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). 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). (PubMed), 151. The protocol also limited microvascular dysfunction (i.e., improved microcirculatory perfusion) and improved left ventricular ejection fraction at discharge (on day 84) (138, 139). 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. Nature. Curr Opin Rheumatol. (PubMed), 185. (PubMed), 119. HIF-dependent antitumorigenic effect of antioxidants in vivo. Oregon State University, Copyright 2000-2023 Linus Pauling Institute. (PubMed), 74. It is not clear whether vitamin C given parenterally could diminish or increase the efficacy of chemotherapy drugsin particular, akylating agents (e.g., cyclophosphamide, busulfan), antitumor antibiotics (e.g., doxorubicin, bleomycin), and arsenic trioxide. It is not intended as nutritional or medical advice for individual problems. (PubMed), 73 Jenab M, Riboli E, Ferrari P, et al. (PubMed), 78. (PubMed), 112. Jane Higdon, Ph.D. 2009;90(5):1252-1263. If you are not getting enough Vitamin C to produce collagen for tissue repair, when your arteries become injured they cannot heal properly. J Am Soc Nephrol. Frei B, Birlouez-Aragon I, Lykkesfeldt J. 17. Victoria J. Drake, Ph.D. High-dose of vitamin C supplementation reduces amyloid plaque burden and ameliorates pathological changes in the brain of 5XFAD mice. 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. 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. Harding AH, Wareham NJ, Bingham SA, et al. 2010;119(3):753-765. (PubMed), 9 Vallance S. Relationships between ascorbic acid and serum proteins of the immune system. Association of vitamin C with the risk of age-related cataract: a meta-analysis. J Res Pharm Pract. Comparison of the absorption and excretion of three commercially available sources of vitamin C. J Am Diet Assoc. Sodium ascorbate and calcium ascorbate are the most common forms, although a number of other mineral ascorbates are available. 2012;69(7):836-841. Potential mechanisms of action for vitamin C in cancer: reviewing the evidence. 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). Serum antioxidant nutrients, vitamin A, and mortality in U.S. Levy MM, Fink MP, Marshall JC, et al. (PubMed), 29. Amelioration of persistent left ventricular function impairment through increased plasma ascorbate levels following myocardial infarction. The recommended dietary calcium intake for adults is 1,000 to 1,200 mg/day. Related to this oxidation-reduction (redox) potential, two major functions of vitamin C are as an antioxidant and as an enzyme cofactor(1). Two large prospective cohort studies assessed the relationship between dietary and supplemental vitamin C intakes and mortality. Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Mirvish SS, Wallcave L, Eagen M, Shubik P. Ascorbate-nitrite reaction: possible means of blocking the formation of carcinogenic N-nitroso compounds. 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). 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). Ascorbic acid and rates of cognitive decline in Alzheimer's disease. Ye Z, Song H. Antioxidant vitamins intake and the risk of coronary heart disease: meta-analysis of cohort studies. (PubMed), 130. Calcium in this form appears to be reasonably well absorbed. Weinstein M, Babyn P, Zlotkin S. An orange a day keeps the doctor away: scurvy in the year 2000. 195. Carol's story is but one in 18 YEARS of consistent testimony which demonstrates that Linus Pauling's rec ommended dosages of the vitamin C, lysine (and proline) (which he and Dr. Rath called Lp (a) binding inhibitors) are almost always effective for reversing symptoms of advanced coronary heart disease within 30 to 90 days after achieving the 2015;4(11). 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). The information on dietary factors and supplements, food, and beverages contained on this website does not cover all possible uses, actions, precautions, side effects, and interactions. (PubMed), 110. Integr Cancer Ther. With the latest RDA published in 2000, a tolerable upper intake level (UL) for vitamin C was set for the first time (Table 4). To get the best results here, I recommend Cardio-C from the Vitamin C Foundation. 10th ed. Making sense of early high-dose intravenous vitamin C in ischemia/reperfusion injury. Carr AC, Maggini S. Vitamin C and immune function. 2004;140(7):533-537. (PubMed), 25. Vitamin C pharmacokinetics: implications for oral and intravenous use. (PubMed), 161. 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. (PubMed), 93. Adjuvant effect of vitamin C on omeprazole-amoxicillin-clarithromycin triple therapy for Helicobacter pylori eradication. Freeman; 1970. McEvoy CT, Schilling D, Clay N, et al. Bowman GL. 2013;1(5):e239-240. JAMA. (PubMed), 139. 1994;35(3):317-322. Galasko DR, Peskind E, Clark CM, et al. Since the antioxidants were taken together in this trial, the individual contribution of vitamin C cannot be determined. At this time, avoidance of vitamin C deficiency or insufficiency, rather than supplementation in replete individuals, seems prudent for the promotion of healthy brain aging (101). 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. 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. (PubMed), 53. Abramovici A, Gandley RE, Clifton RG, et al. Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES). J Am Coll Nutr. The trial did not examine the effect of vitamin C on other outcomes associated with gout (122). Oregon State University, Updated in July 2018 by: A three-year randomized controlled trial in 160 patients with documented coronary heart disease and low blood HDL concentrations found that a combination of simvastatin (Zocor) and niacin increased HDL concentration, inhibited the progression of coronary artery stenosis (narrowing), and decreased the frequency of cardiovascular events, such as myocardial infarction and stroke(202). Ann Intern Med. Available at: https://naturalmedicines.therapeuticresearch.com. 2009;56(5):764-770. Sesso HD, Buring JE, Christen WG, et al. Linus Pauling Institute Hansen SN, Tveden-Nyborg P, Lykkesfeldt J. 2012;95(5):1079-1088. Carr AC, Cook J. The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life. 2007;104(21):8749-8754. If there is inadequate Vitamin C, the next best way to repair your arterial injuries is make a Lp(a) plaque to cover the injury. (PubMed), 152. (PubMed), 13. Linus Pauling's specific therapy for cardiovascular and heart diseases are high dosages of two essential nutrients; vitamin C and the amino acid lysine . BMC Ophthalmol. 2005;102(38):13604-13609. Symptoms of vitamin C deficiency, such as poor wound healing and lethargy, likely result from the impairment of these vitamin C-dependent enzymatic reactions leading to the insufficient synthesis of collagen, carnitine, and catecholamines (see Deficiency). Ann Thorac Surg. Vitamin C likely also plays a role in the maintenance of genome integrity and in the protection against cellular transformation through regulating DNA and histone demethylating enzymes (see Function) (165). A third placebo-controlled trial in mildly cognitively impaired older adults (ages, 60-75 years) found that one-year supplementation with vitamin C (400 mg/day) and vitamin E (300 mg/day) improved antioxidant blood capacity but had no effect on MMSE scores (106). Interestingly, there was no relationship between diet score and risk of hypertension in those with the lowest plasma vitamin C, and plasma vitamin C was positively associated with risk of hypertension in those with low diet scores (44). Phagocytic leukocytes also produce and release cytokines, including interferons, which have antiviral activity (16). Oregon State University, Updated in September 2003 by: 2018;9:809. Carr A, Frei B. 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). Oncologist. Gillani SW, Sulaiman SAS, Abdul MIM, Baig MR. (PubMed), 68 Nagel G, Linseisen J, van Gils CH, et al. Int J Vitam Nutr Res Suppl. Eur J Clin Invest. Wang L, Sesso HD, Glynn RJ, et al. The work of Linus Pauling stimulated public interest in the use of doses greater than 1 g/day of vitamin C to prevent the common cold (177). Levine M, Conry-Cantilena C, Wang Y, et al. Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians' Health Study II randomized trial. Fructose and vitamin C intake do not influence risk for developing hypertension. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Lagowska-Lenard M, Stelmasiak Z, Bartosik-Psujek H. Influence of vitamin C on markers of oxidative stress in the earliest period of ischemic stroke. 1999;91(6):547-556. 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). South Med J. Clinically insignificant effect of supplemental vitamin C on serum urate in patients with gout: a pilot randomized controlled trial. Corvallis, Oregon 97331, phone: 541-737-5075 | fax: 541-737-5077 Cancer Causes Control. Arthritis Rheum. Other trials also failed to show any evidence of an effect of vitamin C on the risk of stroke. J Natl Cancer Inst. Carcinogenesis. Am J Clin Nutr. PLoS One. Hypertension. 2000;70(5):226-237. Roswall N, Olsen A, Christensen J, Dragsted LO, Overvad K, Tjonneland A. Micronutrient intake and breast cancer characteristics among postmenopausal women. Nutrients. 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. Forman JP, Choi H, Curhan GC. 2002;56(1):53-56. Br J Anaesth. Research Associate Professor 2010;21(11):1745-1757. 2005;24(4):269-276. 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). (PubMed), 80. Arch Biochem Biophys. 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). (National Academy Press), 36. Semin Arthritis Rheum. (PubMed), 41. How to Live Longer and Feel Better. 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. Chen Q, Espey MG, Krishna MC, et al. Vitamin C infusion also lowered the concentration of markers of inflammation and endothelial injury in patients compared to placebo (154). Stephenson CM, Levin RD, Spector T, Lis CG. (PubMed), 123. ", Linus Pauling Institute | Oregon State University 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. (PubMed), 184. (PubMed), 207. Some (24, 191, 192), but not all (193-195), studies have reported that supplemental vitamin C increases urinary oxalate concentrations. Notably, this study had several limitations (54), including no measurement of vitamin C status and the recruitment of a well-nourished study population. 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. Several cross-sectional studies have reported an inverse association between vitamin C status and blood lead concentration. Does vitamin C deficiency affect cognitive development and function? (PubMed), 26. Oxidative stress, neuroinflammation, -amyloid plaque deposition, Tau protein-forming tangles, and neuronal cell death in the brain of subjects affected by AD have been associated with cognitive decline and memory loss. 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). 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). In a small, longitudinal biomarker study in 32 individuals with probable AD, a higher CSF-to-plasma vitamin C ratio at baseline was associated with a slower rate of cognitive decline at one year of follow-up (103). Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Despite conflicting results, it may be prudent for individuals predisposed to oxalate kidney stone formation to avoid high-dose vitamin C supplementation. 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). A systematic review and meta-analysis. In the past 40 years, numerous placebo-controlled trials have examined the effect of vitamin C supplementation on the prevention and treatment of colds. (PubMed), 159. 5 Jariwalla RJ, Harakeh S. Antiviral and immunomodulatory activities of ascorbic acid. (PubMed), 28. Cigarette smoking during pregnancy causes intrauterine growth restriction and preterm birth, among other pregnancy complications (90, 91), and is the primary cause of childhood respiratory illness (92). 2009;170(4):472-483. Collagen is required to keep our arteries flexible and strong. 2007;10(2):75-83. In a 1974 radio interview, he noted that "the first 250 mg is more important than any later 250 mg. Science. Khaw KT, Bingham S, Welch A, et al. 1995;59(6):1519-1523. 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. 33. 2014;5:e1083. 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). Chuang CH, Sheu BS, Kao AW, et al. 2016;73(8):1645-1658. (PubMed), 85. 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). However, leukocyte vitamin C concentration does not accurately reflect vitamin C in several tissues and may specifically underestimate vitamin C uptake into skeletal muscle (26). Proc Natl Acad Sci U S A. Cochrane Database Syst Rev. Higher doses (>500 mg) result in fractionally less vitamin C being absorbed as the dose increases. 2005;17(3):341-345. Conde-Agudelo A, Althabe F, Belizan JM, Kafury-Goeta AC. (PubMed), 147. Taylor EN, Stampfer MJ, Curhan GC. 2015;6(4):570-581. Traxer O, Huet B, Poindexter J, Pak CY, Pearle MS. Effect of ascorbic acid consumption on urinary stone risk factors. (PubMed), 42. You can achieve a higher volume [concentration] in the blood by a larger intake, but you get much better improvement for the first 250 mg than for additional grams." 201. Thus, in vitro vitamin C sensitivity assays may provide predictive value for the clinical response to intravenous vitamin C treatment. 2010;12(2):209-217. Twenty-five years. Intake of antioxidant nutrients and risk of non-Hodgkin's Lymphoma in the Women's Health Initiative. 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. Dr. Pauling, for whom the Linus Pauling Institute has great respect, based his own recommendations for vitamin C largely on theoretical arguments. Anitra C. Carr, Ph.D. 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). 2012;130(1):147-158. An analysis that combined data from three, large, independent prospective cohorts, (1) Nurses Health Study 1 (NHS1; 88,540 women, median age 49 years); (2) Nurses Health Study 2 (NHS2; 97,315 women, median age 36 years); and (3) Health Professionals Follow-up Study (HPFS; 37,375 men, median age 52 years), found no association between the level of vitamin C intake and risk of developing hypertension (40). Cancer Cell. (PubMed), 132. Int J Cancer. Roberts LJ, 2nd, Traber MG, Frei B. Vitamins E and C in the prevention of cardiovascular disease and cancer in men. The results of this study also indicated that supplemental vitamin C may be helpful in the prevention of gout (119). 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. 1996;155(6):1847-1851. Vitamin C (L-ascorbic acid) is available in many forms, but there is little scientific evidence that any one form is better absorbed or more effective than another. Hemorrhagic stroke occurs when a weakened blood vessel ruptures and bleeds into the surrounding brain tissue. Molecular Biology of the Cell.
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