Stearidonic acid improves eicosapentaenoic acid status: studies in humans and cultured hepatocytes.

Background: Ahiflower oil from the seeds of Buglossoides arvensis is rich in α-linolenic acid (ALA) and stearidonic acid (SDA). ALA and SDA are potential precursor fatty acids for the endogenous synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are n3-long chain polyunsaturated fatty acids (n3-LC-PUFAS), in humans. Since taurine, an amino sulfonic acid, is often associated with tissues rich in n3-LC-PUFAS (e.g., in fatty fish, human retina), taurine may play a role in EPA- and DHA-metabolism. Objective: To examine the capacity of the plant-derived precursor fatty acids (ALA and SDA) and of the potential fatty acid metabolism modulator taurine to increase n3-LC-PUFAS and their respective oxylipins in human plasma and cultivated hepatocytes (HepG2 cells). Methods: In a monocentric, randomized crossover study 29 healthy male volunteers received three sequential interventions, namely ahiflower oil (9 g/day), taurine (1.5 g/day) and ahiflower oil (9 g/day) + taurine (1.5 g/day) for 20 days. In addition, cultivated HepG2 cells were treated with isolated fatty acids ALA, SDA, EPA, DHA as well as taurine alone or together with SDA. Results: Oral ahiflower oil intake significantly improved plasma EPA levels (0.2 vs. 0.6% of total fatty acid methyl esters (FAMES)) in humans, whereas DHA levels were unaffected by treatments. EPA-levels in SDA-treated HepG2 cells were 65% higher (5.1 vs. 3.0% of total FAMES) than those in ALA-treated cells. Taurine did not affect fatty acid profiles in human plasma in vivo or in HepG2 cells in vitro. SDA-rich ahiflower oil and isolated SDA led to an increase in EPA-derived oxylipins in humans and in HepG2 cells, respectively. Conclusion: The consumption of ahiflower oil improves the circulating levels of EPA and EPA-derived oxylipins in humans. In cultivated hepatocytes, EPA and EPA-derived oxylipins are more effectively increased by SDA than ALA.

A comprehensive in-vitro/in-vivo screening toolbox for the elucidation of glucose homeostasis modulating properties of plant extracts (from roots) and its bioactives.

Plant extracts are increasingly recognized for their potential in modulating (postprandial) blood glucose levels. In this context, root extracts are of particular interest due to their high concentrations and often unique spectrum of plant bioactives. To identify new plant species with potential glucose-lowering activity, simple and robust methodologies are often required. For this narrative review, literature was sourced from scientific databases (primarily PubMed) in the period from June 2022 to January 2024. The regulatory targets of glucose homeostasis that could be modulated by bioactive plant compounds were used as search terms, either alone or in combination with the keyword "root extract". As a result, we present a comprehensive methodological toolbox for studying the glucose homeostasis modulating properties of plant extracts and its constituents. The described assays encompass in-vitro investigations involving enzyme inhibition (α-amylase, α-glucosidase, dipeptidyl peptidase 4), assessment of sodium-dependent glucose transporter 1 activity, and evaluation of glucose transporter 4 translocation. Furthermore, we describe a patch-clamp technique to assess the impact of extracts on KATP channels. While validating in-vitro findings in living organisms is imperative, we introduce two screenable in-vivo models (the hen's egg test and Drosophila melanogaster). Given that evaluation of the bioactivity of plant extracts in rodents and humans represents the current gold standard, we include approaches addressing this aspect. In summary, this review offers a systematic guide for screening plant extracts regarding their influence on key regulatory elements of glucose homeostasis, culminating in the assessment of their potential efficacy in-vivo. Moreover, application of the presented toolbox might contribute to further close the knowledge gap on the precise mechanisms of action of plant-derived compounds.

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.

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.

Effects of a Short-Term Vegan Challenge in Older Adults on Metabolic and Inflammatory Parameters-A Randomized Controlled Crossover Study.

SCOPE: A long-term vegan diet carries the risk of insufficient protein and micronutrient intake for older adults. However, even a short-term (48 h) vegan diet exerts positive metabolic effects in younger adults. In this study, we investigate the feasibility and effects of a short-term vegan challenge on metabolic and inflammatory markers in older adults. METHOD AND RESULTS: In this randomized controlled crossover-study, 30 healthy older adults (≥65 years) are assigned to either a 48 h ad libitum vegan or omnivorous diet. During the vegan diet, participants exhibit lower protein (p = 0.001) and fat intake as well as higher carbohydrate and dietary fiber intake, resulting in a lower caloric intake (all p < 0.001). Insulin concentrations (p = 0.042) and insulin resistance (p = 0.036) decline only after the vegan diet. The study observes reductions in serum glucose (p < 0.001), triglyceride (p = 0.005), and hsCRP (p = 0.044) concentrations and weight (p < 0.001), independent of the diet. Participants with low-grade inflammation exhibit notable metabolic improvements after the vegan diet. CONCLUSION: Improvements in insulin homeostasis are observed after the vegan diet, but meeting protein requirements are not feasible during the short-term vegan challenge despite dietary counseling, which warrants concern.

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.

Interindividual variability in energy intake and expenditure during a weight loss intervention.

INTRODUCTION: Behavioral compensations may occur as a response to a negative energy balance. The aim of this study was to explore the associations between changes in energy intake (EI) and changes in physical activity (PA, min/day; kcal/d) as a response to a weight loss (WL) intervention and to understand if interindividual differences occur in EI and energy expenditure (EE). METHODS: Eighty-one participants [mean (SD): age = 42.8 (9.4)y, BMI = 31.2 (4.4)kg/m2, 37% females] divided in intervention (IG, n = 43) and control group (CG, n = 38) were included. The IG underwent a moderate energy restriction (300-500 kcal/d). EI was measured through the intake-balance method. Non-exercise PA (NEPA) and exercise (through logbook) were assessed by accelerometery. The EE in NEPA (NEAT) and in exercise (EiEE) was calculated by applying the Freedson Combination'98 algorithm over the time spent in these activities. Pearson correlations were performed in IG to examine associations between EE components, EI and body composition. To understand if interindividual differences were observed, the SD of individual response (SDIR) and the smallest worthwhile change (SWC, SDbaselineCG×0.2) were calculated. RESULTS: Changes in EI [Δ EI, (kcal/d)] was negatively associated with Δ exercise (min/d:r = -0.413, p = 0.045; %:r = -0.846, p = 0.008) and with Δ EiEE (kcal/d:r = -0.488, p = 0.016; %:r = -0.859, p = 0.006). A negative correlation was found between Δ sedentary time and Δ NEPA (min/d:r = -0.622, p = 0.002; %:r = -0.487, p = 0.018). An interindividual variability was found for EI(SDIR = 151.6, SWC = 72.3) and EE (SDIR = 165, SWC = 134). CONCLUSIONS: Decreases in EI were not associated to compensatory responses such as decreases in PA and/or increases in sedentary time. Interindividual variability was found for EI and EE. Nevertheless, behavioral compensations and the interindividual variability should be considered when implementing WL interventions, to increase the likelihood of achieving sustainable results. (clinicaltrials.gov ID: NCT03031951).

Impact of one-day fasting, ketogenic diet or exogenous ketones on control of energy balance in healthy participants.

BACKGROUND & AIMS: Oral ketone supplements may mimic the beneficial effects of endogenous ketones on energy metabolism as ß-hydroxybutyrate has been proposed to increase energy expenditure and improve body weight regulation. Therefore, our objective was to compare the effects of a one-day isocaloric ketogenic diet, fasting and supplementation with ketone salts on energy expenditure and appetite perception. METHODS: Eight healthy young adults (4 women, 4 men, age 24 ± 3 years, BMI 24.3 ± 3.1 kg/m2) participated in a randomized cross-over trial with four 24 h-interventions in a whole room indirect calorimeter at a physical activity level of 1.65: (i) total fasting (FAST), (ii) isocaloric ketogenic diet (3.1% energy from carbohydrates (CHO), KETO), (iii) isocaloric control diet (47.4% energy from CHO, ISO), and (iv) ISO supplemented with 38.7 g/d ketone salts (exogenous ketones, EXO). Effects on serum ketone levels (15 h-iAUC), energy metabolism (total energy expenditure, TEE; sleeping energy expenditure, SEE; macronutrient oxidation) and subjective appetite were measured. RESULTS: Compared to ISO, ketone levels were considerably higher with FAST and KETO and little higher with EXO (all p > 0.05). Total and sleeping energy expenditure did not differ between ISO, FAST and EXO whereas KETO increased TEE (+110 ± 54 kcal/d vs. ISO, p < 0.05) and SEE (+201 ± 90 kcal/d vs. ISO, p < 0.05). CHO oxidation was slightly decreased with EXO compared to ISO (-48 ± 27 g/d, p < 0.05) resulting in a positive CHO balance (p < 0.05). No differences between the interventions were found for subjective appetite ratings (all p > 0.05). CONCLUSION: A 24 h-ketogenic diet may contribute to maintain a neutral energy balance by increasing energy expenditure. Exogenous ketones in addition to an isocaloric diet did not improve regulation of energy balance. CLINICAL TRIAL REGISTRATION: NCT04490226 https://clinicaltrials.gov/.

Validity and reproducibility of a whole-room indirect calorimeter for the estimation of VO2 , VCO2 , and resting metabolic rate.

Whole-room indirect calorimeters (WRICs) provide accurate instruments for the measurement of respiratory exchange, energy expenditure, and macronutrient oxidation. Here, we aimed to determine the validity and reproducibility of a 7500 L WRIC for the measurement of ventilation rates and resting metabolic rate (RMR). Technical validation was performed with propane combustion tests (n = 10) whereas biological reproducibility was tested in healthy subjects (13 women, 6 men, mean ± SD age 39.6 ± 15.3) in two 60 min measurements separated by 24 h. Subjects followed a run-in protocol prior to measurements. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for ventilation rates of O2 (VO2), CO2 (VCO2), the respiratory quotient (RQ; VCO2/VO2), and RMR. Technical validation showed good validity with CVs ranging from 0.67% for VO2 to 1.00% for energy expenditure. For biological reproducibility, CVs were 2.89% for VO2 ; 2.67% for VCO2 ; 1.95% for RQ; and 2.68% for RMR. With the exception of RQ (74%), ICCs were excellent for VO2 (94%), VCO2 (96%) and RMR (95%). Excluding participants that deviated from the run-in protocol did not alter results. In conclusion, the 7500 L WRIC is technically valid and reproducible for ventilation rates and RMR.

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.

Normal values for body composition in adults are better represented by continuous reference ranges dependent on age and BMI.

BACKGROUND & AIMS: Reference values for body composition parameters like skeletal muscle mass index (SMI) depend on age and BMI. To ensure reference intervals reflect these changes, they have traditionally been separated into groups of young adults based on sex and BMI. However, this static stratification oversimplifies the dynamic and gradual changes of body composition with increasing age and BMI. The aim was therefore to provide continuous reference ranges for body composition parameters. METHODS: Cross-sectional data of 1958 healthy men and women with an age between 18 and 97 years and a BMI between 17.1 und 45.6 kg/m2 were obtained between 2011 and 2019. Multiple regression analyses stratified by sex with age, age2 and BMI as independent variables were conducted to predict fat mass index (FMI), visceral adipose tissue (VAT), SMI, appendicular lean soft tissue index (ALSTI) and the ratio between extracellular to total body water (ECW/TBW). RESULTS: The regression models explained between 61 (VAT in women and ALSTI in men) and 93% of the variance in the respective body composition parameters (FMI in women). Age had only a minor impact (2-16%) whereas BMI substantially increased the explained variance of reference models for FMI, VAT and ALSTI (total explained variance 61-93%). In SMI, age is a major determinant of the explained variance (36% in men and 38% in women) with BMI equally contributing to the explained variance (total explained variance 72% in men and 75% in women). For ECW/TBW-ratio, age nearly completely explained the variance (79% in men and 74% in women) whereas BMI added only 2-3% to the explained variance. CONCLUSIONS: In conclusion, the derived continuous reference ranges are expected to improve body composition evaluation especially in very overweight and very old persons. Future studies applying these reference equations need to validate these assumptions. STUDY REGISTRATION, CLINICALTRIALS.GOV: NCT01368640, NCT01481285, NCT03779932, NCT04028648.

Determinants of bone mass in older adults with normal- and overweight derived from the crosstalk with muscle and adipose tissue.

Lower bone mass in older adults may be mediated by the endocrine crosstalk between muscle, adipose tissue and bone. In 150 community-dwelling adults (59-86 years, BMI 17-37 kg/m2; 58.7% female), skeletal muscle mass index, adipose tissue and fat mass index (FMI) were determined. Levels of myokines, adipokines, osteokines, inflammation markers and insulin were measured as potential determinants of bone mineral content (BMC) and density (BMD). FMI was negatively associated with BMC and BMD after adjustment for mechanical loading effects of body weight (r-values between -0.37 and -0.71, all p < 0.05). Higher FMI was associated with higher leptin levels in both sexes, with higher hsCRP in women and with lower adiponectin levels in men. In addition to weight and FMI, sclerostin, osteocalcin, leptin × sex and adiponectin were independent predictors of BMC in a stepwise multiple regression analysis. Muscle mass, but not myokines, showed positive correlations with bone parameters that were weakened after adjusting for body weight (r-values between 0.27 and 0.58, all p < 0.01). Whereas the anabolic effect of muscle mass on bone in older adults may be partly explained by mechanical loading, the adverse effect of obesity on bone is possibly mediated by low-grade inflammation, higher leptin and lower adiponectin levels.

Total and regional appendicular skeletal muscle mass prediction from dual-energy X-ray absorptiometry body composition models.

Sarcopenia, sarcopenic obesity, frailty, and cachexia have in common skeletal muscle (SM) as a main component of their pathophysiology. The reference method for SM mass measurement is whole-body magnetic resonance imaging (MRI), although dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) serves as an affordable and practical SM surrogate. Empirical equations, developed on relatively small and diverse samples, are now used to predict total body SM from ALM and other covariates; prediction models for extremity SM mass are lacking. The aim of the current study was to develop and validate total body, arm, and leg SM mass prediction equations based on a large sample (N = 475) of adults evaluated with whole-body MRI and DXA for SM and ALM, respectively. Initial models were fit using ordinary least squares stepwise selection procedures; covariates beyond extremity lean mass made only small contributions to the final models that were developed using Deming regression. All three developed final models (total, arm, and leg) had high R2s (0.88-0.93; all p < 0.001) and small root-mean square errors (1.74, 0.41, and 0.95 kg) with no bias in the validation sample (N = 95). The new total body SM prediction model (SM = 1.12 × ALM - 0.63) showed good performance, with some bias, against previously reported DXA-ALM prediction models. These new total body and extremity SM prediction models, developed and validated in a large sample, afford an important and practical opportunity to evaluate SM mass in research and clinical settings.

Resting Energy Expenditure in the Critically Ill and Healthy Elderly-A Retrospective Matched Cohort Study.

The use of indirect calorimetry to measure resting energy expenditure (mREE) is widely recommended as opposed to calculating REE (cREE) by predictive equations (PE). The aim of this study was to compare mREE with cREE in critically ill, mechanically ventilated patients aged ≥ 75 years and a healthy control group matched by age, gender and body mass index. The primary outcome was the PE accuracy rate of mREE/cREE, derived using Bland Altman plots. Secondary analyses included linear regression analyses for determinants of intraindividual mREE/cREE differences in the critically ill and interindividual mREE differences in the matched healthy cohort. In this retrospective study, 90 critically ill patients (median age 80 years) and 58 matched healthy persons were included. Median mREE was significantly higher in the critically ill (1457 kcal/d) versus the healthy cohort (1351 kcal/d), with low PE accuracy rates (21% to 49%). Independent predictors of mREE/cREE differences in the critically ill were body temperature, heart rate, FiO2, hematocrit, serum sodium and urea. Body temperature, respiratory rate, and FiO2 were independent predictors of interindividual mREE differences (critically ill versus healthy control). In conclusion, the commonly used PE in the elderly critically ill are inaccurate. Respiratory, metabolic and energy homeostasis variables may explain intraindividual mREE/cREE as well as interindividual mREE differences.

Analysis of the adiponectin paradox in healthy older people.

BACKGROUND: It remains unknown why adiponectin levels are associated with poor physical functioning, skeletal muscle mass and increased mortality in older populations. METHODS: In 190 healthy adults (59-86 years, BMI 17-37 kg/m2 , 56.8% female), whole body skeletal muscle mass (normalized by height, SMI, kg/m2 ), muscle and liver fat were determined by magnetic resonance imaging. Bone mineral content (BMC) and density (BMD) were assessed by dual X-ray absorptiometry (n = 135). Levels of insulin-like growth factor 1 (IGF-1), insulin, inflammation markers, leptin and fibroblast growth factor 21 were measured as potential determinants of the relationship between adiponectin and body composition. RESULTS: Higher adiponectin levels were associated with a lower SMI (r = -0.23, P < 0.01), BMC (r = -0.17, P < 0.05) and liver fat (r = -0.20, P < 0.05) in the total population and with higher muscle fat in women (r = 0.27, P < 0.01). By contrast, IGF-1 showed positive correlations with SMI (r = 0.33), BMD (r = 0.37) and BMC (r = 0.33) (all P < 0.01) and a negative correlation with muscle fat (r = -0.17, P < 0.05). IGF-1 was negatively associated with age (r = -0.21, P < 0.01) and with adiponectin (r = -0.15, P < 0.05). Stepwise regression analyses revealed that IGF-1, insulin and leptin explained 18% of the variance in SMI, and IGF-1, leptin and age explained 16% of the variance in BMC, whereas adiponectin did not contribute to these models. CONCLUSIONS: Associations between higher adiponectin levels and lower muscle or bone mass in healthy older adults may be explained by a decrease in IGF-1 with increasing adiponectin levels.