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VITAMIN E AND NEUROMUSCULAR DISEASES
431
pendent of each other in metabolism. Ilowever, BeneOsterberg in 1923 were able to demonstrate
,diet and
an increase in creatinine excretion after feeding large doses of creatine. This provided some, though not conclusive, experimental support for the belief that
creatinine is derived from creatine in the
course
of
metabolism. In 1933 Schrire and Zwarenstein showed that injections of an acid extract of the anterior pituitary produces an increase in urinary creatinine. In 1936 Zwarenstein and I were able to show that the same extract produced an increase in muscle creatine. Braier (1931) showed that hypophysectomised dogs excreted a diminished amount of creatinine, while Zwarenstein and I (1936) found that hypophysectomy decreased the muscle creatine in toads. It is true that all these experiments were not performed on the same species of animal. Nevertheless, the fact that one type of procedure was able to increase both muscle creatine and urinary creatinine, and another procedure was able to decrease both creatine and creatinine does, I think, provide a suggestive experimental basis for the common assumption that urinary creatinine is derived from muscle creatine. I am, Sir, yours faithfully, B. G. SHAPIRO. London, W.C.1. ,
zie and McCollum" and Morris7 found that not only prevention but also cure of the symptoms could be effected by natural and synthetic pure tocopherol. Evans,8 to whom the credit for the discovery of the antisterility activity of vitamin E belongs, described the neuromuscular symptoms in young rats due to its lack in 1928. He has in addition shown the efficacv of pure tocopherol in muscular dystrophy of the guineapig.’ Lately Anderson, Elvehjem and Gonce 10 have described the successful treatment of muscular dystrophy in dogs with ∬-tocopherol acetate, whereas Knowlton, Hines and Brinkhous 11 have confirmed the results with this substance in rats. The proof of the therapeutic equivalence of pure tocopherol and its acetate with natural vitamin E is of considerable practical importance since it makes possible the use of this vitamin in a stable and standardised form and the administration of the required high doses which would be difficult to supply regularly for long periods in the form of wheat germ or wheat-germ oil. Preliminary reports on trials made with tocopherol acetate (ephynal) in doses of 30 mg. and more daily in cases of progressive muscular
dystrophy are encouraging (private communication). During the trials on young rats, I was struck by the relatively late onset of the neuromuscular dis-
turbances. The rats looked completely normal for about 3 weeks-i.e., till they reached about 2/5th VITAMIN E AND NEUROMUSCULAR DISEASES of their maturity. An observer not acquainted with SIR,—In his interesting paper on the successful their previous history would therefore have been unable to ascertain the origin of the degenerative treatment of muscular and neuromuscular disorders states starting after the age of 21 days or more, ,with vitamin E (Lancet, Jan. 6, 1940, p. 10), Dr. Bicknell expressed doubts as to whether the neuroalthough histological studies would; have revealed and musculo-tropic factor of wheat germ is identical muscular changes even prior to this. Since myopathies in children also appear only after some years no-one with pure vitamin E ( x-tocopherol). His doubts are based on observations of Goettsch has hitherto thought of tracing such states back to and Ritzmann,who demonstrated the efficacy of any " congenital avitaminosis," not only because of tocopherol in muscular disturbances in the young rat the lapse of time from birth to the onset of the disbut were led to doubt the identity of the neuromuscular turbances but also because the paediatrician attending factor with tocopherol from trials with wheat-germ the child would have to communicate with the obstetrician who was in charge of the mother during oil in which the natural vitamin E had been destroyed (although apparently only partially) by previous pregnancy and delivery. I.suggest that efforts should treatment with ferric chloride. After this treatment be made in cases of myatrophy to ascertain the history the oil still maintained the normal neuromuscular of the child and if possible of the mother as regards functions of young rats on a diet lacking vitamin E, miscarriages, premature births or neurological troubles but was unable to prevent abortion in adult rats who during pregnancy, in the hope of finding the missing had been kept for months without vitamin E. Appar- link between the antisterility and neuromuscular ently the continuous administration of the minimal effects. amount’ of vitamin E still present was capable of According to our animal experiments not only the maintaining the muscular functions of the young muscles but also the sensory organs (e.g., olfactory animals, whereas it was insufficient to reach the level and auditory nerves) and the intelligence may suffer,12 required for normal pregnancy. Various other papers and that in birds lack of vitamin E is connected with substantiate the full activity of natural and synthetic states of encephalomalacia,13 It is therefore not ’tocopherol in neuromuscular disturbances. The experi- impossible that in addition to tabes and poliomyelitis, mental proof is steadily increasing. suggested by Dr. Bicknell, other disturbances of the In young rats born of mothers kept on a low higher centres appearing in children, or as a sequel vitamin-E diet Barrie and ourselves (Demole and to infections or chemical intoxications in adults, might Pfaltz3) found that synthetic tocopherol and its benefit from vitamin E. I believe my remarks support Dr. Bicknell’s asseracetate (ephynal) were capable of completely preventing the appearance of muscular or neurological dis- tion that the discovery of the importance of vitamin E in the treatment of muscular and nervous diseases turbances. Similar observations have been made by Verzar and myselfin adult male and female rats " opens up new lines of thought and treatment in suffering from vitamin-E deficiency, confirming the many diseases." results described in the monograph of Einarson and I am, Sir, yours faithfully, ’Ringsted with natural vitamin E. In experimental V. DEMOLE. Basle, Switzerland. nutritional muscular dystrophy of the rabbit Macken,
-
7. Ibid, 1939, 90, 424. 8. J. biol. Chem. 1928, 76, 273. 9. Science, 1939, 90, 89. 10. Proc. Soc. exp. Biol., N.Y. 1939, 42, 750. 11. Proc. Soc. exp. Biol., N.Y. 1939, 42, 804. 12. Int. Cong. Neurol. Copenhagen, 1939. 13. Pappenheimer and Goetsch, J. exp. Med. 1931, 53, 11; Dam, Glavind, Bernth and Hagens, Nature, Lond. 1938,
6. Science, 1939, 89, 370. 1. 2. 3. 4. 5.
J.
Nutrit. 1939, 17,
371.
Nature, Lond. 1938, 142, 799. Schweiz. med. Wschr. 1939, 69, 123. Verh. Schweiz. Physiol. Berne, 1939. Effect of Chronic Vitamin-E Deficiency on the Nervous System and the Skeletal Musculature in Adult Rats,
London, 1938.
142, 1157.
pendent of each other in metabolism. Ilowever, BeneOsterberg in 1923 were able to demonstrate
,diet and
an increase in creatinine excretion after feeding large doses of creatine. This provided some, though not conclusive, experimental support for the belief that
creatinine is derived from creatine in the
course
of
metabolism. In 1933 Schrire and Zwarenstein showed that injections of an acid extract of the anterior pituitary produces an increase in urinary creatinine. In 1936 Zwarenstein and I were able to show that the same extract produced an increase in muscle creatine. Braier (1931) showed that hypophysectomised dogs excreted a diminished amount of creatinine, while Zwarenstein and I (1936) found that hypophysectomy decreased the muscle creatine in toads. It is true that all these experiments were not performed on the same species of animal. Nevertheless, the fact that one type of procedure was able to increase both muscle creatine and urinary creatinine, and another procedure was able to decrease both creatine and creatinine does, I think, provide a suggestive experimental basis for the common assumption that urinary creatinine is derived from muscle creatine. I am, Sir, yours faithfully, B. G. SHAPIRO. London, W.C.1. ,
zie and McCollum" and Morris7 found that not only prevention but also cure of the symptoms could be effected by natural and synthetic pure tocopherol. Evans,8 to whom the credit for the discovery of the antisterility activity of vitamin E belongs, described the neuromuscular symptoms in young rats due to its lack in 1928. He has in addition shown the efficacv of pure tocopherol in muscular dystrophy of the guineapig.’ Lately Anderson, Elvehjem and Gonce 10 have described the successful treatment of muscular dystrophy in dogs with ∬-tocopherol acetate, whereas Knowlton, Hines and Brinkhous 11 have confirmed the results with this substance in rats. The proof of the therapeutic equivalence of pure tocopherol and its acetate with natural vitamin E is of considerable practical importance since it makes possible the use of this vitamin in a stable and standardised form and the administration of the required high doses which would be difficult to supply regularly for long periods in the form of wheat germ or wheat-germ oil. Preliminary reports on trials made with tocopherol acetate (ephynal) in doses of 30 mg. and more daily in cases of progressive muscular
dystrophy are encouraging (private communication). During the trials on young rats, I was struck by the relatively late onset of the neuromuscular dis-
turbances. The rats looked completely normal for about 3 weeks-i.e., till they reached about 2/5th VITAMIN E AND NEUROMUSCULAR DISEASES of their maturity. An observer not acquainted with SIR,—In his interesting paper on the successful their previous history would therefore have been unable to ascertain the origin of the degenerative treatment of muscular and neuromuscular disorders states starting after the age of 21 days or more, ,with vitamin E (Lancet, Jan. 6, 1940, p. 10), Dr. Bicknell expressed doubts as to whether the neuroalthough histological studies would; have revealed and musculo-tropic factor of wheat germ is identical muscular changes even prior to this. Since myopathies in children also appear only after some years no-one with pure vitamin E ( x-tocopherol). His doubts are based on observations of Goettsch has hitherto thought of tracing such states back to and Ritzmann,who demonstrated the efficacy of any " congenital avitaminosis," not only because of tocopherol in muscular disturbances in the young rat the lapse of time from birth to the onset of the disbut were led to doubt the identity of the neuromuscular turbances but also because the paediatrician attending factor with tocopherol from trials with wheat-germ the child would have to communicate with the obstetrician who was in charge of the mother during oil in which the natural vitamin E had been destroyed (although apparently only partially) by previous pregnancy and delivery. I.suggest that efforts should treatment with ferric chloride. After this treatment be made in cases of myatrophy to ascertain the history the oil still maintained the normal neuromuscular of the child and if possible of the mother as regards functions of young rats on a diet lacking vitamin E, miscarriages, premature births or neurological troubles but was unable to prevent abortion in adult rats who during pregnancy, in the hope of finding the missing had been kept for months without vitamin E. Appar- link between the antisterility and neuromuscular ently the continuous administration of the minimal effects. amount’ of vitamin E still present was capable of According to our animal experiments not only the maintaining the muscular functions of the young muscles but also the sensory organs (e.g., olfactory animals, whereas it was insufficient to reach the level and auditory nerves) and the intelligence may suffer,12 required for normal pregnancy. Various other papers and that in birds lack of vitamin E is connected with substantiate the full activity of natural and synthetic states of encephalomalacia,13 It is therefore not ’tocopherol in neuromuscular disturbances. The experi- impossible that in addition to tabes and poliomyelitis, mental proof is steadily increasing. suggested by Dr. Bicknell, other disturbances of the In young rats born of mothers kept on a low higher centres appearing in children, or as a sequel vitamin-E diet Barrie and ourselves (Demole and to infections or chemical intoxications in adults, might Pfaltz3) found that synthetic tocopherol and its benefit from vitamin E. I believe my remarks support Dr. Bicknell’s asseracetate (ephynal) were capable of completely preventing the appearance of muscular or neurological dis- tion that the discovery of the importance of vitamin E in the treatment of muscular and nervous diseases turbances. Similar observations have been made by Verzar and myselfin adult male and female rats " opens up new lines of thought and treatment in suffering from vitamin-E deficiency, confirming the many diseases." results described in the monograph of Einarson and I am, Sir, yours faithfully, ’Ringsted with natural vitamin E. In experimental V. DEMOLE. Basle, Switzerland. nutritional muscular dystrophy of the rabbit Macken,
-
7. Ibid, 1939, 90, 424. 8. J. biol. Chem. 1928, 76, 273. 9. Science, 1939, 90, 89. 10. Proc. Soc. exp. Biol., N.Y. 1939, 42, 750. 11. Proc. Soc. exp. Biol., N.Y. 1939, 42, 804. 12. Int. Cong. Neurol. Copenhagen, 1939. 13. Pappenheimer and Goetsch, J. exp. Med. 1931, 53, 11; Dam, Glavind, Bernth and Hagens, Nature, Lond. 1938,
6. Science, 1939, 89, 370. 1. 2. 3. 4. 5.
J.
Nutrit. 1939, 17,
371.
Nature, Lond. 1938, 142, 799. Schweiz. med. Wschr. 1939, 69, 123. Verh. Schweiz. Physiol. Berne, 1939. Effect of Chronic Vitamin-E Deficiency on the Nervous System and the Skeletal Musculature in Adult Rats,
London, 1938.
142, 1157.