We use essential cookies (authentication, your saved goals/stack) by default. With your permission we’ll also enable privacy-respecting analytics (Vercel Web Analytics, anonymous load-time metrics) and error-replay diagnostics (Sentry — DOM snapshots only when an error fires) so we can fix bugs faster. Learn more about cookies
Co6.0
Choline Research
Mixed evidence
114 peer-reviewed studies
What the evidence says
Too few graded studies
Choline doesn't have enough studies with structured effect-size data yet to pool a verdict. Browse the studies below for individual findings.
Most evidence is from high-quality meta-analyses and randomised trials published 1978–2026 with a typical study size of 288 participants.
Based on 114 studies · 14 meta-analyses · 77 RCTs · 534,993 total participants
Confidence
High confidence
What the studies found
1helped1didn't help· 112 more without graded effect data
By outcome
Cognitive functionAn acetylcholine precursor. No cited adult memory trial of choline itself · 2-4 weeks
Too few graded studies33 studies
Women's healthNo cited study measured hormones or cycle symptoms · 4-8 weeks · Most pregnant women fall short of the recommended intake, and small trials suggest more choline in late pregnancy may help the baby's memory and attention · Ongoing
Neuroprotection & brain agingNeeded to make acetylcholine and nerve-cell membranes. No trial measured protection of the brain · Ongoing
Too few graded studies1 study
By the numbers
Pulled from 27 studies with measurable effects
Likely real effects
100%
across studies
People studied
535k
typical study: 288 people
Strongest designs
91
14 pooled, 77 randomised
Showed benefit
50%
1/2 studies
How long studies ran
1–3 months
2
3+ months
1
Populations Studied
General population4
Pregnant women3
Adults2
Patients with neurological conditions associated with cerebrovascular injury1
Active research area
48 studies in the last 5 years · Latest meta-analysis: 2026
197820022026
1Cognitive function improvementMeta-AnalysisCited 35×2023
In plain English: 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.
2Cardiovascular disease risk and all-cause mortalityMeta-AnalysisCited 14×n=33,009 · very large study2023
In plain English: 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).
3All-cause and cardiovascular disease mortalityMeta-AnalysisCited 2×n=482,778 · very large study2024
In plain English: 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)
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.
4Incident coronary heart diseaseCohortCited 119×n=14,430 · very large study2007
In plain English: Higher intakes of choline and betaine were not protective for incident CHD.
Bidulescu A et al. · BMC cardiovascular disorders (2007)
Compared with the lowest quartile of intake, incident CHD risk was slightly and non-significantly higher in the highest quartile of choline and choline plus betaine, HR = 1.22 (0.91, 1.64) and HR = 1.14 (0.85, 1.53).
No association was found between dietary choline intake and incident CHD when correcting for measurement error.
Higher intakes of choline and betaine were not protective for incident CHD.
5Muscle fat metabolism and protein homeostasisReviewCited 43×2020
In plain English: 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)
Scoping review of choline and skeletal muscle: 14 studies included from 1,239 screened, of which 3 were in vitro, 9 in animals and 2 clinical.
The authors describe roles for choline in muscle fat metabolism, muscle protein balance, inflammation and autophagy, drawn mostly from laboratory and animal work.
6Dementia riskCohortCited 75×n=2,497 · very large study2019
In plain English: 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
7cognitive performanceCohortCited 116×n=1,391 · large study2011
In plain English: In this community-based population of nondemented individuals, higher concurrent choline intake was related to better cognitive performance, whereas higher remote choline intake was associated with little to no WMHV.
Poly C et al. · The American Journal of Clinical Nutrition (2011)
Performance on the verbal memory and visual memory factors was better with higher concurrent choline intake in multivariable-adjusted models.
Remote choline intake was inversely related to log-transformed white-matter hyperintensity volume.
An inverse association was observed between remote higher choline intake and presence of large white-matter hyperintensity volume (OR: 0.56; 95% CI: 0.34, 0.92; P = 0.01).
In plain English: The existing guidelines highlight the importance of choline in supporting maternal health and fetal development during pregnancy.
Nguyen HT et al. · Nutrition reviews (2025)
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.
In plain English: 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)
Meta-analysis of observational studies of dietary methionine, choline and betaine and breast cancer, 21 studies reviewed and 18 pooled.
Higher choline intake was linked to lower breast cancer risk in case-control studies (OR 0.38, 95% CI 0.16 to 0.86) but not in prospective cohorts (HR 1.01, 95% CI 0.92 to 1.12).
The authors conclude the data do not suggest an effect of choline on breast cancer risk, because the pooled estimates were imprecise.
13Tardive dyskinesia deteriorationMeta-AnalysisCited 21×n=288 · medium study2018
In plain English: TD remains a major public health problem.
Tammenmaa-Aho I et al. · The Cochrane database of systematic reviews (2018)
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).
In plain English: 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.
In plain English: 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.
17Heart failure incidence and adverse clinical outcomesMeta-Analysis2026
In plain English: Choline metabolites are implicated in HF development and progression.
Shokravi A et al. · Biochimica et biophysica acta. Molecular basis of disease (2026)
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.
In plain English: 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.
In plain English: 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)
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.