Is high fructose corn syrup bad for me?

High fructose corn syrup (HFCS) is a glucose-fructose mixture that commonly contains either 42% or 55% fructose by molecular weight.¹ The remainder is composed of glucose and water. Its effect on health has been a subject of concern since its rise in consumption has been found to parallel the rise in obesity.² Additionally, studies suggest that HFCS consumption may be associated with other conditions such as non-alcoholic fatty liver disease (NAFLD)³ and vascular risk factors.⁴ It is not clear, however, from the available data if the association with disease is due to HFCS itself or to the increase in sugar and calorie consumption in general. ⁵ Multiple studies have found that the consumption of HFCS leads to similar outcomes as the consumption of other sugars, including sucrose.^6-9

Some individual studies report a negative effect of HFCS on various metabolic markers.^10,11 Stanhope et al. conducted a double-blind, nonrandomized study to examine the effect  of HFCS consumption on lipid risk factors for CVD.¹⁰ Eighty-five healthy participants consumed either 0% (aspartame control), 10%, 17.5%, or 25% of energy requirements through HFCS-sweetened beverages in additon to an ad libitum diet. After two weeks, the authors found significant dose-dependent linear increases in several risk factors, including post-prandial triglycerides and fasting low-density lipoprotein cholesterol, but not in body weight The authors concluded that because these dose-dependent patterns were statistically independent of weight gain, they support the increase of CVD risk with increased HFCS intake.

Kellar et al. also found support for the correlation of sugar-sweetened beverages (SSBs) with vascular risk factors.⁴ In a systematic review of six studies (n=241,718) with follow-up between four weeks and one year, SSB consumption was associated with vascular risk factors such as high blood pressure, triacylglycerol, and  cholesterol. Unlike Stanhope’s systematic reivew., this systematic review included beverages sweetened by high fructose corn syrup and sucrose without differentiation, making it unclear if sucrose had the same effect as HFCS.

In making the distinction between HFCS and other sugars, studies comparing different sweeteners find that they produce similar effects.^9,12,13 Kuzma et al. conducted a double-blind, cross-over randomized controlled trial (RCT) to examine the difference between beverages sweetened with fructose, HFCS, and glucose on health outcomes such as systemic inflammation. Twenty-four adults were assigned a random order in which 25% of their estimated calorie needs would be consumed through beverages sweetened with 100% fructose, HFCS, or glucose. Between each eight day diet period, there was a 20 day wash-out period. Overall, they were assigned 150% of their estimated daily calorie needs: 125% from ad libitum diet and 25% from sweetened beverages. The authors found no effect of diet on day nine concentrations of interleukin-6, C-reactive protein, and adiponectin as well as no significant difference between interventions. In their interpretation, the source of sugar in SSBs does not differentially affect markers of  inflammation. A systematic review and meta-analysis of 13 studies (n=1141) by Della Corte et al. supported these findings between glucose and fructose, and also found no differences between HFCS and sucrose interventions in similar experiments.⁸

Tappy et al. conducted a systematic review to investigate the association between the consumption of suagrs and several common diseases.¹⁴ With regards to obesity, they examined multiple high-quality meta-analyses. One such meta-analysis of seven cohort studies (n=174 252) in adults found that one daily serving increment of SSBs was associated with a 0.12 kg (95% confidence interval [CI] [0.10 – 0.14]) weight gain in adults over one year in a fixed effect model.¹⁵ As mentioned prior, Tappy et al. did not specify which sugar, HFCS or not, was the sweetener in these beverages. Similarly, five RCTs studied in this meta-analysis found an increase in body weight of 0.85 kg (95% CI [0.50 – 1.20]) when SSBs were added to their diets.¹⁴ Tappy et al. concluded that the association between dietary sugar and weight gain is likely explainable by the excess energy consumption associated with sugar intake. This conclusion was based on past findings of positive associations between sugar consumption from SSBs and total energy intake, in which an increased total energy intake was also associated with weight gain.¹⁴

With regards to diabetes, the authors analyzed three prospective cohort studies and three meta-analyses, concluding that there is a lack of evidence for an association between sugar intake in this context and incidence of diabetes. Results had been markedly attenuated when accounting for weight gain.¹⁴

With regards to NAFLD, they found three studies with similar results. One was a case-control study in which fructose consumption in NAFLD patients was significantly higher than in non-NAFLD controls (365 kcal vs. 170 kcal, p<0.05).¹⁶ Fructose consumption was ascertained by asking participants to estimate number of servings of fructose containing beverages. Tappy et al. concluded that very high fructose intakes can increase intrahepatic fat concentration, but the evidence at present is not sufficient to make substantial claims about associations between sugar intake and NAFLD.¹⁴

Overall, studies indicate that HFCS may not inherently be worse than other forms of sugar. Although some studies find detrimental health effects, the results are often confounded with abnormally high non -HFCS sugar or energy intakes. More RCTs should be conducted before making a substantial conclusion. In either case, an increased sugar consumption, HFCS or not, may lead to health detriments such as weight gain, NAFLD, and cardiovascular risk factors.

^References

1. US Food and Drug Administration. High Fructose Corn Syrup Questions and Answers. 2018; https://www.fda.gov/food/food-additives-petitions/high-fructose-corn-syrup-questions-and-answers. Accessed October 24, 2019.
2. Bray GA. Energy and fructose from beverages sweetened with sugar or high-fructose corn syrup pose a health risk for some people. Adv Nutr. 2013;4(2):220-225.
3. Jensen T, Abdelmalek MF, Sullivan S, et al. Fructose and sugar: A major mediator of non-alcoholic fatty liver disease. J Hepatol. 2018;68(5):1063-1075.
4. Keller A, Heitmann BL, Olsen N. Sugar-sweetened beverages, vascular risk factors and events: a systematic literature review. Public Health Nutr. 2015;18(7):1145-1154.
5. Chung M, Ma J, Patel K, Berger S, Lau J, Lichtenstein AH. Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis. Am J Clin Nutr. 2014;100(3):833-849.
6. Wiebe N, Padwal R, Field C, Marks S, Jacobs R, Tonelli M. A systematic review on the effect of sweeteners on glycemic response and clinically relevant outcomes. BMC Med. 2011;9:123.
7. Lowndes J, Sinnett SS, Rippe JM. No effect of added sugar consumed at median American intake level on glucose tolerance or insulin resistance. Nutrients. 2015;7(10):8830-8845.
8. Della Corte KW, Perrar I, Penczynski KJ, Schwingshackl L, Herder C, Buyken AE. Effect of dietary sugar intake on biomarkers of subclinical inflammation: a systematic review and meta-analysis of intervention studies. Nutrients. 2018;10(5).
9. Kuzma JN, Cromer G, Hagman DK, et al. No difference in ad libitum energy intake in healthy men and women consuming beverages sweetened with fructose, glucose, or high-fructose corn syrup: a randomized trial. Am J Clin Nutr. 2015;102(6):1373-1380.
10. Stanhope KL, Medici V, Bremer AA, et al. A dose-response study of consuming high-fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults. Am J Clin Nutr. 2015;101(6):1144-1154.
11. Collison KS, Saleh SM, Bakheet RH, et al. Diabetes of the liver: the link between nonalcoholic fatty liver disease and HFCS-55. Obesity (Silver Spring). 2009;17(11):2003-2013.
12. Raatz SK, Johnson LK, Picklo MJ. Consumption of honey, sucrose, and high-fructose corn syrup produces similar metabolic effects in glucose-tolerant and -intolerant individuals. J Nutr. 2015;145(10):2265-2272.
13. Kuzma JN, Cromer G, Hagman DK, et al. 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. Am J Clin Nutr. 2016;104(2):306-314.
14. Tappy L, Morio B, Azzout-Marniche D, et al. French recommendations for sugar Intake in adults: a novel approach chosen by ANSES. Nutrients. 2018;10(8).
15. Malik VS, Pan A, Willett WC, Hu FB. Sugar-sweetened beverages and weight gain in children and adults: a systematic review and meta-analysis. Am J Clin Nutr. 2013;98(4):1084-1102.
16. Ouyang X, Cirillo P, Sautin Y, et al. Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol. 2008;48(6):993-999.