Ellisons Landmark Trial and Other Therapeutic Trials of Vitamin A the Anti Infective Vitamin 19201940

Vitamin A became known as the "anti-infective" vitamin, and from 1920 through 1940, this vitamin underwent considerable evaluation in at least 30 therapeutic trials, from dental caries to pneumonia to measles. These studies were conducted during a period when there was an increased awareness of the problem of infant and child mortality in Europe

Fig. 2. Frequency distribution of 72 children admitted to the Rigshospital, Copenhagen for xerophthalmia from 1912 to 1919. (Reprinted from ref. 48.)

and the United States (56). It should be emphasized that these trials were not conducted in populations with clinical vitamin A deficiency, i.e., xerophthalmia, was widespread; it was thought that vitamin A would reduce morbidity and mortality from infections in children and adults with subclinical vitamin A deficiency. Among the important discoveries during these trials was that vitamin A supplementation reduced mortality from measles in children (57,58) and reduced the morbidity of puerperal sepsis in women (59,60).

In 1932, Joseph Ellison (b. 1898), a physician in London, discovered that providing vitamin A to children with measles could reduce their mortality by 58% (57). During the 1931-1932 measles epidemic in London, Ellison assigned 600 children with measles at the Grove Fever Hospital (Fig. 3) to one of two groups of 300 children each. One group received vitamin A and the other group did not receive vitamin A. Overall mortality rates in the vitamin A and control groups were 3.7% and 8.7%, respectively, representing a 58% reduction in mortality with vitamin A treatment. Ellison's study, published in the British Medical Journal in 1932, was the first trial to show that vitamin A supplementation reduces mortality in young children with vitamin A deficiency. With the introduction of antibiotics in the mid-1930s, greater attention was paid to sulfa antibiotics and later penicillin, and there was an accompanying decline in the number of vitamin A trials.

Fig. 3. Grove Fever Hospital in Tooting, London, site of Ellison's landmark trial in 1932 that showed that vitamin A treatment reduced mortality in young children with measles. (Photo courtesy of the St. George's Medical School Library.)

Vitamin A became a mainstream preventive measure: cod-liver oil was part of the morning routine for millions of children—a practice promoted by physicians and popularized by the pharmaceutical industry (56). The production and importation of cod-liver oil in the United States totaled 4,909,622 lbs in 1929 (61). In the early 1930s in England, the annual consumption of cod-liver oil was 500,000 gallons per year (62). Much of the world's supply of cod-liver oil, and hence, vitamins A and D, came from the commercial fisheries of New England, Norway, and Newfoundland. As noted in the British Medical Journal, "cod-liver oil was in use in almost every working-class household, and local authorities spent considerable sums in purchasing bulk supplies for hospitals and sanitariums" (63). In England, a proposal to tax cod-liver oil in the Ottawa Agreements Bill in the House of Commons in 1932 raised protests, as there was concern that child mortality would increase if the price of cod-liver oil increased and it became less accessible to poor people. As reported in both The Lancet and the British Medical Journal, one legislator who supported an amendment to exempt cod-liver oil from the proposed taxation noted that many a child in the north of England "owed its life to being able to obtain cod-liver oil" (62,64). Two British physicians also supported the amendment in letters published in The Lancet (62). One expert from the Lister Institute of Preventive Medicine noted: "It is evident that any steps which may raise the price and lower the consumption of cod-liver oil, especially in the winter, would have deleterious effect on the health of the population, involving particularly the well-being of the children of the poorer classes"

(62). The concerns of physicians and legislators alike that children receive sufficient vitamin A to protect against the well-known morbidity and mortality of vitamin A deficiency were clearly expressed.

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