Do fructose-containing sugars lead to
adverse health consequences?
Results of recent systematic reviews and
meta-analyses
...
Disclosures (over past 24 mos)
Board Member/Advisory Panel
–Canadian Diabetes Association (CDA) 2013 Clinical Practice
Gui...
1972
John Yudkin
1964
Ancel Keys
19701952
The great debate: Fat versus sugar
Vuilleumier S.. Am J Clin Nutr 1993;58(suppl):733S–6S.
Flegal KM, et al. JAMA 2002;288:1723–7.
Bray GA, et a. Am J Clin Nu...
Harper's Illustrated Biochemistry, 27th ed, 2006
Fructose as an unregulated substrate for de
novo lipogenesis (DNL)
Phosph...
Metabolic fate of fructose in humans:
A review of oral and liver catheterization, stable isotope studies
Sun SZ, Empie MW....
A fructose-centric champion emerges
http://www.youtube.com/watch?v=dBnniua6-oM
A fructose-centric view becomes doctrine
Lustig et al. Nature 2012;482:27-29 http://www.cbsnews.com/video/watch/?
Sugars the new dominant public health issue
http://www.who.int/nutrition/sugars_public_consultation/en
“It is all about fructose” (Bray 2010)
Lustig et al. Nature 2012;482:27-29
WHAT IS THE
EVIDENCE?
http://www.sign.ac.uk/guidelines/fulltext/50/annexb.html
http://www.cnpp.usda.gov/Publications/NutritionInsights/Insight38...
http://www.sign.ac.uk/guidelines/fulltext/50/annexb.html
http://www.cnpp.usda.gov/Publications/NutritionInsights/Insight38...
PROSPECTIVE
COHORTS
Fructose-containing
Sugar Sweetened Beverages (SSBs)
Fructose-containing Sugar-sweetened beverages
(SSBs) and Incident Cardiometabolic Disease
SSBs
Diabetes/MetS (epi)
Overwei...
Malik et al. Diabetes Care. 2010 33:2477–2483
Individuals in the highest quantile of SSB intake (most often 1–2 servings/d...
How do SSBs compare with other risk
factors?
Population attributable mortality risk in the U.S.:
How do SSBs compare with other risk factors?
Danaei et al. PLoS Med 6(...
Why are SSBs associated with
increased cardiometabolic risk?
1. is it because liquid calories are poorly compensated?
2. i...
Why are SSBs associated with
increased cardiometabolic risk?
1. is it because liquid calories are poorly compensated?
2. i...
Does impaired compensation from liquid calorie
preloads lead to weight gain?
A systematic review and meta-analysis of the
...
Why are SSBs associated with
increased cardiometabolic risk?
1. is it because liquid calories are poorly compensated?
2. i...
Mozaffarian et al. NEJM 2011;364:2392-2404
+3.35lb
+1.69lb
+0.57lb
+1.00lb
+0.95 lb
+0.28 to 0.36lb
+0.65lb
Increased serv...
A Western Dietary pattern increases diabetes risk more
than any one dietary component:
NHS I (1984-1994, N=35 340) and NHS...
Why are SSBs associated with
increased cardiometabolic risk?
1. is it because liquid calories are poorly compensated?
2. i...
Fructose-containing sugars
Meta-analyses of Fructose-containing Sugars and
Incident Cardiometabolic Disease (NCT01608620)
Fructose
Diabetes/MetS (epi...
Meta-analyses of Fructose-containing Sugars and
Incident Cardiometabolic Disease (NCT01608620)
Fructose
Diabetes/MetS (epi)
Tsilias et al., unpublished
Consort statement (through May 25, 2012)
Screened: 4642
Included cohorts: 7
4642 reports ident...
Lack of relation of fructose with diabetes risk:
A meta-analysis of prospective cohort studies
(7 cohorts, N=163,132, mean...
Meta-analyses of Fructose-containing Sugars and
Incident Cardiometabolic Disease (NCT01608620)
Fructose
Diabetes/MetS (epi...
CONCLUSIONS
Conclusions: Observational studies
1. Prospective cohorts studies have shown significant positive
association between suga...
http://www.sign.ac.uk/guidelines/fulltext/50/annexb.html
http://www.cnpp.usda.gov/Publications/NutritionInsights/Insight38...
CONTROLLED
DIETARY TRIALS
SUGARS
(FRUCTOSE-CONTAINING)
Isocaloric “substitution trials”= Energy from sugars
substituted for other sources of energy in the diet
Hypercaloric “add...
“Substitution trials”
Isoenergetic exchange of free sugars with other macronutrients
does not affect body weight: WHO-commissioned systematic re...
“Addition trials”
Addition of excess energy from sugars increases weight in adults:
WHO commissioned systematic review and meta-analysis of ...
Addition of excess energy from SSBs results in weight gain
proportional to the increase in excess energy:
A systematic rev...
Addition of excess energy from SSBs results in weight gain:
A systematic review and meta-analysis of 5 RCTs in adults (n=2...
“Subtraction trials”
Reduction in energy from sugar reduces excess body fatness in
adults but not children:
WHO commissioned systematic review ...
Reduction in energy from SSBs does not affect weight across trials
but leads to less weight gain in overweight/obese subje...
Malik et al. AJCN. 2013 Oct;98(4):1084-102.
Reduction in energy from SSBs may not reduce weight in children:
A systematic ...
What about other endpoints?
Sucrose and cardiometabolic risk: Systematic
review of 25 controlled dietary trials
Gibson et al. Crit Rev Food Sci Nutr. ...
FRUCTOSE
Isocaloric “substitution trials”= comparisons
are matched for energy with fructose substituted for
other sources of carboh...
Effect of fructose on metabolic control in humans:
A meta-analysis to provide evidence-based guidance for
future nutrition...
“Substitution trials”
Lack of harm in isocaloric comparisons:
>50 trials (N >1000), dose = 22.5-300g/d, FU = 1-52wk
Benefit Harm
Cardiometabolic...
“Addition trials”
Harm in hypercaloric trials:
An effect more attributable to energy (up to +250g/d +50% E)
Benefit Harm
Cardiometabolic end...
CONCLUSIONS
Conclusions: Trials
1. There is a moderate body of consistent evidence from controlled feeding trials
that fructose at low...
Take away message
Take away message
1. Like with the earlier fat story, it is difficult to separate the
contribution of fructose-containing ...
Acknowledgements
Arash Mirrahimi, HBSc, MSc (Coordinator, Co-I)
Amanda J Carleton, MSc (MD student, Co-P)
Dr. Sonia Blanco...
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Do fructose-containing sugars lead to adverse health consequences? Results of recent systematic reviews and meta-analyses

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At Experimental Biology 2014, the Sponsored Satellite Program “Sugars and Health Controversies: What Does the Science Say?” held in conjunction with the American Society for Nutrition’s Scientific Sessions took place on Saturday, April 26, 2014.
Panelist John L Sievenpiper, MD, PhD, presented science about sugars and their associated health outcomes.

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Do fructose-containing sugars lead to adverse health consequences? Results of recent systematic reviews and meta-analyses

  1. 1. Do fructose-containing sugars lead to adverse health consequences? Results of recent systematic reviews and meta-analyses John L Sievenpiper, MD, PhD1,2,3 1 Scientist, Li Ka Shing Knowledge Institute, Toronto, ON, CANADA 2 Knowledge Synthesis Lead Toronto 3D Knowledge Synthesis and Clinical Trials Unit Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital, Toronto, ON, CANADA 3 Resident Physician, Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, CANADA. Sugars and Health Controversies: What does the science say? Experimental Biology San Diego, CA
  2. 2. Disclosures (over past 24 mos) Board Member/Advisory Panel –Canadian Diabetes Association (CDA) 2013 Clinical Practice Guidelines Expert Committee for Nutrition therapy –European Association for the Study of Diabetes (EASD) 2015 Clinical Practice Guidelines Expert Committee for Nutrition therapy –American Society for Nutrition (ASN) writing panel for a scientific statement on the metabolic and nutritional effects of fructose, sucrose and high fructose corn syrup –International Life Science Institute (ILSI) North America, Food, Nutrition, and Safety Program (FNSP) Advisory Board –Transcultural Diabetes Algorithm (tDNA) Group –Diabetes Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD) executive committee Research Support –Canadian Institutes of Health Research (CIHR) –Calorie Control Council –The Coca Cola Company (**unrestricted, investigator initiated education grant**) –Pulse Canada –International Tree Nut Council Nutrition Research & Education Foundation –Dr. Pepper Snapple Group(**unrestricted, investigator initiated donation**) Honouria and Speaker fees –National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of health (NIH) –American College of Physicians (ACP) –American Society for Nutrition (ASN) –American Heart Association (AHA) –Canadian Nutrition Society (CNS) –Canadian Diabetes Association (CDA) –International Life Sciences Institute (ILSI) North American –International Life Sciences Institute (ILSI) Brazil –Pulse Canada –Abbott Laboratories –Calorie Control Council –The Coca Cola Company –Canadian Sugar Institute –Dr. Pepper Snapple Group Other –Spouse is an employee of Unilever Canada –Editorial Board, American Journal of Clinical Nutrition –Associate Editor, Frontiers in Nutrition, Nutrition Methodology –Special Issue ("Sugar and Obesity“) Editor, Nutrients
  3. 3. 1972 John Yudkin 1964 Ancel Keys 19701952 The great debate: Fat versus sugar
  4. 4. Vuilleumier S.. Am J Clin Nutr 1993;58(suppl):733S–6S. Flegal KM, et al. JAMA 2002;288:1723–7. Bray GA, et a. Am J Clin Nutr. 2004 Apr;79(4):537-43 Ecological relationship between fructose intake and prevalence of Overweight/Obesity:1961-2000 George Bray 2004 Overweight Obesity Total fructose Free fructose HCFS
  5. 5. Harper's Illustrated Biochemistry, 27th ed, 2006 Fructose as an unregulated substrate for de novo lipogenesis (DNL) Phosphofructokinase Dietary Fructose Dietary Glucose Glycerol-3P Fatty acid synthesis ↑TAGs
  6. 6. Metabolic fate of fructose in humans: A review of oral and liver catheterization, stable isotope studies Sun SZ, Empie MW. Nutr Metab 2012;9:89 DNL <3% Tappy et al. Physiol Rev. 2010 90:23-46 (<0.198 µmol/L) (50-100g)
  7. 7. A fructose-centric champion emerges http://www.youtube.com/watch?v=dBnniua6-oM
  8. 8. A fructose-centric view becomes doctrine Lustig et al. Nature 2012;482:27-29 http://www.cbsnews.com/video/watch/?
  9. 9. Sugars the new dominant public health issue http://www.who.int/nutrition/sugars_public_consultation/en
  10. 10. “It is all about fructose” (Bray 2010) Lustig et al. Nature 2012;482:27-29
  11. 11. WHAT IS THE EVIDENCE?
  12. 12. http://www.sign.ac.uk/guidelines/fulltext/50/annexb.html http://www.cnpp.usda.gov/Publications/NutritionInsights/Insight38.pdf http://www.nice.org.uk/niceMedia/pdf/GDM_Chapter7_0305.pdf Hierarchy of evidence in evidence based medicine Systematic review/ meta-analysis RCTs RCT Systematic review/meta-analysis NRCTs Non-randomized controlled trial (NRCT) Systematic review/meta-analysis cohort/case-control studies cohort study/case-control study Cross-sectional study Case series/time series Expert opinion Decreasing bias
  13. 13. http://www.sign.ac.uk/guidelines/fulltext/50/annexb.html http://www.cnpp.usda.gov/Publications/NutritionInsights/Insight38.pdf http://www.nice.org.uk/niceMedia/pdf/GDM_Chapter7_0305.pdf Hierarchy of evidence in evidence based medicine Systematic review/ meta-analysis RCTs RCT Systematic review/meta-analysis NRCTs Non-randomized controlled trial (NRCT) Systematic review/meta-analysis cohort/case-control studies cohort study/case-control study Cross-sectional study Case series/time series Expert opinion Decreasing bias
  14. 14. PROSPECTIVE COHORTS
  15. 15. Fructose-containing Sugar Sweetened Beverages (SSBs)
  16. 16. Fructose-containing Sugar-sweetened beverages (SSBs) and Incident Cardiometabolic Disease SSBs Diabetes/MetS (epi) Overweight/Obesity (epi) Hypertension (epi) Gout (epi) CHD (epi) Stroke (epi)
  17. 17. Malik et al. Diabetes Care. 2010 33:2477–2483 Individuals in the highest quantile of SSB intake (most often 1–2 servings/day) compared with those in the lowest quantile (none or 1 serving/month) had a higher risk of… **SSB drinkers in these cohorts consumed more energy, exercised less, and smoked more** Effect of fructose-containing SSBs on risk of type 2 diabetes and metabolic syndrome: Meta-analysis of 11 prospective studies (n=310,819) Risk of Type 2 diabetes Risk of Metabolic syndrome Adjusted for energy
  18. 18. How do SSBs compare with other risk factors?
  19. 19. Population attributable mortality risk in the U.S.: How do SSBs compare with other risk factors? Danaei et al. PLoS Med 6(4): e1000058. doi:10.1371/journal.pmed.1000058 SSBs 467,000 395,000 216,000 191,000 190,000 102,000 110,000 84,000 82,000 64,000 55,000 15,000 25,000 http://circ.ahajournals.org/cgi/content/meeting_abstract/127/12_MeetingAbstracts/AMP22
  20. 20. Why are SSBs associated with increased cardiometabolic risk? 1. is it because liquid calories are poorly compensated? 2. is it because SSBs are a maker of an unhealthy lifestyle? 3. Is it the fructose?
  21. 21. Why are SSBs associated with increased cardiometabolic risk? 1. is it because liquid calories are poorly compensated? 2. is it because SSBs are a maker of an unhealthy lifestyle? 3. Is it the fructose?
  22. 22. Does impaired compensation from liquid calorie preloads lead to weight gain? A systematic review and meta-analysis of the effect of 253 acute preload interventions on Energy compensation RCTs of the effect of liquid calories on weight gain Crossover trial SSBs vs Jelly beans N = 15 FU = 4-weeks ∆body weight, P=NS Crossover trial Liquid vs solid fruit N = 34 FU = 8-weeks ∆body weight, P=NS Almiron-Roig et al. Nutr Rev. 2013 Jul;71(7):458-73 Houchins et al. Obesity. 2012;20:1844-50 DiMeglio et al. Int J Obes. 2000; 24:794-800.
  23. 23. Why are SSBs associated with increased cardiometabolic risk? 1. is it because liquid calories are poorly compensated? 2. is it because SSBs are a maker of an unhealthy lifestyle? 3. Is it the fructose?
  24. 24. Mozaffarian et al. NEJM 2011;364:2392-2404 +3.35lb +1.69lb +0.57lb +1.00lb +0.95 lb +0.28 to 0.36lb +0.65lb Increased servings of different foods contribute to weight change over 4 year intervals: NHS I (1986-2006), NHS II (1991-2003) and HPFS (1986-2006), N=120 877 +0.93 lb **Multivariate adjustment for age, BMI, sleep, physical activity, alcohol, television watching, smoking, and all dietary factors**
  25. 25. A Western Dietary pattern increases diabetes risk more than any one dietary component: NHS I (1984-1994, N=35 340) and NHS II (1991-1995, N=89 311) Schulze et al. Am J Clin Nutr 2005;82:675–84 Western Dietary pattern = high in refined grains, other vegetables, processed meat , and sugary beverages, diet soft drinks
  26. 26. Why are SSBs associated with increased cardiometabolic risk? 1. is it because liquid calories are poorly compensated? 2. is it because SSBs are a maker of an unhealthy lifestyle? 3. Is it the sugar (fructose)?
  27. 27. Fructose-containing sugars
  28. 28. Meta-analyses of Fructose-containing Sugars and Incident Cardiometabolic Disease (NCT01608620) Fructose Diabetes/MetS (epi) Overweight/Obesity (epi) Hypertension (epi) Gout (epi) CHD (epi) (J Am Coll Nutr, in press)
  29. 29. Meta-analyses of Fructose-containing Sugars and Incident Cardiometabolic Disease (NCT01608620) Fructose Diabetes/MetS (epi)
  30. 30. Tsilias et al., unpublished Consort statement (through May 25, 2012) Screened: 4642 Included cohorts: 7 4642 reports identified through searching 2694 EMBASE (through to May week 3 2012) 1220 MEDLINE (through to May week 3 2012) 494 CINAHL (through to May week 3 2012) 234 Cochrane Library (through to May week 3 2012) 0 Manual Searches 4597 reports excluded on the basis of title or abstract 1329 duplicate reports 1214 review papers/meta-analyses/editorials/commentaries/letters/ proceedings/practice guidelines/reports 914 other observational studies (including cross-sectional, retrospective cohort, case control, case report, case series, and ecological) 566 intervention trials 495 animal or in vitro studies 79 studies with irrelevant endpoints 45 reports reviewed in full 41 reports excluded 17 studies with no assessment of fructose-containing sugar exposure 12 review papers/meta-analyses/editorials/commentaries/letters/ proceedings/practice guidelines/reports 3 other observational studies (cross-sectional, retrospective cohort, case control, case report, case series, and ecological analyses) 3 intervention trials 2 studies with irrelevant endpoints 2 studies with diabetes data not presented 2 non-retrievable studies 4 reports (7 analyses) included in the meta-analysis
  31. 31. Lack of relation of fructose with diabetes risk: A meta-analysis of prospective cohort studies (7 cohorts, N=163,132, mean follow-up=6 years) Tsilias et al., unpublished
  32. 32. Meta-analyses of Fructose-containing Sugars and Incident Cardiometabolic Disease (NCT01608620) Fructose Diabetes/MetS (epi) Overweight/Obesity (epi) Hypertension (epi) Gout (epi) CHD (epi) (J Am Coll Nutr, in press)
  33. 33. CONCLUSIONS
  34. 34. Conclusions: Observational studies 1. Prospective cohorts studies have shown significant positive association between sugary beverages (?added sugars) and incident obesity, diabetes, gout, CHD, and stroke. 2. These associations, however, are only significant when comparing the highest with the lowest levels of intake and do not hold when modeling total fructose or fructose- containing sugars (with the exception of gout). 3. These data are limited by residual confounding , collinearly effects, and unexplained heterogeneity between studies.
  35. 35. http://www.sign.ac.uk/guidelines/fulltext/50/annexb.html http://www.cnpp.usda.gov/Publications/NutritionInsights/Insight38.pdf http://www.nice.org.uk/niceMedia/pdf/GDM_Chapter7_0305.pdf Hierarchy of evidence in evidence based medicine Systematic review/ meta-analysis RCTs RCT Systematic review/meta-analysis NRCTs Non-randomized controlled trial (NRCT) Systematic review/meta-analysis cohort/case-control studies cohort study/case-control study Cross-sectional study Case series/time series Expert opinion Decreasing bias
  36. 36. CONTROLLED DIETARY TRIALS
  37. 37. SUGARS (FRUCTOSE-CONTAINING)
  38. 38. Isocaloric “substitution trials”= Energy from sugars substituted for other sources of energy in the diet Hypercaloric “addition trials”= Energy from sugars “added” to the diet Hypocaloric “subtraction trials” = Energy from sugars “subtracted” from the diet 4 trial designs: To interpret results, follow the energy…
  39. 39. “Substitution trials”
  40. 40. Isoenergetic exchange of free sugars with other macronutrients does not affect body weight: WHO-commissioned systematic review and meta-analysis of 13 RCTs (n=144) Te Morenga et al. BMJ. 2012;345:e7492
  41. 41. “Addition trials”
  42. 42. Addition of excess energy from sugars increases weight in adults: WHO commissioned systematic review and meta-analysis of 30 RCTs Te Morenga et al. BMJ. 2012;345:e7492
  43. 43. Addition of excess energy from SSBs results in weight gain proportional to the increase in excess energy: A systematic review and meta-analysis of 7 RCTs (n=333) Mattes et al. Obes Rev. 2011;12:346-65 Kaiser et al. Obes Rev. 2013 Jun 7. doi: 10.1111/obr.12048.
  44. 44. Addition of excess energy from SSBs results in weight gain: A systematic review and meta-analysis of 5 RCTs in adults (n=272) Malik et al. AJCN. 2013 Oct;98(4):1084-102.
  45. 45. “Subtraction trials”
  46. 46. Reduction in energy from sugar reduces excess body fatness in adults but not children: WHO commissioned systematic review and meta-analysis of 30 RCTs Te Morenga et al. BMJ. 2012;345:e7492 Children Adults
  47. 47. Reduction in energy from SSBs does not affect weight across trials but leads to less weight gain in overweight/obese subjects: A systematic review and meta-analysis of 8 RCTs (n=3281) All subject types Overweight/obese subset Mattes et al. Obes Rev. 2011;12:346-65 Kaiser et al. Obes Rev. 2013 Jun 7. doi: 10.1111/obr.12048.
  48. 48. Malik et al. AJCN. 2013 Oct;98(4):1084-102. Reduction in energy from SSBs may not reduce weight in children: A systematic review and meta-analysis of 5 RCTs (n=2772)
  49. 49. What about other endpoints?
  50. 50. Sucrose and cardiometabolic risk: Systematic review of 25 controlled dietary trials Gibson et al. Crit Rev Food Sci Nutr. 2013;53(6):591-614 “It would appear that a moderate dietary sucrose intake at levels up to 25% of energy appears to have no significant adverse effects on lipid or carbohydrate metabolism in normal healthy adults when substituted for starch, at least in the medium term (several weeks).”
  51. 51. FRUCTOSE
  52. 52. Isocaloric “substitution trials”= comparisons are matched for energy with fructose substituted for other sources of carbohydrate in the diet Hypercaloric “addition trials”= comparisons are unmatched for energy with energy from fructose “added” to the diet Two trial designs: To interpret results, follow the energy…
  53. 53. Effect of fructose on metabolic control in humans: A meta-analysis to provide evidence-based guidance for future nutrition guidelines development (NCT01363791 ) Fructose Fasting lipids Body weight Glycemic control Blood pressure Uric acid (Diabetes Care 2009;32:1930-7) (Ann Intern Med 2012;156:291-304) (Diabetes Care 2012;35:1611-20) (Hypertension 2012;59:787-95) (J Nutr 2012;142:916-23) Postprandial lipids NAFLD (Atherosclerosis 2014;232:125-133) (Eur J Clin Nutr. 2014;68:416-423)
  54. 54. “Substitution trials”
  55. 55. Lack of harm in isocaloric comparisons: >50 trials (N >1000), dose = 22.5-300g/d, FU = 1-52wk Benefit Harm Cardiometabolic endpoint Comparisons N Standardized Mean Difference (SMD) with 95% CI I2 Body weight (22) 31 637 -0.22 (-0.58, 0.13) 37%* Fasting Lipids (16,159) TG TC LDL-C HDL-C 48 31 20 27 809 569 313 425 0.24 (-0.05, 0.52) 0.30 (-0.05, 0.65) -0.09 (-0.53, 0.35) 0.38 (0.00, 0.75) 77%* 96%* 100%* 100%* Postprandial TG (160) 14 290 0.14 (-0.02, 0.30) 54%* Glycemic control (20,158) GBP FBG FBI 19 43 32 276 823 563 -0.28 (-0.45, -0.11) -0.10 (-0.40, 0.20) -0.32 (-0.66, 0.03) 50%* 78%* 87%* Blood pressure (21) SBP DBP MAP 13 13 13 352 352 352 -0.39 (-0.93, 0.16) -0.68 (-1.23, -0.14) -0.64 (-1.19, -0.10) 31% 47%* 97%* Uric acid (157) 18 390 0.04 (-0.43, 0.50) 0% NAFLD (161) IHCL ALT 4 6 95 164 -0.09 (-0.36, 0.18) 0.07 (-0.73, 0.87) 0% 0%
  56. 56. “Addition trials”
  57. 57. Harm in hypercaloric trials: An effect more attributable to energy (up to +250g/d +50% E) Benefit Harm Cardiometabolic endpoint Comparisons N Standardized Mean Difference (SMD) with 95% CI I2 Body weight (22) 10 119 1.24 (0.61, 1.85) 30% Fasting lipids (16,159) TG TC LDL-C HDL-C 7 5 4 4 122 102 95 79 1.05 (0.31, 1.79) 0.39 (-0.50, 1.25) 0.22 (-0.77, 1.19) 0.00 (0.00, 0.00) 87%* 89%* 96%* 100%* Postprandial TG (160) 2 32 0.65 (0.30, 1.01) 22% Glycemic control (20,158) GBP FBG FBI 2 8 8 31 98 98 -0.33 (-0.62, -0.04) 1.32 (0.63, 2.02) 0.95 (0.26, 1.64) 0% 59%* 41% Blood pressure (21) MAP 2 24 -0.76 (-2.15, 0.62) 24% Uric acid (157) 3 35 2.26 (1.13, 3.39) 0% NAFLD (161) IHCL ALT 5 4 60 59 0.45(0.18, 0.72) 0.99 (0.01, 1.97) 51%* 28%
  58. 58. CONCLUSIONS
  59. 59. Conclusions: Trials 1. There is a moderate body of consistent evidence from controlled feeding trials that fructose at low to moderate doses does not harm body weight, serum fasting or postprandial lipids, uric acid, and NAFLD and may even benefit blood pressure and glycemic control in humans. 2. There is an emerging body of consistent evidence from controlled feeding trials that fructose consumed under hypercaloric feeding conditions may promote weight gain, fasting and postprandial dyslipidemia, raised uric acid levels, and NAFLD, effects which appear more attributable to the excess energy than the fructose itself. 3. The shorter duration, poor quality and heterogeneity in the available trials creates some uncertainty about the true effects of fructose. There is a need for larger, longer-term, higher quality “real world” feeding trials to guide our understanding of the metabolic effects of fructose.
  60. 60. Take away message
  61. 61. Take away message 1. Like with the earlier fat story, it is difficult to separate the contribution of fructose-containing sugars from that of other factors in the epidemic of obesity and cardiometabolic disease, owing to the small effect sizes and lack of demonstrated harm over other sources of excess energy in the diet 2. There are many pathways to overconsumption leading to weight gain and its downstream consequences. Dietary patterns have the greatest influence on weight gain and cardiometabolic risk and represent the best opportunity for successful interventions. 3. Attention needs to remain focused on reducing overconsumption of all caloric foods (including sugary beverages and foods!) and promoting greater physical activity.
  62. 62. Acknowledgements Arash Mirrahimi, HBSc, MSc (Coordinator, Co-I) Amanda J Carleton, MSc (MD student, Co-P) Dr. Sonia Blanco MD, MSc (Coordinator) Laura Chiavaroli, MSc (PhD Candidate) Adrian I Cozma, HBSc (Research Assistant) Vanessa Ha, HBSc (MSc Candidate) David Wang, HBSc (Project Student) Simon Chiu (Project Student) Matt E Yu, HBSc (Project Student) Viranda (Jay) Jayalath (Project Student) Christine Tsilias (Project Student) Reem Tawfik (Project Student) Sara Rehman (Project Student) Vivian Choo (Project Student) Dr. Alexandra L Jenkins, PhD, RD (Decision Maker) Prof. Lawrence A Leiter, MD (Decision Maker) Prof. Thomas MS Wolever, MD, PhD (Decision Maker) Dr. Russell J de Souza, ScD, RD (PDF, Co-I) Dr. Marco DiBuono, PhD (Decision Maker) Prof. Joseph Beyene, PhD (Co-I) Prof. David JA Jenkins MD, PhD, DSc (PI) Prof. Cyril WC Kendall, PhD (Co-I)

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