Excess free fructose, high-fructose corn syrup and adult asthma: the Framingham Offspring Cohort

Br J Nutr. 2018 May;119(10):1157-1167. doi: 10.1017/S0007114518000417. Epub 2018 Mar 28.


There is growing evidence that intakes of high-fructose corn syrup (HFCS), HFCS-sweetened soda, fruit drinks and apple juice - a high-fructose 100 % juice - are associated with asthma, possibly because of the high fructose:glucose ratios and underlying fructose malabsorption, which may contribute to enteral formation of pro-inflammatory advanced glycation end products, which bind receptors that are mediators of asthma. Cox proportional hazards models were used to assess associations between intakes of these beverages and asthma risk, with data from the Framingham Offspring Cohort. Diet soda and orange juice - a 100 % juice with a 1:1 fructose:glucose ratio - were included for comparison. Increasing intake of any combination of HFCS-sweetened soda, fruit drinks and apple juice was significantly associated with progressively higher asthma risk, plateauing at 5-7 times/week v. never/seldom, independent of potential confounders (hazard ratio 1·91, P<0·001). About once a day consumers of HFCS-sweetened soda had a 49 % higher risk (P<0·011), moderate apple juice consumers (2-4 times/week) had a 61 % higher risk (P<0·007) and moderate fruit drink consumers had a 58 % higher risk (P<0·009), as compared with never/seldom consumers. There were no associations with diet soda/orange juice. These associations are possibly because of the high fructose:glucose ratios, and fructose malabsorption. Recommendations to reduce consumption may be inadequate to address asthma risk, as associations are evident even with moderate intake of these beverages, including apple juice - a 100 % juice. The juice reductions in the US Special Supplemental Nutrition Program for Women, Infants, and Children in 2009, and the plateauing/decreasing asthma prevalence (2010-2013), particularly among non-Hispanic black children, may be related. Further research regarding the consequences of fructose malabsorption is needed.

Keywords: AGE advanced glycation end products; CDC US Centers for Disease Control; EFF excess free fructose; FHS-OS Framingham Heart Study Original-Cohort Study; HFCS high-fructose corn syrup; HR hazard ratio; NHANES (US) National Health and Nutrition Examination Survey; SSB sugar-sweetened beverages; T2D type 2 diabetes; enFruAGE extracellular newly identified fructose associated advanced glycation end products; Apple juice; Excess free fructose; Fructositis; Fruit drinks; Glycation; High-fructose corn syrup; Receptor of advanced glycation endproducts.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Asthma / epidemiology*
  • Body Mass Index
  • Carbonated Beverages / adverse effects
  • Carbonated Beverages / analysis
  • Citrus sinensis
  • Cohort Studies
  • Energy Intake
  • Female
  • Follow-Up Studies
  • Fructose / administration & dosage*
  • Fructose / adverse effects
  • Fructose / analysis
  • Fruit
  • Fruit and Vegetable Juices / analysis
  • Glucose / analysis
  • High Fructose Corn Syrup / administration & dosage*
  • High Fructose Corn Syrup / adverse effects
  • High Fructose Corn Syrup / analysis
  • Humans
  • Male
  • Malus
  • Middle Aged
  • Obesity / epidemiology
  • Overweight / epidemiology
  • Prospective Studies
  • Risk Factors
  • Sweetening Agents / administration & dosage


  • High Fructose Corn Syrup
  • Sweetening Agents
  • Fructose
  • Glucose