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Co9.0
Choline Research
Mixed evidenceHigh safety
32 peer-reviewed studies
What the evidence says
Mixed evidence
Studies are split: Choline helped in 5 of 11 cases, with the rest inconclusive or showing no benefit.
Most evidence is from high-quality meta-analyses and randomised trials published 2005–2026 with a typical study size of 1,200 participants.
Based on 32 studies · 12 meta-analyses · 11 RCTs · 916,515 total participants
Confidence
High
What the studies found
5helped3unclear3didn't help· 21 more without graded effect data
Patients with neurological conditions associated with cerebrovascular injury1
Active research area
23 studies in the last 5 years · Latest meta-analysis: 2026
200520152026
1Cognitive 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.
2Cardiovascular 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).
3All-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.
5Muscle 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.
6Dementia 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.
9Breast 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.
10Tardive 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.
14Type 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.
15Heart 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.
17Hyperphagia improvementRCTCited 30×n=127 · medium study2023
DCCR did not significantly improve hyperphagia in the primary analysis but did in participants with severe baseline hyperphagia and in the pre-COVID analysis.
Miller JL et al. · The Journal of clinical endocrinology and metabolism (2023)
Noticeable benefit
← WorseNo effectBetter →
Could be chance
DCCR did not significantly improve hyperphagia (HQ-CT least-square mean (LSmean) [SE] -5.94 [0.879] vs -4.27 [1.145]; P = .198), but did so in participants with severe hyperphagia (LSmean [SE] -9.67 [1.429] vs -4.26 [1.896]; P = .012).
In general, DCCR was well tolerated with 83.3% in the DCCR group experiencing a treatment-emergent adverse event and 73.8% in the placebo group (not significant).
DCCR did not significantly improve hyperphagia in the primary analysis but did in participants with severe baseline hyperphagia and in the pre-COVID analysis.
19memory performanceRCTCited 25×n=100 · medium study2021
Dietary supplementation of citicoline for 12 wk improved overall memory performance, especially episodic memory, in healthy older males and females with AAMI.
Nakazaki E et al. · The Journal of nutrition (2021)
Noticeable benefit
← WorseNo effectBetter →
Likely real
Composite memory (secondary outcome), calculated using the scores of 4 memory tests, also significantly improved to a greater extent following citicoline supplementation (mean: 3.78) compared with placebo (mean: 0.72, P = 0.0052).
Dietary supplementation of citicoline for 12 wk improved overall memory performance, especially episodic memory, in healthy older males and females with AAMI.
The findings suggest that regular consumption of citicoline may be safe and potentially beneficial against memory loss due to aging.