Topical application of chemotherapy drug may improve appearance of aging skin

Topical application of the chemotherapy medication fluorouracil appears to reduce potentially precancerous skin patches and improve the appearance of sun-damaged skin, according to a report in the June issue of Archives of Dermatology, one of the JAMA/Archives journals.

Fluorouracil stops the body from synthesizing thymine, a building block of DNA, according to background information in the article. This drug is used to treat cancers of the colon, head and neck, pancreas and other organs. In early studies of patients with cancer undergoing treatment with systemic fluorouracil, clinicians noticed changes in skin appearance, which led to the development of a topical therapy for the treatment of actinic keratoses (skin lesions that may develop into skin cancer).

Dana L. Sachs, M.D., of the University of Michigan Medical School, Ann Arbor, and colleagues evaluated molecular and clinical changes in the skin of 21 healthy volunteers with actinic keratoses and sun-damaged skin. Participants applied 5 percent fluorouracil cream to the face twice daily for two weeks; skin biopsies and clinical evaluations were performed at the beginning of the study and periodically throughout treatment. Photographs were also taken at the beginning of the study and after one, two, four, six, 10 and 24 weeks, and were evaluated by three dermatologists who were not involved in examining the patients during the study. Nineteen patients completed all aspects of the study, and 20 responded to a questionnaire at week 10.

The number of actinic keratoses was significantly reduced following treatment, from an average of 11.6 lesions to an average of 1.5. Clinical evaluations also identified overall improvements in aging-related damage, including decreases in fine (small) and course (large) wrinkling, lentigines (dark skin spots), hyperpigmentation (skin that has become darker) and sallowness (a yellow skin tone).

One day after the final fluorouracil treatment, testing of the skin biopsies revealed an increase in the levels of compounds related to skin injury, inflammation and degradation of the extracellular matrix (the non-living tissue that supports skin), in addition to the precursor of collagen, which rebuilds damaged skin. “Topical fluorouracil causes epidermal [outer skin layer] injury, which stimulates wound healing and dermal remodeling resulting in improved appearance,” the authors write. “The mechanism of topical fluorouracil in photo-aged skin follows a predictable wound healing pattern of events reminiscent of that seen with laser treatment of photo-aging.”

The treatment was generally well tolerated. On the 10-week questionnaire, most patients rated their skin as improved (19, or 95 percent) and were willing to undergo the therapy again (17, or 89 percent).

“For patients in whom a course of topical fluorouracil is indicated for the treatment of actinic keratoses, there will likely be the additional benefit of a restorative effect from sun damage; this may provide further motivation for these patients to undergo the rigorous treatment,” the authors conclude. “It is possible that for some patients topical fluorouracil may have an important role against photo-aging. For others, however, it may not be cosmetically acceptable given that a standard course of therapy may last two to three weeks and the ensuing reaction can persist for several more weeks. Undoubtedly, there will be patients who desire a therapy such as topical fluorouracil for cosmetic purposes given the relatively low cost of this therapy compared with ablative laser resurfacing.”

(Arch Dermatol. 2009;145[6]:659-666. Available pre-embargo to the media at www.jamamedia.org.)

For the duration of the experiment, I consumed approximately 25mg doxycycline in the morning on top of my usual stack of supplements. Unfortunately, due to laziness and lack of time, I don’t have any objective observational data of the effects (i.e., comparative photos taken under identical conditions), so I’ll instead talk about how things appeared. I wouldn’t normally be satisfied with such subjective measurement, but the outcome was so resoundingly bad that I don’t think it matters! :/

Initially, I was perplexed that an ulcer I developed in my mouth was seeming to take far longer than normal to heal; however, this may have something to do with my expectation that healing, especially of oral wounds, would be accelerated.

The one important factor that I intended to measure was if doxycycline supplementation would do anything to increase the production of collagen in the skin. As someone who has experienced the obvious and profound (and positive) effect of oral retinoids on skin texture and quality, I was somewhat disappointed in doxycycline’s effect. Not only was there no (subjective) reduction in the number, severity, or depth of the photo-aging induced wrinkles on my face, but the doxycycline appeared to be making the condition worse!

About two weeks into the experimental period, I was continually dismayed every time I looked into the mirror at what appeared to be a ‘thinning’ of the skin on my face, particularly noticeable on my forehead, as well as more noticeable wrinkles and an overall reduction in any remnants of the youthful glow that Father Time has yet to wrestle from me. Even within the short duration of the experiment, the skin on my face started to take on that ‘papery’ stiffness one associates with the skin of the elderly.

It really was difficult to persist with the regimen in the face of what I felt to be outright failure of my idea, but I did anyway.

About ten days after ceasing the medication, I already feel my skin has mostly regained its normal texture, but I can’t be sure because I didn’t carry out any real quantitative analysis. It has definitely reverted to its normal elasticity.

All in all, I recommend not employing doxycycline to improve the quality of one’s skin. As for why this happened, I can only speculate. If we assume that doxycycline does in fact inhibit the breakdown of collagen, I suppose it could have caused a ’stiffening’ of the skin, which then caused it to appear more wrinkly and deeply lined. The perceived reduction in facial subcutaneous fat my have just been my interpretation of the changed texture. Perhaps it skews the ratio of collagen to elastin, again resulting in a reduced elasticity of the skin.

Regardless, I seem to have discovered for myself why there is apparently no research taking place regarding doxycycline as a potential ‘cosmaceutical’!

Which is to say, you’re less likely to get melanoma if you spend all day out in the sun smoking cigarettes. Of course, your chances of getting lung cancer will be greatly enhanced, but whatever.

It appeared to be the degree of ’skin aging’ – the loss of elastin and collagen that makes skin look old and saggy (a process that occurs sooner in smokers) – that conferred resistance to melanoma.

I don’t really know what to make of this! Personally, I’d avoid the cigarettes but continue with my fairly lax approach to UV protection. What do you think?

Here’s the abstract:

Skin aging from ultraviolet irradiance and smoking reduces risk of melanoma: epidemiological evidence.

Anticancer Res. 2008 Nov-Dec;28(6B):4003-8. PMID: 1919266

Grant WB.
Sunlight, Nutrition, and Health Research Center (SUNARC), P.O. Box 641603, San Francisco, CA 94164-1603, USA. wbgrant@infionline.net

Long-term smoking appears to be inversely correlated with development of melanoma. Chronic ultraviolet (UV) irradiance also reduces and/or delays the development of melanoma. Thus, a common process is indicated. To examine the link between smoking and melanoma, articles reporting the relation between incidence of lung cancer and melanoma for individuals were sought. A very strong inverse correlation (r = -0.96) was found between the standardized incidence ratios for lung cancer and melanoma, passing through the value of 1 for each with a slope of -0.74. Smoking increases skin aging or elastosis in a manner similar to that of UV irradiance. Development of elastosis seems to explain why long-term smoking and chronic UV irradiance reduce the risk of melanoma. Further work is required to elucidate the mechanism whereby elastosis retards and reduces the development of melanoma.

That is to say, the perception of cleanliness, whether it be in oneself (say, after having taken a shower), or in ‘the accused’ can generate less severe moral judgement.

In the experiment, they had university students exposed (or not) to suggestions of cleanliness; then, they were asked to pass judgement on a series of moral dilemmas, including keeping money found inside a wallet, putting false information on a resume, and killing a terminally ill plane crash survivor in order to avoid starvation.

The second experiment saw the students watch a ‘disgusting’ film clip before rating the same moral dilemmas. However, half the group were asked to first wash their hands.

The findings from both experiments demonstrated that those who were subject to the cognitive feeling of cleanliness exercised less severe moral judgment than their counterparts.

Although intuitively obvious, the extension of this is that a person who appears ‘clean’ will attract less severe moral remonstration for anything untoward they do. This should serve as a warning to those who revel in excessively grungy fashion styles or deliberately poor personal hygiene – life is going to be harder for you. That is all.

This was brought to my attention by Eurekalert!