In 1969, researchers proposed the strange behavior of the monarch who reigned during the American Revolution resulted from a rare hereditary blood disorder called porphyria.
However, a study this week in The Lancet medical journal found high concentrations of arsenic in the king's hair and contends the severity and duration of his episodes of illness may have been caused by the toxic substance.
The 18th-century king, under whose reign Britain mastered the oceans, defeated Napoleon and expanded its empire to superpower dimensions, was best remembered for the humiliating loss of the American colonies and for the periods when he lost his mind.
While on the throne, George had five episodes of prolonged and profound mental derangement. At the time, his malady was thought to be a psychiatric disorder.
But in 1969, psychiatrists investigating his documented symptoms such as lameness, acute abdominal pain, red urine and temporary mental disturbance, proposed he suffered from porphyria. Subsequent studies that examined records of his ancestors, descendants and other relatives refined the diagnosis to a certain type of porphyria.