Vitamin C is an important biological antioxidant and has been a popular nutritional supplement for decades. Vitamin C is often used to prevent or ameliorate a wide variety of infections and to enhance the effectiveness of the immune system. It is popular as a promoter of connective-tissue health in conditions such as minor trauma and capillary fragility.
ascorbic acid, calcium ascorbate
Actions & Pharmacology
Vitamin C has antioxidant, atherogenic, anticarcinogenic, antihypertensive, antiviral, antihistamine, immunomodulatory, ophthalmoprotective, airway-protective, and heavy-metal detoxifying properties.
Antioxidant effects have been demonstrated as increased resistance of red blood cells to free radical attack in elderly persons and reduced activated oxygen species in patients receiving chemotherapy and radiation. Antioxidant mechanisms have been shown in the reduction of LDL oxidation as well, though studies on the prevention of heart disease and stroke are conflicting.
Vitamin C and vitamin E supplements in combination were associated with reduced prevalence and incidence of Alzheimer's disease (AD) in a cross-sectional, prospective study. A population of 4,740 adults 65 years of age and older were assessed for cognitive status, and their use of vitamin supplements was determined. Vitamin C users were those who took at least 500 mg of ascorbic acid, either as a single supplement or as part of a multivitamin preparation. Vitamin E users were defined as those who took a multivitamin preparation or an individual vitamin E supplement providing more than 400 IU per day. Multiple vitamin users were those whose preparation provided lower amounts of vitamin E and vitamin C. There were 200 prevalent cases of AD in the starting population. At the end of follow-up (up to 5 years), there were 104 incident cases of AD and 3,123 subjects who were free of dementia. The group of 1,429 people lost to follow-up comprised individuals who were older, less educated, and had performed less well on their cognitive screen than those who completed the protocol. Hence, AD incidence during the follow-up period may have been underestimated. After adjustment for age, sex, education, and apolipoprotein E genotype, prevalence analysis showed a significant inverse relation between prevalence of AD and vitamin E and multivitamin use. Vitamin E alone, vitamin C alone, or vitamin C in combination with multivitamins were not associated with AD prevalence. The strongest association was with the combination of vitamin E and vitamin C, with or without multivitamins (multivariate adjusted odds ratio, 0.22; 95% confidence interval (CI), 0.05 to 0.6). The combination of vitamin E and vitamin C also apparently reduced incidence (adjusted hazard ratio, 0.36; 95% CI, 0.09 to 0.99). For incidence, associations were not significant for vitamin E alone, vitamin C alone, multivitamin use alone or in combination (Zandi et al, 2004).
Antioxidant Defense Status
Supplementation with antioxidant vitamins, including vitamin C, improved antioxidant defense status in elderly subjects. Eighty-one subjects were stratified by sex and age and randomized to receive daily either placebo, a mineral combination (20 mg zinc, 100 mcg selenium), a vitamin combination (120 mg vitamin C, 6 mg beta-carotene, 15 mg vitamin E) or both combinations for a period of 2 years. Antioxidant defense, measured by in vitro challenge of red blood cells with free radicals, was improved in the vitamin group only (Girodon et al, 1997).
Supplementation with antioxidant vitamins, including vitamin C, prior to conditioning therapy (chemotherapy and radiation) for bone-marrow transplantation resulted in less of a rise in plasma lipid hydroperoxides than did conditioning therapy without presupplementation. Sixteen patients with leukemia were supplemented with alpha-tocopherol 825 mg, beta-carotene 45 mg, and ascorbic acid 450 mg for 3 weeks before beginning conditioning therapy. Ten other patients received conditioning therapy without supplementation with antioxidant vitamins. The rise in plasma lipid hydroperoxide level between the start of conditioning therapy and the completion of transplantation was from 20.1 to 36.2 mmol/liter in the supplemented group and from 23.3 to 83.5 mmol/liter in the unsupplemented group. The increase was significant (p<0.05) only in the unsupplemented group. Conditioning therapy causes delayed toxic effects in several tissues, which is thought to be caused by free-radical damage. The authors speculated that reducing lipid peroxide formation may reduce the toxicity of conditioning therapy (Clemens et al, 1997).
Vitamin C Deficiency
Serum concentrations of vitamin C rose sharply in one group of subjects receiving high-dose vitamin C (500 mg/day; n=161). Those who completed 5 years' supplementation with the high-dose form had significant increases in serum levels of vitamin C; mean levels differed significantly from those observed at baseline (p<0.05) (Kim et al, 2004).
Ascorbic acid deficiency in the institutionalized elderly may be corrected by daily vitamin C supplements. In a double-blind, placebo-controlled trial of 94 elderly inpatients with low levels of plasma and leukocyte vitamin C, patients received placebo or vitamin C 1 g for 60 days. Plasma and leukocyte vitamin C levels rose significantly during therapy. Treated patients showed significant increases in the mean values of body weight (0.41 kg), plasma albumin (0.46 g/liter), and prealbumin (25.4 mg/liter), and untreated patients showed decreases of these values, 0.6 kg, 0.53 g/liter, and 7 mg/liter, respectively. Reductions in purpura and petechial hemorrhages were also noted in the vitamin C group; however, no change in mood or mobility was observed (Schorah et al, 1981).
Cardiovascular Disease Protection
A 2006 review noted that levels of vitamin C are reduced in heart failure. In patients with chronic cardiac failure (CCF), IV or oral administration of vitamin C has been associated with sharp improvements in vasomotor function as reported in 2 studies cited. Administration of vitamin C in patients with CCF may reduce endothelial and cardiomyocyte apoptosis. Another study mentioned in the review found that oral administration of vitamin C reversed endothelial vasomotor dysfunction in patients with coronary artery disease (CAD), with benefits observed after 30 days (Witte and Clark, 2006).
Discrepancies exist between studies of subjects with adequate plasma levels of vitamin C and those obtaining vitamin C from diet or supplementation. For example, in a 2005 review, several studies with conflicting results are mentioned. One study examining older adults (aged 74-84 years) found a marked inverse trend for plasma levels of vitamin C and all-cause and cardiovascular disease (CVD) mortality. Following adjustments for CVD risk factors and variations in diet, subjects with higher plasma levels of vitamin C (>66 mm) were observed to have about half the mortality risk as subjects with lower plasma levels of vitamin C (<17 mm). However, in this study, no association was found between dietary intakes of vitamin C and all-cause or CVD mortality. The Nurses' Health Study examined the association between levels of vitamin C (obtained from either diet or supplementation) and risk of coronary heart disease (CHD). A group of women representing 1,240,566 person-years was followed; by study end, the investigators observed that although supplementation with vitamin C was associated with a significantly reduced risk of CHD, no association could be found between dietary vitamin C and risk of CHD. Another study of postmenopausal women with type 2 diabetes found just the opposite. In that study, subjects were from the Iowa Women's Health Study Cohort, and had high intakes of vitamin C. After adjusting for CVD risk factors and variations in diet, the authors found that total vitamin C and supplemental vitamin C were positively associated with risk of CVD mortality, whereas dietary vitamin C was not. Finally, a pooled analysis of 9 older cohort studies cited in the review inferred that supplemental vitamin C was associated with a reduced relative risk of CHD (Baldwin et al, 2005).
In a Finnish prospective population study (n=1605), subjects with low plasma vitamin C (less than 11.4 mmol/liter, or 2 mg/liter) had a relative risk of acute myocardial infarction of 2.5 compared with those who were not deficient, after adjustments of the model for the strongest risk factors of myocardial infarction. The authors suggest that supplementation of vitamin C may be beneficial in individuals with low plasma levels but not in those whose plasma levels are above 2 mg/liter (Nyyssonen et al, 1997).
Unlike some other studies, one double-blind, randomized trial found an inverse relationship between supplementation with vitamin C and common cold incidence, but reported no effect of supplementation on cold duration or severity. Among subjects who completed the 5-year study, the low-dose group received 50 mg/day vitamin C (n=120) and the high-dose group received 500 mg/day (n=124). By study end, the total number of common colds (per 1000 person-months) was 21.3 in the low-dose group and 17.1 in the high-dose group. These findings differ from other studies, and should be interpreted cautiously. The authors point out several disadvantages of the study, including the lack of a placebo arm, the limitations of self-reporting, a relatively small sample size, and a large dropout rate (Sasazuki et al 2006).
Different findings were reported in an update to a recent Cochrane review. Three meta-analyses of placebo-controlled studies using doses of 200 mg or more of vitamin C were presented. Distinctions were made between using vitamin C as continuous prophylaxis or after the onset of cold symptoms. For the incidence of colds during prophylaxis, 29 studies involving 11,077 subjects were identified for inclusion in the review. Although doses as high as 2 g/day did not affect incidence in a subgroup of 23 community studies (n=10,435), a subgroup of 6 studies (n=642) showed a 50% reduction in common cold incidence among runners, skiers, and soldiers exposed to significant cold and/or stress. Duration of colds occurring during prophylaxis was examined in 30 studies involving 9,676 subjects; of these, 12 involved children (n=2,434) and 18 involved adults (n=7,242). Supplementation with vitamin C was associated with significant reductions in duration in both groups. The average reduction in symptom days was 14% in children and 8% in adults. Finally, of the 7 studies that evaluated the duration of colds treated at onset of symptoms, no benefits were observed for duration of episodes in the 3,294 adult participants (Douglas and Hemila, 2005).
These findings are more in line with other controlled trials, which found no significant effect of ascorbic acid on the incidence of colds, except for individuals under heavy acute physical stress. According to these earlier studies, the effect of ascorbic acid supplementation on severity and duration of cold symptoms has been repeatedly, though not consistently, shown to be measurable and statistically significant, with a median decrease of 22% compared to placebo (Hemila, 1997a). Some authorities have called these effects minor at best (AMA, 1986).
Three earlier studies reported significant reductions in incidence of pneumonia with ascorbic acid supplementation, including a randomized, double-blind, placebo-controlled trial (Hemila, 1997b). These studies were again cited in a recent Cochrane review, which searched the literature from 1945 to 2006 for trials examining the use of vitamin C to prevent and/or treat pneumonia. In the 3 prophylactic trials included in the review, 37 cases of pneumonia were identified in a total of 2,335 subjects. Subjects who received vitamin C had an 80% or greater reduction in the incidence of pneumonia. Only 2 therapeutic trials were identified, involving 197 patients with pneumonia. Of these, just one was a double-blind, randomized trial. One trial examined elderly subjects and found that administration of vitamin C was associated with lower mortality and reduced respiratory symptom scores among those most ill; the other study found a dose-dependent reduction in recovery time with 2 doses of vitamin C (Hemila and Louhiala, 2007).
A combination of calcium, ascorbic acid, and vitamin D3 reversed dental, clinical, and early skeletal fluorosis in children in a double-blind, placebo-controlled study. Twenty-five children (aged 6 to 12 years) living in an area where the drinking water contained 4.5 mg fluoride/liter were administered either placebo (n=10) or ascorbic acid 250 mg and calcium compound (125 mg elemental calcium) twice a day and vitamin D3 60,000 IU once a week (n=15) for 180 days. Intake of fluoride-rich water continued as usual. At the end of the treatment period, there was significant improvement in dental, clinical, and skeletal grades of fluorosis in the treated children (p<0.05) but not in the placebo group. There were significantly reduced fluoride levels in the blood and serum and increased urinary fluoride levels in the treated group (p<0.05 for all 3 parameters) but not in the placebo group, indicating increased removal of fluoride from the body. The results of this small study indicate that calcium, ascorbic acid, and vitamin D3 supplementation can reverse fluorosis in children (Gupta et al, 1996).
Oral ascorbic acid reduced blood pressure and arterial stiffness in patients with type 2 diabetes. In a randomized, double-blind, placebo-controlled trial, 30 patients (aged 45 to 70 years) with type 2 diabetes that was controlled with diet or hypoglycemic agents received either placebo or oral ascorbic acid 500 mg daily. After 4 weeks of treatment, mean brachial systolic pressure was reduced from 142 to 132 mm Hg in the ascorbic acid group (p=0.001 in comparison to baseline), and brachial diastolic pressure was reduced from 83.9 to 79.5 (p=0.003 in comparison to baseline). In the placebo group, blood pressure was not changed. The difference between treatments was statistically significant (p<0.001). The aortic augmentation index and the time to wave reflection, both indicators of aortic stiffness, showed improvement in the ascorbic acid group but not in the placebo group. Differences between treatments were significant (p=0.026 and p<0.01, respectively) (Mullan et al, 2002).
Vitamin C reduced daytime ambulatory but not nighttime blood pressure in older persons with hypertension; blood pressure of normotensive older persons was unaffected. In a double-blind, randomized, placebo-controlled crossover study (1 week washout between treatments), 40 nonsmokers between the ages of 60 and 80 years took ascorbic acid 250 mg twice daily or placebo, each for 3 months. Within the group of 17 participants who were hypertensive (systolic blood pressure 140 mm Hg or greater), SBP decreased significantly, by 3.7 mm Hg (95% confidence interval 1.5 to 5.9 mm Hg), with ascorbic acid treatment. Ascorbic acid treatment also increased HDL cholesterol in women but not in men (Fotherby et al, 2000).
Ascorbic acid 500 mg per day reduced systolic, diastolic, and mean blood pressure in healthy hypertensive individuals. In a randomized, double-blind trial, 39 hypertensive patients were given ascorbic acid 500 mg or placebo for 1 month. At the end of treatment, systolic blood pressure had been reduced from 155 to 142 mm Hg in the ascorbic acid group (p<0.001) and mean blood pressure from 110 to 100 mm Hg (p<0.001). The changes were significantly greater than those in the placebo group (p=0.03 and p=0.02, respectively). Heart rate was not affected by ascorbic acid treatment (Duffy et al, 1999).
Early administration of vitamin C and vitamin E to critically ill patients who had experienced trauma or were to undergo surgery reduced the incidence of multiple organ failure and the length of time required in the intensive care unit (ICU). Eligible patients (n=595) were randomized within 24 hours of injury or emergency operation to receive antioxidant supplementation or standard care. d,l-alpha-tocopheryl acetate 1000 IU was given by naso- or orogastric tube every 8 hours, and ascorbic acid 1000 mg was given intravenously in 100 mL D5W (5% dextrose in water) every 8 hours for the shorter of either 28 days or the time in the ICU. The relative risk of pulmonary morbidity (acute respiratory distress syndrome or pneumonia) in patients receiving antioxidants was 0.81 (95% confidence interval (CI) 0.6-1.1). The relative risk of multiple organ failure was 0.43 (95% CI, 0.19-0.96). Patients in the antioxidant group required 1.2 fewer days in the ICU (95% CI, 0.81-1.5) and 0.4 fewer days in the hospital (95% CI: -0.2- 1.0). There were no difference between groups in occurrence of renal failure, and there were no other adverse effects attributable to the antioxidants (Nathens et al, 2002).
Indications & Usage
- Prophylaxis of Vitamin C deficiency
- Iron absorption
Vitamin C has been used in the prevention of heart disease, pneumonia, sunburn, and hyperlipidemia, and for cancer prevention, muscle soreness, asthma, common cold, erythema (after CO2 laser skin resurfacing), fluorosis, wound healing after severe trauma, and as an antioxidantKnown for fighting the common cold, but also supports heart health. Get Pure Matters Vitamin C.
Precautions & Adverse Reactions
Avoid rapid intravenous injections. Adverse effects of parenteral vitamin C include faintness or dizziness, hemolysis, renal failure, and injection site pain. Adverse effects of oral vitamin C include diarrhea, esophagitis (rare), and intestinal obstruction (rare).
Use cautiously in patients with preexisting kidney stone disease, erythrocyte G6PD deficiency, hemochromatosis, thalassemia, or sideroblastic anemia.
Avoid supplemental vitamin C before conducting laboratory examinations for acetaminophen, AST (SGOT), bilirubin, carbamazepine, creatinine, glucose, LDH, stool guiac, theophylline, and uric acid.
Concurrent use of amygdalin and ascorbic acid may result in increased metabolism of amygdalin, leading to increased cyanide levels. Clinical Management: Use amygdalin and ascorbic acid concomitantly with caution or use a therapeutic alternative. High doses of ascorbic acid may increase the hydrolysis of amygdalin, leading to increased levels of the metabolite hydrogen cyanide, and also reduce body stores of cysteine, which is used to detoxify cyanide. Monitor the patient for signs of cyanide toxicity, including headache, tachycardia, confusion, convulsions, and cardiac arrhythmias.
Concurrent use of ascorbic acid and indinavir may result in decreased indinavir plasma concentrations. Clinical Management: Advise patients to use caution with ascorbic acid (Vitamin C) doses above the recommended daily allowance. Decreased indinavir plasma concentrations may occur, potentially making indinavir less effective.
Concurrent use of ascorbic acid and antacids may result in aluminum toxicity (personality changes, seizures, coma). Clinical Management: Concurrent administration of antacids and high-dose ascorbic acid is not recommended, especially in patients with renal insufficiency. If concurrent use cannot be avoided, monitor patients for possible acute aluminum toxicity (e.g., encephalopathy, seizures, or coma) and adjust the doses accordingly.
Concurrent use of ascorbic acid and cyanocobalamin may result in reduced amounts of cyanocobalamin available for serum and body stores. Clinical Management: Ascorbic acid (Vitamin C) should be administered 2 or more hours after a meal or vitamin B12 supplements.
Increased ascorbic requirements with concomitant use. Clinical Management: Increased dietary or supplemental vitamin C intake (100 to 200 mg daily) should be considered for patients on chronic high-dose aspirin.
Mode of Administration
oral, intramuscular, intravenous
capsule, injectable, lozenge, solution, tablet
The following chart lists the Recommended Dietary Allowance (RDA) for vitamin C. Individuals who smoke require an additional 35 mg/day of vitamin C over the established RDA.
|0 to 6 months||40 mg/day||40 mg/day|
|7 to 12 months||50 mg/day||50 mg/day|
|1 to 3 years||15 mg/day||15 mg/day|
|4 to 8 years||25 mg/day||25 mg/day|
|9 to 13 years||45 mg/day||45 mg/day||80 mg/day||115 mg/day|
|14 to 18 years||75 mg/day||65 mg/day||80 mg/day||115 mg/day|
|19 years and older||90 mg/day||75 mg/day||85 mg/day||120 mg/day|
Antioxidant effects: 120 to 450 mg/day (Girodon et al, 1997; Clemens et al, 1997).
Asthma: 500 to 2000 mg/day or prior to exercise (Cohen et al, 1997; Bielory & Gandhi, 1994).
Atherosclerosis prevention: 45 to 1000 mg/day (Jialal & Fuller, 1995; Gale et al, 1995; Kritchevsky et al, 1995).
Delayed-onset muscle soreness: 3000 mg/day (Kaminski & Boal, 1992).
Gastric cancer: 50 mg/day (Anon, 1993).
Histamine detoxification: 2000 mg/day (Johnston et al, 1992).
Hypercholesterolemia: 300 to 3000 mg/day (Simon, 1992).
Respiratory Infection: 1000 to 2000 mg/day (Hemila, 1997a; Hemila, 1997b).
Scurvy: The recommended dose for the treatment of scurvy is 1 to 2 g administered intravenously or orally for the first 2 days, then 500 mg intravenously or orally daily for a week (Oeffinger, 1993). However, the AMA recommends 100 mg 3 times a day for 1 week then 100 mg daily for several weeks until tissue saturation is normal (AMA, 1990).
Sunburn prevention: 2000 mg/day (Eberlein-Konig et al, 1998).
Urine acidification: 3 to 12 g/day titrated to desired effect (Krupp & Chatton, 1980) and given as divided doses every 4 hours (AMA, 1980).
Wound healing: 1000 to 1500 mg/day (Mazzotta, 1994).
Scurvy: The recommended dose for the treatment of scurvy in adults and children is 100 mg 3 times a day for 1 week, then 100 mg daily for several weeks until tissue saturation is normal. This dosage can be administered intramuscularly, intravenously, or orally (AMA, 1990).
Vitamin deficiency: 100 to 500 milligrams/day (Krupp & Chatton, 1980).
Cancer: A dosing protocol for adjunctive therapy for cancer, based on more than 20 years of experience and isolated case reports (Riordan et al, 2003) is as follows: By intravenous (IV) drip (not push) week 1: 15 g/d IV 2 to 3 times/week ; week 2: 30 g/day IV 2 to 3 times/week; week 3: 65 g/day IV 2 to 3 times/week; week 4: 100 g/day IV 2 to 3 times/week; The dose should then be adjusted to achieve transient plasma concentrations of 400 mg/dL, or 200 mg/dL if lipoic acid (300 mg twice daily) is also being given. This protocol should be continued for at least a year. Patients are advised to supplement orally with at least 5 g daily when no infusion is given to maintain basal tissue levels and to prevent a rare but possible rebound scurvy.
Scurvy: The recommended dose for the treatment of scurvy is 1 to 2 g administered intravenously or orally for the first 2 days then 500 mg orally or intravenously daily for a week (Oeffinger, 1993). However, the American Medical Association recommends 100 mg 3 times a day for 1 week then 100 mg daily for several weeks until tissue saturation is normal (AMA, 1990).
Topical wound healing, skin erythema, aqueous solution: 10% solution applied once daily (Alster & West, 1998).
The recommended prophylactic dose for infants on formula feedings is 35 mg/day orally or intramuscularly for the first few weeks of life. If the formula contains 2 to 3 times the amount of protein in human milk, the dose should be 50 mg/day orally or intramuscularly (AMA, 1980).
Infants and children require 30 to 60 mg of crystalline ascorbic acid daily. This may be taken as oral tablets or as part of the normal diet (i.e., 2 to 4 oz. of orange juice) (AMA, 1980).
Flourosis: 500 mg/day (Gupta et al, 1996).
Scurvy: The recommended dose for the treatment of scurvy in adults and children is 100 mg 3 times a day for 1 week, then 100 mg daily for several weeks until tissue saturation is normal. The regimen may be administered intramuscularly, intravenously, or orally (AMA, 1990).
Scurvy: See Adult Dosage. The recommended prophylactic dose for infants on formula feedings is 35 mg/day orally or intramuscularly for the first few weeks of life. If the formula contains 2 to 3 times the amount of protein in human milk, the dose should be 50 mg/day orally or intramuscularly (AMA, 1980).
Scurvy: See Adult Dosage. In patients 17 years and younger, ascorbic acid should be diluted in at least an equal volume of fluid and infused over a minimum of 10 minutes. Direct intravenous push is not recommended. The final solution should be protected from light (Anon, 1984). The maximum recommended intravenous dose for ascorbic acid in pediatric patients (17 years and younger) is 100 mg/kg/day up to 6 g/day (Anon, 1984).