User:Andrew Nutter/Artificial Sweetener

In the 1970s, several politically motivated studies with questionable methodology took place in an attempt to sway public opinion against artificial sweeteners as a whole. It was largely successful, and artificial sweeteners remain notorious among the masses despite countless studies since that have shown there to be no toxic effects associated with any FDA approved artificial sweeteners.

However, there are psychological effects of consuming mass quantities of artificial sweeteners. It has been suggested in recent findings that the psychological effects alter metabolism in a similar way to sugar. This might suggest that a significant portion of the physical health problems associated with sugar over-consumption may in fact be caused by psychological processes. It has also been hypothesized that artificial sweeteners contribute as much as sugar to an addiction of sweet food, though this is a recent development with minimal evidence in need of further study.

The following is a collection of studies relevant to both topics--direct and indirect effects of artificial sweetener consumption--primarily focusing on aspartame because of its widespread use. Studies are organized first by topic, then in ascending order according to time of publication. It should not be assumed that the findings from the studies for aspartame also apply to any other sweeteners; they warrant their own individual research.

= Direct Physical Effects = These are the studies regarding questions of artificial sweeteners causing toxicity and related physical issues. === Effect of Aspartame and Aspartate Loading Upon Plasma and Erythrocyte Free Amino Acid Levels in Normal Adult Volunteers (1977) === This is one of the earlier studies that was done in response to the initial outrage against artificial sweeteners. They found no evidence that one of the major criticisms of aspartame is actually an issue.

Abstract: Aspartame is a dipeptide (L-aspartyl-L-phenylalanyl-methyl ester) with a sweeting potential 180 to 200 times that of sucrose. Questions have been raised about potential toxic effects of its constituent amino acids, aspartate and phenylalanine when the compound is ingested in large amounts. Plasma and erythrocyte amino acid levels were measured in 12 normal subjects after administration of either Aspartame (34 mg/kg) or equimolar quantities of aspartate (13 mg/kg) in a crossover design. No changes in either plasma or erythrocyte aspartate levels were noted at any time after either Aspartame or aspartate ingestion. Plasma phenylalanine levels decrease slightly after aspartate loading, and increased from fasting levels (4.9 +/- 1 mumoles/100 ml) to 10.7 +/- 1.9 mumoles/100 ml about 45 to 60 minutes after Aspartame loading. Phenylalanine levels returned to baseline by 4 hours. Erythrocyte phenylalanine levels showed similar changes.

=== Aspartame Consumption in Relation to Childhood Brain Tumor Risk: Results From a Case–Control Study (1997) === This study examined the brain cancer rates in children to identify whether it correlates to aspartame consumption. No correlation was found to link directly to aspartame. This study is not in a standard format with an abstract.

Selected Text: Brain cancer incidence rates in the United States have been increasing in both adults (1) and children (2). The possibility that aspartame, a widely ingested artificial sweetener, may be a cause of brain cancer in humans was suggested in a recent report by Olney et al. (3). From a descriptive analysis of national cancer data, they noted increased brain cancer incidence rates in the United States that coincided with the introduction of aspartame into food stuffs in the early 1980s. [...] Thus, our review revealed little biologic or experimental evidence that aspartame is likely to act as a human brain carcinogen.

=== In vivo cytogenetic studies on blends of aspartame and acesulfame-K (2000) === This study found no link between aspartame and genotoxicity (the cause of cancer).

Abstract: Aspartame and acesulfame-K, non-nutritive sweeteners, are permitted individually in diets and beverages. These sweeteners of different classes, used in combination, have been found to possess a synergistic sweetening effect. Whether they also have a synergistic genotoxic effect is unknown. Swiss Albino male mice were exposed to blends of aspartame (3.5, 35, 350mg/kg body weight) and acesulfame-K (1.5, 15 and 150mg/kg body weight) by gavage. Bone marrow cells isolated from femora were analysed for chromosome aberrations. Statistical analysis of the results show that aspartame in combination with acesulfame-K is not significantly genotoxic.

=== Lack of DNA-damaging activity of five non-nutritive sweeteners in the rat hepatocyte/DNA repair assay (2000) === Abstract: The non-nutritive sweeteners acesulfame-K, aspartame, cyclamate, saccharin and sucralose were tested for DNA damaging activity in the rat hepatocyte/DNA repair assay. Using hepatocytes from F344 and Sprague–Dawley male rats, all were inactive despite strong responses for the positive control, 2-aminofluorene.

=== Artificial sweeteners—do they bear a carcinogenic risk? (2003) === Unlike the other entries in this article, this study is actually a literature review and not a direct experiement. However, it is peer reviewed and published in a very reputable medical journal. It suggests no link between aspartame and cancer.

Abstract: Artificial sweeteners are added to a wide variety of food, drinks, drugs and hygiene products. Since their introduction, the mass media have reported about potential cancer risks, which has contributed to undermine the public's sense of security. It can be assumed that every citizen of Western countries uses artificial sweeteners, knowingly or not. A cancer-inducing activity of one of these substances would mean a health risk to an entire population. We performed several PubMed searches of the National Library of Medicine for articles in English about artificial sweeteners. These articles included ‘first generation’ sweeteners such as saccharin, cyclamate and aspartame, as well as ‘new generation’ sweeteners such as acesulfame-K, sucralose, alitame and neotame. Epidemiological studies in humans did not find the bladder cancer-inducing effects of saccharin and cyclamate that had been reported from animal studies in rats. Despite some rather unscientific assumptions, there is no evidence that aspartame is carcinogenic. Case–control studies showed an elevated relative risk of 1.3 for heavy artificial sweetener use (no specific substances specified) of >1.7 g/day. For new generation sweeteners, it is too early to establish any epidemiological evidence about possible carcinogenic risks. As many artificial sweeteners are combined in today's products, the carcinogenic risk of a single substance is difficult to assess. However, according to the current literature, the possible risk of artificial sweeteners to induce cancer seems to be negligible.

=== Consumption of aspartame-containing beverages and incidence of hematopoietic and brain malignancies. (2006) === BACKGROUND: In a few animal experiments, aspartame has been linked to hematopoietic and brain cancers. Most animal studies have found no increase in the risk of these or other cancers. Data on humans are sparse for either cancer. Concern lingers regarding this widely used artificial sweetener.

OBJECTIVE: We investigated prospectively whether aspartame consumption is associated with the risk of hematopoietic cancers or gliomas (malignant brain cancer).

METHODS: We examined 285,079 men and 188,905 women ages 50 to 71 years in the NIH-AARP Diet and Health Study cohort. Daily aspartame intake was derived from responses to a baseline self-administered food frequency questionnaire that queried consumption of four aspartame-containing beverages (soda, fruit drinks, sweetened iced tea, and aspartame added to hot coffee and tea) during the past year. Histologically confirmed incident cancers were identified from eight state cancer registries. Multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression that adjusted for age, sex, ethnicity, body mass index, and history of diabetes.

RESULTS: During over 5 years of follow-up (1995-2000), 1,888 hematopoietic cancers and 315 malignant gliomas were ascertained. Higher levels of aspartame intake were not associated with the risk of overall hematopoietic cancer (RR for >/=600 mg/d, 0.98; 95% CI, 0.76-1.27), glioma (RR for >/=400 mg/d, 0.73; 95% CI, 0.46-1.15; P for inverse linear trend = 0.05), or their subtypes in men and women.

CONCLUSIONS: Our findings do not support the hypothesis that aspartame increases hematopoietic or brain cancer risk.

=== Carcinogenicity of Aspartame in Rats Not Proven (2008) === This is a literature review in a peer reviewed journal pointing out the flaws in previous experiments to show that there is no evidence of aspartame carcinogenicity.

Selected Text: In summary, considering that there are no significant differences in cancer rates between high-dose groups and historical controls, plus the many deficiencies in the experimental design and data, Soffritti et al. (2007) failed to provide convincing evidence of aspartame carcinogenicity. Given the effort expended by many government review agencies to document shortcomings of the first article by this group (Soffritti et al. 2006), it is disappointing that the editor and reviewers of this paper (Soffritti et al. 2007) did not require the authors to address those problems that appear again in this study. Diligence is especially necessary on topics of great public interest and relevance because the public is relying upon the scientific community to assure that only high quality, well-documented, and controlled studies appear in peer-reviewed journals.

Artificial Sweeteners and Cancer
This is not a peer reviewed journal article. It is a brief article summarizing the health effects of all major artificial sweeteners. It cites studies on disagreeing sides of this issue, critiquing them and explaining their implications.

Selected Text: Questions about artificial sweeteners and cancer arose when early studies showed that cyclamate in combination with saccharin caused bladder cancer in laboratory animals. However, results from subsequent carcinogenicity studies (studies that examine whether a substance can cause cancer) of these sweeteners have not provided clear evidence of an association with cancer in humans. Similarly, studies of other FDA-approved sweeteners have not demonstrated clear evidence of an association with cancer in humans.

= Indirect Health Effects = These studies relate to resulting issues from consuming artificial sweeteners instead of sugars. This may mean physical effects, such as gaining or losing weight, or psychological effects (which can have future effects on weight gain). === Effect of drinking soda sweetened with aspartame or high-fructose corn syrup on food intake and body weight (1990) === This study showed that artificial sweeteners do result in lower calorie consumption and increased likelihood of weight loss. Regardless of psychological effects, artificial sweeteners are a healthier alternative to sugar. This does not address whether artificial sweeteners would be healthier compared to neither.

Abstract: To examine whether artificial sweeteners aid in the control of long-term food intake and body weight, we gave free-living, normal-weight subjects 1150 g soda sweetened with aspartame (APM) or high-fructose corn syrup (HFCS) per day. Relative to when no soda was given, drinking APM-sweetened soda for 3 wk significantly reduced calorie intake of both females (n = 9) and males (n = 21) and decreased the body weight of males but not of females. However, drinking HFCS-sweetened soda for 3 wk significantly increased the calorie intake and body weight of both sexes. Ingesting either type of soda reduced intake of sugar from the diet without affecting intake of other nutrients. Drinking large volumes of APM-sweetened soda, in contrast to drinking HFCS-sweetened soda, reduces sugar intake and thus may facilitate the control of calorie intake and body weight.

=== Effects of diets high in sucrose or aspartame on the behavior and cognitive performance of children (1994) === BACKGROUND: Both dietary sucrose and the sweetener aspartame have been reported to produce hyperactivity and other behavioral problems in children.

METHODS: We conducted a double-blind controlled trial with two groups of children: 25 normal preschool children (3 to 5 years of age), and 23 school-age children (6 to 10 years) described by their parents as sensitive to sugar. The children and their families followed a different diet for each of three consecutive three-week periods. One diet was high in sucrose with no artificial sweeteners, another was low in sucrose and contained aspartame as a sweetener, and the third was low in sucrose and contained saccharin (placebo) as a sweetener. All the diets were essentially free of additives, artificial food coloring, and preservatives. The children's behavior and cognitive performance were evaluated weekly.

RESULTS: The preschool children ingested a mean (+/- SD) of 5600 +/- 2100 mg of sucrose per kilogram of body weight per day while on the sucrose diet, 38 +/- 13 mg of aspartame per kilogram per day while on the aspartame diet, and 12 +/- 4.5 mg of saccharin per kilogram per day while on the saccharin diet. The school-age children considered to be sensitive to sugar ingested 4500 +/- 1200 mg of sucrose per kilogram, 32 +/- 8.9 mg of aspartame per kilogram, and 9.9 +/- 3.9 mg of saccharin per kilogram, respectively. For the children described as sugar-sensitive, there were no significant differences among the three diets in any of 39 behavioral and cognitive variables. For the preschool children, only 4 of the 31 measures differed significantly among the three diets, and there was no consistent pattern in the differences that were observed.

CONCLUSIONS: Even when intake exceeds typical dietary levels, neither dietary sucrose nor aspartame affects children's behavior or cognitive function.

=== Aspartame: neuropsychologic and neurophysiologic evaluation of acute and chronic effects (1998) === BACKGROUND: Neurobehavioral symptoms have been reported anecdotally with aspartame.

OBJECTIVE: This study sought to determine whether aspartame can disrupt cognitive, neurophysiologic, or behavioral functioning in normal individuals.

DESIGN: Forty-eight healthy volunteers completed a randomized, double-blind, placebo-controlled, crossover study. The first month was aspartame free. Subjects then consumed sodas and capsules with placebo, aspartame, or sucrose for 20 d each. Order was randomized and subjects were assigned to either a high- (45 mg x kg body wt(-1) x d(-1)) or low- (15 mg x kg body wt(-1) x d(-1)) dose aspartame group. Neuropsychologic and laboratory testing was done on day 10 of each treatment period to determine possible acute effects and on day 20 for possible chronic effects.

RESULTS: Plasma phenylalanine concentrations increased significantly during aspartame treatment. Neuropsychologic results; adverse experiences; amino acid, insulin, and glucose values; and electroencephalograms were compared by sex and by treatment. No significant differences were found for any dependent measure.

CONCLUSION: Large daily doses of aspartame had no effect on neuropsychologic, neurophysiologic, or behavioral functioning in healthy young adults.

=== Does diet-beverage intake affect dietary consumption patterns? Results from the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial (2013) === Background: Little is understood about the effect of increased consumption of low-calorie sweeteners in diet beverages on dietary patterns and energy intake.

Objective: We investigated whether energy intakes and dietary patterns were different in subjects who were randomly assigned to substitute caloric beverages with either water or diet beverages (DBs).

Design: Participants from the Choose Healthy Options Consciously Everyday randomized clinical trial (a 6-mo, 3-arm study) were included in the analysis [water groups: n = 106 (94% women); DB group: n = 104 (82% women)]. For energy, macronutrient, and food and beverage intakes, we investigated the main effects of time, treatment, and the treatment-by-time interaction by using mixed models.

Results: Overall, the macronutrient composition changed in both groups without significant differences between groups over time. Both groups reduced absolute intakes of total daily energy, carbohydrates, fat, protein, saturated fat, total sugar, added sugar, and other carbohydrates. The DB group decreased energy from all beverages more than the water group did only at month 3 (P-group-by-time < 0.05). Although the water group had a greater reduction in grain intake at month 3 and a greater increase in fruit and vegetable intake at month 6 (P-group-by-time < 0.05), the DB group had a greater reduction in dessert intake than the water group did at month 6 (P-group-by-time < 0.05).

Conclusions: Participants in both intervention groups showed positive changes in energy intakes and dietary patterns. The DB group showed decreases in most caloric beverages and specifically reduced more desserts than the water group did. Our study does not provide evidence to suggest that a short-term consumption of DBs, compared with water, increases preferences for sweet foods and beverages. This trial was registered at clinicaltrials.gov as NCT01017783.

=== Artiﬁcial sweeteners produce the counterintuitive effect of inducing metabolic derangements (2013) === This was published in a peer reviewed journal. However, it is not available for public viewing, so the early press release version has been provided as a reference and contains the same text. This study suggests that the psychological effects of experiencing the sweet taste of artificial sweeteners leads to numerous metabolic problems when consumed in excess.

Abstract: The negative impact of consuming sugar-sweetened beverages on weight and other health outcomes has been increasingly recognized; therefore, many people have turned to high-intensity sweeteners like aspartame, sucralose, and saccharin as a way to reduce the risk of these consequences. However, accumulating evidence suggests that frequent consumers of these sugar substitutes may also be at increased risk of excessive weight gain, metabolic syndrome, type 2 diabetes, and cardiovascular disease. This paper discusses these findings and considers the hypothesis that consuming sweet-tasting but noncaloric or reduced-calorie food and beverages interferes with learned responses that normally contribute to glucose and energy homeostasis. Because of this interference, frequent consumption of high-intensity sweeteners may have the counterintuitive effect of inducing metabolic derangements.

= References =