A similar finding was obtained in a double-blind, randomized controlled trial in which combined supplementation with vitamin C (500 mg/day), vitamin E (800 IU/day), and -lipoic acid (900 mg/day) for 16 weeks reduced lipoprotein oxidation in CSF but elicited no clinical benefit in individuals with mild-to-moderate AD (n=78) (105). Improved endothelial function was observed with daily vitamin C doses above 500 mg (39). Dr. Pauling, for whom the Linus Pauling Institute has great respect, based his own recommendations for vitamin C largely on theoretical arguments. 1995;59(6):1519-1523. Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial. Plasma and dietary vitamin C levels and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). You may not copy, modify, distribute, display, transmit, perform, publish or sell any of the copyrightable material on this website. Ames, Iowa: Wiley-Blackwell; 2012:248-260. These, together with a general anti-oxidant recommendation which included vitamin A and E, were his specific recommendation for the prevention and treatment of cardiovascular disease. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. (PubMed), 158. 1996;155(6):1847-1851. J Infect Dis. If you are not getting enough Vitamin C to produce collagen for tissue repair, when your arteries become injured they cannot heal properly. Nutr Res. Only one large trial in more than 14,000 older men participating in the Physicians Health Study II (PHS II) reported on cardiovascular outcomes. Accessed 7/2/18. (PubMed), 114. However, no difference in the infarct size between antioxidant vitamin treatment and placebo was seen (138). Sodium ascorbate and calcium ascorbate are the most common forms, although a number of other mineral ascorbates are available. Vitamin C and A1c relationship in the National Health and Nutrition Examination Survey (NHANES) 2003-2006. ascorbic acid in advanced malignancy. European Prospective Investigation into Cancer and Nutrition. A number of observational studies have found increased dietary vitamin C intake to be associated with decreased risk of gastric (stomach) cancer, and laboratory experiments indicate that vitamin C inhibits the formation of carcinogenic N-nitroso compounds in the stomach (70-72). (PubMed), 176. (PubMed), 83. The dietary fructose: vitamin C intake ratio is associated with hyperuricemia in African-American adults. Ascorbic Acid: Biochemistry and Biomedical Cell Biology. Overall, an inverse association between fruit and vegetable intake and risk of NHL was observed. 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). 2017;151(6):1229-1238. The Linus Pauling Protocol - Vitamin C Vitamin C Deficiency Has Major Impact on Collagen Production Vitamin C is required to make a protein called collagen which is the major component of connective tissues. 1999;13(9):1007-1024. J Pharm Biomed Anal. How to Live Longer and Feel Better. Proc Natl Acad Sci U S A. Moran JP, Cohen L, Greene JM, et al. 2012(6):Cd004567. Collagen is the most abundant protein in the body. J Transl Med. Cardiovasc Diabetol. (PubMed), 19. (PubMed), 42. Lancet Glob Health. Cognition in MCI and Alzheimer's disease: baseline data from a longitudinal study of the NTB. Science. Int J Surg. 2014;4:283. Buijsse B, Jacobs DR, Jr., Steffen LM, Kromhout D, Gross MD. (PubMed), 183. Reiss GR, Werness PG, Zollman PE, Brubaker RF. One 12-month randomized placebo-controlled trial in 456 participants with type 2 diabetes treated with metformin examined the effect of vitamin C (500 mg/day) or acetylsalicylic acid (aspirin; 100 mg/day) on risk factors for diabetes-related complications such as CVD (147). Linus Pauling Institute The effect of vitamin therapy on the progression of coronary artery atherosclerosis varies by haptoglobin type in postmenopausal women. 2015;122(13):1740-1747. (PubMed), 160. A 2013 meta-analysis of 17 prospective cohort studies reported a 19% lower risk of stroke with the highest versus lowest dietary vitamin C intakes and a 38% lower risk with the highest versus lowest circulating vitamin C concentrations (59). 1996;93(8):3704-3709. Angioplasty involves temporarily inserting and inflating a tiny balloon into the clogged artery to help restore the blood flow to the heart. Am J Clin Nutr. 2011;30(6):477-483. Gerontology. Moreover, several dioxygenases involved in the regulation of gene expression and the maintenance of genome integrity require vitamin C as a cofactor. J Am Soc Nephrol. Regarding the incidence of colds, a difference was observed between two groups of participants. (PubMed), 185. People with impaired kidney function may be at risk for aluminum toxicity when supplemental vitamin C is taken at the same time as these compounds (200, 201). Indeed, research has recently uncovered the crucial role played by enzymes, such as the TET dioxygenases and Jumonji domain-containing histone demethylases, in the fate of cells and tissues (seeTable 1). The lens of the eye focuses light, producing a clear, sharp image on the retina, a layer of tissue on the inside back wall of the eyeball. The mechanism(s) by which vitamin C reduces blood lead concentration is not known, yet it has been proposed that vitamin C could inhibit intestinal absorption (184)or enhance urinary excretion of lead (185). 2013;177(6):548-555. Nutr J. (PubMed), 89. 1997;17(3):415-425. 2014;235(1):9-20. Thorac Cardiovasc Surg. 2009;16(1):93-98. Zhu Y, Pandya BJ, Choi HK. The effect of antioxidant vitamins E and C on cognitive performance of the elderly with mild cognitive impairment in Isfahan, Iran: a double-blind, randomized, placebo-controlled trial. (PubMed), 3 Camarena V, Wang G. The epigenetic role of vitamin C in health and disease. 2nd ed. Vitamin C | Linus Pauling Institute | Oregon State University J Natl Cancer Inst. 2011;63(10):3136-3141. 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). Montvale: Thomson Reuters; 2008. In the three trials that included a total of 40 participants with exercise-induced bronchoconstriction, vitamin C administration before exercise (a 0.5-g dose on two subsequent days in one trial, a single dose of 2 g in the second trial, and 1.5 g daily for two weeks in the third trial) significantly reduced the exercise-induced decline in FEV1. Myocardial reperfusion injury: Reperfusion injury refers to tissue damage occurring at the time of blood flow restoration (reperfusion) following transient ischemia. 1996;173(6):1502-1505. 2013;5(12):5161-5192. 2016;6(2):243-250. Specifically, plasma vitamin C ranged from approximately 23 to 70 mol/L in men and 33 to 82 mol/L in women; across this range, every 20 mol/L increase in plasma vitamin C was associated with a 9% reduction in risk of heart failure. Trials. 2011;40(6):483-500. Linus Pauling Institute 2008;19(11):1969-1974. 2001;21(3):235-237. Combined effect of metformin with ascorbic acid versus acetyl salicylic acid on diabetes-related cardiovascular complication; a 12-month single blind multicenter randomized control trial. Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. (PubMed), 28. Nutrients. No association between fruit, vegetables, antioxidant nutrients and risk of renal cell carcinoma. 16. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice. About the Pauling Therapy - Heart Disease Cause and Cure Cabanillas F. Vitamin C and cancer: what can we conclude--1,609 patients and 33 years later? 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. Linus Pauling Institute 2014;13(4):280-300. Yokoyama T, Date C, Kokubo Y, Yoshiike N, Matsumura Y, Tanaka H. Serum vitamin C concentration was inversely associated with subsequent 20-year incidence of stroke in a Japanese rural community. Clin Chem Lab Med. Semin Arthritis Rheum. 5 Jariwalla RJ, Harakeh S. Antiviral and immunomodulatory activities of ascorbic acid. Science. Most (~80%) cerebrovascular events in high-income countries are ischemic in nature and associated with atherosclerosis as an underlying condition (55, 56). Vitamin C intake and serum uric acid concentration in men. (PubMed), 49. 2016;33(3):307-315. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Mathew MC, Ervin AM, Tao J, Davis RM. 2018;24(4):248-255. (PubMed), 115. 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. 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. (PubMed), 153. 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. 1977;47(3):248-257. Large doses of vitamin C may block the action of warfarin and thus lower its effectiveness. Additionally, work by Linus Pauling Institute investigators has shown that cellular uptake of vitamin C declines with age, supporting the notion that vitamin C requirements are increased in the elderly. 2007;104(21):8749-8754. Current evidence of the efficacy of intravenous vitamin C in cancer patients is limited to observational studies, uncontrolled interventions, and case reports(174, 175). In contrast, a much larger trial in more than 20,000 men and women with coronary heart disease or diabetes mellitus found that simvastatin and an antioxidant combination (600 mg vitamin E, 250 mg vitamin C, and 20 mg -carotene daily) did not diminish the cardioprotective effects of simvastatin therapy over a five-year period (203). 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). 2010;91(2):487-493. PDF THE COLLAGEN CONNECTION - LINUS PAULING - Vitamin C Arch Intern Med. Asleh R, Levy AP. After 14 years of follow-up, it was found that men who consumed 1,000 mg/day of vitamin C had a 41% higher risk of kidney stones compared to men consuming <90 mg of vitamin C daily. J Stroke. Criteria and recommendations for vitamin C intake. Each of the cohort studies used self-administered food frequency questionnaires at baseline to assess vitamin C intake. Age-related decline of sodium-dependent ascorbic acid transport in isolated rat hepatocytes. Production of both collagen and elastin requires vitamin C, lysine and proline. (PubMed), 101. (PubMed), 167. The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach. Polymeropoulos E, Bagos P, Papadimitriou M, Rizos I, Patsouris E, Tauoumpoulis I. Vitamin C for the prevention of postoperative atrial fibrillation after cardiac surgery: a meta-analysis. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. Christchurch, New Zealand, Reviewed in December 2018 by: A 2014 meta-analysis of 44 randomized controlled trials in subjects with or without chronic diseases summarized the effect of supplemental vitamin C on endothelial function by measuring FMD (19 studies), assessing forearm blood flow (20 studies), or by pulse wave analysis (5 trials) (39). 2010;103(9):1251-1259. In order to overcome such limitations, some prospective studies measured plasma or serum concentrations of vitamin C as a more reliable index of vitamin C intake and biomarker of body vitamin C status. 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. Similarly, the EPIC-Norfolk study, a 10-year prospective cohort study in 20,649 adults, found that individuals with plasma vitamin C concentrations in the top quartile (25%) had a 42% lower risk of stroke compared to those in the lowest quartile (66 mol/L vs. <41 mol/L) (58). An eight-week, open-label, controlled trial randomized 40 subjects with gout to receive either allopurinol (standard-of-care), vitamin C, or both treatments (122). Vitamin C in Health and Disease. A lower dose of 200 mg/day did not significantly affect blood lead concentration, although serum vitamin C concentrations were not different from those in the group who took 1,000 mg/day. Effect of one-year vitamin C- and E-supplementation on cerebrospinal fluid oxidation parameters and clinical course in Alzheimer's disease. (PubMed), 40. Oregon State University, Updated in November 2002 by: Two large prospective cohort studies assessed the relationship between dietary and supplemental vitamin C intakes and mortality. Dietary intakes of antioxidant vitamins and mortality from cardiovascular disease: the Japan Collaborative Cohort Study (JACC) study. (PubMed), 11. 2009;170(4):472-483. Information regarding vitamin C and the prevention of chronic disease is based on both observational prospective cohort studies and randomized controlled trials(29, 37). 202 Brown BG, Zhao XQ, Chait A, et al. 2005;17(3):341-345. 2017;16(1):103. Vitamin C is known to function as a highly effective antioxidant in living organisms. Dr. Pauling significantly increased his recommendation in his 1986 book How To Live Longer and Feel Better. Relationship between oxidative stress, lipid peroxidation, and ultrastructural damage in patients with coronary artery disease undergoing cardioplegic arrest/reperfusion. 2016;5(2):94-100. PDF The Cure for Heart Disease: Condensed - Cardiacos.net Chen Q, Espey MG, Sun AY, et al. A 2017 review of eight published randomized controlled trials found inconsistent results from seven trials reporting on the effect of vitamin C supplementation on serum cholesterol and triglycerides, established risk factors for cardiovascular disease(52). 2009;90(5):1252-1263. In most trials, participants received 2 g of vitamin C prior to undergoing CABG or valve replacement surgery and 1 to 2 g/day for five days post-surgery. 2017;37:58-64. Cochrane Database Syst Rev. The most recent large prospective cohort study found an inverse association between dietary vitamin C intake and CHD mortality in Japanese women, but not in men (48). Retrospective in vitro colony formation assays revealed that patient leukemic cells displayed variable sensitivity to vitamin C treatment: leukemic cells from seven out of the nine patients who experienced a significant clinical benefit were sensitive to vitamin C in vitro (i.e., "responders"); the leukemic cells from the remaining six patients were not sensitive to vitamin C (i.e., "non-responders"). Ye Z, Song H. Antioxidant vitamins intake and the risk of coronary heart disease: meta-analysis of cohort studies. This is typically observed at doses between 200 to 400 mg/day in healthy young adults, with some degree of individual variation (23, 24). Vitamin C also limited endothelial dysfunction that was experimentally induced in healthy volunteers (39). 1951;113:628-631. Good quality long-term trials are needed to examine whether the anti-hypertensive effect of vitamin C is sustained over time and eventually results in a reduced risk of cardiovascular events. Levine M, Wang Y, Padayatty SJ, Morrow J. J Am Heart Assoc. (PubMed), 84. Am J Clin Nutr. 2016;8(6). It is important for individuals with significantly elevated blood pressure not to rely on vitamin C supplementation alone to reduce their hypertension. Ashor AW, Lara J, Mathers JC, Siervo M. Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomised controlled trials. Al-Khudairy L, Flowers N, Wheelhouse R, et al. (PubMed), 86. (PubMed), 85. Natural Medicines. Vitamin C. In: Erdman JWJ, Macdonald IA, Zeisel SH, eds. 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. Oregon State University, Reviewed in December 2018 by: Overall, observational prospective cohort studies have reported no or modest inverse associations between vitamin C intake and the risk of developing a given type of cancer(37, 61-63). Integr Cancer Ther. Alberts B, Bray D, Lewis J, Raff M. Differentiated cells and the maintenance of tissues. JACC Cardiovasc Interv. Cell Death Dis. A secondary analysis of a multicenter, randomized, double-blind, placebo-controlled trial in nearly 10,000 pregnant women found no reduction in the risk of preeclampsia with supplemental vitamin C (1,000 mg/day) and vitamin E (400 IU/day), regardless of womens smoking status during pregnancy. Clinically insignificant effect of supplemental vitamin C on serum urate in patients with gout: a pilot randomized controlled trial. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. The Linus Pauling Institute's Micronutrient Information Center provides scientific information on the health aspects of dietary factors and supplements, food, and beverages for the general public. Reversing Heart Disease | Linus Pauling | Tower Laboratories In addition, there is currently little evidence to support a role for vitamin C in the management of patients with gout (123). Kook SY, Lee KM, Kim Y, et al. 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. Michels KB, Holmberg L, Bergkvist L, Ljung H, Bruce A, Wolk A. Dietary antioxidant vitamins, retinol, and breast cancer incidence in a cohort of Swedish women. A vitamin C deficiency equals a collagen deficiency. A recent randomized controlled trial assessed the effect of vitamin C and vitamin E administration on reperfusion damage in patients who experienced acute myocardial infarction and underwent coronary angioplasty (see below) (132). Jane Higdon, Ph.D. Corvallis, Oregon 97331, phone: 541-737-5075 | fax: 541-737-5077 2013;13:52. A meta-analysis of 10 trials that examined antioxidant vitamins, of which five included vitamin C, found no association between any antioxidant vitamin (vitamin C, vitamin E, or -carotene), administered alone or in combination, and risk of stroke (60). (PubMed), 208. (PubMed). (PubMed), 151. Padayatty SJ, Sun H, Wang Y, et al. (PubMed), 137. Cardiovascular disease (CVD) is the leading cause of death in individuals with diabetes mellitus. The majority of large, population-based studies examining the relationship of vitamin C intake or supplementation with AD incidence have reported null results (100). Plasma vitamin C predicts incident heart failure in men and women in European Prospective Investigation into Cancer and Nutrition-Norfolk prospective study. (PubMed), 136. 2001;292(5524):2083-2086. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. The Linus Pauling Institute's Micronutrient Information Center provides scientific information on the health aspects of dietary factors and supplements, food, and beverages for the general public. Antioxidant effects of vitamins in type 2 diabetes: a meta-analysis of randomized controlled trials.
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