Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble
vitamin
A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nutrie ...
found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a
topical
A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
'serum' ingredient to treat
melasma
Melasma (also known as chloasma faciei,James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . or the mask of pregnancy when present in pregnant women) is a tan or dark ...
(dark pigment spots) and wrinkles on the face. It is used to prevent and treat
scurvy
Scurvy is a disease resulting from a lack of vitamin C (ascorbic acid). Early symptoms of deficiency include weakness, feeling tired and sore arms and legs. Without treatment, decreased red blood cells, gum disease, changes to hair, and bleeding ...
enzymatic
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...
production of certain neurotransmitters. It is required for the functioning of several enzymes and is important for
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
function. It also functions as an
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
ape
Apes (collectively Hominoidea ) are a clade of Old World simians native to sub-Saharan Africa and Southeast Asia (though they were more widespread in Africa, most of Asia, and as well as Europe in prehistory), which together with its sister g ...
s (including humans) and monkeys (but not all primates), most
bat
Bats are mammals of the order Chiroptera.''cheir'', "hand" and πτερόν''pteron'', "wing". With their forelimbs adapted as wings, they are the only mammals capable of true and sustained flight. Bats are more agile in flight than most ...
s, some rodents, and certain other animals must acquire it from dietary sources.
There is some evidence that regular use of supplements may reduce the duration of the
common cold
The common cold or the cold is a viral infectious disease of the upper respiratory tract that primarily affects the respiratory mucosa of the nose, throat, sinuses, and larynx. Signs and symptoms may appear fewer than two days after exposu ...
, but it does not appear to prevent infection. It is unclear whether supplementation affects the risk of
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
. It may be taken by mouth or by injection.
Vitamin C is generally well tolerated. Large doses may cause gastrointestinal discomfort, headache, trouble sleeping, and flushing of the skin. Normal doses are safe during
pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
. The United States Institute of Medicine recommends against taking large doses.
Vitamin C was discovered in 1912, isolated in 1928, and, in 1933, was the first vitamin to be chemically produced. It is on the
World Health Organization's List of Essential Medicines
The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
. Vitamin C is available as an inexpensive
generic
Generic or generics may refer to:
In business
* Generic term, a common name used for a range or class of similar things not protected by trademark
* Generic brand, a brand for a product that does not have an associated brand or trademark, other ...
and
over-the-counter
Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...
medication. Partly for its discovery,
Albert Szent-Györgyi
Albert Imre Szent-Györgyi de Nagyrápolt ( hu, nagyrápolti Szent-Györgyi Albert Imre; September 16, 1893 – October 22, 1986) was a Hungarian biochemist who won the Nobel Prize in Physiology or Medicine in 1937. He is credited with fi ...
Nobel Prizes
The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfre ...
Chemistry
Chemistry is the science, scientific study of the properties and behavior of matter. It is a natural science that covers the Chemical element, elements that make up matter to the chemical compound, compounds made of atoms, molecules and ions ...
, respectively. Foods containing vitamin C include
citrus fruits
''Citrus'' is a genus of flowering trees and shrubs in the rue family, Rutaceae. Plants in the genus produce citrus fruits, including important crops such as oranges, lemons, grapefruits, pomelos, and limes. The genus ''Citrus'' is nativ ...
,
kiwifruit
Kiwifruit (often shortened to kiwi in North American, British and continental European English) or Chinese gooseberry is the edible berry of several species of woody vines in the genus '' Actinidia''. The most common cultivar group of kiwi ...
,
guava
Guava () is a common tropical fruit cultivated in many tropical and subtropical regions. The common guava ''Psidium guajava'' (lemon guava, apple guava) is a small tree in the myrtle family ( Myrtaceae), native to Mexico, Central America, the ...
,
broccoli
Broccoli (''Brassica oleracea'' var. ''italica'') is an edible green plant in the cabbage family (family Brassicaceae, genus ''Brassica'') whose large flowering head, stalk and small associated leaves are eaten as a vegetable. Broccoli is cla ...
,
Brussels sprout
The Brussels sprout is a member of the Gemmifera cultivar group of cabbages (''Brassica oleracea''), grown for its edible buds. The leaf vegetables are typically 1.5–4.0 cm (0.6–1.6 in) in diameter and resemble miniature cabbages ...
potato
The potato is a starchy food, a tuber of the plant ''Solanum tuberosum'' and is a root vegetable native to the Americas. The plant is a perennial in the nightshade family Solanaceae.
Wild potato species can be found from the southern Unit ...
es, and
strawberries
The garden strawberry (or simply strawberry; ''Fragaria × ananassa'') is a widely grown hybrid species of the genus '' Fragaria'', collectively known as the strawberries, which are cultivated worldwide for their fruit. The fruit is widely ap ...
. Prolonged storage or cooking may reduce vitaminC content in foods.
Definition
Vitamin C is an essential nutrient for certain animals including humans. The term ''vitamin C'' encompasses several
vitamer
Vitamins occur in a variety of related forms known as vitamers. A vitamer () of a particular vitamin is one of several related compounds that performs the functions of said vitamin and prevents the symptoms of deficiency of said vitamin.
Early r ...
s that have vitamin C activity in animals. Ascorbate salts such as sodium ascorbate and calcium ascorbate are used in some dietary supplements. These release ascorbate upon digestion. Ascorbate and ascorbic acid are both naturally present in the body, since the forms interconvert according to pH. Oxidized forms of the molecule such as
dehydroascorbic acid
Dehydroascorbic acid (DHA) is an oxidized form of ascorbic acid (vitamin C). 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 othe ...
are converted back to ascorbic acid by reducing agents.
Vitamin C functions as a cofactor in many
enzymatic
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...
reactions in animals (including humans) that mediate a variety of essential biological functions, including
wound healing
Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.
In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...
and collagen synthesis. In humans, vitamin C deficiency leads to impaired collagen synthesis, contributing to the more severe symptoms of
scurvy
Scurvy is a disease resulting from a lack of vitamin C (ascorbic acid). Early symptoms of deficiency include weakness, feeling tired and sore arms and legs. Without treatment, decreased red blood cells, gum disease, changes to hair, and bleeding ...
. Another biochemical role of vitamin C is to act as an
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricant ...
(a
reducing agent
In chemistry, a reducing agent (also known as a reductant, reducer, or electron donor) is a chemical species that "donates" an electron to an (called the , , , or ).
Examples of substances that are commonly reducing agents include the Earth me ...
) by donating electrons to various enzymatic and non-enzymatic reactions. Doing so converts vitamin C to an oxidized state - either as semidehydroascorbic acid or dehydroascorbic acid. These compounds can be restored to a reduced state by
glutathione
Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...
and NADPH-dependent enzymatic mechanisms.
In plants, vitamin C is a substrate for
ascorbate peroxidase
Ascorbate peroxidase (or L-ascorbate peroxidase, APX) () is an enzyme that catalyzes the chemical reaction
:L-ascorbate + H2O2 \rightleftharpoons dehydroascorbate + 2 H2O
It is a member of the family of heme-containing peroxidases. Heme peroxi ...
. This enzyme utilizes ascorbate to neutralize excess hydrogen peroxide (H2O2) by converting it to water (H2O) and oxygen.
Deficiency
Vitamin C blood serum levels are considered saturated at levels (1.1 mg/dL), achieved by consuming amounts which are at, or above, the
Recommended Dietary Allowance
The Dietary Reference Intake (DRI) is a system of nutrition recommendations from the National Academy of Medicine (NAM) of the National Academies (United States). It was introduced in 1997 in order to broaden the existing guidelines known as Reco ...
, while adequate levels are defined as .
Hypovitaminosis
Vitamin deficiency is the condition of a long-term lack of a vitamin. When caused by not enough vitamin intake it is classified as a ''primary deficiency'', whereas when due to an underlying disorder such as malabsorption it is called a ''seconda ...
in the case of vitamin C is defined as and
deficiency
A deficiency is generally a lack of something. It may also refer to:
*A deficient number, in mathematics, a number ''n'' for which ''σ''(''n'') < 2''n''
*
occurs at . For those 20 years of age or above, data from the U.S. 2003-04 NHANES survey showed mean and median serum concentrations of 49.0 and 54.4μmol/L, respectively. The percent of people reported as deficient was 7.1%.
Scurvy
Scurvy is a disease resulting from a lack of vitamin C (ascorbic acid). Early symptoms of deficiency include weakness, feeling tired and sore arms and legs. Without treatment, decreased red blood cells, gum disease, changes to hair, and bleeding ...
is a disease resulting from a deficiency of vitamin C. Without this vitamin, collagen made by the body is too unstable to perform its function and several other
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s in the body do not operate correctly. Scurvy is characterized by spots on and
bleeding
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
under the skin, spongy gums, 'corkscrew' hair growth, and poor wound healing. The skin lesions 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, loss of
teeth
A tooth ( : teeth) is a hard, calcified structure found in the jaws (or mouths) of many vertebrates and used to break down food. Some animals, particularly carnivores and omnivores, also use teeth to help with capturing or wounding prey, t ...
, bone abnormalities and, eventually, death.
Notable human dietary studies of experimentally induced scurvy were conducted on
conscientious objector
A conscientious objector (often shortened to conchie) is an "individual who has claimed the right to refuse to perform military service" on the grounds of freedom of thought, conscience, or religion. The term has also been extended to object ...
s during World War II in Britain and on Iowa state prisoners in the late 1960s to the 1980s. Men in the prison study developed the first signs of scurvy about four weeks after starting the vitamin C-free diet, whereas in the earlier 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 had blood levels of ascorbic acid too low to be accurately measured by the time they developed signs of scurvy. These studies both reported that all obvious symptoms of scurvy could be completely reversed by supplementation of only 10 mg a day.
People in
sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
or septic shock may have micronutrient deficiencies, including low levels of vitamin C.
Medical uses
Vitamin C has a definitive role in treating scurvy, which is a disease caused by vitaminC deficiency. Beyond that, a role for vitaminC as prevention or treatment for various diseases is disputed, with reviews reporting conflicting results. A 2012 Cochrane review reported no effect of vitaminC supplementation on overall mortality. It is on the
World Health Organization's List of Essential Medicines
The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
.
Scurvy
The disease
scurvy
Scurvy is a disease resulting from a lack of vitamin C (ascorbic acid). Early symptoms of deficiency include weakness, feeling tired and sore arms and legs. Without treatment, decreased red blood cells, gum disease, changes to hair, and bleeding ...
is caused by vitaminC deficiency and can be prevented and treated with vitaminC-containing foods or dietary supplements. It takes at least a month of little to no vitaminC before symptoms occur. Early symptoms are malaise and lethargy, progressing to shortness of breath, bone pain, bleeding gums, susceptibility to bruising, poor wound healing, and finally fever, convulsions and eventual death. Until quite late in the disease the damage is reversible, as healthy collagen replaces the defective collagen with vitaminC repletion. Treatment can be oral supplementation of the vitamin or by intramuscular or intravenous injection. Scurvy was known to
Hippocrates
Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history of ...
in the classical era. The disease was shown to be prevented by citrus fruits in an early controlled trial by a
Royal Navy
The Royal Navy (RN) is the United Kingdom's naval warfare force. Although warships were used by English and Scottish kings from the early medieval period, the first major maritime engagements were fought in the Hundred Years' War against F ...
surgeon,
James Lind
James Lind (4 October 1716 – 13 July 1794) was a Scottish doctor. He was a pioneer of naval hygiene in the Royal Navy. By conducting one of the first ever clinical trials, he developed the theory that citrus fruits cured scurvy.
Lind ...
, in 1747, on board HMS Salisbury. From 1796 onward, lemon juice was issued to all Royal Navy crewmen.
Common cold
Research on vitaminC in the common cold has been divided into effects on prevention, duration, and severity. A
Cochrane review
Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profes ...
which looked at at least 200 mg/day concluded that vitaminC taken on a regular basis was not effective in prevention of the common cold. Restricting analysis to trials that used at least 1000 mg/day also saw no prevention benefit. However, taking vitaminC on a regular basis did reduce the average duration by 8% in adults and 14% in children, and also reduced severity of colds. A subset of trials in adults reported that supplementation reduced the incidence of colds by half in marathon runners, skiers, or soldiers in subarctic conditions. Another subset of trials looked at therapeutic use, meaning that vitaminC was not started unless the people started to feel the beginnings of a cold. In these, vitaminC did not affect duration or severity. An earlier review stated that vitaminC did not prevent colds, did reduce duration, did not reduce severity. The authors of the Cochrane review concluded that:
Vitamin C distributes readily in high concentrations into
immune cells
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
, has
antimicrobial
An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ar ...
and
natural killer cell
Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and repres ...
activities, promotes
lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
proliferation, and is consumed quickly during infections, effects suggesting a prominent role in immune system regulation. The
European Food Safety Authority
The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, ...
found a cause and effect relationship exists between the dietary intake of vitamin C and functioning of a normal immune system in adults and in children under three years of age.
Several studies found Vitamin C to have specific antiviral effects in which it inactivates the RNA or DNA of viruses or in the assembly of the virus.
COVID-19
According to
ClinicalTrials.gov
ClinicalTrials.gov is a registry of clinical trials. It is run by the United States National Library of Medicine (NLM) at the National Institutes of Health, and is the largest clinical trials database, holding registrations from over 329,000 tri ...
, as of early 2021 there were 50 completed or ongoing COVID-19 clinical trials including vitamin C as a treatment. A meta-analysis of six published trials was published in October 2021. Treatments were either oral or intravenous. Dose ranged from 50 mg/kg/day to 24 g/day. Reported outcomes were mortality, hospitalization duration, intensive care duration and need for ventilation. From the Conclusion: "The present meta-analysis showed that administration of vitamin C did not have any effect on major health outcomes in COVID infected patients, in comparison to either placebo/standard therapy. Sub-group analysis also revealed that irrespective of its dosage, route of administration and disease severity, it didn't have discernible benefit in such patients. Hence, larger prospective randomized trials are needed in order to evaluate the effect of isolated vitamin C administration, separately for both vitamin C replete and deplete individuals."
During March through July 2020, vitamin C was the subject of more US FDA warning letters than any other ingredient for prevention and/or treatment of COVID-19.
As of April 2021, the
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
(NIH) ''COVID-19 Treatment Guidelines'' stated that "there are insufficient data to recommend either for or against the use of vitaminC for the prevention or treatment of COVID-19."
Cancer
There is no evidence that vitamin C supplementation reduces the risk of lung cancer in healthy people or those at high risk due to smoking or asbestos exposure. A second meta-analysis found no effect on the risk of prostate cancer. Two meta-analyses evaluated the effect of vitamin C supplementation on the risk of colorectal cancer. One found a weak association between vitamin C consumption and reduced risk, and the other found no effect from supplementation. A 2011 meta-analysis failed to find support for the prevention of breast cancer with vitamin C supplementation, but a second study concluded that vitamin C may be associated with increased survival in those already diagnosed. A 2015 meta-analysis showed no antitumor effect nor improvement in quality-of-life measures from high-dose vitamin C. This review included trials of oral and intravenous vitamin C.
Cardiovascular disease
In 2017, an independent study evaluating 15,445 participants found no evidence to show vitamin C decreases the risk cardiovascular disease. These results supported one 2013 review which found no evidence that antioxidant vitamin supplementation reduces the risk of
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
, stroke, cardiovascular mortality, or all-cause mortality (it did not provide subset analysis for trials that just used vitamin C).
However, another 2013 review found an association between higher circulating vitamin C levels or dietary vitamin C and a lower risk of stroke.
A 2014 review found a positive effect of vitamin C on
endothelial dysfunction
In vascular diseases, endothelial dysfunction is a systemic pathological state of the endothelium. Along with acting as a semi-permeable membrane, the endothelium is responsible for maintaining vascular tone and regulating oxidative stress by ...
when taken at doses greater than 500 mg per day. The endothelium is a layer of cells that line the interior surface of blood vessels.
Brain function
A 2017 systematic review found lower vitamin C concentrations in people with cognitive impairment, including
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
and
dementia
Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
, compared to people with normal cognition. The cognitive testing, however, relied on the Mini-Mental State Examination, which is only a general test of cognition, indicating an overall low quality of research assessing the potential importance of vitamin C on cognition in normal and impaired people. A review of nutrient status in people with Alzheimer's disease reported low plasma vitamin C, but also low blood levels of
folate
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing an ...
vitamin E
Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vi ...
.
Iron deficiency
One of the causes of
iron-deficiency anemia
Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, shor ...
is reduced absorption of iron. Iron absorption can be enhanced though ingestion of vitamin C alongside iron-containing food or supplements. The instability of vitamin C during cooking and/or storage limits the number of foods suitable for this. Vitamin C helps to keep iron in the reduced ferrous state, which is more soluble and more easily absorbed.
Other diseases
Studies examining the effects of vitamin C intake on the risk of
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
have reached conflicting conclusions. Maintaining a healthy dietary intake is probably more important than supplementation for achieving any potential benefit. A 2010 review found no role for vitamin C supplementation in the treatment of
rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are invol ...
. Vitamin C supplementation does not prevent or slow the progression of age-related
cataract
A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble ...
. A systematic review reported that low intake and low serum concentration was associated with greater progression of periodontal disease.
Side effects
Vitamin C is a water-soluble vitamin, with dietary excesses not absorbed, and excesses in the blood rapidly excreted in the urine, so it exhibits remarkably low acute toxicity. More than two to three grams may cause indigestion, particularly when taken on an empty stomach. However, taking vitamin C in the form of
sodium ascorbate
Sodium ascorbate is one of a number of mineral salts of ascorbic acid (vitamin C). The molecular formula of this chemical compound is C6H7NaO6. As the sodium salt of ascorbic acid, it is known as a mineral ascorbate. It has not been demonstrate ...
and calcium ascorbate may minimize this effect. Other symptoms reported for large doses include nausea, abdominal cramps and diarrhea. These effects are attributed to the osmotic effect of unabsorbed vitamin C passing through the intestine. In theory, high vitamin C intake may cause excessive absorption of iron. A summary of reviews of supplementation in healthy subjects did not report this problem, but left as untested the possibility that individuals with hereditary
hemochromatosis
Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatos ...
might be adversely affected.
There is a longstanding belief among the mainstream medical community that vitamin C increases risk of
kidney stone
Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...
s. "Reports of kidney stone formation associated with excess ascorbic acid intake are limited to individuals with renal disease". Reviews state that "data from epidemiological studies do not support an association between excess ascorbic acid intake and kidney stone formation in apparently healthy individuals", although one large, multi-year trial did report a nearly two-fold increase in kidney stones in men who regularly consumed a vitamin C supplement.
Diet
Recommended levels
Recommendations for vitamin C intake by adults have been set by various national agencies:
*40 milligrams per day: India
National Institute of Nutrition, Hyderabad
The National Institute of Nutrition (NIN) is an Indian public health, nutrition and translational research centre located in Hyderabad, India. The institute is one of the oldest research centres in India, and the largest centre, under the India ...
*45 milligrams per day or 300 milligrams per week: the
World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
*80 milligrams per day: the
European Commission
The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...
Council on nutrition labeling
*90 mg/day (males) and 75 mg/day (females): Health Canada 2007ealth Canada, 2007>
*90 mg/day (males) and 75 mg/day (females):
United States National Academy of Sciences
The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...
.
*100 milligrams per day: Japan National Institute of Health and Nutrition.
*110 mg/day (males) and 95 mg/day (females):
European Food Safety Authority
The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, ...
In 2000, the chapter on Vitamin C in the North American
Dietary Reference Intake
The Dietary Reference Intake (DRI) is a system of nutrition recommendations from the National Academy of Medicine (NAM) of the National Academies (United States). It was introduced in 1997 in order to broaden the existing guidelines known as Re ...
was updated to give the
Recommended Dietary Allowance
The Dietary Reference Intake (DRI) is a system of nutrition recommendations from the National Academy of Medicine (NAM) of the National Academies (United States). It was introduced in 1997 in order to broaden the existing guidelines known as Reco ...
(RDA) as 90 milligrams per day for adult men, 75 mg/day for adult women, and setting a
Tolerable upper intake level
The Dietary Reference Intake (DRI) is a system of nutrition recommendations from the National Academy of Medicine (NAM) of the National Academies (United States). It was introduced in 1997 in order to broaden the existing guidelines known as Re ...
(UL) for adults of 2,000 mg/day. The table (right) shows RDAs for the United States and Canada for children, and for pregnant and lactating women, as well as the ULs for adults.
For the European Union, the EFSA set higher recommendations for adults, and also for children: 20 mg/day for ages 1–3, 30 mg/day for ages 4–6, 45 mg/day for ages 7–10, 70 mg/day for ages 11–14, 100 mg/day for males ages 15–17, 90 mg/day for females ages 15–17. For pregnancy 100 mg/day; for lactation 155 mg/day.
India, on the other hand, has set recommendations much lower: 40 mg/day for ages 1 through adult, 60 mg/day for pregnancy, and 80 mg/day for lactation. Clearly, there is not consensus among countries.
Cigarette smokers and people exposed to secondhand smoke have lower serum vitamin C levels than nonsmokers. The thinking is that inhalation of smoke causes oxidative damage, depleting this antioxidant vitamin. The U.S. Institute of Medicine estimated that smokers need 35 mg more vitamin C per day than nonsmokers, but did not formally establish a higher RDA for smokers. One meta-analysis showed an inverse relationship between vitamin C intake and lung cancer, although it concluded that more research is needed to confirm this observation.
The U.S. National Center for Health Statistics conducts biannual National Health and Nutrition Examination Survey (NHANES) to assess the health and nutritional status of adults and children in the United States. Some results are reported as What We Eat In America. The 2013-2014 survey reported that for adults ages 20 years and older, men consumed on average 83.3 mg/d and women 75.1 mg/d. This means that half the women and more than half the men are not consuming the RDA for vitamin C. The same survey stated that about 30% of adults reported they consumed a vitamin C dietary supplement or a multi-vitamin/mineral supplement that included vitamin C, and that for these people total consumption was between 300 and 400 mg/d.
Tolerable upper intake level
In 2000, the Institute of Medicine of the U.S. National Academy of Sciences set a
Tolerable upper intake level
The Dietary Reference Intake (DRI) is a system of nutrition recommendations from the National Academy of Medicine (NAM) of the National Academies (United States). It was introduced in 1997 in order to broaden the existing guidelines known as Re ...
(UL) for adults of 2,000 mg/day. The amount was chosen because human trials had reported diarrhea and other gastrointestinal disturbances at intakes of greater than 3,000 mg/day. This was the Lowest-Observed-Adverse-Effect Level (LOAEL), meaning that other adverse effects were observed at even higher intakes. ULs are progressively lower for younger and younger children. In 2006, the
European Food Safety Authority
The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, ...
(EFSA) also pointed out the disturbances at that dose level, but reached the conclusion that there was not sufficient evidence to set a UL for vitamin C, as did the Japan National Institute of Health and Nutrition in 2010.
Food labeling
For U.S. food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value (%DV). For vitamin C labeling purposes, 100% of the Daily Value was 60 mg, but as of May 27, 2016, it was revised to 90 mg to bring it into agreement with the RDA. A table of the old and new adult daily values is provided at
Reference Daily Intake
The Reference Daily Intake (RDI) used in nutrition labeling on food and dietary supplement products in the U.S. and Canada is the daily intake level of a nutrient that is considered to be sufficient to meet the requirements of 97–98% of healt ...
.
European Union regulations require that labels declare energy, protein, fat, saturated fat, carbohydrates, sugars, and salt. Voluntary nutrients may be shown if present in significant amounts. Instead of Daily Values, amounts are shown as percent of Reference Intakes (RIs). For vitamin C, 100% RI was set at 80 mg in 2011.
Sources
Although also present in other foods, the richest natural sources of vitamin C are fruits and vegetables. The vitamin is the most widely taken dietary supplement.
Plant sources
While plant foods are generally a good source of vitamin C, the amount in foods of plant origin depends on the 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. Generally, cooking reduces the amount of vitamin C. As some plants were analyzed fresh while others were dried (thus, artificially increasing concentration of individual constituents such as vitamin C), the data are subject to potential variation and difficulties for comparison. The amount is given in milligrams per 100 grams of the edible portion of the fruit or vegetable:
Animal sources
Compared to plant sources, animal-sourced foods do not provide so great an amount of vitamin C, and what there is, is largely destroyed by the heat used when it is cooked. For example, raw chicken liver contains 17.9 mg/100 g, but fried, the content is reduced to 2.7 mg/100 g. Smoked products, such as beef sticks, retain some vitamin C however.
Vitamin C is present in human breast milk at 5.0 mg/100 g. One tested sample of infant formula contained 6.1 mg/100 g. Cow's milk contains only 1.0 mg/ 100 g, but the heat of pasteurization destroys it. Goat's milk contains 1.3mg/100 g, unless pasteurized.
Chicken eggs contain no vitamin C, whether raw or cooked.
Food preparation
Vitamin C chemically decomposes 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 at which they are stored. Cooking can reduce the vitamin C content of vegetables by around 60%, possibly due to increased enzymatic destruction. Longer cooking times may add to this effect.
Another cause of vitaminC loss from food is
leaching
Leaching is the loss or extraction of certain materials from a carrier into a liquid (usually, but not always a solvent). and may refer to:
* Leaching (agriculture), the loss of water-soluble plant nutrients from the soil; or applying a small amou ...
, which transfers vitaminC to the cooking water, which is decanted and not consumed.
Broccoli
Broccoli (''Brassica oleracea'' var. ''italica'') is an edible green plant in the cabbage family (family Brassicaceae, genus ''Brassica'') whose large flowering head, stalk and small associated leaves are eaten as a vegetable. Broccoli is cla ...
may retain vitaminC during cooking or storage more than most vegetables.
Supplements
Vitamin C dietary supplements are available as tablets, capsules, drink mix packets, in multi-vitamin/mineral formulations, in antioxidant formulations, and as crystalline powder. Vitamin C is also added to some fruit juices and juice drinks. Tablet and capsule content ranges from 25 mg to 1500 mg per serving. The most commonly used supplement compounds are ascorbic acid, sodium ascorbate and calcium ascorbate. Vitamin C molecules can also be bound to the fatty acid palmitate, creating
ascorbyl palmitate
Ascorbyl palmitate is an ester formed from ascorbic acid and palmitic acid creating a fat-soluble form of vitamin C. In addition to its use as a source of vitamin C, it is also used as an antioxidant food additive (E number E304). It is approved ...
, or else incorporated into liposomes.
Food fortification
In 2014, the
Canadian Food Inspection Agency
The Canadian Food Inspection Agency (CFIA; french: Agence canadienne d'inspection des aliments) is a regulatory agency that is dedicated to the safeguarding of food, plants, and animals (FPA) in Canada, thus enhancing the health and well-being of ...
evaluated the effect of fortification of foods with ascorbate in the guidance document, ''Foods to Which Vitamins, Mineral Nutrients and Amino Acids May or Must be Added''. Voluntary and mandatory fortification was described for various classes of foods. Among foods classified for mandatory fortification with vitaminC were fruit-flavored drinks, mixes, and concentrates, foods for a low-energy diet,
meal replacement
A meal replacement is a drink, bar, soup, etc. intended as a substitute for a solid food, usually with controlled quantities of calories and nutrients. Some drinks come in powdered form or pre-mixed health shakes that can be cheaper than solid fo ...
products, and
evaporated milk
Evaporated milk, known in some countries as "unsweetened condensed milk", is a shelf-stable canned cow’s milk product where about 60% of the water has been removed from fresh milk. It differs from sweetened condensed milk, which contains adde ...
.
Food additives
Ascorbic acid and some of its
salts
In chemistry, a salt is a chemical compound consisting of an ionic assembly of positively charged cations and negatively charged anions, which results in a compound with no net electric charge. A common example is table salt, with positively c ...
and
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
s are common
additives
Additive may refer to:
Mathematics
* Additive function, a function in number theory
* Additive map, a function that preserves the addition operation
* Additive set-functionn see Sigma additivity
* Additive category, a preadditive category with fi ...
added to various foods, such as canned fruits, mostly to slow
oxidation
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...
and
enzymatic browning
Browning is the process of food turning brown due to the chemical reactions that take place within. The process of browning is one of the chemical reactions that take place in food chemistry and represents an interesting research topic regardin ...
. It may be used as a
flour treatment agent
A dough conditioner, flour treatment agent, improving agent or bread improver is any ingredient or chemical added to bread dough to strengthen its texture or otherwise improve it in some way. Dough conditioners may include enzymes, yeast nutrients ...
used in breadmaking. As food additives, they are assigned
E number
E numbers ("E" stands for "Europe") are codes for substances used as food additives, including those found naturally in many foods such as vitamin C, for use within the European Union (EU) and European Free Trade Association (EFTA). Commonly ...
s, with safety assessment and approval the responsibility of the
European Food Safety Authority
The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, ...
. The relevant E numbers are:
# E300 ascorbic acid (approved for use as a food additive in the UK,UK Food Standards Agency: U.S.U.S. Food and Drug Administration: Canada,Health Canada Australia and New ZealandAustralia New Zealand Food Standards Code)
# E301
sodium ascorbate
Sodium ascorbate is one of a number of mineral salts of ascorbic acid (vitamin C). The molecular formula of this chemical compound is C6H7NaO6. As the sodium salt of ascorbic acid, it is known as a mineral ascorbate. It has not been demonstrate ...
(approved for use as a food additive in the UK, U.S., Canada, Australia and New Zealand)
# E302
calcium ascorbate
Calcium ascorbate is a compound with the molecular formula CaC12H14O12. It is the calcium salt of ascorbic acid, one of the mineral ascorbates
Mineral ascorbates are a group of salts of ascorbic acid (vitamin C). They are composed of a mineral c ...
(approved for use as a food additive in the UK, U.S. Canada, Australia and New Zealand)
# E303
potassium ascorbate
Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...
(approved in Australia and New Zealand, but not in the UK, U.S. or Canada)
# E304 fatty acid esters of ascorbic acid such as
ascorbyl palmitate
Ascorbyl palmitate is an ester formed from ascorbic acid and palmitic acid creating a fat-soluble form of vitamin C. In addition to its use as a source of vitamin C, it is also used as an antioxidant food additive (E number E304). It is approved ...
(approved for use as a food additive in the UK, U.S., Canada, Australia and New Zealand)
The stereoisomers of Vitamin C have a similar effect in food despite their lack of efficacy in humans. They include
erythorbic acid
Erythorbic acid (isoascorbic acid, D-araboascorbic acid) is a stereoisomer of ascorbic acid (vitamin C). It is synthesized by a reaction between methyl 2-keto-D-gluconate and sodium methoxide. It can also be synthesized from sucrose or by strains ...
and its sodium salt (E315, E316).
Pharmacology
Pharmacodynamics
Vitamin C – specifically, in the form of ''ascorbate'' – performs numerous physiological functions in the human body by serving as an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
electron donor
In chemistry, an 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.
Typical reducing agents undergo permanent chemi ...
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
; and the metabolism of
microsome
In cell biology, microsomes are heterogeneous vesicle-like artifacts (~20-200 nm diameter) re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, liv ...
s. During biosynthesis, ascorbate acts as a reducing agent, donating electrons and preventing oxidation to keep iron and copper atoms in their reduced states.
Vitamin C functions as a cofactor for the following
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
lysyl hydroxylase
Lysyl hydroxylases (or procollagen-lysine 5-dioxygenases) are alpha-ketoglutarate-dependent hydroxylases enzymes that catalyze the hydroxylation of lysine to hydroxylysine. Lysyl hydroxylases require iron and vitamin C as cofactors for their ...
hydroxyl groups
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
to the amino acids proline or lysine in the collagen molecule via
prolyl hydroxylase
Procollagen-proline dioxygenase, commonly known as prolyl hydroxylase, is a member of the class of enzymes known as alpha-ketoglutarate-dependent hydroxylases. These enzymes catalyze the incorporation of oxygen into organic substrates through a mec ...
and
lysyl hydroxylase
Lysyl hydroxylases (or procollagen-lysine 5-dioxygenases) are alpha-ketoglutarate-dependent hydroxylases enzymes that catalyze the hydroxylation of lysine to hydroxylysine. Lysyl hydroxylases require iron and vitamin C as cofactors for their ...
, both requiring vitamin C as a cofactor. The role of vitamin C as a cofactor is to oxidize prolyl hydroxylase and lysyl hydroxylase from Fe to Fe and to reduce it from Fe to Fe. Hydroxylation allows the collagen molecule to assume its triple
helix
A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is formed as two intertwined helic ...
structure, and thus vitamin C is essential to the development and maintenance of
scar tissue
Scar tissue may refer to:
Medicine
* Scar, an area of fibrous tissue that replaces normal skin after injury
* Granulation tissue, a product of healing in major wounds
Film and television
* ''Scar Tissue'' (1975 film), or ''Wanted: Babysitter'' ...
,
blood vessel
The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away ...
fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...
s into
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
Hypoxia-inducible factor-proline dioxygenase
Hypoxia-inducible factor-proline dioxygenase (, ''HIF hydroxylase'') is an enzyme with systematic name ''hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating)''. This enzyme catalyses the following chemical rea ...
enzymes (isoforms:
EGLN1
Hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PH2), or prolyl hydroxylase domain-containing protein 2 (PHD2), is an enzyme encoded by the ''EGLN1'' gene. It is also known as Egl nine homolog 1. PHD2 is a α-ketoglutarate/2-oxoglutarate-depe ...
,
EGLN2
Egl nine homolog 2 is a protein that in humans is encoded by the ''EGLN2'' gene. ELGN2 is an alpha-ketoglutarate-dependent hydroxylase, a superfamily of non-haem iron-containing proteins.
The hypoxia inducible factor
Hypoxia-inducible fact ...
Dopamine beta-hydroxylase
Dopamine beta-hydroxylase (DBH), also known as dopamine beta-monooxygenase, is an enzyme () that in humans is encoded by the DBH gene. Dopamine beta-hydroxylase catalyzes the conversion of dopamine to norepinephrine.
The three substrates of ...
participates in the biosynthesis of
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...
Peptidylglycine alpha-amidating monooxygenase
Peptidyl-glycine alpha-amidating monooxygenase is an enzyme that catalyzes the conversion of glycine amides to amides and glyoxylate.
The enzyme is involved in the biosynthesis of many signaling peptides and some fatty acid amides.
In humans, t ...
amidates
peptide hormone
Peptide hormones or protein hormones are hormones whose molecules are peptide, or proteins, respectively. The latter have longer amino acid chain lengths than the former. These hormones have an effect on the endocrine system of animals, including h ...
s by removing the glyoxylate residue from their c-terminal glycine residues. This increases peptide hormone stability and activity.
Absorption, metabolism and excretion
From the U.S. National Institutes of Health: n humans"Approximately 70%–90% of vitamin C is absorbed at moderate intakes of 30–180 mg/day. However, at doses above 1,000 mg/day, absorption falls to less than 50%." It is transported through the intestine via both glucose-sensitive and glucose-insensitive mechanisms, so the presence of large quantities of sugar in the intestine can slow absorption.
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 transporter proteins required for active absorption. SVCT1 and SVCT2 import the reduced form of ascorbate across plasma membranes.
GLUT1
Glucose transporter 1 (or GLUT1), also known as solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1), is a uniporter protein that in humans is encoded by the ''SLC2A1'' gene. GLUT1 facilitates the transport of glucose across ...
and
GLUT3
Glucose transporter 3 (or GLUT3), also known as solute carrier family 2, facilitated glucose transporter member 3 (SLC2A3) is a protein that in humans is encoded by the ''SLC2A3'' gene. GLUT3 facilitates the transport of glucose across the plas ...
are glucose transporters, and transfer only the dehydroascorbic acid (DHA) 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.
SVCTs appear to be the predominant system for vitamin C transport in the body, the notable exception being red blood cells, which lose SVCT proteins during maturation. In both vitamin C synthesizers (example: rat) and non-synthesizers (example: human) cells with few exceptions maintain ascorbic acid concentrations much higher than the approximately 50 micromoles/liter (µmol/L) found in plasma. For example, the ascorbic acid content of pituitary and adrenal glands can exceed 2,000 µmol/L, and muscle is at 200-300 µmol/L. The known coenzymatic functions of ascorbic acid do not require such high concentrations, so there may be other, as yet unknown functions. A consequence of all this high concentration organ content is that plasma vitamin C is not a good indicator of whole-body status, and people may vary in the amount of time needed to show symptoms of deficiency when consuming a diet very low in vitamin C.
Excretion can be as ascorbic acid, via urine. In humans, during times of low dietary intake, vitamin C is reabsorbed by the kidneys rather than excreted. Only when plasma concentrations are 1.4 mg/dL or higher does re-absorption decline and the excess amounts pass freely into the urine. This salvage process delays onset of deficiency. Ascorbic acid also converts (reversibly) to dehydroascorbate (DHA) and from that compound non-reversibly to 2,3-diketogulonate and then oxalate. These three compounds are also excreted via urine. Humans are better than guinea pigs at converting DHA back to ascorbate, and thus take much longer to become vitamin C deficient.
Chemistry
The name "vitamin C" always refers to the -enantiomer of ascorbic acid and its
oxidized
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...
forms, such as dehydroascorbate (DHA). Therefore, unless written otherwise, "ascorbate" and "ascorbic acid" refer in the nutritional literature to -ascorbate and -ascorbic acid respectively. Ascorbic acid is a weak
sugar acid A Sugar acid or acidic sugar is a monosaccharide with a carboxyl group at one end or both ends of its chain.
Main classes of sugar acids include:
* Aldonic acids, in which the aldehyde group (−CHO) located at the initial end ( position 1) of an ...
structurally related to
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
. In biological systems, ascorbic acid can be found only at low pH, but in solutions above pH 5 is predominantly found in the
ionized
Ionization, or Ionisation is the process by which an atom or a molecule acquires a negative or positive charge by gaining or losing electrons, often in conjunction with other chemical changes. The resulting electrically charged atom or molecule ...
form, ascorbate. All of these molecules have vitamin C activity and thus are used synonymously with vitamin C, unless otherwise specified.
Numerous analytical methods have been developed for ascorbic acid detection. For example, vitamin C content of a food sample such as fruit juice can be calculated by measuring the volume of the sample required to decolorize a solution of
dichlorophenolindophenol
2,6-Dichlorophenolindophenol (DCPIP, DCIP or DPIP) is a chemical compound used as a redox dye. When oxidized, DCPIP is blue with a maximal absorption at 600 nm; when reduced, DCPIP is colorless.
DCPIP can be used to measure the rate of p ...
(DCPIP) and then calibrating the results by comparison with a known concentration of vitamin C.
Testing
Simple tests are available to measure the levels of vitamin C in
urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra.
Cellular ...
and serum. These better reflect recent dietary intake rather than total body content. It has been observed that while serum concentrations follow a circadian rhythm or reflect short-term dietary influence, content within cells or tissues is more stable and can give a better view of the availability of ascorbate within the entire organism. However, very few hospital laboratories are adequately equipped and trained to carry out such detailed analyses.
Synthesis
Most animals and plants are able to synthesize vitamin C through a sequence of
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
-driven steps, which convert
monosaccharides
Monosaccharides (from Greek '' monos'': single, '' sacchar'': sugar), also called simple sugars, are the simplest forms of sugar and the most basic units ( monomers) from which all carbohydrates are built.
They are usually colorless, water ...
to vitamin C. Yeasts do not make -ascorbic acid but rather its
stereoisomer
In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...
,
erythorbic acid
Erythorbic acid (isoascorbic acid, D-araboascorbic acid) is a stereoisomer of ascorbic acid (vitamin C). It is synthesized by a reaction between methyl 2-keto-D-gluconate and sodium methoxide. It can also be synthesized from sucrose or by strains ...
. In plants, synthesis is accomplished through the conversion of
mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ...
or
galactose
Galactose (, '' galacto-'' + ''-ose'', "milk sugar"), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epimer of glucose. A galactose molecu ...
to ascorbic acid. In animals, the starting material is
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
. In some species that synthesize ascorbate in the liver (including
mammal
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
s and
perching bird
A passerine () is any bird of the order Passeriformes (; from Latin 'sparrow' and '-shaped'), which includes more than half of all bird species. Sometimes known as perching birds, passerines are distinguished from other orders of birds by ...
s), the glucose is extracted from glycogen; ascorbate synthesis is a glycogenolysis-dependent process. In humans and in animals that cannot synthesize vitamin C, the enzyme -gulonolactone oxidase (GULO), which catalyses the last step in the biosynthesis, is highly mutated and non-functional.
Animal synthesis
There is some information on serum vitamin C concentrations maintained in animal species that are able to synthesize vitamin C. One study of several breeds of dogs reported an average of 35.9 μmol/L. A report on goats, sheep and cattle reported ranges of 100–110, 265-270 and 160-350 μmol/L, respectively.
The biosynthesis of ascorbic acid in
vertebrates
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...
starts with the formation of UDP-glucuronic acid. UDP-glucuronic acid is formed when UDP-glucose undergoes two oxidations catalyzed by the enzyme UDP-glucose 6-dehydrogenase. UDP-glucose 6-dehydrogenase uses the co-factor NAD+ as the electron acceptor. The transferase UDP-glucuronate pyrophosphorylase removes a UMP and glucuronokinase, with the cofactor ADP, removes the final phosphate leading to -glucuronic acid. The aldehyde group of this compound is reduced to a primary alcohol using the enzyme glucuronate reductase and the cofactor NADPH, yielding -gulonic acid. This is followed by lactone formationutilizing the hydrolase
gluconolactonase
The enzyme gluconolactonase (EC 3.1.1.17) catalyzes the reaction
:D-glucono-1,5-lactone + H2O \rightleftharpoons D-gluconate
This enzyme belongs to the family of hydrolases, specifically those acting on carboxylic ester bonds. The systematic na ...
between the carbonyl on C1 and hydroxyl group on C4. -Gulonolactone then reacts with oxygen, catalyzed by the enzyme
L-gulonolactone oxidase
L-Gulonolactone oxidase ( ECbr>1.1.3.8 is an enzyme that produces vitamin C, but is non-functional in Haplorrhini (including humans), in some bats, and in guinea pigs. It catalyzes the reaction of L-gulono-1,4-lactone with oxygen to form L ...
(which is nonfunctional in humans and other
Haplorrhini
Haplorhini (), the haplorhines ( Greek for "simple-nosed") or the "dry-nosed" primates, is a suborder of primates containing the tarsiers and the simians (Simiiformes or anthropoids), as sister of the Strepsirrhini ("moist-nosed"). The name is ...
primates; see Unitary pseudogenes) and the cofactor FAD+. This reaction produces 2-oxogulonolactone (2-keto-gulonolactone), which spontaneously undergoes
enolization
In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). The t ...
primate
Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians ( monkeys and apes, the latter including ...
suborders,
Haplorrhini
Haplorhini (), the haplorhines ( Greek for "simple-nosed") or the "dry-nosed" primates, is a suborder of primates containing the tarsiers and the simians (Simiiformes or anthropoids), as sister of the Strepsirrhini ("moist-nosed"). The name is ...
. This group includes humans. The other more primitive primates ( Strepsirrhini) have the ability to make vitamin C. Synthesis does not occur in most bats nor in species in the rodent family
Caviidae
Caviidae, the cavy family, is composed of rodents native to South America and includes the domestic guinea pig, wild cavies, and the largest living rodent, the capybara. They are found across South America in open areas from moist savanna to tho ...
, which includes
guinea pig
The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus '' Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ...
s and capybaras, but does occur in other rodents, including rats and
mice
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
bird
Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweigh ...
s make ascorbic acid in their kidneys. Recent orders of birds and most mammals make ascorbic acid in their liver. A number of species of
passerine
A passerine () is any bird of the order Passeriformes (; from Latin 'sparrow' and '-shaped'), which includes more than half of all bird species. Sometimes known as perching birds, passerines are distinguished from other orders of birds by t ...
birds also do not synthesize, but not all of them, and those that do not are not clearly related; there is a theory that the ability was lost separately a number of times in birds. In particular, the ability to synthesize vitamin C is presumed to have been lost and then later re-acquired in at least two cases. The ability to synthesize vitaminC has also been lost in about 96% of fish (the
teleosts
Teleostei (; Greek ''teleios'' "complete" + ''osteon'' "bone"), members of which are known as teleosts ), is, by far, the largest infraclass in the class Actinopterygii, the ray-finned fishes, containing 96% of all extant species of fish. Teleo ...
).
Most tested families of bats (order
Chiroptera
Bats are mammals of the order Chiroptera.''cheir'', "hand" and πτερόν''pteron'', "wing". With their forelimbs adapted as wings, they are the only mammals capable of true and sustained flight. Bats are more agile in flight than most bir ...
), including major insect and fruit-eating bat families, cannot synthesize vitamin C. A trace of gulonolactone oxidase was detected in only 1 of 34 bat species tested, across the range of 6 families of bats tested. There are at least two species of bats, frugivorous bat ('' Rousettus leschenaultii'') and insectivorous bat ('' Hipposideros armiger''), that retain (or regained) their ability of vitamin C production.
Some of these species (including humans) are able to make do with the lower amounts available from their diets by recycling oxidised vitamin C.
On a milligram consumed per kilogram of body weight basis, most simian species consume the vitamin in amounts 10 to 20 times higher than what is 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 simians on a far smaller dietary intake, perhaps by recycling oxidized vitamin C.
Evolution of animal synthesis
Ascorbic acid is a common enzymatic cofactor in mammals used in the synthesis of collagen, as well as a powerful
reducing agent
In chemistry, a reducing agent (also known as a reductant, reducer, or electron donor) is a chemical species that "donates" an electron to an (called the , , , or ).
Examples of substances that are commonly reducing agents include the Earth me ...
capable of rapidly scavenging a number of
reactive oxygen species
In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
The reduction of molecular oxygen () p ...
(ROS). Given that ascorbate has these important functions, it is surprising that the ability to synthesize this molecule has not always been conserved. In fact, anthropoid primates, ''
Cavia porcellus
The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus '' Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the a ...
'' (guinea pigs),
teleost
Teleostei (; Greek ''teleios'' "complete" + ''osteon'' "bone"), members of which are known as teleosts ), is, by far, the largest infraclass in the class Actinopterygii, the ray-finned fishes, containing 96% of all extant species of fish. Tele ...
fishes, most bats, and some
passerine
A passerine () is any bird of the order Passeriformes (; from Latin 'sparrow' and '-shaped'), which includes more than half of all bird species. Sometimes known as perching birds, passerines are distinguished from other orders of birds by t ...
birds have all independently lost the ability to internally synthesize vitamin C in either the kidney or the liver. In all of the cases where genomic analysis was done on an ascorbic acid
auxotroph
Auxotrophy ( grc, αὐξάνω "to increase"; ''τροφή'' "nourishment") is the inability of an organism to synthesize a particular organic compound required for its growth (as defined by IUPAC). An auxotroph is an organism that displays this ...
, the origin of the change was found to be a result of loss-of-function mutations in the gene that encodes L-gulono-γ-lactone oxidase, the enzyme that catalyzes the last step of the ascorbic acid pathway outlined above. One explanation for the repeated loss of the ability to synthesize vitamin C is that it was the result of
genetic drift
Genetic drift, also known as allelic drift or the Wright effect, is the change in the frequency of an existing gene variant (allele) in a population due to random chance.
Genetic drift may cause gene variants to disappear completely and there ...
; assuming that the diet was rich in vitaminC, natural selection would not act to preserve it.
In the case of the simians, it is thought that the loss of the ability to make vitamin C may have occurred much farther back in evolutionary history than the emergence of humans or even apes, since it evidently occurred soon after the appearance of the first primates, yet sometime after the split of early primates into the two major suborders
Haplorrhini
Haplorhini (), the haplorhines ( Greek for "simple-nosed") or the "dry-nosed" primates, is a suborder of primates containing the tarsiers and the simians (Simiiformes or anthropoids), as sister of the Strepsirrhini ("moist-nosed"). The name is ...
(which cannot make vitamin C) and its sister suborder of non-tarsier prosimians, the Strepsirrhini ("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 million years ago. Approximately three to five million years later (58 million years ago), only a short time afterward from an evolutionary perspective, the infraorder
Tarsiiformes
Tarsiiformes are a group of primates that once ranged across Europe, northern Africa, Asia, and North America, but whose extant species are all found in the islands of Southeast Asia. Tarsiers (family Tarsiidae) are the only living members o ...
, 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 million years ago).
It has also been noted that the loss of the ability to synthesize ascorbate strikingly parallels the inability to break down
uric acid
Uric 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 a product of the metabolic breakdown ...
, also a characteristic of primates. Uric acid and ascorbate are both strong
reducing agent
In chemistry, a reducing agent (also known as a reductant, reducer, or electron donor) is a chemical species that "donates" an electron to an (called the , , , or ).
Examples of substances that are commonly reducing agents include the Earth me ...
s. This has led to the suggestion that, in higher primates, uric acid has taken over some of the functions of ascorbate.
Plant synthesis
There are many different biosynthesis pathways for ascorbic acid in plants. Most of these pathways are derived from products found in glycolysis and other pathways. For example, one pathway goes through the plant cell wall polymers. The plant ascorbic acid biosynthesis pathway most principal seems to be -galactose. -Galactose reacts with the enzyme -galactose dehydrogenase, whereby the lactone ring opens and forms again but with lactone between the carbonyl on C1 and hydroxyl group on C4, resulting in -galactonolactone. -Galactonolactone then reacts with the mitochondrial flavoenzyme -galactonolactone dehydrogenase. to produce ascorbic acid. -Ascorbic acid has a negative feedback on -galactose dehydrogenase in spinach.
Ascorbic acid efflux by embryo of dicots plants is a well-established mechanism of iron reduction, and a step obligatory for iron uptake.
All plants synthesize ascorbic acid. Ascorbic acid functions as a cofactor for enzymes involved in photosynthesis, synthesis of plant hormones, as an antioxidant and also regenerator of other antioxidants. Plants use multiple pathways to synthesize vitamin C. The major pathway starts with glucose, fructose or
mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ...
(all simple sugars) and proceeds to L-
galactose
Galactose (, '' galacto-'' + ''-ose'', "milk sugar"), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epimer of glucose. A galactose molecu ...
, L-galactonolactone and ascorbic acid. There is feedback regulation in place, in that the presence of ascorbic acid inhibits enzymes in the synthesis pathway. This process follows a diurnal rhythm, so that enzyme expression peaks in the morning to support biosynthesis later on when mid-day sunlight intensity demands high ascorbic acid concentrations. Minor pathways may be specific to certain parts of plants; these can be either identical to the vertebrate pathway (including the GLO enzyme), or start with inositol and get to ascorbic acid via L-galactonic acid to L-galactonolactone.
Industrial synthesis
Vitamin C is produced from
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
by two main routes. The
Reichstein process The 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. This process was devised by Nobel Prize winner Tadeusz Reichstein and his colleagu ...
, developed in the 1930s, uses a single pre-fermentation followed by a purely chemical route. The modern two-step fermentation process, originally developed in
China
China, officially the People's Republic of China (PRC), is a country in East Asia. It is the world's most populous country, with a population exceeding 1.4 billion, slightly ahead of India. China spans the equivalent of five time zones and ...
in the 1960s, uses additional fermentation to replace part of the later chemical stages. The Reichstein process and the modern two-step fermentation processes use sorbitol as the starting material and convert it to
sorbose
Sorbose is a ketose belonging to the group of sugars known as monosaccharides. It has a sweetness that is equivalent to sucrose (table sugar). The commercial production of vitamin C
Vitamin C (also known as ascorbic acid and ascorbate) ...
using fermentation. The modern two-step fermentation process then converts sorbose to 2-keto-l-gulonic acid (KGA) through another fermentation step, avoiding an extra intermediate.
Both processes yield approximately 60% vitamin C from the glucose feed.
In 2017, China produced about 95% of the world supply of ascorbic acid (vitamin C), which is China's most exported vitamin, having total revenue of US$880 million in 2017. Due to pressure on Chinese industry to discontinue burning
coal
Coal is a combustible black or brownish-black sedimentary rock, formed as rock strata called coal seams. Coal is mostly carbon with variable amounts of other elements, chiefly hydrogen, sulfur, oxygen, and nitrogen.
Coal is formed when dea ...
normally used for vitamin C manufacturing, the price of vitamin C rose three-fold in 2016 alone to US$12 per kg.
History
Scurvy at sea
In the 1497 expedition of Vasco da Gama, the curative effects of citrus fruit were known. Later, the Portuguese planted fruit trees and vegetables in
Saint Helena
Saint Helena () is a British overseas territory located in the South Atlantic Ocean. It is a remote volcanic tropical island west of the coast of south-western Africa, and east of Rio de Janeiro in South America. It is one of three constitu ...
, a stopping point for homebound voyages from Asia, which sustained passing ships.
Authorities occasionally recommended plant food to prevent scurvy during long sea voyages.
John Woodall
John Woodall (1570–1643) 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. He i ...
, the first surgeon to the
British East India Company
The East India Company (EIC) was an English, and later British, joint-stock company founded in 1600 and dissolved in 1874. It was formed to trade in the Indian Ocean region, initially with the East Indies (the Indian subcontinent and South ...
, recommended the preventive and curative use of
lemon
The lemon (''Citrus limon'') is a species of small evergreen trees in the flowering plant family Rutaceae, native to Asia, primarily Northeast India (Assam), Northern Myanmar or China.
The tree's ellipsoidal yellow fruit is used for culin ...
juice in his 1617 book, ''The Surgeon's Mate''. In 1734, the
Dutch
Dutch commonly refers to:
* Something of, from, or related to the Netherlands
* Dutch people ()
* Dutch language ()
Dutch may also refer to:
Places
* Dutch, West Virginia, a community in the United States
* Pennsylvania Dutch Country
People E ...
writer
Johann Bachstrom
Jan Fryderyk or Johann Friedrich Bachstrom (24 December 1688, near Rawitsch, now Rawicz, Poland - June 1742, Nieswiez, now Nyasvizh, Belarus) was a writer, scientist and Lutheran theologian who spent the last decade of his life in Leiden. His surn ...
gave the firm opinion, "scurvy is solely owing to a total abstinence from fresh vegetable food, and greens."
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."
The first attempt to give scientific basis for the cause of this disease was by a ship's surgeon in the
Royal Navy
The Royal Navy (RN) is the United Kingdom's naval warfare force. Although warships were used by English and Scottish kings from the early medieval period, the first major maritime engagements were fought in the Hundred Years' War against F ...
,
James Lind
James Lind (4 October 1716 – 13 July 1794) was a Scottish doctor. He was a pioneer of naval hygiene in the Royal Navy. By conducting one of the first ever clinical trials, he developed the theory that citrus fruits cured scurvy.
Lind ...
. 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
cider
Cider ( ) is an alcoholic beverage made from the fermented juice of apples. Cider is widely available in the United Kingdom (particularly in the West Country) and the Republic of Ireland. The UK has the world's highest per capita consumption, ...
,
vinegar
Vinegar is an aqueous solution of acetic acid and trace compounds that may include flavorings. Vinegar typically contains 5–8% acetic acid by volume. Usually, the acetic acid is produced by a double fermentation, converting simple sugars to eth ...
,
sulfuric acid
Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular formu ...
or
seawater
Seawater, or salt water, is water from a sea or ocean. On average, seawater in the world's oceans has a salinity of about 3.5% (35 g/L, 35 ppt, 600 mM). This means that every kilogram (roughly one liter by volume) of seawater has appro ...
, along with their normal rations, in one of the world's first controlled experiments. The results showed that citrus fruits prevented the disease. Lind published his work in 1753 in his ''Treatise on the Scurvy''. In the 1757 edition of his work, Lind discusses his experiment starting o page 149.
Fresh fruit was expensive to keep on board, whereas boiling it down to juice allowed easy storage but destroyed the vitamin (especially if boiled in copper kettles). It was 1796 before the British navy adopted
lemon
The lemon (''Citrus limon'') is a species of small evergreen trees in the flowering plant family Rutaceae, native to Asia, primarily Northeast India (Assam), Northern Myanmar or China.
The tree's ellipsoidal yellow fruit is used for culin ...
juice as standard issue at sea. In 1845, ships in the West Indies were provided with
lime
Lime commonly refers to:
* Lime (fruit), a green citrus fruit
* Lime (material), inorganic materials containing calcium, usually calcium oxide or calcium hydroxide
* Lime (color), a color between yellow and green
Lime may also refer to:
Botany ...
juice instead, and in 1860 lime juice was used throughout the Royal Navy, giving rise to the American use of the nickname "limey" for the British.
Captain James Cook
James Cook (7 November 1728 Old Style date: 27 October – 14 February 1779) was a British explorer, navigator, cartographer, and captain in the British Royal Navy, famous for his three voyages between 1768 and 1779 in the Pacific Ocean and ...
had previously demonstrated the advantages of carrying "Sour krout" on board, by taking his crews to the
Hawaiian Islands
The Hawaiian Islands ( haw, Nā Mokupuni o Hawai‘i) are an archipelago of eight major islands, several atolls, and numerous smaller islets in the North Pacific Ocean, extending some from the island of Hawaii in the south to northernmost Kur ...
without losing any of his men to scurvy. For this, the British Admiralty awarded him a medal.
The name ''antiscorbutic'' was used in the eighteenth and nineteenth centuries for foods known to prevent scurvy. These foods included lemons, limes, oranges, sauerkraut, cabbage, malt, and
portable soup
Portable soup was a kind of dehydrated food of English origin used in the 18th and 19th centuries. It was a precursor of meat extract and bouillon cubes, and of industrially dehydrated and instant food. It is also known as pocket soup or veal ...
. In 1928, the Canadian Arctic anthropologist
Vilhjalmur Stefansson
Vilhjalmur Stefansson (November 3, 1879 – August 26, 1962) was an Arctic explorer and ethnologist. He was born in Manitoba, Canada.
Early life
Stefansson, born William Stephenson, was born at Arnes, Manitoba, Canada, in 1879. His parents had ...
showed that the
Inuit
Inuit (; iu, ᐃᓄᐃᑦ 'the people', singular: Inuk, , dual: Inuuk, ) are a group of culturally similar indigenous peoples inhabiting the Arctic and subarctic regions of Greenland, Labrador, Quebec, Nunavut, the Northwest Territories ...
avoid scurvy on a diet of largely raw meat. Later studies on traditional food diets of the
Yukon
Yukon (; ; formerly called Yukon Territory and also referred to as the Yukon) is the smallest and westernmost of Canada's three territories. It also is the second-least populated province or territory in Canada, with a population of 43,964 as ...
First Nations
First Nations or first peoples may refer to:
* Indigenous peoples, for ethnic groups who are the earliest known inhabitants of an area.
Indigenous groups
*First Nations is commonly used to describe some Indigenous groups including:
**First Natio ...
,
Dene
The Dene people () are an indigenous group of First Nations who inhabit the northern boreal and Arctic regions of Canada. The Dene speak Northern Athabaskan languages. ''Dene'' is the common Athabaskan word for "people". The term "Dene" ha ...
,
Inuit
Inuit (; iu, ᐃᓄᐃᑦ 'the people', singular: Inuk, , dual: Inuuk, ) are a group of culturally similar indigenous peoples inhabiting the Arctic and subarctic regions of Greenland, Labrador, Quebec, Nunavut, the Northwest Territories ...
, and Métis of Northern Canada showed that their daily intake of vitamin C averaged between 52 and 62 mg/day, comparable with the Estimated Average Requirement.
Discovery
Vitamin C was discovered in 1912, isolated in 1928 and synthesized in 1933, making it the first vitamin to be synthesized. Shortly thereafter
Tadeus Reichstein
Tadeusz Reichstein (20 July 1897 – 1 August 1996) was a Polish-Swiss chemist and the Nobel Prize in Physiology or Medicine laureate (1950), which was awarded for his work on the isolation of cortisone.
Early life
Reichstein was born into a Po ...
succeeded in synthesizing the vitamin in bulk by what is now called the
Reichstein process The 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. This process was devised by Nobel Prize winner Tadeusz Reichstein and his colleagu ...
. This made possible the inexpensive mass-production of vitamin C. In 1934
Hoffmann–La Roche
F. Hoffmann-La Roche AG, commonly known as Roche, is a Swiss multinational healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX ...
trademarked synthetic vitamin C under the brand name
Redoxon
Redoxon was the brand name of the first artificially synthesized ascorbic acid (vitamin C). Redoxon was first marketed to the general public by Hoffman-La Roche in 1934, making it the first mass-manufactured synthetic vitamin in history. The bran ...
and began to market it as a dietary supplement.
In 1907 a laboratory animal model which would help to identify the antiscorbutic factor was discovered by the Norwegian physicians Axel Holst and Theodor Frølich, who when studying shipboard
beriberi
Thiamine deficiency is a medical condition of low levels of thiamine (Vitamin B1). A severe and chronic form is known as beriberi. The two main types in adults are wet beriberi and dry beriberi. Wet beriberi affects the cardiovascular system, ...
, fed
guinea pig
The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus '' Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ...
s their test diet of grains and flour and were surprised when scurvy resulted instead of beriberi. By luck, this species did not make its own vitamin C, whereas mice and rats do. In 1912, the
Polish
Polish may refer to:
* Anything from or related to Poland, a country in Europe
* Polish language
* Poles
Poles,, ; singular masculine: ''Polak'', singular feminine: ''Polka'' or Polish people, are a West Slavic nation and ethnic group, w ...
biochemist
Casimir Funk
Kazimierz Funk (; February 23, 1884 – November 19, 1967), commonly anglicized as Casimir Funk, was a Polish-American biochemist generally credited with being among the first to formulate (in 1912) the concept of vitamins, which he called "vit ...
developed the concept of
vitamin
A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nutrie ...
s. One of these was thought to be the anti-scorbutic factor. In 1928, this was referred to as "water-soluble C", although its chemical structure had not been determined.
From 1928 to 1932,
Albert Szent-Györgyi
Albert Imre Szent-Györgyi de Nagyrápolt ( hu, nagyrápolti Szent-Györgyi Albert Imre; September 16, 1893 – October 22, 1986) was a Hungarian biochemist who won the Nobel Prize in Physiology or Medicine in 1937. He is credited with fi ...
and Joseph L. Svirbely's Hungarian team, and Charles Glen King's American team, identified the anti-scorbutic factor. Szent-Györgyi isolated hexuronic acid from animal adrenal glands, and suspected it to be the antiscorbutic factor. In late 1931, Szent-Györgyi gave Svirbely the last of his adrenal-derived 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. This led to a bitter dispute over priority. In 1933, Walter Norman Haworth chemically identified the vitamin as -hexuronic acid, proving this by synthesis in 1933. Haworth and Szent-Györgyi proposed that L-hexuronic acid be named a-scorbic acid, and chemically -ascorbic acid, in honor of its activity against scurvy. The term's etymology is from Latin, "a-" meaning away, or off from, while -scorbic is from Medieval Latin ''scorbuticus'' (pertaining to scurvy), cognate with Old Norse ''skyrbjugr'', French ''scorbut'', Dutch ''scheurbuik'' and Low German ''scharbock''. Partly for this discovery, Szent-Györgyi was awarded the 1937
Nobel Prize in Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, according ...
, and
Haworth
Haworth () is a village in the City of Bradford, West Yorkshire, England, in the Pennines, south-west of Keighley, west of Bradford and east of Colne in Lancashire. The surrounding areas include Oakworth and Oxenhope. Nearby villages inc ...
shared that year's
Nobel Prize in Chemistry
)
, image = Nobel Prize.png
, alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
.
In 1957, J. J. Burns showed that some mammals are susceptible to scurvy as their
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
does not produce the
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
-gulonolactone oxidase, the last of the chain of four enzymes that synthesize vitamin C. American biochemist
Irwin Stone
Irwin Stone (1907–1984) was an American biochemist, chemical engineer, and writer. He was the first to use ascorbic acid in the food processing industry as a preservative, and originated and published the hypothesis that humans require much la ...
was the first to exploit vitamin C for its food preservative properties. He later developed the theory that humans possess a mutated form of the -gulonolactone oxidase coding gene.
In 2008, researchers at the
University of Montpellier
The University of Montpellier (french: Université de Montpellier) is a public research university located in Montpellier, in south-east of France. Established in 1220, the University of Montpellier is one of the oldest universities in the wor ...
discovered that in humans and other primates the
red blood cell
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s have evolved a mechanism to more efficiently utilize the vitamin C present in the body by recycling oxidized -dehydroascorbic acid (DHA) back into ascorbic acid for reuse by the body. The mechanism was not found to be present in mammals that synthesize their own vitamin C.
Large doses
Vitamin C megadosage is a term describing the consumption or injection of vitamin C in doses comparable to or higher than the amounts produced by the livers of mammals which are able to synthesize vitamin C. The theory behind this, although not the actual term, was described in 1970 in an article by Linus Pauling. Briefly, his position was that for optimal health, humans should be consuming at least 2,300 mg/day to compensate for the inability to synthesize vitamin C. The recommendation also fell into the consumption range for gorillas - a non-synthesizing near-relative to humans. A second argument for high intake is that serum ascorbic acid concentrations increase as intake increases until it plateaus at about 190 to 200 micromoles per liter (µmol/L) once consumption exceeds 1,250 milligrams. As noted, government recommendations are a range of 40 to 110 mg/day and normal plasma is approximately 50 µmol/L, so 'normal' is about 25% of what can be achieved when oral consumption is in the proposed megadose range.
Pauling popularized the concept of high dose vitamin C as prevention and treatment of the common cold in 1970. A few years later he proposed that vitamin C would prevent cardiovascular disease, and that 10 grams/day, initially (10 days) administered intravenously and thereafter orally, would cure late-stage cancer. Mega-dosing with ascorbic acid has other champions, among them chemist
Irwin Stone
Irwin Stone (1907–1984) was an American biochemist, chemical engineer, and writer. He was the first to use ascorbic acid in the food processing industry as a preservative, and originated and published the hypothesis that humans require much la ...
and the controversial
Matthias Rath
Matthias Rath (born 1955) is a doctor, businessman, and vitamin salesman. He earned his medical degree in Germany. Rath claims that a program of dietary supplement, nutritional supplements (which he calls "cellular medicine"), including formulati ...
and
Patrick Holford
Patrick Holford is a British author and entrepreneur who endorses a range of controversial vitamin tablets. As an advocate of alternative nutrition and diet methods, he appears regularly on television and radio in the UK and abroad. He has 36 b ...
, who both have been accused of making unsubstantiated treatment claims for treating cancer and
HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
infection.
The mega-dosing theory is to a large degree discredited. Modest benefits are demonstrated for the common cold. Benefits are not superior when supplement intakes of more than 1,000 mg/day are compared to intakes between 200 and 1,000 mg/day, and so not limited to the mega-dose range. The theory that large amounts of intravenous ascorbic acid can be used to treat late-stage cancer is - some forty years after Pauling's seminal paper - still considered unproven and still in need of high quality research. However, a lack of evidence has not stopped individual physicians from prescribing intravenous ascorbic acid to thousands of people with cancer.
Society and culture
In February 2011, the
Swiss Post
Swiss Post (french: La Poste suisse, it, La Posta Svizzera, german: Die Schweizerische Post, rm, La Posta Svizra) is the national postal service of Switzerland. A public company owned by the Swiss Confederation, it is the country's second lar ...
issued a postage stamp bearing a depiction of a model of a molecule of vitamin C to mark the
International Year of Chemistry
The International Year of Chemistry 2011 (IYC 2011) was a year-long commemorative event for the achievements of chemistry and its contributions to humankind.
Brand names
Vitamin C is sold around the world as a stand-alone product at amounts up to 1,000 mg and as part of
fixed-dose combination
A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC pr ...
products, under many brand names.
Pharmacopoeias
* ''
British Pharmacopoeia
The ''British Pharmacopoeia'' (''BP'') is the national pharmacopoeia of the United Kingdom. It is an annually published collection of quality standards for medicinal substances in the UK, which is used by individuals and organisations involv ...
''
* ''
Japanese Pharmacopoeia
The is the official pharmacopoeia of Japan. It is published by the . The first edition was published on 25 June 1886, with revisions being issued from time to time. The current revision is number 18, issued electronically on 7 June 2021. An offi ...