Ascorbic acid, vitamin C, E300 (Latin acidum ascorbicum) – an organic chemical compound from the group of unsaturated polyhydric alcohols. It is necessary for the functioning of living organisms. For some animals, including humans, it is a vitamin, that is, it must be supplied in food. It is also an antioxidant used as a food additive.
Construction and chemical properties
It occurs naturally as a compound with L configuration in the side chain and D configuration of the furan system. Under the influence of the methanolic solution, the NaOH is epimerized to the erythoric acid (D-isoascorbic acid, E315), differing in the configuration of the side chain.
L-ascorbic acid is sometimes incorrectly called “left-handed vitamin C” due to the confusion of the relative configuration with the optical activity. In fact, L-ascorbic acid turns the plane of polarized light to the right. D-ascorbic acid, on the other hand, is an antioxidant, but it also has no biological significance – it does not act as a cofactor, so it is not a vitamin.
Occurrence and synthesis
L-ascorbic acid occurs naturally in many plant and animal organisms. In both kingdoms, the substrate for the biosynthesis of this compound is D-glucose, however, it proceeds in different ways. In plants, glucose is oxidized at the C-2 position, followed by the epimerisation of the C-5 atom and subsequent oxidation at the C-1 position. In animals, the metabolic pathway passes through glucuronic acid followed by inversion of the carbon backbone, resulting in the C-1 and C-6 glucose atoms becoming the C-6 and C-1 atoms of ascorbic acid, respectively.
Inability to synthesize
In a number of animals, including primates and species that are far away, guinea pigs or fish excellent (they include rainbow trout and carp), ascorbic acid must be supplied in the diet, because their organisms do not produce it. In primates, this is the result of mutations in the gene responsible for the production of L-gulono-γ-lactone oxidase (GLO), which in the liver catalyzes the last step of the biosynthesis of ascorbic acid from D-glucose, ie the oxidation of L-gulonolactone. It is estimated that the inactivation of this gene occurred about 60-75 million years ago, shortly after the separation of the righteous monkeys and apes. On the other hand, in the fish of good nature, in addition to mutations in GLO, there are also other mutations that prevent the synthesis of vitamin C; the inability to produce this compound appeared in them about 200 million years ago.
Most of the ascorbic acid produced industrially is produced by the method developed in 1934 by Reichstein and Grüssner, in which the substrate is also natural D-glucose.
Role in the human body
It is an antioxidant. Activates many enzymes, facilitates the assimilation of iron, affects the synthesis of corticosteroids and some neurotransmitters. It maintains the normal state of connective tissue (it is necessary in the synthesis of collagen), strengthens the gums and teeth, and kills bacteria that cause tooth decay. It strengthens the body’s resistance to infections. Facilitates wound healing. It stabilizes the psyche. Takes part in the transformation of tyrosine. It also affects the maintenance of the proper oxidative potential in the cell.
Research indicates the lack of effect of taking vitamin C on the risk of colds and a small impact on its duration (reduction of time by 14% for children and 8% for adults). The exception was the group of participants of marathons, skiers and soldiers staying in very low temperatures or subjected to intense physical effort, in whom a 50% reduction in the occurrence of a cold when using 2 g of vitamin C per day was observed.
The recommended intake of vitamin C for an adult human is from 45 to 90 mg a day. The organisms of most animals and plants produce this compound. The exceptions are organisms of primates (including humans), guinea pigs and some species of bats (due to the mutation and loss of the enzyme L-gulonolactone oxidase), which must be supplied from the outside.
The effects of scarcity
Scurvy (bleeding and gum sores, tooth loss), brittleness and cracking of blood vessels, weakened immunity of the body, swollen and painful joints, abnormal fusion of bones, slow wound healing.
Western societies consume much more vitamin C in the diet than is necessary to prevent the development of scurvy.
Its deficiency is often suffered by tobacco smokers, hence the numerous fine wrinkles characteristic of their skin.
The effects of excess
Ascorbic acid is not toxic, but if taken in excess (doses above 2 g per day) can cause stomach complaints, nausea, diarrhea, vomiting, skin rash, reduce immunity after a radical reduction of the dose. Usually, however, its excess is excreted from the body along with urine.
Due to the metabolic effect of vitamin C, it is recommended to avoid the consumption of higher doses (ie more than 500 mg daily) in the presence or incidence of kidney stones, which include calcium oxalate or uric acid. The same recommendation applies to people suffering from diseases such as hemochromatosis, thalassemia and sideroblastic anemia. It is estimated that intravenous high doses of vitamin C, limited in time, should not increase the risk of urolithiasis. A prospective cohort analysis from 2015 showed that supplementation of vitamin C increases the risk of kidney stones in men, but not in women.
The use of higher than recommended doses of vitamin C during pregnancy can be harmful to the fetus. High doses of this vitamin, according to the FDA classification of the risk of medication during pregnancy, belong to category C. This means that in animal studies an adverse effect on the fetus has been demonstrated, however, its effect on human pregnancy is not confirmed in clinical trials.
Scientific studies on the potential positive health effects of vitamin C supplementation provide conflicting results. A study conducted by U.S. Preventive Disease Task Force showed no evidence of the protective effect of vitamin C supplementation against the development of cardiovascular disease and cancer. It has also failed to clinically prove the effect of vitamin C on life expectancy.
Prevention of cancer development
The 2013 study did not show that supplementation with vitamin C reduces the risk of developing lung cancer in healthy and high-risk patients (smokers and those exposed to inhaling asbestos fibers). A meta-analysis from 2014 showed a weak relationship between vitamin C supplementation and reduced incidence of lung cancer. Another meta-analysis did not show a connection of vitamin C with the risk of prostate cancer.
In order to estimate the effect of vitamin C supplementation on the incidence of colorectal cancer, two meta-analyzes were performed. One of the studies showed a weak relationship between vitamin C consumption and reduced incidence of this disease. The other did not show such dependencies.
Analysis of 2011 metadata did not confirm that vitamin C prevents the development of breast cancer, but another study showed that vitamin C may be associated with increased survival in patients already sick.
The meta-analysis from 2013 did not show the effect of vitamin C supplementation on reducing the risk of heart attack, stroke, death due to cardiovascular disease or total death. Another analysis, however, showed an inverse relationship between vitamin C and the risk of stroke.
A meta-analysis of 44 clinical trials showed a significant positive effect of supplementation with daily doses of vitamin C above 500 mg for endothelial function. It was shown that this effect was stronger in people with an increased risk of developing cardiovascular disease.
The effect of vitamin C supplementation on the treatment of rheumatoid arthritis has not been demonstrated.
Studies investigating the effect of vitamin C on the development of Alzheimer’s disease have achieved conflicting results. Maintaining a healthy intake of vitamin C in the diet is probably more important than supplementation.
Study of the effect of consuming doses of vitamin C exceeding RDA did not show its significant effect on the prevention and inhibition of development of senile cataract.
The influence of vitamin C on the treatment of colds has been the object of many scientific studies. It has been shown that it is not effective in preventing or treating colds except in special cases (especially in people who practice sport in a cold environment). Routine supplementation with vitamin C does not reduce the likelihood or severity of colds in the general population, but may reduce the duration of the disease.
Application in the food industry
Ascorbic acid is an antioxidant and as such is used in the food industry, as well as its salts and esters. Symbols used to denote these compounds:
• E300 – ascorbic acid
• E301 – sodium ascorbate
• E302 – calcium ascorbate
• E303 – potassium ascorbate
• E304 – esters of fatty acids and ascorbic acid
E304 (i) – ascorbyl palmitate
E304 (ii) – ascorbyl stearate
• E315 – isoascorbic acid (erythritol).
Symptoms of scurvy were described for the first time in reports from crusades. In times of great geographical discoveries (XV-XVI centuries) it became the main cause of death and disability of sailors on long cruises. It was not until 1753 that Scottish doctor James Lind discovered that the disease prevents and cures the consumption of citrus juice. At the beginning of the 20th century, it was discovered that guinea pig is also susceptible to this disease and may be an animal model for its research. This made it possible to prove that the scurvy base is actually the wrong diet.
Vitamin C was isolated in 1928 by the Hungarian biochemist Albert Szent-Györgyi from bovine adrenal cortex and orange juice, and then from paprika. He showed that the isolated compound has anticorrosive properties and gave it the name “hexuronic acid” (hexuronic acid). In 1933 W.N. Haworth and E.L. Hirst established its structure, and in addition Haworth and T. Reichstein and colleagues independently described the synthesis of both of its enantiomers. In the same year, Szent-Györgyi and Haworth proposed changing the name of the compound to “ascorbic acid” to illustrate its anticorbital properties. In 1937, both scientists were awarded the Nobel Prize for the study of Vitamin C – Szent-Györgyi received it in the field of physiology or medicine, and Haworth in the field of chemistry.