Approximately 20% of the US population aged 2 years and older consume diet drinks on any given day, according to data from the CDC. And while diet drinks may seem like healthier alternatives to sugar-laden sodas and juices, researchers have shown that this may not be the case. Despite previous positive safety studies, emerging research on the long-term health effects of certain artificial sweeteners, such as aspartame, have elicited particular concern among health experts, given their pervasiveness in diet drinks. 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 counterintuitive medical phenomena, realities are less clear-cut. In those who experience migraines, large amounts of aspartame (900-3,000 mg/kg body weight/day) have been found to induce headaches or make headaches worse. Alternatively, formaldehyde, which is a byproduct of aspartame, could do the same. Researchers of one randomized, controlled study—in what probably amounts to the best among low-powered studies on the topic—reported the following: “There was no significant treatment difference in the length or intensity of headaches or in the occurrence of side effects associated with the headaches. This experiment provides evidence that, among individuals with self-reported headaches after ingestion of aspartame, a subset of this group report more headaches when tested under controlled conditions. It appears that some people are particularly susceptible to headaches caused by aspartame and may want to limit their consumption.” In the trial, 18 participants were randomized to receive aspartame (~30 mg/kg/d) and placebo in a 2-treatment, 4-period crossover design. Upon aspartame exposure, participants reported headaches on 33% of treatment days, compared with only 24% with placebo (P = 0.04). Notably, patients who were “very sure” before beginning the study that aspartame led to headaches were more likely to experience treatment differences. Interestingly, this trial was cut short by participant attrition, with seven patients finding the headaches unbearable. Cardiovascular effects Other artificial sweeteners aside from aspartame have been implicated as factors in cardiovascular events. Some of these other low-calorie sweeteners found in food and drink include acesulfame potassium (ace-K), saccharin, and sucralose. According to results from the high-powered, prospective Women’s Health Initiative Observational Study that included over 80,000 participants, consumption of artificially sweetened beverages predicted stroke—especially among those with small artery occlusion, coronary heart disease, and all-cause mortality. Notably, 64.1% of participants never or hardly consumed artificially sweetened beverages, with only 5.1% consuming ≥ 2 such drinks a day. Bottom line Because emerging evidence on the adverse health effects of diet drinks with artificial sweeteners is largely being supported by low-powered studies, further investigation with higher powered, randomized, controlled trials is needed. However, those with migraine and cardiovascular risk factors should probably err on the side of caution and avoid drinking such beverages. Source
