Choline Supplementation and Cardiovascular Risk
Choline supplementation does not provide cardiovascular benefits in the general population and may actually increase cardiovascular risk through conversion to the harmful metabolite trimethylamine-N-oxide (TMAO). 1
Key Evidence Against Cardiovascular Benefit
The most recent and authoritative guideline evidence from ESPEN (2022) explicitly warns that enteral administration of choline can be converted by gut microflora into trimethylamine-N-oxide (TMAO), a uremic toxin with potential negative long-term impact on cardiovascular health. 1 This represents a critical safety concern that outweighs any theoretical benefits from homocysteine lowering.
The Homocysteine Hypothesis Has Failed
While choline supplementation (as phosphatidylcholine) can lower homocysteine levels by 18% at fasting and 29% post-methionine loading 2, this biochemical effect does not translate to cardiovascular benefit:
Eight large randomized controlled trials failed to demonstrate reduced cardiovascular events or mortality with homocysteine-lowering interventions (including B-vitamins and related compounds), despite substantial reductions in homocysteine concentrations. 1
The European Heart Journal guidelines emphasize that pharmacological treatment with folate and B vitamins on top of adequate dietary intake provides no additional cardiovascular benefit in subjects with normal-range homocysteine. 1
Divergent Effects of Choline vs. Betaine
Plasma choline and betaine show opposite associations with cardiovascular risk factors, suggesting disruption of normal choline metabolism may be harmful: 3
High plasma choline is associated with unfavorable cardiovascular profiles: elevated triglycerides, glucose, BMI, body fat, waist circumference, and lower HDL cholesterol 3
High plasma betaine shows favorable associations: lower non-HDL cholesterol, triglycerides, BMI, body fat, waist circumference, and blood pressure 3
Observational Data Shows Mixed Results
Recent epidemiological studies provide conflicting evidence:
Higher dietary choline intake was associated with lower stroke risk in both the National Health and Nutrition Examination Survey 2011-2016 (OR 0.693 for highest vs. lowest quartile) 4 and the Jackson Heart Study 5
However, dietary choline and betaine intakes were not significantly associated with overall CVD risk in systematic reviews 6
Higher choline intake was paradoxically associated with elevated inflammatory markers (CRP, IL-6, TNF-α) 6
Clinical Recommendations
When Choline May Be Indicated
Choline supplementation should be reserved for specific deficiency states only: 1
Patients on home parenteral nutrition with unexplained liver steatosis/steatohepatitis or subclinical muscle damage (elevated creatine kinase) 1
Cystic fibrosis patients with documented choline depletion despite enzyme treatment 1
Dosing: 550 mg to 2 g/day for proven deficiency 1
Critical Pitfall to Avoid
Do not supplement choline for cardiovascular disease prevention or treatment. The conversion to TMAO represents a mechanistic pathway for cardiovascular harm that supersedes any theoretical benefit from homocysteine lowering. 1 This mirrors the failed B-vitamin trials where biochemical improvements did not translate to clinical benefit. 1
Upper Limit of Safety
The tolerable upper limit for adults is 3.5 g/day, with acute high doses potentially causing hypotension and fishy body odor. 1