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). Present Knowledge in Nutrition. 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. Hendler SS, Rorvik DM. It is not known whether supplemental vitamin C could improve markers of glycemic control in subjects at risk of diabetes. 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. Pauling Therapy: Short Version South Med J. Am J Clin Nutr. Linus Pauling Institute In the Cohort of Swedish Men study, self-reported use of single-nutrient vitamin C supplements (taken seven or more times per week) at baseline was associated with a two-fold higher risk of incident kidney stones among 48,840 men (ages 45-79 years) followed for 11 years (199). 2003;90(2):148-154. In this context, it is important to note that data from the National Institutes of Health (NIH) have indicated that vitamin C levels in plasma and circulating cells become fully saturated at intakes of about 400 mg/day in young, healthy nonsmokers. (PubMed), 179. Carter P, Gray LJ, Troughton J, Khunti K, Davies MJ. (PubMed), 95. 1996;93(8):3704-3709. The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life. 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). Nutr Res. Collagen is the most abundant protein in the body. Sodium ascorbate provides 111 mg of sodium (889 mg of ascorbic acid) per 1,000 mg of sodium ascorbate, and calcium ascorbate generally provides 90 to 110 mg of calcium (890-910 mg of ascorbic acid) per 1,000 mg of calcium ascorbate. Another meta-analysis of trials found no effect of vitamins E and C, alone or in combination, on measures of -cell function and insulin resistance(146). 2016;8(6). The concern of kidney stone formation with vitamin C supplementation is discussed below. (PubMed), 114. Allergy Asthma Clin Immunol. Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial. Divergent effects of alpha-tocopherol and vitamin C on the generation of dysfunctional HDL associated with diabetes and the Hp 2-2 genotype. Arthritis Rheum. Proc Natl Acad Sci U S A. (PubMed), 187. 2005;192(6):1856-1862; discussion 1862-1853. Linus Pauling's Vit C-Lysine-Proline protocol - Ward Dean, MD 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. Plasma concentrations of ascorbate reach steady-state at concentrations between 60 and 80 micromoles/L (mol/L). Additionally, dietary, but not supplemental, intake of vitamin C and other antioxidant nutrients (carotenoids, proanthocyanidins, and manganese) was inversely associated with NHL risk. 1998;43(3):322-326. (PubMed), 81. Of note, it is possible that genetic differences among diabetic patients influence the effect of vitamin C supplementation on cardiovascular risk. 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"). Although free metal ions are not generally found under physiological conditions, the idea that high doses of vitamin C might be able to promote oxidative damage in vivo has received a great deal of attention. Antioxidant effects of vitamins in type 2 diabetes: a meta-analysis of randomized controlled trials. (PubMed), 102. 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). Food and Nutrition Board, Institute of Medicine. The protocol also limited microvascular dysfunction (i.e., improved microcirculatory perfusion) and improved left ventricular ejection fraction at discharge (on day 84) (138, 139). Zabet MH, Mohammadi M, Ramezani M, Khalili H. Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock. 2018;9:1182. Sensitivity to vitamin C may also be determined by the expression of sodium-dependent vitamin C transporter-2 (SVCT-2), which transports vitamin C into cells (173). 2017;21(1):300. 2012;37(12):2706-2714. 2012;38(2):114-122. 2013;106(5):310-315. Pediatrics. Contents Summary Function Playing in immunity Bioavailability Deficiency Aforementioned RDA Disease Prevention Cardio-vascular disease Cancer Print 2 diabetes mellitus Adverse pregnancy outcomes Although liposomal encapsulation could increase vitamin C bioavailability, plasma vitamin C concentrations were much lower than those achieved with intravenous vitamin C administration (190). Ye Z, Song H. Antioxidant vitamins intake and the risk of coronary heart disease: meta-analysis of cohort studies. Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. The mechanisms underlying differential sensitivity to vitamin C are under investigation. However, no such associations were found in pooled analyses of prospective cohort studies(109). Eur J Cardiovasc Prev Rehabil. The recommended dietary calcium intake for adults is 1,000 to 1,200 mg/day. Vitamin C Foundation Approved Cardio-C (Pauling-therapy) drink mix provides Linus Pauling's specific vitamin C and lysine. Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. 2010;341:c4229. (PubMed), 168. 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. Ann Thorac Surg. Hemila H, Suonsyrja T. Vitamin C for preventing atrial fibrillation in high risk patients: a systematic review and meta-analysis. 21. Cancer Epidemiol Biomarkers Prev. Michels AJ, Frei B. Myths, artifacts, and fatal flaws: identifying limitations and opportunities in vitamin C research. Arch Neurol. Asleh R, Levy AP. 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. Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts. Compared to standard-of-care, this intervention cocktail more than halved the mean duration of vasopressor use (18.3 h versus 54.9 h) and reduced the odds of mortality by nearly 90% (156). There is little evidence that the flavonoids in most commercial preparations increase the bioavailability or efficacy of vitamin C (187). Ischemic stroke occurs when an obstruction within a blood vessel blocks blood flow to the brain. Lessons learned from randomised controlled trials. (PubMed), 48 Kubota Y, Iso H, Date C, et al. ACS Chem Neurosci. 202 Brown BG, Zhao XQ, Chait A, et al. Other trials also failed to show any evidence of an effect of vitamin C on the risk of stroke. These products are all Lp (a) binding inhibitors. Oregon State University, Updated in July 2018 by: Two large prospective studies found dietary vitamin C intake to be inversely associated with breast cancer incidence in certain subgroups. (PubMed), 25. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. 2001;21(3):235-237. Can J Cardiol. Without collagen to repair the inevitable damage from mechanical and oxidative stress, your blood vessels grow weaker and weaker, and you eventually die from scurvy. 2012;12:61. PLoS One. (PubMed), 172. 2013(10):Cd010391. 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). (PubMed), 145. (PubMed), 182. Mirvish SS, Wallcave L, Eagen M, Shubik P. Ascorbate-nitrite reaction: possible means of blocking the formation of carcinogenic N-nitroso compounds. The lack of Vitamin C is a deficiency disease called Scurvy. 2013;32(12):1508-1517. Calcium in this form appears to be reasonably well absorbed. Am J Clin Nutr. 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. 2011;42(6):1665-1672. Vitamin C and the Common Cold. 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), 26. (PubMed), 56. 1986;104(5):753-755. Kuiper C, Molenaar IG, Dachs GU, Currie MJ, Sykes PH, Vissers MC. (PubMed), 42. Krajewska B, Brindell M. Urease activity and L-ascorbic acid. Tessier F, Moreaux V, Birlouez-Aragon I, Junes P, Mondon H. Decrease in vitamin C concentration in human lenses during cataract progression. 2009;56(5):764-770. Ascorbate is depleted by smoking and repleted by moderate supplementation: a study in male smokers and nonsmokers with matched dietary antioxidant intakes. Linus Pauling Recommendations 1. 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). Cardiovascular disease (CVD) is the leading cause of death in individuals with diabetes mellitus. 2004;27(4):925-930. Liu C, Russell RM. (PubMed), 162. (PubMed), 10. (PubMed), 70. Pharmacol Rep. 2010;62(4):751-756. Limitations inherent to dietary assessment methodology, such as recall bias, measurement error, and residual confounding, may account for some of the inconsistent associations between vitamin C intake and CHD risk. Roberts LJ, 2nd, Traber MG, Frei B. Vitamins E and C in the prevention of cardiovascular disease and cancer in men. Hypertension is a major risk factor for cardiovascular disease, including coronary heart disease, stroke, and atrial fibrillation. 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). (PubMed), 128. 2011;34(1):108-114. Goyal A, Terry MB, Siegel AB. Cardiovasc Diabetol. Oregon State University, Updated in November 2013 by: Additionally, several cross-sectional studies reported inverse associations between circulating vitamin C concentrations and markers of insulin resistance or glucose intolerance, such as glycated hemoglobin (HbA1c) concentration (50, 85, 86). Overall, evidence suggesting specific drugs can lower blood vitamin C concentrations in humans is limited. (PubMed), 113. 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). Carcinogenesis. J Natl Cancer Inst. It is widely thought by the general public that vitamin C boosts immune function, yet human studies published to date are conflicting. No association between dietary or supplemental intake of vitamin C and mortality was found after approximately 14 years of follow-up. Milner AD, Rao H, Greenough A. The MRC/BHF Heart Protection Study: preliminary results. (PubMed), 18. (PubMed), 203. PDR for Nutritional Supplements. One randomized, placebo-controlled trial has examined the effect of intravenous vitamin C administered to patients with stable angina undergoing elective coronary angioplasty (130). Clin Neuropsychol. 2012;95(5):1079-1088. 2017;17(1):49. 1999;281(24):2289-2293. (PubMed), 186. (PubMed), 30. Accessed 6/22/18. (PubMed), 170. 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. One small placebo-controlled, cross-over trial in 11 men showed that the oral administration of 4 g of vitamin C resulted in a greater vitamin C concentration in plasma over a four-hour period when vitamin C was encapsulated in liposomes compared to unencapsulated vitamin C (190). 2016;94(3):e170-176. Science. Stroke. In vitro experiments performed using 11 different cancer cell lines demonstrated that sensitivity to vitamin C correlated with the expression of catalase, an enzyme involved in the decomposition of hydrogen peroxide (172). 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. Am J Epidemiol. Age-related decline of sodium-dependent ascorbic acid transport in isolated rat hepatocytes. Kositsawat J, Freeman VL. Ann Intern Med. Similar results have been reported in septic patients given intravenous vitamin C (1.5 g/6 h), hydrocortisone (50 mg/6 h), and thiamin (200 mg/12 h) until hospital discharge. Leuk Lymphoma. 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. Choi HK, Gao X, Curhan G. Vitamin C intake and the risk of gout in men: a prospective study. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Dr. Pauling, for whom the Linus Pauling Institute has great respect, based his own recommendations for vitamin C largely on theoretical arguments. Pfister R, Sharp SJ, Luben R, Wareham NJ, Khaw KT. It contains the highest quality vitamin C that I have been able to find. Curhan GC, Willett WC, Rimm EB, Stampfer MJ. (PubMed), 121. 2005;102(38):13604-13609. 2017;13(3):558-567. Bowman GL. Lowell JA. Molecular Biology of the Cell. These contradictory findings indicate that further research is needed on potential interactions between antioxidant supplements and cholesterol-lowering drugs, such as HMG-CoA reductase inhibitors (statins). ", Linus Pauling Institute | Oregon State University BMC Cardiovasc Disord. Years later, Dr. Linus Pauling, two-time Nobel Prize winner, is ignored for reporting that large amounts of vitamin C and lysine are needed to prevent coronary attacks. 2006;114(3):350-354. Zheng Selin J, Rautiainen S, Lindblad BE, Morgenstern R, Wolk A. High-dose supplements of vitamins C and E, low-dose multivitamins, and the risk of age-related cataract: a population-based prospective cohort study of men. Reiss GR, Werness PG, Zollman PE, Brubaker RF. Roswall N, Olsen A, Christensen J, et al. Levine M, Padayatty SJ, Espey MG. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. J Infect Dis. 5 Jariwalla RJ, Harakeh S. Antiviral and immunomodulatory activities of ascorbic acid. High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice. 307 Linus Pauling Science Center 2017;3:Cd011114. Sepsis and septic shockdefined as persistent sepsis-induced low blood pressureare associated with elevated mortality rates in critically ill patients (150, 151). 2012;7(1):e29794. *Source of intake should be from foods or formula only. (PubMed), 132. See also the section on Sepsis in the Symposium on Vitamin CPart of the LPIs 9th International Conference on Diet and Optimum Health. JAMA. Yet, plasma concentrations of vitamin C 50 mol/L are sufficient to saturate muscle tissue vitamin C. There is also some limited evidence suggesting that individuals who carry certain polymorphisms in genes involved in vitamin C transport and detoxification mechanisms may have lower plasma vitamin C concentrations even with high vitamin C intakes (see also Vascular complications of diabetes mellitus) (reviewed in 27). There is a need for better quality studies to examine the effect of vitamin C on cardiovascular endpoints in participants with elevated risk of cardiovascular disease. DeRitter E, Cohen N, Rubin SH. 2014;6(9):3818-3846. Intravenous administration of 50 mg or 200 mg of vitamin C per kg per day for 96 hours to patients with sepsis admitted in intensive care unit was found to correct vitamin C deficiency. 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). Freeman; 1970. Calcium ascorbate: Calcium ascorbate generally provides 90-110 mg of calcium (890-910 mg of ascorbic acid) per 1,000 mg of calcium ascorbate. Making sense of early high-dose intravenous vitamin C in ischemia/reperfusion injury. Regular supplementation with vitamin C (0.25 to 2 g/day) did not reduce the incidence of colds in the general population (23 trials); however, in participants undergoing heavy physical stress (e.g., marathon runners, skiers, or soldiers in subarctic conditions), vitamin C supplementation halved the incidence of colds (5 trials). In: Harris JR, ed. JAMA Intern Med. Low ascorbate levels are associated with increased hypoxia-inducible factor-1 activity and an aggressive tumor phenotype in endometrial cancer. Vitamin C. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Pauling, two-time Nobel laureate and the world's foremost vitamin C proponent, entertained an overflow crowd in the Bldg. 2nd ed. Association between plasma vitamin C concentrations and blood pressure in the European prospective investigation into cancer-Norfolk population-based study. 2011;40(6):483-500. One trial found that vitamin C supplementation (1 g/day) for 14 weeks reduced the risk of asthma attacks precipitated by respiratory infection. Originally written in 2000 by: Tower drink mixes replace handfuls of pills and are made with pharmaceutical-grade, bioidentical ingredients. 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). (PubMed), 109. (PubMed), 156. Redox Rep. 2016;21(2):75-83. 2017;16(1):103. Hong SW, Lee SH, Moon JH, et al. Compared to placebo, both treatments were found to be more likely to limit risk factors contributing to diabetes-related complications, as well as to lower the risk of future cardiovascular events over a 10-year period (estimated using the Framingham risk score) (147). (PubMed), 205. In this case, vitamin C is esterified to the saturated fatty acid, palmitic acid, resulting in a fat-soluble form of vitamin C. Ascorbyl palmitate has been added to a number of skin creams due to interest in its antioxidant properties, as well as its importance in collagen synthesis (see the separate article, Vitamin C and Skin Health) (188). 2008;35(9):1853-1858. If you wish to check foods for their vitamin C content, search USDA's FoodData Central. 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). Johnston CS. Stability of vitamin C derivatives in solution and topical formulations. Adults. 2014;28(2):252-268. Sauberlich HE. Myint PK, Luben RN, Welch AA, Bingham SA, Wareham NJ, Khaw KT. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. Hammoud AO, Bujold E, Sorokin Y, Schild C, Krapp M, Baumann P. Smoking in pregnancy revisited: findings from a large population-based study. Reversing Heart Disease | Foundation for Alternative and Integrative Cochrane Database Syst Rev. After a mean follow-up of 12.8 years, plasma vitamin C was inversely associated with incident cases of heart failure. (PubMed), 183. 2009;29(3):809-815. 1998;147(12):1162-1174. 97. 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). In his Unified Theory, Linus Pauling often recommended 3,000 to 5,000 mg per day as an effective dose. Nutrients. Lysine Reported to Halt Coronaviruses: An Interview with Bill Sardi Pauling L. Vitamin C therapy and advanced cancer (letter). 2003;410(1):112-120. 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). (PubMed), 146. Several cross-sectional studies have reported an inverse association between vitamin C status and blood lead concentration. Corvallis, Oregon 97331, phone: 541-737-5075 | fax: 541-737-5077 $54.95 Add: Max: 12 Cardio-C XL Pauling-therapy Drink Mix (60 Servings) The Cardio-C XL (Pauling-therapy) drink mix provides Linus Pauling's specific Vitamin C and Lysine recommendations per the Unified Theory of. (PubMed), 193. The history of these products might make the reasons for (and differences in them) easier to understand. Vitamin C (L-ascorbic acid) is a potent reducing agent, meaning that it readily donates electrons to recipient molecules ( Figure 1 ). JAMA. Wei L, Liang G, Cai C, Lv J. In response to increasing oral doses of vitamin C, plasma vitamin C concentration rises steeply at intakes between 30 and 100 mg/day. Prospective cohort studies can examine the incidence of a specific disease in relation to vitamin C intake or body status in a cohort of participants who are followed over time. *Monooxygenases catalyze the hydroxylation of one substrate, whereas dioxygenases catalyze a reaction that couples the hydroxylation of a specific substrate with the conversion (decarboxylation) of -ketoglutarate into succinate. 2000;71(2):530-536. (PubMed), 20. P R Health Sci J. 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.