America's youngest president was suffering from more conditions, was in greater pain and was taking more medications than the public knew at the time, according to a new biography to be published next year.
Historian Robert Dallek was given access to files covering the eight years leading up to Kennedy's assassination in 1963 and he examined them with a physician, Jeffrey A Kelman.
Both men told the New York Times they found evidence that Kennedy took hormones to treat a kidney disease as well as painkillers, anti-anxiety agents, stimulants and sleeping pills.
Writing in next month's issue of The Atlantic magazine, Mr Dallek says the records show the "quiet stoicism of a man struggling to endure extraordinary pain and distress".
Back injections
During his 1961-63 presidency, Kennedy was known to suffer from a bad back.
After his death, details of other illnesses began to emerge, including persistent digestive problems and Addison's disease, a hormonal deficiency which affects the kidneys.
Mr Dallek told the New York Times that at times Kennedy took up to eight different medications a day.
The records also show that before White House news conferences and other events, the president received seven to eight injections of procaine (an anaesthetic) in his back in the same sitting, according to Dr Kelman.
"The most remarkable thing," he said, "was the extent to which Kennedy was in pain every day of his presidency."
Medications
Three fractured vertebrae caused by osteoporosis reportedly gave Kennedy so much pain that he could not put a sock or a shoe on his left foot without help.
To combat pain, Kennedy is reported to have taken variously codeine, Demerol and methadone.
The files are also said to record him taking the stimulant Ritalin, meprobamate and Librium for anxiety and barbiturates.
At the time of the 1962 missile crisis, Kennedy was taking antispasmodics to control colitis, antibiotics to treat a urinary infection, and increased doses of hydrocortisone and testosterone, according to the New York Times.
Until now a committee of Kennedy family associates had refused all requests to look at the medical records.
Mr Dallek - who has written several books about American presidents - was given access because of his "tremendous reputation", committee member Theodore C Sorensen said.