Choline is an organic, water-soluble compound that was recognized as an essential nutrient by the National Academy of Medicine in 1998. Choline is required for numerous physiological processes, but the body cannot synthesize enough to meet daily needs, making dietary intake necessary. Despite its status as a required nutrient, public discussion has raised questions about its safety, specifically concerning a potential link between high choline consumption and an increased risk of cancer. This article investigates the scientific basis for this safety concern and evaluates the current research evidence regarding choline intake and cancer development.
Choline’s Critical Functions in Biological Systems
Choline maintains the structural integrity of every cell in the body. It serves as a precursor for phosphatidylcholine and sphingomyelin, the two most abundant phospholipids that form the bilayer of cell membranes. This structural role supports cell signaling and the normal function of tissues and organs throughout the body.
The nutrient also plays a part in liver function and fat metabolism. Choline is necessary for creating the very-low-density lipoprotein (VLDL) particles required to transport fats and cholesterol out of the liver. A deficiency can impair this process, potentially leading to the accumulation of fat in the liver, known as nonalcoholic fatty liver disease (NAFLD).
In the nervous system, choline is a precursor for the neurotransmitter acetylcholine. Acetylcholine is involved in functions including muscle control, memory, and mood regulation. Furthermore, choline is a source of methyl groups, which are used to form the metabolite betaine, supporting metabolic pathways that regulate gene expression and aid in DNA synthesis.
Tracing the Link Between Choline, TMAO, and Cancer Risk
The hypothesis linking choline to potential cancer risk arises from a specific metabolic pathway involving the gut microbiome. When certain gut bacteria encounter dietary choline, they metabolize it into a gaseous compound called trimethylamine (TMA).
Once TMA is produced in the gut, it is absorbed into the bloodstream and travels to the liver. In the liver, an enzyme called flavin-containing monooxygenase 3 (FMO3) rapidly converts TMA into trimethylamine N-oxide (TMAO). TMAO is the metabolite that has been the focus of most research into cardiovascular disease and, subsequently, cancer risk.
Initial observational studies, particularly those focused on aggressive forms of prostate cancer, first suggested an association between high dietary choline intake and elevated levels of TMAO. This research proposed that TMAO generated from high choline consumption might promote inflammation or other cellular processes that could encourage cancer progression. This association primarily established a correlation between high choline intake and lethal prostate cancer, prompting deeper investigation into a possible causal link.
Evaluating the Current Scientific Evidence
The scientific community has investigated the initial correlation between circulating TMAO levels and various cancer risks, including colorectal and hepatocellular carcinoma. This research has highlighted the distinction between correlation and causation. High TMAO levels may simply be a marker of a specific dietary pattern, such as a high intake of animal products, or an existing alteration in the gut microbiome rather than a direct cause of cancer.
A comprehensive meta-analysis pooling data from multiple studies on TMAO and cancer incidence found an overall insignificant association. While some studies suggested a positive link between serum TMAO and cancer, the pooled data did not confirm a clear, consistent relationship across all cancer types. The results remain inconsistent, indicating that the role of TMAO in cancer development is far more complex than initially theorized.
The current scientific consensus does not support the idea that normal, dietary intake of choline increases cancer risk in the general population. Choline remains a required nutrient for health, and the focus is shifting to how the gut microbiome and genetics influence TMAO production. Theoretical risks may be heightened with high-dose supplementation that pushes intake far beyond the established upper limits, but there is no strong evidence linking typical food consumption to increased risk.
Dietary Sources and Safety Guidelines
Given its importance for health, consuming adequate choline is a recognized dietary goal. The Adequate Intake (AI) for adults is set at 550 milligrams per day for men and 425 milligrams per day for women. These intake levels are based on the amount required to prevent liver dysfunction.
Choline is widely available in many common foods, especially those from animal sources. Rich sources include beef liver, eggs, fish such as salmon, and poultry. Plant-based sources, including certain legumes and cruciferous vegetables like broccoli and cauliflower, also contribute to daily intake.
The Tolerable Upper Intake Level (UL) for choline in adults is established at 3,500 milligrams (3.5 grams) per day. This maximum level is based on preventing adverse effects such as a fishy body odor and low blood pressure, which are symptoms of excess consumption. Consuming this amount from food alone is difficult, and toxicity concerns generally only arise when individuals take high-dose supplements far exceeding the UL.