Aspartame was discovered in 1965 by James Schlatter^[40] and can be made using either chemical or enzymatic synthesis methods.^[3][41][42]

Chemical synthesis methods couple the two amino acids that aspartame is composed of, L-aspartic acid and L-phenylalanine. However, chemical synthesis has the limitation that it produces a bitter isomer (β-aspartame) as well as the sweet isomer (α-aspartame) used in aspartame products. These isomers then have to be separated.

Enzymatic methods are preferable because they use Thermolysin, an enzyme derived from a bacterium called Bacillus thermoproteolyticus, which only produces the sweet isomer (α-aspartame).^[43][44][45]

Due to a lack of information on different manufacturers’ websites, it is unclear exactly which methods are used to produce aspartame by different manufacturers (Canderel, Hermesetas Gold, NutraSweet, Pal Sweet, etc.).

In 2016, an “umbrella” systematic review compiled all known reviews examining the effects of artificially sweetened beverages on weight outcomes.^[39] The systematic review sought to determine whether study findings were influenced by authors’ conflicts of interest, finding that reviews sponsored by the artificial sweetener industry were seventeen times more likely to have favorable results and two times more likely to have favorable conclusions than non-industry-sponsored reviews. Furthermore, reviews performed by authors with a food industry-related financial conflict of interest were seven times more likely to have favorable conclusions than reviews performed by authors without conflicts of interest.

Some case studies of individual people have reported headaches or migraine occurring after aspartame ingestion.^[4][5][6] Furthermore, the Center for Disease Control (CDC) found that 67% (346/517) of people submitting a complaint about aspartame reported neurological/behavioral symptoms, including headaches, dizziness, and mood alterations after consuming aspartame-containing products.^[7] Therefore, headaches are among the complaints about aspartame, but neither the data from the CDC nor observations from isolated case studies prove that aspartame causes headaches in all people.

To explore whether there is a causal link between aspartame and headaches, some randomized controlled trials have been completed. They show that the incidence of headaches after a single dose of aspartame does not differ from that after a placebo.^[8] Meanwhile, daily administration of aspartame has increased headache frequency in some^[9][10] but not all studies.^[11] However, it is important to note that these studies include a small number of participants and the quality of their design and statistical approaches have been debated.^[12][13][14]

Consequently, the low number of case studies and complaints suggests that aspartame-associated headaches are rare in the general population, and it is currently unclear whether aspartame consumption directly causes headaches or not. Further high-quality clinical trials would help remedy that lack of clarity. In the meantime, people who are susceptible to headaches following consumption of aspartame or aspartame-containing foods can choose to avoid such products.

The clinical evidence is mixed: Some observational studies show that higher levels of dietary aspartame intake are associated with an increased risk of some cancers,^[28] while other observational studies do not support that relationship.^[29] The current evidence also doesn’t show a dose response between aspartame intake and cancer risk,^[28][29] and no long-term randomized controlled trials of aspartame intake have investigated cancer outcomes. Therefore, the direct causality between aspartame exposure and cancer cannot yet be determined.

For these reasons, aspartame has been classified by the International Agency for Research on Cancer (IARC) and the Joint Food and Agriculture Organization and World Health Organisation Expert Committee on Food Additives (JECFA) as a “Group 2B” (possibly carcinogenic) compound in a four-group classification system.^[2]

To help put this classification in context, Group 1 means “carcinogenic to humans”, and includes things like solar radiation, processed meat, tobacco smoking, and air pollution. Group 2A means “probably carcinogenic to humans”, and includes eating red meat, anabolic steroids, indoor fireplace emissions, etc. Group 3 means “not classifiable regarding its carcinogenicity to humans”. Interestingly, the classification for aspartame — Group 2B — contains other common foods and supplements including pickled vegetables, aloe vera, kava extract, and caffeic acid (which is found in all plants, including coffee), and many other substances humans are exposed to daily.

Consequently, while aspartame is “possibly carcinogenic” (has the potential to cause cancer), aspartame intake in the amounts that are typically consumed is unlikely to cause cancer in humans (a person weighing 70 kg would have to consume approximately 9–14 cans of diet soda per day to exceed the acceptable daily intake level of 40 mg/kg/day). This is the current message conveyed by food regulatory bodies in the US — the FDA — and in Europe — the EFSA.^[3] However, this message might change when more high-quality clinical studies are completed.

It’s also important to note that it is challenging to prove that foods cause cancer in humans, because much of the evidence relies on observational studies that are unable to prove causality. For example, observational studies have shown that most common food ingredients are associated with both an increased and a decreased cancer risk, whereas meta-analyses of such studies find that the claimed benefits of such foods are nonexistent.^[38]

To summarize, the current evidence does not show that aspartame causes cancer in humans but the evidence doesn’t rule out that it can — absence of evidence is not evidence of absence. While aspartame is unlikely to pose a major risk, it is a food additive and not an essential nutrient; therefore, people can choose to avoid foods that contain aspartame to remove the exposure to any potential hazard.

Diet Soda and Fat loss

Biochemically speaking

First, let's define 'diet soda' as any drink that is sweetened with low to no calorie sweeteners (like sucralose, aspartame, acesulfame-potassium, etc.) in order to taste like regular (sugared) soda.

In short, there are no direct causative studies that show the use of artificial sweeteners slows your metabolism or promotes fat storage.^[46]

Intervention studies

The CHOICE randomized study, lasting 6 months and observing how different diet changes affect weight loss adherence, found that diet soda is an effective substitution for regular soda and had no significant differences in health or weight loss relative to water.^[47]

Data from the NHANES (03-04) study suggest that increased servings of non-caloric beverages are not related to an increase in total calories.^[48] Additionally, the PREMIER trial found that a reduction in intake of non-caloric beverage is not associated with weight loss.^[49]

What is the source of confusion?

The real problem is that people tend to under-estimate caloric intake. By thinking about the zero calories in the soda, they end up eating an excess of calories, thus increasing fat storage^[50]. This makes the well known correlation (relationship) between diet soda and obesity; one does not cause the other, but they tend to co-exist. Drinking diet soda does not make one fat, but people with obesity tend to drink diet soda.

In regards to insulin, diet soda can potentially increase insulin secretion by both an anticipatory response and the artificial sweetener aspartame can (through the amino acid, phenylalanine). However, both of these insulin spikes are too small to matter practically, and the latter mechanism doesn't seem to occur at all with many commonly ingested dosages.

Devil's advocate: Diet soda for weight loss?

As mentioned on our Aspartame and Appetite page, aspartame (via phenylalanine) might also suppress appetite.

Simply put...

Currently available research into diet soda and long-term health risks is insufficient, although there are specific areas where risks are unlikely. Contrary to popular belief, diet soda (defined as calorie free carbonated beverages sweetened with aspartame, sucralose, acesulfame-potassium, or other non-caloric or minimally caloric sweeteners) doesn't inhibit fat loss, or spike insulin levels.

Current research that attempts to link diet soda with type 2 diabetes and metabolic syndrome^[51][52] did not have equal caloric consumption. Excess caloric consumption has a direct correlation with many health issues, and in fact one of the studies^[51] distinctly states:

Consequently, the previously observed diet soda–metabolic syndrome associations are generally speculated to be the result of residual confounding by other dietary behaviors, lifestyle factors, or demographic characteristics (1,2). Biological mechanisms possibly explaining these associations are few and largely focus on artificial sweeteners in beverages/foods increasing the desire for (and consumption of) sugar-sweetened, energy-dense beverages/foods (3) or disrupting consumers' ability to accurately estimate energy intake and remaining energy needs (4). Thus, diet soda consumption may result in overconsumption, increased body weight, and consequent metabolic dysfunction.

In short, many people who have bad diets may consume diet soda in an attempt to do "less damage" - this could result in an incorrect association of diet soda consumption with health conditions.

What about those studies that I read saying diet soda was bad?

That was most likely a survey or epidemiological research. This is research that aims to find correlations (relationships) between two variables, and sets up future studies to find which variable causes what.

There are many studies that note that diet soda is frequently consumed by unhealthy people,^[51][52] but no studies that compare people with equivalent diets. One study (Northern Manhattan Study) was able to control a fair number of variables and found a weak correlation between diet soda and vascular events, but these differences disappeared when 'pre-existing health conditions' were considered.^[53]

When comparing diet soda against other non-caloric beverages in an intervention study, and you control the rest of the diet, no difference in weight loss is noted. This suggests that the problem is likely the habits of people who drink diet soda, rather than the diet soda itself.^[51] The Northern Manhattan study suggested that diet soda use may be correlated with disease as it its consumption was an attempt by (already unhealthy) individuals to reduce calories and take control of their health.^[53]

What are the legitimate downsides to diet soda?

Soda (in general) has been linked to poor dental health numerous times, especially children.^[54][55] Although sucrose (sugar) plays a major role, the general acidity of diet sodas can also negatively influence dental health.^[54] Overconsumption of soft drinks without adequate dental intervention may result in cavities and yellowing of teeth, and this applies to both sugared and diet sodas; although sugared are worse in this regard.^[56]

Like most things, overconsumption may not be a good idea, especially for your teeth. Otherwise if you want to enjoy a Diet Coke, Coke Zero, Diet Pepsi, or whatever diet soda you enjoy most, don't feel guilty about it.