Scurvy, clinical trial

At this point, it may be useful to the reader to understand some of the background that has led to the contemporary design of human clinical trials. Although the concept of a comparative trial was known in the ninth century bc, it remained for James Lind in 1774 to perform his famous trial. Lind was concerned with comparing several different recommended treatments of the day for scurvy. Lind demonstrated that when all of the proposed treatments were compared in a controlled study in human volunteers, only one proved efficacious—citrus fruit. It is important to realize that each of the treatments tested was recommended by recognized authorities of the day. It took the comparative trial to prove that citrus juice cured scurvy and the other treatments were worthless. In the process of applying this scientific method, Lind did much to destroy the credibility of testimonials. 

His Treatise of the Scurvy published in 1753 is the first example of a controlled clinical trial experiment. In his treatise, Lind gave a thorough review of other authors who had written on scurvy along with a careful clinical description of the condition. It was not until the end of the eighteenth century that the British navy finally had its sailors drink a daily portion of lime or lemon juice to prevent scurvy. 

When James Lind, a surgeon in the British Royal Navy, performed his famous experiment (perhaps the first controlled clinical trial) in 1746, he compared the curative effects of several treatments on 12 sailors who had scurvy. Two men were assigned to each of six daily treatments for two weeks. Briefly, the treatments... 

Lind was not quick to publish his most famous treatise reporting this clinical trial (Lind 1753). Indeed, in 1748, his Edinburgh MD thesis was on an entirely unrelated subject. Subsequently, Lind was Treasurer of the Royal College of Surgeons of Edinburgh, and then appointed physician to the Royal Naval Hospital, Haslar (one-fifth of his first 6000-odd admissions were for scurvy). He... 

Clinical trials prove that citrus fruit cures scurvy (James Lind) Others had suggested citrus fruit as a cure for scurvy, but Lind gives scientific proof. It still will be another fifty years before preventive doses of foods containing vitamin C are routinely provided for British sailors. 

Tests measuring the plasma ascorbic acid levels a few hours following the test dose were more useful for rapid evaluation of tissue storage of ascorbic acid (W7, S26, RIO). The clinical usefulness of such a test was reported (D23) in a trial in which nine scorbutic patients had serum concentrations less than 0.25mg/100ml three hours after an oral dose of 15 mg ascorbic acid/kg body weight. Some individuals with normal intakes and low initial levels also had equally small rises. But rises to levels greater than 0.25 mg/100 ml were not consistent with scurvy. 

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