Aspartame: Sweet Dangers

By Jodi Friedlander, N.C. and Edward Bauman, M.Ed, Ph.D.

Aspartame, accidentally discovered by a researcher working on a stomach ulcer remedy in 1965, has been in use in the United States since the 1980s and is currently one of the most widely used artificial sweeteners in the world. Aspartame is a dipeptide (two bonded amino acids) and breaks down in the intestinal tract into its component amino acids – phenylalanine (50%) and aspartic acid (40%) – and into methanol (10%), which is a toxic alcohol. These amino acids, as with all dietary proteins (chains of aminos), provide four calories per gram, so aspartame is not a non-caloric, non-metabolized sweetener. However, because it is almost 200 times sweeter than sucrose (table sugar), so little is required for sweetening purposes that its caloric contribution is negligible.

While it is well known that people with inborn errors in phenylalanine metabolism (phenylketonuria) need to avoid aspartame, less is known about its effects in those who are able to, and do, use it regularly. Aspartame has often been in the news, with battle lines drawn between those who promote its beneficial effects and those who consider it toxic, both sides equally adamant. This isn’t surprising, because differing conclusions are often reached when research is performed on food additives. Why is this so?

If researchers want their studies to show no harmful effects, they can use healthy subjects and a limited dosing of the substance and stop the project before adverse effects occur. When highly sensitive people – such as children, the chemically sensitive, the metabolically damaged, and the elderly – are subjected to larger quantities or longer term use, however, the results can be very damaging. These are often the typical users, but they are not the typical test subjects.

Such bias is common in the testing of food-like chemicals. Those who fund research have a great deal to gain from positive tests and so much to lose from negative ones that they may manipulate outcomes to their liking. Typically in these studies, animals — usually mice and rats — are used to ascertain an LD50 (a lethal dose). These animals may or may not be appropriate surrogates for human subjects, however, as the way they metabolize substances may differ from the way humans do.

When subsequent human testing is conducted, not only does human metabolic variation come into play, but biochemical individuality becomes an issue: there are many variations in the way individuals metabolize substances, based on genetic and environmental influences. Again, the people at greatest risk of an adverse reaction to any food, chemical, or drug are the very young, the chronically ill, those on medication, and the elderly. In the case of aspartame, while manufacturers and distributors hailed the FDA approval of aspartame as a sign of its safety, several thousand complaints per year are reported from aspartame ingestion.

What Can We Learn From the Studies?

A review of the scientific literature paints quite a complex picture, as aspartame is one of the most studied food additives ever, and independent researchers are pitted against chemical industry scientists. As advocates point out, most studies show that aspartame is safe to use in moderate doses for most people, which is how it achieved FDA approval, an approval that this government watchdog organization still supports (Hattan, 2010). However, until 2012, human studies were done using very few subjects over very short periods of time — the longest study being only four and a half months (Mercola, 2012), making it impossible to understand the consequences of regular use over time.


There is a long-simmering debate regarding whether aspartame causes cancer. Aspartame advocates, including the American Cancer Society (2011), point out that studies showing carcinogenicity have used doses well in excess of those normally consumed, and that these were performed on animals, not humans. However, Soffritti et al. (2007) demonstrated an increased risk of leukemia and lymphoma from aspartame consumption. Though the study involved lab animals, aspartame consumption was at levels similar to acceptable human doses. Human studies have not shown such a link — until 2012.

Harvard researchers, in the longest evaluation ever undertaken on the effects of aspartame, looked back over 22 years of the Nurse’s Health Study — 48,000 men and over 77,000 women over the age of 20 —  to determine whether aspartame could be linked to risk of blood-borne cancers. Their results showed increased rates of non-Hodgkin’s lymphoma and multiple myeloma in men who drank more than one diet soda daily, but not in women (Schernhammer et al., 2012). They also found an increased risk for leukemia from diet soda ingestion in both genders (Mercola, 2012). The specific compound or metabolite responsible for this reaction is unknown, though methanol is strongly suspected; nor is it known why men are at greater risk.


Perhaps the bigger issue is that aspartame is a neurotoxin – meaning that it negatively alters brain chemicals. The sweetener itself has been shown to lead to increased oxidative stress and inflammation in the brain (Abdel-Salam et al., 2012), and mental health practitioners commonly find that mood disorders — depression, anxiety, or bipolar disorder — are exacerbated by aspartame and easier to treat when the sweetener is eliminated from the diet (Warner, 2006).

Breaking it down further, excess levels of the amino acid phenylalanine can affect our mood chemicals — neurotransmitters — by lowering the production and availability of serotonin and dopamine (Rycerz & Jaworska-Adamu, 2013), low levels of which are most commonly associated with depression. Aspartate, aspartame’s other amino acid, is a well-known precursor of amino acids that cause neuron hyperexcitability, leading to what is known as excitotoxicity, one of the factors that leads to the death of brain and nervous system cells (Rycerz & Jaworska-Adamu, 2013).

Most studies of brain cell toxicity have focused on aspartame alone. But there is one that tested aspartame with non-nutritive additives like commonly used food-coloring agents, in concentrations consistent with daily intake, and found a cumulative effect that increased cellular toxicity to significant levels (Lau et al., 2006).


Artificial sweeteners have long been considered essential for those who wish to lose weight or maintain what’s been lost. Intuitively it makes sense that if one limits sugar calories, the pounds should melt away. It doesn’t get much better than being able to lose weight and have our sweets, too. If only it were true.

With overweight and obesity on the rise, especially among our nation’s young, researchers have been scrambling to assign guilt to most processed foods. Sugar and high-fructose corn syrup have, naturally, been particularly targeted. Yet public health statistics consistently reveal that, while weight gain may be associated with caloric sweeteners, it is also undeniably associated with the use of artificial sweeteners, including aspartame (Yang, 2010). Study after study has demonstrated increased body mass index (BMI) in those, especially, who drink diet sodas. What’s going on here?

It appears, once again, that it’s the brain, though it’s not about toxicity. Natural sweeteners activate what are known as “reward pathways” in the brain. Eat a sugar-containing food and the brain reacts with, “Ah, that was good and I feel satisfied.” Artificial sweeteners are now known to be unable to activate these pathways and create that sense of satisfaction, and they can even increase appetite (Yang, 2010). And it’s not just that artificial sweetener use may lead to more eating. Even when caloric intakes are equal, users of artificial sweeteners gain more weight than non-users and are more likely to have blood sugar imbalances, which can lead to diabetes (Frincu-Mallos, 2009).


It appears that there may be no good reason to use aspartame or any artificial sweeteners. As man-made chemicals, they do nothing to improve not only over all health, but even that all-important factor, appearance. Why be guinea pigs for the chemical companies that produce these additives, giving them our money while we wait for the final results of toxicity testing?

Are aspartame’s problems due to the compound itself, the user, or the amount ingested? We believe the answer is “all of the above.” Simple common sense should steer us toward natural compounds and away from synthetics that are foreign to nature and our bodies. No chemicals in our bodies are isolated. Compounds such as aspartame will interact with food, alcohol, medicines, and environmental toxins in unique and unpredictable ways. In the interest of maintaining good brain function and minimizing volatile chemical reactions in our bodies, we should seriously consider avoiding aspartame.


Abdel-Salam, O.M.E., Salem, N.A., & Hussein, J.S. (2012). Effect of aspartame on oxidative stress and monamine neurotransmitter levels in lipopolysaccharide-treated mice [Abstract]. Neurotoxicity Research, 21(3):245-255. doi:  10.1007/s12640-011-9264-9

American Cancer Society (ACS). (2011). Aspartame. Retrieved from

Frincu-Mallos,C. (2009, Jun 15). Use of artificial sweeteners linked to 2-fold increase in diabetes [Electronic version]. Medscape Medical News, ENDO 2009: The Annual Meeting of the Endocrine Society: Abstract P2-478. Presented June 11, 2009.  Retrieved from

Hattan, D.G. (2010, Feb 2 update). Aspartame. Retrieved from

Lau, K., McLean, W.G., Williams, D.P., & Howard, C.V. (2006, Mar). Synergistic interactions between commonly used food additives in a developmental neurotoxicity test [PDF]. Toxicol Sci, 90(1):178 – 187. doi:10.1093/toxsci/kfj073

Mercola, J. (2012, Nov 7). Aspartame associated with increased risk of blood cancers in long-term human study. Retrieved from

Schernhammer, E.S., Bertrand, K.A., Birmann, B.M., Sampson, L., Willett, W.C., & Feskanich, D. (2012, Dec).   Consumption of artificial sweetener– and sugar-containing soda and risk of lymphoma and leukemia in men and women [Abstract]. Am J Clin Nutr, 96(6):1419-1428. doi: 10.3945/ajcn.111.030833

Soffritti, M., Belpoggi, F., Tibaldi, E., Esposti, D.D., & Lauriola, M. (2007, Sep). Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats [PDF]. Environmental Health Perspectives, 115(9):1293-7. PMID: 17805418

Warner, M. (2006, Feb 12). The lowdown on sweet? New York Times. Retrieved from

Yang, Q. (2010, Jun). Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings [Article]. Yale J Biol Med, 83(2):101–108. Published online 2010 June. PMCID: PMC2892765