Choline is an essential nutrient vital for liver function, lipid metabolism, and cellular health. Whilst the body produces small amounts, dietary intake is necessary to meet physiological needs. Research shows that choline deficiency can rapidly induce hepatic steatosis (fatty liver) by impairing the liver's ability to package and export fats. Non-alcoholic fatty liver disease (NAFLD) affects a significant proportion of UK adults and has multiple causes, including obesity and insulin resistance. Understanding choline's role in liver health—and whether choline supplements for fatty liver offer therapeutic benefit—is increasingly relevant for patients and clinicians managing metabolic liver conditions.

What Is Choline and How Does It Affect Liver Health?

Choline is an essential nutrient that plays a crucial role in numerous physiological processes, including liver function, lipid metabolism, and cellular membrane integrity. Whilst the body can synthesise small amounts of choline endogenously through the enzyme phosphatidylethanolamine N-methyltransferase (PEMT), dietary intake remains necessary to meet physiological requirements. The UK does not currently have a Reference Nutrient Intake (RNI) for choline, though the European Food Safety Authority (EFSA) has established Adequate Intake values of 400 mg/day for adult women and 550 mg/day for adult men.

In hepatic metabolism, choline serves as a precursor for phosphatidylcholine, the predominant phospholipid in very-low-density lipoproteins (VLDL). These lipoproteins are essential for transporting triglycerides from the liver to peripheral tissues. Without adequate choline, the liver cannot efficiently package and export lipids, leading to intrahepatic accumulation of fat. Choline deficiency can therefore contribute to the risk of hepatic steatosis (fatty liver) via impaired VLDL assembly and export, though it is important to recognise that non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition with multiple contributing factors including insulin resistance, obesity, and metabolic syndrome. Current UK clinical guidance, including NICE, primarily uses the term 'NAFLD', though the emerging international nomenclature 'metabolic dysfunction-associated steatotic liver disease' (MASLD) is increasingly recognised.

Choline also contributes to one-carbon metabolism, providing methyl groups necessary for various biochemical reactions, including the synthesis of S-adenosylmethionine (SAMe). This compound is vital for hepatic methylation reactions and antioxidant defence mechanisms. Furthermore, choline is a precursor to acetylcholine, a neurotransmitter, and betaine, which supports homocysteine metabolism. The multifaceted roles of choline underscore its importance in maintaining hepatic health and preventing metabolic dysfunction.

The Link Between Choline Deficiency and Fatty Liver Disease

Substantial evidence from controlled feeding studies demonstrates that choline deficiency can rapidly induce hepatic steatosis in humans. Research conducted in healthy volunteers placed on choline-deficient diets has shown that a significant proportion develop fatty liver within weeks, with the condition reversing upon choline repletion. The susceptibility to choline deficiency-induced fatty liver varies considerably between individuals, influenced by genetic polymorphisms, sex, and menopausal status.

Genetic variations in choline metabolism genes, particularly PEMT and MTHFR (methylenetetrahydrofolate reductase), may affect individual choline requirements. Postmenopausal women and men are at higher risk of deficiency-related liver dysfunction compared to premenopausal women, as oestrogen upregulates PEMT activity, enhancing endogenous choline synthesis. Single nucleotide polymorphisms in PEMT and other related genes can impair the body's ability to produce choline, potentially increasing dietary requirements. It is important to note that routine genetic testing for these variants is not currently recommended in NHS practice; these findings provide background biological context rather than a basis for clinical testing.

Population studies suggest that suboptimal choline intake may be more common than previously recognised, particularly among individuals following plant-based diets, as choline is predominantly found in animal products. Observational research has identified associations between lower choline intake and increased prevalence of NAFLD, though establishing causality remains complex due to confounding dietary and lifestyle factors.

The mechanistic pathway is well characterised: insufficient choline impairs VLDL synthesis and secretion, causing triglycerides to accumulate within hepatocytes. This steatosis can progress to steatohepatitis (liver inflammation with injury), fibrosis, and potentially cirrhosis, though only a subset of individuals progress and risk is modified by factors including obesity, type 2 diabetes, age, obstructive sleep apnoea, and alcohol intake. Whilst choline deficiency is not the sole cause of fatty liver disease—insulin resistance, obesity, and metabolic syndrome being primary drivers—it represents a modifiable nutritional factor that warrants clinical attention in at-risk individuals.

Evidence for Choline Supplements in Treating Fatty Liver

The evidence base for choline supplementation as a therapeutic intervention for established fatty liver disease remains limited and requires cautious interpretation. Whilst mechanistic studies clearly demonstrate that correcting choline deficiency can reverse experimentally induced hepatic steatosis, translating this to clinical practice for patients with NAFLD is more complex. Most individuals with fatty liver disease have multifactorial aetiologies involving insulin resistance, obesity, and dietary excess rather than isolated choline deficiency.

A small number of clinical trials have investigated choline supplementation (as phosphatidylcholine or choline salts) in NAFLD populations, with mixed results. Some studies have reported modest improvements in liver enzymes (alanine aminotransferase and aspartate aminotransferase) and hepatic fat content measured by imaging or biopsy. However, these studies have generally been small, short-term, and of variable methodological quality. Larger, well-designed randomised controlled trials are needed to establish efficacy definitively.

It is important to note that NICE guidance on NAFLD (NG49) does not currently recommend choline supplementation as a specific treatment. The cornerstone of management remains lifestyle modification, including weight loss through caloric restriction and increased physical activity, which have robust evidence for reducing hepatic steatosis and improving metabolic parameters. Choline supplements are food supplements in the UK and are not licensed medicines for the treatment of NAFLD or MASLD. Supplementation might be considered as an adjunctive measure in individuals with documented deficiency or those at high genetic risk, but should not replace evidence-based lifestyle interventions. Biomarkers of choline status are not routinely available in NHS practice, which limits the ability to identify deficiency in clinical settings.

Clinicians should be aware that routine choline supplementation is not recommended by NICE or NHS guidance for the general NAFLD population. Supplementation may be most relevant for specific subgroups, such as those with genetic polymorphisms affecting choline metabolism, pregnant women (who have increased requirements), or individuals following restrictive diets. Any decision to supplement should be individualised and ideally guided by assessment of dietary intake.

Recommended Choline Dosage and Food Sources for Liver Support

As the UK lacks official choline recommendations, healthcare professionals often reference EFSA Adequate Intake values: 400 mg/day for women and 550 mg/day for men. Pregnant women require approximately 480 mg/day, and lactating women 520 mg/day, reflecting increased demands for foetal development and breast milk production. These values represent intakes considered sufficient to maintain health in most individuals, though requirements may be higher in those with genetic variants affecting choline metabolism.

Dietary sources of choline are predominantly animal-based. Excellent sources include:

• Eggs – particularly the yolk, providing approximately 150 mg per large egg

• Beef liver – exceptionally rich, containing over 350 mg per 100 g serving

• Chicken, beef, and pork – providing 70–100 mg per 100 g

• Fish – especially salmon and cod (60–90 mg per 100 g)

• Dairy products – milk and yoghurt contribute moderate amounts

Plant-based sources contain lower concentrations but can contribute meaningfully to intake:

• Soya products, including tofu and soya milk

• Cruciferous vegetables (broccoli, Brussels sprouts)

• Nuts and seeds, particularly peanuts

• Whole grains and legumes

(Note: Choline content values are approximate and vary by food composition database and preparation method.)

Individuals following vegan or vegetarian diets may find it challenging to meet choline requirements through food alone and might benefit from supplementation. When supplements are indicated, typical doses range from 250–550 mg daily, often provided as choline bitartrate, phosphatidylcholine, or CDP-choline (citicoline). Readers should ensure that total intake from diet plus supplements does not exceed the EFSA Tolerable Upper Intake Level of 3,500 mg/day for adults. Higher doses should only be taken under medical supervision. Choline supplements are regulated as foods in the UK and are not a substitute for a varied, balanced diet.

For patients with fatty liver disease, dietary counselling should emphasise whole-food sources of choline within the context of an overall healthy eating pattern. According to NICE guidance (NG49), the first-line management of NAFLD focuses on weight loss through calorie restriction and increased physical activity. Specialist guidance from the British Society of Gastroenterology and European associations also supports Mediterranean-style dietary patterns—rich in vegetables, fruits, whole grains, legumes, and healthy fats, with moderate portions of lean protein including choline-rich foods—as part of a comprehensive approach to metabolic health.

Potential Side Effects and Safety Considerations

Choline supplementation is generally well tolerated at recommended doses, though adverse effects can occur, particularly at higher intakes. The most commonly reported side effects are gastrointestinal in nature, including nausea, diarrhoea, and abdominal discomfort. These symptoms are typically dose-dependent and may be minimised by taking supplements with food or dividing the daily dose.

A characteristic adverse effect of excessive choline intake is a fishy body odour, resulting from the bacterial conversion of choline to trimethylamine (TMA) in the gut. TMA is normally oxidised to trimethylamine N-oxide (TMAO) by hepatic enzymes, but this capacity can be overwhelmed at high intakes. Some individuals have genetic variations affecting TMA metabolism, making them more susceptible to this effect even at moderate doses. The EFSA has established a Tolerable Upper Intake Level of 3,500 mg/day for adults based on adverse effects including fishy body odour, hypotension, and increased sweating and salivation observed at high doses.

Emerging research has raised questions about the cardiovascular implications of elevated TMAO levels, which have been associated with increased atherosclerosis risk in some observational studies. However, there is no official link established between choline supplementation at recommended doses and adverse cardiovascular outcomes. The relationship between dietary choline, gut microbiome composition, TMAO production, and cardiovascular disease remains an active area of investigation requiring further clarification.

Patients should be advised to:

• Start with lower doses and increase gradually if needed

• Inform their GP or pharmacist about all supplements being taken

• Seek medical advice before supplementing if pregnant, breastfeeding, or managing chronic health conditions, including liver disease

• Contact their GP if they experience persistent gastrointestinal symptoms, unusual body odour, or any concerning effects

• Report any suspected side effects via the MHRA Yellow Card scheme at https://yellowcard.mhra.gov.uk

Individuals with trimethylaminuria (fish odour syndrome), a rare metabolic disorder, should avoid choline supplementation. Those with existing liver disease should only supplement under medical supervision. A balanced, food-first approach remains the safest strategy for most individuals, with supplementation reserved for those with identified deficiency or increased requirements.

Frequently Asked Questions