I benefici della vitamina C ad alte dosi

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A pilot study to ascertain
carotid artery status in high
potency vitamin C supplement takers

by Paul Wand, M.D. Neurologist

Atherosclerosis is an insidious disease that begins in youth, but often accelerates as humans age resulting in the manifestation of cardiovascular disease. 1,2,92,93 Vitamin C has been explored as an agent that may pro- tect against atherosclerosis and cardiovascular disease. 3-14 The most significant finding came from a published study involving 11,348 adults over a 10 year period. This study showed that males taking the highest amount of vitamin C had a 45% reduction in all cause mortality, a 22% reduction in cancer incidence and a 42% reduction in heart attack risk.15
An in-depth analysis of published studies on vitamin C and cardiovascular disease, however, makes it difficult for the vitamin C user to extrapolate how the results may apply to them individually. For instance, some studies define high-dose as only 250-500 mg a day of vitamin C, 16-19 whereas the serious vitamin user often consumes between 2,000 and 12,000 mg a day of vitamin C.

To put this into perspective, we conducted a Medline search to evaluate published studies showing the effects on humans of various doses of vitamin C as it related to any parameter of cardiovascular disease risk. This database search covered the time period of January 1, 1990 to April 25, 2000. Table 1 reveals the results of this search as it relates to vitamin C dosage and cardiovascular risk factors.
Table 1. Effects of Vitamin C on Cardiovascular Disease Risk1 study showed favorable response when under 500 mg was administered 53 30 studies showed favorable response when over 500 mg was administered 54-83 3 studies showed no response when under 500 mg was administered 84-86 4 studies showed no response when over 500 mg was administered 87-90

Based on the published literature over the last ten years, it would appear that higher potency vitamin C supplements have some effect in reducing cardiovascular disease risk, whereas potencies lower than 500 mg a day may have no effect. It is important to note that the human studies presented on Table 1 on the following page do not include the published molecular research of Linus Pauling, Matthias Rath and others who are largely responsible for convincing health conscious people that supplementation with greater than 2000 mg a day of vitamin C reduces cardiovascular disease risk. More on the research of Linus Pauling, et al will appea
 

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Why some people take very high doses of vitamin C

An impressive body of research indicates potential health benefits when very high doses of vitamin C are taken over an extended time period. We will define every high dose from here on out as vitamin C intake in excess of 2000 mg a day.

Some of the notable doctors and scientists who have endorsed very high dose vitamin C supplementation include Linus Pauling, Abram Hoffer, Robert Cathcart, Matthias Rath, Irwin Stone, Frederick R. Klenner, Durk Pearson and Sandy Shaw and host of others. These doctors and scientists have authored books and scientific papers that document the benefits of very high dose vitamin C supplementation. In response to these publications, a sub-fraction of the American public has chosen to personally consume 2000 to 12,000 mg a day of vitamin C.

A consistent theory among doctors endorsing very high dose vitamin C supplementation is that it works by specially defined mechanisms to reduce the incidence of artery disease. Linus Pauling, along with his associate Matthias Rath, MD, have published data showing that arteries harden in the absence of sufficient vitamin C. They cite research showing that when the dietary intake of vitamin C is low, collagen production is limited, and arteries tend to become thinner and weaker from wear and tear. Plaque deposits (atherosclerosis) then form to compensate for this weakness. The Pauling/Rath theory, published in both conventional and alternative medicine circles, holds that the root cause of atherosclerotic plaque deposits is a chronic vitamin deficiency. 94-98

Given the credentials of the doctors and scientists advocating very high dose vitamin C supplementation, and the widespread dissemination of their publications in the United States, a sub-fraction of the American population believes that very high dose vitamin C supplementation (along with nutrients such as vitamin E, B6, folate, coenzyme Q10, etc.) will reduce the formation of atherosclerotic plaque and the subsequent development of common forms of cardiovascular disease.
 

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Why conventional doctors doubt the value of vitamin C

The medical profession has traditionally been biased against dietary supplements for a variety of economic and political reasons. As mentioned earlier in this article, there are published studies that show that vitamin C fails to confer a protective effect in reducing cardiovascular disease risk. While the majority of studies (31 favorable studies compared to 7 showing no response) indicate that vitamin C supplements reduce cardiovascular disease risk factors, it appears that the few studies showing no benefit carry great weight in the medical profession. Conventional physicians also tend to be unenlightened about 76 additional human studies published since 1990 showing that vitamin C confers other health benefits such as lowered risks of cancer and other diseases. 99-174

Mainstream organizations have a propensity to look at studies showing no health benefit when vitamin C is consumed in low doses, and then make a public announcement that insufficient evidence exists to recommend widespread vitamin supplementation. The news media is quick to report on studies that show that vitamin C may not protect against cardiovascular disease, without presenting the counter view that not enough vitamin C was consumed in the particular study to provide the expected benefit.

So, despite a rather intensive amount of research that has occurred over the past 10 years, we are still without a scientific consensus as to whether vitamin C is protective against cardiovascular or other diseases, ergo the continued debate over the value of vitamin C supplementation.
The latest controversy

At a meeting of the American Heart Association held on March 2, 2000, a presentation was made of an unpublished trial indicating that those who consumed high amounts of vitamin C supplements had increased carotid intima-media wall thickening over an 18-month time period. 41 The doctors who made this presentation described high amounts of vitamin C as up to 500 mg a day. This presentation contradicts previous published studies showing that vitamin C protects against carotid atherosclerosis and intima-media wall thickening. 42

In response to this unpublished American Heart Association presentation, The Life Extension Foundation asked me to oversee a pilot study of 30 people who had been taking very high doses of vitamin C (and other nutrients) for at least four years.

The objective of this study was to ascertain whether those who have consumed more than 2000 mg a day of vitamin C have a greater or lesser degree of carotid artery wall thickening and atherosclerotic plaque in relationship to their age and other risk factors.

The subjects in our test group ranged from age 45 to 81 years, with a median age of 61. Our test subjects were significantly older than the group tested by the American Heart Association.

The procedure used to evaluate the carotid arteries of these 30 subjects was a high resolution ultrasound of the carotids with doppler evaluation. Multiple sonographic scans were obtained through the area of the right and left carotid systems. This test enabled me to ascertain if there was atherosclerotic plaque present, the degree of intimamedia thickening if any, blood flow velocity and the percentage of stenosis (narrowing or blockage), if any. I routinely use this test to help determine if neurologic deficit is caused by carotid artery disease. It is not uncommon for me to detect 60% to 90% blockage in the carotid arteries of patients, along with significant increase of carotid blood flow velocity and severe intimamedia thickening. Lay readers should know that increased blood flow velocity is indicative of greater carotid artery stenosis (narrowing).

I was surprised that the doctors who made the presentation at the American Heart Association conference only tested for carotid intimamedia thickening. This is only one of four parameters that can be evaluated via carotid ultrasound testing. I believe the American Heart Association doctors should have also checked for carotid atherosclerotic plaque, stenosis and blood flow velocity, in addition to intima-media thickening. Of all parameters that can be evaluated, intima-media wall thickening is the least important factor. Atherosclerotic plaque, stenosis and blood flow velocity are far more important indicators of underlying carotid disease.
 

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The results of The Life Extension Foundation™s four-pronged carotid ultrasound test showed that in 23 out of 30 of these very high vitamin C supplement takers, there was no evidence of carotid plaque formation, obstruction (stenosis) or intima-media thickening. Blood flow velocity through the carotids was completely normal in these 23 subjects.

In seven cases, there was some evidence of carotid pathology, but the extent of disease was insignificant with the exception of two persons who showed carotid stenosis of 30% and 40%. Based on the advanced age of these two subjects, the 30 and 40% stenosis observed was not considered abnormal and was not indicative of a clinically significant disease state.

In the seven cases showing some evidence of carotid pathology, preliminary follow up has at the time of this publication revealed elevated levels of homocysteine, LDL cholesterol and/or glucose as potential causative factors. Additional blood testing of these seven subjects will be conducted to evaluate serum iron, Creactive protein, LDL particle size, fibrinogen and other potential risk factors for carotid stenosis. When adjusting for age and other confounding factors such as high cholesterolhomocysteine, the slight to moderate carotid pathology detected in these 7 out of 30 subjects is below what would be normally expected.

Overall, this group of very high vitamin C supplement takers showed remarkably healthy carotid arteries, with 23 out of 30 having absolutely no sign of intima-media thickening, blood flow restriction, atherosclerosis or stenosis.

Our pilot study of 30 subjects differed from the American Heart Association study in the following ways

The American Heart Association tested people aged 40 to 60. We thought age 40 was too young to observe significant carotid artery disease in asymptomatic people, so we tested people beginning at age 45. We had no upper age cutoff limit, and tested many people in their 60s, 70s and one 81-year-old.

The American Heart Association only tested for carotid intimamedia thickening, while we tested for carotid atherosclerosis, stenosis and blood flow velocity, in addition to intima-media thickening. Atherosclerotic plaque, stenosis and blood flow velocity are far more important indicators of underlying disease than intima- media thickening.

The upper limit for vitamin C intake was apparently 500 mg in the American Heart Association study. Our subjects, on the other hand, consumed well over 2,000 mg a day of vitamin C along with potent doses of other nutrients purported to reduce risk of atherosclerosis and cardiovascular disease.

If we had set a cutoff of 60 years of age like the American Heart Association did, we would have found that none of our test subjects would have shown clinically significant carotid artery pathology. In other words, had we used the same narrow parameters (under age 60) that were presented at the American Heart Association meeting, we would have had no carotid artery pathology to report in this group of people who take very high doses of supplements.

Since aging is a risk factor in the development of carotid artery disease, we choose to evaluate a much older group (45 to 81 years) of people consuming greater levels of vitamin C and other nutrients. By testing an older age group, we obtained a more clinically significant picture of the carotid artery status of people who have consumed very high doses of vitamin C and other nutrients for long periods of time.

Additional considerations

It is well established that excess iron accelerates atherosclerosis, and one study specifically showed that high levels of iron cause carotid atherosclerosis 43 . It is therefore possible that the people in the American Heart Association study who were taking low potency vitamin C supplements were consuming a multi-vitamin that contained a relatively high level of iron. There is also a possibility that these relatively low-potency vitamin C supplements where causing excess iron absorption from food, but not enough vitamin C to protect against iron-induced LDL cholesterol oxidation that could have contributed to the intima-media thickening observed in the American Heart Association presentation.

Previously published research shows vitamin C as either having a protective effect, or no effect in the development of carotid artery disease. The most significant positive study was published in the American Heart Association™s own journal 42 and measured the relationship between the intake of dietary and supplemental vitamin C, vitamin E and provitamin A carotenoids and average carotid artery wall thickness. In 6,318 female and 4,989 male participants 45 to 64 years old, carotid artery intima-media wall thickness was measured as an indicator of atherosclerosis at multiple sites with ultrasound testing. Among men and women over age 55 who had not recently begun a special diet, those in the high vitamin C intake group showed significantly less average carotid artery wall thickness adjusted for age, body mass index, fasting serum glucose, systolic and diastolic blood pressures, HDL and LDL cholesterol, total caloric intake, cigarette use, race and education. Vitamin C showed an 81% protective effect in women and a 65% protective effect in men. The doctors concluded by stating:
These data provide limited support for the hypothesis that dietary vitamin C and alpha- tocopherol may protect against atherosclerotic disease, especially in individuals over 55 years old.

Carotid endarterectomy is a surgical procedure used to remove atherosclerotic plaque in the carotid artery. In a study of 45 people undergoing this procedure, the lower the plasma content in vitamin C over a 12-month period, the higher the percentage of vessel re-narrowing after endarterectomy. This study implies that even in advanced cases of carotid stenosis, supplemental vitamin C may be of benefit in preventing further occlusion. 44

Another study involved the feeding of oxidized lab chow along with vitamin C and iron to rabbits for four weeks to induce experimental atherosclerosis. These rabbits had been fed a trans-fatty acid rich diet for 36 weeks prior. Administration of coenzyme Q10 after the feeding of a trans-fatty acid-rich diet showed a decrease in coronary atherosclerosis, artery plaque size and atherosclerosis scores when compared to the placebo group. 45 This study indicates that supplemental coenzyme Q10 may be required when people take vitamin C and iron supplements.

While Linus Pauling, Matthias Rath and others make a good case that vitamin C protects against atherosclerosis, there are studies suggesting that garlic, 46 homocsyteine-lowering nutrients folate, 30-38 B6, 28 B12, 26,27 TMG (trimetheylglycine), 47-50 and calcium regulating nutrients such as vitamin K 51 provide even greater benefits. One study on people with elevated homocysteine showed that supplementation with folic acid, vitamins B12 and B6 resulted in a regression in carotid artery stenosis within one year as measured by ultrasound testing. 52

Conclusions

Our direct observation, based on carotid ultrasound testing, show that very high vitamin C supplement users have remarkably healthy carotid arteries. When adjusted for other factors such as age, elevated homocysteine, LDL cholesterol and glucose, these very high vitamin C takers as a group appear to have less carotid pathology than the general population. A review of previously published findings indicates that consuming a wide variety of very high potency dietary supplements, combined with blood screening to monitor cholesterol, homocysteine, glucose, iron and other atherogenic risk factors, confers a significant protective effect against the development of carotid artery disease

 

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122. Reilly M, et al. Modulation of oxidant stress in vivo in chronic cigarette smokers. Circulation 1996 Jul 1;94(1):19-25.
123. Levy R, et al. VITAMIN C for the treatment of recurrent furunc**osis in patients with imparied neutrophil functions. J Infect Dis 1996 Jun;173(6):1502-5.
124. Curhan GC, et al. A prospective study of the intake of vitamins C and B6, and the risk of kidney stones in men. J Urol 1996 Jun;155(6):1847-51.
125. McAlindon ME, et al. Effect of allopurinol, sulphasalazine, and VITAMIN C on aspirin induced gastroduodenal injury in human volunteers. Gut 1996 Apr;38(4):518-24.
126. Jarrar K, et al. [A case-control study for the recognition of nonoccupational risk factors for tumors of the lower urinary tract]. Dtsch Med Wochenschr 1996 Mar 15;121(11):325-30.
127. Boffa MJ, et al. A double-blind, placebo-controlled, crossover trial of oral VITAMIN C in erythropoietic protoporphyria. Photodermatol Photoimmunol Photomed 1996 Feb;12(1):27-30.
128. Waring AJ, et al. Ascorbic acid and total VITAMIN C concentrations in plasma, gastric juice, and gastrointestinal mucosa: effects of gastritis and oral supplementation. Gut 1996 Feb;38(2):171-6.
129. Lonnrot K, et al. The effect of ascorbate and ubiquinone supplementation on plasma and CSF total antioxidant capacity. Free Radic Biol Med 1996;21(2):211-7.
130. Nadgrodkiewicz K. [The effect of intravenous Ascorbic acid on urinary 17-hydroxysteroid excretion at an early stage of cerebral stroke]. Neurol Neurochir Pol 1996 Jan-Feb;30(1):49-56.
131. Wang H, et al. Experimental and clinical studies on the reduction of erythrocyte sorbitol-glucose ratios by Ascorbic acid in diabetes mellitus. Diabetes Res Clin Pract 1995 Apr;28(1):1-8.
132. Sharma DC, et al. Correction of anemia and iron deficiency in vegetarians by administration of Ascorbic acid. Indian J Physiol Pharmacol 1995 Oct;39(4):403-6
133. Paolisso G, et al. Metabolic benefits deriving from chronic VITAMIN C supplementation in aged noninsulin dependent diabetics. J Am Coll Nutr 1995 Aug;14(4):387-92.
134. Gastaldello K, et al. Resistance to erythropoietin in iron-overloaded haemodialysis patients can be overcome by Ascorbic acid administration. Nephrol Dial Transplant 1995;10 Suppl 6:44-7.
135. Vaxman F, et al. Effect of pantothenic acid and Ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial. Eur Surg Res 1995;27 (3):158-66.
136. Wang H, et al. [Reduction of erythrocyte sorbitol by Ascorbic acid in patients with diabetes mellitus]. Chung Hua I Hsueh Tsa Chih 1994 Sep;74(9):548- 51, 583.
137. Herbaczynska-Cedro K, et al. Inhibitory effect of vitamins C and E on the oxygen free radical production in human polymorphonuclear leucocytes. Eur J Clin Invest 1994 May;24(5):316-9.
138. Lamm DL, et al. Megadose vitamins in bladder cancer: a double-blind clinical trial. J Urol 1994 Jan;151(1):21-6.
139. Lockwood K, et al. Apparent partial remission of breast cancer in ™high risk™ patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Mol Aspects Med 1994;15 Suppl:s231-40.
140. Cunningham JJ, et al. VITAMIN C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus. J Am Coll Nutr 1994 Aug;13(4):344-50.
141. Rifici VA, et al. Dietary supplementation with vitamins C and E inhibits in vitro oxidation of lipoproteins. J Am Coll Nutr 1993 Dec;12(6):631-7
142. Levy R, et al. Successful treatment of a patient with recurrent furunc**osis by VITAMIN C: improvement of clinical course and of impaired neutrophil functions. Int J Dermatol 1993 Nov;32(11):832-4.
143. Zamah NM, et al. Absence of an effect of high VITAMIN C dosage on the systemic availability of ethinyl estradiol in women using a combination oral contraceptive. Contraception 1993 Oct;48(4):377-91.
144. Cahill RJ, et al. Effects of vitamin antioxidant supplementation on cell kinetics of patients with adenomatous polyps. Gut 1993 Jul;34(7):963-7.
145. Johnston CS, et al. VITAMIN C elevates red blood cell glutathione in healthy adults. Am J Clin Nutr 1993 Jul;58(1):103-5.
146. Roncucci L, et al. Antioxidant vitamins or lactulose for the prevention of the recurrence of colorectal adenomas. Colorectal Cancer Study Group of the University of Modena and the Health Care District 16. Dis Colon Rectum 1993 Mar;36(3):227-34.
147. Kataoka A, et al. [Intermittent high-dose VITAMIN C therapy in patients with HTLV-I-associated myelopathy]. Rinsho Shinkeigaku 1993 Mar;33(3):282-8
148. Dumitrescu C, et al. Effect of VITAMIN C administration on the ratio between the pro and antioxidative factors. Rom J Endocrinol 1993;31(1-2):81-4.
149. Karduss Urueta A, et al. [Results of the treatment of chronic idiopathic thrombocytopenic purpura with Ascorbic acid]. Gac Med Mex 1993 Jan-Feb;129 (1):23-5.
150. Dawson EB, et al. Effect of Ascorbic acid supplementation on the sperm quality of smokers. Fertil Steril 1992 Nov;58(5):1034-9.
151. Triana Mantilla ME, et al. [The effect of VITAMIN C on the lipolytic activity in type-II diabetics with angiopathy]. Angiologia 1991 Mar-Apr;43(2):77-81.
152. Reed PI, et al. Effect of Ascorbic acid on the intragastric environment in patients at increased risk of developing gastric cancer. IARC Sci Publ 1991; (105):139-42.
153. Beser E. The effects of short-term VITAMIN C on plasma bun, uric acid, cholesterol and triglyceride levels. Acta Med Hung 1991;48(1-2):73-8.
154. Bucca C, et al. Effect of VITAMIN C on histamine bronchial responsiveness of patients with allergic rhinitis. Ann Allergy 1990 Oct;65(4):311-4.
155. Hunt JR, et al. Ascorbic acid: effect on ongoing iron absorption and status in iron-depleted young women. Am J Clin Nutr 1990 Apr;51(4):649-55.
156. Johnston CS. Effect of a single oral dose of Ascorbic acid on body temperature and trace mineral fluxes in healthy men and women. J Am Coll Nutr 1990 Apr;9(2):150-4.
157. Holmes LG Effects of smoking and/or VITAMIN C on crevicular fluid flow in clinically healthy gingiva. Quintessence Int 1990 Mar;21(3):191-5.
158. Mai J, et al. High dose antioxidant supplementation to MS patients. Effects on glutathione peroxidase, clinical safety, and absorption of selenium. Biol Trace Elem Res 1990 Feb;24(2):109-17.
159. Park E, et al. Effects of multivitamin/mineral supplementation, at nutritional doses, on plasma antioxidant status and DNA damage estimated by sister chromatid exchanges in lymphocytes in pregnant women. Int J Vitam Nutr Res 1999 Nov;69 (6):396-402.
160. Mirvish SS, et al. Effect of ascorbic acid dose taken with a meal on nitrosoproline excretion in subjects ingesting nitrate and proline. Nutr Cancer 1998;31(2):106-10.
161. Howard DJ. Oxidative stress induced by environmental tobacco smoke in the workplace is miti
 

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The Body Covers:The 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy



High Dose of Vitamin C Significantly Reduces Indinavir Levels in Pilot StudyCoverage provided by Myles HelfandBackground Disturbingly few studies to date have focused on the potential impact of vitamins, minerals, herbal medicines and other supplements on the blood plasma levels of HIV antiretrovirals, particularly protease inhibitors. There are any number of possible explanations for this dearth in research: a lack of available funding, the U.S. government's failure to regulate such substances, Western medicine's lack of faith in complementary therapies or the limited respect afforded to research published in this area. Clearly, however, such research is essential, primarily because a massive number of HIV-positive patients in the Western world use complementary and alternative medicine (CAM). A recent survey in Ontario, Canada, for instance, found that 89 percent of HIV-positive patients used vitamins, minerals, supplements or other forms of CAM.1 A larger study conducted in the U.S. by the University of California-Los Angeles found that more than half of HIV-positive Americans surveyed used some form of CAM -- and that a quarter of those individuals were using a substance that could interfere with antiretroviral therapy.2 Knowledge of how these substances interact with HIV medications is pivotal to ensure the optimal efficacy and safety of the antiretrovirals that patients are prescribed. In recent years, a small number of reliable studies have been conducted on the effects of some complementary medicines on HIV antiretrovirals. Most of these studies have focused on the interactions between CAMs and protease inhibitors; the most notable was the finding that St. John's wort can dramatically reduce plasma levels of indinavir (IDV, Crixivan),3 a revelation that has since been expanded to include a potentially massive number of other medications,4 including all protease inhibitors. Other studies have highlighted the impact of St. John's wort on NNRTIs, specifically nevirapine (NVP, Viramune),5 and of garlic supplements on the protease inhibitor saquinavir (SQV, Fortovase, Invirase),6 among others. The reason for many of these interactions appears to be the substances' effect on P450 enzymes, which metabolize protease inhibitors and NNRTIs. Much has yet to be learned about the precise mechanism of these interactions, though, and due to a lack of research, the vast majority of potential CAM/antiretroviral interactions are unknown. Study Findings This pilot study (Poster A-1610, Effect of High-Dose Vitamin C on the Steady-State Pharmacokinetics of the Protease Inhibitor Indinavir in Healthy Volunteers7) by Douglas Slain, Pharm.D., and colleagues at West Virginia University marks the first attempt to study potential interactions between antiretrovirals and vitamin C -- widely held to be one of the most heavily used supplements in the developed world, particularly by immunocompromised people. Though the patient sample involved in this study was quite small and was not conducted on HIV-positive patients, its findings raise alarms about vitamin C's impact on protease inhibitor concentrations -- and point to just how important it is that healthcare practitioners be well aware of any vitamins, minerals or supplements their HIV-positive patients are taking. Dr. Slain's study involved seven healthy, HIV-negative volunteers (six of whom were male) between 18 and 55 years of age. Each was given four 800-mg doses of indinavir eight hours apart, so the drug's steady-state pharmacokinetic parameters could be determined before vitamin C was added to the equation. After a seven-day wash-out period, the volunteers were given a seven-day daily regimen of 1,000 mg vitamin C -- a concentration that is about 12 times the U.S. recommended daily allowance, but well within the dosing range of many HIV-positive patients in the U.S. On the sixth day after they began taking the vitamin C, the subjects were once again administered four 800-mg doses of indinavir, each eight hours apart, with the vitamin C and indinavir doses always separated by at least three hours. Blood plasma was taken from the subjects at several points during the original administration of indinavir, and again after the final four indinavir doses were given. Throughout the course of the study, the volunteers were kept on a diet in which vitamin C content was controlled. Testing of the plasma samples revealed striking results: The additional vitamin C resulted in a 20 percent mean reduction in peak blood levels of indinavir, or Cmax (p=0.04), and a 14 percent mean reduction in area under the curve (p<0.05). Vitamin C also caused a 32 percent mean reduction in minimum blood levels (Cmin) of indinavir, as well as changes in indinavir clearance, though these findings were not statistically significant. Five of the seven study subjects experienced significant reductions in indinavir levels. Intriguingly, one of the two who did not exhibit a reduction was the only female volunteer. Dr. Slain emphasized, however, that the limited size and scope of the study preclude any assumptions about the significance of this. Discussion Dr. Slain's findings are the first to document an interaction between vitamin C and protease inhibitors in humans. It potentially groups the substance with St. John's wort, garlic supplements and other substances that impact protease inhibitor levels by affecting the metabolism of cytochrome P450 CYP3A4 isoenzymes, a subset of the P450 enzyme family that is primarily responsible for the metabolism of protease inhibitors. Obviously, the study is limited by its minute sample size. Dr. Slain emphasized that no broad-reaching conclusions can yet be drawn from these findings, and there is not yet sufficient cause for physicians or patients to drastically alter their use of either vitamin C or indinavir -- although he did make a case for the use of therapeutic drug monitoring in this context. There also remains a yawning research gap in the area of CAM/antiretroviral interactions; it is up to those who fund and publish HIV-related research to realize it -- and do something about it. Finally, it is becoming increasingly clear just how important it is for HIV-positive persons to understand that complementary therapies such as vitamins can't simply be popped like candy and forgotten about. As this study suggests -- and earlier studies on St. John's wort and garlic supplements have proven -- sometimes these therapies can help cause an HIV treatment regimen to fail. That's an outcome nobody wants to see, and one that can be prevented. Read the poster of the abstract covered in this article.
 

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1. Furler M., Einarson T., Walmsley S. et al. Use of Complementary and Alternative Medicine by HIV-Infected Outpatients in Ontario, Canada. AIDS Patient Care and STDs. 2003; 17(4):155-168. 2. Hsiao A., Wong M., Kanouse D. et al. Complementary and Alternative Medicine Use and Substitution for Conventional Therapy by HIV-Infected Patients. Journal of Acquired Immune Deficiency Syndromes. 2003; 33(2):157-165. 3. Piscitelli S., Burstein A., Chaitt D. et al. Indinavir Concentrations and St John's Wort. Lancet. 2000 Feb 12; 355(9203):547-548. 4. Markowitz J.S., Donovan J.L., DeVane C.L. et al. Effect of St John's Wort on Drug Metabolism by Induction of Cytochrome P450 3A4 Enzyme. Journal of the American Medical Association. 2003; 290:1500-1504. 5. de Maat M. M. R., Hoetelmans R. M. W., Mathôt R. A. A. et al. Drug Interaction Between St John's Wort and Nevirapine. AIDS. 2001; 15(3):420-421. 6. Piscitelli S. C., Burstein A. H., Welden N. et al. Garlic Supplements Decrease Saquinavir Plasma Concentrations. Presented at: 8th Conference on Retroviruses and Opportunistic Infections; February 4-8, 2001; Chicago, Ill. Abstract 743. 7. Slain, D., Amsden, J. R., Khakoo, R.A. et al. Effect of High-Dose Vitamin C on the Steady-State Pharmacokinetics of the Protease Inhibitor Indinavir in Healthy Volunteers. Presented at: 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; Sept. 14-17, 2003; Chicago, Ill. Abstract A-1610.September 16, 2003
 

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Linus Pauling investigates vitamin C



Linus Pauling first became interested in vitamin C in the 1960’s when he met Irwin Stone, a biochemist who had been investigating the vitamin’s properties since the 1930’s. Stone believed that it had distinctive healing qualities, and he was convinced of vitamin C’s efficacy when he and his wife had an accident involving a head on collision with a drunk driver. They used large doses of vitamin C as an aid in their recovery, and as a result they healed with remarkable speed (Hager, 1995).

Stone began to research certain animal’s abilities to synthesize their own vitamin C. He realized that humans, chimpanzees, fruit bats and guinea pigs were the only mammals that didn’t posses an enzyme necessary for vitamin C synthesis. Therefore, they had to obtain it from their diet. He concluded that the loss of this ability in humans likely occurred as the result of a mutational deviation in primates, the human predecessor, 25 million years ago (Zuckerkandl and Pauling, 1962).

In 1448, Portuguese sailors on long sea voyages were notably inflicted with an initial swelling of their feet, hands and gums, which would later spread to the rest of their bodies until they eventually died. They realized that when they ate oranges and lemons their health was restored. Historical accounts suggest that sailors in the fourteenth century were aware of the medicinal properties of oranges and lemons. In 1589, British sailors would call this illness “skurvie” or scurvy. It was not until 1911, that scurvy was recognized as a vitamin deficiency (Carpenter, 1986).

Overall, the symptoms of scurvy include a feeling of weakness, restlessness, rapid exhaustion and sallow skin. A patient will also experience muscle pain, depression and hemorrhaging of muscles and tissues. In later stages a patient will exhibit extreme exhaustion, kidney and pulmonary problems, as well as diarrhea, which consequently leads to death (Pauling, 1976).

International standards were established in the 1930’s regarding a recommended requirement for vitamin C. The league of the United Nations (presently the United Nations) concluded that 30 milligrams was adequate in order to prevent scurvy. Stone didn’t believe that a minimal dosage was adequate for optimal health, as he proposed that the inability of humans to synthesize vitamin C was actually a genetic disease and not the result of a simple vitamin deficiency. Moreover, he suggested that studies on rats showed that humans needed between 1.4 grams and 4 grams of vitamin C per day to coincide with the amounts of vitamin C that rats naturally synthesized daily (Hager, 1995).


At first, Pauling was skeptical of Stones ideas, but Stone’s theory regarding genetic mutations and genetic deficiencies intrigued him. Pauling knew that George Beadle’s research revealed that genetic mutations occurred in mold spores, which resulted in the mutated spore’s altered need for new nutrients such as amino acids and vitamins (Hager, 1995).

Pauling decided to follow Stone’s advice and quietly took 3 grams of vitamin C daily for 3 years. He immediately noted that as he took the vitamin his sense of wellness improved and he wasn’t experiencing the dreaded cold that plagued him for 40 years (Hager, 1995). He concluded that the intake of vitamin C could enhance, as well as prolong life expectancy, and therefore went forth to advocate its use for the remaining 30 years of his life.


Pauling’s scientific support for vitamin C


For many years, Pauling studied the physiological activity of molecular substances in the body. As his research progressed he began to study the use of vitamins as a therapy in addressing mental disorders such as schizophrenia. His personal experience with vitamin C led him to believe that vitamin C, also known as ascorbic acid, is a food that could effectively treat a common cold or similar disorders. In contrast, he believed that “a treatment using drugs may help to ease symptoms of a cold, but does not effect the duration of the cold” (Pauling, 1976).

Ascorbic acid is a nontoxic substance that is vital for human existence. A human being will die with in a few months if ascorbic acid is eliminated from the diet. In 1974, the National Research Council recommended 35 mg for infants, 40 mg for children and 45 mg for adults (60 for pregnant women and 80 mg for lactating women). 10 mg of ascorbic acid is needed to prevent scurvy, but Pauling believed that people’s individual needs varied, and though he wasn’t sure what the optimal requirement was he thought that people needed between 250 mg to 10 g per day (Pauling, 1976).

Many foods such as oranges, limes, peppers, spinach, cucumbers, asparagus, lettuce and cranberries contain varying amounts of ascorbic acid. Cooked foods lose about half of the ascorbic acid compared to raw foods. Although a decent diet may provide about 100 mg of ascorbic acid, studies conducted in the 1970’s showed that many people did not obtain this amount. Furthermore, one- half of the people ingested less than 57.9 mg and one-third of the people did not obtain the recommended daily allowance (RDA) of 45 mg per day for adults (Pauling, 1976).

Pauling recommended that L-Ascorbic acid be used to supplement the diet. It is water soluble and can be found as a white crystalline powder. L-Ascorbic acid is a synthetic form of vitamin C that is identical to natural vitamin C found in plants. It’s manufactured by using dextrose, which exist in honey and other plants, but it is also known as glucose, grape sugar, honey sugar, corn sugar or starch sugar. Its chemical formula is C6H12O6 and it is converted to C6H8O6 by an oxidation reaction, which remove 4 hydrogen atoms to form water. Animals that make their own ascorbic acid can synthesize ascorbic acid from dextrose in either the liver or the kidney (Pauling, 1976).



Vitamin C can be taken orally as ascorbic acid, but its salts; sodium ascorbate and calcium ascorbate can only be injected. Ascorbic acid is considered a weak acid, a little stronger than acetic acid, which is found in vinegar, yet somewhat weaker than citric acid (oranges, lemons), lactic acid (milk, sauerkraut) and tartaric acid (grapes). Ascorbic acid thoroughly dissociates into hydrogen ions, which combine with basic groups of proteins or carbonate ion. The ascorbate ion is responsible for the synthesis of collagen and other physiological processes. The salts of ascorbic acid, sodium ascorbate and calcium ascorbate also dissociates to produce ascorbate ions, and they function exactly as ascorbic acid does. The acid in ascorbic acid by injection damages veins or tissues; therefore sodium ascorbate and calcium ascorbate is used by injection (Pauling, 1976).

Although ascorbic acid’s function in the body is not fully understood, it does act as a strong reducing agent, otherwise known as a compound that donates its electrons or hydrogen atoms. In this case ascorbic acid donates its hydrogen atoms, then it is converted into dehydroascorbic acid (C6H8O6 ) in which dehydroascorbic acid accepts the ascorbic acid’s hydrogen atoms. Dehydroascorbic acid is considered the oxidizing agent. This process is reversible and the reducing of ascorbic acid, as well as the oxidation of dehydroascorbic acid is thought to account for some of the physiological qualities of vitamin C (Pauling, 1976).

Studies have shown that animals, such as guinea pigs and monkeys that require ascorbic acid will exhibit symptoms of scurvy if they do not acquire a sufficient amount through their diet. These symptoms include, intramuscular and subcutaneous hemorrhages, tender joints, loss of appetite, anemia, sluggishness, as well as a weakening of connective tissue such as skin, tendons and walls of blood vessels. The studies also showed that low intakes of ascorbic acid resulted in the slow healing of wounds and burns, as ascorbic acid is essential for maint
 

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Vitamin C and the common cold


Pauling believed that the presence of vitamin C in the intercellular glue obstructs virus particles from moving through cells and tissues. He also hypothesized that it was involved in interferon activity. Interferons are proteins that are manufactured by most cells, which interfere with virus production and infection (Pauling, 1976).

The common cold is the result of an infection by a virus, which leads to an inflammation of the upper respiratory tract. The common cold can last from three to ten days and on the average can affect a person three times per year (Pauling, 1976).

Many studies regarding the effect of vitamin C on the common cold have been conducted since the late 1930’s. In 1938, Dr. Roger Korbash of St. Elisabeth Hospital, Oberhausen, Germany published that vitamin C was used in effectively treating several diseases. He used vitamin C to treat gastritis and ulcers. He then tried vitamin C in treating rhinitis, or inflammation of the mucus membranes of the nose. He found that the therapy was valuable and decided to try 250 or 500-mg injections of vitamin C on a person suffering from a cold. He concluded that the vitamin C therapy always led to an immediate disappearance of the cold symptoms, but sometimes another injection may be needed the following day. Overall, Korbash believed that vitamin C could be safely administered in large doses. He also stated that vitamin C was far superior to cold medicines (Pauling, 1976).

Another trial in Germany (Ertel, 1941) apportioned 357 million daily doses of vitamin C among 3.7 million pregnant women, nursing mothers, infants and children. The study concluded that the participants experienced better health than the corresponding control population. Furthermore, statistical data indicated that school children with illnesses relating to respiratory infections decreased by 20 % over the previous year (Pauling, 1976).

Controlled studies were also carried out in the 1970’s. A team in Toronto (Anderson et al., 1975) used 488 subjects who completed a fifteen-week test. 150 subjects received a weekly 500-mg vitamin C tablet (two-thirds sodium ascorbate and one third calcium ascorbate), 152 received a weekly 500-mg timed release capsule of ascorbic acid, and 145 received a placebo tablet with the same appearance and taste of ascorbic acid. The subjects were instructed that if symptoms of illness should appear they should take an additional tablet or capsule, and if the symptoms continued they should repeat the dose twice at four-hour intervals on the first day and once every twelve hours for up to 4 more days (Pauling, 1976).

The team concluded that the ascorbic groups reported on an average of 62 to 98 percent fewer symptoms than the placebo group. The symptoms included fever, chills, achy heavy limbs, runny nose, sore throat, chest soreness or tightness, as well as a lack of ambition and depression. Also the two vitamin group’s averages of the symptoms were very close, 75 and 78 percent respectively. The results showed that “subjects in both vitamin groups experienced less severe illness than subjects in the placebo group, with approximately 25 percent fewer days spent indoors because of illness.” Finally, the team suggested that large doses of ascorbic acid produce “ a generalized nonspecific improvement in the host’s ability to cope with infection (or possibly any type of stress?).” They also firmly stated that they had little doubt that ingesting additional vitamin C led to a reduction in “winter illness” (Pauling, 1976).
Vitamin C, influenza and other viral diseases
Historically, when an epidemic of a contagious disease advanced through an undernourished population, an epidemic of scurvy would sometimes follow. Pauling believed that it was evident that there is a direct correlation between ascorbic acid and many diseases, including viral diseases, if not all diseases (Pauling, 1976). Research has shown that ascorbic acid inactivates the herpes virus, vaccina virus, hepatitis virus, bacterial viruses and other viruses (Stone, 1972, for references). A Japanese microbiologist, Akira Murata and his collaborators concluded that ascorbic acid could inactivate many bacterial viruses (viruses that attack bacteria). They found that the rate of inactivation varied. A concentration as small as 3 mg per deciliter in the blood was effective. Likewise, they discovered that intravenous injections of 20 g of sodium ascorbate in adult human beings inactivated 99 percent of many types of viruses with in 20 minutes (Murata, Kitagawa, and Saruno, 1971).

Murata and his coworkers also observed that the inactivation of the virus occurs only if free oxygen and ascorbic acid are both present. Moreover, they discovered that scavengers of free radicals (a highly reactive molecule with an odd number of electrons) block the inactivation. Copper ions in small concentrations, which naturally reside in the blood, can increase the rate of inactivation as well. These two contributing factors indicate that ascorbic acid reduces the oxygen molecules to a free radical, which in turn destroys the nucleic acid of the virus (Pauling, 1976).

High doses of vitamin C has also been reported to be effective in preventing poliomyelitis, hepatitis and other viral diseases. Dr. Fred R. Klenner, a physician in North Carolina first investigated treating polio with ascorbic acid. He successfully treated viral hepatitis with 400 to 600 mg injections per kilogram body weight (28 g to 42 g for a 150-pound person) and repeated this dose every eight to 12 hours (Klenner, 1949, 1951). He also treated other viral diseases with twice this dosage (Klenner, 1971, 1974).

A viral disease called hepatitis or serum hepatitis can be transferred through a blood transfusion as a result of a surgical procedure. Dr. F. Morishige, was a chief surgeon in Fukuoka General Hospital, Fukuoka, Japan. He had studied the use of vitamin C in relation to wound healing; thus he decided to investigate ascorbic acid’s effect on hepatitis. Dr. Morishige conducted a trial with some of his surgical patients by giving a number of his patients large doses of vitamin C, but others received no vitamin C or very little of the vitamin. 11 of the 150 patients (7 percent) who received less than 1.5 g per day of vitamin C developed serum hepatitis (Pauling, 1976). However, out of 1095 patients who received 2 g per day or more, not one patient developed the virus (Murata, 1975). Dr. Morishige continued to have his patients take 10 g of vitamin C per day while they stayed in the hospital, as well as 6 g per day thereafter. He also successfully used ascorbic acid in treating other viral diseases including, measles, mumps, viral pneumonia, viral orchitis, herpes zoster (chicken pox, shingles), herpes simplex (canker sores), encephalomyelitis, and viral meningitis (Murata, 1975).

Pauling noted that as of 1976, a significant body of evidence had shown that vitamin C was effective in controlling viral diseases, yet no thorough studies had been conducted regarding the use of vitamin C in treating influenza. Nevertheless, he was confident that vitamin C would provide the same defense against influenza as it had for the common cold (Pauling, 1976).

Klenner successfully treated severe cases of influenza with doses as large as 24 g every 12 hours (Klenner, 1949, 1971). It was also reported that using a few grams per day in treating influenza produced significant results (Albanese, 1947 & Magne, 1963). Moreover, smaller doses such as 300 mg were found to be effective in reducing the duration of the illness by 25 percent (Kimbarowksi and Mokrow, 1967).

Investigators have also reported that vitamin C had been used in treating bacterial infections. A study in 1937 showed that an ascorbate concentration of 1 mg per deciliter inhibits the growth of tuberc**osis bacterium (Boissevin, Spillane 1937). Likewise, ascorbate has been effect
 

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Vitamin C and other diseases




The evidence regarding the ability of ascorbate acid to inactivate viruses and bacteria clearly indicates its value in staving off bacterial and viral infections. Pauling believed that the attributes of ascorbic acid could be applied to warding off other diseases as well. He concluded that vitamin C not only inactivated bacteria and viruses, but it also functioned naturally as an internal defense mechanism (Pauling, 1976).

Cardiovascular disease, a disease of the heart and blood vessels is related to environmental and dietary factors. Smoking, a high intake of saturated fats, and high cholesterol levels can all contribute to heart disease. Vitamin C is an antioxidant that can counteract saturated fats that are converted by oxidation into dangerous peroxides. Also, human beings naturally produce 700 mg of cholesterol in the body daily, but higher concentrations of cholesterol in the blood may lead to cardiovascular complications (Pauling, 1976). Research has found that an increased intake of vitamin C reduces the concentration of cholesterol in the blood (Ginter, 1970, 1973, 1975; Spittle, 1971).


The study examined twenty-four subjects with ages ranging from forty to seventy-five years that took 1 g of ascorbic acid daily for 6 months. The subjects had moderately high cholesterol levels, averaging 253 mg per deciliter. Six months of daily intake of 1 g of ascorbic acid reduced their cholesterol levels to 210 mg per deciliters on average. Control subjects who hadn’t received any ascorbic acid showed a slight increase of 12 mg per deciliter (Pauling, 1976).

Overall, Pauling compared the cholesterol intake of one egg per day, which produces on average 8 mg of cholesterol per deciliter in the blood. He concluded from the study that an intake of 1 g per day of ascorbic acid could reduce cholesterol levels by 43 mg per deciliter, which comparably is equivalent to eliminating 5 eggs per day from the diet (Pauling, 1976).

Ascorbic Acid is necessary for collagen synthesis in the body, and sufficient wound healing depends on adequate amounts of the vitamin. Pauling suggested that persons undergoing surgery should receive increased doses of ascorbic acid (Pauling, 1976). One study revealed that a patient with a bilateral hernia only had a plasma concentration of 0.9 mg per liter. The patient was administered 100 mg of ascorbic acid per day after the herniorrhaphy on one side, and was given 1,100 mg following a second operation on another side. The skin and fascia wounds from the first operation did not heal well, yet the wounds from the second operation healed properly (Bartlet, Jones & Ryan, 1942).

A number of reports indicating the efficacy of vitamin C on wound healing after surgery have been cited by Stone (1972). Likewise many studies have shown that large doses of ascorbic acid resulted in accelerating wound healing. Some surgeons have suggested that their patients take additional vitamin C before a surgery, and then administered 5 g or more to each liter of intravenous fluid prior to performing the surgery. Other physicians have observed that increased doses of vitamin C decreased postsurgical pain, reduced the time needed for regaining normal bodily functions, expedited rapid wound healing, and decreased the overall length of time spent in the hospital (Pauling, 1976).
 

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November 28, 2003
Linus Pauling: l'ultima intervista del doppio premio nobel per la pace e la chimica

Linus Pauling, Ph.D.: The Last Interview
by Peter Barry Chowka
interview ©1996 by peter barry chowka. all rights reserved.

(Tradotta in italiano per La Leva di Archimede)

Nel 1979 quando la rispettata rivista inglese New scientist incluse Linus Pauling nella sua lista dei 20 piu' importanti scienziati di tutti i tempi, non fu' altro che uno dei tanti traguardi di Pauling che includono due premi nobel non condivisi con altri e alcuni sorprendentemente originali contributi alla biologia, chimica e fisica.
Al tempo della sua scomparsa all'eta' di 93 anni (Agosto 1994), Pauling probabilmente era conosciuto per i suoi piu' recenti lavori nel campo della scienza della nutrizione e della vitamia C. Grazie ai suoi bestsellers sulla vitamia C, raffreddori comuni e cancro, le frequenti apparizioni televisive, il numero di studi pubblicati e presentazioni scientifiche sulla nutrizione curativa battezzata da lui con il nome di medicina ortomolecolare, Linus Pauling fu l'unico reppresentante ufficiale per l'emergente scienza della nutrizione e della salute.





Secondo Pauling, la sua alta militanza nelle controversie politiche durante gli anni '50 e '60 (inclusa l'organizzazione di una vittoriosa campagna internazionale per bandire i test della armi nucleari per la quale gli fu' assegnato il nobel nel 1962), lo prepararono al difficile dibattito degli anni '70 e '80 quando di fatto divento' il leader della medicina nutrizionale in un periodo in cui la medicina ufficiale denigrava questo tipo di interessi. Durante l'ultimo ventennio della sua vita, Pauling focalizzo' il suo interesse sulle basi scientifiche della nutrizione e la sua difesa incondizionata per le megadosi vitaminiche lo pose al centro di questa controversia.

Anche dopo la sua morte la controversia continuo'. Il giornalista Lee Dembart, rivisito' due nuove biografie di Pauling, definendo l'interesse dello scienziato per la vitamina C imbarazzante e eccentrico. La maggior parte degli americani, ad ogni modo, ricordano l'eredita' di Pauling in maniera molto differente: un combattente umanitario che aiuto' il campo della scienza nutrizionale ad avanzare e anche per aver portato alla conoscienza di molti che ne hanno benificiato - l'importanza della vitamina C.

Mentre la fama scientifica di Pauling e' certamente meritata, rimasi profondamente colpito, durante le numerose volte che ho potuto intervistarlo, dalla sua profonda accessibilita', inesauribile energia, dal suo aspetto positivo e il buon umore.

Il 9 aprile del 1994, quattro mesi prima che Linus Pauling mori', lo intervistai telefonicamente per conto di una radio privata. Anche se malato e confinato nella sua casa sulla costa pacifica vicino Big Sur (California), Pauling nell'occasione della diretta radiofonica e fu il solito articolato, ottimistico e avvincente uomo che avevo sempre conosciuto. Era la sua ultima intervista.

Peter Barry Chowka
febbraio del 1996
---------------------------------------------------------------------


PETER BARRY CHOWKA: Dr. Pauling, potrebbe sintetizzare il ruolo che la vitamina C ha nella salute dell'uomo e la sua importanza nella salute di tutta la nazione?

LINUS PAULING: La vitamina C - acido ascorbico, sodio ascorbato o calcio ascorbato - e' coinvolta in un gran numero di reazioni biochimiche nel corpo umano. Due delle sue maggiori interazioni sono il potenziamento del sistema immunitario e la sintesi del collagene, una sostanza molto importante che tiene unito il corpo umano. Il collagene rinforza i vasi sanguigni, la pelle, i muscoli e le ossa. L'uomo non puo' creare collagene senza la vitamina C.

Quello che mi impressiono' 20 anni fa' fu quando Irwine Stone (Ph.D.), indico' che la maggior parte degli animali, escluso l'uomo e le scimmie, producevano vitamina C (2). Non fanno affidamento al cibo o alle pasticche di vitamine, gli animali producono vitamina C nel fegato proporzionata al loro peso corporeo. Per un uomo adulto le proporzioni dovrebbero essere una media di 10-12 gr (12.000 mg) al giorno. Questo valore e' 200 volte superiore all'RDA (Raccomended Dietary Allowance - Dosaggio giornaliero raccomandato) - 200 volte rispetto a quello che la gente assume normalmente dalla sua dieta.

Questo e' il motivo per il quale dovremmo prendere 200 volte il dosaggio di vitamina C che la FNB (Food and Nutrition Board) ci raccomanda. Il dosaggio di 60 mg stabilito dagli RDA e' troppo lontano e sottolinea l'importante necessita' di assumere integratori di Vitamina C.

CHOWKA: Durante gli ultimi 20 anni lei ha studiato i pazienti malati di cancro che sono stati trattati con alti dosaggi di vitamina C. Recentemente ha pubblicato diversi studi insieme con Abram Hoffer (M.D., Ph.D.) riguardante il trattamento del cancro con la vitamina C (3,4). I risultati sembrano essere molto promettenti.

PAULING: Oh, si! Mi sono interessato della vitamina C e cancro nel 1971 e ho cominciato a lavorare con Ewan Cameron (M.B., Ch.B.) chirurgo primario dell'ospedale Vale of Leven in Scozia. Cameron dava 10 gr di vitamina C al giorno a malati con cancro terminale non piu' trattabile (5). Questi pazienti furono poi comparati da Cameron e me con pazienti con lo stesso tipo di cancro alla stessa fase terminale che erano trattati nello stesso ospedale ma da altri medici -- medici che non usavano la vitamina C e che utilizzavano i trattamenti convenzionali.

I malati terminali curati da Cameron vissero molto piu' a lungo paragonandoli a quelli che non assumevano 10 gr di vitamina C al giorno. Gli altri pazienti vissero una media di 6 mesi dopo che furono diagnosticati come terminali, mentre i pazienti di Cameron vissero una media di 6 anni.

Recentemente ho collaborato con Hoffer, un fisico che vive a Victoria (British Columbia, Canada).
Hoffer tratto' 300 pazienti malati di cancro (6) e raccomando' a tutti loro essenzialmente lo stesso trattamento di Cameron. Ma circa un quarto o un terzo dei pazienti non seguirono il trattamento per una ragione o per un'altra: il medico di famiglia potrebbe aver detto loro che alte dosi di vitamina C li avrebbe uccisi o i pazienti potrebbero aver avuto dei problemi di stomaco e non hanno voluto continuare a prendere le vitamine.

I pazienti malati terminali di cancro che non seguirono il regime di Hoffer ebbero un tempo di sopravvivenza di circa 6 mesi. Quelli che seguirono la terapia di Hoffer ottennero risultati ancora migliori di quelli di Cameron. In media sopravvissero circa 12 anni dopo che furono diagniosticati come malati terminali non trattabili.
 

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La terapia di Hoffer includeva 12 gr di vitamina C al giorno, circa la stessa quantita' di Cameron, ma includeva anche quantita' significative di altri nutrienti: 800 U.I. di vitamina E, 1000 o 2000 mg di niacina, grosse quantita' di altre vitamine B e la vitamina A sotto forma di betacarotene. Apperentemente le altre vitamine interagiscono con la vitamina C e danno una difesa ancora maggiore contro il cancro.

Per molto tempo Cameron e io sostenevamo che ogni paziente affetto da cancro, cominciando il prima possibile nel corso della malattia, dovrebbe prendere 10 gr di vitamina C in aggiunta alle appropriate terapie convenzionali. Adesso, insieme con Hoffer, sostengo che ogni paziente malato di cancro, cominciando il prima possibile nel corso della malattia, dovrebbe prendere 10-12 e piu' gr di vitamina C, 800 U.I. di vitamina E, alti dosaggi di altre vitamine e 200 mcg di selenio al giorno. Io penso che la terapia di Hoffer e' la terapia che i malati di cancro dovrebbero seguire - sempre in aggiunta ad un'appropriata terapia convenzionale, dove appropriata significa una terapia convenzionale che abbia mostrato il suo valore per pazienti con lo stesso tipo di cancro.

CHOWKA: Lei vede progressi nella guerra al cancro?

PAULING: Si, penso di si. Ma sara' grazie alle vitamine e non con i farmaci. Sicuramente.

CHOWKA: Cosi' lei vede progressi nel potenziale delle vitamine e degli antiossidanti e non molti nel trattamento di tipo convenzionale che abbiamo visto fino a questo punto?

PAULING: Di certo non cercando farmaci e trattamenti miracolosi, no. Sento forte che la vitamina C ed altre sostanze ortomolecolari, come la lisina, provvederanno a controllare in maniera efficace le malattie cardiovascolari molto di piu' di quanto sara' possibile sul cancro. Sono molto positivo nella soluzione dei problemi cardiocircolatori.

CHOWKA: Lei ha recentemente pubblicato diversi studi sulla nutrizione e i problemi cardiocircolatori (7-8).
PAULING: Gli studi contengono un argomento molto semplice. Ho avuto molti problemi nel capire perche' le persone che si sono occupate dei problemi cardiocircolatori non hanno pensato a questo quando 20-30 anni fa fu' accettato dai cardiologi che la causa primaria dell'aterosclerosi e delle malattie cardiocircolatorie e' una lesione delle pareti delle arterie in un periodo di forte stress. Cosi' mi sono chiesto due o tre anni fa perche' le pareti delle arterie subiscono una lesione?. Gli animali non subiscono queste lesioni quando sono stressati. Noi subiamo queste lesione perche' le nostre arterie sono deboli.

Perche' son deboli? Normalmente, le arterie degli animali vengono fortificate dai depositi di collagene. L'uomo non puo' produrre collagene senza la vitamina C. Gli uomini non assumono vitamina C a sufficienza, cosi' le loro arterie sono deboli. Cosi' a seguito delle varie fasi di sviluppo delle malattie cardiovascolari, arrivano le lesioni. Quindi, la carenza di vitamina C e' la causa primaria delle malattie cardiovascolari.

CHOWKA: Possiamo pensare che la diminuzione dell'incidenza delle malattie cardiocircolatorie in questo paese e' dovuta al fatto che gli americani prendono piu' integratori vitaminici e in particolar modo la vitamina C?

PAULING: Oh, si. Nel 1979, Emil Ginter (Ph.D.) pubblico' una lettera dicendo che c'era un parallelismo tra la diminuita mortalita' a causa di malattie cardiocircolatorie e l'aumentata assunzione di vitamina C negli Stati Uniti (9).

CHOWKA: Per molti anni lei e i suoi colleghi avete affrontato una battaglia contro il potere della medicina ufficiale per portare alla conoscienza di tutti le sue idee sulla vitamina C e per la medicina nutrizionale in generale.

PAULING: Io penso che sta' cambiando. Gli scienziati tendono a seguire le mie raccomandazioni ma ho molti piu' problemi con l'establishment medico. Sembrano essere prevenuti, non hanno la mente aperta rispetto all'informazione disponibile a riguardo delle vitamine e altri nutrienti in relazione a malattie come il cancro e molte altre.

Recentemente, durante l'ultimo anno, parte delle mie fatiche sono state dedicate a contrastare questa strana posizione dell'establishment medico: ora hanno accettato il fatto che gli antiossidanti assunti dall'alimentazione diminuiscono l'incidenza del cancro. Ma nei loro libri e articoli continuano a dire ma non prendete integratori vitaminici. Questo e' completamente fuori da ogni logica secondo il mio punto di vista. Oltretutto non danno nessuna argomentazione valida per supportare queste dichiarazioni. Uno studio di James Enstrom (Ph.D.) e suoi associati mostra quanto possa essere efficace anche una piccola quantita' in piu' di vitamina C assunta in forma di integratori (10).

CHOWKA: Il suo commento sull'establishment medico suggerisce un'altra domanda. Nel 1982 lei disse che, secondo il suo punto di vista, soprattutto il pubblico americano fu responsabile per i cambiamenti nella medicina moderna, specialmente per gli importanti progressi (11). E' ancora il suo punto di vista oggi?

PAULING: Si! Penso che lo steso pubblico rispose meglio a quanto detto da me insieme a Cameron e me e Hoffer che non il mondo medico in generale. Dieci anni fa la gente mi diceva: Ho detto al mio medico che prendo un grammo di vitamina C al giorno o tre grammi di vitamina C al giorno e lui mi ha risposto: Non farlo, ti potrebbe uccidere, quelle vitamine sono velenose. Cinque anni fa la gente ha cominciato a dirmi: Ho detto al mio medico che prendo diversi grammi di vitamina C al giorno e lui mi ha detto: Bene, non ti fara' male. Va pure avanti se vuoi. Probabilmente non ne avrai nessun giovamento, ma se vuoi prenderle continua pure.

Oggi mi dicono che i medici sono propensi nel dire: Va bene, forse ti possono fare bene, specialmente quando i pazieni mostrano un aspetto migliore di quello che il medico si aspetta da loro e dicono: Penso che la ragione possa essere l'alto dosaggio di vitamina C e vitamina E che sto' prendendo. Adesso i dottori tendono ad essere d'accordo con questo punto di vista. Non so' quanti dottori prendono l'iniziativa di prescrivere vitamine ai loro pazienti seriamente malati, ma penso che molti possano almeno essere aperti a questo.

CHOWKA: Cosa succede al Linus Pauling Institute di Scienze e Medicina in Palo Alto (California) che recentemente ha celebrato il suo 20° anniversario?

PAULING: I ricercatori stanno lavorando a diversi problemi, in particolar modo quelli che riguardano la vitamina C e altre vitamine in relazione alle malattie o, in alcuni casi, semplicemente la chimica di base delle vitamine. Un'osservazione che fecero circa tre anni fa, facendo delle ricerce in vitro e' che l'HIV, il virus implicato nell'AIDS, veniva controllato da concentrazioni moderatamente alte di vitamina C -- concentrazioni che si vedono nel flusso sanguigno prendendo dai 10 ai 20 grammi di vitamina C al giorno. Questa scoperta ha attratto l'attenzione dei ricercatori sull'AIDS del National Institutes of Health (NIH) a hanno preparato un test per determinare l'efficacia degli alti dosaggi di vitamina C nel cotrollare l'AIDS o l'infezione da HIV.

CHOWKA: Dr. Pauling, c'e' un certo numero di altri pionieri della scienza e medicina innovativa di questo secolo come Albert Szent-Gyorgyi (M.D., Ph.D.), che scopri la vitamina C. Sfortunatamente, sembra che molta della gente di oggi non e' cosi' informata circa il contributo di scienziati come lei e Szent-Gyorgyi. Mi piacerebbe chiederle, quindi, come le piacerebbe essere pensato e ricordanto, specialmente dalla gioventu' americana?

PAULING: Questa' e' una domanda complicata e per me e' difficile rispondere. Credo che le future generazioni penseranno a me come l'uomo della vitamina C. Ma certamente questo non e' quello che io penso di me. Per vent'anni ho solamente ripetuto le cose che diceva Stone, cosi' come Szent-Gyorgyi stesso, circa il grande valore di alti dosaggi di vitamina C e altre vitamine.
 

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REFERENZE:

1. Dembart, L. Los Angeles Times: E-4, February 2, 1996.
2. Stone, I. Vitamin C: The Healing Factor Against Disease. New York: Grosset and Dunlap, 1972.
3. Hoffer, A., & Pauling, L. Jnl Orthomolecular Med, 5: 143-154, 1990.
4. Hoffer, A., & Pauling, L. Jnl Orthomolecular Med, 8: 157-167, 1993.
5. Cameron, E., & Pauling, L. Op cit.
6. Since then, Hoffer writes, my series has expanded to over 700 patients, and the data we first reported shows the same beneficial response, Personal communication, Feb. 7, 1996.
7. Rath, M., & Pauling, L. Jnl Orthomolecular Med, 6: 125-134, 1991.
8. Rath, M., & Pauling, L. Jnl Orthomolecular Med, 7: 5-15, 1992.
9. Ginter, E. Am Jnl Clin Nutr, 32: 511, 1979.
10. Enstrom, J.E., Kanin, L.E., & Klein, M.A. Epidem, 3: 194-202, 1992.
11. Chowka, P.B. New Age , 8: 36-39, December 1982.
12. Osmond, H., & Hoffer, A. Lancet, 1: 316-319, 1962.

Questa intervista e' stata pubblicata per la prima volta nell'Aprile 1996 su Nutrition Science News.
 

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Medical Hypotheses, 14(4):423-433, Aug 1984.



VITAMIN C IN THE TREATMENT OF ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)
Dr. Robert F. Cathcart III, MD
ABSTRACT
My previous experience with the utilization of ascorbic acid in the treatment of viral diseases led me to hypothesize that ascorbate would be of value in the treatment of AIDS (acquired immune deficiency syndrome). Preliminary clinical evidence is that massive doses of ascorbate (50-200 grams per 24 hours) can suppress the symptoms of the disease and can markedly reduce the tendency for secondary infections. In combination with usual treatments for the secondary infections, large doses of ascorbate will often produce a clinical remission which shows every evidence of being prolonged if treatment is continued. This clinical remission is achieved despite continuing laboratory evidence of helper T-cell suppression. There may be a complete or partial destruction of the helper T-cells during an initial infection that does not necessitate a continuing toxicity from some source to maintain a permanent or prolonged helper T-cell suppression. However, it is possible ascorbate may prevent that destruction if used adequately during that prodrome period. Emphasis is put upon the recognition and treatment of the frequent intestinal parasites. Food and chemical sensitivities occur frequently in the AID syndrome and may aggravate symptoms considered to be part of the AID syndrome. A topical C-paste has been found very effective in the treatment of herpes simplex and, to a lesser extent, in the treatment of some Kaposi's lesions. Increasingly, clinical research on other methods of treating AIDS is being contaminated by patients taking ascorbate.

INTRODUCTION
I had previously described that the amount of ascorbic acid which can be tolerated orally by a patient without producing diarrhea, increases somewhat proportionately to the toxicity of his disease (1,2,3,4). Among the roughly 80% of persons who tolerate ascorbic acid very well, -bowel tolerance- will be reached when in excess of 10 to 15 grams of ascorbic acid dissolved in water is taken in 4 to 6 divided doses per 24 hours. The astonishing finding was that when that same person is acutely ill with a mild cold, that tolerance may increase to approximately 50 grams per 24 hours. A severe cold can increase tolerance to 100 grams; an influenza, even up to 150 grams; and mononucleosis or viral pneumonias, to as much as 200 grams per 24 hours. These higher doses may have to be divided as frequently as hourly.

These large amounts of ascorbate are being drawn off the GI tract at a rate sufficient to prevent significant amounts from reaching the rectum and producing diarrhea. Measurements of ascorbate in urine, saliva, or serum indicate that if sufficient doses of ascorbate are not given when a patient is ill, the body level of vitamin C drops rapidly. In such a case, there is not enough vitamin C left in the body, particularly in the cells directly involved by the disease, to guarantee all the known housekeeping functions of the vitamin. Those functions known to be dependent on vitamin C, including several metabolic reactions necessary for proper functioning of the immune system, are put at risk of malfunctioning. I call this condition -acute induced scurvy.-

PREMIERE FREE RADICAL SCAVENGER
The reason ascorbate ameliorates so many conditions is that it functions as the -premiere free radical scavenger- (5). This function is not because it is the most powerful free radical scavenger, but because it is possible to saturate every cell of the body with more molecules of ascorbate than any other free radical scavenger. The reason that it takes such massive doses for optimal effect is because high concentrations of ascorbate must be driven into the cells directly affected by the disease process sufficient to neutralize all of the free radicals produced by that process, and have some left over for vitamin C housekeeping functions. When a disease process involves free radicals, that disease process is capable of being ameliorated by massive doses of ascorbate. In the case of many infectious diseases, the relief from free radical suppression of the immune system, allows for more effective attack on the pathogen by that immune system.

-Note: this premiere free radical scavenger function has little to do with nutrition but is a pharmacologic effect of ascorbate when utilized in unnatural amounts for humans.-

Actually, the complete neutralization of free radicals requires several steps involving other substances, e.g. glutathione. However clinically, the most frequent limiting factor in the reduction of free radicals is ascorbate. In certain conditions such as chemical allergies, certain other limiting factors may become critically important, e.g. selenium and glutathione. Some have worried that a buildup of dehydroascorbate would be toxic in certain of these conditions. Clinically, this consideration has not created a problem when very large doses of ascorbate are used. Perhaps it is the high ratio of ascorbate to dehydroascorbate, I am careful to maintain in these patients, that protects against any temporarily accumulating dehydroascorbate. Further, I should like to point out that the dehydroascorbate formed should not be as toxic as that free radical the ascorbate reduces as it itself is oxidized into dehydroascorbate.

In a way, it is unfortunate that this free radical scavenger and vitamin C are the same substance. When ascorbate is destroyed in the process of destroying free radicals, the vitamin C stores, particularly in the cells directly involved in the disease process, are so depleted as to cause disorders of known housekeeping functions of vitamin C.

It is certain that AIDS causes this depletion. The sicker the patient is, the more ascorbate will be destroyed by the disease process. This depletion certainly contributes to the terminal events and probably plays a key role in the increased susceptibility of AIDS patients to various pathogens.

ASCORBATE VS. AN AIDS SUPPRESSOR FACTOR
A recent article describes the discovery of a -suppressor factor- in AIDS patients. This suppressor factor was found to be neutralized in the test tube by concentrations of ascorbate equivalent to that which would be achieved in a man who ingested 10 to 20 grams of ascorbate a day. It was thought that this amount was -far too toxic- to use in humans and that a less toxic antioxidant should be found (6).

-Actually, 10 to 20 grams/24 hours of ascorbate is easily tolerated and is not toxic- (1,2,3,4,7,8,9,10,11,12,13,14). Unfortunately, clinically I have shown that the AIDS disease process destroys even larger amounts of ascorbate than the 10 to 20 grams because bowel tolerance is regularly increased to the range of from 40 to 185 grams of C per 24 hours in the patient who has moderate Kaposi's lesions and/or moderate lymphadenopathy. -Therefore, the 10 to 20 gram equivalent of ascorbate in the test tube will not be adequate in vivo-.

PRELIMINARY STUDY
Because of the hypothesis that AIDS patients would benefit from large doses of ascorbate, I began the actual treatment of AIDS patients and have found that ascorbate is indeed very valuable when used in conjunction with certain conventional treatments.

The following preliminary recommendations are based partly upon an anecdotal group of approximately 90 AIDS patients who sought medical care from physicians but who also took high doses of ascorbate on their own. Additionally, it is based upon 12 of my AIDS patients, 6 of whom were given intravenous ascorbate for a short period of time. Most of these patients have had considerable improvement in their condition. This improvement seems somewhat proportional to the amount of ascorbate taken by the patient relative to the severity of his disease. If the patient tolerates enough ascorbate to neutralize the toxicity of his disease and
 

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sniffle > cold > flu > pneumonia



Vitamin C can help stop this series before it starts.



The further you've gone down the path of sickness, the more C it will take to heal. The faster a locomotive is going, the more braking power it takes to stop it. Dr. Linus Pauling says to start taking more C at the very first sniffle. Good idea.



It is common for people to raise their eyebrows when many therapeutic claims are made for a single vitamin. Vitamin C for colds, maybe. But pneumonia? C'mon!



My central thesis may help explain it: The reason one vitamin can CURE so many conditions is that a deficiency of one vitamin can CAUSE many conditions. Disease is often the aggravated result of vitamin deficiency. If this seems to be too much emphasis on nutrition and not enough on microbes, we must remember that we live with viruses and bacteria all about us, all the time. Yet everyone is not sick all of the time. Differing nutritional status is at least as important a consideration as any other. A deficiency of any one vitamin can eventually cause death. Still, the aggressive use of vitamins to cure disease is seldom advocated.



Take vitamin C, for example. Because it is so good for so many illnesses, to the medical profession it is seen as TOO good for TOO MANY conditions. What a nice problem to have. This substance is too useful. Mmm. Can't have that, now, can we!



Of course, doctors use the same antibiotic for dozens of different infectious diseases. Their argument is that there is cause (pathogenic bacteria) that must be stopped. Antibiotics kill bacteria like an A-bomb. Vitamin C stops bacteria in a different way: it works through the body's immune system, like the French Resistance. You can probably win the war either way, but I'd rather avoid the negative effects of both the Bomb and the antibiotics.



A discussion of bacteria here is not entirely off-topic. Doctors (including a board-certified internist friend of mine who treated me, long ago) will give antibiotics for viral illnesses, such as pneumonia, to treat or prevent a secondary infection.



Robert F. Cathcart III, M.D., writes:



“Massive doses of ascorbate assist the immune system to kill bacteria within the body but also have the ability to kill bacteria by some mechanism, which does not seem to involve the immune system. These bacteria and L-forms of bacteria hide out in cells, especially when antibiotics are used, and explain some of the resistance acquired by bacteria against antibiotics. I have yet to see bacteria that can become resistant to massive doses of ascorbate in combination with first and second-generation antibiotics. Admittedly in a private practice, I do not see the most resistant bacteria, but this combination has been impressive and deserves to be tried against the most resistant bacteria. It may solve the impending problem of increasingly resistant bacteria.”



COLDS AND FLU

Dr. Robert Cathcart says vitamin C works exceptionally well as an antiviral (and antibiotic) if you take enough. Enough is called saturation, and is indicated by loose bowels and/or intestinal gas. Try taking vitamin C until saturation is reached.



Additional suggestions:

20,000 IU of Vitamin A daily and a few grams of bioflavonoid supplements will also help. When sick, I drink lots of carrot juice and don't need to take extra vitamin A. During illness, if you eat almost entirely fruits and vegetables, you won't need the bioflavonoid supplement either.



The biggest difference you will find in treating influenza is that your saturation level of vitamin C will be higher (perhaps MUCH higher) than with the common cold. Dr. Linus Pauling has been saying this for decades, starting with his classic book, Vitamin C, The Common Cold and The Flu (Freeman, 1970). His more recent book, How To Live Longer and Feel Better (1986, revised 2006 and reviewed at http://www.doctoryourself.com/livelonger.html ), is even better. It is practical, clear, and contains hundreds of supporting scientific references.



BRONCHITIS AND PNEUMONIA

Preventing is obviously easier than treating severe illness. Immediate use of hourly gram doses of vitamin C up to saturation will usually stop bronchitis or pneumonia from ever starting. But if they have, treat serious illness seriously: in the very young or the very old, pneumonia can kill. Do not hesitate to seek medical attention.

Here is a second opinion. Dr. Cathcart advocates treating pneumonia with up to 200,000 milligrams of vitamin C daily, often intravenously. You and I can simulate a 24 hour IV of Vitamin C by taking it by mouth very, very often. When I had pneumonia, it took 2,000 mg of vitamin C every six minutes to get me to saturation. My oral daily dose was over 100,000 mg. Fever, cough and other symptoms were reduced in hours; complete recovery took just a few days. Bronchitis clears up even faster. That is performance at least as good as any antibiotic will give, and the vitamin is both safer and cheaper.

May I suggest consulting the Journal of Orthomolecular Medicine for additional support for mega-vitamin therapies? The research is done, the write-ups are out there, and you can read hundreds of papers free of charge right now at http://orthomolecular.org/library/jom/ .

Treating respiratory infections with massive amounts of vitamin C is not a new idea at all. Frederick R. Klenner, M.D. and William J. McCormick, M.D. used this approach successfully for decades beginning back in the 1940's. You will want to consult their works, listed in the Bibliography under Vitamin C, or do a website search for their names. Doctors who think that vitamin C generally has merit, but that massive doses are ineffective or somehow harmful will do well to read the original papers for themselves. Clinical evidence confirms the powerful antibiotic effect of vitamin C when used in sufficient quantity.

Speaking as a parent, I can confirm that vitamin C works as well as antibiotics since our children have never needed antibiotics, not even once. That is not because we did nothing; we used vitamin C instead.

Vitamin C can be used alone or right along with medicines if one so chooses. Prescription drugs are not doing the job. 75,000 Americans die from pneumonia each year (Vital Statistics of the U.S., Department of Health and Human Services, Vol. 2, 1989). There is no question that aggressive use of vitamin C would lower that figure a great deal. There is no excuse for excluding it.



POLLY WANT A FLU SHOT?

by Andrew W. Saul

(The DOCTOR YOURSELF NEWSLETTER, Vol. 5, No. 14, Nov. 2005)



My daughter's parakeet is in grave danger.



Need you ask why? Because the Bird Flu is coming!



With all this terrifying talk about bird flu, I have a lingering question: Has anyone thought about protecting the birds? Living near Lake Ontario, I regularly feed entirely too many seagulls. They come inland as well. Just this weekend, I fed a characteristically ravenous flock of them at an interstate highway parking lot. The gulls encircled me like a Hitchcock movie. Another time, I was ungraciously harassed by a renegade herd of emus that I was, perhaps unwisely, attempting to feed. I had to climb up onto some boulders to get out of range.



Nice ol' birds; they just wanted a nosh.



Too bad they are all going to die. And soon, too.



Yes, every one of them. There will not be a gull (or at the lake, a bouy) left standing. Surely, now, if bird flu is truly dangerous, the birds are at terrible risk. All of them. No more starlings. No more pigeons. Goodbye, Mr. Hawk. Goodbye, Mrs. Robin. No more Woody; no more Beep-Beeps; Donald is doomed.



And then there's all the gorgeous song birds, all those tiny little dickie birds, like the ones I've held in my hand while they were being banded: they are all dead
 

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Journal of Applied Nutrition Vol. 23, No's 3 & 4, Winter 1971
Observations On the Dose and Administration of Ascorbic Acid When Employed Beyond the Range of A Vitamin in Human Pathology
Frederick R. Klenner, M.D., F,C,C.P.
Editor's Note:

Because of the unusually high amounts of ascorbic acid used in Dr. Klenner's treatment, as reported in his paper, we asked him to verify amounts mentioned. Following is his answer:

To the Editor of the ICAN Journal: This will confirm that all 'quantity' factors given in my paper are correct and can be confirmed from hospital and medical office records. The notation relative to 150 grams represents the amount used for reversing pathology in a given case and was the amount given over a period of 24 hours. (The I.V. was continuous.) This was given in three bottles of 5D water, decanting only enough from 1000 cc to be replaced by the 'C' ampules.

Recently the FDA has published a 'warning' that too much soda-ascobate might be harmful, referring to the sodium ion. In reply to this I can state that for many years I have taken 10 to 20 grams of sodium ascorbate by mouth daily, and my blood sodium remains normal. These levels are checked by an approved laboratory. 20 grams each day and my urine remains at or just above pH 6.

Signed:

FRED R. KLENNER, M.D.

Ancient History and Homespun Vitamin C Therapies

Folklore of past civilizations report that for every disease afflicting man there is an herb or its equivalent that will effect a cure. In Puerto Rico the story has long been told that to have the health tree Acerola in one's back yard would keep colds out of the front door.1 The ascorbic acid content of this cherry-like fruit is thirty times that found in oranges. In Pennsylvania, U.S.A., it was, and for many still is, Boneset, scientifically called Eupatorium perfoliatum2. Although it is now rarely prescribed by physicians, Boneset was the most commonly used medicinal plant of eastern United States. Most farmsteads had a bundle of dried Boneset in the attic or woodshed from which a most bitter tea would be meted out to the unfortunate victim of a cold or fever. Having lived in that section of the country we qualified many times for this particular drink. The Flu of 1918 stands out very forcefully in that the Klenners survived when scores about us were dying. Although bitter it was curative and most of the time the cure was overnight. Several years ago my curiosity led me to assay this herbal medicine and to my suprise and delight I found that we had been taking from ten to thirty grams of natural vitamin C at one time. Even then it was given by body weight. Children one cupful; adults two to three cupfuls. Cups those days held eight ounces. Twentieth century man seemingly forgets that his ancestors made crude. drugs from various plants and roots, and that these decoctions, infusions, juices, powders, pills and ointments served his purpose. Elegant pharmacy has only made the forms and shapes more acceptable.

Early specifications, action and dosages for administrations.

To understand the chemical behavior of ascorbic acid in human pathology, one must go beyond its present academic status either as a factor essential for life or as a substance necessary to prevent scurvy. This knowledge is elementary. Listen to what appeared in Food and Life Yearbook 1939, U.S. Department of Agriculture:3 In fact even when there is not a single outward sympton of trouble, a person may be in a state of vitamin C deficiency more dangerous than scurvy itself. When such a condition is not detected, and continues un-corrected, the teeth and bones will be damaged, and what may be even more serious, the blood stream is weakened to the point where it can no longer resist or fight infections not so easily cured as scurvy. It is true that without these infinitesimal amounts myriads of body processes would deteriorate and even come to a fatal halt.

Ascorbic acid has many important functions. It is a powerful oxidizer and when given in massive amounts; that is, 50 grams to 150 grams, intravenously, for certain pathological conditions, and run in as fast as 20 Gauge needle will allow, it acts as a Flash Oxidizer,4 often correcting the pathology within minutes. Ascorbic acid is also a powerful reducing agent. Its neutralizing action on certain toxins, exotoxins, virus infections, endotoxins and histamine is in direct proportion to the amount of the lethal factor involved and the amount of ascorbic acid given. At times it is necessary to use ascorbic acid intramuscularly. It should always be used orally, when possible, along with the needle.

Scurvy historically the target; todays goal of high blood levels to cope with selfinduced abuses and physiological traumas.

If one is to employ ascorbic acid intelligently, some index for requirements must be realized. Unfortunately there exists today a sort of brand called minimum daily requirements. This illegitmate child has been co-fathered by the National Academy of Science and The National Re-search Council and represents a tragic error in judgement. There are many factors which increase the demand by the body for ascorbic acid, and unless these are appreciated, at least by physicians, there can be no real progress. It is vitally important that cognizance be taken of the demand by the body for ascorbic acid far beyond so-called scorbutic levels. Briefly these demands can be summarized: 1) The age of the individual; 2) Habits -- such as smoking, the use of alcohol, playing habits; 3) Sleep, especially when induced artificially; 4) Trauma.-- trauma caused by a pathogen, the trauma of work, the trauma of surgery, the trauma to the body produced accidentally or intentionally; 5) Kidney threshold; 6) Environment; 7) Physiological stress; 8) Season of the year; 9) Loss in the stool; 10) Variations in individual absorption; 11) Variations in binders in commercial tablets; 12) Body chemistry; 13) Drugs; 14) Pesticides; 15) Body weight; 16) Inadequate storage.

Flexible dosage standards explained as minimal standards.

With such knowledge it is no longer possible to accept a set numerical unit in terms of minimal daily requirements. This is true because of the simple fact that people are different and these same people experience different situations at various times. With ascorbic acid, today's adquate supply means little or nothing in terms of the needs for tomorrow. Let us start thinking in terms of maximum requirements. For too long a time we have under supplied our children and ourselves by accepting through negative ignorance and acquiescence so-called standards. Based on scant data on mammalian synthesis, available for the rat, a 70-Kg. individual would produce 1.8 grams5 to 4.0 grams6 of ascorbic acid per day in the unstressed condition. Under stress, up to 15.2 grams.7 Compare this to the 70 mg recommended for daily requirements without stress and 200 mg for the simple stress of the obstetrical patient, and you will recognize the disparity and understand why we have been waging a one man war against the establishment in Washington for 23 years.

Ascorbic acid not synthesized by man

Work on mammalian biosynthesis of ascorbic acid indicates that the vitamin C story as is generally accepted represents an over simplication of available evidence.8,9,10 This often leads to misinterpretations and false impressions. It has been proposed that the biochemical lesion which produces the human need for exogenous sources of ascorbic acid, is the absence of the active enzyme, l-gulonolactone oxidase from the human liver11. A defect or loss of the gene controlling the synthesis of this enzyme in man, blocks the final phase in the series for converting glucose to ascorbic acid. Virus can mutate cells, X-Rays can do it and it can occur by chance. Such a mutation could have happened, denying all progenies of this mutated animal the ability to produce ascorbic acid.
 

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Regarding personal and environmental pollution-carbon monoxide.

We are all plagued with varying degrees of chronic carbon monoxide poisoning. This is the price we pay for putting our railroads on our highways, smoking and being too lazy to walk. Small amounts of carbon monoxide, if constantly maintained in the alveoli, can produce serious effects. Carbon monoxide in the inspired air leads to oxygen deficiency in the tissues causing extreme exhaustion. The affinity of carbon monoxide for hemoglobin is roughly 300 times as great as that for oxygen. In addition to active replacement of oxy-hemoglobin the presence of some proportion of carboxy-hemoglobin decreases the dissociability of such oxy-hemoglobin as remains. Carbon monoxide can be released from hemoglobin if the patient is exposed to high pressure of oxygen, 93% along with 7% carbon dioxide. This is not always available. Ascorbic acid in the blood is constantly losing molecules of water. Perfectly dry carbon monoxide and oxygen cannot unite to form carbon dioxide, but carbon monoxide and water may give rise to carbon dioxide in the complete absence of oxygen. The reactions which take place are CO + H2O = HCOOH CO2 + H2 (Wright). Here the oxygen of the water has been used to oxidize carbon monoxide to carbon dioxide with the liberation of hydrogen. Glutathione may facilitate this cellular oxidation by acting as a hydrogen acceptor (Hopkins). Clinical experience suggests that if sufficient ascorbic acid is suddenly placed into the blood stream - 12 grams to 50 grams - that through Flash Oxidation a concentration of oxygen is made high enough to pull carbon monoxide from hemoglobin to form carbon dioxide. This rapidly formed carbon dioxide acts with the high oxygen tension to serve the same purpose as when given by mask, further enhancing the chemical action taking place. Ascorbic acid will also prevent residuals such as paralysis, blindness, interference with sensations, muscle spasms or twitchings which in some cases can be permanent.

Primary and lasting benefits in pregnancy.

Observations made on over 300 consecutive obstetrical cases using supplemental ascorbic acid, by mouth, convinced me that failure to use this agent in sufficient amounts in pregnancy borders on malpractice. The lowest amount of ascorbic acid used was 4 grams and the highest amount 15 grams each day. (Remember the rat-no stress manufactures equivalent C up to 4 grams and with stress up to 15.2 grams). Requirements were roughly 4 grams first trimester, 6 grams second trimester and 10 grams third trimester. Approximately 20 percent required 15 grams, each day, during last trimester. Eighty percent of this series received a booster injection of 10 grams, intravenously, on admission to the hospital. Hemoglobin levels were much easier to maintain. Leg cramps were less than three percent and always was associated with getting out of Vitamin C tablets. Striae gravidarum was seldom encountered and when it was present there existed an associated problem of too much eating and too little walking. The capacity of the skin to resist the pressure of an expanding uterus will also vary in different individuals. Labor was shorter and less painful. There were no postpartum hemmorhages. The perineum was found to be remarkably elastic and episiotomy was performed electively. Healing was always by first intention and even after 15 and 20 years following the last child the firmness of the perineum is found to be similar to that of a primigravida in those who have continued their daily supplemental vitamin C. No patient required catheterization. No toxic manifestations were demonstrated in this series. There was no cardiac stress even though 22 patients of the series had rheumatic hearts. One patient in particular was carried through two pregnancies without complications. She had been warned by her previous obstetrician that a second pregnancy would terminate with a maternal death. She received no ascorbic acid with her first pregnancy. This lady has been back teaching school for the past 10 years. She still takes 10 grams of ascorbic acid daily. Infants born under massive ascorbic acid therapy were all robust. Not a single case required resuscitation. We experienced no feeding problems. The Fultz quadruplets were in this series. They took milk nourishment on the second day. These babies were started on 50 mg ascorbic acid the first day and, of course, this was increased as time went on. Our only nursery equipment was one hospital bed, an old, used single unit hot plate and an equally old 10 quart kettle. Humidity and ascorbic acid tells this story. They are the only quadruplets that have survived in southeastern United States. Another case of which I am lustly proud is one in which we delivered 10 children to one couple. All are healthy and good looking. There were no miscarriages. All are living and well. They are frequently referred to as the vitamin C kids, in fact all of the babies from this series were called Vitamin C Babies by the nursing personnel--they were distinctly different.

How concerned should we be about oxalic acid and kidney stones? A technical explanation.

One of the scare weapons used by the critics on high daily doses of ascorbic acid is the oxalic acid-kidney stone hypothesis. Meakins36 states that the chief factors in the formation of renal calculi are perversions of metabolic processes, infection and stasis in the urinary tract. There are two schools of thought on stone formation: 1) That there is a central nucleus of colloids on which the crystalloids are precipitated; 2) That the crystalloids are deposited from the urine in which they are present in concentrated solution, in which salt and hydrogen ion concentrations are important factors. In all cases stasis and a concentrated urine appear to be the chief physiological factors. The only way that oxalic acid can be produced from ascorbic acid is through splitting of the lactone ring. This happens above pH5. The reaction of urine when 10 grams of vitamin C is taken daily is usually pH6. Oxalic acid precipitates out of solution only from a neutral or alkaline solution-pH7 to pH10. Kelli and Zilva37 reported that Nutrition experiments showed that dehydroascorbic acid is protected in vivo from rapid transformation to the antiscorbutically impotent diketogulonic acid from which oxalic acid is derived. Values reported in the literature for normal 24 hour urinary oxalate excretions for humans range from 14 mg to 56 mg. Lamden et al.38 found in a group of volunteers that the ingestion of 9 grams ascorbic acid daily resulted in oxalate spills as high as 68 mg for 24 hours and in the controls without extra vitamin C the high was 64 mg for a 24 hour period. These critics have overlooked the individual with diabetes mellitue. The amount of oxalic acid found in the diabetic patient approximates that found in the urine of a normal person taking 10 grams vitamin C each day. With the diabetic we find a paradox. Give this individual 10 grams ascorbic acid daily, by mouth, and the urinary oxalate excretion remains relatively unchanged. Diabetics are known for their diuresis. The individual who takes 10 or more grams of vitamin C each day will find that this organic compound is an excellent diuretic. No urinary stasis; no urine concentration. The ascorbic acid kidney stone story is a myth. Methylene blue will dissolve calcium oxalate stones giving 65 mg orally 2 to 3 times a day. (Dr. M. J. Vernon Smith: Med. World News, Dec. 4, 1970)

Why death from insect and snake bites?

It is estimated that 6500 deaths occur each year in the United States from snake bite. Many more from various flying insects, spiders, certain plants and some caterpillars.These are needless deaths. Several factors are at work in these pathologies: 1) The tox-albumin of the snake bite, like the copperhead or rattler; 2) Formic acid plus a toxin with a protein cover, called proteotox
 

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Cholesterol not a problem, when daily intake of ascorbic acid is high.

Mention should be made of the role54 played by vitamin C as a regulator of the rate at which cholesterol is formed in the body; deficiency of the vitamin speeding the formation of this substance. In experimental work, guinea pigs fed a diet free of ascorbic acid showed a 600 percent acceleration in cholesterol formation in the adrenal glands. Ten grams or more each day and then eat all the eggs you want. That is my schedule and my cholesterol remains normal, Russia has published many articles demonstrating these same benefits.

Lock-law relieved.

Ascorbic acid has no equal as a adjuvant with other drugs in many conditions. With Tolserol it is curative in the treatment of Lockjaw. Both drugs must be used in proper amounts. In our case 1000 mg Tolserol given intravenously to a boy weighing 20 Kg. was the optimal amount to use. In 48 hours he was given 90 grams ascorbic acid and 3000 mg Tolserol, all intravenously.55 Jungeblut56 reported that vitamin C, when added to tetanus toxin in vitro, brings about inactivation of the toxin. Two cases of Trichinosis was treated and cured using Vitamin C: and Para-Aminobenzoic acid.57 Although the temperature curve was returned to normal in 36 hours it was found that nine days of treatment was necessary for permanent cures.

Infectious hepatitis relieved.

Viral hepatitis needs brief mentioning. There are two types: 1) Infectious hepatitis; 2) Needle hepatitis. Physical activity has always been considered to increase the severity and prolong the course of the disease.58 In Vietnam, Freebern and Repsher showed that pick-and-shovel details had no effects on the 199 controls as against 199 kept at bed rest.59 One thing is certain. Given massive intravenous ascorbic acid therapy and patients are well and back to work in from 3 to 7 days. In these cases the vitamin is also employed by mouth as follow-up therapy. Dr. Bauer at the University Xxxxxx, Basel, Switzerland, reported that just 10 grams daily, intravenously, proved the best treatment available.

Ascorbic acid therapy applied to various maladies.

We could continue indefinitely extolling the merits of ascorbic acid. Boyd and Campbell60 reported excellent results in the healing of corneal ulcers even though their massive doses was 1.5 grams daily. In one case of a corneal burn from the phosphorus off an old time match, the pain was relieved immediately with the intravenous injection of 12 grams vitamin C with a 50 c.c syringe. One gram was prescribed each hour for 50 grams. The cornea was normal in less than 24 hours. One single injection of ascorbic acid calculated at 500 mg per Kg. body weight will reverse heat stroke and one to three injections of the vitamin in a dose range of 400 mg Kg. body weight will effect a dramatic cure in Virus Pancarditis. One gram taken every one to two hours during exposure will prevent sunburn and intravenous injections will quickly relieve the pain and erathema, even the second degree burns when precautions are not taken. One to three injections of 400 mg per Kg. given every eight hours will dry up chicken-pox in 24 hours. If nausea is present it will stop the nausea. These injections are usually given with a syringe in a dilution of one gram to 5 c.c fluid. This concentration will produce immediate thirst. This is prevented by having the patient drink a glass of juice just before giving the injection. Forty grams ascorbic acid by vein and 1000 mg to 2000 mg vitamin B1 intramuscularly will neutralize the person intoxicated by alcohol and will save the life if one drinks after using Antibuse. 5 per cent ointment using a water soluable base will cure acute fever blisters if applied 10 or more times a day and we have removed several small basal cell epithelionhas with a 30 percent ointment. Dr. Virno61 at the eye Xxxxxx, University of Rome, Italy, reported very promising results in glaucoma with a dose schedule of 100 mg per Kg. body weight taken after meals and bed hour. He also reported that these large doses have proved to be safe. In arthritis at least 10 grams daily and those taking 15 to 25 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 vaccinia necrosum is good psychology. In herpes zoster two grams vitamin C intramuscularry and 50 mg Adenosine 5-Monophosphoric acid, aqueous solution, also intramuscularly every 12 hours. Compound tincture benzoin locally is helpful. In massive shingles ascorbic acid should also be given by vein. Always as much by mouth as can be tolerated. Heavy metal intoxication is also resolved with adequate vitamin C therapy.

General all around benefits uia one to ten grams ascorbic acid per day.

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 ten at least one gram for each year of life will find that the brain will be clearer, the mind more active, the body less wearied and the memory more retentive.

SUMMARY
The types of pathology treated with massive doses of ascorbic acid run the entire gamut of medical knowledge. Body needs are so great that so called minimal daily requirements must be ignored. A genetic error is the probable cause for our inability to manufacture ascorbic acid, thus requiring exogenous sources of vitamin C. Simple dye or chemical test are available for checking individual needs. Ascorbic acid destroys virus bodies by taking up the protein coat so that new units cannot be made, by contributing to the break-down of virus nucleic acid with the result of controlled purine metabolism. Its action in dealing with virus pneumonia and virus encephalitis has been outlined. The clinical use of vitamin C in pneumonia has a very sound foundation. In experimental tests monkeys kept on a vitamin C free diet all died of pneumonia while those with adequate diets remained healthy.62 Many investigators have shown an increased need for ascorbic acid iq this condition.63,64 Brody in 1953 after studying vitamin C and colds in college students advised that ascorbic acid be given early and often in sufficient amounts. Regnier65 reporting in review of Allergy found that the larger the dose of ascorbic acid the better were the results. Our findings resulted in a schedule of one gram each hour for 48 hours and then 10 grams each day by mouth. Those under ten at least one gram for each year of life.

Virus Encephalitis.

Virus encephalitis is a deadly syndrome and must be treated heroicly with intravenous and/or intramuscular injections of ascorbic acid. We recommend a dose schedule of from 350 mg to 700 mg per Kg. body weight diluted to at least 18 c.c. of 5D water to each gram of C. In small children, 2 and 3 grams can be given intramuscularly, every 2 hours. An ice cap to the buttock will prevent soreness and induration. Ascorbic acid in amounts under 400 mg per Kg. body weight can be administered intravenously with a syringe in dilutions of 5 c.c. to each one gram provided the ampoule is buffered with sodium bicarbonate with sodium Bisulfite added. As much as 12 grams can be given in this manner with a 50 c.c. syringe. Larger amounts must be diluted with bottle dextrose or saline solutions and run in by needle drip. This is true because amounts like 20 to 25 grams which can be given with a 100 c.c. syringe can suddenly dehydrate the cerebral cortex so as to produce convulsive movements of the legs. This represents a peculiar syndrome, symptomatic epilepsy, in which the patient is mentally clear and experiences