Vicine is a naturally occurring glycoside alkaloid, a white, crystalline substance found in certain plants. In its natural state, vicine is composed of a glucose molecule bonded to an aglycone structure. This compound was first isolated in 1870 from the seeds of the vetch plant.
Vicine in Fava Beans
The most significant dietary source of vicine is the fava bean, also known as the broad bean (Vicia faba). Within the bean, vicine does not act alone; a similar compound named convicine is also present and contributes to the same biological effects. The concentration of both vicine and convicine can differ considerably among various types of fava beans.
These levels are also influenced by the plant’s stage of growth, with different amounts present in young pods versus mature, dried seeds. The processes by which the Vicia faba plant synthesizes vicine have been a subject of scientific study, but the precise pathway of its formation is not fully understood.
The Mechanism of Favism
Upon consumption, vicine itself is relatively inert. Its potential for harm begins when it reaches the digestive tract, where intestinal microorganisms chemically alter it. Bacteria in the gut hydrolyze the vicine molecule, which involves splitting off its glucose component. This process transforms vicine into a different, highly reactive molecule called divicine.
Divicine is a potent oxidizing agent that is absorbed from the intestine into the bloodstream. Once in circulation, it targets red blood cells and disrupts their internal balance by oxidizing a protective compound called glutathione. In most people, this is not an issue because their cells can quickly regenerate glutathione using an enzyme named Glucose-6-phosphate dehydrogenase (G6PD). This enzyme is part of a metabolic pathway that produces NADPH, a molecule that helps recycle oxidized glutathione.
However, individuals with the genetic condition G6PD deficiency do not produce enough functional G6PD enzyme, impairing their ability to generate sufficient NADPH. Without adequate NADPH, their red blood cells cannot counteract the oxidizing effects of divicine. This leaves the cells vulnerable to damage, leading to their premature destruction in a process called hemolysis.
Symptoms and At-Risk Populations
The destruction of red blood cells triggered by divicine leads to a condition called favism, a form of acute hemolytic anemia. Symptoms typically manifest rapidly, often within 24 to 48 hours of consuming fava beans. An individual may experience a sudden onset of extreme tiredness, pale skin, and shortness of breath. As red blood cells break down, they release bilirubin, causing a yellowing of the skin and eyes known as jaundice. Another telltale sign is the appearance of dark, often brown or red-colored urine, which results from the excretion of byproducts from hemoglobin breakdown.
G6PD deficiency is not uniformly distributed across the global population. The genetic trait is most common in individuals of Mediterranean, African, and some Asian ancestries. This geographical distribution is thought to be linked to evolutionary pressures in regions where malaria has historically been widespread. Scientific theories suggest that the cellular changes associated with G6PD deficiency may confer a degree of resistance to the malaria parasite, providing a survival advantage that has allowed the trait to persist in these populations.