Guideline-Recommended, Yet Unavailable: Addressing Choline Deficiency in Patients Dependent on Parenteral Nutrition
By Jacqueline Zummo, PhD, MPH
Co-founder, Chief Scientific and Operations Officer, Protara Therapeutics
Choline is an essential quaternary amine that is naturally available in some foods and is widely utilized throughout the human body as an important contributor to many steps of metabolism. It serves as a key methyl donor in multiple metabolic pathways and is abundantly stored as phospholipid throughout the human body. Choline plays an important role in liver function, specifically the synthesis of very-low-density lipoprotein (VLDL), which is necessary for normal triglyceride export from the liver. Choline-derived phospholipids comprise most of the VLDL particle monolayer and are equally abundant in the membranes of the cellular secretory pathway. Importantly, no other phospholipids are able to substitute for choline phospholipids in the synthesis of VLDL. In addition to the critical role that choline plays in liver function, choline is the precursor to the neurotransmitter, acetylcholine, which plays a key role in brain development and functioning throughout life. Choline also modulates gene expression and cell membrane signaling and contributes to bone mineral density.
Given its ubiquity in oral-food diets, most people receive sufficient choline through their diet. However, patients who are unable to absorb nutrients via oral or enteral sources rely on parenteral support (PS), a medical intervention where liquid nutrition and fluids are delivered directly into the bloodstream through an intravenous (IV) catheter.
The American Society for Parenteral and Enteral Nutrition (ASPEN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), two of the most important guidance-issuing bodies for PS in the U.S. and Europe, recommend that PS patients receive supplemental choline. The only problem? Currently, there are no approved IV choline products globally.
According to a clinical study completed in 2023, 78% of patients dependent on parenteral nutrition (PN) are choline-deficient, and 63% of those individuals have some degree of liver dysfunction, which can lead to hepatic failure.[1] Choline deficiency leads to signs of hepatic injury, neuropsychological impairment (including memory abnormalities), and muscle damage, as well as thrombotic abnormalities.
Who Needs Parenteral Nutrition?
There are many reasons why a person may become dependent on PN. Most commonly, PN is used in patients with conditions such as gastric cancers, short bowel syndrome, ulcerative colitis and bowel blockages. Beyond etiological causes, acute traumatic injuries may also necessitate PN.
Every year in the U.S. there are approximately 90,000 people who require PN at home and, of those, approximately 30,000 are on long-term PN for more than 6 months. These patients are reliant upon PN to deliver the nutrients they need.
What Are We Doing to Help Patients in Need?
Though it’s hard to believe, there are no currently FDA-approved IV formulations of choline available for PN patients. This significant unmet need has resulted in healthcare providers limiting lipid intake to potentially slow the progression of liver complications. However, this approach does not solve the other health implications of choline deficiency, such as muscle wasting, bone wasting, difficulty breathing or brain fog.
When considering the question of what must be done for PN patients, the answer is obvious: per the recommendations of ASPEN and ESPEN, an IV formulation of choline, that can be added to PS (liquid nutrition + fluids), must be made available.
Protara Therapeutics is developing IV Choline Chloride, which has the potential to become the first IV choline formulation approved by the U.S. Food and Drug Administration (FDA). IV Choline Chloride is being studied in a registrational Phase 3 clinical trial and has been granted Orphan Drug Designation and Fast Track by the FDA, underscoring the significant unmet need it seeks to address. This compound was also previously studied in an independent Phase 2 study, which demonstrated significant improvements in serum choline concentrations and a clinically meaningful impact on steatosis, as well cholestasis and other hepatobiliary disfunction.2
Beyond clinical development, advocacy continues to drive momentum in addressing this urgent unmet need. In partnership with organizations such as The Oley Foundation and The Gutsy Perspective, Protara is working to better understand the lived realities of choline deficiency and what meaningful progress looks like for patients and families who rely on PN every day. These dedicated advocates help ensure that Protara’s innovation remains guided by real-world experiences and focused on improving awareness, access, and care for those who need it most.
Protara appreciates the dedication of the patient advocates and healthcare providers caring for PN patients, who are eagerly following the clinical progress of IV Choline Chloride in the hope that there will soon be an intervention to help prevent the complications of choline deficiency. It is long overdue.
Learn more about Protara’s IV Choline Chloride here.
[1] Micic D, Muhic E et al., JPEN J Parenter Enteral Nutr. 2025;49(6):e2733.