Vitamin A and Its Influence on Skin - Essay Example

Vitamin A and Skin Introduction Skin aging leads to a creased appearance of skin with progressive loss of elasti and smoothness. Aging like in any other human organ appears in the skin is associated with loss of biologic and physiologic properties of skin. There is another variant of skin aging which occurs with exposure to sun rays, where ultraviolet radiations forms sun causes similar changes, leading to an appearance of the skin which appears to the similar to the natural aging of skin, albeit prematurely (Fisher et al., 2002). Research in this area has been consistently shown a process of degeneration in the skin tissues which called for different remedies. Consequently there are different claims from different quarters about efficacy of different remedies which can reverse or delay the processes of both intrinsic skin aging through different means. While some claims have some rationale and are based on adequate research, it must be accepted that some of these claims are quite spurious with lack of adequate and extensive evidence from research before them being recommended to be used (Weiss et al., 1988). In this assignment one such claim published in a reputed newspaper will be critically examined whether local dermal application of vitamin A could be recommended to delay or reverse aging of the skin, whether it is intrinsic or extrinsic aging. The Media Report The report that will be examined here was published in Science Daily, May 22, 2007, issue with the heading "Vitamin A Helps Reduce Wrinkles Associated With Natural Skin Aging" which states essentially that there has been research which supports a claim that local application of vitamin A to the skin apparently improves the wrinkled appearance of the skin associated with natural aging. This claim has been correlated to the findings from research that locally applied vitamin A may promote repair of these age wrinkles through production of "skin building compounds". The claims can be quoted here. The main claim was "Topical retinol improves fine wrinkles associated with natural aging" and to support this, in this report there are two other claims which point to the scientific basis of the claim, which are "Significant induction of glycosaminglycan, which is known to retain substantial water, and increased collagen production are most likely responsible for wrinkle effacement" and "With greater skin matrix synthesis [production of compounds that form skin], retinol-treated aged skin is more likely to withstand skin injury and ulcer formation along with improved appearance" (JAMA and Archives Journals, 2007, May 22). Identical reports supporting these claims also appeared in the Internet version of Cosmetics Design (Pitman, 2007). Scientific Evidence for the Claim The authors of this media report bases on a scientific journal article published in the Archive of Dermatology from the American Medical Association. For the purpose of better critical analysis of the rationale behind such claims, this writer has accessed that article by Kafi et al. (2007). The findings from that critical review will be presented in a subsequent section of this assignment. However, it appears from this report that the reporter in this media report utilizes quotation from that article to provide the lay reader a grasp of scientific rationale behind such claim. In the beginning of the report, the two different forms of aging of skin have been discussed. It is well known that age-associated wrinkles and brown spots appear prominently in the exposed skin, and although sun exposure has been related to aging through a less dramatic identical process, the intrinsic aging process in the skin that occurs naturally causes the skin to lose its appearance due to changes in its texture. The natural aging renders the skin "thinner, laxer and more finely wrinkled", more prominent in specific areas such as upper inner arm (JAMA and Archives Journals, 2007, May 22). Histologically, this can be correlated to a reduced synthesis of collagens and elastic tissues in the skin. It has further been reported that there are currently no "safe and effective therapies" that can reverse the process of skin aging (Pitman, 2007). To find a solution to this problem, Kafi et al. (2007) evaluated the effectiveness of topical vitamin A through a randomized, double-blind vehicle controlled comparison study in 36 elderly individuals of mean age 87 in elderly residential facilities to see whether such applications improve the clinical signs of natural skin aging (Kafi et al. 2007). This scientific media report indicates that the researchers intervened these skins with application of a 4% lotion of vitamin A to either left or right upper inner arms with a placebo on the opposite side which did not contain any retinol or vitamin A, for up to three times a week for a duration of 24 weeks to observe that the overall wrinkles, roughness, and aging severity were significantly reduced. To back this observation up, the researchers used a grading scale for visual assessment in a range of 0 to 9 indicating respectively absence of these to severe changes. The histopathologic correlation was done with a 4-mm skin biopsy at the beginning and end of the study. The scale instrument was used to measure the reversal of age-related changes in 2, 4, 8, 16, and 24 weeks. Although 13 subjects withdrew from the study, the statistical analysis of the data indicated that all parameters of age-related changes in the skin were positively affected by local application of vitamin A. As a causal correlation, application of vitamin A led to increased synthesis of glycosaminoglycan and procollagen as structural components of the skin, which would retain substantial amount of water and increased matrix of the skin, which could lead to reversal of wrinkles (JAMA and Archives Journals, 2007, May 22). Scientific Background Gillum et al. (1995) reports earlier literature indicating a tendency towards a decrease in vitamin A level with aging (Gillum et al. 1995). Bayerl (2005) indicates use of vitamin A acid derivatives as topical application to prevent skin aging (Bayerl, 2005). Sorg et al. (2005) state that vitamin A derivatives are lipophilic molecules, and they penetrate the epidermis easily. They have further suggested that biologically active forms of this vitamin may modulate gene expression through their ability to bind with nuclear receptors and specific sequences in the DNA, which may help modulate cellular proliferation and differentiation leading to increased synthesis of glycoaminoglycans such as hyaluronic acid and collagen. These in turn happen to be major constituents of the dermal matrix, which are affected in the process of aging, which involves alteration and progressive decrease. Literature indicates positive effects of various retinoids on their enhanced synthesis, and therefore administration of a retinoid may enhance their concentrations in the skin and at the same time reduce their rates of degradation, which are common with aging. Moreover photoaging and age-related oxidative injury may also play dominant roles in dermal aging, which retinoids may be able to effectively treat due to their chemical structures with multiple conjugated double bonds, rendering them efficient in trapping free radicals (Sorg et al. 2005). Varani et al. (2000) in their study investigated both photoaging and chronological aging processes from the point of view of damage to the dermal connective tissue. It has been found that aging skin elaborates higher amounts of matrix metalloproteinases which degrade the skin collagen matrix with aging process. With aging, it had been known that the skin fibroblast matrix metalloproteinases increase, which may be a function of oxidant stress and may be associated with reduced collagen synthesis. In this experiment, the authors performed their study in 72 individuals in different age groups to find that in the elderly, the histologic and cellular markers of abnormal dermal connective tissue are increased. In the elderly, it was demonstrated that the levels of matrix metalloproteinases increase leading to enhanced damage of connective tissue. Compared to the younger age groups, in the elderly, there was also associated decreased collagen synthesis and expression. To examine the role of topical vitamin A in reversing these changes, the authors performed a study involving 53 elderly individuals, where they intervened with 1% topical vitamin A for 7 days. Histopathologic examination revealed increased fibroblast growth and collagen synthesis which was also associated with demonstrably reduced levels of matrix-metalloproteinases. This study concluded that the processes of natural aging in the skin which involved connective tissue damage at the molecular level. These processes included connective tissue damage, reduced collagen production, and elevated matrix-metalloproteinases. In naturally aged skins topical treatment with vitamin A reduces matrix-metalloproteinases and stimulates collagen synthesis thus providing support to the concept highlighted in the media report (Varani et al. 2000). Therefore, it is evident that these studies support the claims in the media reports. However, the use of 4% retinol as a preparation has not been established in this article. The findings from the study indicate that these can be rationally correlated. Natural aging of the skin is associated with less procollagen formation (Gilchrest, 1996). Evidence from the studies above indicates that topical vitamin A stimulates enhanced procollagen synthesis and increased matured collagen bands in the dermis which causes effacement of wrinkles. All-trans-retinol used in this study is a precursor of retinoic acid with less potential for irritation and when applied to skin can penetrate easily and induce such changes as evident from visual comparison and histopathologic studies. Thus the claims are supported in all aspects, and there is no contradiction. The data from the experiment have been presented in a logical manner where the reader has no problem reaching the conclusion of the study. Data from clinical evaluations and results from skin biopsy specimens have been presented in separate sections, and the organisation of the presentation is clear, succinct, and rational. The results indicate that there were withdrawals from the study for different reasons, but the retinol bioactivity results indicated that the dermal application penetrated the skin and induced molecular changes in the dermal tissue. The clinical results were estimated through a visual scale and the attrition of the participants were adjusted through intent-to-treat analysis with last-observation-carried-forward method of three parameters, tactile roughness, fine wrinkling, and overall severity, the details of which were presented in a tabulated fashion (Kafi et al., 2007). These were correlated with biochemical results and histopathologic studies. From these, it is apparent that the claims and the data are basically and technically correct and their presentations are rational and not misleading. Since two groups of data with different variables were compared, the statistical analysis of paired t-test was optimum and the summary data indicate there were no discrepancies, and the conclusion arrived from this data was unbiased. The only limitation that can be ascribed to the conclusion which must affect validity, reliability and hence generalisability of the conclusion is too small a sample size with high attrition that needed to be manipulated through a 2-tailed analysis of p values with a Last-Observation-Carried-Forward Method. Despite appropriate statistical adjustment this does not preclude the need for further studies with a larger sample size (Kafi et al., 2007). Therefore, it can be commented that the claims are technically correct and have been presented in a logical manner. However, there is one source of potential harm, which was the preparation of retinol used in this study. The authors report that the preparation was well tolerated by all the subjects enrolled in the study. Retinol has a low irritation potential due to its chemical nature. However in local application studies of this nature the signs and symptoms of irritation is often overlooked by the researchers. In order to obviate this, the authors took an approach of deliberate erring on the conservative side through trained treatment providers and gentle treatment approach with instruction to withhold treatment when signs of irritation appear. This would have reduced harm and irritation but added to possible bias and deblinding (Kafi et al., 2007). When the patients are allowed to use it themselves, it may not be possible to reduce the harm as expected. Therefore, this study is methodologically sound, and the authors appear to make no claims which are not scientifically accurate. From this study, it appears that the scientific report in discussion here legitimately claims that topical retinol can be a useful and potentially promising local treatment for intrinsic chronological aging in the elderly which is reasonably safe and useful in increasing matrix tissues of the skin. This would therefore improve the clinical features associated with wrinkled and aged skin. Conclusion Based on the available data, the claims made in this report are valid. However, although the protocol of treatment has been highlighted clearly, there are sources of potential bias and deblinding in reporting and recording skin irritation and thus reporting potential harm. The authors report that the average applications were 1.6 per week instead of reported there (Kafi et al., 2007). Another limitation was the number of participants and high attrition. This indicates need for further study with a larger sample size, more aggressive application regimen, study of greater clinical effects, and study of more robust biochemical changes is needed. Moreover, aging of skin has been correlated with poor wound healing and skin ulcer formation, which is a cause of morbidity in the elderly and is a public health problem. A more rigorous future study design may also study the effects of local retinol in preventing these. Reference List Bayerl, C., (2005). Topical treatment of skin aging. Hautarzt; 56(4): 328, 330-4, 336-9. Fisher, GJ., Kang, S., Varani, J. et al., (2002). Mechanisms of photoaging and chronological skin aging. Archives of Dermatology;138:1462-1470. Gilchrest, BA., (1996). A review of skin ageing and its medical therapy. British Journal of Dermatology;135:867-875. Gillum, HL., Morgan, AF., and Sailer, F., (1995). Nutritional Status of the Aging: V. Vitamin A and Carotene - Four Figures. Journal of Nutrition; 55: 655 - 670. JAMA and Archives Journals (2007, May 22). Vitamin A Helps Reduce Wrinkles Associated With Natural Skin Aging. ScienceDaily. Retrieved September 27, 2009, from http://www.sciencedaily.com/releases/2007/05/070521162324.htm Kafi, R., Kwak, HSR., Schumacher, WE., Cho, S., Hanft, VN., Hamilton, TA., King, AL., Neal, JD., Varani, J., Fisher, GJ., Voorhees, JJ., and Kang, S., (2007). Improvement of Naturally Aged Skin With Vitamin A (Retinol). Archives of Dermatology; 143: 606 - 612. Pitman, S., (2007). New study proves vitamin A fights wrinkles. Cospemtic Design:Formulation & Science, Skin Care. Retrieved September 27, 2009, from creased appearance of skin with progressive loss of elasticity and smoothness. Aging like in any other human organ appears in the skin is associated with loss of biologic and physiologic properties of skin. There is another variant of skin aging which occurs with exposure to sun rays, where ultraviolet radiations forms sun causes similar changes, leading to an appearance of the skin which appears to the similar to the natural aging of skin, albeit prematurely (Fisher et al., 2002). Research in this area has been consistently shown a process of degeneration in the skin tissues which called for different remedies. Consequently there are different claims from different quarters about efficacy of different remedies which can reverse or delay the processes of both intrinsic skin aging through different means. While some claims have some rationale Read More