Choline: History and Discovery

The story of choline begins not with a vitamin hunt or a deficiency epidemic but with a curious chemist boiling down animal bile. In 1849, the German chemist Adolph Strecker separated a strange nitrogen-rich substance from pig bile; in 1862 he gave it the name we still use, choline, from the Greek chole, meaning "bile." For the next half-century the same molecule was found again and again under different names — pulled from mustard seeds, from brain tissue, from egg yolk — before a young Adolf von Baeyer proved they were all one and the same. This article traces that real, documented history: the chemists who isolated and named it, the tangle of rival names that took decades to sort out, its surprising link to the very first neurotransmitter, the dogs that revealed it could prevent a fatty liver, and the long road that ended in 1998 with choline being recognized as something the human body genuinely needs. Where the record is firm we say so; where a detail is uncertain or still being worked out, we mark it as such.

Table of Contents

  1. A Vitamin That Is Not Quite a Vitamin
  2. Adolph Strecker and the Naming of Choline (1849–1862)
  3. One Molecule, Many Names: Sinkaline, Neurine, and the Confusion
  4. Adolf von Baeyer Sorts It Out (1867)
  5. Choline's Famous Relative: Acetylcholine and a Nobel Prize
  6. The Dogs That Changed Everything: Best, Huntsman, and the Lipotropic Effect (1932)
  7. Mapping the Metabolism: Kennedy, Bremer, and Greenberg
  8. From Animal Curiosity to Human Necessity (1991–1998)
  9. What the History Leaves Us
  10. Research Papers and References
  11. Connections
  12. Featured Videos

A Vitamin That Is Not Quite a Vitamin

Before telling choline's discovery story, it is worth being honest about what choline actually is — because its history is unusual among the nutrients we file under "vitamins." Choline is an essential nutrient: the body can make some of it on its own, but generally not enough, so most of us must get the rest from food. That much is settled. What is also true, and often glossed over, is that choline is not formally classified as a vitamin. It behaves more like an amino acid in its chemistry and metabolism, it is needed in far larger amounts than any true vitamin (hundreds of milligrams a day rather than micrograms or a few milligrams), and it can be partly synthesized in the human liver. For these reasons nutrition authorities place it in its own category, sometimes described loosely as "vitamin-like" or grouped near the B-complex because of its role in methylation, but never given a B-number of its own.

This matters for the history that follows. Choline was not discovered the way the classic vitamins were — there was no dramatic deficiency disease in sailors or rice-eating populations that sent scientists hunting for a missing factor, and choline plays no part in Casimir Funk's famous 1912 coining of the word vitamine. Instead, choline was discovered decades earlier, in the 1840s and 1850s, as a piece of pure organic chemistry. Its career as a nutrient came much later and almost by accident, out of insulin research in the 1920s and 1930s. So choline's story runs in two distinct chapters: first the chemists who isolated and named the molecule, and only generations later the physiologists who realized the body could not do without it.

Back to Table of Contents

Adolph Strecker and the Naming of Choline (1849–1862)

The discovery of choline belongs, first and most clearly, to the German chemist Adolph Strecker (1822–1871) — the same Strecker remembered today for the Strecker amino-acid synthesis. In 1849, while studying the chemistry of animal bile, Strecker became the first person to isolate choline, obtaining it from pig bile. At that stage it was simply an unfamiliar nitrogen-containing compound separated out of a complex biological fluid; the significance of what he had in hand would not be clear for many years.

The naming came in 1862. Working again with bile — this time from both pig and ox — Strecker found that lecithin (a fatty membrane substance) released a distinct nitrogenous chemical when it was boiled. He called this substance choline, coining the name from the Greek word chole, meaning "bile," in honor of the material it had come from. The name stuck, and it is the one we still use today. That a molecule so central to the brain and liver should be named after bile is a small accident of history: Strecker simply named it after where he happened to find it.

It helps to set Strecker's work beside a closely related discovery. In 1850, the French chemist and pharmacist Theodore Nicolas Gobley, working in Paris, named lecithine (lecithin) — the very substance Strecker would later boil to release choline — building on his isolation of the material from egg yolk in the preceding years. Gobley took his name from the Greek lekithos, meaning "egg yolk," the rich source from which he had purified it. Lecithin and choline are intimately bound together — choline is the head-group of the phospholipid we now call phosphatidylcholine, the main component of lecithin — so Gobley's and Strecker's discoveries are really two ends of the same thread, pulled apart by a dozen years and the chemistry of the day.

Back to Table of Contents

One Molecule, Many Names: Sinkaline, Neurine, and the Confusion

What makes choline's early history genuinely interesting — and a useful lesson in how nineteenth-century chemistry worked — is that the same molecule was discovered independently several times, in completely different materials, and given a different name each time. Without modern tools for determining molecular structure, chemists in different laboratories had no quick way to know they were all holding the same compound.

In 1852, the chemists L. Babo and M. Hirschbrunn extracted a substance from white mustard seeds and named it sinkaline (sometimes spelled sincalin). They had, in fact, found choline — but coming from a plant rather than from bile, and arriving by a different chemical route, it looked to them like a new discovery deserving its own name.

The confusion deepened in 1865, when the German physician and pharmacologist Oscar Liebreich isolated a nitrogen-rich substance from animal brain tissue and called it neurine — a name that pointed to its origin in nervous tissue and reflected his belief that he had found a fundamental building block of the brain. For a time, then, the scientific literature carried three names — choline, sinkaline, and neurine — for what would turn out to be a single molecule, plus a fourth, closely related compound (also confusingly called neurine in some sources) that complicated matters further. This is exactly the kind of tangle that was common before structural chemistry matured: a substance's identity was tied to where it was found and how it was prepared, not to a settled picture of its atoms.

Back to Table of Contents

Adolf von Baeyer Sorts It Out (1867)

The person who untangled the knot was one of the giants of organic chemistry: Adolf von Baeyer (1835–1917), who would go on to win the Nobel Prize in Chemistry in 1905 for his work on dyes and aromatic compounds, including the synthesis of indigo. (His Nobel Prize was for that later body of work, not for choline — an important distinction to keep straight.)

In 1867, von Baeyer worked out the structural formulas of the disputed substances. By establishing what these molecules actually were at the atomic level, he was able to show that Liebreich's "neurine" and Babo and Hirschbrunn's "sinkaline" were in fact identical to Strecker's choline. The three names collapsed into one, and the name that survived was the one Strecker had given it: choline. With its structure now known, choline ceased to be a mystery isolated from this or that tissue and became a defined chemical entity that could be studied, synthesized, and reasoned about.

This resolution is a clean example of how chemistry advanced in the period. The isolation work of the 1840s through 1860s gave science the substance; von Baeyer's structural work of 1867 gave it an identity. Only once a molecule had a settled structure could the next, much later chapter — understanding what choline actually does in a living body — even begin.

Back to Table of Contents

Choline's Famous Relative: Acetylcholine and a Nobel Prize

Choline's most celebrated claim to fame is not really about choline itself but about a molecule built from it: acetylcholine, the very first chemical messenger of the nervous system ever identified. Acetylcholine is simply choline with an acetyl group attached, and the body assembles it from the choline we eat. Its discovery as a biological signal is one of the landmark stories of twentieth-century physiology — and, unusually for this page, a story with a clear Nobel Prize attached.

Acetylcholine itself was first chemically synthesized in the laboratory well before its biological role was known. Its importance to living things emerged through two researchers whose work is forever linked. The Austrian-born pharmacologist Otto Loewi, in a famous experiment in 1921, showed that stimulating the nerve to a frog's heart released a chemical — he called it Vagusstoff ("vagus substance") — that could slow a second heart when the fluid was transferred to it. This was the first proof that nerves communicate by releasing chemicals, not purely by electricity. The English physiologist Sir Henry Dale, who had isolated acetylcholine and studied its powerful effects on the body, recognized that Loewi's mysterious Vagusstoff was acetylcholine.

For establishing that nerve impulses are passed from cell to cell by chemical transmission, Otto Loewi and Sir Henry Dale shared the Nobel Prize in Physiology or Medicine in 1936, awarded, in the committee's words, "for their discoveries relating to the chemical transmission of nerve impulses." This is the deepest reason choline matters to the brain: the entire cholinergic system — the network of nerves that depend on acetylcholine for memory, attention, and muscle movement — ultimately runs on a supply of dietary choline. The molecule Strecker named after bile turned out to sit at the root of how the nervous system talks to itself.

Back to Table of Contents

The Dogs That Changed Everything: Best, Huntsman, and the Lipotropic Effect (1932)

For nearly eighty years after Strecker named it, choline was a molecule of interest to chemists but not something anyone thought of as a nutrient. That changed because of an accidental observation made during one of the most famous episodes in medical history: the discovery of insulin.

Charles Best — the Canadian physiologist who, as a young man in the summer of 1922, had worked alongside Frederick Banting to isolate insulin — noticed something troubling in the laboratory dogs whose pancreases had been removed and who were being kept alive with insulin: their livers became clogged with fat. Best and his colleagues set out to understand why. In a key paper published in 1932, Best and his co-worker Margaret Huntsman reported in the Journal of Physiology that feeding lecithin — and specifically the choline within it — could prevent the buildup of fat in the liver. Choline, in other words, was the active ingredient that kept the liver from turning fatty.

This property earned choline the label lipotropic, meaning "fat-moving" — a substance that helps the liver export fat rather than store it. Through the 1930s, 1940s, and 1950s, a large body of animal work followed: choline deficiency was shown to cause fatty liver, a bone disorder called perosis in growing chickens, kidney damage and hemorrhages in young rats, and — strikingly — by the mid-1950s, even liver cancers in choline-deficient animals. The modern understanding that links choline to non-alcoholic fatty liver disease descends in a direct line from Best and Huntsman's dogs. Their 1932 paper is the true birth of choline as a nutrient, even though it would take another sixty-six years for that insight to be formally applied to human beings.

Back to Table of Contents

Mapping the Metabolism: Kennedy, Bremer, and Greenberg

Knowing that choline prevented fatty liver was one thing; understanding how the body uses choline at the molecular level was another, and that work belongs to the middle of the twentieth century. Two discoveries stand out, because together they explain why the body needs choline at all and why it can make only some of its own.

In 1954, the biochemist Eugene Kennedy, then at the University of Chicago, described the pathway by which cells build phosphatidylcholine — the main choline-containing phospholipid of every cell membrane — from dietary choline. This route, which runs through an intermediate called cytidine diphosphate-choline (CDP-choline), is still known in his honor as part of the Kennedy pathway. It is the body's primary way of turning the choline we eat into the structural fabric of our cells.

Then, around 1960, Jon Bremer and David Greenberg, working at the University of California, San Francisco, characterized a second route — the PEMT pathway — by which the liver can manufacture phosphatidylcholine (and thus choline) on its own, by methylating a related phospholipid using the universal methyl donor S-adenosylmethionine. This was the molecular discovery that explained a crucial fact: the human body is not entirely dependent on food for choline, because the liver can make some itself. But — as the next section shows — this internal supply is limited, and for most people it is not enough. The existence of the PEMT pathway is also why choline requirements differ so much from person to person, and why hormones and genetics can tip someone into deficiency while sparing someone else.

Back to Table of Contents

From Animal Curiosity to Human Necessity (1991–1998)

Despite Best and Huntsman's dogs and decades of animal data, a stubborn question lingered well into the late twentieth century: did humans actually need to eat choline, or could the liver's PEMT pathway make all a person required? Settling this took careful, and rather demanding, human experiments.

The decisive work was led by Steven H. Zeisel, whose laboratory (later at the University of North Carolina at Chapel Hill) conducted controlled feeding studies beginning around 1991 in which healthy adults were placed on diets deliberately low in choline. The result was clear: men fed a choline-deficient diet developed signs of liver damage and fatty liver, and the damage resolved when choline was restored to their diet. This was the human proof that had been missing for over a century — direct evidence that the body cannot reliably make all the choline it needs. Later studies refined the picture, revealing that requirements vary with sex, menopausal status, and genetics: estrogen switches on the liver's PEMT pathway, which is why some premenopausal women are relatively protected, while many men and postmenopausal women are not. A related, very practical confirmation came from patients fed entirely by vein (total parenteral nutrition), who developed fatty liver that improved with added choline — work reported by Alan Buchman and colleagues in the mid-1990s.

The official milestone arrived in 1998, when the Food and Nutrition Board of the US Institute of Medicine (now part of the National Academies) reviewed the accumulated evidence and, for the first time, set an Adequate Intake for choline — formally recognizing it as a nutrient essential to human health. Because the data were not yet sufficient to set a precise Recommended Dietary Allowance, the board used the more cautious "Adequate Intake" designation, and those reference values (on the order of 425–550 mg per day for adults, with higher amounts in pregnancy and lactation) are the ones still in use. It had taken from Strecker's 1849 isolation to this 1998 recognition — about a century and a half — for choline to travel from a curiosity in bile to a nutrient officially declared necessary for people.

Back to Table of Contents

What the History Leaves Us

Choline's history is a different shape from the classic vitamin stories, and that difference is the point. There was no single deficiency disease that announced its existence, no lone discoverer crowned for finding it, and no place for it in Casimir Funk's original roll-call of vitamines. Instead the credit is genuinely shared and spread across more than a century: Strecker isolated and named it; Babo, Hirschbrunn, and Liebreich rediscovered it under other names; von Baeyer proved it was all one molecule; Loewi and Dale won a Nobel Prize for the messenger built from it; Best and Huntsman revealed it could save a liver from fat; Kennedy, Bremer, and Greenberg mapped how the body uses and makes it; and Zeisel and the Institute of Medicine finally established that humans need it.

Two honest closing notes belong here. First, choline remains an essential nutrient that is not a true vitamin — a member of the nutritional family by need rather than by formal classification, which is why you will find it discussed alongside the B-vitamins on this site even though it carries no B-number. Second, the history is not finished: research today is still working out choline's role in brain aging, in fetal brain development — including a notable Cornell University trial showing that extra choline in late pregnancy sped up infants' information processing — and in heart disease, where the gut-bacteria byproduct TMAO has complicated the simple picture. The detailed modern evidence, mechanisms, dosing, and cautions are covered in the companion Choline Benefits articles and on the main Choline page. This history exists to explain something easy to forget: that one of the nutrients most of us fall short on was hiding, for a very long time, in plain sight.

Back to Table of Contents

Research Papers and References

The list below combines key peer-reviewed sources on choline's history, biochemistry, and essentiality with curated PubMed topic-search links and authoritative reference pages. Historical nineteenth-century work (Strecker, Gobley, Babo and Hirschbrunn, Liebreich, and von Baeyer) is named in the article as historical scholarship rather than as modern citations; the consolidated, sourced account of that early history is given in the Zeisel review below. Author names, titles, and journals are written as plain text; only the stable DOI, PMID, or archive link is hyperlinked, and each opens in a new tab.

  1. Zeisel SH. A brief history of choline. Annals of Nutrition and Metabolism. 2012;61(3):254-258. — doi:10.1159/000343120 · PMID: 23183298
  2. Zeisel SH, da Costa KA. Choline: an essential nutrient for public health. Nutrition Reviews. 2009;67(11):615-623. — doi:10.1111/j.1753-4887.2009.00246.x · PMID: 19906248
  3. Best CH, Huntsman ME. The effects of the components of lecithine upon deposition of fat in the liver. The Journal of Physiology. 1932;75(4):405-412. — doi:10.1113/jphysiol.1932.sp002899 · PMID: 16994325
  4. Caudill MA, Strupp BJ, Muscalu L, Nevins JEH, Canfield RL. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study. The FASEB Journal. 2018;32(4):2172-2180. — doi:10.1096/fj.201700692RR · PMID: 29217669
  5. Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Choline. In: Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academies Press; 1998. — NCBI Bookshelf: NBK114308
  6. Choline — history and discovery — PubMed: choline history and discovery
  7. Acetylcholine — discovery and chemical neurotransmission — PubMed: acetylcholine discovery (Loewi and Dale)

External Authoritative Resources

Back to Table of Contents

Connections

Back to Table of Contents