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Co9.0
Choline Research
Probably helpsHigh safety
43 peer-reviewed studies
What the evidence says
Probably helps
Choline helped in about half (10/16) of the studies that measured an effect — promising, but not unanimous.
Most evidence is from high-quality meta-analyses and randomised trials published 2005–2026 with a typical study size of 884 participants.
Based on 43 studies · 17 meta-analyses · 11 RCTs · 929,410 total participants
Confidence
High
What the studies found
10helped3unclear3didn't help· 27 more without graded effect data
34 studies in the last 5 years · Latest meta-analysis: 2026
200520152026
1neurometabolite levels in cortico-striatal-thalamo-cortical circuitsMeta-Analysisn=1,270 · large study2025
Conclusion This study reveals neurometabolic dysregulation within the cortico-striatal-thalamo-cortical circuits in OCD, offering integrated insights into its underlying neurobiological mechanisms.
Zhu F, Wen Q, Liu S, Gao Z, Tao B, Hu N, Zhao Q, Yu W, Xiao Y, Lui S. · Psychiatry and clinical neurosciences (2025)
Hedge's g with random effects model was employed to calculate the effect sizes for the between-group differences in neurometabolite levels.
Additionally, significantly increased thalamic Cho in OCD patients was also observed in the unmedicated, adult, 3.0T, and non-comorbid subgroups.
The symptom severity of OCD patients showed positive associations with Cho in the striatum.
2Cognitive outcomesMeta-AnalysisCited 27×n=1,326 · large study2023
α-GPC alone or in combination with donepezil improved cognition, behavior, and functional outcomes among patients with neurological conditions associated with cerebrovascular injury.
Sagaro GG et al. · Journal of Alzheimer's disease : JAD (2023)
Noticeable benefit
← WorseNo effectBetter →
We found significant effects of α-GPC in combination with donepezil on cognition [4 RCTs, mean difference (MD):1.72, 95% confidence interval (CI): 0.20 to 3.25], functional outcomes [3 RCTs, MD:0.79, 95% CI: 0.34 to 1.23], and behavioral outcomes [4 RCTs; MD: -7.61, 95% CI: -10.31 to -4.91].
We also observed that patients who received α-GPC had significantly better cognition than those who received either placebo or other medications [MD: 3.50, 95% CI: 0.36 to 6.63].
α-GPC alone or in combination with donepezil improved cognition, behavior, and functional outcomes among patients with neurological conditions associated with cerebrovascular injury.
3Cardiovascular disease risk and all-cause mortalityMeta-AnalysisCited 13×n=33,009 · very large study2023
Higher levels of circulating choline were associated with a higher risk of CVD and all-cause mortality.
Yang Q et al. · European journal of clinical investigation (2023)
Large harm
← WorseNo effectBetter →
Random-effects model results showed that highest versus lowest quantile of circulating choline concentrations were associated with the risk of CVD (RR = 1.29, 95% CI: 1.04-1.61) and all-cause mortality (RR = 1.62, 95% CI: 1.12-2.36).
We also observed the risk of CVD were increased 13% (5%-22%) with per SD increment.
Furthermore, highest versus lowest quantile of circulating betaine concentrations were not associated with the risk of CVD (RR = 1.07, 95% CI: 0.92-1.24) and all-cause mortality (RR = 1.39, 95% CI: 0.96-2.01).
4All-cause and cardiovascular disease mortalityMeta-AnalysisCited 2×n=482,778 · very large study2024
This study showed that each 100 mg/day increment in choline consumption was significantly associated with a 6% and 11% higher risk of all-cause and cardiovascular disease mortality respectively.
Sharifi-Zahabi E et al. · Nutrition research (New York, N.Y.) (2024)
Noticeable benefit
← WorseNo effectBetter →
This study showed that each 100 mg/day increment in choline consumption was significantly associated with a 6% and 11% higher risk of all-cause and cardiovascular disease mortality respectively.
In addition, a significant positive relationship between betaine intake and stroke mortality at doses of 50 to 250 mg/day was observed.
Due to the small number of the included studies and heterogeneity among them more well-designed prospective observational studies considering potential confounding variables are required.
6Muscle fat metabolism and protein homeostasisSystematic ReviewCited 39×n=1,239 · large study2020
Our scoping review elucidates and summarizes the crucial role of choline in modulating muscle fat metabolism, muscle proteins homeostasis, and the modulation of inflammation and autophagy.
Moretti A et al. · Nutrients (2020)
Our scoping review elucidates and summarizes the crucial role of choline in modulating muscle fat metabolism, muscle proteins homeostasis, and the modulation of inflammation and autophagy.
7Dementia riskCohortCited 71×n=2,497 · very large study2019
Higher phosphatidylcholine intake was associated with a lower risk of incident dementia; total choline intake was associated with better cognitive performance.
Ylilauri MPT et al. · The American Journal of Clinical Nutrition (2019)
Highest vs lowest phosphatidylcholine-intake quartile had 28% lower incident-dementia risk
Total choline intake showed no association with incident dementia risk
Both total choline and phosphatidylcholine intake were associated with better cognitive performance
The existing guidelines highlight the importance of choline in supporting maternal health and fetal development during pregnancy.
Nguyen HT et al. · Nutrition reviews (2025)
No clear effect
← WorseNo effectBetter →
Meta-analysis of 12 prevalence studies revealed a concerning 11.24% (95% confidence interval, 6.34-17.26) prevalence of pregnant women with adequate choline intake recommendations.
A meta-analysis of 6 studies indicated a significant association between high maternal choline levels and a reduced risk of developing APOs, with an odds ratio of 0.51 (95% confidence interval, 0.40-0.65).
The existing guidelines highlight the importance of choline in supporting maternal health and fetal development during pregnancy.
10Breast cancer riskMeta-AnalysisCited 12×n=21 · very small study2023
This study did not suggest an effect of dietary intake of methionine, choline, nor betaine on breast cancer risk, mainly due to the lack of precision of the combined risk estimates as few studies are available.
Van Puyvelde H et al. · Cancer epidemiology (2023)
This study did not suggest an effect of dietary intake of methionine, choline, nor betaine on breast cancer risk, mainly due to the lack of precision of the combined risk estimates as few studies are available.
To overcome this uncertainty, more well-designed studies with relevant individual-level covariates are needed.
11Tardive dyskinesia deteriorationMeta-AnalysisCited 20×n=60 · small study2018
TD remains a major public health problem.
Tammenmaa-Aho I et al. · The Cochrane database of systematic reviews (2018)
No clear effect
← WorseNo effectBetter →
Eight trials found that cholinergic drugs may make little or no difference to deterioration of TD symptoms (low-quality evidence, RR 1.11, 95% CI 0.55 to 2.24; 147 people).
Again, due to very low-quality evidence, we are uncertain about the effects on mental state (RR 0.50, 95% CI 0.10 to 2.61; 77 people, 5 RCTs), adverse events (RR 0.56, 95% CI 0.15 to 2.14; 106 people, 4 RCTs), and leaving the study early (RR 1.09,95% CI 0.56 to 2.10; 288 people 12 RCTs).
Low maternal choline intake/circulating concentrations were associated with a higher OR for NTDs among 1131 mothers of newborns with NTDs and 4439 control mothers (pooled estimate = 1.36; 95% CI: 1...
Obeid R et al. · Advances in nutrition (Bethesda, Md.) (2022)
Large harm
← WorseNo effectBetter →
Low maternal choline intake/circulating concentrations were associated with a higher OR for NTDs among 1131 mothers of newborns with NTDs and 4439 control mothers (pooled estimate = 1.36; 95% CI: 1.11, 1.67).
The 95% prediction intervals were 0.78, 2.36.
The risk could be up to 2.36-fold in some populations.
Health policies and guidelines should consider re-evaluation to help communicate and impart potential choline benefits through diet and/or supplementation approaches across this critical life stage.
Derbyshire E et al. · Nutrients (2020)
In total, 813 publications were subject to the title/abstract review, and 38 animal and 16 human studies were included after evaluation.
Overall, most offspring would benefit from increased choline supply during the first 1000 days of life, particularly in relation to helping facilitate normal brain development.
Health policies and guidelines should consider re-evaluation to help communicate and impart potential choline benefits through diet and/or supplementation approaches across this critical life stage.
15choline levels across brain regionsMeta-Analysisn=5,178 · very large study2026
Increased variability in psychosis and greater differences in treatment-resistant cohorts suggest increased choline levels might identify a subgroup who do not respond to dopamine antagonist treatment.
Standardized mean differences (SMDs) and log coefficient of variation ratios were pooled using random-effects meta-analysis, stratified by brain region and clinical subgroup.
Choline levels were elevated in people with psychosis in the anterior cingulate cortex (ACC: SMD = 0.23, CI 0.12-0.33), medial prefrontal cortex (mPFC: SMD = 0.12, CI 0.01-0.23), and dorsolateral prefrontal cortex (dlPFC: SMD = 0.15, CI 0.01-0.28).
Elevations were also seen in CHR cohorts (ACC: SMD 0.19, CI 0.03-0.36; mPFC: SMD 0.36, CI 0.16-0.57), with the largest effects in treatment-resistant schizophrenia (ACC: SMD 0.65, CI 0.38-0.91; dlPFC: SMD 1.13, CI 0.65-1.60).
16Type 2 diabetes incidenceMeta-Analysisn=76,678 · very large study2026
The findings of this study do not advocate the role of dietary choline/betaine in T2D incidence.
Sharifi-Zahabi E et al. · Journal of diabetes research (2026)
No clear effect
← WorseNo effectBetter →
Borderline
Compared with the lowest category of dietary choline, the combined RR for the diabetes incidence was 1.15 (95% CI: 1.00, 1.33; p = 0.058; I 2 = 63.1%) for the highest category of dietary choline.
Compared with the lowest category of dietary betaine, the combined RR for the diabetes incidence was 0.99 (95% CI: 0.90, 1.10; p = 0.871; I 2 = 58.1%).
The findings of this study do not advocate the role of dietary choline/betaine in T2D incidence.
17Heart failure incidence and adverse clinical outcomesMeta-Analysisn=267,569 · very large study2025
Choline metabolites are implicated in HF development and progression.
Shokravi A et al. · Biochimica et biophysica acta. Molecular basis of disease (2025)
Large harm
← WorseNo effectBetter →
Likely real
Elevated choline and PC were significantly associated with an increased incidence of HF respectively HR 1.33 (95 % CI 1.07-1.66, p = 0.0107) and HR 1.25 (95 % CI 1.16-1.34, p < 0.0001).
In established HF, elevated betaine levels were significantly associated with a composite of adverse clinical outcomes (HR 1.15, 95 % CI 1.02-1.30, p = 0.0206).
Choline metabolites are implicated in HF development and progression.
Conclusions Alongside folic acid recommendations, choline supplementation should be considered in dietary recommendations by clinicians during crucial life stages such as pregnancy and lactation when physiological demands for this critical nutrient substantially increase.
Derbyshire EJ. · Nutrients (2025)
However, there are clear present-day gaps between habitual choline intakes and intake recommendations with the majority of pregnant and lactating women not meeting adequate intake recommendations for choline.
This gap is anticipated to widen given transitions towards plant-based diets which tend to be lower in choline.
Conclusions Alongside folic acid recommendations, choline supplementation should be considered in dietary recommendations by clinicians during crucial life stages such as pregnancy and lactation when physiological demands for this critical nutrient substantially increase.
Conclusions Current evidence is insufficient to support or refute the hypothesis that increasing choline intake in pregnancy improves the neurodevelopmental outcomes of the child.
Gould JF, Hines S, Best KP, Grzeskowiak LE, Jansen O, Green TJ. · Nutrients (2025)
Still, each trial included multiple outcomes, and most were null.
Observational studies were mixed as to whether an association between prenatal choline and an aspect of child neurodevelopment was identified.
Critical limitations were present across clinical trials and observational studies, preventing confidence in the results and evidence base.