High Fructose Corn Syrup

1. High Fructose Corn Syrup Does It Have Unique Unhealthy Effects? County of Los Angeles Public Health Department Nutrition Program Christopher J. Jarosz, Ph.D. July 13, 2007

2. Preface After reviewing a wide variety of literature sources my sense is this brief analysis—or possibly any analysis on high fructose corn syrup—will change few minds about a contentious nutritional issue.

3. A Historical Perspective It can be said with near certainty that Willy Wonka didn’t use high fructose corn syrup in his chocolates since HFCS wasn’t in production in 1964, and is still not used to any great extent in the United Kingdom. Picture Source: Roald Dahl, Charlie and the Chocolate Factory (illustrated by Quentin Blake). New York: Alfred A. Knopf, 1964.

4. Contents • The vibe • Background • Sources of fructose • Chemistry • Biological mechanisms • Role of sweetness • Obesity and overweight rates • Caloric sweeteners in other countries • Future of HFCS? • Summary and conclusion • The role of complex root causes • References • Organizational associations

5. The Vibe Many concerns have been expressed about possible unhealthy aspects of HFCS compared to cane and beet sugars. • HFCS is an artificial, manufactured product and not a natural food for healthy living. • HFCS may have been produced with genetically modified corn and enzymes. • HFCS has adverse biological effects equal to those observed with 100 percent fructose. • HFCS circumvents normal metabolic pathways and hormonal control loops for appetite and satiety. • HFCS is much sweeter than sucrose, which makes it a more desirable product. • HFCS is profoundly bad—for example, a Florida state legislator called HFCS the crack of sweeteners. (References 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12)

6. The Vibe (continued) • HFCS use coincides with steady and substantial increases in overweight and obesity rates since its introduction in the early 1980’s. • HFCS is aggressively promoted by agribusiness with government support and even complicity (depending on point of view). • Many countries continue to use sucrose as the primary caloric sweetener in foods and beverages.

7. Background • The HFCS conversion process was perfected in the 1970s, and HFCS was introduced as a lower-cost substitute in soft drinks, baked goods, and other foods starting in the early-1980s. • The United States and Canada are the two principal countries to use HFCS possibly due to the abundance of corn, agribusiness influence, politics, and economics. • HFCS with few exceptions is used in calorically-sweetened soft drinks, and in some juices. • HFCS is used in many bakery, processed, and canned foods as a caloric sweetener, shelf-life extender, and browning agent, among other functions. • Many countries have not made a major shift to HFCS possibly because of the low cost of sucrose (table sugar) in markets absent sugar protectionist measures. (References 11, 12, 13, 14, and 15)

8. Background (continued) • HFCS is a liquid, and is easier to transport (often by tanker truck), handle, and store than table sugar in its granular form. HFCS also has amenable cooking and baking properties. • The low cost of HFCS may have promoted increased sugar consumption during the past 25 years by stimulating production, introduction into many foods, and promotion of “super-sizing,” among other food industry practices. • Sweeteners are typically a small component of food production, distribution, and marketing costs although a few cents at the unit level can result in many dollars across an entire inventory.

9. Sources of Fructose (References 14 and 16)

10. Chemistry—HFCS • Glucose and glucose polymers in corn starch are converted through enzymatic reactions to corn syrup, and then to high fructose corn syrup. The process is performed on an industrial scale. • The enzymes consist of: 1) alpha-amylase to break the polysaccharides into shorter chains; 2) glucoamylase to break the shorter chains into glucose; and 3) glucose isomerase to convert glucose to a mixture of glucose and fructose. • Corn starch, alpha-amylase and glucoamylase in some instances are thought to be genetically modified, although residue may not be detectable in HFCS. • HFCS consists of 55 percent fructose (e.g., soft drinks) or 42 percent fructose (e.g., baked goods). The fructose-to-glucose ratio can be modified by adding corn syrup, which consists of glucose and its polymers. • HFCS has about the same percentage of fructose as disaccharide sucrose (table sugar) and honey, but less than fruit since fructose is its only natural sugar. • “High fructose” is in reference to corn syrup, which contains no fructose but only glucose and its polymers. The “HF” in HFCS has been a key aspect in the ongoing debate and has led to confusion over what is the true referent. (References 3, 14, and 15)

11. Chemistry—Glucose and Fructose • Fructose has the same molecular formula and structural shape regardless of its source (e.g., HFCS, sucrose, honey, and fruit). • Fructose and glucose are isomers—identical molecular formulas (C6H12O6) but different structural shapes. • In HFCS fructose and glucose are monosaccharides, or free molecules (absent the glycosidic bond found in disaccharides). • In honey glucose and fructose are monosaccharides formed through hydrolysis of the sucrose in nectar. • In sucrose glucose and fructose are a disaccharide formed in sugar cane and sugar beets through dehydration synthesis. • Sucrose is rapidly broken into its monosaccharides (glucose and fructose) by hydrolysis in the small intestine, which is facilitated by the enzyme, sucrase. • An acidic environment, such as in soft drinks and the stomach, can facilitate breakage of the glycosidic bond. • HFCS and honey require no breakage since their constituent sugars exist as monosaccharides. (References 14, 15, and 17)

12. Chemistry—Glucose and Fructose (continued) • Glucose and fructose are transported across the small intestine epithelium to the portal vein. Absorption rates and completeness of the process are about equal. • Fiber can slow absorption rate of fructose and glucose to modulate glycemic load. • Glucose and fructose are monosaccharides in the circulatory system (i.e., they don’t exist as HFCS and sucrose in the blood serum, contrary to a few media reports).

13. Biological Mechanisms—Glucose • Glucose and fructose have different biological mechanisms for absorption and metabolism. • Glucose is absorbed by a sodium-glucose hexose transporter (SGLUT-1) in the small intestine for entry into portal circulation. • Blood glucose levels are normally regulated with great precision by a negative feedback mechanism involving insulin secretion by the B cells of the pancreas. • Insulin receptors are found in many different cells in the body, and insulin has wide ranging effects including on hypoglycemic action, amino acid and electron transport, enzyme regulation, and cellular growth. • In response to glucose another pancreatic cell type secretes glucagon, which provides satiety signals to the brain and regulates other aspects of metabolism. • Glucose is used in the glycolysis stage of cellular respiration to generate ATP, provide pyruvic acid to the Krebs cycle, and contribute high-energy electrons to NAD+ for the electron transport chain in the mitochondrial membrane. ATP is generated for performing cellular work. (References 17 and 18)

14. Biological Mechanisms—Fructose • Fructose is absorbed in the small intestine by a non-sodium dependent process and enters portal circulation. • Fructose is transported to the liver for conversion to glucose, and a portion also passes to general circulation. • Fructose does not stimulate insulin production since the pancreatic B cells lack the fructose transporter, GLUT-5. • High levels of fructose provide a unregulated source of carbon precursors for lipid production in the liver (hepatic lipogenesis). • Leptin, a polypeptide, is released by fat cells to reduce food intake through a feedback loop with deep brain structures (most notably the ventromedial area of the hypothalamus). • Insulin increases leptin secretion through the regulation of glucose metabolism in fat cells; but this mechanism is not activated by circulating levels of fructose. (References 18, 19, and 20)

15. Biological Mechanisms—Fructose (continued) • The release of the polypeptide, ghrelin, from the stomach is apparently not inhibited by even high levels of fructose in the blood serum (unlike glucose). Ghrelin acts on the hypothalamus to signal the need to increase food intake. • Although glucose can directly provide satiety signals to the hypothalamus, fructose does not because the molecule cannot pass the blood-brain barrier. • Substantial fructose ingestion (regardless of its source) can produce weight gain since the control mechanisms for glucose are not activated in response to fructose. • In animals substantial fructose intake has been implicated in the classic insulin resistance syndrome including insulin resistance, impaired glucose tolerance, hyperinsulinemia (excess insulin), hyperlipidemia (excess triglycerides), and hypertension. • In contrast, for beverages sweetened with HFCS or sucrose, no differences were found for fasting plasma glucose, insulin, leptin, and ghrelin in normal-weight women. • Previous studies often used pure fructose, which has a much higher fructose content than HFCS.

16. Biological Mechanisms—Summary • Glucose and fructose exist as monosaccharides in the circulatory system, and have different metabolic pathways and different effects on biological control mechanisms. • HFCS is not pure fructose although the two terms are used interchangeably in some media reports. • The biological effects of fructose on metabolism, appetite, and satiety should apply to both sucrose and HFCS since each contains similar ratios of glucose and fructose. • Although sucrose is a disaccharide and HFCS contains free molecules prior to ingestion, there is no reason to believe absorption and metabolism are different for one source of fructose versus another source since sucrose is hydrolyzed in the small intestine. • Fructose and glucose in honey are ingested as monosaccharides. Any parallels between free fructose molecules in HFCS and honey apparently have not been explored. (Added reference 21)

17. Biological Mechanisms—Summary (continued) • Conceivably,100 percent fructose in fruit would have adverse effects on lipid production, appetite control, and weight gain; however, fruits have much lower amounts of fructose than foods and beverages containing HFCS or sucrose. • Some fruit juices have a very high concentration of naturally-occurring fructose. The glycemic load can be mitigated to an extent by the fiber content.

18. Role of Sweetness • Sweetness is a sensation that is not directly measurable due to the complex interaction of biological, psychological, and environmental factors. • Taste sensations are generally assessed through psychophysical methods involving systematic, controlled comparisons and associated verbal reports. • In biological sensory systems an incremental, threshold changes in stimulus intensity must be achieved for the change in the sensation to be detectable. • This is because biological systems process sensory input logarithmically (the base number varies among sensory modalities), which reduces sensitivity to small stimulus changes. • Neither glucose nor corn syrup convey a high sensation of sweetness, which makes them ineffective sweeteners. • Pure fructose is very sweet (which at least one study attempted to generalize to HFCS). • HFCS conveys a sweetness sensation in approximate relationship to fructose content. (References 12 and 22)

19. Role of Sweetness (continued) • HFCS-55 could presumed to be about ten percent sweeter than sucrose by applying simple mathematics (55 versus 50 percent fructose). • Sensory thresholds and neural processing, however, would also need to be considered. • Food consumers are probably not getting specifically hooked on HFCS since it produces, at most, a slightly greater sensation of sweetness than sucrose.

20. Obesity and Overweight Rates • In the U.S. overweight and obesity rates have climbed almost simultaneously with the introduction of HFCS. (Some increases had occurred in the previous 20 years.) • The association between HFCS and increasing obesity and overweight rates in the U.S. is intriguing • Food marketing and promotional practices became increasingly aggressive starting in the early-1980’s, which may have also played a substantial role. • For example, super-sizing originated in the early-1980’s which complicates a potential causal relationship. • Associations exist between the overconsumption of sugar and overweight and obesity, but very little empirical data exist for singling-out HFCS as the unique sugar culprit. • Barry M. Popkin, who hypothesized a causal link between HFCS and recent obesity and overweight rates, has supposedly backed-off the claim of HFCS being any worse than sucrose. (References 3, 11, 13, and 21)

21. Obesity and Overweight Rates (continued) • A public health problem exists with overconsumption of sugars, but it is not unique to HFCS.

22. Caloric Sweeteners in Other Countries • HFCS is not used to a substantial degree outside of the U.S. and Canada. • The price of sugar cane is much lower in other countries due to the lack of trade barriers. • Weight gains among adults and children have apparently been noted in a number of other countries where sucrose is the primary caloric sweetener. • The weight gains are in parallel with the general trend in the United States. • However, I haven’t done any research to substantiate these observations. (References 11, 13, and 15)

23. Future of HFCS? • The economics of caloric sweeteners may change substantially in the next few years. • The diversion of corn to ethanol production and accompanying price increases could spur food and beverage companies in the U.S. to consider other sources of caloric sweeteners including sucrose and sucralose (trade name, Splenda). • In Brazil, however, ethanol is produced from cane sugar on a large scale to meet the government’s goal of replacing 40 percent of the country’s gasoline requirements. • General Motors touts the gasoline/ethanol blend, E85, as its “green” solution (probably because it has few hybrid and alternative energy vehicles in design or production). • The U.S. President and some members of Congress view corn-based ethanol as a way to reduce our dependence on foreign oil. Potential adverse effects on food production, availability, and costs are not being addressed. HFCS might become a less desirable sweetener for food and beverage producers for reasons unrelated to any nutritional concerns. Cane sugar and beet sugar production could also face pressure from energy needs. (References 23 and 24)

24. Summary

25. Conclusion • For equal amounts of consumption, HFCS is no better or worse than sucrose in its health effects including on the insulin response, appetite and satiety control, and lipogenesis and weight gain. • HFCS is sometimes equated with 100 percent fructose in its adverse effects on metabolic control including poor insulin regulation and excess lipid production. • This is an inaccurate comparison, though, since HFCS typically contains either 55 or 42 percent fructose and 40 percent or more glucose, and in approximate ratios found in sucrose. • HFCS is in many foods and beverages as a sweetener among other functions. Its ubiquity probably contributes to obesity and overweight rates although it is not the sole factor. • What caloric sweetener would replace HFCS if it disappeared from foods? A substantial shift to sucrose would probably have similar effects on obesity and overweight rates.

26. The Role of Complex Root Causes It seems to be human nature to seek a one predominant cause although major problems often have complex etiologies. The overweight and obesity problem has many contributing factors including overconsumption of sugars and empty calories, food ubiquity (it’s everywhere), aggressive food advertising and marketing practices, national and regional politics, lobbying and government response, school nutrition policies and practices, physical education policies and practices, availability of nutrition education, aspects of the built environment, lifestyle trends, and socioeconomic disparities, among other factors.

27. References The first 12 references, except for the third reference, are from media sources to depict some of the popular thinking about HFCS • ________. High fructose corn syrup. www.menstuff.org, accessed 21 June 2007. • Alston, W.D. Does high-fructose corn syrup have to be in everything? www.lewrockwell.com, accessed 21 June 2007. • Bray, G.A., Nielsen, S.J., and Popkin, B.M. Consumption of high-fructose corn syrup in beverages may play a role in the obesity epidemic. American Journal of Clinical Nutrition, 2004;79:537-543. • Grace, R.M. High fructose corn syrup: danger of current era. www.metnews.com, accessed 21 June 2007. • Lempert, P. High-fructose corn syrup: sugar on crack? www.nbc.com, accessed 21 June 2007. • Mercola, J. Fructose: the stealth sugar. www.mercola.com, accessed 21 June 2007. • Mirkin, G. High fructose corn syrup and obesity. www.drmirkin.com, accessed 21 June 2007. • .

28. References (continued) • Sanda, B. The double danger of high fructose corn syrup. westonaprice.org, accessed 21 June 21 2007. • Sears, A. Want corn syrup with that? Health Alert 187. www.alsearsmd.com, accessed 21 June 2007 • Severson, K. Sugar coated: we’re drowning in high fructose corn syrup. Do the risks go beyond the waistline? www.sfgate.com, accessed 21 June 2007. • Warner, M. A sweetener with a bad rap. New York Times, 6 July 2006 (also can be found at www.nytimes.com). • White, J.S. and Foreyt, J.P. Ten myths about high-fructose corn syrup. Food Technology. October 2006. www.ift.org, accessed 21 June 2007. • Nuttall, F.Q. Editorial: How Sweet It Is. Nutrition Today. 2005;40:246-247. • Schorin, M.D. High fructose corn syrups, part I. Nutrition Today. 2005;40:248-252. (Preparation of the paper was funded by the American Beverage Association and the Corn Refiners Association.) • White, J.S. High fructose corn syrup and sucrose: reassuring similarities and complementary differences. Corn Annual 2004. Corn Refiners Association, 2004. • Nestle, M. What to Eat. New York: North Point Press, 2006. • .

29. References (continued) • Hein, G.L., Storey, M.L., White, J.S., and Lineback, D.R. Highs and lows of high fructose syrup. Nutrition Today. 2005;40:253-256. • Ganong. W.F. Review of Medical Physiology, 22e. New York: Lange Medical Books, 2005. • Elliott, S.S., Klein, N.L. Stern, J.S., Teff, K., and Havel, P.J. Fructose, weight gain, and the insulin resistance syndrome. American Journal Of Clinical Nutrition, 2002; 76:911-922. • Melanson, K.J., Zukley, L., Lowndes, J., Nguyen, V., Angelopoulos, T.J., and Rippe, J.M. Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women. Nutrition. 2007;23:103-112. (Research was funded by PepsiCo.) • Schorin, M.D. High fructose corn syrups, part 2: health effects. Nutrition Today. 2006;41:70-77. • Boff, K.R., Kaufman, L., and Thomas, J.P. (eds.) Handbook of Sensation and Perception, Volume 1: Sensory Processes and Perception. New York: John Wiley and Sons, 1986. • .

30. References (continued) • Philpott, T. ADM, high-fructose corn syrup, and ethanol. www.gristmill.grist.org, accessed 21 June 2007. • ________. Coke concerned about corn syrup prices. www.reuters.com, accessed 10 July 2007. • .

31. Organizational Associations • Several websites cited in “the vibe” section focus on natural foods and natural healing. • Marilyn D. Schorin is the president of Focus Nutrition LLC, “a consulting firm specializing in strategic planning, project management, and media outreach for the food and functional food industry.” • John S. White is the principal of White Technical Research in Argenta, Illinois, a consulting firm focusing on “the physical, functional, and metabolic properties of nutritive sweeteners.”