Ascorbic Acid Mega Compile 2 2019

2. Fifty Years of Research on Ascorbate and the Genetics of Scurvy: From a Better Flavored Beer To Homo Sapiens Ascorbicus Irwin Stone, D.Sc.

3. INACTIVATION OF POLIOMYELITIS VIRUS IN VITRO BY CRYSTALLINE VITAMIN C (ASCORBIC ACID) BY CLAUS W. JUNGEBLUT, M.D. July 3, 1935 In the course of this work it was observed that the same endocrine secretions (adrenalin, cortin) (4) as well as certain antitoxic sera (5) were frequently capable of inactivating not only poliomyelitisvirus but also diphtheria toxin. When it was furthermore found that an important constituent of the adrenal gland, i.e. vitamin C or ascorbic acid, possessed the power of inactivating diphtheria toxin in vitro and in vivo in extraordinarily small amounts (6) it became an important problem to determine whether or not poliomyelitisvirus is vulnerable, in a like manner, to the injurious effect of this substance. This paper presents experiments bearing on this point. The experimental data described in this report are interesting in several ways. First, they show that extraordinarily small amounts of vitamin C are capable of rendering non-infectious multiple paralytic doses of poliomyelitis virus. Second, they reveal a remarkable similarity in the quantitative aspects of this inactivation when compared with the neutralization of diphtheria toxin by vitamin C. The fact that two such heterogenous substances as diphtheria toxin and poliomyelitis virus, one a lifeless poison and the other a presumably living agent, should prove to be susceptible to the inactivating effect of no less than three highly reducing substances, i.e. adrenalin, cortinand vitamin C, all of which are present in the adrenal gland, seems to us particularly worthy of emphasis since it may serve to provide a common basis for a biochemical explanation of their destruction.

4. Further investigations will have to show whether the neutralization phenomenon observed when certain normal human and animal sera are brought into contact with poliomyelitis virus, is in any way influenced by the presence of vitamin C in the serum; also, whether the natural resistance of certain species of animals to intracerebral injection of this virus shows any correlation with the concentration of vitamin C in the brain or cord. Experiments are now under way to determine whether vitamin C possesses any prophylactic or therapeutic properties in the treatment or prevention of experimental poliomyelitis. SUMMARY AND CONCLUSIONS The experimental evidence presented in this paper shows that multiple paralytic doses of poliomyelitis virus, when mixed with very small amounts of crystalline vitamin C (ascorbic acid), are rendered non-infectiousas determined by intracerebral injection of such mixtures into rhesus monkeys. 4. Jungeblut, C. W., Meyer, K., and Engle, E. T., J. Immunol., 1934, ~/, 43. Zwemer, R. L., and Jungeblut, C. W., Proc. Soc. Exp. Biol. and Med., 1935, 32, 1583. Jungeblut, C. W., and Zwemer, R. L., in preparation. 5. Jungeblut, C. W., J. Immunol., 1934, 27, 17. 6. Harde, E., Compt rend. Acad., 1934,199, 618. Jungeblut, C. W., and Zwemer, R. L., Proc. Soc. Exp. Biol. and Med., 1935, 32, 1229.

5. FURTHER OBSERVATIONS ON VITAMIN C THERAPY IN EXPERIMENTAL POLIOMYELITIS BY CLAUS W. JUNGEBLUT, M.D. June 29, 1937 We have previously presented data to show that the parenteral administration of natural vitamin C during the incubation period of poliomyelitisin experimentally infected monkeys is followed by a distinct change in the severity of the disease (1). It remained also to be determined whether or not synthetic vitamin C possessed resistance-enhancing properties similar to that of the natural preparation. It is therefore evident that the percentage of non-paralytic survivors following treatment with natural vitamin C was about six times as large as that of the untreated controls. In the animals treated with synthetic vitamin C this percentage was only twice that of the controls. In both treated groups the percentage of animals developing atypical paralysis was approximately the same between 5 and 6 times as large as that observed among controls. However the difference between the two treated groups is again clearly demonstrated by the fact that treatment with natural vitamin C had reduced the incidence of typical paralysis by about one-third as compared with the controls More conclusive results are obtained with animals in which vitamin C treatment was not begun until the 5th day of the disease. At this time distinctly larger doses of vitamin C are apparently required to obtain significant results. Thus the percentage of non-paralytic survivors increases progressively from 11.1 per cent (5 rag.) to 20 per cent (25 mg.), and reaches a maximum of 30 per cent when doses of 50 to 100 rag. are used.

6. It would appear, therefore, that the measure of therapeutic success depends upon certain variables which, in order of significance, may be listed as follows: First, the kind of vitamin C; second, the dosage of vitamin C; third, the rapidity of the infection as determined by the amount of virus and type of strain; and fourth, the time of first administration of vitamin C. As a fifth factor, equally as important as the other four, we should mention differences in individual response from monkey to monkey which necessitate running large series of animals if significant results are to be obtained. While our data are still too limited to make deductions certain, it would appear that during the first few days of the infectiondoses of 5 to 25 mg. produce an optimum therapeutic effect and that definitely larger doses, ranging from 50 to 100 mg., are required for treatment which is delayed until shortly before the expected onset of paralytic symptoms. The size of the effective dose of vitamin C therefore seems to be directly proportional to the speed of the infection and the stage at which the infectious process is advanced. From the results of our vitamin C titrations of various monkey tissues it would seem possible that the protected animals may utilize vitamin C more effectively than the unprotected ones (2). Whether the degree of this utilization depends upon an unknown endocrine factor is an open question. The mechanism by which vitamin C accomplishes its therapeutic effectstill remains obscure.

7. Since it is commonly suspected that one of the functions of vitamin C is to regulate the oxidation-reduction potential of cellular respiration (14), it becomes relatively easy to imagine that an increased supply of the vitamin, which has a tendency to diminish during the infection, serves to maintain the oxidation-reduction system of nerve cells at a level at which the oxylabile virus is restrained from intracellular propagation. The Use of Vitamin C as an Antibiotic (1949) Fred R. Klenner – Paper presented at AAN Convention, May 1953 Measleswas singled out more so than the others because of the knowledge that it was a small virus like the one causing poliomyelitis. It was reasonable to assume that if measlescould be controlled then poliomyelitis too, would have a drug that could prevent as well as cure the disease. The Use of vitamin C in measles proved to be a medical curiosity. For the first time a virus infection could be handled as if it were a dog on a leash. In this experiment it was found that 1000mg every four hours, by mouth, would modify the attack. Smaller doses allowed the disease to progress. When 1000mg was given every two hours all evidence of the infection cleared in 48 hours. If the drug was then discontinued for a similar period (48 hours) the above syndrome returned. We observed this off and on picture for 30 days at which time the drug (vitamin C) was given 1000mg every 2 hours around the clock for 4 days. This time the picture cleared and did not return.

8. Unless the virus was completely destroyed, as demonstrated in the experiments with the virus using measles, the infection will again manifest itself after a short incubation period. Small, single doses do not even modify the course of the infection Jungeblut(1937) stated that the parenteral administration of natural vitamin C during the incubation period of poliomyelitisin monkeys is always followed by a distinct change in the severity of the disease; that after the 5th day of the disease LARGER doses are required. He realised, at that early date, that for fast progressing infection such as results from the R.M strain, very large doses must be given; for the Aycock virus with its slower infection potential small amounts of vitamin C would suffice Under certain conditions 1000mg. To 3000mg. per day were by Kyhos et al (1945) to be necessary to keep the body saturated. There is a wide individual variation in the renalthreshold for vitamin C. Many patients receive as much as 1500mg. of vitamin C per day without significant urinary loss (Shaw et al, 1945). All of us have witnessed ‘nose bleeds’ in certain children sick with measles who prior to taking the disease were apparently healthy. Epitaxis(nose bleed) is one of the signs of Scurvy. Is this true Scurvy? I have, many times, stopped nose bleed in children, sick with measles, with one single dose of 2 grams of vit.C Dolldorf (1945) reported that many conditions may be present in the body that call for a greater supply of vitamin C. He lists fever, infection, physical stress, gastrointestinal disorders, diarrhea,anorexia, and vomiting along with many others.

9. Case 1: Measles in a 10-month old baby – 1000 mg – I.M every 4 hours 1000 mg were continued – Baby made an uneventful recovery and was discharged after 60 hours. No measles rash developed. 4 years have now elapsed and there has been no measles. Case 2: A case of virus pneumonia – 4 grams – I.M along with 1000 c.c dextrose 5 in saline solution. 4 hours later, vitamin C resumed with doses ranging from 2 to 4 grams every two to three hours. Vitamin C was continued for 2 weeks; the frequency was cut to every 12 hours, two grams at a dose. The rational of this continued use of vitamin C was to assist the body to clear up the debris in the right lung. It required 3 months to clear the lung by X-ray Case 3: A case of Encephalitis following measles and mumps – 2000 mg I.V . A 2ND injection of 2000 mg was given intravenously and 1000 mg, of “C” prescribed every 2 hours by mouth. The next day was fever-and-symptom free. As a precautionary measure a 3rd 2000 mg, was given with directions to continue the drug by mouth for at least 48 hours. He (8-year old) has experienced no residual pathology as determined by examination 5 years following the episode. (Similar cases seen in the interim have shown more dramatic response when the drug was given by needle every 2 or 4 hours)

10. Case 4: Poliomyelitis(symptoms of photophobia, conjunctivitis, sore throat, back-of-eyes type headache, nausea and vomiting. Two grams (2000mg,) vitamin C intravenously. 2nd injection of 2 grams upon arrival at local hospital then every 4 hours. 6 hours after, neck pain was gone, the headache was completely relieved. Eyes were dry and redness was definitely clearing. Nausea and vomiting disappeared (without receiving any pain medication). Discharged after receiving 24 grams in 48-hour period. Vitamin C was continued by mouth, 1500 mg. every 2 hours taken with citrus fruit. This Schedule was followed for one week after which time a change was made to Vitamin B1 (thiamine), 25 mg. before meals and bed hour, Vitamin B1 was given in view of McCormick (1938-39) theory that inflammatory and degenerative diseases of the Nervous System [are] due to avitaminosis of this particular vitamin. Vitamin B1 in these cases (Polio) should be continued for a period of at least 3 months as nerve tissue is slow in recovering from even mild damage. The usual dose of vitamin C is calculated on the basis of 65 mg. per Kg. of body weight, and given every 2 to 4 hours by needle, Under certain conditions larger single injections can be used to good advantage. In using “C” as an adjuvant in the treatment of infectionscaused by the more common bacteria the single 250 mgmper Kg. of body weight injection behaves like other synergistic drug combinations. Likewise when treating an upper respiratory infection, this one single massive “shot” will precipitate the pathology.

11. Thewlis Clinic (1953) is interesting in this respect: “Upper respiratory tract infections may severely tax the vitamin C reserve. It is usually during or following a cold that patients have epitaxis (nose bleeds) or cough up blood-streaked sputum. Local inflammation and depletionof vitamin Cmay be responsible for this haemorrhagic tendency. On numerous occasions, we have observed a dramatic alleviation of symptoms of a upper respiratory tract infection after an injection of 500 mgm of ascorbic acid (vitamin C)” Vitamin C response when taken by mouth is not predictable. Wright and Lilenfield(1936) reported that the scorbutic state could develop even though the patient was taking large doses of vitamin C by mouth. In the opinion of Musser (1945) poor absorption and equally poor storage are cardinal factors in leading to vitamin C deficiencies. It was our privilege to observe this mechanism in one of our daughters several years ago. She had contracted Chickenpox. Vitamin C was started when the macules first put in their appearance. In spite of the fact she was given 24 grams every 24 hours there was no interruption in the progress of the disease. Itching was intense. One gram administered intravenously stopped the itch within 30 minutes and she went on to peaceful sleep for the next 8 hours. Although feeling fine, a second injection was given at this time, following which there were no new macules and recovery was fast and uneventful. In the past few years we have noted that in Chickenpoxwhen massive injections are employed there [are] no repeating waves of macules, and the usual 7-9 days required for crusting is reduced to less that 24 hrs

12. The antibiotic power of vitamin C can also be augmented by other biochemical fractions. One of these is a colloidal solution of denatured proteolytic enzyme called ‘Protamide’ In HerpesSimplex and Herpes Zoster this “enzyme” proved to be of definitive value, and in Herpes Zoster (Shingles) did influence the dorsal nerve root pain. Of course it’s common knowledge that vitamin C, especially when injected intramuscularly, possesses the same anti-neuritic properties. Vitamin C itself can also be called a ‘cousin’ of the proteolyticenzymes. This suggested that vitamin C and Protamide should be used at the same time. The clinical results justified this assumption. Cures were obtained in from one to three days. Vitamin C was given as usual, but protamide was limited to one ampoule per day. The same ‘improved’ results were obtained in influenzaand definite synergistic action was seen in one case of poliomyelitisin a boy of 10 years.Calciumtoo, is also a good adjuvant especially in treatinginfluenza. In vivo calcium duplicates the chemical behaviour of vitamin C in many respects. From our experience it would seem that the inclusion of at least 10 c.c vial of calcium gluconate or calcium levulinatein the treating of a virus infection is good therapeutics Pathologic changes due to excessive amounts of vitamin C are unknown. Plasma concentrations twenty times normal have been obtained without any ill-effects (Youmans; 1941). We have found that a No.23 G needle 3/4 inch long is ideal for intravenous use and a No.22 G needle one inch long for the intramuscular routes. A needle 1 ½ inches long if the latter is employed in adults

13. The relatively small store of ascorbic acid maintained by the body even under good conditions, the relatively narrow margin between health and pathological changes and the evidence of a considerable incidence to hyporvitaminosis C combine to emphasize the importance of prevention by an adequate diet. Parents must learn that commercial orange drinks which do not contain freshly prepared orange juice are practically free from ascorbic acid. The trend must be away from the carbonated drinks and back to the “old fashiion” citrus fruit juices. If parents will make their children drink as many glasses of citrus fruit each day as they now allow them bottles of carbonated drinks, Polioand diseasein general will rapidly assume a less important role in our lives (See Aspartameand Sodium Fluoride Studies) SUMMARY Vitamin C possesses abilities which are catagorised by its capacity to antagonise many of the pharmacological effects of Histamine. It should be employed with the antihistamine drugs in all allergic states. It is because of this factor that it serves so well in the treatment of acute Rheumatic fever. Aside from this and the virus disease it is of tremendous value in all diseases which an exotoxin is produced. It neutralise al exotoxins. It is directly concerned with antibody formation and this in turn leads to an increase in gamma globulin of the blood serum. It joins with the virus to form a new compound which is destroyed by oxidation. It makes all body cells more permeable which allows entrance of immune factors otherwise denied. It lessens or prevents tissue damage. It serves as a hydrogen transport in cellular respiration. It is the Key to good health.. Don’t lose THIS key for it might lock or unlock your life

14. On the Genetic Etiology of Scurvy - Irwin Stone Man’s liver lacks the last enzyme in the series needed to convert glucoseto ascorbic acid. The lack of this one enzyme, L-gulonolactone oxidase, completely blocks the synthesis even though the human liver contains the other intermediate enzymes in the series (Chatterjeeet al.,1961). The loss of the gene for the synthesis of the active enzyme, L-gulonolactone oxidase, probably took place in some remote Primate ancestor of Man by a conditional lethal mutation (Gluecksohn-Waelsch, 1963), possibly some fifty million years ago. It may be possible to better pinpoint where in time this mutation occurred if the author’s suggestion for examining various members of the Primate order for this enzyme system, is followed (Stone, 1965). The reason that this unfavorable mutation did not eradicate the mutated animals was the presence of small amounts of ascorbic acid in their available foodstuffs, adequate to insure their survival.

15. Man has suffered from this genetic defect throughout his entire existence and has been absolutely dependent upon his food supply to provide him with marginal amounts of this important physiological substance that his liver fails to synthesize. He was never able to obtain in his foods amounts of ascorbic acid that his liver should have been producing, if we judge this by the amounts synthesized by another mammal, the rat, endowed with the complete enzyme system. The unstressed normal rat synthesizes ascorbic acid at the rate of 70 mg per Kg. of body weight per day (Salomon and Stubbs, 1961) and the stressed rat increases this to 215 mg. per Kg. per day (Conneyet al.,1961). This is equivalent to the production of 4.9 to 15.0 gm. of ascorbic acid per day calculated to the 70 Kg. weight of an adult human. Because of the meager amounts of the unstable ascorbic acid in foods, it is just physically impossible to ingest enough weight of food material to supply these gram quantities of ascorbic acid. Bourne (1949) also suggested that the currently recommended mg. per day intakes may be wide of the optimal amount and perhaps should be measured in gm. per day instead. He stated “Perhaps it is normal for our blood and tissues always to be saturated with the vitamin and for large quantities to be flushing constantly through our urinary system and excreted in our sweat. We may find that continuous doses of vitamin C at this (high) level over a considerable period of time may have pronounced and unequivocal anti-infective action”.

16. Due to the lack of L-gulonolactone oxidase, human is one of the few species not capable of synthesizing the chemically instable ascorbic acid (vitaminC) (Chatterjee et al.1961). This mutational loss, which probably took place in a remote primate ancestor of man (Gluecksohn-Waelsch 1963), causes a dependency on dietary vitamin C sources, but can also be considered as an advantage since ascorbic acid synthesis requires a lot of costly glucose reserves. On average, the human body loses approximately 3% of its vitamin C content per day, which is the percentual daily loss corresponding with the first-order elimination process of vitamin C assuming no intake. This severely limits the disease-free and survival time when subjects are on a diet poor in vitamin C, because this nutrient is a first-line antioxidant acting as a free radical scavenger. The half-life of ascorbic acid is approximately 16 days (Yung et al.1978). In subjects without vitamin C intake, ascorbic acid is no longer detected in blood after 35–40 days (Willet 1998). In 1939, a Harvard surgeon deliberately went on to a C-free diet, and although his blood vitamin level dropped rapidly, it was only after 12 weeks that he began to have feelings of fatigue (Crandon et al. 1940). In a larger British trial during World War II, it took 17–20 weeks for any signs to appear among 120 volunteers (No authors listed 1948). In a later trial using 4 American prisoners, using a purified liquid diet, skin changes appeared after 8–13 weeks and gum changes in 5–27 weeks (Hodges et al. 1969). So, the clinical symptoms due to vitamin C deficiency develop very slowly. In the early history of mankind, a successful mutation took place, which proved to be beneficial in terms of conservation of iron, although it had a major impact on vitamin C stability in vivo (Kamel and ‘Umar 1975).

17. The first four papers describing the genetics of scurvy and the human "inborn error of carbohydrate metabolism", Hypoascorbemia, appeared in the period 1965-1967. Hypoascorbemiais a potentially-fatal genetic liver-enzyme disease, a human birth defect caused by a defective gene in the human gene pool for the synthesis of the active enzyme protein, L-gulonolactone oxidase(GLO). This defective gene appears to be present in 100 percent of the human populationand is the biochemical reason that the human liver is unable to complete the normal stress-related mammalian biochemical conversion of blood sugar, glucose, into ascorbic acid. This is an extremely vital biochemical pathway that proceeds normally and continuously throughout the lifetime of the non-Primate mammals carrying the intact gene for GLO, producing large stress-related daily amounts of ascorbate in the liver, which is funneled directly into the blood stream to give the necessary high blood and tissue levels of ascorbate required for the maintenance of biochemical homeostasis throughout the body. Mammals with the intact gene for GLO also have an inherited biochemical feedback mechanism that increases the liver synthesis of ascorbate in response to various stresses. This feedback mechanism was a great factor in assuring the survival and dominance of the Earth by the mammals during the past 165 million years of evolution. Homo sapiens have paid a very high cost in deaths, disease and misery during the past few million years of evolution in trying to survive without the benefit of the intact gene for GLO. I regard Homo as our most endangered mammal, scheduled for extinction in the 21st Century from overpopulation pollution, unless humans take evolutionary destiny into their own hands and convert themselves into the robust human subspecies, Homo Sapiens Ascorbicus I have been taking about 20 grams of ascorbate a day for many yearswhich is over three hundred times the current RDA, enjoying full health during this time. In my 1983 paper on the effect of megascorbate on Aging and Alzheimer's disease, I cite as shining examples of the value of this daily megascorbic regimen in maintaining a long healthy active, disease-free life: they are my long time friends and colleagues, Albert Szent-Gyorgyi, 91; Linus Pauling, 83; Frederick Klenner, 77; and myself, 77; all still working..

18. The Pioneering Work of William J. McCormick, M.D. McCormick said: “Once the acute febrile or toxic stage of an infectious disease is brought under control by massive ascorbic acid administration, a relatively small maintenance dose of the vitaminwill be adequate in most cases to prevent relapses, just as in fire protection small chemical extinguishers may be adequate to prevent fires in their incipiency, whereas when large fires have developed,water from large high-pressure fire hoses becomes necessary.” McCormick considered vitamin C to be the pivotal therapeutic nutrient “by reason of its chemical action as a reducing agent, and sometimes as an oxidizing agent, vitamin C is also a specific antagonist of chemical and bacterial toxins.” Furthermore, in “Ascorbic Acid as a Chemotherapeutic Agent” he stated: Fifty years ago, McCormick wrote: “The writer has found, in clinical and laboratory research, that the smoking of one cigarette neutralizes in the body approximately 25 mg of ascorbic acid, or the equivalent of the vitamin C content of one average-size orange. On this basis, the ability of the heavy smoker to maintain normal vitamin C status from dietary sources is obviously questionable, and this alone may account for the prevalence of vitamin C deficiency in our modern adult population.” This was quite a statement in 1954

19. The first four papers describing the genetics of scurvy and the human "inborn error of carbohydrate metabolism", Hypoascorbemia, appeared in the period 1965-1967. Hypoascorbemiais a potentially-fatal genetic liver-enzyme disease, a human birth defect caused by a defective gene in the human gene pool for the synthesis of the active enzyme protein, L-gulonolactone oxidase(GLO). This defective gene appears to be present in 100 percent of the human populationand is the biochemical reason that the human liver is unable to complete the normal stress-related mammalian biochemical conversion of blood sugar, glucose, into ascorbic acid. This is an extremely vital biochemical pathway that proceeds normally and continuously throughout the lifetime of the non-Primate mammals carrying the intact gene for GLO, producing large stress-related daily amounts of ascorbate in the liver, which is funneled directly into the blood stream to give the necessary high blood and tissue levels of ascorbate required for the maintenance of biochemical homeostasis throughout the body. Mammals with the intact gene for GLO also have an inherited biochemical feedback mechanism that increases the liver synthesis of ascorbate in response to various stresses. This feedback mechanism was a great factor in assuring the survival and dominance of the Earth by the mammals during the past 165 million years of evolution.

20. Homo sapiens have paid a very high cost in deaths, disease and misery during the past few million years of evolution in trying to survive without the benefit of the intact gene for GLO. I regard Homo as our most endangered mammal, scheduled for extinction in the 21st Century from overpopulation pollution, unless humans take evolutionary destiny into their own hands and convert themselves into the robust human subspecies, Homo Sapiens Ascorbicus I have been taking about 20 grams of ascorbate a day for many yearswhich is over three hundred times the current RDA, enjoying full health during this time. In my 1983 paper on the effect of megascorbate on Aging and Alzheimer's disease, I cite as shining examples of the value of this daily megascorbic regimen in maintaining a long healthy active, disease-free life: they are my long time friends and colleagues, Albert Szent-Gyorgyi, 91; Linus Pauling, 83; Frederick Klenner, 77; and myself, 77; all still working..

22. I started publication of my megascorbicleukemia ideas in 1974. In 1975, as a result of my collaboration with my good friend, Wendell O. Belfield, D.V.M., we wrote a paper showing the need for and the good results obtained with megascorbic therapy in cats and dogs, even though they had the intact gene for GLO. We found that cats and dogs were poor producers of daily ascorbate in their livers. They made about one-fifth the daily amount produced in other mammals with the intact gene for GLO. For many years, Wendellhad been independently using Megascorbicswith great success in canine distemper (viral encephalitis) and in hip dysplasia in large dogs. He also recently megascorbicallysolved the problem of cat leukemia, the number one killer of pet cats. He, like his counterparts in human medicine, has had his problems with the veterinary medical establishment. His two books on dogs (1981) and cats(1983) are classics in maintaining these pets in good health.

23. Clinical Guide to the Use of Vitamin C - The Clinical Experiences of Frederick R. Klenner, M.D. abbreviated, sumarized and annotated by Lendon H. Smith, M.D. 2233 SW Market Street, Portland, Oregon 97201 What follows is a review, and abbreviation, a summary and a critique of the 27 scientific papers he (Fredrick Klenner) wrote. In the light of the recent developments and research in the use of Vitamin C, it is essential that the roots of its usage be reviewed. Briefly, Vitamin C does attenuate most virus infections by aiding the production of interferon, controls many cancers, relieves some depression, modifies much pain and changes the course of many diseases, like multiple sclerosis, amyotrophic lateral sclerosis, spider bites, the bites of poisonous insects and reptiles. The watchword is, “If in doubt, give Vitamin C.” He inspired Linus Pauling and Irwin Stone to expand the research on the great benefits of Vitamin C. Dr. Klenner died in 1984 General Remarks He believed in the healing power of nature, but believed that natural remedies could enhance that power and were safer and usualiy more effective than drugs. Hippocrates said, “Of several remedies the physician should choose the least sensational”. Vitamin C fills that criterion. In 1948, he published his first paper on the use of large doses of Vitamin C in the treatment of virus diseases. In 1960, he realized, “Every head cold must be considered as a probable source of brain pathology.” Hold on to this thought; it is significant for the understanding of diseases like multiple sclerosis. He also felt—as do Archie Kalikarinosand Glen Dettman of Australia—that the dreaded Sudden Infant Death Syndrome was basically a Vitamin C deficiency. His maxim: the patient should “get large doses of Vitamin C in all pathological conditions while the physician ponders the diagnosis.”

24. We have misled ourselves with the mistaken notion that all C was supposed to do was keep us from scurvy. If, however, we base our needs on the amounts other mammals manufacture with their intact enzyme it comes to 2-4 grams daily in the unstressed condition. Under stress 70 kg of rats make 15 grams of C. [Burns; Salomon; Conney] Can’t we accept the fact that we all have a genetic deficiency of the enzyme, L-gulonolactone oxidase and have to take Vitamin C for health, even for life? [Burns,1959] Irwin Stone calls this human genetic lack, this inability, hypoascorbemia. The point that Dr. Klenner is making: “The physiological requirements in man are no different from other mammals capable of carrying out this syntheses.” If one is anemic due to poor iron intake, is it cheating to swallow iron tablets for a while? If you are hypoascorbemic because you cannot manufacture Vitamin C from sugar, extra glucose in your diet will not help, you need to take Vitamin C (ascorbic acid). He reports that one of the Pilgrim Fathers wrote to a friend in England in 1621: “Bring juice of lemon, and take it fasting. It is of good use.” Scurvy develops slowly. Crandon (in 1940) found that the Vitamin C level of the blood plasma fell to zero for 90 days before there was obvious clinical evidence and that this was as long as *132 days before the first signs appeared. (*20 weeks is 140 days total)

25. It works as an oxidizing agent massive amounts, i.e., 5-150 grams, intravenously, for certain pathological conditions, if allowed to run in rapidly (20 gauge needle), acts as a “Flash Oxidizer” and may correct the condition in minutes. It can be a reducing agent. It neutralized toxins, viruses and histamine. The more serious the condition, the more C is required. It appears that Vitamin C acts as a reducing agent, an oxidizing agent, an anticlotting agent, an antihistamine, and as an anti-infective agent. He summarized the function of C in poliomyelitis: 1. Virus destruction. 2. Dehydrates the brain and the spinal cord safely. 3. Supports and normalized the stressed adrenal glands. 4. It preserves the lining of the central canal and maintains more regular spacing and less crowding of ependymal cells (surface cells of the spinal cord). Ascorbic acid enters all cells. It “proceeds to take up the protein coats being manufactured by the virus nucleic acid, thus preventing the assembly of new virus units.” Cells expand, rupture and die, but there is no virus particles available to enter and infect new cells. If a virus has invaded a cell, the Vitamin C contributes to its breakdown to adenosine deaminase, which convertsadenosine to inosine. Purinesare formed which are catabolized (broken down) andcannot be used to make more virus nucleic acid. Viral nucleic acid has a protein coat which protects this parasite as it rides the bloodor lymph highwayto gain specific cell entry. [Larson] it is possible that if the ascorbic acid can remove that protective protein coat in the blood stream or in the cells, the white cell phagocytes and immune globulin could then neutralize these vulnerablevirus particles. I like this from Dr. Klenner: “Ascorbic acid also joins with the available virus protein, making a new macromolecule which acts as the repressor factor.” (interferon?) Multiplication of new virus bodies is inhibited.

26. He summarizes the study of Lojkin, (1937), who discovered the inactivation of one virus was due to a specific intermediate product formed in the course of the oxidation of C but needed the stimulation of copper ions. It is a peroxideand is decomposed as rapidly as it is formed. This study indicates why Vitamin C works better in the body and not the test tube. Every function of the body requires enzymes, some vitamins and some minerals to act as coenzymes. If enough Vitamin C is supplied, the enzyme system that breaks down invading viruses and bacteria, will be able to do its job properly. Quote: “Unless the white blood cells are saturated with ascorbic acid, they are like soldiers without bullets.”

27. The Treatment of Poliomyelitisand Other Virus Diseases with Vitamin C Fred R. Klenner, M.D., Reidsville, North Carolina, July 1949 Poliomyelitisis in most instances an acute febrile disease of sudden onset, with symptoms of a systemic infection which either abruptly abort or develop to hyperesthesia, asymmetry of reflexes and flaccid paralysis or palsies of muscle groups Only slight contact between the carrier of the virus and the susceptible person suffices in some cases for the transfer of the causative organism. In this respect and also in that the virus can be demonstrated in the nasal washings as early as six days before onset of symptoms, poliomyelitis resembles measles. We never have an epidemic of poliomyelitis preceding an epidemic of measles; the opposite is frequently true. Transmission(Brodie, 1934) is by means of droplets from the mucous membrane of the upper respiratory tract. Experiments show the cerebral cortex to be the most unsatisfactory site for growth, that large amounts of the virusplaced in this area are apt to disappear in a short time. Observations in monkeys and in man show that the anterior horn cells, particularly those of the lumbar cord, are the most favourable sites for proliferation of the virus.

28. The viruscan make a direct assault through the olfactory bulb, to the brain, medullaand spinal cord. The virus can enter the blood stream directly or through the lymph channels. Following damage to the natural protective barrier, the choroid plexus, it can make its way to the central nervous system, or it can be excreted back onto the nasal mucous membrane where it will pick up the direct route of the olfactory bulb. Since there is always a period of septicaemiain the first few days of poliomyelitis, it might be that this is the all-important route and that the virus is grown on a living tissue, the blood, and then is deposited out on the surface of the olfactory bulb. From this we conclude that the time to destroy the virus is during this incubation period which varies more with virulence and power of multiplication than with size of initial dose. Poliomyelitisin man is always more severe if exercise is taken at time of the infection. Also, that, by the acceleration of the blood flow caused by greater oxygen demand in physical effort, a marked increase in the percentage of the virus deposited on the nasal mucosa would result. Heaslip found a definite relationship between the severity of the infection and the level of vitamin C nutrition. It is consistent with accepted physiological action of vitamin C to expect and anti-edema effect in any given affected area. It is worthy of note that bacterial toxins can cause losses of from 50 to 85 per cent of thevitamin C normally contained in the adrenals. Jungeblut's investigations seemed to justify the conclusion that vitamin Cwas the "antibiotic" that would destroy the virus organism.

29. Diphtheriacan be cured in man by the administration of massive frequent doses of hexuronic acid(vitamin C) given intravenously and/or intramuscularly. To the syntheticdrug, by mouth, there is little response, even when 1000 to 2000 mg. is used every two hours. The only disadvantage of the ascorbic acid therapy is the inconvenience of the multiple injections. This concept of the action of vitamin C against certain toxinshas led to treating other diseases producing exotoxins. With the work of Kligler, Warburg and others who believed that the detoxification effected by hexuronic acid is brought about by a direct combination of the vitamin with the toxinor virus, this followed by oxidation of the new compound which destroys both the virus or toxin and the vitamin. Borsooket al. decided that the main chemical action of ascorbic acid is as a powerful reducing agent, and the virus causing poliomyelitisis known to be susceptible to the oxidizing action of various agents. It is in point here to remark that vitamin C is an integral part of the oxidation-reduction system of the body, thus playing a definite part in natural resistance. (1) Flexner and Amosshad warned that "simple lumbar puncture attended with even very slight hemorrhage opens the way for the passage of the virus from the blood into the central nervous system and thus promotes infection."

30. In herpes zoster 2000 to 3000 mg. of vitamin C was given every 12 hours, this supplemented by 3 000 mg. in fruit juice by mouth every two hours. Eight cases were treated in this series, all of adults. Seven experienced cessation of pain within two hours of the first injection and remained so without the use of any other analgesic medication. Seven of these cases showed drying of the vesicles within 24 hours and were clear of lesions within 72 hours. They received from five to seven injections In several cases 10 mg. of riboflavin (vitamin b3) by mouth t.i.d. in conjunction with the vitamin C injectionsappeared to cause faster healing. Chickenpoxgave equally good response, the vesicles responding in the same manner as did those ofherpes. These vesicles were crusted after the first 24 hours, and the patient well in three to four cays. We interpreted this similarity of response in these three diseases to suggest that the viruses responsible were closely related to one another. The response ofvirus encephalitis to ascorbic acid therapy was dramatic. Six cases of virus encephalitis were treated and cured with vitamin C injections. Two cases were associated with virus pneumonia; one followed chickenpox, one mumps, one measles and one a combination of measles and mumps. In the case that followed themeasles-mumps complex, definite evidence was found to confirm the belief that massive, frequent injections are necessary in treating virus infections with vitamin C.

31. Whenever a patient presented a mixed-virus infection, such as receding mumps and developing measles, it was found that double the calculated dose of vitamin C was necessary to obtain the usual results A second boy, aged 11, was allowed to develop mumps to the point of maximum swelling without any therapy, then given vitamin C, 1000 mg. intramuscularly, every two to four hours. This lad was entirely well in 48 hours. In using vitamin C as an antibiotic no factor of toxicity need be considered. To confirm this observation 200 consecutive hospital patients were given ascorbic acid, 500 to 1000 mg. every four to six hours, for five to ten days. One volunteer received 100,000 mg. in a 12-day period. It must be remembered that 90 per cent of these patients did not have a virus infection to assist in destroying the vitamin. In no instance did examination of the blood or urine indicate any toxic reaction, and at no time were there any clinical manifestations of a reaction to the drug. When vitamin C was given by mouth one per cent of these patients vomited shortly after taking the drug. In half of these cases the vomiting was controlled by increasing the carbohydrate content of the mixture. This reaction was not interpreted as representing a toxic manifestation; rather it was thought to be due to a hypersensitive gastric mucosa. The dose was reduced from 1000to 100 mg. in young children showing this complex; vomiting occurred as before. However, in these same patients administration of massive, frequent doses of vitamin C by needle affected a cure of the infection without causing vomiting

32. Massive doses of Vitamin C destroys A cow is valuable to a farmer not only for her ability to produce milk, but also as a source for organic fertiliser. 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 fibres and bundles in tissues of mesenchymal origin; but, also, because of its function as a reducing agent or the precursor of such response. In this latter capacity, it fulfils the requirements of an antibiotic. A striking phenomenon of vitamin C is the similarity of response, whether to correct pathogenic processes due to deficiency of this compound, acting as a vitamin, or to destroy the ferments of micro-organisms, acting as an antibiotic. Cases 5 and 6 are of pulmonary virus infection. 31 grams (31,000 mg) 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 (255 mgm. Per Kg 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 the boy. 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 ++. 26 grams (26,000 mg.) was given IV to this patient in a 44 hour period. A point of great interest was that at subsequent examinations the urine was consistently negative for sugar. The course in these cases emphasises 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 tissue..

34. In poliomyelitisvitamin C performs three important functions: 1) It destroys the virus2) acting as a 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 response excited by the virus (interleukin release), acts as a haemostat to cut-off the blood supply to the anterior horn cells. This compression of their vessels denies to the horn cellsthe essentials for function, for life even. The paralysis which complicates acute poliomyelitis appears to be due to a vitamin B1 avitaminosis. Vitamin C, by removing edemafluid, relieves from pressure these vessels that supply nutrient to the horn cells, thus allowing the normal complement of vitamin B1 to reach these cells. (special note: Vitamin B1 (Thiamine) and reducing potential for Paralysis/Palsy/flaccid limbs Magnesium sulfate compress on injection sites alleviates pain and swelling IV push speeds need careful monitoring due to syncope or fainting –slower IV push) That the adrenal glands and vitamin C are closely allied in the defence of the body has been proven by experimentation and by autopsy. In normal people, any excess of vitamin C is excreted in the urine. In people suffering with an acute infection, particularly virus infection, vitamin C is not only absent from the urine, but it is also missing from the blood serum. This is true even when moderate amounts are given intravenously.

35. At this 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 bloodwill be removed and abnormal amounts of free adrenalin will disappear from the blood stream. Following this 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. (*As a result of avitaminosis C, liver glycogen is mobilized – glycogenlysis; and further storing of sugar in the liver is prevented – glycogenesis. 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) Loijkin (1937), studying the various phases of the inactivationof crystaline tobacco mosaic virus by L-Ascorbic Acid, suggested that the action was not due to reduced vitamin C, nor to the irreversibly oxidised dehydroascorbic acid. Loijkin 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-catalysed oxidation of vitamin C. 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

36. Ascorbic Acid in Chronic Psychiatric Patients — A Controlled Trial G. MILNER, M.B., Ch.B. Registrar in Psychiatry, The Towers Hospital, Leicester British Journal of Psychiatry, 1963, Volume 109, pp. 294-299 Anxietyand excitement have been shown by Maas (1961) to increase the rate of breakdown of ascorbic acid, and in schizophrenics this process may be exaggerated by an abnormality of adrenaline metabolism (Briggs, 1962). Schizophrenics receiving “adequate” dietary amounts of vitamin C, as judged by the requirements of the normal population, are commonly found to have low blood ascorbate levels The human organism depends on external sources for its supply of vitamin C, a daily intake of about 30—100 mg. being adequate for normal subjects (M.R.C. Report, 1948; McIntosh, 1959). Stress, anxietyand excitement accelerate the depletion of ascorbic acid, and the results of this trial indicate that these chronic psychiatric patients were suffering from subscurvy. Especially significant was the improvement in the depressed state of the patients.  Harris and Ray (1935) claimed that patients with scurvy(Cancer: sic) or on the borderline of scurvy, required 7 to 10 days for saturation. Normal subjects can be saturated with the vitamin within 24—48, hours, by giving them 1 Gram of the vitamin per day. The suggestion from the results is that saturation with vitamin C has brought about an improvement in overall personality functioning.  If the signs of development of cancer and scurvy are similar, could they be fundamentally the same disease under different names?

37. Ascorbic Acid in Chronic Psychiatric Patients — A Controlled Trial By G. MILNER, M.B., Ch.B.1963 Registrar in Psychiatry, The Towers Hospit al, Leicester The suggestion from the results is that saturation with vitamin C has brought about an improvement in overall personality functioning. Conversely, the psychological and physical improvement shown by these long-stay psychiatricpatients after saturation with ascorbic acid indicates that their diet has been unsatisfactorily low in vitamin C content. This had led to a deficiency state— subscurvy—having quite definite psychiatric symptoms, the most important of which are marked depression and irritability SUMMARY (1) A controlled, blind trial of ascorbic acid saturation, involving 40 male, chronic psychiatric patients, is described. (2) Standardized (objective and subjective) psychological techniques were used to assess changes dependent upon ascorbic acid intake. (3) A clinical state of subscurvy was found in these patients. (4) Psychiatric patients are shown to have an unusually high demand for ascorbic acid. (5) Statistically significant improvement in the depressive, manic and paranoid symptom-complexes, together with an improvement in overall personality functioning, was obtained following saturation with ascorbic acid. (6) It is suggested that chronic psychiatric patients would benefit from the administration of ascorbic acid.

38. INDIVIDUALITY IN VITAMIN C NEEDS BY ROGER J. WILLIAMS AND GARY DEASON Read before the Academy, April 26, 1967 Does high variability of vitamin C needs really exist to a significant degree in the human population? We have sought to help answer this question by determining the incidence of such variation in guinea pigs. Individual human needs vary greatly; intakes of vitamin C which may be regarded as safe for the average person may be far below what is necessary to prevent deficiency in some individuals. In particular circumstances, back injury for example, an individual may benefit from large doses because the presence of an abundant supply of vitamin C speeds the building of supportive tissue necessary for healing.

39. Why extreme variation exists is a subject for speculation. We suspect from our experiments and other observations that guinea pigs, monkeys, and human beings may have varying abilities hitherto undetected to produce ascorbic acid endogenously but unlike other mammals cannot produce it fast enough to maintain health.

40. Observations on the dose and administration of Ascorbic Acid when employed beyond the range of a Vitamin in Human Pathology, 1971 Adenovrisuesand Vitamin C The simple structure characteristic of tobacco mosaic virus was soon found to be a basic property of human viruses such as coxsackie virus(which I believe to be the cause of Multiple Sclerosis), Echoviruses and polioviruses – they all contain only ribonucleic acid and protein. There exists minor variations. Adenovirusescontain deoxyribonucleic acid(DNA) and protein. Other viruses such as that causing influenzacontain added lipid and polysaccharides. Deoxyribonucleic acid is used to program the large viruses, like mumps, ribonucleic acid is used to program the small viruses, like measles. The role of the protein coat is to protect the parasitic but unstable nucleic acid as it rides the “blood highway” or “lymphatic system” to gain specific cell entry. Pure viral nucleic acid without its protein coat can be inactivated by constituents of normal blood Bakay (24) reported that the permeability of the blood-brain barrier can be changed by introducing toxic agents into the blood circulation. Chambers and Zweifach(25) emphasized the importance of the intracellular cement of the capillary wall in regulating permeability of the blood vessels of the Central Nervous System (CNS). In this syndrome (Encephalitis) the toxic substance is an adenovirus. Ascorbic Acid will repair and maintain integrity of the capillary wall.

41. Klasson (32) although limiting the amount of ascorbic acid to a dose range of 300 mg. to 2000 mg. daily, in divided doses, found that it hastened the healing of wounds (burns) by producing healthy granulation tissue and also that it reduced local edema. He rationalised that ascorbic acid used locally as a 2%-3% dressing possessed astringent properties similar to hydrogen peroxide. He also reported that antibiotic therapy was rarely necessary. The Ascorbic Acid kidney stone story is a myth. Methylene Blue will dissolve calcium Oxalate stones giving 65 mg orally 2 to 3 times daily (Dr. M.J. Vernon Smith: Med. World News, December 4, 1970) It is demonstrated principle that the production of histamine and other end products from deaminized cell proteins released by injury to cells are a cause of shock. The clinical value of ascorbic acid in combating shock is explained when we realise that the deaminizing enzymes from the damaged cells are inhibited by vitamin C (42) It has been shown by Chambers and Pollock (43) that mechanical damage to a cell results in pH changes which reverse the cell enzymes from constructive to destructive. The pH changes spread to other cells. This destructive activity releases histamine, a major shock-producing substance, The presence of vitamin C inhibits this enzyme transition into the destructive phase. Clark and Rossiter(44) reported that conditions of shock and stress cause depletion of the ascorbic acid content of the plasma. As with the virus bodies, ascorbic acid also joins with the protein factor of these toxins effecting quick destruction. The answer to these emergencies is simple. Large amounts of ascorbic acid 350 mg to 700 mg per Kg. body weight given intravenously. Ascorbic acid can be given intramuscularly in amounts up to 2 grams at one site.

42. Large doses of intravenous “vitamin C” has a striking influence on the course of mononucleosis. In one patient who was given the last rites of her church, the girls’ mother took things into her own hands when the attending physician refused to give ascorbic acid. In each bottle of intravenous fluids she would quickly “tap in” 20 to 30 grams of vitamin C. The patient made an uneventful recovery. Her mother has her B.S in Nursing and has been a long-time advocate of massive doses of vitamin C. In Malignancy At least one research team has demonstrated that in Cancer, all available “C” is mobilised at the site of the malignancy. Lauber and Rosenfieldreported that “C” is mobilised from the tissues of the body and selectively concentrated in traumatised areas, Schlegel (from Tulane University)found that even a dose of 1.5 grams a day, by mouth, would prevent bladder cancer. He and biochemist Pipkinhave been able to demonstrate that in the presence of ascorbic acid, carcinogenic metabolites will not develop in the urine. They suggest that spontaneous tumour formation is the result of faulty tryptophan metabolism while urine is retained in the bladder. Schlegel termed ascorbic acid “an Anticancer vitamin” Along this line, Glick and Hosoda(51) reported on work by Von Numers and Petterssonthat the depletion of Mast Cells from guinea pigs skin was due to ascorbic acid deficiency. The possibilities indicated are that vitamin C is necessary either directly or indirectly for formation of Mast Cells, or for their maintenance once formed, or both. Ascorbic acid will control myelocyticleukemiaprovided 25 to 30 grams are taken orally each day

43. In arthritisat least 10 grams daily and those taking 15 to 15 grams daily will experience commensurate benefit. Supportive treatment must also be given. Repair of collagenous tissue is dependent of adequate ascorbic acid. Complications of smallpox vaccination are usually handled by adequate oral ascorbic acid. Several times we found it necessary to give the “C” intravenously along with Adenosine. Twenty percent ichthammol used locally with vaccinianecrosumis good psychology. In Herpes Zoster, 2 grams vitamin C intramuscularly and 50 mg Adenosine 5-Monophosphoric acid, aqueous solution, also intramuscularly every 12 hours. In massive “shingles” ascorbic acid should be given by vein.Always as much as can be tolerated. Heavy metal intoxication is also resolved with adequate vitamin C therapy. It has been suggested that ascorbic acid metabolism may be an index of total metabolism and thus serve as a general diagnostic guide. Adults taking at least 10 grams of ascorbic acid daily, and children under 10 at least one gram for each year of life that one will find that the brain will be clearer, the mind more active, the body less wearied and the memory more retentive. 10 grams of vitamin C and 200 mg to 400 mg of vitamin B6, by mouth daily, will shield one frommosquito bites (see Mosquirix, TRS,S/AS01 adjuvant and Vaccines powerpoint)

44. Pregnancy and nursing mothers The simple stress of pregnancy demands supplemental vitamin C. Vitamin C seems especially concerned with mesenchymal tissue. When one considers the demands of the fetus and infant, especially premature babies, it is obvious that high vitamin C intakes are required during pregnancy because this “parasite” will drain available “C” from the mother. Greenblatt (67) reports excellent results following oral administration of vitamin C in the therapy of habitual abortion. The German literature is “stacked” with articles recommending high doses of vitamin C during gestation because they believe that this substance is of great benefit in influencing the health of the mother and in preventing infections. The vital contribution of ascorbic acid to the body tissues can be summed up in the formation and maintenance of normal intercellular material, especially the connective tissue, bones, teeth, and blood vessels. Genetic errors might be prevented if prospective mothers were advised to take 10 grams or more of ascorbic acid daily. It is significant that we found simple stress of pregnancy, a normal physiological process, that equivalent requirements paralleled those found in a rat when under stress. Experiments by King et. Al (68) have shown that the need for supplemental vitamin C begins in the embryo. One can only speculate on what massive therapy would do in all forms of cancer. Manypathologic conditions are cured by giving 5 million to 100,000 million units of penicillin as an intravenous drip over a period of 4 to 6 weeks. How long must we wait for someone to start continuous ascorbic acid drip for 2 months, giving 100 to 300 grams each day, for various malignant conditions?

45. Sodium ascorbate potentiates the growth inhibitory effect of certain agents on neuroblastoma cells in culture, 1979 We report that sodium ascorbate at nonlethal concentrations potentiates the growth inhibitory effect of 5-fluorouracil (5-FUra), bleomycin sulfate, sodium butyrate, cyclic AMP stimulating agents, and x-irradiationon neuroblastoma(NB) cells, RESULTS Effect of Ascorbic Acid and Glutathione. Sodium L-ascorbate at 500 ,ug/ml (2.53 mM) produced >99% lethality in NB cells in culture within 48 hr of treatment, whereas glioma cellsrequired a higher concentration for a similar effect Sodium D-isoascorbate was equally effective, but glutathione, another reducing agent, was more toxic to NB cells than was L- or D-ascorbate DISCUSSION The present study shows that sodium ascorbate produces a cytotoxic effect on NB cells in culture. This confirms previous studies on Ehrlich ascitic carcinoma (9) and chicken embryo fibroblasts and other mammalian cells in culture (10). Thus, in vitro studies support Cameron and Pauling'sreports (3) that vitamin C at high doses exhibits antitumor activity.

46. Because sodium ascorbate inhibits catalase activity in vitro (14), we suggest that this mechanism could become important in those tumor cells that have predominantly catalase activity with little or no peroxidase because of a mutational event. The inhibition of catalase would lead to an accumulation of H202 in such cells and thereby would cause cell death. A complete deficiency of peroxidase in amniotic fluid of pregnant patients with carcinoma of cervix has been noted (18). In addition to the mechanisms leading to an accumulation of H202, other mechanisms such as an inhibition of superoxide dismutase by sodium ascorbate, leading to an accumulation of free radicals, may account for the cytotoxic effect of this agent. The present study also points out the possibility that sodium ascorbate may modulate the effect of various pharmacological agents.(toxins/exotoxins/pathogens/metals)

47. Massive Vitamin C as an Adjunct inMethadoneMaintenanceandDetoxification Jordan Scher, M.D., Harry Rice, M.D., Suck-oo Kim, M.D., Ralph DiCamelli, Ph.D., and Helen O'Connor, R.N.- 1 Presented at the North American Congress on Alcohol and Drug Problems, December 12-18, 1974, San Francisco, California. Vitamin C has been implicated in cellular respiration. It can be oxidized by cytochrome oxidase plus cytochrome C. Dehydroascorbic acid (DHAA) can be reduced by glutathione. Ascorbic acid is important in maintaining SH-activated enzyme systems in their reduced form, and it can act as a hydrogen donor. Ascorbic acid is also involved in carbohydrate metabolism, since scorbutic animals exhibit hyperglycemia, reduced glucose tolerance, low hepatic glycogen content, and are resistant to insulin. Vitamin C is also important in the conversion of folic acid to folinic acid (Goodman and Gilman, 1970). Ascorbic acid is highly concentrated in the cortex and medulla of the adrenals. In the latter location it tends to prevent the oxidation of epinephrine. Under the stress of administering ACTH, there is an increased secretion of adrenocorticosteroids, associated with a rapid decrease in the amount of adrenal ascorbic acid and cholesterol. GOODMAN, L. S., and GILMAN, A.: The Pharmacological Basis of Therapeutics. MacMillan, 4th Ed., p. 1666, 1970

48. Professor Roger Williams, Biochemical Individuality (1956), stated: "Some inbred rats on identical diets excreted eleven times as much urinary phosphate as others . . . some voluntarily consumed consistently sixteen times as much sugar as others . . . some appeared to need about forty times as much vitamin A as others . . . some young guinea pigs required for good growth at least twenty times as much vitamin C as others." E. S. Wagner (1973) who found that despite the fact that the usual claim is that excess vitamin C is readily excreted, only about half appears in the urine. There seems, therefore, to be an unknown reservoir for storing the vitamin with which we have not been familiar before. Should he persist in the chronic misuse of the particular agent, or agents, he may discover a number of additional symptoms beginning to develop as well. There will be a tendency toward acute and chronic exhaustion and tirednessdespite the use of what had previously been a stimulating and relieving agent. There will be a kind of "brain fog," in which will occur problems of retention of recent events and experiences, as well as difficulty in holding, conceiving, and developing ideas, as well as finding and using the right words. There will generally be a progressively reduced level of effective functioning intellectually. There may also develop a number of physical symptoms, including reduced libido, impotence, constipation, cold clammy skin, inefficiency in finer movements of limbs, headaches resembling, imitating, or conceived as migraine, pains of chest, stomach, back, and other body parts.

49. But as in many scientific discoveries, serendipity and accident were to have a role. A friend, perhaps caught up in the then fashionable and still current vitamin faddery, suggested he try some vitamin C, since it might make him feel better on general principles. To his great amazement, the food-allergic individual mentioned above, after scoffing a handful of vitamin C tablets, very shortly noticed a distinct tendency toward alleviation and relief of the exhaustion, brain fog, and tension phenomena. It became possible to overcome for a considerable period of time most, if not all, of the phenomena associated with hisparticular food-allergic coffee addiction problem. In fact, 20-50,000 mg per day was not unusual. Unfortunately, ultimately the protective effect of vitamin C seemed to diminish and be overcome by the more prominent and pervasivefood-allergic symptoms, so that the individual in question was compelled again to completely abstain from the offending agent perhaps for the final time. In a strictly empirical basis we have observed that patients in a state of narcotic withdrawal often show symptoms of irritability, muscular tensions, a tendency toward exhaustion, and other phenomena suggestive of both the food allergic syndrome as well as the magnesium depletion syndrome. Based on the analogy of similar symptoms in the food-allergic patient, it was decided to administer mega-doses of vitamin C with a suggested average of 5,000 mg per day to all methadone-maintained patients

50. For example, many methadone patients will show low-grade irritability, minor and discomforting emotionality, debility, and mood shifts. After vitamin C, these patients will seem to feel an enhanced sense of comfort and well-being. Thesesymptoms, though minimal and annoying, are discovered to be more disturbing than the patients had originally realizedwhen they are relieved through the use of large doses of vitamin C. In fact, they frequently comment that they had not expected the vitamin C to do anything at all, but are quite surprised by the fact that they feel considerably better in a general way when they are using it. Again, based on the analogy of the use of vitamin C on an empirical basis to relieve the acute and chronic symptoms of food allergy otherwise, it was decided that ascorbic acid might well play an alleviating role in the course of detoxification andmethadone withdrawal. Ascorbic acid has a role in oxidative processes, collagen, muscular, vascular, and adrenal metabolism. It was therefore hypothesized that since all of these areas seem to be implicated symptomatically in the process of detoxification, ascorbic acid may very well play a role here, too. Furthermore, it would appear that ascorbic acid seems to have a moderating and tranquillizing influence on behaviorand emotional states, so that it is of great assistance in the management of patients who are in the process of detoxification.