Effect of exogenous and endogenous ketones on respiratory exchange ratio and glucose metabolism in healthy subjects.

This study examined the effect of exogenous ketone bodies (KB) on oxygen consumption (V̇o2), carbon dioxide production (V̇co2), and glucose metabolism. The data were compared with the effects of endogenous ketonemia during both, a ketogenic diet or fasting. Eight healthy individuals [24.1 ± 2.5 yr, body mass index (BMI) 24.3 ± 3.1 kg/m2] participated in a crossover intervention study and were studied in a whole-room indirect calorimeter (WRIC) to assess macronutrient oxidation following four 24-h interventions: isocaloric controlled mixed diet (ISO), ISO supplemented with ketone salts (38.7 g of ß-hydroxybutyrate/day, EXO), isocaloric ketogenic diet (KETO), and total fasting (FAST). A physical activity level of 1.65 was obtained. In addition to plasma KB, 24-h C-peptide and KB excretion rates in the urine and postprandial glucose and insulin levels were measured. Although 24-h KB excretion increased in response to KETO and FAST, there was a modest increase in response to EXO only (P < 0.05). When compared with ISO, V̇o2 significantly increased in KETO (P < 0.01) and EXO (P < 0.001), whereas there was no difference in FAST. V̇co2 increased in EXO but decreased in KETO (both P < 0.01) and FAST (P < 0.001), resulting in 24-h respiratory exchange ratios (RER) of 0.828 ± 0.024 (ISO) and 0.811 ± 0.024 (EXO) (P < 0.05). In response to EXO there were no differences in basal and postprandial glucose and insulin levels, as well as in insulin sensitivity. When compared with ISO, EXO, and KETO, FAST increased homeostatic model assessment ß-cell function (HOMA-B) (all P < 0.05). In conclusion, at energy balance exogenous ketone salts decreased respiratory exchange ratio without affecting glucose tolerance.NEW & NOTEWORTHY Our findings revealed that during isocaloric nutrition, additional exogenous ketone salts increased V̇o2 and V̇co2 while lowering the respiratory exchange ratio (RER). Ketone salts had no effect on postprandial glucose metabolism.

Impact of energy turnover on fat balance in healthy young men during energy balance, energetic restriction and overfeeding.

Body weight control is thought to be improved when physical activity and energy intake are both high (high energy turnover (ET)). The aim of the present study was to investigate the short-term impact of ET on fat balance during zero energy balance (EB), energetic restriction (ER) and overfeeding (OF). In a randomised crossover study, nine healthy men (BMI: 23·0 (SD 2·1) kg/m2, 26·6 (SD 3·5) years) passed 3 × 3 d in a metabolic chamber: three levels of ET (low, medium and high; physical activity level = 1·3-1·4, 1·5-1·6 and 1·7-1·8) were performed at zero EB, ER and OF (100, 75 and 125 % of individual energy requirement). Different levels of ET were obtained by walking (4 km/h) on a treadmill (0, 165 and 330 min). Twenty-four-hour macronutrient oxidation and relative macronutrient balance (oxidation relative to intake) was calculated, and NEFA, 24-h insulin and catecholamine secretion were analysed as determinants of fat oxidation. During EB and OF, 24-h fat oxidation increased with higher ET. This resulted in a higher relative fat balance at medium ET (EB: +17 %, OF: +14 %) and high ET (EB: +23 %, OF: +17 %) compared with low ET (all P < 0·05). In contrast, ER led to a stimulation of 24-h fat oxidation irrespective of ET (no differences in relative fat balance between ET levels, P > 0·05). In conclusion, under highly controlled conditions, a higher ET improved relative fat balance in young healthy men during OF and EB compared with a sedentary state.

The case of GWAS of obesity: does body weight control play by the rules?

As yet, genome-wide association studies (GWAS) have not added much to our understanding of the mechanisms of body weight control and of the etiology of obesity. This shortcoming is widely attributed to the complexity of the issues. The appeal of this explanation notwithstanding, we surmise that (i) an oversimplification of the phenotype (namely by the use of crude anthropometric traits) and (ii) a lack of sound concepts of body weight control and, thus, a lack of a clear research focus have impeded better insights most. The idea of searching for polygenetic mechanisms underlying common forms of obesity was born out of the impressive findings made for monogenetic forms of extreme obesity. In the case of common obesity, however, observational studies on normal weight and overweight subjects never provided any strong evidence for a tight internal control of body weight. In addition, empirical studies of weight changes in normal weight and overweight subjects revealed an intra-individual variance that was similar to inter-individual variance suggesting the absence of tight control of body weight. Not least, this lack of coerciveness is reflected by the present obesity epidemic. Finally, data on detailed body composition highlight that body weight is too heterogeneous a phenotype to be controlled as a single entity. In summary GWAS of obesity using crude anthropometric traits have likely been misled by popular heritability estimates that may have been inflated in the first place. To facilitate more robust and useful insights into the mechanisms of internal control of human body weight and, consequently, the genetic basis of obesity, we argue in favor of a broad discussion between scientists from the areas of integrative physiologic and of genomics. This discussion should aim at better conceived studies employing biologically more meaningful phenotypes based on in depth body composition analysis. To advance the scientific community-including the editors of our top journals-needs a re-launch of future GWAS of obesity.

Validating the use of bioimpedance spectroscopy for assessment of fluid status in children.

BACKGROUND: Bioimpedance spectroscopy (BIS) with a whole-body model to distinguish excess fluid from major body tissue hydration can provide objective assessment of fluid status. BIS is integrated into the Body Composition Monitor (BCM) and is validated in adults, but not children. This study aimed to (1) assess agreement between BCM-measured total body water (TBW) and a gold standard technique in healthy children, (2) compare TBW_BCM with TBW from Urea Kinetic Modelling (UKM) in haemodialysis children and (3) investigate systematic deviation from zero in measured excess fluid in healthy children across paediatric age range. METHODS: TBW_BCM and excess fluid was determined from standard wrist-to-ankle BCM measurement. TBW_D2O was determined from deuterium concentration decline in serial urine samples over 5 days in healthy children. UKM was used to measure body water in children receiving haemodialysis. Agreement between methods was analysed using paired t test and Bland-Altman method comparison. RESULTS: In 61 healthy children (6-14 years, 32 male), mean TBW_BCM and TBW_D2O were 21.1 ± 5.6 and 20.5 ± 5.8 L respectively. There was good agreement between TBW_BCM and TBW_D2O (R2 = 0.97). In six haemodialysis children (4-13 years, 4 male), 45 concomitant measurements over 8 months showed good TBW_BCM and TBW_UKM agreement (mean difference - 0.4 L, 2SD = ± 3.0 L). In 634 healthy children (2-17 years, 300 male), BCM-measured overhydration was - 0.1 ± 0.7 L (10-90th percentile - 0.8 to + 0.6 L). There was no correlation between age and OH (p = 0.28). CONCLUSIONS: These results suggest BCM can be used in children as young as 2 years to measure normally hydrated weight and assess fluid status.

Estimation of Skeletal Muscle Mass and Visceral Adipose Tissue Volume by a Single Magnetic Resonance Imaging Slice in Healthy Elderly Adults.

BACKGROUND: Assessing skeletal muscle (SM) and visceral adipose tissue (VAT) by a single MRI slice at lumbar vertebra (L) 3 can replace whole-body MRI in young and middle-aged adults. However, this technique has not been proven in older adults. OBJECTIVE: The aim of this analysis was to reinvestigate the best estimate for SM and VAT in an independent population of healthy elderly people. METHODS: SM and VAT were assessed by whole-body MRI in 84 subjects ≥60 y [45 men; mean ± SD age: 68.4 ± 5.4 y, mean ± SD body mass index (in kg/m2): 25.5 ± 3.5]. SM and VAT areas of 9 slices at the lumbar spine were analyzed. The best estimate was investigated by Pearson correlations. Total volumes (in liters) were predicted by the area at lumbar vertebra 3 (AL3). Besides Bland-Altman analysis, linear regressions were performed to explain the variance of the bias by age, height, and percentage of fat mass (%FM). In a mixed population (healthy elderly plus reference population), linear regression with total SM and VAT volume as dependent variables and AL3, age, and height as independent variables was applied. RESULTS: When comparing the correlation coefficients between the tissue areas and total volumes, L3 was identified as the best estimate (r range: 0.71-0.94; all P < 0.05). However, Bland-Altman analysis showed a positive SM bias in men (mean ± SD: -1.0% ± 9.0%; P < 0.05) and a negative SM bias in women (mean ± SD: 3.7% ± 9.6%; P < 0.05). Contrary to SM, no significant bias was observed for VAT. In the elderly, stepwise linear regression showed height as a predictor for SM bias (R2 = 0.21, SEE = 2.07 L; P < 0.05) and %FM and age as predictors of the nonsignificant VAT bias (R2 = 0.26, SEE = 0.22L, P < 0.05), in men only. In the mixed population, AL3 and height were predictors for total SM, and AL3 for total VAT, independent of sex. CONCLUSIONS: AL3 was confirmed as the best estimate for SM and VAT volumes in healthy elderly adults. Contrary to VAT, there is a bias for SM, and height has to be added to the algorithm.

Assessment of fat and lean mass by quantitative magnetic resonance: a future technology of body composition research?

PURPOSE OF REVIEW: For the assessment of energy balance or monitoring of therapeutic interventions, there is a need for noninvasive and highly precise methods of body composition analysis that are able to accurately measure small changes in fat and fat-free mass (FFM). RECENT FINDINGS: The use of quantitative magnetic resonance (QMR) for measurement of body composition has long been established in animal studies. There are, however, only a few human studies that examine the validity of this method. These studies have consistently shown a high precision of QMR and only a small underestimation of fat mass by QMR when compared with a 4-compartment model as a reference. An underestimation of fat mass by QMR is also supported by the comparison between measured energy balance (as a difference between energy intake and energy expenditure) and energy balance predicted from changes in fat mass and FFM. Fewer calories were lost and gained as fat mass compared with the value expected from measured energy balance. SUMMARY: Current evidence in healthy humans has shown that QMR is a valid and precise method for noninvasive measurement of body composition. Contrary to standard reference methods, such as densitometry and dual X-ray absorptiometry, QMR results are independent of FFM hydration. However, despite a high accuracy and a low minimal detectable change, underestimation of fat mass by QMR is possible and limits the use of this method for quantification of energy balance.

Impact of carbohydrates on weight regain.

PURPOSE OF REVIEW: Research on obesity treatment has shifted its focus from weight loss to weight-loss maintenance strategies. The conventional approach of a low-fat diet is challenged by insights from glycemic effects of carbohydrates on body weight regulation. RECENT FINDINGS: Metabolic and endocrine adaptations to weight loss that contribute to weight regain involve reduced energy expenditure, increased insulin sensitivity, and enhanced orexigenic signals. This review summarizes the impact of carbohydrates on energetic efficiency, partitioning of weight regain as fat and lean mass, and appetite control. Both the amount and frequency of postprandial glycemia add to body weight regulation after weight loss and strengthen the concept of glycemic index and glycemic load. In addition, dietary fiber and slowly or poorly absorbable functional sugars modify gastrointestinal peptides involved in appetite and metabolic regulation and exert prebiotic effects. SUMMARY: Current evidence suggests that a low-glycemic load diet with a preference for low-glycemic index foods and integration of slowly digestible, poorly absorbable carbohydrates may improve weight-loss maintenance. Future studies should investigate the health benefits of low glycemic functional sweeteners (e.g., isomaltulose and tagatose).

Low Recent Protein Intake Predicts Cancer-Related Fatigue and Increased Mortality in Patients with Advanced Tumor Disease Undergoing Chemotherapy.

Cancer patients, in general, suffer from anorexia hence diminished nutritional intake. In a prospective observational study, we investigated the impact of recent energy and protein intake on cancer-related fatigue and 6-month mortality in patients undergoing chemotherapy. Recent protein and energy intake was assessed by 24-h recall in 285 patients. Cancer-related fatigue was determined by Brief Fatigue Inventory, and fat free mass index (FFMI) was assessed with bioelectrical impedance analysis. Symptoms with the validated German version of European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (30 questions) and 6-month mortality was documented. Risk factors of cancer-related fatigue and predictors of mortality were investigated with logistic regression analysis and stepwise Cox regression analysis, respectively. Low protein intake (<1 g/kg body weight) was found in 66% of patients, who were characterized by higher age, weight, and body mass index. Recent protein intake emerged as the strongest contributor to cancer-related fatigue followed by nausea/vomiting, insomnia, and age. Reduced protein intake, male sex, number of comorbidities, and FFMI were identified as significant predictors for increased 6-month mortality. In conclusion, a low recent protein intake assessed by 24-h recall is associated with a more than twofold higher risk of cancer-related fatigue and 6-month mortality. Every effort should be taken to assess and guarantee proper nutritional intake in patients undergoing chemotherapy.

Measuring the impact of weight cycling on body composition: a methodological challenge.

PURPOSE OF REVIEW: The impact of weight cycling on body composition and metabolic risk remains controversial. Very few studies, however, meet the methodological requirements to analyze and normalize changes in body composition with weight loss and regain. RECENT FINDINGS: Methodological drawbacks that limit the interpretation of results are as follows:first, a small and only partial weight regain, second, the choice of an obese study population who experiences only small changes in fat-free mass, third, a lack of adjustment for the age-related decline in fat-free mass when examining elderly people and fourth, a lack of validity and precision of the body composition method that are important in a nonstable condition of weight loss and for measuring small changes in body composition. Normalization of changes in fat and lean mass for baseline body composition and measurement of fat and lean tissue distribution lead to further insights into the etiology and consequences of weight cycling. SUMMARY: Current evidence does not support an adverse effect of weight cycling on body composition. By contrast, severe weight loss in normal-weight people that comprises a large loss of lean mass may shift the partitioning toward a transient higher regain in total and abdominal fat mass.

Re-entering obesity prevention: a qualitative-empirical inquiry into the subjective aetiology of extreme obese adolescents.

BACKGROUND: While numerous studies highlight the relevance of socio-cultural factors influencing incidence and prevalence of obesity, only a few address how obese people perceive causes and prevention of or intervention for obesity. This study contributes to a more thorough understanding of subjective aetiologies and framing themes for a mainly understudied but promising field. Thus it may serve for the development of effective public health strategies to combat obesity. METHODS: Autobiographically based in-depth interviews were conducted with 20 patients (adolescents and young adults) institutionalised in the obesity rehabilitation centre INSULA in Bischofswiesen (Germany). The data were analysed with Atlas.ti with regard to two main perspectives: (1) How the interviewees perceive 'their' obesity from a subjective point of view and (2) which conclusions they draw from their own 'story' concerning prevention/intervention strategies. RESULTS: The interviewees did not indicate a clear starting point for their overweight. Nevertheless, certain life-events (e.g. divorce or illness of parents) were identified as catalysing weight gain. As a consequence of coping with distress, body weight rises rapidly and not continuously. Obesity was generally framed as a problem primarily located within the family and not in the wider environment. Corresponding to this, the family was identified as the main and most important addressee of preventive measures. The interviewees highlighted the importance of personal responsibility as a prerequisite for self-determined action against obesity, but denied any link between responsibility and guilt. CONCLUSIONS: This study contributes substantially to a broader perspective on the prevention of obesity. First, more attention has to be paid to the interactions of medical aspects and the social dimension of obesity. Second, prevention efforts should be more aware of the relevance of subjective aetiology when it comes to the definition of reasonable and effective governance strategies in tackling obesity. Third, current assumptions concerning the importance of personal responsibility for obesity prevention might underestimate the relevance of self-determined action of the obese.

Perspective: Do Scientists Become Part of the Obesity Problem?

Obesity is fundamentally a condition where physiology and behavior of individuals meet the environment, and the emerging global obesity pandemic reflects the contribution of a wide range of cultural, societal, economic and systemic driving forces. Today, different areas of obesity research are relatively separated from each other in discrete silos, with biomedical research determining most of our understanding and solution strategies. This has led to the Y in the road, which means the questionable assumption that effective drug treatment of individual patients is also an effective measure to improve population health. Since human obesity is a condition of population health and planetary impact a better integration of biomedical and public health approaches is based on critical (self-)reflection and communicative understanding of scientists from various research areas who should be on an equal footing.

Proportion of caloric restriction-induced weight loss as skeletal muscle.

OBJECTIVE: This study's objective was to develop models predicting the relative reduction in skeletal muscle (SM) mass during periods of voluntary calorie restriction (CR) and to validate model predictions in longitudinally monitored samples. METHODS: The model development group included healthy nonexercising adults (n = 897) who had whole-body SM mass measured with magnetic resonance imaging. Model predictions of relative SM changes with CR were evaluated in two longitudinal studies, one 12 to 14 weeks in duration (n = 74) and the other 12 months in duration (n = 26). RESULTS: A series of SM prediction models were developed in a sample of 415 males and 482 females. Model-predicted changes in SM mass relative to changes in body weight (i.e., ΔSM/Δbody weight) with a representative model were (mean ± SE) 0.26 ± 0.013 in males and 0.14 ± 0.007 in females (sex difference, p < 0.001). The actual mean proportions of weight loss as SM in the longitudinal studies were 0.23 ± 0.02/0.20 ± 0.06 in males and 0.10 ± 0.02/0.17 ± 0.03 in females, similar to model-predicted values. CONCLUSIONS: Nonelderly males and females with overweight and obesity experience respective reductions in SM mass with voluntary CR in the absence of a structured exercise program of about 2 to 2.5 kg and 1 to 1.5 kg per 10-kg weight loss, respectively. These estimates are predicted to be influenced by interactions between age and body mass index in males, a hypothesis that needs future testing.

Advances in the understanding of specific metabolic rates of major organs and tissues in humans.

PURPOSE OF REVIEW: To present recent evidence on organ and tissue metabolic rates in humans to explain the variance in resting energy expenditure (REE). RECENT FINDINGS: In humans, present knowledge on specific metabolic activities (i.e. ki-values) refers to seven organs and tissues - brain, heart, liver, kidneys, skeletal muscle, adipose tissue and residual mass - with ki-values of 240, 440, 200, 440, 13, 4.5 and 12 kcal/kg/day, provided by Elia in 1992. Detailed body composition data, as derived from whole body MRI together with measurements of whole body REE, were used to validate ki-values in nonobese, healthy and middle-aged adults. There is no sex difference, but minor, that is 2 and 3% deviations are found for age above 55 years and obesity, respectively. By contrast, in adolescents, differences of about 100 kcal/day or 7.3% of measured REE were observed. There is first evidence for changes in ki-values with either weight loss or weight regain after weight loss. Altogether these data suggest that in adolescence and at age above 55 years, in the obese and with weight change, organ and tissue masses differ in cellularity and/or their specific metabolic rates. Presently, direct assessment of specific organ and tissue metabolic rates in humans by either NMR spectroscopy or PET, together with detailed body composition analysis, has not been performed systematically. SUMMARY: We need to become more skilled in methods and models used for detailed body composition analysis together with detailed assessment of energy expenditure in humans.

Carbohydrate quality and quantity affect glucose and lipid metabolism during weight regain in healthy men.

In this controlled, parallel-group feeding trial, we examined the impact of carbohydrate (CHO) intake and glycemic index (GI) on glucose and lipid metabolism during refeeding after weight loss. Healthy men (n = 32 total, age: 25.5 ± 3.9 y, BMI: 23.5 ± 2.0 kg/m2) overconsumed diets containing either 50% or 65% CHO for 1 wk (+50% of energy requirements) and then underwent 3 wk of calorie restriction (CR; -50%) followed by 2 wk of overconsuming (refeeding, +50%) the same diet but with either a low or high GI (40 vs.70 during CR, 41 vs.74 during refeeding) so that glycemic load (GL; dietary CHO content x GI) differed between groups during all phases. Glucose profiles were assessed by continuous interstitial glucose monitoring, insulin sensitivity (IS) by fasting blood sampling, oral glucose tolerance test (OGTT) and hyperinsulinemic-euglycemic clamp, and liver fat by MRI. Daytime area under the curve-glucose during refeeding was higher with high compared with low GI (P = 0.01) and 65% compared with 50% CHO intake (P = 0.05) and correlated with dietary GL (r = 0.71; P < 0.001). IS increased with CR and decreased again with refeeding in all groups. The decrease in OGTT-derived IS was greater with high- than with low-GI diets (-41 vs. -15%; P-interaction = 0.01) and correlated with dietary GL during refeeding (r = -0.51; P < 0.01). Serum triglycerides (TGs) and liver fat also improved with CR (-17 ± 38 mg/dL and -1.1 ± 1.3%; P < 0.05 and <0.001) and increased again with refeeding (+48 ± 48 mg/dL and +2.2 ± 1.6%; P < 0.001). After refeeding, serum TGs and liver fat were elevated above baseline values with 65% CHO intake only (+59.9 ± 37.5 mg/dL and +1.1 ± 1.7%, P-interaction <0.001 and <0.05). In conclusion, a diet low in GI and moderate in CHO content (i.e., low GL) may have health benefits by positively affecting daylong glycemia, IS, and liver fat.

Evaluation of methods to assess reduced body fat in patients with anorexia nervosa.

OBJECTIVE: To evaluate skinfold anthropometry and dual-energy x-ray absorptiometry (DXA) to estimate percentage of body fat (%BF) in adolescent patients with anorexia nervosa (AN). METHODS: We examined 80 female AN patients (age 15.6 ± 1.4 years) and 31 healthy, normal weight sex- and age-matched controls with DXA and skinfold anthropometry to estimate %BF. Reference values for %BF of the same participants were obtained from a 4-compartment (4C) model, which was based on measurements of total body protein (with in vivo neutron activation), total body water (with deuterium dilution), and mineral content (with DXA). We compared the different methods to assess %BF with Bland-Altman analysis of agreement. RESULTS: In the AN group, average %BF was well predicted with DXA and skinfold measurements in combination with the Deurenberg equation based on 2 skinfolds (DXA 13.9 ± 6.2 %BF; skinfold 14.5 ± 4.3 vs 14.1 ± 6.8 %BF by the 4C model). In the control group, average %BF was closely predicted by skinfold measurements in combination with the Slaughter formula (26.1 ± 4.5 vs 25.2 ± 5.2 %BF by the 4C model) but was overestimated with DXA (31.3 ± 5.8 %BF). When compared with the 4C model, all methods under investigation showed considerable limits of agreement when predicting %BF in any given individual. CONCLUSIONS: In our group of patients with AN, the Deurenberg skinfold model and DXA were similar in performance; however, DXA overestimated %BF in healthy subjects.

Impact of glycaemic index and dietary fibre on insulin sensitivity during the refeeding phase of a weight cycle in young healthy men.

Previous studies suggest that a low-glycaemic index (LGI) diet may improve insulin sensitivity (IS). As IS has been shown to decrease during refeeding, we hypothesised that an LGI- v. high-GI (HGI) diet might have favourable effects during this phase. In a controlled nutritional intervention study, sixteen healthy men (aged 26·8 (SD 4·1) years, BMI 23·0 (SD 1·7) kg/m2) followed 1 week of overfeeding, 3 weeks of energy restriction and of 2 weeks refeeding at ^50% energy requirement (50% carbohydrates, 35% fat and 15% protein). During refeeding, subjects were divided into two matched groups receiving either high-fibre LGI or lower-fibre HGI foods (GI 40 v. 74, fibre intake 65 (SD 6) v. 27 (SD 4) g/d). Body weight was equally regained in both groups with refeeding (mean regain 70·5 (SD 28·0)% of loss). IS was improved by energy restriction and decreased with refeeding. The decreases in IS were greater in the HGI than in the LGIgroup (group £ time interactions for insulin, homeostasis model assessment of insulin resistance (HOMAIR), Matsuda IS index (MatsudaISI);all P,0·05). Mean interstitial glucose profiles during the day were also higher in the HGI group (DAUCHGI-LGI of continuous interstitial glucose monitoring: 6·6 mmol/l per 14 h, P»0·04). At the end of refeeding, parameters of IS did not differ from baseline values in either diet group (adiponectin, insulin, HOMAIR, Matsuda ISI, M-value; all P.0·05). In conclusion, nutritional stress imposed by dietary restriction and refeeding reveals a GI/fibre effect in healthy non-obese subjects. LGI foods rich in fibre may improve glucose metabolism during the vulnerable refeeding phase of a weight cycle.

Changes in body composition and homeostatic control of resting energy expenditure during dietary weight loss.

Adaptive thermogenesis (AT) is the mass-independent decrease in energy expenditure (EE) in response to caloric restriction and weight loss. AT becomes manifest throughout all periods of weight loss and persists during subsequent weight maintenance. AT occurs in resting and nonresting energy expenditure as ATREE and ATNREE , respectively. ATREE appears in different phases of weight loss, each with likely different mechanisms. By contrast, during weight maintenance after weight loss, ATNREE exceeds ATREE . Some of the mechanisms of AT are known now and others are not. Future studies on AT will need an appropriate conceptual framework within which to design experiments and interpret results.

Issues related to the assessment of energy balance during short-term over-, under- and refeeding in normal weight men.

BACKGROUND: In humans, it is unclear how different estimates of energy balance (EB) compare with each other and whether the resulting changes in body weight (bw) and body composition (BC) are predictable and reproducible. METHODS: This is a secondary data analysis of effects of sequential 7d over- (OF), 21d under- (UF) and 14d refeeding (RF) on EB. Energy intake (EI) was controlled at +/- 50% of energy needs in a 32 normal weight men (see Am J Clin Nutr. 2015; 102:807-819). EB was calculated (i) directly from the difference between EI and energy expenditure (EE) and (ii) indirectly from changes in BC. Changes in fat mass (FM) were compared with predicted changes according to Hall et al. (Lancet 2011; 378:826-37). Finally, within-subject reproducibility of changes in bw and BC was tested in a subgroup. RESULTS: There were interindividual and day-by-day variabilities in changes in bw and BC. During OF and RF, the two estimates of EB were similar while with UF the indirect approach underestimated the direct estimate by 10593 ± 7506 kcal/21d (p < 0.001). Considerable differences became evident between measured and predicted changes in FM. Adjusting measured for predicted values did not reduce their interindividual variance. During UF, changes in bw and BC were reproducible, while corresponding changes during OF were not. CONCLUSION: During hypercaloric nutrition the direct estimate of EB corresponded to the indirect estimate whereas this was not true during UF. Changes in bw and BC in response to OF were not reproducible while they were during UF.