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The recommendation to prefer unprocessed/minimally processed foods and freshly made meals instead of ultra-processed foods (following the Nova food classification system) is being increasingly adopted in new official dietary guidelines issued by national governments and international health associations. This recommendation is supported by systematic reviews and meta-analyses of nationally representative dietary surveys and long-term cohort studies. These data show that increased intake of ultra-processed foods is associated with poor-quality diets and with increased morbidity and mortality from several chronic diseases. Various attributes of ultra-processed foods acting through known, plausible, or suggested physiologic and behavioral mechanisms relate them to ill health, and it is likely that different combinations of attributes and mechanisms affect different health outcomes. Although more research should be done to identify these mechanisms, existing evidence is sufficient to recommend the avoidance of ultra-processed foods to optimize health and policies to support and make feasible this recommendation.

This Viewpoint considers the best approaches for treating obesity in youth and argues that better funding is needed for new dietary treatments and reimbursement for behavioral interventions.

BackgroundThe extent to which physical activity attenuates the detrimental effects of sugar (SSBs)- or artificially-sweetened beverages (ASBs) on the risk of cardiovascular disease is unknown.MethodsWe used Cox proportional-hazards models to calculate hazard ratios and 95% confidence interval [HR (CI)] between SSB or ASB intake and physical activity with cardiovascular disease risk among 65,730 women in the Nurses’ Health Study (1980-2016) and 39,418 men in the Health Professional’s Follow-up Study (1986-2016), who were free from chronic diseases at baseline. SSBs and ASBs were assessed every 4-years and physical activity biannually.ResultsA total of 13,269 cardiovascular events were ascertained during 3,001,213 person-years of follow-up. Compared with those that never/rarely consumed SSBs or ASBs, HR and 95% CI for cardiovascular disease for participants consuming ≥2 servings/day were 1.21 (95% CI,1.12 to 1.32;P-trendP-trend=0.06), respectively. In the joint analyses, for participants meeting and not meeting physical activity guidelines (ConclusionsOur findings suggest that among physically active participants, higher SSB intake, but not ASBs, is associated with a higher cardiovascular risk. Our results support current recommendations to limit the intake of SSB and maintain adequate physical activity levels.Clinical PerspectiveWhat is new?Consumption of sugar- or artificially-sweetened beverages and physical activity are independently associated with cardiovascular disease; nevertheless, the role that physical activity plays in the associations between sugar- and artificially-sweetened beverages consumption and cardiovascular disease warrants further analysis since physical activity could offset the health risk that would have been induced by their consumption.In two US cohorts, not meeting physical activity guidelines jointly with a greater intake of sugar- or artificially-sweetened beverages was associated with a higher risk of cardiovascular disease; however, even when individuals were physically active, higher consumption of sugar-sweetened beverages was associated with a higher cardiovascular risk.What are the clinical implications?Our results provide further evidence of the intake of sugar-sweetened beverages and low physical activity as factors negatively impacting cardiovascular health.Our results support public health recommendations and policies to limit the intake of sugar-sweetened beverages and meet and maintain adequate physical activity levels.

Background The aim of obesity treatment is to promote loss of fat relative to lean mass. However, body composition changes with calorie restriction differ among individuals. Objectives The goal of this study was to test the hypothesis that insulin secretion predicts body composition changes among young and middle-age adults with high BMI (in kg/m2) following major weight loss. Methods Exploratory analyses were conducted with pre-randomization data from 2 large feeding trials: the Framingham, Boston, Bloomington, Birmingham, and Baylor study (FB4; n = 82, 43.9% women, BMI ≥27) and the Framingham State Food Study [(FS)2; n = 161, 69.6% women, BMI ≥25]. Participants in the 2 trials consumed calorie-restricted moderate-carbohydrate or very-low-carbohydrate diets to produce 12-18% weight loss in ∼14 wk or 10-14% in ∼10 wk, respectively. We determined insulin concentration 30 min after a 75-g oral glucose load (insulin-30) as a measure of insulin secretion and HOMA-IR as a measure of insulin resistance at baseline. Body composition was determined by DXA at baseline and post-weight loss. Associations were analyzed using general linear models with adjustment for covariates. Results In FB4, higher insulin-30 was associated with a smaller decrease in fat mass (0.441 kg per 100 μIU/mL increment in baseline insulin-30; P = 0.005; -1.20-kg mean difference between the first compared with the fifth group of insulin-30) and a larger decrease in lean mass (-0.465 kg per 100 μIU/mL; P = 0.004; 1.27-kg difference). Participants with higher insulin-30 lost a smaller proportion of weight loss as fat (-3.37% per 100 μIU/mL; P = 0.003; 9.20% difference). Greater HOMA-IR was also significantly associated with adverse body composition changes. Results from (FS)2 were qualitatively similar but of a smaller magnitude. Conclusions Baseline insulin dynamics predict substantial individual differences in body composition following weight loss. These findings may inform understanding of the pathophysiological basis for weight regain and the design of more effective obesity treatment. Registered at clinicaltrials.gov as NCT03394664 and NCT02068885.

Adipocyte mitochondrial respiration may influence metabolic fuel partitioning into oxidation versus storage, with implications for whole-body energy expenditure. Although insulin has been shown to influence mitochondrial respiration, the effects of dietary macronutrient composition have not been well characterized. The aim of this exploratory study was to test the hypothesis that a high-carbohydrate diet lowers the oxygen flux of adipocyte mitochondria ex vivo. Among participants in a randomized-controlled weight-loss maintenance feeding trial, those consuming a high-carbohydrate diet (60% carbohydrate as a proportion of total energy, n = 10) had lower rates of maximal adipose tissue mitochondrial respiration than those consuming a moderate-carbohydrate diet (40%, n = 8, p = 0.039) or a low-carbohydrate diet (20%, n = 9, p = 0.005) after 10 to 15 weeks. This preliminary finding may provide a mechanism for postulated calorie-independent effects of dietary composition on energy expenditure and fat deposition, potentially through the actions of insulin on fuel partitioning.

Background Carbohydrate restriction shows promise for diabetes, but concerns regarding high saturated fat content of low-carbohydrate diets limit widespread adoption. Objectives This preplanned ancillary study aimed to determine how diets varying widely in carbohydrate and saturated fat affect cardiovascular disease (CVD) risk factors during weight-loss maintenance. Methods After 10–14% weight loss on a run-in diet, 164 participants (70% female; BMI = 32.4 ± 4.8 kg/m2) were randomly assigned to 3 weight-loss maintenance diets for 20 wk. The prepared diets contained 20% protein and differed 3-fold in carbohydrate (Carb) and saturated fat as a proportion of energy (Low-Carb: 20% carbohydrate, 21% saturated fat; Moderate-Carb: 40%, 14%; High-Carb: 60%, 7%). Fasting plasma samples were collected prerandomization and at 20 wk. Lipoprotein insulin resistance (LPIR) score was calculated from triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P). Other outcomes included lipoprotein(a), triglycerides, HDL cholesterol, LDL cholesterol, adiponectin, and inflammatory markers. Repeated measures ANOVA was used for intention-to-treat analysis. Results Retention was 90%. Mean change in LPIR (scale 0–100) differed by diet in a dose-dependent fashion: Low-Carb (–5.3; 95% CI: –9.2, –1.5), Moderate-Carb (–0.02; 95% CI: –4.1, 4.1), High-Carb (3.6; 95% CI: –0.6, 7.7), P = 0.009. Low-Carb also favorably affected lipoprotein(a) [–14.7% (95% CI: –19.5, –9.5), –2.1 (95% CI: –8.2, 4.3), and 0.2 (95% CI: –6.0, 6.8), respectively; P = 0.0005], triglycerides, HDL cholesterol, large/very large TRL-P, large HDL-P, and adiponectin. LDL cholesterol, LDL-P, and inflammatory markers did not differ by diet. Conclusions A low-carbohydrate diet, high in saturated fat, improved insulin-resistant dyslipoproteinemia and lipoprotein(a), without adverse effect on LDL cholesterol. Carbohydrate restriction might lower CVD risk independently of body weight, a possibility that warrants study in major multicentered trials powered on hard outcomes. The registry is available through ClinicialTrials.gov: https://clinicaltrials.gov/ct2/show/NCT02068885.

Background: Consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) and physical activity are independently associated with type 2 diabetes (T2D) risk; however, it is unknown whether there is an interaction of SSB/ASB intake and physical activity on risk of T2D. Methods: We examined the independent and joint associations between habitual SSB/ASB intake and physical activity with incident T2D risk among 196,101 women and men from the Nurses’ Health Study (NHS, 1980-2016), NHSII (1991-2017), and Health Professional’s Follow-up Study (HPFS, 1986-2016), who were free from chronic diseases at baseline. Cox proportional hazards regressions were used to estimate hazard ratios and 95% confidence intervals (HR; CI), adjusting for demographic and lifestyle T2D risk factors. Results: There were 20,430 incident T2D cases over follow-up of 36, 26, and 30 years in NHS, NHSII, and HPFS, respectively. In multivariable-adjusted models, we confirmed that participants with higher SSBs, ASBs and lower physical activity were independently at higher T2D risk, compared to lower intakes and higher activity levels. In joint analyses for these exposures, participants who did not meet physical activity guidelines and consumed gt 2 servings/day of SSBs had a significantly higher risk of T2D than those who met physical activity guidelines and never/rarely consumed SSBs (1.51; 1.43, 1.60); we observed similar findings for ASBs: 1.29; 1.23, 1.36). Among participants who met physical activity guidelines, those who consumed gt 2 servings/day of SSBs had a HR of 1.23 (1.16, 1.30); the HR for ASBs was 1.07 (1.02, 1.13). Consistent results were observed for women and men. Conclusions: Long-term habitual intake of SSBs or ASBs combined with lower physical activity was associated with higher risk of T2D in three large prospective cohort studies. These findings suggest that even when individuals are physically active, higher consumption of SSBs is associated with a higher risk of T2D. Our results support recommendations and policies to limit the intake of SSB and increase physical activity levels.

BackgroundRecent three-dimensional optical (3DO) imaging advancements have provided more accessible, affordable, and self-operating opportunities for assessing body composition. 3DO is accurate and precise with respect to clinical measures made by dual-energy X-ray absorptiometry (DXA). However, the sensitivity for monitoring body composition change over time with 3DO body shape is unknown.ObjectiveTo evaluate 3DO’s ability to monitor body composition changes across multiple intervention studies.MethodsA retrospective analysis was performed using intervention studies on healthy adults that were complimentary to the cross-sectional study, Shape Up! Adults. Each participant received a DXA (Hologic Discovery/A system) and 3DO (Fit3D ProScanner) scan at baseline and follow-up. 3DO meshes were digitally registered and reposed using Meshcapade to standardize the vertices and pose. Using an established statistical shape model, each 3DO mesh was transformed into principal components (PCs), which were used to predict whole-body and regional body composition values using published equations. Body composition changes (follow-up minus baseline) were compared to DXA with linear regression.ResultsThe analysis included 133 participants (45 females) in six studies. The mean (SD) length of follow-up was 13 (5) weeks, range 3-23 weeks. Agreement between 3DO and DXA (R2) for changes in total fat mass (FM), total fat-free mass (FFM), and appendicular lean mass, respectively, were 0.86, 0.73, and 0.70 with RMSEs of 1.98 kg, 1.58 kg, and 0.37 kg in females, and 0.75, 0.75, and 0.52 with RMSEs of 2.31 kg, 1.77 kg, and 0.52 kg in males. Further adjustment with demographic descriptors improved the 3DO change agreement to changes observed with DXA.ConclusionsAs compared to DXA, 3DO was highly sensitive in detecting body shape changes over time. The 3DO method was sensitive enough to detect even small changes in body composition during intervention studies. The safety and accessibility of 3DO allows users to self-monitor on a frequent basis throughout interventions.

The obesity pandemic continues unabated despite a persistent public health campaign to decrease energy intake (“eat less”) and increase energy expenditure (“move more”). One explanation for this failure is that the current approach, based on the notion of energy balance, has not been adequately embraced by the public. Another possibility is that this approach rests on an erroneous paradigm. A new formulation of the energy balance model (EBM), like prior versions, considers overeating (energy intake > expenditure) the primary cause of obesity, incorporating an emphasis on “complex endocrine, metabolic, and nervous system signals” that control food intake below conscious level. This model attributes rising obesity prevalence to inexpensive, convenient, energy-dense, “ultra-processed” foods high in fat and sugar. An alternative view, the carbohydrate-insulin model (CIM), proposes that hormonal responses to highly processed carbohydrates shift energy partitioning toward deposition in adipose tissue, leaving fewer calories available for the body’s metabolic needs. Thus, increasing adiposity causes overeating to compensate for the sequestered calories. Here, we highlight robust contrasts in how the EBM and CIM view obesity pathophysiology and consider deficiencies in the EBM that impede paradigm testing and refinement. Rectifying these deficiencies should assume priority, as a constructive paradigm clash is needed to resolve long-standing scientific controversies and inform the design of new models to guide prevention and treatment. Nevertheless, public health action need not await resolution of this debate, as both models target processed carbohydrates as major drivers of obesity.

BACKGROUND The effect of macronutrient composition on total energy expenditure (TEE) remains controversial, with divergent findings among studies. One source of heterogeneity may be study duration, as physiological adaptation to lower carbohydrate intake may require 2 to 3 wk. OBJECTIVE We tested the hypothesis that the effects of carbohydrate [expressed as % of energy intake (EI)] on TEE vary with time. METHODS The sample included trials from a previous meta-analysis and new trials identified in a PubMed search through 9 March 2020 comparing lower- and higher-carbohydrate diets, controlled for EI or body weight. Three reviewers independently extracted data and reconciled discrepancies. Effects on TEE were pooled using inverse-variance-weighted meta-analysis, with between-study heterogeneity assessed using the I2 statistic. Meta-regression was used to quantify the influence of study duration, dichotomized at 2.5 wk. RESULTS The 29 trials ranged in duration from 1 to 140 d (median: 4 d) and included 617 participants. Difference in carbohydrate between intervention arms ranged from 8% to 77% EI (median: 30%). Compared with reported findings in the prior analysis (I2 = 32.2%), we found greater heterogeneity (I2 = 90.9% in the reanalysis, 81.6% in the updated analysis). Study duration modified the diet effect on TEE (P

The obesity pandemic continues unabated despite a persistent public health campaign to decrease energy intake ("eat less") and increase energy expenditure ("move more"). One explanation for this failure is that the current approach, based on the notion of energy balance, has not been adequately embraced by the public. Another possibility is that this approach rests on an erroneous paradigm. A new formulation of the energy balance model (EBM), like prior versions, considers overeating (energy intakeexpenditure) the primary cause of obesity, incorporating an emphasis on "complex endocrine, metabolic, and nervous system signals" that control food intake below conscious level. This model attributes rising obesity prevalence to inexpensive, convenient, energy-dense, "ultra-processed" foods high in fat and sugar. An alternative view, the carbohydrate-insulin model (CIM), proposes that hormonal responses to highly processed carbohydrates shift energy partitioning toward deposition in adipose tissue, leaving fewer calories available for the body's metabolic needs. Thus, increasing adiposity causes overeating to compensate for the sequestered calories. Here, we highlight robust contrasts in how the EBM and CIM view obesity pathophysiology and consider deficiencies in the EBM that impede paradigm testing and refinement. Rectifying these deficiencies should assume priority, as a constructive paradigm clash is needed to resolve long-standing scientific controversies and inform the design of new models to guide prevention and treatment. Nevertheless, public health action need not await resolution of this debate, as both models target processed carbohydrates as major drivers of obesity.

OBJECTIVE: The carbohydrate-insulin model (CIM) claims that chronic exposure to hyperinsulinemia induced by dietary carbohydrates explains development of obesity via direct effects of insulin and/or low postprandial metabolic fuel levels. We aimed at testing whether indices of hyperinsulinemia and postprandial glucose levels can predict increases in the degree of obesity over time. RESEARCH DESIGN AND METHODS: Children and adolescents with obesity attending a pediatric obesity clinic performed oral glucose tolerance tests (OGTTs) and received standard obesity management. Indices of hyperinsulinemia and insulin secretion were derived from the OGTT and evaluated in the face of changes in the degree of obesity over time. RESULTS: A total of 591 children (217 males and 374 females) participated, and the mean follow-up was 1.86 ± 1.29 years. OGTT-derived area under the curve of insulin, peak insulin, fasting insulin, the insulinogenic index, or insulin at 30 min were not associated with greater changes in the degree of obesity in univariate or multivariate analyses (adjusted for baseline age, BMI z score, sex, and ethnicity). Low postprandial glucose 4 years, none of these parameters was associated with greater increases in the degree of obesity. CONCLUSIONS: In children and adolescents with obesity, exposure to hyperinsulinemia, greater insulin secretion, or low postprandial glucose is not associated with greater increases in the degree of obesity over 2–4 years. The CIM should be evaluated in children with lower BMI and for longer follow-up periods.

Background Longer-term feeding studies suggest that a low-carbohydrate diet increases energy expenditure, consistent with the carbohydrate-insulin model of obesity. However, the validity of methodology utilized in these studies, involving doubly labeled water (DLW), has been questioned. Objective The aim of this study was to determine whether dietary energy requirement for weight-loss maintenance is higher on a low- compared with high-carbohydrate diet. Methods The study reports secondary outcomes from a feeding study in which the primary outcome was total energy expenditure (TEE). After attaining a mean Run-in weight loss of 10.5%, 164 adults (BMI ≥25 kg/m2; 70.1% women) were randomly assigned to Low-Carbohydrate (percentage of total energy from carbohydrate, fat, protein: 20/60/20), Moderate-Carbohydrate (40/40/20), or High-Carbohydrate (60/20/20) Test diets for 20 wk. Calorie content was adjusted to maintain individual body weight within ± 2 kg of the postweight-loss value. In analyses by intention-to-treat (ITT, completers, n = 148) and per protocol (PP, completers also achieving weight-loss maintenance, n = 110), we compared the estimated energy requirement (EER) from 10 to 20 wk of the Test diets using ANCOVA. Results Mean EER was higher in the Low- versus High-Carbohydrate group in models of varying covariate structure involving ITT [ranging from 181 (95% CI: 8–353) to 246 (64–427) kcal/d; P ≤0.04] and PP [ranging from 245 (43–446) to 323 (122–525) kcal/d; P ≤0.02]. This difference remained significant in sensitivity analyses accounting for change in adiposity and possible nonadherence. Conclusions Energy requirement was higher on a low- versus high-carbohydrate diet during weight-loss maintenance in adults, commensurate with TEE. These data are consistent with the carbohydrate-insulin model and lend qualified support for the validity of the DLW method with diets varying in macronutrient composition. This trial was registered at clinicaltrials.gov as NCT02068885.

A large feeding study reported that total energy expenditure (TEE) was greater on a low- versus high-carbohydrate diet, supporting the carbohydrate-insulin model of obesity. Recently, the validity of this finding was challenged in a post-hoc analysis excluding participants with putative non-adherence to the study diets. Here, we show why that analysis, based on a post-randomization variable linked to the outcome, introduced severe confounding bias. With control for confounding, the diet effect on TEE remained strong in a reanalysis. Together with sensitivity analyses demonstrating robustness to plausible levels of non-adherence, these data provide experimental support for a potentially novel metabolic effect of macronutrients that might inform the design of more effective obesity treatment.

OBJECTIVE Consuming ≥150 g/day carbohydrate is recommended for 3 days before an oral glucose tolerance test (OGTT) for diabetes diagnosis. For evaluation of this recommendation, time courses of glycemic changes following transition from a very-low-carbohydrate (VLC) to high-carbohydrate diet were assessed with continuous glucose monitoring (CGM). RESEARCH DESIGN AND METHODS After achieving a weight loss target of 15% (±3%) on the run-in VLC diet, participants (18–50 years old, BMI ≥27 kg/m2) were randomly assigned for 10 weeks to one of three isoenergetic diets: VLC (5% carbohydrate and 77% fat); high carbohydrate, high starch (HC-Starch) (57% carbohydrate and 25% fat, including 20% refined grains); and high carbohydrate, high sugar (HC-Sugar) (57% carbohydrate and 25% fat, including 20% sugar). CGM was done throughout the trial (n = 64) and OGTT at start and end (n = 41). All food was prepared in a metabolic kitchen and consumed under observation. RESULTS Glucose metrics continued to decline after week 1 in the HC-Starch and HC-Sugar groups (P < 0.05) but not VLC. During weeks 2–5, fasting and 2-h glucose (millimoles per liter per week) decreased in HC-Starch (fasting −0.10, P = 0.001; 2 h −0.10, P = 0.04). During weeks 6–9, 2-h glucose decreased in HC-Starch (−0.07, P = 0.01) and fasting and 2-h glucose decreased in HC-Sugar (fasting −0.09, P = 0.001; 2 h −0.09, P = 0.003). The number of participants with abnormal glucose tolerance by OGTT remained 10 (of 16) in VLC at start and end but decreased from 17 to 9 (of 25) in both high-carbohydrate groups. CONCLUSIONS Physiological adaptation from a low- to high-carbohydrate diet may require many weeks, with implications for the accuracy of diabetes tests, interpretation of macronutrient trials, and risks of periodic planned deviations from a VLC diet.

Global challenges such as climate change, food security, or public health have become dominant concerns in research and innovation policy. This article examines how responses to these challenges are addressed by governance actors. We argue that appeals to global challenges can give rise to a ‘solution strategy' that presents responses of dominant actors as solutions and a ‘negotiation strategy' that highlights the availability of heterogeneous and often conflicting responses. On the basis of interviews and document analyses, the study identifies both strategies across local, national, and European levels. While our results demonstrate the co-existence of both strategies, we find that global challenges are most commonly highlighted together with the solutions offered by dominant actors. Global challenges are ‘wicked problems' that often become misframed as ‘tame problems’ in governance practice and thereby legitimise dominant responses.

Adipocyte mitochondrial respiration may influence metabolic fuel partitioning into oxidation versus storage, with implications for whole-body energy expenditure. Although insulin has been shown to influence mitochondrial respiration, the effects of dietary macronutrient composition have not been well characterized. The aim of this exploratory study was to test the hypothesis that a high-carbohydrate diet lowers the oxygen flux of adipocyte mitochondria ex vivo. Among participants in a randomized-controlled weight-loss maintenance feeding trial, those consuming a high-carbohydrate diet (60% carbohydrate as a proportion of total energy, n = 10) had lower rates of maximal adipose tissue mitochondrial respiration than those consuming a moderate-carbohydrate diet (40%, n = 8, p = 0.039) or a low-carbohydrate diet (20%, n = 9, p = 0.005) after 10 to 15 weeks. This preliminary finding may provide a mechanism for postulated calorie-independent effects of dietary composition on energy expenditure and fat deposition, potentially through the actions of insulin on fuel partitioning.

Background The “carnivore diet,” based on animal foods and excluding most or all plant foods, has attracted recent popular attention. However, little is known about the health effects and tolerability of this diet, and concerns for nutrient deficiencies and cardiovascular disease risk have been raised. Objectives We obtained descriptive data on the nutritional practices and health status of a large group of carnivore diet consumers. Methods A social media survey was conducted 30 March–24 June, 2020 among adults self-identifying as consuming a carnivore diet for ≥6 mo. Survey questions interrogated motivation, dietary intake patterns, symptoms suggestive of nutritional deficiencies or other adverse effects, satisfaction, prior and current health conditions, anthropometrics, and laboratory data. Results A total of 2029 respondents (median age: 44 y, 67% male) reported consuming a carnivore diet for 14 mo (IQR: 9–20 mo), motivated primarily by health reasons (93%). Red meat consumption was reported as daily or more often by 85%. Under 10% reported consuming vegetables, fruits, or grains more often than monthly, and 37% denied vitamin supplement use. Prevalence of adverse symptoms was low (, In a survey of >2000 adults following a “carnivore diet” (i.e., one that aims to avoid plant foods), health benefits and satisfaction were generally reported.

Instigating dialogue with heterogeneous stakeholders is commonly presented as a necessary ingredient to develop science with and for society. Such objectives are central to the framework of responsible innovation designed to align the process and the outcomes of science and innovation to the values, needs, and expectations of society. However, what conditions need to be in place for dialogue to fulfil these goals? In this chapter we analyse two case studies that make use of societal dialogues on the future of gene editing. In the first case, we analyse dynamics of inclusion and exclusion at a recent CRISPRcon conference at Wageningen University. While presenting itself as a forum for diverse voices, we find the conference constructed an affective frame about revolutionary promises that reinforced the perspectives of dominant stakeholders. In the second case, we describe an alternative approach making use of focus group discussions with lay publics, designed to open up context, framing, and moderation for collaborative negotiation of heterogeneous concerns. While not providing simple solutions, they created a space in which competing values and views could be shared and negotiated, and which, we argue, can better contribute to responsible, just, and inclusive innovation.

According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body—resulting from the hormonal responses to a high-glycemic-load diet—drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence.

The Netherlands has a well-established tradition of gearing science and technology to economic interests as well as societal and ethical concerns. This article outlines how national dynamics in the Netherlands have not only contributed to the adoption of Responsible Research and Innovation (RRI) frameworks but also to a distinctly Dutch meaning and institutionalization of responsibility. It identifies three core features of the Dutch context that have shaped this meaning and institutionalization: 1) a strong focus on the societal and economic relevance of research and innovation, 2) a political culture that emphasizes inclusive deliberation and collaboration, and 3) a focus on integration and synergy with respect to RRI. The integration of RRI in a collaborative system of companies, government and universities is embraced as contributing to a global leadership of the Netherlands in response to grand challenges. However, this integrative approach also limits the potential of Dutch RRI to function as a disruptive concept that challenges the status of interactions between science, technology, and society.

This article develops a framework for addressing racial ontologies in transnational perspective. In contrast to simple contextualist accounts, it is argued that a globally engaged metaphysics of race needs to address transnational continuities of racial ontologies. In contrast to unificationist accounts that aim for one globally unified ontology, it is argued that questions about the nature and reality of race do not always have the same answers across national contexts. In order address racial ontologies in global perspective, the article develops a framework that accounts for both continuities and discontinuities by looking beyond the referents of narrowly defined core concepts. By shifting the focus from narrow concepts to richer conceptions of race, racial ontologies become comparable through globally related but nonetheless distinct mappings between conceptions and property relations. The article concludes by showing how this framework can generate novel insights in case studies from Asia, Europe, and Latin America.

Summary The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (, Graphical Abstract, Highlights 5,756 doubly labeled water (DLW) measures highlight variation from calculation equation We derive here new equations for calculating CO2 production when using DLW These equations outperform previous equations in validation studies We recommend these equations should be adopted in future studies using DLW in humans, Speakman et al. use a large database of doubly labeled water measurements to show the choice of equation for the calculation of energy expenditure introduces significant variation into the final estimate. They then derive new equations that outperform previous equations in validation studies against chamber calorimetry.

Carbohydrate restriction, used since the 1700s to prolong survival in people with diabetes, fell out of favor after the discovery of insulin. Despite costly pharmacological and technological developments in the last few decades, current therapies do not achieve optimal outcomes, and most people with diabetes remain at high risk for micro- and macrovascular complications. Recently, low-carbohydrate diets have regained popularity, with preliminary evidence of benefit for body weight, postprandial hyperglycemia, hyperinsulinemia, and other cardiometabolic risk factors in type 2 diabetes and, with more limited data, in type 1 diabetes. High-quality, long-term trials are needed to assess safety concerns and determine whether this old dietary approach might help people with diabetes attain clinical targets more effectively, and at a lower cost, than conventional treatment.

Adapting to anthropogenic climate change requires informed citizens capable of managing personal and societal risks. This study explores the contribution of climate change education (CCE) to build adolescents’ cognitive adaptive capacity. As defined by Grothmann and Patt’s (2005) Model of Private Proactive Adaptation to Climate Change (MPPACC), cognitive dimensions of adaptive capacity correspond to climate change risk perception and adaptation appraisal as preconditions for individual adaptation actions. Their model has been operationalised to examine adolescents’ cognitive adaptive capacity in a pre-test–post-test design, and the educational programme Generation F3–Fit for Future is presented as a quasi-experiment linking this concept with CCE. Because cognitive adaptive capacity is a complex and multifaceted concept, this contribution also studies the influence of CCE on knowledge and thinking skills, which are important dimensions as well. Overall, 173 upper-secondary school students aged between 16 and 18 years actively collaborated with 57 scientific and practical experts on climate change adaptation (CCA) in North and South Tyrol. Additionally, the programme included control groups. Over two school years, Generation F3–Fit for Future encouraged students to follow constructivist inquiry-based CCE, and they carried out their own research-oriented CCA projects. A mixed methods approach compared data from a multivariate multilevel mixed model collected by web-based questionnaires (N = 231) and qualitative data from problem-centred interviews (N = 47), which were analysed by documentary method. The results suggest a mismatch between quantitative and qualitative data. Quantitative data do not show any change in adolescents’ risk perception and adaptation appraisal, but qualitative data reveal that intervention group students demonstrated increased levels of adaptation knowledge and elaborated critical as well as forward thinking skills. Control group students did not show such capacities after standard curriculum education. It is concluded that CCE holds potential to build several dimensions of adolescents’ cognitive adaptive capacity. Upcoming research should further explore mixed research approaches and advance adaptive capacity theory to better understand this concept.

Researchers have become increasingly concerned with the relation between traditional ecological knowledge (TEK) and academic ecological knowledge (AEK). TEK includes complex predictive resources that often remain insufficiently reflected in ecological research, conservation practices, and ecosystem services. At the same time, knowledge integration comes with methodological and political challenges of negotiating differences between knowledge systems. In this article, we provide evidence from different scales (population, community, and ecosystems) about how TEK and AEK can be related when addressing the same phenomena. Finally, we discuss the possibilities of relating TEK and AEK through a perspective of complementarity of knowledge, taking existing differences as opportunities for dialogue.

The rapid development of CRISPR-based gene editing has been accompanied by a polarized governance debate about the status of CRISPR-edited crops as genetically modified organisms. This article argues that the polarization around the governance of gene editing partly reflects a failure of public engagement with the current state of research in genomics and postgenomics. CRISPR-based gene-editing technology has become embedded in a narrow narrative about the ease and precision of the technique that presents the gene as a stable object under technological control. By tracing the considerably destabilized scientific understanding of the gene in genomics and postgenomics, this article highlights that this publicly mediated ontology strategically avoids positioning the “ease of CRISPR-based editing” in the wider context of the “complexity of the gene.” While this strategic narrowness of CRISPR narratives aims to create public support for gene-editing technologies, we argue that it stands in the way of socially desirable anticipatory governance and open public dialogue about societal promises and the unintended consequences of gene editing. In addressing the polarization surrounding CRISPR-based editing technology, the article emphasizes the need for engagement with the complex state of postgenomic science that avoids strategic simplifications of the scientific literature in promoting or opposing the commercial use of the gene-editing technology.

"This book develops an integrated perspective on the practices and politics of making knowledge work in inclusive development and innovation. While debates about development and innovation commonly appeal to the authority of academic researchers, many current approaches emphasize the plurality of actors with relevant expertise for addressing livelihood challenges. Adopting an action-oriented and reflexive approach, this volume explores the variety of ways in which knowledge works, paying particular attention to dilemmas and controversies. The six parts of the book address the complex interplay of knowledge and politics, starting with the need for knowledge integration in the first part and decolonial perspectives on the politics of knowledge integration in the second part. The following three parts focus on the practices of inclusive development and innovation through three major themes of transformative learning, evidence, and digitization. The final part of the book addresses the governance of knowledge and innovation in the light of political struggles about inclusivity. Exploring conceptual and practical themes through case studies from the Global North and South, this book will be of great interest to students, scholars and practitioners researching and working in development studies, epistemology, innovation studies, science and technology studies and sustainability studies more broadly"