Darlene McCord – Vitamins and Vitamin Derivatives

In addition to antioxidant application, specific micronutrients, including vitamins and vitamin derivatives, have been deemed invaluable for nourishing skin and protecting against radiation dermatitis. Moreover, micronutrient deficiency actually mimics radiation damage by causing DNA single- and double-strand breaks and oxidative lesions in normal skin cells. Supplementing micronutrients via the topical application of vitamin precursors and vitamin derivatives protects against radiation-induced skin injury. Accordingly, retinyl palmitate, the precursor to retinoic acid and a biological form of vitamin A, has been shown to prevent radiation-induced DNA damage and erythema in normal skin cells. The topical application of retinyl palmitate counteracts vitamin A depletion caused by radiotherapy and promotes recovery. Retinyl palmitate also helps treat radiation-induced skin ulcerations by nourishing the migratory epithelial cells responsible for closing the wound. Overall, retinyl palmitate has been found to increase radiation’s effect on tumor cells in vivo, while decreasing symptoms associated with radiation dermatitis.

Ascorbyl palmitate is another important vitamin derivative that nourishes human skin and helps prevent radiation dermatitis. The micornutrient is a lipid-soluble derivative of ascorbic acid capable of penetrating the stratum corneum to target sites of cell-signaling pathways that are not accessible to water-soluble molecules. Ascorbyl palmitate has been found to maintain tissue integrity while protecting against erythema and desquamation via its potent moisturizing effect. Furthermore, ascorbyl palmitate is an effective free radical scavenger and guards well against radiation-induced DNA damage in epithelial cell lines. Ascorbyl palmitate may play a critical role in preventing radiation-induced tissue damage by providing proper cell nourishment and antioxidative protection.

Cholecalciferol (CF), or vitamin D₃, is hydroxylated in the kidney to produce 1,25-dihydroxyvitmain D, which is an active metabolite and hormone that sustains proper cell function by binding to vitamin D receptors. In particular, the derivative demonstrates strong immunoreactivity in skin and hair follicle vitamin D receptors, thereby protecting against radiation toxicity and preventing radiation dermatitis. The topical application of certain micronutrients and subsequent uptake by the stratum corneum, epidermis and dermis, has a synergistic effect with radiotherapy. Altogether, CF, ascorbyl palmitate and retinyl palmitate have been shown to increase tumor response during radiation treatment while protecting against radiation dermatitis.

Table III. Beneficial anticancer effects and protective skin care functions of topical vitamins and vitamin derivatives. Specified micronutrients may work synergistically with radiotherapy while preventing symptoms associated with radiation dermatitis.

Amino Acids

Symptoms associated with radiation dermatitis are a result of tissue breakdown involving a decline in both collagen and glycosaminoglycans, as well as from changes in their chemical structure and 3-dimensional organization. The transdermal delivery of certain amino acids has been shown to restore collagen synthesis and deposition, while thickening the epidermal skin layer. Selected amino acids have been shown to inhibit the genotoxicity of reactive oxygen species in dermal and epidermal skin cells during radiotherapy. In particular, N-acetyl-l- cysteine (NAC) exhibits significant protective effects on skin, including the extracellular inhibition of mutagenic agents from exogenous sources such as irradiation.

NAC modulates reactive metabolic pathways, protects normal DNA and nuclear enzymes, and prevents the formation of carcinogen-DNA adducts. The amino acid exerts its effects via its potent antioxidative properties, as well as its unique ability to sequester nitric oxide (NO) and reverse TNFα toxicity in human cells. NO production was found to be significantly increased in cancer patients, especially in individuals being treated for breast cancer. Breast cancer patients are known to exhibit increased levels of both nitrate and nitrite, which may be in response to the inflammation characteristic of breast tumor growth. Since radiotherapy further increases NO activity and induces inflammation, the topical application of amino acids such as NAC should be considered. NAC reacts directly with NO to reduce the increased NO generation while reversing harmful glutathione depletion.

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