(Xa No.8 EICHERT: VITA, ny nm VITAMIN E A ‘THERAPEUTIC PERPETRATION* ‘By Heesenr Excuerr, M.D. Miami, Florida { It is the purpose of this presentation to review the status of vitamin E and alpha-tocopherol in the treatment of cardiovascular disease, This substance came into widespread use in 1946, following the publication of extravagant claims by Shute and Vogelsang7} Although this group Jf investigators and their disciples have. con- tinued to report fabulous success in the treat | ment of almost every known type of ‘cardi | vascular disorder, all other authors who have | investigated this "treatment find it to be vit. | tually worthless8 71011 Tn spite of the dubious value of this drug, its widespread use continues. The perpetration of this nostrum upon a gullible public is a reflee- tion of the influence which lay publications exert ‘on medical practice. It is the secondary purpose Jof this article to point out how a small group | of physicians were able, literally, to force thou- ‘sands of other physicians to treat cases of heart disease with vitamin E by presenting their opin- ons to the public through the lay press before these had been corroborated, or before the aver- || age physician was aware that such a treatment | existed. Under ordinary circumstances a remedy of | such questionable merit would Jong since have faded fom the attention of the medical pro- jon and the cardiac invalid, but the diminish sme has been repeatedly kindled by new | ales appearing in the lay pres, which are waitten in a manner designed to create hope in otherwise hopeless invalids. Such an article ap- | eared in Coronet magazine’ as recently as | August, 1948. Although admitting the existence | of a controversy, the article implied that there [vos a possibility that vitamin E might do some | good in heart disease. Tt is easy to understand hhow such an article would have far greater | appeal to the average cardiac invalid than would the serious, factual and frequently pessimistic autitude of his physician. , A THERAPEUTIC PERPETRATION m7 In the June 10, 194, issue of Time magazine! the story “broke” and vitamin E made its debut as a reputed specific in the treatment of heart disease. In a news “scoop” Time magazine ballyhooed the claims of Dr. Shute and Vogel- sang of Ontario regarding thei alleged discovery, tis significant that this article in the lay press preceded the publication of any report in a medi- cal journal, Thus a widely read lay publication presented fantastic claims to the public, before the average physician had even an inkling of their being. Consequently the swarm of patients who trekked to their doctors requesting that they be given this new treatment, which had been described in Time magazine, found their doctors unprepared to administer the treatment, and tunable to discuss the subject intelligently”. The article in Time magazine made vitamin E appear to be a panacea in practically every known {ype ‘of heart disease, a discovery comparable in mag- nitude to that of penicillin or sulfanilamide in theit respective fields. The articie carried photo- sraphs of patients who bad been helpless cardiac invalids until vitamin E had cured them and enabled them to resume strenuous occupations, Incisive demands by patients sent many phy cians scurrying to libraties to look up the litera- | ture on vitamin E and heart disease, but this effort was fruitless for at that time there had| been no published medical reports. ‘The chagrin of such an experience led thi essayist to send a basty communication to Shutel and Vogelsang requesting a reprint of their pub- lished work. None was received but instead a sketchy mimeographed reply was returned, a full paragraph, the contents of which were vaguely analogous to the information which one might ‘expect om the label of the average patent medi- cine. Before dismissing the subject of the article in Time magazine, and without wishing to dwell too strongly on the policy of the lay press in its attitude of reporting medical topics, this escayist ishes to bring up a relevant incident. A recent| personal communication vas sent to the editors of Time magazine questioning the propriety of the article in question. A rather apologetic reply| was received in which it was stated among ozher things that “Time's medicine staff has been com-| pletely changed since 1946,” and that they arens now ‘making every effort to present material that has more respect from the medical pro- fession.” Time's editors did admit that they had “gone out on a limb” in publishing the article. A short review of the preliminary work of Shute and Vogelsang leading to the use of vita- ‘min E in the treatment of heart disease has a significant bearing on the nature of their subse- quent claims. For many years Shute had published reports of the effect of vitamin E on certain disturb- inces of the reproductive organs. Noting that this vitamin had an apparent effect on hemor- Thagic tendencies, he conceived the idea that it right exert a favorable effect on diseased blood vessels. Observers had noted that rats fed a vitamin E deficient diet showed myocardial lesions at autopsy. Other investigators noted that cattle on vitamin E deficient diets showed dlectrocardiographic evidence of myocardial dam- age. This latter observation was not corrobo- rated by a subsequent investigator. From this it was hypothecated that clinical heart disease ight be due to vitamin E deficiency. ‘The ‘experiment which spurred these investigators on was the treatment of a hunting dog with vitamin E, This animal was said to have been moribund due to heart disease, but after several days of vitamin E therapy, was well enough to run with the pack. ‘This laborious investigation ap- Parently justified the clinical trials on patients, and as had been anticipated, these scientists found that practically every case of heart dis- ase showed some improvement following vita- min E therapy. After a few more clinical trials, unbelievable results were obtained and a pre- liminary report fell into the hands of an avi reporter resulting in the sensational article in Time magazine Each group of clinical trials by Shute and Vogelsang resulted in extension of their claims. ‘Most of these articles appeared in the Medical Record.) Although this medical journal is a time- honored publication, it does not have a large circulation and is not too well known. In our local library, which subscribes to over 125 medi cal publications, the Medical Record is not i cluded, With no intention of reflecting on the quality of the publication, it must be empha. sized that the medical data which were reported by Shute and Vogelsang were never readily avail- SOUTHERN MEDICAL JOURNAL August 1949 able for the average physician to perase and evaluate critically. The only nationally por tant mea journal which evied an article by these authors was a reentdition of Surgery, Gynecology and Obsterncd®) On the otter and it ts been easy for the wishful thinker, either ly. or eda, to read Jn Coronet magasine tat Vogssang and Shute ave tented 3000 cases of heart disease wth 80 ‘per cent improvement and that 3,300 physicians inthe United States are now wing Vitamin E in heart disease. Following the apparent clinical success of this new method it became necessary to explain the rationale of its action, There are no detailed reports in the literature of biochemical or tissue studies to explain the apparent marvelous effect of vitamin E in heart disease; nevertheless, Shute and Vogelsang postulate from their clini- cal studies, that vitamin E has “beneficial effects ‘on blood vessels, on the myocardium, on the pacemaker and influences the thrombotic fea- tures of coronary artery disease by improving the collateral circulation in the ischemic area.” In their studies of vascular disease they state that the tocopherols “have a direct effect on the| thrombi. The clot itself is directly attacked! and literally melts away.’ i Shute and Vogelsang also claim to have re- duced 10-75 per cent of the disability of pa- tients with old cerebral thromboses even when they have existed in some cases for periods as long as six years.* This essayist has sent questionnaires to repre- sentative department heads of medical unive ties throughout the United States requesting the results of their experiences with vitamin EB in the treatment of heart disease.” Not a single favorable reply was received] These comments will be discussed later but apropos of the effect of vitamin E on thrombi claimed by Shute and Vogelsang, the opinion of Wright might be interesting Wright stated that he had observed patients who Had received vitamin E, some of them for as long as a year. Objective results were definitely disappointing particularly in peripheral vascular disease. Fe described a ease in which large gangrenous uleers appeared while the patient was on vitamin E therapy. Another personal communication prompted a reply thatVol. 42 No, 8 (vitamin £) ‘has no value other than a psycho-| “from my knowledge, I am convinced that it somatic one.” BICHERT: VITAMIN £, A THERAPEUTIC PERPETRATION ng Dosage of the drug was 200 to 800 mg. per day and in most patients, plasma levels of alpha- tocopherol were determined before the vitamin ‘This series included five cases of chronic Be {doses over long] angina pectoris, 3 cases of active angina pec. Fterely fens until some of the patients were] tors and five cases of congeative hee failure, Iiterally sick, and discontinued substance because not a single one of the pa, Uients seemed appreciably benefited? Replies from these questionnaizes. were rel ceived from Johns Hopkins, the Mayo Clini and medical universities in New York, Boston Chicago, and many others. In each instance the correspondent declared that in his estimation vitamnin E was of no specific value in the treat. ment of cardiovascular disease 1? These replies furnish @ clue to the paucity of published reports condemning the use of vite, min E in heart disease. Most of the clin abandoned ther trials because of the utter lack of response during the preliminary phases of their Investigations. Tt is unfortunate in’ the ight of subsequent developments that these| >inions were not published since if volume is) any criterion the literature on the pros and cons | vitamin E therapy in heart disease is dis. inetly one sided. Meanwhile, without editorial | omment, abstracts of the published papers of | ute and Vogelsang continue to appear in vast us medical and trade journals some of which re widely reads 6 Unfortunately, the publication of such an ab- tact Is sometimes tantamount to.a degree of mplied endorsement. Thus the original work { Shute and Vogelsang has acquired a specious otency by glib quotation in the lay press aed eless inclusion in other medical publications ad trade journals. A number of publications contradicting the| ork of Shute and Vogelsang have appeared hich although small in seope, represent oy reful and scientific study. Probably the moc tical evaluation of the therapeutic merit of pha-tocopheral in the treatment of heart dis: ss that reported by Levy and once} the | refully selected series of caces had bea pre sly studied for long periods of time end hibited relatively stable pattern of sywpn mS at the time the studies ‘were undertaken, the use of this pressure. None of the anginal attacks in the patients studied, as a re- sult of vitamin E administration. None of the cases of congestive failure showed | There was no change in the pattern of =| any amelioration of signs or symptoms while the vitamin E was being administered:) how. ‘ever, when four of these cases were switched to the conventional low salt diet, an immediate and dramatic improvement with matked diuresis occurred, Tn conclusion the authors stated that they| found no clinical evidence to warrant the ce of vitamin E in the types of heart disease dis. cussed, Baer et ali” studied twenty-two patients of which eleven were patients with congestive heart failure, five patients with angina pectoris, and 5 Patients with hypertension and/or arlro- | sclerotic heart disease. Vitamin E was admin. | istered to these patients in dosage of 300-400 | mg. daily In no case was there any demonstrable effect fon the clectrocardiogram, orthodiagram or blood patlents was markedly ‘or moderately improved, ‘These authors concluded thet their results Were not encouraging enough to recommend the use of vitamin E in the treatment of angina Pectoris, congestive failure or hypertension, Makinsoa!®/and his co-workers felt that the work of Vogelsang and Shute was not critical or adequately controlled. Accordingly they selected group of twenty-two patients with typical angina of effort and treated them with vitamin E, phenobarbital, aminophyllin, and calcium lactate, Each drug was given for three weeks, and the patients were asked to compare the! effect of the different drugs. 1 From this study, it was concluded that vitamin, E is of no value in the routine treatment of| angina pectoris, i ‘These authors call attention to the work of i720 ‘Evans and Hoyle that all remedies used in the treatment of angina pectoris bring about some degree of improvement. Even the administta- tion of a placebo will bring about an improve ‘ment in as many as 40 per cent of the cases. ‘This author's series of cases (Table 1) were SOUTHERN MEDICAL JOURNAL August 1949 (3) There is an alarming need for wider publication of studies and comment on the true \value, if any, of vitamin E in heart disease, to combat the unsupported claims for this product { which are being widely disseminated in lay pub- (licetions and trade journals. REFERENCES peers oo 0m AVON'S SERIES Gv CSE) Aes , ii Wlae Be else Reem Hy ote ee ee Ee RY endltem ond REAR eats | Attala Yt de A fe RPS Caas Uk fa toe Gan oe Ciconey Beart dinase———__ 2 ithe Ee ed Pa itamia, Bin React Dies, Spent a aa Ce eT eee a tame t seo de ' ooo, SHRP RE SiS GC ote act im — B i tie Bae da GRP Tale -eonsecutive cardiac cases encountered in private practice in 1947, Alpha-tocopherol was admi istered in dosages of 200-300 mg. dally for Periods of three weeks to four months. Three ‘of the cases died while receiving the drug. In rno single instance of the series was the course ‘of the illness dramatically altered. in addition to vitamin E most of the cases received other remedies for heart disease; there- fore, where some improvement occurred it was difficult to ascribe it solely to vitamin BE, Be- ‘cause of the apparent lack of response, further investigation of this vitamin was abandoned, In summary, no appreciable benefit could be noted in this series of nineteen cases as a result of vitamin E administration, concLustons |. @) The wide and unbridled publicity which has been given to the unproved reports by Shute and Vogelsang regarding the beneficial effects of vitamin E in the treatment of heart disease | is deplored, (2) With the exception of the claims made by Shute and Vogelsang and their group, every published, written, or verbal report which this, essayist has been able to obtain indicates that vitamin E has no value in the treatment of heart disease, ‘Ror Pais, 147477, 1986, 515 N.E, 15th St. RELIEF OF THE SYMPTOMS OF ACUTE GOUT AND RHEUMATOID ARTHRITIS BY MEANS OF PITUITARY ADRENO- CORTICOTROPIC HORMONE (ACTH)* By Toxt D. Spurs, M.D. and Rosezr E. Stone, M.D, Birmingham, Alabama ‘The monumental work of Hench, Kendall, Slocumb, and Polley? in showing that fourteen ‘cases of rheumatoid arthritis were relieved by compound E (the adrenal cortical hormone, 17-hydroxy-11-dehydrocorticosterone) and two ‘cases by pituitary adrenocorticotropic hormone, marks a milestone in the investigation of this disease. For the past few years we have been studying the effect of a number of nutrients and hormones on the so-called diseases of later ecred for pubeaon Jly 19, 190. Mesto, Sarthe itt athe toni, Hea "Aas tpi study an aded by grants fo the Mtr Lead Sbet- wig Fund'and toe Birangha Clues Conaice Ta cy emer rms wa te neh Tsbormonee PF sears {Chston Foundation Felon.