Expert consensus on low-calorie sweeteners: facts, research gaps and suggested actions.

A consensus workshop on low-calorie sweeteners (LCS) was held in November 2018 where seventeen experts (the panel) discussed three themes identified as key to the science and policy of LCS: (1) weight management and glucose control; (2) consumption, safety and perception; (3) nutrition policy. The aims were to identify the reliable facts on LCS, suggest research gaps and propose future actions. The panel agreed that the safety of LCS is demonstrated by a substantial body of evidence reviewed by regulatory experts and current levels of consumption, even for high users, are within agreed safety margins. However, better risk communication is needed. More emphasis is required on the role of LCS in helping individuals reduce their sugar and energy intake, which is a public health priority. Based on reviews of clinical evidence to date, the panel concluded that LCS can be beneficial for weight management when they are used to replace sugar in products consumed in the diet (without energy substitution). The available evidence suggests no grounds for concerns about adverse effects of LCS on sweet preference, appetite or glucose control; indeed, LCS may improve diabetic control and dietary compliance. Regarding effects on the human gut microbiota, data are limited and do not provide adequate evidence that LCS affect gut health at doses relevant to human use. The panel identified research priorities, including collation of the totality of evidence on LCS and body weight control, monitoring and modelling of LCS intakes, impacts on sugar reduction and diet quality and developing effective communication strategies to foster informed choice. There is also a need to reconcile policy discrepancies between organisations and reduce regulatory hurdles that impede low-energy product development and reformulation.

Daily consumption of pistachios over 12 weeks improves dietary profile without increasing body weight in healthy women: A randomized controlled intervention.

Dietary guidelines around the world recommend the regular intake of nuts because of their nutrient contribution to the diet and reported health benefits. However, consumers are often reluctant to include nuts in their diet due to the high caloric density of nuts. In a 12-week randomized, controlled intervention, we investigated how adding a pistachio portion to the daily diet affects body weight and composition, satiety, energy and nutrient intake. Sixty healthy pre-menopausal women who did not typically consume nuts were randomly assigned to a control or an experimental groups. Experimental participants (n = 30) consumed 44 g (250 kcal) pistachios mid-morning while controls (n = 30) maintained their current eating habits for 12 weeks. Ad libitum food intake and appetite sensations following the pistachio portion were assessed in all participants before and after the intervention in four 2-consecutive-day test sessions (under laboratory and then free-living conditions). Body weight and composition (DXA) were unchanged in both groups after 12 weeks. Pre- and post-intervention tests showed that ad libitum intake adjusted to the pistachio portion, mostly via reduced intakes of carbohydrates and starch, in parallel with decreased hunger and increased satiety following the morning snack. Intakes of MUFA, PUFA, linoleic acid, thiamin, pyridoxine, copper, manganese, and zinc were significantly higher among women consuming the pistachio snack, in spite of compensatory adjustments in intake. In conclusion, daily intake of 44 g pistachios improved nutrient intake without affecting body weight or composition in healthy women. The additional calories provided by the pistachios induced satiety and sufficient adjustment of intake to prevent body weight changes. CLINICAL TRIAL REGISTRY NUMBER: NCT03526120https://clinicaltrials.gov/ct2/show/NCT03526120.

Reprint of "Beverages containing low energy sweeteners do not differ from water in their effects on appetite, energy intake and food choices in healthy, non-obese French adults".

The usefulness of replacement of caloric sugars by low-calorie sweeteners (LCS) for weight management has been questioned on the grounds that the uncoupling of LCS sweet taste and dietary energy may confuse physiological mechanisms, leading potentially to higher energy and sugar intake. The aim of the present study was to determine whether LCS beverages compared to water, when consumed with meals, differ in their effects on energy and food intake in acute trials and after long-term habituation. Ad libitum food intake of 166 (80 women; 86 men) healthy non-obese adults (BMI between 19 and 28 kg/m2), infrequent consumers of LCS was measured in four 2-consecutive-day testing sessions (Day 1 in the laboratory, Day 2 free-living). During the first 3 sessions, held one-week apart, participants were required to drink either water or commercial non-carbonated LCS lemonade (330 ml) with their main meals (randomised cross-over design). On Day 1, motivational ratings were obtained using visual analogue scales and ad libitum food intakes (amounts and types of foods selected) were measured using the plate waste method. On Day 2, participants reported their ad libitum intakes using a food diary. After Session 3, participants were randomly assigned to the LCS habituation group or to the water control group. The habituation (660 ml LCS lemonade daily vs 660 ml water) lasted 5 weeks. The fourth and final test session measured food intakes and motivational ratings after habituation. Water and LCS beverage did not differ in their effects on total energy intake, macronutrient intakes or the selection of sweet foods and on motivational ratings. Similar results were obtained in both LCS-naïve and LCS-habituated individuals.

Beverages containing low energy sweeteners do not differ from water in their effects on appetite, energy intake and food choices in healthy, non-obese French adults.

The usefulness of replacement of caloric sugars by low-calorie sweeteners (LCS) for weight management has been questioned on the grounds that the uncoupling of LCS sweet taste and dietary energy may confuse physiological mechanisms, leading potentially to higher energy and sugar intake. The aim of the present study was to determine whether LCS beverages compared to water, when consumed with meals, differ in their effects on energy and food intake in acute trials and after long-term habituation. Ad libitum food intake of 166 (80 women; 86 men) healthy non-obese adults (BMI between 19 and 28 kg/m2), infrequent consumers of LCS was measured in four 2-consecutive-day testing sessions (Day 1 in the laboratory, Day 2 free-living). During the first 3 sessions, held one-week apart, participants were required to drink either water or commercial non-carbonated LCS lemonade (330 ml) with their main meals (randomised cross-over design). On Day 1, motivational ratings were obtained using visual analogue scales and ad libitum food intakes (amounts and types of foods selected) were measured using the plate waste method. On Day 2, participants reported their ad libitum intakes using a food diary. After Session 3, participants were randomly assigned to the LCS habituation group or to the water control group. The habituation (660 ml LCS lemonade daily vs 660 ml water) lasted 5 weeks. The fourth and final test session measured food intakes and motivational ratings after habituation. Water and LCS beverage did not differ in their effects on total energy intake, macronutrient intakes or the selection of sweet foods and on motivational ratings. Similar results were obtained in both LCS-naïve and LCS-habituated individuals.

Nutrient intakes of children aged 1-2 years as a function of milk consumption, cows' milk or growing-up milk.

OBJECTIVE: To evaluate the nutritional adequacy of diets in early childhood as a function of milk intake, cows' milk (CM) or growing-up milk (GUM). DESIGN: From a cross-sectional food consumption survey, two groups of children aged 1-2 years were defined: group CM fed exclusively on CM ≥ 250 ml/d and group GUM fed on GUM ≥ 250 ml/d. Proportions of children at risk of nutrient excess or insufficiency were estimated relative to the French recommended daily allowances, estimated average requirements or adequate intakes. SETTING: Parents participating in the survey were recruited from all regions of France by a polling organization. Distribution was adjusted to that of the French population. SUBJECTS: Sixty-three (group CM) and fifty-five (group GUM) children. RESULTS: Total energy and macronutrient intakes were similar in the two groups except protein intake of group CM, which was much higher than the Recommended Daily Allowance and significantly higher than in group GUM. A high percentage of children of Group CM had intake of linoleic acid (51%) and α-linolenic acid (84%) below the lower limit of the adequate intake, and intake of Fe (59%) vitamin C (49%) and alimentary vitamin D (100%) less than the Estimated Average Requirement. Significant differences were observed in the proportions of children with a risk of dietary inadequacy between the two groups for all the mentioned nutrients (P < 0.001). In group GUM, this imbalance was only observed for vitamin D. Intake of foods other than milk and dairy products could not account for these discrepancies. CONCLUSIONS: Consumption of CM (≥250 ml/d) entails the risk of insufficiency in α-linolenic acid, Fe, vitamin C and vitamin D. Use of GUM (≥250 ml/d) significantly reduces the risk of insufficiencies in the mentioned nutrients.

Role of lipids in the control of food intake.

PURPOSE OF REVIEW: The classical hypothesis that a decrease in glucose utilization, registered by specific sensors in the brain, leads to hunger was challenged as lipids and amino acids also provide energy for cell metabolism. This review presents recent progress in the knowledge on lipid signals associated with feeding initiation or inhibition. RECENT FINDINGS: Although the brain does not utilize fatty acids as primary energy sources, recent evidence indicates that intermediates of fatty acids metabolism in the hypothalamus serve as sensors of energy status. Pharmacological or genetic inhibition of brain fatty-acid synthase and carnitine palmitoyltransferase-1c results in profound decreases in feeding and body weight in rodents. These effects depend on changes in the intracytoplasmic pool of long-chain fatty-acyl-CoA and malonyl-CoA, an intermediate of the de-novo fatty acid synthesis in neurons that integrate hormonal and nutrient-derived signals to control feeding behaviour. The central regulatory enzyme is AMP-activated protein kinase, which reversibly phosphorylates acetyl-CoA carboxylase and malonyl-CoA decarboxylase, two enzymes that increase the level of malonyl-CoA in the cells when phosphorylated in response to a low intracellular ratio of AMP/ATP due to decrease in glucose oxidation. SUMMARY: Such a mechanism is compatible with a central energostatic control of feeding based on glucose utilization by neurons and opens new therapeutic perspectives to develop pharmacological compounds that act at the level of pivotal enzymes such as AMP-activated protein kinase, acetyl-CoA carboxylase, malonyl-CoA decarboxylase, and module malonyl-CoA level in cells, to favour central inhibition of feeding.

Safety and efficacy of novel dermal and epidermal microneedle delivery systems for rabies vaccination in healthy adults.

In the present pilot study, intradermal ID delivery systems with a BD microneedle from 1 to 3mm in length, and epidermal delivery (BD skin abrader) through abraded skin surface relative to standard intramuscular injection were evaluated. Circulating neutralizing antibodies were measured against the rabies virus after the Vero cells rabies vaccine was administered at D0, D7, D21 and D49. This clinical evaluation in 66 healthy volunteers shows that ID delivery using BD microneedle technology of 1/4 the IM antigen dose is safe, efficient and reliable, resulting in a protective seroconversion rate. In contrast, the epidermal delivery route did not produce an immune response against the rabies vaccine.

Consequence of omitting or adding a meal in man on body composition, food intake, and metabolism.

OBJECTIVE: To investigate in man the consequence on body composition and related biological and metabolic parameters of omitting or adding a meal. RESEARCH METHODS AND PROCEDURES: Twenty-four young normal-weight male subjects were recruited, 12 usual four-meal and 12 usual three-meal eaters, differing only in the consumption of an afternoon meal. They omitted or added a fourth meal during a 28-day habituation period and were asked to report their intake on three 3-day occasions. Before and after this habituation period, subjects participated in a session with a time-blinded procedure, and blood was collected continuously from lunch to the spontaneously requested dinner. Body composition, respiratory quotient, and biochemical parameters were measured in the late evening preceding each session. RESULTS: Omitting a meal was followed by increases in fat mass (360 +/- 115 grams, p < 0.05), late evening leptin concentration (20.7 +/- 11.0%, p < 0.05), and respiratory quotient (3.7 +/- 1.4%, p < 0.05). Increase in the percentage of dietary fat during the habituation period (+4.1 +/- 2.0%, p < 0.05) was correlated with fat mass (r = 0.66, p < 0.05). Adding a meal had no effect, but, in both groups, the change in energy content at this fourth eating occasion was correlated with the change in adiposity. DISCUSSION: Our results suggest that adiposity may increase when young lean male subjects switch from a four- to a three-meal pattern by removing their usual afternoon meal. This effect could be partly mediated by a change in the macronutrient composition of the diet.

Snacks consumed in a nonhungry state have poor satiating efficiency: influence of snack composition on substrate utilization and hunger.

BACKGROUND: Several epidemiologic studies suggest that snacking may play an etiologic role in obesity. OBJECTIVE: We assessed the behavioral and metabolic consequences of a high-carbohydrate (HC) or high-protein (HP) snack consumed 215 min after lunch, thereby investigating ways that snacking in a nonhungry state could be involved in the etiology of obesity. DESIGN: Eight lean young men attended 3 sessions (basal, HP snack, and HC snack) in a counterbalanced order with 2 wk between sessions. During all sessions, subjects were time-blinded while we measured the temporal pattern of plasma glucose, insulin, and fatty acid concentrations; hunger ratings; substrate oxidation; and energy expenditure from 215 min after the beginning of lunch until the spontaneous dinner request. RESULTS: Compared with the basal (no snack) session, the HP snack delayed the spontaneous dinner request (by 38 +/- 16 min, P < 0.05) but the HC snack did not. Energy and macronutrient intakes at dinner were unaffected by both snacks. After the HP snack, plasma fatty acid concentrations were lower (P < 0.05), but glucose and insulin were unchanged compared with the basal session. After the HC snack, plasma glucose and insulin concentrations were higher and plasma fatty acid concentrations were lower than those in the basal session (P < 0.05 for both). Both snacks promoted carbohydrate utilization (P < 0.05), and the HC snack depressed fat oxidation (P < 0.05). CONCLUSION: This study showed that a snack consumed in a satiety state has poor satiating efficiency irrespective of its composition, which is evidence that snacking plays a role in obesity.

Behavioral, plasma, and calorimetric changes related to food texture modification in men.

We hypothesized that food texture modifications might alter anticipatory reflexes, feeding behavior, and the postabsorptive consequences of ingestion. Two sets of complete meals with different textures but the same macronutrient composition were prepared. The first set was either a soup containing chunks of food (mixture) or the same soup blended until smooth (purée). The second set was either a rusk (R), a sandwich loaf (SL), or a liquid rusk meal (LR). We measured hunger and fullness feelings after ingestion of each food in a calibrated lunch, the ingestion rate, the duration between lunch and a spontaneous dinner request, the energy value, and the macronutrient composition of the ad libitum dinner. We also studied plasma modifications and respiratory gas exchanges from lunch to dinner. Feelings of hunger and fullness were not affected by texture modifications. The purée soup was consumed faster than the mixture (P < 0.05), and insulin, triacylglycerol, and energy expenditure were greater with the purée (P < 0.05). LR was less palatable than the other rusk lunch versions (P < 0.001), and R was ingested more slowly (P < 0.05). The lowest increase in plasma glucose occurred with SL, and the highest energy expenditure was seen with LR (P < 0.05). In humans, food texture modification affects not only eating patterns and palatability of ingestants but also metabolic management.