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’!

This is because, while the ability to degrade the matrix is extremely important in growth and wound healing, if the processes of synthesis and degradation fall out of balance in favour of degradation, the overall amount of collagen will decrease.

In youth, these processes are in balance, but as we age, the degradative enzyme activity begins to overpower that of synthesis, leading to a loss of skin quality. Other factors that increase MMPs are photodamage and smoking.

In the past, I’ve boosted my skin’s balance in favour of collagen synthesis with isotretinoin, which worked beautifully but has drawbacks that in my opinion make it unacceptable for chronic use (cracking lips, sun sensitivity, etc.). I’ve also heard that the skin’s response to collagen-synthesis stimulating retinoids decreases with age.

So, in theory, one could boost its overall levels by instead interfering with the breakdown of collagen by inhibiting MMPs.

At present, the only MMP inhibitor that’s available readily and cheaply is doxycycline hyclate, an antibiotic often used to combat acne. Apparently, by taking a subantimicrobial dose (i.e., too little to kill bacteria) one can benefit from its anti-MMP activity while minimizing its side effects. Doxycycline is also used in this way in dentistry, where it is used to facilitate healing of the connective tissue in the gums.

There was also a study where doxycycline’s effect on wound healing was investigated because it was suspected it may *interfere* with normal wound healing as a side-effect, but it was instead found that the wounds actually healed either at the same rate or faster.

So, lately I’ve been noticing the accumulation with age and decades of intense sunlight a slight loss of skin elasticity (yes, wrinkles), so I decided to start taking 25mg/day doxycycline for a couple of months and see if this has any effect on the quality of my skin. I’ve taken some ‘before’ photos that highlight the problem, and I intend to compare these with pictures taken in 1 and 2 months to see if I can identify any change.

The literature is at first glance almost entirely free of this kind of experiment, with most papers focussing on doxycycline’s antibacterial and anti-inflammatory effects for the treatment of acne and rosacea. I’m sure there’s a good reason for this that I in my limited capacity don’t have time to dig up, so I’m pressing ahead regardless.

I’ll post the results, including before/after shots and analysis in about a month

Here’s some reading in the meantime:

• Inhibition of matrix metalloproteinases: a new skin care frontier
• Matrix metalloproteinases
• Doxycycline

Facial scarring was downright sexy to these women test subjects, especially those who were seeking short-term relationships (read ‘one-night stands’). This is because when it comes to choosing a partner, women prefer super-masculine men with through-the-roof testosterone levels when they’re looking for a good, hard shag; and softer, more effeminate men when they’re looking for someone to imprison in a state of life-long matrimonial servitude.

As for women with facial scars, men didn’t seem to even notice. They were probably looking elsewhere.

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This research will be published in the journal of Personality and Individual Differences, and was brought to my attention by Eurekalert!

I’m shocked and saddened on a daily basis at the intense ugliness of humanity that simply does not need to be. Fat people who refuse to lose weight, thin people who think that thinness alone is sufficient to look good (as opposed to thinness and a fit, muscular physique), people who proudly allow their acne to flourish (go to the dermatologist and GET AN ACCUTANE PRESCRIPTION FFS), etc.

So to the extent that these things could easily be rectified but persist due to the general inertia of people, I will continue to bitch and remind fatties of their impending premature death.

To that end, I now report on another study that correlates waist size as opposed to BMI alone as a marker for premature removal from the gene pool.

If you’re up-to-date with these things, it’s probably something you’ve heard before, but now the New England Journal of Medicine gives us further evidence that waist circumference is directly proportional to risk of death. In fact, the risk of premature death increased in an exactly linear fashion as the waist circumference increased of the study subjects, with each 5 cm raising the risk of mortality by 17% in men and 13% in women.

An increased risk of mortality may be particularly related to storing fat around the waistline because fatty tissue in this area secretes cytokines, hormones and metabolically active compounds that can contribute to the development of chronic diseases, particularly cardiovascular diseases and cancers, suggest the authors

Interestingly, with regard to BMI alone, the lowest risk of death occurred at a BMI of 25.3 for men and 24.3 for women.

I find this to be somewhat bizarre, as a BMI of 24 for a woman is actually pretty chunky (e.g., for a 5′4″ woman (162 cm), this corresponds to a weight of 140 lbs or 63.5kg!! Whereas, if we consider a BMI of about 18 to be ideal (your average model), the 5′4″ girl in question would weigh in at 47kg or 105 lbs. A difference of 16 kg on a 162 cm girl is significant indeed. One wonders if this is being reported correctly, and just goes to show that BMI is not a good indicator of, well, anything really.

A better metric is the waist-to-hip ratio:

Lower waist-hip ratios indicate that the waist is comparatively small in relation to the hips. The ratio is calculated by dividing the waist measurement by the hip measurement.

Waist to hip ratio varied quite widely in the European populations in the study. In 98 percent of the study population, waist to hip ratio ranged between 0.78 and 1.10 in men and between 0.66 and 0.98 in women. Within these ranges, each 0.1 unit higher waist-hip-ratio was related to a 34% higher mortality risk in men and a 24% higher risk in women.

This was a very large study, looking at 359,387 participants with a follow-up period of 9.7 years.

One wonders if the surprisingly high optimal BMI for reducing death risk was because the thinner people were thinner on account of their smoking. Not sure if that was taken into account, but it would perhaps explain the results.

Adapted from materials provided by Eurekalert.

I’m just going to summarize this quickly, but as it happened, men couldn’t really have cared less about the male models; however, and surprisingly, when they viewed enticing images of females, particularly those in more suggestive poses as you would find in your typical ‘lad’ magazine, they exhibited an enhanced sense of body self-consciousness a year later.

Aubrey attributes this to men realizing that if ever they were to stand a chance of attracting these desirable females, they would first have to lose about 60% of their body weight and basically just get off their fat hairy asses and down to the gym and tanning salon and waxing parlour etc. etc.

I’ve got to say that in my own experience, this is definitely the case. Whenever I’m walking along contentedly pondering the non-sexual mysteries of the world and a highly delicious female walks into my vicinity, my thoughts turn immediately to… well, after that they turn directly to when I went to the gym last and when I can go again and whether I should up the weight on my squat.

I don’t see this as a bad thing! I know all those politically vociferous fatospherians bitch and moan about the negative self image engendered by the ‘unrealistic expectations’ promulgated by the fashion world and whatnot, but surely any kick in the guts in the direction of a healthy or at least dietarily conservative lifestyle is a good thing.

I think this may be why my gym has ten plasma screen playing sexy music videos the whole time. It may be an uncomfortable feeling, that you’re not good enough as you are, but if the ends justify the means, as they often do, I think it’s an effect to be embraced.

So, while the original press release referred to it as a ‘negative effect on men’, I wholeheartedly beg to differ!

Adapted from materials provided by Eurekalert