tumor growth and cancer risk as calorie restriction.

Side effects of calorie restriction

Calorie restriction at the levels practiced in CALERIE has been shown to be safe and generally well tolerated. It did not significantly affect the circulating levels of growth factors, in particular IGF-1, a growth hormone mediator, involved in several processes linked to aging and certain cancers. However, calorie restriction significantly increased circulating levels of proteins that bind IGF-1, which could have favorable consequences for cancer risk, but also less favorable consequences for muscle and bone. In fact, the researchers noted a slight decrease in bone mineral density in the volunteers, but not beyond the changes linked to the weight loss observed.