In Part I, we discussed an overview of retinol metabolism in the skin. It delved into the actual steps and corresponding classes of enzymes responsible for the conversion process. Part II examined and analyzed the various issues about retinol use such as: retinol strength, and concomitant use with acidic products.
In this final part, we will discuss whether or not retinol can be viewed as a complete substitute for tretinoin.
Can Retinol Replace Tretinoin?
Well, the answer of course is NO.
From a therapeutic point of view, of the naturally-occurring retinoids, tretinoin is the most biologically active. Retinol would first have to convert to retinaldehyde, before becoming tretinoin in order to function. Therefore, for more serious conditions (ranging from psoriasis to leukemia), the most potent and effective compound for treatment is tretinoin because there are no conversion factors to consider.
Think of it like this: If you didn’t eat for a week, you’d be very hungry, right? To treat this “ailment,” what would you rather eat: a tray of lasagna (tretinoin)? Or would you rather buy all the ingredients (retinol), prepare and bake them (retinaldehyde), before being able to call it lasagna (tretinoin)?
***Please note that this is simply a metaphor and does not mean that tretinoin and retinol give identical results.
However, from a cosmetic point of view, the answer is less clear. Because it’s been thoroughly established that retinol does indeed convert to tretinoin, which is the only way the former can become active in the skin, the only relevant aspect that can affect the efficacy of retinol is the actual conversion process.
Therefore, here’s what we have to analyze…
What Intrinsic Attributes Can Hinder Retinol Metabolism?
The intrinsic attributes that will be discussed include the following:
- Chronological Aging
- Behavioral Aging
While it’s likely that the conversion rates will vary from person to person, it is accurate to conclude that generally, retinol will convert to tretinoin at approximately the same amounts for younger individuals. As the body ages however, it becomes less efficient at performing the same tasks, accumulates non-recyclable biological waste, and repairs itself less quickly. Therefore, while there is no conclusive or even suggestive study done on how the different types of aging directly and specifically affect retinol metabolism, it’s still an interesting topic to analyze.
Unfortunately, I can point to no study that even remotely suggests or infers an effect of age on retinol metabolism efficiency. In fact, this study suggested that even very advanced individuals (80+ years) were able to properly metabolize retinol, which was indicated by physiological retinoid-specific changes in the skin compared to the vehicle. However, because this study doesn’t actual examine the conversion process, it doesn’t tell us whether or not the conversion of retinol to tretinoin was impaired or reduced in efficacy when compared to say, a group of college students.
This type of aging is attributed primarily to the damaging UV rays of the sun, which with chronic exposure, can harm the skin in many ways; one of which is free radical or reactive oxygen species generation. This leads to oxidative stress in a variety of forms such as lipid peroxidation and immunosuppression. This study demonstrated that lipid peroxidation products inhibited the activity of retinol dehydrogenase 12, which led to decreased levels of retinoic acid (tretinoin = all-trans-retinoic acid). And as we learned in Part I of this series, because retinol dehydrogenases are one of the main classes of enzymes responsible for the conversion of retinol to retinaldehyde, it can be suggested that chronic UV exposure can reduce the activity and efficiency of those enzymes.
Now, I realize that the study linked was done on variant 12, which is active in the eye. Variant 10 is the most active in the skin. However, given the close resemblance of all retinol dehydrogenases, it can’t be completely denied that chronic UV exposure may reduce the rates of retinol metabolism (in the oxidation direction; towards tretinoin). We’ll have to wait until more specific and relevant studies are conducted.
This type of aging is attributed to a person’s behavioral tendencies. For example, smoking, drinking, etc… Now, I’m not going to tell my readers how to live their lives; I just want them to be healthy. However, I won’t deny that certain activities will increase physiological aging. In terms of this post, chronic ethanol consumption was postulated to inhibit retinoic acid synthesis in developing embryos by acting as a competitive substrate for alcohol dehydrogenase, which is another class of enzymes responsible for the retinol conversion process. This blocking of retinol by ethanol, effectively reduced the amount of retinoic acid formation.
Another interesting study demonstrated that diabetic mice had not only irregular retinol metabolism, but also exhibited significantly reduced levels of tretinoin in the kidneys. This reduction was attributed partly to a drastic decrease in the expression of alcohol dehydrogenase 1, another enzyme responsible for retinol conversion.
***Keep in mind that both of these studies did not measure retinol conversion activity in the skin; I could not find a study that does so. Usually, I would not casually link nor approve of using a result seem in a study done systemically to justify a similar effect when applied topically. For example, just because it was shown that oxybenzone was estrogenic or an “endocrine disruptor” when administered orally, doesn’t mean that will happen in the skin. However, in this case, we’re not discussing the effect of an EXTERNAL aspect. Instead, we’re talking about the enzymes of the skin, which are INTERNAL aspects. Furthermore, it has been established that both excess ethanol and sugar intake do have significant and deleterious effects to the skin. Again however, more specific studies need to be done before I can give a more conclusive answer.
So what does all this mean? Due to the lack of relevant data, this just means that tretinoin CANNOT be replaced by retinol. Furthermore, taken as a whole, the cited data suggests that the retinol metabolism process may be negatively altered by the various types of aging.
However, does that mean that old(er) people can only apply tretinoin to their faces to get noticeable results? Absolutely not. Will they get BETTER results with tretinoin? Maybe. Ultimately, any retinoid use is better than none! This post was more of an experimental or theoretical assay into an interesting topic; rather than a practical debate over the efficacy of retinol over a lifetime.
This (finally) concludes this exciting series on retinol metabolism. I hope it was informational and please let me know what you guys think of it!