Efficacy of antipsychotics in dementia depended on the definition of patients and outcomes: a meta-epidemiological study.

OBJECTIVES: Postulating that efficacy of antipsychotics for agitation and psychosis in dementia is best estimated in trials among patients with these symptoms and with symptom-specific outcomes, we investigated whether clinically broader definitions affected the pooled efficacy. STUDY DESIGN AND SETTING: Trials were searched in multiple databases and categorized according to patient population (agitated, psychotic, and mixed) and outcome scale (agitation, psychosis, and generic). Standardized mean differences with 95% confidence intervals were calculated for conventional and atypical antipsychotics separately. RESULTS: Thirty trials met our inclusion criteria. Conventional antipsychotics might have a small effect in agitated patients on agitation scales (-0.44, -0.88, 0.01) and in psychotic patients on psychosis scales (-0.31, -0.61, -0.02). There was no effect on generic scales. Efficacy of atypical antipsychotics was not established in agitated patients on agitation scales (-0.15, -0.43, 0.13) and in psychotic patients on psychosis scales (-0.11, -0.20, -0.03) but was small in mixed patients on agitation scales (-0.29, -0.40, -0.18). CONCLUSION: Pooled efficacy of antipsychotics for agitation and psychosis in dementia is biased when based on trials that included patients without these target symptoms or on results measured with generic scales. This finding is important for reviewers and guideline developers who select trials for reviews.

Amino acid utilization and body composition of growing pigs fed processed soybean meal or rapeseed meal with or without amino acid supplementation.

Feed ingredients used in swine diets are often processed to improve nutritional value. However, (over-)processing may result in chemical reactions with amino acids (AAs) that decrease their ileal digestibility. This study aimed to determine effects of (over-)processing of soybean meal (SBM) and rapeseed meal (RSM) on post-absorptive utilization of ileal digestible AAs for retention and on body AA composition of growing pigs. Soybean meal and RSM were processed by secondary toasting in the presence of lignosulfonate to obtain processed soybean meal (pSBM) and processed rapeseed meal (pRSM). Four diets contained SBM, pSBM, RSM or pRSM as sole protein source. Two additional diets contained pSBM or pRSM and were supplemented with crystalline AA to similar standardized ileal digestible (SID) AA level as the SBM or RSM diet. These diets were used to verify that processing affected AA retention by affecting ileal AA digestibility rather than post-absorptive AA utilization. The SID AA levels of the protein sources were determined in a previous study. In total, 59 pigs were used (initial BW of 15.6±0.7 kg) of which five were used to determine initial body composition at the start of the experiment. In total, 54 pigs were fed one of six experimental diets and were slaughtered at a BW of 40 kg. The organ fraction (i.e. empty organs plus blood) and carcass were analyzed separately for N and AA content. Post-absorptive AA utilization was calculated from AA retention and SID AA intake. An interaction between diet type, comprising effects of processing and supplementing crystalline AA, and protein source was observed for CP content in the organ fraction, carcass and empty body and for nutrient retention. Processing reduced CP content and nutrient retention more for SBM than for RSM. Moreover, processing reduced (P<0.001) the lysine content in the organ fraction for both protein sources. Supplementing crystalline AA ameliorated the effect of processing on these variables. Thus, the data indicated that processing affected retention by reducing digestibility. Correcting AA retention for SID AA intake was, therefore, expected to result in similar post-absorptive AA utilization which was observed for the RSM diets. However, post-absorptive AA utilization was lower for the pSBM diet than for the SBM diet which might be related to an imbalanced post-absorptive AA supply. In conclusion, processing negatively affected nutrient retention for both protein sources and post-absorptive utilization of SID AA for retention for SBM. Effects of processing were compensated by supplementing crystalline AA.

Processing of soybean meal and 00-rapeseed meal reduces protein digestibility and pig growth performance but does not affect nitrogen solubilization along the small intestine.

An experiment was conducted to determine the effects of processing of soybean meal (SBM) and 00-rapeseed meal (RSM) on N solubilization in chyme, CP digestibility along the small intestine, metabolic load as determined by organ weight, body composition, and growth performance in growing pigs. The SBM and RSM were processed by secondary toasting (at 95°C for 30 min) in the presence of lignosulfonate, resulting in processed SBM (pSBM) and processed RSM (pRSM) as a model for overprocessed protein sources. Fifty-four growing pigs were each fed 1 of the 6 experimental diets. Four of the diets contained SBM, pSBM, RSM, or pRSM as the sole protein source. The remaining 2 experimental diets contained pSBM or pRSM and were supplemented with crystalline AA to the same standardized ileal digestible AA levels as the SBM or RSM diet. Pigs were slaughtered at 40 kg, and organ weights were recorded. The organs plus blood and empty carcass were analyzed for CP content. The small intestine was divided into 3 segments, and chyme samples were taken from the last meter of each segment. Chyme of the SBM, pSBM, RSM, and pRSM diets was centrifuged to separate the soluble and insoluble fractions, and N content was determined in the latter. The amount of insoluble N as a fraction of N in chyme at each small intestinal segment was not affected by processing. Diet type, comprising effects of processing and supplementing crystalline AA, affected ( < 0.05) the G:F and standardized ileal digestibility (SID) of CP. Processing reduced G:F from 0.56 to 0.38 for SBM and 0.49 to 0.40 for RSM, whereas supplementing crystalline AA increased G:F to the level of the SBM and RSM diets. Processing reduced the SID of CP from 87.2% to 69.2% for SBM and 71.0% to 52.2% for RSM. Diet type affected ( < 0.05) the CP content in the empty body, with processing reducing this content from 170 to 144 g/kg empty BW for SBM and 157 to 149 g/kg empty BW for RSM and supplementing crystalline AA restoring this content. Processing reduced ( < 0.05) the weight of several organs, and supplementing crystalline AA restored organ weight. In conclusion, processing increased the amount of N in the chyme, reduced organ weight, body CP content, and G:F. These effects were caused by a reduction in available AA as supplementing crystalline AA restored organ weight, body CP content, and G:F.

Assessment of protein quality of soybean meal and 00-rapeseed meal toasted in the presence of lignosulfonate by amino acid digestibility in growing pigs and Maillard reaction products.

An experiment was conducted to determine protein quality in processed protein sources using the content of AA, -methylisourea (OMIU)-reactive Lys, Maillard reaction products (MRP), and cross-link products; the standardized ileal digestibility (SID) of CP and AA; and growth performance in growing pigs as criteria. Differences in protein quality were created by secondary toasting (at 95°C for 30 min) of soybean meal (SBM) and rapeseed meal (RSM) in the presence of lignosulfonate resulting in processed SBM (pSBM) and processed RSM (pRSM). The processing treatment was used as a model for overprocessed protein sources. Ten growing pigs were each fed 1 of the 4 diets containing SBM, pSBM, RSM, or pRSM in each of 3 periods. Ileal chyme was collected at the end of each period and analyzed for CP, AA, and OMIU-reactive Lys. Diets were analyzed for furosine and carboxymethyllysine (CML) as an indicator for MRP and lysinoalanine (LAL), which is a cross-link product. The SBM and RSM diets contained furosine, CML, and LAL, indicating that the Maillard reaction and cross-linking had taken place in SBM and RSM, presumably during the oil extraction/desolventizing process. The amounts of furosine, CML, and LAL were elevated in pSBM and pRSM due to further processing. Processing resulted in a reduction in total and OMIU-reactive Lys contents and a decrease in G:F from 0.52 to 0.42 for SBM and 0.46 to 0.39 for RSM ( = 0.006), SID of CP from 83.9 to 71.6% for SBM and 74.9 to 64.6% for RSM ( < 0.001), and SID of AA ( < 0.001), with the largest effects for total and OMIU-reactive Lys. The effects of processing could be substantial and should be taken into account when using processed protein sources in diets for growing pigs. The extent of protein damage may be assessed by additional analyses of MRP and cross-link products.

Chronobiology, endocrinology, and energy- and food-reward homeostasis.

Energy- and food-reward homeostasis is the essential component for maintaining energy balance and its disruption may lead to metabolic disorders, including obesity and diabetes. Circadian alignment, quality sleep and sleep architecture in relation to energy- and food-reward homeostasis are crucial. A reduced sleep duration, quality sleep and rapid-eye movement sleep affect substrate oxidation, leptin and ghrelin concentrations, sleeping metabolic rate, appetite, food reward, hypothalamic-pituitary-adrenal (HPA)-axis activity, and gut-peptide concentrations, enhancing a positive energy balance. Circadian misalignment affects sleep architecture and the glucose-insulin metabolism, substrate oxidation, homeostasis model assessment of insulin resistance (HOMA-IR) index, leptin concentrations and HPA-axis activity. Mood disorders such as depression occur; reduced dopaminergic neuronal signaling shows decreased food reward. A good sleep hygiene, together with circadian alignment of food intake, a regular meal frequency, and attention for protein intake or diets, contributes in curing sleep abnormalities and overweight/obesity features by preventing overeating; normalizing substrate oxidation, stress, insulin and glucose metabolism including HOMA-IR index, and leptin, GLP-1 concentrations, lipid metabolism, appetite, energy expenditure and substrate oxidation; and normalizing food reward. Synchrony between circadian and metabolic processes including meal patterns plays an important role in the regulation of energy balance and body-weight control. Additive effects of circadian alignment including meal patterns, sleep restoration, and protein diets in the treatment of overweight and obesity are suggested.

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.

Effects of dietary fibre on subjective appetite, energy intake and body weight: a systematic review of randomized controlled trials.

Dietary fibres are believed to reduce subjective appetite, energy intake and body weight. However, different types of dietary fibre may affect these outcomes differently. The aim of this review was to systematically investigate the available literature on the relationship between dietary fibre types, appetite, acute and long-term energy intake, and body weight. Fibres were grouped according to chemical structure and physicochemical properties (viscosity, solubility and fermentability). Effect rates were calculated as the proportion of all fibre-control comparisons that reduced appetite (n = 58 comparisons), acute energy intake (n = 26), long-term energy intake (n = 38) or body weight (n = 66). For appetite, acute energy intake, long-term energy intake and body weight, there were clear differences in effect rates depending on chemical structure. Interestingly, fibres characterized as being more viscous (e.g. pectins, ß-glucans and guar gum) reduced appetite more often than those less viscous fibres (59% vs. 14%), which also applied to acute energy intake (69% vs. 30%). Overall, effects on energy intake and body weight were relatively small, and distinct dose-response relationships were not observed. Short- and long-term effects of dietary fibres appear to differ and multiple mechanisms relating to their different physicochemical properties seem to interplay. This warrants further exploration.

Appetite control: methodological aspects of the evaluation of foods.

This report describes a set of scientific procedures used to assess the impact of foods and food ingredients on the expression of appetite (psychological and behavioural). An overarching priority has been to enable potential evaluators of health claims about foods to identify justified claims and to exclude claims that are not supported by scientific evidence for the effect cited. This priority follows precisely from the principles set down in the PASSCLAIM report. The report allows the evaluation of the strength of health claims, about the effects of foods on appetite, which can be sustained on the basis of the commonly used scientific designs and experimental procedures. The report includes different designs for assessing effects on satiation as opposed to satiety, detailed coverage of the extent to which a change in hunger can stand alone as a measure of appetite control and an extensive discussion of the statistical procedures appropriate for handling data in this field of research. Because research in this area is continually evolving, new improved methodologies may emerge over time and will need to be incorporated into the framework. One main objective of the report has been to produce guidance on good practice in carrying out appetite research, and not to set down a series of commandments that must be followed.

Nonabsorbable fat (sucrose polyester) and the regulation of energy intake and body weight.

A substantial number of people have difficulties in controlling their body weight and energy/fat intake. Fat substitutes may be helpful in solving these problems. We here report the first study on the longer-term effects of the nonabsorbable fat sucrose polyester (SPE) on energy intake in normal-weight subjects. We studied the longer-term (12 days) effects of the consumption of warm meals with normal dietary fat (5.0 MJ, 1,195 kcal) or meals in which 52 g of fat were replaced by the fat replacer SPE (3.1 MJ, 740 kcal) on spontaneous food intake (measured by dietary records), body weight, and gastrointestinal complaints in healthy volunteers in two studies. In the first study the 48 subjects were unaware of the treatment, whereas in the second study the 47 subjects were informed of what they received. In both studies men and women consumed less energy per day during the SPE (11.2 MJ) compared with the fat treatment (12.7 MJ) (P values < 0.0001) for the whole 12-day period. This was accompanied by equivalent changes in body weight. The percentage of energy from fat decreased from 43% during the fat treatment to 32% during the SPE treatment. During the SPE treatment, more gastrointestinal complaints and a higher frequency of defecation were reported. Information about the treatment did not affect. the outcomes. It is concluded that the use of a fat replacer such as SPE helps in reducing fat and energy intake in normal-weight people.

Effects of weight and energy content of preloads on subsequent appetite and food intake.

This study was done to determine the relative effects of energy content and weight of ingested food on subsequent satiety and food intake. The weight/volume and the energy content of nine preloads were manipulated, in a 3 x 3 factorial design, to give three weight levels, 250, 500 and 750 g, and three energy levels 0, 1.26 and 2.51 MJ (0, 300 and 600 kcal). The weights were varied by the addition of water, while the energy levels were varied by using yogurt and cream. Each of the 1.26 and 2.51 MJ preloads contained 27 g of protein and 31 g of carbohydrates. The 1.26 MJ preloads contained 8 g of fat and the 2.51 MJ preloads had 41 g of fat. Each of the nine preloads was presented as a lunch to 21 female and 16 male subjects. Two hours after the preloads, subjects consumed sweet and savory snacks and various drinks ad libitum from a buffet. The weight of the preload had a small but statistically significant effect on feelings of hunger and satiety between preload and buffet, and on energy intake during the buffet (5.34, 5.05 and 5.04 MJ after 250, 500 and 750 g preloads). There was a large difference between 0 and 1.26 MJ, but little difference in effect between 1.26 and 2.51 MJ preloads. Mean energy intakes in the buffet after the 0, 1.26 and 2.51 MJ preloads were 6.17, 4.83 and 4.42 MJ. These results suggest that the weight or amount of food affects subsequent appetite and food intake, but the effect of energy is stronger.

The effect of non-absorbable fat on energy and fat intake.

One of the main issues with respect to the usefulness of fat-replacers is their effectiveness. The question is whether or not people compensate for the "missing" energy due the replacement of fat by the fat-substitute. The present paper is concerned with the results of a number of studies carried out on the effects of the fat-replacer sucrose-polyester on food intake. Sucrose-polyester (SPE) is a substance with similar sensory and physical-chemical properties as fat, but it contains no metabolizable energy, because it is not digested in the human gastrointestinal tract. In the first two short-term studies, we replaced the fat by SPE in croissants. Thirty-three subjects in the first study and 34 subjects in the second study consumed 2 1/2 croissants, either with fat or SPE. After ingestion they rated subjective feeling of hunger, and recorded their ad libitum food intake. The results of both studies showed that the croissants with SPE had a similar satiating effect as the croissants with fat. In two subsequent short-term studies, we added either fat, SPE or water to warm meals served as lunch. The high water and high SPE lunches contained about 450 kcal, whereas the high fat lunches contained about 900 kcal. After ingestion of the lunches, subjects (39 in study 3; 35 in study 4) recorded their feelings of hunger. Two hours after the lunches, subjects were presented with an attractive buffet from which they could eat ad libitum. The results showed that hunger and food intake were similar after the water, SPE and fat lunches. The subjects did not detect the 450 kcal energy difference in the lunches. The last two studies with SPE lasted for 12 days. The results of these two longer-term studies were similar to the results of the short-term studies. There was little energy compensation and no fat compensation. It is concluded that fat replacers can be helpful in reducing fat and energy intake.

Short-term satiating effect of the fat replacer sucrose polyester (SPE) in man.

The effects of different amounts of the non-absorbable fat replacer sucrose polyester (SPE), water, and fat added to six warm preload lunches on feelings of appetite and food intake were investigated in two studies that were replicates of each other. In the first study thirty-nine subjects consumed rice preloads; in the second study thirty-five subjects consumed macaroni preloads. The six preloads were fixed on three energy levels: 1.8, 2.7, or 3.7 MJ. At 2 h after preload consumption a test-meal buffet of thirty-one products was presented. Food intake was recorded on the study day, and the day after the study day. For women no energy compensation occurred in either study. Men showed a tendency to compensate for the energy differences between the preloads. However, when the fat of the preloads was replaced by SPE, energy compensation was less than 50% and non-significant. Statistically significant energy compensation (66%) was found when fat was replaced by water. No macronutrient-specific compensation occurred in men or women in either study. Lower total fat and energy intakes were found with the preloads where fat was replaced by SPE compared with the preloads containing fat. The appetite ratings were in line with the energy intake values, with no differences in women, and higher appetite ratings after the lower energy preloads in men. This short-term study indicates that SPE may be a useful aid to reduce fat and energy intakes.

Short-term effects of high-fat and low-fat/high-SPE croissants on appetite and energy intake at three deprivation periods.

The short-term satiating effects of croissants with different amounts of fat and sucrose polyester (SPE) followed by three lengths of deprivation were investigated. Sixteen male and 18 female normal-weight subjects each received six different experimental conditions in a two x three factorial design. Energy content was the first factor with two levels: 1.80 MJ and 3.45 MJ. The second factor was the deprivation period after the lunch preload with three levels: 0.25, 2.25, and 4.75 h. Subjects ate ad lib after the deprivation period. The effects of the croissants were determined by motivational ratings and reported food consumption on the study day and the day after the study day. The SPE croissants (1.80 MJ) and the high-fat croissants (3.45 MJ) did not result in different subsequent energy intakes. Differences in energy intake were found between the three deprivation conditions, with the lowest intake with the 4.75-h deprivation condition. This was due to differences in the energy intake during the afternoon. The two energy levels of the preloads had similar effects on the motivational ratings. Higher appetite ratings were found after the 4.75-h compared to the 0.25 h and the 2.25-h deprivation condition.

The effects of preloads varying in physical state and fat content on satiety and energy intake.

This study investigated the effect of the physical state and fat content of a preload on feelings of hunger and satiety and subsequent energy intake. Thirty-three normal-weight female subjects each received nine different 550-ml preloads which were served as breakfast. The preloads differed in physical state and fat level. There were three types of physical state (liquid, solid with locust bean gum, and solid with gelatin) combined with three energy levels (0.42, 1.67, and 3.35 MJ). The energy differences were due only to differences in fat content. Subjects were not allowed to eat or drink (except water) for 3.5 h after preload consumption. In this period they rated their feelings of appetite. Subjects recorded their voluntary food intake for the remainder of the study day and the day after the study day. There were no effects of the different amounts of fat or the three different physical states on energy intake during the remainder of the day or the day after. With respect to the appetite ratings, however, it appeared that the solid preloads were more satiating than the liquid preloads and the solid preloads were more satiating with fibre (locust bean gum) than without fibre (gelatin). The high-fat preloads were more satiating than the low-fat preloads.

Short-term effects of different amounts of protein, fats, and carbohydrates on satiety.

This study investigated the satiating efficiencies of proteins, fats, and carbohydrates (CHOs). Twenty-nine female, normal-weight subjects each received 10 liquid breakfasts, which varied in energy and macronutrient contents. Besides a zero condition [0.3 MJ (8 kcal)], there were three energy levels [0.42, 1.05, and 1.67 MJ (100, 250, and 400 kcal)] combined with three dominant sources of macronutrients (99% of energy from CHO, 92% of energy from fat, and 77% of energy from protein). After breakfast the subjects were not allowed to eat or drink (except water) for 3.5 h. They then recorded their voluntary food intake for the remainder of the day. Subjects also rated their subjective feelings concerning food intake on five different types of appetite. The results showed that neither energy content nor macronutrient composition of the liquid breakfasts had any effect on energy and macronutrient intake during lunch and the remainder of the day. Ratings of different types of appetite showed an increasing satiating effect with increasing energy content of the breakfasts. Proteins, fats, and CHOs had similar effects on appetite.

Assessment of body composition by bioelectrical impedance in a population aged greater than 60 y.

Body composition was measured in a group of 35 healthy men and 37 healthy women aged 60-83 y. Body mass index (BMI) in men was 25.0 +/- 2.2 kg/m2 (means +/- SD) and in women, 25.9 +/- 3.2 kg/m2. BMI was low in relation to body fat percentage as determined by skinfold-thickness measurements or densitometry in comparison with the relation found in younger adults. Mean body fat percentage of the male subjects (aged 70.4 +/- 5.2 y) as determined by densitometry was 31.0 +/- 4.5%, whereas in women (aged 68.0 +/- 5.2 y) it was 43.9 +/- 4.3%. Body impedance correlated with fat-free mass (FFM). The best prediction formulas for the FFM from body impedance and anthropometric variables were 1) FFM (kg) = (0.671 x 10(4) x H2/R) + 3.1S + 3.9 where H is body height (m), R is resistance (omega), and S is gender (females, 0; males, 1) (r = 0.94; SEE = 3.1 kg) and 2) FFM (kg) = (0.360 x 10(4) x H2/R) + 0.359BW + 4.5S - 20T + 7.0 where BW is body weight (kg) and T is thigh circumference (m) (r = 0.96; SEE = 2.5 kg). The prediction equations from the literature, generally determined in younger populations, overestimated FFM in elderly subjects by approximately 6 kg and are not applicable to elderly subjects.

Body mass index as a measure of body fatness in the elderly.

Body composition was assessed in a group of 35 apparently health elderly males and 37 elderly females, aged 60-83 years, by means of anthropometry and densitometry. Mean body mass index (BMI) of the males was 25.0 +/- 2.2 kg/m2 and of the females 25.9 +/- 3.2 kg/m2, which indicates normal weight to only minor overweight. Body fat as assessed by densitometry was 31 per cent in men and 44 per cent in women, a rather high value, especially when compared to the rather low BMI. Body fat percentage as calculated from the sum of four skinfolds (bicipitalis, tricipitalis, subscapularis and supra-iliacalis) using regression equations from the literature was 27.9 +/- 2.5 per cent and 38.7 +/- 3.2 per cent for men and women respectively. These values are probably an underestimation of the body fat, due to a higher proportion of internal fat in elderly subjects, which is not measured by skinfolds. Body fat percentage as determined by the BMI has an estimation error of about 4 per cent when derived from sex- and age-specific regression equations. The body fat percentage as predicted from skinfold thicknesses had a comparable error of estimate. These prediction errors in the body fat percentage in the elderly are comparable with the prediction errors found in young and middle-aged subjects as reported in the literature.