Comprehensive Guide to Vitamins by Dr. James Meschino - HTML preview

Vitamin C - Ascorbic Acid

Introduction

The name Ascorbic Acid is derived from the Latin ascorbutus meaning “without scurvy”. In the winter of 1534, local Canadian Indians provided Jacques Cartier with the cure for scurvy, which had claimed twenty-five of his 110 men, with more than fifty in critical condition. The cure included a tea containing evergreen foliage from the Northern white cedar.

Ascorbic Acid itself was not identified as the anti-scorbutic agent until the early 1930s. It was first synthesized in 1933.

Absorption and Metabolism

Vitamin C is readily absorbed through the mucosa of the intestine. Humans store a total of 1,500 mg with moderate reserves in the liver and spleen, and high concentrations in the adrenal glands where it may be involved in the synthesis of adrenal steroids. Serum and tissue levels are in equilibrium; therefore, white blood cell levels of Vitamin C reflect Vitamin C stores in general.

The body excretes Vitamin C as Ascorbic Acid and as the metabolite oxalic acid in the urine. Thus, high Vitamin C intakes (above 750 mg) may precipitate the formation of calcium-oxalate kidney stones, in susceptible individuals.

Functions

1. Cartilage Formation
   Ascorbic Acid is necessary for the transformation of the amino acids proline and lysine into hydroxyproline, which provide the tertiary structure to collagen. This provides stability to collagen, a major component of all connective tissues in the body - skin, bones, teeth, muscle, tendon, cornea, etc. Thus, a Vitamin C deficiency manifests itself as swollen limbs, blotched and haemorrhaging gums and skin, loss of teeth, severe weakness, followed by death if untreated (scurvy).
   Vitamin C is required for wound healing. Therapeutic doses are used in the treatment of post-surgical patients and burn victims, primarily to support collagen synthesis.
2. Neurotransmitter Synthesis
   Vitamin C is required for the synthesis of norepinephrine from dopamine.
3. Iron Absorption
   The presence of Vitamin C enhances the absorption of iron from the intestinal tract to the bloodstream.¹
4. Antioxidant
   Vitamin C functions as an antioxidant in aqueous (water) environments in the body, both outside and inside human cells.¹ It also regenerates oxidized Vitamin E back to its antioxidant state, thereby potentiating the free radical quenching capability of Vitamin E.²
5. Immune Function
   Vitamin C is required to maintain optimal function of the immune system.³

Recommended Dietary Allowance (Vitamin C)¹

Vitamin C Deficiency

Scurvy:

Lassitude and general weakness

Swollen joints

Aching bones

Spongy and bleeding gums

Delayed wound healing

Muscle cramps

Dry, scaly skin

Signs of scurvy appear once the body pool of Vitamin C drops below 300 mg. Signs and symptoms of scurvy disappear when the body pool is restored to this level. Groups most at risk in North America include alcoholics and the elderly. Interestingly, Eskimos in the Arctic are able to derive Vitamin C from eating food frozen, raw, or only partially cooked although consuming a diet of almost no plant-based foods. Cooking destroys Vitamin C as it is the least stable of all vitamins (becomes readily oxidized when heated or exposed to light, air or an alkaline solution).¹

Supplementation Studies

Cancer prevention

A significant number of studies link higher intakes of Vitamin C with the prevention of cancer. Reports are most consistent for lung cancer, stomach, esophageal, oral, cervical, colon and pancreatic cancers.⁴ The following are mechanisms through which Vitamin C has been shown to modify cancer risk:

Antioxidant Function: as previously discussed, Vitamin C is a water soluble antioxidant, which has been shown to help contain oxidative stress and other free radical insults that are capable of causing mutations to the cell’s DNA, potentially leading to cancer.^1,4

Nitrosation Inhibitor: Vitamin C is known to block the formation of nitrosamines in the intestinal tract. Certain nitrosamines are known to be cancer-causing agents (carcinogens). Nitrosamines are formed by nitrosation reactions that combine nitrites (found in many processed foods and alcoholic beverages) with derivatives of dietary proteins, known as secondary amines. In test studies using nitrate loads, doses of approximately 1,000 mg per day of Vitamin C have been shown to block 85-100 percent of nitrosamine formation in human subjects. It appears best to take Vitamin C with food (500 mg, twice daily) in divided doses to get the best possible effect in blocking nitrosation reactions.^5,6

Immune Function

Vitamin C supplementation has been shown to boost parameters of immune function in normal volunteers and in elderly subjects. A daily dosage of only 120 mg per day has been shown to boost white blood cell counts back to more youthful levels in older people (average age 76). However, a daily dosage of 500-1,000 mg appears to further strengthen the immune system and reduce the severity and duration of the common cold,^7-10 In patients exposed to toxic chemicals a daily dosage of 60 mg per kilogram of body weight (about 4,000 mg per day) has been shown to greatly enhance natural killer cell function (up to 10-fold) and restore B and T cell function.¹¹

Asthma

Asthmatics may have a higher requirement for Vitamin C than do members of the general population. At least eleven clinical studies of Vitamin C supplementation have been performed with asthmatic patients. Seven of these studies showed significant improvements in respiratory measures and asthma symptoms using 1,000-2,000 mg of Vitamin C supplementation per day. At this level of intake Vitamin C has been shown to have an anti-histamine effect and it helps prevent lung damage from nitrogen oxide, a common dangerous element in air pollution and cigarette smoke.^29,30

Cancer Treatment

As part of an antioxidant and nutritional support cocktail, a daily dosage of 2,850 mg of Vitamin C has been shown to help stop the further spread of breast cancer in a trial of 32 breast cancer patients with axillary lymph node involvement. Researchers having success in this area tend to use high doses of supplementation of various nutrients concurrently (e.g. Vitamin E-2,500 I.U., selenium-387 mg, Coenzyme Q10-350 mg., Beta-carotene-50,000-150,000 I.U.).¹² There is presently sound scientific evidence to consider antioxidant supplementation during and/or following chemotherapy according to a number of published peer-reviewed articles and investigative studies in cancer patients.^13,14

Cataracts

Individuals with higher intakes of Vitamins C and E, selenium and carotenes have a much lower risk for developing cataracts and macular degeneration than do individuals with lower intakes. Vitamin C supplementation at 1,000 mg per day has been shown to significantly reduce the incidence of cataracts, halt cataract progression and, in some cases, improve vision.^15,16

Diabetes Mellitus

Insulin is required to help transport Vitamin C into the cells of the body. Thus many diabetics have a higher requirement for Vitamin C than do nondiabetics.¹⁷ In a 90 day study type II diabetics who were given 600 mg of magnesium and 2,000 mg of Vitamin C per day showed improved glycemic control, fasting blood glucose and a lowering of blood cholesterol and triglycerides.¹⁸ Daily doses of 100 and 600 mg per day of Vitamin C has also been shown to reduce levels of sorbitol in diabetics. Sorbitol is a primary contributor of cataract development in diabetics.^19,20

Furthermore, Vitamin C supplementation in diabetics may help to reduce capillary fragility, which also contributes to vascular complications in the population. Vitamin C has been shown to improve endothelium-dependent vasodilation in patients with type I diabetes, helping to improve peripheral circulation.²¹

As well, a daily dosage of 1,000-3,000 mg per day has been shown to reduce blood levels of glycosylated proteins (e.g. albumin) by an average of 33 percent in diabetic subjects. This is a key marker in diabetes prognosis, with increased glycosylated proteins hastening the damage to the eye, kidneys, blood vessels and other organs.^22,23

Male Fertility

Vitamin C appears to play an important role in protecting the sperm’s genetic material (DNA) from damage and mutations. Low sperm counts are common in smokers, and Vitamin C supplementation has been shown to improve sperm quality and integrity in smokers in a dose-dependent fashion (using 0, 200 or 1,000 mg. per day).²⁴ In infertile men who were non-smokers, Vitamin C supplementation has been shown to increase sperm counts by 140 percent within one week of taking 1,000 mg per day. Supplementation using 200-1,000 mg per day has also been shown to reduce sperm agglutination (agglutination increases the likelihood of infertility).²⁵

Bed Sores

Higher intake levels of Vitamin C are associated with a lower frequency of bed sores in bed-ridden patients. Vitamin C supplementation has also been shown to enhance the healing of bed or pressure sores in a double-blind study.^26,27

Aerobic Exercise Oxidative Stress

Oxidative stress causing free radical attack has been shown to be higher in exercising subjects not taking Vitamin C supplements on a regular basis.²⁸

Dosage Ranges

Cancer Prevention and Nitrosamine Containment: studies suggest that 120-1,000 mg per day may be prudent.^4,5,6 Immune System Function in Aging: 500-1,000 mg per day may return immune function a more youthful level of function.^7-11

Asthma: 1,000-2,000 mg per day.^29,30

Cataract: 500-1,000 mg per day.¹⁶

Diabetes mellitus: 1,000-3,000 mg per day.^17-22

Male Infertility: 200-1,000 mg per day.^24,25

Bed Sores: 500-1,000 mg per day.²⁷

Vitamin C Toxicity and Side Effects

Vitamin C is very non-toxic and is readily excreted due to the body’s inability to store appreciable amounts.

In certain people, Vitamin C supplementation can increase risk of kidney stones (calcium-oxalate) and exacerbate gouty arthritis. Patients with a previous history of kidney stones should limit their intake of Vitamin C to 750 mg or less. Patients with gout should not exceed a daily dose of 500 mg.

Rebound scurvy can develop in newborns whose mothers ingest mega doses of Vitamin C during pregnancy. Once the fetal metabolic system has adapted to the higher amounts by removing the excess Vitamin C more rapidly than normal, even the normal amounts ingested by the newborn are removed at the accelerated rate, depressing serum and tissue levels.¹

Contra-indications

1. Kidney Stones (calcium-oxalate): Vitamin C intake should not exceed 750 mg per day from supplementation.

2. Gout: Vitamin C intake should not exceed 500 mg per day from supplementation.¹

Drug-Nutrient Interactions

Vitamin C depletion can result from the administration of:

1. Adrenal steroids (e.g. coricorteroid drugs which decrease Vitamin C uptake by cells.)^31,32
2. Salicylates – increase urinary loss of Vitamin C.^31,33,34
3. Sulfonamides³¹
4. Tetracycline^31,35
5. Cigarette smoking³¹
6. Oral Contraceptives^31,36,37
7. Loop Diuretics: increase urinary loss of Vitamin C (e.g. furosemide, Bumetanide, ethacrynic acid, torsemide).³⁸

N.B. Large amounts of Vitamin C intake can falsify urine tests in diabetics, disrupting the monitoring process for desirable insulin requirements.³¹

High doses of Vitamin C may decrease the absorption of copper.^39,40

Standard Textbooks of Nutritional Science:

- Shils M, Shike M, Olson J, Ross C. Modern Nutrition in Health and Disease. 9^th ed. Baltimore, MD: Lippincott Williams & Wilkins; 1993.

- Escott-Stump S, Mahan LK, editors. Food, Nutrition and Diet Therapy. 10^th ed. Philadelphia, PA: W.B. Saunders Company; 2000.

- Bowman B, Russell RM, editors. Present Knowledge in Nutrition, 8^th ed. Washington, DC:.ILSI Press; 2001.

- Kreutler PA, Czajka-Narins DM, editors. Nutrition in Perspective. 2^nd ed. Upper Saddle River, NJ: Prentice Hall Inc.; 1987.

Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci 1989;86:6377-81.

Ginter E. Optimum intake of vitamin C for the human organism. Nutr Health 1982;1:66-77.

Block G. Vitamin C and cancer prevention: the epidemiologic evidence. Am J Clin Nutr 1991 ;53(1 ):270-82.

Kyrtopoulos S. Ascorbic acid and the formation of N-nitroso compounds: possible role of ascorbic acid intake and the incidence of gastric cancer. Am J. Clin Nutr 1987;45(5):1344-50.

Tannenbaum SR, et al. Inhibition of nitrosamine formation by ascorbic acid. Am J Clin Nutr 1991 ;53(1 ):247-50.

Anderson R, et al. The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am J Clin Nutr 1980;33:71.

Dahl H, et al. The effect of ascorbic acid on production of human interferon and the antiviral activity in vitro. Acta Pathol Microbiol Scan B 1976;84:280.

Leibovitz B, et al. Ascorbic acid, neutrophils function and the immune response. Ind J Vit Nutr Res 1978;48:159.

Cheraskin E. Vitamin C: who needs it? J Naturopathic Medicine 1993;4(1):81-3.

Heuser G, et al. Enhancement of natural killer cell activity and T and B cell function by buffered Vitamin C in patients exposed to toxic, chemicals. Immunopharmacol Immunotoxicol 1997;3:291-312.

Lockwood K, et al. Apparent partial remission of breast cancer in “High Risk” patients supplemented with nutritional antioxidants, essential fatty acids and Coenzyme Q10. Molecular Aspects of Medicine 1994;15:231-40.

Conklin K. Dietary antioxidants during cancer chemotherapy: impact on chemotherapeutic effectiveness and development of side effects. Nutr and Cancer 2000;37(1):1-18.

Kucuk O. Complementary and Alternative Medicine in the treatment of cancer: current research and future directions. Oncology Issues 2000; 15(6): 17-9.

Bouton S. Vitamin C and the aging eye. Arch Int Med 1939;63:930-45.

Ringvold A, Johnsen H, Blika S. Senile cataract and ascorbic acid loading. Acta Opthalmol 1985;63:277-80.

Sinclari AJ, et al. Low plasma ascorbate levels in patients with type 2 diabetes mellitus consuming adequate dietary Vitamin C. Diabet Med 1994;11:893-8.

Eriksson J, et al. Magnesium and Ascorbic Acid supplementation in diabetes mellitus. Ann Nutr Metab 1995;39(4):217-23.

Cunningham J, et al. Vitamin C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus. J Am Coll Nutr 1994;4:344-50.

Wang H, et al. Experimental and clinical studies on the reduction of erythrocyte sorbitol-glucose ratios by ascorbic acid in diabetes mellitus. Diabetes Res Clin Pract 1995;28:1-8.

Timimi FK, et al. Vitamin C improves endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol 1998;3:552-7.

Paolisso G, et al. Metabolic benefits deriving from chronic Vitamin C supplementation in aged non-insulin dependent diabetics. J Am Coll Nutr 1995;14:387-92.

Davie SJ, Gould BJ, Yudkin JS. Effect of Vitamin C on glycosylation of proteins. Diabetes 1992;41:167-73.

Dawson E, Harris W, Powell L. Effect of Vitamin C supplementation on sperm quality of heavy smokers. FASEB J 1991 ;5:A915.

Dawson EB, et al. Effect of Ascorbic Acid on male fertility. Ann NY Acad Sci; 1987;498:312-23.

Goode HF, Burns E, Walker BE. Vitamin C depletion and pressure sores in elderly patients with femoral neck fracture. BMJ 1993;925:297.

Taylor TV, et al. Ascorbic Acid supplementation in the treatment of pressure sores. Lancet 1974;544-6.

Alessio HM, et al. Exercise-induced oxidate stress before and after Vitamin C supplementation. Int J Sport Nutr 1997;7:1-9

Bielory L, Gandhi R Asthma and Vitamin C. Annals Allergy 1994;73:89-96

Johnston CS, Martin LJ, Cai X. Antihistamine effect of supplemental Ascorbic Acid and neutrophils chemotaxis. J Am Coll Nutr 1992;11:172-6

Healthnotes 1998-2002. Available from: URL: http://www.healthnotes.com.

Levine MA, Pollard HB. Hydrocortisone inhibition of Ascorbic Acid transport by chromaffin cells. FEBS Lett 1983;158(1 ):134-8.

Coffey G, Wilson CWM. Ascorbic Acid deficiency and aspirin induced haematemesis. Brit Med J 1975;1 (5951 ):208.

Sahud MA, et al. Effect of aspirin ingestion on Ascorbic Acid levels in rheumatoid arthritis. Lancet 1971;1 (7706):937-8.

Shah KV, Barbhaiya HC, Srinivasan V. Ascorbic Acid levels in blood during tetracycline administration. J Indian Med Assoc 1986;51(3):127-9.

Webb JL. Nutritional effects of oral contraceptive use: a review. J Reprod Med 1980;25(4):150-6.

Nash AL, Cornish EJ, Hain R. Metabolic effects of oral contraceptives containing 30 micrograms and 50 micrograms of oestrogen. Med J Aust 1979;2(6):277-81.

Mydlik M, et al. The effect of furosemide on urinary excretion of oxalic acid, Vitamin C and Vitamin B6 in chronic kidney failure. Vnitr Lek 1998;44(3):127-31.

Van Campen D, Gross E. Influence of ascorbic acid on the absorption of copper by rats. J Nutr 1968;95(4):617-22.

Finley EB, Cerklewski FL. Influence of Ascorbic Acid supplementation on copper status in young adult men. Am J Clin Nutr 1983;37(4):553-6.