Exerts An Antimicrobial Action
Wounds can get infected at any stage during the healing process. A sufficient intake of vitamin C not only enhances the immune system response by supporting the activity and increasing the responsiveness of various white blood cells and antibodies, but also weakens bacterial cell membranes, making them more susceptible to the action of antibiotics.
Mega-doses of the vitamin, 2 g a day for 2 weeks, significantly increased the bactericidal activity of white blood cells. Effects persisted for 4 weeks after discontinuing supplementation : 1077-81).
Trim Proteins In Membrane Repair And Wound Healing
Tripartite motif family proteins are characterized by the presence of N-terminal Ring -finger domain, zinc-finger B-box domains and a coil-coil domain. There are over 80 identified human TRIM proteins which play important roles in regulating cellular processes such as protein degradation, innate immunity, cell survival/death, oncogenesis, development and intracellular signalling. TRIM proteins exhibit a wide breadth of diversity along their C-termini, resulting in 12 different subfamilies/classifications. Most TRIM proteins contain E3 ubiquitin ligase activity, a class of enzymes which catalyze the final step in the ubiquitination cascade to form an ubiquitin covalent bond with a substrate lysine. TRIM proteins have been widely studied and reviewed within the context of immunology, cell death/survival and cancer , however an emerging role in wound healing has developed.
Maintaining cell membrane integrity is vital to normal cell physiology and function . Repair of damaged cellular membranes requires intracellular vesicle trafficking which leads to an accumulation of vesicles close to the plasma membrane . Subsequent resealing of the cell membrane is imperative for the survival and long-term viability of cells. Disruption of membrane repair contributes to pathophysiological conditions such as dystrophic muscle , diabetes , poor wound healing, chronic ulcer and scarring .
Increase Of Ros In Wounds
There is a lot of data out there that shows ROS increase with times of stress on the body such as intense exercise and wound trauma. Because of this there is a need for increase tissue antioxidants in order to promote proper healing and removal of ROS. Vitamin C = antioxidant = ROS removal = proper wound healing!
There is also data that suggests the amount of vitamin C concentrations within a tissue drop dramatically after that tissue is compromised with a wound. Levels of vitamin C were compared to normal skin at 2, 4, 7, and 14 day old wounds in animals . Vitamin C levels decreased by 60% and didnt recover until after day 14. In addition, antioxidant levels were low and free radical damage was increased. This shows the utilization of Vitamin C during wound healing process. Also, how important it is to keep our vitamin C levels up in order to properly fight wounds and infections.
Vitamin C is a necessity for collagen synthesis, antioxidant status, and immune function. This makes is so important for the wound healing process. There is data that proves low dose of vitamin C administered in people who were deficient helped wound healing, but most doctor believe high doses in people who are not deficient would pack a bigger punch when optimizing wound healing .
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Zinc In Wound Healingclinical Perspectives
Due to the loss of zinc during injury, zinc therapy has been used in wound care to enhance healing in zinc-deficient patients . Topical zinc sulphate application, usually at an optimal 3% concentration, has been widely used in wound healing for its antioxidant effect . Other forms of application include 1% ZnCl2 or the largely insoluble zinc oxide . ZnO provides prolonged supply of zinc to wounds and enhance its healing ability. Additionally, ZnO increases collagen degradation in necrotic wounds . It has been shown that topical zinc application induces mRNA expression of metallothionein, which could account for its anti-UV photoprotective effect . A standard regimen for severe burn care includes regular daily dietary zinc supplementation equivalent or exceeding 22 mg . Moreover, recent advances in drug delivery with zinc oxide nanoparticle technology has received considerable attention for the treatment of wounds due to their effective cell penetration, immunomodulation and antimicrobial capacity . However, in-depth pharmacodynamics and toxicology studies are still needed prior to widespread applications .
Interaction With Cell Signalling Pathways
In vitro studies clearly show that vitamin C can play a role in the differentiation of keratinocytes . For example, vitamin C enhanced the differentiation of rat epidermal keratinocytes cells in an organotypic culture model , with markedly improved ultrastructural organisation of the stratum corneum, accompanied by enhanced barrier function. Vitamin C also increased numbers of keratohyalin granules and levels of the late differentiation marker filaggrin, which appeared to be due to altered gene expression . Others have also shown that vitamin C promotes synthesis and organization of barrier lipids and increased cornified envelope formation during differentiation . The mechanism by which vitamin C modulates keratinocyte differentiation is not yet elucidated however, it has been hypothesized to be under the control of protein kinase C and AP-1 .
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Challenges To The Maintenance Of Skin Health And Potential Protection By Vitamin C
During the course of a normal lifetime, the skin is exposed to a number of challenges that can affect structure, function and appearance, including:
- Deterioration due to normal aging, contributing to loss of elasticity and wrinkle formation.
- Exposure to the elements, leading to discolouration, dryness and accelerated wrinkling.
- Chemical insults including exposure to oxidising beauty and cleansing products .
- Direct injury, as in wounding and burning.
Vitamin C may provide significant protection against these changes and regeneration of healthy skin following insult and injury is a goal for most of us. The following sections, and the summary in Table 3 and Table 4, review the available evidence of a role for vitamin C in the maintenance of healthy skin and the prevention of damage.
Inflammatory Resolution And Tissue Growth Stage
During wound healing, it is important to resolve inflammation and initiate re-epithelization, the process where epithelial cells proliferate and repopulate injured tissue for wound closure. M2 macrophages are one cell type that helps mitigate inflammation but there are numerous other immune cells that aid in this process. Zinc deficiency also has a significant impact on T lymphocyte populations . Regulatory T lymphocytes regulate and suppress inflammation. Zinc supplementation is known to increase the number of Tregs in multiple circumstances: mixed lymphocyte cultures, in response to allergens and when combined with transforming growth factor-Î² . Cutaneous wound studies have shown that Tregs help resolve inflammation, promote re-epithelization and wound contraction . It would be interesting to determine whether zinc supplementation is capable of upregulating a regulatory T-cell response in order to promote accelerated wound repair.
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A Magic Ingredient Or Combination
InflammEnz, an herbal product, contains seven different nutrients and enzymes, including calcium and potassium. But there are four in particular that are suspected of boosting the healing process noted in Rohrich’s study:
- Vitamin C, also known as ascorbic acid, is required for the synthesis of collagen. It is also a highly effective antioxidant protecting cells from damage by free radicals. Studies have shown that the vitamin can help speed the healing process of wounds.
- Bromelain is an anti-inflammatory enzyme found in the stem of pineapple plants. It reduces muscle and tissue swelling especially following injuries or surgery.
- Rutin, a nutrient in plant foods, is believed to protect blood vessels, prevent bruising, and intensify the effect of vitamin C in the body.
- Grape seed extract, a popular health supplement that evidence shows may build new blood vessels and help vitamin C enter cells, strengthening cell membranes and prevent scarring in tissue.
“Obviously, more study is needed before we can routinely recommend this product to plastic surgeons to help their patients heal faster, but it certainly is promising,” Rohrich tells WebMD. “The next step is to separate each of these four ingredients out to better determine which one is really providing the benefit, or if there is an synergetic effect in which all four or some combination of them work together.”
Does Vitamin C Help With Wound Healing
It is also a highly effective antioxidant protecting cells from damage by free radicals, Getting plenty of vitamin C in your diet can speed up the healing of scars caused by acne as vitamin C is essential to the formation of new connective tissue in a healing wound, the most important protein of connective tissue, according to Drugs.com, is rapidly consumed postwounding, vitamin C helps to manufacture collagen, It helps with the growth of new blood vessels which is essential when it comes to wound healing, which states that the most important nutrients for wound healing are protein,4, vitamins C, also known as ascorbic acid,8 Vitamin C is an important antioxidant, During the proliferative phase, can visibly accelerate the wound healing process.Vitamin C is an essential micronutrient with many functions in the body,Vitamin C or ascorbic acid , 2, Deficiencies affect the maturation phase by altering collagen production and scar formation.Cited by: 27Vitamin C is very important in wound healing, secretion and degradation of collagen, plays an important role in collagen synthesis which is
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Functions In Healthy Skin
Vitamin C limits the damage induced by ultraviolet light exposure. Vitamin C is not a âsunscreenâ because it does not absorb light in the UVA or UVB spectrum. Rather, the antioxidant activity of vitamin C protects against UV-induced damage caused by free radicals. Vitamin C transport proteins are increased in keratinocytes in response to UV light, suggesting an increased need for vitamin C uptake for adequate protection .
UV light decreases vitamin C content of skin, an effect that is dependent on the intensity and duration of UV exposure . In cultured keratinocytes, the addition of vitamin C reduces UV-related DNA damage and lipid peroxidation, limits the release of pro-inflammatorycytokines, and protects against apoptosis. Vitamin C also modulates redox-sensitivecell signaling in cultured skin cells and consequently increases cell survival following UV exposure .
In two rodent studies, addition of ascorbic acid to the diet reduced the size and number of dermal neoplasms and skin tumors induced by chronic UV exposure . To date, no other studies with UV exposure and oral ascorbic acid supplementation in animal models have been published.
Summary Of Experimental Wounds
The MRC investigators did not submit the experimental wounding outcome data to statistical hypothesis testingthey did calculate means on scar strengths on certain subgroups. The narrative account based on the eyeball method provided by the MRC investigators on the prevention of collagen-related pathologies is consistent with the WHO’s interpretation: a daily intake of 10 mg vitamin C is sufficient to prevent the appearance of scorbutic wounds, weak scar strength, and histological abnormalities. The narrative account provided by the MRC investigators on the treatment of vitamin Cdepleted tissues is not consistent with the WHO’s interpretation. The MRC investigators reported that restoring scar strength and histological normality was not achieved with 5 mo of 10 mg or 20 mg vitamin C supplementation combined with 650-mg daily vitamin C doses for 12 d.
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Vitamin C Content Of Skin
Normal skin contains high concentrations of vitamin C, with levels comparable to other body tissues and well above plasma concentrations, suggesting active accumulation from the circulation. Most of the vitamin C in the skin appears to be in intracellular compartments, with concentrations likely to be in the millimolar range . It is transported into cells from the blood vessels present in the dermal layer. Skin vitamin C levels have not often been reported and there is considerable variation in the published levels, with a 10-fold range across a number of independent studies . Levels are similar to that found in numerous other body organs. The variation in reported levels most likely reflects the difficulty in handling skin tissue, which is very resilient to degradation and solubilisation, but may also be due to the location of the skin sample and the age of the donor.
Vitc Attenuates Mediators Of Inflammation In Wound Healing
Next we examined the mRNA expression of the proinflammatory genes in healing tissue on days 7 and 14 postwounding. VitC sufficiency or treatment of deficient mice with AscA significantly attenuated transcript levels of these proinflammatory genes when compared to wound tissue from VitC deficient mice at day 7 .3). The transcript levels of the proinflammatory signalling cytokines remained elevated on day 14 in the deficient mice compared to the sufficient and deficient + AscA mice .4). MPO transcripts however were not detectable in all three groups on day 14 . TNF transcript expression on day 14 showed the same trend as IL1 and KC but these differences in expression did not achieve statistical significance. In light of the elevated and persistent expression of proinflammatory mediator transcripts in VitCdeficient animals, we examined whether markers of inflammation resolution might be altered. Galectin1 expression is associated with generation of proresolving lipid mediators and successful resolution of inflammation 24. Therefore, we examined Gal1 expression in day7 wounds. Gal1 transcript levels were significantly higher in VitC sufficient mice compared with the deficient mice .5). Although Gal1 gene expression trended higher in the deficient + AscA group, it did not reach statistical significance.
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The Promotion Of Collagen Formation
Vitamin C acts as a co-factor for the proline and lysine hydroxylases that stabilise the collagen molecule tertiary structure, and it also promotes collagen gene expression . In the skin, collagen formation is carried out mostly by the fibroblasts in the dermis, resulting in the generation of the basement membrane and dermal collagen matrix . The dependence of the collagen hydroxylase enzymes on vitamin C has been demonstrated in a number of studies with fibroblast cells in vitro , with both decreased total synthesis and decreased crosslinking when vitamin C is absent . The activity of the hydroxylases is much more difficult to measure in vivo, as the amount of collagen synthesised may vary only a little . Rather, animal studies with the vitamin-C-deficient GULO mouse indicate that the stability of the synthesised collagen varies with vitamin C availability, reflecting the stabilising function of the collagen crosslinks formed by the hydroxylases . In addition to stabilising the collagen molecule by hydroxylation, vitamin C also stimulates collagen mRNA production by fibroblasts .
Structure of the dermis. Higher magnification of H& E-stained dermis, showing the irregular nature of the bundled collagen fibres and sparse presence of the fibroblasts . Vitamin C present in the fibroblasts supports the synthesis of the collagen fibres.
The Magic Of Vitamin C
Vitamin C, also known as ascorbic acid, is a vitamin you find in foods or as a dietary supplement. Our bodies cannot produce vitamin C, so we have to rely on external sources for it.
Vitamin C has extraordinary properties that assist at all levels of wound healing. From preventing infections to helping the skin rebuild itself, vitamin C provides the benefits needed to accelerate wound recovery.
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Vitc Promotes Hndf Proliferation
Confluent HnDF cells were incubated for 3 hours with two concentrations of AscA . In the absence of exogenous AscA, intracellular VitC concentrations in HnDFs were extremely low. There was a dose and timedependent increase in intracellular VitC concentrations following AscA loading 8A) suggesting that these cells have the ability to transport VitC intracellularly. Additionally, incubating subconfluent HnDF cells with the same AscA concentrations for 24 hours resulted in significant dosedependent increases in HnDF proliferation as seen in Figure Figure88B.
Vitamin C uptake and proliferation by HnDF. HnDF VitC concentrations were determined as described in Methods following exposure to AscA for 3 hours . HnDF loading with AscA at 0·5 and 1·0 mM for 24 hours resulted in a dosedependent increase in cell proliferation .
Vitamin C And Cancer Therapy
Vitamin C may help treat cancer, though experts have not confirmed this.
As an antioxidant, vitamin C protects the body from oxidative stress, which can occur when ROS levels are high. Oxidative stress can lead to cell damage and may play a role in some cancers.
A found that taking high doses of vitamin C may slow the growth of some types of cancerous tissue. The paper suggests that vitamin C could, one day, become a new treatment for colorectal cancer.
Also, the authors of a suggest that vitamin C might work well alongside other treatments to benefit people with cancer.
The note that some alternative therapists already use intravenous vitamin C when treating cancer, fatigue, and infections. However, they note that more research is necessary.
Intravenous vitamin C
Taking too much vitamin C is unlikely to cause any significant problems, but if a person consumes more than 1,000 mg of vitamin C per day, they will not absorb it all. This may lead to diarrhea and gastrointestinal discomfort.
People are unlikely to consume too much through their diet, and their bodies cannot store it. However, having a high intake through supplements may result in kidney stones.
This may also increase the risk of cardiovascular problems in females after menopause, but there is not enough evidence to confirm this.
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Rna Isolation And Realtime Quantitative Pcr Analysis
Total RNA isolation and realtime qPCR were performed as described previously 15. Assays were run in triplicate with no template controls and no reverse transcriptase controls. The mRNA expression from a deficient mouse or a media well was set to 1·0 and mRNA expression of all other samples was compared relative to this sample and represented as a fold change. To normalise for differences in the amount of total RNA added to each cDNA reaction and possible variation in the reverse transcriptase efficiency among the different cDNA reactions, the housekeeping gene 18S rRNA was used. Automated gene expression analysis was performed using the Comparative Quantitation module of MxPro QPCR Software Santa Clara, CA . Both the forward and reverse primers for each target are listed in Table Table11.