2008;35(9):1853-1858. (PubMed), 53. Gastric Cancer. Most (~80%) cerebrovascular events in high-income countries are ischemic in nature and associated with atherosclerosis as an underlying condition (55, 56). 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. Nutrients. Michels AJ, Frei B. Myths, artifacts, and fatal flaws: identifying limitations and opportunities in vitamin C research. You may not copy, modify, distribute, display, transmit, perform, publish or sell any of the copyrightable material on this website. 2012;12:61. 2013;9(1):46. Effect of Helicobacter pylori and its eradication on gastric juice ascorbic acid. 2015;10(12):e0144920. For more information on the difference between Dr Linus Pauling's recommendation and the Linus Pauling Institute's recommendation for vitamin C intake, select the highlighted text. 2018;24(4):248-255. Hendler SS, Rorvik DM. BMC Complement Altern Med. Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress. Related to this oxidation-reduction (redox) potential, two major functions of vitamin C are as an antioxidant and as an enzyme cofactor(1). Cochrane Database Syst Rev. Ischemic stroke occurs when an obstruction within a blood vessel blocks blood flow to the brain. J Am Soc Nephrol. 2017;17(1):49. Science. A vitamin C deficiency equals a collagen deficiency. European Prospective Investigation into Cancer and Nutrition. 15. South Med J. J Am Heart Assoc. The results of this study also indicated that supplemental vitamin C may be helpful in the prevention of gout (119). 2018;148(3):419-426. 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). 307 Linus Pauling Science Center Proc Natl Acad Sci U S A. 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. 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). 195. 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. Potential mechanisms of action for vitamin C in cancer: reviewing the evidence. 66 auditorium with a talk on Vitamin C and Heart Disease. 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). 1976;84B(5):280-284. Donin AS, Dent JE, Nightingale CM, et al. Cochrane Database Syst Rev. Vitamin C. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Am J Clin Nutr. 2000;71(2):530-536. Combined evidence from metabolic, pharmacokinetic, and observational studies, and from randomized controlled trials supports consuming sufficient vitamin C to achieve plasma concentrations of at least 60 mol/L. Symptoms of scurvy include subcutaneous bleeding, poor wound closure, and bruising easily, hair and tooth loss, and joint pain and swelling. Pfister R, Sharp SJ, Luben R, Wareham NJ, Khaw KT. On the other hand, two other large prospective studies reported that a high intake of vitamin C was associated with an increased risk of kidney stone formation in men (198, 199). J Emerg Med. Michels AJ, Joisher N, Hagen TM. The role of vitamin C as a cofactor is also related to its redox potential. The Shibata study. New York: Macel Dekker, Inc.; 1997:309-322. If you are not getting enough Vitamin C to produce collagen for tissue repair, when your arteries become injured they cannot heal properly. (PubMed), 141. Trials. 2016;94(3):e170-176. For some still unclear reasons, smoking has been associated with a lower risk of preeclampsia during pregnancy (93). Another trial randomized 532 patients to receive a 3-g vitamin C infusion or a placebo (saline solution) within six hours prior to coronary angioplasty (131). If you suffer from an acute deficiency of ascorbic acid (Vitamin C) and other nutrients, your body stops producing collagen. Linus Pauling Recommendations 1. Khodaeian M, Tabatabaei-Malazy O, Qorbani M, Farzadfar F, Amini P, Larijani B. Impaired blood-brain barrier integrity may affect the brains ability to retain vitamin C and thus to maintain a high CSF-to-plasma vitamin C ratio. Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials. The mechanism(s) by which vitamin C reduces blood lead concentration is not known, yet it has been proposed that vitamin C could inhibit intestinal absorption (184)or enhance urinary excretion of lead (185). Plasma vitamin C predicts incident heart failure in men and women in European Prospective Investigation into Cancer and Nutrition-Norfolk prospective study. (PubMed), 140. Nutr Res. Int J Surg. (PubMed), 24. Lp(a) is a "sticky bandage" within coronary arteries that may induce blood clots when vitamin C/lysine blood levels are low (9). Linus Pauling Institute (National Academy Press), 36. 2018;9:809. Finally, vitamin C increases the bioavailability of iron from foods by enhancing intestinal absorption of non-heme iron (see the article on Iron) (21). Randomized, double-blind, placebo-controlled trials that have tested the effect of vitamin C supplementation (alone or in combination with other antioxidant nutrients) on cancer incidence or mortality have shown no effect (64). (PubMed), 129. 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. 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). Carr A, Frei B. 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. (PubMed), 81. Of note, it is possible that genetic differences among diabetic patients influence the effect of vitamin C supplementation on cardiovascular risk. Effects of a novel ascorbate-based protocol on infarct size and ventricle function in acute myocardial infarction patients undergoing percutaneous coronary angioplasty. J Urol. (PubMed), 131. While acute scurvy can be prevented by a mere 10 mg vitamin C per day, there is no current research showing how much vitamin C might be required to prevent the atherosclerotic plaques of chronic scurvy. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. 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). Roswall N, Olsen A, Christensen J, et al. (PubMed), 163. Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function. 1999;281(15):1415-1423. (PubMed), 204. 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). The Linus Pauling Protocol - Vitamin C Vitamin C Deficiency Has Major Impact on Collagen Production Vitamin C is required to make a protein called collagen which is the major component of connective tissues. (PubMed), 35. Lassnigg A, Punz A, Barker R, et al. 98. Cardiovascular disease (CVD) is the leading cause of death in individuals with diabetes mellitus. In addition, a 2013 systematic review by the same investigators identified only two small randomized, double-blind, placebo-controlled trials that examined the effect of vitamin C on the incidence of respiratory infection-induced asthma(179). 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). Combined effect of metformin with ascorbic acid versus acetyl salicylic acid on diabetes-related cardiovascular complication; a 12-month single blind multicenter randomized control trial. It is not known whether supplemental vitamin C could improve markers of glycemic control in subjects at risk of diabetes. However, no difference in the infarct size between antioxidant vitamin treatment and placebo was seen (138). Myint PK, Luben RN, Welch AA, Bingham SA, Wareham NJ, Khaw KT. Linus Pauling Institute (PubMed), 106. Periprocedural myocardial injury that occurs in up to one-third of patients undergoing otherwise uncomplicated angioplasty increases the risk of morbidity and mortality at follow-up. (PubMed), 12. Monti DA, Mitchell E, Bazzan AJ, et al. Hypertension. (PubMed), 66. (PubMed), 86. (PubMed), 51. 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). Klingelhoeffer C, Kammerer U, Koospal M, et al. 25. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. A 2012 meta-analysis of 29 trials found no effect of oral vitamin C, given alone or in combination with other antioxidants, on all-cause mortality (127). Freeman; 1970. A lower dose of 200 mg/day did not significantly affect blood lead concentration, although serum vitamin C concentrations were not different from those in the group who took 1,000 mg/day. Zhang S, Hunter DJ, Forman MR, et al. Intake of antioxidant nutrients and risk of non-Hodgkin's Lymphoma in the Women's Health Initiative. 2012;56. In this latter trial, a greater decline in the Mini Mental State Examination (MMSE) score was observed in the supplemented group, however, the significance of this observation remains unclear. (PubMed), 203. A systematic review and meta-analysis. Modern Nutrition in Health and Disease, 11th ed. As mentioned previously, the body produces collagen from lysine and proline. (PubMed). (PubMed), 29. Abnormal growth and development have been observed in infants of women exposed to lead during pregnancy, while children who are chronically exposed to lead are more likely to develop learning disabilities, behavioral problems, and to have a low IQ. Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants: a randomized clinical trial. Linus Pauling is a hard guy to argue with. (PubMed), 184. Subcellular Biochemistry. *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. Available at: https://naturalmedicines.therapeuticresearch.com. The global and regional burden of stroke. A new recommended dietary allowance of vitamin C for healthy young women. (PubMed), 70. Free Radic Biol Med. 2006;8 Suppl 1:S2. Hutchinson J, Lentjes MA, Greenwood DC, et al. Bjog. A cerebrovascular event, or stroke, can be classified as hemorrhagic or ischemic. Cancer Causes Control. Controversy surrounding the efficacy of vitamin C in cancer treatment ensued, leading to the recognition that the route of vitamin C administration is critical (22, 159). Arch Intern Med. Additional detail is provided below for those cancer subtypes with substantial scientific information obtained from prospective cohort studies. (PubMed), 56. Ann Intern Med. While the Sesso study showed no mortality benefit, many previous studies such as the Enstrom Study showed a striking 40% reduction in all-cause mortality over 6 years from the same 500 mg daily vitamin C . 2011;34(1):108-114. Levy R, Shriker O, Porath A, Riesenberg K, Schlaeffer F. Vitamin C for the treatment of recurrent furunculosis in patients with impaired neutrophil functions. 1982;47(3):473-482. ACS Chem Neurosci. Collins R, Peto R, Armitage J. In the National Institutes of Health (NIH)-American Association of Retired Persons (AARP) Diet and Health study that included 232,007 participants, the use of vitamin C supplements for at least seven times a week was associated with a 9% lower risk of developing type 2 diabetes mellitus compared to non-supplement use (83). Tessier F, Moreaux V, Birlouez-Aragon I, Junes P, Mondon H. Decrease in vitamin C concentration in human lenses during cataract progression. 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). Eur Urol. Nutr Metab Insights. 2018;9:1182. Roswall N, Olsen A, Christensen J, Dragsted LO, Overvad K, Tjonneland A. Micronutrient intake and breast cancer characteristics among postmenopausal women. 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"). 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 . Notably, this study had several limitations (54), including no measurement of vitamin C status and the recruitment of a well-nourished study population. Cardiovasc Res. Plasma concentrations of ascorbate reach steady-state at concentrations between 60 and 80 micromoles/L (mol/L). 2016;5(2):94-100. (PubMed), 198. 2013;65(6):1636-1642. Dixit S, Bernardo A, Walker JM, et al. 2010;91(2):487-493. For a more detailed discussion on the bioavailability of different forms of vitamin C, see the article,The Bioavailability of Different Forms of Vitamin C. Severe vitamin C deficiency has been known for many centuries as the potentially fatal disease, scurvy. These enzymes are either monooxygenases or dioxygenases (see Table 1). 97. 1998;43(3):322-326. Alexander J. Michels, Ph.D. 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). 2004;80(6):1508-1520. In addition, vitamin C may bind aluminum in the gut and increase the absorption of aluminum-containing compounds (e.g., aluminum-containing antacids, aluminum-containing phosphate binders). 2012;37(12):2706-2714. (PubMed), 155. 2010;119(3):753-765. BMJ.
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