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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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Abstract
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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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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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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Soft drink intake and the risk of metabolic syndrome: A systematic review and meta-analysis.
Narain, A, Kwok, CS, Mamas, MA
International journal of clinical practice. 2017;(2)
Abstract
BACKGROUND It is unclear whether consumption of sugar- or artificially sweetened beverages is independently associated with the development of metabolic syndrome. A systematic review and meta-analysis was performed to evaluate whether soft drink consumption is associated with the development of metabolic syndrome. METHODS Medline and EMBASE were searched in November 2015 for studies which considered soft drink (sugar-sweetened beverage [SSB] and artificially sweetened beverage [ASB]) intake and risk of metabolic syndrome. Pooled risk ratios for adverse outcomes were calculated using inverse variance with a random effects model, and heterogeneity was assessed using the I2 statistic. RESULTS A total of 12 studies (eight cross-sectional, four prospective cohort studies) with 56 244 participants (age range 6-98 years) were included in the review. Our pooled analysis found that soft drink intake is associated with metabolic syndrome. This relationship is shown in cross-sectional studies of SSB consumption (RR 1.46, 95% CI 1.18-1.91) and both cross-sectional and prospective studies of ASB consumption (RR 2.45; 95% CI 1.15-5.14; RR 1.32, 95% CI 1.21-1.44, respectively). However, pooled results of prospective cohort studies of SSB consumption found no association between intake and risk of developing metabolic syndrome. CONCLUSIONS Sugar-sweetened beverage and ASB intake are both associated with metabolic syndrome. This association may be driven by the fact that soft drink intake serves as a surrogate for an unhealthy lifestyle, or an adverse cardiovascular risk factor profile.
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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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Sugar and artificially sweetened soda consumption linked to hypertension: a systematic review and meta-analysis.
Cheungpasitporn, W, Thongprayoon, C, Edmonds, PJ, Srivali, N, Ungprasert, P, Kittanamongkolchai, W, Erickson, SB
Clinical and experimental hypertension (New York, N.Y. : 1993). 2015;(7):587-93
Abstract
BACKGROUND/OBJECTIVES The risk of hypertension (HTN) in patients who regularly drink soda is controversial. The objective of this meta-analysis was to assess the associations between consumption of sugar and artificially sweetened soda and HTN. METHODS A literature search was performed using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews from inception through January 2015. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk of HTN in patients consuming a significant amount of either sugar or artificially sweetened soda versus those who did not consume soda were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS Eight studies were included in our analysis to assess the association between consumption of sugar-sweetened soda and HTN. The pooled RR of HTN in patients consuming sugar-sweetened soda was 1.12 (95% CI, 1.03-1.23). Four studies were selected to assess the association between consumption of artificially sweetened soda and HTN. The pooled RR of HTN in patients consuming artificially sweetened soda was 1.15 (95% CI, 1.11-1.19). CONCLUSIONS Our study demonstrates statistically significant associations between both sugar and artificially sweetened soda consumption and HTN. This finding may impact clinical management and primary prevention of HTN.
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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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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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Effect of the natural sweetener, steviol glycoside, on cardiovascular risk factors: a systematic review and meta-analysis of randomised clinical trials.
Onakpoya, IJ, Heneghan, CJ
European journal of preventive cardiology. 2015;(12):1575-87
Abstract
INTRODUCTION Many different dietary supplements are currently marketed for the management of hypertension and diabetes, but the evidence for effectiveness is mixed. The objective of this systematic review was to critically appraise and evaluate the evidence for effectiveness of steviol glycosides (stevioside and rebaudioside A) on cardiovascular risk factors, using data from randomised clinical trials (RCTs). METHODS Electronic searches were conducted in Medline, Embase, Amed, Cinahl and The Cochrane Library. We also searched Google Scholar, and hand searched the bibliography of retrieved full texts. The reporting quality of included studies was assessed using the Cochrane criteria. Two reviewers independently determined the eligibility, assessed the reporting quality, and extracted the data. RESULTS Nine studies with a total of 756 participants were included. There was a variation in the reporting quality of included studies. Meta-analysis revealed a non-significant difference in systolic blood pressure between steviol glycoside and placebo, mean difference (MD): -2.98 mm Hg (-6.23 to 0.27). Significant reductions in diastolic blood pressure and fasting blood glucose were observed. There was no significant effect on blood lipid profile. Heterogeneity was significant. Adverse events included abdominal fullness, epigastric pain, and dizziness. CONCLUSION The evidence from published RCTs suggests that stevioside may generate reductions in blood pressure and fasting blood glucose. The sizes of the effects are small, and the substantial heterogeneity limits the robustness of any conclusions. Rebaudioside A does not appear to have any significant effects on blood pressure or cardiovascular risk factors. Available clinical trials vary in design and reporting quality, and some are characterised by inadequate sample sizes. In addition, the participants in most of the trials have high cardiovascular risk. Further clinical trials and regulatory assessments are warranted.
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[Effects of fructose on triglycerides in individuals with diabetes: a Meta-analysis of experimental trials].
Xiang, X, Zhao, J, Zhu, J, Zhang, P, Wang, Z, Yang, Y
Wei sheng yan jiu = Journal of hygiene research. 2015;(3):470-8
Abstract
OBJECTIVE To assess the effects of fructose on the blood triglycerides, particularly examining treatment dose, duration, and control of food in individuals with diabetes. METHODS A systematic review and Meta-analysis of experimental clinical trials were conducted to investigate the effect of isocaloric fructose exchange for carbohydrate on triglycerides, total cholesterol. MedLine, EMBASE, The Cochrane Library, CMBdisc, CNKI (1970-2014), and some related journals were searched. Heterogeneity was assessed by 2 tests and quantified by I2. Meta-analysis was conducted by RevMan 5.3. RESULTS 15 reports (21 trials) met the eligibility criteria. Isocaloric fructose exchange for carbohydrate raised triglycerides under specific conditions in individuals with type 2 diabetes. A triglyceride-raising effect without heterogeneity was seen only in type 2 diabetes when the dose was ≥ 100 g fructose/d (WMD 0.17, 95% CI0.08 - 0.25, P < 0.0001). A triglyceride-raising effect with heterogeneity was seen in type 2 diabetes when the reference carbohydrate was starch (WMD 0.13, 95% CI 0.02 - 0.23 , P = 0.02). CONCLUSION Effect of fructose on the level of TG in type 2 diabetes patients is more sensitive than that in type 1 diabetes. The effect on triglycerides is dose dependent and depends on what kinds of carbohydrate is being exchanged with fructose.