Table 3.
Main clinical studies investigating choline supplementation.
| Trial | Supplementation | Subjects | Results | Ref. |
|---|---|---|---|---|
| Randomized cross-over study (DRKS00020454) | choline chloride, choline bitartrate, GPC, egg-PC | 6 healthy adult men | -All supplements promptly raised choline and betaine levels to a similar extent, with egg-PC showing the latest peak. Considering TMAO may have unfavorable effects, egg-PC might be the best choline supplementation in adults. | (74) |
| Randomized double-blind placebo-controlled parallel clinical trial (IRCT20110123005670N25) |
500 mg/d choline and 500 mg/d magnesium co-supplementation | 96 patients with type 2 diabetes mellitus | -Combination of choline and magnesium intake have better outcomes in improving endothelial dysfunction and inflammation as compared to single supplementation alone | (75) |
| Randomized partially blinded single-center trial (NCT02509728) |
enteral choline (30 mg/kg/day), DHA (60 mg/kg/day), or both | 24 inborn preterm infants < 32-week postmenstrual age | -Co-supplementation may enhance DHA utilization. However, choline supplementation did not increase trimethylamine-N-oxide (TMAO) levels | (76) |
| Clinical open multicenter trial | 1000 mg i.m. for 28 days and orally at the dose of 400 mg t.i.d. during the following 5 months after the first phase | 2044 patients suffering from recent stroke or transient ischemic attacks | -Excellent tolerability and therapeutic role of GPC on cognitive recovery of patients with acute stroke or transient ischemic attack | (18) |
| Randomized, double-blind, controlled feeding study (NCT-1127022) | 480 or 930 mg choline/d | 29 women (≥21y) entering their 3rd trimester of pregnancy, 24 eligible infants | -Infants with higher maternal choline intake demonstrated high information processing speed which lasted for at least the first year of postnatal life | (77) |
| Single-center, randomized, double-blind, parallel-group study (NCT03194659) | 550 mg choline/d | Healthy pregnant person in their second trimester (21-40y) | -Maternal plasma choline metabolome (especially betaine) is very receptive to prenatal choline supplementation | (78) |
| Randomized, double-blind, placebo-controlled trial (PACTR202005864845358) | 2 g of choline/d | 52 infants born to heavy-drinking women who consumed choline supplementation during pregnancy | -Gestational choline supplementation alleviates alcohol exposure effects on neonatal brain volumes, choline may be neuroprotective against brain structural deficits related to prenatal alcohol exposure | (79) |
| Single-center, randomized, double-blind, parallel-group study (NCT03194659) | 500 mg/d choline and 200 mg docosahexaenoic acid | 30 pregnant women | -Prenatal choline supplementation (administered across the second and third trimesters of pregnancy) improved hepatic export of docosahexaenoic acid | (80) |
| Randomized, double‐blind, parallel‐group controlled trial (NCT01127022) | 480 or 930 mg choline/d | Children born to women during their 3rd trimester of pregnancy | -Prenatal choline supplementation enhances child sustained attention (7-year follow up) | (81) |
| Randomized, double‐blind, parallel‐group controlled trial (NCT01127022) | 480 or 930 mg choline/d | 26 healthy third-trimester pregnant women | -Maternal choline supplementation modulates biomarkers of vitamin B12 status in pregnancy | (82) |
| Randomized, Double-Blind, Placebo-Controlled Clinical Trial (NCT03369925) | 500 mg/d citicoline | 100 healthy men and women aged between 50 and 85y with age-associated memory impairment | -Regular consumption of citicoline improved attention and may be beneficial against memory loss due to aging | (83) |
| Randomized double-blind, placebo-controlled trial (NCT00720343) | 20 g of lecithin | 60 women having open gynecological surgery | -No analgesic benefit with oral choline supplementation between groups at rest or with movement. | (84) |
| Randomized controlled trial | 500 mg and 250 mg GPC | 48 healthy college-aged males | -Increased maximum velocity and maximum mechanical power | (56) |
| Double-blind, placebo-controlled crossover | 600 mg GPC | 13 healthy college-aged males | -Enhanced strength and performance especially the lower body force production | (55) |
| Randomized double-blind Placebo-controlled clinical trial (NCT01911299) | 5.25 ml of liquid GPC (~1240 mg GPC), equivalent to 625 mg of choline | 5-10y children with FASD | -General neurocognitive processes such as memory and attention, executive functioning, and hyperactivity pre- and post-intervention were not enhanced questioning the therapeutic window of choline for its efficacy | (85) |
| Randomized, double-blind, placebo-controlled trial (NCT01149538) | 500 mg/d choline bitartrate | 18 children aged 2.5-5y with FASD (after 7-year follow-up) | -Improved processing speed of lower-order executive tasks and better corpus callosum white matter microstructure and neurocognitive outcomes. | (86) |
| Randomized, controlled cross-over clinical trial (NCT03877003) | Three eggs/d, 400 mg/d choline as choline bitartrate | 23 men and women aged 35-70y with metabolic syndrome | -Plasma lutein and zeaxanthin were increased but plasma TMAO did not elevate eggs intake or choline bitartrate supplementation for 4 weeks -no significant effects on gut microbiota |
(87) |
| Randomized, double-blind, placebo-controlled intervention trial (ISRCTN82708510) | 1 g choline per day as choline bitartrate | 42 healthy postmenopausal women aged 49-71y | -Choline supplementation in postmenopausal women increases circulating free choline as well as methyl donor betaine | (88) |
| Placebo-controlled double-blind study | 2 g of choline bitartrate | 30 healthy individuals | -Enhanced visuomotor performance | (70) |