A lifetime of change: Measurements of total and basal energy in a large cohort of subjects at ages spanning from before birth to old age document distinct changes that occur during a human lifetime. Pontzer et al . report that energy expenditure (adjusted for weight) in neonates was like that of adults but increased substantially in the first year of life (see the Perspective by Rhoads and Anderson). It then gradually declined until young individuals reached adult characteristics, which were maintained from age 20 to 60 years. Older individuals showed reduced energy expenditure. Tissue metabolism thus appears not to be constant but rather to undergo transitions at critical junctures. —LBR

The potential endocrine-disrupting effects of perfluoroalkyl substances (PFASs) have been demonstrated in animal studies, but whether PFASs may interfere with body weight regulation in humans is largely unknown. This study aimed to examine the associations of PFAS exposure with changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting. In the 2-year POUNDS Lost randomized clinical trial based in Boston, Massachusetts, and Baton Rouge, Louisiana, that examined the effects of energy-restricted diets on weight changes, baseline plasma concentrations of major PFASs were measured among 621 overweight and obese participants aged 30–70 years. Body weight was measured at baseline and 6, 12, 18, and 24 months. RMR and other metabolic parameters, including glucose, lipids, thyroid hormones, and leptin, were measured at baseline and 6 and 24 months. Participants lost an average of 6.4 kg of body weight during the first 6 months (weight-loss period) and subsequently regained an average of 2.7 kg of body weight during the period of 6–24 months (weight regain period). After multivariate adjustment, baseline PFAS concentrations were not significantly associated with concurrent body weight or weight loss during the first 6 months. In contrast, higher baseline levels of PFASs were significantly associated with a greater weight regain, primarily in women. In women, comparing the highest to the lowest tertiles of PFAS concentrations, the multivariate-adjusted mean weight regain (SE) was 4.0 (0.8) versus 2.1 (0.9) kg for perfluorooctanesulfonic acid (PFOS) (P_trend = 0.01); 4.3 (0.9) versus 2.2 (0.8) kg for perfluorooctanoic acid (PFOA) (P_trend = 0.007); 4.7 (0.9) versus 2.5 (0.9) kg for perfluorononanoic acid (PFNA) (P_trend = 0.006); 4.9 (0.9) versus 2.7 (0.8) kg for perfluorohexanesulfonic acid (PFHxS) (P_trend = 0.009); and 4.2 (0.8) versus 2.5 (0.9) kg for perfluorodecanoic acid (PFDA) (P_trend = 0.03). When further adjusted for changes in body weight or thyroid hormones during the first 6 months, results remained similar. Moreover, higher baseline plasma PFAS concentrations, especially for PFOS and PFNA, were significantly associated with greater decline in RMR during the weight-loss period and less increase in RMR during the weight regain period in both men and women. Limitations of the study include the possibility of unmeasured or residual confounding by socioeconomic and psychosocial factors, as well as possible relapse to the usual diet prior to randomization, which could have been rich in foods contaminated by PFASs through food packaging and also dense in energy. In this diet-induced weight-loss trial, higher baseline plasma PFAS concentrations were associated with a greater weight regain, especially in women, possibly explained by a slower regression of RMR levels. These data illustrate a potential novel pathway through which PFASs interfere with human body weight regulation and metabolism. The possible impact of environmental chemicals on the obesity epidemic therefore deserves attention. ClinicalTrials.gov NCT00072995

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO2 over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies.

Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures^1–3. This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response–energy compensation. We used the largest dataset compiled on adult TEE and BEE (N = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translate into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body composition. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity.

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lacks access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5604 people from the ages of 8 days to 96 years from 23 countries using isotope-tracking ( ² H) methods. Age, body size, and composition were significantly associated with WT, as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People who lived in countries with a low human development index (HDI) had higher WT than people in high-HDI countries. On the basis of this extensive dataset, we provide equations to predict human WT in relation to anthropometric, economic, and environmental factors.

Exercise is recommended for weight management, yet exercise produces less weight loss than expected, which is called weight compensation. The mechanisms for weight compensation are unclear. The aim of this study was to identify the mechanisms responsible for compensation. In a randomized controlled trial conducted at an academic research center, adults (n = 198) with overweight or obesity were randomized for 24 wk to a no-exercise control group or 1 of 2 supervised exercise groups: 8 kcal/kg of body weight/wk (KKW) or 20 KKW. Outcome assessment occurred at weeks 0 and 24. Energy intake, activity, and resting metabolic rate (RMR) were measured with doubly labeled water (DLW; with and without adjustments for change in RMR), armband accelerometers, and indirect calorimetry, respectively. Appetite and compensatory health beliefs were measured by self-report. A per-protocol analysis included 171 participants (72.5% women; mean ± SD baseline body mass index: 31.5 ± 4.7 kg/m²). Significant (P < 0.01) compensation occurred in the 8 KKW (mean: 1.5 kg; 95% CI: 0.9, 2.2 kg) and 20 KKW (mean: 2.7 kg; 95% CI: 2.0, 3.5 kg) groups, and compensation differed significantly between the exercise groups (P = 0.01). Energy intake by adjusted DLW increased significantly (P < 0.05) in the 8 KKW (mean: 90.7 kcal/d; 95% CI: 35.1, 146.4 kcal/d) and 20 KKW (mean: 123.6 kcal/d; 95% CI: 64.5, 182.7 kcal/d) groups compared with control (mean: −2.3 kcal/d; 95% CI: −58.0, 53.5 kcal/d). Results were similar without DLW adjustment. RMR and physical activity (excluding structured exercise) did not differentially change among the 3 groups. Participants with higher compared with lower compensation reported increased appetite ratings and beliefs that healthy behaviors can compensate for unhealthy behaviors. Furthermore, they increased craving for sweet foods, increased sleep disturbance, and had worsening bodily pain. Compensation resulted from increased energy intake and concomitant increases in appetite, which can be treated with dietary or pharmacological interventions. Compensation was not due to activity or metabolic changes. This trial was registered at clinicaltrials.gov as NCT01264406.