UPDATE 9.30AM: Bendigo Highway Patrol Acting Sergeant Peter Dyer said police believed a medical issue was the cause of the crash.
"Another car that was driving behind the man saw the car veer off the road and collide with a tree," he said.
"We have ruled out speed, alcohol, drugs, fatigue and poor driving because of the account that witness has given."
POLICE are investigating a fatal crash that claimed the life of a man at Newstead on Wednesday.
Investigators believe the driver and sole occupant of the vehicle was travelling west on the Pyrenees Highway just after 5.30pm when he lost control and left the road.
The vehicle struck a tree approximately 150 metres west of Monash Street, trapping the 56-year-old driver.
Ambulance Victoria spokesman John Mullen said the Newstead man was airlifted from the Newstead football oval to the Alfred Hospital in a critical condition, where he later died.
Police will prepare a report for the Coroner.