By T.W. Gullikson and C.E. Calverley
Summary: In 1922 researchers at the University of California at Berkeley showed that rats deprived of an unidentified substance found in leafy greens and wheat germ failed to reproduce. The fat-soluble nutrient was named vitamin E, and soon research groups around the world were studying the effects of its deficiency in species ranging from turkeys to the tree-kangaroo. In this 1946 report, researchers at the Minnesota Agricultural Station reveal the surprising results of a ten-year investigation into the effects of vitamin E deficiency on the reproductive health of cows. While the animals were able to reproduce, many of them suffered another, unforeseen calamity: sudden, fatal heart failure. Meanwhile, clinicians were reporting a variety of successful applications of vitamin E therapy in humans, as epitomized by the famous Shute brothers, two Canadian doctors who documented the effective use of vitamin E in nearly ten thousand heart patients—results discredited and ignored by the medical community to this day. From Science, 1946. Reprinted by the Lee Foundation for Nutritional Research.[The following is a transcription of the original Archives document. To view or download the original document, click here.]
Cardiac Failure in Cattle on Vitamin-E-free Rations as Revealed by Electrocardiograms
During the past 8 or 10 years, in connection with an extensive study designed to determine the role of vitamin E in the nutrition and reproduction of cattle, a considerable number of the animals fed vitamin-E-free rations throughout their entire lives have died suddenly and without evident cause as revealed by gross postmortem examinations. The deaths have occurred among animals of both sexes and at ages ranging from 18 months to 5 years. The manner and suddenness of the deaths strongly suggested that the heart was involved.
A variety of effects of vitamin E deficiency have been reported in different species of animals, muscular dystrophy in some form being the most common. Recently, Houchin and Smith3 produced muscular dystrophy in vitamin-E-deficient New Zealand white rabbits 5 weeks of age. They found such animals to be highly susceptible to the action of posterior pituitary extract, being killed by much smaller doses than were easily tolerated by controls receiving alpha-tocopherol. The dystrophic rabbits were, however, more resistant to normally lethal doses of cardiac glucosides. Radiographic examinations of the thorax showed the probable existence of cardiac dilatation. They concluded that the sudden death that occurs in advanced cases of muscular dystrophy is due directly to cardiac failure.
The electrocardiograph is constantly being used in the study of heart conditions in human subjects. That it can be put to similar use with the bovine has recently been shown in the comprehensive studies of Alfredson and Sykes1,2,3 and Sykes and Moore.5 With these facts as a basis, beginning on 2 November 1945 and at monthly intervals or oftener thereafter, electrocardiographs were obtained on all animals on experiment. The instrument used and methods employed were essentially the same as those of Alfredson and Sykes.1
Selected recordings indicating the progressive changes that occurred in the cardiac cycle of [subject] E541 are presented in Figure 1. This heifer is the only animal that has died since the electrocardiogram recordings were started. Her dam and sire were both raised on vitamin-E-free rations and died suddenly, in the same manner as their daughter. E541 was born on 8 July 1944, was bred on 19 February 1945, and calved normally on 27 November 1945, when less than 17 months old. She died suddenly on 4 April 1946.
Study of the series of electrocardiograms obtained on this animal reveals that a gradual and progressive change occurred, the later recordings showing definite indications of the presence of cardiac abnormalities. The first definite changes appear in the recordings of 21 December 1945, as shown by an increase in PR interval, a condition that persisted throughout the remaining records. The QRS complexes in leads II and III also were changed, the potential in lead II was reduced, and the QRS in lead III changed from an RS type to an R type, an indication of axis deviation.
A clearly apparent increase in the QRS interval appeared in the record of 19 March 1946. The QRS in lead II also changed from an RS type to an R type. In the record of 26 March 1946, the potential of the various deflections has decreased and remains so in the subsequent recordings.[Image of electrocardiograms, with caption:] Figure 1. Electrocardiograms of E541 on dates indicated. (Leads I, II, and III, top to bottom in order.) Dates: 11-2-45, 12-21-45, 3-19-46, 3-26-46, 4-1-46. [See original for image].
In general the electrocardiograms obtained on this animal appear to show a decreased functional activity of the myocardium in the terminal stages of the deficiency, as indicated by the decrease in the potential of the deflection of the QRS complex and by the increase in duration of the PR, QRS, and QT intervals. The extra systoles that are apparent in the last record indicate dissociation of atrial and ventricular impulses and possibly damage to the conducting tissue. As has been stated, there also was a change in the electrical axis of the heart as the deficiency progressed.
Microscopic studies of heart sections, especially involving the Purkinje network of this and other animals in the study, are being made. It can be stated, even though this work has not been completed, that definite abnormalities have been noted. Atrophy and scarring of the cardiac muscle fibers is clearly indicated. An increase in cellular elements is noted, in some instances strikingly resembling though smaller than the Aschoff nodules seen in human endocarditis.
The authors express their sincere thanks and appreciation to Joseph F. Sykes, Bureau of Dairy Industry, U.S Department of Agriculture, for his assistance and aid in interpreting the electrocardiograms.
By Thor W. Gullickson and Chas. E. Calverley, Minnesota Agricultural Experiment Station, St. Paul. Science (Technical Papers), Vol. 104, No. 2701, October 1946. [Originally] published, with the approval of the director, as Paper No. 2307, Scientific Journal Series, Minnesota Agricultural Experiment Station. Reprinted by the Lee Foundation for Nutritional Research.
1. Alfredson, B.V., and Sykes, J.F. Proc. Soc. Exp. Biol. Med., 1940, 43:580.
2. Alfredson, B.V., and Sykes, J.F. J. Agric. Res., 1942, 65:61.
3. Houchin, O.B., and Smith, P.W. Amer. J. Physiol., 1944, 141:242.
4. Sykes, J.F., and Alfredson, B.V. Proc. Soc. Exp. Biol. Med., 1940, 43:575.
5. Sykes, J.F., and Moore, L.A. Arch. Path., 1942, 33:467.