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The consumption of high-fructose corn syrup (HFCS or glucose–fructose syrup) and its relationship to a healthy diet is a subject of investigation. Evidence does not indicate it is less healthy than sugar consumption in general. Concerns center around excessive sugar intake and its contribution to obesity, type-2 diabetes, metabolic syndrome, and cardiovascular disease.
The term high-fructose corn syrup was developed to distinguish it from all-glucose corn syrups that existed in the past, and does not accurately describe the composition of the syrup (which is composed of a mixture of 42-55% fructose, 41-45% glucose and 0-5% glucose polymers depending on the specific blend). In the 1980s it replaced sucrose as the main sweetener of soft drinks in the United States. Sucrose is a disaccharide that when consumed, is hydrolysed into 50% glucose and 50% fructose. Rates of obesity subsequently rose, paralleling an increase in the consumption of soft drinks in general, but have not been linked to the usage of HFCS. Additional concerns have been raised due to laboratory research that suggested a link between consuming large amounts of fructose and changes to various proxy health measures including elevated blood triglycerides, size and type of low-density lipoproteins and uric acid levels.
Numerous agencies in the United States recommend reducing the consumption of all sugars, including HFCS, without singling it out as presenting extra concerns. The Mayo Clinic cites the American Heart Association's recommendation that women limit the added sugar in their diet to 100 calories a day (~6 teaspoons) and that men limit it to 150 calories a day (~9 teaspoons), noting that there is not enough evidence to support HFCS having more adverse health effects than excess consumption of any other type of sugar. The United States departments of Agriculture and Health and Human Services recommendations for a healthy diet state that consumption of all types of added sugars be reduced.:p.27 Barry Popkin, Ph.D., a nutrition professor at the University of North Carolina stresses that the real obesity problem doesn’t lie just with HFCS. Rather, it’s the fact that sugars from all sources have become so prevalent in our food supply, especially in our beverages. He scoffs at the “natural” sweeteners sometimes added to upscale processed foods like organic crackers and salad dressings. “They all have the same caloric effects as sugar,” he explains. “I don’t care whether something contains concentrated fruit juice, brown sugar, honey or HFCS. The only better sweetener option is ‘none of the above.’”
A 2004 commentary in The American Journal of Clinical Nutrition suggested that the altered metabolism of fructose when compared to glucose may be a factor in increasing obesity rates since, as compared to glucose, fructose may be more readily converted to fat and the sugar causes less of a rise in insulin and leptin, both of which increase feelings of satiety. The authors suggested reducing intake of sugars by using sugar substitutes instead. In subsequent interviews, two of the study's authors stated the article was distorted to place emphasis solely on HFCS when the actual issue was the overconsumption of any type of sugar. While fructose absorption and modification by the intestines and liver does differ from glucose initially, the majority of the fructose molecules are converted to glucose or metabolized into byproducts identical to those produced by glucose metabolism. Consumption of moderate amounts of fructose has also been linked to positive outcomes, including reducing appetite if consumed before a meal, lower blood sugar increases compared to glucose, and (again compared to glucose) delaying exhaustion if consumed during exercise.
In 2007 an expert panel assembled by the University of Maryland's Center for Food, Nutrition and Agriculture Policy reviewed the links between HFCS and obesity and concluded there was no ecological validity in the association between rising body mass indexes (a measure of obesity) and the consumption of HFCS. The panel stated that since the ratio of fructose to glucose had not changed substantially in the United States since the 1960s when HFCS was introduced, the changes in obesity rates were probably not due to HFCS specifically but rather a greater consumption of calories overall, and recommended further research on the topic. In 2009 the American Medical Association published a review article on HFCS and concluded that based on the science available at the time it appeared unlikely that HFCS contributed more to obesity or other health conditions than sucrose, and there was insufficient evidence to suggest warning about or restricting use of HFCS or other fructose-containing sweeteners in foods. The review did report that studies found direct associations between high intakes of fructose and adverse health outcomes, including obesity and the metabolic syndrome. Other authors have disagreed, suggesting a link between HFCS and metabolic syndrome that is independent of obesity.
Part of the concern over fructose arises from animal testing in which the injection of fructose directly into the brain of rats led to increased eating and subsequent research in mice seemed to confirm this effect. Re-examination of the results suggested that the results in rodents would have little meaning in humans due to the dosage given (equivalent to a 75 kg human consuming 660 grams of fructose, whereas a "normal" daily intake is approximately 50 grams) and the strict control over the amount of fructose that crosses the blood–brain barrier. Subsequent testing with humans using both short- and long-term experiments found no important differences between the consumption of HFCS versus other sugars. Most of the studies linking fructose consumption to higher blood triglycerides have been in rodents through mechanisms different from those in humans, and therefore it is unlikely that high-fructose diets would have comparable effects in humans. Tests in humans suggest that for people with insulin resistance, diets with 50 grams or more per day (high consumption) may result in elevated triglycerides, but there is no effect with normal levels of fructose consumption.
Epidemiological research has suggested that the increase in obesity is linked to increased consumption of sugars and/or calories in general, and not due to any special effect of fructose alone. Although this may be true, there is also evidence that the type of fat that is gained during fructose consumption is more dangerous than normal table sugar. "Researchers in California recruited volunteers to drink a glass of Kool-Aid with every meal for 10 weeks; half took their soft drinks sweetened with fructose, the other half with glucose. By the end of the study period, both groups had put on weight, but the subjects getting fructose had more visceral fat—the kind that adheres to our organs and is associated with heightened risk for atherosclerosis, cardiovascular disease, and type 2 diabetes. The fructose group also showed higher levels of LDL cholesterol and lower insulin sensitivity." 
Consumption of HFCS has been associated with non-alcoholic fatty liver disease, as it is thought that fructose may cause increased fat deposits in the abdomen though it has also been suggested that this association is not unique to fructose and may be due to glucose consumption as well.
The presence of carbonyl compounds found in HFCS-containing beverages has been suggested as a contributor to poor health and problems for people with diabetes, though this concern is unfounded as HFCS is of no more concern than other sources and the compounds are produced endogenously by the body.
The possibility that significant consumption of products containing high fructose corn syrup with detectable levels of mercury could result in neurotoxicity was raised by studies in 2009. In 2011 the Corn Refiners Association announced that “no mercury or mercury-based technology is used in the production of high fructose corn syrup in North America.” By the end of 2012, most chlor-alkali plants in the United States had phased out older "mercury cell" technology linked to mercury contamination of HFCS, except for two chlor-alkali plants - one in Ohio and one in West Virginia, run by ASHTA Chemicals and PPG Industries, respectively. Mercury cell technology is still widely used outside of the United States and there are no restrictions on importing mercury-grade caustic soda for use in HFCS production.