Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity-a randomised crossover trial from the SWEET consortium.

BACKGROUND: Sweeteners and sweetness enhancers (S&SE) are used to replace energy yielding sugars and maintain sweet taste in a wide range of products, but controversy exists about their effects on appetite and endocrine responses in reduced or no added sugar solid foods. The aim of the current study was to evaluate the acute (1 day) and repeated (two-week daily) ingestive effects of 2 S&SE vs. sucrose formulations of biscuit with fruit filling on appetite and endocrine responses in adults with overweight and obesity. METHODS: In a randomised crossover trial, 53 healthy adults (33 female, 20 male) with overweight/obesity in England and France consumed biscuits with fruit filling containing 1) sucrose, or reformulated with either 2) Stevia Rebaudioside M (StRebM) or 3) Neotame daily during three, two-week intervention periods with a two-week washout. The primary outcome was composite appetite score defined as [desire to eat + hunger + (100 - fullness) + prospective consumption]/4. FINDINGS: Each formulation elicited a similar reduction in appetite sensations (3-h postprandial net iAUC). Postprandial insulin (2-h iAUC) was lower after Neotame (95% CI (0.093, 0.166); p < 0.001; d = -0.71) and StRebM (95% CI (0.133, 0.205); p < 0.001; d = -1.01) compared to sucrose, and glucose was lower after StRebM (95% CI (0.023, 0.171); p < 0.05; d = -0.39) but not after Neotame (95% CI (-0.007, 0.145); p = 0.074; d = -0.25) compared to sucrose. There were no differences between S&SE or sucrose formulations on ghrelin, glucagon-like peptide 1 or pancreatic polypeptide iAUCs. No clinically meaningful differences between acute vs. two-weeks of daily consumption were found. INTERPRETATION: In conclusion, biscuits reformulated to replace sugar using StRebM or Neotame showed no differences in appetite or endocrine responses, acutely or after a two-week exposure, but can reduce postprandial insulin and glucose response in adults with overweight or obesity. FUNDING: The present study was funded by the Horizon 2020 program: Sweeteners and sweetness enhancers: Impact on health, obesity, safety and sustainability (acronym: SWEET, grant no: 774293).

Comparison of a Daily Steviol Glycoside Beverage compared with a Sucrose Beverage for Four Weeks on Gut Microbiome in Healthy Adults.

BACKGROUND: Recent studies suggest that some nonnutritive sweeteners (NNS) have deleterious effects on the human gut microbiome (HGM). The effect of steviol glycosides on the HGM has not been well studied. OBJECTIVE: We aimed to evaluate the effects of stevia- compared with sucrose-sweetened beverages on the HGM and fecal short-chain fatty acid (SCFA) profiles. METHODS: Using a randomized, double-blinded, parallel-design study, n = 59 healthy adults [female/male, n = 36/23, aged 31±9 y, body mass index (BMI): 22.6±1.7 kg/m2] consumed 16 oz of a beverage containing either 25% of the acceptable daily intake (ADI) of stevia or 30 g of sucrose daily for 4 weeks followed by a 4-week washout. At weeks 0 (baseline), 4, and 8, the HGM was characterized via shotgun sequencing, fecal SCFA concentrations were measured using ultra-high performance liquid chromatography-tandem mass spectrometry and anthropometric measurements, fasting serum glucose, insulin and lipids, blood pressure, pulse, and 3-d diet records were obtained. RESULTS: There were no significant differences in the HGM or fecal SCFA between the stevia and sucrose groups at baseline (P > 0.05). At week 4 (after intervention), there were no significant differences in the HGM at the phylum, family, genus, or species level between the stevia and sucrose groups and no significant differences in fecal SCFA. At week 4, BMI had increased by 0.3 kg/m2 (P = 0.013) in sucrose compared with stevia, but all other anthropometric and cardiometabolic measures and food intake did not differ significantly (P > 0.05). At week 8 (after washout), there were no significant differences in the HGM, fecal SFCA, or any anthropometric or cardiometabolic measure between the stevia and sucrose groups (P > 0.05). CONCLUSIONS: Daily consumption of a beverage sweetened with 25% of the ADI of stevia for 4 weeks had no significant effects on the HGM, fecal SCFA, or fasting cardiometabolic measures, compared with daily consumption of a beverage sweetened with 30 g of sucrose. TRIAL REGISTRATION: clinicaltrials.gov as NCT05264636.

Impact of acute consumption of beverages containing plant-based or alternative sweetener blends on postprandial appetite, food intake, metabolism, and gastro-intestinal symptoms: Results of the SWEET beverages trial.

Project SWEET examined the barriers and facilitators to the use of non-nutritive sweeteners and sweetness enhancers (hereafter "S&SE") alongside potential risks/benefits for health and sustainability. The Beverages trial was a double-blind multi-centre, randomised crossover trial within SWEET evaluating the acute impact of three S&SE blends (plant-based and alternatives) vs. a sucrose control on glycaemic response, food intake, appetite sensations and safety after a carbohydrate-rich breakfast meal. The blends were: mogroside V and stevia RebM; stevia RebA and thaumatin; and sucralose and acesulfame-potassium (ace-K). At each 4 h visit, 60 healthy volunteers (53% male; all with overweight/obesity) consumed a 330 mL beverage with either an S&SE blend (0 kJ) or 8% sucrose (26 g, 442 kJ), shortly followed by a standardised breakfast (∼2600 or 1800 kJ with 77 or 51 g carbohydrates, depending on sex). All blends reduced the 2-h incremental area-under-the-curve (iAUC) for blood insulin (p < 0.001 in mixed-effects models), while the stevia RebA and sucralose blends reduced the glucose iAUC (p < 0.05) compared with sucrose. Post-prandial levels of triglycerides plus hepatic transaminases did not differ across conditions (p > 0.05 for all). Compared with sucrose, there was a 3% increase in LDL-cholesterol after stevia RebA-thaumatin (p < 0.001 in adjusted models); and a 2% decrease in HDL-cholesterol after sucralose-ace-K (p < 0.01). There was an impact of blend on fullness and desire to eat ratings (both p < 0.05) and sucralose-acesulfame K induced higher prospective intake vs sucrose (p < 0.001 in adjusted models), but changes were of a small magnitude and did not translate into energy intake differences over the next 24 h. Gastro-intestinal symptoms for all beverages were mostly mild. In general, responses to a carbohydrate-rich meal following consumption of S&SE blends with stevia or sucralose were similar to sucrose.

Acute and repeated impact of sweeteners and sweetness enhancers in solid and semi-solid foods on appetite: protocol for a multicentre, cross-over, RCT in people with overweight/obesity - the SWEET Project.

INTRODUCTION: Intake of free sugars in European countries is high and attempts to reduce sugar intake have been mostly ineffective. Non-nutritive sweeteners and sweetness enhancers (S&SEs) can maintain sweet taste in the absence of energy, but little is known about the impact of acute and repeated consumption of S&SE in foods on appetite. This study aims to evaluate the effect of acute and repeated consumption of two individual S&SEs and two S&SE blends in semisolid and solid foods on appetite and related behavioural, metabolic and health outcomes. METHODS AND ANALYSIS: A work package of the SWEET Project; this study consists of five double-blind randomised cross-over trials which will be carried out at five sites across four European countries, aiming to have n=213. Five food matrices will be tested across three formulations (sucrose-sweetened control vs two reformulated products with S&SE blends and no added sugar). Participants (body mass index 25-35 kg/m2; aged 18-60 years) will consume each formulation for 14 days. The primary endpoint is composite appetite score (hunger, inverse of fullness, desire to eat and prospective food consumption) over a 3-hour postprandial incremental area under the curve during clinical investigation days on days 1 and 14. ETHICS AND DISSEMINATION: The trial has been approved by national ethical committees and will be conducted in accordance with the Declaration of Helsinki. Results will be published in international peer-reviewed open-access scientific journals. Research data from the trial will be deposited in an open-access online research data archive. TRIAL REGISTRATION NUMBER: NCT04633681.

Mapping the Homeostatic and Hedonic Brain Responses to Stevia Compared to Caloric Sweeteners and Water: A Double-Blind Randomised Controlled Crossover Trial in Healthy Adults.

Non-nutritive sweeteners have potential effects on brain function. We investigated neural correlates of responses to beverages differing in sweetness and calories. Healthy participants completed 4 randomised sessions: water vs. water with stevia, glucose, or maltodextrin. Blood-oxygenation level-dependent (BOLD) contrast was monitored for 30 min post-ingestion by functional Magnetic Resonance Imaging. A food visual probe task at baseline was repeated at 30 min. A significant interaction of taste-by-calories-by-time was demonstrated mainly in motor, frontal, and insula cortices. Consumption of the stevia-sweetened beverage resulted in greater BOLD decrease, especially in the 20-30 min period, compared to other beverages. There was a significant interaction of taste-by-time in BOLD response in gustatory and reward areas; sweet beverages induced greater reduction in BOLD compared to non-sweet. The interaction calories-by-time showed significantly greater incremental area under the curve in thalamic, visual, frontal, and parietal areas for glucose and maltodextrin 10-20 min post-consumption only, compared to water. In the visual cue task, the water demonstrated an increased response in the visual cortex to food images post-consumption; however, no difference was observed for the three sweet/caloric beverages. In conclusion, both sweet taste and calories exert modulatory effects, but stevia showed a more robust and prolonged effect.

Stevia Beverage Consumption prior to Lunch Reduces Appetite and Total Energy Intake without Affecting Glycemia or Attentional Bias to Food Cues: A Double-Blind Randomized Controlled Trial in Healthy Adults.

BACKGROUND: Stevia is a zero-calorie alternative to caloric sugars. Substituting caloric sweeteners with noncaloric sweeteners reduces available energy, but their effects on appetite, subsequent food intake, and neurocognitive responses are still unclear. OBJECTIVE: The aim was to examine whether sweetness with or without calories influences food intake, appetite, blood glucose concentrations, and attentional bias (AB) to food cues. METHODS: This was a randomized, controlled, double-blind crossover study. Healthy participants [n = 20; aged 27 ± 5 y,  55% female; BMI (kg/m2): 21.8 ± 1.5] completed 5 visits, consuming 5 study beverages: 330 mL water (control, no sweet taste, no calories) and either 330 mL water containing 40 g glucose or sucrose (sweet taste; calories, both 160 kcal), maltodextrin (no sweet taste; calories, 160 kcal), or 240 ppm stevia (sweet taste, no calories). Glucose and stevia beverages were matched for sweetness. Subjective appetite ratings and blood glucose were measured at baseline and at 15, 30, and 60 min postprandially. At 15 min participants performed a visual-dot probe task to assess AB to food cues; at 30 min, participants were offered an ad libitum lunch; food intake was measured. RESULTS: Subjective appetite ratings showed that preload sweetness and calorie content both affected appetite. The total AUC for glycemia was significantly higher after the caloric beverages (mean ± SD: maltodextrin, 441 ± 57.6;  glucose, 462 ± 68.1;  sucrose, 425 ± 53.6 mmol × min × L-1 ) compared with both stevia (320 ± 34.2 mmol × min × L-1) and water (304 ± 32.0 mmol × min × L-1) (all P < 0.001). Total energy intake (beverage and meal) was significantly lower after the stevia beverage (727 ± 239 kcal) compared with water (832 ± 198 kcal,  P = 0.013), with no significant difference between the water and caloric beverages (P = 1.00 for water vs. maltodextrin, glucose, and sucrose). However, food-related AB did not differ across conditions (P = 0.140). CONCLUSIONS: This study found a beneficial and specific effect of a stevia beverage consumed prior to a meal on appetite and energy intake in healthy adults. This trial is registered at clinicaltrials.gov as NCT03711084.

Transient cavitation in high-quality-factor resonators at high static pressures.

It is well known that cavitation collapse can generate intense concentrations of mechanical energy, sufficient to erode even the hardest metals and to generate light emissions visible to the naked eye [sonoluminescence (SL)]. Considerable attention has been devoted to the phenomenon of "single bubble sonoluminescence" (SBSL) in which a single stable cavitation bubble radiates light flashes each and every acoustic cycle. Most of these studies involve acoustic resonators in which the ambient pressure is near 0.1 MPa (1 bar), and with acoustic driving pressures on the order of 0.1 MPa. This study describes a high-quality factor, spherical resonator capable of achieving acoustic cavitation at ambient pressures in excess of 30 MPa (300 bars). This system generates bursts of violent inertial cavitation events lasting only a few milliseconds (hundreds of acoustic cycles), in contrast with the repetitive cavitation events (lasting several minutes) observed in SBSL; accordingly, these events are described as "inertial transient cavitation." Cavitation observed in this high pressure resonator is characterized by flashes of light with intensities up to 1000 times brighter than SBSL flashes, as well as spherical shock waves with amplitudes exceeding 30 MPa at the resonator wall. Both SL and shock amplitudes increase with static pressure.

Effect of conjugated linoleic acid on body fat accretion in overweight or obese children.

BACKGROUND: Conjugated linoleic acid (CLA) is a supplemental dietary fatty acid that decreases fat mass accretion in young animals. OBJECTIVE: The aim of this study was to determine CLA's efficacy with regard to change in fat and body mass index (BMI; in kg/m(2)) in children. DESIGN: We conducted a 7 +/- 0.5-mo randomized, double-blind, placebo-controlled trial of CLA in 62 prepubertal children aged 6-10 y who were overweight or obese but otherwise healthy. The subjects were randomly assigned to receive 3 g/d of 80% CLA (50:50 cis-9,trans-11 and trans-10,cis-12 isomers) or placebo in chocolate milk. RESULTS: Fifty-three subjects completed the trial (n = 28 in the CLA group, n = 25 in the placebo group). CLA attenuated the increase in BMI (0.5 +/- 0.8) compared with placebo (1.1 +/- 1.1) (P = 0.05). The percentage change in body fat measured by dual-energy X-ray absorptiometry was smaller (P = 0.001) in the CLA group (-0.5 +/- 2.1%) than in the placebo group (1.3 +/- 1.8%). The change in abdominal body fat as a percentage of total body weight was smaller (P = 0.02) in the CLA group (-0.09 +/- 0.9%) than in the placebo group (0.43 +/- 0.6%). There were no significant changes in plasma glucose, insulin, or LDL cholesterol between groups. Plasma HDL cholesterol decreased significantly more (P = 0.05) in the CLA group (-5.1 +/- 7.3 mg/dL) than in the placebo group (-0.7 +/- 8 mg/dL). Bone mineral accretion was lower (P = 0.04) in the CLA group (0.05 +/- 0.03 kg) than in the placebo group (0.07 +/- 0.03 kg). Reported gastrointestinal symptoms did not differ significantly between groups. CONCLUSIONS: CLA supplementation for 7 +/- 0.5 mo decreased body fatness in 6-10-y-old children who were overweight or obese but did not improve plasma lipids or glucose and decreased HDL more than in the placebo group. Long-term investigation of the safety and efficacy of CLA supplementation in children is recommended.

The effect of Korean pine nut oil on in vitro CCK release, on appetite sensations and on gut hormones in post-menopausal overweight women.

Appetite suppressants may be one strategy in the fight against obesity. This study evaluated whether Korean pine nut free fatty acids (FFA) and triglycerides (TG) work as an appetite suppressant. Korean pine nut FFA were evaluated in STC-1 cell culture for their ability to increase cholecystokinin (CCK-8) secretion vs. several other dietary fatty acids from Italian stone pine nut fatty acids, oleic acid, linoleic acid, alpha-linolenic acid, and capric acid used as a control. At 50 muM concentration, Korean pine nut FFA produced the greatest amount of CCK-8 release (493 pg/ml) relative to the other fatty acids and control (46 pg/ml). A randomized, placebo-controlled, double-blind cross-over trial including 18 overweight post-menopausal women was performed. Subjects received capsules with 3 g Korean pine (Pinus koraiensis) nut FFA, 3 g pine nut TG or 3 g placebo (olive oil) in combination with a light breakfast. At 0, 30, 60, 90, 120, 180 and 240 minutes the gut hormones cholecystokinin (CCK-8), glucagon like peptide-1 (GLP-1), peptide YY (PYY) and ghrelin, and appetite sensations were measured. A wash-out period of one week separated each intervention day.CCK-8 was higher 30 min after pine nut FFA and 60 min after pine nut TG when compared to placebo (p < 0.01). GLP-1 was higher 60 min after pine nut FFA compared to placebo (p < 0.01). Over a period of 4 hours the total amount of plasma CCK-8 was 60% higher after pine nut FFA and 22% higher after pine nut TG than after placebo (p < 0.01). For GLP-1 this difference was 25% after pine nut FFA (P < 0.05). Ghrelin and PYY levels were not different between groups. The appetite sensation "prospective food intake" was 36% lower after pine nut FFA relative to placebo (P < 0.05). This study suggests that Korean pine nut may work as an appetite suppressant through an increasing effect on satiety hormones and a reduced prospective food intake.

The effect of Korean pine nut oil (PinnoThin) on food intake, feeding behaviour and appetite: a double-blind placebo-controlled trial.

Certain free fatty acids have been shown to have potent effects on food intake and self-reported changes in appetite; effects associated with increases in the release of endogenous cholecystokinin (CCK) and glucagon like peptide-1 (GLP-1). In the current study, the effects of a Korean pine nut oil product, PinnoThin, at doses 2 g, 4 g and 6 g triglyceride (TG) and 2 g free fatty acid (FFA), on food intake and appetite were examined in a cross-over double-blind placebo-controlled randomised counter-balanced design in 42 overweight female volunteers. 2 g FFA PinnoThin, given 30 minutes prior to an ad-libitum buffet test lunch, significantly reduced food intake (gram) by 9% (F(4,164) = 2.637, p = 0.036) compared to olive oil control. No significant effect of PinnoThin on macronutrient intake or ratings of appetite were observed. Given the recent data showing that the TG form of PinnoThin may also reduce appetite by increasing CCK release, the lack of any effect of the TG form found in this study could be attributed to the timing of the dosing regime. Collectively, these data suggest that PinnoThin may exert satiating effects consistent with its known action on CCK and GLP-1 release, and previously observed effects on self-reported appetite ratings.