Choline Deficiency in Long-Term Intravenous Feeding

Some people cannot get enough nourishment through their gut, often because much of the bowel has been removed or does not work. They live on total parenteral nutrition (TPN): a complete liquid feed of sugar, protein building blocks, fat, vitamins and minerals that runs straight into a large vein, often overnight at home for years. This page is about one gap in that feed. Free choline, the form the body uses most directly, is present only in tiny amounts in standard intravenous nutrition, and a series of studies from the early 1990s onward measured low blood choline in many long-term patients, linked it to fatty liver and raised liver enzymes, and then tested what happened when choline was added to the feeding bag. It covers who is affected, what the feeding formulas contain, the placebo-controlled trials, the findings in children, where an intravenous choline product stands according to the published literature, and what is still unknown.

For the general picture of choline shortfall, see the Choline Deficiency hub; for the liver biology in ordinary eaters, see Choline Deficiency and Fatty Liver.

Table of Contents

  1. Who Lives on Intravenous Feeding
  2. What the Feeding Bag Contains, and What It Lacks
  3. Low Blood Choline in Home Intravenous Feeding
  4. The Liver Consequences
  5. The First Treatment Studies
  6. The Placebo-Controlled Trial of Intravenous Choline
  7. Memory in Long-Term Intravenous Feeding
  8. Choline and Catheter Clots
  9. Children and Infants with Intestinal Failure
  10. The Missing Intravenous Choline Product
  11. What Is Not Known
  12. Key Research Papers
  13. Connections
  14. Featured Videos

Who Lives on Intravenous Feeding

The people in these studies have what doctors call intestinal failure: the gut cannot absorb enough food and fluid to keep them alive and growing. A common reason is short bowel syndrome, where much of the intestine has been removed or lost. When the gut cannot be used, nutrition goes into a central vein through a long-term catheter.

A 2025 review of intestinal failure-associated liver disease describes long-term parenteral nutrition as a treatment that "has considerably improved the management" of intestinal failure in children and adults, particularly those with short bowel syndrome, while carrying a significant risk of liver injury. Many of the patients studied for choline received their feeds at home, at night, for years: one adult group had been on parenteral nutrition for an average of 5.5 years, with a range from 0.1 to 14.5 years, and a group of four patients in a later study had been on it for an average of 9.7 years.

Choline matters to these patients because the feed is their entire diet. A person who eats eggs, meat, fish or beans takes in choline every day. A person whose only nourishment is a bag of intravenous fluid receives only what is in that bag, plus whatever their own liver can make.

What the Feeding Bag Contains, and What It Lacks

Choline comes in two broad forms. Free choline is the small, water-soluble molecule. Phospholipid-bound choline is choline built into fats such as phosphatidylcholine, the main fat in cell membranes and in the fat droplets of intravenous lipid emulsions.

The fat emulsion in parenteral nutrition is made from oil droplets coated with phospholipid, so it does carry bound choline. A 1993 study measured the emulsion its patients were receiving: it held 24 nmol/mL of free choline and about 11,630 nmol/mL of phospholipid-bound choline. Even so, the patients' blood free choline was low, and the amount of lipid emulsion each patient received did not relate to their choline levels. The authors concluded that intravenous lipid emulsion is an inadequate source of choline for this patient group. A 2010 study in infants described parenteral nutrition and lipid emulsions as containing phosphatidylcholine but "insignificant free choline", and a 2021 study of extremely preterm infants stated that neonatal parenteral nutrition lacks free choline and contains small amounts of phosphatidylcholine.

The body can make some choline itself in the liver, starting from the amino acid methionine. A 2009 review by the lead investigator of the American trials states that fatty liver during parenteral nutrition develops because the body's own production of choline from methionine given into the vein is deficient. A 2006 paper from the same group describes a defect in the liver's transsulfuration pathway in people with malabsorption, which it links to their risk of choline deficiency.

Choline is also tied to vitamin B12 and folate, which share the same chemistry for recycling homocysteine. A 2002 study of long-term home parenteral nutrition patients found that 52% had markedly low choline, 33% had low choline and 14% had normal choline, and that 47% had raised methylmalonic acid, a sign of low vitamin B12 activity. Choline was significantly lower in the patients with raised methylmalonic acid. The authors suggest that when the vitamin B12 side of the pathway cannot be used, choline may be drawn on instead, deepening the shortfall.

Low Blood Choline in Home Intravenous Feeding

The first systematic measurements came from a group at the University of California, Los Angeles. In a 1993 study of 41 people (19 male, 22 female, aged 0.1 to 79 years) receiving long-term parenteral nutrition, plasma free choline was low in 33 of the 41. The group average was 7.15 nmol/mL, against a normal value of 11.4 nmol/mL. Phospholipid-bound choline, by contrast, was normal in 34 of the 41.

The low free choline tracked with liver damage. Higher levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly correlated with lower plasma free choline (correlation coefficients of −0.34 and −0.37), but not with bound choline. Age, how long the person had been on intravenous feeding and how much lipid emulsion they received showed no relationship with choline levels.

A 1995 study of four long-term patients recorded an average plasma free choline of 4.8 nmol/mL, again against a normal value of 11.4 nmol/mL. A 2006 study of 41 patients found average free choline of 7.7 nmol/mL in patients without catheter clots and 6.2 nmol/mL in those with them.

There is no routine hospital blood test for choline status. These figures come from research laboratories that measured free and bound choline separately, which is part of why the shortfall went unnoticed in ordinary care.

The Liver Consequences

Liver trouble is a well-known complication of long-term intravenous feeding. The older name is parenteral nutrition-associated liver disease; the newer name, intestinal failure-associated liver disease (IFALD), reflects that the gut problem itself plays a part. A 2025 review lists several contributors: the lipid emulsions, plant sterols (phytosterols) in some emulsions, an imbalance of gut bacteria, a disturbed gut-liver connection, and episodes of bloodstream infection. Together these disrupt bile acid handling and drive liver inflammation, leading to bile flow blockage (parenteral nutrition-associated cholestasis) and a more chronic fatty, scarring inflammation (steatohepatitis with fibrosis). The same review lists choline supplementation among the treatments under study.

Choline deficiency therefore explains one part of this liver disease, not all of it. Its clearest link is to fat building up in the liver (hepatic steatosis). Choline is needed to make phosphatidylcholine, which the liver uses to package fat into very-low-density lipoproteins and ship it out into the blood. Without enough, fat stays in the liver cells. A 1992 study found fatty liver in 50% of a group of 15 home parenteral nutrition patients with low plasma free choline.

The 2009 review summarises the wider picture reported in these patients: fatty liver, memory deficits, skeletal muscle abnormalities, and signs that choline deficiency activates cell death (apoptosis). For the muscle findings in more detail, see Choline Deficiency: Muscle Damage.

The First Treatment Studies

Lecithin by mouth (1992)

Before any intravenous choline was tested, the Los Angeles group gave oral lecithin, a phosphatidylcholine-rich fat, to 15 home parenteral nutrition patients with low plasma free choline, in a double-blind trial against placebo for 6 weeks. In the lecithin group, plasma free choline rose by 53.4% at 2 weeks and stayed up at 6 weeks. In the placebo group it did not change at 2 weeks and fell by 25.4% at 6 weeks. Liver fat, judged by computed tomography (CT) scans, decreased progressively in the lecithin group. The authors called choline "a conditionally essential nutrient" in this population. These patients could still absorb some lecithin by mouth; people with almost no working gut cannot.

How intravenous choline is handled (1994)

A 1994 study infused choline chloride into four long-term patients on consecutive days at 7, 14, 28 and 56 mmol, each over 12 hours, and tracked blood and urine levels. The body's removal of choline from the blood followed a pattern that becomes saturated at higher amounts. The study gave researchers the basic numbers for planning later dosing.

Intravenous choline in four patients (1995)

Four patients (1 man, 3 women, average age 50) who had been on parenteral nutrition for an average of 9.7 years and had low plasma free choline then received feeding solutions with 1 to 4 g of choline chloride a day for 6 weeks. In all four, plasma free choline rose into the normal range within 1 week and stayed there, then fell back to baseline when the choline was stopped. On CT, the fatty liver resolved completely. A CT measure of liver density relative to the spleen rose from −14.2 Hounsfield units at the start to 8.4 at week 2, 9.6 at week 4 and 13.1 at week 6, and was 13.8 four weeks after stopping. Fatty liver returned in one patient after 10 weeks back on choline-free feeding. With four patients and no comparison group, this was a pilot.

The Placebo-Controlled Trial of Intravenous Choline

The central study was published in 2001. Fifteen patients (10 men, 5 women) who depended on parenteral nutrition for at least 80% of their nutritional needs were randomly assigned either to their usual feed (8 patients) or to the same feed with 2 g of choline chloride added (7 patients) for 24 weeks. Liver and spleen CT scans and a panel of blood tests were done at the start and at weeks 2, 4, 6, 12, 16, 20, 24 and 34. Week 34 was 10 weeks after the choline stopped.

The authors concluded that choline deficiency is a significant contributor to parenteral nutrition-associated liver disease and that their data suggest choline is a required nutrient for long-term home parenteral nutrition patients. The subtitle of the paper calls it "proof of a human choline requirement".

The trial is small. Fifteen patients cannot show whether added choline prevents cirrhosis, liver failure or death; it measured liver fat and blood enzymes over 34 weeks. The patients had normal bilirubin, so the trial says little about the bile-flow (cholestatic) form of liver disease.

Memory in Long-Term Intravenous Feeding

Choline is the raw material for acetylcholine, a chemical messenger used in memory. A 2001 pilot trial enrolled 11 adults (8 men, 3 women) who had received nightly parenteral nutrition for more than 80% of their needs for at least 12 weeks and who had low choline. Six continued their usual feed and five received the same feed plus 2 g of choline chloride, for 24 weeks, with a battery of memory and thinking tests before and after.

Delayed visual recall improved significantly in the choline group (a change of 7.0 points against −0.33 with the usual feed, p = .028). Two other tests showed borderline improvements (p = .06 and p = .067), and no other test changed significantly. The authors concluded that verbal and visual memory may be impaired in long-term parenteral nutrition patients and may improve with choline. With 11 participants and many tests, this is an early signal rather than a settled result. More on choline and memory is on Choline Deficiency: Memory and Cognitive.

Choline and Catheter Clots

Blood clots in the feeding catheter are a recognised complication of long-term intravenous feeding, and the catheter is the patient's lifeline. A 2006 study measured plasma choline in 41 long-term patients and counted catheter clots from the start of their intravenous feeding.

Sixteen of the 41 (39%) had developed a catheter clot, and 5 of them had more than one. Average free choline was 7.7 nmol/mL in those without a clot history and 6.2 nmol/mL in those with one, a difference that did not reach statistical significance (p = .076). After allowing for how long each catheter had been in place, lower free choline was linked to more frequent clots (partial correlation −0.33, p = .038). Patients with free choline below 8 nmol/mL had a relative risk of 10.0 for catheter clots, with a very wide 95% confidence interval of 1.134 to 88.167. The authors concluded that choline deficiency is a significant risk factor for catheter clots in this group.

This was an observational study. It shows an association in a small group, and the width of the confidence interval reflects how few patients it rests on. No trial has tested whether adding choline lowers the clot rate.

Children and Infants with Intestinal Failure

Children on home intravenous feeding. A 1999 study compared 21 children on long-term home parenteral nutrition (for an average of 75 months, range 3 to 206 months) with 31 healthy children eating an ordinary mixed diet. Plasma free choline was significantly lower in the children on intravenous feeding (6.6 against 8.0 nmol/mL, p = .002) and fell steadily as they grew older, by 0.03 nmol/mL per month. Lower free choline correlated with higher liver enzymes (correlation coefficients of −0.72 for aspartate aminotransferase and −0.80 for alanine aminotransferase). The amount of lipid emulsion the children received again showed no relationship with their choline levels.

Infants. A 2010 study measured whole-blood choline compounds in 14 infants on parenteral nutrition for at least 4 weeks and 14 infants fed through the gut. Average free choline did not differ significantly between the groups. However, the 6 infants who got more than 90% of their energy from the vein had a much lower level of phosphocholine, a choline compound, than the 8 who got less than 90% that way (5.7 against 22.5 nmol/mL) and than the controls (22.0 nmol/mL). The authors proposed phosphocholine as a marker to monitor.

Extremely preterm babies. A 2021 Swedish study followed 87 babies born before 28 weeks of pregnancy. Their median serum free choline fell from 33.7 µM on the first day of life to 18.4 µM by day 7, and then rose over the following months without returning to the first-day level. The more of their fluid intake came by vein, the lower their free choline.

Oral choline in children. In a small open-label 2011 study, 7 children with intestinal failure on parenteral nutrition had their plasma free choline measured and, if it was low, were given choline by mouth or tube at Adequate Intake doses. When rechecked 4 to 6 weeks later, the authors reported that, unlike adults, the infants did not respond to oral choline at these doses.

Short bowel syndrome in children. A 2026 study from a German intestinal rehabilitation program analysed 127 blood samples from 80 children with short bowel syndrome, aged 0.2 to 17.9 years, with and without parenteral nutrition. Plasma choline, betaine (a choline breakdown product used in methylation) and phosphatidylcholine were low, and 25% of patients had markedly reduced choline below 6.4 µmol/L and betaine below 16 µmol/L. The only difference found between children with and without fatty liver was lower choline and betaine in those with fatty liver. The authors list three reasons for the shortfall in short bowel syndrome: choline lost in the stool because bile phosphatidylcholine is not reabsorbed, gut bacteria breaking choline down before it can be absorbed (their marker for this, trimethylamine N-oxide, was inversely related to blood choline), and parenteral nutrition that does not meet choline needs. They state that controlled trials of choline in these children are warranted.

The Missing Intravenous Choline Product

In 1998 the US Institute of Medicine's Food and Nutrition Board set choline as a required dietary nutrient, as the 2009 review records. The feeding solutions did not follow.

In its 2012 position paper on parenteral vitamins and trace elements, the American Society for Parenteral and Enteral Nutrition (ASPEN) recommended that choline be routinely added to adult and pediatric parenteral nutrition, but noted that "a commercially available parenteral product needs to be developed". Its 2015 call to action repeated that "a parenteral choline product needs to be developed and available", described choline as an essential nutrient in all age groups according to the Food and Nutrition Board, and said efforts were under way to engage the US Food and Drug Administration and the parenteral nutrient industry.

A 2024 narrative review from a German neonatal group reported that current total parenteral nutrition interrupts the choline supply, causing a rapid drop in plasma choline and an accumulating deficit. It found that studies of intravenous choline in newborns and older children are lacking, and called for choline formulations suitable for adding to feeding solutions and for clinical trials of them, particularly in growing children and preterm babies. The 2025 liver disease review lists choline supplementation among treatments still being studied.

None of the papers read for this page reports an approved intravenous choline product for adding to parenteral nutrition. A search of DailyMed, the US National Library of Medicine's drug-label database, for choline chloride, made while this page was written in November 2026, returned no label for an intravenous product. In the trials above, choline chloride was added to the patients' feeding solutions as part of the research.

What Is Not Known

Decisions about intravenous feeding, its contents and its monitoring belong with the specialist nutrition team that manages it.

Key Research Papers

  1. Buchman AL, Dubin M, Jenden D, Moukarzel A, Roch MH, Rice K, et al. Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients. Gastroenterology. 1992;102(4 Pt 1):1363-70. PubMed PMID: 1551541
  2. Buchman AL, Moukarzel A, Jenden DJ, Roch M, Rice K, Ament ME. Low plasma free choline is prevalent in patients receiving long term parenteral nutrition and is associated with hepatic aminotransferase abnormalities. Clin Nutr. 1993;12(1):33-7. PubMed PMID: 16843274
  3. Buchman AL, Jenden DJ, Moukarzel AA, Roch M, Rice KM, Chang AS, et al. Choline pharmacokinetics during intermittent intravenous choline infusion in human subjects. Clin Pharmacol Ther. 1994;55(3):277-83. PubMed PMID: 8143393
  4. Buchman AL, Dubin MD, Moukarzel AA, Jenden DJ, Roch M, Rice KM, et al. Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology. 1995;22(5):1399-403. PubMed PMID: 7590654
  5. Misra S, Ahn C, Ament ME, Choi HJ, Jenden DJ, Roch M, et al. Plasma choline concentrations in children requiring long-term home parenteral nutrition: a case control study. JPEN J Parenter Enteral Nutr. 1999;23(5):305-8. PubMed PMID: 10485444
  6. Buchman AL, Sohel M, Brown M, Jenden DJ, Ahn C, Roch M, et al. Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: a pilot study. JPEN J Parenter Enteral Nutr. 2001;25(1):30-5. PubMed PMID: 11190987
  7. Buchman AL, Ament ME, Sohel M, Dubin M, Jenden DJ, Roch M, et al. Choline deficiency causes reversible hepatic abnormalities in patients receiving parenteral nutrition: proof of a human choline requirement: a placebo-controlled trial. JPEN J Parenter Enteral Nutr. 2001;25(5):260-8. PubMed PMID: 11531217
  8. Compher CW, Kinosian BP, Stoner NE, Lentine DC, Buzby GP. Choline and vitamin B12 deficiencies are interrelated in folate-replete long-term total parenteral nutrition patients. JPEN J Parenter Enteral Nutr. 2002;26(1):57-62. PubMed PMID: 11833752
  9. Buchman AL, Ament ME, Jenden DJ, Ahn C. Choline deficiency is associated with increased risk for venous catheter thrombosis. JPEN J Parenter Enteral Nutr. 2006;30(4):317-20. PubMed PMID: 16804129
  10. Buchman AL. The addition of choline to parenteral nutrition. Gastroenterology. 2009;137(5 Suppl):S119-28. PubMed PMID: 19874943
  11. Sentongo TA, Kumar P, Karza K, Keys L, Iyer K, Buchman AL. Whole-blood-free choline and choline metabolites in infants who require chronic parenteral nutrition therapy. J Pediatr Gastroenterol Nutr. 2010;50(2):194-9. PubMed PMID: 20038853
  12. Guerrerio AL, Mattis L, Conner KG, Hampsey J, Stasinopoulos DM, DeJong R, et al. Oral choline supplementation in children with intestinal failure. J Pediatr Gastroenterol Nutr. 2011;53(1):115-9. PubMed PMID: 21694550
  13. Vanek VW, Borum P, Buchman A, Fessler TA, Howard L, Jeejeebhoy K, et al. A.S.P.E.N. position paper: recommendations for changes in commercially available parenteral multivitamin and multi-trace element products. Nutr Clin Pract. 2012;27(4):440-91. PubMed PMID: 22730042
  14. Vanek VW, Borum P, Buchman A, Fessler TA, Howard L, Shenkin A, et al. A Call to Action to Bring Safer Parenteral Micronutrient Products to the U.S. Market. Nutr Clin Pract. 2015;30(4):559-69. PubMed PMID: 26113560
  15. Nilsson AK, Pedersen A, Malmodin D, Lund AM, Hellgren G, Löfqvist C, et al. Serum choline in extremely preterm infants declines with increasing parenteral nutrition. Eur J Nutr. 2021;60(2):1081-1089. PubMed PMID: 32588218
  16. Bernhard W, Böckmann KA, Minarski M, Wiechers C, Busch A, Bach D, et al. Evidence and Perspectives for Choline Supplementation during Parenteral Nutrition-A Narrative Review. Nutrients. 2024;16(12):1873. PubMed PMID: 38931230
  17. Abi-Aad SJ, Lovell M, Khalaf RT, Sokol RJ. Pathogenesis and Management of Intestinal Failure-Associated Liver Disease. Semin Liver Dis. 2025;45(1):66-80. PubMed PMID: 40015320
  18. Hilberath J, Shunova A, Heister L, Poets CF, Bernhard W. Choline and Choline-Related Metabolites in Pediatric Short Bowel Syndrome. Nutrients. 2026;18(10):1553. PubMed PMID: 42197014

PubMed Topic Searches

  1. PubMed: Choline and parenteral nutrition
  2. PubMed: Choline and intestinal failure-associated liver disease
  3. PubMed: Plasma free choline in home parenteral nutrition
  4. PubMed: Choline in preterm infants on parenteral nutrition

Connections