Clare L. Lawton

Resistance and susceptibility to weight gain: Individual variability in response to a high-fat diet

An obesigenic environment is a potent force for promoting weight gain. However, not all people exposed to such an environment become obese; some remain lean. This means that some people are susceptible to weight gain (in a weight-promoting environment) and others are resistant. Identifying the characteristics of appetite control and food motivation in these two groups could throw light on the causes of weight gain and how this can be either treated or prevented. We have investigated the issue experimentally by identifying people who habitually consume a high-fat diet (greater than 43% fat energy). These individuals have been termed high-fat phenotypes. We have compared individuals, of the same age (mean=37 years old) and gender (male), who have gained weight (BMI=34) or who have remained lean (BMI=22). The susceptible individuals are characterised by a cluster of characteristics including a weak satiety response to fatty meals, a maintained preference for high-fat over low-energy foods in the post-ingestive satiety period, a strong hedonic attraction to palatable foods and to eating, and high scores on the TFEQ factors of Disinhibition and Hunger. The analysis of large databases suggests that this profile of factors contributes to an average daily positive energy balance from food of approximately 0.5 MJ. This profile of characteristics helps to define the symptomatology of a thrifty phenotype.

Serotonergic drugs : effects on appetite expression and use for the treatment of obesity.

Over 35 years of research suggests that endogenous hypothalamic serotonin (5-hydroxytryptamine) plays an important part in within-meal satiation and post-meal satiety processes. Thus, the serotonin system has provided a viable target for weight control, critical to the action of at least two effective anti-obesity treatments, both producing clinically significant weight loss over a year or more. Numerous serotonin receptor subtypes have been identified; of these, serotonin 5-HT1B and 5-HT2C receptors have been specifically recognised as mediators of serotonin-induced satiety.A number of serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs), dexfenfluramine and 5-HT2C receptor agonists, have been shown to significantly attenuate rodent bodyweight gain. This effect is strongly associated with marked hypophagia and is probably mediated by the hypothalamic melanocortin system. Additionally, sibutramine, dexfenfluramine, fluoxetine and the 5-HT2C receptor agonist chlorophenylpiperazine (mCPP) have all been shown to modify appetite in both lean and obese humans, resulting in reduced caloric intake. Clinical studies demonstrate serotonergic drugs specifically reduce appetite prior to and following the consumption of fixed caloric loads, and cause a reduction in pre-meal appetite and caloric intake at ad libitum meals. Weight loss in the obese has also been produced by treatment with both the serotonin precursor 5-hydroxytryptophan and the preferential 5-HT2C receptor agonist mCPP.A new generation of 5-HT2C receptor selective agonists have been developed and at least one, lorcaserin (APD356), is currently undergoing clinical trials. In addition, 5-HT6 receptor antagonists such as PRX-07034 and BVT74316 have been shown to potently reduce food intake and bodyweight gain in rodent models and have recently entered clinical trials. However, the role of the 5-HT6 receptor in the expression of appetite remains to be determined. The hope is that these drugs will not only be free of their predecessors’ adverse effect profiles, but will also be equally or more effective at regulating appetite and controlling bodyweight.

A systematic review of the effect of breakfast on the cognitive performance of children and adolescents

Breakfast is recommended as part of a healthy diet because it is associated with healthier macro- and micronutrient intakes, BMI and lifestyle. Breakfast is also widely promoted to improve cognitive function and academic performance, leading to the provision of breakfast initiatives by public health bodies. Despite this positive and intuitive perception of cognitive benefits, there has been no systematic review of the evidence. Systematic review methodology was employed to evaluate the effects of breakfast on cognitive performance in well-nourished children and nutritionally at-risk or stunted children. Acute experimental studies, school feeding programmes and studies of habitual breakfast intake are reviewed. Comparisons of breakfast v. no breakfast and breakfasts differing in energy and macronutrient composition are discussed. Included are forty-five studies described in forty-one papers published between 1950 and 2008. The evidence indicates that breakfast consumption is more beneficial than skipping breakfast, but this effect is more apparent in children whose nutritional status is compromised. There is a lack of research comparing breakfast type, precluding recommendations for the size and composition of an optimal breakfast for childrens cognitive function. Few studies examined adolescents. Studies of school breakfast programmes suggest that such interventions can have positive effects on academic performance, but this may be in part explained by the increased school attendance that programmes encourage. The present systematic review considers methodological issues in this field and makes recommendations for future research design and policy priorities.

Dietary fat and the control of energy intake: evaluating the effects of fat on meal size and postmeal satiety.

Three separate experiments in lean subjects confirmed that a 1.52-MJ (362-kcal) carbohydrate supplement at breakfast suppressed appetite 90 min later but had no effect on a test meal given after 270 min. A 1.52-MJ (362-kcal) fat supplement produced no detectable action on measures of appetite at any time point. Therefore, fat and carbohydrate do not have identical effects on the appetite profile. In a further study in obese subjects, a novel experimental design was used to assess the satiating efficiency and compensatory response of fat. Eating from a range of either high-fat or high-carbohydrate foods, obese subjects voluntarily consumed twice as much energy from the fat items, thereby indicating a weak action of fat on satiation. In turn, this large intake of fat exerted a disproportionately weak effect on satiety. These studies suggest that the appetite-control system may have only weak inhibitory mechanisms to prevent the passive overconsumption of dietary fat. The results indicate how this action could induce a positive energy balance and lead to a gradual upward drift in body mass index.

The degree of saturation of fatty acids influences post-ingestive satiety.

Two studies were designed to compare the effects on post-ingestive satiety of manipulating the degree of saturation of fatty acids, at a fixed chain length (18 C atoms), in a fixed energy (5.68 MJ for males; 3.97 MJ for females), high-fat (55% energy) lunch meal. Two different groups of twenty subjects (ten males and ten females) took part in each study. All forty subjects were of normal weight and aged between 18 and 36 years. Study 1 compared the effects of fat A (oleic blend, high in monounsaturated fatty acids (MUFA)) with those of fat B (linoleic blend, high in polyunsaturated fatty acids (PUFA)) and fat C (stearic-oleic blend, high in saturated fatty acids (SFA)). Study 2, which was designed to confirm and extend the findings of Study 1, compared the effects of fats A, B and C with those of fat D (a linoleic-oleic blend). Energy and nutrient intakes were monitored for the rest of the day and for the following day. Profiles of hunger, fullness and other sensations were monitored by continuous tracking and end-of-day questionnaires. In each meal the fat content was exclusively composed of one particular type (A, B, C or D) and was divided equally between the main course and dessert. Study 1 revealed a significant effect of fat type (degree of saturation) on intake of nutrients at the following (dinner) meal (smallest F[2,36] 3.38, P < 0.05), on post-ingestive ratings of motivation to eat (smallest F[2,36] 4.18, P = 0.02) and on energy intake over the whole test day (F[2,36] 3.39, P < 0.01). Subjects consumed significantly more energy after consumption of the lunch containing fat A than after the lunches containing fats B or C and there was a trend for these effects to continue into the second day. In Study 2, fat C produced more similar effects on appetite to fat A and there was a tendency for subjects to consume more over the whole test day when they had consumed the lunch containing fat A than when they had consumed the lunch containing fat B. Furthermore, when the data from fat conditions A and B in both studies were combined (n 40) the results of Study 1 were confirmed. Overall, the results of these short-term studies indicate that PUFA may exert a relatively stronger control over appetite than MUFA and SFA.

Impact of postprandial glycaemia on health and prevention of disease.

Postprandial glucose, together with related hyperinsulinemia and lipidaemia, has been implicated in the development of chronic metabolic diseases like obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In this review, available evidence is discussed on postprandial glucose in relation to body weight control, the development of oxidative stress, T2DM, and CVD and in maintaining optimal exercise and cognitive performance. There is mechanistic evidence linking postprandial glycaemia or glycaemic variability to the development of these conditions or in the impairment in cognitive and exercise performance. Nevertheless, postprandial glycaemia is interrelated with many other (risk) factors as well as to fasting glucose. In many studies, meal‐related glycaemic response is not sufficiently characterized, or the methodology with respect to the description of food or meal composition, or the duration of the measurement of postprandial glycaemia is limited. It is evident that more randomized controlled dietary intervention trials using effective low vs. high glucose response diets are necessary in order to draw more definite conclusions on the role of postprandial glycaemia in relation to health and disease. Also of importance is the evaluation of the potential role of the time course of postprandial glycaemia.

Problems in identifying predictors and correlates of weight loss and maintenance: Implications for weight control therapies based on behaviour change

Weight management is a dynamic process, with a pre‐treatment phase, a treatment (including process) phase and post‐treatment maintenance, and where relapse is possible during both the treatment and maintenance.

Impairments in glucose tolerance can have a negative impact on cognitive function: A systematic research review

There is an increasing body of research investigating whether abnormal glucose tolerance is associated with cognitive impairments, the evidence from which is equivocal. A systematic search of the literature identified twenty-three studies which assessed either clinically defined impaired glucose tolerance (IGT) or variance in glucose tolerance within the clinically defined normal range (NGT). The findings suggest that poor glucose tolerance is associated with cognitive impairments, with decrements in verbal memory being most prevalent. However, the evidence for decrements in other domains was weak. The NGT studies report a stronger glucose tolerance-cognition association than the IGT studies, which is likely to be due to the greater number of glucose tolerance parameters and the more sensitive cognitive tests in the NGT studies compared to the IGT studies. It is also speculated that the negative cognitive impact of abnormalities in glucose tolerance increases with age, and that glucose consumption is most beneficial to individuals with poor glucose tolerance compared to individuals with normal glucose tolerance. The role of potential mechanisms are discussed.

Acute effects of macronutrient manipulations on cognitive test performance in healthy young adults: a systematic research review.

The potential for foods to exert effects on behaviour is increasingly recognised. Previous studies have incorporated both well-known and lesser-known cognitive tests in the evaluation of relationships between macronutrient interventions and mental performance. Systematic review methodology was used to identify studies of macronutrient effects on cognition, limited to acute effects in young, fasted, healthy adults. Thirty-one studies met the inclusion criteria, yielding a total of 134 outcome measures. The studies reviewed displayed a predominance of soluble glucose manipulations, and a paucity of complex carbohydrate, protein or fat manipulations. Memory performance was most commonly measured, but verbal fluency, attention, reaction time, psychomotor skill and problem solving were also assessed. Significant differences in performance tended to occur under circumstances of more intense cognitive demand and after delays. Memory emerged as the most sensitive cognitive modality to macronutrient manipulations. Tasks identified as sensitive included Serial Sevens, Free Word Recall and Cued Word Recall, with tentative support for the Word Recognition Task. Findings also suggested that visuo-spatial memory may be influenced by macronutrient manipulations.

The effects of breakfast on behavior and academic performance in children and adolescents

Breakfast consumption is associated with positive outcomes for diet quality, micronutrient intake, weight status and lifestyle factors. Breakfast has been suggested to positively affect learning in children in terms of behavior, cognitive, and school performance. However, these assertions are largely based on evidence which demonstrates acute effects of breakfast on cognitive performance. Less research which examines the effects of breakfast on the ecologically valid outcomes of academic performance or in-class behavior is available. The literature was searched for articles published between 1950–2013 indexed in Ovid MEDLINE, Pubmed, Web of Science, the Cochrane Library, EMBASE databases, and PsychINFO. Thirty-six articles examining the effects of breakfast on in-class behavior and academic performance in children and adolescents were included. The effects of breakfast in different populations were considered, including undernourished or well-nourished children and adolescents from differing socio-economic status (SES) backgrounds. The habitual and acute effects of breakfast and the effects of school breakfast programs (SBPs) were considered. The evidence indicated a mainly positive effect of breakfast on on-task behavior in the classroom. There was suggestive evidence that habitual breakfast (frequency and quality) and SBPs have a positive effect on childrens academic performance with clearest effects on mathematic and arithmetic grades in undernourished children. Increased frequency of habitual breakfast was consistently positively associated with academic performance. Some evidence suggested that quality of habitual breakfast, in terms of providing a greater variety of food groups and adequate energy, was positively related to school performance. However, these associations can be attributed, in part, to confounders such as SES and to methodological weaknesses such as the subjective nature of the observations of behavior in class.