Choline – The Forgotten Nutrient

Choline is often overlooked in discussions of methylation and broader metabolic health, yet its influence extends across multiple systems in the body. This article explores choline’s biochemical roles, genetic influences, clinical implications of suboptimal levels, and strategies to address insufficiency through diet and supplementation.

Choline in Methylation

Within the methylation cycle, choline provides a crucial “shortcut” route for homocysteine (Hcy) recycling, particularly in the liver – where approximately half of all Hcy is remethylated via this pathway.

While around 30% of choline can be synthesised endogenously through the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, roughly 70% must come from dietary sources. When intake is insufficient, the consequences are widespread and clinically significant.

Signs of Suboptimal Choline Status

Suboptimal choline status can manifest in numerous and diverse ways. Clients may present with:

Non-alcoholic fatty liver disease (NAFLD)
Dyslipidaemia or abnormal liver biomarkers
Insulin resistance, metabolic syndrome, or diabetes
Muscle weakness, poor exercise tolerance, or slow recovery
Cognitive decline, brain fog, or poor memory
Nerve pain or neuropathy
Sympathetic dominance
Bloating or burping (e.g., after fish oils)
Chronic dysbiosis
Gallstones or biliary sludge
Persistently low vitamin D or omega-3 levels
Dry or itchy skin
Elevated homocysteine
Detoxification issues
Male infertility
Increased requirements during pregnancy or post-menopause
Vegan or vegetarian diets, or egg allergy

This extensive list reflects choline’s diverse biological roles – from structural and neurological to metabolic and detoxification-related.

Choline: Forms and Functions

Choline is a remarkably versatile molecule, serving as a precursor for several critical compounds:

Phosphatidylcholine (PC): The primary structural phospholipid in cell membranes and a key component of very-low-density lipoprotein (VLDL) particles required for lipid transport from the liver.
Acetylcholine (ACh): A neurotransmitter essential for memory, learning, neuromuscular transmission, and parasympathetic nervous system function.
Sphingomyelin: A phospholipid vital for myelin sheath integrity and nerve signal conduction.
Betaine: An oxidised derivative of choline that donates methyl groups to support homocysteine remethylation.
Lecithin: A mixture of phospholipids rich in phosphatidylcholine, found in foods such as eggs, soy, and sunflower seeds.

Choline and Cellular Membranes

Choline-derived phospholipids form the backbone of cell and organelle membranes. The structural integrity of these membranes dictates the functionality of embedded proteins and receptors.

For example, mitochondrial membranes, which are highly dependent on phospholipid composition, are essential for efficient oxidative phosphorylation. Similarly, in the liver, phosphatidylcholine is critical for assembling VLDL particle membranes and transporting triglycerides and cholesterol to peripheral tissues.

Choline and Liver Health

Choline is necessary for the formation of VLDL particles, which transport triglycerides and cholesterol to peripheral tissues. When choline supply is inadequate, VLDL synthesis falters, leading to lipid accumulation within hepatocytes – a hallmark of hepatic steatosis.

Experimental evidence underscores choline’s importance for hepatic integrity. In a controlled 2007 study, healthy adults placed on a choline-deficient diet developed fatty liver at strikingly high rates:

80% of postmenopausal women
77% of men
44% of premenopausal women

Reintroduction of choline reversed these abnormalities. The protective effect in premenopausal women is largely attributed to oestrogen’s stimulation of PEMT, enhancing endogenous phosphatidylcholine synthesis. Conversely, PEMT polymorphisms (SNPs) heighten susceptibility to choline deficiency, particularly in men and postmenopausal women.

Choline and Gallbladder Function

Choline plays a pivotal role in bile composition and gallbladder health. Phosphatidylcholine is a key bile component, helping to solubilise cholesterol and bile acids and thereby preventing cholesterol crystallisation and gallstone formation.

When choline is deficient, bile may become thick and stagnant, leading to biliary sludge and gallstone risk. Impaired bile flow, in turn, compromises:

Fat and omega-3 absorption
Fat-soluble vitamin (A, D, E, K) uptake
Detoxification
Gut microbial balance

Clinically, this may present as bloating, burping (especially after fatty foods or fish oils), abdominal or referred back pain, and dry or flaky skin.

Unresolved gallbladder dysfunction often perpetuates gut dysbiosis – a point frequently overlooked in functional medicine practice.

Choline and Muscle Function

Choline deficiency can also affect skeletal muscle. In the same 2007 study, participants developed muscle damage alongside liver abnormalities. This occurs because choline supports muscle function through both membrane integrityand acetylcholine synthesis, the neurotransmitter required at the neuromuscular junction.

Low acetylcholine results in muscle weakness, poor endurance, and slower recovery. Over time, this can reduce physical activity, promoting metabolic dysfunction.

Choline and the Nervous System

Acetylcholine, derived from choline and acetyl-CoA, is a key neurotransmitter for learning, memory, neuromuscular control, and parasympathetic tone. Deficiency has been associated with neural tube defects, poor memory, sympathetic dominance, and neuropathic pain.

Choline is also essential for myelin formation, underscoring its importance in neurodevelopment and cognitive health across the lifespan.

Genetic Influences on Choline Metabolism

PEMT

The PEMT enzyme catalyses the sequential methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) using S-adenosylmethionine (SAMe) as a methyl donor. This process connects methylation capacity directly to choline synthesis.

When methylation is sluggish – due to low folate, B12, or SAMe – PEMT activity declines, reducing choline availability. Conversely, low choline impairs methylation, creating a self-reinforcing cycle.

Activators of this gene include oestrogen and SAMe, while inhibitors include alcohol and high homocysteine.

Men and postmenopausal women with PEMT variants rely heavily on dietary choline.

CHDH

Choline dehydrogenase (CHDH) mediates the entry of choline into the mitochondria as well as catalyses the first step of choline oxidation to betaine. Variants in CHDH can significantly influence choline and betaine levels, affecting methylation and mitochondrial function.

Reduced CHDH activity increases the risk of organ dysfunction on a low-choline diet, even in premenopausal women. In men, it is associated with reduced sperm motility and quality.

Supportive nutrients: choline, betaine (beets, spinach, quinoa), riboflavin (B2), and PQQ (found in kiwi, parsley, and green tea).

BHMT

Betaine-homocysteine methyltransferase (BHMT) remethylates homocysteine using betaine as the methyl donor – a crucial “backup” pathway when folate-dependent remethylation is impaired.

SNPs in BHMT can reduce enzyme activity, increasing homocysteine levels and methylation demand. Supporting choline and betaine intake is therefore essential, particularly in clients with sluggish folate cycles.

Interconnected Pathways

Low 5-MTHF (folate) availability increases reliance on the BHMT pathway, and vice versa. For this reason, it is unhelpful to focus on a single gene in isolation. The clinical picture emerges only when pathways and interdependencies are considered as a whole.

Dietary Sources of Choline

Egg yolk: approximately 800 mg per 100 g (around six large egg yolks)
Beef liver (cooked): 350–420 mg per 100 g
Chicken liver (cooked): 290–330 mg per 100 g
Beef (cooked, muscle meat): 65–100 mg per 100 g
Chicken (cooked): 70–80 mg per 100 g
Fish (cooked, varies by species):
- Salmon: 55–60 mg per 100 g
- Cod: 70 mg per 100 g
- Tuna: 65–80 mg per 100 g
Plant sources (lower amounts): soybeans, peanuts, and cruciferous vegetables such as broccoli and Brussels sprouts

Vegans, vegetarians, individuals with egg allergies, and those avoiding animal proteins are particularly at risk of inadequate choline intake due to the low choline content of plant-based foods.

Requirements and Intake

Women: 425 mg/day
Men: 550 mg/day
Pregnancy: 440 mg/day
Lactation: 550 mg/day

Average UK intake is only 250–300 mg/day, with the lowest intakes observed in women of childbearing age and in vegan populations. Individuals with PEMT, CHDH, or BHMT variants often require higher intakes to maintain optimal status.

Excess and Safety Considerations

Excessive choline intake (≥7,500 mg/day) may cause sweating, gastrointestinal distress, hypotension, and a fishy odour. The tolerable upper limit for adults is 3,500 mg/day.

High intake may elevate trimethylamine N-oxide (TMAO), in the presence of specific gut bacteria (Clostridium, Escherichia, Proteus), which metabolise choline to TMA, which is later oxidised in the liver to TMAO.

Rarely, mutations in FMO3 (as in trimethylaminuria or “fish odour syndrome”) prevent TMA oxidation, leading to accumulation and odour.

Clinical Summary

Choline deficiency or insufficiency should be considered in clients with:

Fatty liver or gallbladder issues
Dyslipidaemia or metabolic syndrome
Fatigue, poor recovery, or muscle weakness
Cognitive or mood issues
Dry skin or low omega-3 status
Digestive symptoms after fatty foods
Elevated homocysteine
Fertility challenges or hormonal transitions

Given that many people neither meet the basic requirements nor realise their increased genetic need, it is critical that nutritional practitioners address choline status in both clinical assessment and client education.

Key Takeaway

Choline is an essential yet under appreciated nutrient with fundamental roles in methylation, liver and gallbladder function, neurological health, and cellular integrity. Understanding its biochemical pathways, genetic influences, and dietary sources enables more precise and effective personalised nutrition interventions.