The retinoids are classes of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth.
Retinoids have many important and diverse functions throughout the body including roles in vision, regulation of cell proliferation and differentiation, growth of bone tissue, immune function, and activation of tumor suppressor genes.
Research is also being done into their ability to treat skin cancers. Currently 9-cis retinoic acid may be used topically to help treat skin lesions from Kaposi’s sarcoma.
There are three generations of retinoids:
First generation retinoids: which include retinol, retinal, tretinoin (retinoic acid, Retin-A), isotretinoin, and alitretinoin.
Second generation retinoids: which include etretinate and its metabolite acitretin.
Third generation retinoids: which include tazarotene, bexarotene and Adapalene.
The basic structure of the retinoid molecule consists of a cyclic end group, a polyene side chain and a polar end group. The conjugated system formed by alternating C=C double bonds in the polyene side chain are responsible for the color of retinoids (typically yellow, orange, or red). Hence, many retinoids are chromophores. Alternation of side chains and end groups creates the various classes of retinoids.
First and Second generation retinoids are able to bind with several retinoid receptors due to the flexibility imparted by their alternating single and double bonds.
Third generation retinoids are less flexible than First and Second generation retinoids and therefore, interact with fewer retinoid receptors.
The major source of retinoids from the diet is retinyl esters derived from animal sources. Retinyl esters are hydrolyzed in the intestinal lumen to yield free retinol and the corresponding fatty acid (i.e. palmitate or stearate). After hydrolysis, retinol is taken up by the enterocytes. Retinyl ester hydrolysis requires the presence of bile salts that serve to solubilize the retinyl esters in mixed micelles and to activate the hydrolyzing enzymes.
Several enzymes that are present in the intestinal lumen may be involved in the hydrolysis of dietary retinyl esters. Cholesterol esterase is secreted into the intestinal lumen from the pancreas and has been shown in vitro to display retinyl ester hydrolase activity.
In addition, a retinyl ester hydrolase that is intrinsic to the brush-border membrane of the small intestine has been characterized in the rat as well as in the human. The different hydrolyzing enzymes are activated by different types of bile salts and have distinct substrate specificites.
For example, whereas the pancreatic estrase is selective for short-chain retinyl esters, the brush-border membrane enzyme preferentially hydrolyzes retinyl esters containing a long-chain fatty acid such as palmitate or stearate. Retinol enters the absorptive cells of the small intestine, preferentially in the all-trans-retinol form.
Use of retinoids:
Topical retinoids are part of the foundation for most adult acne treatment. All adult acne lesions start as a clogged pore (comedone), and effective adult acne therapy requires the removal of this clogged orifice (comedolysis). Retinoids continue to be our most effective topical medicines for this. Additionally, they have anti-inflammatory properties that further help to decrease the red pimples and pustules of adult acne.
Retinoids are substances derived from Vitamin A, which attempt to cure adult acne by normalizing the lifecycle of follicle cells. There are two types of such substances, based on application: external (topical) and oral. The best known external retinoids are Retin-A, Differin and Tazorac, while the oral retinoids list is headed by the popular Accutane.
Retinoids are derivatives of Vitamin A and share the parent substance’s effects of reducing the secretion of oil from the glands located in the skin. This primary effect is what makes retinoids so effective against adult acne.
The long-term (4-6 months) decrease in oil secretion means that hair follicles are less likely to clog and turn into pimples and, in most cases, adult acne is gone for good by the end of the treatment period. However, about one quarter of the patients who used Accutane or other drugs based on isotretinoin may relapse and require additional treatment.
The first 1-2 months of starting any retinoid will be an adjustment period for your skin. Most people’s skin will get dry, red, and mildly irritated. For some people, this can be quite severe. In order for the medicine to work well, follow these steps:
- At night, after brushing your teeth, wash your face and pat dry. Sunlight may breakdown retinoids, so they are best to apply at night. I find medicine spreads easier and is less irritating on moist skin.
- While your face is still moist, apply a small “finger tip” amount of medicine in small dots around the face, then spread over the whole face to a thin film. Be careful to avoid the sensitive skin under the eyes, next to the nose, and the in corners of the mouth.
- After rubbing the medicine in well, apply a moisturizer of your choice. Reapply the moisturizer in the morning, along with a daily sunscreen.
- If you find your skin becoming very irritated, hold the medicine for a few days, then start applying it only 2-3 times per week. Increase application by 1 day per week every few weeks as tolerated. For patients with sensitive skin, I often start them at this 2-3 times per week regimen.
- For some very sensitive skin, we may use short contact therapy. This means applying the medicine for 15 minutes before washing it off, and slowly increasing over time as tolerated.
Remember — this is medicine, not magic. Adult acne may initially get a little worse in the first 2-4 weeks of treatment. Continued improvement may occur for up to 4-6 months! So be patient and persistent!
The most common side effect of retinoids is irritation. Retinoids exfoliate your skin from the inside-out and during the process; your skin can become extra sensitive. It can peel, turn red, flake, randomly flush, and grow dry. Many people also purge, or experience adult acne flares, during their initial use.
Irritation, redness, and dry skin:
Irritation from retinoids comes in many forms. When people say their skin is irritated by a retinoid, they usually mean the retinoid makes their skin red and more sensitive. Retinoids turn my skin a pinkish shade, especially immediately upon application, and they make my skin feel prickly for one to two days afterwards.
My skin does seem to be a little more sensitive than the average person, but when I was using Differin, it made my normal moisturizer and cleanser (sometimes even water) sting. I had redness, almost to the point of itchiness, under my eyes and around my cheekbones. My skin would also randomly flush red and hot and then disappear.
You can tell if something is irritation versus allergic reaction if the symptoms subside once you stop using the retinoid. I had to give my skin breaks every few days to recuperate and after a day or two of not using retinoids, my skin went back to normal.
Aside from redness and sensitivity, another common side effect of retinoids is dry skin. Your skin may peel, flake, and be all kinds of ugly (regardless of how much moisturizer you slather on) until it gets used to the retinoid. From personal experience, my skin looked horrible under foundation when I was first using Differin. There was nothing I could do to smooth out the skin-colored flakes, but after I got used to Differin, the dryness gradually subsided.
Irritation around the eyes:
You can use retinoids under your eyes, but be careful because the skin there is already thinner and more sensitive than other areas of your face. I received an email from a reader saying that her eyelids got swollen after every time she applied a retinoid, even though she wasn’t putting the product anywhere near her eyes.
One reason could be because the natural oils on her face caused the product to migrate. If your eyes are extremely sensitive, I would suggest putting a layer of Vaseline around your eyes to protect them from any treatment products, retinoids or otherwise.
Initial breakouts and purging:
Initial breakouts are another common side effect of retinoids. To tell if you are purging or simply breaking out from the product (ingredients-wise), take a good look at where your breakouts are occurring.
Purging is usually the worsening of already-present adult acne symptoms. So, for example, if you have clogged pores, they may turn into bigger pimples. If you have small whiteheads, they may turn into inflamed whiteheads.
If you are experiencing breakouts in areas of your face where you normally don’t break out or are experiencing breakouts that occur in tiny, red clusters, you may be suffering from an allergic reaction instead. Whatever you do, consult your dermatologist to see if you should stick through with the adult acne flares or if you should switch to a new product.
Sometimes giving your skin a break from the retinoid and then starting up again a week later can help calm your skin down. Though if it doesn’t calm down after taking a few days off, then your skin probably just doesn’t like that particular retinoid. Also, it may be a better idea to start retinoids in the summer time instead of winter, as cold winter air can exacerbate the irritation and dryness side effects.
When you are using retinoids, you should try to stay out of the sun. Whenever you do go outside or even when you are inside, you should always wear a good sunscreen (because UV rays can still penetrate through windows). Not only will sunscreen protect you from getting further sun damage, it will also prevent your skin from getting worse because retinoids do make you more sensitive to the sun.
If you absolutely can’t wear sunscreen, try to stay out of the sun whenever possible, wear big floppy hats, giant sunglasses, and get your windows UV tinted for extra protection.
Retinoid use with other products:
It’s also a good idea to avoid using any exfoliants while you are on retinoids. Chemical or manual exfoliation could cause your skin to be even more sensitive and irritated. Retinoids offer a hefty amount of exfoliation on their own. However, if you feel like your retinoid is not strong enough, you can use AHAs or BHAs for extra exfoliation.
Some people believe that AHAs and BHAs can help increase a retinoid’s penetration. However, it will depend on the formulation of the product. For example, if you use a BHA lotion, the emollients in the lotion may decrease penetration more than the acid would increase penetration. But if you use a BHA liquid or something alcohol-based, it may enhance penetration.
Retinoids during pregnancy:
Lastly, do not use retinoids while you are pregnant, breastfeeding, or trying to conceive. Retinoids, like all other skin care products, are absorbed into the body through your skin. Since there haven’t been enough studies done on how retinoids affect developing fetuses, it’s best to go the safe route and not use them at all.
Using retinoids means dealing with the side effects, but if you use retinoids the right way and take the proper precautions, many of these side effects can be minimized. If retinoids agree with your skin, you will find that the short term side effects are worth the long term benefits.