Scientists have identified a significant link between low levels of choline and the prevalence of anxiety disorders, suggesting that upping intake of this essential nutrient found in a range of foods – from eggs to seeds – could potentially improve symptoms of these debilitating conditions.
University of California Davis (UC Davis) researchers analyzed data from 25 studies that compared levels of neurometabolites in a total of 370 patients with at least one anxiety disorder diagnosis and 342 controls. Neurometabolites are the chemical products of metabolism in the brain, indicating neural activity, and have increasingly been the focus of scientists for conditions like schizophrenia and myalgic encephalomyelitis/chronic fatigue syndrome. In the study, the researchers looked at a range of these brain metabolites including n-acetlyaspartate (NAA), total creatine, total choline, myo-inositol, glutamate, glutamate and glutamine, GABA and lactate.
Observing measures produced through proton magnetic resonance spectroscopy (H-MRS), the scientists identified that levels of choline were significantly lower – average of 8% – in the brains of people with anxiety disorders compared with the control, and the difference was most pronounced and consistent in scans of the prefrontal cortex, the region that regulates emotion, behavior and executive function.
“This is the first meta-analysis to show a chemical pattern in the brain in anxiety disorders,” said study co-author Jason Smucny, an assistant professor in the Department of Psychiatry and Behavioral Sciences at UC Davis. “It suggests nutritional approaches – like appropriate choline supplementation – may help restore brain chemistry and improve outcomes for patients.”
Choline is an essential nutrient, which we need to get from our diet because the levels produced in the liver (as phosphatidylcholine) isn’t sufficient. The most common dietary sources of it are as the fat-soluble phospholipids phosphatidylcholine and sphingomyelin found in a broad range of foods including eggs, beef liver, red meat, chicken, potatoes, yogurt, fish, cruciferous vegetables and grains. About 90% of US adults are not meeting their daily choline requirements (550 mg/day for men, 425 mg/day for women who aren’t pregnant or menopausal).
While the chemical plays a large role in cell function, it’s also key in the production of acetylcholine, an important neurotransmitter for memory, mood and other brain and nervous system functions. So low levels in the prefrontal cortex, which is charged with many of these functions, could impair vital brain operations for our mental health. Anxiety disorders are linked to dysfunction in the fear-sensing amygdala – and the prefrontal cortex.
“Anxiety disorders are the most common mental illness in the United States, affecting about 30% of adults. They can be debilitating for people, and many people do not receive adequate treatment,” said senior author Richard Maddock, a psychiatrist and research professor at UC Davis.
In the study, the conditions under the “anxiety” umbrella included social anxiety disorder, generalized anxiety disorder, and panic disorder. They’re linked to imbalances in neurotransmitters, including norepinephrine that plays a critical role in the body’s “fight or flight” stress response. The researchers suggest that, for people with anxiety, this fight-or-flight response may demand higher levels of choline than in non-anxious brains, which could be draining this chemical’s levels as a result.
“An 8% lower amount doesn’t sound like that much, but in the brain it’s significant,” said Maddock, who has spent decades treating patients with anxiety disorders and undertaking research to better understand brain chemical imbalances. “We don’t know yet if increasing choline in the diet will help reduce anxiety. More research will be needed.”
In 2008, Maddock identified a link between choline levels and anxiety disorders, and while he expected to uncover this to be consistent in the latest meta-analysis, it was a surprise to see just how consistent and meaningful the association was. The research remains observational – low choline doesn’t cause anxiety – but it certainly warrants further investigation.
The researchers caution the use of choline supplements, but note that the role of diet on mental health is often overlooked. And use of advanced H-MRS technology – a non-invasive MRI scan that uses the magnetic fields and radio waves to detail the chemical makeup of tissue – could help identify key deficits.
“Someone with an anxiety disorder might want to look at their diet and see whether they are getting the recommended daily amount of choline,” Maddock said. “Previous research has shown that most people in the US, including children, don’t get the recommended daily amount.”
“Some forms of omega-3 fatty acids, like those found in salmon, may be especially good sources for supplying choline to the brain,” he added.
The research was published in the Nature journal Molecular Psychiatry.
Source: University of California, Davis

