Arizona Advanced Medicine Clinic

High-fructose Corn Syrup: What's the Big Deal?

High-fructose corn syrup (HFCS) is a liquid sweetener similar to sucrose (table sugar) first introduced in the 1970s. Chemically it is similar to other sweeteners like agave, honey, and fruit juice concentrates which also contain Fructose and Glucose. But unlike table sugar, which has a 1:1 ratio of glucose to fructose, the ratio in HFCS is often modified to 42-55% fructose.[1] When combined with other ingredients, popular beverages made with HFCS can have even higher total fructose-to-glucose ratios. Fruit juices can have twice as much fructose as glucose.[2] To metabolize sucrose, stomach acids have to break apart the bonds between glucose and fructose but, in HFCS, there are no bonds to break, effectively bypassing this important digestion step. The result of this bypass appears to be that fructose in HFCS is absorbed much faster into the blood stream than for sucrose. Likely the small amounts of fructose present in natural foods (such as fruit) are slowly absorbed and then completely or almost completely metabolized by the intestines and liver, therefore little or no fructose would pass into the blood stream.[3] So, even though fructose is present in natural foods, it is contained in a way that it was perhaps never destined to reach our blood stream intact.

To make HFCS, corn starch (glucose) is modified by acids and enzymes to convert some of it into fructose.[4] The mixture of glucose and fructose is HFCS, and different formulations are created by changing the amounts of fructose.[5] HFCS also goes by other names such as Maize syrup, Glucose syrup, Tapioca syrup, Dahlia syrup, Fruit fructose, Fruit sugar, and Crystalline fructose, so identifying it on a food label is not always easy.[2] The Corn Refiners Association recently petitioned the FDA to change the name to "corn sugar." [6] Their petition was ultimately rejected. Look at the first ingredient listed for the popular children's drink Juice Plus+®.

From 1970 to 2000 there was a 25% increase in “added sugars” in the U.S., and HFCS replaced sucrose as the main sweetener of soft drinks.[7, 8] During this same time, obesity rates in the US increased, leading many to question if the two are related. It is to be noted that the consumption of flour, cereal products, and added fats also increased.[1, 8] The European Union did not experience this massive switch to this corn-based, chemically modified sweetener, where it is known as Fructose-Glucose Syrup (GFS) or Isoglucose. In the EU, GFS is limited to only 5% of the total sugar production and, soft drinks continue to be sweetened mostly with sucrose. In the US, they are sweetened with HFCS. Obesity rates have also risen in the EU without a rise in GFS intake. Therefore the increase in obesity does not seem to be related entirely to GFS/HFCS consumption.[9]

HFCS makes up 40 percent of caloric sweeteners added to foods and beverages.[10] (Non-caloric sweeteners include Aspartame, Saccharin, and Sucralose, although they are not necessarily healthier than HFCS.[11]) The use of HFCS in our food chain is not likely to decrease any time soon. Government subsidies for corn keep HFCS cheaper to use than table sugar. Still, there are some signs of change. Recently Kraft foods decided to remove HFCS from Capri Sun 12 but Pepsi Co. is not willing to follow suit, despite Panera's request.[13]

Since HFCS is so ubiquitous in the US foods, what is the big deal? For starters, a study from Columbia University demonstrated more than one HFCS soda per day was associated with increased risk of having gout, kidney stones, and chronic kidney disease.[14, 15, 16, 17] Consumption of sweetened beverages (containing either sucrose or HFCS) is associated with obesity, diabetes, heart disease, accelerated aging, non-alcoholic fatty liver disease, high cholesterol and lipids, and irritable bowel syndrome, just to name a few.[1, 3] To explore further, we should look at how our body processes fructose and glucose.

Fructose is rapidly metabolized almost exclusively in the liver, whereas glucose is metabolized in many other organs. In the liver, fructose metabolism leads to a transient depletion of phosphate and results in the production of an acid called lactic acid, which is released into the systemic circulation.[1] (Lactic acid is more typically produced in muscle cells and red blood cells during intense exercise.) This fructose-induced hyperlactatemia may contribute to the suppression of breakdown of fat cells, providing an additional mechanism for causing obesity.[18]

Fructose is also converted into glucose and fatty acids. A substantial portion of fructose-derived glucose is stored in the liver as glycogen. Glycogen is typically used during times of fasting to maintain normal blood glucose levels. More glycogen is stored from fructose than from an equivalent dose of glucose.[19] But fructose also decreases sensitivity to insulin and it does not require insulin for transport, unlike glucose.[10] When someone is less sensitive to insulin, glucose production remains activated and does not receive the signal (insulin) to turn off. This is especially a problem for diabetic patients who have shown a markedly enhanced insulin response to fructose compared with nondiabetic people, potentially dropping their blood glucose levels to dangerously low levels. [20, 21]

A high-fructose diet leads to elevated fatty acid and lipid levels, especially two components of cholesterol: triglycerides (TGs) and Very Low Density Lipoproteins (VLDLs), and was shown to occur in healthy people after just one week of a high-fructose diet, through increased lipid production in the liver and decreased clearance. [22,23] For unclear reasons, this effect occurs to a greater extent in obese people and to a lesser degree in premenopausal, healthy females.[24, 25] High VLDL and TG levels are associated with increased risk of heart disease and stroke. When lipids are stored in the liver, this can lead to nonalcoholic fatty liver disease (NAFLD), which is also is tightly linked to insulin resistance. Thankfully, these effects can be reversed. In some studies, the effect of fructose on lipid levels can be ameliorated with fish oil supplementation, using honey for sweetener instead of corn syrup, and changing the bacteria in the intestines.[26, 27, 28]

Changing the types and amounts of bacteria in the intestinal tract can be accomplished through the use of prebiotics and probiotics. Sometimes in severe cases, a short course of antibiotics are given initially, especially for Small Intestine Bacterial Overgrowth (SIBO). In our experience, the amounts of probiotics necessary to see clinical improvement often exceed what are sold in health-food stores, groceries, and retail pharmacies.

In addition to its effects on the chronic diseases like diabetes and hyperlipidemia described above, fructose causes an increase in blood pressure, which is not seen with glucose.[29]

There is evidence to suggest that fructose decreases a person's sensation of fullness after a meal, called satiety, which typically signals to the brain to stop eating. After eating a meal high in fructose, the rise in blood glucose is blunted since its glycemic index is about fivefold lower than that of glucose. A rise in glucose level and resultant release of insulin is one way the brain knows it is time to stop eating. A high fructose meal also blunts the suppression of the appetite-stimulating hormone ghrelin, compared to a meal containing an equivalent amount of glucose. Leptin is a hormone released from fat cells which signals to the brain to decrease the overall appetite. Obese people often have increased leptin levels but are resistant to its effects. In addition to producing a lesser secretion of leptin compared with equivalent doses of glucose, it has been observed that high fructose intake impairs leptin’s actions, suggesting fructose-induced leptin resistance.[30, 31] Leptin resistance may also contribute to causing fructose-induced NAFLD.[32]

In summary, HFCS contains the same fructose and glucose molecules as "natural" table sugar (sucrose) but they are manufactured in varying ratios and are not bound together. The increase in obesity does not seem to be related entirely to HFCS consumption, but HFCS is present in many processed foods in the US. Consumption of sweetened beverages is associated with increased rates of gout, kidney stones, chronic kidney disease, obesity, diabetes, heart disease, accelerated aging, non-alcoholic fatty liver disease, high cholesterol and lipids, and irritable bowel syndrome. The fructose is of particular concern for several reasons. It increases lactic acid production, which may cause obesity. A substantial portion of fructose-derived glucose is stored in the liver as glycogen and fatty acids. Over time these can build up and cause NAFLD. Fructose decreases sensitivity to insulin, keeping glucose production going even when there is an abundance of sugars. A high-fructose diet leads to increased lipid production and decreased clearance fatty acids and lipids, including cholesterol, which is associated with increased risk of heart disease and stroke. These effects can be reversed with fish oil, honey, and changing the intestinal tract flora. Fructose causes an increase in blood pressure and increases appetite.

Finally, many are familiar with one of the most socially undesirable effects of fructose. When it is incompletely absorbed from the gut and is fermented by intestinal bacteria, gas is produced. And we all know how much fun gas is, when you are a kid, and how much not fun it is when you grow up.

For more information or for assistance with modifying your diet, give our office a call at 480-240-2600. We are happy to schedule a free 15-minute phone consultation with one of our practitioners, to help you determine whether we are the best medical office for you.

[1] Luc Tappy, Kim-Anne Lê. Metabolic Effects of Fructose and the Worldwide Increase in Obesity. Physiological Reviews Jan 2010, 90 (1) 23-46.
[2] Walker RW, Dumke KA, Goran MI. Fructose content in popular beverages made with and without high-fructose corn syrup. Nutrition. Volume 30, Issues 7-8, July-August 2014, Pages 928-935.
[3] Gaby AR. Adverse effects of dietary fructose. Altern Med Rev. 2005 Dec;10(4):294-306.
[4] Marshall RO, Kooi ER. Enzymatic conversion of D-glucose to D-fructose. Science 125: 648-649, 1957.
[5] High Fructose Corn Syrup: Questions and Answers. FDA. http://www.fda.gov/Food/IngredientsPackagingLabeling/FoodAdditivesIngredients/ucm324856.htm
[6] Parker-Pope T. A New Name for High-Fructose Corn Syrup. New York Times Blogs. SEPTEMBER 14, 2010. http://well.blogs.nytimes.com/2010/09/14/a-new-name-for-high-fructose-corn-syrup/?_r=0
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[8] White JS. Straight talk about high-fructose corn syrup: what it is and what it ain’t. Am J Clin Nutr. 2008 Dec;88(6):1716S-1721S.
[9] European Food Information Council. http://www.eufic.org/page/en/page/FAQ/faqid/glucose-fructose-syrup/
[10] Mohr CR. The Dangers of High Fructose Corn Syrup. Diabetes Health. http://www.diabeteshealth.com/uncategorized/the-dangers-of-high-fructose-corn-syrup/
[11] Suez J., et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, 181-186, 2014.
[12] Hogan B. Kraft’s Capri Sun drinks to drop high-fructose corn syrup. Chicago Tribune. Feb. 10, 2015. http://www.chicagotribune.com/business/breaking/chi-capri-sun-drops-corn-syrup-20150210-story.html
[13] Unglesbee B. Panera head chef to PepsiCo: High-fructose corn syrup going off menu. St. Louis Business Journal. Jul 6, 2015. http://www.bizjournals.com/stlouis/news/2015/07/06/panera-head-chef-to-pepsico-high-fructose-corn.html
[14] Bomback AS. Sugar-sweetened soda consumption, hyperuricemia, and kidney disease. Kidney International (2010) 77, 609-616.
[15] Choi HK, Curhan G. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. BMJ 336: 309-312, 2008.
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[20] Crapo PA, Insel JI, Sperling M, Kolterman OG. Comparison of serum glucose, insulin and glycogen responses to different types of complex carbohydrates in non insulin dependent diabetic patients. Am J Clin Nutr 34: 184-190, 1981.
[21] Crapo PA, Kolterman OG, Olefsky JM. Effects of oral fructose in normal, diabetic, and impaired glucose tolerance subjects. Diabetes Care 3: 575-582, 1980.
[22] Livesey G, Taylor R. Fructose consumption and consequences for glycation, plasma triacylglycerol, and body weight: meta-analyses and meta-regression models of intervention studies. Am J Clin Nutr 88: 1419-1437, 2008.
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[24] Teff KL, et al. Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: influence of insulin resistance on plasma triglyceride responses. J Clin Endocrinol Metab 94: 1562-1569, 2009.
[25] Ashley JM, St Jeor ST, Perumean-Chaney S, Schrage J, Bovee V. Meal replacements in weight intervention. Obes Res 9 Suppl 4:312S-320S, 2001.
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[27] Busserolles J, et al. Substituting honey for refined carbohydrates protects rats from hypertriglyceridemic and prooxidative effects of fructose. J Nutr 132: 3379-3382, 2002.
[28] Bergheim I, et al. Antibiotics protect against fructose induced hepatic lipid accumulation in mice: role of endotoxin. J Hepatol 48: 983-992, 2008.
[29] Brown CM, Dulloo AG, Yepuri G, Montani JP. Fructose ingestion acutely elevates blood pressure in healthy young humans. Am J Physiol Regul Integr Comp Physiol 294: R730-R737, 2008.
[30] Teff KL, et al. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab 89: 2963-2972, 2004.
[31] Le KA, et al. A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans. Am J Clin Nutr 84: 1374-1379, 2006.
[32] Vila L, et al. Suppressor of cytokine signaling-3 (SOCS-3) and a deficit of serine/threonine (Ser/Thr) phosphoproteins involved in leptin transduction mediate the effect of fructose on rat liver lipid metabolism. Hepatology 48: 1506-1516, 2008.
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