The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents

Obesity is a global epidemic associated with significant morbidity and mortality in adults and ill health in children. A proven successful approach in weight management has been the disruption of nutrient digestion, with orlistat having been used to treat obesity for the last 10 years. Although orlistat-induced weight loss remains modest, it produces meaningful reductions in risk factors for obesity-related conditions such as diabetes and cardiovascular disease. Moreover, this lipase inhibitor is free of the serious side effects that have dogged appetite-suppressing drugs. This success had driven investigation into new generation nutraceuticals, supplements and pharmaceutical agents that inhibit the breakdown of complex carbohydrates and fats within the gut. This review focuses on agents purported to inhibit intestinal enzymes responsible for macronutrient digestion. Except for some synthetic products, the majority of agents reviewed are either botanical extracts or bacterial products. Currently, carbohydrate digestion inhibitors are under development to improve glycemic control and these may also induce some weight loss. However, colonic fermentation induced side effects, such as excess gas production, remain an issue for these compounds. The α-glucosidase inhibitor acarbose, and the α-amylase inhibitor phaseolamine, have been used in humans with some promising results relating to weight loss. Nonetheless, few of these agents have made it into clinical studies and without any clinical proof of concept or proven efficacy it is unlikely any will enter the market soon

Beyond-brand effect of television food advertisements on food choice in children: The effects of weight status

Copyright © The Authors 2007.Objective - To investigate the effect of television food advertising on children’s food intake, specifically whether childhood obesity is related to a greater susceptibility to food promotion. Design - The study was a within-subject, counterbalanced design. The children were tested on two occasions separated by two weeks. One condition involved the children viewing food advertisements followed by a cartoon, in the other condition the children viewed non-food adverts followed by the same cartoon. Following the cartoon, their food intake and choice was assessed in a standard paradigm. Setting - The study was conducted in Liverpool, UK. Subjects - Fifty-nine children (32 male, 27 female) aged 9–11 years were recruited from a UK school to participate in the study. Thirty-three children were normal-weight (NW), 15 overweight (OW) and 11 obese (OB). Results - Exposure to food adverts produced substantial and significant increases in energy intake in all children (P < 0·001). The increase in intake was largest in the obese children (P = 0·04). All children increased their consumption of high-fat and/or sweet energy-dense snacks in response to the adverts (P < 0·001). In the food advert condition, total intake and the intake of these specific snack items correlated with the children’s modified age- and gender-specific body mass index score. Conclusions - These data suggest that obese and overweight children are indeed more responsive to food promotion, which specifically stimulates the intake of energy-dense snacks.University of Liverpoo

Do low-calorie sweetened beverages help to control food cravings? Two experimental studies

Low-calorie sweetened (LCS) beverages may help consumers to satisfy hedonic food cravings without violating dieting goals, however this remains unexplored. The present research investigated the effect of priming hedonic eating motivations on ad libitum energy intake in frequent and non-consumers of LCS beverages. It was hypothesised that energy intake would be greater after the hedonic eating prime relative to a control prime in non-consumers, but that frequent LCS beverage consumers would be protected from this effect. In Study 1 (N = 120), frequent and non-consumers were exposed to either chocolate or neutral cues (craving vs. control condition) and then completed a beverage-related visual probe task with concurrent eye-tracking. Ad libitum energy intake from sweet and savoury snacks and beverages (including LCS) was then assessed. Study 2 followed a similar protocol, but included only frequent consumers (N = 172) and manipulated the availability of LCS beverages in the ad libitum eating context (available vs. unavailable). Measures of guilt and perceived behavioural control were also included. In Study 1, as hypothesised, non-consumers showed greater energy intake in the craving condition relative to the control condition, but frequent consumers had similar energy intake in both conditions. Frequent consumers (but not non-consumers) also demonstrated an attentional bias for LCS beverage stimuli compared to both sugar and water stimuli. In contrast, in Study 2 frequent consumers showed greater energy intake in the craving condition relative to the control condition; however, overall energy intake was significantly greater when LCS beverages were unavailable compared to when they were available. Ratings of guilt were higher and perceived control was lower in the LCS-unavailable condition relative to the LCS-available condition. Conclusions: LCS beverages did not consistently protect consumers from craving-induced increases in energy intake. However, frequent consumers consumed fewer calories overall when LCS beverages were available (relative to unavailable), as well as perceiving more control over their food intake and feeling less guilty

When does food refusal require professional intervention?

Food refusal can have the potential to lead to nutritional deficiencies, which increases the risk of a variety of communicable and non-communicable diseases. Deciding when food refusal requires professional intervention is complicated by the fact that there is a natural and appropriate stage in a child's development that is characterised by increased levels of rejection of both previously accepted and novel food items. Therefore, choosing to intervene is difficult, which if handled badly can lead to further food refusal and an even more limited diet. Food refusal is often based on individual preferences; however, it can also be defined through pathological behaviours that require psychological intervention. This paper presents and discusses several different types of food refusal behaviours; these are learningdependent, those that are related to a medical complication, selective food refusal, fear-based food refusal and appetiteawareness-autonomy-based food refusal. This paper describes the behaviours and characteristics that are often associated with each; however, emphasis is placed on the possibility that these different types of food refusal can often be co-morbid. The decision to offer professional intervention to the child and their family should be a holistic process based on the level of medical or psychological distress resulting from the food refusal

Effects of a group-based weight management programme on anxiety and depression: A randomised controlled trial (RCT).

Funder: national institute for health researchFunder: nihr oxford biomedical research centreOBJECTIVES: The aim was to investigate the impact of a group-based weight management programme on symptoms of depression and anxiety compared with self-help in a randomised controlled trial (RCT). METHOD: People with overweight (Body Mass Index [BMI]≥28kg/m2) were randomly allocated self-help (n = 211) or a group-based weight management programme for 12 weeks (n = 528) or 52 weeks (n = 528) between 18/10/2012 and 10/02/2014. Symptoms were assessed using the Hospital Anxiety and Depression Scale, at baseline, 3, 12 and 24 months. Linear regression modelling examined changes in Hospital Anxiety and Depression Scale between trial arms. RESULTS: At 3 months, there was a -0.6 point difference (95% confidence interval [CI], -1.1, -0.1) in depression score and -0.1 difference (95% CI, -0.7, 0.4) in anxiety score between group-based weight management programme and self-help. At subsequent time points there was no consistent evidence of a difference in depression or anxiety scores between trial arms. There was no evidence that depression or anxiety worsened at any time point. CONCLUSIONS: There was no evidence of harm to depression or anxiety symptoms as a result of attending a group-based weight loss programme. There was a transient reduction in symptoms of depression, but not anxiety, compared to self-help. This effect equates to less than 1 point out of 21 on the Hospital Anxiety and Depression Scale and is not clinically significant

Associations between hedonic hunger and BMI during a two-year behavioural weight loss trial.

ObjectiveProspective studies on relationships between hedonic hunger and BMI (Body Mass Index) during weight management are lacking. This study examined if hedonic hunger reduced during a behavioural weight management programme, and if hedonic hunger predicted future BMI.MethodsParticipants were 594 community-dwelling, UK-based adults(396 female; age 56.43 years, s.d. = 12.50, range 20-83 years); 490 participants (82.5%) had obesity. Participants were randomised to a 12- or 52-week behavioural weight management intervention (WW12 or WW52, respectively) or a brief self-help intervention (BI). Relationships between hedonic hunger and BMI over 24 months (baseline, 3, 12, 24 months) were analysed using an autoregressive cross-lagged model.ResultsHedonic hunger scores decreased from 2.71 (s.d. = .91) at baseline to 2.41 (s.d. = .88) at 3 months (p .05). Baseline hedonic hunger scores predicted 3-month scores (B = .76, SE = .03, p .05). BMI at 12 months was lower in WW52 30.87kg/m2, s.d. = 5.02) than WW12 (32.12 kg/m2, s.d. = 5.58, p = .02, CI .16 to 2.34) and BI (32.74 kg/m2, s.d. = 4.15, p = .01, CI .30 to 3.45). BMI was not affected by intervention at any other time point (p's>.05).ConclusionHedonic hunger reduced during weight management irrespective of intervention. Early reductions in hedonic hunger appear to be associated with lower BMI in the medium-term. Identifying ways to reduce hedonic hunger during weight loss could aid weight management for some people

The Health Halo Trend in UK Television Food Advertising Viewed by Children: The Rise of Implicit and Explicit Health Messaging in the Promotion of Unhealthy Foods

Monitoring the creative content within food marketing to children is strongly advocated by public health authorities, but few studies address the prevalence of health-related messaging in television adverts. Food and beverage adverts (n = 18,888 in 2008, n = 6664 in 2010) from UK television channels popular with children were coded and analyzed. Physical-activity depiction displayed an 18.8 percentage point increase from 2008 (4.4%) to 2010 (23.2%). Of the food adverts containing physical-activity depiction in 2010, 81.1% were for non-core foods. The appearance of health claims in food adverts in 2010 increased 4.1 percentage points from 2008 levels (20.7% to 24.8%) where the majority of food adverts featuring health and nutrition claims were for non-core foods (58.3%). Health-related (e.g., health/nutrition, weight loss/diet) appeals were used in 17.1% of food adverts during peak child-viewing times, rising to 33.0% of adverts shown on dedicated children’s channels in 2010. Implicit (physical activity) and explicit (health claims) health messages are increasingly prevalent in UK television food advertising viewed by children, and are frequently used to promote unhealthy foods. Policy makers in the UK should consider amendments to the existing statutory approach in order to address this issue

Circulating Metabolites Associated with Body Fat and Lean Mass in Adults with Overweight/Obesity

The interplay between fat mass and lean mass within human metabolism is not completely understood. We aimed to identify specific circulating metabolomic profiles associated with these body composition compartments. Cross-sectional analyses were conducted over 236 adults with overweight/obesity from the Satiety Innovation (SATIN) study. Body composition was assessed by dual-energy X-ray absorptiometry. A targeted multiplatform metabolite profiling approach was applied. Associations between 168 circulating metabolites and the body composition measures were assessed using elastic net regression analyses. The accuracy of the multimetabolite weighted models was evaluated using a 10-fold cross-validation approach and the Pearson's correlation coefficients between metabolomic profiles and body compartments were estimated. Two different profiles including 86 and 65 metabolites were selected for % body fat and lean mass. These metabolites mainly consisted of lipids (sphingomyelins, phosphatidylcholines, lysophosphatidylcholines), acylcarnitines, and amino acids. Several metabolites overlapped between these body composition measures but none of them towards the same direction. The Pearson correlation coefficients between the metabolomic profiles and % body fat or lean mass were 0.80 and 0.79, respectively. Our findings suggest alterations in lipid metabolism, fatty acid oxidation, and protein degradation with increased adiposity and decreased lean body mass. These findings could help us to better understand the interplay between body composition compartments with human metabolic processes

Weight loss referrals for adults in primary care (WRAP) : Protocol for a multi-centre randomised controlled trial comparing the clinical and cost-effectiveness of primary care referral to a commercial weight loss provider for 12 weeks, referral for 52 weeks, and a brief self-help intervention [ISRCTN82857232]

Background: Recent trials demonstrate the acceptability and short term efficacy of primary care referral to a commercial weight loss provider for weight management. Commissioners now need information on the optimal duration of intervention and the longer term outcomes and cost effectiveness of such treatment to give best value for money. Methods/Design. This multicentre, randomised controlled trial with a parallel design will recruit 1200 overweight adults (BMI ≥28 kg/m2) through their primary care provider. They will be randomised in a 2:5:5 allocation to: Brief Intervention, Commercial Programme for 12 weeks, or Commercial Programme for 52 weeks. Participants will be followed up for two years, with assessments at 0, 3, 12 and 24 months. The sequential primary research questions are whether the CP interventions achieve significantly greater weight loss from baseline to 12 months than BI, and whether CP52 achieves significantly greater weight loss from baseline to 12 months than CP12. The primary outcomes will be an intention to treat analysis of between treatment differences in body weight at 12 months. Clinical effectiveness will be also be assessed by measures of weight, fat mass, and blood pressure at each time point and biochemical risk factors at 12 months. Self-report questionnaires will collect data on psychosocial factors associated with adherence, weight-loss and weight-loss maintenance. A within-trial and long-term cost-effectiveness analysis will be conducted from an NHS perspective. Qualitative methods will be used to examine the participant experience. Discussion. The current trial compares the clinical and cost effectiveness of referral to a commercial provider with a brief intervention. This trial will specifically examine whether providing longer weight-loss treatment without altering content or intensity (12 months commercial referral vs. 12 weeks) leads to greater weight loss at one year and is sustained at 2 years. It will also evaluate the relative cost-effectiveness of the three interventions. This study has direct implications for primary care practice in the UK and will provide important information to inform the decisions of practitioners and commissioners about service provision