Common ingredients or characteristics of Diet Soda that may influence health include:
Artificial sweeteners such as Aspartame
Sweetening enhancers like Acesulfame-Potassium
Coloring (of which caramel coloring is of interest for colas)
Carbonation and General pH (acidity)
Other ingredients may exist in certain diet sodas, and the label should be looked at to see what may be of concern to you. This page will cover general topics, and link to relevant and sourced FAQ pages.
Aspartame is the most widely used and controversial artifical sweetener currently on the market, and is implicated in a wide-variety of concerns.
Concern of aspartame appears to be overblown for the most part. Its ability to 'cause headaches' is not well known and highly confounded with placebo/hypochondriacs, as well as being an underresearched topic. FAQ
Despite being sweet, aspartame does not appear to increase appetite. In actuality, it may actually suppress appetite due to the amino acids that make up the structure of aspartame. FAQ
Aspartame also does not seem to be a large concern when it comes to spiking insulin in the dosages commonly consumed through diet soda. FAQ Subsequently, fat loss is not impaired with diet soda use and it can be a safe addition to a lifestyle designed to lose body fat. FAQ
The acidity of diet sodas are one of the legitimate concerns, as diet soda (and to a greater degree, regular soda) are risk factors for dental caries in children. Mentioned in this FAQ
Caramel coloring in some cola products (Coke, Pepsi) is due to a molecule called 4-methylimidazole (henceforth 4-MEI), which is produced during browning reactions (not limited to cola). It has also been noted in Soy and Worcestershire sauce as well as coffee and dark beers, although it is most well known for being in caramel soda.
4-MEI appears to be involved in carcinogenesis, although its role is not clear. Toxicology studies in rats fed high doses of 4-MEI appear to indicate that it has carcinogenic (cancer-promoting) activities, however some argue that it may be anti-carcinogenic when looking at other tumor colonies. It should be noted that this review received funding from the 'American Beverage Association'.
When looking at the severity of 4-MEI exposure, an oral dosage of greater than 115-120mg/kg bodyweight daily over 106 weeks is associated with metabolic aberrations. Dosages below this do not appear to be much of a concern within this time frame.
The incidence of mononuclear cell leukemia at an oral dose of 250mg/kg bodyweight was significantly greater than control in females (dose not tested in males) and dosages above 115-120mg/kg bodyweight were associated with increased hepatocellular foci. This high dose was also associated with a 25-fold decrease in mammary tumors as noted by Murray, FJ in a review on the topic. Overall, there were no differences in mortality at any dosage, and body weight was decreased in the highest dosages.
The mechanism of action may be acting as a co-carcinogen, by inhibiting an enzyme (in P450, CYP2E1) that metabolizes carcinogens.
The dosage commonly found in soda is 250ppm max in the European Union and is unregulated in the US; common levels found in soft drinks in the US range from 0.3-0.36mcg/mL of beverage, which gives a range of 108-130mcg per 12 ounce beverage (375mL). One study estimated an intake of "2.3 and 5.7 mcg/kg body weight/day, in Europe and the United States, respectively" Relatively small dosages when considering the level of 4-MEI that was significant in the rat toxicology study, measured in mg/kg bodyweight.
Assuming the highest human estimate (5.7mcg/kg daily) and the lowest animal estimate that resulted in difference than control (30mg/kg bodyweight in female rats for alveolar hyperplasia), there is a greater than 5,000-fold difference.
The most concern you should have from 4-methylimidazole, or 4-MEI, is how it can make your teeth look brown if you don't rinse your mouth.