title: No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial.
abstract: BACKGROUND
  Sugar-sweetened beverage (SSB) consumption and low-grade chronic inflammation are both independently associated with type 2 diabetes and cardiovascular disease. Fructose, a major component of SSBs, may acutely trigger inflammation, which may be one link between SSB consumption and cardiometabolic disease.
  
  
  OBJECTIVE
  We sought to determine whether beverages sweetened with fructose, high-fructose corn syrup (HFCS), and glucose differentially influence systemic inflammation [fasting plasma C-reactive protein and interleukin-6 (IL-6) as primary endpoints] acutely and before major changes in body weight. Secondary endpoints included adipose tissue inflammation, intestinal permeability, and plasma fetuin-A as potential mechanistic links between fructose intake and low-grade inflammation.
  
  
  METHODS
  We conducted a randomized, controlled, double-blind, crossover design dietary intervention (the Diet and Systemic Inflammation Study) in 24 normal-weight to obese adults without fructose malabsorption. Participants drank 4 servings/d of fructose-, glucose-, or HFCS-sweetened beverages accounting for 25% of estimated calorie requirements while consuming a standardized diet ad libitum for three 8-d periods.
  
  
  RESULTS
  Subjects consumed 116% of their estimated calorie requirement while drinking the beverages with no difference in total energy intake or body weight between groups as reported previously. Fasting plasma concentrations of C-reactive protein and IL-6 did not differ significantly at the end of the 3 diet periods. We did not detect a consistent differential effect of the diets on measures of adipose tissue inflammation except for adiponectin gene expression in adipose tissue (P = 0.005), which was lowest after the glucose phase. We also did not detect consistent evidence of a differential impact of these sugars on measures of intestinal permeability (lactulose:mannitol test, plasma zonulin, and plasma lipopolysaccharide-binding protein).
  
  
  CONCLUSIONS
  Excessive amounts of fructose, HFCS, and glucose from SSBs consumed over 8 d did not differentially affect low-grade chronic systemic inflammation in normal-weight to obese adults. This trial was registered at clinicaltrials.gov as NCT01424306.
authors.affiliation: Cancer Prevention Program, Division of Public Health Sciences, and Departments of Epidemiology and.
authors.forename: Jessica N
authors.identifier: http://orcid.org/0000-0003-0897-3512
authors.initials: JN
authors.lastname: Kuzma
authors.affiliation: Cancer Prevention Program, Division of Public Health Sciences, and.
authors.forename: Gail
authors.initials: G
authors.lastname: Cromer
authors.affiliation: Cancer Prevention Program, Division of Public Health Sciences, and.
authors.forename: Derek K
authors.identifier: http://orcid.org/0000-0003-2877-2304
authors.initials: DK
authors.lastname: Hagman
authors.affiliation: Prevention Center, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
authors.forename: Kara L
authors.initials: KL
authors.lastname: Breymeyer
authors.affiliation: Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.
authors.forename: Christian L
authors.initials: CL
authors.lastname: Roth
authors.affiliation: Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, and.
authors.forename: Karen E
authors.identifier: http://orcid.org/0000-0002-4937-7621
authors.initials: KE
authors.lastname: Foster-Schubert
authors.affiliation: Cancer Prevention Program, Division of Public Health Sciences, and.
authors.forename: Sarah E
authors.identifier: http://orcid.org/0000-0001-7569-3700
authors.initials: SE
authors.lastname: Holte
authors.affiliation: Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, and.
authors.forename: David S
authors.initials: DS
authors.lastname: Weigle
authors.affiliation: Cancer Prevention Program, Division of Public Health Sciences, and Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, and Departments of Epidemiology and mkratz@fredhutch.org.
authors.forename: Mario
authors.identifier: http://orcid.org/0000-0003-2660-8033
authors.initials: M
authors.lastname: Kratz
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D001628:Beverages; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D004032:Diet; D004311:Double-Blind Method; D005247:Feeding Behavior; D005260:Female; D005632:Fructose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006601:Hexoses / Q000494:pharmacology*; D066248:High Fructose Corn Syrup / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000473:pathology*; D012016:Reference Values; D013549:Sweetening Agents / Q000494:pharmacology; D055815:Young Adult
chemical_list: D052242:Adiponectin; D006601:Hexoses; D066248:High Fructose Corn Syrup; C508600:IL6 protein, human; D015850:Interleukin-6; D013549:Sweetening Agents; D005632:Fructose; D002097:C-Reactive Protein; D005947:Glucose
keywords: adipose tissue inflammation; fructose; intestinal permeability; sugar-sweetened beverages; systemic inflammation