Thompson CA, Cerhan JR. Fruit and vegetable intake and survival from non-Hodgkin lymphoma: does an apple a day keep the doctor away? Ascorbic acid, cognitive function, and Alzheimer's disease: a current review and future direction. (PubMed), 82. Endothelial dysfunction results in widespread vasoconstriction and coagulation abnormalities. Specific measures of functions stimulated by vitamin C include cellular motility (10), chemotaxis(10, 11), and phagocytosis(11). An upper intake level of 2 g/day is recommended in order to prevent some adults from experiencing diarrhea and, Supplemental vitamin C increases urinary oxalate concentrations, but whether an increase in urinary oxalate elevates the risk for. A meta-analysis of 36 studies on the relationship between vitamin C intake and plasma concentrations found that the elderly require a substantially higher daily intake of vitamin C to attain plasma concentrations that younger adults achieve at a lower intake. Reports since 1991 indicate that the Pauling Therapy works as a cure by itself, but in theory, Pauling's protocol makes an ideal oral adjunct to EDTA Chelation therapy and other more conventional therapies for all forms of cardiovascular disease, except intra . The effects of antenatal smoking on lung function and respiratory symptoms in infants and children. Pauling, two-time Nobel laureate and the world's foremost vitamin C proponent, entertained an overflow crowd in the Bldg. 2007;83(11):707-711. See also the section on Sepsis in the Symposium on Vitamin CPart of the LPIs 9th International Conference on Diet and Optimum Health. 2008;7:35. 2013;173(5):386-388. 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. Vitamin C in Health and Disease. South Med J. J Am Soc Nephrol. Diabetol Metab Syndr. The potential effect of antioxidants during chemotherapy is not well understood, yet only likely to be an issue if a specific chemotherapeutic agent acts through an oxidative mechanism, which is uncommon (171). Sisto T, Paajanen H, Metsa-Ketela T, Harmoinen A, Nordback I, Tarkka M. Pretreatment with antioxidants and allopurinol diminishes cardiac onset events in coronary artery bypass grafting. However, in test tube experiments, vitamin C can interact with some free metal ions and lead to the generation of potentially damaging free radicals. 2010;119(3):753-765. Although liposomal encapsulation could increase vitamin C bioavailability, plasma vitamin C concentrations were much lower than those achieved with intravenous vitamin C administration (190). Relationship of ascorbic acid to blood lead levels. 2008;26(3):297-304. Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract. Alberts B, Bray D, Lewis J, Raff M. Differentiated cells and the maintenance of tissues. Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. (PubMed), 199. THERAPEUTIC: Pauling recommended that those who have had a heart attack or stroke should take at least 6 or more grams of vitamin C and 4 to 6 grams of lysine. Cardiovasc Diabetol. Front Physiol. 201. Levy MM, Fink MP, Marshall JC, et al. PLoS One. 2016;94(3):e170-176. Only one large trial in more than 14,000 older men participating in the Physicians Health Study II (PHS II) reported on cardiovascular outcomes. (PubMed), 136. 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). Myint PK, Luben RN, Welch AA, Bingham SA, Wareham NJ, Khaw KT. Faseb J. Effect of oral vitamin C supplementation on serum uric acid: a meta-analysis of randomized controlled trials. Ascorbate increases human oxaluria and kidney stone risk. Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials. 2013;106(5):310-315. Both vitamin C and aspirin reduced fasting blood glucose and HbA1c concentrations and improved blood lipid profile in metformin-treated patients. 2005;135(7):1673-1677. Whether any increase in oxalate levels would translate to an elevation in risk for kidney stones has been examined in several epidemiological studies. Int J Vitam Nutr Res Suppl. (PubMed), 30. Oregon State University, Updated in January 2006 by: Few studies have measured vitamin C concentration in the CSF, which more closely reflects the vitamin C status of the brain. Jane Higdon, Ph.D. 2016;73(8):1645-1658. Adv Nutr. In both the Japanese (57)and EPIC-Norfolk (58)populations, blood vitamin C concentrations were highly correlated with fruit and vegetable intake. The recommended dietary allowance (RDA) for vitamin C is based on the amount of vitamin C intake necessary to maintain neutrophil vitamin C concentration with minimal urinary excretion of vitamin C and is proposed to provide sufficient antioxidant protection (Table 2) (35). 2012;95(5):1079-1088. 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. Oregon State University, Updated in November 2013 by: Plasma ascorbic acid, a priori diet quality score, and incident hypertension: a prospective cohort study. Am J Clin Nutr. (PubMed), 35. Gillani SW, Sulaiman SAS, Abdul MIM, Baig MR. (PubMed), 139. Dr. Pauling, for whom the Linus Pauling Institute has great respect, based his own recommendations for vitamin C largely on theoretical arguments. Dihydropyridine calcium channel blockers (e.g., nicardipine, nifedipine) can inhibit vitamin C uptake by intestinal cells in vitro. J Transl Med. (National Academy Press), 36. Nutr Cancer. 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. Does vitamin C deficiency affect cognitive development and function? As mentioned previously, the body produces collagen from lysine and proline. 1998;392(6676):559. 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). (PubMed), 56. (PubMed). 2018;20(2):145-166. Kitsantas P, Christopher KE. Bergsten P, Amitai G, Kehrl J, Dhariwal KR, Klein HG, Levine M. Millimolar concentrations of ascorbic acid in purified human mononuclear leukocytes. Dr. Pauling significantly increased his recommendation in his 1986 book How To Live Longer and Feel Better. 2007;104(21):8749-8754. 2001;357(9257):657-663. 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. 2014;6(9):3818-3846. Valls N, Gormaz JG, Aguayo R, et al. Angioplasty involves temporarily inserting and inflating a tiny balloon into the clogged artery to help restore the blood flow to the heart. Sauberlich HE. 2011;51(5):1068-1084. Chest. (PubMed), 62. (PubMed), 74. Although trials do not currently support the use of high-dose supplementation with vitamin C in cataract prevention, there is a consistent inverse association observed between high daily intake of fruit and/or vegetables (>5 servings/day) and risk of cataract (113). Unlike plants and most animals, humans have lost the ability to synthesize vitamin C endogenously and therefore have an essential dietary requirement for this vitamin (see The Recommended Dietary Allowance). High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice. J Am Heart Assoc. Authors' perspective: What is the optimum intake of vitamin C in humans? Ascorbyl palmitate is a vitamin C ester (i.e., ascorbic acid linked to a fatty acid). 2017;9(11). Pharmacol Rep. 2010;62(4):751-756. (PubMed), 189. (PubMed), 147. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Christchurch, New Zealand, Reviewed in December 2018 by: Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. 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). Biofactors. (PubMed), 168. The significance of the CSF-to-plasma vitamin C ratio in AD progression requires further study. 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 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. 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). 2013;5(12):5161-5192. Roswall N, Olsen A, Christensen J, Dragsted LO, Overvad K, Tjonneland A. Micronutrient intake and risk of urothelial carcinoma in a prospective Danish cohort. 2013;13:52. A UL of 2 g (2,000 mg) daily was recommended in order to prevent generally healthy adults from experiencing diarrhea and gastrointestinal disturbances (35). (PubMed), 105. (PubMed), 27. The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach. Arch Intern Med. McEvoy CT, Schilling D, Clay N, et al. (PubMed), 70. The results of this study also indicated that supplemental vitamin C may be helpful in the prevention of gout (119). Accessed 6/22/18. 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. Several cross-sectional studies have reported an inverse association between vitamin C status and blood lead concentration. Arch Med Sci. 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). Linus Pauling Institute 2010;19(5):360-365. Why is Collagen Important ? Ischemic stroke occurs when an obstruction within a blood vessel blocks blood flow to the brain. Although these metabolites are purported to increase the bioavailability of vitamin C, the only published study in humans addressing this issue found no difference between Ester-C and commercially available vitamin C tablets with respect to the absorption and urinary excretion of vitamin C (187). Cochrane Database Syst Rev. (PubMed), 164. 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 some evidence, though controversial, that vitamin C interacts with anticoagulant medications like warfarin (Coumadin). Conversely, there are case reports suggesting that supplemental vitamin C may lower blood concentrations of some medications, such as fluphenazine (the antipsychotic drug, Prolixin) and indinavir (the antiretroviral drug, Crixivan) (200). 200. Vitamin C is required to strengthen arteries so that the body does not try to patch arteries with "plaster casts" (atherosclerosis). (PubMed), 44. Intake of antioxidant nutrients and risk of non-Hodgkin's Lymphoma in the Women's Health Initiative. Cell Mol Life Sci. 2003;410(1):112-120. 2009;20(4):863-871. Infection with the bacteria, Helicobacter pylori (H. pylori), is known to increase the risk of stomach cancer and is associated with lower vitamin C content of stomach secretions (74, 75). 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). A few observational studies in cancer patients undergoing chemotherapy and/or radiotherapy reported that complementary intravenous vitamin C treatment was associated with a reduction in treatment-associated side effects and an improved quality of life (171). (PubMed), 67. 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. Breast Cancer Res Treat. Most (~80%) cerebrovascular events in high-income countries are ischemic in nature and associated with atherosclerosis as an underlying condition (55, 56). 2009;90(5):1252-1263. (PubMed), 148. J Am Soc Nephrol. Intravenous vitamin C for cancer therapy - identifying the current gaps in our knowledge. Another meta-analysis of 40 randomized controlled trials in 276,820 women found no effect of vitamin C, alone or combined with vitamin E or multivitamins, when supplemented during pregnancy (starting prior to 20 weeks gestation), on the risks of overall fetal loss, miscarriage, stillbirth, and congenital malformation(89). Association of vitamin C with the risk of age-related cataract: a meta-analysis. Freeman; 1970. Spoelstra-de Man AME, Elbers PWG, Oudemans-van Straaten HM. 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). 2013;9(1):46. J Emerg Med. Periprocedural myocardial injury: Coronary angioplasty (also called percutaneous transluminal coronary angioplasty) is a nonsurgical procedure for treating obstructive coronary heart disease (CHD), including unstable angina pectoris, acute myocardial infarction, and multivessel CHD. Ascorbate is depleted by smoking and repleted by moderate supplementation: a study in male smokers and nonsmokers with matched dietary antioxidant intakes. (PubMed), 29. Jariwalla RJ, Harakeh S. Mechanisms underlying the action of vitamin C in viral and immunodeficiency disease. The information is made available with the understanding that the author and publisher are not providing medical, psychological, or nutritional counseling services on this site. Lowell JA. Michels AJ, Hagen TM, Frei B. Basili S, Tanzilli G, Mangieri E, et al. 1999;181(4):1026-1035. 2013;33:45-70. The effect of vitamin C supplementation, in combination with other antioxidants, on CSF biomarkers and cognitive function has been examined in only a few trials involving AD patients. Gout, a condition that afflicts more than 4% of US adults (114), is characterized by abnormally high blood concentrations of uric acid (urate) (115). (PubMed), 91. (PubMed), 196. (PubMed), 128. In addition, hypovitaminosis C is common in critically ill patients, especially in those with septic shock, and persists despite enteral/parenteral nutritional therapy providing recommended amounts of vitamin C (152). Higher plasma concentrations achieved via intravenous vitamin C administration are comparable to those that are toxic to cancer cells in culture. Oregon State University, Updated in July 2018 by: Lp(a) is a substitute for ascorbate (Vitamin C). J Rheumatol. San Francisco: W.H. There is a need for larger, longer-duration phase II clinical trials that test the efficacy of intravenous vitamin C in disease progression and overall survival (176). He was introduced to the The information should not be used in place of a consultation with a competent health care or nutrition professional. 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). Rautiainen S, Lindblad BE, Morgenstern R, Wolk A. Vitamin C supplements and the risk of age-related cataract: a population-based prospective cohort study in women. Shock. Anderson R, Oosthuizen R, Maritz R, Theron A, Van Rensburg AJ. Linus Pauling Recommendations 1. Vitamin C also limited endothelial dysfunction that was experimentally induced in healthy volunteers (39). 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. Hemila H, Chalker E. Vitamin C for preventing and treating the common cold. Adjuvant effect of vitamin C on omeprazole-amoxicillin-clarithromycin triple therapy for Helicobacter pylori eradication. (PubMed), 41. 15. Effect of high dose vitamin C on urinary oxalate levels. Weinstein M, Babyn P, Zlotkin S. An orange a day keeps the doctor away: scurvy in the year 2000. 1976;73(10):3685-3689. Hammoud AO, Bujold E, Sorokin Y, Schild C, Krapp M, Baumann P. Smoking in pregnancy revisited: findings from a large population-based study. Pauling LC. Basically, it's high Vitamin C doses, accompanied by high L-Lysine, L-Proline. 2017;21(1):300. An intervention trial in 75 adult male smokers found that supplementation with 1,000 mg/day of vitamin C resulted in significantly lower blood lead concentration over a four-week treatment period compared to placebo(184). Milei J, Forcada P, Fraga CG, et al. Intravenous ascorbic acid infusion improves myocardial perfusion grade during elective percutaneous coronary intervention: relationship with oxidative stress markers. (PubMed), 48 Kubota Y, Iso H, Date C, et al. Potential mechanisms of action for vitamin C in cancer: reviewing the evidence. Association between plasma vitamin C concentrations and blood pressure in the European prospective investigation into cancer-Norfolk population-based study. Cancer Epidemiol Biomarkers Prev. (PubMed), 59. 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). 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). In developing his recommendations, he used cross-species comparisons, evolutionary arguments, the concept of biochemical individuality, and the amount of vitamin C likely consumed in a raw plant food diet. (PubMed), 130. Pravda J. Metabolic theory of septic shock. 202 Brown BG, Zhao XQ, Chait A, et al. 2011;34(1):108-114. In particular, a specific allele of the haptoglobin gene (Hp), namely Hp2, appears to be associated with an increased risk of diabetic vascular complications. In a cohort of 21,831 adults followed for 12 years in the EPIC-Norfolk study, high plasma vitamin C was found to be strongly associated with a reduced risk of diabetes(84). 2001;98(17):9842-9846. Al-Khudairy L, Flowers N, Wheelhouse R, et al. Proc Natl Acad Sci U S A.