Vitamin C
Vitamin C
| |
Systematic name | |
IUPAC name 2-oxo-L-threo-hexono-1,4- lactone-2,3-enediol or (R)-3,4-dihydroxy-5-((S)- 1,2-dihydroxyethyl)furan-2(5H)-one | |
Identifiers | |
CAS number | 50-81-7 |
ATC code | A11G |
PubChem | 644104 |
Chemical data | |
Formula | C6H8O6 |
Mol. weight | 176.13 grams per mol |
Synonyms | L-ascorbate |
Physical data | |
Melt. point | 190°C (374°F) |
Pharmacokinetic data | |
Bioavailability | rapid & complete |
Protein binding | negligible |
Metabolism | ? |
Half life | 30 minutes |
Excretion | renal |
Therapeutic considerations | |
Pregnancy cat. | A |
Legal status | general public availability |
Routes | oral |
Vitamin C or L-ascorbate is an essential nutrient for higher primates, and a small number of other species. The presence of ascorbate is required for a range of essential metabolic reactions in all animals and in plants and is made internally by almost all organisms, (humans being one notable exception). It is widely known as the vitamin that prevents scurvy in humans
The pharmacophore of vitamin C is the ascorbate ion. In living organisms, ascorbate is an antioxidant, as it protects the body against oxidative stress, and is a cofactor in several vital enzymatic reactions.
As a nutrient, its uses and the daily requirement are matters of on-going debate. As a food additive, vitamin C is used as an antioxidant preservative and an acidity regulator.
The structure and properties of ascorbic acid
Ascorbic acid is an organic acid with antioxidant properties. Its appearance is white to light yellow crystals or powder. It is water soluble. The L-enantiomer of ascorbic acid is commonly known as vitamin C. The name is derived from a- and scorbuticus (Scurvy) as a shortage of this molecule may lead to scurvy. In 1937 the Nobel Prize for chemistry was awarded to Walter Haworth for his work in determining the structure of ascorbic acid (shared with Paul Karrer, who received his award for work on vitamins), and the prize for Physiology or Medicine that year went to Albert Szent-Györgyi for his studies of the biological functions of L-ascorbic acid (cite ref: nlm.nih.gov).
Vitamin C is purely the L-enantiomer of ascorbate; the opposite D-enantiomer has no physiological significance. Both forms are mirror images of the same molecular structure. When L-ascorbate, which is a strong reducing agent carries out its reducing function, it is converted to its oxidized form, [[Dehydroascorbic acid|L-dehydroascorbateL-dehydroscorbate can then be reduced back to the active L-ascorbate form in the body by enzymes and glutathione. L-ascorbate is a weak sugar acid structurally related to glucose which naturally occurs either attached to a hydrogen ion, forming ascorbic acid, or to a metal ion, forming a mineral ascorbate.
Biological functions
In humans, vitamin C is a highly effective antioxidant, acting to lessen oxidative stress, a substrate for ascorbate peroxidase,[1] as well as an enzyme cofactor for the biosynthesis of many important biochemicals. Vitamin C acts as an electron donor for eight different enzymes (Levine, et al., 2000):
Three participate in collagen hydroxylation (Prockop, et al., 1995; Peterofsky, 1991; Kivirikko and Myllyla, 1985These reactions add hydroxyl groups to the amino acids proline or lysine in the collagen molecule (via prolyl hydroxylase and lysyl hydroxylase), thereby allowing the collagen molecule to assume its triple helix structure and making vitamin C essential to the development and maintenance of scar tissue, blood vessels, and cartilage (McGee, date).
Biological tissues that accumulate over 100 times the level in blood plasma of vitamin C are the adrenal glands, pituitary, thymus, corpus luteum, and retina (Hediger, 2002).
Biosynthesis
The vast majority of animals and plants are able to synthesize their own vitamin C, through a sequence of four enzyme-driven steps, which convert glucose to vitamin C. The glucose needed to produce ascorbate in the liver (in mammals and perching birds) is extracted from glycogen; ascorbate synthesis is a glycogenolysis-dependent process (Bánhegyi and Mándl, 2001). In reptiles and birds the biosynthesis is carried out in the kidneys.
Among the animals that have lost the ability to synthesise vitamin C are simians, guinea pigs, the red-vented bulbul,and fruit-eating bats (UKFSA Risk).[2] Most notably, along with the rest of the ape family in which we reside, humans have no capability to manufacture vitamin C. The cause of this phenomenon is that the last enzyme in the synthesis process, L-gulonolactone oxidase, cannot be made by the listed animals because the gene for this enzyme is defective (Harris, 1996). The mutation has not been lethal because vitamin C is prevalent in their food sources, with many of these species' natural diets consisting largely of fruit.
Most simians consume the vitamin in amounts 10 to 20 times higher than that recommended by governments for humans (Milton, 1999). It has been noted that the loss of the ability to synthesize ascorbate strikingly parallels the evolutionary loss of the ability to break down uric acid. Uric acid and ascorbate are both strong reducing agents. This has led to the suggestion that in higher primates, uric acid has taken over some of the functions of ascorbate (Proctor, 1970).
An adult goat, a typical example of a vitamin C-producing animal, will manufacture more than 13,000 mg of vitamin C per day in normal health and as much as 100,000 mg daily when faced with life-threatening disease, trauma or stress (Stone, 1978). Biochemical research in the 1950’s showed that the lesion in scurvy is the absence of the enzyme, L-Gulonolactone oxidase (GLO) in the human liver It is thought that the human Vitamin C requirement is far lower than that of Vitamin C-synthesizing mammals due to increased Vitamin C recycling efficiency (Linster and van Schaftingen, 2006).
Trauma or injury has also been demonstrated to use up large quantities of vitamin C in humans (Long, et al., year).
Vitamin-C deficiency has been linked to scurvy
Scurvy is an avitaminosis resulting from lack of vitamin C, as without this vitamin, the synthesised collagen is too unstable to meet its function. Scurvy leads to the formation of liver spots on the skin, spongy gums, and bleeding from all mucous membranes. The spots are most abundant on the thighs and legs, and a person with the ailment looks pale, feels depressed, and is partially immobilized. In advanced scurvy there are open, suppurating wounds and loss of teeth and, eventually, death. The human body cannot store vitamin C, and so the body soon depletes itself if fresh supplies are not consumed through the digestive system (McGee, date).
condense: The need to include fresh plant food or raw animal flesh in the diet to prevent disease was known from ancient times. Native peoples living in marginal areas incorporated this into their medicinal lore. For example, spruce needles were used in temperate zones in infusions, or the leaves from species of drought-resistant trees in desert areas. In 1536, the French explorer Jacques Cartier, exploring the St. Lawrence River, used the local natives' knowledge to save his men who were dying of scurvy. He boiled the needles of the arbor vitae tree to make a tea that was later shown to contain 50 mg of vitamin C per 100 grams (Martini, 2002).
Throughout history, the benefit of plant food to survive long sea voyages has been occasionally recommended by authorities. While the earliest documented case of scurvy was described by Hippocrates around the year 400 B.C.E., the first attempt to give scientific basis for the cause of this disease was by a ship's surgeon in the British Royal Navy, James Lind. Scurvy was common among those with poor access to fresh fruit and vegetables, such as remote, isolated sailors and soldiers.
Lind's work was slow to be noticed. It was 1795 before the British navy adopted lemons or lime as standard issue at sea.
The name "antiscorbutic" was used in the eighteenth and nineteenth centuries as general term for those foods known to prevent scurvy, even though there was no understanding of the reason for this. These foods included but were not limited to: lemons, limes, and oranges; sauerkraut, cabbage, malt, and portable soup.
In 1907, Axel Holst and Theodor Frølich, two Norwegian physicians studying beriberi contracted aboard ship's crews in the Norwegian Fishing Fleet, wanted a small test mammal to substitute for the pigeons they used. They fed guinea pigs their test diet, which had earlier produced beriberi in their pigeons, and were surprised when scurvy resulted instead. Until that time scurvy had not been observed in any organism apart from humans, and had been considered an exclusively human disease.
In 1912, the Polish-American biochemist Casimir Funk, while researching deficiency diseases, developed the concept of vitamins to refer to the nutrients which are essential to health. Then, from 1928 to 1933, the Hungarian research team of Joseph L Svirbely and Albert Szent-Györgyi and, independently, the American Charles Glen King, first isolated vitamin C and showed it to be ascorbic acid. For this, Szent-Györgyi was awarded the 1937 Nobel Prize in Medicine.
Daily requirements
The North American Dietary Reference Intake recommends 90 milligrams per day and no more than 2 grams per day (2000 milligrams per day) (us rda). Other related species sharing the same inability to produce vitamin C and requiring exogenous vitamin C consume 20 to 80 times this reference intake. There is continuing debate within the scientific community over the best dose schedule (the amount and frequency of intake) of vitamin C for maintaining optimal health in humans (newswire, 2004). It is generally agreed that a balanced diet without supplementation contains enough vitamin C to prevent acute scurvy in an average healthy adult, while those who are pregnant, smoke tobacco, or are under stress require slightly more (us rda).
High doses (thousands of milligrams) may result in diarrhea, which is harmless if the dose is reduced immediately.
United States vitamin C recommendations[3] | |
---|---|
Recommended Dietary Allowance (adult male) | 90 mg per day |
Recommended Dietary Allowance (adult female) | 75 mg per day |
Tolerable Upper Intake Level (adult male) | 2000 mg per day |
Tolerable Upper Intake Level (adult female) | 2000 mg per day |
Government recommended intakes
Recommendations for vitamin C intake have been set by various national agencies:
- 40 milligrams per day — the United Kingdom's Food Standards Agency
*45 milligrams per day — the World Health Organization (who, 2004)
- 60-95 milligrams per day — United States' National Academy of Sciences
Vitamin C as macronutrient
There is a strong advocacy movement for large doses of vitamin C, promoting a great deal of added benefits. Many pro-vitamin C organizations promote usage levels well beyond the current Dietary Reference Intake. The movement is led by scientists and doctors such as Robert Cathcart, Ewan Cameron, Steve Hickey, Irwin Stone and the twice Nobel Prize laureate Linus Pauling and the more controversial Matthias Rath. There is an extensive and growing scientific literature critical of governmental agency dose recommendations (Forman, 1981). The biological halflife for vitamin C is fairly short, about 30 minutes in blood plasma, a fact which high dose advocates say that mainstream researchers have failed to take into account (Sardi, 2004).
Stone and Pauling calculated, based on the diet of our primate cousins (similar to what our common descents are likely to have consumed when the gene mutated), that the optimum daily requirement of vitamin C is around 2300 milligrams for a human requiring 2500 kcal a day (Stone, 1972; Pauling, date; Milton, 2003). The established RDA has been criticized by Pauling to be one that will prevent acute scurvy, and is not necessarily the dosage for optimal health.
Since its discovery vitamin C has been considered by some enthusiastic proponents a "universal panacea", although this led to suspicions by others of it being over-hyped. Other proponents of high dose vitamin C consider that if it is given "in the right form, with the proper technique, in frequent enough doses, in high enough doses, along with certain additional agents and for a long enough period of time, it can prevent and, in many cases, cure, a wide range of common and/or lethal diseases, notably the common cold and heart disease (Levy, 2002; Rath, date; Pauling, date). Some proponents issued controversial statements involving it being a cure for AIDS,[4] bird flu, and SARS.[5][6][7]
Probably the most controversial issue, the putative role of ascorbate in the management of AIDS, is still unresolved, more than 16 years after the landmark study published in the prestigious Proceedings of National Academy of Sciences (USA) showing that non toxic doses of ascorbate suppress HIV replication in vitro.[8] Other studies expanded on those results, but still, no large scale trials have yet been conducted.[9][10][11]
A 1986 study indicates that vitamin C may be important in regulation of endogenous cholesterol synthesis.[12]
In January 2007 the US Food and Drug Administration approved a new trial of intravenous vitamin C as a cancer treatment for "patients who have exhausted all other conventional treatment options." Additional studies over several years would be needed to demonstrate whether it is effective.[13]
Natural and artificial dietary sources
The richest natural sources are fruits and vegetables, and of those, the camu camu fruit and the Kakadu plum contain the highest concentration of the vitamin. It is also present in some cuts of meat, especially liver. Vitamin C is the most widely taken nutritional supplement and is available in a variety of forms, including tablets, drink mixes, crystals in capsules or naked crystals.
Plant sources
While plants are generally a good source of vitamin C, the amount in foods of plant origin depends on: the precise variety of the plant, the soil condition, the climate in which it grew, the length of time since it was picked, the storage conditions, and the method of preparation.[14]
The following table is approximate and shows the relative abundance in different raw plant sources (nutrient database, date). The amount is given in milligrams per 100 grams of fruit or vegetable and is a rounded average from multiple authoritative sources:
Plant source | Amount (mg / 100g) |
---|---|
Kakadu plum | 3150 |
Camu Camu | 2800 |
Rose hip | 2000 |
Acerola | 1600 |
Amla | 720 |
Jujube | 500 |
Baobab | 400 |
Blackcurrant | 200 |
Red pepper | 190 |
Parsley | 130 |
Seabuckthorn | 120 |
Guava | 100 |
Kiwifruit | 90 |
Broccoli | 90 |
Loganberry | 80 |
Redcurrant | 80 |
Brussels sprouts | 80 |
Lychee | 70 |
Cloudberry | 60 |
Persimmon | 60 |
Plant source | Amount (mg / 100g) |
---|---|
Papaya | 60 |
Strawberry | 60 |
Orange | 50 |
Lemon | 40 |
Melon, cantaloupe | 40 |
Cauliflower | 40 |
Grapefruit | 30 |
Raspberry | 30 |
Tangerine | 30 |
Mandarin orange | 30 |
Passion fruit | 30 |
Spinach | 30 |
Cabbage raw green | 30 |
Lime | 20 |
Mango | 20 |
Potato | 20 |
Melon, honeydew | 20 |
Mango | 16 |
Tomato | 10 |
Blueberry | 10 |
Pineapple | 10 |
Plant source | Amount (mg / 100g) |
---|---|
Pawpaw | 10 |
Grape | 10 |
Apricot | 10 |
Plum | 10 |
Watermelon | 10 |
Banana | 9 |
Carrot | 9 |
Avocado | 8 |
Crabapple | 8 |
Peach | 7 |
Apple | 6 |
Blackberry | 6 |
Beetroot | 5 |
Pear | 4 |
Lettuce | 4 |
Cucumber | 3 |
Eggplant | 2 |
Fig | 2 |
Bilberry | 1 |
Horned melon | 0.5 |
Medlar | 0.3 |
Food preparation
Vitamin C chemically decomposes under certain conditions, many of which may occur during the cooking of food. Normally, boiling water at 100°C is not hot enough to cause any significant destruction of the nutrient, which only decomposes at 190°C, despite popular opinion. However, pressure cooking, roasting, frying and grilling food is more likely to reach the decomposition temperature of vitamin C. Longer cooking times also add to this effect, as will copper food vessels, which catalyse the decomposition.
Another cause of vitamin C being lost from food is leaching, where the water-soluble vitamin dissolves into the cooking water, which is later poured away and not consumed. However, vitamin C doesn't leach in all vegetables at the same rate; research shows broccoli seems to retain more than any other.[15] Research has also shown that fresh-cut fruit don't lose significant nutrients when stored in the refrigerator for a few days.[16]
Vitamin C supplements
Vitamin C is the most widely taken dietary supplement (diet channel, date). It is available in many forms including caplets, tablets, capsules, drink mix packets, in multi-vitamin formulations, in multiple antioxidant formulations, as chemically pure crystalline powder, timed release versions, and also including bioflavonoids such as quercetin, hesperidin and rutin. In supplements, vitamin C most often comes in the form of various mineral ascorbates, as they are easier to absorb, more easily tolerated and provide a source of several dietary minerals.
Absorption of Vitamin C
Vitamin C is absorbed by the intestines using a sodium-ion dependent channel. It is transported through the intestine via both glucose-sensitive and glucose-insensitive mechanisms. Having a lot of sugar either in your intestines or in your blood (as in diabetes mellitus) can slow absorption, which is relevant when megadosing.[17]
ReferencesISBN links support NWE through referral fees
- Padayatty, S., Katz, A., Wang, Y., Eck, P., Kwon, O., Lee, J., Chen, S., Corpe, C., Dutta, A., Dutta, S., and M. Levine. 2003. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 22(1):18-35.
- Svirbelf, J.L. and A. Szent-Gyorgyi. 1932. The Chemical Nature Of Vitamin C. The National Library of Medicine. Accessed June 30, 2007.
- Meister, A. 1994. Glutathione-ascorbic acid antioxidant system in animals. J Biol Chem 269(213): 9397-400. PMID 8144521
- Milton, K. 1999. Nutritional characteristics of wild primate foods: do the diets of our closest living relatives have lessons for us? Nutrition 15(6):488-98.
- Expert Group on Vitamins and Minerals. 2003. Vitamin C – Risk Assessment. UK Food Standards Agency. Retrieved February 19, 2007.
- Harris, J.R. 1996. Ascorbic Acid: Subcellular Biochemistry. New York: Springer. ISBN 0-306-45148-4
- Stipanuk, M.H. 2000. "Biochemical and Physiological Aspects of Human Nutrition." Philadelphia: Saunders.
- Prockop, D.J. and K.I. Kivirikko. 1995. Collagens: molecular biology, diseases, and potentials for therapy. Annu Rev Biochem 64:403–34.
- Peterkofsky, B. 1991. Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Am J Clin Nutr 54:1135S–40S.
- Kivirikko, K.I. and R. Myllyla. 1985. Post-translational processing of procollagens. Ann NY Acad Sci 460:187–201.
- McGee, W. 2007. Ascorbic acid. Medical Encyclopedia. Retrieved June 30, 2007.
- Hediger, M.A. 2002. New view at C. Nature Medicine 8:445-6.
- Bánhegyi, G. and J. Mándl. 2001. The hepatic glycogenoreticular system. Pathol Oncol Res 7(2):107-10. PMID 11458272
- Proctor, P. 1970. Similar functions of uric acid and ascorbate in man? Nature 228(5274): 868.
- Stone, I. 1979. Eight Decades of Scurvy. The Case History of a Misleading Dietary Hypothesis. Orthomolecular Psychiatry 8(2):58-62. Retrieved April 4, 2007.
- Linster, C. and E. Van Schaftingen. 2006. Vitamin C: Biosynthesis, recycling and degradation in mammals. Retrieved April 30, 2007.
- Long, C. et al. 2003. Ascorbic acid dynamics in the seriously ill and injured. Journal of Surgical Research 109(2):144–8.
- Martini, E. 2002. Jacques Cartier witnesses a treatment for scurvy. Vesalius 8(1):2-6. Retrieved February 25, 2007.
- Sardi, B. 2004. Linus Pauling Vindicated; Researchers Claim RDA For Vitamin C is Flawed. Knowledge of Health. Retrieved February 20, 2007.
- Institute of Medicine of the National Academies. 2001. US Recommended Dietary Allowance (RDA). Retrieved February 19, 2007.
- World Health Organization. 2004. Vitamin and mineral requirements in human nutrition, 2nd ed. Retrieved February 20, 2007.
- Forman, R. 1981. Medical Resistance to Innovation. Medical Hypotheses 7(8):1009-17. Retrieved February 23, 2007.
- Sardi, B. 2004. The Vitamin C Fanatics Were Right All Along. Knowledge of Health. Retrieved February 22, 2007.
- Milton, K. 2003. Micronutrient intakes of wild primates: are humans different? Comp Biochem Physiol 136(1):47-59. PMID 14527629
- Stone, I. 1972. The Healing Factor: Vitamin C Against Disease. New York:Grosset and Dunlap. ISBN 0-448-11693-6
- Pauling, L. 1970. Evolution and the need for ascorbic acid. Proc Natl Acad Sci 67(4):1643-8.
- Levy, T.E. 2002. Curing the Incurable: Vitamin C, Infectious Diseases, and Toxins. Livon Books. ISBN 1-4010-6963-0
- The Diet Channel. 2007. Vitamin C: General Info. Retrieved June 30, 2007.
Further reading
- Journals
- Dolske, M.C., et al. (1993). A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog. Neuropsychopharmacol. Biol. Psychiatry 17 (5): 765-74.
- Green VA, Pituch KA, Itchon J, Choi A, O'Reilly M, Sigafoos J (2006). Internet survey of treatments used by parents of children with autism. Research in developmental disabilities 27 (1): 70-84.
- Books
- Pauling, Linus (1970). Vitamin C and the Common Cold. W. H. Freeman & Company. ISBN 071670160X.
- Pauling, Linus (1976). Vitamin C, the Common Cold, and the Flu. W H Freeman & Co. ISBN 0716703610.
- Cameron, Ewan and Linus Pauling, (1979). Cancer and Vitamin C. Pauling Institute of Science and Medicine. ISBN 0393500004.
- Kent, Saul (1980). Life Extension Revolution. Morrow.
- Pearson, Durk and Sandy Shaw (1982). Life Extension: A Practical Scientific Approach. Warner Books. ISBN 0446387355. see Part IV, Chapter 7: Vitamin C
- Pelton, Ross (1986). Mind Food and Smart Pills: How to Increase Your Intelligence and Prevent Brain Aging. T & R Pub. ISBN 0936809000. see Chapter 3: Vitamin C, The Champion Free Radical Scavenger
- Clemetson, C.A.B (1989). Vitamin C. Boca Raton, Florida: CRC Press. ISBN 0-8493-4841-2. Monograph - Volumes I, II, III.
- Levy, Thomas E. (2002). Vitamin C Infectious Diseases, & Toxins. Xlibris. ISBN 1401069630.
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External links
- Jane Higdon, "Vitamin C", Micronutrient Information Center, Linus Pauling Institute
- AscorbateWeb — a collection of twentieth century medical & scientific literature on vitamin C in the treatment and prevention of human disease at seanet.com
- Healing Thresholds — Research on Vitamin C in the treatment of autism. at healingthresholds.com
- U.S. Patent 5278189 (PDF) — "Prevention and treatment of occlusive cardiovascular disease with ascorbate and substances that inhibit the binding of lipoprotein (a)", Inventors: Matthias W. Rath and Linus C. Pauling
- vitamin C at United Kingdom Food Standards Agency
- Naidu KA (2003). Vitamin C in human health and disease is still a mystery? An overview. Nutrition journal 2: 7.
- For Doctors: Preparation of Vitamin C IV's — by Andrew W. Saul, PhD. at doctoryourself.com
- Information regarding treatment of the Bird Flu with massive doses of ascorbate. — by Robert Cathcart, M.D. at orthomed.com
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- ↑ Nigeria: Vitamin C Can Suppress HIV/Aids Virus. allAfrica.com (2006-05-22). Retrieved 2006-06-16.
- ↑ Hemilä H (2003). Vitamin C and SARS coronavirus. J Antimicrob Chemother 52 (6): 1049-50.
- ↑ Boseley, Sarah. "Discredited doctor's 'cure' for Aids ignites life-and-death struggle in South Africa", The Guardian, 2005-05-14. Retrieved 2007-02-21.
- ↑ Rath, Matthias (2005). Open letter from Dr. Matthias Rath MD to German Chancellor Merkel. Dr. Rath Health Foundation. Retrieved 2007-02-21.
- ↑ Harakeh S, Jariwalla R, Pauling L (1990). Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells. Proc Natl Acad Sci U S A 87 (18): 7245-9.
- ↑ Harakeh S, Jariwalla R (1991). Comparative study of the anti-HIV activities of ascorbate and thiol-containing reducing agents in chronically HIV-infected cells. Am J Clin Nutr 54 (6 Suppl): 1231S-1235S.
- ↑ Harakeh S, Jariwalla R (1997). NF-kappa B-independent suppression of HIV expression by ascorbic acid. AIDS Res Hum Retroviruses 13 (3): 235-9.
- ↑ Harakeh S, Jariwalla R. Ascorbate effect on cytokine stimulation of HIV production. Nutrition 11 (5 Suppl): 684-7.
- ↑ Harwood H, Greene Y, Stacpoole P (1986). Inhibition of human leukocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase activity by ascorbic acid. An effect mediated by the free radical monodehydroascorbate. J Biol Chem 261 (16): 7127-35.
- ↑ FDA OKs vitamin C trial for cancer. Physorg.com (January 12, 2007). Retrieved 2007-04-06.
- ↑ The vitamin and mineral content is stable. Danish Veterinary and Food Administration. Retrieved 2007-03-07.
- ↑ Combs GF. The Vitamins, Fundamental Aspects in Nutrition and Health. 2nd ed. San Diego, CA: Academic Press, 2001:245–272
- ↑ Hitti, Miranda (2 June 2006). Fresh-Cut Fruit May Keep Its Vitamins. WebMD. Retrieved 2007-02-25.
- ↑ Wilson JX (2005). Regulation of vitamin C transport. Annu. Rev. Nutr. 25: 105-25.
- ↑ National Nutrient Database. Nutrient Data Laboratory of the US Agricultural Research Service. Retrieved 2007-03-07.