Vitamin C

Overview

Vitamin C cures the world’s oldest known nutritional deficiency disease, scurvy. It was first isolated by Albert Szent-Gyorgyi in 1928 from pork adrenal glands and called hexuronic acid. In 1933, its chemical structure was established. It was successfully synthesized, and the name was changed to ascorbic acid.

Vitamin C is a water-soluble vitamin that is stored in many tissues throughout the body, but the adrenal glands contain the highest concentration.

Humans are one of the few species that cannot manufacture vitamin C. We must depend on our diet, or nutritional supplements, as the source of this vitamin. Vitamin C exists in nature in both its reduced form, l-ascorbic acid, and in its oxidized form, l-dehydroascorbic acid. L-ascorbic acid is the most active form. However, in the body they convert back and forth to each other in a reversible equilibrium, and both prevent scurvy (antiscorbutic). Buffered vitamin C refers to the sodium, calcium, magnesium, and potassium ascorbate salts. These forms of vitamin C are less acidic and may be less likely to cause gastric irritation when taken in higher doses.

Dosage Info

Dosage Range

60-2,000mg daily. (1) , (2) Some therapeutic applications may go much higher. (3)

Most Common Dosage

250mg daily.

Dosage Forms

Capsules, tablets, liposomal sprays, effervescent tablets, bulk powder, and injectables (Rx only).

Adult RDI

60mg

Adult ODA

250-1,000mg

RDA

• Infants < 6 months: 40mg (Adequate Intake, AI)
• Infants 7-12 months: 50mg (AI)
• Children 1-3 years: 15mg
• Children 4-8 years: 25mg
• Children 9-13 years: 45mg
• Males 14-18 years: 75mg
• Females 14-18 years: 65mg
• Males >19 years: 90mg
• Females >19 years: 75mg
• Pregnancy 19 years: 85mg
• Lactation 19 years: 120mg

Interactions and Depletions

Depletions

• Salicylates
• Corticosteroid medications
• Loop diuretics
• Oral contraceptives
• Tetracyclines
• copper

Active Forms

Ascorbic acid, calcium ascorbate, magnesium ascorbate, sodium ascorbate, Ester C, ascorbyl palmitate.

Absorption

Vitamin C is a water-soluble vitamin that is easily absorbed from the small intestine.

Toxicities & Precautions

General

There are no known toxicities associated with vitamin C.

Large doses of vitamin C may interfere with tests to determine occult blood in the stool and tests to monitor blood glucose levels in diabetics.

Side Effects

Diarrhea can occur due to large doses or an overdose of vitamin C and can generally be controlled by lowering the dose of vitmain C until the diarrhea no longer occurs.

Approximately 15 percent of people taking moderately high doses of vitamin C experience abdominal gas, bloating, and cramping. The mineral ascorbates such as calcium or magnesium ascorbate are not acidic and may solve this problem.

Functions in the Body

Enzyme Activity

Involved in oxidation-reduction reactions, energy production, tyrosine metabolism, reduction and storage of iron, and the activation of folic acid. It is essential in the synthesis of collagen, serotonin, norepinephrine, thyroxine, and some of the corticosteroids.

Collagen and Elastin

Plays a role in the synthesis of collagen and elastin, the major structural components of skin, tendons, bone matrix, tooth dentin, blood vessels, and connective tissues between cells.

Antioxidant

Ability to donate hydrogen atoms from its two hydroxyl (OH) positions to neutralize free radicals. Capable of regenerating the antioxidant form of vitamin E. Low antioxidant levels could increase the incidence of side effects due to chemotherapy. (4)

Stress

Required for the synthesis of the body’s main stress response hormones in the adrenal glands, including epinephrine, norepinephrine, cortisol, and histamine. Stresses, such as fever, burns, exposure to cold, physical trauma, fractures, high altitude and radiation all require larger doses of vitamin C.

Cancer Prevention

Prevents the formation of cancer causing nitrosamines.

Fat Synthesis:

a) aids in the conversion of cholesterol to bile acids for excretion
b) is necessary for synthesis of collagen and elastin which maintains strength and elasticity of blood vessels
c) decreases free radical oxidation of cholesterol
d) decreases levels of lipoprotein(a) or Lp(a)

Atherosclerotic Plaques:

Calcium/phospholipid/cholesterol plaque (insoluble) reacts with sodium ascorbate to form sodium/phospholipid/cholesterol (soluble) and calcium ascorbate (soluble).

Increases:

a) production of white blood cells (neutrophils, lymphocytes, and natural killer cells)
b) levels of antibodies IgA, IgG, and IgM
c) production of interferon
d) modulates prostaglandin synthesis

Histamine Inhibitor

Functions as both a histamine inhibitor (it inhibits the release and enhances the degradation of histamine) and as a phosphodiesterase inhibitor.

Antiviral

Reported to have antiviral activity.

Wound healing:

Increases the healing of scars, broken bones, burns, etc.

Detoxifies

Heavy metal toxins such as mercury, lead, cadmium, and nickel.

Clinical Applications

Circulation

A small study investigated the role of vitamin C in the circulation of smokers. This study involved 13 smokers and 12 non-smokers as the control group. Coronary blood flows were measured at rest and when an intravenous chemical increased the blood flow. The participants ingested 2 grams of vitamin C and the blood flow was measured at baseline and 2 and 4 hours after ingestion. The results showed that blood flow was significantly better in the non-smokers than the smokers. After the vitamin C, the blood flow increased in the smokers, but not in the non-smokers. (5)

Arthritis

A preliminary study found that higher intakes of vitamin C may reduce the risk of arthritis. (6)

Diabetes Mellitus

Several studies have found that low vitamin C intake is associated with increased risk of diabetes (7) , (8) and that vitamin C may support overall health of diabetics. (9)

Atherosclerosis.

Evaluation of an association between vitamin C and athersclerosis has been studied for decades and continues to this day. (10) Studies have noted the association between low levels of vitamin C and the presence of various forms of atherosclerotic disease (11) , (12) but a link to myocardial infarction is questioned. (13) In studies, vitamin C and vitamin E demonstrated retardation of the early progression of coronary arteriosclerosis. (14) , (15)

Cataracts

Long-term vitamin C supplementation substantially reduced the risk of developing cataracts. (16) , (17) In fact, 158 patients were followed for three years and daily use of beta-carotene, vitamin C, and vitamin E demonstrated a small deceleration in the progression of age-related cataracts. (18)

Cervical Dysplasia

Women with cervical dysplasia were found to have low levels of vitamin C. (19)

Common Cold

Analysis of 14 placebo-controlled trials shows a 35 percent average reduction in the duration of colds and a decrease in the severity of symptoms using vitamin C at dosages above RDA levels. (20) In a double-blind, placebo-controlled survey the results were the group taking vitamin C having fewer colds and recovery if infected was faster than the placebo group. (21)

Immunity

1-3 grams daily provides a variety of immunostimulatory effects. (22)

Aids

Preliminary research and observation has noted that extremely high doses, 50-200 grams daily, can suppress the symptoms of the disease and can markedly reduce the tendency for secondary infections. (23) In order to assess the immunological and virological effects of short-term, high-dose antioxidant treatment in patients with HIV infection, 8 patients with HIV infection were given high doses of N-acetylcysteine (NAC) and vitamin C for 6 days. Though further study is warranted, the 5 patients with the most advanced immunodeficiency did experience a rise in CD4+ lymphocyte count, a reduction in HIV RNA plasma level as well as improvements in other measures. (24)

Asthma

Evidence shows that low vitamin C intake is a risk factor for asthma. (25) Though not well defined, multiple therapeutic reviews and meta-analyses have evaluated the role of vitamin c in the treatment of asthma. (26) , (27) , (28)

Cancer

A large meta analysis and epidemiological studies have shown that vitamin C along with other dietary vitamins reduces the risk of many different types of cancers especially those along the digestive tract. (29) , (30) , (31)

Cholesterol Lowering

Vitamin C increases HDL levels (32) and prevents the oxidation of LDL cholesterol. (33) However there has been some debate regarding the clincal impact of using antioxidants such as vitamin C in conjunction with standard western medical practices. A study involving one hundred and fifty three patients with coronary artery disease evaluated the clinical impact of antioxidant supplementation, including vitamin C, vitamin E, beta-carotene and selenium, on people with low HDL levels in an effort to improve the HDL-C:LDL-C ratio. The participants were followed for 12 months after randomization to one of three groups. They received either placebo, simvastatin and niacin, or simvastatin, niacin plus antioxidants (vitamin C, vitamin E, Beta-carotene and selenium). The treatment groups compared to the placebo group had significant reductions in plasma cholesterol, triglycerides and LDL-C. The desired increases in HDL-C were higher in the simvastatin/niacin group than in the simvastatin/niacin/antioxidant group. The investigators noted that the increases in the HDL2-C, Lp(A-I), and HDL particle size noted in the simvastatin/niacin group were apparently blunted by the additional use of the antioxidants. (34)

Wound Healing

Overall, studies identify a possible role and some support the role of vitamin C in properly caring for and treating healing wounds. (35) , (36) , (37)

Allergies

Vitamin C’s antihistamine activity helps reduce allergy symptoms. (38) It has also been hypothesized that the antioxidant and free radical scavenging activity of vitamin C may reduce the inflammatory or hypersensitivity responses in the body. (39)

Symptoms and Causes of Deficiency

Scurvy is rare in the United States, but sub-clinical deficiencies are common. Deficiency symptoms include capillary fragility, hemorrhage, muscular weakness, easy bruising, gums that bleed easily, poor wound healing, anemia, poor appetite and growth, and tender, swollen joints.

Stressful situations (both physical and emotional) tend to deplete the body’s stores of vitamin C quickly. (40)

Individuals most likely to experience deficiencies include elderly people on poor diets, alcoholics, people who are severely ill or under chronic stress, and infants who are only fed cow’s milk.

A study identified 12 patients from a surgical service who had bleeding diatheses, low plasma ascorbic acid levels (

Dietary Sources

The best sources of vitamin C are fresh fruits, especially citrus fruits, strawberries, cantaloupe and currants, and fresh vegetables, especially Brussels sprouts, collard greens, lettuce, cabbage, peas, and asparagus.

References

1. View Abstract: Hemila H. Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit. Med Hypotheses. Feb1999;52(2):171-8.
2. View Abstract: Douglas RM, Chalker EB, Treacy B. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev. 2000;(2):CD000980.
3. View Abstract: Daniel TA, Nawarskas JJ. Vitamin C in the prevention of nitrate tolerance. Ann Pharmacother. Oct2000;34(10):1193-1197.
4. View Abstract: Kennedy DD, Tucker KL, Ladas ED, Rheingold SR, Blumberg J, Kelly KM. Low antioxidant vitamin intakes are associated with increases in adverse effects of chemotherapy in children with acute lymphoblastic leukemia. Am J Clin Nutr. Jun2004;79(6):1029-36.
5. View Abstract: Teramoto K, et al. Acute effect of oral vitamin C on coronary circulation in young healthy smokers. Am Heart J. Aug 2004;148(2):300.
6. View Abstract: Pattison DJ, et al. Vitamin C and the risk of developing inflammatory polyarthritis: prospective nested case-control study. Ann Rheum Dis. July 2004;36:843-7.
7. View Abstract: Zhang C, Williams MA, Frederick IO, et al. Vitamin C and the risk of gestational diabetes mellitus: a case-control study. J Reprod Med. Apr2004;49(4):257-66.
8. View Abstract: Bates CJ, Lean ME, Mansoor MA, Prentice A. Nutrient intakes; biochemical and risk indices associated with Type 2 diabetes and glycosylated haemoglobin, in the British National Diet and Nutrition Survey of people aged 65 years and over. Diabet Med. Jul2004;21(7):677-84.
9. View Abstract: Sinclair AJ, et al. Low Plasma Ascorbate Levels in Patients with Type 2 Diabetes Mellitus Consuming Adequate Dietary Vitamin C. Diabet Med. Nov1994;11(9):893-98.
10. Willis GC. Serial Arteriography in Atherosclerosis. Can Med Assoc J. 1954;71:562-68.
11. View Abstract: Langlois M, Duprez D, Delanghe J, De Buyzere M, Clement DL. Serum vitamin C concentration is low in peripheral arterial disease and is associated with inflammation and severity of atherosclerosis. Circulation. Apr2001;103(14):1863-8.
12. View Abstract: Clemetson CA. The key role of histamine in the development of atherosclerosis and coronary heart disease. Med Hypotheses. Jan1999;52(1):1-8.
13. View Abstract: Riemersma RA, Carruthers KF, Elton RA, Fox KA. Vitamin C and the risk of acute myocardial infarction. Am J Clin Nutr. May2000;71(5):1181-6.
14. View Abstract: Fang JC, Kinlay S, Beltrame J, Hikiti H, Wainstein M, Behrendt D, et al. Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial. Lancet. Mar2002;359(9312):1108-13.
15. View Abstract: Salonen RM. Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study. Circulation. Feb2003;107(7):947-53.
16. View Abstract: Jacques PF, et al. Long-term Vitamin C Supplement Use and Prevalence of Early Age-related Lens Opackies. Am J Clin Nutr. Oct1997;66(4):911-161.
17. View Abstract: Moeller SM, Taylor A, Tucker KL, et al. Overall Adherence to the Dietary Guidelines for Americans Is Associated with Reduced Prevalence of Early Age-Related Nuclear Lens Opacities in Women. J Nutr. Jul2004;134(7):1812-1819.
18. View Abstract: Chylack LT Jr, Brown NP, Bron A, Hurst M, Kopcke W, Thien U, Schalch W. The Roche European American Cataract Trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract. Ophthalmic Epidemiol. Feb2002;9(1):49-80.
19. View Abstract: Romney SL, et al. Plasma Vitamin C and Uterine Cervical Dysplasia. Am J Obstet Gynecol. Apr1985;151(7):976-80.
20. Pauling L. How to Live Longer and Feel Better. New York: W.H. Freeman and Company; 1986:118-21.
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22. Anderson R. The Immunostimulatory, Anti-inflammatory and Anti-allergic Properties of Ascorbate. Adv Nutr Res. 1984;6:19-45.
23. View Abstract: Cathcart RF 3rd. Vitamin C in the Treatment of Acquired Immune Deficiency Syndrome (AIDS). Med Hypotheses. Aug1984;14(4):423-33.
24. View Abstract: Muller F, Svardal AM, Nordoy I, Berge RK, Aukrust P, Froland SS. Virological and immunological effects of antioxidant treatment in patients with HIV infection. Eur J Clin Invest. Oct2000;30(10):905-14.
25. View Abstract: Hatch GE. Asthma, Inhaled Oxidants, and Dietary Antioxidants. Am J Clin Nutr. Mar1995;61(3 Suppl):625S-30S.
26. View Abstract: Bielory L, et al. Asthma and Vitamin C. Ann Allergy. Aug1994;73(2):89-96.
27. View Abstract: Kaur B, Rowe BH, Ram FS. Vitamin C supplementation for asthma. Cochrane Database Syst Rev. 2001;(4):CD000993.
28. View Abstract: Falliers CJ, Tinkelman DG. Alternative drug therapy for asthma. Clin Chest Med. Sep1986;7(3):383-91.
29. View Abstract: Block G. Epidemiologic Evidence Regarding Vitamin C and Cancer. Am J Clin Nutr. Dec1991;54(6 Suppl):1310S-314S.
30. View Abstract: Kasum CM, Jacobs DR Jr, Nicodemus K, Folsom AR. Dietary risk factors for upper aerodigestive tract cancers. Int J Cancer. May2002;99(2):267-72.
31. Lee KW, Lee HJ, Kang KS, Lee CY. Preventive effects of vitamin C on carcinogenesis. Lancet. Jan2002;359(9301):172.
32. View Abstract: Simon JA, et al. Relation of Serum Ascorbic Acid to Serum Lipids and Lipoproteins in US Adults. J Am Coll Nutr. Jun1998;17(3):250-55.
33. View Abstract: Jialal I, et al. Physiologic Levels of Ascorbate Inhibit the Oxidative Modification of Low Density Lipoprotein. Atherosclerosis. Jun1990;82(3):185-91.
34. View Abstract: Cheung MC, Zhao XQ, Chait A, Albers JJ, Brown BG. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol. Aug2001;21(8):1320-6.
35. View Abstract: Ringsdorf WM Jr, et al. Vitamin C and Human Wound Healing. Oral Surg Oral Med Oral Pathol. Mar1982;53(3):231-36.
36. View Abstract: Scholl D, Langkamp-Henken B. Nutrient recommendations for wound healing. J Intraven Nurs. Mar2001;24(2):124-32.
37. View Abstract: Ringsdorf WM Jr, Cheraskin E. Vitamin C and human wound healing. Oral Surg Oral Med Oral Pathol. Mar1982;53(3):231-6.
38. Johnston CS. The Antihistamine Action of Ascorbic Acid. Subcell Biochem. 1996;25:189-213.
39. View Abstract: Cathcart RF 3rd. The vitamin C treatment of allergy and the normally unprimed state of antibodies. Med Hypotheses. Nov1986;21(3):307-21.
40. View Abstract: Gariballa SE, Hutchin TP, Sinclair AJ. Antioxidant capacity after acute ischaemic stroke. QJM. Oct2002;95(10):685-90.