Â Harding AH, Wareham NJ, Bingham SA, et al. 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). Vitamin-C as anti-Helicobacter pylori agent: More prophylactic than curative- Critical review. Linus Pauling Institute Nutr Rev. Vol. 2013;8(2):e56803. Cardiovasc Diabetol. 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. Â (PubMed), 45. Â Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Vitamin C in plasma is inversely related to blood pressure and change in blood pressure during the previous year in young Black and White women. Supplementation with vitamin C had no effect on the overall risk of cancer or on the risk of prostate, bladder, or pancreatic cancer; there was a marginal reduction in colorectal cancer incidence with vitamin C compared to placebo (82). Â Al-Khudairy L, Flowers N, Wheelhouse R, et al. Due to the pharmacokinetics and tight regulation of plasma vitamin C, supplementation with vitamin C will have variable effects in vitamin C-replete (plasma concentrations near saturation) versus sub-optimal (plasma concentrations <50 Î¼mol/L), marginally deficient (plasma concentrations <23 Î¼mol/L), or severely deficient (plasma concentrations <11 Î¼mol/L) individuals (28). The urine specific gravity primarily reflects the ability of the renal tubules to respond to the activity of antidiuretic hormone (ADH) to produce concentrated urine. These enzymes contribute to the epigenetic regulation of gene expression by catalyzing reactions involved in the demethylation of DNA and histones. Copyright © 2021 Elsevier B.V. or its licensors or contributors. 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).Â. Â Carr AC, Cook J. Cochrane Database Syst Rev. Â (PubMed), 57. J Biol Chem. 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. Shock. 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). Endothelial dysfunction results in widespread vasoconstriction and coagulation abnormalities. Â Carr A, Frei B. 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). To achieve this, agribusinesses keep livestock such as cattle, poultry, and fish at high stocking densities, at large scale, and using â¦ Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials. Ames, Iowa: Wiley-Blackwell; 2012:248-260.Â Â, 22. However, in test tube experiments, vitamin C can interact with some free metal ions and lead to the generation of potentially damaging free radicals. Present Knowledge in Nutrition. Â (PubMed), 134. Nutr J. Â Zhang S, Hunter DJ, Forman MR, et al. Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis. Criteria and recommendations for vitamin C intake. 1994;42(5):276-278. 2017;9(11). Â Tsugane S, Sasazuki S. Diet and the risk of gastric cancer: review of epidemiological evidence. Whether any increase in oxalate levels would translate to an elevation in risk for kidney stones has been examined in several epidemiological studies. Current research indicates that urine high in calcium, citrates, or oxalates and is acidic predisposes a pet to developing calcium oxalate urinary crystals and stones. This is typically observed at doses between 200 to 400 mg/day in healthy young adults, with some degree of individual variation (23, 24). Relationship between oxidative stress, lipid peroxidation, and ultrastructural damage in patients with coronary artery disease undergoing cardioplegic arrest/reperfusion. Flavonoids are a class of water-soluble plant pigments that are often found in vitamin C-rich fruit and vegetables, especially citrus fruit and berries (see the article on Flavonoids). Ascorbic Acid: Biochemistry and Biomedical Cell Biology. Â Banerjee S, Hawksby C, Miller S, Dahill S, Beattie AD, McColl KE. 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. As shown in Table 3, different fruit and vegetables vary in their vitamin C content, but five servings (2Â½ cup-equivalents) of a variety of fruit and vegetables should average out to about 150 to 200 mg of vitamin C, especially if vitamin C-rich fruits are consumed. Â Choi HK, Curhan G. Gout: epidemiology and lifestyle choices. 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). 2010;341:c4229. 2012;52(9):815-829. 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). 1999;281(24):2289-2293. Am J Obstet Gynecol. Eur J Cardiovasc Prev Rehabil. 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. With the latest RDA published in 2000, a tolerable upper intake level (UL) for vitamin C was set for the first time (Table 4). Finally, no significant effect of vitamin C supplementation (1-8 g/day) was observed in therapeutic trials in which vitamin C was administered after cold symptoms occurred. A 2015 meta-analysis of 29 randomized controlled trials found that administration of vitamin C during pregnancy, alone or in combination with a few other supplements, failed to reduce the risks of stillbirth, perinatal death, intrauterine growth restriction, preterm birth, premature rupture of membranes, and preeclampsia (88).Â Nonetheless, vitamin C supplementation led to a 36% lower risk of placental abruption and to a significant increase in gestational age at birth (88). Â Stephenson CM, Levin RD, Spector T, Lis CG. Â Juraschek SP, Guallar E, Appel LJ, Miller ER, 3rd. Authors' perspective: What is the optimum intake of vitamin C in humans? Â (PubMed), 7 Â Panush RS, Delafuente JC, Katz P, Johnson J. Modulation of certain immunologic responses by vitamin C. III. However, it is imperative that the horse is carefully monitored during the test to avoid dangerous dehydration. Redox Rep. 2016;21(2):75-83. Â (PubMed), 55. Diabet Med. However, no difference in the infarct size between antioxidant vitamin treatment and placebo was seen (138). Â (PubMed), 95. Four phase I clinical trials in patients with advanced cancer found that intravenous administration of vitamin C at doses up to 1.5 g/kg of body weight (equivalent to about 100 g/day for an average weight [70 kg] person) and 70 to 80 g/m2 was well tolerated and safe in pre-screened patients (167-170). 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). Some (24, 191, 192), but not all (193-195), studies have reported that supplemental vitamin C increases urinary oxalate concentrations. Prenatal vitamin C and E supplementation in smokers is associated with reduced placental abruption and preterm birth: a secondary analysis. Clinically, this is only a problem in patients with diabetes mellitus or heavy proteinuria. 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). 2007;73(4):710-719. Â (PubMed), 87. Gastric Cancer. 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. Â (PubMed), 94. Clinical trials of antioxidants as cancer prevention agents: past, present, and future. Bjog. 1999;181(4):1026-1035. Â (PubMed), 115. When deprived of water for 24 to 72 hours, horses with normal renal function produce urine with a specific gravity > 1.045 and an Uosm > 1500 mOsm/kg.30 In contrast, neonatal foals typically have hyposthenuric urine because their diet consists largely of milk.31 Because the volume of fluid intake as milk by foals up to 60 days of age is nearly fivefold the fluid intake of an adult horse (on an mL/kg basis), healthy foals are polyuric and their urine appears clear with little yellow color. Â Carr AC, Frei B. Â (PubMed), 59. Â Alzheimer's Association. 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. Â Reiss GR, Werness PG, Zollman PE, Brubaker RF. These observations need to be confirmed in larger, well-designed trials. 2008;26(3):297-304. It is widely thought by the general public that vitamin C boosts immune function, yet human studies published to date are conflicting. Vitamin C in health and disease. Antioxidant effects of vitamins in type 2 diabetes: a meta-analysis of randomized controlled trials. Science. Dennis J. Chew DVM, DACVIM, ... Patricia A. Schenck DVM, PhD, in Canine and Feline Nephrology and Urology (Second Edition), 2011. J Pharm Biomed Anal. 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). 2010;51(6):963-964. Effect of oral vitamin C supplementation on serum uric acid: a meta-analysis of randomized controlled trials. 2011;58(3):372-379. Â (PubMed), 11. 2001;292(5524):2083-2086. Coronary heart disease (CHD) is characterized by the buildup of plaque inside the arteries that supply blood to the heart (atherosclerosis). Proc Natl Acad Sci U S A. Â (PubMed), 181. Â Michels AJ, Hagen TM, Frei B. The urinary system consists of the kidneys, ureters, urinary bladder, and urethra.The system produces urine by a process of filtration, reabsorption, and tubular secretion. 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). Annu Rev Nutr. Â (PubMed), 52. Cancer Res. USG may be falsely increased 0.004 to 0.005 for every 1 g/dL of glucose in the urine. 2008;168(14):1493-1499. Does vitamin C act as a pro-oxidant under physiological conditions? 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. 2011;63(9):1295-1306. Â Johnston CS, Luo B. Persistent use of low-protein diets can result in inability to maximally concentrate urine (usually blood urea nitrogen [BUN] concentrations are below normal in this situation). Available at: https://naturalmedicines.therapeuticresearch.com. Oregon State University, Updated in September 2003 by:Â Â In fact, two prospective cohort studies in Swedish men (110)Â and women (111)Â reported that high-dose single nutrient supplements of vitamin C were associated with an increased risk of cataract, especially in those on corticosteroid therapy. Average USG throughout the day should be >1.020 in dogs. Â (PubMed), 111. Such a reduction falls within the range of assay variability and is unlikely to be clinically significant (121). Â (PubMed), 182. 2016;6(2):243-250. The effect of vitamin C, alone or with allopurinol, decreasing serum uric acid was modest and much less than that of allopurinol alone. Nature. Intravenous vitamin C and cancer: a systematic review. 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. 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). Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. Â Valls N, Gormaz JG, Aguayo R, et al. Over years of buildup and accumulated damage to the coronary arteries, CHD may culminate in a myocardial infarction or heart attack. Linus Pauling InstituteÂ Â Urine is denser than pure water because it contains excreted solutes. 2001;357(9257):657-663. 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. Finally, mutations in genes coding for vitamin C-dependent TET demethylases, mutations that are common in cancer cells, may also contribute to resistance to vitamin C treatment (165). Â (PubMed), 31. Bilirubinuria (<2+ on a dipstick) can be a normal finding in dogs (especially males).82 Bilirubinuria in dogs without hemolytic or hepatobiliary disease can occur as a consequence of the loss of unconjugated bilirubin that is bound to albumin in proteinuric patients and renal filtration of small amounts of conjugated bilirubin that has leaked from the liver. Symptoms of scurvy include subcutaneous bleeding, poor wound closure, and bruising easily, hair and tooth loss, and joint pain and swelling. 2015;122(13):1740-1747. Int J Cancer. Early symptoms of scurvy like fatigue may result from diminished levels of carnitine, which is needed to derive energy from fat, or from decreased synthesis of the catecholamine norepinephrine (see Function). Â Galasko DR, Peskind E, Clark CM, et al. Â (PubMed), 18. Â (PubMed), 58. In contrast, a 2014 meta-analysis of 10 prospective cohort studies in 17,696 women with breast cancer found a lower risk of total and breast cancer-specific mortality with higher supplemental and dietary vitamin C intakes (126). Â (PubMed), 27. Â Roswall N, Olsen A, Christensen J, et al. 2010;3(2):221-229. Most of the fluid you drink should be water. Baltimore, MD: Lippincott Williams & Wilkins; 2014:416-426.Â Â, 2. Â (PubMed), 136. Despite conflicting results, it may be prudent for individuals predisposed to oxalate kidney stone formation to avoid high-dose vitamin C supplementation. Â (PubMed), 43. Linus Pauling InstituteÂ Â 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 womenâs smoking status during pregnancy. In contrast, trials are intervention studies that can establish a causal relationship between an exposure and an outcome, e.g., by evaluating the effect of vitamin C supplementation on the incidence of chronic disease in participants randomly assigned to receive either vitamin C or placebo for a given length of time. For example, in response to water deprivation for 24 to 72 hours, horses with normal renal function often produce urine with a specific gravity greater than 1.045 and an osmolality greater than 1500 mOsm/kg.194,195,200 In contrast, foals typically have hyposthenuric urine consequent to their mostly milk diet.169 Although constant polyuria decreases the ability of the neonate to generate a large osmotic gradient in the medullary interstitium, dehydrated foals still can produce urine with a specific gravity greater than 1.030. These enzymes are either monooxygenases or dioxygenases (see Table 1). Â (PubMed), 72. Specific gravity test pads on reagent strips are unreliable in equine urine. While plasma vitamin C concentration reflects recent dietary intake, leukocyte (white blood cell) vitamin C is thought to be an indicator of body stores. Additional studies have reported that vitamin C enhances the chemotactic and microbial killing capacities of neutrophils and stimulates the proliferation and differentiation of B- and T-lymphocytes (reviewed in 18). Â (PubMed), 125. JAMA. 2018;22(1):70. 1977;47(3):248-257. Â Moran JP, Cohen L, Greene JM, et al. Â (PubMed), 25. Â (PubMed), 206. The specific gravity of normal equine urine varies between 1.020 and 1.050. Â Simon JA, Hudes ES. Front Oncol. Impacts of waste from concentrated animal feeding operations on water quality. Jane Higdon, Ph.D.Â Â Thompson CA, Cerhan JR. Fruit and vegetable intake and survival from non-Hodgkin lymphoma: does an apple a day keep the doctor away? Few studies have measured vitamin C concentration in the CSF, which more closely reflects the vitamin C status of the brain. Â (PubMed), 129. 2008;87(1):64-69. 1998;43(3):322-326. Oxidative stress, neuroinflammation, Î²-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. Â Padayatty SJ, Sun H, Wang Y, et al. Plasma and dietary vitamin C levels and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). However, a reduction in blood vitamin C concentrations with these drugs has not been reported in humans (200). Impaired blood-brain barrier integrity may affect the brainâs ability to retain vitamin C and thus to maintain a high CSF-to-plasma vitamin C ratio. Am J Clin Nutr. In the second prospective cohort study, the Diet, Cancer and Health Study, 55,543 Danish adults (ages 50-64 years) were questioned at baseline about their lifestyle, diet, and supplement use during the previous 12 months (125). The majority of large, population-based studies examining the relationship of vitamin C intake or supplementation with AD incidence have reported null results (100). Â Dingchao H, Zhiduan Q, Liye H, Xiaodong F. The protective effects of high-dose ascorbic acid on myocardium against reperfusion injury during and after cardiopulmonary bypass. 2013;106(5):310-315. An increase in insulin sensitivity has been reported in individuals with congenital (inborn) deficiency of most selenoproteins . 2007;6:41. Originally written in 2000 by: The crystals grow into larger masses (stones), which can make their way through the urinary tract. Â Traxer O, Huet B, Poindexter J, Pak CY, Pearle MS. Effect of ascorbic acid consumption on urinary stone risk factors. J Am Coll Nutr. Â Carr AC, Pullar JM, Bozonet SM, Vissers MC. Â (PubMed), 166. 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. A refractometer should be used for USG measurements. Cigarette smoking or second-hand exposure to cigarette smoke contributes to increased blood lead concentration and a state of chronic low-level lead exposure. 2004;80(6):1508-1520. 2012;37(1):4-16. Â (PubMed), 3 Â Camarena V, Wang G. The epigenetic role of vitamin C in health and disease. Vitamin C treatment substantially reduced the incidence of periprocedural myocardial injury, as assessed by a reduction in the concentrations of two markers of myocardial injury, namely creatine kinase and troponin-I (131). Jane Higdon, Ph.D.Â 2016;33(3):307-315. 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). Â (PubMed), 146. 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). San Francisco: W.H. In the Swedish Mammography Cohort, overweight women who consumed an average of 110 mg/day of vitamin C had a 39% lower risk of breast cancer compared to overweight women who consumed an average of 31 mg/day (66). 2017;37:58-64. Recent Advances in Primary and Secondary Prevention of Atherosclerotic Stroke. Eur J Clin Nutr. Â (PubMed), 38. Eur J Cancer Prev. Â (PubMed), 107. JAMA. Concentrated urine is commonly seen in horses fed a high percentage of hay and those living in hot environments. The only way to be sure that a bladder stone is â¦ J Infect Dis. Â Pal J, Sanal MG, Gopal GJ. Freeman; 1970.Â Â, 178. Â (PubMed), 80. Another large, multi-center, prospective studyÂ âÂ the Womenâs Health InitiativeÂ âÂ that followed 154,363 postmenopausal women for 11 years found that dietary and supplemental vitamin C intake at baseline was inversely associated with diffuse B-cell lymphoma, a subtype of NHL (81). 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. Fruit, vegetable and vitamin C intakes and plasma vitamin C: cross-sectional associations with insulin resistance and glycaemia in 9-10 year-old children. A US national survey of more than 10,000 adults found that blood lead concentrations were inversely related to serum vitamin C concentrations (183). Â Carter P, Gray LJ, Troughton J, Khunti K, Davies MJ. Association of vitamin C with the risk of age-related cataract: a meta-analysis. Further, although this fluid intake decreases a foal's ability to generate an osmotic gradient in the medullary interstitium, foals can still produce urine with a specific gravity > 1.03 when dehydrated. Â Dawson EB, Evans DR, Harris WA, Teter MC, McGanity WJ. Curr Opin Crit Care. 2010;12(2):209-217. USG should be determined before treatment with fluids, diuretics, corticosteroids, or other medications. 1999;13(9):1007-1024. 2003;31(4):1250-1256. Â Bergsten P, Amitai G, Kehrl J, Dhariwal KR, Klein HG, Levine M. Millimolar concentrations of ascorbic acid in purified human mononuclear leukocytes. 2001;91(4):563-567. Â Carr AC, Rosengrave PC, Bayer S, Chambers S, Mehrtens J, Shaw GM. In contrast, with intrinsic renal failure urinary concentrating ability is lost: specific gravity and Uosm are typically <1.02 and < 500 mOsm/kg, respectively, in the face of dehydration.32 Assessment of urine tonicity can be problematic, however, because it is only valid when performed on urine collected before initiating fluid therapy or administering medications (e.g., α2-receptor agonists or furosemide) that can affect urine flow and tonicity.33, In Canine and Feline Gastroenterology, 2013. 2008;105(32):11105-11109. 2010;103(9):1251-1259. 2009;170(4):472-483. 2000;31(10):2287-2294. Â (PubMed), 168. Â (PubMed), 207. Â (PubMed), 12. Vitamin C: should we supplement? Â (PubMed), 147. 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. Â Song Y, Xu Q, Park Y, Hollenbeck A, Schatzkin A, Chen H. Multivitamins, individual vitamin and mineral supplements, and risk of diabetes among older U.S. adults. Ester-CÂ® should not be confused with ascorbyl palmitate, which is also marketed as "vitamin C ester" (see below). Sometimes, the kidney stone can travel down the ureter, the tube between the â¦ Adv Nutr. 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. Ammonium biurate crystals are detected in the urine sediment by light microscopy. Â Arlt S, Muller-Thomsen T, Beisiegel U, Kontush A. 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. Arch Biochem Biophys. Comparison of mortality associated with sepsis in the burn, trauma, and general intensive care unit patient: a systematic review of the literature.
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