Sucrose, High-Fructose Corn Syrup, and Fructose, Their Metabolism and Potential Health Effects: What Do We Really Know?12

Both controversy and confusion exist concerning fructose, sucrose, and high-fructose corn syrup (HFCS) with respect to their metabolism and health effects. These concerns have often been fueled by speculation based on limited data or animal studies. In retrospect, recent controversies arose when a scientific commentary was published suggesting a possible unique link between HFCS consumption and obesity. Since then, a broad scientific consensus has emerged that there are no metabolic or endocrine response differences between HFCS and sucrose related to obesity or any other adverse health outcome. This equivalence is not surprising given that both of these sugars contain approximately equal amounts of fructose and glucose, contain the same number of calories, possess the same level of sweetness, and are absorbed identically through the gastrointestinal tract. Research comparing pure fructose with pure glucose, although interesting from a scientific point of view, has limited application to human nutrition given that neither is consumed to an appreciable degree in isolation in the human diet. Whether there is a link between fructose, HFCS, or sucrose and increased risk of heart disease, metabolic syndrome, or fatty infiltration of the liver or muscle remains in dispute with different studies using different methodologies arriving at different conclusions. Further randomized clinical trials are needed to resolve many of these issues. The purpose of this review is to summarize current knowledge about the metabolism, endocrine responses, and potential health effects of sucrose, HFCS, and fructose.

[1]  E. Parks,et al.  Dietary sugars stimulate fatty acid synthesis in adults. , 2008, The Journal of nutrition.

[2]  P. Trumbo,et al.  Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. , 2002, Journal of the American Dietetic Association.

[3]  R. Kreis,et al.  Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. , 2009, The American journal of clinical nutrition.

[4]  A. Astrup,et al.  Sucrose compared with artificial sweeteners: different effects on ad libitum food intake and body weight after 10 wk of supplementation in overweight subjects. , 2002, The American journal of clinical nutrition.

[5]  J. Manson,et al.  Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. , 2002, The American journal of clinical nutrition.

[6]  P. Havel Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. , 2005, Nutrition reviews.

[7]  P. Havel,et al.  Endocrine and metabolic effects of consuming beverages sweetened with fructose, glucose, sucrose, or high-fructose corn syrup. , 2008, The American journal of clinical nutrition.

[8]  Tonutti,et al.  Antioxidant defences are reduced during the oral glucose tolerance test in normal and non‐insulin‐dependent diabetic subjects , 1998, European journal of clinical investigation.

[9]  E. Jéquier,et al.  Effects of infused fructose on endogenous glucose production, gluconeogenesis, and glycogen metabolism. , 1994, The American journal of physiology.

[10]  J. Buzby,et al.  Dietary Assessment of Major Trends in U.S. Food Consumption, 1970-2005 , 2012 .

[11]  K. Tuttle,et al.  Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome , 2005, Nature Clinical Practice Nephrology.

[12]  John S. White,et al.  High-Fructose Corn Syrup: Controversies and Common Sense , 2010 .

[13]  P. Mayes,et al.  Intermediary metabolism of fructose. , 1993, The American journal of clinical nutrition.

[14]  J. Rippe The Health Implications of Sucrose, High-Fructose Corn Syrup, and Fructose: What Do We Really Know? , 2010, Journal of diabetes science and technology.

[15]  Judith Wylie-Rosett,et al.  Dietary sugars intake and cardiovascular health: a scientific statement from the American Heart Association. , 2009, Circulation.

[16]  In-kyu Lee,et al.  Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells. , 2005, Journal of the American Society of Nephrology : JASN.

[17]  K. Flegal,et al.  Prevalence and trends in obesity among US adults, 1999-2008. , 2010, JAMA.

[18]  D. Curry Effects of Mannose and Fructose on the Synthesis and Secretion of Insulin , 1989, Pancreas.

[19]  J. McGahan,et al.  Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein-4, and gamma-glutamyl transferase activity in overweight/obese humans , 2012, Nutrition & Metabolism.

[20]  S. Merhar,et al.  Letter to the editor , 2005, IEEE Communications Magazine.

[21]  J. McGahan,et al.  Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women , 2011, European Journal of Clinical Nutrition.

[22]  F. Schick,et al.  Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial , 2011, British Journal of Nutrition.

[23]  R. Reynolds,et al.  Hyperglycemia-induced ascorbic acid deficiency promotes endothelial dysfunction and the development of atherosclerosis. , 2001, Atherosclerosis.

[24]  E. Ford,et al.  Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessment. , 2004, The American journal of clinical nutrition.

[25]  E. Block,et al.  Hyperuricemia induces endothelial dysfunction. , 2005, Kidney international.

[26]  A. Astrup,et al.  Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. , 2012, The American journal of clinical nutrition.

[27]  Patricia S. Williamson-Hughes,et al.  Lack of association between dietary fructose and hyperuricemia risk in adults , 2010, Nutrition & metabolism.

[28]  M. Hellerstein,et al.  A dual sugar challenge test for lipogenic sensitivity to dietary fructose. , 2011, The Journal of clinical endocrinology and metabolism.

[29]  Lawrence A Leiter,et al.  Effect of Fructose on Body Weight in Controlled Feeding Trials , 2012, Annals of Internal Medicine.

[30]  G. Bray Fructose: Pure, White, and Deadly? Fructose, by Any other Name, is a Health Hazard , 2010, Journal of diabetes science and technology.

[31]  J. Rippe,et al.  Consumption of beverages sweetened with high fructose corn syrup and sucrose produce similar levels of glucose, leptin, insulin and ghrelin in obese females. , 2007 .

[32]  A. Skulberg,et al.  Letter: Occupational hazard of halothane. , 1974, Lancet.

[33]  R. Iles,et al.  Hepatic intralobular mapping of fructose metabolism in the rat liver. , 2000, The Biochemical journal.

[34]  L. Tappy,et al.  Effects of dexamethasone on hepatic glucose production and fructose metabolism in healthy humans. , 1997, The American journal of physiology.

[35]  Barry M. Popkin,et al.  The World Is Fat: The Fads, Trends, Policies, and Products That Are Fattening the Human Race , 2008 .

[36]  V. Fulgoni High-fructose corn syrup: everything you wanted to know, but were afraid to ask. , 2008, The American journal of clinical nutrition.

[37]  Wei Zhang,et al.  Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. , 2009, The Journal of clinical investigation.

[38]  K. Raivio,et al.  Fructose-induced hyperuricaemia. , 1967, Lancet.

[39]  L. Tappy,et al.  Metabolic effects of fructose , 2006, Current opinion in clinical nutrition and metabolic care.

[40]  Takahiko Nakagawa,et al.  Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. , 2007, The American journal of clinical nutrition.

[41]  Manabu T. Nakamura,et al.  Dietary fructose induces a wide range of genes with distinct shift in carbohydrate and lipid metabolism in fed and fasted rat liver. , 2008, Biochimica et biophysica acta.

[42]  M. Tordoff,et al.  Effect of drinking soda sweetened with aspartame or high-fructose corn syrup on food intake and body weight. , 1990, The American journal of clinical nutrition.

[43]  B. Heitmann,et al.  Intake of calorically sweetened beverages and obesity , 2009, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[44]  G. Burdock,et al.  Evidence-Based Review on the Effect of Normal Dietary Consumption of Fructose on Blood Lipids and Body Weight of Overweight and Obese Individuals , 2010, Critical reviews in food science and nutrition.

[45]  Ralph B. D'Agostino,et al.  Soft Drink Consumption and Risk of Developing Cardiometabolic Risk Factors and the Metabolic Syndrome in Middle-Aged Adults in the Community , 2007, Circulation.

[46]  Lawrence A Leiter,et al.  Effect of Fructose on Blood Pressure: A Systematic Review and Meta-Analysis of Controlled Feeding Trials , 2012, Hypertension.

[47]  W. Glinsmann,et al.  Evaluation of health aspects of sugars contained in carbohydrate sweeteners. Report of Sugars Task Force, 1986. , 1986, The Journal of nutrition.

[48]  R. Townsend,et al.  Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. , 2004, The Journal of clinical endocrinology and metabolism.

[49]  M. Westerterp-Plantenga,et al.  No differences in satiety or energy intake after high-fructose corn syrup, sucrose, or milk preloads. , 2007, The American journal of clinical nutrition.

[50]  E. Hultman,et al.  Liver and muscle glycogen in man after glucose and fructose infusion. , 1974, Scandinavian journal of clinical and laboratory investigation.

[51]  N. Keim,et al.  Fructose, weight gain, and the insulin resistance syndrome. , 2002, The American journal of clinical nutrition.

[52]  G. Bray,et al.  Fructose: should we worry? , 2008, International Journal of Obesity.

[53]  G. Bray Fructose and Risk of Cardiometabolic Disease , 2012, Current Atherosclerosis Reports.

[54]  P A Shaffer,et al.  Federation of American Societies for Experimental Biology , 1938, Nature.

[55]  J. Winkler Pure, White and Deadly , 2012 .

[56]  L. Tappy,et al.  Metabolic effects of fructose and the worldwide increase in obesity. , 2010, Physiological reviews.

[57]  John S. White,et al.  Straight talk about high-fructose corn syrup: what it is and what it ain't. , 2008, The American journal of clinical nutrition.

[58]  Patricia S. Williamson-Hughes,et al.  Fructose and non-fructose sugar intakes in the US population and their associations with indicators of metabolic syndrome. , 2011, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[59]  N. Keim,et al.  Twenty-four-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose-, and glucose-sweetened beverages with meals. , 2008, The American journal of clinical nutrition.

[60]  A. Truax,et al.  High fructose corn syrup. , 2011, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.

[61]  K. Brownell,et al.  Effects of soft drink consumption on nutrition and health: a systematic review and meta-analysis. , 2007, American journal of public health.

[62]  G. Bray,et al.  Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. , 2004, The American journal of clinical nutrition.

[63]  K. Raivio,et al.  FRUCTOSE-INDUCED HYPERURICÆMIA , 1967 .

[64]  G. Burdock,et al.  Evidence-Based Review on the Effect of Normal Dietary Consumption of Fructose on Development of Hyperlipidemia and Obesity in Healthy, Normal Weight Individuals , 2009, Critical reviews in food science and nutrition.

[65]  A. Harper,et al.  Dietary guidelines for Americans. , 1981, The American journal of clinical nutrition.

[66]  P. Havel,et al.  Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance , 2008, Current opinion in lipidology.

[67]  A. Astrup,et al.  Effect of sucrose on inflammatory markers in overweight humans. , 2005, The American journal of clinical nutrition.

[68]  J. Rippe,et al.  The effect of high-fructose corn syrup consumption on triglycerides and uric acid. , 2009, The Journal of nutrition.

[69]  F. Hu,et al.  Intake of sugar-sweetened beverages and weight gain: a systematic review. , 2006, The American journal of clinical nutrition.

[70]  J. Rippe,et al.  Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women. , 2007, Nutrition.

[71]  Kevin D Hall,et al.  Energy balance and its components: implications for body weight regulation. , 2012, The American journal of clinical nutrition.

[72]  M. Hellerstein No common energy currency: de novo lipogenesis as the road less traveled. , 2001, The American journal of clinical nutrition.

[73]  W. Willett,et al.  Sugar-Sweetened Beverages and Risk of Metabolic Syndrome and Type 2 Diabetes , 2010, Diabetes Care.

[74]  M. Chong,et al.  Mechanisms for the acute effect of fructose on postprandial lipemia. , 2007, The American journal of clinical nutrition.

[75]  M. Wicklmayr,et al.  [Utilization of glucose and fructose in human liver and muscle]. , 1976, Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Beiheft.

[76]  E. Ravussin,et al.  A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans. , 2006, The American journal of clinical nutrition.

[77]  P. Marckmann Dietary treatment of thrombogenic disorders related tothe metabolic syndrome , 2000, British Journal of Nutrition.

[78]  Roseanne Menorca,et al.  Consumption of fructose and high fructose corn syrup increase postprandial triglycerides, LDL-cholesterol, and apolipoprotein-B in young men and women. , 2011, The Journal of clinical endocrinology and metabolism.

[79]  R. Phillips,et al.  Intestinal metabolism of orally administered glucose and fructose in Yucatan miniature swine. , 1984, The Journal of nutrition.

[80]  M. Segal,et al.  How safe is fructose for persons with or without diabetes? , 2008, The American journal of clinical nutrition.

[81]  M. Hellerstein,et al.  Regulation of hepatic de novo lipogenesis in humans. , 1996, Annual review of nutrition.

[82]  A. Prentice,et al.  De novo lipogenesis during controlled overfeeding with sucrose or glucose in lean and obese women. , 2001, The American journal of clinical nutrition.

[83]  K. Keim,et al.  Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. , 2012, Journal of the Academy of Nutrition and Dietetics.

[84]  B. Tomlinson,et al.  A study of the effect of oral glucose loading on plasma oxidant:antioxidant balance in normal subjects , 2005, European journal of nutrition.

[85]  G. Anderson Much ado about high-fructose corn syrup in beverages: the meat of the matter. , 2007, The American journal of clinical nutrition.

[86]  S. Turner,et al.  Short-term alterations in carbohydrate energy intake in humans. Striking effects on hepatic glucose production, de novo lipogenesis, lipolysis, and whole-body fuel selection. , 1995, The Journal of clinical investigation.

[87]  W. Thomas,et al.  Effects of dietary fructose on plasma lipids in healthy subjects. , 2000, The American journal of clinical nutrition.

[88]  John S. White,et al.  Misconceptions about high-fructose corn syrup: is it uniquely responsible for obesity, reactive dicarbonyl compounds, and advanced glycation endproducts? , 2009, The Journal of nutrition.

[89]  D. Ludwig,et al.  Hepatic Steatosis and Increased Adiposity in Mice Consuming Rapidly vs. Slowly Absorbed Carbohydrate , 2007, Obesity.