A sour struggle between sweeteners is underway in a Los Angeles federal courtroom. The multi-billion-dollar case, pitting corn refiners against big sugar processors, centers around whether high fructose corn syrup (HFCS) is a “natural” type of “corn sugar” that is, for all intents and purposes, equivalent to sugar.

Several sugar refiners, including American Sugar Refining, Inc, sued corn refiners for $1.5 billion in damages, alleging that their advertisements making such claims about HFCS being a natural sugar are false. Corn refiners, including Archer Daniels Midland Co and Cargill Inc, counter sued for around $530 million, saying that sugar producers falsely claimed that HFCS has negative health effects, including causing obesity.

Heaps of scientific data tip toward the side of table sugar, finding that fructose, also called fruit sugar, has negative health effects not caused by other sugars. But, the data on whether that alone has driven epidemics of obesity and diabetes is shaky, researchers say. It’s likely that increased consumption of all types of sugar have fed bad health trends.

Both industries are keen to argue their cases, particularly amid consumers’ shifting sweet tooth. In 1999, corn refiners, with their cheap alternative to sugar, were in a tight race with their competitors. US corn refiners filled orders equivalent to 65.4 pounds of HFCS per US consumer, while sugar refiners delivered 66.4 pounds per consumer, according to the US Department of Agriculture. But the tables turned in subsequent years as concern over the health effects of HFCS took hold. By 2014, corn refiners were serving up only 45.6 pounds of HFCS per US consumer, while sugar producers delivered 68.4 pounds.

To regain the lead, corn refiners tried relabeling HFCS as “corn sugar.” In a 2008 to 2012 advertisement campaign, the producers touted the friendly sounding name and breezily noted that “sugar is sugar.” But the ads hit a sticking point in 2012 when the Food and Drug Administration ruled that corn refiners could not call HFCS “corn sugar.” According to the agency, a sugar is a food that is “solid, dried, and crystallized”—not a syrup. And “corn sugar” has been the common name for dextrose for more than 30 years. The agency found no justification for swapping sweetener names, which would potentially cause confusion.

Sweet studies

Meanwhile, scientists were busily working out the health effects of both HFCS and table sugar, which is the sugar sucrose. The two sweeteners have similar chemical composition: sucrose is made up of glucose and fructose chemically linked together. HFCS is made from enzymatically treated corn starch and largely consists of unlinked glucose and fructose. The main difference between the two is the amount of fructose in each. Sucrose is 50 percent fructose, while HFCS can be up to 65 percent [PDF] fructose.

Fructose is a simple sugar naturally found in fruits. When eaten in small amounts, with all the water, fiber, vitamins, and minerals in fruit, the sugar is fine, researchers say. But added in higher concentrations to processed foods and sweetened beverages, it becomes a problem.

In both human and animal studies, fructose decreased adenosine triphosphate content in the liver and boosted fat production, which could lead to insulin resistance and fat accumulation in the liver. It may also alter sugar production in that organ, resulting in higher serum glucose levels and, potentially, global insulin resistance. That can in turn lead to diabetes. Eating sucrose is also known to increase insulin resistance, but remember that it contains both glucose and fructose—in a small trial comparing diets supplemented with either isolated fructose or isolated glucose, fructose was responsible for insulin resistance.

Growing evidence also suggests that fructose can alter neuronal systems. By boosting the appetite-inducing hormone ghrelin, the sugar may slow down areas of the brain responsible for feeling full. The net effect could lead people to eat more. Animal studies have also found that fructose can increase insulin resistance in the brain, which was associated with impaired memory in male hamsters and rats.

Outside of clean animal studies and into messier human trials, data suggests that swapping glucose for fructose-containing sucrose results in increased insulin resistance. And those negative effects were more profound as the dose of fructose increased.

“If some is bad, more is worse,” Sean Lucan, associate professor of family and social medicine at Albert Einstein College of Medicine, told Ars. The finding suggests that the seemingly small difference in the amount of fructose between sucrose and HFCS makes the latter the worse option between sweeteners.

But, Lucan cautions, in real-life dieting, the difference may be moot. If you’re eating a food with 10 grams of sweetener, whether that’s 10 grams of sugar or HFCS, the absolute difference is going to be small. “You’re kind of parsing hairs,” he said. “It’s still just a bad idea to eat a bunch of food with added sugars.” And substituting real sugar for HFCS in things like soda and ketchup may give those products a “false halo,” suggesting that they’re somehow healthful, he added.

Cloying controversy

Of course, those points may be lost in the court battle between HFCS producers and sugar refiners. Also, not everyone agrees that the scientific literature paints a clear picture that fructose is more problematic than other types of caloric sweeteners.

That may be partly due to bias and conflict of interest in some studies, Lucan and colleagues noted in a literature review. For instance, among trials that were funded by or had other financial ties to the food industry, 83 percent concluded that there was a lack of data to link sugar-sweetened beverages to risks of weight gain. On the other hand, of studies with no financial conflicts of interest, 83 percent found that there was a link between sweetened beverages and risk of weight gain.

The review, which concluded that fructose and overall increases in sugar consumption are drivers of diabetes, got immediate backlash. In a rebuttal letter, researchers alleged that the studies and trials in the review were of low quality. In particular, the letter writers, led by John Sievenpiper of the University of Toronto (who has financial ties to the industry), noted that some of the clinical trials didn’t adjust for calorie differences when they compared diets with different sugars. Thus, differences in health consequences may be due to caloric intake and not specific effects of the sweeteners. The authors reference other studies finding that fructose may have positive health effects, including improvements in controlling blood sugar.

Sievenpiper did not respond to requests for comment.

In response, Lucan and coauthors acknowledge that sugar “substitution” trials and adding things to people’s diets are tricky and more research is needed. But they hold to their conclusions and note that other studies have clearly shown that when people in real life switch up their diets—perhaps swapping HFCS-containing drinks for sugar-sweetened ones—they don’t carefully calculate and match their calorie intake.

Future research should tease out the effects of substituting one type of sugar for another versus adding sugars, Lucan said. “But no added sugar is a good thing,” he said.

Mayo Clinic Proceedings, 2015. DOI: 10.1016/j.mayocp.2014.12.019 (About DOIs).