title: A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes.
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.
authors.affiliation: Department of Medicine, 13-103 Clinical Sciences Building, University of Alberta, Edmonton, Alberta, T6G 2G3 Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Wiebe
authors.forename: Raj
authors.initials: R
authors.lastname: Padwal
authors.forename: Catherine
authors.initials: C
authors.lastname: Field
authors.forename: Seth
authors.initials: S
authors.lastname: Marks
authors.forename: Rene
authors.initials: R
authors.lastname: Jacobs
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
mesh_terms: D006801:Humans; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000628:therapy; D004032:Diet / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D013549:Sweetening Agents / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D002784:Cholesterol; D013549:Sweetening Agents
references.citation: Int J Food Sci Nutr. 2009;60 Suppl 3:48-55
references.pmid: 19180358
references.citation: Ann Intern Med. 1996 Mar 1;124(5):485-9
references.pmid: 8602706
references.citation: Diabetologia. 1985 Apr;28(4):204-7
references.pmid: 2410317
references.citation: JAMA. 2004 Oct 13;292(14):1724-37
references.pmid: 15479938
references.citation: Stat Med. 2010 Mar 30;29(7-8):932-44
references.pmid: 20213715
references.citation: J Med Food. 2008 Sep;11(3):424-8
references.pmid: 18800887
references.citation: Br J Nutr. 2010 Apr;103(7):939-43
references.pmid: 19930762
references.citation: Horm Metab Res. 1989 Jun;21(6):338-40
references.pmid: 2673967
references.citation: Int J Food Sci Nutr. 2010 Sep;61(6):643-51
references.pmid: 20367218
references.citation: Diabet Med. 1985 Sep;2(5):371-3
references.pmid: 2951092
references.citation: Nutrition. 2007 Feb;23(2):103-12
references.pmid: 17234503
references.citation: Basic Clin Pharmacol Toxicol. 2005 Aug;97(2):61-73
references.pmid: 15998351
references.citation: Physiol Behav. 1993 Mar;53(3):459-66
references.pmid: 8451310
references.citation: Am J Clin Nutr. 1982 Aug;36(2):256-61
references.pmid: 7048890
references.citation: Eur J Clin Nutr. 2008 Dec;62(12):1364-71
references.pmid: 17717534
references.citation: Am J Clin Nutr. 2008 May;87(5):1194-203
references.pmid: 18469239
references.citation: J Clin Endocrinol Metab. 2009 May;94(5):1562-9
references.pmid: 19208729
references.citation: Guys Hosp Rep. 1973;122(1-2):155-9
references.pmid: 4804325
references.citation: Control Clin Trials. 1996 Feb;17(1):1-12
references.pmid: 8721797
references.citation: Neth J Med. 1985;28(4):157-63
references.pmid: 4000324
references.citation: Regul Toxicol Pharmacol. 2001 Apr;33(2):257-67
references.pmid: 11350207
references.citation: Am J Clin Nutr. 1989 Apr;49(4):667-74
references.pmid: 2648796
references.citation: Diabetologia. 1981 Jul;21(1):37-40
references.pmid: 7024026
references.citation: Clin Physiol Biochem. 1990;8(5):267-72
references.pmid: 2103901
references.citation: BMC Public Health. 2009 Mar 25;9:88
references.pmid: 19320986
references.citation: ScientificWorldJournal. 2008 Apr 20;8:463-9
references.pmid: 18454257
references.citation: Br J Nutr. 2007 Jan;97(1):193-203
references.pmid: 17217576
references.citation: Diabetes Educ. 1982 Winter;7(4):22-5
references.pmid: 6915841
references.citation: JAMA. 1995 Feb 1;273(5):408-12
references.pmid: 7823387
references.citation: JPEN J Parenter Enteral Nutr. 2009 Jan-Feb;33(1):67-70
references.pmid: 19011145
references.citation: Am J Physiol. 1992 Apr;262(4 Pt 1):E394-401
references.pmid: 1566826
references.citation: Am J Physiol Regul Integr Comp Physiol. 2010 Apr;298(4):R1068-74
references.pmid: 20071608
references.citation: Am J Clin Nutr. 2000 Nov;72(5):1128-34
references.pmid: 11063439
references.citation: Am J Physiol. 1988 Feb;254(2 Pt 1):E201-7
references.pmid: 3279802
references.citation: Diabetes Care. 1990 Apr;13(4):382-5
references.pmid: 2180658
references.citation: Stat Med. 2004 Oct 30;23(20):3105-24
references.pmid: 15449338
references.citation: BMJ. 1997 Sep 13;315(7109):629-34
references.pmid: 9310563
references.citation: Am J Cardiol. 1987 Nov 1;60(13):1087-91
references.pmid: 3314457
references.citation: Metabolism. 2002 Aug;51(8):949-57
references.pmid: 12145765
references.citation: N Engl J Med. 2001 May 3;344(18):1343-50
references.pmid: 11333990
references.citation: J Clin Epidemiol. 2006 Apr;59(4):342-53
references.pmid: 16549255
references.citation: J Clin Endocrinol Metab. 1993 Aug;77(2):388-92
references.pmid: 8345042
references.citation: Am J Clin Nutr. 2002 Oct;76(4):721-9
references.pmid: 12324283
references.citation: Diabetes Metab. 2002 Nov;28(5):385-90
references.pmid: 12461475
references.citation: Br J Nutr. 2009 Nov;102(10):1408-13
references.pmid: 19671200
references.citation: J Nutr. 2000 Jun;130(6):1572-7
references.pmid: 10827212
references.citation: Physiol Behav. 1991 Nov;50(5):941-4
references.pmid: 1805284
references.citation: Am J Clin Nutr. 2005 Nov;82(5):1011-6
references.pmid: 16280432
references.citation: Diabetes Care. 2009 Oct;32(10):1930-7
references.pmid: 19592634
references.citation: J Clin Endocrinol Metab. 2004 Jun;89(6):2963-72
references.pmid: 15181085
references.citation: Am J Clin Nutr. 1999 Jan;69(1):64-9
references.pmid: 9925124
references.citation: BMJ. 2009 Jul 21;339:b2535
references.pmid: 19622551
references.citation: Int J Obes (Lond). 2007 Nov;31(11):1696-703
references.pmid: 17593904
references.citation: Am J Physiol. 1986 Jun;250(6 Pt 1):E718-24
references.pmid: 3521319
references.citation: Appetite. 2000 Jun;34(3):245-51
references.pmid: 10888287
references.citation: Nature. 1978 Feb 9;271(5645):493-5
references.pmid: 340963
references.citation: Metabolism. 1996 Oct;45(10):1235-42
references.pmid: 8843178
references.citation: Diabetes Care. 1990 Jul;13(7):733-40
references.pmid: 2201496
references.citation: Cell Metab. 2009 Jan 7;9(1):52-63
references.pmid: 19117546
references.citation: Am J Clin Nutr. 2007 Jun;85(6):1511-20
references.pmid: 17556686
references.citation: N Engl J Med. 1983 Jul 7;309(1):7-12
references.pmid: 6343873
references.citation: Obes Rev. 2003 May;4(2):91-9
references.pmid: 12760444
references.citation: N Engl J Med. 2002 Feb 7;346(6):393-403
references.pmid: 11832527
references.citation: Clin Sci. 1971 Aug;41(2):123-9
references.pmid: 5564302
references.citation: Metabolism. 1995 May;44(5):630-8
references.pmid: 7752912
references.citation: JAMA. 1986 Dec 19;256(23):3241-6
references.pmid: 3783868
references.citation: Diabetes Care. 1988 Mar;11(3):230-4
references.pmid: 3046854
references.citation: Br J Nutr. 2010 Nov;104(10):1415-20
references.pmid: 20619074
references.citation: Eur J Clin Nutr. 2007 Jun;61(6):691-700
references.pmid: 17299484
references.citation: Br J Nutr. 2005 May;93(5):575-9
references.pmid: 15975155
references.citation: Am J Clin Nutr. 1996 Jun;63(6):939-45
references.pmid: 8644690