Side Effects of Aspartame: Dangers of this Common Sweetener

Written by Tim Skwiat, MEd, CSCS, Pn2

4 Dangerous Side Effects of Aspartame

Aspartame is a non-caloric, high-intensity artificial sweetener that’s 200 times sweeter than sugar. Chemically speaking, aspartame is a “dipeptide.” This simply means it’s composed of two amino acid-like compounds—aspartic acid and the methyl ester (i.e., methanol) of phenylalanine.

It’s true that the components that make up aspartame (i.e., aspartic acids and phenylalanine) are similar to those found in everyday foods. However, similar does not mean alike. And there is nothing in nature quite like this lab-created additive.

Aspartame is the artificial sweetener in little blue packets. It is best known under the brand name Equal®. You may also remember NutraSweet®, which shut its production of aspartame down in 2014 citing foreign competition that made it “impossible for us to sustain a profitable business.”

This sweetener is found in over 6,000 foods, medications, and beverages (most notably, diet drinks). Millions of American adults and children consume aspartame daily (often unknowingly). Despite its widespread use, aspartame remains one of the most controversial food additives.

On one side, you have scientists and health zealots providing compelling evidence that aspartame (and its metabolites) are responsible for a broad range of adverse effects, such as headaches, compromised memory, anxiety and depression, behavioral disturbances, hair loss, weight gain, and cancer.

On the flipside, you have groups arguing that aspartame is safe, hanging their collective hats on decades’ old safety data and approval of numerous international bodies, such as the United States Food and Drug Administration (FDA), Health Canada, and the European Food Safety Authority.

Is Aspartame Safe?

As with most questions, the irritating answer is “it depends.” And in this case, it depends on who you ask. On one hand, if you play Dr. Google, you’ll have no trouble finding one frightening personal account after another attributing multiple health disasters as the side effects of aspartame. In contrast, aspartame marketing paints an entirely different picture, implying it embodies a healthy way of life and is a useful tool for weight and glucose management.

Since 1981, when the FDA first approved aspartame—which, by the way, was launched by Monsanto (the same company notorious for the weed killer glyphosate/Roundup, not to mention the dissemination of genetically modified plants and foods)—researchers have debated both its recommended safe amounts and its general safety to organ systems. The World Health Organization and regulatory food authorities in Canada and Europe consider safe doses (i.e., acceptable daily intake, ADI) of aspartame to be below 40 mg per kilogram of body weight per day (mg/kg/day). Meanwhile, the FDA draws the line for the ADI at 50 mg/kg/day.

To put it into perspective, a 150-pound person weighs about 68 kilograms, for which the ADI would be between 2,720 and 3,400 mg of aspartame. According to the University of Alabama at Birmingham, a single packet of Equal contains 37 mg of aspartame while a 12-ounce can of diet soda contains 200 mg.

Unless you’re using 90-plus packets of Equal a day or drinking 200-plus ounces of diet soda daily, you shouldn’t have anything to worry about, right? Not so fast. While the safety data can be useful (for getting a patent, for instance), it doesn’t always tell the whole story. For instance, rodent studies (which are typically the basis for safety data studies) don’t tell us the functional impact or practical significance.

In a study published in the journal Research in Nursing & Health, researchers from the University of North Dakota examined the real-life effects of considerably lower amounts of aspartame. When folks consumed diets containing 25 mg/kg/day aspartame (half the “safe” amount, according to the FDA guidelines) for 8 days, they were more irritable, more depressed, and scored worse on tests of cognitive function.1

While it may seem outrageous to use 45 packets of Equal, believe it or not, there are people drinking 100-plus ounces of diet soda on the regular. Although that may be an extreme example, there’s certain to be folks who are sweetening their food and drinks with Equal, drinking diet soda, and chewing sugar-free gum, eating breakfast cereals, yogurt, sugar-free candy, and other reduced-calorie and sugar-free food products sweetened with aspartame.

It all adds up, and so, too, may the cumulative effects. In other words, it may not just be a matter of how much. It may also come down to frequency and duration.

4 Scary Side Effects of Aspartame

1. Cognitive Dysfunction, Behavior Issues, and Mood Disorders

There’s at least a handful of potential reasons why aspartame may be harmful. According to one recent review study published in the journal Nutrition Reviews, for example, “The existing animal studies and limited human studies suggest aspartame and its metabolites, whether consumed in quantities significantly higher than the recommended safe dosage or within recommended safe levels, may disrupt the oxidant/antioxidant balance, induce oxidative stress, and damage cell membrane integrity, potentially affecting a variety of cells and tissues and causing a deregulation of cellular function, ultimately leading to systemic inflammation.”2

Chances are you’ve heard by now that chronic systemic inflammation is bad news. It’s an underlying factor (if not key cause) of almost all chronic degenerative diseases.3 While there are multiple factors that can contribute to chronic inflammation, excess oxidative stress is a major trigger.4 In a study published in the journal Drug and Chemical Toxicology, researchers found long-term consumption of aspartame significantly reduced concentrations of glutathione, the body’s “master antioxidant,” in the brain.5

From a neurobiological standpoint, it’s also important to understand a bit of biochemistry about aspartame. Once ingested, aspartame is metabolized to yield aspartic acid, phenylalanine, and methanol. Phenylalanine is involved in neurotransmitter regulation, and aspartic acid is an “excitatory” neurotransmitter.

Disturbances in neurotransmitter regulation can result in neurobehavioral disturbances. Aspartame also compromises the blood-brain barrier, increasing its permeability and altering concentrations of neurotransmitters (such as dopamine).

It’s also worth noting that part of the reason aspartame is thought to increase the risk of neurologic deficits (and even cancer) is because of its conversion to methanol and formaldehyde.6 When stored near or above room temperature, methanol (one of the components of aspartame) is metabolized into formaldehyde, which is a known human carcinogen.

Given these effects on the nervous system, aspartame has been linked to mental disorders, cognitive dysfunction, headaches, and more. Along those lines, randomized controlled trials (yes, involving humans) have shown that some of the dangerous side effects of aspartame are:1

  • Longer memory lapses
  • Impaired memory and word recall
  • Slower reaction times
  • Impaired attention and focus
  • More irritable mood
  • Greater feelings of depression
  • Impaired performance on tests of cognitive function

One study had to be stopped prematurely due to the severity of adverse reactions in depressed participants who consumed aspartame. The researchers concluded, “Individuals with mood disorders are particularly sensitive to this artificial sweetener, and its use in this population should be discouraged.”7

In a study published in the journal PLOS ONE, researchers from the National Cancer Institute evaluated the connection between soft drink consumption and the risk of depression among a sample of over 260,000 participants in the NIH-AARP Diet and Health Study. They found that frequent consumption of diet sodas (which are typically sweetened with aspartame) significantly increased the risk for depression among older adults.8

2. Weight Gain & Obesity

As a zero-calorie sugar substitute, it seems like it would be a no-brainer that aspartame would help with weight loss. After all, if it’s 200 times sweeter than sugar, swapping 5 g of aspartame (which is considered an average amount annually) for its equivalent of 1,000 g (or 1 kg) of sugar, which represents about 4,000 kcal, would lead to a theoretical 1 pound or so loss in weight.

Even the astute Academy of Nutrition and Dietetics takes the position that non-nutritive sweeteners can help limit energy intake as a strategy to manage weight and blood glucose.9

As intuitive as that conclusion may seem, however, it doesn’t seem to work that way in the real world. At best, the evidence that aspartame prevents weight gain or obesity is inconclusive. Worse, there’s compelling evidence that aspartame may prevent, not promote, weight loss.

In a recent study published in the Canadian Medical Association Journal, researchers found that potential side effects of aspartame are long-term weight gain and increased risk of obesity, as well as increased risk of diabetes, high blood pressure, and heart disease.10

In general, increased awareness of the health consequences of excess sugar consumption has fueled a dramatic uptick in the consumption of zero-calorie artificial sweeteners, such as aspartame. However, new research published in the journal Experimental Biology shows sugar substitutes like aspartame can cause health changes that are linked with diabetes and obesity. This suggests switching from regular to diet soda, for example, may be a case of “out of the frying pan, into the fire.”

According to lead researcher Brian Hoffman, PhD, assistant professor in the department of biomedical engineering at the Medical College of Wisconsin and Marquette University, “In our studies, both sugar and artificial sweeteners seem to exhibit negative effects linked to obesity and diabetes, albeit through different mechanisms from each other. We also observed that replacing sugars with non-caloric artificial sweeteners leads to negative changes in fat and energy metabolism.”

If that’s not worrisome enough, check this out: Recent research reveals that women who drank artificially-sweetened beverages like diet soda (presumably containing aspartame at least a majority of the time) every day while pregnant were more likely a year later to have infants with a higher body mass index (BMI). In other words, women who consumed more aspartame and other artificial sweeteners were more likely to have overweight babies. To put it differently, the dangers of aspartame consumption seems to affect offspring, trickling down at least one generation.

3. Type 2 Diabetes & Metabolic Syndrome

Zero calories and sugar-free, there shouldn’t be any concern about aspartame when it comes to blood sugar management and metabolic health, right? That’s a rational thought process. In fact, it’s why many healthcare practitioners recommend its use to type 2 diabetics. After all, it’s 200 times sweeter than sugar yet has a negligible effect on blood glucose levels.

However, research shows that the side effects of aspartame may include increased risk of weight gain (rather than weight loss) and impaired glucose tolerance in type 2 diabetics.11

In a report published in the journal Applied Physiology, Nutrition and Metabolism, a team of Massachusetts General Hospital investigators found a possible mechanism explaining why the use of aspartame may lead to metabolic syndrome—a group of symptoms associated with type 2 diabetes and cardiovascular disease.12

In the study, the researchers showed how the aspartame breakdown byproduct phenylalanine blocks the action of an enzyme (i.e., intestinal alkaline phosphatase) that can prevent obesity, diabetes, and metabolic syndrome. In the study, they also showed mice receiving aspartame in their drinking water gained more weight and developed other symptoms of metabolic syndrome than animals fed similar diets without aspartame.

And according to another study published in the journal Applied Physiology, Nutrition and Metabolism, aspartame intake is associated with greater glucose intolerance in individuals with obesity. The researchers at York University’s Faculty of Health said, “Individuals with obesity who consume artificial sweeteners, particularly aspartame, may have worse glucose management than those who don’t take sugar substitutes.”13

While human studies are somewhat limited and inconsistent, rodent studies paint a fairly clear picture that common side effects of aspartame include glucose intolerance, insulin resistance, and hyperinsulinemia.14

It’s believed aspartame may act as a chemical stressor by increasing levels of the hormone cortisol, which has many bodily functions, including raising levels of blood glucose. As mentioned, aspartame may lead to the production of excess free radicals, triggering systemic oxidative stress and inflammation, which are well-established factors linked to type 2 diabetes.

Aspartame may also alter the activity and balance of gut microbes, and it may interfere with the N-methyl D-aspartate (NMDA) receptor, resulting in insulin deficiency or resistance.11 That’s a lot of mumbo jumbo, I know, but the point is that despite being a non-nutritive sugar substitute that doesn’t impact blood glucose, there’s compelling evidence that aspartame may do more harm than good when it comes to glycemic control and variability.

4. Negative Gut Bacteria

In addition to its potential impact on metabolism, appetite, weight management, cognitive function, and mood, aspartame may also have negative effects on the digestive system, namely on gut bacteria. In fact, negative alterations in the gut microbiota seem to underlie at least some of the other negative effects of aspartame mentioned above (e.g., glucose intolerance).

While artificial sweeteners like aspartame are touted because they’re sugar-free, recent research shows that gut bacteria may be able to break down artificial sweeteners, resulting in negative health effects.

Admittedly, it’s challenging to understand exactly how aspartame influences the gut microbiota because it tends to be rapidly broken down in the small intestine. Be that as it may, there’s compelling evidence that despite being metabolized in the upper intestine, gut bacteria still used and are affected by aspartame (perhaps via the byproducts of its metabolism), or maybe yet-to-be-determined mechanisms are involved.14

According to a new paper published in Molecules by researchers at Ben-Gurion University of Negev in Israel and Nanyang Technological University in Singapore, artificial sweeteners, including aspartame, are toxic to gut bacteria. Researchers say the consumption of artificial sweeteners, such as aspartame, can adversely affect gut microbial activity, causing a wide range of health issues from cancers to type 2 diabetes.15

While they are considered safe, there is increasing controversy regarding the potential of artificial sweeteners, including aspartame, to promote metabolic derangements. Recent research suggests that alterations in glucose metabolism (e.g., glucose intolerance) seem to be functionally mediated by alterations of the gut microbiome.

How to Avoid the Side Effects of Aspartame

While the rationale for aspartame and other non-nutritive artificial sweeteners makes enormous sense, studies show counterintuitive links between non-caloric artificial sweeteners and the same ailments of metabolic syndrome they are meant to prevent, such as weight gain, heart disease, type 2 diabetes, and more. Several physiological explanations have been suggested, such as increased sugar absorption, disruption of the ability of sweet taste to signal caloric consequences, an increase in appetite, impaired glycemic or insulin responses, and disturbances in the gut microbiota.14


Put differently, there’s drastically less upside to aspartame than we have been led to believe. Even worse, there’s compelling and significant evidence to believe it may be harmful, especially when consumed in meaningful amounts for prolonged periods of time. While you could potentially make a case for its application as a sugar substitute for someone who’s consuming a substantial amount of added sugar and excess calories, that would be a very short-term approach. Even then, there are much safer, better options.

Having said all that, while I would like to take a more agnostic viewpoint, I just don’t see any benefit to the regular, long-term consumption of this artificial sweetener, especially given all the potential side effects of aspartame. With that in mind, here are some action steps:

  • Take attendance. The first step is being mindful of your consumption of aspartame. While diet sodas are the most recognizable suspect, aspartame is found in a wide variety of products:
    • Diet soda
    • Sugar-free gum
    • Sugar-free mints
    • Sugar-free candy
    • Sugar-free condiments (e.g., ketchup, syrup)
    • Cereals
    • Coffee syrups
    • Sugar-free ice cream and toppings
    • Diet drinks (e.g., iced tea)
    • Sugar-free fruit drinks
    • Meal replacement shakes/snacks
    • Nutrition/protein bars
    • Sugar-free sports drinks
    • Yogurt
    • Fiber supplements
    • Most obvious: The blue packets used to sweeten coffee, tea, etc.
  • Cut back. If you find you’re consuming a lot of the products mentioned above—either a wide variety, a lot of a single category, and/or both—then work on cutting back. There’s more on this below, but the constant hankering for something sweet is something that needs to be addressed in and of itself.
  • Make better choices. As mentioned, the potential costs far outweigh the benefits when it comes to aspartame. The good news is there are better choices, such as stevia, monk fruit, erythritol, isomaltose, and xylitol, which have far fewer downsides and even some potential upsides.

In general, I think you could make an argument that most people could stand to reduce the amount of “sweet stuff” they eat. Between added sugars and non-nutritive, high-intensity sweeteners, many people are persistently exposed to sweet-tasting foods, which tend to be highly reinforcing and lend to the development of a “sweet palate” (notably at an alarming rate among children).16,17

One of my favorite conclusions comes from an editorial published in the British Medical Journal and written by Professor Michael Lean, Chair of Human Nutrition (Medicine) at the University of Glasgow, who said, “The cynical conclusion is that there is probably too much sweetness and never enough light, and the public probably needs protection against misleading websites.”16

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References

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  • 2. Choudhary AK, Pretorius E. Revisiting the safety of aspartame. Nutr Rev. 2017;75(9):718-730. doi:10.1093/nutrit/nux035
  • 3. Pahwa R, Jialal I. Chronic Inflammation. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2019.
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  • 10. Azad MB, Abou-Setta AM, Chauhan BF, et al. Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ Can Med Assoc J J Assoc Medicale Can. 2017;189(28):E929-E939. doi:10.1503/cmaj.161390
  • 11. Choudhary AK. Aspartame: should individuals with Type II diabetes be taking it? Curr Diabetes Rev. 2018;14(4):350-362. doi:10.2174/1573399813666170601093336
  • 12. Gul SS, Hamilton ARL, Munoz AR, et al. Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice. Appl Physiol Nutr Metab. 2016;42(1):77-83. doi:10.1139/apnm-2016-0346
  • 13. Kuk JL, Brown RE. Aspartame intake is associated with greater glucose intolerance in individuals with obesity. Appl Physiol Nutr Metab. 2016;41(7):795-798. doi:10.1139/apnm-2015-0675
  • 14. Suez J, Korem T, Zilberman-Schapira G, Segal E, Elinav E. Non-caloric artificial sweeteners and the microbiome: findings and challenges. Gut Microbes. 2015;6(2):149-155. doi:10.1080/19490976.2015.1017700
  • 15. Harpaz D, Yeo LP, Cecchini F, et al. Measuring artificial sweeteners toxicity using a bioluminescent bacterial panel. Molecules. 2018;23(10):2454. doi:10.3390/molecules23102454
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