The universal appeal of sweet food and drink is likely a result of evolutionary adaptations that make efficient sources of energy more desirable. This is a useful adaptation when food is scarce. In our society, however, we usually take in far more energy than our bodies need to function properly. The result is alarming: almost two-thirds of all U.S. adults are overweight or obese (1).

There are two primary ways to induce weight loss: we must either expend more energy through exercise, or we must reduce our daily intake of energy. An easy means of achieving the latter is by replacing the sugar in common high-calorie foods or beverages, such as soda, with artificial sweeteners. Since artificial sweeteners can be up to 600 times as sweet as sugar, they can be used in very small amounts without caloric impact (2). It sounds like an ideal way to satisfy our natural sweet tooth without adding an excessive amount of calories. However, there is currently heated debate surrounding the efficacy of diet sodas and the safe levels of consumption for various sugar substitutes.

Saccharin

The first sugar substitute, saccharin, was synthesized in 1897 and immediately became popular in the early twentieth century to reduce monetary costs, not calories (2). During shortages in WWI and WWII, it was far cheaper than regular sugar. It later gained appeal when dieting became popular in the 1960s, and was especially valued by diabetics. Still, the bitter aftertaste left room for improvement. Also, several studies during the 1970s demonstrated that sufficiently high concentrations of it could cause bladder cancer in rats, which weakened its reputation in the public eye and prompted the FDA to mandate a warning label on all saccharin-containing products (3-5). Although it was later demonstrated that the mechanism by which saccharin causes cancer in rats may not apply to humans, and the warning label requirement was lifted in 2001 (2), the market called for an improved alternative.

Cyclamate

Cyclamate arrived on the scene in the 1950s. It was used synergistically with saccharin to reduce the unpleasant aftertaste. However, studies linking it to cancer in rats induced the FDA to ban it in the United States, though it is still used elsewhere (2). For example, Sweet’n’Low contains both saccharin and cyclamate in Europe, but only saccharin in the U.S. The mechanism by which it causes cancer in rats is not clear, and interpretation of the results of these studies is controversial, leading to its approval in Europe and Canada, but not in the U.S. (2).

Aspartame

Aspartame, until recently the most widely used artificial sweetener in the U.S., was immediately popular upon its introduction in 1981 primarily due to a lack of scientific evidence of harmful health effects. Currently, the acceptable daily intake (ADI) for aspartame is set at 50 mg/kg body weight in the United States, the equivalent of about 20 cans of Diet Coke. Until recently, experiments using lab rats demonstrated no adverse effects even for concentrations well above normal human exposure.

However, one recent experiment with a large population of rats did find a significant increase in the rates of various cancers, even with concentrations of aspartame lower than current FDA-approved standards (acceptable levels of various chemicals are determined for humans based on animal models using standard formulae; in this experiment, the ADI for humans was found to be 20mg/kg, much lower than the current ADI of 50mg/kg) (6). While these results are certainly not unanimously agreed upon, they have prompted discussion of the reliability of previous studies. Most recently, a European conference concluded that there was no reason to revise the current ADI of 40mg/kg in Europe (7).

New Generation Sweeteners

Neither acesulfame-K, sucralose, or neotame, three “new generation” sweeteners currently approved by the FDA, are currently suspected to cause cancer (8). However, critics say these sweeteners have not been studied adequately (9). With time, they may follow the same pattern of controversy as their forerunners.
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Artificial Sweeteners In Humans

Despite chain e-mails and online articles warning of a plethora of health concerns such as brain tumors, multiple sclerosis, epilepsy, and even Alzheimer’s Disease, the current scientific literature on the effects of artificial sweeteners on humans fails to reach a consensus.
It is likely that some of these rumors are based on the fact that one of the three breakdown products of aspartame is phenylalanine, which should be avoided by people with phenylketonuria, a rare genetic disease occurring at a rate of about 1 in every 15,000 births. The other two products of aspartame are aspartic acid and methanol, which are metabolized by the body and either used or excreted (6). These products can be toxic in very high doses, but even tomato juice, for example, produces more methanol when metabolized than does diet soda.

Since many products typically contain a mix of several artificial sweeteners, it is difficult to isolate the effects of a single one. Therefore, most studies look at artificial sweetener use in general. A number of smaller studies as well as a large study in 2006 failed to find a link between artificial sweetener use and several types of cancer (2, 10). However, a study in 1994 with 1860 bladder cancer patients and 3934 controls found an elevated risk of bladder cancer in patients with a history of heavy artificial sweetener use (defined as 1680 mg/day, the equivalent of almost 10 cans of Diet Coke) (11, 12). These results seem to indicate that there are no significant negative effects at normal levels of consumption, but intake of higher levels, even within the ADI, may be a significant risk factor for bladder cancer.

Scientists have performed intense investigation of the toxicity of artificial sweeteners, but the question still remains: aside from their unquestionable value to diabetics, do artificial sweeteners actually help people to lose weight? The answer seems to be yes, but inadvertent behavioral effects may mitigate the results.

Numerous studies have shown that the use of aspartame may help achieve long-term weight reduction (13-17). However, some worry that conscious compensation may occur. Consumers may opt for dessert after drinking a diet soda, perhaps as a “reward” to themselves. In other words, “lost” calories from diet soda are replaced by other calories. Serious dieters are presumably aware of this danger, but casual consumers of diet sodas should not expect weight loss if they substitute other sources of calories.

Another cause for concern is that sweeteners may unconsciously increase hunger following consumption, an outcome referred to as the “paradoxical effect” (18). The mechanism is not well understood, and it is unclear whether this augmented hunger actually results in increased food consumption (14).

Despite a number of potential health hazards, including a possible increased risk of cancer with unusually high consumption, artificial sweeteners are currently in high demand. The choice to use artificial sweeteners is entirely personal, and should be based on careful consideration of benefits and risks. For example, artificial sweeteners are invaluable to overweight individuals as well as diabetics whose health risks from continuing to use regular sugar far outweigh most possible negative effects. Diet drinks are not a magical panacea, but if used in conjunction with a carefully considered program, they can be effective in reducing weight in the long-term.

References:
1. “Overweight and Obesity” (Centers for Disease Control and Prevention, 2007).
2. M. R. Weihrauch, V. Diehl, Annals of Oncology 15, 1460 (2004).
3. S. Fukushima, et al., Gann 74, 8 (1983).
4. R. M. Hicks, S. J. Wakefield, J. Chowaniec, Nature 243, 347 (1973).
5. S. Cohen, Aral, Jacobs, Friedell, Cancer Research 39, 1207 (1979).
6. M. Soffritti, et al., Environ Health Perspect 114, 379 (2006).
7. “Opinion of the Scientific Panel AFC Related to a New Long-Term Carcinogenicity Study on Aspartame” (European Food Safety Authority, 2006).
8. “Artificial Sweeteners: No Calories … Sweet!” (U.S. Food and Drug Administration, 2006).
9. M. Karstadt, Environmental Health Perspectives 114, A 516 (2006).
10. S. Gallus et al., Annals of Oncology 18, 40 (2007).
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13. G. Blackburn, B. Kanders, T. Lavin, T. Keller, J. Whatley, Am J Clin Nutr 65, 409 (1997).
14. A. de la Hunty, S. Gibson, M. Ashwell, Nutrition Bulletin 31, 115 (2006).
15. A. G. Renwick, H. Nordmann, Food and Chemical Toxicology 45, 1308 (2007).
16. B. Rolls, Am J Clin Nutr 53, 872 (1991).
17. M. G. Tordoff, A. M. Alleva, The American Journal of Clinical Nutrition 51, 963 (1990).
18. J. E. Blundell, A. J. Hill, Lancet 1, 1092 (1986).
19. “Sweetener,” Encyclopædia Britannica Online (2007).