Goyal A, Terry MB, Siegel AB. The history of these products might make the reasons for (and differences in them) easier to understand. Eur J Cancer Prev. Am J Clin Nutr. J Emerg Med. In most trials, participants received 2 g of vitamin C prior to undergoing CABG or valve replacement surgery and 1 to 2 g/day for five days post-surgery. J Infect Dis. Balbi ME, Tonin FS, Mendes AM, et al. (PubMed), 65. Oncogene. Arch Neurol. (PubMed), 124. Vitamin C also limited endothelial dysfunction that was experimentally induced in healthy volunteers (39). Johnston CS, Luo B. 2012(3):Cd007176. Higher plasma concentrations achieved via intravenous vitamin C administration are comparable to those that are toxic to cancer cells in culture. 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). (PubMed), 151. Barbara Delage, Ph.D. 2004;27(4):925-930. 2017;3:Cd011114. Thus, the Linus Pauling Institute recommends a vitamin C intake of 400 mg daily for adults to ensure replete tissue concentrations (29)an amount substantially higher than the RDA yet with minimal risk of side effects. JAMA. The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach. (PubMed), 89. 2013;106(5):310-315. (PubMed), 156. Int J Surg. 15. Carr AC, Pullar JM, Bozonet SM, Vissers MC. (PubMed), 10. A meta-analysis of 29 small randomized controlled trials of short durations (median duration, 8 weeks) in 1,407 participants (10 to 120 subjects per trial; including both normotensive and hypertensive subjects) found that daily supplementation with 60 to 4,000 mg of vitamin C (median dose, 500 mg) reduced systolic blood pressure by 3.84 mm Hg and diastolic blood pressure by 1.48 mm Hg (45). Phagocytic leukocytes also produce and release cytokines, including interferons, which have antiviral activity (16). Carr AC, Maggini S. Vitamin C and immune function. (PubMed), 34. 2006;27(11):2250-2257. 2012;56. Linus Pauling Institute 2012;52(9):815-829. 2018;148(3):419-426. A prospective study of the intake of vitamins C and B6, and the risk of kidney stones in men. Alterations in the structure and function of the vascular endothelium that lines the inner surface of all blood vessels are associated with the loss of normal nitric oxide-mediated endothelium-dependent vasodilation. (PubMed), 111. Vitamin C (L-ascorbic acid) is a potent reducing agent, meaning that it readily donates electrons to recipient molecules ( Figure 1 ). 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). By pooling data from 13 prospective cohort studies comprising 676,141 participants, it was determined that dietary intake of vitamin C was not associated with colon cancer, while total intake of vitamin C (i.e., from food and supplements) was associated with a 19% reduced risk of colon cancer (79). Neurochem Res. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Chest. You may hyperlink to this website but must include the following statement: "This link leads to a website provided by the Linus Pauling Institute at Oregon State University. (PubMed), 197. Am J Clin Nutr. 2010;51(6):963-964. Kabat GC, Kim MY, Wactawski-Wende J, Shikany JM, Vitolins MZ, Rohan TE. The capacity of vitamin C to influence the methylation status of DNA and histones in mammalian cells supports a role for the vitamin in health and disease beyond what was previously understood, in particular by safeguarding genome integrity (3, 4). Pauling L. The immune system. Br J Nutr. (PubMed), 145. Donin AS, Dent JE, Nightingale CM, et al. (PubMed), 138. Nutr Metab Insights. Leuk Lymphoma. (PubMed), 27. The information should not be used in place of a consultation with a competent health care or nutrition professional. J Am Coll Nutr. Contemp Clin Trials. Adults. However, none of these alleged adverse health effects have been confirmed in subsequent studies, and there is no reliable scientific evidence that doses of vitamin C up to 10 g/day in adults are toxic or detrimental to health. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. 2017;16(1):103. Annu Rev Nutr. J Urol. 1983;29(5):305-310. Jane Higdon, Ph.D. Weinstein M, Babyn P, Zlotkin S. An orange a day keeps the doctor away: scurvy in the year 2000. A comprehensive review of the literature found no credible scientific evidence that supplemental vitamin C promotes oxidative damage under physiological conditions or in humans (206). Effect of one-year vitamin C- and E-supplementation on cerebrospinal fluid oxidation parameters and clinical course in Alzheimer's disease. 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. 2016;73(8):1645-1658. Vitamin C in Health and Disease. *Source of intake should be from foods or formula only. Front Oncol. One randomized, placebo-controlled trial has examined the effect of intravenous vitamin C administered to patients with stable angina undergoing elective coronary angioplasty (130). There is little evidence that the flavonoids in most commercial preparations increase the bioavailability or efficacy of vitamin C (187). 2013;13:52. J Stroke. 2014(10):Cd010156. 2015;6(4):570-581. These enzymes contribute to the epigenetic regulation of gene expression by catalyzing reactions involved in the demethylation of DNA and histones. Cabanillas F. Vitamin C and cancer: what can we conclude--1,609 patients and 33 years later? Nutrients. 2015;45(11):1161-1174. 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). 1999;281(15):1415-1423. 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). Coronary heart disease (CHD) is characterized by the buildup of plaque inside the arteries that supply blood to the heart (atherosclerosis). The lack of Vitamin C is a deficiency disease called Scurvy. 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. Authors' perspective: What is the optimum intake of vitamin C in humans? 2008;26(3):297-304. 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. 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). The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. However, cases have occurred in children and the elderly on very restricted diets (33, 34). Lysine also prevents collagen-digesting enzymes from destroying collagen. Roberts LJ, 2nd, Traber MG, Frei B. Vitamins E and C in the prevention of cardiovascular disease and cancer in men. Linus Pauling's Recommendations for Vitamin C and Lysine - The Ezekiel Diet Files Linus Pauling's Recommendations for Vitamin C and Lysine by EzekielDiet.com Posted on Sep 22, 2021 Pauling's Vitamin C and Lysine dosage recommendations from his Unified Theory Lecture on Heart Disease. In some patients, vitamin C dosages may rise as high as 18 grams per day (Linus Pauling's daily dosage), and at high levels, the mineral dosages could cause problems/imbalances. Symptoms of scurvy include subcutaneous bleeding, poor wound closure, and bruising easily, hair and tooth loss, and joint pain and swelling. 2014;5:e1083. Thus, in vitro vitamin C sensitivity assays may provide predictive value for the clinical response to intravenous vitamin C treatment. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice. Lp(a) is a "sticky bandage" within coronary arteries that may induce blood clots when vitamin C/lysine blood levels are low (9). Potential mechanisms of action for vitamin C in cancer: reviewing the evidence. (PubMed), 188. (PubMed), 186. Efficacy and safety of vitamin C for atrial fibrillation after cardiac surgery: A meta-analysis with trial sequential analysis of randomized controlled trials. Low ascorbate levels are associated with increased hypoxia-inducible factor-1 activity and an aggressive tumor phenotype in endometrial cancer. (PubMed), 68 Nagel G, Linseisen J, van Gils CH, et al. 2008;87(1):64-69. Stability of vitamin C derivatives in solution and topical formulations. 2003;170(2 Pt 1):397-401. (PubMed), 103. Balogun OO, da Silva Lopes K, Ota E, et al. The effect of ascorbic acid supplementation on the blood lead levels of smokers. 2004;80(6):1508-1520. Collagen is the most abundant protein in the body. Plasma and dietary vitamin C levels and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). (PubMed), 164. While most generally healthy young adults can achieve these plasma concentrations with daily vitamin C intake of at least 200 mg/day, some individuals may have a lower vitamin C absorptive capacity than what is currently documented. Vitamin C is required to strengthen arteries so that the body does not try to patch arteries with "plaster casts" (atherosclerosis). 201. Vissers MCM, Das AB. 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). Although only a minority of trials delivered vitamin C intravenously, this administration route appeared to be more effective at reducing the risk of atrial fibrillationpresumably due to higher plasma concentrations achieved (140). Reiss GR, Werness PG, Zollman PE, Brubaker RF. Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Gerontology. 2005;4:5. 1999;13(9):1007-1024. Most experimental and clinical research uses ascorbic acid or its sodium salt, called sodium ascorbate. Michels AJ, Frei B. Myths, artifacts, and fatal flaws: identifying limitations and opportunities in vitamin C research. It is not intended as nutritional or medical advice for individual problems. 1980;33(1):71-76. Accessed 7/2/18. Bjog. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. I don't think it will interfere with the citrulline/arginine doses, as long as they are taken separately on an empty stomach (When we start mixing too many amino acids at the same time, we may . 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. 2010;341:c4229. 2009;16(1):93-98. (PubMed), 134. (PubMed), 158. In another AD mouse model that was lacking the ability to synthesize vitamin C, supplementation with a high versus low dose of vitamin C reduced amyloid deposition in the cortex and hippocampus and limited blood-brain barrier impairments and mitochondrial dysfunction (99). Thompson CA, Cerhan JR. Fruit and vegetable intake and survival from non-Hodgkin lymphoma: does an apple a day keep the doctor away? Lassnigg A, Punz A, Barker R, et al. By maintaining enzyme-bound metals in their reduced forms, vitamin C assists mixed-function oxidases in the synthesis of several critical biomolecules (1). 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). Clinical trials of antioxidants as cancer prevention agents: past, present, and future. 202 Brown BG, Zhao XQ, Chait A, et al. Am J Epidemiol. (PubMed), 45. Higher doses (>500 mg) result in fractionally less vitamin C being absorbed as the dose increases. 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). (PubMed), 131. Oregon State University, Updated in January 2006 by: After approximately four years of follow-up in 19,496 men and women (ages 45-79 years), a dose-response relationship was observed such that each 20 mol/L increase in plasma vitamin C was associated with an estimated 20% risk reduction in all-cause mortality. 2008;168(14):1493-1499. 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). Pauling L. Vitamin C therapy and advanced cancer (letter). Vitamin C also prevented the rise of Sequential Organ Failure Assessment (SOFA) and Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scoresused to assess severity of illness and risk of mortalityobserved in placebo-treated patients (154). Both vitamin C and aspirin reduced fasting blood glucose and HbA1c concentrations and improved blood lipid profile in metformin-treated patients. 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). Contents Summary Function Playing in immunity Bioavailability Deficiency Aforementioned RDA Disease Prevention Cardio-vascular disease Cancer Print 2 diabetes mellitus Adverse pregnancy outcomes 2007;12(3):230-238. Such symptoms appear to be related to the weakening of blood vessels, connective tissue, and bone, which all contain collagen. email:[emailprotected], Chlorophyll and Metallo-Chlorophyll Derivatives, Healthcare Professional Continuing Education. While plasma vitamin C concentration reflects recent dietary intake, leukocyte (white blood cell) vitamin C is thought to be an indicator of body stores. Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. 1997;17(3):415-425. Cognition in MCI and Alzheimer's disease: baseline data from a longitudinal study of the NTB. Arch Intern Med. New York: Marcel Decker, Inc.; 1997:1-24. The amount of vitamin C required to help prevent chronic disease is higher than the amount required for prevention of scurvy. The national study identified smokers and those of lower socioeconomic status to both be at higher risk for vitamin C deficiency (36). The confirming scientific experiments of Dr. Pauling were published in the Proceedings of the National Academy of Science (1990, Vol 87, pgs 6204-6207) and Dr. Pauling was . 2013;8(2):e56803. Related to this oxidation -reduction ( redox) potential, two major functions of vitamin C are as an antioxidant and as an enzyme cofactor (1). 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). Levine M, Wang Y, Padayatty SJ, Morrow J. Eur J Nutr. Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins. Nutrients. cholesterol. (PubMed), 198. J Am Soc Nephrol. (PubMed), 141. Few studies have measured vitamin C concentration in the CSF, which more closely reflects the vitamin C status of the brain. (PubMed), 71. (PubMed), 20. Neutrophils, mononuclear phagocytes, and lymphocytes accumulate vitamin C to high concentrations, which can protect these cell types from oxidative damage(12-14). Pal J, Sanal MG, Gopal GJ. Because systemic inflammatory responses involve excessive oxidative stress, it has been suggested that providing antioxidant nutrients like vitamin C may improve the outcome of critically ill patients in intensive care units. Similarly, the EPIC-Norfolk study, a 10-year prospective cohort study in 20,649 adults, found that individuals with plasma vitamin C concentrations in the top quartile (25%) had a 42% lower risk of stroke compared to those in the lowest quartile (66 mol/L vs. <41 mol/L) (58). Hutchinson J, Lentjes MA, Greenwood DC, et al. Andres M, Sivera F, Falzon L, Buchbinder R, Carmona L. Dietary supplements for chronic gout. 2013;2(6):e000329. Environ Health Perspect. Overall, evidence suggesting specific drugs can lower blood vitamin C concentrations in humans is limited. Most (~80%) cerebrovascular events in high-income countries are ischemic in nature and associated with atherosclerosis as an underlying condition (55, 56). Comparison of mortality associated with sepsis in the burn, trauma, and general intensive care unit patient: a systematic review of the literature. (PubMed), 133. 2013;22(12):2202-2211. Int J Vitam Nutr Res. 2005;135(7):1673-1677. This recommendation can be met through food if the diet includes at least several servings of vitamin C-rich fruit and vegetables (e.g., citrus fruit, kiwifruit, peppers; see Food sources) as part of the daily recommended fruit and vegetable intake (see article on Fruit and Vegetables).