Meta-analysis indicates reduced brain choline levels in individuals with anxiety disorders — Evidence Review

People with anxiety disorders have, on average, lower levels of the brain nutrient choline, according to a new meta-analysis from UC Davis Health. Prior research generally supports a link between reduced choline and greater anxiety symptoms.

• Multiple observational and experimental studies report that lower choline levels are associated with heightened anxiety and that dietary choline supplementation can reduce anxiety-like behaviors, especially in animal models 1 2 3 4.
• Population-level data show that individuals with low plasma choline are more likely to experience high anxiety, but not necessarily depression, suggesting a specific relationship between choline and anxiety 1.
• Genetic and dietary factors influencing choline metabolism may play a role in anxiety risk, and nutritional interventions targeting choline have shown promise for certain vulnerable groups 12 10.

Study Overview and Key Findings

Research into the biological underpinnings of anxiety disorders is ongoing, and this new analysis provides important evidence linking a specific brain nutrient—choline—to these conditions. The study is the first meta-analysis to systematically compare brain choline levels between individuals with anxiety disorders and healthy controls, using data from noninvasive brain imaging studies. As anxiety disorders remain common and often undertreated, identifying modifiable factors such as nutritional status is timely and relevant for both clinical and public health perspectives.

Property	Value
Organization	UC Davis Health
Journal Name	Molecular Psychiatry
Authors	Jason Smucny, Richard Maddock
Population	Individuals with anxiety disorders + controls
Sample Size	n=370, n=342
Methods	Meta-Analysis
Outcome	Choline levels in the brain
Results	Choline was 8% lower in those with anxiety disorders.

Literature Review: Related Studies

We searched the Consensus paper database, which contains over 200 million research papers, to identify how the new findings fit within the broader scientific literature. The following search queries were used:

1. choline levels anxiety disorders
2. brain nutrients anxiety connection
3. choline deficiency mental health effects

Topic	Key Findings
Does choline status influence anxiety risk and symptoms?	- Lower blood or brain choline is associated with higher anxiety symptoms in both population and animal studies 1 2 3 4 12. - Supplementation during key periods (perinatal, prenatal) can lower anxiety-like behaviors, especially in animal models 2 3 4 11.
How do dietary patterns and nutrition affect anxiety?	- Diets low in choline or containing high levels of refined carbohydrates are linked to higher anxiety and neuroinflammation 6 7. - “Healthy” dietary patterns (rich in micronutrients, omega-3s) are associated with lower anxiety 7 9 10.
What mechanisms link choline to brain health and mental disorders?	- Choline is critical for acetylcholine synthesis, cell membranes, and methylation pathways, all of which are involved in brain function and mood regulation 1 4 10. - Genetic variants affecting choline metabolism may alter risk for anxiety and depression 12 10.
Can nutritional interventions mitigate anxiety or related conditions?	- Supplemental choline can reverse or lessen anxiety-like behaviors and improve outcomes in models of stress, inflammatory bowel disease, and early-life nutrient deficiency 2 3 4 11. - Effects may be sex-specific or influenced by timing of supplementation 2 3.

Does choline status influence anxiety risk and symptoms?

Several studies support the conclusion that lower choline levels—whether measured in plasma or brain tissue—are linked to increased anxiety symptoms. In large-scale human studies, individuals in the lowest quintile of plasma choline had higher odds of experiencing anxiety, but not depression, suggesting a specific association 1. Animal research further demonstrates that dietary choline supplementation, especially during pregnancy and early life, can reduce anxiety-like behaviors in offspring 2 3 11. The new meta-analysis extends these findings by quantifying an 8% reduction in brain choline among adults with diagnosed anxiety disorders, strengthening the evidence for a link between choline status and anxiety.

• Both human and animal studies report that low choline is associated with higher anxiety symptoms, but not necessarily with depression, indicating specificity 1 2 3.
• Choline supplementation during pregnancy or perinatal periods can prevent anxiety-related behaviors in animal offspring 2 3.
• Sex-specific effects have been observed, with female offspring sometimes benefiting more from supplementation 2.
• The new study provides direct evidence from brain imaging, supporting and extending previous findings 1 2 3 11.

How do dietary patterns and nutrition affect anxiety?

Nutritional status and dietary patterns play a significant role in mental health, including anxiety. Diets high in refined carbohydrates or low in key micronutrients—including choline—have been associated with increased risk of anxiety and neuroinflammation in both animal and human studies 6 7. Conversely, diets rich in fruits, vegetables, omega-3 fatty acids, and other micronutrients are linked to lower anxiety and improved mental well-being 7 9 10. The current study’s suggestion that inadequate dietary choline may contribute to brain chemical imbalances in anxiety is consistent with these broader nutritional findings.

• Chronic consumption of high-refined carbohydrate diets induces anxiety-like behaviors and neuroinflammation in mice 6.
• “Unhealthy” dietary patterns (high fat, low micronutrient) correlate with increased anxiety, while “healthy” patterns are protective 7 9.
• Most people in the U.S. do not meet recommended choline intake levels, which may have implications for mental health 7 9 10.
• Omega-3-rich foods, also sources of choline, may offer dual benefits 7 9 10.

What mechanisms link choline to brain health and mental disorders?

Choline’s biological functions—including its role as a precursor for acetylcholine (a neurotransmitter involved in mood and cognition), maintenance of cell membranes, and participation in methylation reactions—are central to brain health. Studies indicate that disruptions in choline metabolism can impact gene expression, neurotransmitter synthesis, and neural circuits involved in mood and anxiety 1 4 10 12. Genetic factors, such as variants in the PEMT gene, influence individual choline requirements and may alter susceptibility to anxiety and depression 12 10.

• Choline is required for acetylcholine synthesis, which is critical for neural signaling and emotional regulation 1 4.
• Choline and related micronutrients influence epigenetic regulation of genes involved in mental health 10.
• Inflammatory and gut-brain axis pathways involving choline metabolism may contribute to anxiety in specific medical conditions 4.
• Genetic polymorphisms affecting choline biosynthesis can modulate dietary needs and mental health outcomes 12.

Can nutritional interventions mitigate anxiety or related conditions?

A number of animal studies have demonstrated that choline supplementation, particularly during gestation or early development, can mitigate anxiety-like behaviors and other neuropsychiatric outcomes following stress or nutrient deficiency 2 3 4 11. In conditions such as inflammatory bowel disease, choline supplementation not only improved anxiety-like behaviors but also restored markers of gut-brain axis health 4. Some evidence suggests these effects are more pronounced in females or depend on the timing of intervention 2 3. While clinical data in humans remain limited, these findings support further research into nutritional strategies for anxiety prevention and management.

• Prenatal and perinatal choline supplementation reduces anxiety-like behaviors in animal offspring, especially under stress or nutrient deficiency conditions 2 3 11.
• Choline interventions can restore gut and brain biochemical imbalances in models of inflammation-induced anxiety 4.
• Sex differences in response to supplementation have been documented 2 3.
• Clinical trials in humans are needed to assess efficacy and optimal intervention strategies 7 9.

Future Research Questions

While this meta-analysis advances understanding of choline’s role in anxiety disorders, further research is required to clarify causality, mechanisms, and effective interventions. Important questions remain about optimal choline intake, the impact of supplementation in clinical populations, and how dietary patterns or genetic factors may interact with choline status to influence anxiety risk.

Research Question	Relevance
Does choline supplementation improve anxiety disorder symptoms in humans?	Human intervention data are lacking; animal studies suggest benefit, but randomized controlled trials are needed to test efficacy, safety, and optimal dosing in people with anxiety disorders 2 3 4 7.
How do genetic differences in choline metabolism affect anxiety risk?	Variations in genes such as PEMT may alter choline requirements and susceptibility to anxiety, but the interaction between genetics, diet, and mental health requires further study 12 10.
What is the impact of choline-rich dietary patterns on long-term mental health?	While cross-sectional and animal evidence links diet to anxiety risk, prospective human studies are needed to determine if increasing choline intake through diet can prevent or reduce anxiety disorders over time 1 7 9 10.
Are there critical developmental periods when choline status is most important for anxiety risk?	Animal studies highlight prenatal and early life as key windows for intervention, but human data are scarce; identifying sensitive periods could guide nutritional recommendations 2 3 10 11.
How does choline interact with other nutrients (e.g. omega-3s) in modulating anxiety?	Choline and omega-3s may have synergistic effects on brain health and anxiety reduction, but the mechanisms and combined effects have not been fully explored in clinical studies 7 9 10.