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

  • Luanne R. DeChristopher (a1) and Katherine L. Tucker (a2)

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.

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* Corresponding author: L. R. DeChristopher, email
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1. DeChristopher, LR (2012) Consumption of fructose and high fructose corn syrup: is fructositis triggered bronchitis, arthritis, & auto-immune reactivity merely a side bar in the etiology of metabolic syndrome II (to be defined)? – evidence and a hypothesis. (accessed February 2018).
2. Park, S, Blanck, HM, Sherry, B, et al. (2013) Regular-soda intake independent of weight status is associated with asthma among US high school students. J Acad Nutr Diet 113, 106111.
3. Park, S, Akinbami, LJ, McGuire, LC, et al. (2016) Association of sugar-sweetened beverage intake frequency and asthma among U.S. adults, 2013. Prev Med 91, 5861.
4. DeChristopher, LR, Uribarri, J & Tucker, KL (2016) Intakes of apple juice, fruit drinks and soda are associated with prevalent asthma in US children aged 2–9 years. Public Health Nutr 19, 123130.
5. Wright, LS, Rifas-Shiman, S, Oken, E, et al. (2015) Maternal prenatal intake of fructose is associated with asthma in children. J Aller Clin Immunol 135, AB228.
6. National Institute of Allergy and Infectious Diseases of the National Institute of Health (2011) Guidelines for the Diagnosis and Management of Food Allergy in the United States. Bethesda, MD: US Department of Health and Human Services. (accessed February 2018).
7. DeChristopher, LR, Uribarri, J & Tucker, KL (2016) The link between soda intake and asthma: science points to the high-fructose corn syrup, not the preservatives: a commentary. Nutr Diabetes 6, e234.
8. Coca Cola New Zealand (2015) (accessed May 2015).
9. Wickens, K, Barry, D, Friezema, A, et al. (2005) Fast foods – are they a risk factor for asthma? Allergy 60, 15371541.
10. Shi, Z, Dal Grande, E, Taylor, AW, et al. (2012) Association between soft drink consumption and asthma and chronic obstructive pulmonary disease among adults in Australia. Respirology 17, 363369.
11. Watkins, NG, Neglia-Fisher, CI, Dyer, DG, et al. (1987) Effect of phosphate on the kinetics and specificity of glycation of protein. J Biol Chem 262, 72077212.
12. Zhang, Q, Ames, JM, Smith, RD, et al. (2009) A perspective on the Maillard reaction and the analysis of protein glycation by mass spectrometry: probing the pathogenesis of chronic disease. J Proteome Res 8, 754769.
13. Rizzi, GP (2004) Role of phosphate and carboxylate ions in Maillard browning. J Agric Food Chem 52, 953957.
14. The Coca Cola Company (2016) (accessed May 2016).
15. Pepsico (2016) (accessed May 2016).
16. Bains, Y & Gugliucci, A (2016) Ilex paraguariensis and its main component chlorogenic acid inhibit fructose formation of advanced glycation endproducts with amino acids at conditions compatible with those in the digestive system. Fitoterapia. 117, 610.
17. Bains, Y, Gugliucci, A & Caccavello, R (2017) Advanced glycation endproducts form during ovalbumin digestion in the presence of fructose: inhibition by chlorogenic acid. Fitoterapia 120, 15.
18. Riby, JE, Fujisawa, T & Kretchmer, N (1993) Fructose absorption. Am J Clin Nutr 58, 5 Suppl., 748S753S.
19. Gibson, PR, Newnham, E, Barrett, JS, et al. (2007) Review article: fructose malabsorption and the bigger picture. Aliment Pharmacol Ther 25, 349363.
20. Biesiekierski, JR (2014) Fructose-induced symptoms beyond malabsorption in FGID. United Eur Gastroenterol J. 2, 1013.
21. Ebert, K & Witt, H (2016) Fructose malabsorption. Mol Cell Pediatr 3, 10.
22. United States Food & Drug Administration (2017) Code of Federal Regulations Title 21, Volume 3. 21CFR184.1866. (accessed February 2018).
23. Federal Register (1996) Rules and regulations, Volume 61, Number 165, 23 August, pp. 43447, 43450. FR Doc No.: 9621482. (accessed December 2017).
24. US Department of Agriculture & Economic Research Service (2012) The ERS food availability (Per Capita) data system.
25. Mellado-Mojica, E & López, MG (2015) Identification, classification, and discrimination of agave syrups from natural sweeteners by infrared spectroscopy and HPAEC-PAD. Food Chem 167, 349357.
26. Willems, JL & Low, NH (2012) Major carbohydrate, polyol, and oligosaccharide profiles of agave syrup. Application of this data to authenticity analysis. J Agric Food Chem 60, 87458754.
27. US Department of Agriculture & Agricultural Research Service (2012) USDA National Nutrient Database for Standard Reference, Release 26. (accessed December 2015).
28. Ventura, EE, Davis, JN & Goran, MI (2011) Sugar content of popular sweetened beverages based on objective laboratory analysis: focus on fructose content. Obesity (Silver Spring) 19, 868874.
29. Walker, RW, Dumke, KA & Goran, MI (2014) Fructose content in popular beverages made with and without high-fructose corn syrup. Nutrition 30, 928935.
30. Morrison, R, , M & Buzby, JC (2010) Guess who’s turning 100? Tracking a century of American eating. Washington, DC: US Department of Agriculture, Economic Research Service, Amber Waves. (accessed December 2015).
31. Wells, HF & Buzby, JC (2008) High-fructose corn syrup usage may be leveling off. Washington, DC: US Department of Agriculture, Economic Research Service. (accessed December 2015).
32. Duffey, KJ & Popkin, BM (2008) High-fructose corn syrup: is this what’s for dinner? Am J Clin Nutr 88, 1722S1732S.
33. Bray, GA (2013) Energy and fructose from beverages sweetened with sugar or high-fructose corn syrup pose a health risk for some people. Adv Nutr 4, 220225.
34. Bray, GA, Nielsen, SJ & Popkin, BM (2004) Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 79, 537543.
35. Buckley, ST & Ehrhardt, C (2010) The receptor for advanced glycation end products (RAGE) and the lung. J Biomed Biotechnol 2010, 917108.
36. Milutinovic, PS, Alcorn, JF, Englert, JM, et al. (2012) The receptor for advanced glycation end products is a central mediator of asthma pathogenesis. Am J Pathol 181, 12151225.
37. DeChristopher, LR, Uribarri, J & Tucker, KL (2015) Intake of high fructose corn syrup sweetened soft drinks is associated with prevalent chronic bronchitis in U.S. Adults, ages 20-55 y. Nutr J 14, 107.
38. Berentzen, NE, van Stokkom, VL, Gehring, U, et al. (2015) Associations of sugar-containing beverages with asthma prevalence in 11-year-old children: the PIAMA birth cohort. Eur J Clin Nutr 69, 303308.
39. DeChristopher, LR (2015) Excess free fructose and childhood asthma. Eur J Clin Nutr 69, 1371.
40. The Framingham Heart Study (2017) A project of the National Heart, Lung, and Blood Institute and Boston University. (accessed February 2018).
41. Warner, M (2006) A sweetener with a bad rap. New York Times.
42. Bovard, J (1998) The great sugar shaft. Freedom Daily, April. (accessed February 2018).
43. Han, E & Powell, LM (2013) Consumption patterns of sugar-sweetened beverages in the United States. J Acad Nutr Diet 113, 4353.
44. Ogden, CL, Kit, BR, Carroll, MD, et al. (2011) Consumption of sugar drinks in the United States, 2005–2008. NCHS Data Brief. (accessed February 2018).
45. Vartanian, LR, Schwartz, MB & Brownell, KD (2007) Effects of soft drink consumption on nutrition and health: a systematic review and meta-analysis. Am J Public Health 97, 667675.
46. Yun, HD, Knoebel, E, Fenta, Y, et al. (2012) Asthma and proinflammatory conditions: a population-based retrospective matched cohort study. Mayo Clin Proc 87, 953960.
47. de Koning, L, Malik, VS, Kellogg, MD, et al. (2012) Sweetened beverage consumption, incident coronary heart disease, and biomarkers of risk in men. Circulation 125, 17351741.
48. Pradeu, T & Vivier, E (2016) The discontinuity theory of immunity. Sci Immunol 1, AAG0479.
49. Jones, HF, Burt, E, Dowling, K, et al. (2011) Effect of age on fructose malabsorption in children presenting with gastrointestinal symptoms. J Pediatr Gastroenterol Nutr 52, 581584.
50. Smith, MM, Davis, M, Chasalow, FI, et al. (1995) Carbohydrate absorption from fruit juice in young children. Pediatrics 95, 340344.
51. Haley, S (2011) Sugars and sweeteners outlook. SSS-M-270. Washington, DC: US Department of Agriculture, pp. 6–9. (accessed December 2015).
52. Haley, S (2012) Sugars and sweeteners outlook. SSM-M-286. Washington, DC: US Department of Agriculture. pp. 16–19. (accessed December 2015).
53. Strom, S (2012) US cuts estimate of sugar intake. The New York Times. 26 October. December 2015).
54. Sosland, J (2011) Study raises national food waste estimates. Food Business News. 4 January. December 2015).
55. Hoekstra, JH, van Kempen, AA, Bijl, SB, et al. (1993) Fructose breath hydrogen tests. Arch Dis Child 68, 136138.
56. Gomara, RE, Halata, MS, Newman, LJ, et al. (2008) Fructose intolerance in children presenting with abdominal pain. J Pediatr Gastroenterol Nutr 47, 303308.
57. Rumessen, JJ & Gudmand-Hoyer, E (1988) Functional bowel disease: malabsorption and abdominal distress after ingestion of fructose, sorbitol, and fructose-sorbitol mixtures. Gastroenterology 95, 694700.
58. Rumessen, JJ (1992) Fructose and related food carbohydrates. sources, intake, absorption, and clinical implications. Scand J Gastroenterol 27, 819828.
59. Beyer, PL, Caviar, EM & McCallum, RW (2005) Fructose intake at current levels in the united states may cause gastrointestinal distress in normal adults. J Am Diet Assoc 105, 15591566.
60. Xue, J, Rai, V, Singer, D, et al. (2011) Advanced glycation end product recognition by the receptor for AGEs. Structure 19, 722732.
61. Dötsch, V (2011) How to create a specific recognition for an unspecific interaction. Structure 19, 601602.
62. Oczypok, EA, Perkins, TN & Oury, TD (2017) All the ‘RAGE’ in lung disease: the receptor for advanced glycation endproducts (RAGE) is a major mediator of pulmonary inflammatory responses. Paediatr Respir Rev 23, 4049.
63. Martinez-Saez, N, Fernandez-Gomez, B, Cai, W, et al. (2017) In vitro formation of Maillard reaction products during simulated digestion of meal-resembling systems. Food Res Int (Epublication ahead of print version 21 September 2017).
64. Iribarren, C, Tolstykh, IV, Miller, MK, et al. (2012) Adult asthma and risk of coronary heart disease, cerebrovascular disease, and heart failure: a prospective study of 2 matched cohorts. Am J Epidemiol 176, 10141024.
65. Patel, MR, Janevic, MR, Heeringa, SG, et al. (2013) An examination of adverse asthma outcomes in U.S. Adults with multiple morbidities. Ann Am Thorac Soc 10, 426431.
66. Song, Y, Klevak, A, Manson, JE, et al. (2010) Asthma, chronic obstructive pulmonary disease, and type 2 diabetes in the Women’s Health Study. Diabetes Res Clin Pract 90, 365371.
67. DeChristopher, LR, Uribarri, J & Tucker, KL (2016) Intake of high-fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is associated with prevalent arthritis in US adults, aged 20–30 years. Nutr Diabetes 6, e199.
68. DeChristopher, LR, Uribarri, J & Tucker, KL (2017) Intake of high fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is associated with prevalent coronary heart disease, in US adults, ages 45–59 y. BMC Nutr 3, 51.
69. DeChristopher, LR (2017) Perspective: the paradox in dietary advanced glycation end-products research: the source of the elevated serum and urinary AGEs is the intestines, not the food. Adv Nutr 8, 679683.
70. Oliveira, V & Frazao, E (2015) The WIC Program: Background, Trends, and Economic Issues, 2015 Edition. Economic Information Bulletin no. 134. Washington, DC: US Department of Agriculture, Economic Research Service. (accessed February 2018).
71. US Department of Agriculture Food and Nutrition Service (2011) WIC Food Packages Policy Options Study Final Report. Report no. WIC-11-FOOD. US Department of Agriculture Food and Nutrition Service, Nutrition Assistance Program Report Series, Office of Research and Analysis, Special Nutrition Programs, June. (accessed February 2018).
72. Akinbami, LJ, Simon, AE & Rossen, LM (2016) Changing trends in asthma prevalence among children. Pediatrics 137, 1–7.
73. Wright, LS, Rifas-Shiman, SL, Oken, E, et al. (2018) Prenatal and early-life fructose, fructose-containing beverages, and mid-childhood asthma. Ann Am Thorac Soc 15, 217–224.
74. Akinbami, LJ, Rossen, LM, Fakhouri, THI, et al. (2017) Asthma prevalence trends by weight status among US children aged 2–19 years, 1988–2014. Pediatr Obes (Epublication ahead of print version 12 November 2017).
75. Cisneros, R, Gonzalez, M, Brown, P, et al. (2016) Soda consumption and hospital admissions among Californian adults with asthma. J Asthma 5, 15.
76. Walker, RW, , KA, Davis, J, et al. (2012) High rates of fructose malabsorption are associated with reduced liver fat in obese African Americans. J Am Coll Nutr 31, 369374.
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