Pramod Kayathi, M.D., Gurpreet Singh, M.D., Vivek C. Shah, M.D., Steven Lippmann, M.D.   

Introduction
Artificial sweeteners are synthetic or natural substances utilized as a substitute for table sugar. These sweeteners contain few calories, thus they are a frequent dietary choice. Since they are sweeter than sucrose, small amounts of these substances are taste-equivalent to sugar. Approximately 180 million Americans consume these sweeteners daily in “sugar-free” foods and beverages (1). They have gained popularity due to being marketed as low calorie options, thus expected to minimize obesity as a health-aid for weight loss or control. Recently, however, there is inconclusive data suggesting that such sweeteners might even induce weight gain.

Effects
The body responds to the amount of calories that are contained in food; yet, the ingestion of artificial sweeteners yields a faulty perception of calorie consumption. Artificial sweeteners provide less calories than anticipated, thus, the person could then have a tendency to crave satisfaction by consuming more food and/or sweets; this results in eating and/or drinking more, favoring further calorie intake. A sweet taste tends to prepare the intestinal system via brain signals for anticipated calories. However, this does not follow during the ingestion of artificial sweeteners. This results in insulin, other hormones, and a metabolic system that is not being stimulated as it would have been with sugar consumption. Dopamine, not being released, makes eating less rewarding, so the individual might still feel an appetite or hunger and continue eating when satisfaction would have otherwise been more prominent. This tends to induce overeating and the intake of too many calories, yielding weight gain. It may predispose to a metabolic syndrome with obesity and/or diabetes mellitus.

Eating low-calorie foods might have psychological implications that may be a confounding factor. Some people may feel that by having “good behavior” through eating few calories that they can now eat more, or even reward themselves for previous dietary precautions. Low-fat foods similarly are sometimes fortified with artificial sweeteners and might result in continued appetite. This may stimulate further consumption. The net result is a positive calorie imbalance. While some people do lose weight by ingesting low calorie beverages, others could be giving themselves “permission” to consume calories elsewhere, leading to weight gain.
Aspartame has been one of the most commonly used artificial sweeteners. It should be avoided by people with phenylketonuria. It can also cause various neurological and gastrointestinal concerns (2). Metabolites of aspartame include phenylalanine, aspartic acid, methanol, and diketoperazine. Phenylalanine can cause headaches, seizures, potentiate uncontrolled muscle movements such as tardive dyskinesia, and predispose to depression. Aspartic acid, a precursor of glutamate, can induce neuronal excitotoxicity and astrocyte degeneration. Metabolites of methanol can lead to visual disturbances. Diketoperazine may increase a tendency for neuronal neoplasms (3).

Research
Investigations utilizing mice fed with aspartame, saccharin, and/or sucralose evidenced alterations in gastrointestinal microbiome, as compared to those fed sugar. Changes in bacterial flora tends to induce glucose intolerance. Human studies have documented conflicting results regarding the effect of artificial sweeteners on weight gain. One study of 3,682 subjects reveals a 47% increase in body mass index in participants who consistently consumed artificially sweetened drinks, despite exercise, diabetic status, and diet being controlled (4). Other research involving 318 obese individuals demonstrated a 2% weight loss when sugar containing beverages were replaced by low calorie substitutes (5). While most people believe that consumption of artificial sweeteners will help them better manage their weight, several studies do not universally support that impression; the data remains inconclusive. This leaves many open questions regarding the metabolic influence of artificial sweetener ingestions.

Conclusion
Artificial sweeteners are frequently consumed in place of sugar to help weight control by decreasing caloric intake. They are often utilized by people wanting to lose weight; however, it remains still open as to whether they might actually, counterintuitively induce weight gain. Since sweeteners change brain perception of food, their metabolic effects are still in question. In addition, most of these sweeteners can result in undesirable effects, and aspartame, in particular, is cited as an offender for adverse neurological consequences. Aspartame is never to be utilized by people with phenylketonuria. Otherwise, a complete understanding about the implications of artificial sweetener ingestions remains unclear.

References
1.    Sweet Choices. http://www.caloriecontrol.org/sites/default/files/pdfs/lcs_broch4_1.pdf last accessed November 24, 2014
2.    Americas Deadliest Sweetener Betrays Millions, Then Hoodwinks You With Name Change. http://www.huffingtonpost.com/dr-mercola/americas-deadliest-sweete_b_630549.html last accessed November 24, 2014
3.    Effects of aspartame metabolites on astrocytes and neurons. http://rmforall.blogspot.com/2013/04/effects-of-aspartame-metabolites-on.html last accessed November 24, 2014
4.    Artificial Sweeteners. http://www.hsph.harvard.edu/nutritionsource/healthy-drinks/artificial-sweeteners/ last accessed November 24, 2014
5.    Replacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial. http://www.ncbi.nlm.nih.gov/pubmed/22301929 last accessed November 24, 2014