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.

Highlights d Vancomycin but not amoxicillin treatment alters human gut microbiota composition d Vancomycin treatment alters short-chain fatty acid and bile acid concentrations d Modulation of adult microbiota by 7-day antibiotics does not affect host metabolism d Host metabolism remained unchanged at 8-week follow-up, despite deviant microbiota

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Calorie restriction (CR) triggers benefits for healthspan including decreased risk of cardiometabolic disease (CVD). In an ancillary study to CALERIE 2, a 24-mo 25% CR study, we assessed the cardiometabolic effects of CR in 53 healthy, nonobese (BMI: 22-28 kg/m) men ( n = 17) and women ( n = 36). The aim of this study was to investigate whether CR can reduce risk factors for CVD and insulin resistance in nonobese humans and, moreover, to assess whether improvements are exclusive to a period of weight loss or continue during weight maintenance. According to the energy balance method, the 25% CR intervention ( n = 34) produced 16.5 ± 1.5% (mean ± SE) and 14.8 ± 1.5% CR after 12 and 24 mo (M12, M24), resulting in significant weight loss (M12 -9 ± 0.5 kg, M24 -9 ± 0.5 kg, P < 0.001). Weight was maintained in the group that continued their habitual diet ad libitum (AL, n = 19). In comparison to AL, 24 mo of CR decreased visceral (-0.5 ± 0.01 kg, P < 0.0001) and subcutaneous abdominal adipose tissue (-1.9 ± 0.2kg, P < 0.001) as well as intramyocellular lipid content (-0.11 ± 0.05%, P = 0.031). Furthermore, CR decreased blood pressure (SBP -8 ± 3 mmHg, P = 0.005; DBP -6 ± 2 mmHg, P < 0.001), total cholesterol (-13.6 ± 5.3 mg/dl, P = 0.001), and LDL-cholesterol (-12.9 ± 4.4 mg/dl, P = 0.005), and the 10-yr risk of CVD-disease was reduced by 30%. Homeostasis model assessment of insulin resistance (HOMA-IR) decreased during weight loss in the CR group (-0.46 ± 0.15, P = 0.003), but this decrease was not maintained during weight maintenance (-0.11 ± 0.15, P = 0.458). In conclusion, sustained CR in healthy, nonobese individuals is beneficial in improving risk factors for cardiovascular and metabolic disease such as visceral adipose tissue mass, ectopic lipid accumulation, blood pressure, and lipid profile, whereas improvements in insulin sensitivity were only transient.

We demonstrated that 12-week EGCG+RES supplementation affected the gut microbiota composition in men but not in women. Baseline microbiota composition determined the increase in fat oxidation after EGCG+RES supplementation in men.

Twelve weeks of EGCG+RES supplementation increased mitochondrial capacity and stimulated fat oxidation compared with placebo, but this did not translate into increased tissue-specific insulin sensitivity in overweight and obese subjects. This trial was registered at clinicaltrials.gov as NCT02381145.

The prevalence of excess gestational weight gain is increasing worldwide and is associated with pregnancy complications, including gestational diabetes mellitus, pre-eclampsia, preterm birth, macrosomia, and development of obesity in offspring. Whereas gestational weight gain positively correlates with the gain in fat mass (FM), fat-free mass (FFM) gain is relatively consistent across pregnancies. Commonly used methods to assess body composition include anthropometry, densitometry (air displacement plethysmography, underwater weighing), and hydrometry (isotope dilution, bioimpedance analysis). While these techniques can be applied to pregnancy, they require specific adjustments to assumptions inherent within each method, most importantly to accommodate for the hydration of FFM which is transient throughout gestation. Here we discuss the application of the abovementioned methods to pregnant women and the relevant adjustments needed to more accurately calculate FM based on body weight, body volume, or total body water. We also present a novel application of classical data to provide FFM density estimates for pregnant women at any stage of pregnancy. Use of these adjustments will help standardize assumptions on FFM hydration and minimize error in FM estimation. Techniques still fail, however, to fully distinguish tissue gains between mother and fetus. To fill this important gap, imaging techniques such as ultrasound and magnetic resonance imaging are being used more frequently and will provide more insight into fetal development, fetal adiposity, and depot specificity of maternal FM acquisition. Efforts to synchronize protocols are necessary to allow seamless comparison of data to advance the understanding of maternal body composition changes that contribute to pregnancy-related complications.

Energy intake requirements in pregnancy match the demands of resting metabolism, physical activity, and tissue growth. Energy balance in pregnancy is, therefore, defined as energy intake equal to energy expenditure plus energy storage. A detailed understanding of these components and their changes throughout gestation can inform energy intake recommendations for minimizing the risk of poor pregnancy outcomes. Energy expenditure is the sum of resting and physical activity-related expenditure. Resting metabolic rate increases during pregnancy as a result of increased body mass, pregnancy-associated physiological changes, i.e., cardiac output, and the growing fetus. Physical activity is extremely variable between women and may change over the course of pregnancy. The requirement for energy storage depends on maternal pregravid body size. For optimal pregnancy outcomes, women with low body weight require more fat mass accumulation than women with obesity, who do not require to accumulate fat mass at all. Given the high energy density of fat mass, these differences affect energy intake requirements for a healthy pregnancy greatly. In contrast, the energy stored in fetal and placental tissues is comparable between all women and have small impact on energy requirements. Different prediction equations have been developed to quantify energy intake requirements and we provide a brief review of the strengths and weaknesses and discuss their application for healthy management of weight gain in pregnant women.