In plain terms: Choline shows early signals in human research but the evidence is limited -- small trials, surrogate endpoints, or not yet independently replicated. It is an emerging area, not yet a proven one.
Choline
The evidence as the record states it
Caudill et al. (FASEB J, 2018; PMID 29217669): 26 women in the third trimester randomized to 930 or 480 mg choline/day in a controlled feeding study, no placebo arm; infants of the 930 mg group (24 tested) had faster mean reaction time across 4 to 13 months; funded by the USDA and NIH with part funding from the Egg Nutrition Center and The Beef Checkoff, bodies that promote choline-rich foods, which the paper states had no role in the study. Bahnfleth et al. (FASEB J, 2022; PMID 34962672): 7-year follow-up of the same children (20 tested), better sustained attention in the 930 mg group. Null: Cheatham et al. (Am J Clin Nutr, 2012; PMID 23134891), 140 pregnant women randomized to phosphatidylcholine 750 mg or placebo from 18 weeks to 90 days postpartum, 99 infants tested, no difference in memory, language or global development. Gould et al. (Nutrients, 2025; PMID 40077755): systematic review of 4 trials and 5 observational studies; most neurodevelopmental outcomes did not support benefit, and the authors find the evidence insufficient to support or refute it. Adults: Deuster et al. (Mil Med, 2002; PMID 12502178), 13 men, choline 50 mg/kg, no effect on physical or cognitive performance after exhaustive exercise. Grade C for the infant endpoint: one small dose-comparison trial with a positive follow-up against a larger null placebo-controlled trial; the endpoint is measured in the offspring, not in the person taking the supplement. Adult use is ungraded.
Why Grade C and not Grade B
Grade C reflects early or limited human evidence -- small trials, surrogate endpoints, or preliminary findings not yet independently replicated. The evidence points in a promising direction but does not yet meet the standard for Grade B. A single well-powered, independently replicated trial with a meaningful endpoint would move this to Grade B or higher.
What would move this grade
A well-powered randomized trial with an objective, clinically meaningful primary endpoint and at least one independent replication would support Grade B or higher.