What choline does for the aging brain, how much you need, why it is hard to test, the foods that supply it, the APOE4 angle, and when a supplement makes sense
Really thought-provoking perspective. We were just discussing citicoline here in California, so coming across your piece at exactly the right moment felt particularly timely. Your work highlights how profoundly micronutrients influence brain health. These nutrients are far more than metabolic fuel; they serve as essential cofactors for neurotransmitter synthesis, mitochondrial function, myelination, and cellular repair. It is fascinating how seemingly modest deficiencies can exert disproportionately large effects on cognition, mood, and neurological function.
I also think it is important to recognize that brain health rarely depends on any single nutrient. Sleep, exercise, metabolic health, vascular health, and overall dietary patterns all interact with micronutrient status, and supplementation is most effective when guided by individual physiology rather than one-size-fits-all recommendations.
Ultimately, it is a valuable reminder that optimal brain function depends not only on what we think about, but also on the biochemical foundations that make those thoughts possible. Thank you for sharing such an insightful overview.
The interesting part is that phospholipids are not just brain nutrients, they are structural biology.
Every cell membrane is built from phospholipids, and phosphatidylcholine is one of the major phospholipids in mammalian membranes. So this is not only about memory or cognition. It is about membrane architecture, bile flow, lipid transport, and the basic coherence of every cell.
Observational studies link dietary phosphatidylcholine to dementia risk, but clinical studies of supplementation do not show cognitive benefit in Alzheimer's in meta-analysis. There is one small study of egg-yolk-derived phosphatidylcholine that found slightly better verbal memory in middle-aged to older adults, but the effects were small and did not extend to other cognitive domains. The evidence for citicoline is better if you want to pick a supplement because it crosses the blood brain barrier more effectively.
Any suggestions for support during pregnancy, especially when on mostly vegan diet? Some prenatal daily supplements include choline, but not necessarily in citicoline form
The default guidance is caution. Information on the safety and efficacy of citicoline in pregnancy and lactation is lacking at doses above those usually consumed nutritionally. It is not known whether citicoline affects pregnancy or could harm a fetus. Some consumer health references go further and advise that people who are pregnant or nursing not use citicoline because its safety in those groups is unknown. Those are precautionary statements reflecting absence of data rather than evidence of harm, but the bottom line is that supplemental citicoline at nootropic doses has not been studied for pregnancy outcomes the way plain choline has.
Definitely talk with your doctor about your specific case but here's what I found.
A 2018 Cornell trial by Caudill and colleagues, pregnant women given 930 mg a day in the third trimester had infants with better sustained attention at one year than those given 480 mg, and follow-up showed improved sustained attention at age 7 and faster infant information processing. The trial was small and unreplicated at scale, but it drove changes in pregnancy nutrition guidance. The American Medical Association in 2017 advised that prenatal supplements contain evidence-based choline, and the American Academy of Pediatrics in 2018 called it a brain-building nutrient and urged adequate intake in pregnancy.
The forms that were studied and used in pregnancy are plain choline and phosphatidylcholine (sold as choline bitartrate), not the brain-targeted adult nootropic forms. This is because the goal is raising whole body and fetal choline rather than specifically crossing the blood brain barrier.
-Emphasize the densest plant sources, soybeans and tofu and edamame, other legumes, quinoa, cruciferous vegetables, wheat germ, and peanuts, while recognizing they are less concentrated than animal foods.
-Check the prenatal's choline content and add choline bitartrate to make up the difference, since most prenatals cover little of the 450 mg.
Not surprised to see your work reaching me. I'm a pediatric stroke survivor now in my late 50s. Recently had symptoms and diagnosed with early and mild small vessel cognitive decline. I was prescribed Donepazil but have chosen not to take it. I'm unsure about its effectiveness and am more holistic based. I do take omega 3s and other supplements but now I want to look at what you've mentioned here.
For small vessel cognitive decline, I would focus on cardiac and metabolic risk factors since this is a cardiovascular problem manifesting in the brain. Ensure blood pressure, cholesterol, triglycerides, ApoB, hsCRP, fasting glucose, and HgA1C are not just in the normal range but in the optimal range through lifestyle and/or pharmaceutical strategies. Best of luck to you!
Really thought-provoking perspective. We were just discussing citicoline here in California, so coming across your piece at exactly the right moment felt particularly timely. Your work highlights how profoundly micronutrients influence brain health. These nutrients are far more than metabolic fuel; they serve as essential cofactors for neurotransmitter synthesis, mitochondrial function, myelination, and cellular repair. It is fascinating how seemingly modest deficiencies can exert disproportionately large effects on cognition, mood, and neurological function.
I also think it is important to recognize that brain health rarely depends on any single nutrient. Sleep, exercise, metabolic health, vascular health, and overall dietary patterns all interact with micronutrient status, and supplementation is most effective when guided by individual physiology rather than one-size-fits-all recommendations.
Ultimately, it is a valuable reminder that optimal brain function depends not only on what we think about, but also on the biochemical foundations that make those thoughts possible. Thank you for sharing such an insightful overview.
The interesting part is that phospholipids are not just brain nutrients, they are structural biology.
Every cell membrane is built from phospholipids, and phosphatidylcholine is one of the major phospholipids in mammalian membranes. So this is not only about memory or cognition. It is about membrane architecture, bile flow, lipid transport, and the basic coherence of every cell.
Thank you, Dr. Glorioso for this article.
Dr. Glorioso, I would really like to get your comments on phosphatidylcholine supplementation.
How does it affect the choline levels you are interested in for dementia.
Particularly for APOE4 carriers.
Adverse effects of phosphatidylcholine?
Thank you very much in advance.
Observational studies link dietary phosphatidylcholine to dementia risk, but clinical studies of supplementation do not show cognitive benefit in Alzheimer's in meta-analysis. There is one small study of egg-yolk-derived phosphatidylcholine that found slightly better verbal memory in middle-aged to older adults, but the effects were small and did not extend to other cognitive domains. The evidence for citicoline is better if you want to pick a supplement because it crosses the blood brain barrier more effectively.
Any suggestions for support during pregnancy, especially when on mostly vegan diet? Some prenatal daily supplements include choline, but not necessarily in citicoline form
Why not just use citocholine in pregnancy?
The default guidance is caution. Information on the safety and efficacy of citicoline in pregnancy and lactation is lacking at doses above those usually consumed nutritionally. It is not known whether citicoline affects pregnancy or could harm a fetus. Some consumer health references go further and advise that people who are pregnant or nursing not use citicoline because its safety in those groups is unknown. Those are precautionary statements reflecting absence of data rather than evidence of harm, but the bottom line is that supplemental citicoline at nootropic doses has not been studied for pregnancy outcomes the way plain choline has.
Definitely talk with your doctor about your specific case but here's what I found.
A 2018 Cornell trial by Caudill and colleagues, pregnant women given 930 mg a day in the third trimester had infants with better sustained attention at one year than those given 480 mg, and follow-up showed improved sustained attention at age 7 and faster infant information processing. The trial was small and unreplicated at scale, but it drove changes in pregnancy nutrition guidance. The American Medical Association in 2017 advised that prenatal supplements contain evidence-based choline, and the American Academy of Pediatrics in 2018 called it a brain-building nutrient and urged adequate intake in pregnancy.
The forms that were studied and used in pregnancy are plain choline and phosphatidylcholine (sold as choline bitartrate), not the brain-targeted adult nootropic forms. This is because the goal is raising whole body and fetal choline rather than specifically crossing the blood brain barrier.
-Emphasize the densest plant sources, soybeans and tofu and edamame, other legumes, quinoa, cruciferous vegetables, wheat germ, and peanuts, while recognizing they are less concentrated than animal foods.
-Check the prenatal's choline content and add choline bitartrate to make up the difference, since most prenatals cover little of the 450 mg.
Not surprised to see your work reaching me. I'm a pediatric stroke survivor now in my late 50s. Recently had symptoms and diagnosed with early and mild small vessel cognitive decline. I was prescribed Donepazil but have chosen not to take it. I'm unsure about its effectiveness and am more holistic based. I do take omega 3s and other supplements but now I want to look at what you've mentioned here.
Any advice is appreciated.
For small vessel cognitive decline, I would focus on cardiac and metabolic risk factors since this is a cardiovascular problem manifesting in the brain. Ensure blood pressure, cholesterol, triglycerides, ApoB, hsCRP, fasting glucose, and HgA1C are not just in the normal range but in the optimal range through lifestyle and/or pharmaceutical strategies. Best of luck to you!
so vegans are the ones with deficiency. If you are to believe the u shaped curve, bacon and eggs puts you over the top.