By Hunter McGuire Doles
Summary: A medical journal report on the newly discovered role of vitamin K in the etiology of coronary thrombosis. Important vitamin research that still has not penetrated medical thinking. From the Tri-State Medical Journal, 1959. Lee Foundation for Nutritional Research reprint 129.
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The Etiology of Acute Coronary Thrombosis[spacer height=”20px”]
The morphology and pathology of acute coronary thrombosis with or without myocardial infarction is more or less clearly understood, but little is known of its etiology. A better understanding of the cause of this disease can be had if one looks back over a period of thirty or more years and compares its frequency then [with its frequency] today. It would be helpful if we include areas in different parts of the world and a study of the animal kingdom, in which it is almost unknown.
The use of anticoagulant therapy has gained a tremendous following in the treatment of thromboembolic disease. As pointed out by Sebrell,1 it is an empirical form of treatment.
It has been established that a normal prothrombin activity varies from 85 to 100 percent (Quick2). Since those cases that develop thromboembolic episodes have hypoprothrombinemia, we must conclude that a deficiency of prothrombin is responsible. The results of prothrombin deficiency is hemorrhage—either intimal, subintimal, or in the atheromatous plaque (Wartman,3 Winternitz,4 Patterson,5 Boyd,6 Durlacher7). Thus the anticoagulant therapy is the only form of treatment in use today that attempts to convert a normal condition into an abnormal one.
[The following observations are] from the private pavilions of the Norfolk General and Leigh Memorial Hospitals. I wish to thank Dr. Edward Levy, Clinical Pathologist of the Norfolk General Hospital, and Mr. A.D. Fanner, Director of the Norfolk City Laboratories, and also the technicians and dietitians of both hospitals, for their assistance in this work.[spacer height=”20px”]Prothrombin determinations have been routine procedure on all patients, either in the hospital or office, during the past fifteen years. During this period I have never seen a case of acute coronary thrombosis that was not associated with hypoprothrombinemia. In many instances a temporary rise in the prothrombin activity may reach as high as 95 percent following an acute episode, which may be nature’s effort to offset the injury, but the supply of prothrombin stored is not [sufficient] to maintain its activity within the level to prevent further hemorrhage and further thrombosis. Shapiro8 has attributed this temporary rise to thromboplastin released from the thrombus.
A series of investigations brought out a new fat-soluble vitamin known as Koagulation Factor, later shortened to K Factor and finally called vitamin K (Dam9, Alquist,10 and Stokstad11). Stokstad showed that the product of this vitamin was prothrombin. Dam showed that when chicks were fed on a diet deficient in this vitamin, they hemorrhaged and were then controlled by supplying vitamin K. It was found that vitamin K is absorbed in the small [intestine] and a portion of the large bowel, through the action of bacteria and bile present in the intestines, and from there it is carried to the liver through the bloodstream, where it is synthesized into prothrombin, an active element in blood clotting.
In determining the prothrombin level, the Quick Method still gives the most consistent results, since it determines the prothrombin activity by the logarithmic curve. This method shows a lower reading warning of the early danger of hemorrhage [than other methods do].
Primary factors entering into the mechanism of blood clotting (Alexander12):
- Platelets plus foreign substance: Thromboplastin
- Thromboplastin plus prothrombin plus calcium: Thrombin
- Thrombin plus fibrinogen: Fibrin (clot)
It is now known that the richest source of vitamin K isfound in pig liver, fish meal, and vegetables such as cabbage, tomatoes, spinach, kale, turnip greens, collards, broccoli, outer leaves of lettuce, cauliflower, and all of the pea and bean group. Any two of the above, eaten daily, will maintain a prothrombin level within safe limits.
Vitamin K is stable to heat but apparently not to extreme cold or freezing. The following chart shows the effect of frozen vegetables and fresh or canned vegetables on the prothrombin activity of 150 cases admitted to the hospital from June 1, 1952, to June 1, 1955. There were no coronaries in this group.
| Sex | No. Cases | Admissions |
Frozen |
Fresh & Canned 8th Day |
Maintained |
| M | 64 | 77.3% | 59.5% | 92% | 94.3% |
| F | 86 | 80.0% | 61.5% | 96% | 96.1% |
In this paper we are not referring to the type of heart that is the result of sclerosis of the coronary arteries, resulting in lack of blood supply to the heart muscle. The pain is usually associated with excitement, stress, or strain, and while the patient may die, there need be no disturbance in the prothrombin level.
Certain drugs have a decided effect on producing hypoprothrombinemia. Penicillin, sulfaguanadine, and the entire -mycin group lower the prothrombin level as the result of sterilization of the intestinal tract. Mineral oil and its derivatives inhibit the action of vitamin K because K is a fat-soluable vitamin. Although the barbiturates and salicylates lower the prothrombin level, the action is not known. When these drugs are prescribed, a daily check on the prothrombin activity should be carried out, and when the level begins to drop, vitamin K should be given intramuscularly or intravenously.
Hypoprothrombinemia is a common finding in patients with edema.
I should like to give the findings from the report by the Committee of the American Heart Association in cooperation with the Society for the Study of Arteriosclerosis:13
“The fact is that the basic problem is not lipemia, hypercholesterolemia, or hepatic lipid excess, but it is atheromatosis and in particular myocardial infarction. Atheromas have not been described or associated clinically or experimentally with fatty acid deficiency. With the exception of Hartcroft and Thomas’ recent production of myocardial infarction in animals on certain dietary regimens high in fat, myocardial infarction has not been precipitated in animals by excessive intake of any particular fat or of cholesterol or by a deficiency of pyridoxine or any unsaturated fatty acid.”
Regarding the production of myocardial infarction in animals fed on a high fat diet: this would have no meaning if the animals were restricted in foods containing vitamin K or if they were penned up and not allowed to supply themselves naturally.
The ratio of acute coronary thrombosis with myocardial infarction is approximately six to one in favor of the white male over the negro male. Let us give some thought to the southern section of the United States, where we have a lower income bracket and a vast population of negroes, which means that they live as cheaply as possible—a large number having their own vegetable gardens in backyards. We find them for about eighty years relying chiefly on a diet of salt pork and fresh green vegetables. Why then did they not outstrip the white male in coronary thrombosis?
Elliott14 quotes J.C. Gilroy, V.H. Wilson, A.B. Gillanders, and I.J. Grek as agreeing that all forms of arteriosclerosis, atherosclerosis, and Monckeberg’s sclerosis are common in the Bantu tribe of Africa, yet he comments that it may be safely stated that coronary disease is extremely rare. In East Africa, Davies (1948) reports that one of the most puzzling features of atheroma in negroes is the rarity of coronary thrombosis. Edington (1954) confirms the low incidence of myocardial infarction in the West African negro. These people rely heavily on a diet of vegetables, as shown by Dr. Frederick Stare, Department of Nutrition, Harvard Medical School.
If one takes the mortality rate from acute coronary thrombosis throughout the world, as shown by the American Heart Association (1953), and then refers to the book on food consumption per dollar value by M.K. Bennett, Director, Food Research Institute, Stanford University, there will be little difficulty in determining which countries have a high or low rate of coronary thrombosis.
Acute coronary thrombosis is practically unknown in cattle, dogs, or rabbits, although thrombosis occurs in the superficial vessels [of these animals] as the result of trauma or infection. The prothrombin activity is far greater in animals than it is in the human, yet when six rabbits were put on a diet of frozen vegetables and given antibiotics, the prothrombin time became prolonged, just as it does in the human.
Six rabbits—using a 13-second prothrombin activity as normal—showed an average [prothrombin activity] of 3.5 to 4 seconds. They were then divided, using two for controls, which were put on packaged animal food; the other four were put on frozen vegetables. It took far longer to produce a drop in the prothrombin level in the rabbits than in a human. However, at about the end of the twelfth week, the prothrombin level of one rabbit had dropped as low as 103 seconds before death. When one of the controls dropped dead, it was found that the packaged food [it was being fed] contained antibiotics that the manufacturer had refused to disclose. This rabbit showed massive hemorrhage in the pericardium, pleural, and peritoneal cavities. Two of the four rabbits on frozen foods died. One was diagnosed as tubercular. As for the second, a lapse of five days took place before the autopsy; enteritis was given as the cause of death, but the rabbit showed no symptoms to confirm this. The remaining three rabbits were placed on fresh vegetables, and in a short time their prothrombin levels returned to normal.
In another investigation five male and five female dogs were used. With a 13-second prothrombin activity as normal, the ten dogs showed an average [prothrombin activity] of 3.2 seconds. In nine cattle the average prothrombin activity was 5 seconds for the steers and 6 to 7 seconds for the cows.
From the University of Moscow comes this report on vitamin K. In rats with ligated bile ducts, the prothrombin concentration began to fall ten to fifteen days after operation and reached 20 percent of the initial value. The capillary strength was 60 percent of initial value. When they were given vitamin K, the prothrombin rose to 90 percent—and the capillary strength to 78 percent—of initial values. The vitamin K was given in two doses of approximately 23 mg for every pound and a half of rat. In normal rats given 25 mg of vitamin K per 200 g bodyweight, with two doses, the capillary strength was increased by 20 percent and the prothrombin concentration by 18 percent.15
Studying the mortality rate throughout the United States shows that there has been a decided increase in the past thirty years. In the state of Virginia in 1930, the mortality [report] from coronary thrombosis showed 113 white males and 13 negro males. In 1956 the mortality rate had risen to 2,614 white males, 1,122 white females, 448 negro males, and 270 negro females.
It is of great interest to note the rural areas surpassing the urban areas in coronary thrombosis by 1950. In 1930 the urban areas showed 65 deaths, and the rural areas showed 61 deaths. In 1950 the urban areas showed 1,621 deaths, and the rural areas showed 1,978 deaths, while the year 1955 brought 1,929 deaths in the urban areas and 2,306 deaths in the rural areas.16
In 1947 the deep-freeze ice boxes were installed in the rural areas, and most of the people are making use of them for the storing of vegetables through the winter months, rather than use the old canning procedure.
I should like to conclude this paper by saying that in a case of coronary thrombosis with or without myocardial infarction, keeping the prothrombin level at what may be considered a low safe by the use of anticoagulants is not the answer to the problem of hemorrhage. Vitamin K should be given at the time of the initial attack to restore the prothrombin level to normal, thereby reducing further danger of hemorrhage and thrombosis.
By Hunter McGuire Doles, Norfolk, Virginia. Reprinted from the Tri-State Medical Journal, February 1959, by the Lee Foundation for Nutritional Research.
Bibliography
1. Sebrell Jr., W.H., and Harris, R.S. The Vitamins.
2. Quick, Armed J. American Journal Clinical Pathology, 10:222, 1940.
3. Wartman, W.B. “Occlusion into the Arterial Wall: A Cause of Peripheral Vascular Disease.” American Heart Journal, 39:78, 1950; Wartman, W.B. “Occlusion of the Coronary Arteries by Hemorrhage into Their Walls: Preliminary Report.” Clin. Bull. Univ. Hospital, Cleveland, 1938.
4. The Biology of Arteriosclerosis. Springfield, Ill, 1938.
5. Patterson, J.C. “Capillary Rupture with Intimal Hemorrhage: A Causative Factor in Coronary Thrombosis.” Arch. Path., 25:474, 1938; Patterson, J.C. “Vascularization and Hemorrhage of the Intima of Arterio-Sclerotic Coronary Arteries.” Arch. Path., 22:313, 1936.
6. Boyd, William. Text-Book of Pathology, sixth edition. Revised 1953.
7. Boyd, William. Text-Book of Pathology, sixth edition. Revised 1953.
8. Shapiro, Shepard. “Hypoprothrombinemia: A Premonitory Sign of Thrombo-embolization.” Ex. Medicine and Surgery, May 1944.
9. Dam, H. Nature, 135:652, 1935; Dam, H. Biochemistry Journal, 29:1273, 1935.
10–11. Alquist, H.J., and Stokstad, E.L.R. Nature, 136:31, 1935.
12. Alexander, Benjamin. “Coagulation, Hemorrhage and Thrombosis.” New England Journal of Medicine, 252:432, 1955.
13. J.A.M.A., 164, 18:2048–2051, August 31, 1957.
14. G.A. Elliott. The Leech, 23:25, 1953.
15. Pastorova, V.E. Dokl. Akad. Nauk SSSR, 113:1379–1382, 1957. (Gosud. University of Moscow.)
16. Department of Health and Vital Statistics, State of Virginia, Driver Building.
Reprint No. 129
Lee Foundation for Nutritional Research
Milwaukee, Wisconsin
Note: Lee Foundation for Nutritional Research is a nonprofit, public-service institution, chartered to investigate and disseminate nutritional information. The attached publication is not literature or labeling for any product, nor shall it be employed as such by anyone. In accordance with the right of freedom of the press guaranteed to the Foundation by the First Amendment of the U.S. Constitution, the attached publication is issued and distributed for informational purposes.
