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  Minerals
Boron

Calcium

Chromium

Cobalt

Copper

Fluoride

Iodine

Iron

Magnesium

Manganese

Molybdenum

Potassium

Selenium

Zinc

Vitamin C

Red Arrow  Facts Red Arrow  Functions
Red Arrow  Deficiency signs and symptoms Red Arrow  Toxicity
Red Arrow  Dietary Sources Red Arrow  Populations w/ Special Needs
Red Arrow  Requirements & Recommendations Red Arrow  Drug-Vitamin Interaction
Red Arrow  Research Summary

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 Facts Topic header down arrow
  • Vitamin C or ascorbic acid has a biological role as a reducing agent in hydroxylation reactions in the body.
  • Vitamin C is structurally similar to six-carbon glucose.
  • Vitamin C has antioxidant activity.
  • Vitamin C aids in absorption of iron by reducing it to the ferrous state in the stomach.
  • Intake of up to 100 mg of vitamin C daily is 80 to 90% absorbed.
  • The classic disease of vitamin C is scurvy, where the body cannot make collagen proteins that are needed in connective tissues and joints.
  • Vitamin C is stable when dry, but is easily oxidized by air and easily destroyed during food processing and cooking.
  • Vitamin C works as a cofactor for enzymes essential for collagen synthesis.
  • Vitamin C is essential for maintenance of connective tissues and wound healing.
  • Age-related lens opacities, which may be due to oxidative stress, appear to be prevented by vitamin C supplementation.1
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 Functions Topic header down arrow
  • Vitamin C acts as a reducing agent in a number of hydroxylation reactions in the body such as proline 4-hydroxylase, which is essential for collagen synthesis.
  • Vitamin C is a water-soluble antioxidant and can quench both reactive oxygen species and reactive nitrogen species. This antioxidant activity diminishes lipid peroxidation, oxidative DNA damage and oxidative protein damage. Oxidation of low density lipoprotein (LDL) has been suggested to be a factor causing atherosclerosis. Vitamin C prevents LDL from being oxidized. Vitamin C increases high density lipoprotein (HDL) cholesterol, probably resulting in decreased risk of atherosclerosis.
  • Vitamin C can prevent the formation of carcinogens as nitrosamines in foods and in the gastrointestinal tract.
  • Vitamin C is required for the enzyme reaction that converts tryptophan to 5-hydroxytryptophan, a precursor of neurotransmitter serotonin.
  • Vitamin C has many biological activities in addition to antioxidant activity:
    • antihypertensive
    • antiviral
    • immunomodulation
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 Deficiency signs and symptoms Topic header down arrow
2

Severe vitamin C deficiency results in scurvy, an acute or chronic disease characterized by hemorrhagic manifestations and abnormal osteoid and dentin formation.
  • In adults, scurvy remains latent for 3 to 12 months following onset of severe vitamin C deficiency.
  • Symptoms are weakness irritability, weight loss, and vague myalgias and may form a crescent near the distal end of the nail.
  • The gums become swollen, purple, spongy, and readily bleed.
  • In secondary infection gangrene is seen, loosening of the teeth, and gum changes. Old scars break down, new wounds fail to heal and spontaneous hemorrhages may occur in any part of the body.
  • Other symptoms and signs of scurvy include:
    Bulbar conjunctival hemorrhage
    Femoral neuropathy
    Oliguria
    Edema of the lower extremities
    Impaired vascular reactivity
    Arthritis resembling Rheumatoid Arthritis
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 Toxicity Topic header down arrow
4
  • Massive doses of vitamin C increase the amount of oxalate excreted, although the amount usually remains within a normal and safe range. Only persons predisposed to urolithiasis are likely to be troubled by oxalate stones.
  • Large doses of ascorbic acid (4 g) will increase the amount of uric acid excreted in the urine, which may cause urate crystals.
  • Ascorbic acid when ingested with sources of non-heme iron increases iron absorption. Chronic high doses may be unsafe for individuals with hemochromatosis, thalassemia and sideroblastic anemia.
  • Excessive doses of vitamin C can cause diarrhea. Ascorbate in the feces and urine can interfere with a variety of clinical laboratory tests.
  • High intake of vitamin C (more than 1500 mg) may decrease the absorption of copper in the intestine.
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 Dietary Sources Topic header down arrow
Almost 90% of dietary vitamin C comes from foods of plant origin. Vitamin C can be found in fruits (especially citrus) and vegetables, including green and red peppers, tomatoes, potatoes, and green, leafy varieties (e.g. spinach and collard greens).
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 Populations w/ Special Needs Topic header down arrow
  • Diarrhea increases fecal loss of vitamin C and achlorhydria decreases the amount absorbed.
  • Surgery, acute and chronic inflammatory diseases, and burns significantly increase the body's requirements for vitamin C.
  • It is recommended that cigarette smokers ingest at least 100 mg of vitamin C per day, since smoking seems to increase metabolic turnover of the vitamin, leading to lower concentration in the blood.
  • Other populations associated with increased risk of vitamin C deficiency include those suffering from alcoholism, elderly and institutionalized individuals, and surgical and cancer patients.
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 Requirements & Recommendations Topic header down arrow
Vitamin C: Dietary Reference Intake 3
mg/day Tolerable
Upper Intake Levels
(UL)
Infants
0 to 6 months
7 to 12 months
40*
50*
ND
ND
Children
1 to 3 years
4 to 8 years
15
25
400
650
Male
9 to 13 years
14 to 18 years
19 to 70 years
Female
13 to 19 years
14 to 18 years
19 to 70 years
45
75
90

45
65
75
1200
1800
2000

1200
1800
2000
Pregnancy
<= 18 years
19 to 50 years
80
85
1800
2000
Lactation
<= 18 years
19 to 50 years
115
120
1800
2000


*Values are Adequate Intakes (AI), others are RDA.
ND=Not determinable due to lack of data of adverse effects in this age group and concern with regard to lack of ability to handle excess amounts.
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 Drug-Vitamin Interaction Topic header down arrow
5 6 7
  • Increased urinary loss of vitamin C may occur when aspirin is taken concurrently with ascorbic acid. Patients taking high dosages of aspirin who have signs or symptoms of ascorbic acid deficiency should be evaluated for deficiency, and routine administration of vitamin C supplements is recommended.
  • People who take warfarin [Coumadinâ] can have decreased anticoagulant effects by vitamin C. It is advisable to consult a physician or pharmacist during drug therapy.
  • The concurrent administration of vitamin C and fluphenazine [Prolixinâ], an antipsychotic agent, results in decreased fluphenazine plasma concentrations. It is advisable to consult a physician or pharmacist during drug therapy.
  • Vitamin C concentrations are decreased by use of estrogen or estrogen-containing oral contraceptives. The clinical significance is unclear. It is advisable to take the vitamin 1 to 2 hours before or 3 to 4 hours after the administration of the contraceptives.
  • A large dose of vitamin C (more than 500 mg) may cause false-negative urine glucose determinations. No exogenous vitamin C should be ingested for 48 to 72 hours before amine-dependent stool occult blood tests.
  • Three grams of vitamin C with acetaminophen [Tylenolâ], an analgesic agent, was shown to prolong the amount of time acetaminophen stays in the body. People who take the drug should consult with a physician or pharmacist before adjusting the dose.
Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature. In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship.
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 Research Summary Topic header down arrow
Mortality: The follow up study from the Second National Health and Nutrition Examination Survey showed that men in the lowest compared with the highest serum ascorbate quartile had a 57% higher risk of dying from any cause of death and a 62% higher risk of dying from cancer. However, this is not the case among women.8

Bone Mineral Density: Vitamin C is involved in synthesis of collagen, a precursor of bone matrix mineralization. A study showed a clear relationship between vitamin C supplementation and bone mineral density (BMD) in postmenopausal women. Vitamin C users had BMD concentrations approximately 3% higher at the midshaft radius, femoral neck, and total hip after adjusted BMI and calcium intake. Women taking both estrogen and vitamin C had significantly higher BMD. The addition of calcium to estrogen and vitamin C showed the highest BMD at the femoral neck, total hip, ultradistal radius and lumbar spine. The average intake of vitamin C was 745 mg, ranging from 100 to 500 mg from supplement. The average duration of use was 12.4 years. 9

Diabetes: A large population based study examined the association between plasma vitamin C concentrations and glucose tolerance. Findings in this study confirm the observation that subjects with diabetes have lower plasma vitamin C concentrations than subjects without diabetes. Therefore, dietary measures to increase plasma vitamin C concentrations may be an important public health strategy for reducing the prevalence of diabetes.10

Photoprotection: Antioxidants such as vitamins C and E have been found to be photo-protective to acute adverse effects from sunburn, photosensitivity reactions, photo-aging or malignant skin tumors. Subjects given 2 g of vitamin C and 1000 IU of vitamin E for 8 days, had reduced sunburn reaction which was determined by the threshold UV dose for eliciting sunburn and cutaneous blood flow. 11

Cognitive Function: The Honolulu-Asian Aging Study of Japanese-American men, looked at the association of vitamin E and C supplement use with cognitive function and dementia. More than 3300 men, aged 71 to 93 years, were surveyed on their supplement use and cognitive functions. As a result, taking both vitamins C and E were protective against vascular dementia and mixed other dementia, but not Alzheimer's dementia. 12

Blood Pressure: In a study done in 2001, one month of vitamin C depletion was followed by repletion of 117 mg/d 2 times a day of vitamin C. Plasma ascorbic acid concentrations were inversely associated with diastolic blood pressure 1 month later. Even after adjustment of confounding factors such as BMI and nutrient intake, this inverse relation was significant, indicating that vitamin C intake and tissue vitamin C concentrations are a determinant factor in maintaining blood pressure.13
  • To see how vitamin C concentrations are related to inflammation and severity of peripheral arterial disease (PAD), vitamin C status was measured in PAD patients, hypertensives without PAD and healthy subjects. Serum ascorbic acid concentrations were low in PAD patients, regardless of smoking and dietary intake. PAD patients had a higher serum C-reactive protein (CRP) concentration, a marker of inflammation, and CRP was inversely associated with low ascorbic acid concentrations. PAD patients with low serum vitamin C concentrations had shorter absolute claudication distance, indicating that inflammation in atherosclerosis may be due to high oxidative stress because of low antioxidant activity.14

Cataract: Although pathogenesis of cataract is multi-factorial, maintenance of sufficient vitamin C in the blood is required to prevent oxidative damage to the lens. Tessier et al15 found a relation between ascorbate concentrations in the lens, increasing age and increasing cataract severity.
  • Cataract formation is believed to result from an oxidative insult that decreases antioxidant defense of the lens, particularly vitamin C concentration. Upon oxidation, vitamin C contributes with glucose to protein glycation. A study looked at the relationship between vitamin C and cataract by analyzing lenticular vitamin C in 48 cataractous lens nuclei. The lens vitamin C concentration significantly decreased with cataract severity, but mostly in severe brown cataracts. The fluorescence of insoluble advanced glycated end products was significantly higher in severe cataracts than in milder ones. Overall, vitamin C content appears to be a good indicator of cataract severity and oxidation may take part in cataract progression.15
Smoking: Long-term smoking is known to be related to chronic diseases such as cardiovascular disease and cancer. To see whether smoking affects plasma antioxidant status and whether supplementation improves various concentrations of antioxidants, smokers and non-smokers were supplemented with > 72 mg of vitamin C, 31 mg of tocopheryl acetate and 400 mcg of folic acid. Smoking depleted only plasma vitamin C, but not plasma a-tocopherol or carotenoids. After 3 months of supplementation, plasma vitamin C concentrations were normalized.16

Cardiovascular Disease: More than 6600 US men and women enrolled in NHANES II were surveyed to determine whether there is a link between serum ascorbic acid concentrations and the prevalence of cardiovascular disease (CVD). The findings showed that women had higher serum ascorbic acid concentrations than men and non-smokers had higher concentrations than smokers. Serum ascorbic acid concentrations were correlated with the prevalence of CVD and strokes. A 0.5 mg/dl increase in the serum ascorbic acid concentration was associated with an 11% reduction in the prevalence of CVD and stroke.17
Safety of Vitamins E and C
A review article published in the 2005 Journal of Clinical Nutrition evaluated over 45 published clinical trials and several meta-analyses on the safety of vitamin E, vitamin C, or the combination of the two. The data consistently shows the safety of both these vitamins, alone or combined. More than 20 published clinical trials involving 80,000 subjects or more have documented the safety of vitamin E supplements. Three meta-analyses that combined the results of randomized controlled trials designed to evaluate the efficacy of vitamin E supplements for the prevention or treatment of cardiovascular disease (CVD) found no evidence that E supplementation up to 800 IU/day significantly increased or decreased CVD mortality or all-cause mortality. In addition, few reports have cited any adverse effects, such as bleeding, for vitamin E. Regarding vitamin C, the authors include over 20 published clinical trials with doses ranging from 60 mg to 10 grams. No pattern of evidence supports concerns about safety of vitamin C other than the occasional gastrointestinal upset or mild diarrhea. Both AREDS and MRC/BHF Heart Protection Study support the safety of vitamin E and C in combination. The Food and Nutrition Board of the Institute of Medicine established upper limits for vitamin E at 1000 mg (1600 IU), and 2000 mg for vitamin C. These recommendations support the consensus of published studies that vitamin E doses up to 1000 mg/day and vitamin C doses up to 2000 mg/day are safe for use by the general population.[~18~] [~19~] [~20~]
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ARTICLES

Vitamin C Deficiency Not Uncommon in the US

Antioxidants Beneficial for Graves’ Disease
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