Elevated Resting Energy Expenditure Research Articles

The Acute Effects of a Commercially Available Caffeinated and Caffeine-Free Thermogenic Dietary Supplement on Resting Energy Expenditure, Hunger, and Hemodynamic Responses

There has been a rise in popularity of “stimulant-free” or caffeine-free fat loss supplements, but it is not well understood whether those fat loss supplements are effective at enhancing thermogenesis without caffeine’s influence. The purpose of this study was to examine the effects of a caffeinated and non-caffeinated commercially available fat loss supplement on resting energy expenditure (REE), hunger, and hemodynamic variables in healthy adults. Twenty-five healthy male and female participants completed three separate laboratory visits after overnight fasts. Baseline assessments of REE, subjective hunger, heart rate (HR), and blood pressure (BP) were followed by ingestion of a caffeinated (Phoenix, Legion®; CAF), non-caffeinated (Phoenix Caffeine-Free, Legion®; NCAF), or placebo (PL) fat loss supplement. REE, hunger, HR, and BP assessments were repeated at 60-, 120-, and 180-min post-ingestion. CAF, but not NCAF, significantly elevated REE greater than PL at all time points (p < 0.05). NCAF significantly reduced hunger compared to CAF and PL at the 120-min time point (p = 0.006). CAF significantly increased diastolic BP 60-min post-ingestion and significantly increased systolic BP 120- and 180-min post-ingestion compared to NCAF and PL. Further research is warranted with respect to investigating non-caffeinated ingredients and their effects on REE.

CFTR regulates brown adipocyte thermogenesis via the cAMP/PKA signaling pathway

BackgroundCystic fibrosis (CF) is characterized by reduced growth and lower body weight, which are multifactorial. CF mouse models lack key disease characteristics that predispose to a negative energy balance, such as pulmonary infections or exocrine pancreatic insufficiency, and yet they still exhibit a growth defect and an abnormally increased energy expenditure. Whether adipocyte thermogenesis contributes to the elevated resting energy expenditure in CF mice is unknown. MethodsWe examined the expression of CFTR in thermogenic brown adipose tissue (BAT) and investigated a functional role for CFTR using BAT-specific CFTR null mice (CFTRBATKO). ResultsThe CFTR protein is expressed in mouse BAT at levels comparable to those in the lungs. BAT-specific inactivation of CFTR in mice increases whole-body energy expenditure associated with sympathetic stimulation by cold exposure. Weight gain on a high-fat diet is attenuated in these mice. However, CFTR-deficient brown adipocytes themselves have impaired, rather than enhanced, thermogenic responses. These cells feature decreased lipolysis and blunted activation of the cAMP/PKA signaling pathway in response to adrenergic stimulation. This suggests that compensatory heat production in other tissues likely accounts for the increased systemic energy expenditure seen in CFTRBATKO mice. ConclusionsOur data reveal a new role for CFTR in the regulation of adipocyte thermogenesis.

Energy expenditure profiles and the risk of early limiting toxicity in older patients with cancer: The ELCAPA-25 prospective cohort survey

Predicting the risk of early limiting toxicity (ELT) is major challenge for the clinician seeking an effective, safe treatment for older patients with cancer. The Cancer and Aging Research Group (CARG) and CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) toxicity scores were designed to predict chemotherapy-related toxicity. Elevated resting energy expenditure (REE) may predispose to cachexia and increase ELT and mortality in older patients with cancer. The primary objective was to assess the association between elevated REE and ELT in older patients with cancer. The secondary objectives were to assess the discriminant ability of a predictive model including REE (relative to the CARG and CRASH scores) and the prognostic value of elevated REE. We assessed patients aged 70 or over included in the prospective ELCAPA cohort between 2014 and 2018. The inclusion criteria were a solid tumour, a measurement of REE at baseline (mREE, by indirect calorimetry), and a geriatric assessment prior to cancer treatment in a teaching hospital (Paris, France). The mREE was compared with the predicted REE (pREE), as defined by the Harris-Benedict equation. Depending on the mREE/pREE ratio, study participants were classified as hypermetabolic, hypometabolic or normometabolic. The primary endpoint was 3-month ELT, defined as any unplanned hospitalization or any event leading to dose reduction, a treatment delay of more than 7 days, or treatment discontinuation within 3 months of initiation. The secondary endpoint was the 3-month mortality rate. A total of 179 patients were included. The median age was 80 [interquartile range: 76-84] years, 37% of the patients were female, 81.8% had metastatic disease, 67.6% received chemotherapy, 20.7% received hormone therapy, and 11.7% received targeted therapies. According to the mREE/pREE ratio, 85 patients (47%) were hypermetabolic, 63 (35%) were normometabolic, and 31 (18%) were hypometabolic. Sixty patients (33.5%; 95% confidence interval (CI): 26.7-40.9) experienced ELT. The discriminant ability (as assessed by the C-index) of a multivariate model including REE and adjustment factors was 0.82 [95%CI: 0.73-0.91]. In comparison, the discriminant ability of the CARG and CRASH models was 0.57 [0.45-0.68] and 0.51 [0.40-0.62], respectively. In our model, hypermetabolism was an independent risk factor for ELT (adjusted odds ratio=2.44; 95%CI: 1.02-5.80). Other risk factors were the cancer type and stage, the treatment protocol, a clinical diagnosis of depression, the presence of grade 3 or 4 comorbidities, and the serum lactate dehydrogenase level. Hypermetabolism status is an independent predictor of ELT in older patients with cancer, relative to normometabolic status. Baseline REE measurement might improve the ELT risk assessment and decision-making process.

Resting Energy Expenditure Is Elevated in Asthma.

Background: Asthma physiology affects respiratory function and inflammation, factors that may contribute to elevated resting energy expenditure (REE) and altered body composition. Objective: We hypothesized that asthma would present with elevated REE compared to weight-matched healthy controls. Methods: Adults with asthma (n = 41) and healthy controls (n = 20) underwent indirect calorimetry to measure REE, dual-energy X-ray absorptiometry (DEXA) to measure body composition, and 3-day diet records. Clinical assessments included spirometry, fractional exhaled nitric oxide (FENO), and a complete blood count. Results: Asthmatics had greater REE than controls amounting to an increase of ~100 kcals/day, even though body mass index (BMI) and body composition were similar between groups. Inclusion of asthma status and FENO in validated REE prediction equations led to improved estimates. Further, asthmatics had higher white blood cell (control vs. asthma (mean ± SD): 4.7 ± 1.1 vs. 5.9 ± 1.6, p < 0.01) and neutrophil (2.8 ± 0.9 vs. 3.6 ± 1.4, p = 0.02) counts that correlated with REE (both p < 0.01). Interestingly, despite higher REE, asthmatics reported consuming fewer calories (25.1 ± 7.5 vs. 20.3 ± 6.0 kcals/kg/day, p < 0.01) and carbohydrates than controls. Conclusion: REE is elevated in adults with mild asthma, suggesting there is an association between REE and the pathophysiology of asthma.

Abstract 14928: The Factors Impacting on Resting Energy Expenditure in Refractory Heart Failure Patients and the Probability of Urine Amino Acids Analysis as an Indicator for Calorie Intake Insufficiency

Introduction: Cachexia is a critical issue in patients with refractory heart failure (HF). Although the elevation of resting energy expenditure (REE) can progress cachexia through relatively insufficient calorie intake, the detail of REE in HF patients remains uncertain and no useful marker for predicting insufficient calorie intake has been established. This study aimed to assess the REE of HF patients and to evaluate the detectability of serum and urine laboratory markers for insufficient calorie intake. Methods: We measured REE using indirect calorimetry in 69 HF patients (NYHA class II-IV) in our hospital. In 25 out of 69 patients, serum albumin, amino acids, and 24-hour urine amino acids were measured. The calorie intake insufficiency was determined based on measured REE multiplied by activity index Results: As compared to the predicted values by Harris-Benedict equation, 43 patients (63%) had an elevated REE and the mean REE was approximately 4% elevated. There was no significant correlation between the REE and parameters indicating HF severity, including cardiac index on right heart catheterization and BNP level. Only body mass index (BMI) negatively correlated with the REE (r=-0,66, p&lt;0.01). Of 25 patients, 16 (64%) had calorie intake insufficiency. The excreted amount of urine essential amino acids was lower and mostly under normal range, especially significantly decreased in Histidine and Phenylalanine levels in the patients with calorie intake insufficiency compared to those without calorie intake insufficiency, whereas serum levels of albumin and essential amino acids were kept within a normal range in the both. Conclusions: Our findings suggest that the patients with refractory HF, especially having low BMI, are likely to be under inadequate calorie intake due to elevated REE. The calorie intake insufficiency could not be identified with serum levels of albumin nor essential amino acids. Instead, urine essential amino acids would decrease first prior to plasma levels, indicating this measurement would be a useful marker to detect calorie intake insufficiency.

The Effect Of Thermogenic Nutritional Supplementation On Resting Metabolism In College-age Females

BACKGROUND: Global increases in the incidence of obesity and the ensuing clinical co-morbidities has increased interest in the use of thermogenic supplements formulated to increase resting metabolism to increase energy expenditure and fat utilization. PURPOSE: The purpose of this study was to assess the effect of new capsaicin-based thermogenic supplements on resting oxygen consumption (VO2), carbon dioxide production (VCO2) and respiratory quotient (RQ). METHODS: Twenty-two untrained females (21.1±4.2 years) visited the lab on six occasions for measurements of pre-supplementation (PRE) resting energy expenditure (REE) for 30-60 min followed by the ingestion of a placebo or supplement (Shred, Shred 2.0, Capsimax 50, Capsimax 100, Capsimax 200) with at least three days separating conditions. Resting VO2, VCO2, and RQ were re-assessed for 90-120 minutes post-supplementation (POST). Changes in metabolic markers between treatment groups and over time were assessed in 5-minute intervals over the course of the 90-minute assessment using a two-way repeated measures ANOVA. RESULTS: PRE VO2 (2.5 ± 0.3 ml•kg-1•min-1; 0.21±0.03 L•min-1), VCO2 (0.18 ± 0.03 L•min-1), and RQ (0.85 ± 0.06) were lower than any given 5-minute interval POST (p<0.05). VO2 (ml•kg-1•min-1) was elevated at 5 min POST (2.99 ± 0.5 ml•kg-1•min-1) compared to each subsequent 5 min interval (p<0.05) with no differences noted after 10 minutes (2.7 ± 0.4 ml•kg-1•min-1). VCO2 and VO2 (L•min-1) were elevated at 5 min POST compared to subsequent 5-minute intervals until 80 min (VCO2; 0.22 ± 0.04 to 0.19 ± 0.03 L•min-1) and 70 min (VO2; 0.25 ± 0.04 to 0.23 ± 0.03 L•min-1; p<0.05). There were no changes in VCO2 at 10 minutes (0.19 ± 0.03 L•min-1) compared to any other time point POST. VO2 (L•min-1) briefly increased from 35-45 minutes POST (0.23 ± 0.04 L•min-1) compared to 20 min POST (0.22 ± 0.03 L•min-1; p=0.002); no further changes occurred after 45 minutes. There were no changes in RQ during POST. There were no interaction effects (time*treatment) or treatment differences in metabolic markers. CONCLUSIONS: Observed time effects are postulated as a result of the elevated REE caused by changes in subject position during supplement consumption, rather than supplementation. This study suggests that new thermogenic supplementation has no effect on metabolism.

Hypermetabolism is an independent prognostic factor of survival in metastatic non-small cell lung cancer patients.

Metastatic non-small cell lung cancer (NSCLC) is the first cause of cancer death worldwide. Increased resting energy expenditure (REE) is frequent among cancer patients and may contribute to cancer cachexia. The aim of this study was to examine the prognostic value of increased REE in metastatic NSCLC patients. This observational study was conducted between June 2012 and November 2017 in the outpatient unit of the oncology department of Cochin hospital, Paris. Consecutive patients with newly diagnosed stage IV NSCLC underwent measurement of REE by indirect calorimetry before treatment initiation. Uni- and multivariate analysis of overall survival (OS, Cox models) included age, sex, smoking habit, histological subtype, performance status, body mass index, weight loss, albumin and CRP levels and the ratio of measured REE to the REE predicted by the Harris Benedict formula (mREE/pREE). 144 patients were enrolled: mean age 64 years, 63% male, 90% non-squamous carcinoma, including 17% with ALK/EGFR alteration. In univariate analysis, tobacco consumption (p=0.007), histo-molecular subtype (p<10-3), performance status (p=0.04), weight loss (p<10-4), albumin (p<10-4), CRP (p=0.001) and mREE/pREE ratio (>vs≤120%: HR=2.16, p<10-3) were significant prognostic factors of OS. Median OS were 6.1 and 17.3 months in patients with mREE/pREE ratio>and ≤120%, respectively. In multivariate analysis, histo-molecular subtype (non-squamous ALK/EGFR mutated vs squamous carcinoma: HR=0.25, p=0.006), weight loss (>vs≤5%: HR=1.98, p=0.004), albumin (≥vs<35g/L: HR=0.56, p=0.02) and mREE/pREE ratio (> vs ≤120%: HR=1.90, p=0.004) were identified as independent prognostic factors. Elevated resting energy expenditure emerges as an independent prognostic factor in metastatic NSCLC.

Resting Energy Expenditure and Substrate Oxidation in Malnourished Patients With Type 1 Glycogenosis.

Type 1a and 1b glycogenosis [glycogen storage disorder (GSD)1a, GSD1b] are rare diseases generally associated with malnutrition. Although abnormal substrate oxidation rates and elevated energy expenditures might contribute to malnutrition, this issue has not been investigated. To investigate whether abnormal resting energy expenditure (REE) and substrate oxidation rate characterize patients with GSD1. Cross-sectional study. Outpatient referral center for rare diseases and laboratory of clinical nutrition at the University Hospital of Palermo. Five consecutive patients with GSD1 (4 type a, 1 type b; 3 men, 2 women; age range, 19 to 49 years). The usual clinical procedures for patients with malnutrition, including REE and basal substrate oxidation rate (both indirect calorimetry), body composition (bioimpedance method), muscle strength (hand-grip test), and the usual laboratory tests, were performed. Malnutrition was clearly diagnosed in 2 patients (1 GSD1a and 1 GSD1b), with REE elevated in all five patients, and especially, in the two malnourished patients (+124% and +32.1% vs predictive values using Harris-Benedict equations). The two malnourished patients also exhibited lower basal protein oxidation rates (7.7% and 6.6%) than the nourished patients (range, 12.1% to 24.7%), with higher carbohydrate or lipid oxidation rates. Additionally, the two malnourished patients exhibited higher blood concentrations of lactic acid than the nourished patients. According to data obtained from our small sample of patients with GSD1, elevated REEs seem to be a common characteristic that might contribute to malnutrition. Low basal protein oxidation rates and elevated blood lactic acid concentrations appear to be associated with malnutrition.

Pathophysiological Response to Burn Injury in Adults.

The aim of this study was to compare the hypermetabolic, and inflammatory trajectories in burned adults to gain insight into the pathophysiological alterations and outcomes after injury. Burn injury leads to a complex response that is associated with hypermetabolism, morbidity, and mortality. The underlying pathophysiology and the correlations between humoral changes and organ function have not been well delineated in adult burn patients. Burned adult patients (n = 1288) admitted to our center from 2006 to 2016 were enrolled in this prospective study. Demographics, clinical data, metabolic and inflammatory markers, hypermetabolism, organ function, and clinical outcomes were obtained throughout acute hospitalization. We then stratified patients according to burn size (<20%, 20% to 40%, and >40% total body surface area [TBSA]) and compared biomedical profiles and clinical outcomes for these patients. Burn patients were hypermetabolic with elevated resting energy expenditure (REE) associated with increased browning of white adipose tissue from weeks 2 to 4. Hyperglycemia and hyperinsulinemia peaked 7 to 14 days after injury. Oral glucose tolerance and insulin resistance (QUICKI, HOMA2) tests further confirmed these findings with similar areas under the curve for moderate (20% to 40% TBSA) and severe burn (>40% TBSA). Lipid metabolism in sera revealed elevated pro-inflammatory stearic and linoleic acid, with complementary increases in anti-inflammatory free fatty acids. Similar increases were observed for inflammatory cytokines, chemokines, and metabolic hormones. White adipose tissue from the site of injury had increased ER stress, mitochondrial damage, and inflammasome activity, which was exacerbated with increasing burn severity. In this large prospective trial, we delineated the complexity of the pathophysiologic responses postburn in adults and concluded that these profound responses are time and burn size dependent. Patients with medium-size (20% to 40% TBSA) burn demonstrated a very robust response that is similar to large burns.

Potential Causes of Elevated REE after High-Intensity Exercise.

Resting energy expenditure (REE) increases after an intense exercise; however, little is known concerning mechanisms. The purpose of this study was to determine effects of a single bout of moderate-intensity continuous (MIC) aerobic exercise, or high-intensity interval (HII) exercise on REE under energy balance conditions. Thirty-three untrained premenopausal women were evaluated at baseline, after 8-16 wk of training, 22 h after either MIC (50% peak V˙O2) or HII (84% peak V˙O2). Participants were in a room calorimeter during and after the exercise challenge. Food intake was adjusted to obtain energy balance across 23 h. REE was measured after 22 h after all conditions. Twenty-three-hour urine norepinephrine concentration and serum creatine kinase activity (CrKact) were obtained. Muscle biopsies were obtained in a subset of 15 participants to examine muscle mitochondrial state 2, 3, and 4 fat oxidation. REE was increased 22 h after MIC (64 ± 119 kcal) and HII (103 ± 137 kcal). Markers of muscle damage (CrKact) increased after HII (9.6 ± 25.5 U·L) and MIC (22.2 ± 22.8 U·L), whereas sympathetic tone (urine norepinephrine) increased after HII (1.1 ± 10.6 ng·mg). Uncoupled phosphorylation (states 2 and 4) fat oxidation were related to REE (r = 0.65 and r = 0.55, respectively); however, neither state 2 nor state 4 fat oxidation increased after MIC or HII. REE was not increased after 8 wk of aerobic training when exercise was restrained for 60 h. Under energy balance conditions, REE increased 22 h after both moderate-intensity and high-intensity exercise. Exercise-induced muscle damage/repair and increased sympathetic tone may contribute to increased REE, whereas uncoupled phosphorylation does not. These results suggest that moderate- to high-intensity exercise may be valuable for increasing energy expenditure for at least 22 h after the exercise.

Abnormal Glucose Metabolism and High-Energy Expenditure in Idiopathic Pulmonary Arterial Hypertension.

Insulin resistance has emerged as a potential mechanism related to the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH). However, direct measurements of insulin and glucose metabolism have not been performed in patients with IPAH to date. To perform comprehensive metabolic phenotyping of humans with IPAH. We assessed plasma insulin and glucose, using an oral glucose tolerance test and estimated insulin resistance, and β-cell function in 14 patients with IPAH and 14 control subjects matched for age, sex, blood pressure, and body mass index. Body composition (dual-energy X-ray absorptiometry), inflammation (CXC chemokine ligand 10, endothelin-1), physical fitness (6-min walk test), and energy expenditure (indirect calorimetry) were also assessed. Patients with IPAH had a higher rate of impaired glucose tolerance (57 vs. 14%; P < 0.05) and reduced glucose-stimulated insulin secretion compared with matched control subjects (IPAH: 1.31 ± 0.76 μU/ml⋅mg/dl vs. control subjects: 2.21 ± 1.27 μU/ml⋅mg/dl; P < 0.05). Pancreatic β-cell function was associated with circulating endothelin-1 (r = -0.71, P < 0.01) and CXC chemokine ligand 10 (r = -0.56, P < 0.05). Resting energy expenditure was elevated in IPAH (IPAH: 32 ± 3.4 vs. control subjects: 28.8 ± 2.9 kcal/d/kg fat-free mass; P < 0.05) and correlated with the plasma glucose response (r = 0.51, P < 0.01). Greater insulin resistance was associated with reduced 6-minute walk distance (r = 0.55, P < 0.05). Independent of age, sex, blood pressure, and body mass index, patients with IPAH have glucose intolerance, decreased insulin secretion in response to glucose, and elevated resting energy expenditure. These abnormalities are associated with circulating markers of inflammation and vascular dysfunction.

High prevalence of malnutrition and deranged relationship between energy demands and food intake in advanced non-small cell lung cancer.

The relation between dietary intake and metabolic profile in non-small cell lung cancer (NSCLC) was evaluated. Patients with NSCLC were recruited and their caloric requirement and resting energy expenditure (REE) were calculated using the Harris-Benedict equationand Katch-McArdle formula respectively. Hypermetabolic state was defined as REE more than 10% above the basal metabolic rate (BMR). Body composition parameters were calculated by bioelectric impedance method. The 24-h dietary intake method and Malnutrition Universal Screening Tool assessed nutritional intake. One hundred and forty-eight subjects were included (87% males). Of these, 46.6% subjects were hypermetabolic and 31% cachexic, with lower calorie and protein intakes than recommended, although per cent of total energy derived from protein, fat and carbohydrates were similar. Hypermetabolic patients had lower BMI, though the per cent deficit in energy and protein consumption was similar. Cachexia was associated with lower BMR but not with deficit in energy or protein consumption. No correlation was seen between dietary intake and body composition parameters. The calorie and protein intake of NSCLC patients is lower than recommended. The discordance between elevated REE and dietary intake implies that the relationship between increased energy demands and food intake may be altered.

Energy expenditure and growth failure after intestinal transplantation: A case report

We present a 12-yr-old boy who received a combined liver-pancreas small bowel transplantation at the age of two. The post-operative period was complicated by wound closure problems resulting in a large asymptomatic abdominal wall defect. Further follow-up was uneventful, with the exception of new onset growth failure not explained by extensive routine investigations. An indirect calorimetry was performed. The resting energy expenditure (REE) was significantly increased (126% of predicted), demanding a daily caloric intake of 123 kcal/kg body weight (normal for age: 80 kcal/kg). In the absence of classic reasons for increased REE, a thermal camera revealed increased dermal heat loss at the abdominal wall defect (estimated surplus in energy loss of at least 29 kcal/day: 10.4% of the elevated REE). In addition, we found lower total lung capacity due to impaired abdominal breathing. In the exploration of growth failure in children after (ITx), increased REE must be taken into account. Indirect calorimetry can serve as a valuable diagnostic tool for evaluating individual energy requirements and nutritional support. In this child, exaggerated heat loss through an aberrant abdominal wall could be a potential important contributor to the patient's increased energy requirements.

Hypermetabolism: should cancer types, pathological stages and races be considered in assessing metabolism and could elevated resting energy expenditure be the therapeutic target in patients with advanced cancer?

Hypermetabolism, defined as elevated resting energy expenditure (REE), was common in cancer cachectic patients1 as published before in cancer patients2 and might result in poor outcomes. In this study, there was no significant difference in age, cancer type, gender, cancer treatment and inflammation between elevated REE group and normal REE group. As authors indicated, the small sample size, the heterogeneous population and the selection bias could have some impacts on the findings. Regarding the sample size, a moderately large study, including 714 cancer patients, suggested that cancer type, pathological stage and duration of disease are contributors to metabolic activity.2 To keep the homogeneity of the study population, Wu et al. enrolled 56 male patients as newly diagnosed with esophageal cancer and showed that the rate of weight loss positively correlated with the ration of REE to body weight and high-sensitivity C-reactive protein.3 In addition, it is well known that less than 5% of cancer patients participate in clinical studies and that non-enrollment in cancer research was associated with older age and sex (female),4 which might facilitate the selection bias. In this study, hypermetabolism is more common in non-Caucasian patients than in Caucasian patients.1 Interestingly, non-Caucasian healthy subjects had a lower REE compared with Caucasian healthy subjects,5 and a similar trend was observed in obese patients.6 It is still controversial whether racial background influences metabolic response in various pathophysiological conditions such as obesity, diabetes and cancer cachexia. At present, the number of cachexia research is critically lacking compared with that of obesity research, and7 no other evidence has been published on racial differences in REE among cancer patients, in particular cancer cachectic patients. It remains unclear whether hypermetabolism could be the therapeutic target in advanced cancer patients; however, recently, Ma et al. reported that administration of omega-3 polyunsaturated fatty acids resulted in a significant decrease in REE and a significant increase in overall survival in patients with pancreatic cancer.8 As sustained hypermetabolism leads to muscle wasting, some drugs such as ghrelin agonists, selective androgen receptor molecules, megestrol acetate, activin receptor antagonists, espindolol, and fast skeletal muscle troponin inhibitors,9 as well as physical exercise,10 which are promising for the treatment or the prevention of muscle wasting, could be the candidates as therapeutic options for this condition. To clarify the pathophysiology of hypermetabolism in cancer patients, validation studies on larger samples, various cancer types, different pathological stages and races are needed. In addition, hypermetabolism could be the therapeutic target at least in a sub-population of cancer patients. To confirm it, further research is needed.

Modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia

BackgroundCachexia affects most patients with incurable cancer. We hypothesize that in metastatic cancer the mass of the tumor as well as its level of anaerobic energy metabolism play a critical role in describing its energetic cost, which results in elevated resting energy expenditure and glucose utilization, leading to cachexia. Prior models of cancer cachexia may have underestimated the specific energetic cost of cancer as they have not taken the range of tumor mass and anaerobic energy metabolism fully into account.MethodsWe therefore modelled the energetic cost of cancer as a function of the percentage of energy the cancer produces anaerobically, based on resting energy expenditure, glucose turnover, glucose recycling, and oxygen consumption in cancer patients found in previous studies.ResultsData from two clinical studies where tumor burden was estimated and resting energy expenditure or oxygen consumption were measured lead to a broad range of estimates of tumor cost from 190 to 470 kcal/kg tumor/day. These values will vary based of the percentage of energy the cancer produces anaerobically (from 0 to 100 %), which in and of itself can alter the cost over a 2 to 3-fold range. In addition to the tumor cost/kg and the degree of anaerobic metabolism, the impact on a given individual patient will depend on tumor burden, which can exceed 1 kg in advanced metastatic disease. Considering these dimensions of tumor cost we are able to produce a 2-dimensional map of potential values, with an overall range of 100–1400 kcal/day.ConclusionsQuantifying the energetic cost of cancer may benefit an understanding of the tumor’s causation of cachexia. Our estimates of the range of tumor cost include values that are higher than prior estimates and suggest that in metastatic disease the tumor cost could be expected to eclipse attempts to stabilize energy balance through nutrition support or by drug therapies. Tumor mass and the percentage of anaerobic metabolism in the tumor contribute to the cost of the tumor on the body and potentially lead directly to negative energy balance and increased muscle wasting.Electronic supplementary materialThe online version of this article (doi:10.1186/s12976-015-0015-0) contains supplementary material, which is available to authorized users.

Hypermetabolism and symptom burden in advanced cancer patients evaluated in a cachexia clinic.

BackgroundElevated resting energy expenditure (REE) may contribute to weight loss and symptom burden in cancer patients.AimsThe aim of this study was to compare the velocity of weight loss, symptom burden (fatigue, insomnia, anxiety, and anorexia—combined score as measured by the Edmonton Symptom Assessment Score), high-sensitivity C-reactive protein, and survival among cancer patients referred to a cachexia clinic with hypermetabolism, elevated REE > 110% of predicted, with normal REE.MethodsA retrospective analysis of 60 advanced cancer patients evaluated in a cachexia clinic for either >5% weight loss or anorexia who underwent indirect calorimetry to measure REE. Patients were dichotomized to either elevated or normal REE. Descriptive statistics were generated, and a two-sample Student's t-tests were used to compare the outcomes between the groups. Kaplan–Meier and Cox regression methodology were used to examine the survival times between groups.ResultsThirty-seven patients (62%) were men, 41 (68%) were White, 59 (98%) solid tumours, predominantly 23 gastrointestinal cancers (38%), with a median age of 60 (95% confidence interval 57.0–62.9). Thirty-five patients (58%) were hypermetabolic. Non-Caucasian patients were more likely to have high REE [odds ratio = 6.17 (1.56, 24.8), P = 0.01]. No statistical difference regarding age, cancer type, gender, active treatment with chemotherapy, and/or radiation between hypermetabolic and normal REE was noted. The velocity of weight loss over a 3 month period (−8.5 kg vs. −7.2 kg, P = 0.68), C-reactive protein (37.3 vs. 55.6 mg/L, P = 0.70), symptom burden (4.2 vs. 4.5, P = 0.54), and survival (288 vs. 276 days, P = 0.68) was not significantly different between high vs. normal REE, respectively.ConclusionHypermetabolism is common in cancer patients with weight loss and noted to be more frequent in non-Caucasian patients. No association among velocity of weight loss, symptom burden, C-reactive protein, and survival was noted in advanced cancer patients with elevated REE.

Oral β-blockade in relation to energy expenditure in clinically stable patients with liver cirrhosis: A double-blind randomized cross-over trial

Elevated resting energy expenditure (REE) is seen in liver cirrhosis and is associated with reduced transplant-free survival. Non-selective β-blockers reduce REE in acute hypermetabolic conditions. We examined whether non-selective β-blockers reduce REE in patients with stable liver cirrhosis. Twenty-two stable cirrhotic patients (Child–Pugh grading: 19A, 2B, 1C) were randomized to 3-month treatment with nadolol (titrated to decrease resting pulse rate by 20%) or placebo and after a 1-month washout period crossed to the alternative treatment for a further 3months. REE was measured by indirect calorimetry and total body protein by neutron activation analysis at the beginning and end of each 3-month period of treatment. A predicted REE was calculated for each patient based on total body protein. A measured to predicted REE ratio >1.22 indicated significantly elevated REE. The primary outcome was REE at the end of 3-month treatment with nadolol compared with placebo. Elevated REE was seen in one patient at study entry. After 3months on placebo REE was 1506±40 (SEM) kcal/d and on nadolol, 1476±40kcal/d, a mean reduction of 31±16kcal/d (P=.076). Total body protein changes were not significant. Nadolol was well tolerated with no increase in the rate of adverse events. In stable cirrhotic patients, nadolol was not associated with reduction in REE. A larger, longer-term study with different eligibility criteria is required to investigate whether this treatment offers benefits additional to its use for prevention of variceal hemorrhage.

Mitochondrial Biogenesis and Increased Uncoupling Protein 1 in Brown Adipose Tissue of Mice Fed a Ketone Ester Diet

We investigated the in vivo physiological responses to a diet in which D‐β‐hydroxybutyrate – (R)‐1,3 butanediol monoester (ketone ester, KE) replaced equicaloric amounts of carbohydrate in eight week old male C57BL/6J. The KE‐fed group had blood D‐β‐hydroxybutyrate (β HB) levels that were much greater than that achieved with high fat ketogenic diets. Voluntary food intake reduced dose‐dependently with KE in the diet. Feeding the KE diet for a month significantly increased the number of mitochondria, uncoupling protein 1 (UCP1), PPARγ, PGC‐1α as well as Sirt1 in the interscapular brown adipose tissue (IBAT). The KE group also had significantly greater 18F‐fluorodeoxyglucose (FDG) uptake in IBAT, indicating functional activation of the tissue. The ketone fed mice had greater plasma leptin levels and increased sympathetic nervous system activity to IBAT. KE‐fed mice exhibited elevated resting energy expenditure, but no difference in the total energy expenditure or body weight. The quantitative insulin‐sensitivity check index (QUICKI) was also significantly greater in the KE group. These results demonstrate KE as a potential anti‐obesity supplement.

Nuts and healthy body weight maintenance mechanisms.

Nuts are rich sources of multiple nutrients and phytochemicals associated with health benefits, including reduced cardiovascular disease risk. This has prompted recommendations to increase their consumption. However, they are also high in fat and are energy dense. The associations between these properties, positive energy balance and body weight raise questions about such recommendations. Numerous epidemiological and clinical studies show that nuts are not associated with weight gain. Mechanistic studies indicate this is largely attributable to the high satiety and low metabolizable energy (poor bioaccessibility leading to inefficient energy absorption) properties of nuts. Compensatory dietary responses account for 55-75% of the energy provided by nuts. Limited data suggest that routine nut consumption is associated with elevated resting energy expenditure and the thermogenic effect of feeding, resulting in dissipation of another portion of the energy they provide. Additionally, trials contrasting weight loss through regimens that include or exclude nuts indicate improved compliance and greater weight loss when nuts are permitted. Nuts may be included in the diet, in moderation, to enhance palatability, nutrient quality, and chronic disease risk reduction without compromising weight loss or maintenance.

Energy metabolism, respiratory heat loss, and lung functions in patients with chronic obstructive pulmonary disease and pulmonary fibrosis

Resting energy expenditure (REE) and respiratory heat loss (RHL) were measured in 17 patients with chronic obstructive pulmonary disease (COPD), 7 patients with pulmonary fibrosis (PF), and 8 normal healthy subjects, three hours after a light breakfast. Correlations between these values, and also predicted basal metabolic rate (PreBMR) and normalized lung functions were assessed. REE, REE/Pre BMR, RHL and RHL/REE in all patients increased significantly compared with those of control subjects. When all the studied subjects were combined, significant negative relationships were found between REE, REE/PreBMR, RHL and RHL/REE and percent predicted values of forced expiratory volume in one second (FEV1.0), between RHL and RHL/REE and percent predicted values of vital capacity (VC), and between REE/PreBMR, RHL and RHL/REE and percent predicted values of carbon monoxide diffusing capacity (DLCO). These results indicate that resting energy expenditure and respiratory heat loss increase in patients with COPD and PF in association with even slight to moderate deterioration of lung function. Therefore, elevated resting energy expenditure and respiratory heat loss need to be taken into account in determining caloric and water requirements of these patients.