The main source of vitamin C for human beings is mainly found in fruits and vegetables. Citrus fruits and other types are particularly rich sources of vitamin C as; cantaloupe, water melon, berries, pineapple, strawberries, cherries, kiwi fruits, mangoes, and tomatoes. Furthermore, vegetables are considered the main source of vitamin C due to its higher content and availability for longer period throughout the year such as cabbage, broccoli, Brussels sprouts, bean sprouts, cauliflower, mustard greens, peppers, peas and potatoes [ 5 ].
Although vitamin C is the generic name of l -ascorbic acid, it has many other chemical names as ascorbate and antiscorbutic vitamin.
It forms a clear colorless to slightly yellow solution. It has two p K a values: 4. Chemical structure of vitamin C [ 6 ]. The chemical structure of ascorbic acid determines its physical and chemical properties. It is a weak, water soluble, unstable organic acid which can be easily oxidized or destroyed in light, aerobic condition oxygen , high temperature, alkali, humidity, copper and heavy metals.
Ascorbic acid is usually found in the form of white or slightly yellowish crystalline powder. Its crystalline form is chemically stable in dryness. However L-ascorbic acid is highly soluble in water, it shows great difficulty to be soluble in alcohol, chloroform, ether and benzene. In water, it forms clear colorless slightly yellow solution which is rapidly oxidized [ 8 , 10 ].
There are many derivatives of ascorbic acid as sodium l -ascorbate sodium ascorbate , calcium l -ascorbate calcium ascorbate , zinc-ascorbate, 6-palmityl- l -ascorbic acid ascorbyl palmitate and ascorbyl monophosphate calcium sodium salt sodium calcium ascorbyl phosphate [ , ].
Ascorbic acid is obtained from sodium ascorbate by cation exchange. While sodium ascorbate results from reacting methyl- d -sorbosonate or ketogulonic acid methyl ester with sodium carbonate. Calcium ascorbate is produced by the interaction of ascorbic acid with calcium carbonate in water and ethanol, which it is then isolated and dried.
Ascorbyl palmitate is prepared by reaction of ascorbic acid with sulfuric acid followed by esterification with palmitic acid. Sodium calcium ascorbyl phosphate resulted from the reaction of ascorbic acid alone or in combination with sodium ascorbate with calcium hydroxide and sodium trimetaphosphate.
The previous ascorbic acid derivatives have superior properties in comparison to ascorbic acid as the light resistance, skin irritation [ , ]. Vitamin C functions depend mainly on its main character as a reducing agent and the results of its oxidation mechanisms either reversible or irreversible [ , ]. These reactions depend only on the pH changes and not on the presence of air or oxidizing agents [ ].
Ascorbic acid undergoes a 3-step oxidation process. In the beginning, ascorbic acid can reversibly oxidize into dehydroascorbic acid on the exposure to copper, low alkaline media and heat [ 11 ].
Dehydroascorbic acid is a very short half-life few minutes product which can either reversibly or irreversibly oxidize in the tissues. In pH 4. However, the dehydroascorbic acid oxidation begins in mild acidic media pH 4.
The resultant diketogulonic acid is a stronger reducing agent, not reduced by glutathione or H2S and not an anti-ascorbutic agent. It was found that below pH 4. In acidic media and the presence of H 2 S, dehydroascorbic acid can also reversibly change into ascorbic acid. Ascorbic acid and dehydroascorbic acid have the same anti-ascorbutic effect [ , ]. The third oxidation product is l -threonic acid and oxalic acid which proceed only in alkaline media pH 7—9 [ 11 ].
All reversible changes can be done in the presence of H 2 S and glutathione in neutral or alkaline media.
Sometimes, carbon dioxide may be the result of vitamin C oxidation at high doses [ ]. In human beings, ascorbic acid is reversibly oxidized into dehydroascorbic acid, which can be reduced back to ascorbic acid or hydrolyzed to diketogulonic acid and then oxidized into oxalic acid, threonic acid, xylose, xylonic acid and lyxonic acid.
Further oxidation decomposition may occur by the oxidizing agents in food. According to the oxidation-reduction reactions, ascorbic acid is the reduced form of vitamin C while dehydroascorbic acid is the oxidized form of vitamin C.
The l -isomer of ascorbic acid is the only active form. Other isomers as d -ascorbic acid, d -isoascorbic acid and l -isoascorbic acid are present. These stereoisomers have no effect in the treatment of scurvy [ , ]. The absorbed and the unabsorbed forms of ascorbic acid can be excreted in conjugated or non-conjugated pattern. Ascorbic acid may undergo limited conjugation with sulfate to form ascorbatesulphate, which is excreted in the urine. Unchanged ascorbic acid and its metabolites are excreted in the urine.
In the presence of intestinal flora, high doses of ascorbic acid unabsorbed part can oxidized into carbon dioxide which is the main excretory mechanism of vitamin C in guinea pigs, rats and rabbits. There exists equilibrium between ascorbic acid and dehydroascorbic acid, dependent on the redox status of the cells [ 12 ]. The bioavailability is a measure of the efficiency of gastrointestinal tract absorption [ 13 ].
The hydrophilic nature of ascorbic acid facilitates its absorption through buccal mucosa, stomach and small intestine. Its absorption depends mainly on passive diffusion through the buccal mucosa [ 14 ].
Vitamin C absorption occurs through small intestine distal intestine by active transport mechanism. Sodium electrochemical gradient is the process by which active transport of ascorbic acid occurs.
This is the same transporter responsible for vitamin C transport in retina. SVCT2 is responsible for transporting vitamin C into brain, lung, liver, heart and skeletal muscles [ 15 ]. The absorption process is usually inhibited by glucose [ ]. The majority of ascorbate is transported by SVCT1 in epithelial cells e.
The main concentrations of vitamin C are located in brain and adrenal cells. The oxidative products of vitamin C as dehydroascorbic acid are transported faster into cells than the pure form [ 17 ].
In human blood, ascorbic acid is always found in the reduced form ascorbic acid. It was also found that the red blood corpuscles are not permeable for ascorbic acid and also to glucose. It oxidized very slowly in blood than in plasma no oxidation reactions occur [ ]. Increasing the plasma level and the intracellular level is not a dose dependent. Its intracellular level is higher than the plasma level. The plasma level does not increase above the normal range even by increasing the intake into mg because of its excellent excretion from kidneys through urine [ 13 ].
Vitamin C is widely distributed in all the body tissues. Its level is high in adrenal gland, pituitary gland, and retina. Its level decreases in kidneys and muscles. Vitamin C metabolites oxalate salts and unmetabolized vitamin C are excreted by kidneys. Few percentage of vitamin C is excreted through feces.
The urinary excretion of vitamin C is dose dependent. At high doses, large amount of unmetabolized vitamin C is excreted. The higher doses of vitamin C intake, the higher vitamin C concentration in blood and tissues occurs.
As a response for high doses, vitamin C excretion from kidneys and sweat occur. The antiviral and anti-bacterial effect of vitamin C protects skin and kidneys from infection [ 1 ]. Also in extra doses, the oxidation components were used as an anticancer effect more the vitamin C itself [ ]. This percent decreases in diseased patients due to higher consumption. Repeated low doses about mg are highly recommended in diseased individuals due to theses low doses saturate the body.
Therefore, limited renal clearance of ascorbic acid is usually detected. This level controls the excretion of the ascorbic acid through kidneys. The intravenous route exerts 30—70 folds of vitamin C plasma levels than the oral route [ 19 ]. The rapid excretion due to its water soluble nature limits its harmful effect and makes it totally safe product in normal doses. It also found that the upper tolerable limit UL is 2 g.
Depending on the depletion-repletion study, it was found that the RDA is 75 mg for women and 90 mg for men. It was modified by Levine et al. The maximum bioavailability and absorption of vitamin C achieved at mg [ 20 ]. In , Marinesco et al. Plaut and Billow detected the ascorbic acid lowering not only in the organs but also in body fluids as CSF, blood and urine.
They also detected this deficiency in neural diseases and alcoholism. Many reasons were thought to be the cause of vitamin C deficiency in old people. Decreased intestinal absorption and dietary deficiency are the main causes. In , Yavorsky et al. Vitamin C has an important role in the maintenance of a healthy immune system and its deficiency causes immune insufficiency and multiple infections. The ascorbic acid level is lowered in various body fluids during bacterial infections.
Thus, it is commonly used as adjunctive treatment in many infectious diseases such as hepatitis, HIV, influenza and periodontal diseases [ 22 ]. Vitamin C administration modifies and enhances both the innate and adaptive immune response. It neutralizes the bacterial toxins especially endotoxins by blocking the essential signal for lipopolysaccharides LPS formation. On the other hand, LPS block the passage of ascorbic acid through blood brain barrier and inhibits its uptake by various cells [ 22 ].
Ascorbic acid improves the phagocytic properties and activity of various immune cells including neutrophils, natural killer cells, macrophages and lymphocytes. Vitamin C increases lymphocytes proliferation and antibody production [ 23 , 24 ]. The ROS are classified into 3 classes; the first are reactive free radicals as oxygen related radicals superoxide, hydroxyl radical or peroxyl radicals.
The second class is reactive species but not free radicals as hypochlorous acid. The third class is radicals resulted from the reaction with ascorbic acid [ 26 ].
Antioxidants are also classified into enzymatic and non-enzymatic. The enzymatic antioxidants include catalase enzyme, thiol-containing agents cysteine, methionine, taurine , glutathione and lipoic acid [ 27 ]. Vitamin C is one of the nutrient non-enzymatic anti-oxidants [ 28 , 29 , 30 ]. Its antioxidant effect is by electron donation process where vitamin C easily donates two electrons reduction reaction to other compounds in order to prevent its oxidation.
When ascorbic acid donates the first electron, it is transformed into a free radical called ascorbyl radical semi-dehydroascorbic acid. It is a relatively stable, unreactive free radical with unbound electron in its outer shell but it has a short life time 10—15 s. The unreactivity of this radical makes it unharmful to the surrounding cells.
This process is called free radical scavenging or quenching. When it donates the second electron, it transformed into dehydroascorbic acid. Its stability may only last for few minutes [ 28 , 31 ]. As a general rule, it was detected that vitamin C acts as a pro-oxidant at low doses and acts as an antioxidant in high doses.
It was also detected that the level of vitamin C in the skin usually exposed to ultraviolet radiation is lower than that exposed lesser.
The antioxidant activity of vitamin C enhances the epidermal turn over, and the movement of young cells to the surface of the skin where they replace old cells [ 32 ]. The study conducted by Frank in [ ] showed that RNA improved the ability of the skin cells to utilize oxygen. Ascorbyl radical and dehydroascorbic acid are reversible agents which can easily rebound into ascorbic acid.
These reversible agents can irreversibly transformed into 2,3-diketogulonic acid which is further metabolized into xylose, xylonate, lyxonate and oxalate Figure 2 [ 34 ].
Redox metabolism of ascorbic acid [ 33 ]. Vitamin C is considered as a strong anti-inflammatory agent as it inhibits many types of inflammatory mediators as tumor necrosis factor alpha [ 35 ]. This property is commonly used in the treatment of postoperative erythema formed after CO 2 laser in skin resurfacing [ 36 ]. In , Halliwell [ 37 ] detected significant reduction of plasma levels of ascorbic acid in association with elevated histamine in inflammatory diseases as ulcerative colitis and rheumatoid arthritis.
This was explained by the discovery of the anti-histaminic effect of vitamin C. It was also found that the higher ascorbic acid content in joints, the higher protection levels against damage which directed many physicians to use ascorbic acid in combination therapy with drugs aiming to joint protection as glucosamine [ 37 , 38 ].
It was discovered that vitamin C has an efficient chemotherapeutic effect. The cytotoxic effect of vitamin C is dose and route dependent. The tumor cells are more sensitive to high intravenous cytotoxic levels of vitamin C than the normal ones [ ]. On the contrary to the cancer cells, normal cells can compensate the damage occurred by these oxidative species [ ]. It was also found that these mega doses of vitamin C are essential in other diseases as diabetes, cataracts, glaucoma, macular degeneration, atherosclerosis, stroke and heart diseases [ 40 ].
Vitamin C improves the immune system and its deficiency causes immune insufficiency and multiple infections. It was found that vitamin C modifies the behavior and activity of the immune cells; it also improves the phagocytic properties of neutrophils and macrophages.
In addition, vitamin C increases the antibody production, concentration of antibodies and the activity of lymphocytes [ 41 ]. It was detected that the level of vitamin C in leukocytes is higher than its level in plasma because they have the ability to store it [ ]. Vitamin C is commonly used as an adjunctive treatment in many infectious diseases as hepatitis, HIV, common cold and influenza. It has an important role in the antibacterial reactions performed in our body by neutralization of the bacterial toxins especially endotoxins [ 42 ].
Sufficient amount of vitamin C causes blockage of the signaling essential for lipopolysaccharides LPS formation. It also stops the production of ROS especially reactive nitrogen species which is mainly produced during infection [ 42 ]. In bacterial infections, the level of ascorbic acid in various body fluids is lower than usual which perform further depression due to the action of LPS in blocking the passage of ascorbic acid through blood brain barrier.
LPS also inhibits the uptake of various cells to ascorbic acid [ ]. The anti-aging effect of vitamin C is regarding to its potent antioxidant effect, its stimulatory effect of enhancing the collagen formation, protection of the persistent collagen especially elastin against damage and finally, inhibits the cross-linking effect formed in wrinkles [ ]. It was found that the amount of ascorbic acid changes with age. The younger the age, the higher the ascorbic acid level present.
It was found that the higher the ROS is, the deeper the pigmentation produced. Anti-oxidants act a great role in lowering the melanin formation [ 43 ]. Vitamin C is considered a potent depigmenting agent which is used in the treatment of various cases of skin hyperpigmentation [ 44 , 45 , 46 , 47 , 48 ]. It can be used as an adjunctive treatment in melasma and severe cases of hyperpigmentation and as a treatment in mild and moderate cases [ 49 ].
Vitamin C inhibits melanogenesis in different steps via more than one mechanism [ ]. Being an anti-oxidant, ascorbic acid prevents production of free radicals which triggers melanogenesis [ 50 ].
It reduces o-dopaquinone back to dopa, preventing dopachrome of 5,6-DHICA [ 51 ] and reduces oxidized melanin changing the pigmentation from jet black to light tan [ 52 ]. Furthermore, the direct suppression of tyrosinase enzyme exhibits a great property [ 53 ].
The higher the ROS is, the deeper the pigmentation produced. Antioxidants act a great role in lowering the melanin formation [ 43 ]. Other mechanisms of blocking melanogenesis include inhibition of tyrosinase activity by interacting with copper ions at active sites of the enzyme [ 51 , 53 ]. In , Pauling and Cameron [ ] discovered that vitamin C has an efficient chemotherapeutic effect.
The cytotoxic effect of vitamin C is due to the action of the ascorbyl free radical and it is dose as well as route dependent [ 55 ]. The tumor cells are more sensitive to high intravenous cytotoxic levels of vitamin C than the normal ones [ 23 , 56 ]. A synergistic effect is detected between the intravenous vitamin C administrations accompanying the tumor cytotoxic agent in patients suffering from advanced cancer [ 57 ].
Melanoma is the most commonly treated malignant tumors using vitamin C due to the high susceptibility and sensitivity of its cells to vitamin C. It induces sodium ascorbate induced apoptosis of melisma.
The lethal effect of ascorbic acid is attributed to inhibiting the production of IL essential for melanoma proliferation , change the intracellular iron level [ 56 , 58 ]. Besides the antioxidant role, ascorbic acid also acts as an electron donor for eight enzymes. Three of these enzymes are involved in collagen formation [ 34 ].
Other two enzymes are responsible for carnitine formation, one enzyme is responsible for epinephrine production from dopamine, and the other is responsible for the addition of the amide groups into peptide hormones. Finally, it is essential for tyrosine metabolism and melanin production. The anti-tyrosinase enzyme occurs at 0. The role of vitamin C in collagen formation is well known. Vitamin C is an essential factor for the hydroxylation of proline, cofactor during collagen processing, activation of pro-collagen messenger RNA, inhibition of matrix metalloproteinases MMPs that are responsible for collagen fibers degradation and fibroblast activation intended for new and proper collagen formation [ 12 , 59 , 60 , 61 ].
As regards the effect of ascorbic acid on periodontal ligament, it enhances the periodontal ligament maturation and renewal by induction of the collagen formation especially collagen III young collagen and keeps the balance between collagen I mature collagen and III for tissue maturation.
It was detected that thicker periodontal ligament were detected near the CEJ and narrower ones were detected in the middle one third of the root due to the effect of vitamin C in keeping the collagen bundles, well organized and more resistant to tension.
Furthermore, it also activates the fibroblast itself; proliferation, production and differentiation. By the vitamin C role in modifying the produced collagen type IV through its role as a cofactor in hydroxyproline synthesis and improving the endothelial cell vitality, its role in angiogenesis could not be forgotten. In periodontal disease, it is recommended to use an adequate well calculated dosage of vitamin C to achieve higher level of healing, minimal bleeding, higher quality of the newly formed tissues and increasing the resistance of tissues to future destruction [ 12 , 62 ].
Collagen is the main component of bone matrix. Many publications had confirmed the role of vitamin C in bone formation. In postmenopausal women, higher levels of vitamin C are needed in order to reduce the incidence of osteoporosis [ 63 , 64 ]. When vitamin C is used with scaffolds in tissue engineering, the sustained release of vitamin C stimulates the formation of type I collagen and alkaline phosphatase enzyme [ 65 ].
Vitamin C is a potent factor in the extracellular bone matrix proteins formation as collagen type I, osteonectin and osteocalcin. Its combination with vitamin E has an essential role in the proliferation and differentiation of the osteoblasts [ 66 ].
The amount of ascorbic acid in human body changes with age. The younger the age is, the higher the ascorbic acid level present [ 67 ]. Vitamin C enhances the collagen formation collagen type I and protects the persistent collagen to resist damage. Finally, it inhibits the cross-linking effect found in wrinkles [ 68 ]. The anti-oxidant property is also involved in the anti-aging effect; vitamin C plays an important role in protecting the cellular integrity as it scavenges the ROS, prevents oxidation of the cellular proteins, lipids as well as DNA and protects the cellular junctions.
It also improves the tissue vasculature [ 69 ]. Thicker periodontal ligament were detected near the cement-enamel junction CEJ and narrower ones were detected in the middle one third of the root due to the effect of vitamin C in keeping the collagen bundles, well organized and more resistant to tension. It also modifies the rate of fibroblast proliferation [ 12 , 62 , 70 ] Figure 3.
Vitamin C increases the absorption of heavy metals from the intestine as iron. Vitamin C has an important role in the carnitine synthesis which is an enzyme co-factor that increases the absorption of non-haem iron in GIT. It also enhances production of reduced iron which is the preferred form for the intestinal absorption [ 72 ]. It was found that factory workers have high oxidative stress. By the administration of combination dosage of vitamin C 1 g and vitamin E IU , great improvement of the general health with the plasma levels returned to its non-lead levels [ 73 ].
Combination of vitamin C supplements with aspirin and opiates has a strong synergistic effect on these drugs [ 54 , 74 ]. On the other hand, oral contraceptive pills increases ascorbic acid turnover and reduce level of ascorbic acid [ 75 ]. The combination of vitamin C and E enhance the efficiency and life span of vitamin E by providing sustained release effect and regeneration of the oxidized vitamin E [ 59 , 77 ].
Thus, vitamin C deficiency is considered a cause of some of these vitamins deficiency such as folic acid deficiency [ 78 , 79 , 80 ]. Furthermore, marked increase of ascorbic acid turnover was reported on consumption of estrogen containing medications [ 81 ]. As a result of oxidation reaction, the production of hydrogen peroxide is enhanced by cations as iron and copper [ 19 ]. EDTA is the only permissible preservative that could be used with injectable vitamin C products [ 82 ].
Limited evidence suggests that ascorbic acid may influence the intensity and duration of action of bishydroxycoumarin. Although vitamin C is water soluble, it has great effects on the lipids either intracellularly or extracellularly.
Vitamin C is an essential factor protecting the lipids of cell membrane from oxidation. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer.
In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Chemie , , 65; Article Google Scholar.
Okuda, J. Kyushu Imp. CAS Google Scholar. Sullivan and Hess, U. Boyland, Bioch. Download references. You can also search for this author in PubMed Google Scholar. Reprints and Permissions. Glutathione and Vitamin C in the Crystalline Lens. Nature , — Download citation.
0コメント