Therefore, as in many studies of vitamin C intake and chronic disease risk, it is difficult to separate the effects of vitamin C from the effects of other components of fruit and vegetables. Collagen is required to keep our arteries flexible and strong. Ann Thorac Surg. (PubMed), 186. Administration of a 1-gram (g) vitamin C infusion one hour prior to the angioplasty reduced the concentrations of oxidative stress markers and improved microcirculatory perfusion compared to placebo (130). Two large prospective studies found dietary vitamin C intake to be inversely associated with breast cancer incidence in certain subgroups. How to Live Longer and Feel Better. By maintaining enzyme-bound metals in their reduced forms, vitamin C assists mixed-function oxidases in the synthesis of several critical biomolecules (1). Smoking and respiratory conditions in pregnancy: associations with adverse pregnancy outcomes. 2016;9:25-30. Linus Pauling Institute Over years of buildup and accumulated damage to the coronary arteries, CHD may culminate in a myocardial infarction or heart attack. Baltimore, MD: Lippincott Williams & Wilkins; 2014:416-426. (PubMed), 9 Vallance S. Relationships between ascorbic acid and serum proteins of the immune system. Ames, Iowa: Wiley-Blackwell; 2012:248-260. Conversely, a 2008 meta-analysis of 14 cohort studies concluded that dietary, but not supplemental, vitamin C intake was inversely related to CHD risk (47). Production of both collagen and elastin requires vitamin C, lysine and proline. The measurement of brachial artery flow-mediated dilation (FMD) is often used as a functional marker of endothelial function; FMD values are inversely correlated with the risk of future cardiovascular events (38). 2013;9(1):46. Vitamin C. In: Erdman JWJ, Macdonald IA, Zeisel SH, eds. See also the section on Sepsis in the Symposium on Vitamin CPart of the LPIs 9th International Conference on Diet and Optimum Health. 1976;84B(5):280-284. Dosage is a key factor: low doses are ineffective. Liu C, Russell RM. This is typically observed at doses between 200 to 400 mg/day in healthy young adults, with some degree of individual variation (23, 24). Urate crystals may form in joints, resulting in inflammation and pain, as well as in the kidneys and urinary tract, resulting in kidney stones. Short-term supplementation with vitamin C was found to reduce endothelial dysfunction in subjects with heart failure, atherosclerosis, or diabetes mellitus, but it had no effect in those with hypertension. Endothelial dysfunction results in widespread vasoconstriction and coagulation abnormalities. In 2004, a pooled analysis of nine prospective cohort studies found that supplemental vitamin C intake (400 mg/day for a mean of 10 years), but not dietary vitamin C intake, was inversely associated with CHD risk (46). Br J Nutr. Vitamin C/Professional handout/Interactions with drugs. 2012;95(5):1079-1088. Carriers of two copies of the Hp2 allele (Hp2-2) express a Hp protein that has a lower capacity to bind and remove pro-oxidant, free hemoglobin (Hb) from plasma, compared to Hp proteins coded by the Hp1-1 and Hp1-2 genotypes. Pauling's therapeutic dosage of vitamin C for those diagnosed with cardiovascular disease is from 6,000 mg up to 18,000 mg (or bowel tolerance). Levy R, Shriker O, Porath A, Riesenberg K, Schlaeffer F. Vitamin C for the treatment of recurrent furunculosis in patients with impaired neutrophil functions. 1. Linus Pauling's specific therapy for cardiovascular and heart diseases are high dosages of two essential nutrients; vitamin C and the amino acid lysine . 2012;69(7):836-841. Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial. It may involve the production of high levels of hydrogen peroxide, selectively toxic to cancer cells (22, 160-162), or the deactivation of hypoxia inducible factor, a prosurvival transcription factor that protects cancer cells from various forms of stress (159, 163, 164). (PubMed), 184. Alberts B, Bray D, Lewis J, Raff M. Differentiated cells and the maintenance of tissues. Symptoms of vitamin C deficiency, such as poor wound healing and lethargy, likely result from the impairment of these vitamin C-dependent enzymatic reactions leading to the insufficient synthesis of collagen, carnitine, and catecholamines (see Deficiency). Oregon State University, Updated in December 2004 by: Klingelhoeffer C, Kammerer U, Koospal M, et al. Spoelstra-de Man AME, Elbers PWG, Oudemans-van Straaten HM. 2007;6:41. (PubMed), 107. (PubMed), 83. Website https://www.paulingtherapy.comPauling Therapy for Heart Disease:-Vitamin C 12,000 mg-Lysine 6,000 mg-Proline 2,000 mg Nutr Metab Insights. The dosage of vitamin C was set too low, at one tenth the dosage recommended by the Linus Pauling protocol, and lysine was not provided. Contents Summary Function Playing in immunity Bioavailability Deficiency Aforementioned RDA Disease Prevention Cardio-vascular disease Cancer Print 2 diabetes mellitus Adverse pregnancy outcomes In a 1974 radio interview, he noted that "the first 250 mg is more important than any later 250 mg. Leuk Lymphoma. These enzymes are either monooxygenases or dioxygenases (see Table 1). These enzymes contribute to the epigenetic regulation of gene expression by catalyzing reactions involved in the demethylation of DNA and histones. Phagocytic leukocytes also produce and release cytokines, including interferons, which have antiviral activity (16). Clinical trials of antioxidants as cancer prevention agents: past, present, and future. 2001;108(3):E55. 2003;31(4):1250-1256. A much larger study of 19,578 people, including 4,214 children from 6 to 16 years of age, found higher serum vitamin C concentrations to be associated with significantly lower blood lead concentrations (182). Stability of vitamin C derivatives in solution and topical formulations. Two randomized controlled trials conducted in the 1990s reported a reduction in reperfusion-induced oxidative stress and myocardial injury with intravenous(136)or oral (137)vitamin C administration prior to CABG surgery (reviewed in 135). (PubMed), 54. Intravenous vitamin C and cancer: a systematic review. 2016;5(2):94-100. Matsuzawa Y, Kwon TG, Lennon RJ, Lerman LO, Lerman A. Prognostic value of flow-mediated vasodilation in brachial artery and fingertip artery for cardiovascular events: a systematic review and meta-analysis. Ascorbic acid, cognitive function, and Alzheimer's disease: a current review and future direction. (PubMed), 163. Br J Nutr. Specifically, the Health Professionals Follow-Up Study collected data on dietary and supplemental vitamin C intake every four years in 45,619 male health professionals (ages 40-75 years) (198). Effect of one-year vitamin C- and E-supplementation on cerebrospinal fluid oxidation parameters and clinical course in Alzheimer's disease. (PubMed), 166. The effect of intravenous vitamin C infusion on periprocedural myocardial injury for patients undergoing elective percutaneous coronary intervention. Gao P, Zhang H, Dinavahi R, et al. The majority of large, population-based studies examining the relationship of vitamin C intake or supplementation with AD incidence have reported null results (100). 2010;119(3):753-765. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. These products are all Lp (a) binding inhibitors. (PubMed), 42. Specific measures of functions stimulated by vitamin C include cellular motility (10), chemotaxis(10, 11), and phagocytosis(11). The first 250 mg leads you up to the level where the blood is saturated. Vitamin C and the Common Cold. 177. Am J Obstet Gynecol. Since the antioxidants were taken together in this trial, the individual contribution of vitamin C cannot be determined. The Normative Aging Study. 2018 Alzheimer's Disease Facts and Figures. Some, yet not all, studies in animal models such as vitamin C-deficient guinea pigs or genetically scorbutic rats found an increased uptake of vitamin C in peripheral circulation and specific organs in the presence of flavonoids. Trials. Am J Epidemiol. (PubMed), 175. Chuang CH, Sheu BS, Kao AW, et al. Oregon State University, Updated in November 2002 by: Nutrients. Linus Pauling believed that chronic scurvy can be prevented with an orthomolecular daily intake of between 3,000 to 10,000 mg or more vitamin C. This amount approximates what the animals synthesize, and matching animal production is the reason Pauling ingested 18,000 mg daily. One supplement, Ester-C, contains mainly calcium ascorbate and includes small amounts of the vitamin C metabolites, dehydroascorbic acid (oxidized ascorbic acid), calcium threonate, and trace amounts of xylonate and lyxonate. Bertoia M, Albanes D, Mayne ST, Mannisto S, Virtamo J, Wright ME. Gillani SW, Sulaiman SAS, Abdul MIM, Baig MR. Science. Carr A, Frei B. 2010;126(6):1504-1512. Banerjee S, Hawksby C, Miller S, Dahill S, Beattie AD, McColl KE. 2017;9(11). 2007;12(3):230-238. Nutr J. Fowler AA, 3rd, Syed AA, Knowlson S, et al. Linus Pauling Institute In adults, lead toxicity may result in kidney damage, high blood pressure, and anemia. 1998;392(6676):559. A small randomized controlled trial performed in 60 ischemic stroke patients showed that intravenous vitamin C administration (500 mg/day for 10 days, initiated day 1 post-stroke) had no effect on serum markers of oxidative stress or neurological outcomes compared to placebo(143). (PubMed), 11. Johnston CS. A nested case-control study in the EPIC study found a 45% lower risk of gastric cancer incidence in individuals in the highest (51 mol/L) versus lowest (<29 mol/L) quartile of plasma vitamin C concentration; no association was observed between dietary vitamin C intake and gastric cancer (73). 2011;51(5):1068-1084. Environ Health Perspect. Alzheimer's Association. Because oxalate is a metabolite of vitamin C, there is some concern that high vitamin C intake could increase the risk of calcium oxalate kidney stones. A 2018 meta-analysis of randomized controlled trials investigating the effect of antioxidant vitamin supplementation in patients with type 2 diabetes found that most improvement in markers of oxidative stress and blood glucose control could be attributed to vitamin E(145). While most generally healthy young adults can achieve these plasma concentrations with daily vitamin C intake of at least 200 mg/day, some individuals may have a lower vitamin C absorptive capacity than what is currently documented. The capacity of vitamin C to influence the methylation status of DNA and histones in mammalian cells supports a role for the vitamin in health and disease beyond what was previously understood, in particular by safeguarding genome integrity (3, 4). With the latest RDA published in 2000, a tolerable upper intake level (UL) for vitamin C was set for the first time (Table 4). Human skeletal muscle ascorbate is highly responsive to changes in vitamin C intake and plasma concentrations. In another randomized, double-blind, controlled trial in 28 critically ill patients with septic shock, infusion of 25 mg of vitamin C per kg every six hours for 72 hours significantly limited the requirement to vasopressor norepinephrinedecreasing both the dose and duration of treatmentand dramatically improved the 28-day survival rate (155). Using this approach, Dr. Pauling suggested in the early 1970s that the optimum daily intake may be about 2,000 milligrams of vitamin C and that everyone should get at least 200 to 250 mg/day. J Biol Chem. Liability for individual actions or omissions based upon the contents of this site is expressly disclaimed. (PubMed), 179. Bowman GL, Dodge H, Frei B, et al. 1951;113:628-631. 2008;26(3):297-304. In the National Institutes of Health (NIH)-American Association of Retired Persons (AARP) Diet and Health study that included 232,007 participants, the use of vitamin C supplements for at least seven times a week was associated with a 9% lower risk of developing type 2 diabetes mellitus compared to non-supplement use (83). Gut. It is important for individuals with significantly elevated blood pressure not to rely on vitamin C supplementation alone to reduce their hypertension. (PubMed), 105. Linus Pauling Institute Front Oncol. Proc Natl Acad Sci U S A. Eur J Cancer. 17. (PubMed), 198. Cochrane Database Syst Rev. Food Nutr Res. ACS Chem Neurosci. Levine M, Padayatty SJ, Espey MG. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Cancer Epidemiol Biomarkers Prev. Early Hum Dev. (PubMed), 55. Corvallis, Oregon 97331, phone: 541-737-5075 | fax: 541-737-5077 Cochrane Database Syst Rev. Pharmacol Rep. 2010;62(4):751-756. As shown in Table 3, different fruit and vegetables vary in their vitamin C content, but five servings (2 cup-equivalents) of a variety of fruit and vegetables should average out to about 150 to 200 mg of vitamin C, especially if vitamin C-rich fruits are consumed. Does vitamin C act as a pro-oxidant under physiological conditions? 2001;292(5524):2083-2086. Although liposomal encapsulation could increase vitamin C bioavailability, plasma vitamin C concentrations were much lower than those achieved with intravenous vitamin C administration (190). 2016;73(8):1645-1658. A comprehensive review of the literature found no credible scientific evidence that supplemental vitamin C promotes oxidative damage under physiological conditions or in humans (206). J Emerg Med. Donin AS, Dent JE, Nightingale CM, et al. Intake of antioxidant nutrients and risk of non-Hodgkin's Lymphoma in the Women's Health Initiative. (PubMed), 190. He explained that two-time Nobel Prize winner Linus Pauling had given vitamin C a "bad name." In the 3 government's eyes, he was too vocal about its benefits. Vitamin C has been shown to increase interferon production in vitro(17). Oncogene. Bergsten P, Amitai G, Kehrl J, Dhariwal KR, Klein HG, Levine M. Millimolar concentrations of ascorbic acid in purified human mononuclear leukocytes. Simon JA, Hudes ES. Nutrients. Association between plasma vitamin C concentrations and blood pressure in the European prospective investigation into cancer-Norfolk population-based study. (PubMed), 30. 2013;1(5):e239-240. Padayatty SJ, Sun H, Wang Y, et al. email:[emailprotected], Chlorophyll and Metallo-Chlorophyll Derivatives, Healthcare Professional Continuing Education. 1980;33(1):71-76. 2017;17(1):49. While these NIH studies are the best we currently have regarding the pharmacokinetics of vitamin C in the human body, they have numerous limitations, including the fact that they are based on a small number of young, healthy men and women. Br Med J. Available at: https://naturalmedicines.therapeuticresearch.com. Thus, individuals suffering from certain diseases may require substantially larger amounts of vitamin C to achieve optimum body levels or derive therapeutic benefits, areas that were of great interest to Linus Pauling and need to be further explored. PHS II found that vitamin C supplementation (500 mg/day) for an average of eight years had no significant effect on major cardiovascular events, total myocardial infarction, or cardiovascular mortality (53). However, leukocyte vitamin C concentration does not accurately reflect vitamin C in several tissues and may specifically underestimate vitamin C uptake into skeletal muscle (26). By the late 1700s, the British navy was aware that scurvy could be cured by eating oranges or lemons, even though vitamin C would not be isolated until the early 1930s. Because systemic inflammatory responses involve excessive oxidative stress, it has been suggested that providing antioxidant nutrients like vitamin C may improve the outcome of critically ill patients in intensive care units. Fructose and vitamin C intake do not influence risk for developing hypertension. Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES). Individuals on anticoagulants should limit their vitamin C intake to <1 g/day and have their prothrombin time monitored by the clinician following their anticoagulant therapy (200). (PubMed), 26. 21. Even in small amounts, vitamin C can protect indispensable molecules in the body, such as proteins, lipids (fats), carbohydrates, and nucleic acids (DNA and RNA), from damage by free radicals and reactive oxygen species (ROS) that are generated during normal metabolism, by active immune cells, and through exposure to toxins and pollutants (e.g., certain chemotherapy drugs and cigarette smoke). There is no scientific evidence that large amounts of vitamin C (up to 10 grams [g]/day in adults) exert any adverse or toxic effects. Related to this oxidation-reduction (redox) potential, two major functions of vitamin C are as an antioxidant and as an enzyme cofactor(1). 2000;70(5):226-237. (PubMed), 20. Chen GC, Lu DB, Pang Z, Liu QF. 2014;30(1):96-101. Cardiovasc Diabetol. J Nutr. Sodium ascorbate and calcium ascorbate are the most common forms, although a number of other mineral ascorbates are available. Lessons learned from randomised controlled trials. Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract. 2013;8(2):e56803. Curhan GC, Willett WC, Rimm EB, Stampfer MJ. (PubMed). Harris HR, Orsini N, Wolk A. Vitamin C and survival among women with breast cancer: a meta-analysis. Johnston CS, Luo B. Dr. Pauling, for whom the Linus Pauling Institute has great respect, based his own recommendations for vitamin C largely on theoretical arguments. You can achieve a higher volume [concentration] in the blood by a larger intake, but you get much better improvement for the first 250 mg than for additional grams." HIF-dependent antitumorigenic effect of antioxidants in vivo. Levy MM, Fink MP, Marshall JC, et al. Weinstein M, Babyn P, Zlotkin S. An orange a day keeps the doctor away: scurvy in the year 2000. (PubMed), 155. Pharmacokinetic studies in older adults have not yet been conducted, but there is some evidence suggesting that the efficiency of one of the molecular mechanisms for the cellular uptake of vitamin C declines with age (208). Michels AJ, Hagen TM, Frei B. One hundred percent absorption efficiency is observed when ingesting vitamin C at doses up to 200 mg at a time. Carol's story is but one in 18 YEARS of consistent testimony which demonstrates that Linus Pauling's rec ommended dosages of the vitamin C, lysine (and proline) (which he and Dr. Rath called Lp (a) binding inhibitors) are almost always effective for reversing symptoms of advanced coronary heart disease within 30 to 90 days after achieving the Linus Pauling Institute Ascorbic acid levels in the aqueous humor of nocturnal and diurnal mammals. 2005;4:5. Harrison J, Rentz DM, McLaughlin T, et al. Mirvish SS, Wallcave L, Eagen M, Shubik P. Ascorbate-nitrite reaction: possible means of blocking the formation of carcinogenic N-nitroso compounds. Although two intervention studies failed to show a reduction in stomach cancer incidence with vitamin C supplementation(35), some research suggests that vitamin C supplementation may be a useful addition to standard H. pylori eradication therapy in reducing the risk of gastric cancer (76). Stamp LK, O'Donnell JL, Frampton C, Drake JM, Zhang M, Chapman PT. (PubMed), 167. Although ascorbyl palmitate is also available as an oral supplement, most of it is likely hydrolyzed to ascorbic acid and palmitic acid in the digestive tract before it is absorbed (189). Massey LK, Liebman M, Kynast-Gales SA. (PubMed), 162. Ramos C, Brito R, Gonzalez-Montero J, et al. You may hyperlink to this website but must include the following statement: "This link leads to a website provided by the Linus Pauling Institute at Oregon State University. 2001;345(22):1583-1592. (PubMed), 112. (PubMed), 113. Additionally, dietary, but not supplemental, intake of vitamin C and other antioxidant nutrients (carotenoids, proanthocyanidins, and manganese) was inversely associated with NHL risk.
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