Artificial sweeteners

Because they are widely used in beverages and other foods and consumed by many people as a way to avoid the calories and health drawbacks of sugar, artificial sweeteners have been extensively studied.  Although stevia and agave are naturally derived sweeteners many of the chemicals used for this purpose are not found in nature and the public has been suspicious that they may be harmful to health.  However, artificial sweeteners, also known as non-nutritive sweeteners, chemical sweeteners and sugar substitutes, require evaluation of their safety and approval by the FDA before they are allowed to be used for human consumption.  The safety of the older compounds including aspartame, saccharin, and sucralose has been the most thoroughly studied and the more recently introduced artificial sweeteners including sorbitol,xylitol, mannitol, refined stevia and agave are considered to be to be safe at the moderate levels consumed in human diets. The FDA has not permitted the use of whole-leaf Stevia or crude Stevia extracts because these substances have not been proven to be safe.  However FDA has not objected to the use of certain highly refined Stevia preparations in food products.^[1]

Aspartame is the most common low-calorie sweetener used in the United States and its use is most commonly associated with low-calorie/low-sugar versions of carbonated and non-carbonated beverages.  However aspartame is also used in many other foods including in low-calorie/low-sugar versions of canned fruits and juices; instant cereals; baked goods; ice cream and frozen ices; candy and chocolate products; jams, jellies, syrups, and condiments; yogurt; and beer.^[2]

The six FDA Approved artificial sweeteners are: ^{[3] [4]}

• acesulfame potassium (acesulfame K) (also known as ACK, Sweet One®, and Sunett®)
• aspartame.
• saccharin.
• sucralose (also known as Splenda®).
• neotame. (similar to aspartame)
• advantame.

Before approving these six sweeteners, the FDA reviewed hundreds of safety studies including studies to assess cancer risk. The results of these studies are reassuring in that available evidence shows that these sweeteners do not cause cancer or pose any other threat to human health. ^[5]

Sugar alcohols, another class of sweeteners, can also be used as sugar substitutes.  Examples include sorbitol, xylitol, lactitol, mannitol, erythritol, and maltitol. Their sweetness varies from 25% to 100% as sweet as sugar.  Sugar alcohols are slightly lower in calories than sugar and do not promote tooth decay or cause a rapid increase in blood glucose.  They are used primarily to sweeten sugar-free candies, cookies, and chewing gums.^[6]

Based on the very high doses used in animal studies, artificial sweeteners such as saccharin, cyclamates, and aspartame were at one time considered to be possible causes of cancer.  Many chemical additives, including some sweeteners, can be shown to be carcinogenic in animals when consumed in massive amounts, far greater than humans would consume in foods and drinks and cyclamates are no longer approved for use in the U.S. 

Extensive toxicology studies in laboratory animals, using much greater doses than people would possibly consume are reassuring about the safety of aspartame and the other FDA approved artificial sweeteners.  The evidence from epidemiological studies does not suggest that chemical sweeteners have a detectable effect on the risk of any human cancer.^[7]  For example, a 2009 study concluded that the use of artificial sweeteners did not increase the risk of endometrial, gastric or pancreatic cancers.^[8] A National Cancer Institute study looked at data from nearly 500,000 older men and women in the NIH-AARP Diet and Health Study.  It found no increase in risk of lymphoma, leukemia, or brain cancer in the highest categories of consumption of aspartame-sweetened beverages (>1,200 or 2,000 mg/day, which is equivalent to 7 to 11 cans of soft drinks daily) compared with the lowest categories of consumption.^[9]

The 2015 Dietary Guidelines Advisory Committee (DGAC) Report generally concurs with the conclusions of the European Food Safety Authority (EFSA) Panel on Food Additives^[10]that aspartame in amounts commonly consumed is safe and poses minimal health risk for healthy individuals without phenylketonuria (PKU).  And that “Its safety has been further confirmed through studies in several human subpopulations, including: healthy infants, children, adolescents and adults; obese individuals with or without diabetes; lactating women; and individuals heterozygous for the genetic disease phenylketonuria (PKU), who have a decreased ability to metabolize phenylalanine.” ^[11][12]  However the DGAC noted that additional monitoring of safety is advisable because there is limited and inconsistent evidence suggests a possible association between aspartame and risk of some blood cancers (non-Hodgkin lymphoma and multiple myeloma) in men (but not women), indicating a need for more long-term human studies.^[13] In addition, limited and inconsistent evidence indicates a potential for risk of preterm delivery for pregnant women.^[14]

There is a popular belief that sugar and artificial sweeteners are associated with hyperactive behavior and cognition problems among children.  The DGAC considered two U.S. RCTs and two U.S. non-randomized controlled trials to evaluate the evidence on the effects of aspartame on behavior and cognition in children.  One RCT compared diets high in sucrose to diets high in aspartame in 25 preschool and 23 primary school-age children and found that neither high consumption of sucrose nor aspartame affected children’s behavior or cognitive function.^[15] Another RCT examined the effect of 10 times the usual consumption of aspartame on behavioral/cognitive function in children with attention deficit disorder (ages 5 to 13 years) and found no effect of aspartame on cognitive, attentive, or behavioral testing.^[16]

Observational studies among children have found similar results.  When preschool children were given a challenge of sucrose- or aspartame-containing drinks on alternate days there was no significant difference in locomotion, task orientation, or learning.^[17] A study that investigated the effect of sugar, aspartame, saccharin, and glucose on disruptive behavior in 30 preschool boys on four separate experimental days found no significant difference in scores of aggression or observer’s ratings of behavior in response to any of the treatments.^[18]

The DGAC considered seven studies on the effect of aspartame on adult behavior.  The studies found no significant differences between aspartame and placebo in performance cognition, memory, mood and well-being and no neuropsychologic, neurophysiologic, or behavioral effects linked to aspartame consumption.^{[19][20][21][22][23][24]}One case-control study was conducted with 40 adults with unipolar depression and a similar number of subjects without a psychiatric history.  Participants were given aspartame (30 mg/kg) or placebo for 7 days and individuals with depression reported an increase in severity of self-scored symptoms between aspartame and placebo; whereas the non-depressed matched subjects reported no difference. This suggested that individuals with mood disorders may be sensitive to aspartame.^[25]Overall, the DGAC noted the limited number of participants, the short duration of the studies, and the inconsistency of the reporting of the results in all adult studies. However, despite these limitations, the European Food Safety Authority (EFSA) Panel on Food Additives concluded that there was no evidence that aspartame affects behavior or cognitive function in adults.^[26]

The DGAC  noted that due to very limited evidence it is not possible to draw any conclusions on the relationship between aspartame consumption and headaches.^[27]  The European Food Safety Authority (EFSA) Panel on Food Additives also considered studies that examined a possible link between aspartame headaches and seizures.  Some studies have found no difference in the incidence rate of headaches.^[28]  Other studies suggest that aspartame increases the frequency and intensity of migraine headaches in subjects with medical diagnosis of migraine and that a subset of the population may be susceptible to headaches induced by aspartame.^[29][30]  A survey study of 171 patients at a headache unit, found that 8 % reported that aspartame was a trigger of headaches compared to 2.3 % for carbohydrates and 50 % for alcohol.^[31] Overall, the Panel concluded the studies on a possible effect of aspartame on headaches reported conflicting results, ranging from no effect to the suggestion that a small subset of the population may be susceptible to aspartame-induced headaches. 

The Panel noted that because of the limitations of the studies, it was not possible to draw a conclusion on the relationship between aspartame consumption and headaches. ^[32][33]The Panel considered several small studies assessed seizures.^[34] Overall, the Panel concluded that the available data do not provide evidence for a relationship between aspartame consumption and seizures.  The Panel considered that a realistic dietary intake of aspartame would not be a risk of adverse effects on pregnancy in the general population at the current Acceptable Daily Intake (ADI). ^[35]

At one time it was thought and reported in the medical literature, that low-calorie sweeteners stimulate appetite or adversely affect mechanisms that regulate hunger and satiety.  According to a Canadian Diabetes Association National Nutrition Committee Technical Review, current evidence does not support this belief. Daily consumption (up to ADI levels) of aspartame, sucralose, saccharin, cyclamate and D-tagatose does not appear to have any significant effect on glycemic control or blood lipids in persons with diabetes. And according to the Technical Review: “Current evidence indicates that intense sweeteners, used as an adjunct to multidisciplinary programs, may improve weight loss and weight control in obese persons,” and “In pregnancy, saccharin and cyclamate are not recommended, while other intense sweeteners have not been shown to be unsafe during this time.” The review suggests that artificial sweeteners are most beneficial when they are used to replace energy-dense and nutrient-diluted foods including sucrose, and are least beneficial when used to displace nutrient-dense foods.^[36]

The DGAC recommends that if individuals choose to drink beverages or eat foods that are sweetened with aspartame, they should stay below the aspartame Acceptable Daily Intake (ADI) of no more than 50 mg/kg/day or 3500 mg/day for a 70 kg person.  Since a 12-ounce diet beverage contains approximately 180 mg of aspartame this would imply a limit of nineteen 12-ounce servings per day for a 154-pound person.  The bottom line is that for most of us, usual levels of consumption of aspartame, the most commonly used artificial sweetener, present a very low, if any risk to health but water is cheaper and a preferable drink.^[37]

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