With this in mind, let's examine some of the serious, clinically proven health risks associated with artificial sweeteners found in diet drinks.
Aspartame mechanism of action
Aspartame is one of the most popular and widely used artificial sweeteners on the market. It is a second-generation artificial sweetener, and is about 200 times sweeter than sucrose (table sugar). Aspartame is metabolized into aspartic acid, methanol, and phenylalanine. Aspartic acid is an excitatory neurotransmitter, and phenylalanine plays a role in neurotransmitter regulation, with resultant alterations in neurotransmitter levels yielding neurobehavioral disturbances.
A jump in phenylalanine and aspartic acid levels has been linked to decreased serotonin and dopamine production, further exacerbating neurological side effects. Moreover, high levels of aspartame increase the permeability of the blood-brain barrier, and change levels of dopamine and other catecholamines.
Cognitive effects
In some small studies involving participants who drank either sucrose-sweetened beverages or aspartame-sweetened beverages, immediate measures of spatial memory, word recall, and reaction times were better in those who consumed sucrose-sweetened beverages. Of note, however, these studies only investigated cognitive effects following one-time consumption.
In a more robust (albeit low-power) trial published in Research in Nursing & Health, researchers randomized participants to either a high-aspartame (25 mg/kg body weight/day) or low-aspartame diet (10 mg/kg body weight/day) for 8 days, with a 2-week washout between diet crossover. They found that those who consumed a high-aspartame diet performed worse on spatial-orientation tests. However, the researchers observed no differences in working memory between both groups.
Mental-health effects
Per the research, the effects of aspartame on mood are mixed but nonetheless concerning. In one early crossover trial, investigators randomized 40 patients with unipolar depression to receive either aspartame 30 mg/kg/day or placebo for 7 days. Only 13 patients completed the study, with the study truncated by the Institutional Review Board due to the severity of depression in those taking aspartame.
"Despite the small [sample size], there was a significant difference between aspartame and placebo in number and severity of symptoms for patients with a history of depression, whereas for individuals without such a history there was not. We conclude that individuals with mood disorders are particularly sensitive to this artificial sweetener and its use in this population should be discouraged," wrote the authors.
The authors of the Research in Nursing & Health publication offered one explanation for the mixed results of previous studies investigating the link between aspartame intake and mood, stating that:
"The conflicting reports of the neurobehavioral effects (cognition, mood, depression, and headaches) of aspartame consumption may be due to study design issues including use of single doses of aspartame, placebo, or a sugar-based treatment, followed by a one-time assessment, without calculating dosages according to body weight or participant energy requirements, or only estimating dose by retrospective dietary recall. No reports were found of indirect calorimetry to determine individual energy needs and portion sizes."
These authors attempted to reconcile such limitations in their own study, and found that when participants were their own controls, irritability and depression more commonly occurred with high-aspartame intake compared with low-aspartame intake.
Neurological effects
From a physiologic perspective, it would make sense that aspartame exacerbates headache. After all, diet can mediate catecholamine and neuronal pathways. But guess what? As with so many other counter-intuitive medical phenomena, realities are less clear-cut.
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