Vitamin C

Vitamin C is different from all other vitamins, the chemistry and biochemistry of this compound make it unique in many ways. Vitamin C is found in both the animal and plant kingdoms, and its role is often not entirely clear. The synthetic vitamin is widely used as a food additive and its antioxidant properties help preserve food products and, therefore, has an E number (K300). Even today, there is still controversy about the importance of vitamin C for human health, as well as the optimal doses of the vitamin that should be taken: recommendations from various authors range from 30 mg to 10 g per day.

General information about vitamin C

Vitamin C has other names - it is an antiscorbutic vitamin, an antiscorbutic vitamin, and it is also called ascorbic acid. Water-soluble vitamin C is considered the main vitamin of vegetables, berries, and fruits.

The biochemistry of vitamin C in mammals is so far from being understood that even today its biochemical role in such systems remains unclear. The chemical structure of L-ascorbic acid has been clearly determined by X-ray structural analysis, but the structure of the product of its two-electron oxidation, dehydroascorbic acid, has not been definitively established, since it has not yet been possible to obtain this compound in pure crystalline or even solid form.

Among higher organisms, only a very few are incapable of biosynthesizing vitamin C. Homo sapiens is one of them, so it is not surprising that most of what is known about the biochemistry of L-ascorbic acid pertains to mammals.

In 1927, Szent-Györi discovered vitamin C from the juice of cabbage, orange and red pepper. These were crystals with clearly expressed restorative properties. They were called hexuronic acid. Scientists proved the antiscorbutic properties of vitamin C in 1932, then it was named ascorbic acid (from Greek "scorbutus" is translated as "scurvy").

Vitamin C absorption

Taking vitamin C after meals will help it be better absorbed.

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The beneficial effects of vitamin C on the body

The antiscorbutic vitamin helps produce collagen and connective tissue, strengthens bone tissue, blood vessels, skin and joints. It stimulates metabolism.

One of the most important properties of vitamin C is its antioxidant properties. Thanks to them, it neutralizes toxic radicals that occur in the body during heavy physical exertion, during illnesses, and during negative environmental impacts on the body.

Vitamin C is able to neutralize many dangerous poisons in the body: it combines with them and makes them harmless, then these compounds are excreted in the urine. It also helps to increase the body's resistance to adverse conditions, overheating, cooling, stress, infections and allergies.

Ascorbic acid prevents the oxidation of important fats and fat-soluble vitamins A and E, helps heal wounds and burns. Increasing the elasticity and strength of blood vessels, activating the glands of the endocrine system, improving liver function, utilizing cholesterol from the liver and vessel walls, protecting the heart - all this is the work of vitamin C.

Oxidation and hydroxylation

It is known that ascorbic acid is involved in the metabolism of some amino acids, promoting the formation of hydroxyproline, hydroxylysine, norepinephrine, serotonin, homogentisic acid and carnitine.

Hydroxyproline and hydrosilizine are found in animal tissues almost exclusively in collagen, which accounts for about one third of all proteins in the mammalian body. Collagen synthesized with a lack or absence of vitamin C is not capable of forming full-fledged fibers, which is the cause of skin lesions, vascular fragility, etc.

Restorative properties

It is known that life on Earth is completely dependent on oxygen supply. But when it is in excess, in the wrong form or in the wrong place, oxygen is a potential hell. Particularly harmful are its reactive forms and oxidizing radicals, such as superoxide anion and hydroxyl radical. These are well-known active oxidants that can cause serious damage to the lipid components of cell membranes due to oxidation by peroxides. The protective antioxidant role of vitamin E and essential fatty acids has been established. However, they are fat-soluble compounds and, obviously, the function they perform inside the membrane is transferred to ascorbic acid on its surface. Here, in an aqueous environment, vitamin C helps to trap potentially dangerous oxidants with another water-soluble antioxidant, the tripeptide glutathione. Paradoxically, it has been suggested that one of the functions of glutathione is to maintain ascorbic acid in a reduced state!

To say that vitamins E and C perform identical antioxidant functions in the lipid matrix and in the aqueous cellular environment, respectively, is an oversimplification. These vitamins have been shown to act synergistically, and it is possible that at the lipid/aqueous interface, ascorbic acid provides protection for vitamin E or restores its oxidized form after free radical attack.

The reducing power of ascorbic acid is "used" by another vitamin, folic acid. To perform its function, folic acid must be in the reduced tetrahydrofolate form, and this state is ensured and/or maintained in the presence of ascorbic acid.

A major problem is the tendency of the aggressive superoxide free radical to oxidize the iron atom in red blood cells, which leads to the formation of functionally inactive methemoglobin (metHb). This process is reversed by the enzyme metHb reductase, which functions in the presence of cytochrome bs and ascorbic acid. The superoxide free radical is usually destroyed by vitamin C-dependent superoxide cismutase (SOD), so SOD prevents the formation of a very aggressive hydroxyl radical.

It is well known that ascorbic acid promotes the absorption of iron through the intestinal wall. This may be due to the fact that it maintains the element in a reduced form, in which it is more easily absorbed by the mucous membrane.

Electronic transport

The oxidation-reduction properties of ascorbic acid have long been used in in vitro studies of electron transport in mitochondrial membranes.

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Distribution in tissues

Vitamin C participates in hydroxylation reactions in the biosynthesis of collagen, serotonin, and noradrenaline in animals. The key to resolving the issue of the role of ascorbic acid in the metabolic process in animals can be found based on the results of its tissue distribution analysis. The analyzed animal tissues contain the following amounts of vitamin C (in descending order): adrenal glands (55 mg%) pituitary gland and leukocytes, brain, eye lenses and pancreas, kidneys, spleen and liver, heart muscle, milk (female 3 mg%, cow's 1 mg%), plasma (1 mg%). In most of these tissues, the function of vitamin C is to maintain structural integrity by participating in collagen biosynthesis. Elevated levels of ascorbic acid reflect more specialized functions, such as participation in the synthesis of hormones and neurotransmitters of the adrenal glands and brain, as well as in the formation of an immune response in the spleen and leukocytes, stimulation of the pentose phosphate cycle in the liver, and maintenance of the transparency of the lens and cornea of the eye.

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Intake, excretion and metabolism

To prevent scurvy, the human body needs 10 mg of vitamin C per day, the daily recommended dose in the UK is 30 mg, and a laboratory rat can synthesize the equivalent of 2000 mg (2 g) per day! There is a school of thought in medicine, not popular today, that recommends taking megadoses (1 - 10 g per day). Perhaps this makes sense. But the argument against this is that the body of an adult (human) is able to accumulate only a limited amount of the vitamin, usually 2-3 g, possibly 4 g. At the same time, the level in plasma reaches 1.4 mg%.

Ascorbic acid is metabolized in the liver and kidneys, undergoing a series of sequential transformations, the final result of which is the formation of oxalic acid, which is excreted in the urine.

The reducing properties of vitamin C make it an excellent co-substrate in monooxygenase hydroxylation reactions leading to the formation of amino acids and catecholamines. Due to these same properties, vitamin C provides protection not only to cells by eliminating free radicals, but also to other antioxidants such as vitamin E. Its chelating and/or reducing properties facilitate the absorption of iron compounds in the intestine. It has been suggested that it can function as a circulating redox pair in electron transport and in the creation of membrane potential, and its status corresponds to that of cytochrome c. Vitamin C is optimal, but not the only factor necessary for maintaining numerous iron- and copper-containing enzymes in a reducing state in which they are most functionally active.

M. Davis et al. (1999) believe that our understandable interest in various aspects of the chemistry and biochemistry of vitamin C, fueled by the very tangible income from its production, is not the best incentive to resolve the riddle of the existence of one basic biological function in this simple molecule or its absence. Our enthusiasm is due simply to the absence of gulonolactone oxidase in all of us. And the culprit is a single gene, which our distant ancestors lost 25 million years ago, which doomed humans, along with other primates, as well as some species of birds, bats, beetles and, of course, guinea pigs, to be partly "unwilling vegetarians."

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Interaction with other elements of the body

With the help of vitamin C, iron (Fe), which affects hematopoiesis, is well absorbed.

What influences the amount of vitamin C in foods?

Vitamin C is one of the most sensitive vitamins. It is known that cooking vegetables and fruits often entails the loss of ascorbic acid. Any heat treatment of products or exposure to direct sunlight quickly reduces the content of this vitamin. Thus, when chopping products, the enzymatic activity of ascorbate oxidase, contained in plants rich in vitamin C, increases significantly. This enzyme is present in all plant tissues. Another enzyme that causes the loss of ascorbic acid, phenolase, catalyzes the oxidation of polyphenolic compounds by atmospheric oxygen, due to which fruits such as apples darken. The process is accompanied by the formation of dehydroascorbic acid, which quickly turns into 2,3-diketogulonic acid, and is catalyzed by Ca ions and other transition metals. This is why it is not recommended to cook vegetables and fruits in copper and iron utensils.

And of course, the main factor affecting the loss of vitamin C during cooking is simply its dissolution in water. It should be noted that vegetables cooked in a microwave oven retain much more vitamin C than those cooked in conventional ways. Thus, vitamin C loss can be prevented not only by avoiding long boiling of vegetables in copper cookware, but also by cooking them whole. In order to preserve vitamin C in products, it is recommended to freeze them and store them in a cool, dark place, for example, in a cellar or basement.

Vitamin C requirement per day

For an adult, 70-100 mg of vitamin C will compensate for all losses of this vitamin by the body.

Under what conditions does the need for vitamin C increase?

If you play sports, you need to consume 150-500 mg of antiscorbutic vitamin per day. Pregnant women need to consume about 120-150 mg of this vitamin. In case of colds, it is recommended to increase the daily dose of vitamin C to 2000 mg. Also, in unfavorable climates, you need to increase the content of this vitamin in the body.

Why does vitamin C deficiency occur in the body?

A deficiency of ascorbic acid in the body can occur due to improper heat treatment of fruits and vegetables (up to 60% of vitamin C is lost during cooking). It can also occur due to improper storage of vegetables (if fresh potatoes in 100 g contain about 20 mg of antiscorbutic vitamin, then after six months of storage – only 10 mg).

Deficiency of this vitamin also occurs when there is insufficient amount of vegetables and fruits in the diet.

There is a point of view that in Western countries vitamin deficiencies are no longer encountered. But this is not true. It is recognized that chronically ill, elderly and lonely people suffer from vitamin C deficiency. The level of ascorbic acid in plasma is 1.2 mg% on average (permissible limits are 0.6-2.5 mg%), the ascorbate content in leukocytes is normally 25 mcg per 10 ⁸ cells.

Recommended Dietary Allowances for Daily Intake of Vitamin C

Recommended Dietary Allowances	mg per day
Babies	35
Children	45
Teenagers	50
Adults	60
Pregnant women	80
Nursing mothers	100
Old people	150

Plasma ascorbic acid levels increase only with intake of up to 150 mg per day. The level of ascorbic acid in plasma is an indicator of the level of vitamin C in the body. A state of deficiency is indicated by its fall below 0.5 mg%. It has been found that plasma levels decrease in many pathological conditions, such as infectious diseases, congestive heart failure, liver and kidney diseases, gastrointestinal and endocrine disorders, purpura (hemorrhagic rash), and malignant tumors. Patients in a febrile state, who have undergone surgery or trauma, require large intakes of vitamin C with food.

Signs of Vitamin C Deficiency in the Body

If a person suffers from a lack of vitamin C, then wounds may heal poorly, gums may bleed, bruises may appear on the body, the face may swell, blood vessels in the eyes may become weak, joint pain may appear, the body may have a weak reaction to colds. Such people often lose hair, have frequent nosebleeds and may develop scurvy. Signs of scurvy include: severe bleeding gums, tooth loss, depression, loss of appetite, fatigue, skin bleeding, hysteria and anemia.

Signs of Vitamin C Excess

Signs of vitamin C overdose may include frequent urination, nausea, headaches, vomiting, and mild diarrhea. Sometimes, people with an excess of ascorbic acid experience colic in the lower abdomen and reddened skin on the face.

Foods that contain vitamin C

Many foods contain vitamin C, and we don’t even know it!

Most living organisms can convert D-glucose into L-ascorbic acid. Homo sapiens is entirely dependent on vitamin C from food. The only animal product containing significant amounts of vitamin C is milk (1-5 mg/100 g); it is also found in the liver. The richest sources of ascorbic acid are fresh vegetables and fruits (especially citrus fruits, tomatoes and green peppers), baked potatoes (17 mg/100 g) and leafy vegetables. Guava (300 mg/100 g) and blackcurrant (200 mg/100 g) are very rich in vitamin C, but they are not very common in Western countries.

Thus, rose hips contain up to 1000 mg of antiscorbutic vitamin, sweet peppers – 250 mg, kiwi – about 180 mg, and sea buckthorn contains about 200 mg of this vitamin. If you like cabbage, you will not suffer from vitamin C deficiency, because it contains from 70 to 100 mg of the vitamin. Everyone’s favorite strawberry is saturated with ascorbic acid by 60 mg, as well as an orange, and a sour lemon is saturated with it by 40 mg. Eat these products more often, and you will not know what a cold is. The table provides comprehensive data on the content of vitamin C in the most commonly used vegetables and fruits.

Vitamin C Content of Common Fruits and Vegetables

Vegetables/fruits	Ascorbic acid content, mg per 100 g
Rose hips	1000
Blackcurrant	200
Cabbage	186
Green pepper	128
Horseradish	120
Broccoli cabbage	FROM
Brussels sprouts	109
Watercress	79
Cauliflower	78
Strawberry	59
Spinach	51
Oranges/lemons	50
Leafy cabbage	47
New potatoes	30
Peas	25
Old potatoes	8
Carrot	6
Apples	6
Plums	3

Vitamin C in medicine

The widespread use of vitamin C creates the basis for a large international business, from chemical synthesis to the formation of tablets. Its physiological role in the body is still not fully understood, despite the successful use of vitamin C in the treatment of various pathological conditions, often seemingly unrelated to it. For hundreds of years it was used to treat scurvy, and in recent years it has been shown that vitamin C induces a state of remission in some patients with autoimmune thrombocytopenia.

Therapeutic use

Vitamin C is usually prescribed in a daily dose of 3 x 100 mg. Vitamin C not only promotes wound healing, but also strengthens the body's immune system, which prevents dangerous infections. That is why ascorbic acid is prescribed for infectious diseases, feverish conditions and diarrhea, as well as in cases where there is a high risk of infection and inflammation. To acidify urine in chronic urinary tract infections, 0.5 - 0.3 g per day is prescribed. Vitamin C is known as an immunomodulator that acts on various points of the immune system. For example, it inhibits histidine decarboxylase, thereby suppressing the formation of the immunosuppressant histamine; promotes the activity of neutrophilic leukocytes; neutralizes excess levels of reactive oxidants produced by phagocytes during chronic infection.

Vitamin C is used to treat some diseases of the blood and circulatory system. Vitamin C is also indicated for common anemia caused by iron deficiency in the body. However, treatment with iron preparations is also necessary. Ascorbic acid promotes the absorption of iron by the body by forming soluble complexes with it and restoring iron, thus preventing iron from being bound in the intestine by phytates and tannins from food. The level of restored iron in the blood can be maintained by choosing a suitable iron-containing diet with the addition of 25-50 mg of ascorbic acid to each meal.

In order for hemoglobin to participate in oxygen transport, the iron atom in the heme molecule must be in the reduced iron state. Typically, over 98% of hemoglobin in the body is present in this form and less than 2% is in the form of functionally inactive methemoglobin with oxidized iron. Usually, these small amounts of methemoglobin are reduced to hemoglobin by the enzyme NADH (methemoglobin reductase, also called erythrocyte cytochrome reductase). Several types of congenital methemoglobinemia are known, caused by deficiency of the cytochrome reductase system. In this case, oral daily intake of 500 mg ascorbic acid or 100-300 mg methylene blue is prescribed. Apparently, ascorbic acid directly, although slowly, restores methemoglobin, whereas methylene blue activates the normally latent NADPH dehydrogenase, thus ensuring the continuity of the chain of transformations in the NADH system. This type of methemoglobinemia is a mild form of the disease, and treatment simply eliminates the manifestations of cyanosis.

Methemoglobinemia is ultimately caused by the presence of O2 peroxide radicals in the patient's body, which are normally controlled by the enzyme superoxide dismutase (SOD), which requires the presence of vitamin C as a coenzyme. It is believed that taking ascorbic acid can relieve the acute condition in patients with sickle cell anemia, when red blood cells are depleted of the vitamin and are susceptible to the destructive action of oxidants.

It has been proven that in higher doses the vitamin helps improve lipid metabolism in the body. As a result, cholesterol deposits on the arterial walls are prevented and the risk of coronary insufficiency is reduced. In coronary insufficiency, the level of ascorbic acid in plasma and leukocytes decreases, and it is not yet clear what is the cause and what is the effect. However, it is believed that vitamin C helps prevent atherosclerosis, as it maintains the integrity of arterial walls (due to the proper level of hydroxyproline, necessary for collagen biosynthesis), reduces the level of cholesterol in the blood (promoting the biosynthesis of bile acid) and triglycerides (activating plasma lipase).

Vitamin C is also beneficial for healthy metabolism because it reduces platelet aggregation and increases fibrinolytic activity in the blood. Vitamin C was once even dubbed the “heart vitamin.” Although a correlation can be traced between cases of coronary heart disease (CHD) and low plasma ascorbic acid levels, the latter is more likely a consequence of the former, rather than the other way around.

However, according to some experts, a risk factor for coronary heart disease is the presence of various aggressive forms of oxygen, for example, the superoxide radical, the existence of which is under the control of vitamin C-dependent superoxide dismutase.

Thus, ascorbic acid takes part in many metabolic processes. Vitamin C is involved in collagen synthesis, tyrosine oxidation, catecholamine synthesis, iron and copper mobilization, histamine degradation, modulation of prostaglandin production, detoxification, cholesterol metabolism, immune control, etc. With an average daily requirement of vitamin C of 100 mg, a number of factors require an increase in vitamin C intake. These include taking certain medications (contraceptives, antibiotics, aspirin, anti-inflammatory drugs), smoking, alcohol consumption, stress, old age, diabetes, pregnancy. Although clear indications for the clinical use of vitamin C have not yet been developed, its widespread use in medical practice is recommended (to accelerate wound healing, reduce inflammatory reactions, enhance immune functions, in the treatment of respiratory diseases, iron deficiency, atherosclerosis, arthritis).

Vitamin C is usually prescribed for the threat of miscarriage, thyrotoxicosis, idiopathic thrombocytopenic purpura (2 g daily), and thalassemia (Mediterranean anemia).

The physiological basis of vitamin C therapy is not always completely clear, except in cases of achlorhydria and diarrhea, where there is a risk of anemia due to decreased intestinal absorption of non-heme iron, which is corrected with vitamin C.

The main content of ascorbic acid in the CNS is located in the hippocampus-hypothalamus compared to other parts of the CNS.

Low vitamin C status is associated with cataracts and increased intraocular pressure, diabetes, smoking and alcohol abuse. Daily intake of 1 g of vitamin C stops the development of cataracts at an early stage.

It has been found that the level of vitamin C in the body of patients with diabetes is 70-80% lower than in healthy people. This gives reason to believe that this is the root of such complications as heart and kidney failure, blindness and gangrene. According to one hypothesis, chronic hyperglycemia may be associated with an intracellular deficiency of ascorbic acid in leukocytes due to the fact that glucose and ascorbic acid are quite similar to each other and can be transported into the cell using the same membrane system. This leads to the fact that untreated patients with diabetes have a weakened response to acute inflammation, increased susceptibility to infection and pathology in wound healing. It is not yet clear whether these patients are able to absorb less vitamin than healthy people, or excrete it in large quantities. It is suggested that their condition should be positively affected by doses of the vitamin that increase glucose tolerance. However, very large doses should also be avoided, as this leads to an increase in the level of dehydroascorbic acid in the blood, which in turn causes diabetes in rats!

The role of vitamin C as a cofactor in major biological processes is well established. The mammalian brain contains relatively high concentrations of ascorbic acid. In rats, ascorbic acid concentrations are highest at birth and then decline with growth and aging. Fetal levels are twice those in adults. As men age, over 50% of their plasma ascorbic acid concentrations are less than 0.3 mg/dL (normal = 1 mg/dL) and require a daily intake of 40 to 50 mg of vitamin C for men and 30 mg for women. Since 1953, when Willis showed that ascorbic acid deficiency causes atherosclerotic lesions, a relationship has been established between ascorbic acid levels and blood cholesterol levels. Ascorbic acid increases the amounts of prostacyclin metabolites (6-keto-PGP1;1) and thromboxane B2. AA is the main stimulator of prostaglandin synthesis. The lungs have a surface area the size of a football field and exchange up to 9,000 liters of air per day. Vitamin C and E act as antioxidants and PG may be involved in these mechanisms, as both vitamins have a complex effect on arachidonic acid metabolism.

The well-known toxic effect of alcohol can be reduced by taking vitamin C, which in this case is involved in the detoxification process in the liver, participating in the oxidation of the cytochrome P450 system.

• Vitamin C helps maintain the tone and reactivity of the respiratory system.

Smoking causes plasma levels to fall to 0.2 mg%, and smokers need to take an additional 60 to 70 mg daily to compensate for this decrease. It is not clear whether smokers' low plasma ascorbate levels are due to increased metabolic rate, decreased absorption, or simply inadequate dietary intake of vitamin C due to their habit of excluding fruit from their diet.

• Vitamin C is also recommended for the treatment and prevention of colds, mental illness, infertility, cancer and AIDS.

Vitamin C may provide significant protection against gastric cancer due to its ability (demonstrated in vitro) to inhibit the formation of nitrosamines. Nitrosamines can be formed by the interaction of nitrites with amines in the diet and are considered to be the most important cause of gastric and esophageal cancer. Small amounts of nitrites are usually ingested in the diet, but they can be formed by the reduction of nitrates by intestinal bacteria, which is why the increase in nitrate levels in drinking water is of concern. Ascorbic acid has been shown to be effective in preventing uterine cancer.

• Vitamin C is effective in the prevention and treatment of at least forty pathological conditions.

Scientists have investigated in vitro the role of human placenta in cellular transport and metabolism of toxic oxidized ascorbic acid (AA) (dehydro-AA; DHAA) and its beneficial reduced form. They have shown that placental tissue helps regulate the maternal and fetal AA/DHAA redox potential and clears the toxic DHAA from maternal blood, restoring and supplying the fetus with the beneficial form of AA. Ascorbic acid readily passes to the fetus by simple diffusion. Pregnancy reduces serum AA levels. At the same time, smoking reduces serum AA levels in pregnant women. During pregnancy and lactation, the need for vitamin C increases from 45 mg/day to 60 and 80 mg/day, respectively. There are no reports of adverse effects of vitamin C on the human fetus, pregnant women, or the course of pregnancy when taking vitamin C. Vitamin C passes into breast milk. Animal experiments (guinea pigs, mice and rats) conducted in the 1960s and 1970s showed that ascorbic acid can be teratogenic and dangerous during pregnancy. In guinea pigs, hypervitaminosis C leads to complicated pregnancy and fetal death with subsequent development of infertility. However, a true embryofetotoxic effect is not observed. In mice, intravenous administration of 20 mg of AC on the 8th day of pregnancy leads to a significant increase in malformations of the brain and spinal cord. In rats, a dose of 1 g/kg of body weight of AC from the 6th to the 15th day or throughout pregnancy did not have a harmful effect on the fetus.