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Acute glycemic and insulinemic effects of low-energy sweeteners: a systematic review and meta-analysis of randomized controlled trials.
Greyling, A, Appleton, KM, Raben, A, Mela, DJ
The American journal of clinical nutrition. 2020;(4):1002-1014
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BACKGROUND It has been suggested that low-energy sweeteners (LES) may be associated with an increased risk of metabolic diseases, possibly due to stimulation of glucose-responsive mechanisms. OBJECTIVE We conducted a systematic review and meta-analysis of human intervention studies examining the acute effect of LES intake on postprandial glucose (PPG) and postprandial insulin (PPI) responses, in order to comprehensively and objectively quantify these relations. METHODS We systematically searched the Medline, OVID FSTA, and SCOPUS databases until January 2020. Randomized controlled trials comparing acute postprandial effects on PPG and/or PPI after exposure to LES, either alone, with a meal, or with other nutrient-containing preloads to the same intervention without LES were eligible for inclusion. PPG and PPI responses were calculated as mean incremental area under the curve divided by time. Meta-analyses were performed using random effects models with inverse variance weighing. RESULTS Twenty-six papers (34 PPG trials and 29 PPI trials) were included. There were no reports of statistically significant differences in the effects of LES on PPG and PPI responses compared with control interventions. Pooled effects of LES intake on the mean change difference in PPG and PPI were -0.02 mmol/L (95% CI: -0.09, 0.05) and -2.39 pmol/L (95% CI: -11.83, 7.05), respectively. The results did not appreciably differ by the type or dose of LES consumed, cointervention type, or fasting glucose and insulin levels. Among patients with type 2 diabetes, the mean change difference indicated a smaller PPG response after exposure to LES compared with the control (-0.3 mmol/L; 95% CI: -0.53, -0.07). CONCLUSIONS Ingestion of LES, administered alone or in combination with a nutrient-containing preload, has no acute effects on the mean change in postprandial glycemic or insulinemic responses compared with a control intervention. Apart from a small beneficial effect on PPG (-0.3 mmol/L) in studies enrolling patients with type 2 diabetes, the effects did not differ by type or dose of LES, or fasting glucose or insulin levels. This review and meta-analysis was registered at PROSPERO as CRD42018099608.
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New insight into human sweet taste: a genome-wide association study of the perception and intake of sweet substances.
Hwang, LD, Lin, C, Gharahkhani, P, Cuellar-Partida, G, Ong, JS, An, J, Gordon, SD, Zhu, G, MacGregor, S, Lawlor, DA, et al
The American journal of clinical nutrition. 2019;(6):1724-1737
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BACKGROUND Individual differences in human perception of sweetness are partly due to genetics; however, which genes are associated with the perception and the consumption of sweet substances remains unclear. OBJECTIVE The aim of this study was to verify previous reported associations within genes involved in the peripheral receptor systems (i.e., TAS1R2, TAS1R3, and GNAT3) and reveal novel loci. METHODS We performed genome-wide association scans (GWASs) of the perceived intensity of 2 sugars (glucose and fructose) and 2 high-potency sweeteners (neohesperidin dihydrochalcone and aspartame) in an Australian adolescent twin sample (n = 1757), and the perceived intensity and sweetness and the liking of sucrose in a US adult twin sample (n = 686). We further performed GWASs of the intake of total sugars (i.e., total grams of all dietary mono- and disaccharides per day) and sweets (i.e., handfuls of candies per day) in the UK Biobank sample (n = ≤174,424 white-British individuals). All participants from the 3 independent samples were of European ancestry. RESULTS We found a strong association between the intake of total sugars and the single nucleotide polymorphism rs11642841 within the FTO gene on chromosome 16 (P = 3.8 × 10-8) and many suggestive associations (P < 1.0 × 10-5) for each of the sweet perception and intake phenotypes. We showed genetic evidence for the involvement of the brain in both sweet taste perception and sugar intake. There was limited support for the associations with TAS1R2, TAS1R3, and GNAT3 in all 3 European samples. CONCLUSIONS Our findings indicate that genes additional to those involved in the peripheral receptor system are also associated with the sweet taste perception and intake of sweet-tasting foods. The functional potency of the genetic variants within TAS1R2, TAS1R3, and GNAT3 may be different between ethnic groups and this warrants further investigations.
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Association between soft drinks consumption and asthma: a systematic review and meta-analysis.
Al-Zalabani, AH, Noor Elahi, I, Katib, A, Alamri, AG, Halawani, A, Alsindi, NM, Almatrafi, M, Wesselius, A, Stewart, KFJ
BMJ open. 2019;(10):e029046
Abstract
OBJECTIVES To carry out meta-analysis and systematic review on the association between soft drinks consumption and asthma prevalence among adults and children. DESIGN Systematic review and meta-analysis of observational research. DATA SOURCES Medline, Scopus, ISI Web of Science and the Cochrane Library were searched up to December 2018. ELIGIBILITY CRITERIA We included observational studies investigating the association between soft drinks consumption (including maternal consumption during pregnancy) and asthma or wheeze. DATA EXTRACTION AND SYNTHESIS Data were extracted by one author and reviewed independently by two other authors. The most adjusted estimate from each original study was used in the meta-analysis. Meta-analysis was conducted using random-effects model. The quality of studies was assessed using the Newcastle-Ottawa scale and heterogeneity was evaluated using I2 statistic. RESULTS Of 725 publications originally identified, 19 were included in this systematic review, including 3 cohort studies and 16 cross-sectional studies. Ten articles reported on children up to 18 years, 5 articles on adults (>18 years) and 2 articles on prenatal exposure. In total, 468 836 participants were included, with more than 50 000 asthma cases. Soft drinks consumption was associated with significantly increased odds of asthma in both adults (OR=1.37; 95% CI, 1.23 to 1.52) and children (OR=1.14; 95% CI, 1.06 to 1.21). Prenatal exposure had marginally statistically significant association (OR=1.11; 95% CI, 1.00 to 1.23) with asthma in children. In subgroup analysis for childhood exposure, the association persists for sugar-sweetened soft drinks but not for carbonated drinks. CONCLUSION Our findings show a positive association between soft drinks consumption and asthma prevalence, mostly from cross-sectional studies. Therefore, more longitudinal research is required to establish causality.
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Prospective association of sugar-sweetened and artificially sweetened beverage intake with risk of hypertension.
Kim, Y, Je, Y
Archives of cardiovascular diseases. 2016;(4):242-53
Abstract
BACKGROUND Several observational studies have suggested that high consumption of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) is associated with increased blood pressure, but this relationship has not been investigated comprehensively. AIMS To quantitatively examine the association between sugar-sweetened and artificially sweetened beverage intake and risk of hypertension. METHODS We performed a systematic review and meta-analysis of eligible prospective cohort studies, identified by searching PubMed, Embase and Web of Science databases up to May 2015. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least-squares trend estimation was used to assess dose-response relationships. RESULTS Six studies (246,822 subjects and 80,628 incident cases of hypertension) were identified for the meta-analysis of SSBs and hypertension. The pooled RR of hypertension in the highest category of SSB consumption (≥1 serving/day, mean) compared with the lowest category of SSB (<0.6 serving/month, mean) was 1.12 (95% CI: 1.07, 1.17). In a dose-response analysis, a 1 serving/day increase in SSB intake was associated with an 8% increased risk of hypertension (RR: 1.08, 95% CI: 1.06, 1.11). Four studies (227,254 subjects and 78,177 incident cases of hypertension) were included in the meta-analysis of ASBs and hypertension. The pooled RRs were 1.14 (95% CI: 1.10, 1.18) for highest versus lowest analysis and 1.09 (95% CI: 1.06, 1.11) for every additional 1 serving/day increase in ASB consumption. The positive association did not vary significantly by sex, duration of follow-up or adjustment for body mass index. CONCLUSIONS Our findings indicate that high SSB and ASB consumption is associated with an increased risk of hypertension.
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Sweet tasting solutions for reduction of needle-related procedural pain in children aged one to 16 years.
Harrison, D, Yamada, J, Adams-Webber, T, Ohlsson, A, Beyene, J, Stevens, B
The Cochrane database of systematic reviews. 2015;(5):CD008408
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BACKGROUND Extensive evidence exists showing analgesic effects of sweet solutions for newborns and infants. It is less certain if the same analgesic effects exist for children one year to 16 years of age. This is an updated version of the original Cochrane review published in Issue 10, 2011 (Harrison 2011) titled Sweet tasting solutions for reduction of needle-related procedural pain in children aged one to 16 years. OBJECTIVES To determine the efficacy of sweet tasting solutions or substances for reducing needle-related procedural pain in children beyond one year of age. SEARCH METHODS Searches were run to the end of June 2014. We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Cochrane Methodology Register, Health Technology Assessment, the NHS Economic Evaluation Database, MEDLINE, EMBASE, PsycINFO, and ACP Journal Club (all via OvidSP), and CINAH (via EBSCOhost). We applied no language restrictions. SELECTION CRITERIA Published or unpublished randomised controlled trials (RCT) in which children aged one year to 16 years, received a sweet tasting solution or substance for needle-related procedural pain. Control conditions included water, non-sweet tasting substances, pacifier, distraction, positioning/containment, breastfeeding, or no treatment. DATA COLLECTION AND ANALYSIS Outcome measures included crying duration, composite pain scores, physiological or behavioral pain indicators, self-report of pain or parental or healthcare professional-report of the child's pain. We reported mean differences (MD), weighted mean difference (WMD), or standardized mean difference (SMD) with 95% confidence intervals (CI) using fixed-effect or random-effects models as appropriate for continuous outcome measures. We reported risk ratio (RR), risk difference (RD), and the number needed to treat to benefit (NNTB) for dichotomous outcomes. We used the I(2) statistic to assess between-study heterogeneity. MAIN RESULTS We included one unpublished and seven published studies (total of 808 participants); four more studies and 478 more participants than the 2011 review. Six trials included young children aged one to four years receiving sucrose or candy lollypops for immunisation pain compared with water or no treatment. Usual care included topical anaesthetics, upright parental holding, and distraction. All studies were well designed blinded RCTs, however, five of the six studies had a high risk of bias based on small sample sizes.Two studies included school-aged children receiving sweet or unsweetened chewing gum before, or before and during, immunisation and blood collection. Both studies, conducted by the same author, had a high risk of bias based on small sample sizes.Results for the toddlers/pre-school children were conflicting. Duration of cry, using a random-effects model, was not significantly reduced by sweet taste (six trials, 520 children, WMD -15 seconds, 95% CI -54 to 24, I(2) = 94%).Composite pain score at time of first needle was reported in four studies (n = 121 children). The scores were not significantly different between the sucrose and control group (SMD -0.26, 95% CI -1.27 to 0.75, I(2) = 86%).A Children's Hospital of Eastern Ontario Pain Scale score > 4 was significantly less common in the sucrose group compared to the control group in one study (n = 472, RR 0.55, 95% CI 0.45 to 0.67; RD -0.29, 95% CI -0.37 to -0.20; NNTB 3, 95% CI 3 to 5; tests for heterogeneity not applicable.For school-aged children, chewing sweet gum before needle-related painful procedures (two studies, n = 111 children) or during the procedures (two studies, n = 103 children) did not significantly reduce pain scores. A comparison of the Faces Pain Scale scores in children chewing sweet gum before the procedures compared with scores of children chewing unsweetened gum revealed a WMD of -0.15 (95% CI -0.61 to 0.30). Similar results were found when comparing the chewing of sweet gum with unsweetened gum during the procedure (WMD 0.23, 95% CI -0.28 to 0.74). The Colored Analogue Scale for children chewing sweet gum compared to unsweetened gum before the procedure was not significantly different (WMD 0.24 (-0.69 to 1.18)) nor was it different when children chewed the gum during the procedure (WMD 0.86 (95% CI -0.12 to 1.83)). There was no heterogeneity for any of these analyses in school-aged children (I(2) = 0%). AUTHORS' CONCLUSIONS Based on the eight studies included in this systematic review update, two of which were subgroups of small numbers of eligible toddlers from larger studies, and three of which were pilot RCTs with small numbers of participants, there is insufficient evidence of the analgesic effects of sweet tasting solutions or substances during acutely painful procedures in young children between one and four years of age. Further rigorously conducted, adequately powered RCTs are warranted in this population. Based on the two studies by the same author, there was no evidence of analgesic effects of sweet taste in school-aged children. As there are other effective evidence-based strategies available to use in this age group, further trials are not warranted.Despite the addition of four studies in this review, conclusions have not changed since the last version of the review.
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Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction.
Imamura, F, O'Connor, L, Ye, Z, Mursu, J, Hayashino, Y, Bhupathiraju, SN, Forouhi, NG
BMJ (Clinical research ed.). 2015;:h3576
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OBJECTIVES To examine the prospective associations between consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice with type 2 diabetes before and after adjustment for adiposity, and to estimate the population attributable fraction for type 2 diabetes from consumption of sugar sweetened beverages in the United States and United Kingdom. DESIGN Systematic review and meta-analysis. DATA SOURCES AND ELIGIBILITY PubMed, Embase, Ovid, and Web of Knowledge for prospective studies of adults without diabetes, published until February 2014. The population attributable fraction was estimated in national surveys in the USA, 2009-10 (n = 4729 representing 189.1 million adults without diabetes) and the UK, 2008-12 (n = 1932 representing 44.7 million). SYNTHESIS METHODS Random effects meta-analysis and survey analysis for population attributable fraction associated with consumption of sugar sweetened beverages. RESULTS Prespecified information was extracted from 17 cohorts (38,253 cases/10,126,754 person years). Higher consumption of sugar sweetened beverages was associated with a greater incidence of type 2 diabetes, by 18% per one serving/day (95% confidence interval 9% to 28%, I(2) for heterogeneity = 89%) and 13% (6% to 21%, I(2) = 79%) before and after adjustment for adiposity; for artificially sweetened beverages, 25% (18% to 33%, I(2) = 70%) and 8% (2% to 15%, I(2) = 64%); and for fruit juice, 5% (-1% to 11%, I(2) = 58%) and 7% (1% to 14%, I(2) = 51%). Potential sources of heterogeneity or bias were not evident for sugar sweetened beverages. For artificially sweetened beverages, publication bias and residual confounding were indicated. For fruit juice the finding was non-significant in studies ascertaining type 2 diabetes objectively (P for heterogeneity = 0.008). Under specified assumptions for population attributable fraction, of 20.9 million events of type 2 diabetes predicted to occur over 10 years in the USA (absolute event rate 11.0%), 1.8 million would be attributable to consumption of sugar sweetened beverages (population attributable fraction 8.7%, 95% confidence interval 3.9% to 12.9%); and of 2.6 million events in the UK (absolute event rate 5.8%), 79,000 would be attributable to consumption of sugar sweetened beverages (population attributable fraction 3.6%, 1.7% to 5.6%). CONCLUSIONS Habitual consumption of sugar sweetened beverages was associated with a greater incidence of type 2 diabetes, independently of adiposity. Although artificially sweetened beverages and fruit juice also showed positive associations with incidence of type 2 diabetes, the findings were likely to involve bias. None the less, both artificially sweetened beverages and fruit juice were unlikely to be healthy alternatives to sugar sweetened beverages for the prevention of type 2 diabetes. Under assumption of causality, consumption of sugar sweetened beverages over years may be related to a substantial number of cases of new onset diabetes.
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Do sugar-sweetened beverages cause adverse health outcomes in adults? A systematic review protocol.
Hamel, C, Stevens, A, Singh, K, Ansari, MT, Myers, E, Ziegler, P, Hutton, B, Sharma, A, Bjerre, LM, Fenton, S, et al
Systematic reviews. 2014;:108
Abstract
BACKGROUND Chronic diseases, such as cardiovascular disease and type 2 diabetes, impose significant burden to public health. Most chronic diseases are associated with underlying preventable risk factors, such as elevated blood pressure, blood glucose, and lipids, physical inactivity, excessive sedentary behaviours, overweight and obesity, and tobacco usage. Sugar-sweetened beverages are known to be significant sources of additional caloric intake, and given recent attention to their contribution in the development of chronic diseases, a systematic review is warranted. We will assess whether the consumption of sugar-sweetened beverages in adults is associated with adverse health outcomes and what the potential moderating factors are. METHODS/DESIGN Of interest are studies addressing sugar-sweetened beverage consumption, taking a broad perspective. Both direct consumption studies as well as those evaluating interventions that influence consumption (e.g. school policy, educational) will be relevant. Non-specific or multi-faceted behavioural, educational, or policy interventions may also be included subject to the level of evidence that exists for the other interventions/exposures. Comparisons of interest and endpoints of interest are pre-specified. We will include randomized controlled trials, controlled clinical trials, interrupted time series studies, controlled before-after studies, prospective and retrospective comparative cohort studies, case-control studies, and nested case-control designs. The MEDLINE, Embase, The Cochrane Library, CINAHL, ERIC, and PsycINFO databases and grey literature sources will be searched. The processes for selecting studies, abstracting data, and resolving conflicts are described. We will assess risk of bias using design-specific tools. To determine sets of confounding variables that should be adjusted for, we have developed causal directed acyclic graphs and will use those to inform our risk of bias assessments. Meta-analysis will be conducted where appropriate; parameters for exploring statistical heterogeneity and effect modifiers are pre-specified. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for outcomes. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42014009638.
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[Randomized clinical trials of the effect of sugar sweetened beverages consumption on adiposity in youngers than 16 y old; systematic review].
Jiménez-Cruz, A, Gómez-Miranda, LM, Bacardí-Gascón, M
Nutricion hospitalaria. 2013;(6):1797-801
Abstract
INTRODUCTION Association between sugar sweetened beverages consumption and several metabolic diseases has been observed. AIM: To analyze randomized studies among ≤ 16 yo children of ≥ 52 weeks of intervention assessing the effect of the reduction of sugar sweetened beverages, carbonated drinks, flavored drinks, and fruit juices on adiposity indicators. METHODS Medline was searched for randomized controlled trials published up to August 21st, 2013. The following search terms were used: "Sugar Sweetened Beverages" and "Weight gain". Papers without basal or final data, without accurate description of control groups and those without the eligibility criteria were excluded. RESULTS Three studies met the eligibility criteria. In the three studies an increase among the adiposity indicators were observed among those with sugar beverage consumption or a reduction in the prevalence of overweight and obesity among those with reduction of sugar beverages. CONCLUSION This result show the evidence of a positive effect of the consumption of sugar sweetened beverages on adiposity indicators.
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Very high fructose intake increases serum LDL-cholesterol and total cholesterol: a meta-analysis of controlled feeding trials.
Zhang, YH, An, T, Zhang, RC, Zhou, Q, Huang, Y, Zhang, J
The Journal of nutrition. 2013;(9):1391-8
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Fructose is widely used as a sweetener in the production of many foods, yet the relation between fructose intake and cholesterol remains uncertain. In this study, we performed a systematic review and meta-analysis of human, controlled, feeding trials involving isocaloric fructose exchange for other carbohydrates to quantify the effects of fructose on serum total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) in adult humans. Weighted mean differences were calculated to determine changes from baseline cholesterol concentrations by means of generic, inverse variance, random-effect models. The Heyland Methodological Quality was used to assess the quality of the study. Subgroup analyses and meta-regression were conducted to explore the possible influences of study characteristics. Twenty-four trials (with a total of 474 participants) were included in the meta-analysis. In an overall pooled estimate, it was shown that fructose exerted no effect on HDL-C. Meta-regression analysis indicated that fructose dose was positively correlated with the effect sizes of TC and LDL-C. Subgroup analyses showed that isocaloric fructose exchange for carbohydrates increased TC by 13.0 mg/dL [(95% CI: 4.7, 21.3); P = 0.002] and LDL-C by 11.6 mg/dL [(95% CI: 4.4, 18.9); P = 0.002] at >100 g fructose/d. However, no effect was shown on TC or LDL-C when the fructose intake was ≤100 g/d. In conclusion, it was shown that very high fructose intake (>100 g/d) increases serum LDL-C and TC concentrations. Larger, longer, and higher-quality human, controlled, feeding trials are needed to confirm these results.
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A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes.
Wiebe, N, Padwal, R, Field, C, Marks, S, Jacobs, R, Tonelli, M
BMC medicine. 2011;:123
Abstract
BACKGROUND The major metabolic complications of obesity and type 2 diabetes may be prevented and managed with dietary modification. The use of sweeteners that provide little or no calories may help to achieve this objective. METHODS We did a systematic review and network meta-analysis of the comparative effectiveness of sweetener additives using Bayesian techniques. MEDLINE, EMBASE, CENTRAL and CAB Global were searched to January 2011. Randomized trials comparing sweeteners in obese, diabetic, and healthy populations were selected. Outcomes of interest included weight change, energy intake, lipids, glycated hemoglobin, markers of insulin resistance and glycemic response. Evidence-based items potentially indicating risk of bias were assessed. RESULTS Of 3,666 citations, we identified 53 eligible randomized controlled trials with 1,126 participants. In diabetic participants, fructose reduced 2-hour blood glucose concentrations by 4.81 mmol/L (95% CI 3.29, 6.34) compared to glucose. Two-hour blood glucose concentration data comparing hypocaloric sweeteners to sucrose or high fructose corn syrup were inconclusive. Based on two ≤10-week trials, we found that non-caloric sweeteners reduced energy intake compared to the sucrose groups by approximately 250-500 kcal/day (95% CI 153, 806). One trial found that participants in the non-caloric sweetener group had a decrease in body mass index compared to an increase in body mass index in the sucrose group (-0.40 vs 0.50 kg/m2, and -1.00 vs 1.60 kg/m2, respectively). No randomized controlled trials showed that high fructose corn syrup or fructose increased levels of cholesterol relative to other sweeteners. CONCLUSIONS Considering the public health importance of obesity and its consequences; the clearly relevant role of diet in the pathogenesis and maintenance of obesity; and the billions of dollars spent on non-caloric sweeteners, little high-quality clinical research has been done. Studies are needed to determine the role of hypocaloric sweeteners in a wider population health strategy to prevent, reduce and manage obesity and its consequences.