In addition, ascorbic acid catalyzes other enzymatic reactions involving amidation necessary for maximal activity of hormones oxytocin, vasopressin, cholecystokinin and alpha-melanotripin [ 23 ]. In ascorbic acid deficiency, this reaction becomes slowed down thus, resulting in an accumulation of cholesterol in liver, hypercholesterolemia, formation of cholesterol gall stones etc [ 24 ].
Ascorbic acid is known to enhance the availability and absorption of iron from non-heme iron sources [ 25 ]. Ascorbic acid supplementation is found to facilitate the dietary absorption of iron. The reduction of iron by ascorbic acid has been suggested to increase dietary absorption of non-heme iron [ 26 ]. It is well known that in the presence of redox-active iron, ascorbic acid acts as a pro-oxidant in vitro and might contribute to the formation of hydroxyl radical, which eventually may lead to lipid, DNA or protein oxidation [ 27 ].
Thus, ascorbic acid supplementation in individuals with high iron and or bleomycin-detectable iron BDI in some preterm infants could be deleterious because it may cause oxidative damage to biomolecules [ 28 — 31 ].
However, no pro-oxidant effect was observed on ascorbic acid supplementation on DNA damage in presence or absence of iron [ 32 ]. The most widely known health beneficial effect of ascorbic acid is for the prevention or relief of common cold.
The role of oral vitamin C in the prevention and treatment of colds remains controversial despite many controlled trials. Several clinical trails with varying doses of ascorbic acid showed that ascorbic acid does not have significant prophylactic effect, but reduced the severity and duration of symptoms of cold during the period of infection. Randomized and non-randomized trials on vitamin C to prevent or treat the common cold showed that consumption of ascorbic acid as high as 1.
For both preventive and therapeutic trials, there was a consistent beneficial but generally modest therapeutic effect on duration of cold symptoms. There was no clear indication of the relative benefits of different regimes of vitamin C doses. However, in trials that tested vitamin C after cold symptoms occurred, there was some evidence of greater benefits with large dose than with lower doses [ 34 ]. There has been a long-standing debate concerning the role of ascorbic acid in boosting immunity during cold infections.
Ascorbic acid has been shown to stimulate immune system by enhancing T-cell proliferation in response to infection. These cells are capable of lysing infected targets by producing large quantities of cytokines and by helping B cells to synthesize immunoglobulins to control inflammatory reactions.
Further, it has been shown that ascorbic acid blocks pathways that lead to apoptosis of T-cells and thus stimulate or maintain T cell proliferation to attack the infection.
This mechanism has been proposed for the enhanced immune response observed after administration of vitamin C during cold infections [ 35 ]. Adequate supplies of ascorbic acid are necessary for normal healing process especially for post-operative patients. Hence, administration of mg to 1. Lipid peroxidation and oxidative modification of low density lipoproteins LDL are implicated in development of atherosclerosis [ 37 ]. Vitamin C protects against oxidation of isolated LDL by different types of oxidative stress, including metal ion dependent and independent processes [ 38 ].
Addition of iron to plasma devoid of ascorbic acid resulted in lipid peroxidation, whereas endogenous and exogenous ascorbic acid was found to inhibit the lipid oxidation in iron-over loaded human plasma [ 39 ]. Ascorbic acid is known to prevent the oxidation of LDL primarily by scavenging the free radicals and other reactive oxygen species in the aqueous milieu [ 41 ]. In addition, in vitro studies have shown that physiological concentrations of ascorbic acid strongly inhibit LDL oxidation by vascular endothelial cells [ 42 ].
Adhesion of leukocytes to the endothelium is an important step in initiating atherosclerosis. In vivo studies have demonstrated that ascorbic acid inhibits leukocyte-endothelial cell interactions induced by cigarette smoke [ 43 , 44 ] or oxidized LDL [ 45 ].
Further, lipophilic derivatives of ascorbic acid showed protective effect on lipid-peroxide induced endothelial injury [ 46 ].
The findings are inconclusive as ascorbic acid supplementation showed a reduction or no change in lipid peroxidation products [ 10 , 47 — 50 ]. In this context, it is important to note that during ex vivo LDL oxidation studies, water soluble ascorbic acid is removed during initial LDL isolation step itself.
Therefore, no change in ex vivo would be expected [ 15 ]. Overall, both in vitro and in vivo experiments showed that ascorbic acid protects isolated LDL and plasma lipid peroxidation induced by various radical or oxidant generating systems.
However, a recent report demonstrated that large doses of exogenous iron mg and ascorbic acid 75 mg promoted the release of iron from iron binding proteins and also enhanced in vitro lipid peroxidation in serum of guinea pigs.
This finding supports the hypothesis that high intake of iron along with ascorbic acid could increase in vivo lipid peroxidation of LDL and therefore could increase risk of atherosclerosis [ 51 ]. However, Chen et al. Numerous studies have looked at the association between ascorbic acid intake and the risk of developing cardiovascular disease CHD.
A large prospective epidemiological study in Finnish men and women suggested that high intake of ascorbic acid was associated with a reduced risk of death from CHD in women and not in men [ 53 ]. Similarly, another study showed that high intake of ascorbic acid in American men and women appeared to benefit only women [ 54 , 55 ].
A third American cohort study suggested that cardiovascular mortality was reduced in both sexes by vitamin C [ 56 ]. In the UK, a study showed that the risk of stroke in those with highest intake of vitamin C was only half that of subjects with the lowest intake and no evidence suggestive of lower rate of CHD in those with high vitamin C intake [ 57 ].
However, a recent meta analysis on the role of ascorbic acid and antioxidant vitamins showed no evidence of significant benefit in prevention of CHD [ 58 ]. Thus, no conclusive evidence is available on the possible protective effect of ascorbic acid supplementation on cardiovascular disease.
However, clinical studies on cancer patients carried out at Mayo Clinic showed no significant differences between vitamin C and placebo groups in regard to survival time [ 63 ]. Cameron and Pauling [ 23 ] believed that ascorbic acid combats cancer by promoting collagen synthesis and thus prevents tumors from invading other tissues. However, researchers now believe that ascorbic acid prevents cancer by neutralizing free radicals before they can damage DNA and initiate tumor growth and or may act as a pro-oxidant helping body's own free radicals to destroy tumors in their early stages [ 64 — 66 ].
Extensive animal, clinical and epidemiological studies were carried out on the role of ascorbic acid in the prevention of different types of cancers. A mixture of ascorbic acid and cupric sulfate significantly inhibited human mammary tumor growth in mice, while administered orally [ 67 ]. Ascorbic acid decreased the incidence of kidney tumors by estradiol or diethylstilbesterol in hamsters due to decrease in the formation of genotoxic metabolites viz.
Ascorbic acid and its derivatives were shown to be cytotoxic and inhibited the growth of a number of malignant and non-malignant cell lines in vitro and in vivo [ 69 — 72 ].
Ascorbic acid has been reported to be cytotoxic to some human tumor cells viz. Roomi et al. Ascorbatepalmitate and ascorbatestearate, the fatty acid esters of ascorbic acid were found to be more potent inhibitors of growth of murine leukemia cells compared to ascorbate 2-phosphate, ascorbate 6-phosphate and or ascorbate 6-sulfate respectively [ 75 ]. Among ascorbic acid derivatives, fatty acid esters of ascorbic acid viz.
Ascorbic acid and ascorbyl esters have been shown to inhibit the proliferation of mouse glioma and human brain tumor cells viz. Ascorbyl stearate was found to be more potent than sodium ascorbate in inhibiting proliferation of human glioblastoma cells [ 80 ]. AscorbylO-palmitate and ascorbylO-phosphateO-palmitate also showed anti-metastatic effect by inhibiting invasion of human fibrosarcoma HT cells through matrigel and pulmonary metastasis of mouse melanoma model systems [ 81 ].
Numerous reports are available in literature on cytotoxic and anti-carcinogenic effect of ascorbic acid and its derivatives in different tumor model systems.
However, the molecular mechanisms underlying the anti-carcinogenic potential of ascorbic acid are not completely elucidated. Recently, Naidu et al [ 80 ] demonstrated that ascorbyl stearate inhibited cell proliferation by interfering with cell cycle, reversed the phenotype and induced apoptosis by modulation of insulin-like growth factor 1-receptor expression in human brain tumor glioblastoma T98G cells.
They also studied the effect of ascorbyl stearate on cell proliferation, cell cycle, apoptosis and signal transduction in a panel of human ovarian and pancreatic cancer cells.
A plethora of epidemiological studies were carried out to find out the association of ascorbic acid with various types of cancers including breast, esophageal, lung, gastric, pancreatic, colorectal, prostate, cervical and ovarian cancer etc.
The results were found to be inconclusive in most types of cancers except gastric cancer [ 84 ]. One of the most consistent epidemiological findings on vitamin C has been an association with high intake of ascorbic acid or vitamin C rich foods and reduced risk of stomach cancer. Considerable biochemical and physiological evidence suggests that ascorbic acid functions as a free radical scavenger and inhibit the formation of potentially carcinogenic N-nitroso compounds from nitrates, nitrite in stomach and thus offer protection against stomach cancer [ 85 — 87 ].
Low intake of ascorbic acid and other vitamins was associated with an increased risk of cervical cancer in two of three studies reported [ 88 — 91 ]. This relationship needs further study because the results suggest that other nutrients including vitamin E, carotenoids, retinoic acid either individually or in synergy with ascorbic acid may impart a protective effect against various cancers.
Current evidences suggest that vitamin C alone may not be sufficient as an intervention in the treatment of most active cancers, as it appears to be preventive than curative. However, vitamin C supplementation has shown to improve the quality of life and extend longevity in cancer patients, hence it could be considered as an adjuvant in cancer therapy.
Dehydroascorbic acid, the oxidized form of ascorbic acid was shown to cross the blood brain barrier by means of facilitative transport and was suggested to offer neuroprotection against cerebral ischemia by augmenting antioxidant levels of brain [ 92 ]. Vitamin C is an important dietary antioxidant, it significantly decreases the adverse effect of reactive species such as reactive oxygen and nitrogen species that can cause oxidative damage to macromolecules such as lipids, DNA and proteins which are implicated in chronic diseases including cardiovascular disease, stroke, cancer, neurodegenerative diseases and cataractogenesis [ 93 ].
Adapted from Carr and Frei [ 15 ]. These radical species are highly reactive and can trigger lipid peroxidation reactions. Thus the question arises whether vitamin C acts as a pro-oxidant in in vivo conditions? The answer appears to be "no" as though these reactions occur readily in vitro , its relevance in in vivo has been a matter of debate concerning ready availability of catalytically active free metal ions in vivo [ 94 ]. In biological systems, iron is not freely available, but it is bound to proteins like transferrin, hemoglobin and ferretin.
Mobilization of iron from these biomolecules may be required before it can catalyze lipid peroxidation. Further, the concentration of free metal ions in in vivo is thought to be very low as iron and other metals are sequestered by various metal binding proteins [ 94 ]. Another factor that may affect pro-oxidant vs antioxidant property of ascorbic acid is its concentration.
The in vitro data suggest that at low concentrations ascorbic acid act as a pro-oxidant, but as an antioxidant at higher levels [ 96 ]. Moreover, a recent report demonstrated that large doses of exogenous iron mg and ascorbic acid 75 mg promote the release of iron from iron binding proteins and also enhance in vitro lipid peroxidation in serum of guinea pigs. This finding supports the hypothesis that high intake of iron along with ascorbic acid could increase in vivo lipid peroxidation of LDL and therefore could increase risk of atherosclerosis [ 52 ].
However, another study demonstrated that in iron-overloaded plasma, ascorbic acid acts as an antioxidant and prevent oxidative damage to lipids in vivo [ 97 ]. Agus et al [ 98 ] have reported that the tumor cells contain large amounts of ascorbic acid, although the role of ascorbic acid in tumors is not yet known. They have established that vitamin C enters through the facilitative glucose transporters GLUTs in the form of dehydroascorbic acid, which is then reduced intracellularly and retained as ascorbic acid.
It is speculated that high levels of ascorbic acid in cancer cells may interfere with chemotherapy or radiation therapy since these therapies induce cell death by oxidative mechanism. Thus, ascorbic acid supplementation might make cancer treatment less effective because, ascorbic acid being a strong antioxidant may scavenge or neutralize the oxidative stress induced by chemotherapy in cancer patients.
However, more studies are needed to understand the role of ascorbic acid in tumors cells and the speculative contraindication of ascorbic acid for cancer chemotherapy. Recently, it has been reported that lipid hydroperoxide can react with ascorbic acid to form products that could potentially damage DNA, suggesting that it may form genotoxic metabolites from lipid hydroperoxides implicating that ascorbic acid may enhance mutagenesis and risk of cancer.
Lee et al [ 99 ], demonstrated that ascorbic acid induces decomposition of lipid hydroperoxide S -hydroperoxy- Z,E -9,octadecadienoic acid; HPODE in presence of transition metals to DNA-reactive bifunctional electro-philes namely 4-oxononenal, 4,5-epoxy-2 E -decenal and 4-hydroxynonenal. Thus, the above process can give rise to substantial amounts of DNA damage in vivo.
However there are many questions, which need to be considered before we accept the hypothesis that ascorbic acid can cause cancer by producing genotoxic metabolites from lipids. The hydroperoxides formed through lipid peroxidation reaction are rapidly reduced to aldehydes by a number of enzymes. Further, ascorbic acid being a strong antioxidant effectively inhibits the formation of lipid peroxides as ascorbic acid forms the first line of antioxidant defense mechanism in human plasma.
The formation of lipid hydroperoxides occur only after ascorbic acid has been exhausted. Hence, interaction of ascorbic acid and hydroperoxide may not arise in human plasma. Recently, high intracellular vitamin C was reported to prevent oxidation-induced mutations in human cells [ ]. Thus, the physiological relevance of these results is yet to be established in in vivo experiments. Ascorbic acid is one of the important and essential vitamins for human health.
It is needed for many physiological functions in human biology. Fresh fruits, vegetables and also synthetic tablets supplement the ascorbic acid requirement of the body. However, stress, smoking, infections and burns deplete the ascorbic acid reserves in the body and demands higher doses of ascorbic acid supplementation.
In view of its antioxidant property, ascorbic acid and its derivatives are widely used as preservatives in food industry. Many health benefits have been attributed to ascorbic acid namely antioxidant, anti-atherogenic and anti-carcinogenic activity. Lately some of these beneficial effects of ascorbic acid are contradicted. The relation between ascorbic acid and cancer is still a debatable as the molecular mechanism underlying anti-carcinogenic activity of ascorbic acid is not clearly elucidated.
Regarding the pro-oxidant activity of vitamin C in presence of iron, there is compelling evidence for antioxidant protection of lipids by ascorbic acid both with and without iron co-supplementation in animals and humans. Current evidences also suggest that ascorbic acid protects against atherogenesis by inhibiting LDL oxidation. The data on vitamin C and DNA damage are conflicting and inconsistent.
The following populations may be at risk for vitamin C deficiency and may require a supplement:. Free radicals are normal by-products of metabolism, but they can cause chain reactions that result in cell damage. This cell damage can, in turn, increase the risk of chronic diseases, including certain forms of cancer and cardiovascular disease.
Antioxidants have the ability to stop this chain reaction. Vitamin C functions in the body as an antioxidant. Because of this antioxidant capability, vitamin C is being studied for a possible role in prevention of certain conditions like age-related macular degeneration, cataracts, cancer, and cardiovascular diseases. Currently there is not sufficient evidence to recommend vitamin C for any of these conditions. Many people believe that taking mega-doses of vitamin C will cure a cold.
There is no scientific evidence to support this idea in the general population. However, there may be some preventative benefit in people exposed to extreme physical stress, cold environments, or those not getting enough vitamin C normally. Studies have found that taking vitamin C daily may help slightly reduce the symptoms and the duration of a cold. But taking vitamin C after the onset of the cold does not appear to effect the course of the illness.
In addition, a review of studies on vitamin C found that it may be able to prevent and treat pneumonia , particularly in people who do not get enough vitamin C in their diet. Ascorbic acid. Updated July 7, Accessed July 21, Vitamin C. Updated February 11, Updated January 14, Vitmin C deficiency. Updated April 27, Vitamin C for preventing and treating pneumonia.
Cochrane Database Syst Rev. Exceptional Nurses Winchester Hospital was the first community hospital in the state to achieve Magnet designation, recognition for nursing excellence.
Supporting Our Community Our tremendous staff gives back to our community by coordinating free health screenings, educational programs, and food drives.
What Our Patients are Saying A leading indicator of our success is the feedback we get from our patients. Home Health Library. It is recommended that smokers take 35 mg more per day than the applicable RDA. People who drink excessive amounts of alcohol—This may, in part, be due to a nutritionally inadequate diet.
The elderly—Studies have shown that older adults have lower levels of serum vitamin C. The oxidative damage including the oxidative modification of low-density lipoproteins is a major cause of cardiovascular disease.
The antioxidant property of vitamin C helps to reduce this to a certain extent [ 16 , 17 ]. Pauling in suggested that vitamin C can be used for the treatment of common cold [ 18 ]. There are so many reports in Cochrane Database Syst. Review showing the use of prophylactic vitamin C reduces the cold duration in adults and children [ 19 ]. The use of vitamin C might reduce the duration of common cold due to its anti-histamine effect of high dose of vitamin C [ 20 ].
However, the results are inconsistent and still research is undergoing in this field. There are Database Syst. Age-related macular degeneration AMD and cataracts are two of the main causes of vision loss in older. Oxidative stress might contribute to the aetiology of both conditions.
Thus, researchers have taken interest in the role of vitamin C and other antioxidants in the development and treatment of these diseases.
There are many reports to study the role of vitamin C in AMD and cataract [ 21 — 23 ]. All the studies indicate that the vitamin C formulations might slow AMD progression and reduce the high risk of developing advanced AMD.
AMD is shown in Figure 6. Age-related macular degeneration. Vitamins C can protect the body against the destructive effects of free radicals. Antioxidants neutralize free radicals by donating one of their own electrons, ending the electron-stealing reaction, as shown in Figure 7.
The antioxidant nutrients themselves do not become free radicals by donating an electron because they are stable in either form or act as scavengers, helping to prevent cell and tissue damage that could lead to cellular damage and disease. Antioxidant mechanism. Ascorbic acid reacts with free radicals undergoing single-electron oxidation to produce a relatively poor reactive intermediate, the ascorbyl radical, which disproportionates to ascorbate and dehydroascorbate.
Those reactions are likely to be of fundamental importance in all aerobic cells. This reaction is the basis of most of the biological functions of ascorbic acid. The mechanism of free radical action on DNA is shown in Figure 8.
Mechanism of free radical action on DNA. Vitamin C also has role in protecting other vitamins vitamin A and vitamin E from the harmful effects of oxidation. Vitamin C helps in protecting gums and retards ageing. It strengthens the general physical condition by removing toxic metals from the body. Vitamin C reduces the formation of cataract and hence useful in the treatment of glaucoma.
Another important function of vitamin C is its role in the synthesis of protein. Vitamin C helps in the synthesis of collagen. Collagen protects our skin from wrinkling and makes our skin firm and strong. Collagen also protects and supports organs and other soft tissues. One of the amino acids used to build collagen—hydroxyproline—is only synthesized when vitamin C is available. Functions of vitamin C on skin.
Vitamin C reduces the damage caused by UV-light exposure. It cannot act as a sunscreen since it cannot absorb UV light. But the antioxidant activity of vitamin C helps to protect UV damage caused by free radicals [ 26 ].
In response to UV light, vitamin C transport proteins are increased, suggesting an increased need for vitamin C uptake for adequate protection [ 27 , 28 ]. Addition of keratinocytes on vitamin C reduces damages caused by UV light and lipid peroxidation, limits the release of pro-inflammatory cytokines and protects against apoptosis [ 29 ].
Many studies have suggested that vitamin C consumption alone will not reduce the effect of UV exposure; however, a combination of vitamin C and E effectively increases minimal erythemal dose MED the lowest dose of ultraviolet radiation UVR that will produce a detectable erythema 24 hours after UVR exposure and decreases erythema-induced blood flow to damaged areas of skin [ 30 ].
Thus, interactions between the two antioxidant vitamins may be necessary to achieve UV protection. The topical application of vitamin C also reduces the effect of UV exposure and skin wrinkling and skin tumour [ 31 ]. Vitamin C reduced the number of sunburned cells, decreased erythema response and reduced DNA damage induced by UV exposure [ 27 ]. The combination of antioxidant vitamins decreased the immunosuppressive effects of UV exposure, increased MED and decreased cell damage [ 32 , 33 ].
Vitamin C plays a key role in healing wound by the formation of collagen, connective tissue [ 34 — 36 ]. The new tissue is rebuilt with the help of collagen framework. This function is supported by its co-factor vitamin C. Besides this, vitamin C performs as a strong antioxidant and immune system modulator [ 37 , 38 ].
Deficiency of vitamin C in humans causes a major disease called scurvy. The major signs of the disease occur primarily in mesenchymal tissues.
It leads to impaired wound healing; oedema; haemorrhage due to deficient formation of intercellular substance in the skin, mucous membranes, internal organs, and muscles; and weakening of collagenous structures in bone, cartilage, teeth and connective tissues. Those who suffer from scurvy have swollen, bleeding gums with tooth loss. They also show lethargy, fatigue, rheumatic pains in the legs, muscular atrophy and skin lesions, massive sheet hematomas in the thighs, and ecchymoses and haemorrhages in many organs, including the intestines, sub-periosteal tissues and eyes.
All these features are accompanied by psychological changes: hysteria, hypochondria and depression. In children, the syndrome is called Moeller-Barlow disease; it is seen in non-breastfed infants usually at about 6 months of age and is characterized by widening of bone-cartilage boundaries, stressed epiphyseal cartilage of the extremities, severe joint pain and frequently, anaemia and fever.
Children having this disease present with a limp or inability to walk, tenderness of the lower limbs, bleeding of the gums and petechial haemorrhages. Many analytical techniques are used for the determination of vitamin C in different matrices, such as titrimetric [ 39 ], fluorimetric [ 40 ], spectrophotometric [ 41 ], high-performance liquid chromatography [ 42 ], enzymatic [ 43 ], kinetic [ 44 , 45 ] and electrochemical, etc.
High-performance liquid chromatography HPLC methods are preferred earlier because they are faster and more effective than spectrophotometric, titration or enzymatic methods, and they do not usually need derivatization [ 46 ].
In pharmaceutical and cosmetic industries, HPLC is used, which is considered as a sensitive and selective method. Racz et al. The method has been used to deep-frozen raspberry cream analysis together with three commonly used chemical methods of vitamin C analysis.
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