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Is there evidence that artificial sweeteners are useful both while dieting and at a later stage to prevent regaining weight? The influence of artificial sweeteners on aspects of physiology and eating-related behavior is therefore reviewed

• Medline (National Library of Medicine, Bethesda, MD, USA) was used to find relevant literature together with studies referred to in these papers.
• Studies with one day for intervention studies.
  

Review of articles.

Appetite

Some studies found that aspartame was associated with increased appetite.

• Blundell, Hill, 1986: Glucose decreased appetite following its consumption. In contrast, aspartame increased the motivation to eat and decreased feelings of fullness. As ratings of hunger and the amount eaten do not always correspond, it is unfortunate that no food intake data were reported.
• Rogers et al, 1988: The same group found that aspartame, saccharin and acesulfame-K all increased hunger, but they did not increase food intake after one hour
• Tordoff, Alleva, 1990: Using chewing gums containing different concentrations of aspartame found that aspartame increased hunger.
• Stellman, Garfinkel, 1986: Epidemiological evidence at about the same time found that the use of artificial sweeteners was associated with obesity.

Other studies found that aspartame may increase satiety.

Aspartame has been reported to increase satiety in some (Birch et al, 1989; Rogers et al, 1990; Hall et al, 2003) but not all such studies (Anderson et al. 1989; Leon et al. 1989; Rodin, 1990). A key difference may be that when aspartame has been found to induce satiety, it has been administered in a capsule, removing the sensation of sweetness.

The Renwick, 1993, review reported on research concerning three questions.

• Whether artificial sweeteners increase perceived hunger: Subsequent studies failed to confirm the initial findings of Blundell, Hill, 1986. The addition of the sweetener to water without any other flavor may have produced an unnatural stimulus and atypical result.
• Whether artificial sweeteners resulted in an increased intake of food at the next meal: Reviewed fifteen studies and found only one that reported an increased intake of food. He concluded that there was no evidence that artificial sweeteners increased energy intake.
• Whether artificial sweeteners stimulated the release of insulin: Considered ten studies and found only one that had reported an influence on insulin release.

The Regulation of Food Intake

Short-term studies: It was reported that the use of artificial sweeteners results in a later increase in energy intake to compensate for the energy lost.

• Birch et al, 1989, found that children under five years of age compensated completely for the energy removed from soft drinks by the use of artificial sweeteners.
• Lavin et al, 1997, found that on days when sugar, rather than artificially-sweetened lemonade was drunk by young women, there was no difference in total energy intake, although the sugar-containing drink was associated with a lower daily intake of fat and protein.

Other studies have reported only partial energy compensation (Anderson et al, 1989; Rolls et al, 1990; Drewnowski et al, 1994). The extent of energy compensation may reflect the subjects.

• Rolls et al, 1994, reported less-perfect energy compensation in young women who reported dietary restraint, while near-perfect compensation was reported in young men who were prepared to eat freely. Energy compensation is better in children than in adults.

Tables One and Two summarize studies that have examined the use of artificial sweeteners for more than one day. Early studies measured food intake by presenting it as a liquid pumped on demand into the mouth.

• Campbell et al, 1971, reported that lean subjects adjusted the volume consumed when nutritive density was manipulated to maintain a near-constant energy intake. In contrast, subjects who were obese failed to adapt to changes in energy density.
• Wooley, 1971, gave liquid diets to both lean subjects and subjects who were obese and found incomplete compensation when a lower-density food was supplied. The volume drunk increased when consuming a liquid of low energy, although the total energy intake was greater with the higher-density food.
• Spiegel, 1973, found that when a dilute source of energy was introduced, 40% of subjects dramatically compensated by increasing their intake, although she found compensation was not usually complete and began typically two to five days after the start of the dilute diet.
• Porikos et al, 1977, criticized these early studies as they used bland-tasting liquids that subjects who were obese did not consume in sufficient quantities to maintain weight.

Table One includes two studies that consider the addition of an additional source of sugar.

• Raben et al, 2002, found that body weight increased when subjects were instructed to consume traditional soda containing 152g of sugar per day rather than the low-energy equivalent.
• Tordoff, Alleva, 1990, had found that the instruction to consume additional sugar-sweetened soda increased body weight, although the use of artificial sweeteners prevented weight gain.
• Vermut et al, 2003, reported that replacing (added) sugar by low-energy sweeteners might result in lower energy intake and reduced body weight.

Longer-Term Influence of Consuming Foods Containing Sugar or Artificial Sweeteners

Study	Sample	Treatment	Duration	Dietary Changes	Weight
Liquid Diet
Wooley, 1971	Six obese and five lean males	Liquid diet: Days One to Five, high energy; Days Six to 10, low energy	15 days	Incomplete compensation* for low energy	N/S
Campbell et al, 1971	Five lean males, two males and four females who were obese	Days One to Seven, baseline; Days Eight to 30, liquid diet	30 days	Lean, but not obese, compensated for low energy	Declined in obese with more dilute liquids
Spiegel, 1973	Two lean females and 13 males	Standard followed by dilute liquid diet	10 to 21 days	Six of 15 subjects dramatically compensated for dilution	Failure to compensate resulted in weight loss
Porikos et al, 1977	Six females and two males who were obese	Days Four to Six and 10 to 12, 25% less energy due to AS	15 days	No compensation for lost energy	Tended to increase with sugar
Sugar Added to Diet
Tordoff, Alleva, 1990	21 males and nine females of normal weight	One to two litres of soda per day containing sugar or AS	Three weeks	AS reduced energy intake	Sugar increased weight
Raben et al, 2002	35 females who were overweight and six males who were overweight	Instructed to drink soda with 152g of sugar per day or AS	10 weeks	Sugar drink: Fall in intake of fat and protein Sweetener: Fall in intake of sucrose	Sugar increased weight

AS=Artificial sweetener.
* The energy not consumed because of the use of AS was replaced with an increased intake of other nutrients. 

Table Two includes studies that have replaced sugar already in the diet

• Poppitt, Prentice, 1996, suggested that individuals are better able to compensate for the energy dilution of a meal rather than energy supplementation.

Weight and Compensation for Energy Lost in Non-Nutritively Sweetened Foods and Beverages

Weight range has been studied; the energy saved by the use of artificial sweeteners has been included.

• Gatenby et al, 1997, looked over an extended period at the effects of reducing sugar in the diet. The sucrose intake was found to decrease in those using artificial sweeteners, although overall intake did not differ from controls. A slight increase in protein intake was observed, although little overall effect on total energy intake or body weight was seen. Concluded that many reduced-sugar foods in practice are simply added to a pre-existing diet, rather than specifically used to replace sugar-containing foods. 
• Bellisle, Perez, 1994, suggested that those who regularly use artificial sweeteners learn to compensate for the missing energy.
• Louis-Sylvestre et al, 1989, gave low- and high-energy versions of an afternoon snack and measured the amount of food eaten during a meal one hour later. Initially the low-energy snack was not compensated for at a later meal. However, after consuming the snack for five days, precise energy adjustments were made. The authors questioned the value for weight control of food products with a lower than usual energy content.
• Reid, Hammersley, 1998, found only that on Day One out of seven, did the use of drinks sweetened with artificial sweeteners result in a lower carbohydrate intake. The result supports those in the accepted weight range; the substituting of natural for artificial sweeteners does not result in a reduction in energy intake. There is consistent evidence of subsequent energy compensation. Although, on occasion, compensation occurred in the entire sample, in other studies, only some subjects responded. Attention should be directed to establishing the characteristics that determine whether energy compensation does or does not take place. When samples of the obese were considered, a different pattern emerged.
• Kanders et al, 1988, found no significant differences in weight and appetite associated with the use of aspartame-containing products.
• Porikos et al, 1977, found that substituting 25% of energy in normal food by using aspartame did not produce energy compensation. It may be critical that the energy-reduced diets were only consumed for three days, perhaps not sufficient time for energy compensation to occur.
• Blackburn et al, 1977, reported that artificial sweeteners were helpful in a maintenance diet.
• Poppitt, Prentice, 1996, reported that only when some available foods were high in energy did energy compensation tend to occur. When the entire diet was low in energy, compensation tended not to occur. They explained this difference in terms of energy density: If the entire diet was of low energy density and a constant weight of food was consumed, then there would be no opportunity to consume a food of higher energy density to make up the lost energy.

Longer-Term Influence of Replacing Sugar in the Existing Diet with Artificial Sweeteners

Study	Sample	Treatment	Duration	Dietary Changes	Weight
Weight in Accepted Range
Porikos et al, 1982	Six normal-weight males	Days One to Three, high sugar; Days Six to 18, 25% less energy	24 days	Days One to Three, none; Days Four to Six, 40% then 80% compensation* for lost energy	Initial gain prevented by fall in energy intake
Foltin et al, 1988	Six normal-weight males	Days Six to 11, 2,092kJ (500kcal) fewer; Days 12 to 14, original diet	14 days	Days Six to 11, complete compensation; Days 12 to 14, failed to compensate	Not reported
Louis-Sylvestre et al, 1989	17 males	Snack: Normal or low-energy (AS + fat)	Six days	No initial compensation; Day Six, precise compensation	Not reported
Foltin et al, 1990	Six normal-weight men	Lunch: 1,807 or 3,531kJ (432 or 844kcal) with or without fat and aspartame	13 days	Complete compensation for low-energy intake	No change
Naismith, Rhodes, 1995	Ten free-living males	Covertly removed 2,092kJ (500kcal) per day	10 days	85% compensation, drop in fat intake	No change
Gatenby et al, 1997	Forty-nine free-living females	Replaced normal diet with low-sugar items	10 weeks	Compensation, falls in sugar and fat intake; energy intake remained the same	No change
Reid, Hammersley, 1998	14 free-living males and 13 females	Replaced usual soda with sugar or AS	Seven days	Fall in carbohydrate intake on Day One, then compensation	No change
Obese Subjects
Kanders et al, 1988	59 obese males and females	Diet with or without aspartame	12 weeks	Prescribed by study	Weight, appetite N/S, with or without aspartame
Evans, 1989	16 obese women who had slimmed	Diet with or without aspartame	Three weeks	With or without aspartame N/S	Not reported
Kanders et al, 1990	59 obese	Maintenance: Behavior modification and exercise with or without aspartame for one year	Prescribed by study	Less weight regained with aspartame consumption only in males
Blackburn et al, 1997	163 obese females	Diet with or without aspartame Exercise with or without aspartame	19 weeks; one to two years	Prescribed by study	With or without aspartame, N/S Less weight regained with aspartame

 AS=Artificial sweetener
* The energy not consumed because of the use of AS was replaced with an increased intake of other nutrients.

Summary for Macronutrients and Obesity, Energy Density, Glycemic Index and Food Intake; High-Fat Diets

1. Carbohydrates promote a feeling of fullness to a greater extent than fat, making it easier to overeat fatty foods. 
2. The consumption of energy-dense foods is the best predictor of obesity. Energy density is almost entirely predicted by fat and water content. Given the importance of fat rather than carbohydrates, the use of artificial sweeteners by themselves is unlikely to have a major impact on body weight.
3. Diets high in fat result in an increase in weight. Diets high in fat tend to be low in carbohydrates. 
4. Reports of evidence that a low-GI meal enhances satiety are inconsistent. 
5. Carbohydrate intake in general and sugar intake in particular are not the primary concern when considering obesity. In fact, a high-carbohydrate and low-fat intake is associated with a lower body weight.

Summary for Neural Control of Feeding

1. Dopaminergic and opioid mechanisms in the ventral striatum mediate the response to palatable food. Artificial sweeteners and natural sugars have a similar impact on this area of the brain.
2. The suggestion that blood glucose and insulin levels following carbohydrate consumption lead to 5-HT-induced satiety is not supported by the evidence. It has been argued that if the Wurtman hypothesis is valid, the failure of artificial sweeteners to increase blood glucose and insulin levels and hence stimulate 5-HT synthesis, could promote carbohydrate intake. Fernstrom, 1988, considered whether aspartame might disrupt the putative regulatory loop for carbohydrate intake and promote its intake. Aspartame increases phenylalanine and tyrosine levels in the blood, long-chain amino acids that compete with tryptophan for entry into the brain. The concern was that aspartame, via this mechanism, might decrease the levels of brain tryptophan and hence 5-HT synthesis, thus stimulating carbohydrate intake.
3. Insulin plays an important role in the longer-term regulation of body weight, although it is unclear if such mechanisms are influenced by the lower levels of insulin that result from artificial sweetener consumption.

Satiety

Summary:

1. The level of protein, fiber and water in foods predicts satiety. Fat levels are negatively associated with satiety, whereas the levels of sugar and total carbohydrates do not predict satiety.
2. Energy-dense foods are not very satiating, but are highly palatable.
3. The fat content of a food, but not the sugar or total carbohydrate content, predicts how much you want to eat.
4. Artificial sweeteners do not increase energy intake or ratings of hunger.

Surveys of the Use of Artificial Sweeteners

• Anderson, Leiter, 1996, related the consumption of sugar and artificial sweeteners to obesity.
• Chen, Parham, 1991, showed that in female college students, the use of artificial sweeteners
  was associated with the consumption of less sugar; but in men, it was associated with a greater sugar intake. Overall, the use of artificial sweeteners was not associated with significant differences in the intake of carbohydrates, protein, fat or total energy.
• Chen, Parham, 1991, concluded that the pattern of intake indicated that users expressed their weight concerns by choosing to use a high-intensity sweetener rather than by restricting their overall food intake.
• Parham, Parham, 1980, showed the pattern differed from a similar earlier study where, in women, the use of artificial sweeteners had been associated with a lower intake of energy, protein, total carbohydrates and simple sugars. Gender and dietary restraint may be important factors.
• Chen, Parham, 1991, commented that in some individuals, "the use of high-intensity sweeteners may contribute to an excessive sugar intake simply because users are more blasé about their intake of sweets."
• Bellisle et al, 2001, examined a cross-section of the French population and considered those consuming artificial sweeteners. Those using low-sugar products were heavier, had higher triacylglycerols and poorer glucose tolerance.
• de Castro, 1993, considered seven-day food diaries and commented: "Diet soda users ingest significantly less carbohydrate and have lower intakes than non-users. Individuals who used diet soda did not differ in their total caloric intakes on days or in meals during which they drank the non-caloric beverages in comparison to days or in meals during which they did not."
• Tuorila et al, 1990, reported that those using diet soda are generally more concerned with their weight.

Non-Nutritively Sweetened Beverage Use

• Levy, Heaton, 1993, found a common approach among those trying to lose weight is using soft drinks sweetened artificially

• Mattes, 1996, was a meta-analysis of 42 studies that concluded there was little compensation for energy consumed as a liquid.

• Reid, Hammersley, 1998, showed the energy compensation that occurred was replaced by existing soda rather than adding it to the existing diet.

• Raben et al, 2002, considered the effect of artificial sweeteners in a sample of obese individuals who were feeding ad libitum. For 10 weeks they consumed either naturally or artificially sweetened drinks and food. The body weight increased in those consuming naturally sweetened, and decreased in those drinking artificially sweetened drinks.

• James et al, 2004, an English study randomly gave school classes a one-hour session per term on the adverse effects of carbonated drinks. Over one year, those receiving the information drank fewer carbonated drinks, whereas the controls drank a similar number. The proportion of overweight children decreased in those attending the information sessions. There was a decrease in obesity when the consumption of energy-containing and artificially sweetened drinks were added together.