As a student at Johns Hopkins, he worked in William Henry Howell's laboratory and assisted in the research that led to the discovery of heparin.

[2][3] In 1947, he organized the first International Congress of Pediatrics since the end of World War II;[2] that same year, he was awarded the Order of the White Lion for recommending oral feeding as treatment during a Czechoslovak epidemic of diarrhea in children.

[1] Holt retired in 1960 and received the John Howland Award, the highest honor given by the American Pediatric Society, in 1966.

He also studied fat emulsion as a method of intravenous nutrition, the treatment of maple syrup urine disease through diet control,[1] and the human requirements for various B vitamins.

Outside of nutrition, he also published research on topics including lead poisoning, leukemia, meningitis, eczema, and pertussis.