Nutrition and Infectious Disease

Dr. Edward Mellanby's book Nutrition and Disease contains a chapter titled "Nutrition and Infection". It begins:
There is general agreement among medical men that the susceptibility of mankind to many types of infection is closely related to the state of nutrition. The difficulty arises, when closer examination is given to this general proposition, as to what constitutes good and bad nutrition, and the problem is not rendered easier by recent advances in nutritional science.
Dr. Mellanby was primarily concerned with the effect of fat-soluble vitamins on infectious disease, particularly vitamins A and D. One of his earliest observations was that butter protected against pneumonia in his laboratory dogs. He eventually identified vitamin A as the primary protective factor. He found that by placing rats on a diet deficient in vitamin A, they developed numerous infectious lesions, most often in the urogenital tract, the eyes, the intestine, the middle ear and the lungs. This was prevented by adding vitamin A or cabbage (a source of beta-carotene, which the rats converted to vitamin A) to the diet. Mellanby and his colleagues subsequently dubbed vitamin A the "anti-infective vitamin".

Dr. Mellanby was unsure whether the animal results would apply to humans, due to "the difficulty in believing that diets even of poor people were as deficient in vitamin A and carotene as the experimental diets." However, their colleagues had previously noted marked differences in the infection rate of largely vegetarian African tribes versus their carnivorous counterparts. The following quote from
Nutrition and Disease refers to two tribes which, by coincidence, Dr. Weston Price also described in Nutrition and Physical Degeneration:
The high incidence of bronchitis, pneumonia, tropical ulcers and phthisis among the Kikuyu tribe who live on a diet mainly of cereals as compared with the low incidence of these diseases among their neighbours the Masai who live on meat, milk and raw blood (Orr and Gilks), probably has a similar or related nutritional explanation. The differences in distribution of infective disease found by these workers in the two tribes are most impressive. Thus in the cereal-eating tribe, bronchitis and pneumonia accounted for 31 per cent of all cases of sickness, tropical ulcers for 33 per cent, and phthisis for 6 per cent. The corresponding figures for the meat, milk and raw blood tribe were 4 per cent, 3 per cent and 1 per cent.
So they set out to test the theory under controlled conditions. Their first target: puerperal sepsis. This is an infection of the uterus that occurs after childbirth. They divided 550 women into two groups: one received vitamins A and D during the last month of pregnancy, and the other received nothing. Neither group was given instructions to change diet, and neither group was given vitamins during their hospital stay. The result, quoted from Nutrition and Disease:
The morbidity rate in the puerperium using the [British Medical Association] standard was 1.1 per cent in the vitamin group and 4.7 in the control group, a difference of 3.6 per cent which is twice the standard error (1.4), and therefore statistically significant.
This experiment didn't differentiate between the effects of vitamin A and D, but it did establish that fat-soluble vitamins are important for resistance to bacterial infection. The next experiment Dr. Mellanby undertook was a more difficult one. This time, he targeted puerperal septicemia. This is a more advanced stage of puerperal sepsis, in which the infection spreads into the bloodstream. In this experiment, he treated women who had already contracted the infection. This trial was not as tightly controlled as the previous one. Here's a description of the intervention, from Nutrition and Disease:
...all patients received when possible a diet rich not only in vitamin A but also of high biological quality. This diet included much milk, eggs, green vegetables, etc., as well as the vitamin A supplement. For controls we had to use the cases treated in previous years by the same obstetricians and gynecologists as the test cases.
In the two years prior to this investigation, the mortality rate for puerperal septicemia in 18 patients was 92%. In 1929, Dr. Mellanby fed 18 patients in the same hospital his special diet, and the mortality rate was 22%. This is a remarkable treatment for an infection that was almost invariably fatal at the time.

Dr. Mellanby was a man with a lot of perspective. He was not a reductionist; he knew that a good diet is more than the sum of its parts. Here's another quote from
Nutrition and Disease:
It is probable that, as in the case of vitamin D and rickets, the question is not simple and that it will ultimately be found that vitamin A works in harmony with some dietetic factors, such as milk proteins and other proteins of high biological value, to promote resistance of mucous membranes and epithelial cells to invasion by micro-organisms, while other factors such as cereals, antagonise its influence. The effect of increasing the green vegetable and reducing the cereal intake on the resistance of herbivorous animals to infection is undoubted (Glenny and Allen, Boock and Trevan) and may well indicate a reaction in which the increased carotene of the vegetable plays only a part, but an important part.
And finally, let's not forget the effect of vitamin D on infection resistance. Low vitamin D is consistently associated with a higher frequency of respiratory infections, and a controlled trial showed that vitamin D supplements significantly reduce the occurrence of flu symptoms in wintertime. Vitamins A and D are best taken together. Did someone say high-vitamin cod liver oil??

P.S.- I have to apologize, I forgot to copy down the primary literature references for this post before returning the book to the library. So for the skeptics out there, you'll either have to take my word for it, or find a copy of the book yourself.