In the course of the 19th century, chemists and physiologists studying the composition of foods and the nutritional requirements of humans and animals found that our diets needed to include the complex nitrogenous compounds called "proteins" (that, with water, form the bulk of our lean tissues), together with fats, starch and sugars that all provide usable energy during their oxidation in the body. It was also realized that bones contain high concentrations of lime (calcium oxide) and phosphate salts and the body, generally, has a variety of other necessary mineral salts, though it was felt that mixed diets normally supplied adequate quantities of all these without any need for special precautions.

With hindsight, we can see repeated early observations indicating that we also had a need for some other nutrients. Thus, sailors after 10-12 weeks on dry foods, during long sailing ship voyages before the days of refrigeration, typically developed scurvy, a disease characterized by weakness, pains in the joints, loose teeth and blood spots appearing all over the body, and finally sudden death "in the middle of a sentence" from the bursting of a main artery. However, desperately ill men would recover in 10 days or so after reaching land where they could be given fresh fruit or salad greens.

Another disease that seemed to be associated with a restricted diet was beriberi, marked first by weakness and loss of feeling in the feet and legs, then varied effects including edema of the trunk, and finally difficulty in breathing and death from heart failure. It seemed to be particularly associated with a diet of rice and little else. It had been described in some of the earliest medical treatises in China and Japan, but physicians from Europe only saw it in their countries' colonies in Asia. In 1803 Thomas Christie, a physician with the British army in Sri Lanka, wrote: "the chief cause of beriberi is certainly a want of stimulating and nourishing diet... However, giving "acid fruits" which I find of great value in cases of scurvy, has no effect in beriberi... I can suppose the difference to depend on some nice chemical combination." Christie was prophetic but, for the next 100 years, scientific methods were inadequate to pursue what those "nice combinations" might be. Their very existence was also almost forgotten in the time of the Pasteurian revolution, when microbial infection came to be thought of as the likely explanation for every disease.