(PubMed), 79 Park Y, Spiegelman D, Hunter DJ, et al. In adults, lead toxicity may result in kidney damage, high blood pressure, and anemia. At the Linus Pauling Institute, we have based our vitamin C recommendations on the current body of scientific evidence, which is significantly greater than it was at Pauling's time but remains incomplete owing to the many diverse functions of vitamin C in the human body that have yet to be fully understood. However, cases have occurred in children and the elderly on very restricted diets (33, 34). Nature. Scientific studies investigating vitamin C efficacy to prevent or treat disease need to assess baseline vitamin C status before embarking on an intervention or statistical analysis (22, 29-31). Phagocytic leukocytes also produce and release cytokines, including interferons, which have antiviral activity (16). (PubMed), 101. Efficacy and safety of vitamin C for atrial fibrillation after cardiac surgery: A meta-analysis with trial sequential analysis of randomized controlled trials. 2000;71(2):530-536. A 2013 systematic review identified 11 randomized controlled studies that evaluated the effect of vitamin C on asthma (eight trials) or exercise-induced bronchoconstriction (three trials) (180). Only one large trial in more than 14,000 older men participating in the Physicians Health Study II (PHS II) reported on cardiovascular outcomes. Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis. Recent Advances in Primary and Secondary Prevention of Atherosclerotic Stroke. (PubMed), 94. 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. 1977;2(6084):437-438. (PubMed). Am J Clin Nutr. Bergsten P, Amitai G, Kehrl J, Dhariwal KR, Klein HG, Levine M. Millimolar concentrations of ascorbic acid in purified human mononuclear leukocytes. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. 2013;2(6):e000329. 2018;9:809. They should instead seek or continue treatment with anti-hypertensive medication and make dietary and lifestyle changes in consultation with their health care provider. 2013;5(12):5161-5192. 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). Does vitamin C deficiency affect cognitive development and function? Vitamin C affects several components of the human immune system in vitro; for example, vitamin C has been shown to stimulate both the production (5-9)and function (10, 11)of leukocytes (white blood cells), especially neutrophils, lymphocytes, and phagocytes. If you wish to check foods for their vitamin C content, search USDA's FoodData Central. Vitamin C in plasma is inversely related to blood pressure and change in blood pressure during the previous year in young Black and White women. Ascorbate is depleted by smoking and repleted by moderate supplementation: a study in male smokers and nonsmokers with matched dietary antioxidant intakes. The MRC/BHF Heart Protection Study: preliminary results. Dixit S, Bernardo A, Walker JM, et al. Additional studies have reported that vitamin C enhances the chemotactic and microbial killing capacities of neutrophils and stimulates the proliferation and differentiation of B- and T-lymphocytes (reviewed in 18). Oregon State University, Reviewed in December 2018 by: Yet, most studies were small and of short duration and thus did not assess the consequence of long-term use of antioxidant vitamins on the risk of vascular complications in diabetic patients. The effectiveness of antioxidant vitamins C and E in reducing myocardial infarct size in patients subjected to percutaneous coronary angioplasty (PREVEC Trial): study protocol for a pilot randomized double-blind controlled trial. (PubMed), 77. Cognition in MCI and Alzheimer's disease: baseline data from a longitudinal study of the NTB. Despite conflicting results, it may be prudent for individuals predisposed to oxalate kidney stone formation to avoid high-dose vitamin C supplementation. Finally, mutations in genes coding for vitamin C-dependent TET demethylases, mutations that are common in cancer cells, may also contribute to resistance to vitamin C treatment (165). 2018 Alzheimer's Disease Facts and Figures. Oregon State University, Updated in November 2013 by: 2012;66(5):561-568. Vitamin C supplements are available in many forms, but there is little scientific evidence that any one form is better absorbed or more effective than another. (PubMed), 9 Vallance S. Relationships between ascorbic acid and serum proteins of the immune system. Gut. 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. Finally, no significant effect of vitamin C supplementation (1-8 g/day) was observed in therapeutic trials in which vitamin C was administered after cold symptoms occurred. (PubMed), 74. 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. 2016;33(3):307-315. Lower vitamin C concentrations in the cerebrospinal fluid (CSF) and brain extracellular matrix of a mouse model of AD were found to increase oxidative stress and accelerate amyloid deposition and disease progression (98). The Normative Aging Study. Myint PK, Luben RN, Wareham NJ, Khaw KT. Over years of buildup and accumulated damage to the coronary arteries, CHD may culminate in a myocardial infarction or heart attack. A 2012 review of nine randomized controlled trials found no substantial effect of -carotene, vitamin C, and vitamin E, administered individually or in combination over 2.1 to 12 years, on the risk of cataracts or cataract surgery (112). Jane Higdon, Ph.D. Clin Chem Lab Med. 1976;73(10):3685-3689. 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. Curr Opin Crit Care. (PubMed), 47. 2004;15(12):3225-3232. "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 is concentrated in the brain through a combination of active transport into brain tissue and retention via the blood-brain barrier (100). (PubMed), 68 Nagel G, Linseisen J, van Gils CH, et al. (PubMed), 140. 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. Ascorbic acid, cognitive function, and Alzheimer's disease: a current review and future direction. (PubMed), 184. Khodaeian M, Tabatabaei-Malazy O, Qorbani M, Farzadfar F, Amini P, Larijani B. Thomas LD, Elinder CG, Tiselius HG, Wolk A, Akesson A. Ascorbic acid supplements and kidney stone incidence among men: a prospective study. PDF The natural cancer secret: The C6 Protocol - Dr. Micozzi Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Other trials also failed to show any evidence of an effect of vitamin C on the risk of stroke. 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 concentrations predict risk of incident stroke over 10 y in 20 649 participants of the European Prospective Investigation into Cancer Norfolk prospective population study. Effect of Helicobacter pylori and its eradication on gastric juice ascorbic acid. Wei L, Liang G, Cai C, Lv J. J Nutr. 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. In a cross-sectional study conducted in 4,576 African Americans, the odds of having hyperuricemia was associated with dietary intakes high in fructose, low in vitamin C, or with high fructose-to-vitamin C ratios (118). Plasma concentrations of ascorbate reach steady-state at concentrations between 60 and 80 micromoles/L (mol/L). Results from 7,277 participants in the US National Health and Nutrition Examination Survey (NHANES) 2003-2004 indicated that an estimated 7.1% of individuals ages 6 years were deficient in vitamin Cbased on serum vitamin C concentrations <11.4 mol/L (36). 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. Acta Pathol Microbiol Scand B. 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. Oregon State University, Updated in September 2003 by: (PubMed), 65. Can J Cardiol. Endothelial dysfunction is considered to be an early step in the development of atherosclerosis. (PubMed), 135. Comparison of mortality associated with sepsis in the burn, trauma, and general intensive care unit patient: a systematic review of the literature. Levy R, Shriker O, Porath A, Riesenberg K, Schlaeffer F. Vitamin C for the treatment of recurrent furunculosis in patients with impaired neutrophil functions. Due to the pharmacokinetics and tight regulation of plasma vitamin C, supplementation with vitamin C will have variable effects in vitamin C-replete (plasma concentrations near saturation) versus sub-optimal (plasma concentrations <50 mol/L), marginally deficient (plasma concentrations <23 mol/L), or severely deficient (plasma concentrations <11 mol/L) individuals (28). Lassnigg A, Punz A, Barker R, et al. (PubMed), 34. In response to increasing oral doses of vitamin C, plasma vitamin C concentration rises steeply at intakes between 30 and 100 mg/day. Oncologist. (PubMed), 76. 2016;94(3):e170-176. Lykkesfeldt J, Christen S, Wallock LM, Chang HH, Jacob RA, Ames BN. 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. 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. Myint PK, Luben RN, Welch AA, Bingham SA, Wareham NJ, Khaw KT. Oregon State University, Updated in July 2018 by: For example, potassiumfound at high levels in bananas, potatoes, and other fruit and vegetablesis known to be important in blood pressure regulation, and elevated blood pressure is a major risk factor for stroke (see the article on Potassium). Reversal of ionoregulatory disruptions in occupational lead exposure by vitamin C. Environ Toxicol Pharmacol. Roswall N, Olsen A, Christensen J, Dragsted LO, Overvad K, Tjonneland A. Micronutrient intake and risk of urothelial carcinoma in a prospective Danish cohort. Among the five out of eight trials in asthmatic subjects that reported on FEV1 outcomes, none found a difference between vitamin C supplementation and placebo(180). 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. (PubMed), 164. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Hu X, Yuan L, Wang H, et al. Annu Rev Nutr. Results from another study by the same investigators suggested that vitamin C could not prevent the oxidation of high-density lipoprotein (HDL)-cholesterol by glycated Hb-Hp2-2 complexes in vitro nor restore impaired HDL function in diabetic mice carrying the Hp2-2 genotype (149). Int J Vitam Nutr Res. Milei J, Forcada P, Fraga CG, et al. Ascorbate increases human oxaluria and kidney stone risk. Gao P, Zhang H, Dinavahi R, et al. 20th Anniversary ed. The effect of intravenous vitamin C infusion on periprocedural myocardial injury for patients undergoing elective percutaneous coronary intervention. Cardiovasc Diabetol. 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. Ascorbyl palmitate is a vitamin C ester (i.e., ascorbic acid linked to a fatty acid). Alexander J. Michels, Ph.D. (PubMed), 126. Overall, evidence suggesting specific drugs can lower blood vitamin C concentrations in humans is limited. 2011;34(1):108-114. Dr. Pauling, for whom the Linus Pauling Institute has great respect, based his own recommendations for vitamin C largely on theoretical arguments. (PubMed), 166. Effect of one-year vitamin C- and E-supplementation on cerebrospinal fluid oxidation parameters and clinical course in Alzheimer's disease. (PubMed), 183. 2016(5):Cd004073. Cabanillas F. Vitamin C and cancer: what can we conclude--1,609 patients and 33 years later? 25. Linus Pauling is a hard guy to argue with. (PubMed), 129. Linus Pauling's Basic Vitamin Advice is Centered on Vitamin C, and adds: Vitamin E - 800 to 3200 iu Per Doctor Sinatra's Miracle of CoQ10 book, an epidemiological WHO study showed that heart attack is 70% more likely in people with low blood levels of vitamin E, than in people with high blood pressure or high choleserol. (PubMed), 58. DeRitter E, Cohen N, Rubin SH. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. 2017;9(11). Eur J Nutr. In a 1974 radio interview, he noted that "the first 250 mg is more important than any later 250 mg. Barbara Delage, Ph.D. In contrast, a 2014 meta-analysis of 10 prospective cohort studies in 17,696 women with breast cancer found a lower risk of total and breast cancer-specific mortality with higher supplemental and dietary vitamin C intakes (126). Gerontology. A vitamin C intake of at least 400 mg daily may be particularly important for older adults who are at higher risk for age-related chronic diseases. Hemila H, Chalker E. Vitamin C for preventing and treating the common cold. (PubMed), 150. Jane Higdon, Ph.D. Although the use of lead paint and leaded gasoline has been discontinued in the US, lead toxicity continues to be a significant health problem, especially in children living in urban areas. It is not known whether supplemental vitamin C could improve markers of glycemic control in subjects at risk of diabetes. Cochrane Database Syst Rev. A US national survey of more than 10,000 adults found that blood lead concentrations were inversely related to serum vitamin C concentrations (183). Chen GC, Lu DB, Pang Z, Liu QF. 2017;16(1):103. Collins R, Peto R, Armitage J. Ohno S, Ohno Y, Suzuki N, Soma G, Inoue M. High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer. Cochrane Database Syst Rev. Nutrients. Pauling recommended 3 g each of vitamin C and lysine daily as a preventive measure. Shock. Vitamin C intake, circulating vitamin C and risk of stroke: a meta-analysis of prospective studies. (PubMed), 49. Although a primary source of dietary vitamin C, consumption of fruit and vegetablesassessed by food frequency questionnairewas not found to be associated with a lower risk of congestive heart failure (49). Because high doses of vitamin C have also been found to interfere with the interpretation of certain laboratory tests (e.g., serum bilirubin, serum creatinine, and the stool guaiac assay for occult blood), it is important to inform one's health care provider of any recent supplement use. The protocol also limited microvascular dysfunction (i.e., improved microcirculatory perfusion) and improved left ventricular ejection fraction at discharge (on day 84) (138, 139). Vitamin C | Linus Pauling Institute | Oregon State University / Vitamin C The significance of the CSF-to-plasma vitamin C ratio in AD progression requires further study. The general idea is that cholesterol is a natural mechanism of repair in the blood. Approximately one-half of the cell lines tested were resistant to vitamin C cytotoxicity, a response associated with high levels of catalase activity. The mechanisms underlying differential sensitivity to vitamin C are under investigation. 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). 2001;108(3):E55. 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). Cancer Cell. The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Cochrane Database Syst Rev. (PubMed), 18. (PubMed), 54. 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. Such symptoms appear to be related to the weakening of blood vessels, connective tissue, and bone, which all contain collagen. Once plasma vitamin C concentrations reach saturation, additional vitamin C is largely excreted in the urine. 2017;151(6):1229-1238. (PubMed), 189. Mineral salts of vitamin C are considered less acidic than vitamin C and therefore are considered "buffered." Proc Natl Acad Sci U S A. 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. 2007;10(2):75-83. 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). Proc Natl Acad Sci U S A. BMC Cardiovasc Disord. 2005;192(6):1856-1862; discussion 1862-1853. Zabet MH, Mohammadi M, Ramezani M, Khalili H. Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock. You may not copy, modify, distribute, display, transmit, perform, publish or sell any of the copyrightable material on this website. Chest. Levine M, Padayatty SJ. Human skeletal muscle ascorbate is highly responsive to changes in vitamin C intake and plasma concentrations. The distribution of ascorbic acid between various cellular components of blood, in normal individuals, and its relation to the plasma concentration. 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). Bowman GL. 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. Eur Urol. Vitamin C is depleted during and following cardiac surgery (134)and this might be due to the direct quenching of ROS, the regeneration of other antioxidants, and/or a massive synthesis of catecholamines (dopamine, epinephrine, norepinephrine) (135). Ames, Iowa: Wiley-Blackwell; 2012:248-260. Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. (PubMed). (PubMed), 132. Flavonoids are a class of water-soluble plant pigments that are often found in vitamin C-rich fruit and vegetables, especially citrus fruit and berries (see the article on Flavonoids). Such symptoms are not generally serious, especially if they resolve with temporary discontinuation of vitamin C supplementation. Early symptoms of scurvy like fatigue may result from diminished levels of carnitine, which is needed to derive energy from fat, or from decreased synthesis of the catecholamine norepinephrine (see Function). 2011;40(6):483-500. Simon JA, Hudes ES. Spoelstra-de Man AME, Elbers PWG, Oudemans-van Straaten HM. (PubMed), 35. McEvoy CT, Schilling D, Clay N, et al. Most multivitamin supplements provide at least 60 mg of vitamin C. Whether older adults have higher requirements for vitamin C is not yet known with certainty, yet some older populations have been found to have vitamin C intakes considerably below the RDA of 75 and 90 mg/day for women and men, respectively (207). Endothelial dysfunction results in widespread vasoconstriction and coagulation abnormalities. JAMA. The Therapy: Vitamin C, Lysine and Proline The form of vitamin C recommended by Dr. Linus Pauling is pure pharmaceutical grade ascorbic acid: - Not buffered. Front Oncol. Nutrition and gastric cancer risk: an update. Of note, because intravenous administration of 80 g of vitamin C precipitated hemolytic anemia in two subjects with glucose-6-phosphate dehydrogenase deficiency, patients due to receive high-dose vitamin C infusion are systematically screened for this genetic disorder (166). Cochrane Database Syst Rev. Vitamin C also participates in redox recycling of other important antioxidants; for example, vitamin C is known to regenerate vitamin E from its oxidized form (see the article on Vitamin E). Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. Linus Pauling Institute New York: Marcel Decker, Inc.; 1997:1-24. 2013;1(5):e239-240. 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). Ye Z, Song H. Antioxidant vitamins intake and the risk of coronary heart disease: meta-analysis of cohort studies. (PubMed), 105. There is little evidence that the flavonoids in most commercial preparations increase the bioavailability or efficacy of vitamin C (187). Trials. Atherosclerosis. Few studies have measured vitamin C concentration in the CSF, which more closely reflects the vitamin C status of the brain. 2012;95(5):1079-1088. No association between dietary or supplemental intake of vitamin C and mortality was found after approximately 14 years of follow-up. He received these awards for chemistry in 1954 and for peace in 1962. . Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J. Vitamin C exhibits pro-oxidant properties. Supplementation with vitamin C had no effect on the overall risk of cancer or on the risk of prostate, bladder, or pancreatic cancer; there was a marginal reduction in colorectal cancer incidence with vitamin C compared to placebo (82). 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. (PubMed), 160. Stroke. (PubMed), 89. 2010;119(3):753-765. Authors' perspective: What is the optimum intake of vitamin C in humans? Sodium ascorbate and calcium ascorbate are the most common forms, although a number of other mineral ascorbates are available. 2009;20(4):863-871. Dr. Ward Dean, MD answered 5 years ago. Environ Health Perspect. (PubMed), 190. 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). Cancer Epidemiol Biomarkers Prev. 1998;36(3):143-147. The effect of vitamin C, alone or with allopurinol, decreasing serum uric acid was modest and much less than that of allopurinol alone. Roberts LJ, 2nd, Traber MG, Frei B. Vitamins E and C in the prevention of cardiovascular disease and cancer in men. 2010;91(2):487-493.
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