Massive Doses of Vitamin C and the Virus Diseases

Fred R. Klenner, M.D., Reidsville, North Carolina

Presented in the Fifty-second Annual Meeting of the Tri-State Medical Association
of the Carolinas and Virginia, held at Columbia, February 19th and 20th, 1951.

(The Action of Vitamin C)

It has been reported that one of the mold-derived drugs, in addition to being a good antibiotic, is a super-vitamin. Conversely, we argue that vitamin C, besides being an essential vitamin, is a super-antibiotic. Vitamin C in vitro, if maintained at body temperature, inactivates certain toxins at an unbelievable rate. Five parts per thousand of vitamin C with toxins and appropriate controls, incubated at 37°C. for 48 hours showed when tested on mice the minimal lethal dose for the control tubes to be 1/16,000 c.c., while that from the mixture of vitamin C and toxin was only 1/1,000 of a c.c. (Klegler, Guggenheim; Warburg, 1938). In this study the loss of vitamin C in toxin broth and ordinary broth controls followed a constant pattern; the loss, however, was always greater in the toxin broth tube. The difference between the rate of disappearance of vitamin C in toxin and ordinary broth was more striking the greater the concentration of vitamin C. It is, therefore, reasonable to conclude that the degree of neutralization in a virus infection will be in proportion to the concentration of the vitamin and the length of time in which it is employed.

Since it has long been known that the virus organism resembles more the toxins and ferments than the common animate causes of disease, it would seem plausible that the detoxication effected by vitamin C is produced by a direct combination of the vitamin with the toxin and/or virus, this followed by the oxidation of the new compound which destroys both the virus and/or toxin and the vitamin. This destruction of the virus by oxidation has been concurred in by many investigators. Since vitamin C is an integral part of the oxidation-reduction system of the body, its function in the role of an antibiotic becomes intelligible. To appreciate the antagonistic properties of vitamin C against the virus organism and the chemical ferments of exotoxin-producing microörganisms, one must forget its present academic status as a factor essential for life. A cow is valuable to the farmer not only for her ability to produce milk, but also as a source of organic fertilizer. Vitamin C, likewise, is important, not only as a detoxifying agent, as a catalyst aiding cellular respiration by acting as a hydrogen transport, as a catalyst in the assimilation of iron, and as a conservator of collagen fibers and bundles in tissues of mesenchymal origin; but, also, because of its function as a reducing agent or the precursor of such a substance. In this latter capacity it fulfills the requirements of an antibiotic. A striking phenomenon of vitamin C is the similarity of response, whether to correct pathologic processes due to a deficiency of this compound, acting as a vitamin; or to destroy the ferments of microörganisms, acting as an antibiotic.

Within a few hours after institution of adequate vitamin C therapy to correct an avitaminosis, histological evidence of bone improvement is obtainable Fibroblasts begin to form normal connective tissue and capillary buds are invading hemorrhagic areas (Youmans, 1941). Similar is its dramatic antibiotic action, the rule being clear evidence of clinical response within a few hours.

The purpose of this paper is to present clinical proof of such action for this vitamin.

(Case Histories I)

Case 1 is one of premeasles in a ten-months-old baby. The term “premeasles” is adopted to express the syndrome of fever, redness of eyes and throat, catarrh, spasmodic bronchial cough and Koplik spots. Vitamin C, 65 mgm. per Kg. of body weight, was injected intramuscularly every four hours. The fever dropped from 105 to 97.6° F. within 12 hours. All symptoms showed marked clearing. This sudden drop in the fever was thought to be explainable on one of three grounds: 1) Common night drop. 2 ) Due to the antibiotic action of vitamin C. 3) Even if the vitamin C administration had been continued, possibly a moderate rise would have occurred in the late afternoon of the second day, granting a highly virulent organism and a poorly resisting host. To determine which of these deductions was valid, vitamin C was discontinued for a period of eight hours. At this point the rectal temperature was back up to 103.4. Vitamin C therapy was resumed and instead of the expected 8 p.m. climb, the temperature was down to 99.2 (R) eight hours later. The vitamin C injections were continued, the baby made an uneventful recovery and was discharged 60 hours following admission. No measles rash developed. Eighteen months have elapsed since this illness and the child has not had clinical measles. This is not due to the establishment of active immunity but to the lack of a second exposure.

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Case 2 confirms the previous case. This case is that of a 22-months-old infant with symptoms identical with that just described. The same medication was followed; the same clinical course followed. Under parental pressure the child was discharged from the hospital within 36 hours, apparently well. Four days later the child’s brother and sister broke out with measles, which ran the usual course, having received no specific therapy. Seven days later the 22-months child broke out with measles. This time vitamin C was not given. The case was judged as modified.

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The response as observed in measles was characteristic for vitamin C versus virus infections. Two cases of virus pneumonia complicated by encephalitis were so unusual that case histories are given.

Case 3 is that of a colored woman, aged 28, with history (given by a relative) of chills and fever and chest and head cold for 14 days, severe headache for three days. In stupor when first seen, eye lids closed, a white foam at the mouth which she periodically tried to spit out. Temperature by axilla 106.8 Dehydration was much in evidence, breath sounds diminished to absent, tactile fremitus increased over the entire right lung. The sulfa drugs, penicillin and streptomycin with supportive treatment had been exhausted. Four grams of vitamin C was given intravenously along with 1000 c.c. of 5 per cent dextrose in saline solution. Temperature dropped to 100 (Ax.) within 11 hours. Four hours later, vitamin C was resumed — every two to three hours, in dosage of 2 to 4 grams depending upon the response. After 72 hours the patient was awake, sitting up in bed and taking fluids freely by mouth. There was no fever at this time, nor for the remainder of the time in hospital. Vitamin C was continued for a period of two weeks; the frequency was cut to every 12 hours, two grams at a dose. An interesting complication was deafness; her speech gave a, loud, monotonous, bell-sound effect. It was debated whether this was the result of the streptomycin or to the encephalitis. Prostigmin 1:2000, 1 c.c., and vitamin B1, 200 mgm., were given IM twice daily. On the tenth day of treatment the hearing suddenly returned to normal. The x-ray picture of the right lung was one of almost complete consolidation- Although the patient was clinically well of her pneumonia, after 72 hours, the x-ray picture was not completely clear until 90 days later.

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This phenomenon of Nature clearing the debris after killing out the virus organism was observed in five other cases. The time required was in direct proportion to the degree of pulmonary involvement. There is nothing new about this procedure; Nature merely duplicating a stage in the metamorphosis of the frog in getting rid of its tadpole tail.

Case 4, that of a white baby 19 months old, bothered with a little cold for two weeks, not very sick until the last 24 hours, in which the baby had been “running a high fever that could not be broken with aspirin.” Clonic convulsive seizures of the right arm and leg began 12 hours before admission. An undernourished infant, lying rigid in its mother’s arms, skin cold to touch, color cadaver-like, eyes closed, grade -2 mucopurulent nasal discharge, throat red. The temperature was 103.8 (R). Breath and heart sounds practically inaudible. Areas of skin over the back presented an appearance similar to that seen in rigor mortis.

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Vitamin C, 1000 mg. was given IM, repeated every four to six hours. At the first injection the baby did not move and the sensation was like that of sticking an orange. To give rapid external heat, mustard plasters were applied to the anterior and posterior chest in a mixture of one part mustard to three parts flour. A croup teat was set up, the vapor carrying compound tincture benzoin; 50 c.c. of 5 per cent dextrose in saline was given under the skin in the scapular areas. Two hours after the first injection of vitamin C the baby drink 240 c.c. of orange juice, the first food of any type taken by the baby in 24 hours. This was repeated 1½ hours later. At this time there was total paralysis of the right arm and leg. Twelve hours after admission the baby moved its right leg and one hour later grasped a bottle of orange juice with both hands. From this point on the recovery was uneventful. Of secondary importance is the laboratory report of Ascaris lumbricoides ova and hemoglobin 55 per cent.

Cases 5 and 6 are of pulmonary virus infection, (a) in a boy of 14 years, and (b) in a man of 58 years. In the case of the boy the fever curve was of the type showing a fast response to heavy vitamin C injections. The WBC was 4,300, urine sugar ++. Twenty-six grams of vitamin C was given IV to this patient in a 44-hour period.

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In the case of the man, Case 6, the fever decline was after a modified step-ladder fashion. In this instance the amount of vitamin C injected was less than half of the recommended dose. The WBC was 5,850, admission urine sugar +++. Thirty-one grams of vitamin C was injected intravenously over a period of 60 hours. It is to be noted that the same amount of vitamin C (2 grams every four hours) was given to the boy and to the man, disregarding the factor of body weight. Had the man received four or five grams every four hours, or two grams every two hours, his hospital course would probably have followed the same pattern as that of the boy. A point of great interest was that at subsequent examinations the urine was consistently negative for sugar. The course in these cases emphasizes the necessity of administering massive doses of vitamin C at frequent, regular intervals so as to maintain the proper level of this antibiotic in the tissues.

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(Administration of Vitamin C)

The amount of vitamin C for optimal effect will vary greatly with the individual. The type of the disease and the degree of toxemia are important guides in determining the dosage. Although the usual dose of vitamin C is calculated on the basis of 65 mgm. per Kg. of body weight, and given every two to four hours by needle, under certain conditions larger single injections can be used to good advantage. Vitamin C given to a child with measles, mumps or chickenpox will abort or modify the attack, depending upon the intensity of the treatment. If the activity of the pathogen is stopped, the development of active immunity will be interrupted. In handling these particular childhood diseases, when uncomplicated, the treatment should be aimed at modification of the infection as the plan of choice. To accomplish this end vitamin C should be increased to 250 mgm. per Kg. of body weight, and the injection given intramuscularly. It will be necessary, at times, to repeat with half of this amount eight hours later. The vitamin was given in a concentration of 500 mg. per c.c. of solution. Pain was slight and lasted only a few minutes. Procaine, 0.5 to 2 per cent, instilled from a second syringe into the gluteal muscle through a placed needle just before giving the vitamin might solve this problem. The itch of measles and of chickenpox, the occasional vomiting of these illnesses, and the pain of mumps were fully controlled within one hour, when 250 mg./Kg body weight was used. Instead of repeating waves of macules in chickenpox, and the usual seven to nine days required for crusting, following the heavy modifying injection no new eruptions appeared and crusting was present within six hours. Further clinical studies may prove that the routine use of the higher dose (250 mg./Kg. body wt.) replacing the usual (65 mg./Kg. body wt.) is indicated in all virus infections and the results produced may be even more dramatic.

(Vitamin C and Poliomyelitis)

The greatest value of vitamin C in virus infections does not rest with these lesser kinds of diseases, some of which, e.g. measles, can be modified or prevented by the proper use of immune globulin. The value above all others is its positive action against the virus causing poliomyelitis. A report of this usage was published in the official journal of this association in 1949. Many physicians refuse to employ vitamin C in the amounts suggested, simply because it is counter to their fixed ideas of what is reasonable; but it is not against their reason to try some new product being advertised by an alert drug firm. It is difficult for me to reconcile these two attitudes. On the other hand, many physicians who have been willing to try vitamin C against the virus of poliomyelitis have obtained the same striking results as we reported. Scores of letters from practitioners here in the United States and in Canada could be presented in evidence. In some instances doctors have cured their own children of poliomyelitis by giving vitamin C and in other cases doctors themselves have been cured.

In poliomyelitis vitamin C performs three important functions: 1) It destroys the virus; 2) acting as the dehydrator and diuretic of first choice, it removes the edema fluid from the brain and the cord; 3) it preserves the lining of the central canal and maintains more regular spacing and less crowding of the ependymal cells (Altman). The pressure within the bony vault of the central nervous system resulting from the inflammatory process excited by the virus, acts as a haemostat to cut off the blood supply to the anterior horn cells. This compression of their vessels denies to the horn cells the essentials for function, for life even.

(Case Histories II)

It is of more than academic interest to review the findings of McCormick in 50 confirmed cases of poliomyelitis in and around Toronto, Canada, during the epidemic of 1949. This report is that children of families eating brown bread who came down with poliomyelitis did not develop paralysis; whereas in those families eating white bread many of the children having poliomyelitis did develop paralysis. The point here is that brown bread has 28 times more vitamin B1 than does white bread. Obviously, then, the paralysis which complicates acute poliomyelitis appears to be due to a B1 avitaminosis. Vitamin C by removing edema fluid relieves from pressure these vessels that supply nutriment to the horn cells, thus allowing the normal complement of vitamin B1 to reach these cells.

In December, 1949, a 5-year-old white girl, was brought to my office with paralysis of both lower extremities of 4½ days’ duration. The child had been ill for 12 days. There was complete flaccid paralysis of the right leg, 85 per cent paralysis of the left leg. Pain was directed to the knee and to the lumbar back. In hospital the diagnosis of poliomyelitis was confirmed by four consulting physicians. Spinal fluid cells were 82. No medication of any type was given exclusive of vitamin C. Massage was started immediately. The rationale of using early massage had two bases: 1) In the course of general practice patients would give a history of having had poliomyelitis when a child and that their mother rubbed the paralyzed member day and night until function returned. 2) That paralyzed muscle was in profound shock and “artificial respiration” would maintain proper metabolism during the emergency phase. To the first injection of vitamin C there was definite response. After 96 hours the child was moving both legs. The flexion was slow and deliberate. She was discharged from the hospital at this time, vitamin C being continued by mouth — 1000 mg. every two hours with fruit juice for seven days. On the 11th day of treatment the child was walking about the house, but her gait was slow and her posture was poor, being bent forward. Vitamin C was discontinued and vitamin B1 started — 10 mg. before meals and bed hour. Carbonated drinks were encouraged for their sugar content and mild stimulating action. Nineteen days after starting treatment there was complete return of sensory and motor function which has persisted to this date.

A boy of eight years was brought to my office with a history of having had “flu” for a week, and four days previously having developed photophobia, conjunctivitis, sore throat, nausea, vomiting and a back-of-the-eyes type headache of such intensity that adult doses of aspirin had no effect. The boy was either rubbing his neck on the left side or holding his head between his hands, begging for something to relieve his pain. The fever was 104.4 (Ax.). He was tender in the lumbar region and he had a drawing sensation referred to the hamstring attachments at the knee. Two grams of vitamin C was given IV while in the office. He was then sent to the local hospital where he received promptly a second injection of 2 grams of the vitamin, after which it was given every four hours. Six hours after commencing therapy the neck pain was gone, the headache completely relieved, he could tolerate the ceiling light, his eyes were dry and the redness clearing. Nausea and vomiting had disappeared, the fever was down to 100.6 (Ax.), and he was sitting up in bed in a jovial mood while he drank a carbonated beverage. He was discharged from the hospital after receiving 26 grams of the vitamin in a 48-hour period, clinically well. Vitamin C was continued by mouth, 1500 m.g. every two hours with fruit juice for one week, then change was made to vitamin B1, 25 mg. before meals and bed hour. Vitamin B1 in these cases should be continued for a period of no less than three months as nerve tissue is slow in recovering from damage.

In using vitamin C as an antibiotic minor complications were occasionally seen. These fall into six groups:

  1. Diarrhea in two cases. In each instance the preparation contained sodium bisulfate. The enteritis cleared on giving a preparation of vitamin C not containing this salt.
  2. Induration in 42 cases — seen either immediately following the injection (allergy), or delayed. In the latter it was found that the injections were being given too close the surface. Applications of warm magnesium sulfate as a compress gave prompt relief of the pain and swelling. In two of these cases fluctuation ensued and healing was effected by surgical drainage and the application of compresses. The impression in these two cases was that a vein had been opened by the needle. The exudate was dark and both the slide and culture studies were negative for bacteria.
  3. Endothelial irritation in three cases. Acute pain radiated from the site of the injection to the shoulder. In each instance the concentration of the vitamin was one gram to each 5 c.c. solution and the amount given exceeded two grams. After slowing the rate of injection this reaction did not occur.
  4. Venous thrombosis in one case. The concentration was 500 mg. per c.c. solution; the total dose 5 cc. Compressing relieved the pain. The pathology was very similar to that following the use of 50 per cent dextrose solution.
  5. Syncope — In maximum doses given IV a sensation of fainting and dyspnea occurred seven times. Five of these patients were over 55 years of age. The disagreeable symptoms were relieved by slowing the speed of the injections.
  6. Rash — In three cases a pin-point dermatitis occurred, limited to the face and upper third of the torso, identical to that seen in infants taking orange juice. This did not necessitate discontinuance of therapy and cleared spontaneously several days after vitamin C was stopped.

Calcium, in vivo, duplicates the chemical behavior of vitamin C in many respects. Calcium gluconate and calcium lexulinate were used in conjunction with vitamin C therapy in a small series of pulmonary virus infections and in mild cases of influenza. There was a definite synergistic response. Patients witch colds derived most benefit from this combined treatment. Because of its action on cardiac muscle, the use of calcium was limited to adults and the amount injected to two grams per day. One gram administered IV at moderate speed will so slow the heart as in many cases to produce syncope. If the concentration becomes great enough cardiac arrest in a tonically contracted state might result. It is, however, quite possible that, with the proper ionic balance of calcium and vitamin C in the same solution, larger amounts could be given without side effects. The massive dose schedule limits the usefulness of the calcium ion in virus diseases to that of an adjuvant only.

(Of Vitamin C and Hyperglycemia/Diabetes)

In all of the cases of virus infection reviewed in this study one laboratory finding stood out as of great significance. On admission to the hospital the first routine urine examination showed some degree of glycosuria. The pattern of the qualitative Benedict’s reaction was constant enough to postulate that the higher the reading the more severe was the pathology. Repeat urine sugar studies following vitamin C therapy revealed complete clearing. This was true even though fruit juices were forced to tolerance. This finding confirmed the knowledge that interference with the normal physiology of the adrenal glands, either by the toxins produced by microörganisms or by surgery, has a profound influence on metabolism, especially of the carbohydrates. Adrenalin in the blood stream causes hyperglycemia with resulting glycosuria. Adrenalin acts either by stimulation of the sympathetic nervous system or directly via the blood. This action of adrenalin is via the blood only, because the effect, as demonstrated in experimental animals, is still realized after destruction of the cord and sympathetic plexuses and degeneration of the peripheral post-ganglionic fibers (Evans, 1930). The glycosuria found in these cases was not due to a lowering of the threshold for sugar excretion by the kidney, paralleling a phloridzin diabetes, since the carbohydrate mechanism was associated with a hyperglycemia (Zuelzer, 1901, Metzger, 1902, Paten, 1903). Likewise there was no evidence of kidney damage. Albumin was reported negative and the microscopic examination showed no cells or casts. Apparently this is a condition of artificial diabetes mellitus, which would suggest the answer for the diabetic who loses ability to maintain sugar-insulin balance when embarrassed with an acute infection.

The story of a 7-year-old boy may have a lesson. He has been known to be diabetic since the age of four years. Any incident of infection in this lad produced an alarming interference of his sugar-insulin-diet equilibrium. Recently he contracted measles, and as the disease process developed toward its height the urine sugar curve swung sharply upward. From an occasional dose of 5 units regular insulin his requirement rose to 30 units regular insulin, three times each day, while still running a 3- or 4-plus Benedict’s test. (Other forms of insulin proved by trial to be too dangerous.) At the peak of his infection vitamin C was started in a modifying dose of one gram every four hours. His general condition soon improved and in the course of several days he returned to his usual diet-insulin schedule and his usual urine sugar. In patients with diabetes, vitamin C should be discontinued just as soon as the temperature returns to normal. Prolonged use of vitamin C might prove undesirable due to its dehydrating and diuretic powers.

The pathologic process at work here is only compatible with abnormal amounts of adrenalin in the blood stream. It is not a response to an emotional stimulus to the adrenal medulla, since free adrenalin in the circulating blood has a transitory action, being so rapidly oxidized that none gets into the urine. This suggested that the regulator of the adrenalin mechanism had been removed, so that a constant supply of adrenalin would be present in the blood, making possible a concentration sufficiently high to cause constant vasoconstriction. Ritzmarm (1909) found that adrenalin affected carbohydrate metabolism only when this vasoconstriction phase existed. This finding was concurred in by Lusk (1914), who further concluded that this action on blood vessels caused asphyxia of the tissues which tended to increase the acidity of the blood and the tissues. This superimposed acidity further promotes the production of adrenalin hyperglycemia (Peters and Geyelin, 1917). McDannell and Underhill (1919), studying these phenomena in rabbits, found that slight hyperglycemia could be controlled by the administration of sodium carbonate.

The rationale of forcing fruit juices in the old treatment of colds was based on this theory as postulated by Holey et al. (1936) that a highly alkaline urine would have lower amounts of vitamin C than a highly acid urine; the alkaline ash from the organic acids serving to retain the vitamin C in the blood and tissues where Nature had assigned it to guard against the many enemies of the body — the toxins and ferments of bacteria. As a result of avitaminosis C, liver glycogen is mobilized — glycogenolysis; and further storing of sugar in the liver is prevented — glycogenesis (Mackenzie, 1917). To further enhance the hyperglycemia this vasoconstriction brings about a decrease in the pancreatic secretions by lessening the amount of blood passing through the gland (Mann and McLachlan, 1917).

That the adrenal glands and vitamin C are closely allied in the defense of the body has been proven by experimentation and by autopsy. In normal persons any excess of vitamin C is excreted in the urine. In persons suffering with an acute infection, particularly a virus infection, vitamin C is not only absent from the urine but is also missing from the blood serum. This is true even when moderate amounts are given intravenously. These observations on serum were made with a Klett-Summerson photoelectric colorimeter using the method described by Mindlin and Butler. The observations on the urine were conducted according to the instructions of Goldsmith and Ellenger. Horde and Benjamin (1934-35) found the vitamin C fraction of the adrenal glands greatly reduced in monkeys killed or paralyzed by the virus of poliomyelitis. Yavorsky, Almoden and King (1934) reported identical findings in humans having died of various infectious agents.

(Vitamin C in Virus Diseases)

This gives us an important concept of the value of vitamin C in virus diseases. The explanation for the absence of vitamin C in the infectious states is that this agent joins with the toxin and/or virus to form a new compound which is then destroyed by oxidation. Since the body is dependent on food for vitamin C to meet its daily needs, it is obvious that the body tissues would soon be depleted, and we would expect to find evidence of a prescorbutic state in patients who had hypovitaminosis C. In patients seriously ill with a virus invader, the added strain on the capillaries by the application of a tourniquet, even for a few seconds, produced petechial hemorrhages at the site of constriction. Since not all patients thus demonstrated this capillary weakness, all patients ill with a virus infection were investigated by the aid of a petechiomcter. Increased capillary fragility was found to exist in all cases, and the number of petechiae as expressed in centimeters of mercury followed the urine sugar findings. This deficiency syndrome was reversed as the glycosuria cleared, indicating that both were responsive to a proper plasma level for vitamin C.

At this same time the anaerobic conditions in the tissues will be relieved by the catalytic action of vitamin C acting as a gas transport to aid this cellular respiration. The abnormal acidity of the blood and tissues will be removed and abnormal amounts of free adrenalin will disappear from the blood stream. Following this .the constriction of the blood vessels will cease, allowing the liver and pancreatic tissue to return to normal function. Continuance of frequent injections of properly calculated doses of vitamin C will restore the normal physiology of the body. This is not all of the story.

Lojkin (1937), studying the various phases of the inactivation of crystalline tobacco mosaic virus by L-ascorbic acid, suggested that the action was not due to reduced vitamin C nor to the irreversibly oxidized dehydroascorbic acid. Lojkin felt that it was due to a specific intermediate product which is formed in the course of the catalytic auto-oxidation of vitamin C, an action stimulated by the presence of copper ions. This intermediate product must be a peroxide because a peroxide is formed during copper-catalyzed oxidation of vitamin C. This peroxide is decomposed as rapidly as it is formed (Barrow, De Meio, Klemperer, 1935-36). Lyman and associates (1937) confirmed the peroxide theory by observing that the oxygen uptake, beyond that calculated for the reaction ascorbic acid to dehydroascorbic acid, was not due to further oxidation of dehydroascorbic acid to an irreversible oxidation product, because treatment of the oxidized solution with hydrogen sulfide gave complete recovery of the ascorbic acid. These men also found that copper catalysis accelerates not only the reversible oxidation of vitamin C, but also further oxidation of dehydroascorbic acid. This action of the copper ion elucidates the findings that vitamin C in massive, frequent doses works better in the body than in a laboratory test tube.

Hippocrates declared the highest duty of medicine to be to get the patient well. He further declared that, of several remedies physicians should choose the least sensational. Vitamin C would seem to meet both these requirements.

[Note: No detailed references or citations were found to accompany the article- AscorbateWeb ed.]

From Southern Medicine & Surgery, Volume 103, Number 4, April, 1951, pp. 101-107

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