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THE FAT SOLUBLE VITAMINS

HUGH R. BUTT, M.D.
[+] Author Affiliations

ROCHESTER, MINN.

From the Division of Medicine, the Mayo Clinic.


JAMA. 1942;120(13):1030-1039. doi:10.1001/jama.1942.82830480003010
Text Size: A A A
Published online

An attempt has been made in the present review to outline a few known facts about each fat soluble vitamin and to mention the most recent advances of general interest that have occurred since publication of the symposium on vitamins sponsored by the American Medical Association in 1939. No attempt has been made to delve into many of the details in this field; rather, data have been presented which it is hoped will be of value in orienting conceptions in a rapidly changing subject.

VITAMIN A 

CHEMISTRY AND PHYSIOLOGY  The chemistry and physiology of vitamin A and substances having vitamin A activity have been considered in some detail in previous reviews in The Journal.1Evidence reveals that there exists, in addition to vitamin A, another compound which has been designated as vitamin A2. In chemical structure vitamin A1 is related closely to vitamin A2; biologically the

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Beck, A. C.; Taylor, E. S., and Colburn, R. F.:  Vitamin K Administered to the Mother During Labor as a Prophylaxis Against Hemorrhage in the Newborn Infant , Am. J. Obst. & Gynec. 41:765-773 ( (May) ) 1941;.
Hellman, L. M.; Shettles, L. B., and Eastman, N. J.:  Vitamin K in Obstetrics: A Review of One Year's Experience , Am. J. Obst. & Gynec. 40:844-853 ( (Nov.) ) 1940;.

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Vollmer, Hermann:  Distribution of Vitamin D in the Brain After Repeated Administration of Massive Doses; Histologic Investigation of D-Hypervitaminosis , Arch. Pediat. 58:9-20 ( (Jan.) ) 1941;.
Warkany, Josef, and Mabon, Helen E.:  Estimation of Vitamin D in Blood Serum: II. Level of Vitamin D in Human Blood Serums , Am. J. Dis. Child. 60:606-614 ( (Sept.) ) 1940;.
Liu, S. H.:  The Role of Vitamin D in the Calcium Metabolism in Osteomalacia , Chinese M. J. 57:101-118 ( (Feb.) ) 1940;.
Liu, S. H.; Chu, H. I.; Su, C. C.; Yu, T. F., and Cheng, T. Y.:  Calcium and Phosphorus Metabolism in Osteomalacia: IX. Metabolic Behavior of Infants Fed on Breast Milk from Mothers Showing Various States of Vitamin D Nutrition , J. Clin. Investigation 19:327-347 ( (March) ) 1940;.
Chu, H. I.; Liu, S. H.; Yu, T. F.; Hsu, H. C.; Cheng, T. Y., and Chao, H. C.:  Calcium and Phosphorus Metabolism and Osteomalacia: X. Further Studies on Vitamin D Action: Early Signs of Depletion and Effect of Minimal Doses , J. Clin. Investigation 19:349-363 ( (March) ) 1940;.
Albright, Fuller; Sulkowitch, H. W., and Bloomberg, Esther:  A Comparison of the Effects of Vitamin D, Dihydrotachysterol (A. T. 10), and Parathyroid Extract on the Disordered Metabolism of Rickets , J. Clin. Investigation 18:165-169 ( (Jan.) ) 1939;.
Lindsay, Jessie, and Mottram, V. H.:  Vitamin D in Diet: Palatable Methods of Supply , Brit. M. J. 1:14-15 ( (Jan. 7) ) 1939;.
Gunnarson, Siv:  Treatment of Rickets with a Single Massive Dose of Vitamin D2 , Acta paediat. 25:69-81, 1939;.
Opper, Lincoln:  Effect of Renal Damage on the Toxicity of Hypervitaminosis D in Rats , Arch. Path. 31:569-577 ( (May) ) 1941;.
Jeans, P. C., and Stearns, Genevieve:  The Human Requirement of Vitamin D , in The Vitamins , Chicago, American Medical Association, 1939;, pp. 483-512.
Kramer, Benjamin:  Vitamin D Therapy , J. Mt. Sinai Hosp. 8:188-209 ( (Sept.) -Oct.) 1941;.
Park, E. A.:  The Therapy of Rickets , J. A. M. A. 115:370-379 ( (Aug. 3) ) 1940;.
Ström, Justus:  The Treatment of Spasmophilia with a Single Massive Dose of Vitamin D2 , Acta paediat. 25:251-265, 1939;.
Vollmer, Hermann:  Treatment of Rickets and Tetany by Parenteral Administration of One Massive Dose of Vitamin D , J. Pediat. 16:419-432 ( (April) ) 1940;.
Zelson, Carl:  Prevention of Rickets in Premature Infants with Parenteral Administration of Single Massive Doses of Vitamin D , J. Pediat. 17:73-78 ( (July) ) 1940;.
King, Howard, and Hamilton, C. M.:  Pemphigus Controlled by Vitamin D , Arch. Dermat. & Syph. 39:515-517 ( (March) ) 1939;.
Brandaleone, Harold:  The Effect of the Direct Application of Cod Liver Oil on the Healing of Ulcers of the Feet in Patients with Diabetes Mellitus , Ann. Surg. 108:141-152 ( (July) ) 1938;.
Krafka, Joseph:  Vitamin D Therapy in Psoriasis , J. M. A. Georgia 30:398-400 ( (Sept.) ) 1941;.
Mattill, H. A.:  Vitamin E , in The Vitamins , Chicago, American Medical Association, 1939;, pp. 575-596.
Smith, L. I.:  The Chemistry of Vitamin E , Chem. Rev. 27:287-329 ( (Oct.) ) 1940;.
Vitamin E , New York, Chemical Publishing Co., Inc., 1940;.
Evans, H. M.; Emerson, O. H.; Emerson, G. A.; Smith, L. I.; Ungnade, H. E.; Prichard, W. W.; Austin, F. L.; Hoehn, H. H.; Opie, J. W., and Wawzonek, S.:  The Chemistry of Vitamin E: XIII. Specificity and Relationship Between Chemical Structure and Vitamin E Activity , J. Organ. Chem. 4:376-388 ( (Sept.) ) 1939;.
Ridgway, R. R.; Drummond, J. C., and Wright, Margaret D.:  The Biological Activity of the Oxidation Products of α-Tocopherol , Biochem. J. 34:1569-1573 ( (Dec.) ) 1940;.
Tishler, Max, and Evans, H. M.:  Vitamin E Activities of Some Compounds Related to α-Tocopherol , J. Biol. Chem. 139:241-245 ( (May) ) 1941;.
Pappenheimer, A. M.:  Certain Nutritional Disorders of Laboratory Animals Due to Vitamin E Deficiency , J. Mt. Sinai Hosp. 7:65-76 ( (July) -Aug.) 1940;.
Pappenheimer, A. M., and Goettsch, Marianne, with the assistance of Karsubova, Claudia:  Effect of Nerve Section on Development of Nutritional Muscular Dystrophy in Young Rats , Proc. Soc. Exper. Biol. & Med. 43:313-316 ( (Feb.) ) 1940;.
Anderson, H. D.; Elvehjem, C. A., and Gonce, J. E., Jr.:  Vitamin E Deficiency in Dogs , Proc. Soc. Exper. Biol. & Med. 42:750-755 ( (Dec.) ) 1939;.
Friedman, Irving, and Mattill, H. A.:  The Oxygen Consumption of Skeletal Muscle from Animals Deprived of Vitamin E , Am. J. Physiol. 131:595-600 ( (Jan.) ) 1941;.
Mackenzie, C. G.; Mackenzie, J. B., and McCollum, E. V.:  Uncomplicated Vitamin E Deficiency in the Rabbit and Its Relation to the Toxicity of Cod Liver Oil , J. Nutrition 21:225-234 ( (March) ) 1941;.
Dam, Henrik; Glavind, Johannes; Inge, Prange, and Ottesen, J.:  Some Studies on Vitamin E , Biologiske Meddelelsee , 1941;, vol. 16.
Mackenzie, C. G., and McCollum, E. V.:  The Cure of Nutritional Muscular Dystrophy in the Rabbit by Alpha-Tocopherol and Its Effect on Creatine Metabolism , J. Nutrition 19:345-362 ( (April) ) 1940;.
Adamstone, F. B.:  Brain Degeneration in Young Chicks Reared on an Iron-Treated Vitamin E-Deficient Ration , Arch. Path. 31:603-612 ( (May) ) 1941;.
Drummond, J. C.; Noble, R. L., and Wright, M. D.:  Studies on the Relationship of Vitamin E (Tocopherols) to the Endocrine System , Endocrinology 1:275-286 ( (Nov.) ) 1939;.
Biddulph, C., and Meyer, R. K.:  The Influence of Vitamin E-Deficiency on the Endocrine Glands of Rats, Particularly on the Gonadotropic Hormone Content of the Pituitary Gland , Am. J. Physiol. 132:259-271 ( (Feb.) ) 1941;.
 The Treatment of Habitual Abortion with Vitamin E, Report of the Council on Pharmacy and Chemistry , J. A. M. A. 114:2214-2218 ( (June 1) ) 1940;.
Evans, H. M.:  The William Henry Welch Lectures: New Light on the Biological Role of Vitamin E , J. Mt. Sinai Hosp. 6:233-244 ( (Jan.) -Feb.) 1940;.
Widenbauer, F.:  Versuche mit Weizenkeimöl (vitamin E) bei der Aufzucht von Frühgeburten , Ztschr. f. Kinderh. 60:216-221 ( (Oct. 15) ) 1938;.
Bacharach, A. L.:  Vitamin E and Habitual Abortion , Brit. M. J. 1:890 ( (June 1) ) 1940;.
Mulherin, C. M.:  Vitamin E in Obstetrics , Bull. Univ. Hosp. Augusta, Ga. 3:4-7 ( (March) ) 1941;.
Almquist, H. J., and Klose, A. A.:  Comparative Activities of Certain Antihemorrhagic Compounds , Proc. Soc. Exper. Biol. & Med. 45:55-59 ( (Oct.) ) 1940;.
Bicknell, Franklin:  Vitamin E in the Treatment of Muscular Dystrophies and Nervous Diseases , Lancet 1:10-13 ( (Jan. 6) ) 1940;.
Wechsler, I. S.:  Recovery in Amyotrophic Lateral Sclerosis Treated with Tocopherols (Vitamin E): Preliminary Report , J. A. M. A. 114:948-950 ( (March 16) ) 1940;.
Stone, Simon:  Treatment of Muscular Dystrophies and Allied Conditions: Preliminary Report on Use of Vitamin E (Wheat Germ Oil) , J. A. M. A. 114:2187-2191 ( (June 1) ) 1940;.
Shelden, C. H.; Butt, H. R., and Woltman, H. W.:  Vitamin E (Synthetic Alpha-Tocopherol) Therapy in Certain Neurologic Disorders , Proc. Staff Meet., Mayo Clin. 15:577-580 ( (Sept. 11) ) 1940;.
Doyle, A. M., and Merritt, H. H.:  Vitamin Therapy of Diseases of the Neuromuscular Apparatus , Arch. Neurol. & Psychiat. 45:672-679 ( (April) ) 1941;.
Denker, P. G., and Scheinman, Leonard:  Treatment of Amyotrophic Lateral Sclerosis with Vitamin E (Alpha-Tocopherol) , J. A. M. A. 116:1893-1895 ( (April 26) ) 1941;.
Ferrebee, J. W.; Klingman, W. O., and Frantz, A. M.:  Vitamin E and Vitamin B6; Clinical Experience in the Treatment of Muscular Dystrophy and Amyotrophic Lateral Sclerosis , J. A. M. A. 116:1895-1896 ( (April 26) ) 1941;.
McBryde, Angus, and Baker, L. D.:  Vitamin Therapy in Progressive Muscular Dystrophy: Vitamin B6, Other Factors of the B Complex, and Vitamin E , J. Pediat. 18:727-731 ( (June) ) 1941;.
Worster-Drought, C., and Shafar, J.:  Motor Neurone Degeneration Treated with Vitamin E , Lancet 2:209-212 ( (Aug. 23) ) 1941;.
Harris, M. M.:  Negative Therapeutic and Metabolic Effects of Synthetic Alpha-Tocopherol (Vitamin E) in Muscular Dystrophy , Am. J. M. Sc. 202:258-264 ( (Aug.) ) 1941;.
Fitzgerald, Gerald, and McArdle, Brian:  Vitamins E and B6 in the Treatment of Muscular Dystrophy and Motor Neurone Disease , Brain 64:19-42 ( (March) ) 1941;.
Wechsler, I. S.:  The Treatment of Amyotrophic Lateral Sclerosis with Vitamin E (Tocopherols) , Am. J. M. Sc. 200:765-778 ( (Dec.) ) 1940;.
Wechsler, I. S.:  Amyotrophic Lateral Sclerosis Treated with Synthetic Vitamin E , Arch. Neurol. & Psychiat. 45:873-875 ( (May) ) 1941;.
Butt, H. R., and Snell, A. M.: Vitamin K , Philadelphia, W. B. Saunders Company, 1941;.
Brinkhous, K. M.:  Plasma Prothrombin; Vitamin K , Medicine 19:329-416 ( (Sept.) ) 1940;.
Bay, Ricardo:  Hígadoprotrombina-vitamina K: (estudio experimental y clínico), Buenos Aires , Univ., Inst. de Clin. Quir., Bol. 17:139-231 ( (Feb.) -March) 1941;.
Koller, Fritz: Das Vitamins K und seine klinische Bedeutung , Leipzig, Georg Thieme, 1941;.
Fieser, L. F.:  The Chemistry of Vitamin K , Ann. Int. Med. 15:648-658 ( (Oct.) ) 1941;.
 Menadione, Nonproprietary Term for the Substance 2-Methyl-1, 4-Naphthoquinone, Report of Council on Pharmacy and Chemistry , J. A. M. A. 116:1054 ( (March 15) ) 1941;.
Wilder, R. M.; Browne, H. C., and Butt, H. R.:  Diseases of Metabolism and Nutrition: Review of Certain Recent Contributions: I. Diseases of Metabolism; II. Nutrition , Arch. Int. Med. 65:390-460 ( (Feb.) ) 1940;.
Butt, H. R., and Leary, W. V.:  Diseases of Nutrition: Review of Certain Recent Contributions , Arch. Int. Med. 67:411-465 ( (Feb.) ) 1941;.
Molitor, Hans, and Robinson, H. J.:  Oral and Parenteral Toxicity of Vitamin Ki, Phthiocol and 2-Methyl-1,4-Naphthoquinone , Proc. Soc. Exper. Biol. & Med. 43:125-128 ( (Jan.) ) 1940;.
Shimkin, M. B.:  Toxicity of Naphthoquinones with Vitamin K Activity in Mice , J. Pharmacol. & Exper. Therap. 71:210-214 ( (March) ) 1941;.
Foster, R. H. K. (introduced by E. Chargoff with the technical assistance of H. H. Clark):  Pharmacological Observations on Tetra-Sodium-2-Methyl-1,4-Naphthohydroquinone Diphosphoric Acid Ester , Proc. Soc. Exper. Biol. & Med. 45:412-415 ( (Oct.) ) 1940;.
Stewart, J. D.:  Oral and Parenteral Use of Synthetic Vitamin K-Active Substances in Hypoprothrombinemia , Surgery 9:212-219 ( (Feb.) ) 1941;.
Ansbacher, S.:  Editorial Review: The Bioassay of Vitamin K , J. Nutrition 21:1-12 ( (Jan.) ) 1941;.
Almquist, H. J.:  Vitamin K , Physiol. Rev. 21:194-216 ( (Jan.) ) 1941;.
Trenner, N. R., and Bacher, F. A.:  A Quantitative Reduction-Oxidation Method for the Estimation of Vitamin K1 and Associated Quinones and Naphthoquinones , J. Biol. Chem. 137:745-755 ( (Feb.) ) 1941;.
Irreverre, Filadelfo, and Sullivan, M. X.:  A Colorimetric Test for Vitamin K1 , Science 94:497-498 ( (Nov. 21) ) 1941;.
Scudi, J. V., and Buhs, R. P.:  A Colorimetric Oxidation-Reduction Method for the Determinations of the K Vitamins , J. Biol. Chem. 141:451-464 ( (Nov.) ) 1941;.
Warner, E. D.; Brinkhous, K. M., and Smith, H. P.:  A Quantitative Study on Blood Clotting: Prothrombin Fluctuations Under Experimental Conditions , Am. J. Physiol. 114:667-675 ( (Feb.) ) 1936;.
Herbert, Freda K.:  The Estimation of Prothrombin in Human Plasma , Biochem. J. 34:1554-1568 ( (Dec.) ) 1940;.
Souter, A. W., and Kark, Robert:  Quick's Prothrombin Test Simplified by the Use of a Stable Thromboplastin , Am. J. M. Sc. 200:603-607 ( (Nov.) ) 1940;.
Quick, A. J.; Stanley-Brown, Margaret, and Bancroft, F. W.:  A Study of the Coagulation Defect in Hemophilia and in Jaundice , Am. J. M. Sc. 190:501-511 ( (Oct.) ) 1935;.
Ziffren, S. E.; Owen, C. A.; Hoffman, G. R., and Smith, H. P.:  Control of Vitamin K Therapy: Compensatory Mechanism at Low Prothrombin Levels , Proc. Soc. Exper. Biol. & Med. 40:595-597 ( (April) ) 1939;.
Kato, Katsuji:  Microprothrombin Test with Capillary Whole Blood: A Modification of Quick's Quantitative Method , Am. J. Clin. Path. 10:147-153 ( (Feb.) ) 1940;.
Quick, A. J.:  Determinations of Prothrombin , Proc. Soc. Exper. Biol. & Med. 42:788-789 ( (Dec.) ) 1939;.
Bray, W. E., and Kelley, O. R.:  Prothrombin Studies, Especially in the Newborn , Am. J. Clin. Path. 10:154-167 ( (Feb.) ) 1940;.
Kelley, O. R., and Bray. W. E.:  Prothrombin Time Determination , J. Lab. & Clin. Med. 25:527-530 ( (Feb.) ) 1940;.
Kato, Katsuji, and Poncher, H. G.:  The Prothrombin in the Blood of Newborn Mature and Immature Infants as Determined by the Microprothrombin Test , J. A. M. A. 114:749-753 ( (March 2) ) 1940;.
Kark, Robert, and Souter, A. W.:  Hypoprothrombinaemia and Avitaminosis-K in Man , Brit. M. J. 2:190-194 ( (Aug. 9) ) 1941;.
Smith, H. P., and Owen, C. A.:  Vitamin K: Its Use in Patients with Obstructive Jaundice or with Biliary Fistulas , Rev. Gastroenterol. 7:520-526 ( (Nov.) -Dec.) 1940;.
Hicks, J. D.:  A Review of the Literature Concerning Hemorrhage in Obstructive Jaundice; the Significance of Prothrombin and of Vitamin K Therapy , M. J. Australia 1:46-51 ( (Jan. 11) ) 1941;.
Sharp, E. A.; Konder Heide, E. C., and Good, W. H.:  Vitamin K Activity of 2-Methyl-1,4-Naphthoquinone and 4-Amino-2-Methyl-1-Naphthol in Hypoprothrombinemia , J. Lab. & Clin. Med. 26:818-822 ( (Feb.) ) 1941;.
Kark, Robert; Souter, A. W., and Hayward, J. C.:  A Hemorrhagic Diathesis in Idiopathic Steatorrhea: Observations on Its Association with Vitamin K Deficiency , Quart. J. Med. 9:247-261 ( (Oct.) ) 1940;.
Allen. J. G.:  The Comparative Prothrombin Responses to Vitamin K and Several of Its Substitutes in a Case of Nontropical Sprue , New England J. Med. 224:195-197 ( (Jan. 30) ) 1941;.
Butt, H. R.; Leary, W. V., and Wilder, R. M.:  Diseases of Nutrition: Review of Certain Recent Contributions , Arch. Int. Med. 69:277-343 ( (Feb.) ) 1942;.
Olwin, J. H.:  The Intravenous Use of Vitamin K , J. A. M. A. 117:432-435 ( (Aug. 9) ) 1941;.
Emmett, A. D.; Kamm, Oliver, and Sharp, E. A.:  The Vitamin K Activity of 4-Amino-2-Methyl-1-Naphthol and 4-Amino-3-Methyl-1-Napthol , J. Biol. Chem. 133:285-286 ( (March) ) 1940;.
Anderson, E. R.; Karabin, J. E.; Udesky, Herbert, and Seed, Lindon:  Parenteral Administration of a Water-Soluble Compound with Vitamin K Activity: 4-Amino-2-Methyl-1-Naphthol Hydrochloride , Arch. Surg. 41:1244-1250 ( (Nov.) ) 1940;.
Weir, J. F.; Butt, H. R., and Snell, A. M.:  Further Observations on the Clinical Use of Vitamin K , Am. J. Digest. Dis. 11:485-490 ( (Nov.) ) 1940;.
Tocantins, L. M., and Jones, H. W.:  Hypoprothrombinemia; Effect of Peroral and Parenteral Administration of a Synthetic Vitamin K Substitute (2-Methyl-1,4-Naphthoquinone) , Ann. Surg. 113:276-283 ( (Feb.) ) 1941;.
Seligman, A. M.; Hurwitz, Alfred; Frank, H. A., and Davis, W. A.:  The Intravenous Use of Synthetic Vitamin K1 , Surg., Gynec. & Obst. 73:686-701 ( (Nov.) ) 1941;.
Allen, J. G., and Julian, O. C.:  Response of Plasma Prothrombin to Vitamin K Substitute Therapy in Cases of Hepatic Disease , Arch. Surg. 41:1363-1365 ( (Dec.) ) 1940;.
Andrus, W. DeW.:  The Newer Knowledge of Vitamin K , Bull. New York Acad. Med. 17:116-134 ( (Feb.) ) 1941;.
Lawson, R. B.:  Treatment of Hypoprothrombinemia (Hemorrhagic Disease) of the Newborn Infant , J. Pediat. 18:224-234 ( (Feb.) ) 1941;.
Valentine, Eleanor H.; Reinhold, J. G., and Schneider, Erich:  The Effectiveness of Prenatal Administration of 2-Methyl-1,4-Naphthoquinone in Maintaining Normal Prothrombin Levels in Infants , Am. J. M. Sc. 202:359-364 ( (Sept.) ) 1941;.
Ross, S. G., and Malloy, H. T.:  Blood Prothrombin in the Newborn: The Effect of Vitamin K on the Blood Prothrombin and on Hemorrhagic Disease of the Newborn , Canad. M. A. J. 45:417-421 ( (Nov.) ) 1941;.
Beck, A. C.; Taylor, E. S., and Colburn, R. F.:  Vitamin K Administered to the Mother During Labor as a Prophylaxis Against Hemorrhage in the Newborn Infant , Am. J. Obst. & Gynec. 41:765-773 ( (May) ) 1941;.
Hellman, L. M.; Shettles, L. B., and Eastman, N. J.:  Vitamin K in Obstetrics: A Review of One Year's Experience , Am. J. Obst. & Gynec. 40:844-853 ( (Nov.) ) 1940;.
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To understand the clinical management of acute heart failure syndromes.
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