Folic acid intake, rumination and worry in UK Biobank
What it found
In 72,621 UK Biobank participants, higher folate intake was linked to less worry but not to rumination.
The genetic patterns behind rumination differed between people with suboptimal and optimal folate intake.
What they found
Studies in people
Folate and worry
In the UK Biobank group, folate intake was inversely related to worry. It was unrelated to rumination.
Rumination genes, whole group
The ARNTL gene, a body clock regulator, came up for rumination in the whole sample. Purinergic signaling also appeared as a possible pathway.
Rumination genes, low folate
In the suboptimal folate group, gene sets for DNA replication, blastocyst development, homocysteine metabolism and immune responses appeared for rumination. Many of these genes sit in the same region of chromosome 17q12.
Rumination genes, optimal folate
In the optimal folate group, the KCNH3 gene and pathways for fatty acid and prostaglandin response came up for rumination.
Worry genes
Genetic results for worry did not point to specific biological processes. Most of the few enriched gene sets were related to cancer diseases.
Risk scores in NewMood
Risk variants for rumination found in the optimal folate group explained 0.56% of the variance in rumination scores in the NewMood sample. No other risk score result survived testing.
What the authors conclude
“Our results point to possible benefits of folate in anxiety disorders, and to the importance of simultaneously taking into account genetic and environmental factors to determine personalized intervention in polygenic and multifactorial disorders.”
Also in their conclusions
- They say their results point to possible benefits of folate in anxiety disorders.
- They stress the importance of taking genetic and environmental factors into account together to plan personalized intervention in polygenic and multifactorial disorders.
- They call for further studies to clarify the links between folate and the emergence and treatment of different anxiety disorders.
How it was done
The authors wanted to see whether folate intake changes the genetic background of two types of repetitive negative thinking, rumination and worry, which are linked to depression and anxiety.
They ran a genome-wide association study on two neuroticism items, one about rumination and one about worry, in 72,621 white British UK Biobank participants. These were split into 10,638 people with suboptimal folate intake and 61,983 with optimal folate intake, based on a 24 hour diet recall. They also tested whether risk variants found in UK Biobank explained rumination and neuroticism scores in a separate group of 1,746 people from the NewMood study.
What it can’t tell you
- This kind of study can show links between genes, folate intake and thinking patterns, but it cannot prove that folate causes changes in rumination or worry.
- Folate intake was estimated from a 24 hour diet recall, and in many people only once, so it may not reflect long term habits.
- The authors say future studies with measured blood folate levels and intervention trials are needed to confirm the proposed mechanism.
Who paid
- Funding
- Funded by Hungarian Brain Research Program; Ministry for Innovation and Technology; Sixth Framework Program of the European Union; Medical Research Council; Hungarian Scientific Research Fund; Thematic Excellence Programme; National Research, Development and Innovation Office; National Development Agency (from the PubMed record).
- Conflicts
- G.B. (Gerome Breen) has received honoraria, research or conference grants and consulting fees from Illumina, Otsuka, and COMPASS Pathfinder Ltd. G.B. (Gyorgy Bagdy) is a member of the Board of directors at Gedeon Richter. J.F.W.D. has share options in P1vital, and he has performed research, consultancy, and speaking engagements for AstraZeneca, Autifony, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, P1vital, Schering Plough, and Servier, for which all fees have been paid to the University of Manchester to reimburse them for the time taken. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The remaining authors declare no conflict of interest.
- Authors work at
- Semmelweis University, Hungary; Budapest University of Technology and Economics, Hungary; Kyoto University, Japan
The paper
- Title
- Biology of Perseverative Negative Thinking: The Role of Timing and Folate Intake
- Type
- Study
- Evidence
- Studies in people
- Summarised from
- Full text
- Cite
- Eszlari N, Bruncsics B, Millinghoffer A, et al (2021). Biology of Perseverative Negative Thinking: The Role of Timing and Folate Intake. Nutrients. doi:10.3390/nu13124396Free full textPubMed 34959947DOI
Summary written 26 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error