Key Takeaways

High fructose corn syrup is not to blame for obesity; in fact, obesity rates have risen as HFCS consumption has declined.

• The U.S. Department of Agriculture data shows that consumption of high fructose corn syrup has actually been declining (USDA Sugar and Sweeteners Yearbook Table 52 2025) while obesity rates continue to rise (NCD Risk Factor Collaboration 2022). Around the world, obesity levels are also rising even though HFCS consumption is limited outside of the U.S.
• Since 2000, U.S. per-capita consumption of HFCS has dropped more than 40% with an average year-over-year drop of more than 2% (USDA Sugar and Sweeteners Yearbook Table 52 2025). During that same time period, the American obesity rate has increased from 30.5% (CDC 2002) to more than 40% (CDC 2024).

Research does not directly connect obesity to one specific food, ingredient, or sweetener.

• In 2008, the American Medical Association concluded that HFCS does not contribute to obesity more than other caloric sweeteners (AMA 2008). In 2023, the Association reaffirmed that there is insufficient evidence that HFCS is uniquely responsible for adverse health outcomes (AMA 2023). Scientific evidence consistently shows that obesity is a complex, multifactorial condition resulting from excess calorie intake and reduced physical activity—not from any one ingredient such as HFCS.

Replacing HFCS with sugar is not a solution to obesity.

• Multiple expert reviews, including those from the American Medical Association and the Academy of Nutrition and Dietetics, have concluded that HFCS does not contribute to obesity more than other caloric sweeteners (AMA 2008); (AND 2012). Replacing HFCS with sugar or other sweeteners will not reduce obesity or improve health outcomes, as these ingredients are metabolically equivalent. The key factor in weight gain is the over-consumption of calories from all sources, not the specific type of sweetener.

Obesity results from excessive calorie intake and inactivity, thus the key to battling obesity is living a healthy and balanced lifestyle.

• The most effective approach to combating obesity is living a healthy and balanced lifestyle. In order to achieve a nutritious diet, people should consume plenty of fruits, vegetables and grains along with moderate amounts of lean meat, poultry, fish, eggs and beans, low fat dairy products and healthy fats following the recommendations of the Dietary Guidelines for Americans. HFCS, like other sweeteners, can be part of a balanced diet when consumed in moderation and as part of an overall healthy eating pattern.
• Manufacturers are committed to transparency in labeling and providing consumers with clear information to make informed choices. Supporting public health initiatives that encourage balanced individualized diets, and physical activity aligns with the broader goal of addressing obesity. 

What Research Shows

Huang Y et al. “Dietary sugar consumption and health outcomes: umbrella review.” BMJ 381(2023):e071609. doi: 10.1136/bmj-2022-071609.

• The umbrella review found that high consumption of sugar-sweetened beverages is associated with a higher risk of obesity in both children and adults.
• The authors note that SSBs are less satiating than solid foods. This may lead to increased overall calorie intake and weight gain. Although they hypothesize that excessive fructose intake from SSBs may promote hepatic fat production, insulin resistance, and changes in lipid metabolism, all of which contribute to obesity and related diseases, the authors conclude that fructose is not associated with body weight changes. They further explain that there are many components within SSB that make it difficult to isolate the impact of the SSB sugar from other factors, such as additional ingredients, dietary patterns, and lifestyle behaviors. Moreover, the adverse effects of added sugars on body weight occur when consumed in calorie intake excess, rather than due to any unique property of the sugars themselves. In other words, HFCS is not uniquely harmful.
• Most negative health associations were related to SSB consumption, which can be sweetened with HFCS, sucrose, or other sugars. The authors explicitly state that it is difficult to separate the impact of the sugar in SSBs from other components, and that the health risks associated with SSBs are likely due to overall sugar content and liquid calorie delivery, not the use of HFCS specifically. Notably, in many countries, sucrose (not HFCS) is the primary sweetener in SSBs and processed foods, yet similar associations with health outcomes are observed regardless of the sweetener used.

EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA). “Tolerable upper intake level for dietary sugars.” EFSA Journal 20(2):7074, 2022. doi: 10.2903/j.efsa.2022.7074.

• This scientific opinion from the European Food Safety Authority (EFSA) systematically reviewed the evidence on dietary sugars and their relationship to obesity and related health outcomes, with a focus on both randomized controlled trials and prospective cohort studies. The EFSA panel found moderate-certainty evidence from randomized controlled trials that higher intake of added and free sugars, when consumed ad libitum (without calorie restriction), is causally related to increased risk of obesity. However, when sugars (including fructose) were consumed in isocaloric exchange with other macronutrients (i.e., total calorie intake was kept constant), there was no evidence of a unique effect of sugars on body weight or obesity risk.
• The panel concluded that the risk of obesity is primarily driven by excess calorie intake, especially from added and free sugars in beverages, rather than the specific type of sugar consumed.

Lowndes J, et al., “The effects of four hypocaloric diets containing different levels of sucrose or high fructose corn syrup on weight loss and related parameters,” Nutrition Journal 11:55, August 2012.

• This study examined the effects of consuming either sugar or HFCS as part of a reduced calorie diet. Decreases in weight were observed when overweight individuals were subjected to low calorie diets containing different levels of sucrose or high fructose corn syrup typical of those consumed in the U.S. adult population. The authors concluded that both sucrose and high fructose corn syrup affected weight loss similarly.

Disclosure: CRA provided financial support for the conduct of this study.

White, J.S. “Misconceptions about High-Fructose Corn Syrup: Is It Uniquely Responsible for Obesity, Reactive Dicarbonyl Compounds, and Advanced Glycation End products?” Journal of Nutrition. 139 (6), 1219S-1227S. June 2009.

• This article identifies and corrects common misconceptions about the composition, functionality, metabolism, and use of HFCS and its purported link to obesity. The article also addresses an emerging misconception that HFCS in carbonated soft drinks contributes to physiological levels of reactive dicarbonyl compounds and advanced glycation endproducts. The article presents evidence that HFCS does not pose a unique dietary risk in healthy individuals or diabetics.

Disclosure: CRA provided financial support for the conduct of this study.

Richard A. Forshee, et al. “A Critical Examination of the Evidence Relating High Fructose Corn Syrup and Weight Gain,” Critical Review of Food Science & Nutrition. 47(6):561-82, 2007.

• The Center for Food, Nutrition, and Agriculture Policy convened an expert panel to discuss the published scientific literature examining the relationship between consumption of HFCS and weight gain. The authors conducted original analysis to address certain gaps in the literature. Based on the currently available evidence, the expert panel concluded that HFCS does not appear to contribute to weight gain and obesity any differently than do other energy sources.

Sun, S. and Empie, M. “Lack of findings for the association between obesity risk and usual sugar-sweetened beverage consumption in adults,” Food and Chemical Toxicology. 45, 1523-1536, 2007.

• This peer-reviewed study found that those who frequently consume sweetened soft drinks do not have a higher obesity rate than those who rarely drink them. The authors note, “Obesity is a multi-factorial problem which is rooted in a positive balance between energy intake and expenditure. Lifestyle, behavior, and environment appear to have a more dominant role in obesity prevalence than do individual foods.”

Hein, G.L., Storey, M.S., White, J.S., and Lineback, D.R., “Highs and Lows of HFCS: A Report From the Center for Food and Nutrition Policy,” Nutrition Today. 40(6):253-256, November/December 2005.

• The November/December 2005 issue of Nutrition Today includes a report from the Center for Food, Nutrition, and Agriculture Policy and its Ceres Workshop, which was compiled by scientists who reviewed a number of critical commentaries about HFCS. The authors conclude that, “Currently, there is no convincing evidence to support a link between HFCS consumption and overweight/obesity… The escalating rate of overweight/obesity coincides with many more credible explanations than increased HFCS consumption.”

Disclosure: CRA provided financial support for the conduct of this study.

Key Takeaways

High-quality human studies show no unique effect of fructose or HFCS on diabetes risk or glycemic control.

• Large systematic reviews and meta-analyses of controlled human intervention studies (Choo 2018 and Zafar 2021) have found that when fructose or fructose-containing sugars (including HFCS) are consumed in real-world patterns and amounts, they do not have harmful effects on glycemic markers or increase diabetes risk. In fact, several recent studies showed short- and long-term neutral or even positive effects of fructose consumption (Zafar 2021). The harmful effects were observed only when sugars were added as excess energy, not when they replaced other carbohydrates in the diet. Negative effects observed in some studies are therefore more likely attributable to excess calorie intake, not to fructose or HFCS specifically.
• There is broad scientific agreement that HFCS and table sugar are nutritionally and metabolically equivalent, and the American Medical Association has concluded that “insufficient evidence exists that HFCS consumption has contributed to obesity more than sucrose.” (AMA 2022). Both HFCS and table sugar contain roughly half fructose and half glucose, and there is no credible scientific or medical basis to distinguish HFCS from table sugar in terms of human health effects.
• The Journal of Nutrition published an article titled, “Dietary glycemic index, glycemic load, and digestible carbohydrate intake are not associated with risk of type 2 diabetes in eight European countries” (Sluijs I, et al., “Dietary glycemic index, glycemic load, and digestible carbohydrate intake are not associated with risk of type 2 diabetes in eight European countries. J Nutr. 2013 Jan;143(1):93-9.) The conclusion summed it up well: “Our study shows that digestible carbohydrate intake is not associated with diabetes risk and suggests that diabetes risk with high-GI and -GL diets may be more modest than initial studies suggested.

 There is not one factor, such as a single food or ingredient, that is uniquely responsible for diabetes or obesity.

• Rates of obesity and diabetes do not correlate with consumption rates of HFCS. Research has shown that per capita consumption of high fructose corn syrup is actually on the decline (USDA Sugar and Sweeteners Yearbook Table 52 2025), while obesity and diabetes rates continue to rise
• The American Diabetes Association estimates that 38.4 million children and adults in the United States—11.6% of the population—have diabetes, and that number continues to grow. The Centers for Disease Control cites obesity as the major risk factor for Type 2 diabetes, and the rate of obesity in the U.S. also increased over the last decades.
• HFCS is metabolically similar to sucrose at common intake levels. Sugars can fit within a healthy diet when limited to recommended amounts and overall calories are controlled (Bravo 2013)*.

Earlier studies suggesting a unique link between fructose or HFCS and diabetes were based on less rigorous science.

• Earlier studies (Johnson RJ, et al., “Hypothesis: Could Excessive Fructose Intake and Uric Acid Cause Type 2 Diabetes?, Endocrine Reviews, Volume 30, Issue 1, 1 February 2009, Pages 96–116, https://doi.org/10.1210/er.2008-0033); Rizkalla, SW, “Health implications of fructose consumption: A review of recent data.” Nutr Metab (Lond) 7, 82 (2010). https://doi.org/10.1186/1743-7075-7-82) reporting an association between fructose or HFCS and diabetes were based on either ecological correlations, animal models, or unrealistic conditions (unrealistically large amounts of fructose). As Choo et al. (2018) recognized, however, “higher levels of evidence from systematic reviews and meta-analyses of controlled human intervention studies have failed to show adverse glycaemic effects unique to fructose.” In fact, studies involving the consumption of fructose in isolation do not reflect how people actually consume sugars in their diets (Malik 2015); (Rippe 2013)*. In reality, humans almost always consume fructose together with glucose, whether from HFCS, table sugar, honey, agave, or maple syrup (Malik 2015); (Karjoo 2022). Some earlier studies also failed to account for overall caloric intake, a critical factor in metabolic health (Zafar 2021).

 There is strong scientific evidence pointing to an increased body mass index (BMI) being a more plausible link to diabetes prevalence than HFCS consumption.

• Indeed, obesity is a primary risk factor for diabetes (CDC 2024); Lingvay I, et al., “Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation.” Lancet. 2022 Jan 22;399(10322):394-405; Koirala S, et al., “The Role of Obesity as a Cardiac Disease Risk Factor in Patients with Type 2 Diabetes.” Curr Cardiol Rep. 2024 Nov;26(11):1309-1320.) A study published in the scientific journal PLOS One showed the five countries with the largest increase in diabetes prevalence also saw a decrease in the availability of sugar (per capita) during the same amount of time. (Table 2) (Basu S et al., “The Relationship of Sugar to Population-Level Diabetes Prevalence: An Econometric Analysis of Repeated Cross-Sectional Data.” PLoS ONE 8(2): e57873 (2013). https://doi.org/10.1371/journal.pone.0057873).

* Disclosure: CRA provided financial support for the conduct of these studies.

Research

Goran, M., Ulijaszek, S. and Ventura, E. “High fructose corn syrup and diabetes prevalence: A global perspective.” Global Public Health 8(2012) 1:55-64. I:10.1080/17441692.2012.736257.

• Goran et al. conducted a global ecological analysis of 43 countries to examine the relationship between high-fructose corn syrup (HFCS) availability and type 2 diabetes prevalence. They found that countries with higher HFCS availability had a 20% higher prevalence of type 2 diabetes compared to those with lower HFCS availability, even after adjusting for obesity, total sugar, calorie availability, and other country-level factors. The findings suggest that greater HFCS availability is associated with higher rates of type 2 diabetes, independent of obesity.
• The study has no basis for singling out HFCS compared to sugar and falsely implies that association shows a causal relationship between HFCS and diabetes. See https://www.prnewswire.com/news-releases/caution-new-study-alleging-hfcs-diabetes-link-is-flawed-and-misleading-says-corn-refiners-association-180837621.html.

Cozma A et al. “Effect of Fructose on Glycemic Control in Diabetes: A Systematic Review and Meta-analysis of Controlled Feeding Trials.” Diabetes Care 35(2012):1-10.doi: 10.2337/dc12-0073.

• This study conducted a systematic review (close look at 18 other trials/studies) and found that fructose may actually be beneficial to the body, particularly in the case of diabetes. The participants in the trials (all with either Type 1 or 2 diabetes) ate food where fructose was added to it or incorporated into it. The fructose-containing diets had the same number of calories as the diets without it. Fructose appeared to improve blood sugar control without negative effects on blood pressure, cholesterol levels or body weight. This switch out of fructose to replace other carbohydrates appeared to specifically improve long-term glycemic control (blood sugar control) as measured by HbA1c.

U.S. Department of Agriculture, Economic Research Service. 2025. Table 52—High fructose corn syrup: estimated number of per capita calories consumed daily, by calendar year, and Table 51—Refined cane and beet sugar: estimated number of per capita calories consumed daily, by calendar year. Sugar and Sweeteners Yearbook.

• Dataset of U.S. consumption of caloric sweeteners from 1970 – 2025.
• U.S. Department of Agriculture data shows that though total added sugar consumption, particularly from high fructose corn syrup, has actually gone down in recent years, obesity and diabetes continue to rise.

Melanson KJ, Angelopoulos TJ, Nguyen V, Zukley L, Lowndes J, Rippe JM. “High-fructose corn syrup, energy intake, and appetite regulation.” Am J Clin Nutr. 88(2008)6:1738S-1744S. doi: 10.3945/ajcn.2008.25825E.

• Melanson et al. reviewed the effects of high-fructose corn syrup (HFCS) on energy intake, appetite regulation, and body weight. They found that HFCS and sucrose have similar effects on metabolism, appetite hormones, and energy intake, with no evidence that HFCS uniquely disrupts energy balance or increases diabetes risk compared to other caloric sweeteners.

Disclosure: CRA provided financial support for the conduct of this study.

Bravo, S., Lowndes, J., Sinnett, S., Yu, Z., and Rippe, J. “Consumption of sucrose and high fructose corn syrup does not increase liver fat or ectopic fat deposition in muscles” Applied Physiology, Nutrition, and Metabolism, (2013) DOI: 10.1139/apnm-2012-0322.

• Bravo et al. conducted a 10-week study in which participants consumed typical dietary levels of sucrose or HFCS. They found no increase in liver fat or muscle fat, and no differences between the two sweeteners. Their results suggest that normal consumption of sucrose or HFCS does not promote ectopic fat deposition, a key factor in the development of insulin resistance and type 2 diabetes.

Disclosure: CRA provided financial support for the conduct of this study.

Key Takeaways

There is no causal relationship between a balanced diet containing fructose or HFCS and pancreatic cancer.

• No study in human beings has concluded that HFCS causes pancreatic cancer in humans.
• A recent umbrella review (Huang et al. 2023) reported an association between fructose intake and pancreatic cancer, but it was based on one meta-analysis, Aune et al. (2012). The authors rated the grade of evidence as “low” and noted that “caution is warranted when explaining” the association because confounding factors, like alcohol consumption, diabetes status, and physical activities likely explain the association. When these factors were accounted for, the association between fructose intake and pancreatic cancer was no longer statistically significant.

 It is “speculative” to blame one component of the diet for pancreatic cancer based on Petri dish studies.

• Aune et al. (2012) notes that while a statistical association between fructose intake and pancreatic cancer was observed, the underlying biological mechanism is “speculative.” The authors discuss possible metabolic pathways but emphasize that these are not proven explanations for a causal relationship.
• While studies in Petri dishes have suggested that cancer cells grow well on sucrose, those studies do not identify a unique role for HFCS—as compared to naturally occurring fructose or fructose in table sugar (sucrose)—in tumor growth.
• Cancer cells are well known for having multiple mechanisms to escape the body’s normal controls, which makes controlled laboratory studies poor models for generating meaningful results.

There is no reliable scientific evidence that HFCS increases the risk of pancreatic cancer compared to other sweeteners.

• There is no reliable scientific evidence that fructose or HFCS differ from other sweeteners when it comes to the risk of pancreatic cancer. For instance, White (2010)* demonstrates that there is no evidence that HFCS uniquely increases cancer risks compared to other sweeteners.

* Disclosure: CRA provided financial support for the conduct of this study.

HFCS is not a cause of bowel cancer.

• Annema et al. (2011) has been cited to suggest a link between HFCS and bowel cancer, but this study did not study fructose or HFCS at all. Instead, it examined fruit and vegetable consumption and the risk of bowel cancers in Western Australia.

Research

 Huang Y, Chen Z, Chen B, et al. “Dietary sugar consumption and health: umbrella review.” BMJ 2023;381:e071609.

• Huang, et al. synthesizes evidence from 73 meta-analyses on dietary sugar consumption and a wide range of health outcomes, including cancer. The review evaluates total sugars, monosaccharides (including fructose), disaccharides, free sugars, added sugars, and sugar-sweetened beverages (SSB). The study reports that a 25 g/day increment in fructose intake is associated with a 22% higher risk of pancreatic cancer.
• Although Huang reports that fructose is associated with a higher risk of pancreatic cancer, it relies on a single meta-analysis (Aune et al. (2012)), which did not distinguish by the source of fructose and therefore does not provide evidence that HFCS, as consumed in the diet, is uniquely associated with cancer risk.
• The authors emphasize that most of the evidence linking dietary sugars to cancer is “observational and of low quality” or very low quality. The authors warned that “caution is warranted when explaining the significant associations between dietary sugar consumption and some cancer risks,” in part because the association between fructose and pancreatic cancer was diminished or disappears in studies that adjust for confounding factors such as alcohol intake, diabetes, and physical activity.
• Most negative health associations were related to SSB consumption, which can be sweetened with HFCS, sucrose, or other sugars. The authors explicitly state that it is difficult to separate the impact of the sugar in SSB from other components, and that the health risks associated with SSBs are likely due to overall sugar content and liquid calorie delivery, not the use of HFCS specifically. Notably, in many countries, sucrose (not HFCS) is the primary sweetener in SSBs and processed foods, yet similar associations with health outcomes are observed regardless of the sweetener used.

 Aune D, Chan DSM, Vieira AR, et al. “Dietary fructose, carbohydrates, glycemic indices and pancreatic cancer risk: a systematic review and meta-analysis of cohort studies.” Annals of Oncology 23 (2012): 2536–2546.

• Aune, et al. is a systematic review and meta-analysis examining the association between dietary intake of carbohydrates, glycemic index, glycemic load, and specific sugars (including fructose and sucrose) and the risk of pancreatic cancer. The study does not support an association between diets high in glycemic index, glycemic load, total carbs or sucrose and pancreatic cancer risk.
• This study did not investigate HFCS specifically. Instead, it analyzes total fructose intake from all dietary sources, which may include fruits, sucrose, HFCS, and other sweeteners and does not distinguish between fructose from HFCS, sucrose, or fruit. Thus, the study cannot attribute the observed association to HFCS specifically.
• There was no statistically significant increased risk when analyzing studies that controlled for potential confounding factors like alcohol consumption, diabetes status, and physical activity.
• The association between fructose and pancreatic cancer risk is based on observational cohort studies, which are subject to confounding and cannot establish a causal relationship. In fact, the authors urged caution because the quality of evidence is “low,” and called for further research with better adjustment for confounders.
• The study recognized that the “mechanism that may explain an association between fructose intake and pancreatic cancer remains speculative.”

 Annema N, Heyworth JS, McNaughton SA, Iacopetta B, and Fritschi L., “Fruit and Vegetable Consumption and the Risk of Proximal Colon, Distal Colon, and Rectal Cancers in a Case- Control Study in Western Australia” J Am Diet Assoc., 111 (2011):1479- 1490.

• Annema et al. examines fruit and vegetable consumption and the risk of bowel cancers in Western Australia. Results suggest that different fruits and vegetables may confer different risks for cancer of the proximal colon, distal colon, or rectum.
• Claims that HFCS causes cancer require direct evidence from studies specifically examining HFCS, not just general findings about sugars or fructose. HFCS consists of both fructose and glucose, not pure fructose. Fructose is not high fructose corn syrup, though the two are often confused. High fructose corn syrup is composed of 42% or 55% fructose, with the remainder consisting of glucose and short glucose polymers that are reduced to glucose during digestion. It is well accepted that high fructose corn syrup and sucrose are metabolized similarly, and distinctly from fructose (White et al. 2010)*. Therefore, it is scientifically unsupported to use Annema’s results to link HFCS to cancer risk.
• High fructose corn syrup was not even mentioned in the paper, probably because it isn’t widely used in Australia in comparison to sucrose (table sugar). The use of high fructose corn syrup in foods and beverages is frequently exaggerated. 92% of the caloric sweetener used worldwide is sucrose; and high fructose corn syrup use in the U.S. has been in decline since the early 2000s.

* Disclosure: CRA provided financial support for the conduct of this study.

 Liu, H., Huang, D., McArthur, DL., Boros, LG., Nissen, N., and Heaney, AP. “Fructose Induces Transketolase Flux to Promote Pancreatic Cancer Growth” Cancer Res 70 (2010); 6368.

• Liu et al. investigates how fructose affects pancreatic cancer metabolism and growth. The study found that fructose, unlike glucose, is preferentially used by pancreatic cancer cells to fuel the nonoxidative pentose phosphate pathway, promoting nucleic acid synthesis and tumor proliferation. The results suggest that dietary fructose may contribute to cancer progression and highlight fructose metabolism as a potential therapeutic target in cancer.
• This study does not look at the way fructose is actually consumed by humans. It was conducted in a laboratory, not inside the human body.
• The study narrowly compared pure fructose to pure glucose, neither of which is consumed in isolation in the human diet. Humans consume a wide array of foods that contain both fructose and glucose in combination along with many other sugars and nutrients. Most notably, both sugar (sucrose) and high fructose corn syrup contain roughly 50 percent glucose and 50 percent fructose.
• The study’s authors inaccurately state that high fructose corn syrup is the most significant source of fructose in the diet, whereas in the United States more fructose is still consumed from sugar than from high fructose corn syrup.

 White JS, Foreyt JP, Melanson KJ, Angelopoulos TJ. “High-Fructose Corn Syrup: Controversies and Common Sense.” American Journal of Lifestyle Medicine. 4, 6 (2010):515- 520.

• White et al. reviews controversies related to HFCS use in the U.S. The study concludes that HFCS is essentially interchangeable with other common caloric sweeteners such as sucrose, honey, invert sugar, and concentrated fruit juices. Human research has demonstrated no significant differences in metabolic, endocrine, hormonal, or appetite-related responses among these sweeteners.
• This review specifically examines the metabolic and nutritional effects of HFCS, with a focus on its similarities to sucrose, the sweetener it largely replaced in many food products. The evidence indicates that HFCS does not have unique health effects compared to other similar sweeteners.

Disclosure: CRA provided financial support for the conduct of this study.

White JS. “Straight talk about high-fructose corn syrup: what it is and what it ain’t.” Am J Clin Nutr 88,6 (2008): 1716S-1721S.

• White reviews the composition and metabolism of high-fructose corn syrup (HFCS), finding that HFCS is not meaningfully different from other common sweeteners like sucrose, honey, or fruit juice concentrates. The study concludes there is no evidence that HFCS uniquely promotes obesity or poses special health risks compared to other fructose-glucose sweeteners, and eliminating HFCS from the food supply would not significantly impact obesity rates.
• White demonstrates that there is no evidence that HFCS uniquely increases cancer risks compared to other sweeteners.

Disclosure: CRA provided financial support for the conduct of this study.

Key Takeaways

Current scientific evidence does not support a unique role of HFCS or fructose on the gut microbiome compared to other added sugars such as sucrose.

• Excessive intake of any dietary sugar can alter the composition and diversity of the gut microbiota, but these effects are not exclusive to HFCS and are observed with high consumption of all simple sugars. (Rippe 2013)*.
• Moreover, changes in microbiome are not necessarily bad or good, and the impact of various changes in the in the microbiome are not fully understood.

 There is no proven mechanism by which HFCS alone causes unique or disproportionate disruption to the gut microbiome.

• Studies have not proven a unique mechanism by which HFCS would cause an adverse change in the human microbiome. (Rippe 2013)*. There is no accepted scientific consensus on what constitutes a healthy versus diseased microbiome.
• Although research suggests the potential for fructose to disrupt the microbiome with excessive consumption, a significant amount of fructose is absorbed in the small intestine and therefore not much, if any, makes it to the colon, where the microbiome primarily resides. (Leong, I. “The small intestine — a new player in fructose metabolism.” Nat Rev Endocrinol 14, 190 (2018). https://doi.org/10.1038/nrendo.2018.20).

 The most important factor for gut health is maintaining a healthy, balanced diet, as recommended by leading health organizations.

• While a healthy microbiome is difficult to define, leading health organizations recommend maintaining a healthy and balanced diet to protect microbiome health (2025 CDC and 2020-2025 USDA Dietary Guidelines). This means consuming plenty of fruits, vegetables, whole grains, lean proteins, and healthy fats, while moderating intake of added sugars. HFCS, like other sweeteners, can be part of a balanced diet when consumed in moderation and as part of an overall healthy eating pattern.

 The precise composition of a healthy gut microbiome is difficult to define.

• “Healthy” and “unhealthy” gut microbiomes are difficult to define, without clear scientific consensus. In fact, “as studies have progressively included larger numbers of human volunteers, it has become clear that the microbiome variance among apparently healthy individuals is vast.” (Shanahan, F et al., “What is the definition of a healthy microbiome?” Elsevier Jour Gastr 160(2) (2021) https://doi.org/10.1053/j.gastro.2020.09.057)

* Disclosure: CRA provided financial support for the conduct of this study.

Research

Huang et al. (2023), “Dietary sugar consumption and health: umbrella review,” BMJ 2023;381:e071609.

• This review highlights several potential microbiome-relevant pathways linking fructose-containing sugars and sugar-sweetened beverages (SSBs) to downstream health outcomes. Mechanistically, animal evidence suggests dietary fructose can be converted by gut microbiota to acetate, which in turn enhances hepatic lipogenesis by supplying lipogenic acetyl‑CoA. The authors further note that excessive fructose intake may disturb intestinal flora and impair intestinal barrier function, promoting metabolic endotoxaemia, systemic inflammation, and lipid accumulation.
• Huang underscores that much human evidence regarding sugars and health comes from SSB exposure, which intrinsically bundles sugars with other constituents that may themselves influence the gut microbiome. The review explicitly identifies several non‑sugar ingredients commonly present in SSBs, including 4‑methylimidazole (a caramel-color byproduct), pesticides, artificial sweeteners, sodium benzoate, and sulfites, as potential confounders that could complicate attribution of microbiome effects to sugars alone.

Malik VS & Hu FB (2015), “Fructose and cardiometabolic health: what the evidence from sugar-sweetened beverages tells us.” Journal of the American College of Cardiology, 66(14), 1615–1624.

• This review highlights that the major sources of fructose in the diet are HFCS and sucrose, both of which are metabolized similarly and have similar effects on health. The review notes that high intake of sugar-sweetened beverages (regardless of sweetener type) is associated with adverse metabolic outcomes, including changes in the gut microbiome, but does not identify any unique risk from HFCS compared to other sugars. Thus, while excess sugar intake can affect the microbiome, authors don’t present evidence that HFCS, specifically, leads to inflammation or disease.
• Moreover, much of the evidence is based on consumption of SSBs, which have several other ingredients that can lead to changes in the microbiome (See Huang 2023).
• The study relies on ecological data, which cannot establish causation.

Rippe JM & Angelopoulos TJ (2013), “Sucrose, high-fructose corn syrup, and fructose, their metabolism and potential health effects: what do we really know?” Advances in Nutrition, 4(2), 236–245.

• This review addresses controversies about HFCS, sucrose, and fructose, concluding that there are no significant metabolic or endocrine differences between HFCS and sucrose. Studies comparing the effects of these sugars on health—including the microbiome—show similar outcomes, and the review cautions against attributing unique harm to HFCS.

Disclosure: CRA provided financial support for the conduct of this study.

Key Takeaways

Current evidence does not show that HFCS has any unique impact on liver disease compared to other added sugars.

• Studies do not find differences between fructose and glucose for metabolic dysfunction-associated steatotic liver disease (MASLD) or nonalcoholic steatohepatitis (NASH). For instance, a comprehensive review by the European Food Safety Authority (EFSA) panel concluded that randomized controlled trials comparing isocaloric intakes of fructose and glucose do not show a positive association between fructose consumption and increased risk of MASLD or NASH (EFSA 2022). When fructose and glucose were consumed in equal caloric amounts, there was no statistically significant difference in liver fat accumulation between the two sugars. This evidence indicates that, under conditions where total calorie intake is controlled, fructose does not pose a greater risk for liver fat buildup or related liver diseases compared to glucose.

Despite extensive research, there is currently no proven mechanism by which HFCS causes liver disease, including Metabolic dysfunction-associated steatotic liver disease (MASLD).

• While some studies have reported that fructose intake is associated with increased liver fat production, the underlying mechanisms and their direct relevance to liver disease remain unclear and require further investigation (Karjoo 2022).
• And at least one study has found that the consumption of both HFCS and sucrose (table sugar) at levels consistent with average daily consumption do not increase liver fat in humans. (Bravo 2013)*

 HFCS and fructose have not been proven to be causes of MASLD or responsible for scarring in the liver or other liver diseases.

• People with MASLD are compromised individuals with significant health problems
• The most important factor for liver health is maintaining a balanced diet and healthy body weight, as recommended by leading health organizations.

* Disclosure: CRA provided financial support for the conduct of this study.

Research

Huang Y et al. “Dietary sugar consumption and health: umbrella review.” BMJ 381 (2023): e071609.

• While a recent umbrella review found that high intake of dietary sugars, especially from sugar-sweetened beverages (SSBs), is associated with increased risk of obesity, metabolic syndrome, and MASLD, the evidence was observational and of low quality. The authors recognized that the “[e]xisting evidence is mostly observational and of low quality, and further randomized controlled trials are needed.”
• Most negative health associations were related to SSB consumption, which can be sweetened with HFCS, sucrose, or other sugars. The authors explicitly state that it is difficult to separate the impact of the sugar in SSB from other components, and that the health risks associated with SSBs are likely due to overall sugar content and liquid calorie delivery, not the use of HFCS specifically. Notably, in many countries, sucrose (not HFCS) is the primary sweetener in SSBs and processed foods, yet similar associations with health outcomes are observed regardless of the sweetener used.

EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA). “Tolerable Upper Intake Level for Dietary Sugars.” EFSA Journal 20(2):7074 (2022).

• In a review of the evidence on dietary sugars and liver health, a panel of the European Food Safety Authority (EFSA) found that the results of randomized controlled trials examining the effects of fructose versus glucose on liver fat do not suggest a positive relationship between isocaloric fructose intake and increased risk of MASLD or nonalcoholic steatohepatitis (NASH). In studies where fructose and glucose were consumed in equal calories, there was no statistically significant difference in liver fat accumulation.
• The EFSA concluded that there is evidence for a positive and causal relationship between high intakes of added and free sugars (ad libitum or in excess calories) and risk of MASLD/NASH, but the level of certainty is low.

 Karjoo S et al. “Metabolic dysfunction-associated steatotic liver disease and obesity: Clinical Practice Statement.” Obesity Pillars 3 (2022): 100027.

• While a Clinical Practice Statement from the Obesity Medicine Association discusses studies suggesting that sucrose and HFCS are associated with fatty liver, dyslipidemia, insulin resistance, and other metabolic conditions, the statement is focused on a specific population (individuals with obesity) and recognizes that “[i]t is challenging to determine the relative pathogenic contributions of the fructose versus glucose components of HFCS when compared to high intakes of other sugars.”

Lee D et al. “Important Food Sources of Fructose-Containing Sugars and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Controlled Trials.” Nutrients 14 (2022): 2846.

• This systematic review and meta-analysis, funded by Diabetes Canada and the Canadian Institutes of Health Research, examined the effects of different food sources of fructose-containing sugars on markers of MASLD.
• The study found that when excess energy from sugar-sweetened beverages (SSBs) was added to the diet, there were significant increases in liver fat and small but important increases in the liver enzyme ALT. However, when fructose-containing sugars were substituted isocalorically for other carbohydrates (i.e., without increasing total calorie intake), there was no effect on liver fat or liver enzymes.
• The authors concluded that the impact of fructose-containing sugars on liver health is mediated by both the food source (with SSBs being most impactful) and overall energy intake. There was no evidence that HFCS or fructose-containing sugars, when consumed as part of a calorie-balanced diet, uniquely increase the risk of MASLD. The study did not provide causal evidence that fructose-containing sugars directly cause MASLD, emphasizing the importance of overall dietary patterns and energy balance.

 Bravo, M, et al. “Consumption of sucrose and high fructose corn syrup does not increase liver fat or ectopic fat deposition in muscles” Appl. Physiol. Nutr. Metab. (2013) 10.1139/apnm-2012-0322.

• The study presented compelling data showing the consumption of both high fructose corn syrup (HFCS) and sucrose (table sugar) at levels consistent with average daily consumption do not increase liver fat in humans, a leading cause of non-alcoholic fatty liver disease (MASLD). The findings also add to an already well-established body of science that high fructose corn syrup and table sugar are metabolically equivalent.

Disclosure: CRA provided financial support for the conduct of this study.

Abdelmalek MF, et al. “Increased Fructose Consumption is Associated with Fibrosis Severity in Patients with Nonalcoholic Fatty Liver Disease,” Hepatology 51(6) 2010: 1961-71. doi: 10.1002/hep.23535.

• Duke University incorrectly singled out high fructose corn syrup as being responsible for scarring in the liver and other liver diseases, when the underlying study reviewed dietary intake of fructose containing beverages – not high fructose corn syrup.
• Fructose has not been proven to be a cause of MASLD in humans, and MASLD subjects are compromised individuals with significant health problems which have very little to do with fructose intake.
• This study unnecessarily confuses consumers about the impact of dietary fructose, let alone high fructose corn syrup. Fructose, or “fruit sugar,” is safe and is commonly found in fruits, vegetables, fruit juices, table sugar, honey, high fructose corn syrup, and maple syrup.