Calorie restriction in humans: An update

Abstract

Calorie restriction (CR), a nutritional intervention of reduced energy intake but with adequate nutrition, has been shown to extend healthspan and lifespan in rodent and primate models. Accumulating data from observational and randomized clinical trials indicate that CR in humans results in some of the same metabolic and molecular adaptations that have been shown to improve health and retard the accumulation of molecular damage in animal models of longevity. In particular, moderate CR in humans ameliorates multiple metabolic and hormonal factors that are implicated in the pathogenesis of type 2 diabetes, cardiovascular diseases, and cancer, the leading causes of morbidity, disability and mortality. In this paper, we will discuss the effects of CR in non-obese humans on these physiological parameters. Special emphasis is committed to recent clinical intervention trials that have investigated the feasibility and effects of CR in young and middle-aged men and women on parameters of energy metabolism and metabolic risk factors of age-associated disease in great detail. Additionally, data from individuals who are either naturally exposed to CR or those who are self-practicing this dietary intervention allows us to speculate on longer-term effects of more severe CR in humans.

Intestinal invalidation of the glucose transporter GLUT2 delays tissue distribution of glucose and reveals an unexpected role in gut homeostasis

“…It has been reported that intestinal regulatory function of GLUT2 could be compensated by a ketogenic diet (frequent boluses of slowly absorbed carbohydrates, such as uncooked cornstarch). Caloric restriction without malnutrition is indeed characterized by ketosis and a slow-down of biological processes such as body weight gain, glucose metabolism [15], and gut inflammation [17], [18], [19] as well as decreased microvillus length [20]. Here, the doubling of plasma ketone body β-hydroxybutyrate in GLUT2 ΔIEC mice as a sign of a glucose restriction for tissue, could be attributed to delayed glucose delivery to tissues due to intestinal GLUT2 depletion.…”

The effects of graded caloric restriction: XII. Comparison of mouse to human impact on cellular senescence in the colon

“…To this end, we recruited and studied 12 middle‐aged (61.7 ± 8.4 years), weight‐stable very lean (BMI = 19.1 ± 1.3 kg/m 2 ) members of the Calorie Restriction Society who have been practicing ~30% CR with adequate nutrition (at least 100% of RDI for each nutrient) for an average of 10.1 years (Most, Tosti, Redman & Fontana, 2017; Yang et al., 2016) and a control group of 12 nonobese (BMI = 27.4 ± 2.5 kg/m 2 ) age‐matched sedentary controls eating a typical Western diet (WD‐o; Figure 2a). Furthermore, we compared the CR and WD‐o groups with younger (24.3 ± 2.0 years, range 21–27 years) nonobese (BMI = 25.7 ± 0.9 kg/m 2 ) humans (WD‐y).…”

Effects of Aging in Dry Eye

“…For a detailed review about CR inclusive of NIH-sponsored CALERIE ( C omprehensive A ssessment of L ong-term E ffects of R educing I ntake of E nergy) clinical trial in humans, please see the review by Most and colleagues. 197 In ophthalmology, CR has been shown to substantially decrease infiltration of submandibular glands in aged autoimmune mice prone mice. 198 This was accompanied by a significant decrease in inflammatory mediators such as TNF-α and IL-6 while an increase in TGF-β1 was noted.…”