Sweetener scrutiny: Are sugar substitutes a helpful tool or an ineffective crutch?

The rats in the West Lafayette, Ind., laboratory of Susan Swithers, PhD, don't lose weight when they eat artificially sweetened food. They eat more, and gain more. "Rather than these kind of products making it automatically easier to lose weight, they might make it automatically harder," said Dr. Swithers, a Purdue University associate professor of psychological sciences.

Her study documenting this phenomenon, in the February Behavioral Neuroscience, is the latest flare-up in the decades-long debate regarding the safety of artificial sweeteners and whether they aid weight loss. Cancer fears related to these products may have faded, but the theory they might trigger overeating lives on.

New evidence from some epidemiological studies supports that view. A paper in the Feb. 12 Circulation, for instance, associated drinking one can of diet soda per day with a 34% increased risk of developing metabolic syndrome compared with those who did not drink any carbonated beverages. People who drank the sugar-sweetened versions had a 10% increase in risk.

"I'm wondering if maybe the artificial sweetener makes you feel hungrier somehow," said Lyn Steffen, MPH, PhD, one of the authors and associate professor at the University of Minnesota in Minneapolis. "You drink this artificially sweetened drink, and you might feel satisfied for a short time. At the end of the day, it actually makes you eat more."

It's not clear why artificial sweeteners somehow might make weight gain more likely, but preliminary data suggest that it could be how the brain reacts. A study in the Feb. 15 Neuroimage compared the brain activity of 12 healthy women fed sugar or the artificial sweetener sucralose. Both substances activated areas of the brain associated with pleasant taste, but sugar had a stronger effect in those areas that played a role in expectation and satisfaction. The authors suggest that this finding indicates sugar may turn off the desire for more sweetness, but artificial sweeteners do not. Additional calories are needed to get it to stop.

"If you eat a pound of chocolate, you're done with it. At least for most people, your brain says, 'That's enough.' This is hypothetical and needs to be tested, but maybe the sucralose sets the sweet taste response in motion but it might not turn the brain response off," said Dr. Guido Frank, lead author on that paper and assistant professor of child and adolescent psychiatry at the University of Colorado, Denver.

Artificial sweeteners really to blame?

Despite two decades of suggestive studies like these, the theory that artificial sweeteners may lead to weight gain rather than loss has never been proven. Manufacturers and the Food and Drug Administration, which regulates the sugar substitutes as food additives, say they are safe.

"The causes of obesity are multifactorial. Although surveys have shown that there has been an increase in the use of 'sugar-free' foods over the years, portion sizes of foods have also increased, physical activity has decreased and overall calorie intake has increased," said Beth Hubrich, a registered dietician with the Calorie Control Council, a nonprofit that represents the industry.

And these more recent studies are hardly definitive. Critics of the rat study point out that it may not translate to humans. The number of rats, 27, was small, and the sweetener used was saccharin, which is not the most common human-consumed, noncaloric sweetener.

"They were relatively short-term studies, and there were not a lot of rats," said Keith Ayoob, EdD, director of the nutrition clinic at the children's evaluation and rehabilitation center at Albert Einstein College of Medicine, New York.

Others say the brain studies are too preliminary. The epidemiological studies, for example, don't necessarily prove that diet soda causes obesity instead of being something those who carry excess weight are more likely to choose to consume.

"It's not that drinks with zero calories cause obesity but that people who are overweight or obese are trying to do things to lower their calorie intake, including consuming low-calorie alternatives to sodas," said J. Michael Gonzalez-Campoy, MD, PhD, chief executive officer of the Minnesota Center for Obesity, Metabolism and Endocrinology in Eagan. He also is a Minority Affairs Consortium delegate to the American Medical Association and frequently speaks on obesity-related issues.

Several other studies suggest that artificial sweeteners can play a role in weight loss. Reviews such as one in the June 2007 European Journal of Clinical Nutrition concluded that humans were not that good at regulating food intake when dealing with artificial or real sweeteners.

The policy of the American Dietetic Assn. is that full and reduced-calorie products can be consumed safely. "Using [artificial sweeteners] judiciously can fit into a healthy diet," said Christine Gerbstadt, MD, a registered dietician and ADA spokeswoman.

Still, the doubt continues. Every so often, a paper seems to support this theory, and some experts suggest that persistence may have less to do with science than human nature.

"Whenever people talk about artificial, people have this strange feeling about it. Also, we're all trying to attribute blame on something. This is an easy target," said Michael Tordoff, PhD, a researcher at the Monell Chemical Senses Center in Philadelphia. He investigated this question in the late 1980s and early 1990s, and concluded that artificial sweeteners did not play a role in weight gain.

And their role in weight loss remains an open question for some physicians who advocate reducing the use of all sweeteners in favor of a more natural diet.

"I don't know if I have any science behind my recommendations, but if you asked me to recommend diet soda or water, I think every physician in the world is going to recommend water," said James Cunnar, MD, a family physician and medical director of DuPage Family Medicine in Naperville, Ill. "Personally, I have two cups of coffee every morning, and I use one teaspoon of sugar. It's a total of 30 calories, and in the grand scheme of the day, I would much rather use something more natural than a chemical to give that sweet taste."

More guidance needed

What is clear is that artificial sweeteners are very popular and that patients are unlikely to give them up. When the FDA threatened to pull saccharin from the market in the 1970s and 1980s, the backlash was significant. Gilda Radner sang songs about it on "Saturday Night Live." And according to the Calorie Control Council, that popularity of these products has not ebbed.

In 2007, 194 million Americans consumed low-calorie or sugar-free products -- a significant increase from the 78 million who did so in 1986.

Because the science is so mixed, some physicians faced with an increasingly obese population feel the need for more guidance.

For instance, Abraham Jelin, MD, a pediatric gastroenterologist in Brooklyn, N.Y., proposed at the American Academy of Pediatrics's Annual Leadership Forum last month that the organization issue a report on the appropriate use of artificial sweeteners by children. This issue now has been added to the AAP's agenda as the possible subject of a policy statement or clinical guideline.

"Kids like to have soda and sweet things, and if it's safe to give them food that's artificially sweetened, then I think we shouldn't restrict them," said Dr. Jelin, who is also vice president of his local AAP chapter as well as the head of its youth advocacy committee. "It's important that we have good studies that clearly show they're safe or show that they're not safe or they're safe in moderation."

Current AAP policy advocates limiting the intake of sweetened drinks and increasing consumption of fruits and vegetables.

"There's no official recommendation about using [artificial sweeteners] or not using them," said Ronald Kleinman, MD, chair of the pediatrics department at Massachusetts General Hospital in Boston and editor of the AAP's Pediatric Nutrition Handbook. "I tell parents I don't have any concerns about bad effects of artificial sweeteners, but at the same time, the carbonated beverages that are usually the source of artificial sweeteners are not the best things for kids to be drinking in the first place."

Many physicians also say consuming artificial sweeteners is not the only thing needed to lose weight. The real problem may be that too many patients rely on this to achieve the overarching goal. Weight-loss experts say consuming a diet soda rather than one with sugar or high fructose corn syrup is one of numerous possible choices patients can make.

"Many, many people lose weight by eating artificially sweetened foods as part of their weight-loss plan. There's years of clinical experience demonstrating that," said Mary Vernon, MD, board chair of the American Society of Bariatric Physicians and one of the authors of the Atkins Diabetes Revolution. "But we don't usually counsel people to eat unlimited quantities of artificially sweetened things."

Also, unlike rats, which subconsciously may be eating more, humans may be doing so with awareness.

"Diet soda is one of those interesting quandaries that people use to almost feel better about their other bad behaviors. People order a Double Quarter Pounder and a diet soda. How often do we all observe that happening?" Dr. Cunnar asked.

To answer the question of what role artificial sweeteners may play in weight, researchers plan to continue several lines of study. Dr. Swithers is looking for the physiological mechanisms that may link artificial sweeteners with increased food intake. Dr. Frank will investigate how artificial sweeteners affect the brain development of children and adolescents, and Dr. Steffen will dig into observational studies to determine if an association between diet soda and the development of insulin resistance and other metabolic issues emerges.