Failure of Alpha Tocopherol to Influence Chest Pain in Patients with Heart Disease

Abstract

Claims for vitamin E in angina pectoris have not been based on controlled observations. Even some negative ' DTRING the course of our studies on the visceral and somatic components of chest pain in patients with heart (lisease, 1-4 Vogelsang, Shute and Shute5-9 and ilolotchick'0 reported beneficial effects of vitamin E on "anginal pain" and heart disease. It occurred to us that the relief of pain in such cases might be due, at least in part, to effects of vitamin E on the voluntary muscles rather than on the heart. This concept was supported by the fact that animals deprived of vitamin E show reversible changes in both cardiac'" 12 and skeletal"3 14 musculature, and by reports on the usefulness of vitamin E in the muscular dvstrophies and somatic pain syndromes such as filbromyositis. [5][6][7][8][9][10][11][12][13][14][15][16][17][18] We decided, therefore, to classify chest pain in our cardiac patients according to visceral and somatic components, and to evaluate by the blind-test method the effect of alpha tocopherol on these components in parallel series of control and treated subjects. The need for such a blind-test study is emphasized by Vogelsang, Shute and Shute themselves,9 as well as by recent editorial comment.'9 The latter conclhdes: "Subjective benefits claimed [for vitamin E] may justify a series of well controlled experimental studies in human heart disease

The (Harry) Gold standard: angina, suggestion and the path to the ‘double blind’ test and clinical pharmacology. Part 2: the path to the ‘double blind’

“…In their published February 1950 study of alpha tocopherol on angina, featuring five of the co-authors from the khellin study, the researchers noted the 'doubly blind conditions' under which the alpha tocopherol study was conducted). [20][21][22] The khellin study became an extended opportunity to emphasise the necessity of observer blinding. Holding up LeRoy as a cautionary example, Gold and colleagues publicly noted that an 'evaluation of the physician's enthusiasm (positive suggestion) on the angina of effort would be a study of some interest in itself but it seems self-evident that the physician's enthusiasm is inadmissible in a scientific experiment' (Greiner et al, 18 p. 153).…”

“…In their published February 1950 study of alpha tocopherol on angina, featuring five of the co-authors from the khellin study, the researchers noted the ‘doubly blind conditions’ under which the alpha tocopherol study was conducted). 20–22…”

Evolution of Evidence for Selected Nutrient and Disease Relationships

“…The initial citation is a letter published in the periodical Nature in 1946 that provides a conclusion without actual results; the methods are scant, and it is unclear whether the study is a case series or clinical trial (Vogalsang and Shute, 1946). Subsequently, the D&H report mentions several clinical trials of persons with angina that are nonconfirmatory (Anderson and Reid, 1974;Donegan et al, 1949;Makinson et al, 1948;Rinzler et al, 1950). The trials were typically small in size and of suboptimal design.…”

Guest Editorial - The History of the Double Blind Test and the Placebo

“…In a study``conducted according to stringent blindtest methods'', and published the same year, Rinzler et al (1950) investigated the failure of a-tocopherol to in¯uence chest pain in patients with heart disease.…”