Cell Death Dis. Jane Higdon, Ph.D. 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). (PubMed), 129. Lowell JA. High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice. 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). Studies in the 1970s and 1980s conducted by Linus Pauling, Ewan Cameron, and colleagues suggested that large doses of vitamin C (10 g/day infused intravenously for 10 days followed by at least 10 g/day orally indefinitely) were helpful in increasing the survival time and improving the quality of life of terminal cancer patients (158). Dr. Pauling, for whom the Linus Pauling Institute has great respect, based his own recommendations for vitamin C largely on theoretical arguments. Nutr J. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Angioplasty involves temporarily inserting and inflating a tiny balloon into the clogged artery to help restore the blood flow to the heart. 2006;27(11):2250-2257. Is vitamin C supplementation beneficial? Effect of high dose vitamin C on urinary oxalate levels. 2001;98(17):9842-9846. 2010;126(6):1504-1512. Vitamin supplementation for preventing miscarriage. 1998;36(3):143-147. Food and Nutrition Board, Institute of Medicine. The Physicians Health Study II was a randomized, placebo-controlled trial that examined the effect of vitamin E (400 IU/day), vitamin C (500 mg/day), and a multivitamin supplement on the risk of cancer in 14,641 middle-aged male physicians over 10.3 years (7.6 years of active treatment plus 2.8 years post-treatment follow-up) (82). J Am Soc Nephrol. Johnston CS. Lp(a) is a "sticky bandage" within coronary arteries that may induce blood clots when vitamin C/lysine blood levels are low (9). Ascorbic Acid: Biochemistry and Biomedical Cell Biology. 1997;17(3):415-425. Pauling L. The immune system. (PubMed), 19. J Infect Dis. You may not copy, modify, distribute, display, transmit, perform, publish or sell any of the copyrightable material on this website. 2011;63(10):3136-3141. Of note, a subgroup analysis in one of the meta-analyses showed a reduction of post-operative atrial fibrillation with vitamin C in non US-based trials (10 trials) but no effect of vitamin C in US-based trials (5 trials) (140). Nutrition and gastric cancer risk: an update. 2013;1(5):e239-240. Al-Khudairy L, Flowers N, Wheelhouse R, et al. Cheng Y, Willett WC, Schwartz J, Sparrow D, Weiss S, Hu H. Relation of nutrition to bone lead and blood lead levels in middle-aged to elderly men. 2010;12(2):209-217. 2001;357(9257):657-663. (PubMed), 132. Available at: https://naturalmedicines.therapeuticresearch.com. Am J Clin Nutr. (PubMed), 112. In contrast, trials are intervention studies that can establish a causal relationship between an exposure and an outcome, e.g., by evaluating the effect of vitamin C supplementation on the incidence of chronic disease in participants randomly assigned to receive either vitamin C or placebo for a given length of time. Lee SH, Oe T, Blair IA. (PubMed), 53. Clinically insignificant effect of supplemental vitamin C on serum urate in patients with gout: a pilot randomized controlled trial. (PubMed), 193. Tsivgoulis G, Safouris A, Kim DE, Alexandrov AV. Cognition in MCI and Alzheimer's disease: baseline data from a longitudinal study of the NTB. 1986;6:365-406. A systematic review. 2007;12(3):230-238. The heart muscle may become oxygen-deprived (ischemic) as the result of myocardial infarction or with aortic clamping during coronary artery bypass graft (CABG) surgery. 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. 2013(1):Cd000980. 98. (PubMed), 197. Ramos C, Brito R, Gonzalez-Montero J, et al. DeRitter E, Cohen N, Rubin SH. Natural Medicines. Reiss GR, Werness PG, Zollman PE, Brubaker RF. 2001;91(4):563-567. 2008;105(32):11105-11109. Oncogene. (PubMed), 29. (PubMed), 175. Gao X, Curhan G, Forman JP, Ascherio A, Choi HK. 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). Biofactors. Cancer Chemother Pharmacol. (National Academy Press), 36. 2014;311(20):2074-2082. Calcium in this form appears to be reasonably well absorbed. Vitamin C, also known as L-ascorbic acid, is a water-soluble, There is some evidence to suggest that vitamin C may be a useful, There are insufficient data to suggest a link between vitamin C status and the risk of developing a given type of. 25. 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). In humans, vitamin C concentration is about 15 to 20 times higher in the aqueous humorfluid that fills the anterior and posterior chambers of the eyethan in plasma, suggesting that the vitamin may be playing an important role in the eye (107). These enzymes contribute to the epigenetic regulation of gene expression by catalyzing reactions involved in the demethylation of DNA and histones. 2010;70(14):5749-5758. Song Y, Xu Q, Park Y, Hollenbeck A, Schatzkin A, Chen H. Multivitamins, individual vitamin and mineral supplements, and risk of diabetes among older U.S. adults. Kabat GC, Kim MY, Wactawski-Wende J, Shikany JM, Vitolins MZ, Rohan TE. email:[emailprotected], Chlorophyll and Metallo-Chlorophyll Derivatives, Healthcare Professional Continuing Education. Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. Carr AC, Pullar JM, Bozonet SM, Vissers MC. (PubMed), 28. Vitamin C. In: Erdman JWJ, Macdonald IA, Zeisel SH, eds. Also after Pauling passed, Life Extension reported on Japanese research showing that vitamin K has hormone-like properties, which help move calcium from soft tissue into bones. Vitamin C and A1c relationship in the National Health and Nutrition Examination Survey (NHANES) 2003-2006. (PubMed), 173. (PubMed), 119. Myocardial reperfusion injury: Reperfusion injury refers to tissue damage occurring at the time of blood flow restoration (reperfusion) following transient ischemia. Early Hum Dev. It should also be noted that the Linus Pauling Institute's recommendation is strictly directed towards prevention of disease in healthy individuals, not treatment of disease. (PubMed), 120. Lancet. The role of increased oxidative stress in the occurrence of vascular complications in subjects with diabetes has led to hypothesis that higher intakes of antioxidant nutrients could help lower the risk of CVD in diabetic subjects (144). 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. Harrison J, Rentz DM, McLaughlin T, et al. PLoS One. Two large prospective cohort studies, one following 45,251 men for six years and the other following 85,557 women for 14 years, reported that consumption of 1,500 mg of vitamin C daily did not increase the risk of kidney stone formation compared to those consuming <250 mg daily (196, 197). Phase I clinical trial of i.v. 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. 2004;140(7):533-537. Vitamin C is known to function as a highly effective antioxidant in living organisms. 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. "Vitamin C" Vitamin C and Cancer - Dr. Linus Pauling - How To Live Longer and Feel Better - Vitamin C Dr. Linus Pauling and Dr. Abram HofferVitamin C, Vita. Vitamin C infusion also lowered the concentration of markers of inflammation and endothelial injury in patients compared to placebo (154). (PubMed), 159. It is not known whether supplemental vitamin C could improve markers of glycemic control in subjects at risk of diabetes. 2010;119(3):753-765. Front Oncol. For a more detailed review of scientific research on the bioavailability of different forms of vitamin C, see The Bioavailability of Different Forms of Vitamin C. A number of possible adverse health effects of very large doses of vitamin C have been identified, mainly based on in vitro experiments or isolated case reports, and include genetic mutations, birth defects, cancer, atherosclerosis, kidney stones, "rebound scurvy," increased oxidative stress, excess iron absorption, vitamin B12 deficiency, and erosion of dental enamel. The other trial randomized subjects diagnosed with infection-related asthma to receive 5 g/day of vitamin C or a placebo for one week; a lower proportion of participants was found to present with bronchial hypersensitivity to histaminewhich characterizes chronic asthmain the vitamin C group compared to the control group (reviewed in 179). Vitamin C intake from diary recordings and risk of breast cancer in the UK Dietary Cohort Consortium. With respect to vitamin C and cerebrovascular disease, a prospective cohort study that followed more than 2,000 residents of a rural Japanese community for 20 years found that the risk of stroke in those with the highest serum concentrations of vitamin C was 29% lower than in those with the lowest serum concentrations of vitamin C (57). There is little evidence that the flavonoids in most commercial preparations increase the bioavailability or efficacy of vitamin C (187). Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice. Molecular Biology of the Cell. Chuang CH, Sheu BS, Kao AW, et al. 2008;87(1):64-69. (PubMed), 65. J Am Coll Nutr. Cigarette smoking during pregnancy and risk of preeclampsia: a systematic review. 2014;100(3):915-923. Linus Pauling Institute Faseb J. Padayatty SJ, Sun H, Wang Y, et al. The information should not be used in place of a consultation with a competent health care or nutrition professional. Eur J Clin Nutr. A vitamin C deficiency equals a collagen deficiency. When the results of the Womens Antioxidant Vitamin Estrogen (WAVE) trial were reanalyzed based on Hp genotype, antioxidant therapy (1,000 mg/day of vitamin C + 800 IU/day of vitamin E) was associated with improvement of coronary atherosclerosis in diabetic women with Hp1-1 genotype but worsening of coronary atherosclerosis in those carrying the Hp2-2 genotype (148). 2010;19(5):360-365. Website https://www.paulingtherapy.comPauling Therapy for Heart Disease:-Vitamin C 12,000 mg-Lysine 6,000 mg-Proline 2,000 mg Vitamin C is required to strengthen arteries so that the body does not try to patch arteries with "plaster casts" (atherosclerosis). Such a reduction falls within the range of assay variability and is unlikely to be clinically significant (121). Proc Natl Acad Sci U S A. The tendency to exhibit elevated blood uric acid concentrations and develop gout is often inherited; however, dietary and lifestyle modification may be helpful in both the prevention and treatment of gout (116). 2017;17(1):49. Pastor-Valero M. Fruit and vegetable intake and vitamins C and E are associated with a reduced prevalence of cataract in a Spanish Mediterranean population. Adv Pharm Bull. In the past 40 years, numerous placebo-controlled trials have examined the effect of vitamin C supplementation on the prevention and treatment of colds. Vitamin C: should we supplement? Age-related changes to the lens (thickening, loss of flexibility) and oxidative damage contribute to the formation of cataract, i.e., cloudiness or opacity in the lens that interferes with the clear focusing of images on the retina. Arthritis Res Ther. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. Synthetic or food-derived vitamin C--are they equally bioavailable? In a small (n=23), open-label trial, combined supplementation with vitamin C (1,000 mg/day) and vitamin E (400 IU/day) to AD patients taking a cholinesterase inhibitor significantly increased antioxidant levels and decreased lipoprotein oxidation in CSF after one year, but had no effect on the clinical course of AD compared to controls (104). 1998;43(3):322-326. (PubMed), 176. 2003;90(2):148-154. Relationship of ascorbic acid to blood lead levels. 17. 2014;235(1):9-20. 1994;94(7):779-781. (PubMed), 106. McEvoy CT, Schilling D, Clay N, et al. Vitamin C supplementation in pregnancy. Symptoms of scurvy include subcutaneous bleeding, poor wound closure, and bruising easily, hair and tooth loss, and joint pain and swelling. Trials. 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. (PubMed), 151. Vitamin C infusion (sodium ascorbate: 3.20 mmol/min for 1 hour then 0.96 mmol/min for 2 hours) prior to reperfusion followed by oral supplementation with vitamin C (1 g/day) and vitamin E (400 IU/day) for 84 days effectively prevented a reduction in antioxidant capacity at reperfusion and for the next six to eight hours. In contrast, observational studies reported lower plasma vitamin C concentrations in AD patients compared to cognitively healthy subjects (101)and found better cognitive function or lower risk of cognitive impairment with higher plasma vitamin C (100). Plasma vitamin C level, fruit and vegetable consumption, and the risk of new-onset type 2 diabetes mellitus: the European prospective investigation of cancer--Norfolk prospective study. Authors' perspective: What is the optimum intake of vitamin C in humans? More recent prospective cohort studies have reported no association between dietary and/or supplemental vitamin C intake and breast cancer (67-69). Auer BL, Auer D, Rodgers AL. Eur J Nutr. 2011;51(5):1068-1084. Vitamin C in health and disease. A more recent randomized, double-blind, placebo-controlled trial has been designed to examine the effect of vitamin C and vitamin E administration on ischemia-reperfusion damage in 99 patients with acute myocardial infarction undergoing coronary angioplasty (132). 1977;2(6084):437-438. Allergy Asthma Clin Immunol. These observations are consistent with other data that intakes of about 400 mg/day are associated with reduced risk of heart disease. Effect of vitamins C and E on insulin resistance in diabetes: a meta-analysis study. (PubMed), 207. 1999;91(6):547-556. Because maximizing blood concentrations of vitamin C may be important in protecting against oxidative damage to cells and biological molecules, a vitamin C intake of at least 400 mg daily might benefit older adults who are at higher risk for chronic diseases caused, in part, by oxidative damage, such as heart disease, stroke, certain cancers, and cataract. The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach. [Your name] is not affiliated or endorsed by the Linus Pauling Institute or Oregon State University. 2016;8(6). Similarly, higher serum vitamin C concentrations were associated with decreased risks of cancer-specific and all-cause mortality in 16,008 adults from the US National Health and Nutrition Examination Survey (NHANES) III (1994-1998) (129). The Normative Aging Study. Lee DH, Lim JS, Song K, Boo Y, Jacobs DR, Jr. Graded associations of blood lead and urinary cadmium concentrations with oxidative-stress-related markers in the U.S. population: results from the third National Health and Nutrition Examination Survey. (PubMed), 113. (PubMed), 108. With the latest RDA published in 2000, a tolerable upper intake level (UL) for vitamin C was set for the first time (Table 4). (PubMed), 148. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. 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). A cerebrovascular event, or stroke, can be classified as hemorrhagic or ischemic. 2013;5(11):4284-4304. (PubMed), 46 Knekt P, Ritz J, Pereira MA, et al. 2005;4:5. 2005;192(6):1856-1862; discussion 1862-1853. Basically, it's high Vitamin C doses, accompanied by high L-Lysine, L-Proline. Levine M, Wang Y, Padayatty SJ, Morrow J. Linus Pauling recommended at least 3000mg of vitamin C per day as a preventive dose, and significantly higher levels of both vitamin C and lysine for the treatment of existing heart disease. Vitamin C. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. 1999;281(15):1415-1423. Eur J Clin Invest. The European Investigation into Cancer and Nutrition (EPIC)-Norfolk prospective cohort study investigated the relationship between vitamin C status and incident heart failure in healthy adults (9,187 men and 11,112 women, aged 58.1+/-9.2 years) (49). 2005;17(3):341-345. Stamp LK, O'Donnell JL, Frampton C, Drake JM, Zhang M, Chapman PT. 2013;33:45-70. The global and regional burden of stroke. 2017;37:58-64. Breast Cancer Res Treat. The trial did not examine the effect of vitamin C on other outcomes associated with gout (122). cholesterol. 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. 1972;177(4043):65-68. 1998;392(6676):559. A meta-analysis of observational studies found that a reduced risk of age-related cataract with higher dietary vitamin C intakes in case-control studies and with higher circulating vitamin C concentrations in cross-sectional studies. Mineral salts of vitamin C are considered less acidic than vitamin C and therefore are considered "buffered." Ascorbyl palmitate is marketed as "vitamin C ester," which should not be confused with Ester-C (see above). Sauberlich HE. In an observational study that included 1,387 men, higher intakes of vitamin C were associated with lower serum concentrations of uric acid (117). 2013;22(12):2202-2211. 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. (PubMed), 92. A population-based, prospective study, the Iowa Womens Health Study, collected baseline data on diet and supplement use in 35,159 women (aged 55-69 years) and evaluated the risk of developing non-Hodgkin lymphoma (NHL) over 19 years of follow-up (80). Chen Q, Espey MG, Krishna MC, et al. Phagocytic leukocytes also produce and release cytokines, including interferons, which have antiviral activity (16). 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). 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. Nonetheless, vitamin C supplementation led to a 36% lower risk of placental abruption and to a significant increase in gestational age at birth (88). (PubMed), 179. Gillani SW, Sulaiman SAS, Abdul MIM, Baig MR. For a more detailed discussion on the bioavailability of different forms of vitamin C, see the article,The Bioavailability of Different Forms of Vitamin C. Severe vitamin C deficiency has been known for many centuries as the potentially fatal disease, scurvy. Urate crystals may form in joints, resulting in inflammation and pain, as well as in the kidneys and urinary tract, resulting in kidney stones. The first 250 mg leads you up to the level where the blood is saturated. 2018;20(2):145-166. Dietary intakes of antioxidant vitamins and mortality from cardiovascular disease: the Japan Collaborative Cohort Study (JACC) study. Zhang ZW, Patchett SE, Perrett D, Katelaris PH, Domizio P, Farthing MJ. (PubMed), 182. Over years of buildup and accumulated damage to the coronary arteries, CHD may culminate in a myocardial infarction or heart attack. (PubMed), 114. Br J Nutr. 2012(6):Cd004567. Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress. (PubMed), 188. (PubMed), 38. (PubMed), 56. While acute scurvy can be prevented by a mere 10 mg vitamin C per day, there is no current research showing how much vitamin C might be required to prevent the atherosclerotic plaques of chronic scurvy. 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).

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