New research suggests that moderate calorie restriction in humans has benefits beyond weight loss. In a two-year study researchers saw improved immune function and T cell production, and reduction in inflammation, in participants who reduced calories by approximately 14%.
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Caloric restriction (CR) has been an important topic in aging and longevity research for many years. We’ve learned from studies on many types of animals – from flies to mice to nonhuman primates – that moderate CR without malnutrition prolongs lifespan, slows biological aging, and delays the development of chronic diseases.1,2
More recent research has tried to understand the biology behind the beneficial, longevity-promoting effects of CR, and how it could be used to improve human health. The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial was the first CR trial conducted in healthy humans. Participants in the CR group were instructed to reduce calorie intake moderately (a goal of 20%) for two years.3
Previous results from the CALERIE trial suggested moderate CR reduced fat mass, improved insulin sensitivity, reduced inflammatory markers, and improved cardiovascular risk biomarkers.1,4-7
A new study from the CALERIE trial investigated immune function and gene expression in fat tissue in participants who restricted calories by an average of 14% for 2 years.3
Aging and Caloric Restriction Research: A Biological Perspective With Translational Potential
Caloric restriction in humans reveals immunometabolic regulators of health span
A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity
Calorie restriction enhances T-cell-mediated immune response in adult overweight men and women
Body-composition changes in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE)-2 study: a 2-y randomized controlled trial of calorie restriction in nonobese humans
2 years of calorie restriction and cardiometabolic risk (CALERIE): exploratory outcomes of a multicentre, phase 2, randomised controlled trial
Some research in animals had suggested that CR could impair immunity. However, these studies usually reduced calories more dramatically, by about 40%. These animals lived longer, on average, than control animals but were more susceptible to infection. This suggests that 40% calorie reduction led to insufficient resources for the immune system. Moderate CR of 14%, however, in the CALERIE trial, showed signs of improved immune function in the newly published study.
The researchers chose to analyze the thymus, where T cells (a subset of immune cells) mature, in CALERIE participants because aging of the thymus begins earlier than other organs. Starting in middle age, the thymus begins to shrink, accumulate fat, and release fewer T cells, reducing our capacity for immune surveillance.1
Using MRI and indicators of T cell abundance in the blood, the researchers determined that the thymus glands in the CR participants were larger, less fatty, and were releasing more T cells after two years than they were at the beginning of the study, whereas the control group showed no change.
Since excess fat tissue drives inflammation and inflammation drives aging, the researchers also investigated gene expression in adipose (fat) tissue at baseline, one year, and two years of caloric restriction. They found increases in the expression of 233 genes, and decreases in 131. Several of the largest gene expression changes were indicative of a lower level of inflammation.
They focused on one particular gene: platelet activating factor acetylhydrolase (PLA2G7), whose expression was decreased in response to CR. Little is known about PLA2G7 so far. However, higher circulating levels of PLA2G7 have been linked to inflammation-related diseases, such as cardiovascular disease, autoimmune disease, and type 2 diabetes.1 They investigated PLA2G7 further by deleting the gene in mice, and found lower circulating proinflammatory cytokines, reduced inflammation in fat tissue, limited weight gain, and maintenance of the volume of the thymus compared to control animals. These results are consistent with improved immune health and lower inflammation, and were similar to the results in humans under moderate CR, suggesting PLA2G7 is an important gene underlying benefits of CR.
Overall, the findings from this study suggest that moderate caloric restriction alters gene expression to promote immune function and reduce inflammation, strengthening the evidence that moderate caloric restriction in the context of micronutrient excellence extends lifespan. A Nutritarian diet is unique in that it pays attention to comprehensive micronutrient adequacy using a wide variety of nutrient-rich foods, with the judicious use of supplements (such as DHA and EPA, B12, K2, zinc, and iodine) to prevent any insufficiencies from reducing or eliminating animal products. This Nutritarian approach lowers the instinctual drive for calories, allowing people to be satisfied with fewer calories and enjoy eating more.