Neurophysiological symptoms and aspartame: What is the connection?

Nutr Neurosci. 2018 Jun;21(5):306-316. doi: 10.1080/1028415X.2017.1288340. Epub 2017 Feb 15.


Aspartame (α-aspartyl-l-phenylalanine-o-methyl ester), an artificial sweetener, has been linked to behavioral and cognitive problems. Possible neurophysiological symptoms include learning problems, headache, seizure, migraines, irritable moods, anxiety, depression, and insomnia. The consumption of aspartame, unlike dietary protein, can elevate the levels of phenylalanine and aspartic acid in the brain. These compounds can inhibit the synthesis and release of neurotransmitters, dopamine, norepinephrine, and serotonin, which are known regulators of neurophysiological activity. Aspartame acts as a chemical stressor by elevating plasma cortisol levels and causing the production of excess free radicals. High cortisol levels and excess free radicals may increase the brains vulnerability to oxidative stress which may have adverse effects on neurobehavioral health. We reviewed studies linking neurophysiological symptoms to aspartame usage and conclude that aspartame may be responsible for adverse neurobehavioral health outcomes. Aspartame consumption needs to be approached with caution due to the possible effects on neurobehavioral health. Whether aspartame and its metabolites are safe for general consumption is still debatable due to a lack of consistent data. More research evaluating the neurobehavioral effects of aspartame are required.

Keywords: Aspartame; Aspartic acid; Neurophysiological symptoms; Phenylalanine.

Publication types

  • Review

MeSH terms

  • Affect / drug effects
  • Animals
  • Aspartame / administration & dosage
  • Aspartame / adverse effects*
  • Aspartic Acid / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / diagnosis
  • Disease Models, Animal
  • Dopamine / metabolism
  • Free Radicals / blood
  • Humans
  • Hydrocortisone / blood
  • Migraine Disorders / chemically induced
  • Migraine Disorders / diagnosis
  • Nervous System Diseases / chemically induced*
  • Nervous System Diseases / diagnosis
  • Neurotransmitter Agents / antagonists & inhibitors
  • Neurotransmitter Agents / metabolism
  • Non-Nutritive Sweeteners / administration & dosage
  • Non-Nutritive Sweeteners / adverse effects*
  • Norepinephrine / antagonists & inhibitors
  • Norepinephrine / metabolism
  • Oxidative Stress / drug effects
  • Phenylalanine / metabolism
  • Seizures / chemically induced
  • Seizures / diagnosis
  • Serotonin / metabolism
  • Sleep Initiation and Maintenance Disorders / chemically induced
  • Sleep Initiation and Maintenance Disorders / diagnosis


  • Free Radicals
  • Neurotransmitter Agents
  • Non-Nutritive Sweeteners
  • Aspartic Acid
  • Serotonin
  • Phenylalanine
  • Dopamine
  • Hydrocortisone
  • Norepinephrine
  • Aspartame