Choline: one of the brain’s most overlooked nutrients
- Richard Moore
- 5 minutes ago
- 10 min read
Some nutrients get all the attention.
Choline rarely does.
That is strange, because your neurones would notice if it disappeared. Not because one dramatic system would fail overnight, but because several quieter jobs would begin slipping at once. The messages between cells would be harder to make. Membranes would be harder to maintain. Parts of the chemistry that help cells stay organised under pressure would lose some of their grip (Burns et al., 2025; Wallace et al., 2018).
This is the first in a 3-part series on choline and neurodegeneration.
We have chosen to do it this way for a simple reason. There is too much here to do justice to in one article. Choline does not sit in just one corner of biology. It touches neurotransmission, membrane structure, mitochondrial function, one-carbon metabolism, and inflammation-related pathways, which makes it both fascinating and easy to oversimplify if everything is forced into a single piece (Burns et al., 2025; van der Veen et al., 2017). So this first blog lays the groundwork. The second will focus on ALS specifically. The third will move into the practical questions around food, testing, supplements, and where caution is needed.
What is choline, actually?
Choline is an essential nutrient, which means the body can make some, but not enough to reliably cover its requirements, so a meaningful amount still has to come from food (Burns et al., 2025; Wallace et al., 2018). It is used to make phosphatidylcholine and sphingomyelin, two major phospholipids that help maintain the structural integrity of cell membranes (Burns et al., 2025; van der Veen et al., 2017).
That already tells you something important.
Choline is not simply a “memory nutrient”. It is part of the actual material the nervous system uses. It contributes to acetylcholine, a neurotransmitter involved in muscle control and cognitive processes, and to phosphatidylcholine, a major membrane phospholipid that helps support membrane integrity, growth, repair, fluidity, receptor function, and synaptic signalling (Burns et al., 2025; Derbyshire & Obeid, 2020; van der Veen et al., 2017).
If the brain were a city, choline would not just be the message travelling down the line. It would also be part of the wall, the insulation, and the maintenance team.
Job one: helping neurones send the message
One of choline’s best-known roles is that it helps the body make acetylcholine. That matters because acetylcholine is involved in attention, memory, autonomic signalling, and communication between nerves and muscles (Burns et al., 2025; Davis et al., 2023).
That is one reason choline catches the eye in neurodegeneration research. Choline is needed to make acetylcholine, one of the chemical messengers that helps nerves communicate with muscles. In ALS mouse studies, this messaging system seems to come under pressure early. Casas et al. (2013) found reduced cholinergic activity in the spinal cord of mice before clear symptoms had developed, suggesting that this part of the messaging system may begin to falter early in the disease process. Fil et al. (2017) found something similar in a genetically altered mouse model of motor neuron disease, reporting lower levels of choline acetyltransferase, the enzyme needed to make acetylcholine, alongside mitochondrial damage, activation of support cells in the nervous system, muscle wasting, and shorter survival. In simple terms, these mouse studies suggest that the nerve-to-muscle messaging system may start fraying earlier than we once thought, and that is one reason choline has become biologically interesting in ALS.
That does not prove that low dietary choline causes ALS.
It does something more careful than that. It tells us that cholinergic biology is tangled up with pathways that go wrong in ALS, and that makes it worth paying attention to (Casas et al., 2013; Fil et al., 2017).
Job two: helping hold the cell together
This role often gets less attention, yet it may be one of the most important.
Choline is needed to make phosphatidylcholine, and phosphatidylcholine is a major phospholipid in cell membranes (Burns et al., 2025; van der Veen et al., 2017). Phosphatidylcholine is vital for membrane integrity, growth, repair, fluidity, receptor function, and synaptic signalling, while inadequate choline availability can reduce phosphatidylcholine synthesis and compromise membrane structure (Derbyshire & Obeid, 2020; van der Veen et al., 2017).
That matters because a neurone is not just electrical activity. It is a physical structure with membranes everywhere: around the cell, around the synapse, around the mitochondria, and around the endoplasmic reticulum. When membranes become unstable, poorly repaired, or more vulnerable to oxidative damage, the whole system becomes easier to derail (Falabella et al., 2021; van der Veen et al., 2017).
This is one reason lipid biology keeps appearing in neurodegeneration research. Falabella et al. (2021) describe lipid homeostasis as central to cellular metabolism and note that abnormal lipid profiles are reported across several neurological disorders, including ALS, Alzheimer’s disease, and Parkinson’s disease.
And this is where choline stops looking like a footnote.
Because once membrane biology starts fraying, the problems do not stay neatly separated. Structure affects signalling. Signalling affects calcium handling. Calcium handling affects mitochondria. Mitochondria affect oxidative stress. Oxidative stress then damages membranes further. One unstable layer can feed the next (Dong & Yong, 2022; Falabella et al., 2021).
Job three: supporting the chemistry cells use to stay organised
Choline also feeds into one-carbon metabolism after it is oxidised to betaine, contributing methyl groups for the remethylation of homocysteine to methionine and linking choline to methylation-related cellular processes (Burns et al., 2025; Zeisel, 2012).
For readers without a science background, the easiest way to think about this is not as a complicated pathway diagram, but as part of the cell’s housekeeping system. It is one of the routes cells use to keep important chemistry moving in the right direction.
When that chemistry is under strain, the effects do not necessarily announce themselves with one obvious symptom. They can show up as poorer resilience, less efficient maintenance, or a reduced ability to keep other systems steady under pressure (Burns et al., 2025; Zeisel, 2012).
That does not make choline a magic methylation fix. It does mean it sits at a crossroads where signalling, membrane biology, and metabolic housekeeping overlap (Burns et al., 2025; van der Veen et al., 2017).
Why does this matter in neurodegeneration?
Because neurones are demanding cells.
They are long, metabolically expensive, and unusually dependent on intact membranes, tightly controlled calcium signalling, and a reliable energy supply (Davis et al., 2023; Falabella et al., 2021). In ALS, pathophysiology includes mitochondrial dysfunction, oxidative stress, neuroinflammation, calcium dysregulation, altered cell membranes, altered synaptic function, and glutamate toxicity, although the precise causes remain incompletely understood (Cheng et al., 2025; Davis et al., 2023).
That is why choline becomes interesting. It sits near several of the same systems that appear vulnerable in neurodegeneration: neurotransmission, membrane integrity, mitochondrial function, oxidative stress, and inflammatory signalling (Burns et al., 2025; Davis et al., 2023; van der Veen et al., 2017).
That wording matters.
Near the pressure points is not the same as “proven cause”.
This is a field where much of the evidence is mechanistic, preclinical, metabolomic, or biomarker-based. That is not a reason to dismiss it. It is a reason not to oversell it (Atassi et al., 2017; Bjornevik et al., 2019; Burns et al., 2025).
What about mitochondria, oxidative stress, and inflammation?
This is where the story becomes more compelling, but also more delicate.
Mitochondria are heavily membrane-dependent structures, and lipids help determine how well they maintain shape, energy production, signalling, and quality control (Falabella et al., 2021; van der Veen et al., 2017). Oxidative stress can generate oxidised phospholipids, including oxidised phosphatidylcholines, and Dong and Yong (2022) describe these oxidised phospholipids as potentially important mediators of neurodegeneration rather than passive by-products.
In one ALS animal study, researchers found lower choline in astrocytes, the support cells that help keep neurones stable. Those cells also showed unhealthy mitochondria and were more vulnerable to oxidative stress, suggesting that choline may be tied to how well these cells cope when the system is under strain.
That is interesting, because ALS is not just a story of neurones dying. It is also a story of the surrounding support system becoming less resilient. But when researchers have looked in humans, the picture has been much messier. Some studies have not found a clear choline difference, while others suggest broader metabolic disruption rather than one simple choline problem. So this is better understood as an important clue, not a settled conclusion (Atassi et al., 2017; Bjornevik et al., 2019; Dučić et al., 2019)
That mixed picture is important.
It stops us from pretending the science is cleaner than it is.
So, does low choline cause neurodegeneration?
At this point, no honest reading of the literature should say that.
What the evidence supports is narrower and more useful. Choline is involved in systems that are highly relevant to neurodegeneration, and inadequate choline availability could plausibly reduce resilience in some of those systems. But that is different from saying low choline is a primary cause of disease, and different again from saying supplementation has been shown to reverse it (Burns et al., 2025; Davis et al., 2023; Wallace et al., 2018).
This distinction is not a technicality. It is the difference between responsible science writing and wishful thinking.
People living with neurodegenerative disease do not need inflated claims. They need a clear picture of where the biology is interesting, where the evidence is mixed, and where the real unknowns still sit.
Can you test choline status?
This is one of the messier parts of the topic.
A lot of readers expect there to be a single, reliable “choline test.” There is not. Obeid et al. (2023) concluded that there are currently no optimal blood biomarkers that can accurately reflect choline deficiency or sufficiency. More recent controlled-feeding work suggests that plasma choline and betaine may help predict dietary choline intake under tightly controlled conditions, but that is not the same as having a simple universal clinical test for tissue sufficiency in day-to-day practice (Obeid et al., 2023).
So in practice, this is rarely a one-lab story.
It is more often a pattern. A practitioner may look at dietary intake, digestive capacity, liver health, methylation context, homocysteine, kidney function, and the broader clinical picture, rather than hanging everything on one plasma marker (Burns et al., 2025; Obeid et al., 2023).
Are most people getting enough?
Not always.
Reference values vary slightly by authority. The U.S. National Academies set Adequate Intakes of 425 mg/day for adult women and 550 mg/day for adult men, while the European Food Safety Authority set an Adequate Intake of 400 mg/day for adults (European Food Safety Authority, 2016; Wallace et al., 2018). Choline also appears to be underconsumed in many populations (Wallace et al., 2018).
That does not mean everyone needs to obsess over numbers. It does mean choline deserves more deliberate attention than it usually gets, particularly in people with low intakes of rich food sources, increased physiological demands, or clinical contexts where membrane integrity, liver function, or neurological resilience may already be under pressure (Burns et al., 2025; Wallace et al., 2018).
What foods actually provide choline?
Rich dietary sources of choline include eggs, liver, meat, fish, and dairy, while soy foods, legumes, nuts, seeds, whole grains, and cruciferous vegetables can also contribute, usually in smaller amounts (Burns et al., 2025; Wallace et al., 2018).
For many people, this is the most useful starting point.
Not a supplement stack. Not an elaborate protocol. Just an honest look at whether the diet includes enough of the raw materials the nervous system uses every day.
Egg yolks are one of the best-known sources. Liver is especially rich, although clearly not everyone wants it. Fish, poultry, dairy, soy foods, legumes, and some vegetables can all help, but the pattern matters more than any single hero food (Burns et al., 2025; Wallace et al., 2018).
The real take-home
Choline is not glamorous.
But neurones are not built on glamour. They are built on structure, signalling, energy, and repair.
Choline helps make one of the neurotransmitters neurones use to communicate. It helps build and maintain membranes. It feeds into chemistry that helps cells stay organised under stress. And because neurodegeneration so often involves failing membranes, mitochondrial strain, oxidative pressure, and inflammatory noise, choline belongs in the conversation far more than it usually does (Burns et al., 2025; Falabella et al., 2021; van der Veen et al., 2017).
That does not make it a cure.
But it may make it one of those quiet nutrients sitting much closer to the fault lines of neurodegeneration than most people realise.
This first article is the foundation
In Part 2 of this 3-part series, taken from a recent Scoping Review written by Dr Kirstie Lawton, PhD, Founder and Director of You Nutrition Clinic, for her MSc dissertation, we will narrow the lens and look specifically at ALS. Where exactly does choline fit when the systems that keep motor neurons stable begin to fray? We will dig into the science around membrane breakdown, mitochondrial dysfunction, oxidative stress, calcium signalling, and neuroinflammation, and separate what is genuinely promising from what is still uncertain.
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Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. Always consult with a qualified, registered medical doctor (MD) for diagnosis and treatment decisions.
References
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Cheng, M., et al. (2025). Mitochondrial respiratory complex IV deficiency recapitulates amyotrophic lateral sclerosis. Nature Neuroscience, 28(4), 748-756.
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Falabella, M., et al. (2021). Cardiolipin, mitochondria, and neurological disease. Trends in Endocrinology & Metabolism, 32(4), 224-237.
Fil, D., et al. (2017). Mutant Profilin1 transgenic mice recapitulate cardinal features of motor neuron disease. Human Molecular Genetics, 26(4), 686-701.
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van der Veen, J. N., et al. (2017). The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease. Biochimica et Biophysica Acta - Biomembranes, 1859(9 Pt B), 1558-1572.
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Zeisel, S. H. (2012). A brief history of choline. Annals of Nutrition and Metabolism, 61(3), 254-258.
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