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Non-nutritive sweeteners - NED Infobite
BANT's scientific NED InfoBites are designed to provide key elements of the latest research using plain language. They provide quick overviews on particular health issues and nutrition topics for a speedy introduction to the science. Visually attractive and easily shareable with clients and social media followers.
2024
Abstract
Sugary drinks and excess dietary sugars have been related to the development of many non- communicable diseases such as obesity, heart disease and type 2 diabetes (T2D). This collection of articles brings the science on fructose, sucrose and other non-nutritive sweeteners and their impact on health into the spotlight.
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Obesity and Sex-Related Associations With Differential Effects of Sucralose vs Sucrose on Appetite and Reward Processing: A Randomized Crossover Trial.
Yunker, AG, Alves, JM, Luo, S, Angelo, B, DeFendis, A, Pickering, TA, Monterosso, JR, Page, KA
JAMA network open. 2021;4(9):e2126313
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Added sweeteners are increasingly being used in foods to maintain the sweet taste without the added calories, however the health consequences of this are still unclear. Most of the research that exists is in men of normal weight, however women and individuals with obesity have shown to have differing appetite responses. This randomised crossover trial of 74 adults aimed to determine the effect of consuming sweetener compared to sugar on brain, hormone, and appetite responses and whether these differed by sex and obesity status. The results showed that women had increased food related brain responses and consumed greater calories following ingestion of an artificially sweetened drink. In those with obesity food related brain response was also increased following sweetener consumption. Blood glucose hormone response was decreased following sweetener consumption compared to sugar consumption. It was concluded that females and individuals with obesity have differing brain activity following consumption of sweetener. This study could be used by healthcare professionals to understand that the recommendation of artificial sweeteners for weight loss in women and those who are already suffering from obesity may lead to greater calorie consumption. However further research is needed to confirm this.
Abstract
Importance: Nonnutritive sweeteners (NNSs) are used as an alternative to nutritive sweeteners to quench desire for sweets while reducing caloric intake. However, studies have shown mixed results concerning the effects of NNSs on appetite, and the associations between sex and obesity with reward and appetitive responses to NNS compared with nutritive sugar are unknown. Objective: To examine neural reactivity to different types of high-calorie food cues (ie, sweet and savory), metabolic responses, and eating behavior following consumption of sucralose (NNS) vs sucrose (nutritive sugar) among healthy young adults. Design, Setting, and Participants: In a randomized, within-participant, crossover trial including 3 separate visits, participants underwent a functional magnetic resonance imaging task measuring blood oxygen level-dependent signal in response to visual cues. For each study visit, participants arrived at the Dornsife Cognitive Neuroimaging Center of University of Southern California at approximately 8:00 am after a 12-hour overnight fast. Blood was sampled at baseline and 10, 35, and 120 minutes after participants received a drink containing sucrose, sucralose, or water to measure plasma glucose, insulin, glucagon-like peptide(7-36), acyl-ghrelin, total peptide YY, and leptin. Participants were then presented with an ad libitum meal. Participants were right-handed, nonsmokers, weight-stable for at least 3 months before the study visits, nondieters, not taking medication, and with no history of eating disorders, illicit drug use, or medical diagnoses. Data analysis was performed from March 2020 to March 2021. Interventions: Participants ingested 300-mL drinks containing either sucrose (75 g), sucralose (individually sweetness matched), or water (as a control). Main Outcomes and Measures: Primary outcomes of interest were the effects of body mass index (BMI) status and sex on blood oxygen level-dependent signal to high-calorie food cues, endocrine, and feeding responses following sucralose vs sucrose consumption. Secondary outcomes included neural, endocrine, and feeding responses following sucrose vs water and sucralose vs water (control) consumption, and cue-induced appetite ratings following sucralose vs sucrose (and vs water). Results: A total of 76 participants were randomized, but 2 dropped out, leaving 74 adults (43 women [58%]; mean [SD] age, 23.40 [3.96] years; BMI range, 19.18-40.27) who completed the study. In this crossover design, 73 participants each received water (drink 1) and sucrose (drink 2), and 72 participants received water (drink 1), sucrose (drink 2), and sucralose (drink 3). Sucrose vs sucralose was associated with greater production of circulating glucose, insulin, and glucagon-like peptide-1 and suppression of acyl-ghrelin, but no differences were found for peptide YY or leptin. BMI status by drink interactions were observed in the medial frontal cortex (MFC; P for interaction < .001) and orbitofrontal cortex (OFC; P for interaction = .002). Individuals with obesity (MFC, β, 0.60; 95% CI, 0.38 to 0.83; P < .001; OFC, β, 0.27; 95% CI, 0.11 to 0.43; P = .002), but not those with overweight (MFC, β, 0.02; 95% CI, -0.19 to 0.23; P = .87; OFC, β, -0.06; 95% CI, -0.21 to 0.09; P = .41) or healthy weight (MFC, β, -0.13; 95% CI, -0.34 to 0.07; P = .21; OFC, β, -0.08; 95% CI, -0.23 to 0.06; P = .16), exhibited greater responsivity in the MFC and OFC to savory food cues after sucralose vs sucrose. Sex by drink interactions were observed in the MFC (P for interaction = .03) and OFC (P for interaction = .03) after consumption of sucralose vs sucrose. Female participants had greater MFC and OFC responses to food cues (MFC high-calorie vs low-calorie cues, β, 0.21; 95% CI, 0.05 to 0.37; P = .01; MFC sweet vs nonfood cues, β, 0.22; 95% CI, 0.02 to 0.42; P = .03; OFC food vs nonfood cues, β, 0.12; 95% CI, 0.02 to 0.22; P = .03; and OFC sweet vs nonfood cues, β, 0.15; 95% CI, 0.03 to 0.27; P = .01), but male participants' responses did not differ (MFC high-calorie vs low-calorie cues, β, 0.01; 95% CI, -0.19 to 0.21; P = .90; MFC sweet vs nonfood cues, β, -0.04; 95% CI, -0.26 to 0.18; P = .69; OFC food vs nonfood cues, β, -0.08; 95% CI, -0.24 to 0.08; P = .32; OFC sweet vs nonfood cues, β, -0.11; 95% CI, -0.31 to 0.09; P = .31). A sex by drink interaction on total calories consumed during the buffet meal was observed (P for interaction = .03). Female participants consumed greater total calories (β, 1.73; 95% CI, 0.38 to 3.08; P = .01), whereas caloric intake did not differ in male participants (β, 0.68; 95% CI, -0.99 to 2.35; P = .42) after sucralose vs sucrose ingestion. Conclusions and Relevance: These findings suggest that female individuals and those with obesity may be particularly sensitive to disparate neural responsivity elicited by sucralose compared with sucrose consumption. Trial Registration: ClinicalTrials.gov Identifier: NCT02945475.
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Honey does not adversely impact blood lipids of adult men and women: a randomized cross-over trial.
Al-Tamimi, AM, Petrisko, M, Hong, MY, Rezende, L, Clayton, ZS, Kern, M
Nutrition research (New York, N.Y.). 2020;74:87-95
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Restriction of sugar intake is among the most commonly advocated public health strategies, as it is believed to prevent the development of chronic diseases. Unlike sugar, honey has been shown to have various positive health benefits from increasing antioxidant status to lowering postprandial [after a meal] glycaemia and insulinaemia in healthy subjects when compared to responses of more highly refined sugar mixtures. The aim of this study was to assess responses to both short-term (1 week) and relatively long-term (1 month) ingestion of clover honey consumption versus sucrose on changes in dietary intake and serum lipid concentrations in young to middle-aged adults. This study is a crossover design randomised controlled study for which 40 participants were recruited (male [n = 21] and female [n = 19]) with an age range between 25 and 57 years. Results indicate that consumption of clover honey (1.2 g of carbohydrate per kilogram body weight) for up to 1 month produced modestly positive dietary and triglyceride effects compared to sucrose. - there were no positive lipid effects within the clover honey trial. - compared to sucrose, clover honey consumption resulted in a significantly lower intake of energy, carbohydrate, sugars and fat as well as lower triglycerides concentrations at the end of 4 weeks. Authors conclude that honey produces limited, modest health benefits relative to sucrose. Future studies are needed to investigate the possible mechanisms by which honey influences triglyceride production and/or clearance and the metabolic and hormonal regulators of food intake.
Abstract
Consumption of added sugars in the US is estimated to be approximately 1.5 times recommended levels and has been linked to increased risk for developing chronic diseases. We hypothesized that relative to sugar, honey would reduce energy intake and improve serum lipid profiles. To test this, we assessed the short-term (1-week) and relatively long-term (1-month) effects of honey versus sucrose on changes in dietary intake and serum lipid concentrations. Thirty-seven apparently healthy subjects (21 males; 16 females) aged 24-57 years (BMI = 17.6-37.2 kg/m2) completed two 4-week trials in a randomized, cross-over design separated by ≥4-week washout. During each trial, subjects consumed either clover honey or sucrose providing 1.2 g/kg/day of carbohydrate under free-living conditions with instructions to avoid changing their habitual food intake. Serum triglyceride (TG) concentrations were elevated (P < .05) after 1 week for both trials but only remained elevated (P < .05) at the 4-week time-point during sucrose consumption. The elevation after 1 week during the honey trial was concurrent with a transient increase (P < .05) in body weight. No effects on serum concentrations of insulin, total cholesterol, low density lipoprotein-cholesterol, or high density lipoprotein-cholesterol were detected for either trial. Subjects consumed significantly less energy (P < .05), carbohydrate (P < .005), sugars (P < .05), and saturated fat (P < .05) during the honey trial. These data suggest that honey may serve as a favorable substitute for sucrose with regard to reduced energy intake, carbohydrate and sugars, without negatively influencing serum lipid concentrations.
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Postexercise Glucose-Fructose Coingestion Augments Cycling Capacity During Short-Term and Overnight Recovery From Exhaustive Exercise, Compared With Isocaloric Glucose.
Gray, EA, Green, TA, Betts, JA, Gonzalez, JT
International journal of sport nutrition and exercise metabolism. 2020;30(1):54-61
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Carbohydrate is the dominant energy source during moderate-to-high-intensity exercise. During prolonged exercise, low glycogen availability is inevitable which is associated with the onset of fatigue. The aim of this study was to investigate the effect of post-exercise glucose-fructose co-ingestion versus glucose alone on subsequent cycling capacity. This study consists of two randomized, cross-over experiments. Experiment one (double-blind) employed a 4-h recovery (SHORT-EXPERIMENT), whereas, experiment two (single-blind) used a 15-h overnight recovery (OVERNIGHT-EXPERIMENT). Eight trained male cyclists participated in SHORT-EXPERIMENT whereas three female and five male trained cyclists participated in OVERNIGHT-EXPERIMENT. Results demonstrate that post-exercise glucose-fructose co-ingestion, compared to isocaloric glucose alone, augments cycling capacity following short (4-h) and overnight (15-h) recovery periods in trained cyclists. Authors conclude that endurance athletes competing in multi-stage events where recovery time is limited may benefit from consuming fructose alongside glucose in their post-exercise nutritional strategies.
Abstract
During short-term recovery, postexercise glucose-fructose coingestion can accelerate total glycogen repletion and augment recovery of running capacity. It is unknown if this advantage translates to cycling, or to a longer (e.g., overnight) recovery. Using two experiments, the present research investigated if postexercise glucose-fructose coingestion augments exercise capacity following 4-hr (short experiment; n = 8) and 15-hr (overnight experiment; n = 8) recoveries from exhaustive exercise in trained cyclists, compared with isocaloric glucose alone. In each experiment, a glycogen depleting exercise protocol was followed by a 4-hr recovery, with ingestion of 1.5 or 1.2 g·kg-1·hr-1 carbohydrate in the short experiment (double blind) and the overnight experiment (single blind), respectively. Treatments were provided in a randomized order using a crossover design. Four or fifteen hours after the glycogen depletion protocol, participants cycled to exhaustion at 70% Wmax or 65% Wmax in the short experiment and the overnight experiment, respectively. In both experiments there was no difference in substrate oxidation or blood glucose and lactate concentrations between treatments during the exercise capacity test (trial effect, p > .05). Nevertheless, cycling capacity was greater in glucose + fructose versus glucose only in the short experiment (28.0 ± 8.4 vs. 22.8 ± 7.3 min, d = 0.65, p = .039) and the overnight experiment (35.9 ± 10.7 vs. 30.6 ± 9.2 min, d = 0.53, p = .026). This is the first study to demonstrate that postexercise glucose-fructose coingestion enhances cycling capacity following short-term (4 hr) and overnight (15 hr) recovery durations. Therefore, if multistage endurance athletes are ingesting glucose for rapid postexercise recovery then fructose containing carbohydrates may be advisable.
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Fructose metabolism and metabolic disease.
Hannou, SA, Haslam, DE, McKeown, NM, Herman, MA
The Journal of clinical investigation. 2018;128(2):545-555
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Sugar consumption is thought to be a contributing factor in the increase in diabetes and obesity and the associated risk of cardiovascular disease worldwide. Sucrose (table sugar) and high fructose corn syrup contain almost equal amounts of fructose and glucose and are commonly added to processed foods. Whilst long-term studies are lacking, some short-term intervention studies show that fructose can impair lipid metabolism and insulin sensitivity in humans. This article reviews the biochemistry and molecular genetics of fructose metabolism as well as potential mechanisms by which excessive fructose consumption contributes to cardiometabolic disease. Fructose absorption in the human intestine is saturable, and there is a large range in capacity to absorb fructose between individuals, and unabsorbed fructose may contribute to gastrointestinal symptoms including pain and bloating. Fructose concentrations in the blood can increase 10-fold after consumption, but are rapidly cleared, mostly by the liver, where it provides substrate for metabolic processes, but may also be involved in signalling functions. Fructose may enhance glucose uptake by the liver and storage as glycogen and lipids. It may also increase production of uric acid which is implicated with gout. Excessive fructose consumption affects lipid metabolism and may contribute to fat accumulation in the liver and increase circulating triglycerides, a risk factor for heart disease. In animal models it also induces increased insulin levels. Fructose is one of the sweetest sugars which may affect appetite and overeating. It may also induce addiction-like behaviours such as binging and dependence in part by stimulating dopaminergic pathways. It also appears to induce leptin resistance which further increases food intake and obesity.
Abstract
Increased sugar consumption is increasingly considered to be a contributor to the worldwide epidemics of obesity and diabetes and their associated cardiometabolic risks. As a result of its unique metabolic properties, the fructose component of sugar may be particularly harmful. Diets high in fructose can rapidly produce all of the key features of the metabolic syndrome. Here we review the biology of fructose metabolism as well as potential mechanisms by which excessive fructose consumption may contribute to cardiometabolic disease.
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Relation of total sugars, fructose and sucrose with incident type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.
Tsilas, CS, de Souza, RJ, Mejia, SB, Mirrahimi, A, Cozma, AI, Jayalath, VH, Ha, V, Tawfik, R, Di Buono, M, Jenkins, AL, et al
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2017;189(20):E711-E720
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Sugars, particularly fructose-containing sugars, have been implicated as an important driver in the rise in incidence of type 2 diabetes. The aim of this study was to determine the role of fructose-containing sugars independent of food form in the development of type 2 diabetes. This study is a systemic review and meta-analysis of prospective cohort studies. The study included 15 cohorts from 9 studies. Results indicate that intakes of total sugars and fructose were not associated with type 2 diabetes, whereas intake of sucrose was associated with an 11% decrease in type 2 diabetes. Authors conclude that in the absence of a clear signal for harm, sugars alone do not appear to explain the relation between sugar-sweetened beverages and type 2 diabetes.
Abstract
BACKGROUND Sugar-sweetened beverages are associated with type 2 diabetes. To assess whether this association holds for the fructose-containing sugars they contain, we conducted a systematic review and meta-analysis of prospective cohort studies. METHODS We searched MEDLINE, Embase, CINAHL and the Cochrane Library (through June 2016). We included prospective cohort studies that assessed the relation of fructose-containing sugars with incident type 2 diabetes. Two independent reviewers extracted relevant data and assessed risk of bias. We pooled risk ratios (RRs) using random effects meta-analyses. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS Fiffeen prospective cohort studies (251 261 unique participants, 16 416 cases) met the eligibility criteria, comparing the highest intake (median 137, 35.2 and 78 g/d) with the lowest intake (median 65, 9.7 and 25.8 g/d) of total sugars, fructose and sucrose, respectively. Although there was no association of total sugars (RR 0.91, 95% confidence interval [CI] 0.76-1.09) or fructose (RR 1.04, 95% CI 0.84-1.29) with type 2 diabetes, sucrose was associated with a decreased risk of type 2 diabetes (RR 0.89, 95% CI 0.80-0.98). Our confidence in the estimates was limited by evidence of serious inconsistency between studies for total sugars and fructose, and serious imprecision in the pooled estimates for all 3 sugar categories. INTERPRETATION Current evidence does not allow us to conclude that fructose-containing sugars independent of food form are associated with increased risk of type 2 diabetes. Further research is likely to affect our estimates. TRIAL REGISTRATION ClinicalTrials.gov, no. NCT01608620.
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Fructose and Sucrose Intake Increase Exogenous Carbohydrate Oxidation during Exercise.
Trommelen, J, Fuchs, CJ, Beelen, M, Lenaerts, K, Jeukendrup, AE, Cermak, NM, van Loon, LJ
Nutrients. 2017;9(2)
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During prolonged exercise, the metabolic rate and energy requirement increase severalfold. Carbohydrate oxidation provides energy to muscles during exercise. In this randomised cross-over, double-blind study, researchers examined the effects of fructose or sucrose co-ingestion with glucose on exogenous carbohydrate oxidation rates during prolonged exercise in ten trained male cyclists. The administration of glucose with fructose or sucrose resulted in fewer gastrointestinal complaints than the administration of glucose alone. Co-ingestion of fructose or sucrose with glucose may enhance gastric absorption of carbohydrates and decrease the accumulation of carbohydrates in the gastrointestinal tract, which may explain lower gastrointestinal complaints among participants. Fructose co-ingestion increased exogenous carbohydrate oxidation rate during prolonged exercise by 35-55% more than glucose. Compared to glucose administration alone, fructose or sucrose co-administration also increased plasma lactate production and oxidation. The study concludes that fructose and sucrose can serve as functional ingredients in sports drinks to provide energy during prolonged exercise. As this study only focused on whole-body exogenous oxidation rates, more research is still needed to identify specific oxidation sites. Nevertheless, this study's findings can help healthcare professionals understand how different types of sugar can provide energy during prolonged exercise.
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Peak exogenous carbohydrate oxidation rates typically reach ~1 g∙min-1 during exercise when ample glucose or glucose polymers are ingested. Fructose co-ingestion has been shown to further increase exogenous carbohydrate oxidation rates. The purpose of this study was to assess the impact of fructose co-ingestion provided either as a monosaccharide or as part of the disaccharide sucrose on exogenous carbohydrate oxidation rates during prolonged exercise in trained cyclists. Ten trained male cyclists (VO2peak: 65 ± 2 mL∙kg-1∙min-1) cycled on four different occasions for 180 min at 50% Wmax during which they consumed a carbohydrate solution providing 1.8 g∙min-1 of glucose (GLU), 1.2 g∙min-1 glucose + 0.6 g∙min-1 fructose (GLU + FRU), 0.6 g∙min-1 glucose + 1.2 g∙min-1 sucrose (GLU + SUC), or water (WAT). Peak exogenous carbohydrate oxidation rates did not differ between GLU + FRU and GLU + SUC (1.40 ± 0.06 vs. 1.29 ± 0.07 g∙min-1, respectively, p = 0.999), but were 46% ± 8% higher when compared to GLU (0.96 ± 0.06 g∙min-1: p < 0.05). In line, exogenous carbohydrate oxidation rates during the latter 120 min of exercise were 46% ± 8% higher in GLU + FRU or GLU + SUC compared with GLU (1.19 ± 0.12, 1.13 ± 0.21, and 0.82 ± 0.16 g∙min-1, respectively, p < 0.05). We conclude that fructose co-ingestion (0.6 g∙min-1) with glucose (1.2 g∙min-1) provided either as a monosaccharide or as sucrose strongly increases exogenous carbohydrate oxidation rates during prolonged exercise in trained cyclists.
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Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD.
Lee, T, Clavel, T, Smirnov, K, Schmidt, A, Lagkouvardos, I, Walker, A, Lucio, M, Michalke, B, Schmitt-Kopplin, P, Fedorak, R, et al
Gut. 2017;66(5):863-871
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Iron deficiency is common in patients with Inflammatory Bowel Disease (IBD) and the standard management is with oral iron replacement therapy. However, this is thought to worsen IBD symptoms, as free iron in the gut can alter the composition of the resident gut bacteria and may contribute to inflammation. This open-labelled clinical trial compared oral iron replacement to intravenous iron replacement in subjects with Crohn’s disease (CD), Ulcerative Colitis and iron-deficient, non-inflamed subjects. The data collected included microbiome sequencing, metabolic profiling, serum iron and inflammation markers. Whilst both interventions alleviated deficiency, the intravenous iron replacement was slightly more effective at raising ferritin levels. The results showed that iron replacement therapy shifted the microbiome diversity and composition depending on free iron availability in the gut. A reduced microbiome diversity already distinguishes IBD from healthy subjects and a further decline in abundance following iron replacement therapy was particularly noticeable with oral iron supplementation and in Crohn's Disease subjects. However, over the short course of three months, this was not linked to disease severity in this study. This study affirms the importance of assessing for iron deficiency in IBD clients whilst supporting IV iron replacement being a favourable alternative to oral supplementation for individuals with unstable microbiota.
Abstract
OBJECTIVE Iron deficiency is a common complication in patients with IBD and oral iron therapy is suggested to exacerbate IBD symptoms. We performed an open-labelled clinical trial to compare the effects of per oral (PO) versus intravenous (IV) iron replacement therapy (IRT). DESIGN The study population included patients with Crohn's disease (CD; N=31), UC (N=22) and control subjects with iron deficiency (non-inflamed, NI=19). After randomisation, participants received iron sulfate (PO) or iron sucrose (IV) over 3 months. Clinical parameters, faecal bacterial communities and metabolomes were assessed before and after intervention. RESULTS Both PO and IV treatments ameliorated iron deficiency, but higher ferritin levels were observed with IV. Changes in disease activity were independent of iron treatment types. Faecal samples in IBD were characterised by marked interindividual differences, lower phylotype richness and proportions of Clostridiales. Metabolite analysis also showed separation of both UC and CD from control anaemic participants. Major shifts in bacterial diversity occurred in approximately half of all participants after IRT, but patients with CD were most susceptible. Despite individual-specific changes in phylotypes due to IRT, PO treatment was associated with decreased abundances of operational taxonomic units assigned to the species Faecalibacterium prausnitzii, Ruminococcus bromii, Dorea sp. and Collinsella aerofaciens. Clear IV-specific and PO-specific fingerprints were evident at the level of metabolomes, with changes affecting cholesterol-derived host substrates. CONCLUSIONS Shifts in gut bacterial diversity and composition associated with iron treatment are pronounced in IBD participants. Despite similar clinical outcome, oral administration differentially affects bacterial phylotypes and faecal metabolites compared with IV therapy. TRIAL REGISTRATION NUMBER clinicaltrial.gov (NCT01067547).
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Excessive Sugar Consumption May Be a Difficult Habit to Break: A View From the Brain and Body.
Tryon, MS, Stanhope, KL, Epel, ES, Mason, AE, Brown, R, Medici, V, Havel, PJ, Laugero, KD
The Journal of clinical endocrinology and metabolism. 2015;100(6):2239-47
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It is widely known that people eat to relieve stress. Rodent studies have shown that sugar consumption switches off activity in the networks that mediate the stress induced hypothalamic-pituitary-adrenal (HPA) autonomic nervous system. This study aimed to compare the effects of consuming drinks, sweetened with either sucrose or aspartame, on cortisol responses induced by stress. The researchers found that sucrose consumption was associated reduced stress induced cortisol, and a trend towards lower cortisol. Aspartame did not have the same effect. The Montreal Imaging Stress Task (MIST) was used to map areas of the brain associated with stress. It was found that sugar consumption caused a diminished response to MIST after two weeks of sucrose consumption, and cortisol was elevated after two weeks of aspartame. The study concluded that brain negative feedback pathways are affected by sugar, and consequently may make stressed individuals more reliant or addicted to sugar. In turn, this increases the likelihood of obesity and its associated chronic diseases.
Abstract
CONTEXT Sugar overconsumption and chronic stress are growing health concerns because they both may increase the risk for obesity and its related diseases. Rodent studies suggest that sugar consumption may activate a glucocorticoid-metabolic-brain-negative feedback pathway, which may turn off the stress response and thereby reinforce habitual sugar overconsumption. OBJECTIVE The objective of the study was to test our hypothesized glucocorticoid-metabolic-brain model in women consuming beverages sweetened with either aspartame of sucrose. DESIGN This was a parallel-arm, double-masked diet intervention study. SETTING The study was conducted at the University of California, Davis, Clinical and Translational Science Center's Clinical Research Center and the University of California, Davis, Medical Center Imaging Research Center. PARTICIPANTS Nineteen women (age range 18-40 y) with a body mass index (range 20-34 kg/m(2)) who were a subgroup from a National Institutes of Health-funded investigation of 188 participants assigned to eight experimental groups. INTERVENTION The intervention consisted of sucrose- or aspartame-sweetened beverage consumption three times per day for 2 weeks. MAIN OUTCOME MEASURES Salivary cortisol and regional brain responses to the Montreal Imaging Stress Task were measured. RESULTS Compared with aspartame, sucrose consumption was associated with significantly higher activity in the left hippocampus (P = .001). Sucrose, but not aspartame, consumption associated with reduced (P = .024) stress-induced cortisol. The sucrose group also had a lower reactivity to naltrexone, significantly (P = .041) lower nausea, and a trend (P = .080) toward lower cortisol. CONCLUSION These experimental findings support a metabolic-brain-negative feedback pathway that is affected by sugar and may make some people under stress more hooked on sugar and possibly more vulnerable to obesity and its related conditions.