Wednesday, 1 October 2014

Anti Skin Aging in Dehydroascorbic Acid* (DHA) and Vitamin C Points of View

By Kyle J. Norton Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc,.
Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

Skin aging is one of the most visible aging processes that occur constantly in our skin. According to the Clinical Centre of Nis, certain plant extracts may have the ability to scavenge free radicals to protect the skin matrix through the inhibition of enzymatic degradation, or to promote collagen synthesis in the skin, and affect skin elasticity and tightness (a). Another study suggested that free radicals induced domino effects in production of reactive oxygen species and can react with DNA, proteins, and fatty acids causing oxidative damage and impairment of the antioxidant system, leading to injuries, damage of the regulation pathways of skin causing wrinkles, roughness, appearance of fine lines, lack of elasticity, and de-pigmentation or hyperpigmentation marks (b). Walking through the drug and commercial cosmetic stores, one can see hundreds of anti-aging creams and products displayed. Many of them have also gone through certain studies for its efficacy with advertisement through media and celebrities. In fact, according to statistics, Global Anti-Aging Products Market will be worth $291.9 Billion by 2015. Searching through the key word of Dehydroascorbic Acid (Oxidized Vitamin C, DHAA) and skin has yielded no related studies or clinical trials. It may be the result of the solution having no commercial value as it can be made by any cosmetic purchaser, or the studies indicate that L-ascorbic acid must be formulated at pH levels less than 3.5 to enter the skin with maximal concentration of 20% for optimal percutaneous absorption. But according to Dr. Douglas Q. Kitt, Dehydroascorbic Acid (DHAA) permeates stratum corneum at a rate up to 12 times faster than AA. This supports the concept that lower concentrations of DHAA in topical preparations can enhance skin vitamin C levels with less potential side effects (c).

A. Dehydroascorbic Acid (DHA) (vitamin C supplement oxidized form)  
The Chemical Reaction and Structure 

Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin found in fresh fruits, berries and green vegetables. It is best known for its free radical scavenging activity and regenerating oxidized vitamin E for immune system support. In skin aging, the vitamin may improve solar radiation protection and epidermal aging (1) through production of collagen due to its antioxidant activity (2)(3). Epidemiological studies linking vitamin C in prevention of skin damage and aging have produced some certain results (3a)(3b)(3c), but the large sample size and multi-centred studies are necessary to validate its effectiveness. Vitamin C oxidized form or dehydroascorbic acid (DHA) processed antiviral and virucidal effects (23) showed to prevent H2O2-induced cell death by increasing the GSH levels mediated by the GPx and GR activities and PPP (17), and regulated neuronal energy metabolism, through facilitating the utilization of glucose via the PPP for antioxidant purposes (18) by increasing antioxidant potential in the central nervous system (19). Dehydroascorbic acid (DHA) may be a potential anti-cancer agent to treat aggressive cancers (20)(21). Dr. Toohey at the Cytoregulation Research said "rapidly-dividing tumour cells make unusually large amounts of homocysteine thiolactone and that administered dehydroascorbic acid enters the cells and converts the thiolactone to mercaptopropionaldehyde which kills the cancer cells" (22).

B. Vitamin C
  1. Plasma levels of vitamin C 
 L-ascorbic acid is known for its effects on skin-whitening and against the anti-oxidation causes of skin aging. During the aging process, levels of vitamin C was found to slowly deplete according to the Tokyo Metropolitan Institute of Gerontology in the measurement of plasma and urine of C57BL/6 male mice during 3 to 30 months of aging(4). Therefore, restoration of physiological levels of vitamin C inside the cells might improve the lysosomal degradation (protection of cell from the degradative enzymes through protection of the cytosol) in the outflow pathway cells and prevent the pathogenesis of glaucomadegrade proteins(5). Unfortunately, some researchers suggested that higher levels of circulating vitamin C may not provide protection against incident radiographic knee OA, and be associated with an increased risk of knee OA(6) and the 1Panorama Research Institute and Regenerative Sciences Institute, insisted "careful attention to individual and family medical history and personal genomic data may prove essential to make wise dietary and supplement choices to be combined with exercise”(7).  

2. The effects According to the Minghsin University of Science and Technology, in doses of a dependent manner, the concentration of L-ascorbic acid induced absorption of the collagen solution in exhibition of smoothing wrinkles and clear up spots(8). Ascorbic acid (AA) is essential in stimulating collagen gene expression. In type 1 and type 4 collagen and SVCT2, the vitamin was found to enhance the expression of type 1 and type 4 collagens and SVCT2 mRNA in cultured human skin fibroblasts at 100 μM AA placed every 24h for 5 days to prevent depletion(9). The Chiang Mai University study also supported the effects of ascorbic acid in the anti-aging process through exhibition pro and active MMP-2 inhibitory(10). Other studies suggested the combined vitamins, including vitamin C in a single formulation had a slightly lower degradation rate and more stable formulations as compared to different preparations containing only one of the vitamins(11)(12). Amazingly, in vivo, application of vitamin C showed a significant reduction of oxidative stress in the skin, an improvement of the epidermal-dermal microstructure and a reduction of fine lines and wrinkles in aged skin within a relatively short period of time of product application(13). The Bruce and Associates study also insisted the effectiveness of vitamin C application over a 12 week period as the vitamin enhanced the overall intensity of pigmentation, fine lines and wrinkles, tactile roughness, and laxity with a 100% satisfaction of overall appearance of the tested subjects’ skin(14).
1. Skin roughness and Scaliness
Skin roughness due to aging is a result of dead skin cells shedding more slowly, and building up in the upper layer of skin causing skin complexion to become rough and dull. According to the University of California at San Francisco, they are the result of aging and anatomic site of which demonstrated a significant influence on skin roughness and scaliness(25). Another study suggested that frictional properties of skin are dependent on more than water content or non-apparent sweating and the role of sebum secretion may be one possible factor(26), or it may be result of depletion of surface lipid content(27).
2. Wrinkles  
Wrinkles are also associated with aging, hormonal status, smoking, and intercurrent disease according to the study by the University of California-San Francisco(28). Some researchers suggested that vitamin C may play an important role in collagen production due to its antioxidant properties(28). Another study indicated a positive anti-wrinkle effect through consumption of a mixture of soy isoflavones, lycopene, vitamin C, vitamin E, and fish oil(29).

 3. Skin elasticity and firming
Skin sagging is a result of a loss of collagen and elastin of the skin due to aging in combination with the dreaded pull of gravity. The study of a novel dietary supplement (Imedeen Prime Renewal) including soy extract, fish protein polysaccharides, extracts from white tea, grape seed and tomato, vitamins C and E as well as zinc and chamomile extract, showed to inhibit forehead, periocular and perioral wrinkles, mottled pigmentation, laxity, sagging, under eye dark circles, and overall appearance. After 6 months treatment, it was suggested that the formula may provide improved condition, structure and firmness of the skin in post-menopausal women(30). Other studies insisted that since vitamin C (Vit. C) in the form of L-ascorbic acid (Asc) can accelerate wound healing(33)(32) and protect fatty tissues from oxidation damage(33), it may play an integral role in collagen synthesis of reducing wrinkles and skin sagging(34)(35)

4. Liver and aging spots 
  Liver spot is a condition of brown or black spots appearing on the surface of the skin due to aging and exposure to ultraviolet radiation from the sun. According to skin care guides, high concentration of Vitamin C may improve the skin and lighten the spots(36). Other articles insisted that liver spots may be the result of a deficiency of vitamin C(37). According to the Duke University Medical Center, the application of topical solutions containing vitamins C and E provided protection for human skin against damage caused by ultraviolet radiation(38)(39)(40)(41).

5. Pigmentation  
Skin pigmentation disorder is a result of damage most likely caused by UV sunlight, or unhealthy cells due to aging affecting the production of melanin. Vitamin C topical and by iontophoresis are found effectively in aiding post-laser hyperpigmentation  or short and long term treatment (42) for melism (43). In an experiment where 29 females with melisma enrolled for iontophoresis, a vitamin C solution was applied to one side of the face, while distilled water was applied to the other side as a control, treatment with colorimeter site showed a significant decrease in the luminance value, (a photometric measure of the luminous intensity per unit area of light) compared to that of the control site (44).

6. Acne and Acne scars 
 According to Dr. GEORGE E. MORRIS, M.D., in a study of 60 patients with acne being given 8 oz of citrus juice twice daily and vitamin C in 3 gm a day, after 4 months 43 showed improvement, 10 failed to show improvement and 7 did not return for follow up(45). Some articles showed that vitamin C may be effective in the reduction of the formation of acne scars through it’s anti-inflammatory and free radical scavenger activities(46), but no study has been found through searching on PubMed.

7. Back and White heads 
  Black and white heads are the result of a skin pore becoming clogged with sebum from the body's natural oil and becoming black heads if oxidized. No study has been found specifically for the key word vitamin C and back and white heads on PubMed.

8. Fine Lines  
No study and been found.

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 (*) (The oxidation of ascorbic acid and its reduction in vitro and vivo) 
(a) Skin ageing: natural weapons and strategies by Binic I1, Lazarevic V, Ljubenovic M, Mojsa J, Sokolovic D.(PubMed)
(b) Phytoconstituents as photoprotective novel cosmetic formulations by Saraf S1, Kaur CD.(PubMed)
(c) Topical Dehydroascorbic Acid (Oxidized Vitamin C) Permeates Stratum Corneum More Rapidly Than Ascorbic Acid by Douglas Q Kitt
(1) Active ingredients against human epidermal aging by Lorencini M1, Brohem CA2, Dieamant GC2, Zanchin NI3, Maibach HI(PubMed)
(2) CAM use in dermatology. Is there a potential role for honey, green tea, and vitamin C? by Barbosa NS1, Kalaaji AN2.(PubMed)
(3) The science behind vitamins by Linder J.(PubMed)
(3a) Split-face study of topical 23.8% L-ascorbic acid serum in treating photo-aged skin by Xu TH1, Chen JZ, Li YH, Wu Y, Luo YJ, Gao XH, Chen HD(PubMed)
(3b) Use of topical ascorbic acid and its effects on photodamaged skin topography by Traikovich SS.(PubMed)
(3c) Formulation and in-vivo evaluation of a cosmetic multiple emulsion containing vitamin C and wheat protein by Akhtar N1, Yazan Y(PubMed)
(4) Ascorbic acid levels in various tissues, plasma and urine of mice during aging by Iwama M1, Amano A, Shimokado K, Maruyama N, Ishigami A.(PubMed)
(5) Ascorbic Acid Modulation of Iron Homeostasis and Lysosomal Function in Trabecular Meshwork Cells by Xu P1, Lin Y, Porter K, Liton PB(PubMed)
(6) High plasma levels of vitamin C and E are associated with incident radiographic knee osteoarthritis by Chaganti RK1, Tolstykh I2, Javaid MK3, Neogi T4, Torner J5, Curtis J6, Jacques P7, Felson D4, Lane NE8, Nevitt MC9; Multicenter Osteoarthritis Study Group (MOST)(PubMed)
(7) Trade-offs between anti-aging dietary supplementation and exercise by Mendelsohn AR1, Larrick JW(PubMed)
(8) [The study of absorption efficiency and restoring effects of collagen and ascorbic acid on aged skin by fluorescence and reflection spectroscopy].[Article in Chinese] by Yang BW1, Lin YM, Wang SY, Yeh DC.(PubMed)
(9) Ascorbic acid enhances the expression of type 1 and type 4 collagen and SVCT2 in cultured human skin fibroblasts by Kishimoto Y1, Saito N, Kurita K, Shimokado K, Maruyama N, Ishigami A.(PubMed)
(10) Nanoscale gelatinase A (MMP-2) inhibition on human skin fibroblasts of Longkong (Lansium domesticum Correa) leaf extracts for anti-aging by Manosroi A1, Kumguan K, Chankhampan C, Manosroi W, Manosroi J.(PubMed)
(11) Benefits of combinations of vitamin A, C and E derivatives in the stability of cosmetic formulations by Gianeti MD1, Gaspar LR, Camargo FB Jr, Campos PM.(PubMed)
(12) Stability of vitamin C derivatives in topical formulations containing lipoic acid, vitamins A and E. by Segall AI1, Moyano MA.(PubMed)
(13) Topical activity of ascorbic acid: from in vitro optimization to in vivo efficacy by Raschke T1, Koop U, Düsing HJ, Filbry A, Sauermann K, Jaspers S, Wenck H, Wittern KP.(PubMed)
(14) Evaluation of a prescription strength 4% hydroquinone/10% L-ascorbic acid treatment system for normal to oily skin by Bruce S1, Watson J(PubMed)
(15) Fatal vitamin C-associated acute renal failure by McHugh GJ, Graber ML, Freebairn RC.(PubMed)
(16) Ascorbic acid overdosing: a risk factor for calcium oxalate nephrolithiasis by Urivetzky M, Kessaris D, Smith AD.(PubMed)
(17) Dehydroascorbic acid prevents oxidative cell death through a glutathione pathway in primary astrocytes by Kim EJ1, Park YG, Baik EJ, Jung SJ, Won R, Nahm TS, Lee BH.(PubMed)
(18) The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism by Cisternas P1, Silva-Alvarez C, Martínez F, Fernandez E, Ferrada L, Oyarce K, Salazar K, Bolaños JP, Nualart F.(PubMed)
(19) Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters by Agus DB1, Gambhir SS, Pardridge WM, Spielholz C, Baselga J, Vera JC, Golde DW.(PubMed)
(20) Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many aggressive cancers, suggesting potential utility for sodium bicarbonate and dehydroascorbic acid in cancer therapy by McCarty MF.(PubMed)
(21) Gelatin crosslinked with dehydroascorbic acid as a novel scaffold for tissue regeneration with simultaneous antitumor activity by Falconi M1, Salvatore V, Teti G, Focaroli S, Durante S, Nicolini B, Mazzotti A, Orienti I.(PubMed)
(22) Dehydroascorbic acid as an anti-cancer agent by Toohey JI.(PubMed)
(23) Antiviral and virucidal activities of natural products by Arakawa T1, Yamasaki H, Ikeda K, Ejima D, Naito T, Koyama AH.(PubMed)
(24) Topical L-ascorbic acid: percutaneous absorption studies, by Pinnell SR1, Yang H, Omar M, Monteiro-Riviere N, DeBuys HV, Walker LC, Wang Y, Levine M.(PubMed)
(25) Use of topical ascorbic acid and its effects on photodamaged skin topography by Traikovich SS.(PubMed)
(26) Frictional properties of human skin: relation to age, sex and anatomical region, stratum corneum hydration and transepidermal water loss by Cua AB1, Wilhelm KP, Maibach HI.(PubMed)
(27) Skin surface lipid and skin friction: relation to age, sex and anatomical region by Cua AB1, Wilhelm KP, Maibach HI.(PubMed)
(28) Skin aging. Effect on transepidermal water loss, stratum corneum hydration, skin surface pH, and casual sebum content by Wilhelm KP1, Cua AB, Maibach HI.(PubMed)
(29) Wrinkle reduction in post-menopausal women consuming a novel oral supplement: a double-blind placebo-controlled randomized study by Jenkins G1, Wainwright LJ, Holland R, Barrett KE, Casey J.(PubMed)
(30) Effect of a novel dietary supplement on skin aging in post-menopausal women by Skovgaard GR1, Jensen AS, Sigler ML.(PubMed)
(31) Vitamin C: a wound healing perspective, by Moores J.(PubMed)
(32) Nutrition 411: revisiting vitamin C and wound healing by Collins N.(PubMed)
(33) Ef[The study of absorption efficiency and restoring effects of collagen and ascorbic acid on aged skin by fluorescence and reflection spectroscopy].[Article in Chinese] by Yang BW1, Lin YM, Wang SY, Yeh DC.(PubMed)
(34) Regulation of collagen synthesis in human dermal fibroblasts in contracted collagen gels by ascorbic acid, growth factors, and inhibitors of lipid peroxidation by Gessin JC1, Brown LJ, Gordon JS, Berg RA(PubMed)
(35) Electroporation-mediated topical delivery of vitamin C for cosmetic applications by Zhang L1, Lerner S, Rustrum WV, Hofmann GA.(PubMed)
(36) Liver Spot Removal: Vitamin C Products(Skin care guide)
(37) Lack of vitamin leads to brown spot on hand(livestrong)
(38) A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation by Murray JC1, Burch JA, Streilein RD, Iannacchione MA, Hall RP, Pinnell SR.(PubMed)
(39) UV photoprotection by combination topical antioxidants vitamin C and vitamin E by Lin JY1, Selim MA, Shea CR, Grichnik JM, Omar MM, Monteiro-Riviere NA, Pinnell SR.(PubMed)
(40) Protective effects of topical antioxidants in humans by Dreher F1, Maibach H.(PubMed)
(41) Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants by Darr D1, Dunston S, Faust H, Pinnell S.(PubMed)
(42) Successful short-term and long-term treatment of melasma and postinflammatory hyperpigmentation using vitamin C with a full-face iontophoresis mask and a mandelic/malic acid skin care regimen by Taylor MB1, Yanaki JS, Draper DO, Shurtz JC, Coglianese M.(PubMed)
(43) Intravenous vitamin C in the treatment of post-laser hyperpigmentation for melasma: a short report by Lee GS.(PubMed)
(44) A randomized, double-blind, placebo-controlled trial of vitamin C iontophoresis in melisma by Huh CH1, Seo KI, Park JY, Lim JG, Eun HC, Park KC.(PubMed)
(46) Vitamin C and Acne Scar By Melodie Anne Coffman(Livestrong

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