12
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With this chapter, we begin the discussions of the use of ascorbic acid in the treatment of various diseases other than scurvy. We start with the common cold because it is a most annoying ailment and it is one to which everyone is repeatedly exposed. It is also the one with which the author has had the most personal experience. From this personal experience, it is the author's belief that this disease could be eradicated through the proper use of ascorbic acid. It is the purpose of this chapter to tell how this can be done.
Let us first go over some statistics and current research on the common cold and then take a quick look at the medical literature to see what has been done with ascorbic acid in the treatment of the common cold over the last thirty years.
It has been estimated that Americans get about 500 million colds per year. Besides causing acute physical discomfort and taxing the individual's health and stamina, the common cold is the greatest single cause of industrial absenteeism. Its cost to industry appears to be well over five billion dollars a year in lost time and production.
Much research money is being expended now in the hope of developing a vaccine for colds. The probability of developing a useful vaccine is remote because of the large number of different viruses and associated bacteria found in common cold victims. For instance, the rhinoviruses which can be isolated from more than half the adults with common colds comprise about seventy to eighty different serotypes. Since a vaccine is highly specific and only effective against a particular viral strain or bacterial species, it is doubtful whether a polyvalent vaccine would be useful because of the great number of serotypes and the short duration of induced immunity. What is needed, instead, is a wide=spectrum, nontoxic, virucidal, and bactericidal agent. Ascorbic acid fills this bill.
One of the difficulties in common cold research is the general lack of laboratory animals that are susceptible to this disease. Man and apes are reputed to be the only susceptible hosts to this disease. Easily managed laboratory animals such as rats, mice, rabbits, cats and dogs are said not to catch the disease,thus making laboratory studies very difficult. It is significant that the two species that can catch colds, man and the apes, are the two that cannot make their own ascorbic acid.
Shortly after the discovery of ascorbic acid, it was found that it had a powerful antiviral activity. This activity was found to be nonspecific and a wide spectrum of viruses were attacked and inactivated. These included the viruses of poliomyelitis, vaccinia, herpes, rabies, foot-and-mouth disease, and tobacco mosaic. The ability of ascorbic acid to inactivate viruses extends to many more and probably covers all the viruses, but these were the ones investigated at this early date. Other workers in the 1930s found that ascorbic acid was capable of inactivating a number of bacterial toxins such as those of diphtheria, tetanus, dysentery, staphylococcus, and anaerobic toxins. These result appeared so promising that, in 1939, they led one worker (1) to state: "Vitamin C, therefore, may truthfully be designated the 'antitoxic and antiviral' vitamin." And in addition it is relatively harmless to humans.
The medical literature on ascorbic acid and the common cold from 1939 to 1961 can be divided into two groups: one group contains the clinical tests where the ascorbic acid was administered for the treatment of the common cold at dosage rates measured in milligrams per day (one gram or less); the other group contains those where it was given at higher daily dosages. The milligram group found ascorbic acid to be ineffective in the treatment of colds; the higher-dosage group reported more successful results.
Let us skin through this record, covering over a quarter-century, and see what it shows. We will take the inadequate, low-dosage tests first: Berquist (2), in 1940, used 90 milligrams of ascorbic acid per day. Kuttner (3) used 100 milligrams daily on 108 rheumatic children and found no lessening of the incidence of upper-respiratory infections. Cowan, Diehl, and Baker (4) used 200-milligrams per day. Glazebrook and Thomson (5), in 1942, 200 used between 50 and 300 milligrams daily on boys in a large institution. They reported no difference in the incidence of colds and tonsillitis, and the duration of the colds was the same in the group getting the ascorbic acid and that not getting it. The duration of the tonsillitis was longer, however, in the control group, and cases of rheumatic fever and pneumonia developed; but none occurred in the group getting the ascorbic acid. Even a these threshold levels there seemed t be some protection. In 1944 Dahlberg, Engel, and Rydin (6) used 200 milligrams per day on a regiment of Swedish soldiers and reported, "No difference could be found as regards frequency or duration of colds, degrees of fever, etc." Franz and Heyl (7) and Tebrock, Arminio, and Johnston (8), in 1956, both used about 200 milligrams daily in combination with "bioflavanoids," without reporting notable success. At this late date these workers were still proving the pharmacologic fact that you cannot squeeze consistent good therapeutic results from ineffective threshold dosages. Shekhtman (9), in 1961, used 100 milligrams of ascorbic acid for seven months of the year and then 50 milligrams for the rest of the year. He reported a decreased incidence of colds, but the difference was not striking. These are some of the reports of those who used the threshold of "vitamin-like" dosages of milligrams per day. Now, let us turn to the other side of the picture -- the group that used higher dosages.
This group includes Ruskin (10) who, in 1938, injected 450 milligrams of calcium ascorbate as soon after the onset of cold symptoms as possible. (this report is included among the higher level group because giving ascorbate by injection is several times more effective that the equivalent dosage by mouth.) In over 2,000 injections there were no complications incident to the injections. Forty-two percent of his patients were completely relieved, usually after the first or second injection. Forty-eight percent were reported as "markedly improved." Ruskin, in his summary, states, "Calcium ascorbate would appear to be practically an abortive in the treatment of the common cold." This statement appeared in 1938, and an astronomical number of colds could have been prevented in the intervening years if only this early work had been followed up. Van Alyea (11), in 1942, found 1 gram a day of ascorbic acid a valuable aid in treating rhinosinusitis. Markwell (12), by 1947, using 3/4 gram or more every three or four hours stated:
My experience seems to show that if the dose is given both early enough and in large enough quantity, the chances of stopping a cold are about fifty-fifty, or perhaps better. It is an amazing and comforting experience to realize suddenly in the middle of the afternoon that no cold is present, after having in the morning expected several days of throat torture ... I have never seen any ill effects whatsoever from vitamin C and I do not think there are any ... The number of patients who have taken large doses of vitamin C to abort colds during in the last three years is considerable -- large enough to allow an opinion to be formed, at any rate, as a preliminary to more scientific research.
Albanese (13), in 1947, injected 2 grams of ascorbic acid a day to fight off "la grippe" and reported an immediate alleviation of symptoms, a rapid drop in fever, and shortening of duration of illness. The injections were well tolerated and there were no complications. Albanese reported his observations in the hope that it would stimulate others to try his treatment and obtain additional clinical data. Woolstone (14), in 1954, obtained good results in treating the common cold with 0,8 grams of ascorbic acid hourly and vitamin B complex three times a day. He stated, "although I can only offer my own observations as proof, the results have been so dramatic that I feel others should be given a chance to try it." Miegl (15), three years later, described the excellent relief of 111 of 132 common cold sufferers in half a day by taking 1 gram of ascorbic acid in tea,three times a day. In 1958 (15), he published another paper extending his previous good results and recommended 2 to 5 grams of ascorbic acid a day for the prophylaxis of respiratory diseases, nosebleeds, radiation sickness, postoperative bleeding, and other conditions. Bessel-Lorch (16) in tests on Berlin high school students at a ski camp gave 1 gram a day to twenty-six students and none to twenty others. After nine days,nine members of the "no-ascorbic" group had fallen ill and only one member of the "ascorbic" group. All students catching colds were given 2 grams of ascorbic acid daily, which produced a general improvement within twenty-four hours so that increased physical exertion could be tolerated without special difficulties. The significant observation was made that, "all participants sowed considerable increase in physical stamina under the influence of vitamin C medication." Ritzel (17), in 1961, reported on a larger experiment in a ski camp. One gram of ascorbic acid was given to 139 subjects and 140 others did not receive it. symptoms were reported in 119 cases from the "no-ascorbic" subjects and 42 cases from the "ascorbic" group. Ritzel stated in his summary, "Statistical evaluation of the results confirmed the efficacy of vitamin C in the prophylaxis and treatment of colds."
There are two things that should be noted in these provocative reports. First, the unheeded appeals for additional extensive clinical research on the high-dosage ascorbic acid treatment of the common cold. Second, the levels of ascorbic acid dosages which were considered "high" by these various authors, who still thought of it as vitamin C, were still far below the dosages that would be considered adequate under the teachings of the genetic disease concept.
In keeping with this new concept, the following regimen for the control of the common cold has been devised and should be subjected to thorough clinical testing. The rationale is based on the known virucidal action of ascorbic acid and the general mammalian response to biochemical stresses. The strategy is to raise the blood and tissue levels of ascorbic acid, by repeated frequent doses, to a point where the virus can no longer survive. It is really difficult to understand how this simple and logical idea has escaped so many investigators for so long. This regime is not untried: the author has been his own "guinea pig" and has not had a cold for nearly two decades. Many of the author's family, colleagues, and friends have volunteered to follow it and have reported successful results. When used as directed it has been practically 100 percent effective.
An individual continuously on the "full correction" regimen of 3 to 5 grams of ascorbic acid daily for an unstressed adult will have a high resistance to infectious respiratory diseases. Should the exposure to the infectious agent be unduly heavy or some other uncorrected biochemical stresses be imposed, the infecting virus may gain a foothold and start developing. Treatment is instituted at the very first indication of the cold starting, because it is much easier to abort an incipient cold than to try to treat an advanced case. If a known heavy exposure to the infectious agent is experienced,such as close contacts with a coughing and sneezing cold sufferer, then prophylactic doses of several grams of ascorbic acid, several times a day, may be taken without waiting for cold symptoms to develop.
At the first symptoms of a developing cold I take about 1.5 to 2.0 grams of ascorbic acid, dissolved in a couple of ounces of water, unsweetened or sweetened to taste. Within twenty minutes to half an hour another dose is ingested and this is repeated at twenty-minute to half-hour intervals. Usually by the third dose the virus has been effectively inactivated, and usually no further cold symptoms will appear. I watch for any delayed symptoms nd, if any become evident, I take further doses. If the start of this regimen is delayed and it is instituted only after the virus has spread throughout the body, the results may not be so dramatic, but ascorbic acid will nevertheless be of great benefit. Continued dosages at one- or two-hour intervals will shorten the duration of the attack, often to a day. The great advantage of this common cold therapy is that it utilizes a normal body constituent rather than some foreign toxic material. This regime should be the subject of large-scale, long-range clinical studies in order to establish its efficacy and safety, and to provide the data required by medicine for any new suggested therapy.
In 1966,this regime was sent to Dr. Linus Pauling. As a result of his successful personal experience and other work, he published in 1970 the book (18) Vitamin C and The Common Cold. This volume, the first published book in the new fields of megascorbic prophylaxis and megascorbic therapy, gives a more detailed and practical account of the use of ascorbic acid for this condition than is possible in the space of this short chapter.
With the publication of this book, there was a rash of unjustified criticism heaped upon Dr. Pauling by the medical establishment as well as the lay press. In the second edition of this book, published by Bantam Books in 1971, Dr. Pauling answers these criticisms. Chapter 12 ends with the statement::
With the increasing recognition of the value of vitamin C and the increasing use of this natural and essential substance to strengthen the body's defenses against infections, this universal scourge, the common cold, can be brought under control.
Up to the date of the publication of this book, the author is not aware of any clinical tests planned or started that follow the suggested regimen of: 1. long-term correction of hypoascorbemia to improve resistance against the cold virus,and 2. massive mirucidal therapy with ascorbic acid once the symptoms of the cold appear.
13
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The many different contagious diseases that afflict man may be divided and classified according to the nature and characteristics of the infection agent that causes the disease. Three groups are generally recognized: the viral diseases, the bacterial infections, and the diseases caused by more advanced types of parasitic agents.
It so happens that this classification also denotes the relative size and complexity of the infectious agents. The viruses are the simplest and most primitive forms; in fact,they are sort of transitional substances between living and nonliving matter. They cause a wide variety of diseases such as poliomyelitis, measles, smallpox, chicken pox, influenza, "shingles," mumps, and rabies. The common cold, discussed in the previous chapter, is a virus disease, although various bacteria generally infect the weakened tissues as secondary invaders.
When a virus infects a mammal and gains a foothold in the mammalian body, the mammal reacts by showing the symptoms of the disease and at the same time organizes its own biochemical defenses against the virus. In nearly all mammals,this biochemical defensive reaction is at least twofold: the victim starts to product antibodies against the virus nd also increases the rate of ascorbic acid synthesis in its liver. This is the normal mammalian reaction to the disease process, except in those species, like man, that cannot manufacture their own ascorbic acid.
Let us see what a review of the medical literature reveals about megascorbic therapy and viral disease:
Poliomyelitis
The application of ascorbic acid in the treatment of poliomyelitis is an incredible story of high hopes that end in disappointment, of blunders and lack of insight,of misguided labors and erroneous hypothesis. And then, when a worker finally seemed to be on the right path and had demonstrated success, hardly anyone believed his results, which were systematically ignored.
Within two years after the discovery of ascorbic acid, Jungeblut (1) showed that ascorbic acid would inactivate the virus of poliomyelitis. This was followed, in 1936-1937, in rapid succession by other workers showing similar inactivation of other viruses: by Holden et al. (2), using the herpes virus; by Kligler and Bernkopf (3), on the vaccina virus, by Lagenbusch and Enderling (4), with the virus of hoof-and-mouth disease; by Amato (5), on the rabies virus; by Lominski (6), using bacteriophage; and by Lojkin and Martin (7), with the tobacco mosaic disease virus. Thus, at this early date it was established that ascorbic acid ha the potentiol of being a wide-spectrum antiviral agent. Here was a new "magic bullet" that was effective against a wide variety of viruses and was known to be completely harmless. Materials with such exciting properties do not happen often and a tremendous amount of research time should have been expended in tracking it down in minute detail, but let us see what happened.
The reader should realize that this work was being carried out in the pre-Salk days. Then, all a doctor could do in a polio case was apply symptomatic relief and hope for the best. An epidemic could run its course without much interference from medicine and an effective, harmless virucide would have been a priceless commodity. Jungblut (8) continued his work and published a series of papers from 1936 to 1939 in which he showed that the administration of ascorbic acid to monkeys infected with poliomyelitis produced a distinct reduction in the severity of the disease and enhanced their resistance to it. Sabin (9), attempting to reproduce Jungeblut's work on monkeys, failed to obtain these partially successful results. In further efforts to explain their variable clinical results, both scientists got bogged down chasing the technical details of the tests. It may be easy for us to look back now and say that the size and the frequency of the dosages were insufficient to maintain high levels of ascorbic acid in the blood during the incubation of the disease. The upshot was that the negative findings of Sabin effectively stifled further research in this field for a decade.
In 1949,the first of a remarkable series of papers appeared. Klenner (10) described his successful treatment of poliomyelitis, as well as a variety of many other viral infections, using ascorbic acid. He gave the rationale for his treatment, his technique in detail, and his dramatic case histories. Klenner realized that the secret was in the massive doses he employed, and he tried to impart this knowledge to an unbelieving profession. In his 1952 paper, Klenner further discussed his ascorbic acid treatment of polio and comments on Jungblut's earlier work, stating;
His results were indecisive because the amount of vitamin C given was inadequate to cope with the degree of infection. Sabin's results were not as suggestive as Jungeblut's because he, Sabin, used a greater dose of virus and less vitamin C.
Klenned's suggested optimal dosage rate for virus infections, calculated on the basis of a 70-kilogram (154-pound) adult, was 4.5 to 17.5 grams of ascorbic acid given every two to four hours around the clock (17 to 210) grams per day). This amount goes far beyond anything that had been previously tried. He records one successful case history after another in these papers, as well as in his 1953 report. His results indeed proved that ascorbic acid was a harmless and effective wide-spectrum virucidal agent. If high blood and tissue levels of ascorbic acid are continuously maintained, an extremely unfavorable environment for viral growth and reproduction is created in the human body,
Two other papers appeared in 1952, in which ascorbic acid was used in the therapy of poliomyelitis at daily doses below those recommended by Klenner. Gsell and Kalt (11), using 5 to 25 grams per day, reported that there were no definite effects on the course of the disease. Besides using lower dosages, they also started this treatment on the majority of their patients only after they had had the disease for at least four days. Baur (12), using 10 to 20 grams per day, was able to report beneficial results in shortening the fever and convalescent time.
Greer (13), in 1955, using doses in Klenner's recommended range (50 to 80 grams per day), recorded the good clinical results he had obtained in five serious cases of poliomyelitis.
Over the years, the emphasis of medical research on poliomyelitis has shifted toward the development of vaccines. These are now widely used and have the disease under control. But a polio vaccine is only effective against the polio virus and has no action on the viruses of other diseases. The main value of Klenner's work is in showing that any active viral disease can be successfully borught under control with ascorbic acid if the proper large doses are used. It is inconceivable, but true, that klenner's pioneering work has been almost completely ignored; no large-scale tests have been made to explore the exciting possibilities of his provocative clinical results. Millions of dollars of research money have been spent in unsuccessful attempts to find a nontoxic, effective virucide and all sorts of exotic chemicals have been tried. All the while, harmless, inexpensive, and nontoxic ascorbic acid has been within easy reach of this investigators. It might prove to be the "magic bullet" for the control of the viral diseases.
Hepatitis
Soon after the discovery of ascorbic acid, Bessey and coworkers (14), in 1933,showed that guinea pigs derived of ascorbic acid developed a fatty degeneration of the liver. Ten years later, Russell and Calloway (15) also showed pathologic changes in the livers of guinea pigs with scurvy. Willis (16), in 1957, further investigated and extended these earlier observations and demonstrated the vital importance of ascorbic acid in maintaining healthy liver tissue free of cirrhotic, degenerative changes.
Ascorbic acid should, therefore, be twice as sound for use in the treatment of the viral liver disease, viral hepatitis. When used at the necessary high dosages it should inactivate the hepatitis virus and it should also act on the liver tissue to prevent degenerative changes. In 1954, Bauer and Staub (17) observed good results in the treatment of viral hepatitis with the use of 10 grams of ascorbic acid per day. It accelerated the disappearance of the symptoms of the disease and shortened the duration of the illness. Earlier, in 1937, Spengler (18), using only 100 milligrams per day by injection in a case of liver cirrhosis brought on by the toxemia of pregnancy, noted ascorbic acid's diuretic effect, which helped clear up the disease, and reported good recovery. Twenty years later in Germany, Kirchmair (19) used 10 grams of ascorbic acid daily for five days on sixty-three children with hepatitis and found marked improvement, weight gain and good appetite in the first few days, rapid disappearance of jaundice and half the hospitalization time. The swelling of the liver, which normally took 30 days to subside, only took nine days with ascorbic acid. In 1960, Calleja and Brooks (20) reported successful treatment with 5 grams of ascorbic acid a day for twenty-four days in a refractory case of hepatitis that did not respond to other medication. Beatgen (21), giving 10 grams of ascorbic acid a day to 245 children with hepatitis, obtained result similar to Kirchmair's, with rapid recovery and better tissue repair. Dalton (22), in 1962, also reported dramatic and rapid recovery of a case of hepatitis.
In these clinical reports on hepatitis, the doses of ascorbic acid were below the range postulated by Klenner and also below the quantity considered necessary by the genetic disease concepts. The provocative clinical results reported in the medical literature have not been extended or explored. Further intensive clinical research is needed on the use of ascorbic acid at the proper high-dosage rate for the control of this serious liver disease and also for the prevention and therapy of the degenerative,cirrhotic liver changes that occur, for instance, from the excessive use of alcohol. It is tragic that organizations concerned with alcoholism have not picked up these exciting leads for further exploration to prevent the degenerative liver changes which cause such misery and death to so many. The long-term preventive use of only 10 grams of ascorbic acid a day may be sufficient.
Herpes
This is an acute inflammatory affliction of the skin or mucous membrane and is known in many different forms, all annoying and some quite serious. Two common forms are "fever blisters," or herpes simplex, a more or less serious condition depending upon the location of the "blisters," while "shingles," or herpes zoster, is a serious and painful disorder which seems to follow and inflame the paths of certain nerves. The virus appears to reside in the skin and the disease starts when the victim is exposed to excessive stresses such as overexposure to sunlight or poisons, infections, or physical or emotional stresses. These are all conditions where ascorbic acid is at a low ebb in the body and this may be part of the triggering mechanism that starts the disease.
It was shown early by Holden & Molloy (2) that ascorbic acid inactivated the herpes virus. Clinical tests conducted later indicated provocative improvements. Dainow (23), in 1943, reported successful treatment of 14 cases of "shingles" with injections of ascorbic acid; Zureick (24), in 1950, treated 237 cases of "shingles" and claimed cures in all in 3 days of injections of ascorbic acid; Klenner (10), in 1949, injected eight "shingle" patients with ascorbic acid and seven claimed cessation of pain within two hours after the first injection. Seven also showed drying of the blisters within one day and in three days were clear of the lesions.
Again, no large-scale testings have been made to verify these exciting results, with the numerically and statistically significant volume of cases that medicine demands before it accepts a treatment. This is another job for a government-supported program, but no one has picked it up and carried it through.
Other Viral Diseases
Klenner (25), in 1948, and Dalton (22), in 1962, reported their successful experiences with virus pneumonia treated with ascorbic acid in 42 cases and 3 cases, respectively. Paez de la Torre (26), in 1945, found good results in measles in children. Klenner (10), in 1949, successfully used ascorbic acid as a prophylactic in a measles epidemic and gave a dramatic case history in his 1953 paper in the treatment of a ten-month-old baby with measles. Zureick (24), in 1950, treated seventy-one cases of chicken-pox with ascorbic acid and Klenner 910), in 1949, also mentions the good response he obtained in this disease.
Klenner also cites the dramatic results he obtained in virus encephalitis and also in 33 cases of mumps and many cases of influenza. Vargas Mage (27), in 1963, treated 130 cases of influenza for one to three days using up to 45 grams of ascorbic acid. The patients were both male and female, aged ten to forty years; 114 recovered and 16 did not respond. The present direction of the research on influenza in this country is oriented to lead to the development of a vaccine. There appears to be no provision in this research program for testing massive doses of ascorbic acid in the prevention or treatment of influenza.
Amato (5), in 1937, found that the rabies virus could be inactivated with ascorbic acid. A search of the literature revealed no further work in the thirty-five years since this paper originally appeared. Here could be the nucleus of a possible harmless treatment of this fatal disease if the necessary work would be conducted using large, continuing doses of ascorbic acid. There is a very great need for a relatively harmless treatment of rabies as the present therapy is almost as bad as the disease. This is certainly an area where more work should be done, and done soon in view of the recent findings of large reservoirs of the rabies virus in bats (28, 29).
Still another area, long unexplored, is in the prophylaxis and treatment of smallpox. A 1937 report by Kligler nd Bernkopf (3) stated that ascorbic acid inactivates the vaccinia virus. Nothing further can be found in the medical literature to indicate the use of ascorbic acid in the related disease, smallpox.
Infectious mononucleosis, usually a long drawn-out disease, should be amenable to treatment with ascorbic acid, and one case, with dramatic recovery, has been reported (22).
Many of the papers cited above end with the plea for further work on a large scale to evaluate thoroughly the use of massive doses of ascorbic acid in the therapy of the viral diseases. These pleas have gone unheeded. Was it because there was no rationale for the high dosage rates under the old vitamin C theory? The new genetic disease concept now supplies a logical rationale for the use of these high doses of ascorbic acid in therapy. From the work already conducted, it would appear that ascorbic acid is a most valuable weapon in the fight against the viral diseases when used under the proper conditions. How valuable it is we shall never know unless large-scale clinical tests are undertaken by our presently constituted public health agencies and publicly supported health foundations. Let us see if the record of the next decade is better than the last.
14
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In this chapter we will discuss the use of ascorbic acid in the treatment of the infectious diseases caused by pathogenic bacteria. These include tuberculosis, pneumonia, pertussis (whooping cough), leprosy, typhoid fever, dysentery, and other infections.
There is a tremendous volume of medical literature relating to the treatment of infectious bacterial diseases with ascorbic acid. Much of it appeared in the early days, not too long after the discovery of ascorbic acid, because these early workers had high hopes for the therapeutic potency of ascorbic acid in a wide variety of diseases. Before discussing these clinical tests we will review some elementary facts of pharmacology that seem to have escaped nearly all of these investigators for the past thirty years.
A substance that has the property of killing bacteria is called a "germicide" or "bactericide." The germicidal potency will vary from substance to substance. Because of this variation, a certain specific minimum concentration must be maintained, under stated conditions, for the substance to exert its killing or bactericidal powers. If this minimum concentration is lowered somewhat, so that the killing power is lost, the substance may still be able to have a growth-inhibiting, or bacteriostatic, effect. At these lower levels, the substance prevents the bacteria from growing without actually killing them. Reducing the concentration of a bacteriostatic substance further could permit the bacteria to start growing. Thus, we have certain levels of concentration where the bacteria can be killed, their growth inhibited, or just not affected at all. These simple facts have been known since the nineteenth century.
It has also been known for some time that ascorbic acid has bacteriostatic and bactericidal properties. It was shown 91), in 1941, that various microorganisms could be inhibited by ascorbic acid at 2 milligram percent (mg%) -- that is, 2 parts ascorbic acid in 100,000 parts of bacterial suspension. The bacteria included Staphylococcus aureus (the pus organism), B. typhosus (the germ causing typhoid fever), B. coli (the organism from sewage), and B. subtilis (a nonpathogenic bacteria). At 5 mg % B diphtheriae was inhibited as well as Streptococcus hemolyticus (the cause of many serious infections). Several authors worked with the tuberculosis organism, which was found to be particularly susceptible to attack by ascorbic acid. Boissevain and Spillane (2), in 1937, found a bacteriostatic effect at 1 mg %; Sirsi (3), in 1952, reported 10 mg % to be bactericidal against virulent strains of M. tuberculosis and bacteriostatic at 1 mg %; Myrvik et al. (4), in 1954, also showed the bacteriostatic action of ascorbic acid and confirmed earlier observations that the urine from subjects taking ascorbic acid acquired the property of inhibiting the growth of the tubercle bacilli.
Using these figures, we can make a rough calculation of how much ascorbic acid would be needed to reach a bacteriostatic or a bactericidal level in the body. If we take 10 mg % as our desired level and assume that the ascorbic acid would be equally distributed throughout the whole body and the patient's weight is 70 kilograms (154 pounds), then the minimum initial dose required would be 7 grams, or 7.000 milligrams. Actually, much more would be required each day, for a number of reasons, in order to maintain a 10 mg % concentration; but his figure is good enough for our comparison with the actual amounts used in the clinical tests. It is apparent that none of the investigators paused to make this calculation before planning their tests because the dosages they used are of a completely different order of magnitude -- so low as to be obviously inadequate.
Let us now look into some other useful properties of ascorbic acid. Certain bacteria, during their growth, elaborate and secrete deadly poisons or toxins. In some of the infectious diseases,the most distressing symptoms and toxic effects,such s the choking of diphtheria or the muscle spasms of tetanus, or lockjaw, are caused by these toxins. The toxin produced by bacteria causing a type of food poisoning, the botulinus toxin, is one of the most powerful and deadly poisons known to man. The lethal dose is so small it is invisible to the naked eye.
It was early found that ascorbic acid had the power to neutralize, inactivate,and render harmless a wide variety of these bacterial toxins: diphtheria (5) (Harde and Phillippe, 1934); Jungeblut and Zwemer, 1935; Sigal and King, 1937; Kligler et al., 1937; tetanus (6) (Jungeblut, 1937; Kligler et al., 1938; Schulze and Hecht, 1937; Kuribayashi et al., 1963; Dey, 1966); staphylococcus (7) (Kodama and Kojima, 1939); dysentery (8) (Takahashi, 1938). In 1934, the unusual resistance of the mouse to diphtheria infections was attributed to its ability to synthesize rapidly its own ascorbic acid, while the guinea pig's ready susceptibility to this disease (like man's) was attributed to its inability to replenish its store of ascorbic acid.
Another of the body's defenses against invading pathogenic bacteria is the mobilization of the white blood cells in the site of the infection. These white blood cells actually physically attack the bacteria, engulf the, and digest and destroy them. This process of actually eating the bacteria is called "phagocytosis." The white blood cells are really the scavengers and garbage men of the tissues. This important bodily defense is an ascorbic acid-dependent process. The phagocytic activity depends on the amount of ascorbic acid in the blood and tissues. If the ascorbic acid levels are too low the white blood cells will not attack the invading bacteria, nor ingest or digest them. The fact that phagocytosis proceeds poorly or not at all is a major reason for the increased susceptibility to infections in the prescorbutic or scorbutic state.
Cottingham and Mills (8), in 1943, showed this necessity for the presence of ascorbic acid in maintaining phagocytotic activity of the white blood cells. In their tests there was a marked reduction in this vital defensive measure with ascorbic acid deficiency. This important discovery made no impression at the time. Nearly three decades later this effect was "rediscovered" by DeChatelet et al. (8) and received wide newspaper coverage.
To summarize -- in ascorbic acid we have a theoretically ideal weapon in the fight against the infectious diseases:
1. It is bacteriostatic or bactericidal and will prevent the growth or kill the pathogenic organisms.
2. It detoxicates and renders harmless the bacterial toxins and poisons.
3. It controls and maintains phagocytosis.
4. It is harmless and nontoxic and can be administered in the large doses needed to accomplish the above effects without danger to the patient.
A great volume of work with the infectious diseases was initiated soon after the discovery of ascorbic acid, because of the long-standing suspicion of a causal connection between scurvy and infections. Scurvy and the prescorbutic state were known to lower the body's resistance and predispose both humans and guinea pigs to the infectious diseases (9) (Faulkner and Taylor, 1937; Harris et al., 1937; Perla and Marmorsten, 1937). This was in the days before the antibiotics and sulfonamides, when medicine's armament against infections was still rather primitive and nonspecific and the infections took a high toll in suffering and death. The early workers were intrigued with this newly discovered substance and its unique therapeutic powers, and thought it would be a mighty weapon in the fight against infectious diseases. Hundreds of papers were published; the few cited below are merely a sampling.
Tuberculosis
The medical literature of the two decades before the discovery of ascorbic acid contains many pertinent empirical observations and animal experiments on the relationship among scurvy, tuberculosis, and vitamin C. As early as 1933, McConkey and Smith (10) fed guinea pigs tuberculous sputum daily. One group of animals was maintained on a diet partially deficient in ascorbic acid and in the other group each animal received 2 teaspoons of tomato juice daily as their source of ascorbic acid (about 2 milligrams a day). McConkey got the idea for this test from his earlier observation of the permanent improvement of hospitalized patients with intestinal tuberculosis on being given tomato juice in addition to their regular hospital fare. Of the thirty-seven animals on the partially deficient diet, 26 developed ulcerative intestinal tuberculosis, while only two of the thirty-five tomato juice animals succumbed, despite the extremely low levels of ascorbic acid used. Other workers (11) confirmed these results (de Savitsch et al., 1934) using 2 teaspoons of orange juice per animal per day, and Greene et al., in 1936, published confirmatory data. Birhaug, in 1938, in a very complete series of tests on guineas pigs, using only 10 milligrams of ascorbic acid a day for a 300-gram guinea pig (equivalent to 2300 milligrams for a human adult), came to the following conclusions:
Our study has shown that by compensating for the inevitable state of hypovitaminosis C which occurs in progressive tuberculosis, we render the animal organism more resistant against the inflammatory-necrotizing effect of tuberculosis and the initial invasive onslaught of virulent tubercle bacilli.
As reported in two short papers, in 1936 and 1939, Heise et al. (12), using 20 milligrams of ascorbic acid a day subcutaneously, found no influence on the course of the infection. However when the experimental conditions are examined, it is found that while they had given twice as much ascorbic acid as Birhaug had, they had also increased their inoculation of highly virulent tuberculosis bacteria to 20 to 600 times more than Birkhaug had used. It is quite evident why they did not confirm Birkhaug's work: they expected too much from too little ascorbic acid.
Good results with ascorbic acid in protecting guinea pigs against the effects of tuberculosis were also reported by workers (13) in Germany, the United States, Denmark, and other countries.
Many papers appeared which showed the increased need for ascorbic acid under the heavy biochemical stresses of the tuberculosis infection (14). In a five-year follow-up study of 1,100 men originally free of pulmonary tuberculosis, 28 cases of tuberculosis developed; all the cases came from the group whose ascorbic acid blood levels were substandard (15).
Clinical tests reported from 1935 to 1939 include the following (16): Hasselbach, using 100 milligrams of ascorbic acid a day for treatment, reported some favorable effects. Radford and coworkers gave 500 milligrams a day in cases of advanced and fibroid tuberculosis and obtained improvement in the blood picture. Borsalino, who injected 100 milligrams a day, controlled hemorrhaging and improved the general condition of his patients. Martin and Heise, using 200 milligrams a day, did not obtain any evidence of a beneficial effect. Petter administered 150 milligrams of ascorbic acid a day to forty‑nine tuberculous adults, of which thirty improved, twelve showed no change, and seven were definitely worse; of twenty-four tuberculous children, twenty-one improved, one showed no change, and two were worse. The higher percentage of improved patients among the children was, no doubt, due to their higher dosage per unit of body weight. Albrecht injected 100 milligrams a day and obtained improvement in appetite, well-being, weight gain, blood picture, and temperature. Josewich gave 100 to 150 milligrams a day and reported practically no effect on his tuberculous patients. Baksh and Rabbani injected 500 milligrams a day for 4 days and gave 150 to 200 milligrams orally for the next 6 weeks. They reported it was a valuable adjuvant in treatment.
In spite of this lack of any notable or outstanding success and of the marginal (at best) responses they were obtaining with these low doses,the tests continued at the same low levels. The dogma of the vitamin theory kept these clinicians from thinking of ascorbic acid as an antibiotic and using it at the necessary antibiotic dosages. A sampling of this continuing useless work appearing in the 1940s follows 17): Erwin et al, and Kaplan et al., administered 100 to 200 milligrams a day and both reported no significant favorable effects in tuberculosis. Sweaney at al., giving about 200 milligrams a day in 3 series of patients could report no outstanding success. Vitorero and Doyle injected 500 to 600 milligrams of ascorbic acid a day initially, which was reduced to 400 milligrams as improvement was shown, and then further reduced to 200 milligrams a day. They were quite positive about the benefits of this medication in their few cases and recommended its use in intestinal tuberculosis. Bogen et al., treating 200 patients divided into several groups in a sanatorium with 150 milligrams of ascorbic acid a day, reported subjective improvement in the patients and visible improvement in the tuberculosis lesions. They stated that vitamin C was by no means a cure for tuberculosis, but they recommended its "abundant administration,: which to them meant 150 milligrams a day. They attached no importance to ascorbic acid's controlling of the symptoms of tuberculosis, but said that many patients expressed a feeling of increased well-being. Rudra and Roy, in 1946, and Babar, in 1948, found the same borderline type of improvements using 250 milligrams and 200 milligrams of ascorbic acid per day, respectively.
There were \many more reports in this sickening mass of continued repetition of ineffectual clinical tests where the investigators were correcting a nutritional deficiency instead of using ascorbic acid to actually combat the disease. At last, in 1948, Charpy (18) got the idea that the doses previously used were too low and conducted a test using 15 grams (15,000 milligrams) of ascorbic acid a day on six tuberculous patients. But even this test was bungled: the six patients selected for the test were terminal tuberculosis cases expected to die shortly and, in fact, one of the patients did die before the test could really get under way. Of the other five, they were still alive six to eight months later, had gained from twenty to seventy pounds in weight, were no longer bedridden, and had had a spectacular transformation of their general condition. Charpy stated that while there was not much modification in the physical appearance of their tuberculous lesions, "they gave the impression of becoming in some way unaware of the enormous tuberculous lesions they harbored." He noted that each patient had taken about 3 kilograms (3,000,000 milligrams) of ascorbic acid during the test with safety and perfect tolerance. He also indicated that further work was being done, but a search of the subsequent medical literature failed to reveal any further reports by Charapy or by anyone else using these large doses. No one has taken these exciting results and further explored their possibilities.
The record of the clinical work conducted on the use of ascorbic acid in the treatment of tuberculosis is, indeed, incredible. After thirty years,the crucial and meaningful clinical tests at high dosages have still not been conducted. Uncounted lives have been lost; immeasurable suffering endured; and time, energy, and research money wasted in chasing a will-o'-the wisp by minds looking for a therapeutic effect, but bound by the narrow confines of a vitamin theory. It is unbelievable that so many workers for so long a time could not have suspected the possible reason for their uniform lack of success. To these workers,doses of a few hundred milligrams of ascorbic acid a day were considered "high" because they looked upon it as a vitamin and not as an antibiotic. The correct employment of ascorbic acid could regulate the White Plague to oblivion.
Pneumonia
Hochwald used injections of 500 milligrams of ascorbic acid every one-and-a-half hours in croupous pneumonia until the fever subsided. He noted a quicker disappearance of fever and local symptoms and a normalization of blood counts; the disease could practically be cut short the first day. Gander and Niederberger, injection 500 milligrams intramuscularly and then 900 milligrams orally in the next 3 hours, reported remarkable improvement during the disease and in convalescence. Gunzel and Kroehnert had good results at 1,000 to 1,600 milligrams a day and some failures at 500 milligrams a day. Kienart, Szirmai, and Stein reported good results in pneumonia as well as Biilmann, who injected 500 milligrams of ascorbic acid every 3 hours. Chacko injected 1 gram every 4 hours into infants with pneumonia with excellent results (19).
The encouraging results in pneumonia were obtained using ascorbic acid at levels, which, though "genetically" low, were still higher than those used in tuberculosis. Most of this work was done in the pre-antibiotic era, when a good treatment for pneumonia was vitally needed, and yet ascorbic acid never was widely used or even properly explored for the therapy of pneumonia. Even now, when antibiotics are dominating the field of pneumonia therapy, ascorbic acid in large doses still has a useful function as an adjuvant to antibiotic therapy. In large doses, it will potentiate the effectiveness of the antibiotic and make it possible to use smaller doses of the expensive antibiotic. It will also detoxicate the harmful side reactions incident to the use of these antibiotics, thus assuring the patient a better chance f survival. More work should be conducted in these areas.
Pertussis (Whooping Cough)
In 1936, it was shown that ascorbic acid at 8 mg percent had an inhibiting effect on the growth of the germ causing whooping cough (20). In the same year Otani (20) demonstrated ascorbic acid's ability to neutralize the toxin of the whooping cough bacillus and its usefulness in the management of whooping cough by injection. In a later paper, in 1939, he used 5 to 12 injections of 100 to 200 milligrams of ascorbic acid on 109 cases of whooping cough. He summed up his tests by stating, "the treatment with vitamin C for the whooping couch is a new method superior to all other treatments given heretofore for the patients." He found "remarkable efficiency" in 40 cases (36.7 percent), "some efficiency" in 49 cases (45 percent) and in the remaining 20 cases (18.3 percent) "no efficiency at all." In this later group, the majority of the patients had other complications, such as tuberculosis, measles, influenza, tonsillitis, etc., and this alone should have indicated to subsequent workers the need for increased and higher dosages. But no, the testing at these inadequate "nutritional" levels of treatment proceeded unabated.
Four papers appeared in 1937 - 38 (21) from such widely separated placed as Canada, Germany, England, and Kansas using some marginal measure of success. Gairdner, in 1938, using what he believed to be unusually large doses of ascorbic acid (200 milligrams a day for the first week, and150 milligrams a day for the second week, and 100 milligrams a day thereafter), found no differences between the course of the whooping cough in twenty-one vitamin C-treated cases and twenty control cases without the Vicamin C. Sessa (22), in1940, injecting 100 milligrams a day (in some serious cases 250 or 500 milligrams) into infants, found a reduction in convulsive coughing and a quicker recovery and considered it a valuable therapeutic measure.
Another overlooke clue that should have provided these workers with an important lead that their dosages were inadequate was the fact that infants generally responded to the ascorbic acid treatments much better than adults. This was due to the smaller size of the infants so that they actually received a considerable larger dose of ascorbic acid per unit of body weight.
Meier (22), in1945, found a reduction in coughing and that the coughing spells were more easily tolerated, especially in infants. There was general improvement, the children looked better and were more quiet, their appetite increased and vomiting disappeared. He gave 500 milligrams by injection supplemented by six 300-milligram tablets orally, the dosage totaling 2,300 milligrams daily for the first few dayd. Meier's consistently greater success is probably due to this use of slightly higher dosage levels than his predecessors.
Pfeiffer (23), in1947, injected 500 milligrams daily, intramuscularly, and also supplemented this with ascorbic acid tablets, orally, but she failed to state how much the tablets contained. she reported no success.
The last paper we will discuss comes from Holland (23), where 500 milligrams of ascorbic acid was used per day either by injection or orally for the first week. Then the dosage was reduced stepwise. In the ninety children treated, the duration of the illness was fifteen days for the injected group, twenty days for the oral group, and thirty-four days for the control group, which received vaccine. He stated, "Ascorbic acid given in the catarrhal stages prevented the convulsive stage in 75 percent of the cases, whereas the number of complications were negligible."
This review shows thatthe results of the work on whooping cough, covering a period of about fifteen years, provided somevariable relief, but resulted mostly in inconclusive and confusing reports. The crucial experiment, where ascorbic acid was used at the necessary antibiotic and antitoxic levels of many grams a day, was never conducted.
Leprosy
Leprosy is a disease of much wider occurence than is generally supposed. It is not lilmited to the underdeveloped areas of the Far East but is also present on the American continents.
Ascorbic acid has been tried in the treatment of leprosy over a period of many years. Bechelli (Brazil 1939), using 50 to 100 milligrams by intramuscular injection, reported good results in over half of the twenty cases he treated. Gatti and gaona (Paraguay 1939) noted improvements in two cases of leprosy using daily injections of 100 milligrams of ascorbic acid for several weeks. Ugarriza (Paraguay 139) obtained relief in leprous septicemia with eight 50-milligram tablets of ascorbic acid orally. Ferreira (Brazil 1950) at the Santa Isabel Leper Colony found that the daily injection of 500 milligrams of ascorbic acid improved the well-being of the lepers, their appetite increased, they gained weight, they had fewer nosebleeds and it improved their tolerance to other antileprosy treatments. He stated that it was a valuable auziliary medication. Floch and Sureau (France 1952), using daily injections of 500 milligrams over long periods, observed favorable results in the tuberculoid form of the disease. They also reported better results at twice the daily dosage ( 1 gram a day) and suggested that it would be interesting to continue their work at "2 or even 4 grams daily." but apparently this was never done by them or anyone else (24). From the beneficial results obtained thus far from doses that were obviously too low, the odds would seem to favor success at proper dosage levels. Who will make these tests and when?
Typhoid Fever
By the strict use of control measures, such as improvements in methods of sewage disposal, protection of communal water supplies, pasteurization of selected foods, and exclusion of typhoid carriers from good handling professions, good protection against typhoid fever is obtained. However, sproadic outbreaks do occur in spite of continued alertness: for instance, the 280-cse outbreak in Zermatt, Switzerland, in 1963; the 400-case epidemic in Aberdeen, Scotland, in 1964; and the Atlanta, Georgia, episode in the same year involving 15 cases and 1 death. In the United States,typhoid vaccine inoculations are ordinarily given only to members of the armed forces and to persons traveling abroad. The home folks, not in the armed forces are left unprotected against this serious disease which, even with the newer antibiotic treatments, has a mortality rate of 4.5 percent and a relapse rate of 15 to 20 percent.
In 1937 farah (25), in England, reported outstanding success in reducing mortality and duration of illness in 18 cases of typhoid fever treated with ascorbic acid and cortin. Szirmai (19), in 1940, used ascorbic acid injections in sever cases of typhoid fever, 300 milligrams a day, which completely prevented the intestinal hemorrhaging. In 1943, in a comprehensive paper, Drummond (25) published the very successful results of his treatment of 106 cases of typhoid fever with 1,200 milligrams of ascorbic acid dailly, 400 milligrams by injection and 800 milligrams orally.
The results obtained in these early tests warrant the further exploration of the use of the necessary high doses of ascorbic acid in the prophylaxis and treatment of this and related diseases, either as the sole medicament or as an adjuvant with other antibiotic therapy. While the incidence of typhoid fever, caused by the bacterium, Samonella typhosa, has been declining in the last twenty years, other related diseases caused by similar species of Salmonella have shown very sharp increases. These are the typhoidlike food-borne infections commonly regarded as "food poisoning." The Salmonella organisms are the type that secrete poisonous toxins which are in part responsible for the virulence of the infection. f Ascorbic acid, at the proper high dosags, should be particularly valuable in these Salmonella infections becausde of its antibiotic effect an it stoxin-neutralizing powers.
Dysentery
This is another infectious disease caused by poor sanitation, and the infectious agent is an amoeba. A controlled study has been made of ascorbic acid in guinea pigs experimentally infected with the amoeba of human origin (26). Some of the animals were maintained on an ascorbic acid-deficient diet and otherw were given 20 milligrams of ascorbic acid every other day (this is a nutritioal dosage, not a therapeutic antibiotic level). Higher infectivity, mortality rates, and increased severity of the disease were found in the animals maintained without added ascorbic acid. Two Russian workers (26), in 1957, found a definite relationship between the clinical manifestations of dysentery and the ascorbic acid levels in 106 patients. In the deficient patients there were more hemorrhages and frequent slimy-bloody stools. they only used 150 milligrams a day to try to control the disease. In 1958, another Russian paper appeared in which 500 milligrams a day were used. Whenthe ascorbic acid was combined with other treatments, it rapidly eliminated the clinical sysmptoms of severe dysentery, led to more favorable clinical responsedat the submarginal levels used in this work would indicate good promise of greater success in any future trail of the megascorbic therapy of this disease.
Other Infections
Typhus is a disease caused by minute microorganisms called "rickettsias" which occupy a position between bacteria and viruses. They are usually transmitted to man by lice, fleas, mites, or ticks. Other rickettsial diseases are Rocky Mountain Spotted Fever or tick fever of the eastern and northwestern United States, trench fever of central Europe, tsutsugamushi of the Asiastic-Pacific area, and rickettsialpox of New York City and Boston. If megascorbic therapy is found useful in one of the rickettsial diseases, it will probably control all. Szirmai (19) had been using ascorbic acid in the treatment of typhus since 1936, with seriour cases getting 300-milligram injections of ascorbic acid once or twice daily in addition to 100 milligramsorally three times a day. Dujardin 927) noted that a study of typhus had been made in a Casablanca hospital using 8 to 16 grams of ascorbic acid per day. The use of high doses of ascorbic acid in these serious diseases would open up a completely new mode of treating them. The success of this form of treatment would seem assured in view of Klenner's work on the viral diseases. The rickettsias should be just as vulnerable to ascorbic acid's action as the viruses. Clinical tests should be planned and started in these diseases without further delay.
McCormick (28), in 1951 and 1952, proposed the use of 2 to 4 grams of ascorbic acid,preferably by injection, in various infections. There are so many other papers reporting the use of ascorbic acid in various infection -- n pharyngeal and eye infections (29), in brucellosis (a widespread disease) (30), in sinusitis (31), and a wide variety of other conditions; so many that it is impossible to cover them all adequately in the space of this chapter. In all the referenced cited in this chapter, except in a few isolated instances true megascorbic therapy was never used.
15
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Over half a million people in the United States develop cancer each year and over 280,000 will die in the year ahead. More than 700,000 people are under treatment at all times. It is the number two scourge and one of every five of us is likely to be afflicted; under present conditions it will send one of every eight of us to the grave.
Cancer is not a single disease entity but a large group of closely related, yet different, diseases. Essentially, cancerous growth is uncontrolled tissue development and expansion and is due to the tissue losing the normal restraints on cell divisions and growth. The cancer grows in a wild manner at the expense of the surrounding normal tissues. Cancer can arise in any organ or tissue of the body and, like the infectious diseases, the causes are varied and different. In severity it can range from a relatively innocuous minor illness to a life-threatening disease. The pattern of cancer incidence has been changing over the years, with fewer stomach and uterine cancers and more lung cancer and leukemia.
Present-Day Cancer Therapy
In the therapy of cancer, the first important step is a diagnosis. After diagnosis, the physician has three different paths or a combination of them from which to choose: irradiation, chemotherapy, or surgery. Irradiation is localized exposure to X rays or to the radiant energy of radioactive sources, such a s radium or cobalt 60, to try to kill the fast-growing cancerous tissue without doing too much damage to the rest of the body. Chemotherapy involves the use of chemical substances that tend to damage the cancer tissue more than the normal cells and thus retard the cancer development. Surgery, of course, is the direct approach of going in and physically removing the cancerous tissue, when possible.
Ever since the discovery of ascorbic acid in the early 1930s, there has been a vast amount of animal experimentation and clinical research conducted on the relationship of ascorbic acid to cancer. This has resulted in a mass of conflicting and confusing reports as to the value of ascorbic acid in cancer treatments. Some investigators reported good results in their tests, others reported no effects on the growth of cancer tissue, while still others took the stand that tit stimulated tumor growth. Detailed discussion of the possible reasons for the conflicts of opinion in this work is beyond the scope of this chapter, except to speculate that it may be due to the wide variety of experimental animals, cancer types, and experimental conditions employed by the numerous investigators, As a first step in future cancer research h on ascorbic acid, a responsible, unbiased research agency should review this large volume of early work and assess its value in the light of the more recent research and newer concepts. Any research work which may be required to resolve these unanswered questions and conflicting opinions should be conducted. Because of the long-standing disagreement nd the resulting confusion, there has reportedly been a tendency for research workers to shy away from this area.
One thing, however, is certain. Cancer and its present-day therapy are intense biochemical stresses which deplete the bodies of cancer victims of their ascorbic acid. The irradiation, the surgery, or the chemotherapy wit highly toxic materials, are all severe biochemical stresses. Biochemical stresses, in the majority of the mammals which are able to produce their own ascorbic acid, cause them to produce more ascorbic acid to combat the stresses. Because of their defective genetic inheritance, mammals such as guinea pigs, monkeys, and man are dependent on their food intake for ascorbic acid and their response to stress is ascorbic acid depletion.
Experiments on rats, mice, and guinea pigs are enlightening on this point. When rats and mice (animals that can make their own ascorbic acid) are exposed to cancer-producing agents (carcinogens), they start producing much more ascorbic acid in their livers (1). However, when guinea pigs (animals which, like man, cannot produce their own ascorbic acid) are exposed to the same carcinogens, their ascorbic acid is used up and not replaced (2); to quote the authors of this 1955 paper, when mammals are exposed to carcinogens this will "excite an increased demand for this compound (ascorbic acid) to which the animals capable of synthesizing it respond by over protection, whereas in those lacking this power the store is depleted."
In another experiment on guinea pigs, Russell (3), in 1952, showed that cancers developed sooner in guinea pigs exposed to carcinogens and fed a diet deficient in ascorbic acid as compared to guinea pigs exposed to the same carcinogens but on an adequate ascorbic acid diet. Can we extrapolate this observation to humans and say that people who do not fully "correct" their genetic disease, hypoascorbemia, by continuously taking high levels of ascorbic acid are more susceptible to cancer than fully "corrected" individuals?
An opposite view is taken in the 1955 paper by Miller and Sokologg (3), who proposed that a prescorbutic state in the cancer victim may have beneficial effects on cancer patients during radiation therapy. To settle this question once and for all should not entail much additional research. A person afflicted with cancer will almost always be nearly depleted of ascorbic acid before the usual course of therapy is begun. Radiation therapy using radiant energy in the form of X rays or gamma rays is a potent form of biochemical stress for the body. Exposing a cancer victim to radiant energy only further aggravates a serious shortage of this metabolite and prevents the body from maintaining biochemical homeostasis under the onslaughts of the additional radiation stresses. There have been other papers published which suggested giving ascorbic acid to cancer patients before exposure to radiation and noting its benefits (4). In spite of these many suggestions, further large-scale conclusive research has not been conducted and the practice is little used. These scientists, in their clinical work used, at most, a few grams of ascorbic acid a day. This is another virgin area of megascorbic therapy, just awaiting someone to go in and try it.
Cancer chemotherapy is the use of certain chemicals to selectively poison the cancer cells without killing the patient. We will not go into the chemistry of the different materials used other than to say that they are all very poisonous and dangerous (host toxic). This, of course, limits the amounts which can be given the patient at any one time. One group of materials used in cancer chemotherapy is the so-called nitrogen mustards, which are derivatives of the mustard gases of World War I; you can conceive the type of material used in this therapy. While the chemotherapeutic agent will attack the cancer cells, the patient is left without means to overcome the toxic manifestations of the medicament. In spite of the fact that ascorbic acid has been known to be an efficient detoxicating agent for poisonous substances (see Chapter 24) no reports have been found in the medical literature for the combined administration of these toxic medicaments along with large doses of ascorbic acid as a supportive measure. The presence of high optimal levels of ascorbic acid might also improve the toxic action on the cancer cells(5), but we will never know unless it is thoroughly investigated. The potential benefits, if successful, would seem to make these clinical trials an urgent necessity.
The data contained in the 1969 paper from dean Burk and his group (5) at the National Cancer Institute are very pertinent at this point. They showed that ascorbate is highly toxic to the cancer cells they used (Ehrlich ascites carcinoma cells) and caused profound structural changes in the cancer in their laboratory cultures. They mention that:
The great advantage that ascorbates ... possess as potential anticancer agents is that they are, like penicillin, remarkably nontoxic to normal body tissues, and they may be administered to animals in extremely large doses (up to 5 or more grams per kilogram) without notable harmful pharmacological effects.
5 grams per kilogram on a 70-kilogram adult would amount to 350 grams of ascorbic acid per day. They further state:
In our view, the future of effective cancer chemotherapy will not rest on the use of host-toxic compounds now so widely employed, but upon virtually host-nontoxic compounds that are lethal to cancer cells, of which ascorbate ... represents an excellent prototype example.
They also bring out the amazing fact that in the screening program that has been going on for years to find new cancer-killing materials at the Cancer Chemotherapy National Service Center, ascorbic acid has been bypassed, excluded from consideration, and never tested for its cancer-killing properties. The reason given for not screening ascorbic acid is even more fantastic -- ascorbic acid was too nontoxic to fit into their program!
An almost immediate confirmation of Dean Burk's proposals was contained in the research conducted at Tulane University School of Medicine by Schlegel and coworkers and published in 1969 (5). It was shown that bladder cancer due to smoking and other causes could be prevented by ascorbic acid. They recommended the intake of 1.5 grams of ascorbic acid a day to avoid the recurrence of bladder tumors.
The remaining are of cancer therapy, surgery, is one where ascorbic acid may now be used to some extent. It may be used, not so much for its direct effect on the cancer, but for its beneficial effects in wound healing. For this purpose it is generally used at a gram or so a day, which may be quite inadequate to handle the biochemical stresses of anesthesia, surgical shock, and hemorrhagic shock on an already depleted cancer victim. Full "correction" of the victim's hypoascorbemia may require instituting a preoperative. operative, and postoperative regime at much higher levels. Additional research on a regime of this sort may uncover possibilities for survival and cure far beyond today's hopes.
Use of Ascorbic Acid in Cancer Therapy
Present-day cancer therapy thus virtually ignores the potential of ascorbic acid as a biochemical stress combatant, a detoxicant, an anticarcinogenic agent, a means for maintaining homeostasis, and a mechanism for improving the well-being and survival of the patient.
During the past forty years there have been many papers published in the medical literature in which ascorbic acid has been used for cancer therapy. But no one in all this time has consistently used ascorbic acid in the large doses which may be required to demonstrate a therapeutic effect. There has never been a well-planned program to test ascorbic acid in cancer therapy and no one has used more than a gram or, at most, several grams a day (except in one case, discussed later).
Deucher (4), in 1940, used up to 4 grams of ascorbic acid a day for several days in treating his cancer patients and found it had a remarkably favorable effect on their general condition and increased their tolerance to X rays. On the other hand, Szenes (4), in 1942, stated that the administration of ascorbic acid is contraindicated in tumor patients because it intensifies tumor growth.
It was also use in combination with vitamin A, which only further complicated the picture, in a series of tests. Von Wendt, in 1949, 1950, and 1951, and Huber, in 1953, used 2 grams of ascorbic acid a day combined with large doses of vitamin A and reported favorable effects. Schneider, in 1954, 1955, and 1956, also used ascorbic acid, 1 gram daily in combination with vitamin A and found it "arrested" cancers and that it was more useful against epitheliomas than against sarcomas (6).
Of interest also are three papers by McCormick (7), in 1954, 1959,and 1963, in which he postulates the theory that the factor which preconditions the body to the development of cancer is the degenerative changes caused by continued low levels of ascorbic acid in the body. He gives evidence to support his hypothesis and states, "We maintain that the degree of malignancy is determined inversely by the degree of connective tissue resistance, which in turn is dependent upon the adequacy of vitamin C status." McCormick's ideas have never been adequately tested.
Some additional evidence for the support of this hypothesis comes from the work of Goth and Littmann (8), in 1948, who found that cancers most frequently originate in organs whose ascorbic acid levels are below 4.5 mg % and rarely grow in organs containing ascorbic acid above this concentration. Fully corrected individuals should have tissue levels of ascorbic acid in excess of this seemingly critical 4.5 mg %.
Detoxication of Carcinogens
Another piece of research which has not been properly followed through was reported by Warren (9), in 1943, who showed that certain carcinogens, anthracene, and 3:4-benzpyrene (the type of carcinogen in tobacco smoke), are susceptible to oxidation in the presence of ascorbic acid. In the oxidized form they are no longer carcinogenic.
Here is a possible means for preventing the induction of cancer after exposure to carcinogens merely by maintaining the necessary levels of ascorbic acid in the exposed tissues. This is an area of research that has been stagnant for two decades, which would have the most important consequences for smokers or city dwellers forced to breathe polluted air, or for others exposed to carcinogens.
Leukemia
Leukemia is a cancerous disease of the blood-forming tissues in which there is an over production of the white blood cells (leukocytes). Different types of leukemia are named after the different varieties of leukocytes involved in the disease process. The over-production of the leukocytes causes, i most cases,a marked rise in the number of white blood cells in the circulating blood.
Research work connecting ascorbic acid, the blood elements, and leukemia was started not long after the discovery of ascorbic acid. Stephen and Hawley (10), in 1936, showed that when the blood was separated into plasma, red blood cells, and white blood cells, there was a 20- to 30-fold concentration of ascorbic acid in the white blood cells.
Hemorrhage, being a symptom of both leukemia and scurvy, caused clinicians to early investigate the use of ascorbic acid in leukemia because of its dramatic effects on hemorrhage in scurvy. Eufinger and Gaehtgens (11), in 1936, reported giving 200 milligrams of ascorbic acid a day and came to the conclusion that it had a normalizing influence on the blood picture. Schnetz (11), in 1940, came to the same conclusion: when the leukocytes are high ascorbic acid tends to reduce them, and when they are low it tends to increase them. He used 200 to 900 milligrams a day by injection.
Here is a marked example of the ancient mammalian mechanism of ascorbic acid homeostasis.
In 1936, Plum and Thomsen (12), injecting 200 milligrams of ascorbic acid a day, obtained remissions in two cases of myeloid leukemia, and Heinild and Schiedt (12), using two 100-milligram injections daily, obtained uncertain, variable results. Thiele (12), in 1938, using 500 milligrams of ascorbic acid a day by injections, found no effect in chronic myeloid leukemia, while both Palenque (4) and van Nieuwenhuizen (12), in 1943, observed slight decreases in the white blood counts. Such variable and confusing results are typical when submarginal an inadequate dosages are employed.
Vogt, in 1940, in a review of the work conducted on ascorbic acid in leukemia up to that time, cited twenty-one references. About the only conclusion he reached was that there were high deficits of ascorbic acid i leukemics. These deficits and the very low blood plasma levels of ascorbic acid in leukemics were confirmed in later papers by Kyhos et al., in 1945, and Waldo and Zipf, in 1955, and yet, in all these years, no one was inspired to get away from these pitifully small doses of ascorbic acid and make some clinical tests with heroic doses (13).
In a leukemic, the biochemical stresses of the disease process has reduced the body stores of ascorbic acid to very low levels. Any ascorbic acid circulating in the blood has been scavenged and locked in the excessive numbers of white blood cells contained in the blood. the plasmas level of ascorbic acid is usually zero or close thereto. A zero level in the blood plasma means that he tissues of the body are not being supplied with this most important metabolite. The ascorbic acid contained in the leukocytes are unavailable for the tissues. The tissues are in a condition of biochemical scurvy and this explains why these depleted tissues are so susceptible to the characteristic hemorrhaging of leukemia and the infections that kill so many of the leukemics. A leukemic is not only suffering from leukemia but also from a bad case of biochemical scurvy. To correct this condition, ascorbic acid has to be administered in sufficiently large doses not only to saturate the excess of white blood cells but to provide adequate spillover into the blood plasma and tissues so that the seriously ill leukemic will be given a fighting chance to combat the disease. This may require the administration of ascorbic acid at the rate of 25 or more grams per day, as noted in the following case of leukemia treated with megascorbic levels of ascorbic acid.
This case history, reported by Greer (14), in 1954, was of a seventy-one-year-old executive of an oil company, who was first seen for alcoholic cirrhosis of the liver and polycythemia (excess of red blood cells); some months earlier, symptoms of chronic myocarditis had appeared. Shortly thereafter, he was hospitalized and passed a large uric acid bladder stone, and a diagnosis of chronic myelogenous leukemia was established. He also had intractable pyorrhea and his remaining 17 teeth were removed at one operation. At this time he started taking ascorbic acid at the rate of 24.5 grams to 42 grams per day, "because he reported he felt much better when he took these large doses." Since the diagnosis of leukemia and the removal of the teeth, "the patient has repeatedly remarked about his feeling of well-being and has continued his vocation as executive of an oil company." On two occasions, at the insistence of his attending physician, he stopped taking the ascorbic acid and both times his spleen and liver enlarged and became tender, his temperature rose to 101o, and he complained of general malaise and fatigue (typical leukemia symptoms). When he started the ascorbic acid again, the symptoms cleared and his temperature became normal within 6 hours. Over a year and a half later the patient had a severe attack of epidemic diarrhea and died of acute cardiac decompensation. At the time of death, the spleen was firm, not tender, and had not enlarged since taking the ascorbic acid. The doctor also reported that "the polycythemia, leukemia, cirrhosis, and the myocarditis had shown no progression: in the year and a half while taking the ascorbic acid. The case history concludes with the statement, "The intake of the huge doses of ascorbic acid appeared essential for the welfare of the patient."
One would believe that the exciting results in this 1954 case would be immediately picked up and explored further by the leukemia groups in the national government or the foundations that are continually asking the public for more research money, but no follow-up work has been found in the medical literature of the past sixteen years. If megascorbic therapy could do so much for an aged leukemic with so many other complications, what could it do for the young, uncomplicated leukemic? The answer to this question could be obtained easily and each day lost may mean more lives wasted. At the present time, millions of dollars are spent in screening all sorts of poisonous chemicals for use in leukemia, while a harmless substance like ascorbic acid, with so much potential, lies around neglected and ignored.
Recent work has brought forward evidence that human leukemia may be caused by a virus. While viruses are known to product cancer like diseases in animals, none have been proved in man. If the cause of human leukemia is eventually shown to be due to a virus, the rationale for the use of megascorbic therapy in leukemia will be further strengthened because it has been shown that ascorbic acid is a potent, wide-spectrum, nontoxic virucide when used at megascorbic dosage levels (see Chapter 13).
16
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AND STROKES
The diseases of the heart and the cardiovascular system are the number one killers of present-day Americans. The reported incidence of these diseases has been rising sharply. A few years ago heart diseases accounted for over 700,000 deaths annually and strokes took another 200,000. The number of cardiovascular deaths among persons under sixty-five (about 240,000) was about as high as deaths from cancer at all ages. Besides death, heart diseases cause widespread illness and disability and impose a multi-billion-dollar burden on the economy each year. In a recent health survey, it was found that of every hundred persons between the ages of eighteen and seventy-nine, thirteen had definite heart disease and twelve more were suspect. Nearly one-quarter of the population, therefore, lives in jeopardy of succumbing to a disease of the heart or circulatory system. The incidence increases with age.
Because our cardiovascular system is so important, let us first look into the equipment with which we are endowed. We have a complicated plumbing arrangement comprising a closed system of interconnected flexible pipes. The system has a dual pumping arrangement combined in one hard-working organ, the heart. The flexible arteries carrying the blood, under pressure, away from the pump are the largest, and subdivide into smaller and smaller vessels until those carrying the blood into the tissues, the capillaries, are microscopic in size. The blood in the tissues is then collected in flexible vessels of increasing diameter, the venules and veins, for its trip back to the pump for another strong push into the arteries. This process goes on twenty-four hours a day for the entire lifetime of the individual.
The pump and the flexible pipes in this system must be rugged to start with and must be in a constant state of self-repair and maintenance to withstand the continual wear and tear of the alternating mechanical stresses of fluid flow. Should any structural weakness in the walls occur or leaks develop anywhere in the closed system, we are in serious trouble with heart disease, strokes, and hemorrhaging.
The main structural element, from which this system is build and which provides the strength, elasticity, and ruggedness is the protein collagen. This protein comprises about one-third of the body's protein content and is the cement substance which holds the tissues and organ together. The synthesis of collagen by the body requires the presence of ascorbic acid. Without ascorbic acid, collagen cannot be produced. If too little ascorbic acid is present during the synthesis of collagen, it will be defective and structurally weak. Ascorbic acid is also required for the maintenance of the integrity of the collagen already synthesized in the continuing process of self-repair and self-maintenance of the tissues and the vascular system.
It is necessary, therefore, to have sufficient ascorbic acid available during fetal life to provide structurally sound collagen for the development of the cardiovascular system and to have sufficient ascorbic acid available during the entire lifetime of the individual to maintain this collagen in the proper state of self-repair. Impaired and structurally weak collagen is the cause of the most distressing symptoms of uncorrected hypoascorbemia (clinical scurvy), the scorbutic bleeding gums, the loose teeth, the capillary bleeding, the reopening of old healed wounds and scars, and the brittle bones. Most of our mammalian relatives, whose livers are continually producing large amounts of ascorbic acid, need never worry about this because they do not develop scurvy.
It is the author's belief that the high incidence of cardio-vascular disease in man is brought on because the greater part of the human population is dependent upon their foodstuffs as a source for their ascorbic acid intake and are thus existing on submarginal levels. These intakes are usually inadequate for the production and maintenance of optimal high-strength collagen over long periods of time. Because the system is subjected to many local ascorbic acid-depleting stresses,an abundant supply of ascorbic acid is demanded, not just "vitamin" levels.
Shortly after the discovery of ascorbic acid in the early 1930s, the intimate association of it with the cardiovascular system was surmised. This resulted in a tremendous amount of research and a considerable body of medical literature.
In 1934, Rinehart nd Mettier (1) found that infected guinea pigs deprived of ascorbic acid developed degenerative lesions of the heart valves and muscles. The changes were strikingly similar to those seen in rheumatic fever. Infected guinea pigs maintained with adequate ascorbic acid did not develop these heart lesions. A year later, Mentenand Kind (2) injected sublethal doses of diphtheria toxin into ascorbic acid-deficient guinea pigs and produced myocardial degeneration and arteriosclerosis of the lungs, liver, spleen, and kidneys. In further tests on guinea pigs with acute or chronic scurvy (3), it was indicated they developed inflammation of their heart valves, myocarditis, and occasional pericarditis.
As early as 1941 (4), it was suspected that inadequate intake of ascorbic acid was a factor in coronary thrombosis due to impaired collagen production, causing capillary rupture and hemorrhage in the arterial walls. Blood plasma ascorbic acid measurements were made in 455 consecutive adult patients admitted to the Ottawa Civic Hospital over a seven-month period and it was found that 56 percent had subnormal levels (below 0.5 mg %) and 81 percent of the coronary patients were in this subnormal range. It was "recommended that patients with coronary artery disease be assured of an adequate vitamin C (ascorbic acid) intake." A 1947 paper (5) showed that inadequate ascorbic acid body levels were not limited to cardiac patients of the lower economic brackets. The scurvy included 556 private patients, of which 123 had organic heart disease. Forty-two percent of all patients, 59 percent of the heart patients, and 70 percent of the coronary thrombotic patients had low plasma levels of ascorbic acid (below 0.5 mg %). Sixty-five percent of the coronary group had dangerously low levels (0.35 mg % or less). Again it was suggested that ascorbic acid be used as an adjunct to the usual methods of treatment, especially in the long-range care in the postinfarctive period.
A provocative series of papers was published by Dr. G. C. Willis and coworkers starting in 1953 that showed the importance of ascorbic acid in the maintenance of the integrity of the arterial walls (the intima). Any factor disturbing ascorbic acid metabolism, either systemically or locally, results in wall injury with subsequent fatlike deposits. In his 1953 paper, Willis (6) concludes that acute or chronic ascorbic acid deficiency in guinea pigs produces atherosclerosis and closely simulates the human form of the disease. Cholesterol feeding interferes with the ascorbic acid metabolism of rabbits, and guinea pigs and intraperitoneal injection of ascorbic acid inhibits the atherosclerosis in cholesterol-fed guinea pigs. Finally he states, "Massive doses of parenteral ascorbic acid may be of therapeutic value in the treatment of arthereosclrosis and the prevention of intimal hemorrhage and thrombosis." In 1954, the Willis group (7) studies the actual progression and regression of atherosclerotic plaques in living patients by a serial X-ray technique Both progression and regression were observed over relatively short periods of time but did not coexist in the same cases during one period of observation. The rationale for ascorbic acid therapy is again outlined and preliminary results of such therapy were encouraging. In 1955, there appeared another paper (8), in which scientists actually examined the ascorbic acid levels in the fresh arteries from cases of sudden death, hospital autopsy material, and cases treated with ascorbic acid for various lengths of time before death. The conclusions reached in this study are so exciting and important that they are quoted in full:
1. A gross and often complete deficiency of ascorbic acid frequently exists in the arteries of apparently well-nourished hospital autopsy subjects. Old age seems to accentuate the deficiency.
2. The ascorbic acid depletion is probably not nutritional but rather related to the stress of the fatal illness.
3. A localized depletion often exists in segments of arteries susceptible to atherosclerosis for reasons of mechanical stress. Adjacent segments, whose mechanical stress is less, tend to have a higher ascorbic acid content and atherosclerosis here is rare.
4. The significance of this ascorbic acid depletion lies in the fact that scurvy in guinea pigs results in the rapid onset of atherosclerosis. Furthermore it has been reported that the aorta can synthesize cholesterol and the incorporation of radioactive acetate into cholesterol in tissues is said to be several times more rapid in tissues depleted of ascorbic acid.
5. Ascorbic acid deficiency in arteries with resulting ground substance depolymerization may account for the release of glucoprotein noted in the blood of subjects with severe atherosclerosis.
6. Preliminary studies suggest that it is possible to replenish the ascorbic acid in arteries by ascorbic acid therapy.
A similar concept was proposed in 1957, by McCormick (9), noting the importance of ascorbic acid deficiency in coronary thrombosis. He summarized his work as follows:
Thrombosis is not in itself a pernicioud development but rather a protective response of the organism designed normally to effect repair of damaged blood vessels by cicatrization. High blood pressure, excessive stretching of blood vessels and deficiency of (ascorbic acid) vitamin C, resulting in rupture and bleeding of the intima at the site of such stress initiate the development of the thrombosis by means of the clotting of the blood,which is also a protective reaction. This multiple protective mechanism should be sustained and controlled by physiological means (vitamin C therapy) rather than suppressed by anticoagulants with their dangerous side effects.
McCormick believed that an optimal body level of ascorbic acid offered the best natural means of effecting healthy new tissue, and claims that the initial intimal hemorrhage, precipitating thrombosis, would not occur if adequate prophylactic use of ascorbic acid were made to maintain the integrity of the cardiovascular system.
There is an extensive body of published research showing the intimate relationship between ascorbic acid and cholesterol metabolisms. In fact, the published research on the subject of the relationship of ascorbic acid to heart disease is so extensive that it is quite impossible to review it adequately and still keep within the bounds of a reasonable size for this chapter.
Cholesterol was identified as a major constituent of the arterial deposit over a century ago (10). As early a 1913 it was demonstrated that feeding cholesterol to rabbits resulted in atheromatous deposits in the aortas (11). In 1953, an intimate relationship between ascorbic acid and the synthesis of cholesterol in guinea pigs was shown by C.G. King and his group (12). Ascorbic acid depravation greatly increased cholesterolsynthesis. This observation was confirmed on guinea pigs fed an atherogenic diet (13). This group found that the greater the deprivation of ascorbic acid, the more the cholesterol accumulated in the tissues. The feeding of cholesterol to rabbits and guinea pigs lowers ascorbic acid levels (14) in the body,and coronary atherosclerosis appears to be in part a possible result of deficient ingestion of ascorbic acid (15). Increased intakes of ascorbic acid bring down cholesterol levels in rabbits (16), guinea pigs (17), rats (18),and humans (19).
Further confirmation of the ability of ascorbic acid to reduce cholesterol levels was reported in 1971 by R.O. Mumma and coworkers (20) and C.R. Spittle (20). Ascorbic acid sulfate was found to be a significant metabolite of ascorbic acid in human urine by E.M. Baker III and coworkers in 2971 (20). Spittle observed that the blood serum levels of cholesterol could be varied by changing the ascorbic acid intake. She suggested "that atherosclerosis is a long-term deficiency (or negative balance) of vitamin C which permits cholesterol levels to build up in the arterial system and results in changes in other fractions of the fats."
A most exciting paper by G.C. Willis (20) appeared in 1957 entitled "the Reversibility of Atherosclerosis." In this study atherosclerosis was induced in guinea pigs by depriving them of ascorbic acid. Some guinea pigs were then given large doses of ascorbic acid and it was found that in these animals the beginning atherosclerotic lesions were rapidly resorbed while the more advanced atherosclerotic plaques on the artery walls took longer. There was a steady decline in the incidence of the lesions in direct proportion to the duration of ascorbic acid therapy. The significance of these observations for man is tremendous -- they open the way to the megascorbic prophylaxis of atherosclerosis -- but they never were tested further.
Naturally occurring arteriosclerosis is found in many different mammals besides man. A recent study (21) showed there is a pronounced difference between atherosclerotic disease in various mammals as compared to various primates, including man. Fatty deposits play a relatively minor role in the naturally occurring lesions observed in the coronary arteries of the dog, cat, elephant, and other lower animals. In some of these animals there seems to be virtually no lipid involvement in the diseased arteries. In the primates, lipid deposition in the arteriosclerotic lesion is more pronounced, and distinct atherosclerotic plaques develop in man. The most significant physiological difference between the dog, cat, elephant, and other lower animals and the group of primates studies and man is that the former group of mammals are able to produce ascorbic acid in their livers in large daily amounts while the primates used in this investigation and man cannot do this. This is just another pertinent observation on the importance of this synthetic liver-enzyme system for the mammals and the vital involvement of ascorbic acid in the genesis of atherosclerosis A similar observation was made in 1961 (22) regarding the response of rats and guinea pigs to the development of atherosclerosis. Rats are known to be resistant to atherosclerotic changes, while guinea pigs are not. Here again the difference between these two species is that the rat is a good producer of ascorbic acid in its iver while the guinea pig, like man, is genetically unable to do so.
Another property of ascorbic acid that has been neglected in the treatment of edema of heart disease is its diuretic properties at high dosage levels. Abnormal retention of water throughout the body was noted in the post mortem examination by Lind in 1753 of patients dying of scurvy. Soon after the discovery of ascorbic acid in 1936 and 1937 (23), its diuretic properties were recognized in spite of the small doses of ascorbic acid employed. Its use in heart failure was suggested in 1938 by Evans (24), who pointed out the need for "an adequate supply of vitamin C for all patients with heart failure." Other papers in the period from 1944 to 1952 indicated its diuretic usefulness (25). Still, even at the present time,it is not being used. In intensive care units for coronaries, ascorbic acid is conspicuous by its absence.
Cerebrovascular Accidents - Strokes
Over 200,000 deaths occur annually from strokes, and another 800,000 persons are totally or partially disabled by them. Major brain hemorrhages or thrombosis account for the sudden demise or total disablement. But of even greater incidence is the slow destruction of neural tissues of the brain by repetitive, small local thrombosis, or capillary rupture, with intimal hemorrhage (little strokes). It has been estimated that there are at least 1,200,000 people in the United States who have suffered one or more of these little strokes. They happen, and most of the time pass unnoticed, with nothing more to indicate their passing than a slight dizziness or nausea. It is only when the summation of these minor brain injuries cause mental or physical deterioration, to a point where it is noticeable by the patient or family, that it becomes evident that something is wrong. By that time, it is too late to do anything about it. What is needed is a prophylactic regime to prevent this situation and forestall little strokes.
In order to maintain the integrity of the vascular system of the brain, ascorbic acid is needed, as it is in any other part of the body except more so. The brain itself requires much ascorbic acid for its own active metabolism and functioning so if one is completely dependent on the submarginal levels of ascorbic acid supplied by foodstuffs,asymptomatic chronic vascular damage results which only becomes evident when a major part gives way and massive hemorrhages or thrombi develop. Suboptimal levels of ascorbic acid not only lead to strokes, but when fresh brain tissue from autopsies on patients dying of cerebral vascular disorders were examined, ascorbic acid was found to be entirely lacking or at extremely low, subnormal levels (26). In a four-year study on the continuous administration of varying amounts of ascorbic acid to thirty-two elderly patients with vascular disease, Gale and Thewlis (27), in 1953, reported six deaths. Four were directly due to heart attacks or cerebral episodes. Of these four, not one had taken more than the low level of 100 milligrams of ascorbic acid daily during the test period. They stated:
Many symptoms of vascular disturbances in the aged suggest that latent scurvy may be a frequent occurrence . . . Extended studies should be made by public health departments and geriatric clinics to determine the effectiveness of vitamins C and P in controlling cardiac and cerebrovascular illness.
How often do we hear this refrain, and yet nothing is ever done?
In spite of the dire need to do something effective in the prevention and therapy of this terrible plague of cardiovascular disease and cerebrovascular episodes, all this provocative and suggestive research has been glossed over and ignored and none of the crucial large-scale tests have ever been made. One possible excuse for this neglect might be that nearly all of the work was done by researchers whose viewpoint was clouded by the narrow confines of the vitamin C hypothesis and who had used inadequate dosage levels of ascorbic acid for maximal therapeutic effects. This should no longer be the case,for the description of the genetic disease hyposascorbemia in man (28) supplies the needed rationale for the megascorbic prophylactic doses which may be required to reduce the incidence of heart disease and for the megascorbic therapeutic doses which may be required to treat heart disease when it occurs.
The crucial tests would include taking a large population of individuals and administering continued long-term (for the rest of their lifetime) megascorbic prophylactic levels of ascorbic acid (about 70 milligrams per kilogram of body weight per day, or about 3 to 5 grams a day in spaced doses for an adult) and then measure the incidence and morbidity of disease at intervals and the increase in healthy lifespan as compared to a similar population on placebos. For heart disease therapy, we need to try megascorbic therapy in emergency coronary care units using doses of possibly 1,000 milligrams per kilogram of body weight per day, intravenously at first, and then working out a dosage schedule as the patient comes out of danger. Similarly, in cerebrovascular accident treatments, megascorbic therapy may introduce a new era in post-episode survival and recovery, and prevention of future strokes by the mere elimination of the localized cerebral scurvy that exists in stroke victims.
All of this provocative and suggestive research, conducted all over the world for the last four decades, indicates that the simple ingestion of 3 to 5 grams of ascorbic acid a day in several spaced doses may be sufficient as a megascorbic prophylactic regime to prevent the high incidence of heart disease and strokes. The potential victims of these diseases may live a healthier life far beyond the time when these diseases would be cutting them down. In acute cases of massive coronary or cerebral hemorrhage, the prompt application of megascorbic therapy in intensive care units would seem to assure survival to those now destined to die because of their severe, uncorrected hypoascorbemia.