Ergot alkaloids are natural chemicals made by fungi, mainly the ergot fungus that grows on rye and other grasses.1PubMed Central. Biology, Genetics, and Management of Ergot (Claviceps spp.) in Rye, Sorghum, and Pearl Millet For centuries, people who ate bread from tainted rye suffered mysterious epidemics, while doctors later turned the same chemicals into prescription drugs.2PubMed. Ergotism and Saint Anthony’s fire3PubMed. History of ergot alkaloids from ergotism to ergometrine The chemicals act strongly on the body’s blood vessels and nerve signals, which makes them harmful in uncontrolled amounts and useful in measured doses.
Where Ergot Alkaloids Come From
Ergot is a fungal disease of cereals and grasses caused by fungi in the group Claviceps.4PubMed Central. Biology, Genetics, and Management of Ergot (Claviceps spp.) in Rye, Sorghum, and Pearl Millet The fungus infects young, usually unfertilized flowers and replaces the seed with a dark, hard fungal body.5PubMed Central. Biology, Genetics, and Management of Ergot (Claviceps spp.) in Rye, Sorghum, and Pearl Millet Different species attack different crops: rye and other grains in cooler regions, sorghum worldwide, and pearl millet in Africa and Asia.6PubMed Central. Biology, Genetics, and Management of Ergot (Claviceps spp.) in Rye, Sorghum, and Pearl Millet Rye is pollinated in the open, so its flowers stay exposed longer, which makes it more prone to infection than other grains.7Eurofins WEJ Contaminants. Maxiumum limits ergot alkaloids and ergot sclerotia in grains
In a grain head, the ergot bodies are dark purple to black and stick out of the ear like an oversized kernel. They are often larger than the normal grain, so they can be spotted by eye. Ground into flour they vanish, which is why poisoning happened through bread. Farmers and mills clean grain partly by removing these visible bodies.
The fungus gets through the year in a particular way. Ergot bodies fall to the ground at harvest or get mixed in with the grain, and they can survive the winter in soil. In spring, one that has been through the cold sprouts small stalks that release spores timed to meet blooming grasses. The spores land on open flowers and the fungus grows into the ovary, which is why the timing of flowering matters so much. It then produces a sticky, sugary fluid that insects carry to neighboring plants, so one infected field can seed the disease in others.
The fungus thrives when flowering coincides with damp, cool, humid weather, and shifting climates with heavy rain alternating with drought can favor its spread. It remains an active concern for grain farmers today.
The fungus builds these alkaloids from the amino acid tryptophan, which is also found in our food.8PubMed Central. Biosynthetic Pathways of Ergot Alkaloids All ergot alkaloids share a core ring shape that resembles the body’s own messenger chemicals, such as serotonin. Six main alkaloids dominate in contaminated grain, including ergotamine, ergometrine and ergocristine.9PubMed. Simultaneous determination of six major ergot alkaloids and their epimers in cereals and foodstuffs by LC-MS-MS
What Ergot Poisoning Does to the Body
Ergot poisoning, called ergotism, shows up in two broad forms: gangrenous and convulsive.10Wikipedia. Ergotism Gangrenous ergotism happens because some alkaloids squeeze blood vessels shut.11Wikipedia. Ergotism Fingers and toes, which have the thinnest blood supply, lose feeling, swell, peel, and can eventually die and drop off.12Wikipedia. Ergotism
Convulsive ergotism causes seizures, muscle spasms, nausea, vomiting, diarrhea, tingling, itching and headaches.13Wikipedia. Ergotism It can bring hallucinations, sweating, fever lasting weeks, and even mania or psychosis.14Wikipedia. Ergotism15PubMed. Convulsive ergotism: epidemics of the serotonin syndrome? Because illness worsened with every meal of contaminated bread, taking away the bread supply was the one thing that could stop it.
Historically, gangrene outbreaks dominated west of the Rhine while convulsive outbreaks hit regions to the east.16PubMed. Convulsive ergotism: epidemics of the serotonin syndrome? Ergot from the east may have carried an alkaloid that overstimulated the brain’s serotonin system at levels too low to choke off blood flow.17PubMed. Convulsive ergotism: epidemics of the serotonin syndrome?
Saint Anthony’s Fire and the Salem Question
In the Middle Ages, regions that ate rye as a staple recorded strange epidemics called Saint Anthony’s fire or holy fire.18PubMed. Ergotism and Saint Anthony’s fire Poor families ate rye bread daily, so a contaminated harvest could poison a whole village at once. Sufferers sought help from the monks of the Order of Saint Anthony. Pilgrims often improved, likely because they ate cleaner bread on the road.
One theory holds that ergot caused the Salem witch panic of 1692.19PubMed. Ergotism and the Salem witch panic: a critical analysis and an alternative conceptualization Supporters argued the weather suited ergot, the ages of the afflicted matched, and their fits resembled convulsive ergotism.20PubMed. Ergotism and the Salem witch panic: a critical analysis and an alternative conceptualization Critics examined each argument and rejected it, explaining Salem through social and psychological pressures instead.21PubMed. Ergotism and the Salem witch panic: a critical analysis and an alternative conceptualization
But ergotism usually strikes whole households, adults and children alike, and families eating the same bread should have shown gangrene too, which was not reported. The afflicted at Salem were specific individuals, mostly girls and young women. Ergot poisoning also continues as long as people keep eating contaminated grain, while the Salem fits came and went in ways tied to court events.
Is Ergot in Your Bread Today
Low traces can occur in grain foods, but legal limits keep them far below poisoning amounts. In the EU:
- Unprocessed grains other than rye, corn and rice may contain at most 0.2 g of ergot bodies per kg.22Eurofins WEJ Contaminants. Maxiumum limits ergot alkaloids and ergot sclerotia in grains
- Unprocessed rye keeps a higher limit of 0.5 g/kg because it is more easily infected.23Eurofins WEJ Contaminants. Maxiumum limits ergot alkaloids and ergot sclerotia in grains
- Flour from barley, spelt and oats is limited to 50 µg of ergot alkaloids per kg, with wheat flour moving from 100 to 50 by July 2028.24Eurofins WEJ Contaminants. Maxiumum limits ergot alkaloids and ergot sclerotia in grains
- Milled rye products are limited to 500 µg/kg, with a cut to 250 planned for 2028.25Eurofins WEJ Contaminants. Maxiumum limits ergot alkaloids and ergot sclerotia in grains
- Grain-based foods for babies and toddlers have the strictest limit, 20 µg/kg.26Eurofins WEJ Contaminants. Maxiumum limits ergot alkaloids and ergot sclerotia in grains
The limits work in two ways. Raw grain is limited by the weight of visible ergot bodies, because that is what an inspector can sort and weigh at the elevator. Flour and processed foods are limited by measured alkaloid content, because once grain is ground the bodies cannot be seen. The alkaloid measure is more precise about actual exposure, since two batches with the same weight of ergot bodies can carry different amounts of alkaloids.
Modern grain cleaning removes most ergot bodies before milling. The poisoning epidemics came from heavily infested harvests eaten daily with no cleaning. Rye and wholegrain products tend to carry more traces than refined wheat.
Laboratories can measure the six main alkaloids and their twin forms, which differ in toxicity.27PubMed. Simultaneous determination of six major ergot alkaloids and their epimers in cereals and foodstuffs by LC-MS-MS Food authorities in Europe check cereals against the new limits.28PubMed Central. Undertaking a New Regulatory Challenge: Monitoring of Ergot Alkaloids in Italian Food Commodities US researchers have begun measuring alkaloids in cereal foods on the American market to fill a data gap.29PubMed Central. Analysis of Ergot Alkaloids in Cereal-based Food Products From the US Market using LC-MS/MS
For shoppers, the sensible step is to buy from regulated sources rather than uncleaned home-harvested rye. Varied grains reduce reliance on one product. Foraged wild grass seeds can carry ergot, so inspect them for dark bodies.
How a Poison Became Medicine
Ergot was once used to speed labor, but after 1828 doctors limited it to preventing heavy bleeding after birth.30PubMed. History of ergot alkaloids from ergotism to ergometrine Ergometrine, isolated in 1932, strongly contracts the womb.31PubMed. History of ergot alkaloids from ergotism to ergometrine Ergonovine (ergometrine) is given as an injection of 0.25 mg to clamp the uterus after delivery.32TVASurg – The Toronto Video Atlas of Surgery. Management of Postpartum Hemorrhage Unpredictable side effects mean it is no longer the first choice, and it is avoided in people with high blood pressure.33PubMed. History of ergot alkaloids from ergotism to ergometrine34TVASurg – The Toronto Video Atlas of Surgery. Management of Postpartum Hemorrhage
Ergotamine and dihydroergotamine (DHE) treat migraine attacks at very low blood levels.35PubMed. Ergotamine and dihydroergotamine: history, pharmacology, and efficacy They narrow painful blood vessels around the brain and block pain signals in the nerve carrying headache.36PubMed. Ergotamine and dihydroergotamine: history, pharmacology, and efficacy Evidence is stronger for DHE than for ergotamine.37PubMed. Ergotamine and dihydroergotamine: history, pharmacology, and efficacy Because DHE acts on many receptors at once, it can help migraines that failed other drugs.38Cephalalgia Reports. Dihydroergotamine for migraine: Evidence for multiple modes of action: The single molecule ‘combination’ product—A narrative review
These drugs work best when taken early in an attack, rather than after the pain is well established. DHE comes in forms that bypass the stomach, such as injection or nasal spray, which suits people who vomit during attacks. They treat attacks that have already started, not daily prevention. Because they narrow blood vessels, they are not suitable for people with heart disease or poor circulation.
Cabergoline and bromocriptine are ergot-derived drugs that mimic dopamine.39World Health Organization. Application for inclusion of Bromocriptine and Cabergoline In the WHO Model Lists of Essential Medicines40PubMed. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients Cabergoline brought high prolactin levels back to normal in 86% of patients.41PubMed. Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients Prolactin is the hormone that drives breast milk. Too much can stop periods, cause infertility or lower sex drive, and a small benign pituitary growth is a common cause. For Parkinson’s, levodopa remains the most effective treatment, and these agonists showed no clear advantage.42World Health Organization. Application for inclusion of Bromocriptine and Cabergoline In the WHO Model Lists of Essential Medicines
LSD belongs to the family too. It was made from lysergic acid, the core ergot building block, and it shows how strongly these molecules affect the brain. It is not a medicine in standard use.
Side Effects and Drug Interactions to Know
Taking too much ergotamine can cause gangrenous ergotism, though not the convulsive form.43PubMed Central. Ergot Intoxication: Historical Review and Description of Unusual Clinical Manifestations Certain HIV medicines such as cobicistat can raise ergotamine levels and starve the legs of blood.44Elsevier / Annals of Vascular Surgery. Acute Ischemia of Lower Extremities Caused by Ergotamine Toxicity due to Pharmacologic Interaction With Cobicistat in an HIV-Positive Patient Ergonovine should not be used with protease inhibitors.45TVASurg – The Toronto Video Atlas of Surgery. Management of Postpartum Hemorrhage
Some drugs block the liver enzyme that normally breaks down ergotamine, so the medicine stays in the body at higher levels than intended. Protease inhibitors for HIV and some others work this way, which is why they appear in warnings. A normal dose can then act like an overdose and squeeze blood vessels dangerously. So before an ergot drug is started, tell your prescriber and pharmacist about every other medicine you take, including ones from another doctor.
Warning signs on these medicines include cold, pale, numb or painful fingers or toes, leg pain when walking, chest pain, or new breathlessness. These call for urgent care rather than waiting.
Ergot-type dopamine drugs can rarely cause scarring in the lungs and abdomen.46PubMed. Fibrotic heart-valve reactions to dopamine-agonist treatment in Parkinson’s disease Users of cabergoline had about 5 times the rate of leaky heart valves, and pergolide about 7 times.47PubMed. Dopamine agonists and the risk of cardiac-valve regurgitation Non-ergot dopamine drugs may not be completely free of this risk.48PubMed. Valvular heart disease and fibrotic reactions may be related to ergot dopamine agonists, but non-ergot agonists may also not be spared
Doctors may order an echocardiogram, an ultrasound of the heart, to check the valves. Risk rises with high doses taken for years, as in Parkinson’s. Low prolactin doses carry less concern, but ask your doctor about monitoring.
Ergot Alkaloids in Pastures and Livestock
Some grasses host fungi living inside their leaves that make alkaloids to fend off grazers.49PubMed Central. Anti-herbivory defences delivered by Epichloë fungal endophytes: a quantitative review of alkaloid concentration variation among hosts and plant parts These chemicals cut caterpillar feeding and growth.50Entomologia Experimentalis et Applicata. Contribution of ergot alkaloids to suppression of a grass-feeding caterpillar assessed with gene knockout endophytes in perennial ryegrass But one, ergovaline, also harms mammals.51PubMed Central. Anti-herbivory defences delivered by Epichloë fungal endophytes: a quantitative review of alkaloid concentration variation among hosts and plant parts
The fungus lives inside the grass, spreading through its tissues and passing into the seed, so new plants inherit it. The grass gains protection from insects and grazers, and the fungus gains shelter and a way to spread. Because it is invisible, a pasture can look healthy while carrying the toxin. Tall fescue is widely grown because it is tough and persistent, partly thanks to the fungus.
Fescue toxicosis is a costly livestock disease in temperate regions.52Agronomy Monographs. Physiological Basis of Fescue Toxicosis In summer, cattle overheat, pant and stand in ponds.53PubMed Central. Endophyte Infected Tall Fescue: Plant Symbiosis to Animal Toxicosis In winter, poor circulation can cost them ears, tails and hooves.54PubMed Central. Endophyte Infected Tall Fescue: Plant Symbiosis to Animal Toxicosis The summer slump brings low weight gain, less milk and poorer fertility.55PubMed Central. Endophyte Infected Tall Fescue: Plant Symbiosis to Animal Toxicosis
Making Ergot Medicines Without Ergot
Ergot drugs are largely made from fungus grown in fermentation tanks, then chemically modified.56Royal Society of Chemistry / Nat Prod Rep. Ergot alkaloids: synthetic approaches to lysergic acid and clavine alkaloids Tanks avoid dependence on field infections, which vary from year to year.
Engineered yeast has now produced lysergic acid, the key building block, from sugar.57PubMed Central. Reconstituting the complete biosynthesis of D-lysergic acid in yeast Industrial fungi used in food brewing have been engineered to make these alkaloids too.58Green Chemistry. Engineering industrial fungus Aspergillus oryzae for the sustainable biosynthesis of ergot alkaloids Moving production into yeast removes the need to grow infected crops and could give more consistent purity. Yields are still small, so this is early-stage.