How Sweet It Is: Sweeteners in Health and Disease

Wars have been fought over sugar; people have been enslaved over sugar; and sugar has played large roles in national economies. You are born with a preference for sweet taste. The degree to which we prefer a sweet taste appears to vary because of factors such as genetic differences in taste receptors, age and exposure to sweet foods.

1. monosaccharides such as glucose, galactose or fructose;
2. disaccharides such as sucrose, maltose and lactose;
3. longer chain carbohydrates such as oligosaccharides and polysaccharides;
4. sugar alcohols (polyols), which are derived from carbohydrates but are generally not absorbed completely in the small intestine.

1. monosaccharides or disaccharides that have been modified to prevent absorption or utilization as energy;
2. amino acid molecules that have sweet taste;
3. novel or non-macronutrient molecules

The term "sugars" includes all monosaccharides and disaccharides, and the term "sugar" may refer specifically to sucrose.

Nutritive and nonnutritive sweeteners are considered food additives and are subject to approval by the U.S. Food and Drug Administration (FDA) by one of two mechanisms. Additives may be classified as generally recognized as safe (GRAS), based on experience prior to the 1958 Food Additives Amendment, or by petitioning the FDA for approval as GRAS. Most sugars are considered classified as GRAS, as are some sugar alcohols and novel sugars (see Table 1 below).

The other mechanism is approval under the Food Additives Amendment, which dictates testing for immediate and long-term health effects, toxicity, teratogenicity and carcinogenicity. Nonnutritive sweeteners are generally approved by this method. When approved as a food additive, the FDA may propose a level at which there would be no toxicity, called the acceptable daily intake or ADI. The ADI is a conservative level and is approximately 100 times less than the levels at which no toxicity has occurred in studies.

High fructose corn syrup was introduced commercially in the 1960s and most of it is the product of enzymatic conversion of cornstarch to glucose and fructose, in proportions of 42%, 55% or 90% fructose.

According to food disappearance data from the U.S. Department of Agriculture (USDA), our consumption of nutritive sweeteners has increased approximately 20% over the last three decades (see Figure 1 below). In 2001 the average per capita added nutritive sweetener consumption was 31 teaspoons/day. The estimated percent of total dietary energy derived from sweeteners was 18%. Over the same period, there was a 35% decrease in cane and beet sugars, while corn sweeteners increased by 40% per cent. High fructose corn syrup was introduced commercially in the 1960s and most of it is the product of enzymatic conversion of cornstarch to glucose and fructose, in proportions of 42%, 55% or 90% fructose. In the U.S., the majority of high fructose corn syrup is consumed in soda and fruit drinks.

Survey data from the Continuing Survey of Food Intakes by Individuals (CSFII) and the National Health and Nutrition Examination Survey (NHANES) reveal trends similar to disappearance data. In 1994-1996, caloric intake from added sweeteners as a percent of total energy intake was 16%, and sweeteners from soft drinks and fruit drinks accounted for almost one-third of total daily sweetener intake. Large differences in sweetener consumption were noted among age, gender and ethnic groups. For example, the highest consumption levels were observed in adolescents (20% of energy intake) and particularly among girls age 14-18 years, 10% of whom consumed over 35% of calories from added sweeteners.

Sweetened beverages, such as soda or fruit drinks, may be of particular concern because...[r]esearch suggests that...we do not adjust our intake of other foods to compensate for the liquid calories.

Few intervention studies have been conducted to determine if replacement of added sugars with either complex carbohydrates or nonnutritive sweeteners could influence body weight. In two trials where subjects were trying to reduce weight, recommendations were provided to consume foods with or without aspartame. No significant differences in weight loss were observed, although long-term maintenance of lost weight was better in the group consuming foods with aspartame. In subjects consuming weight loss diets where sugars were replaced with complex carbohydrates, no advantages were found. Based on these limited studies, it appears that replacement of nutritive sweeteners with nonnutritive sweeteners or complex carbohydrates does not help you lose weight. Sweetened beverages, such as soda or fruit drinks, may be of particular concern because excess intake of calories from liquids may be more poorly regulated than from solids. Research suggests that when excess energy is provided in liquids, we do not adjust our intake of other foods very well to compensate for the liquid calories. In contrast, when excess energy is provided as solid food, we better (but not completely) compensate by reducing our subsequent intake to account for the earlier calories.

It should be noted, however, that low to moderate intake of fructose (e.g. <60 g/d, the equivalent of about ten medium-sized pieces of most fruits) has not been shown to produce extra blood fats or interfere with blood sugar levels. Indeed, for diabetics, small amounts of fructose may actually improve blood sugar control.

Nutritive sweeteners include sugar alcohols and novel sugars. Sugar alcohols are derived from carbohydrates. Products containing sugar alcohols can be labeled as "sugar free" if they do not contain other sugars. Sugar alcohols are incompletely absorbed from the gastrointestinal tract. Compared to sugars, sugar alcohols reduce energy intake and don't produce sharp rises in blood sugar. Sugar alcohols are also non-cariogenic and, although still controversial, may help retard dental caries. Because of their incomplete absorption, many products containing sugar alcohols are required to warn of a laxative effect.

Novel sugars include D-tagatose and trehalose. D-tagatose is an isomer of fructose, and only 20% is absorbed by the intestine and is subject to colonic fermentation. Trehalose is a disaccharide found in mushrooms. It is approximately half as sweet as sucrose and is absorbed completely. Trehalose is used as a sweetener, a food texturizer and a stabilizer.

Aspartame is the sweetener most surrounded by controversy. Aspartame is used in liquid, granular and powdered forms in over 6,000 products. It is approximately 200 times sweeter than sucrose and appears in the U.S. by the trade names NutraSweet, Equal and Sugar Twin. It decomposes when exposed to high heat and is inappropriate for baking.

Aspartame is a dipeptide methyl ester that is metabolized to phenylalanine, aspartatic acid and methanol. However, equal volumes of aspartame-sweetened beverages provide less phenynaline and aspartic acid than do equal volumes of beverages such as milk. Aspartame-sweetened beverages also provide less methanol than an equal volume of tomato juice. Bolus doses of aspartame at the ADI of 50 mg/kg body weight/day (the equivalent of over 30 12-ounce cans of aspartame-sweetened soda) have not resulted, after eating, in abnormal levels of the three metabolites in normal subjects or those who are heterozygous for phenylketonuria (PKU).

Claims have been made that aspartame contributes to brain cancer, seizures, headaches, mood changes, cognitive alterations and allergic reactions. Giving subjects a one-time large dose of aspartame at the ADI of 50 mg/kg body weight/day (the equivalent of over 30 12-ounce cans of aspartame-sweetened soda) has not resulted in abnormal levels of break down products in normal subjects or even in those who are carriers for the metabolic disorder phenylketonuria (PKU). Controlled studies in normal adults and children, PKU carriers, those who suffer from depression or attention deficit disorder have similarly not demonstrated that acute or chronic intake of aspartame is associated with seizures, mood disturbances or impaired cognition. In regard to brain cancer, case-control studies in children with brain cancer have demonstrated no link to maternal intake during pregnancy or lactation.

In July 2005, the results of a study in rats were published revealing increased rates of the cancers lymphoma and leukemia in females. Some critics of the study note that the cancer rates were observed over the entire lifespan of the animals (as opposed to shorter periods used in other studies) and questions regarding the historical controls used have arisen. At the very least, this study appears to have rekindled efforts to examine the toxicity of aspartame. Study results are currently being reviewed by the FDA and by European regulatory agencies, with opinions of these agencies expected in the next six months.

Saccharin was first synthesized in 1879 and remains in common use today. Saccharin appears in the U.S. by trade names Sweet'N Low, Sweet Twin, Sweet'N Low Brown and Necta Sweet. Originally considered GRAS, issues arose in 1977 concerning its carcinogenicity. Although never banned by the FDA, saccharin-containing products were required until 2001 to have a warning label that use had caused cancer in laboratory animals. However, it was subsequently concluded that the mechanism of saccharin-induced carcinogenicity in mice does not apply to humans and that saccharin does not pose increased cancer risk to humans. No overall ADI has been issued, though specific recommendations for use as a tabletop sweeter (20 mg/teaspoon) or use in other products (12 mg/ounce of beverages) have been issued.

Sucralose is the disaccharide sucrose that has been modified chemically. The modification makes it poorly absorbed and it is largely excreted unchanged in feces. When absorbed, it undergoes little metabolism and is largely excreted unchanged in the urine. It is approximately 600 times sweeter than sucrose, is heat stable and is used in variety of products. Sucralose appears in U.S. products with the trade name Splenda and has an ADI of 5 mg/kg body weight/day.

Acesulfame potassium (or acesulfame-k) is approximately 200 times sweeter than sucrose, is heat stable and is used in a variety of foods worldwide where it is marketed by the name Sunett. It is often blended with other nonnutritive sweeteners. Acesulfame potassium is excreted largely unchanged and thus does not contribute substantial potassium to the diet. The ADI is 15 mg/kg body weight/day.

Neotame is similar to aspartame but because of its chemical structure does not, unlike aspartame, require a warning label for individuals with phenylketonuria. It is 7,000-13,000 times sweeter than sucrose, is available to be used as a tabletop sweetener and is present in a variety of foods including baked goods. Studies to-date have found no neurologic or other toxiciy. It has an ADI of 18 mg/kg body weight/day, although its intense sweetness suggests that far less would be needed for most sweetening purposes. However, there are some vocal critics who have expressed distrust, especially on Internet sites (www.holisticmed.com/neotame/toxin.html), that research to-date documenting the safety of neotame is inadequate; such criticisms appear to focus most often on potential neurotoxicity and effects on the immune system due to the accumulation of amino acid and metabolites such as formaldehyde.