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- This article is about ascorbic acid as a nutrient; for its chemical properties, see the article ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
; for other uses, see the disambiguation pageVitamin C is an essential nutrient, usually ingested as ascorbic acid. The oxidized form, dehydroascorbic acid, can also be absorbed from the diet, and has similar antiscorbutic effects.Vitamin C may also refer to:...
.
Vitamin C or
L-ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
or
L-ascorbate is an
essential nutrientAn essential nutrient is a nutrient required for normal body functioning that either cannot be synthesized by the body at all, or cannot be synthesized in amounts adequate for good health , and thus must be obtained from a dietary source...
for humans and certain other animal species. In living organisms ascorbate acts as an
antioxidantAn antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
by protecting the body against
oxidative stressOxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
. It is also a
cofactorA cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
in at least eight
enzymaticEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
reactions including several
collagenCollagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
synthesis reactions that, when dysfunctional, cause the most severe symptoms of
scurvyScurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
. In animals these reactions are especially important in wound-healing and in preventing bleeding from capillaries.
Ascorbate (an ion of
ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
) is required for a range of essential
metabolic reactionsMetabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
in all animals and plants. It is
made internallyBiosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
by almost all organisms although notable mammalian group exceptions are most or all of the order chiroptera (bats), guinea pigs,
capybaraThe capybara , also known as capivara in Portuguese, and capibara, chigüire in Venezuela, Colombia, and Ecuador ronsoco in Peru, chigüiro, and carpincho in Spanish, is the largest living rodent in the world. Its closest relatives are agouti, chinchillas, coyphillas, and guinea pigs...
s, and one of the two major
primateA primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...
suborders, the Anthropoidea (
HaplorrhiniThe haplorhines, the "dry-nosed" primates , are members of the Haplorhini clade: the prosimian tarsiers and the anthropoids...
) (tarsiers, monkeys and apes, including human beings). Ascorbic acid is also not synthesized by some species of birds and fish. All species that do not synthesize ascorbate require it in the diet. Deficiency in this
vitaminA vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
causes the disease
scurvyScurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
in humans. It is also widely used as a
food additiveFood additives are substances added to food to preserve flavor or enhance its taste and appearance.Some additives have been used for centuries; for example, preserving food by pickling , salting, as with bacon, preserving sweets or using sulfur dioxide as in some wines...
.
The full extent of the effects and recommended daily intake of vitamin C are matters of ongoing debate, with
RDIThe Reference Daily Intake or Recommended Daily Intake is the daily intake level of a nutrient that is considered to be sufficient to meet the requirements of 97–98% of healthy individuals in every demographic in the United States .The RDI is used to determine the Daily Value of foods,...
ranging from 45mg to 400mg or more per day.
Biological significance
Vitamin C is purely the
L-enantiomerIn chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
of ascorbate; the opposite
D-enantiomerIn chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
has no physiological significance. Both forms are
mirror imagesA chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
of the same molecular structure. When
L-ascorbate, which is a strong
reducing agentA reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...
, carries out its
reducingRedox reactions describe all chemical reactions in which atoms have their oxidation state changed....
function, it is converted to its
oxidizedRedox reactions describe all chemical reactions in which atoms have their oxidation state changed....
form,
L-dehydroascorbateDehydroascorbic acid is an oxidized form of ascorbic acid. It is actively imported into the endoplasmic reticulum of cells via glucose transporters. It is trapped therein by reduction back to ascorbate by glutathione and other thiols. Therefore, L-dehydroascorbic acid is a vitamin C compound much...
.
L-dehydroascorbate can then be reduced back to the active
L-ascorbate form in the body by
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s and
glutathioneGlutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
. During this process semidehydroascorbic acid radical is formed. Ascorbate free radical reacts poorly with oxygen, and thus will not create a superoxide. Instead two semidehydroascorbate radicals will react and form one ascorbate and one dehydroascorbate. With the help of glutathione, dehydroxyascorbate is converted back to ascorbate. The presence of glutathione is crucial since it spares ascorbate and improves antioxidant capacity of blood. Without it dehydroxyascorbate could not convert back to ascorbate.
L-Ascorbate is a
weakA weak acid is an acid that dissociates incompletely. It does not release all of its hydrogens in a solution, donating only a partial amount of its protons to the solution...
sugar acid structurally related to
glucoseGlucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
that naturally occurs attached either to a
hydrogen ionHydrogen ion is recommended by IUPAC as a general term for all ions of hydrogen and its isotopes.Depending on the charge of the ion, two different classes can be distinguished: positively charged ions and negatively charged ions....
, forming
ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
, or to a
metal ionA metal , is an element, compound, or alloy that is a good conductor of both electricity and heat. Metals are usually malleable and shiny, that is they reflect most of incident light...
, forming a mineral ascorbate.
Biosynthesis in different species
The vast majority of animals and plants are able to synthesize their own vitamin C, through a sequence of four
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
-driven steps, which convert
glucoseGlucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
to vitamin C. The glucose needed to produce ascorbate in the liver (in
mammalMammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s and
perching birdA passerine is a bird of the order Passeriformes, which includes more than half of all bird species. Sometimes known as perching birds or, less accurately, as songbirds, the passerines form one of the most diverse terrestrial vertebrate orders: with over 5,000 identified species, it has roughly...
s) is extracted from
glycogenGlycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...
; ascorbate synthesis is a glycogenolysis-dependent process. In
reptileReptiles are members of a class of air-breathing, ectothermic vertebrates which are characterized by laying shelled eggs , and having skin covered in scales and/or scutes. They are tetrapods, either having four limbs or being descended from four-limbed ancestors...
s and
birdBirds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s the biosynthesis is carried out in the
kidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s.
Among the animals that have lost the ability to synthesise vitamin C are
simianThe simians are the "higher primates" familiar to most people: the Old World monkeys and apes, including humans, , and the New World monkeys or platyrrhines. Simians tend to be larger than the "lower primates" or prosimians.- Classification and evolution :The simians are split into three groups...
s and
tarsierTarsiers are haplorrhine primates of the genus Tarsius, a genus in the family Tarsiidae, which is itself the lone extant family within the infraorder Tarsiiformes...
s, which together make up one of two major
primateA primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...
suborders, the anthropoidea, also called
haplorrhiniThe haplorhines, the "dry-nosed" primates , are members of the Haplorhini clade: the prosimian tarsiers and the anthropoids...
. This group includes humans. The other more primitive primates (
strepsirrhiniThe clade Strepsirrhini is one of the two suborders of primates. Madagascar's only non-human primates are strepsirrhines, and others can be found in southeast Asia and Africa...
) have the ability to make vitamin C. Synthesis does not occur in a number of species (perhaps all species) in the small rodent family
caviidaeThe cavy family is a family of rodents native to South America, and including the domestic guinea pig, wild cavies, and the capybara, among other animals...
that includes
guinea pigThe guinea pig , also called the cavy, is a species of rodent belonging to the family Caviidae and the genus Cavia. Despite their common name, these animals are not in the pig family, nor are they from Guinea...
s and
capybaraThe capybara , also known as capivara in Portuguese, and capibara, chigüire in Venezuela, Colombia, and Ecuador ronsoco in Peru, chigüiro, and carpincho in Spanish, is the largest living rodent in the world. Its closest relatives are agouti, chinchillas, coyphillas, and guinea pigs...
s, but occurs in other rodents (rats and mice do not need vitamin C in their diet, for example). A number of species of
passerineA passerine is a bird of the order Passeriformes, which includes more than half of all bird species. Sometimes known as perching birds or, less accurately, as songbirds, the passerines form one of the most diverse terrestrial vertebrate orders: with over 5,000 identified species, it has roughly...
birds also do not synthesise, but not all of them, and those that don't are not clearly related; there is a theory that the ability was lost separately a number of times in birds.
All tested families of bats, including major insect and fruit-eating bat families, cannot synthesise vitamin C. A trace of GLO was detected in only 1 of 34 bat species tested, across the range of 6 families of bats tested.
These animals all lack the
L-gulonolactone oxidaseL-gulonolactone oxidase is an enzyme that catalyzes the reaction of D-glucuronolactone with oxygen to L-xylo-hex-3-gulonolactone and hydrogen peroxide. It uses FAD as a cofactor...
(GULO) enzyme, which is required in the last step of vitamin C synthesis, because they have a differing non-synthesising gene for the enzyme (
PseudogenePseudogenes are dysfunctional relatives of known genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell...
ΨGULO). A similar non-functional gene is present in the genome of the guinea pigs and in primates, including humans. Some of these species (including humans) are able to make do with the lower levels available from their diets by recycling oxidised vitamin C.
Most
simianThe simians are the "higher primates" familiar to most people: the Old World monkeys and apes, including humans, , and the New World monkeys or platyrrhines. Simians tend to be larger than the "lower primates" or prosimians.- Classification and evolution :The simians are split into three groups...
s consume the vitamin in amounts 10 to 20 times higher than that recommended by governments for humans. This discrepancy constitutes much of the basis of the controversy on current recommended dietary allowances. It is countered by arguments that humans are very good at conserving dietary vitamin C, and are able to maintain blood levels of vitamin C comparable with other simians, on a far smaller dietary intake.
An adult
goatThe domestic goat is a subspecies of goat domesticated from the wild goat of southwest Asia and Eastern Europe. The goat is a member of the Bovidae family and is closely related to the sheep as both are in the goat-antelope subfamily Caprinae. There are over three hundred distinct breeds of...
, 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 the biosynthesis will increase "manyfold under stress". Trauma or injury has also been demonstrated to use up large quantities of vitamin C in humans.
Some
microorganismA microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...
s such as the yeast
Saccharomyces cerevisiaeSaccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
have been shown to be able to synthesize vitamin C from
simple sugarsMonosaccharides are the most basic units of biologically important carbohydrates. They are the simplest form of sugar and are usually colorless, water-soluble, crystalline solids. Some monosaccharides have a sweet taste. Examples of monosaccharides include glucose , fructose , galactose, xylose...
.
Vitamin C in evolution
Venturi and Venturi suggested that the antioxidant action of ascorbic acid developed first in the plant kingdom when, about 500 million years ago (mya), plants began to adapt to antioxidant-mineral-deficient fresh-waters of
estuariesAn estuary is a partly enclosed coastal body of water with one or more rivers or streams flowing into it, and with a free connection to the open sea....
. Some biologists suggested that many vertebrates had developed their metabolic adaptive strategies in estuary environment. In this theory, some 400–300 mya, when living
plantPlants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
s and
animalAnimals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...
s first began the move from the sea to rivers and land, environmental
iodine deficiencyIodine is an essential trace element; the thyroid hormones thyroxine and triiodotyronine contain iodine. In areas where there is little iodine in the diet—typically remote inlandareas where no marine foods are eaten—iodine deficiency gives rise to...
was a challenge to the
evolutionEvolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
of terrestrial life. In plants, animals and fishes, the terrestrial diet became deficient in many essential antioxidant marine micronutrients, including
iodineIodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
,
seleniumSelenium is a chemical element with atomic number 34, chemical symbol Se, and an atomic mass of 78.96. It is a nonmetal, whose properties are intermediate between those of adjacent chalcogen elements sulfur and tellurium...
,
zincZinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
,
copperCopper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
,
manganeseManganese is a chemical element, designated by the symbol Mn. It has the atomic number 25. It is found as a free element in nature , and in many minerals...
,
ironIron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
, etc. Freshwater
algaeAlgae are a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms, such as the giant kelps that grow to 65 meters in length. They are photosynthetic like plants, and "simple" because their tissues are not organized into the many...
and terrestrial plants, in replacement of marine
antioxidantAn antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
s, slowly optimized the production of other
endogenousEndogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...
antioxidants such as
ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
,
polyphenolA polyphenol antioxidant is a type of antioxidant containing a polyphenolic substructure. Numbering over 4,000 distinct species, many of these compounds have antioxidant activity in vitro but are unlikely to have antioxidant roles in vivo...
s,
carotenoidCarotenoids are tetraterpenoid organic pigments that are naturally occurring in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some bacteria, and some types of fungus. Carotenoids can be synthesized fats and other basic organic metabolic building...
s,
tocopherolTocopherols are a class of chemical compounds of which many have vitamin E activity. It is a series of organic compounds consisting of various methylated phenols...
s etc., some of which became essential “
vitaminA vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
s” in the diet of terrestrial animals (vitamins C, A, E, etc.).
Ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
or vitamin C is a common enzymatic co-factor in mammals used in the synthesis of
collagenCollagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
. Ascorbate is a powerful
reducing agentA reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...
capable of rapidly scavenging a number of
reactive oxygen speciesReactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
(ROS). Freshwater teleost fishes also require dietary vitamin C in their diet or they will get scurvy. The most widely recognized symptoms of vitamin C deficiency in fishes are
scoliosisScoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
,
lordosisLordosis is a medical term used to describe an inward curvature of a portion of the lumbar and cervical vertebral column. Two segments of the vertebral column, namely cervical and lumbar, are normally lordotic, that is, they are set in a curve that has its convexity anteriorly and concavity...
and dark skin coloration. Freshwater salmonids also show impaired
collagenCollagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
formation, internal/fin hemorrhage, spinal curvature and increased mortality. If these fishes are housed in seawater with algae and phytoplankton, then vitamin supplementation seems to be less important, it is presumed because of the availability of other, more ancient, antioxidants in natural marine environment.
Some scientists have suggested that loss of the vitamin C biosynthesis pathway may have played a role in the theory of rapid evolutionary changes, leading to hominids and the emergence of human beings. However, another theory based on the theory of evolution is that the loss of ability to make vitamin C in simians may have occurred much farther back in evolutionary history than the emergence of humans or even apes, since it evidently occurred rather soon after the appearance of the first primates, yet sometime after the split of early primates into its two major suborders
haplorrhiniThe haplorhines, the "dry-nosed" primates , are members of the Haplorhini clade: the prosimian tarsiers and the anthropoids...
(which cannot make vitamin C) and its sister suborder of non-tarsier prosimians, the
strepsirrhiniThe clade Strepsirrhini is one of the two suborders of primates. Madagascar's only non-human primates are strepsirrhines, and others can be found in southeast Asia and Africa...
("wet-nosed" primates), which retained the ability to make vitamin C. According to molecular clock dating, these two suborder primate branches parted ways about 63 to 60 Mya Approximately three to five million years later (58 Mya), only a short time afterward from an evolutionary perspective, the infraorder
TarsiiformesTarsiiformes are a group of primates that was once ranged across Europe, northern Africa, Asia, and North America, but today all living species are found in the islands of Southeast Asia. Tarsiers are the only living members of the infraorder, and also include the extinct Tarsius eocaenus from the...
, whose only remaining family is that of the tarsier (Tarsiidae), branched off from the other haplorrhines. Since tarsiers also cannot make vitamin C, this implies the mutation had already occurred, and thus must have occurred between these two marker points (63 to 58 Mya).
It has been noted that the loss of the ability to synthesize ascorbate strikingly parallels the inability to break down
uric acidUric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
, also a characteristic of primates. Uric acid and ascorbate are both strong
reducing agentA reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...
s. This has led to the suggestion that, in higher primates, uric acid has taken over some of the functions of ascorbate.
Absorption, transport, and disposal
Ascorbic acid is absorbed in the body by both active transport and simple diffusion. Sodium-Dependent Active Transport—Sodium-Ascorbate Co-Transporters (SVCTs) and Hexose transporters (GLUTs)—are the two transporters required for absorption. SVCT1 and SVCT2 import the reduced form of ascorbate across plasma membrane. GLUT1 and GLUT3 are the two glucose transporters, and transfer only dehydroascorbic acid form of Vitamin C. Although dehydroascorbic acid is absorbed in higher rate than ascorbate, the amount of dehydroascorbic acid found in plasma and tissues under normal conditions is low, as cells rapidly reduce dehydroascorbic acid to ascorbate. Thus, SVCTs appear to be the predominant system for vitamin C transport in the body.
SVCT2 is involved in vitamin C transport in almost every tissue, the notable exception being red blood cells, which lose SVCT proteins during maturation. "SVCT2 knockout" animals genetically engineered to lack this functional gene, die shortly after birth, suggesting that
SVCT2-mediated vitamin C transport is necessary for life.
With regular intake the absorption rate varies between 70 to 95%. However, the degree of absorption decreases as intake increases. At high intake (1.25g), fractional human absorption of ascorbic acid may be as low as 33%; at low intake (<20 mg) the absorption rate can reach up to 98%. Ascorbate concentrations over renal re-absorption threshold pass freely into the urine and are excreted. At high dietary doses (corresponding to several hundred mg/day in humans) ascorbate is accumulated in the body until the plasma levels reach the renal resorption threshold, which is about 1.5 mg/dL in men and 1.3 mg/dL in women. Concentrations in the plasma larger than this value (thought to represent body saturation) are rapidly excreted in the urine with a half-life of about 30 minutes. Concentrations less than this threshold amount are actively retained by the kidneys, and the excretion half-life for the remainder of the vitamin C store in the body thus increases greatly, with the half-life lengthening as the body stores are depleted. This half-life rises until it is as long as 83 days by the onset of the first symptoms of scurvy.
Although the body's maximal store of vitamin C is largely determined by the renal threshold for blood, there are many tissues that maintain vitamin C concentrations far higher than in blood. Biological
tissueTissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
s that accumulate over 100 times the level in blood plasma of vitamin C are the
adrenal glandIn mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
s, pituitary,
thymusThe thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
,
corpus luteumThe corpus luteum is a temporary endocrine structure in mammals, involved in production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A...
, and
retinaThe vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
.
Those with 10 to 50 times the concentration present in blood plasma include the
brainThe human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
,
spleenThe spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
,
lungThe human lungs are the organs of respiration in humans. Humans have two lungs, with the left being divided into two lobes and the right into three lobes. Together, the lungs contain approximately of airways and 300 to 500 million alveoli, having a total surface area of about in...
,
testicleThe testicle is the male gonad in animals. Like the ovaries to which they are homologous, testes are components of both the reproductive system and the endocrine system...
, lymph nodes,
liverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
,
thyroidThe thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
,
small intestinalThe small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
mucosaThe mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
, leukocytes,
pancreasThe pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
,
kidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
and salivary glands.
Ascorbic acid can be oxidized (broken down) in the human body by the enzyme
L-ascorbate oxidaseIn enzymology, a L-ascorbate oxidase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are L-ascorbate and O2, whereas its two products are dehydroascorbate and H2O....
. Ascorbate that is not directly excreted in the urine as a result of body saturation or destroyed in other body metabolism is oxidized by this enzyme and removed.
Deficiency
ScurvyScurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
is an
avitaminosisAvitaminosis is any disease caused by chronic or long-term vitamin deficiency or caused by a defect in metabolic conversion, such as tryptophan to niacin...
resulting from lack of vitamin C, since without this vitamin, the synthesised
collagenCollagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
is too unstable to perform its function. Scurvy leads to the formation of brown spots on the skin, spongy gums, and bleeding from all
mucous membraneThe mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
s. 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 can store only a certain amount of vitamin C, and so the body stores are depleted if fresh supplies are not consumed. The time frame for onset of symptoms of scurvy in unstressed adults switched to a completely vitamin C free diet, however, may range from one month to more than six months, depending on previous loading of vitamin C (see below).
It has been shown that smokers who have diets poor in vitamin C are at a higher risk of lung-borne diseases than those smokers who have higher concentrations of vitamin C in the blood.
Nobel prize winner
Linus PaulingLinus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
and G. C. Willis have asserted that chronic long term low blood levels of vitamin C ("
chronicA chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
scurvy") is a cause of
atherosclerosisAtherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
.
Western societies generally consume far more than sufficient Vitamin C to prevent scurvy. In 2004, a Canadian Community health survey reported that Canadians of 19 years and above have intakes of vitamin C from food of 133 mg/d for males and 120 mg/d for females; these are higher than the RDA recommendations.
Notable human dietary studies of experimentally-induced scurvy have been conducted on conscientious objectors during WW II in Britain, and on Iowa state prisoners in the late 1960s. These studies both found that all obvious symptoms of scurvy previously induced by an experimental scorbutic diet with extremely low vitamin C content could be completely reversed by additional vitamin C supplementation of only 10 mg a day. In these experiments, there was no clinical difference noted between men given 70 mg vitamin C per day (which produced blood level of vitamin C of about 0.55 mg/dl, about 1/3 of tissue saturation levels), and those given 10 mg per day. Men in the prison study developed the first signs of scurvy about 4 weeks after starting the vitamin C free diet, whereas in the British study, six to eight months were required, possibly due to the pre-loading of this group with a 70 mg/day supplement for six weeks before the scorbutic diet was fed.
Men in both studies on a diet devoid, or nearly devoid, of vitamin C had blood levels of vitamin C too low to be accurately measured when they developed signs of scurvy, and in the Iowa study, at this time were estimated (by labeled vitamin C dilution) to have a body pool of less than 300 mg, with daily turnover of only 2.5 mg/day, implying a instantaneous half-life of 83 days by this time (elimination constant of 4 months).
Moderately higher blood levels of vitamin C measured in healthy persons have been found to be prospectively correlated with decreased risk of
cardiovascular diseaseHeart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
and
ischaemic heart diseaseIschaemic or ischemic heart disease , or myocardial ischaemia, is a disease characterized by ischaemia of the heart muscle, usually due to coronary artery disease...
, and an increase life expectancy. The same study found an inverse relationship between blood vitamin C levels and cancer risk in men, but not in women. An increase in blood level of 20 micromol/L of vitamin C (about 0.35 mg/dL, and representing a theoretical additional 50 grams of fruit and vegetables per day) was found epidemiologically to reduce the all-cause risk of
mortalityMortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
, four years after measuring it, by about 20%. However, because this was not an intervention study, causation could not be proven, and vitamin C blood levels acting as a proxy marker for other differences between the groups could not be ruled out. However, the four-year long and prospective nature of the study did rule out proxy effect from any vitamin C lowering effects of immediately terminal illness, or near-end-of-life poor health.
Studies with much higher doses of vitamin C, usually between 200 and 6000 mg/day, for the treatment of infections and wounds have shown inconsistent results. Combinations of antioxidants seem to improve wound healing.
Physiological function in mammals
In humans, vitamin C is essential to a healthy diet as well as being a highly effective
antioxidantAn antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
, acting to lessen
oxidative stressOxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
; a substrate for
ascorbate peroxidaseAscorbate peroxidases are enzymes that detoxify peroxides such as hydrogen peroxide using ascorbate as a substrate. The reaction they catalyse is the transfer of electrons from ascorbate to a peroxide, producing dehydroascorbate and water as products.Ascorbate + Hydrogen peroxide →...
in plants (APX is plant specific enzyme); and an enzyme
cofactorA cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
for the
biosynthesisBiosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
of many important biochemicals. Vitamin C acts as an
electron donorAn electron donor is a chemical entity that donates electrons to another compound. It is a reducing agent that, by virtue of its donating electrons, is itself oxidized in the process....
for important
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s:
Collagen, carnitine, and tyrosine synthesis, and microsomal metabolism
Ascorbic acid performs numerous physiological functions in the human body. These functions include the synthesis of
collagenCollagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
,
carnitineCarnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids for the generation of metabolic energy. It is widely...
, and neurotransmitters; the synthesis and
catabolismCatabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...
of
tyrosineTyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
; and the metabolism of
microsomeIn cell biology, microsomes are vesicle-like artifacts re-formed from pieces of the endoplasmic reticulum when eukaryotic cells are broken-up in the laboratory; by definition, microsomes are not ordinarily present in living cells....
. During biosynthesis ascorbate acts as a reducing agent,
donating electronsAn electron donor is a chemical entity that donates electrons to another compound. It is a reducing agent that, by virtue of its donating electrons, is itself oxidized in the process....
and preventing oxidation to keep iron and copper atoms in their reduced states.
Vitamin C acts as an electron donor for eight different enzymes:
- Three enzymes participate in collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
hydroxylationHydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...
. These reactions add hydroxyl groupsHydroxide is a diatomic anion with chemical formula OH−. It consists of an oxygen and a hydrogen atom held together by a covalent bond, and carrying a negative electric charge. It is an important but usually minor constituent of water. It functions as a base, as a ligand, a nucleophile, and a...
to the amino acids prolineProline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
or lysineLysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
in the collagen molecule via prolyl hydroxylaseProlyl hydroxylase is an enzyme involved in the production of collagen, acting to hydroxylate proline to hydroxyproline....
and lysyl hydroxylaseLysyl hydroxylase is an oxygenase enzyme that catalyzes the hydroxylation of lysine to hydroxylysine. This reaction is necessary to the formation and stabilization of collagen. It takes place following protein synthesis...
, both requiring vitamin C as a cofactorA cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
. Hydroxylation allows the collagen molecule to assume its triple helixA helix is a type of smooth space curve, i.e. a curve in three-dimensional space. It has the property that the tangent line at any point makes a constant angle with a fixed line called the axis. Examples of helixes are coil springs and the handrails of spiral staircases. A "filled-in" helix – for...
structure, and thus vitamin C is essential to the development and maintenance of scar tissueGranulation tissue is the perfused, fibrous connective tissue that replaces a fibrin clot in healing wounds. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size it heals...
, blood vesselThe blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s, and cartilageCartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
.
- Two enzymes are necessary for synthesis of carnitine
Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids for the generation of metabolic energy. It is widely...
. Carnitine is essential for the transport of fatty acidIn chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s into mitochondria for ATPAdenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
generation.
- The remaining three enzymes have the following functions in common, but have other functions as well:
- dopamine beta hydroxylase
Dopamine β-hydroxylase is an enzyme that converts dopamine to norepinephrine.DBH is a 290 kDa copper-containing oxygenase consisting of four identical subunits, and its activity requires ascorbate as a cofactor...
participates in the biosynthesis of norepinephrineNorepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
from dopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
.
- another enzyme adds amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
groups to peptide hormonePeptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.Like other proteins, peptide hormones are synthesized in cells from amino acids according to an mRNA template, which is itself synthesized from a DNA template inside the...
s, greatly increasing their stability.
- one modulates tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
metabolism.
Antioxidant
Ascorbic acid is well known for its antioxidant activity, acting as a reducing agent to reverse oxidation in liquids. When there are more
free radicalsRadicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
(
reactive oxygen speciesReactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
, ROS) in the human body than
antioxidantAn antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
s, the condition is called
oxidative stressOxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
, and has an impact on
cardiovascular diseaseHeart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
,
hypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, chronic inflammatory diseases, diabetes as well as on critically ill patients and individuals with severe burns. Individuals experiencing oxidative stress have ascorbate blood levels lower than 45 µmol/L, compared to healthy individual who range between 61.4-80 µmol/L.
It is not yet certain whether vitamin C and antioxidants in general prevent oxidative stress-related diseases and promote health.
Clinical studiesClinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
regarding the effects of vitamin C
supplementationA dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
on
lipoproteinA lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
s and
cholesterolCholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
have found that vitamin C supplementation does not improve disease markers in the blood. Vitamin C may contribute to decreased risk of cardiovascular disease and strokes through a small reduction in
systolic blood pressureBlood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, and was also found to both increase
ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
levels and reduce levels of
resistinResistin also known as adipose tissue-specific secretory factor or C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein is a cysteine-rich protein that in humans is encoded by the RETN gene....
serum, another likely determinant of
oxidative stressOxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
and cardiovascular risk. However, so far there is no consensus that vitamin C intake has an impact on cardiovascular risks in general, and an array of studies found negative results.
Meta-analysisIn statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
of a large number of studies on antioxidants, including vitamin C supplementation, found no relationship between vitamin C and mortality.
Pro-oxidant
Ascorbic acid behaves not only as an antioxidant but also as a
pro-oxidantPro-oxidants are chemicals that induce oxidative stress, through either creating reactive oxygen species or inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues...
. Ascorbic acid has been shown to reduce transition metals, such as cupric ions (Cu
2+), to cuprous (Cu
1+), and ferric ions (Fe
3+) to ferrous (Fe
2+) during conversion from ascorbate to dehydroascorbate
in vitroIn vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
. This reaction can generate
superoxideA superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...
and other ROS. However, in the body, free transition elements are unlikely to be present while iron and copper are bound to diverse proteins and the
intravenousIntravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
use of vitamin C does not appear to increase pro-oxidant activity. Thus, ascorbate as a pro-oxidant is unlikely to convert metals to create ROS
in vivoIn vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
. However, vitamin C supplementation has been associated with increased DNA damage in the
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s of healthy volunteers.
Immune system
Vitamin C is found in high concentrations in immune cells, and is consumed quickly during infections. It is not certain how vitamin C interacts with the immune system; it has been hypothesized to modulate the activities of
phagocytePhagocytes are the white blood cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are...
s, the production of
cytokineCytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s and
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s, and the number of
cell adhesion moleculeCell Adhesion Molecules are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix in the process called cell adhesion....
s in
monocyteMonocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s.
Antihistamine
Vitamin C is a natural
antihistamineAn H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
. It both prevents
histamineHistamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
release and increases the detoxification of histamine. A 1992 study found that taking 2 grams vitamin C daily lowered blood histamine levels 38 percent in healthy adults in just one week. It has also been noted that low concentrations of serum vitamin C has been correlated with increased serum histamine levels.
Physiologic function in plants
Ascorbic acid is associated with chloroplasts and apparently plays a role in ameliorating the oxidative stress of photosynthesis. In addition, it has a number of other roles in cell division and protein modification. Plants appear to be able to make ascorbate by at least one other biochemical route that is different from the major route in animals, although precise details remain unknown.
Daily requirements
The
North AmericanNorth American generally refers to an entity, people, group, or attribute of North America, especially of the United States and Canada together.-Culture:*North American English, a collective term used to describe American English and Canadian English...
Dietary Reference IntakeThe Dietary Reference Intake is a system of nutrition recommendations from the Institute of Medicine of the U.S. National Academy of Sciences. The DRI system is used by both the United States and Canada and is intended for the general public and health professionals...
recommends 90 milligrams per day and no more than 2 grams (2,000 milligrams) per day. Other related species sharing the same inability to produce vitamin C and requiring
exogenousExogenous refers to an action or object coming from outside a system. It is the opposite of endogenous, something generated from within the system....
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. It is generally agreed that a balanced diet without supplementation contains enough vitamin C to prevent scurvy in an average healthy adult, while those who are pregnant, smoke tobacco, or are under stress require slightly more. However, the amount of Vitamin C necessary to prevent scurvy is less than the amount required for optimal health, as there are a number of other chronic diseases whose risk are increased by a low vitamin C intake, including cancer, heart disease, and cataracts. A 1999 review suggested a dose of 90–100 mg Vitamin C daily is required to optimally protect against these diseases, in contrast to the lower 45 mg daily required to prevent scurvy.
High doses (thousands of milligrams) may result in
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
in healthy adults, as a result of the osmotic water-retaining effect of the unabsorbed portion in the gastrointestinal tract (similar to cathartic osmotic
laxativeLaxatives are foods, compounds, or drugs taken to induce bowel movements or to loosen the stool, most often taken to treat constipation. Certain stimulant, lubricant, and saline laxatives are used to evacuate the colon for rectal and/or bowel examinations, and may be supplemented by enemas under...
s). Proponents of
orthomolecular medicineOrthomolecular medicine is a form of complementary and alternative medicine that seeks to maintain health and prevent or treat diseases by optimizing nutritional intake and/or prescribing supplements...
claim the onset of
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
to be an indication of where the body’s true vitamin C requirement lies, though this has not been clinically verified.
| United States vitamin C recommendations |
| Recommended Dietary Allowance (adult male) |
90 mg per day |
| Recommended Dietary Allowance (adult female) |
75 mg per day |
| Tolerable Upper Intake Level (adult male) |
2,000 mg per day |
| Tolerable Upper Intake Level (adult female) |
2,000 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
The Food Standards Agency is a non-ministerial government department of the Government of the United Kingdom. It is responsible for protecting public health in relation to food throughout the United Kingdom and is led by a board appointed to act in the public interest...
- 45 milligrams per day: the World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
- 90 mg/day (males) and 75 mg/day (females): Health Canada 2007
- 60–95 milligrams per day: United States' National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
.
The United States defined
Tolerable Upper Intake LevelThe Dietary Reference Intake is a system of nutrition recommendations from the Institute of Medicine of the U.S. National Academy of Sciences. The DRI system is used by both the United States and Canada and is intended for the general public and health professionals...
for a 25-year-old male is 2,000 milligrams per day.
Therapeutic uses
Vitamin C functions as an
antioxidantAn antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
and is necessary for the treatment and prevention of
scurvyScurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
, though in nearly all cases dietary intake is adequate to prevent deficiency and supplementation is not necessary. Though vitamin C has been promoted as useful in the treatment of a variety of conditions, most of these uses are poorly supported by the evidence and sometimes contraindicated. Vitamin C may be useful in lowering serum
uric acidUric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
levels, resulting in a correspondingly lower incidence of
goutGout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
. Neither prophylactic nor therapeutic use is supported in the prevention or treatment of
pneumoniaPneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
.
People with a the highest levels of ascorbic acid in their blood stream seem to be at a significantly reduced risk of having a
strokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
and low ascorbic acid has been suggested as a way of identifying those at high risk of stroke.
Vitamin C's effect on the common cold has been extensively researched. It has not been shown effective in prevention or treatment of the common cold, except in limited circumstances (specifically, individuals exercising vigorously in cold environments). Routine vitamin C supplementation does not reduce the incidence or severity of the
common coldThe common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
in the general population, though it may reduce the duration of illness.
Vitamin C megadosage
Several individuals and organizations advocate large doses of vitamin C in excess of 10–100 times RDI in the form of oral or
intravenous therapyIntravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
. Large, randomized
clinical trialClinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s on the effects of high doses on the general population have never taken place. Arguments for megadosage are based on the diets of closely related apes, the hypothesized diet of prehistoric humans, and that most mammals synthesize vitamin C rather than relying on dietary intake.
Linus PaulingLinus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
spent much of the later part of his life advocating for the use of megadose vitamin C and believed the established RDA was sufficient to prevent
scurvyScurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
, but not necessarily the dosage for optimal health. Megadoses have been promoted for the treatment or prevention of various conditions, including
cancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, the common cold, and
coronary diseaseCoronary disease refers to the failure of coronary circulation to supply adequate circulation to cardiac muscle and surrounding tissue. It is already the most common form of disease affecting the heart and an important cause of premature death in Europe, the Baltic states, Russia, North and South...
. These uses are not supported by clinical evidence, and in some cases harm may result.
Testing for ascorbate levels in the body
Simple tests use dichlorophenolindophenol, a
redox indicatorA redox indicator is an indicator that undergoes a definite color change at a specific electrode potential....
, to measure the levels of vitamin C in the
urineUrine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
and in
serumIn physiology, the term serous fluid is used for various bodily fluids that are typically pale yellow and transparent, and of a benign nature, that fill the inside of body cavities. Serous fluid originates from serous glands, with secretions enriched with proteins and water. Serous fluid may also...
or
blood plasmaBlood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
. However these reflect recent dietary intake rather than the level of vitamin C in body stores. Reverse phase
high performance liquid chromatographyHigh-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...
is used for determining the storage levels of vitamin C within
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s and
tissueTissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
.
It has been observed that while serum or blood plasma levels follow the
circadian rhythmA circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...
or short term dietary changes, those within tissues themselves are more stable and give a better view of the availability of ascorbate within the organism. However, very few hospital laboratories are adequately equipped and trained to carry out such detailed analyses, and require samples to be analyzed in specialized laboratories.
Common side-effects
Relatively large doses of ascorbic acid may cause indigestion, particularly when taken on an empty stomach. However, taking vitamin C in the form of
sodium ascorbateSodium ascorbate is a more bioavailable form of vitamin C that is an alternative to taking ascorbic acid as a supplement. The molecular formula of this chemical compound is C6H7NaO6...
and calcium ascorbate may minimize this effect. When taken in large doses, ascorbic acid causes
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
in healthy subjects. In one trial in 1936, doses up to 6 grams of ascorbic acid were given to 29 infants, 93 children of preschool and school age, and 20 adults for more than 1400 days. With the higher doses, toxic manifestations were observed in five adults and four infants. The signs and symptoms in adults were nausea, vomiting, diarrhea, flushing of the face, headache, fatigue and disturbed sleep. The main toxic reactions in the infants were skin rashes.
Possible side-effects
As vitamin C enhances iron absorption,
iron poisoningIron poisoning is an iron overload caused by a large excess of iron intake and usually refers to an acute overload rather than a gradual one. The terms has been primarily associated with young children who consumed large quantities of iron supplement pills, which resemble sweets and are widely...
can become an issue to people with rare
iron overload disorderIn medicine, iron overload indicates accumulation of iron in the body from any cause. The most important causes are hereditary hemochromatosis , a genetic disease, and transfusional iron overload, which can result from repeated blood transfusion....
s, such as
haemochromatosisHaemochromatosis type 1 is a hereditary disease characterized by excessive intestinal absorption of dietary iron resulting in a pathological increase in total body iron stores. Humans, like most animals, have no means to excrete excess iron...
. A genetic condition that results in inadequate levels of the enzyme
glucose-6-phosphate dehydrogenaseGlucose-6-phosphate dehydrogenase is a cytosolic enzyme in the pentose phosphate pathway , a metabolic pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate...
(G6PD) can cause sufferers to develop
hemolytic anemiaHemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
after ingesting specific oxidizing substances, such as very large dosages of vitamin C.
There is a longstanding belief among the mainstream medical community that vitamin C causes kidney stones, which is based on little science.
Although recent studies have found a relationship, a clear link between excess
ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
intake and
kidney stoneA kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...
formation has not been generally established. Some case reports exist for a link between patients with oxalate deposits and a history of high-dose vitamin C usage.
In a study conducted on rats, during the first month of pregnancy, high doses of vitamin C may suppress the production of
progesteroneProgesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
from the
corpus luteumThe corpus luteum is a temporary endocrine structure in mammals, involved in production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A...
. Progesterone, necessary for the maintenance of a pregnancy, is produced by the corpus luteum for the first few weeks, until the placenta is developed enough to produce its own source. By blocking this function of the corpus luteum, high doses of vitamin C (1000+ mg) are theorized to induce an early miscarriage. In a group of spontaneously aborting women at the end of the first trimester, the mean values of vitamin C were significantly higher in the aborting group. However, the authors do state: 'This could not be interpreted as an evidence of causal association.' However, in a previous study of 79 women with threatened, previous spontaneous, or habitual abortion, Javert and Stander (1943) had 91% success with 33 patients who received vitamin C together with bioflavonoids and
vitamin KVitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
(only three abortions), whereas all of the 46 patients who did not receive the vitamins aborted.
A study in rats and humans suggested that adding Vitamin C supplements to an exercise training program lowered the expected effect of training on
VO2 MaxVO2 max is the maximum capacity of an individual's body to transport and use oxygen during incremental exercise, which reflects the physical fitness of the individual...
. Although the results in humans were not statistically significant, this study is often cited as evidence that high doses of Vitamin C have an adverse effect on exercise performance. In rats, it was shown that the additional Vitamin C resulted in lowered mitochondria production. Since rats are able to produce all of their needed Vitamin C, however, it is questionable whether they offer a relevant model of human physiological processes in this regard.
A cancer-causing mechanism of
hexavalent chromiumHexavalent chromium refers to chemical compounds that contain the element chromium in the +6 oxidation state. Virtually all chromium ore is processed via hexavalent chromium, specifically the salt sodium dichromate. Approximately of hexavalent chromium were produced in 1985...
may be triggered by vitamin C.
Chance of overdose
Vitamin C is water soluble, with dietary excesses not absorbed, and excesses in the blood rapidly excreted in the urine. It exhibits remarkably low toxicity. The (the dose that will kill 50% of a population) in rats is generally accepted to be 11.9 grams per kilogram of body weight when given by forced gavage (orally). The mechanism of death from such doses (1.2% of body weight, or 1.8 lbs for a 150 lb human) is unknown, but may be more mechanical than chemical. The LD
50 in humans remains unknown, given lack of any accidental or intentional poisoning death data. However, as with all substances tested in this way, the rat LD
50 is taken as a guide to its toxicity in humans.
Dietary sources
The richest natural sources are fruits and vegetables, and of those, the Kakadu plum and the
camu camuMyrciaria dubia, commonly known as Camu camu, Camucamu, Cacari, and Camocamo, is a small bushy riverside tree from the Amazon rainforest vegetation in Peru and Brazil, which bears a red/purple cherry-like fruit. Its small flowers have waxy white petals and a sweet-smelling aroma. It has bushy...
fruit 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.
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. The presence of large quantities of sugar either in the intestines or in the blood can slow absorption.
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, soil condition, climate where it grew, length of time since it was picked, storage conditions, and method of preparation.
The following table is approximate and shows the relative abundance in different raw plant sources. As some plants were analyzed fresh while others were dried (thus, artifactually increasing concentration of individual constituents like vitamin C), the data are subject to potential variation and difficulties for comparison. The amount is given in milligrams per 100 grams of fruit or vegetable and is a rounded average from multiple authoritative sources:
(mg / 100g)
|-
|
Kakadu plumTerminalia ferdinandiana, also called the gubinge, billygoat plum, Kakadu plum or murunga is a flowering plant in the family Combretaceae, native to Australia, widespread throughout the tropical woodlands from northwestern Australia to eastern Arnhem Land.Its vitamin C concentration may be as high...
|| 1000-5300
|-
|
Camu CamuMyrciaria dubia, commonly known as Camu camu, Camucamu, Cacari, and Camocamo, is a small bushy riverside tree from the Amazon rainforest vegetation in Peru and Brazil, which bears a red/purple cherry-like fruit. Its small flowers have waxy white petals and a sweet-smelling aroma. It has bushy...
|| 2800
|-
|
AcerolaMalpighia emarginata is a tropical fruit-bearing shrub or small tree in the family Malpighiaceae. Common names include acerola, Barbados cherry, West Indian cherry and wild crapemyrtle....
|| 1677
|-
|Seabuckthorn || 695
|-
|Mica Muro || 500
|-
|
Indian gooseberryPhyllanthus emblica , the Indian gooseberry, or aamla, is a deciduous tree of the Phyllanthaceae family. It is known for its edible fruit of the same name.-Plant anatomy and harvesting:...
|| 445
|-
|
Rose hipThe rose hip, or rose haw, is the fruit of the rose plant, that typically is red-to-orange, but ranges from dark purple to black in some species. Rose hips begin to form in spring, and ripen in late summer through autumn.-Usage:...
|| 426
|-
|
BaobabAdansonia is a genus of eight species of tree, six native to Madagascar, one native to mainland Africa and the Arabian Peninsula and one to Australia. The mainland African species also occurs on Madagascar, but it is not a native of that island....
|| 400
|-
|
Chili pepperChili pepper is the fruit of plants from the genus Capsicum, members of the nightshade family, Solanaceae. The term in British English and in Australia, New Zealand, India, Malaysia and other Asian countries is just chilli without pepper.Chili peppers originated in the Americas...
(green) || 244
|-
|
GuavaGuavas are plants in the myrtle family genus Psidium , which contains about 100 species of tropical shrubs and small trees. They are native to Mexico, Central America, and northern South America...
(common, raw) || 228.3
[USDA Guava, common, raw]
|-
|
BlackcurrantBlackcurrant, Ribes nigrum, is a species of Ribes berry native to central and northern Europe and northern Asia, and is a perennial....
|| 200
|-
|
Red pepperCapsicum is a genus of flowering plants in the nightshade family, Solanaceae. Its species are native to the Americas where they have been cultivated for thousands of years, but they are now also cultivated worldwide, used as spices, vegetables, and medicines - and have become are a key element in...
|| 190
|-
|
Chili pepperChili pepper is the fruit of plants from the genus Capsicum, members of the nightshade family, Solanaceae. The term in British English and in Australia, New Zealand, India, Malaysia and other Asian countries is just chilli without pepper.Chili peppers originated in the Americas...
(red) || 144
|-
|
ParsleyParsley is a species of Petroselinum in the family Apiaceae, native to the central Mediterranean region , naturalized elsewhere in Europe, and widely cultivated as an herb, a spice and a vegetable.- Description :Garden parsley is a bright green hairless biennial herbaceous plant in temperate...
|| 130
|-
|
KiwifruitThe kiwifruit, often shortened to kiwi in many parts of the world, is the edible berry of a cultivar group of the woody vine Actinidia deliciosa and hybrids between this and other species in the genus Actinidia....
|| 90
|-
|
BroccoliBroccoli is a plant in the cabbage family, whose large flower head is used as a vegetable.-General:The word broccoli, from the Italian plural of , refers to "the flowering top of a cabbage"....
|| 90
|-
|
LoganberryThe loganberry is an hexaploid hybrid produced from crossing an octaploid blackberry and a diploid red raspberry. The plant and the fruit resemble the blackberry more than the raspberry, but the fruit colour is a dark red, rather than black...
|| 80
|-
|
RedcurrantThe redcurrant , Ribes rubrum, is a member of the genus Ribes in the gooseberry family Grossulariaceae, native to parts of western Europe...
|| 80
|-
|
Brussels sproutThe Brussels sprout is a cultivar of wild cabbage grown for its edible buds. The leafy green vegetables are typically 2.5–4 cm in diameter and look like miniature cabbages. The sprout is Brassica oleracea, in the "gemmifera" group of the family Brassicaceae...
s ||80
|-
|
WolfberryWolfberry, commercially called goji berry, is the common name for the fruit of two very closely related species: Lycium barbarum and L. chinense , two species of boxthorn in the family Solanaceae...
(Goji) || 73 †
|-
|
LycheeThe lychee is the sole member of the genus Litchi in the soapberry family, Sapindaceae. It is a tropical and subtropical fruit tree native to Southern China and Southeast Asia, and now cultivated in many parts of the world...
|| 70
|-
|
PersimmonA persimmon is the edible fruit of a number of species of trees in the genus Diospyros in the ebony wood family . The word Diospyros means "the fire of Zeus" in ancient Greek. As a tree, it is a perennial plant...
(native, raw) || 66.0
[USDA Persimmons, native, raw]
|-
|
CloudberryRubus chamaemorus is a rhizomatous herb native to alpine and arctic tundra and boreal forest, producing amber-colored edible fruit similar to the raspberry or blackberry...
|| 60
|-
|
ElderberrySambucus is a genus of between 5 and 30 species of shrubs or small trees in the moschatel family, Adoxaceae. It was formerly placed in the honeysuckle family, Caprifoliaceae, but was reclassified due to genetic evidence...
|| 60
|}
† average of 3 sources; dried
(mg / 100g)
|-
|
PapayaThe papaya , papaw, or pawpaw is the fruit of the plant Carica papaya, the sole species in the genus Carica of the plant family Caricaceae...
|| 60
|-
|
StrawberryFragaria is a genus of flowering plants in the rose family, Rosaceae, commonly known as strawberries for their edible fruits. Although it is commonly thought that strawberries get their name from straw being used as a mulch in cultivating the plants, the etymology of the word is uncertain. There...
|| 60
|-
|
OrangeAn orange—specifically, the sweet orange—is the citrus Citrus × sinensis and its fruit. It is the most commonly grown tree fruit in the world....
|| 50
|-
|
KaleKale is very high in beta carotene, vitamin K, vitamin C, lutein, zeaxanthin, and reasonably rich in calcium. Kale, as with broccoli and other brassicas, contains sulforaphane , a chemical with potent anti-cancer properties. Boiling decreases the level of sulforaphane; however, steaming,...
|| 41
|-
|
LemonThe lemon is both a small evergreen tree native to Asia, and the tree's ellipsoidal yellow fruit. The fruit is used for culinary and non-culinary purposes throughout the world – primarily for its juice, though the pulp and rind are also used, mainly in cooking and baking...
|| 40
|-
|
Melonthumb|200px|Various types of melonsThis list of melons includes members of the plant family Cucurbitaceae with edible, fleshy fruit e.g. gourds or cucurbits. The word "melon" can refer to either the plant or specifically to the fruit...
, cantaloupe || 40
|-
|
CauliflowerCauliflower is one of several vegetables in the species Brassica oleracea, in the family Brassicaceae. It is an annual plant that reproduces by seed...
|| 40
|-
|
GarlicAllium sativum, commonly known as garlic, is a species in the onion genus, Allium. Its close relatives include the onion, shallot, leek, chive, and rakkyo. Dating back over 6,000 years, garlic is native to central Asia, and has long been a staple in the Mediterranean region, as well as a frequent...
|| 31
|-
|
GrapefruitThe grapefruit , is a subtropical citrus tree known for its sour fruit, an 18th-century hybrid first bred in Barbados. When found, it was named the "forbidden fruit"; it has also been misidentified with the pomelo or shaddock , one of the parents of this hybrid, the other being sweet orange The...
|| 30
|-
|
RaspberryThe raspberry or hindberry is the edible fruit of a multitude of plant species in the genus Rubus, most of which are in the subgenus Idaeobatus; the name also applies to these plants themselves...
|| 30
|-
|
Tangerine__notoc__The tangerine is an orange-colored citrus fruit which is closely related to the Mandarin orange . Taxonomically, it should probably be formally named as a subspecies or variety of Citrus reticulata; further work seems to be required to ascertain its correct scientific name...
|| 30
|-
|
Mandarin orangeThe orange, also known as the ' or mandarine , is a small citrus tree with fruit resembling other oranges. Mandarin oranges are usually eaten plain or in fruit salads...
|| 30
|-
|Passion fruit || 30
|-
|
SpinachSpinach is an edible flowering plant in the family of Amaranthaceae. It is native to central and southwestern Asia. It is an annual plant , which grows to a height of up to 30 cm. Spinach may survive over winter in temperate regions...
|| 30
|-
|
CabbageCabbage is a popular cultivar of the species Brassica oleracea Linne of the Family Brassicaceae and is a leafy green vegetable...
raw green || 30
|-
|
LimeLime is a term referring to a number of different citrus fruits, both species and hybrids, which are typically round, green to yellow in color, 3–6 cm in diameter, and containing sour and acidic pulp. Limes are a good source of vitamin C. Limes are often used to accent the flavors of foods and...
|| 30
|-
|
MangoThe mango is a fleshy stone fruit belonging to the genus Mangifera, consisting of numerous tropical fruiting trees in the flowering plant family Anacardiaceae. The mango is native to India from where it spread all over the world. It is also the most cultivated fruit of the tropical world. While...
|| 28
|-
|
BlackberryThe blackberry is an edible fruit produced by any of several species in the Rubus genus of the Rosaceae family. The fruit is not a true berry; botanically it is termed an aggregate fruit, composed of small drupelets. The plants typically have biennial canes and perennial roots. Blackberries and...
|| 21
|-
|
PotatoThe potato is a starchy, tuberous crop from the perennial Solanum tuberosum of the Solanaceae family . The word potato may refer to the plant itself as well as the edible tuber. In the region of the Andes, there are some other closely related cultivated potato species...
|| 20
|-
|
Melonthumb|200px|Various types of melonsThis list of melons includes members of the plant family Cucurbitaceae with edible, fleshy fruit e.g. gourds or cucurbits. The word "melon" can refer to either the plant or specifically to the fruit...
, honeydew || 20
|-
|
CranberryCranberries are a group of evergreen dwarf shrubs or trailing vines in the subgenus Oxycoccus of the genus Vaccinium. In some methods of classification, Oxycoccus is regarded as a genus in its own right...
|| 13
|-
|
TomatoThe word "tomato" may refer to the plant or the edible, typically red, fruit which it bears. Originating in South America, the tomato was spread around the world following the Spanish colonization of the Americas, and its many varieties are now widely grown, often in greenhouses in cooler...
|| 10
|-
|
BlueberryBlueberries are flowering plants of the genus Vaccinium with dark-blue berries and are perennial...
|| 10
|-
|
PineapplePineapple is the common name for a tropical plant and its edible fruit, which is actually a multiple fruit consisting of coalesced berries. It was given the name pineapple due to its resemblance to a pine cone. The pineapple is by far the most economically important plant in the Bromeliaceae...
|| 10
|-
|
PawpawAsimina triloba, the pawpaw, paw paw, paw-paw, or common pawpaw, is a species of Asimina in the same plant family as the custard-apple, cherimoya, sweetsop, ylang-ylang and soursop...
|| 10
|}
(mg / 100g)
|-
|
GrapeA grape is a non-climacteric fruit, specifically a berry, that grows on the perennial and deciduous woody vines of the genus Vitis. Grapes can be eaten raw or they can be used for making jam, juice, jelly, vinegar, wine, grape seed extracts, raisins, molasses and grape seed oil. Grapes are also...
|| 10
|-
|
ApricotThe apricot, Prunus armeniaca, is a species of Prunus, classified with the plum in the subgenus Prunus. The native range is somewhat uncertain due to its extensive prehistoric cultivation.- Description :...
|| 10
|-
|
PlumA plum or gage is a stone fruit tree in the genus Prunus, subgenus Prunus. The subgenus is distinguished from other subgenera in the shoots having a terminal bud and solitary side buds , the flowers in groups of one to five together on short stems, and the fruit having a groove running down one...
|| 10
|-
|
WatermelonWatermelon is a vine-like flowering plant originally from southern Africa. Its fruit, which is also called watermelon, is a special kind referred to by botanists as a pepo, a berry which has a thick rind and fleshy center...
|| 10
|-
|
BananaBanana is the common name for herbaceous plants of the genus Musa and for the fruit they produce. Bananas come in a variety of sizes and colors when ripe, including yellow, purple, and red....
|| 9
|-
|
CarrotThe carrot is a root vegetable, usually orange in colour, though purple, red, white, and yellow varieties exist. It has a crisp texture when fresh...
|| 9
|-
|
AvocadoThe avocado is a tree native to Central Mexico, classified in the flowering plant family Lauraceae along with cinnamon, camphor and bay laurel...
|| 8
|-
|
CrabappleCrabapple is a term used for several species of Malus in the family Rosaceae, which are characterized by small sour fruit resembling familiar table apples . They are usually small trees or shrubs....
|| 8
|-
|
PersimmonA persimmon is the edible fruit of a number of species of trees in the genus Diospyros in the ebony wood family . The word Diospyros means "the fire of Zeus" in ancient Greek. As a tree, it is a perennial plant...
(Japanese, fresh) || 7.5
[USDA Persimmon, japanese, raw]
|-
|
CherryThe cherry is the fruit of many plants of the genus Prunus, and is a fleshy stone fruit. The cherry fruits of commerce are usually obtained from a limited number of species, including especially cultivars of the wild cherry, Prunus avium....
|| 7
|-
|
PeachThe peach tree is a deciduous tree growing to tall and 6 in. in diameter, belonging to the subfamily Prunoideae of the family Rosaceae. It bears an edible juicy fruit called a peach...
|| 7
|-
|
AppleThe apple is the pomaceous fruit of the apple tree, species Malus domestica in the rose family . It is one of the most widely cultivated tree fruits, and the most widely known of the many members of genus Malus that are used by humans. Apple grow on small, deciduous trees that blossom in the spring...
|| 6
|-
|
AsparagusAsparagus officinalis is a spring vegetable, a flowering perennialplant species in the genus Asparagus. It was once classified in the lily family, like its Allium cousins, onions and garlic, but the Liliaceae have been split and the onion-like plants are now in the family Amaryllidaceae and...
|| 6
|-
|
Horned melonThe horned melon , also called African horned cucumber or melon, jelly melon, hedged gourd, English tomato, melano, kiwano, or cherie, is an annual vine in the cucumber and melon family. It is considered to be the ancestor of the other cultivated melons...
|| 5.3
[USDA Horned melon]
|-
|
BeetrootThe beetroot, also known as the table beet, garden beet, red beet or informally simply as beet, is one of the many cultivated varieties of beets and arguably the most commonly encountered variety in North America, Central America and Britain.-Consumption:The usually deep-red roots of beetroot are...
|| 5
|-
|
ChokecherryPrunus virginiana, commonly called chokecherry, bitter-berry, or Virginia bird cherry, is a species of bird cherry native to North America, where it is found almost throughout the continent except for the Deep South and the far north.-Growth:It is a suckering shrub or small tree growing to 5 m tall...
|| 5
|-
|
PearThe pear is any of several tree species of genus Pyrus and also the name of the pomaceous fruit of these trees. Several species of pear are valued by humans for their edible fruit, but the fruit of other species is small, hard, and astringent....
|| 4
|-
|
LettuceLettuce is a temperate annual or biennial plant of the daisy family Asteraceae. It is most often grown as a leaf vegetable. It is eaten either raw, notably in salads, sandwiches, hamburgers, tacos, and many other dishes, or cooked, as in Chinese cuisine in which the stem becomes just as important...
|| 4
|-
|
CucumberThe cucumber is a widely cultivated plant in the gourd family Cucurbitaceae, which includes squash, and in the same genus as the muskmelon. The plant is a creeping vine which bears cylindrical edible fruit when ripe. There are three main varieties of cucumber: "slicing", "pickling", and...
|| 3
|-
|Eggplant || 2
|-
|
RaisinRaisins are dried grapes. They are produced in many regions of the world. Raisins may be eaten raw or used in cooking, baking and brewing...
|| 2
|-
|
FigFicus is a genus of about 850 species of woody trees, shrubs, vines, epiphytes, and hemiepiphyte in the family Moraceae. Collectively known as fig trees or figs, they are native throughout the tropics with a few species extending into the semi-warm temperate zone. The Common Fig Ficus is a genus of...
|| 2
|-
|
BilberryBilberry is any of several species of low-growing shrubs in the genus Vaccinium , bearing edible berries. The species most often referred to is Vaccinium myrtillus L., but there are several other closely related species....
|| 1
|-
|Medlar || 0.3
|}
Animal sources
The overwhelming majority of species of animals (but
not humans) and plants synthesise their own vitamin C. Therefore, some animal products can be used as sources of dietary vitamin C.
Vitamin C is most present in the liver and least present in the muscle. Since muscle provides the majority of meat consumed in the western human diet, animal products are not a reliable source of the vitamin. Vitamin C is present in mother's milk but, not present in raw cow's milk. All excess vitamin C is disposed of through the urinary system.
The following table shows the relative abundance of vitamin C in various foods of animal origin, given in milligram of vitamin C per 100 grams of food:
(mg / 100g)
|-
|
CalfCalves are the young of domestic cattle. Calves are reared to become adult cattle, or are slaughtered for their meat, called veal.-Terminology:...
liverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
(raw) || 36
|-
|
BeefBeef is the culinary name for meat from bovines, especially domestic cattle. Beef can be harvested from cows, bulls, heifers or steers. It is one of the principal meats used in the cuisine of the Middle East , Australia, Argentina, Brazil, Europe and the United States, and is also important in...
liver (raw) || 31
|-
|
OysterThe word oyster is used as a common name for a number of distinct groups of bivalve molluscs which live in marine or brackish habitats. The valves are highly calcified....
s (raw) || 30
|-
|
CodCod is the common name for genus Gadus, belonging to the family Gadidae, and is also used in the common name for various other fishes. Cod is a popular food with a mild flavor, low fat content and a dense, flaky white flesh. Cod livers are processed to make cod liver oil, an important source of...
roeRoe or hard roe is the fully ripe internal egg masses in the ovaries, or the released external egg masses of fish and certain marine animals, such as shrimp, scallop and sea urchins...
(fried) || 26
|-
|
PorkPork is the culinary name for meat from the domestic pig , which is eaten in many countries. It is one of the most commonly consumed meats worldwide, with evidence of pig husbandry dating back to 5000 BC....
liver (raw) || 23
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|
LambSheep are quadrupedal, ruminant mammals typically kept as livestock. Like all ruminants, sheep are members of the order Artiodactyla, the even-toed ungulates. Although the name "sheep" applies to many species in the genus Ovis, in everyday usage it almost always refers to Ovis aries...
brainThe brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
(boiled) || 17
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ChickenThe chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...
liver (fried) || 13
|}
(mg / 100g)
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|Lamb liver (fried) || 12
|-
|
CalfCalves are the young of domestic cattle. Calves are reared to become adult cattle, or are slaughtered for their meat, called veal.-Terminology:...
adrenalsIn mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
(raw) || 11
|-
|Lamb
heartThe heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
(roast) || 11
|-
|Lamb
tongueThe tongue is a muscular hydrostat on the floors of the mouths of most vertebrates which manipulates food for mastication. It is the primary organ of taste , as much of the upper surface of the tongue is covered in papillae and taste buds. It is sensitive and kept moist by saliva, and is richly...
(stewed) || 6
|-
|
Human milkBreastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
(fresh) || 4
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|Goat milk (fresh) || 2
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|Camel milk (fresh) || 5
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|Cow milk (fresh) || 2
|}
Food preparation
Vitamin C
chemically decomposesChemical decomposition, analysis or breakdown is the separation of a chemical compound into elements or simpler compounds. It is sometimes defined as the exact opposite of a chemical synthesis. Chemical decomposition is often an undesired chemical reaction...
under certain conditions, many of which may occur during the cooking of food. Vitamin C concentrations in various food substances decrease with time in proportion to the temperature they are stored at and cooking can reduce the Vitamin C content of vegetables by around 60% possibly partly due to increased enzymatic destruction as it may be more significant at sub-boiling temperatures. 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
leachingLeaching is the process of extracting minerals from a solid by dissolving them in a liquid, either in nature or through an industrial process. In the chemical processing industry, leaching has a variety of commercial applications, including separation of metal from ore using acid, and sugar from...
, where the water-soluble vitamin dissolves into the cooking water, which is later poured away and not consumed. However, vitamin C does not leach in all vegetables at the same rate; research shows
broccoliBroccoli is a plant in the cabbage family, whose large flower head is used as a vegetable.-General:The word broccoli, from the Italian plural of , refers to "the flowering top of a cabbage"....
seems to retain more than any other. Research has also shown that fresh-cut fruits do not lose significant nutrients when stored in the refrigerator for a few days.
Vitamin C supplements
Vitamin C is the most widely taken dietary supplement. It is available in caplets,
tabletA tablet is a pharmaceutical dosage form. It comprises a mixture of active substances and excipients, usually in powder form, pressed or compacted from a powder into a solid dose...
s, capsules, drink mix packets, in multi-vitamin formulations, in multiple antioxidant formulations, and as crystalline powder. Timed release versions are available, as are formulations containing bioflavonoids such as
quercetinQuercetin , a flavonol, is a plant-derived flavonoid found in fruits, vegetables, leaves and grains. It also may be used as an ingredient in supplements, beverages or foods.-Occurrence:...
,
hesperidinHesperidin is a flavanone glycoside found abundantly in citrus fruits. Its aglycone form is called hesperetin. Its name is derived from the Hesperides nymphs of Greek mythology. Hesperidin is believed to play a role in plant defense. It acts as an antioxidant according to in vitro studies...
, and
rutinRutin, also called rutoside, quercetin-3-O-rutinoside and sophorin, is a citrus flavonoid glycoside found in buckwheat, the leaves and petioles of Rheum species, and asparagus...
. Tablet and capsule sizes range from 25 mg to 1500 mg. Vitamin C (as ascorbic acid) crystals are typically available in bottles containing 300 g to 1 kg of powder (a 5 ml teaspoon of vitamin C crystals equals 5,000 mg).
Industrial synthesis
Vitamin C is produced from
glucoseGlucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
by two main routes. The
Reichstein processThe Reichstein process in chemistry is a combined chemical and microbial method for the production of ascorbic acid from D-glucose that takes place in several steps...
, developed in the 1930s, uses a single pre-fermentation followed by a purely chemical route. The modern two-step
fermentationFermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...
process, originally developed in
ChinaChinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
in the 1960s, uses additional fermentation to replace part of the later chemical stages. Both processes yield approximately 60% vitamin C from the glucose feed.
Research is underway at the
Scottish Crop Research InstituteThe Scottish Crop Research Institute more commonly known as the SCRI was a scientific institute located in Invergowrie near Dundee, Scotland. As of April 2011, when SCRI merged with the Macaulay Land Use Institute it is now part of The James Hutton Institute.-History:The institute was opened in...
in the interest of creating a strain of yeast that can synthesise vitamin C in a single fermentation step from
galactoseGalactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....
, a technology expected to reduce manufacturing costs considerably.
World production of synthesised vitamin C is currently estimated at approximately 110,000 tonnes annually. Main producers have been
BASFBASF SE is the largest chemical company in the world and is headquartered in Germany. BASF originally stood for Badische Anilin- und Soda-Fabrik . Today, the four letters are a registered trademark and the company is listed on the Frankfurt Stock Exchange, London Stock Exchange, and Zurich Stock...
/Takeda,
DSMDSM is a multinational life sciences and materials sciences-based company. DSM's global end markets include food and dietary supplements, personal care, feed, pharmaceuticals, medical devices, automotive, paints, electrical and electronics, life protection, alternative energy and bio-based materials...
,
MerckMerck KGaA is a German chemical and pharmaceutical company. Merck, also known as “German Merck” and “Merck Darmstadt”, was founded in Darmstadt, Germany, in 1668, making it the world's oldest operating chemical and pharmaceutical company. The company was privately owned until going public in 1995...
and the China Pharmaceutical Group Ltd. of the
People's Republic of ChinaChina , officially the People's Republic of China , is the most populous country in the world, with over 1.3 billion citizens. Located in East Asia, the country covers approximately 9.6 million square kilometres...
. By 2008 only the DSM plant in Scotland remained operational outside the strong price competition from China. The world price of vitamin C rose sharply in 2008 partly as a result of rises in basic food prices but also in anticipation of a stoppage of the two Chinese plants, situated at
ShijiazhuangShijiazhuang is the capital and largest city of North China's Hebei province. Administratively a prefecture-level city, it is about south of Beijing...
near
BeijingBeijing , also known as Peking , is the capital of the People's Republic of China and one of the most populous cities in the world, with a population of 19,612,368 as of 2010. The city is the country's political, cultural, and educational center, and home to the headquarters for most of China's...
, as part of a general shutdown of polluting industry in China over the period of the
Olympic gamesThe 2008 Summer Olympics, officially known as the Games of the XXIX Olympiad, was a major international multi-sport event that took place in Beijing, China, from August 8 to August 24, 2008. A total of 11,028 athletes from 204 National Olympic Committees competed in 28 sports and 302 events...
. Five Chinese manufacturers met in 2010, among them Northeast Pharmaceutical Group and North China Pharmaceutical Group, and agreed to temporarily stop production in order to maintain prices. In 2011 a case was filed in a US court against 4 Chinese companies that they colluded to limit production and fix prices of vitamin C in the United States. According to the plaintiffs, after the agreement was made, spot prices for vitamin C shot to as high as $7 per kilogram in December 2002 from $2.50 per kilogram in December 2001.The companies do not deny the accusation but say in their defense that the Chinese government compelled them to act in this way.
Food fortification
In 2005,
Health CanadaHealth Canada is the department of the government of Canada with responsibility for national public health.The current Minister of Health is Leona Aglukkaq, a Conservative Member of Parliament appointed to the position by Prime Minister Stephen Harper.-Branches, regions and agencies:Health Canada...
evaluated the effect of fortification of foods with ascorbate in the guidance document,
Addition of Vitamins and Minerals to Food. Abscorbate was categorized as a ‘Risk Category A nutrients’, meaning it is a nutrient for which an upper limit for intake is set but allows a wide margin of intake that has a narrow margin of safety but non-serious critical adverse effects. Health Canada recommended a minimum of 3 mg or 5% of RDI for the food to claim to be a source of Vitamin C, and maximum fortification of 12 mg (20% of RDI) to claim "Excellent Source".
Compendial status
- British Pharmacopoeia
The British Pharmacopoeia is an annual published collection of quality standards for UK medicinal substances. It is used by individuals and organizations involved in pharmaceutical research, development, manufacture and testing....
- Japanese Pharmacopoeia
History
The need to include fresh plant food or raw animal flesh in the diet to prevent disease was known from ancient times. Native people 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 explorers
Jacques CartierJacques Cartier was a French explorer of Breton origin who claimed what is now Canada for France. He was the first European to describe and map the Gulf of Saint Lawrence and the shores of the Saint Lawrence River, which he named "The Country of Canadas", after the Iroquois names for the two big...
and Daniel Knezevic, exploring the
St. Lawrence RiverThe Saint Lawrence is a large river flowing approximately from southwest to northeast in the middle latitudes of North America, connecting the Great Lakes with the Atlantic Ocean. It is the primary drainage conveyor of the Great Lakes Basin...
, used the local natives' knowledge to save his men who were dying of scurvy. He boiled the needles of the
arbor vitaeThuja is a genus of coniferous trees in the Cupressaceae . There are five species in the genus, two native to North America and three native to eastern Asia...
tree to make a tea that was later shown to contain 50 mg of vitamin C per 100 grams.
Throughout history, the benefit of plant food to survive long sea voyages has been occasionally recommended by authorities.
John WoodallJohn Woodall was an English military surgeon, Paracelsian chemist, businessman, linguist and diplomat. He made a fortune through the stocking of medical chests for the East India Company and later the armed forces of England...
, the first appointed surgeon to the
British East India CompanyThe East India Company was an early English joint-stock company that was formed initially for pursuing trade with the East Indies, but that ended up trading mainly with the Indian subcontinent and China...
, recommended the preventive and curative use of
lemonThe lemon is both a small evergreen tree native to Asia, and the tree's ellipsoidal yellow fruit. The fruit is used for culinary and non-culinary purposes throughout the world – primarily for its juice, though the pulp and rind are also used, mainly in cooking and baking...
juice in his book,
The Surgeon's Mate, in 1617. The
DutchThe Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
writer,
Johann BachstromJan Fryderyk or Johann Friedrich Bachstrom was a writer, scientist and Lutheran theologian who spent the last decade of his life in Leiden. His surname is sometimes spelt Bachstroem or Bachstrohm...
, in 1734, gave the firm opinion that
"scurvy is solely owing to a total abstinence from fresh vegetable food, and greens, which is alone the primary cause of the disease."
Scurvy had long been a principal killer of sailors during the long sea voyages. According to Jonathan Lamb, "In 1499, Vasco da Gama lost 116 of his crew of 170; In 1520, Magellan lost 208 out of 230;...all mainly to scurvy."
While the earliest documented case of
scurvyScurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
was described by
HippocratesHippocrates of Cos or Hippokrates of Kos was an ancient Greek physician of the Age of Pericles , and is considered one of the most outstanding figures in the history of medicine...
around the year 400 BC, the first attempt to give scientific basis for the cause of this disease was by a ship's surgeon in the British
Royal NavyThe Royal Navy is the naval warfare service branch of the British Armed Forces. Founded in the 16th century, it is the oldest service branch and is known as the Senior Service...
,
James LindJames Lind FRSE FRCPE was a Scottish physician. He was a pioneer of naval hygiene in the Royal Navy. By conducting the first ever clinical trial, he developed the theory that citrus fruits cured scurvy...
. Scurvy was common among those with poor access to fresh fruit and vegetables, such as remote, isolated
sailorA sailor, mariner, or seaman is a person who navigates water-borne vessels or assists in their operation, maintenance, or service. The term can apply to professional mariners, military personnel, and recreational sailors as well as a plethora of other uses...
s and
soldierA soldier is a member of the land component of national armed forces; whereas a soldier hired for service in a foreign army would be termed a mercenary...
s. While at sea in May 1747, Lind provided some crew members with two oranges and one lemon per day, in addition to normal rations, while others continued on
ciderCider or cyder is a fermented alcoholic beverage made from apple juice. Cider varies in alcohol content from 2% abv to 8.5% abv or more in traditional English ciders. In some regions, such as Germany and America, cider may be termed "apple wine"...
,
vinegarVinegar is a liquid substance consisting mainly of acetic acid and water, the acetic acid being produced through the fermentation of ethanol by acetic acid bacteria. Commercial vinegar is produced either by fast or slow fermentation processes. Slow methods generally are used with traditional...
,
sulfuric acidSulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
or
seawaterSeawater is water from a sea or ocean. On average, seawater in the world's oceans has a salinity of about 3.5% . This means that every kilogram of seawater has approximately of dissolved salts . The average density of seawater at the ocean surface is 1.025 g/ml...
, along with their normal rations. In the
history of scienceThe history of science is the study of the historical development of human understandings of the natural world and the domains of the social sciences....
, this is considered to be the first occurrence of a controlled experiment. The results conclusively showed that citrus fruits prevented the disease. Lind published his work in 1753 in his
Treatise on the Scurvy.
Lind's work was slow to be noticed, partly because his
Treatise was not published until six years after his study, and also because he recommended a lemon juice extract known as
rob. Fresh fruit was very expensive to keep on board, whereas boiling it down to juice allowed easy storage but destroyed the vitamin (especially if boiled in copper kettles). Ship captains concluded wrongly that Lind's other suggestions were ineffective because those juices failed to prevent or cure scurvy.
It was 1795 before the British navy adopted
lemonThe lemon is both a small evergreen tree native to Asia, and the tree's ellipsoidal yellow fruit. The fruit is used for culinary and non-culinary purposes throughout the world – primarily for its juice, though the pulp and rind are also used, mainly in cooking and baking...
s or
limeLime is a term referring to a number of different citrus fruits, both species and hybrids, which are typically round, green to yellow in color, 3–6 cm in diameter, and containing sour and acidic pulp. Limes are a good source of vitamin C. Limes are often used to accent the flavors of foods and...
as standard issue at sea. Limes were more popular, as they could be found in British West Indian Colonies, unlike lemons, which were not found in
British DominionsA dominion, often Dominion, refers to one of a group of autonomous polities that were nominally under British sovereignty, constituting the British Empire and British Commonwealth, beginning in the latter part of the 19th century. They have included Canada, Australia, New Zealand, Newfoundland,...
, and were therefore more expensive. This practice led to the American use of the nickname
"limey"Alternative names for the British include nicknames and terms, including affectionate ones, neutral ones, and derogatory ones to describe the British people and more specifically English, Scottish, Welsh and Northern Irish/Irish people.- Ang Moh :"Ang Moh" is a term to describe British and other...
to refer to the British.
Captain James CookCaptain James Cook, FRS, RN was a British explorer, navigator and cartographer who ultimately rose to the rank of captain in the Royal Navy...
had previously demonstrated and proven the principle of the advantages of carrying
"Sour krout"Sauerkraut , directly translated from German: "sour cabbage", is finely shredded cabbage that has been fermented by various lactic acid bacteria, including Leuconostoc, Lactobacillus, and Pediococcus. It has a long shelf-life and a distinctive sour flavor, both of which result from the lactic acid...
on board, by taking his crews to the
Hawaiian IslandsThe Hawaiian Islands are an archipelago of eight major islands, several atolls, numerous smaller islets, and undersea seamounts in the North Pacific Ocean, extending some 1,500 miles from the island of Hawaii in the south to northernmost Kure Atoll...
and beyond without losing any of his men to scurvy. For this otherwise unheard of feat, the British Admiralty awarded him a medal.
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,
maltMalt is germinated cereal grains that have been dried in a process known as "malting". The grains are made to germinate by soaking in water, and are then halted from germinating further by drying with hot air...
, and
portable soupPortable soup was a kind of dehydrated food used in the 18th and 19th centuries. It was a precursor of the later meat extract and bouillon cubes, and of industrially dehydrated food. It is also known as pocket soop or veal glew. It is a cousin of the glace de viande of French cooking...
.
Even before the antiscorbutic substance was identified, there were indications that it was present in amounts sufficient to prevent scurvy, in nearly all fresh (uncooked and uncured) foods, including raw animal-derived foods. In 1928, the Arctic anthropologist
Vilhjalmur StefanssonVilhjalmur Stefansson was a Canadian Arctic explorer and ethnologist.-Early life:Stefansson, born William Stephenson, was born at Gimli, Manitoba, Canada, in 1879. His parents had emigrated from Iceland to Manitoba two years earlier...
attempted to prove his theory of how the
EskimoEskimos or Inuit–Yupik peoples are indigenous peoples who have traditionally inhabited the circumpolar region from eastern Siberia , across Alaska , Canada, and Greenland....
s are able to avoid scurvy with almost no plant food in their diet, despite the disease's striking European Arctic explorers living on similar high cooked-meat diets. Stefansson theorised that the natives get their vitamin C from fresh meat that is minimally cooked. Starting in February 1928, for one year he and a colleague lived on an exclusively minimally-cooked meat diet while under medical supervision; they remained healthy. Later studies done after vitamin C could be quantified in mostly-raw traditional food diets of the
YukonYukon is the westernmost and smallest of Canada's three federal territories. It was named after the Yukon River. The word Yukon means "Great River" in Gwich’in....
,
InuitThe Inuit are a group of culturally similar indigenous peoples inhabiting the Arctic regions of Canada , Denmark , Russia and the United States . Inuit means “the people” in the Inuktitut language...
, and Métís of the Northern Canada, showed that their daily intake of vitamin C averaged between 52 and 62 mg/day, an amount approximately the
dietary reference intakeThe Dietary Reference Intake is a system of nutrition recommendations from the Institute of Medicine of the U.S. National Academy of Sciences. The DRI system is used by both the United States and Canada and is intended for the general public and health professionals...
(DRI), even at times of the year when little plant-based food was eaten.
Discovery
In 1907, the needed biological-assay model to isolate and identify the antiscorbutic factor was discovered.
Axel HolstAxel Holst was a Norwegian professor of hygiene and bacteriology at the University of Oslo, known for his contributions to beriberi and scurvy....
and Theodor Frølich, two
NorwegianNorway , officially the Kingdom of Norway, is a Nordic unitary constitutional monarchy whose territory comprises the western portion of the Scandinavian Peninsula, Jan Mayen, and the Arctic archipelago of Svalbard and Bouvet Island. Norway has a total area of and a population of about 4.9 million...
physicians studying shipboard
beriberiBeriberi is a nervous system ailment caused by a thiamine deficiency in the diet. Thiamine is involved in the breakdown of energy molecules such as glucose and is also found on the membranes of neurons...
in the Norwegian fishing fleet, wanted a small test mammal to substitute for the pigeons then used in beriberi research. They fed
guinea pigThe guinea pig , also called the cavy, is a species of rodent belonging to the family Caviidae and the genus Cavia. Despite their common name, these animals are not in the pig family, nor are they from Guinea...
s their test diet of grains and flour, which had earlier produced beriberi in their pigeons, and were surprised when classic scurvy resulted instead. This was a serendipitous choice of model. Until that time, scurvy had not been observed in any organism apart from humans, and had been considered an exclusively human disease. (Pigeons, as seed-eating birds, were also later found to make their own vitamin C.) Holst and Frølich found they could cure the disease in guinea pigs with the addition of various fresh foods and extracts. This discovery of a clean animal experimental model for scurvy, made even before the essential idea of
vitamins in foods had even been put forward, has been called the single most important piece of vitamin C research.
In 1912, the
Polish AmericanA Polish American , is a citizen of the United States of Polish descent. There are an estimated 10 million Polish Americans, representing about 3.2% of the population of the United States...
biochemist
Casimir Funk, while researching beriberi in pigeons, developed the concept of vitamins to refer to the non-mineral micronutrients that are essential to health. The name is a blend of "vital", due to the vital biochemical role they play, and "amines" because Funk thought that all these materials were chemical
amineAmines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
s. Although the "e" was dropped after skepticism that all these compounds were amines, the word
vitaminA vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
remained as a generic name for them. One of the
vitamins was thought to be the anti-scorbutic factor in foods discovered by Holst and Frølich. In 1928, this vitamin was referred to as "water-soluble C," although its chemical structure had still not been determined.
From 1928 to 1932, the
HungarianHungary , officially the Republic of Hungary , is a landlocked country in Central Europe. It is situated in the Carpathian Basin and is bordered by Slovakia to the north, Ukraine and Romania to the east, Serbia and Croatia to the south, Slovenia to the southwest and Austria to the west. The...
research team of
Albert Szent-GyörgyiAlbert Szent-Györgyi de Nagyrápolt was a Hungarian physiologist who won the Nobel Prize in Physiology or Medicine in 1937. He is credited with discovering vitamin C and the components and reactions of the citric acid cycle...
and Joseph L. Svirbely, as well as the
AmericanThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
team led by
Charles Glen KingCharles Glen King was an American biochemist who was a pioneer in the field of nutrition research and who isolated vitamin C at the same time as Albert Szent-Györgyi...
in Pittsburgh, first identified the anti-scorbutic factor. Szent-Györgyi had isolated the chemical hexuronic acid from animal adrenal glands at the Mayo clinic, and suspected it to be the antiscorbutic factor, but could not prove it without a biological assay. At the same time, for five years, King's laboratory at the
University of PittsburghThe University of Pittsburgh, commonly referred to as Pitt, is a state-related research university located in Pittsburgh, Pennsylvania, United States. Founded as Pittsburgh Academy in 1787 on what was then the American frontier, Pitt is one of the oldest continuously chartered institutions of...
had been trying to isolate the antiscorbutic factor in lemon juice, using the original 1907 model of scorbutic guinea pigs, which developed scurvy when not fed fresh foods, but were cured by lemon juice. They had also considered hexuronic acid, but had been put off the trail when a coworker made the explicit (and mistaken) experimental claim that this substance was not the antiscorbutic substance.
Finally, in late 1931, Szent-Györgyi gave Svirbely, formerly of King's lab, the last of this hexuronic acid, with the suggestion that it might be the anti-scorbutic factor. By the spring of 1932, King's laboratory had proven this, but published the result without giving Szent-Györgyi credit for it, leading to a bitter dispute over priority claims (in reality it had taken a team effort by both groups, since Szent-Györgyi was unwilling to do the difficult and messy animal studies).
Meanwhile, by 1932, Szent-Györgyi had moved to Hungary and his group had discovered that paprika peppers, a common spice in the Hungarian diet, was a rich source of hexuronic acid, the antiscorbutic factor. With a new and plentiful source of the vitamin, Szent-Györgyi sent a sample to noted British sugar chemist Walter Norman Haworth, who chemically identified it and proved the identification by synthesis in 1933.
{{pp-move-indef}}
-
- This article is about ascorbic acid as a nutrient; for its chemical properties, see the article ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
; for other uses, see the disambiguation pageVitamin C is an essential nutrient, usually ingested as ascorbic acid. The oxidized form, dehydroascorbic acid, can also be absorbed from the diet, and has similar antiscorbutic effects.Vitamin C may also refer to:...
.
{{drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 408979690
| 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(5
H)-one
| image = L-Ascorbic_acid.svg
| width = 200px
| image2 = Ascorbic-acid-from-xtal-1997-3D-balls.png
| width2 = 200px
| Drugs.com = {{drugs.com|MTM|vitamin_c}}
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| pregnancy_US =
| pregnancy_category = A
| legal_AU =
| legal_CA =
| legal_UK =
| legal_US =
| legal_status = general public availability
| routes_of_administration = oral
| bioavailability = rapid & complete
| protein_bound = negligible
| elimination_half-life = varies according to plasma concentration
| excretion = renal
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 50-81-7
| ATC_prefix = A
| ATC_suffix = 11G
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 29073
| PubChem = 5785
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00126
| ChemSpiderID_Ref =
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| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = PQ6CK8PD0R
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00018
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 196
| chemical_formula =
| C=6 | H=8 | O=6
| molecular_weight = 176.12 g/
moleThe mole is a unit of measurement used in chemistry to express amounts of a chemical substance, defined as an amount of a substance that contains as many elementary entities as there are atoms in 12 grams of pure carbon-12 , the isotope of carbon with atomic weight 12. This corresponds to a value...
| smiles = C([C@@H]([C@@H]1C(=C(C(=O)O1)O)O)O)O
| InChI = 1/C6H8O6/c7-1-2(8)5-3(9)4(10)6(11)12-5/h2,5,7-10H,1H2/t2-,5+/m0/s1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C6H8O6/c7-1-2(8)5-3(9)4(10)6(11)12-5/h2,5,7-10H,1H2/t2-,5+/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = CIWBSHSKHKDKBQ-JLAZNSOCSA-N
| synonyms =
L-ascorbic acid
| density = 1.694
| melting_point = 190
| boiling_point = 553
}}
{{Multiple image|direction=vertical|align=right|image1=Ascorbic acid structure.png|image2=Dehydroascorbic acid.png|width=150|caption1=
ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
(
reduced formA reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...
)|caption2=
dehydroascorbic acidDehydroascorbic acid is an oxidized form of ascorbic acid. It is actively imported into the endoplasmic reticulum of cells via glucose transporters. It is trapped therein by reduction back to ascorbate by glutathione and other thiols. Therefore, L-dehydroascorbic acid is a vitamin C compound much...
(
oxidized formAn oxidizing agent can be defined as a substance that removes electrons from another reactant in a redox chemical reaction...
)}}
Vitamin C or
L-ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
or
L-ascorbate is an
essential nutrientAn essential nutrient is a nutrient required for normal body functioning that either cannot be synthesized by the body at all, or cannot be synthesized in amounts adequate for good health , and thus must be obtained from a dietary source...
for humans and certain other animal species. In living organisms ascorbate acts as an
antioxidantAn antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
by protecting the body against
oxidative stressOxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
. It is also a
cofactorA cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
in at least eight
enzymaticEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
reactions including several
collagenCollagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
synthesis reactions that, when dysfunctional, cause the most severe symptoms of
scurvyScurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
. In animals these reactions are especially important in wound-healing and in preventing bleeding from capillaries.
Ascorbate (an ion of
ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
) is required for a range of essential
metabolic reactionsMetabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
in all animals and plants. It is
made internallyBiosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
by almost all organisms although notable mammalian group exceptions are most or all of the order chiroptera (bats), guinea pigs,
capybaraThe capybara , also known as capivara in Portuguese, and capibara, chigüire in Venezuela, Colombia, and Ecuador ronsoco in Peru, chigüiro, and carpincho in Spanish, is the largest living rodent in the world. Its closest relatives are agouti, chinchillas, coyphillas, and guinea pigs...
s, and one of the two major
primateA primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...
suborders, the Anthropoidea (
HaplorrhiniThe haplorhines, the "dry-nosed" primates , are members of the Haplorhini clade: the prosimian tarsiers and the anthropoids...
) (tarsiers, monkeys and apes, including human beings). Ascorbic acid is also not synthesized by some species of birds and fish. All species that do not synthesize ascorbate require it in the diet. Deficiency in this
vitaminA vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
causes the disease
scurvyScurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
in humans. It is also widely used as a
food additiveFood additives are substances added to food to preserve flavor or enhance its taste and appearance.Some additives have been used for centuries; for example, preserving food by pickling , salting, as with bacon, preserving sweets or using sulfur dioxide as in some wines...
.
The full extent of the effects and recommended daily intake of vitamin C are matters of ongoing debate, with
RDIThe Reference Daily Intake or Recommended Daily Intake is the daily intake level of a nutrient that is considered to be sufficient to meet the requirements of 97–98% of healthy individuals in every demographic in the United States .The RDI is used to determine the Daily Value of foods,...
ranging from 45mg to 400mg or more per day.
Biological significance
{{further|
ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
}}
Vitamin C is purely the
L-enantiomerIn chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
of ascorbate; the opposite
D-enantiomerIn chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
has no physiological significance. Both forms are
mirror imagesA chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
of the same molecular structure. When
L-ascorbate, which is a strong
reducing agentA reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...
, carries out its
reducingRedox reactions describe all chemical reactions in which atoms have their oxidation state changed....
function, it is converted to its
oxidizedRedox reactions describe all chemical reactions in which atoms have their oxidation state changed....
form,
L-dehydroascorbateDehydroascorbic acid is an oxidized form of ascorbic acid. It is actively imported into the endoplasmic reticulum of cells via glucose transporters. It is trapped therein by reduction back to ascorbate by glutathione and other thiols. Therefore, L-dehydroascorbic acid is a vitamin C compound much...
.
L-dehydroascorbate can then be reduced back to the active
L-ascorbate form in the body by
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s and
glutathioneGlutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
. During this process semidehydroascorbic acid radical is formed. Ascorbate free radical reacts poorly with oxygen, and thus will not create a superoxide. Instead two semidehydroascorbate radicals will react and form one ascorbate and one dehydroascorbate. With the help of glutathione, dehydroxyascorbate is converted back to ascorbate. The presence of glutathione is crucial since it spares ascorbate and improves antioxidant capacity of blood. Without it dehydroxyascorbate could not convert back to ascorbate.
L-Ascorbate is a
weakA weak acid is an acid that dissociates incompletely. It does not release all of its hydrogens in a solution, donating only a partial amount of its protons to the solution...
sugar acid structurally related to
glucoseGlucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
that naturally occurs attached either to a
hydrogen ionHydrogen ion is recommended by IUPAC as a general term for all ions of hydrogen and its isotopes.Depending on the charge of the ion, two different classes can be distinguished: positively charged ions and negatively charged ions....
, forming
ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
, or to a
metal ionA metal , is an element, compound, or alloy that is a good conductor of both electricity and heat. Metals are usually malleable and shiny, that is they reflect most of incident light...
, forming a mineral ascorbate.
Biosynthesis in different species
The vast majority of animals and plants are able to synthesize their own vitamin C, through a sequence of four
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
-driven steps, which convert
glucoseGlucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
to vitamin C. The glucose needed to produce ascorbate in the liver (in
mammalMammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s and
perching birdA passerine is a bird of the order Passeriformes, which includes more than half of all bird species. Sometimes known as perching birds or, less accurately, as songbirds, the passerines form one of the most diverse terrestrial vertebrate orders: with over 5,000 identified species, it has roughly...
s) is extracted from
glycogenGlycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...
; ascorbate synthesis is a glycogenolysis-dependent process. In
reptileReptiles are members of a class of air-breathing, ectothermic vertebrates which are characterized by laying shelled eggs , and having skin covered in scales and/or scutes. They are tetrapods, either having four limbs or being descended from four-limbed ancestors...
s and
birdBirds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s the biosynthesis is carried out in the
kidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s.
Among the animals that have lost the ability to synthesise vitamin C are
simianThe simians are the "higher primates" familiar to most people: the Old World monkeys and apes, including humans, , and the New World monkeys or platyrrhines. Simians tend to be larger than the "lower primates" or prosimians.- Classification and evolution :The simians are split into three groups...
s and
tarsierTarsiers are haplorrhine primates of the genus Tarsius, a genus in the family Tarsiidae, which is itself the lone extant family within the infraorder Tarsiiformes...
s, which together make up one of two major
primateA primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...
suborders, the anthropoidea, also called
haplorrhiniThe haplorhines, the "dry-nosed" primates , are members of the Haplorhini clade: the prosimian tarsiers and the anthropoids...
. This group includes humans. The other more primitive primates (
strepsirrhiniThe clade Strepsirrhini is one of the two suborders of primates. Madagascar's only non-human primates are strepsirrhines, and others can be found in southeast Asia and Africa...
) have the ability to make vitamin C. Synthesis does not occur in a number of species (perhaps all species) in the small rodent family
caviidaeThe cavy family is a family of rodents native to South America, and including the domestic guinea pig, wild cavies, and the capybara, among other animals...
that includes
guinea pigThe guinea pig , also called the cavy, is a species of rodent belonging to the family Caviidae and the genus Cavia. Despite their common name, these animals are not in the pig family, nor are they from Guinea...
s and
capybaraThe capybara , also known as capivara in Portuguese, and capibara, chigüire in Venezuela, Colombia, and Ecuador ronsoco in Peru, chigüiro, and carpincho in Spanish, is the largest living rodent in the world. Its closest relatives are agouti, chinchillas, coyphillas, and guinea pigs...
s, but occurs in other rodents (rats and mice do not need vitamin C in their diet, for example). A number of species of
passerineA passerine is a bird of the order Passeriformes, which includes more than half of all bird species. Sometimes known as perching birds or, less accurately, as songbirds, the passerines form one of the most diverse terrestrial vertebrate orders: with over 5,000 identified species, it has roughly...
birds also do not synthesise, but not all of them, and those that don't are not clearly related; there is a theory that the ability was lost separately a number of times in birds.
All tested families of bats, including major insect and fruit-eating bat families, cannot synthesise vitamin C. A trace of GLO was detected in only 1 of 34 bat species tested, across the range of 6 families of bats tested.
These animals all lack the
L-gulonolactone oxidaseL-gulonolactone oxidase is an enzyme that catalyzes the reaction of D-glucuronolactone with oxygen to L-xylo-hex-3-gulonolactone and hydrogen peroxide. It uses FAD as a cofactor...
(GULO) enzyme, which is required in the last step of vitamin C synthesis, because they have a differing non-synthesising gene for the enzyme (
PseudogenePseudogenes are dysfunctional relatives of known genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell...
ΨGULO). A similar non-functional gene is present in the genome of the guinea pigs and in primates, including humans. Some of these species (including humans) are able to make do with the lower levels available from their diets by recycling oxidised vitamin C.
Most
simianThe simians are the "higher primates" familiar to most people: the Old World monkeys and apes, including humans, , and the New World monkeys or platyrrhines. Simians tend to be larger than the "lower primates" or prosimians.- Classification and evolution :The simians are split into three groups...
s consume the vitamin in amounts 10 to 20 times higher than that recommended by governments for humans. This discrepancy constitutes much of the basis of the controversy on current recommended dietary allowances. It is countered by arguments that humans are very good at conserving dietary vitamin C, and are able to maintain blood levels of vitamin C comparable with other simians, on a far smaller dietary intake.
An adult
goatThe domestic goat is a subspecies of goat domesticated from the wild goat of southwest Asia and Eastern Europe. The goat is a member of the Bovidae family and is closely related to the sheep as both are in the goat-antelope subfamily Caprinae. There are over three hundred distinct breeds of...
, 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 the biosynthesis will increase "manyfold under stress". Trauma or injury has also been demonstrated to use up large quantities of vitamin C in humans.
Some
microorganismA microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...
s such as the yeast
Saccharomyces cerevisiaeSaccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
have been shown to be able to synthesize vitamin C from
simple sugarsMonosaccharides are the most basic units of biologically important carbohydrates. They are the simplest form of sugar and are usually colorless, water-soluble, crystalline solids. Some monosaccharides have a sweet taste. Examples of monosaccharides include glucose , fructose , galactose, xylose...
.
Vitamin C in evolution
Venturi and Venturi suggested that the antioxidant action of ascorbic acid developed first in the plant kingdom when, about 500 million years ago (mya), plants began to adapt to antioxidant-mineral-deficient fresh-waters of
estuariesAn estuary is a partly enclosed coastal body of water with one or more rivers or streams flowing into it, and with a free connection to the open sea....
. Some biologists suggested that many vertebrates had developed their metabolic adaptive strategies in estuary environment. In this theory, some 400–300 mya, when living
plantPlants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
s and
animalAnimals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...
s first began the move from the sea to rivers and land, environmental
iodine deficiencyIodine is an essential trace element; the thyroid hormones thyroxine and triiodotyronine contain iodine. In areas where there is little iodine in the diet—typically remote inlandareas where no marine foods are eaten—iodine deficiency gives rise to...
was a challenge to the
evolutionEvolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
of terrestrial life. In plants, animals and fishes, the terrestrial diet became deficient in many essential antioxidant marine micronutrients, including
iodineIodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
,
seleniumSelenium is a chemical element with atomic number 34, chemical symbol Se, and an atomic mass of 78.96. It is a nonmetal, whose properties are intermediate between those of adjacent chalcogen elements sulfur and tellurium...
,
zincZinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
,
copperCopper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
,
manganeseManganese is a chemical element, designated by the symbol Mn. It has the atomic number 25. It is found as a free element in nature , and in many minerals...
,
ironIron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
, etc. Freshwater
algaeAlgae are a large and diverse group of simple, typically autotrophic organisms, ranging from unicellular to multicellular forms, such as the giant kelps that grow to 65 meters in length. They are photosynthetic like plants, and "simple" because their tissues are not organized into the many...
and terrestrial plants, in replacement of marine
antioxidantAn antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
s, slowly optimized the production of other
endogenousEndogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...
antioxidants such as
ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
,
polyphenolA polyphenol antioxidant is a type of antioxidant containing a polyphenolic substructure. Numbering over 4,000 distinct species, many of these compounds have antioxidant activity in vitro but are unlikely to have antioxidant roles in vivo...
s,
carotenoidCarotenoids are tetraterpenoid organic pigments that are naturally occurring in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some bacteria, and some types of fungus. Carotenoids can be synthesized fats and other basic organic metabolic building...
s,
tocopherolTocopherols are a class of chemical compounds of which many have vitamin E activity. It is a series of organic compounds consisting of various methylated phenols...
s etc., some of which became essential “
vitaminA vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
s” in the diet of terrestrial animals (vitamins C, A, E, etc.).
Ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
or vitamin C is a common enzymatic co-factor in mammals used in the synthesis of
collagenCollagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
. Ascorbate is a powerful
reducing agentA reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...
capable of rapidly scavenging a number of
reactive oxygen speciesReactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
(ROS). Freshwater teleost fishes also require dietary vitamin C in their diet or they will get scurvy. The most widely recognized symptoms of vitamin C deficiency in fishes are
scoliosisScoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
,
lordosisLordosis is a medical term used to describe an inward curvature of a portion of the lumbar and cervical vertebral column. Two segments of the vertebral column, namely cervical and lumbar, are normally lordotic, that is, they are set in a curve that has its convexity anteriorly and concavity...
and dark skin coloration. Freshwater salmonids also show impaired
collagenCollagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
formation, internal/fin hemorrhage, spinal curvature and increased mortality. If these fishes are housed in seawater with algae and phytoplankton, then vitamin supplementation seems to be less important, it is presumed because of the availability of other, more ancient, antioxidants in natural marine environment.
Some scientists have suggested that loss of the vitamin C biosynthesis pathway may have played a role in the theory of rapid evolutionary changes, leading to hominids and the emergence of human beings. However, another theory based on the theory of evolution is that the loss of ability to make vitamin C in simians may have occurred much farther back in evolutionary history than the emergence of humans or even apes, since it evidently occurred rather soon after the appearance of the first primates, yet sometime after the split of early primates into its two major suborders
haplorrhiniThe haplorhines, the "dry-nosed" primates , are members of the Haplorhini clade: the prosimian tarsiers and the anthropoids...
(which cannot make vitamin C) and its sister suborder of non-tarsier prosimians, the
strepsirrhiniThe clade Strepsirrhini is one of the two suborders of primates. Madagascar's only non-human primates are strepsirrhines, and others can be found in southeast Asia and Africa...
("wet-nosed" primates), which retained the ability to make vitamin C. According to molecular clock dating, these two suborder primate branches parted ways about 63 to 60 Mya Approximately three to five million years later (58 Mya), only a short time afterward from an evolutionary perspective, the infraorder
TarsiiformesTarsiiformes are a group of primates that was once ranged across Europe, northern Africa, Asia, and North America, but today all living species are found in the islands of Southeast Asia. Tarsiers are the only living members of the infraorder, and also include the extinct Tarsius eocaenus from the...
, whose only remaining family is that of the tarsier (Tarsiidae), branched off from the other haplorrhines. Since tarsiers also cannot make vitamin C, this implies the mutation had already occurred, and thus must have occurred between these two marker points (63 to 58 Mya).
It has been noted that the loss of the ability to synthesize ascorbate strikingly parallels the inability to break down
uric acidUric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
, also a characteristic of primates. Uric acid and ascorbate are both strong
reducing agentA reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...
s. This has led to the suggestion that, in higher primates, uric acid has taken over some of the functions of ascorbate.
Absorption, transport, and disposal
Ascorbic acid is absorbed in the body by both active transport and simple diffusion. Sodium-Dependent Active Transport—Sodium-Ascorbate Co-Transporters (SVCTs) and Hexose transporters (GLUTs)—are the two transporters required for absorption. SVCT1 and SVCT2 import the reduced form of ascorbate across plasma membrane. GLUT1 and GLUT3 are the two glucose transporters, and transfer only dehydroascorbic acid form of Vitamin C. Although dehydroascorbic acid is absorbed in higher rate than ascorbate, the amount of dehydroascorbic acid found in plasma and tissues under normal conditions is low, as cells rapidly reduce dehydroascorbic acid to ascorbate. Thus, SVCTs appear to be the predominant system for vitamin C transport in the body.
SVCT2 is involved in vitamin C transport in almost every tissue, the notable exception being red blood cells, which lose SVCT proteins during maturation. "SVCT2 knockout" animals genetically engineered to lack this functional gene, die shortly after birth, suggesting that
SVCT2-mediated vitamin C transport is necessary for life.
With regular intake the absorption rate varies between 70 to 95%. However, the degree of absorption decreases as intake increases. At high intake (1.25g), fractional human absorption of ascorbic acid may be as low as 33%; at low intake (<20 mg) the absorption rate can reach up to 98%. Ascorbate concentrations over renal re-absorption threshold pass freely into the urine and are excreted. At high dietary doses (corresponding to several hundred mg/day in humans) ascorbate is accumulated in the body until the plasma levels reach the renal resorption threshold, which is about 1.5 mg/dL in men and 1.3 mg/dL in women. Concentrations in the plasma larger than this value (thought to represent body saturation) are rapidly excreted in the urine with a half-life of about 30 minutes. Concentrations less than this threshold amount are actively retained by the kidneys, and the excretion half-life for the remainder of the vitamin C store in the body thus increases greatly, with the half-life lengthening as the body stores are depleted. This half-life rises until it is as long as 83 days by the onset of the first symptoms of scurvy.
Although the body's maximal store of vitamin C is largely determined by the renal threshold for blood, there are many tissues that maintain vitamin C concentrations far higher than in blood. Biological
tissueTissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
s that accumulate over 100 times the level in blood plasma of vitamin C are the
adrenal glandIn mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
s, pituitary,
thymusThe thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
,
corpus luteumThe corpus luteum is a temporary endocrine structure in mammals, involved in production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A...
, and
retinaThe vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
.
Those with 10 to 50 times the concentration present in blood plasma include the
brainThe human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
,
spleenThe spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
,
lungThe human lungs are the organs of respiration in humans. Humans have two lungs, with the left being divided into two lobes and the right into three lobes. Together, the lungs contain approximately of airways and 300 to 500 million alveoli, having a total surface area of about in...
,
testicleThe testicle is the male gonad in animals. Like the ovaries to which they are homologous, testes are components of both the reproductive system and the endocrine system...
, lymph nodes,
liverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
,
thyroidThe thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
,
small intestinalThe small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
mucosaThe mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
, leukocytes,
pancreasThe pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
,
kidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
and salivary glands.
Ascorbic acid can be oxidized (broken down) in the human body by the enzyme
L-ascorbate oxidaseIn enzymology, a L-ascorbate oxidase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are L-ascorbate and O2, whereas its two products are dehydroascorbate and H2O....
. Ascorbate that is not directly excreted in the urine as a result of body saturation or destroyed in other body metabolism is oxidized by this enzyme and removed.
Deficiency
{{Main|Scurvy}}
ScurvyScurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
is an
avitaminosisAvitaminosis is any disease caused by chronic or long-term vitamin deficiency or caused by a defect in metabolic conversion, such as tryptophan to niacin...
resulting from lack of vitamin C, since without this vitamin, the synthesised
collagenCollagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
is too unstable to perform its function. Scurvy leads to the formation of brown spots on the skin, spongy gums, and bleeding from all
mucous membraneThe mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
s. 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 can store only a certain amount of vitamin C, and so the body stores are depleted if fresh supplies are not consumed. The time frame for onset of symptoms of scurvy in unstressed adults switched to a completely vitamin C free diet, however, may range from one month to more than six months, depending on previous loading of vitamin C (see below).
It has been shown that smokers who have diets poor in vitamin C are at a higher risk of lung-borne diseases than those smokers who have higher concentrations of vitamin C in the blood.
Nobel prize winner
Linus PaulingLinus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
and G. C. Willis have asserted that chronic long term low blood levels of vitamin C ("
chronicA chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
scurvy") is a cause of
atherosclerosisAtherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
.
Western societies generally consume far more than sufficient Vitamin C to prevent scurvy. In 2004, a Canadian Community health survey reported that Canadians of 19 years and above have intakes of vitamin C from food of 133 mg/d for males and 120 mg/d for females; these are higher than the RDA recommendations.
Notable human dietary studies of experimentally-induced scurvy have been conducted on conscientious objectors during WW II in Britain, and on Iowa state prisoners in the late 1960s. These studies both found that all obvious symptoms of scurvy previously induced by an experimental scorbutic diet with extremely low vitamin C content could be completely reversed by additional vitamin C supplementation of only 10 mg a day. In these experiments, there was no clinical difference noted between men given 70 mg vitamin C per day (which produced blood level of vitamin C of about 0.55 mg/dl, about 1/3 of tissue saturation levels), and those given 10 mg per day. Men in the prison study developed the first signs of scurvy about 4 weeks after starting the vitamin C free diet, whereas in the British study, six to eight months were required, possibly due to the pre-loading of this group with a 70 mg/day supplement for six weeks before the scorbutic diet was fed.
Men in both studies on a diet devoid, or nearly devoid, of vitamin C had blood levels of vitamin C too low to be accurately measured when they developed signs of scurvy, and in the Iowa study, at this time were estimated (by labeled vitamin C dilution) to have a body pool of less than 300 mg, with daily turnover of only 2.5 mg/day, implying a instantaneous half-life of 83 days by this time (elimination constant of 4 months).
Moderately higher blood levels of vitamin C measured in healthy persons have been found to be prospectively correlated with decreased risk of
cardiovascular diseaseHeart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
and
ischaemic heart diseaseIschaemic or ischemic heart disease , or myocardial ischaemia, is a disease characterized by ischaemia of the heart muscle, usually due to coronary artery disease...
, and an increase life expectancy. The same study found an inverse relationship between blood vitamin C levels and cancer risk in men, but not in women. An increase in blood level of 20 micromol/L of vitamin C (about 0.35 mg/dL, and representing a theoretical additional 50 grams of fruit and vegetables per day) was found epidemiologically to reduce the all-cause risk of
mortalityMortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
, four years after measuring it, by about 20%. However, because this was not an intervention study, causation could not be proven, and vitamin C blood levels acting as a proxy marker for other differences between the groups could not be ruled out. However, the four-year long and prospective nature of the study did rule out proxy effect from any vitamin C lowering effects of immediately terminal illness, or near-end-of-life poor health.
Studies with much higher doses of vitamin C, usually between 200 and 6000 mg/day, for the treatment of infections and wounds have shown inconsistent results. Combinations of antioxidants seem to improve wound healing.
Physiological function in mammals
In humans, vitamin C is essential to a healthy diet as well as being a highly effective
antioxidantAn antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
, acting to lessen
oxidative stressOxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
; a substrate for
ascorbate peroxidaseAscorbate peroxidases are enzymes that detoxify peroxides such as hydrogen peroxide using ascorbate as a substrate. The reaction they catalyse is the transfer of electrons from ascorbate to a peroxide, producing dehydroascorbate and water as products.Ascorbate + Hydrogen peroxide →...
in plants (APX is plant specific enzyme); and an enzyme
cofactorA cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
for the
biosynthesisBiosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
of many important biochemicals. Vitamin C acts as an
electron donorAn electron donor is a chemical entity that donates electrons to another compound. It is a reducing agent that, by virtue of its donating electrons, is itself oxidized in the process....
for important
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s:
Collagen, carnitine, and tyrosine synthesis, and microsomal metabolism
Ascorbic acid performs numerous physiological functions in the human body. These functions include the synthesis of
collagenCollagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
,
carnitineCarnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids for the generation of metabolic energy. It is widely...
, and neurotransmitters; the synthesis and
catabolismCatabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...
of
tyrosineTyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
; and the metabolism of
microsomeIn cell biology, microsomes are vesicle-like artifacts re-formed from pieces of the endoplasmic reticulum when eukaryotic cells are broken-up in the laboratory; by definition, microsomes are not ordinarily present in living cells....
. During biosynthesis ascorbate acts as a reducing agent,
donating electronsAn electron donor is a chemical entity that donates electrons to another compound. It is a reducing agent that, by virtue of its donating electrons, is itself oxidized in the process....
and preventing oxidation to keep iron and copper atoms in their reduced states.
Vitamin C acts as an electron donor for eight different enzymes:
- Three enzymes participate in collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
hydroxylationHydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...
. These reactions add hydroxyl groupsHydroxide is a diatomic anion with chemical formula OH−. It consists of an oxygen and a hydrogen atom held together by a covalent bond, and carrying a negative electric charge. It is an important but usually minor constituent of water. It functions as a base, as a ligand, a nucleophile, and a...
to the amino acids prolineProline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
or lysineLysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
in the collagen molecule via prolyl hydroxylaseProlyl hydroxylase is an enzyme involved in the production of collagen, acting to hydroxylate proline to hydroxyproline....
and lysyl hydroxylaseLysyl hydroxylase is an oxygenase enzyme that catalyzes the hydroxylation of lysine to hydroxylysine. This reaction is necessary to the formation and stabilization of collagen. It takes place following protein synthesis...
, both requiring vitamin C as a cofactorA cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
. Hydroxylation allows the collagen molecule to assume its triple helixA helix is a type of smooth space curve, i.e. a curve in three-dimensional space. It has the property that the tangent line at any point makes a constant angle with a fixed line called the axis. Examples of helixes are coil springs and the handrails of spiral staircases. A "filled-in" helix – for...
structure, and thus vitamin C is essential to the development and maintenance of scar tissueGranulation tissue is the perfused, fibrous connective tissue that replaces a fibrin clot in healing wounds. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size it heals...
, blood vesselThe blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s, and cartilageCartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
.
- Two enzymes are necessary for synthesis of carnitine
Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids for the generation of metabolic energy. It is widely...
. Carnitine is essential for the transport of fatty acidIn chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s into mitochondria for ATPAdenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
generation.
- The remaining three enzymes have the following functions in common, but have other functions as well:
- dopamine beta hydroxylase
Dopamine β-hydroxylase is an enzyme that converts dopamine to norepinephrine.DBH is a 290 kDa copper-containing oxygenase consisting of four identical subunits, and its activity requires ascorbate as a cofactor...
participates in the biosynthesis of norepinephrineNorepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
from dopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
.
- another enzyme adds amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
groups to peptide hormonePeptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.Like other proteins, peptide hormones are synthesized in cells from amino acids according to an mRNA template, which is itself synthesized from a DNA template inside the...
s, greatly increasing their stability.
- one modulates tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
metabolism.
Antioxidant
Ascorbic acid is well known for its antioxidant activity, acting as a reducing agent to reverse oxidation in liquids. When there are more
free radicalsRadicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
(
reactive oxygen speciesReactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
, ROS) in the human body than
antioxidantAn antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
s, the condition is called
oxidative stressOxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
, and has an impact on
cardiovascular diseaseHeart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
,
hypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, chronic inflammatory diseases, diabetes as well as on critically ill patients and individuals with severe burns. Individuals experiencing oxidative stress have ascorbate blood levels lower than 45 µmol/L, compared to healthy individual who range between 61.4-80 µmol/L.
It is not yet certain whether vitamin C and antioxidants in general prevent oxidative stress-related diseases and promote health.
Clinical studiesClinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
regarding the effects of vitamin C
supplementationA dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
on
lipoproteinA lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...
s and
cholesterolCholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
have found that vitamin C supplementation does not improve disease markers in the blood. Vitamin C may contribute to decreased risk of cardiovascular disease and strokes through a small reduction in
systolic blood pressureBlood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, and was also found to both increase
ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
levels and reduce levels of
resistinResistin also known as adipose tissue-specific secretory factor or C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein is a cysteine-rich protein that in humans is encoded by the RETN gene....
serum, another likely determinant of
oxidative stressOxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
and cardiovascular risk. However, so far there is no consensus that vitamin C intake has an impact on cardiovascular risks in general, and an array of studies found negative results.
Meta-analysisIn statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
of a large number of studies on antioxidants, including vitamin C supplementation, found no relationship between vitamin C and mortality.
Pro-oxidant
Ascorbic acid behaves not only as an antioxidant but also as a
pro-oxidantPro-oxidants are chemicals that induce oxidative stress, through either creating reactive oxygen species or inhibiting antioxidant systems. The oxidative stress produced by these chemicals can damage cells and tissues...
. Ascorbic acid has been shown to reduce transition metals, such as cupric ions (Cu
2+), to cuprous (Cu
1+), and ferric ions (Fe
3+) to ferrous (Fe
2+) during conversion from ascorbate to dehydroascorbate
in vitroIn vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
. This reaction can generate
superoxideA superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...
and other ROS. However, in the body, free transition elements are unlikely to be present while iron and copper are bound to diverse proteins and the
intravenousIntravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
use of vitamin C does not appear to increase pro-oxidant activity. Thus, ascorbate as a pro-oxidant is unlikely to convert metals to create ROS
in vivoIn vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
. However, vitamin C supplementation has been associated with increased DNA damage in the
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s of healthy volunteers.
Immune system
Vitamin C is found in high concentrations in immune cells, and is consumed quickly during infections. It is not certain how vitamin C interacts with the immune system; it has been hypothesized to modulate the activities of
phagocytePhagocytes are the white blood cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are...
s, the production of
cytokineCytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s and
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s, and the number of
cell adhesion moleculeCell Adhesion Molecules are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix in the process called cell adhesion....
s in
monocyteMonocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
s.
Antihistamine
Vitamin C is a natural
antihistamineAn H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...
. It both prevents
histamineHistamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
release and increases the detoxification of histamine. A 1992 study found that taking 2 grams vitamin C daily lowered blood histamine levels 38 percent in healthy adults in just one week. It has also been noted that low concentrations of serum vitamin C has been correlated with increased serum histamine levels.{{Citation needed|date=September 2010}}
Physiologic function in plants
Ascorbic acid is associated with chloroplasts and apparently plays a role in ameliorating the oxidative stress of photosynthesis. In addition, it has a number of other roles in cell division and protein modification. Plants appear to be able to make ascorbate by at least one other biochemical route that is different from the major route in animals, although precise details remain unknown.
Daily requirements
The
North AmericanNorth American generally refers to an entity, people, group, or attribute of North America, especially of the United States and Canada together.-Culture:*North American English, a collective term used to describe American English and Canadian English...
Dietary Reference IntakeThe Dietary Reference Intake is a system of nutrition recommendations from the Institute of Medicine of the U.S. National Academy of Sciences. The DRI system is used by both the United States and Canada and is intended for the general public and health professionals...
recommends 90 milligrams per day and no more than 2 grams (2,000 milligrams) per day. Other related species sharing the same inability to produce vitamin C and requiring
exogenousExogenous refers to an action or object coming from outside a system. It is the opposite of endogenous, something generated from within the system....
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. It is generally agreed that a balanced diet{{Clarify|date=July 2011}} without supplementation contains enough vitamin C to prevent scurvy in an average healthy adult, while those who are pregnant, smoke tobacco, or are under stress require slightly more. However, the amount of Vitamin C necessary to prevent scurvy is less than the amount required for optimal health, as there are a number of other chronic diseases whose risk are increased by a low vitamin C intake, including cancer, heart disease, and cataracts. A 1999 review suggested a dose of 90–100 mg Vitamin C daily is required to optimally protect against these diseases, in contrast to the lower 45 mg daily required to prevent scurvy.
High doses (thousands of milligrams) may result in
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
in healthy adults, as a result of the osmotic water-retaining effect of the unabsorbed portion in the gastrointestinal tract (similar to cathartic osmotic
laxativeLaxatives are foods, compounds, or drugs taken to induce bowel movements or to loosen the stool, most often taken to treat constipation. Certain stimulant, lubricant, and saline laxatives are used to evacuate the colon for rectal and/or bowel examinations, and may be supplemented by enemas under...
s). Proponents of
orthomolecular medicineOrthomolecular medicine is a form of complementary and alternative medicine that seeks to maintain health and prevent or treat diseases by optimizing nutritional intake and/or prescribing supplements...
claim the onset of
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
to be an indication of where the body’s true vitamin C requirement lies, though this has not been clinically verified.
| United States vitamin C recommendations |
| Recommended Dietary Allowance (adult male) |
90 mg per day |
| Recommended Dietary Allowance (adult female) |
75 mg per day |
| Tolerable Upper Intake Level (adult male) |
2,000 mg per day |
| Tolerable Upper Intake Level (adult female) |
2,000 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
The Food Standards Agency is a non-ministerial government department of the Government of the United Kingdom. It is responsible for protecting public health in relation to food throughout the United Kingdom and is led by a board appointed to act in the public interest...
- 45 milligrams per day: the World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
- 90 mg/day (males) and 75 mg/day (females): Health Canada 2007
- 60–95 milligrams per day: United States' National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
.
The United States defined
Tolerable Upper Intake LevelThe Dietary Reference Intake is a system of nutrition recommendations from the Institute of Medicine of the U.S. National Academy of Sciences. The DRI system is used by both the United States and Canada and is intended for the general public and health professionals...
for a 25-year-old male is 2,000 milligrams per day.
Therapeutic uses
{{further|
Vitamin C and the common coldThe common cold is caused by several strains of viruses including the rhinovirus and the coronavirus. Colds are the leading cause of doctor's visits and the number one reason for absences from work and school...
}}
Vitamin C functions as an
antioxidantAn antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
and is necessary for the treatment and prevention of
scurvyScurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
, though in nearly all cases dietary intake is adequate to prevent deficiency and supplementation is not necessary. Though vitamin C has been promoted as useful in the treatment of a variety of conditions, most of these uses are poorly supported by the evidence and sometimes contraindicated. Vitamin C may be useful in lowering serum
uric acidUric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
levels, resulting in a correspondingly lower incidence of
goutGout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
. Neither prophylactic nor therapeutic use is supported in the prevention or treatment of
pneumoniaPneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
.
People with a the highest levels of ascorbic acid in their blood stream seem to be at a significantly reduced risk of having a
strokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
and low ascorbic acid has been suggested as a way of identifying those at high risk of stroke.
Vitamin C's effect on the common cold has been extensively researched. It has not been shown effective in prevention or treatment of the common cold, except in limited circumstances (specifically, individuals exercising vigorously in cold environments). Routine vitamin C supplementation does not reduce the incidence or severity of the
common coldThe common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
in the general population, though it may reduce the duration of illness.
Vitamin C megadosage
{{Main|Vitamin C megadosage}}
Several individuals and organizations advocate large doses of vitamin C in excess of 10–100 times RDI in the form of oral or
intravenous therapyIntravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
. Large, randomized
clinical trialClinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s on the effects of high doses on the general population have never taken place. Arguments for megadosage are based on the diets of closely related apes, the hypothesized diet of prehistoric humans, and that most mammals synthesize vitamin C rather than relying on dietary intake.
Linus PaulingLinus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
spent much of the later part of his life advocating for the use of megadose vitamin C and believed the established RDA was sufficient to prevent
scurvyScurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
, but not necessarily the dosage for optimal health. Megadoses have been promoted for the treatment or prevention of various conditions, including
cancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, the common cold, and
coronary diseaseCoronary disease refers to the failure of coronary circulation to supply adequate circulation to cardiac muscle and surrounding tissue. It is already the most common form of disease affecting the heart and an important cause of premature death in Europe, the Baltic states, Russia, North and South...
. These uses are not supported by clinical evidence, and in some cases harm may result.
Testing for ascorbate levels in the body
Simple tests use dichlorophenolindophenol, a
redox indicatorA redox indicator is an indicator that undergoes a definite color change at a specific electrode potential....
, to measure the levels of vitamin C in the
urineUrine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
and in
serumIn physiology, the term serous fluid is used for various bodily fluids that are typically pale yellow and transparent, and of a benign nature, that fill the inside of body cavities. Serous fluid originates from serous glands, with secretions enriched with proteins and water. Serous fluid may also...
or
blood plasmaBlood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
. However these reflect recent dietary intake rather than the level of vitamin C in body stores. Reverse phase
high performance liquid chromatographyHigh-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...
is used for determining the storage levels of vitamin C within
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s and
tissueTissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
.
It has been observed that while serum or blood plasma levels follow the
circadian rhythmA circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...
or short term dietary changes, those within tissues themselves are more stable and give a better view of the availability of ascorbate within the organism. However, very few hospital laboratories are adequately equipped and trained to carry out such detailed analyses, and require samples to be analyzed in specialized laboratories.
Common side-effects
Relatively large doses of ascorbic acid may cause indigestion, particularly when taken on an empty stomach. However, taking vitamin C in the form of
sodium ascorbateSodium ascorbate is a more bioavailable form of vitamin C that is an alternative to taking ascorbic acid as a supplement. The molecular formula of this chemical compound is C6H7NaO6...
and calcium ascorbate may minimize this effect. When taken in large doses, ascorbic acid causes
diarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
in healthy subjects. In one trial in 1936, doses up to 6 grams of ascorbic acid were given to 29 infants, 93 children of preschool and school age, and 20 adults for more than 1400 days. With the higher doses, toxic manifestations were observed in five adults and four infants. The signs and symptoms in adults were nausea, vomiting, diarrhea, flushing of the face, headache, fatigue and disturbed sleep. The main toxic reactions in the infants were skin rashes.
Possible side-effects
As vitamin C enhances iron absorption,
iron poisoningIron poisoning is an iron overload caused by a large excess of iron intake and usually refers to an acute overload rather than a gradual one. The terms has been primarily associated with young children who consumed large quantities of iron supplement pills, which resemble sweets and are widely...
can become an issue to people with rare
iron overload disorderIn medicine, iron overload indicates accumulation of iron in the body from any cause. The most important causes are hereditary hemochromatosis , a genetic disease, and transfusional iron overload, which can result from repeated blood transfusion....
s, such as
haemochromatosisHaemochromatosis type 1 is a hereditary disease characterized by excessive intestinal absorption of dietary iron resulting in a pathological increase in total body iron stores. Humans, like most animals, have no means to excrete excess iron...
. A genetic condition that results in inadequate levels of the enzyme
glucose-6-phosphate dehydrogenaseGlucose-6-phosphate dehydrogenase is a cytosolic enzyme in the pentose phosphate pathway , a metabolic pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate...
(G6PD) can cause sufferers to develop
hemolytic anemiaHemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
after ingesting specific oxidizing substances, such as very large dosages of vitamin C.
There is a longstanding belief among the mainstream medical community that vitamin C causes kidney stones, which is based on little science.
Although recent studies have found a relationship, a clear link between excess
ascorbic acidAscorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
intake and
kidney stoneA kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...
formation has not been generally established. Some case reports exist for a link between patients with oxalate deposits and a history of high-dose vitamin C usage.
In a study conducted on rats, during the first month of pregnancy, high doses of vitamin C may suppress the production of
progesteroneProgesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
from the
corpus luteumThe corpus luteum is a temporary endocrine structure in mammals, involved in production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A...
. Progesterone, necessary for the maintenance of a pregnancy, is produced by the corpus luteum for the first few weeks, until the placenta is developed enough to produce its own source. By blocking this function of the corpus luteum, high doses of vitamin C (1000+ mg) are theorized to induce an early miscarriage. In a group of spontaneously aborting women at the end of the first trimester, the mean values of vitamin C were significantly higher in the aborting group. However, the authors do state: 'This could not be interpreted as an evidence of causal association.' However, in a previous study of 79 women with threatened, previous spontaneous, or habitual abortion, Javert and Stander (1943) had 91% success with 33 patients who received vitamin C together with bioflavonoids and
vitamin KVitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
(only three abortions), whereas all of the 46 patients who did not receive the vitamins aborted.
A study in rats and humans suggested that adding Vitamin C supplements to an exercise training program lowered the expected effect of training on
VO2 MaxVO2 max is the maximum capacity of an individual's body to transport and use oxygen during incremental exercise, which reflects the physical fitness of the individual...
. Although the results in humans were not statistically significant, this study is often cited as evidence that high doses of Vitamin C have an adverse effect on exercise performance. In rats, it was shown that the additional Vitamin C resulted in lowered mitochondria production. Since rats are able to produce all of their needed Vitamin C, however, it is questionable whether they offer a relevant model of human physiological processes in this regard.
A cancer-causing mechanism of
hexavalent chromiumHexavalent chromium refers to chemical compounds that contain the element chromium in the +6 oxidation state. Virtually all chromium ore is processed via hexavalent chromium, specifically the salt sodium dichromate. Approximately of hexavalent chromium were produced in 1985...
may be triggered by vitamin C.
Chance of overdose
Vitamin C is water soluble, with dietary excesses not absorbed, and excesses in the blood rapidly excreted in the urine. It exhibits remarkably low toxicity. The {{LD50}} (the dose that will kill 50% of a population) in rats is generally accepted to be 11.9 grams per kilogram of body weight when given by forced gavage (orally). The mechanism of death from such doses (1.2% of body weight, or 1.8 lbs for a 150 lb human) is unknown, but may be more mechanical than chemical. The LD
50 in humans remains unknown, given lack of any accidental or intentional poisoning death data. However, as with all substances tested in this way, the rat LD
50 is taken as a guide to its toxicity in humans.
Dietary sources
The richest natural sources are fruits and vegetables, and of those, the Kakadu plum and the
camu camuMyrciaria dubia, commonly known as Camu camu, Camucamu, Cacari, and Camocamo, is a small bushy riverside tree from the Amazon rainforest vegetation in Peru and Brazil, which bears a red/purple cherry-like fruit. Its small flowers have waxy white petals and a sweet-smelling aroma. It has bushy...
fruit 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.
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. The presence of large quantities of sugar either in the intestines or in the blood can slow absorption.
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, soil condition, climate where it grew, length of time since it was picked, storage conditions, and method of preparation.
The following table is approximate and shows the relative abundance in different raw plant sources. As some plants were analyzed fresh while others were dried (thus, artifactually increasing concentration of individual constituents like vitamin C), the data are subject to potential variation and difficulties for comparison. The amount is given in milligrams per 100 grams of fruit or vegetable and is a rounded average from multiple authoritative sources:
(mg / 100g)
|-
|
Kakadu plumTerminalia ferdinandiana, also called the gubinge, billygoat plum, Kakadu plum or murunga is a flowering plant in the family Combretaceae, native to Australia, widespread throughout the tropical woodlands from northwestern Australia to eastern Arnhem Land.Its vitamin C concentration may be as high...
|| 1000-5300{{Better source|date=November 2011}}
|-
|
Camu CamuMyrciaria dubia, commonly known as Camu camu, Camucamu, Cacari, and Camocamo, is a small bushy riverside tree from the Amazon rainforest vegetation in Peru and Brazil, which bears a red/purple cherry-like fruit. Its small flowers have waxy white petals and a sweet-smelling aroma. It has bushy...
|| 2800{{Better source|date=November 2011}}
|-
|
AcerolaMalpighia emarginata is a tropical fruit-bearing shrub or small tree in the family Malpighiaceae. Common names include acerola, Barbados cherry, West Indian cherry and wild crapemyrtle....
|| 1677
|-
|Seabuckthorn || 695
|-
|Mica Muro || 500
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Indian gooseberryPhyllanthus emblica , the Indian gooseberry, or aamla, is a deciduous tree of the Phyllanthaceae family. It is known for its edible fruit of the same name.-Plant anatomy and harvesting:...
|| 445
|-
|
Rose hipThe rose hip, or rose haw, is the fruit of the rose plant, that typically is red-to-orange, but ranges from dark purple to black in some species. Rose hips begin to form in spring, and ripen in late summer through autumn.-Usage:...
|| 426
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|
BaobabAdansonia is a genus of eight species of tree, six native to Madagascar, one native to mainland Africa and the Arabian Peninsula and one to Australia. The mainland African species also occurs on Madagascar, but it is not a native of that island....
|| 400
|-
|
Chili pepperChili pepper is the fruit of plants from the genus Capsicum, members of the nightshade family, Solanaceae. The term in British English and in Australia, New Zealand, India, Malaysia and other Asian countries is just chilli without pepper.Chili peppers originated in the Americas...
(green) || 244
|-
|
GuavaGuavas are plants in the myrtle family genus Psidium , which contains about 100 species of tropical shrubs and small trees. They are native to Mexico, Central America, and northern South America...
(common, raw) || 228.3
[USDA Guava, common, raw]
|-
|
BlackcurrantBlackcurrant, Ribes nigrum, is a species of Ribes berry native to central and northern Europe and northern Asia, and is a perennial....
|| 200
|-
|
Red pepperCapsicum is a genus of flowering plants in the nightshade family, Solanaceae. Its species are native to the Americas where they have been cultivated for thousands of years, but they are now also cultivated worldwide, used as spices, vegetables, and medicines - and have become are a key element in...
|| 190
|-
|
Chili pepperChili pepper is the fruit of plants from the genus Capsicum, members of the nightshade family, Solanaceae. The term in British English and in Australia, New Zealand, India, Malaysia and other Asian countries is just chilli without pepper.Chili peppers originated in the Americas...
(red) || 144
|-
|
ParsleyParsley is a species of Petroselinum in the family Apiaceae, native to the central Mediterranean region , naturalized elsewhere in Europe, and widely cultivated as an herb, a spice and a vegetable.- Description :Garden parsley is a bright green hairless biennial herbaceous plant in temperate...
|| 130
|-
|
KiwifruitThe kiwifruit, often shortened to kiwi in many parts of the world, is the edible berry of a cultivar group of the woody vine Actinidia deliciosa and hybrids between this and other species in the genus Actinidia....
|| 90
|-
|
BroccoliBroccoli is a plant in the cabbage family, whose large flower head is used as a vegetable.-General:The word broccoli, from the Italian plural of , refers to "the flowering top of a cabbage"....
|| 90
|-
|
LoganberryThe loganberry is an hexaploid hybrid produced from crossing an octaploid blackberry and a diploid red raspberry. The plant and the fruit resemble the blackberry more than the raspberry, but the fruit colour is a dark red, rather than black...
|| 80
|-
|
RedcurrantThe redcurrant , Ribes rubrum, is a member of the genus Ribes in the gooseberry family Grossulariaceae, native to parts of western Europe...
|| 80
|-
|
Brussels sproutThe Brussels sprout is a cultivar of wild cabbage grown for its edible buds. The leafy green vegetables are typically 2.5–4 cm in diameter and look like miniature cabbages. The sprout is Brassica oleracea, in the "gemmifera" group of the family Brassicaceae...
s ||80
|-
|
WolfberryWolfberry, commercially called goji berry, is the common name for the fruit of two very closely related species: Lycium barbarum and L. chinense , two species of boxthorn in the family Solanaceae...
(Goji) || 73 †
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|
LycheeThe lychee is the sole member of the genus Litchi in the soapberry family, Sapindaceae. It is a tropical and subtropical fruit tree native to Southern China and Southeast Asia, and now cultivated in many parts of the world...
|| 70
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|
PersimmonA persimmon is the edible fruit of a number of species of trees in the genus Diospyros in the ebony wood family . The word Diospyros means "the fire of Zeus" in ancient Greek. As a tree, it is a perennial plant...
(native, raw) || 66.0
[USDA Persimmons, native, raw]
|-
|
CloudberryRubus chamaemorus is a rhizomatous herb native to alpine and arctic tundra and boreal forest, producing amber-colored edible fruit similar to the raspberry or blackberry...
|| 60
|-
|
ElderberrySambucus is a genus of between 5 and 30 species of shrubs or small trees in the moschatel family, Adoxaceae. It was formerly placed in the honeysuckle family, Caprifoliaceae, but was reclassified due to genetic evidence...
|| 60
|}
† average of 3 sources; dried