Photograph by Michael Gottschalk/ Images
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The cupcakes at Cafe Todos in Berlin tempt the sweet tooth.
Photograph by Michael Gottschalk/ Images
The Plate

The Scoop on Real Sugar, Fake Sugar, and No Sugar

Most scientists agree these days that artificial sweeteners have been unfairly maligned, but they are far from perfect substitutes for the sugar we crave.

An article by pediatrician Aaron Carroll of Indiana University in this week’s New York Times lays it on the line when it comes to the health implications of sugar versus artificial sweeteners:  Studies indicate that sugar ups our chances of obesity, Type II diabetes, cardiovascular disease, and premature death. Artificial sweeteners, on the other hand, Carroll concludes, look to be—well, pretty much okay. But not everybody agrees.

The first and oldest of artificial sweeteners is saccharin, discovered in 1878 by Russian chemist Constantin Fahlberg, working in the lab of Ira Remsen at Johns Hopkins University. The new sweetener was a hit, and even got some helpful plugs from Teddy Roosevelt, whose personal physician prescribed it in hopes of getting the portly president to shed a few pounds.

By the 1970s, however, experiments showing that massive doses of saccharin caused bladder cancer in rats had raised a red flag. By the 1980s, any product containing it was required by law to carry the threatening statement “Use of this product may be hazardous to your health. This product contains saccharin, which has been determined to cause cancer in laboratory animals.” The shaken public dropped saccharin like a lead brick.

As it turned out, the alarm was unfounded. The bladder-cancer results have not been confirmed in humans—and re-evaluations of the original rat experiments showed showed that the rats were less effective as stand-ins for people than the researchers had previously believed. Unlike humans, rats have high urinary pH levels and high urinary concentrations of calcium phosphate and protein. Under such conditions, proteins in urine bind to saccharin, forming microcrystals that damage the bladder wall, eventually leading to tumor formation. In 2000, the National Cancer Institute removed saccharin from its carcinogen list.

Recently, saccharin has even undergone an impressive scientific flip-flop. New research by Robert McKenna and colleagues at the University of Florida indicates that saccharin— rather than causing cancer—may actually be effective in combatting some of the nastiest and most aggressive forms of the disease. It appears to do so by inactivating a protein called carbonic anhydrase IX. In normal tissues, carbonic anhydrases act to transport carbon dioxide out of cells, thus maintaining the body’s pH balance. Carbonic anhydrase IX, however, is the odd protein out: It appears to be specific to cancer cells, promoting the growth and spread of tumors in the breast, lung, liver, kidney, pancreas, and brain. Researchers hope that saccharin, with its carbonic anhydrase IX-blocking activity, may eventually be the basis for a new anti-cancer drug.

Next of the sugar substitutes was aspartame, marketed as NutraSweet and Equal, and approved by the FDA in 1981, at the height of the saccharin scare. Like its predecessor, it too soon fell from grace, though subsequent analyses have restored its reputation. An alarming study postulating a link between aspartame and brain tumors proved to be a false correlation. Similarly, though a 2005 study showed that rats fed high doses of aspartame (in some cases the equivalent of over 2000 cans of diet soda a day) developed lymphomas and leukemias, the effect was not found to apply to people, according to a National Cancer Institute analysis of some half a million retirees.

It would be nice to tout artificial sweeteners as safe and sensible alternatives to sugar, but perversely that may not be the case. In a cruel twist of fate, research from Israel’s Weizmann Institute of Science suggests that artificial sweeteners may actually promote obesity and diabetes, conditions that such substances were intended to help us avoid. The problem may reside in our guts, where trillions of bacteria—collectively known as our microbiome—help us digest our food. Experiments in mice indicate that artificial sweeteners disrupt the microbiome balance, boosting the growth of gut bacteria that are particularly effective at extracting energy from food and turning it into fat.

In other words, artificial sweeteners, by favoring certain sub-populations of gut bacteria, may be providing us with a lot of additional unwanted calories, with attendant weight gain and health problems. On the other hand, as countless studies have discovered, mice aren’t necessarily much like people; there’s a lot of research yet to be done.

What about “natural” sugar substitutes such as stevia and agave? Stevia, which is 200 times sweeter than table sugar, comes from Stevia rebaudiana, a plant native to Paraguay and Brazil. Whole-leaf stevia and crude stevia extracts have not been approved by the FDA, but purified stevia derivatives, such as rebaudioside A, are generally regarded as safe and have been given the FDA go-ahead. Some concerns have been raised about stevia’s safety when taken in conjunction with certain medications, such as anti-hypertensive drugs; and some consumers complain of a bitter aftertaste. Further research is in the works.

Agave—the plant to which we owe tequila—is a relative of the yucca. Its nectar or syrup, often touted as a healthy natural alternative to table sugar, is 70 to 90 percent fructose, which may nudge us into weight gain since ingested fructose fails to signal our brains, suppressing appetite by telling us that we’re full. (See The Plate’s Sugary Drinks May Make Us Crave Extra Calories.)

Some nutritionists suggest that, given all this, we may do best sticking to table sugar—just making sure that we’re not eating too much of it. This, as it turns out, is hard to do. The trap is hidden sugar. We all know that we’re getting a good dose of sugar in lollipops, chocolate bars, and ice-cream cones, but manufacturers also add sugar to a wide range of unexpected products to improve tastes and flavors. Among these are barbecue sauce, ketchup, yogurt, pasta sauce, soup, and cereal. According to a 2014 study from the Centers for Disease Control and Prevention, the amount of hidden sugar Americans consume daily is enough to more than double the risk of death from cardiovascular disease, and it’s also enough to make us pack on way too many unwanted pounds.

Other researchers recommend that we bite the bullet, kick the sweet habit, and go sugar-free. Best known proponents of the no-sugar movement are Robert Lustig of the University of California, San Francisco, author of Fat Chance: Beating the Odds Against Sugar, Processed Food, Obesity, and Disease Fat Chance: Beating the Odds Against Sugar, Processed Food, Obesity, and Disease (see Lustig’s Sugar: The Bitter Truth on You Tube), and David Gillespie, author of Sweet Poison: Why Sugar Makes Us Fat. Sugar is an addiction, Gillespie explains, but once you go cold turkey, you adjust quickly. The bennies: lost weight, increased energy, and overall improved health.

Still, many scientists point out, sugar isn’t the big bad wolf that anti-sugar activists claim it to be. Sugar, in moderation, is an integral part of a normal healthy diet­—found in fruits and vegetables, dairy products, eggs, grains, and nuts. Read labels and avoided added sugar, they suggest.

Note: This post has been updated to reflect the distinction between whole-leaf stevia and purified stevia derivatives.