Spotlight On: Tretinoin

Ingredients, Skin Care

About the author: is proud to introduce John Su on our staff as a Contributing Writer.  John is an established skin care expert and aspiring dermatologist.   He also runs a blog, The Triple Helix Liaison, dedicated to providing unbiased, meaningful, and insightful information about skin care. For his full bio, please visit our About page.

Tretinoin is available in prescription Retin-A, Renova, Avita, Atilinac, and Atralin. It is also available in lesser concentrations in products like Obagi Refissa and RP Pharmaceuticals Tretinoin Cream, shown above.

Today’s article will be similarly limited to the discussion of tretinoin. Other retinoids like tazarotene and adapalene are quite structurally different and will be discussed in the future.

What is Tretinoin?

Tretinoin or all-trans retinoic acid is a lipid-soluble molecule that possesses an acidic component (specifically a carboxylic acid group) at one end and a lipid-soluble component (specifically a beta-ionone ring) at the other, with a long polyunsatured carbon chain linking the two.

Retinol conversion pathwayRetinol or Vitamin A is simply the alcohol form of tretinoin that has yet to be enzymatically oxidized, meaning that it needs to lose electrons.  Retinol must first be converted into retinal (aldehyde) and then ultimately tretinoin.

What Can Tretinoin Do For the Skin?

Before and after tretinoin
Before and after tretinoin, via Dr. Obagi. Note the improvement in fine lines, wrinkles, texture, and signs of acne.

Tretinoin is fantastic because it can address acne and photodamage, which is a rare quality. Tied with hydroxy acids, it is my most recommended ingredient because of this unique duality.

How Does Tretinoin Help with Acne?

Before and after tretinoin
Before and after tretinoin.

Tretinoin functions by reducing the positive and negative polarities of skin cells – think about reducing charge across a magnet!  These skin cells are called keratinocytes.  This decrease in charge allows for more even and normalized natural exfoliation.

Tretinoin also decreases the levels of transglutaminase, an enzyme that cross-links the trans-membrane proteins present on keratinocyte surfaces (1). Therefore, tretinoin is effective at loosening impactions (2); think mini blackheads and whiteheads.

Not to mention that tretinoin’s exfoliant properties allow for deeper penetration of other treatments such as salicylic acid and topical antibiotics.  Together with these ingredients, acne breakouts are decreased both mutually and synergistically.

How Does Tretinoin Treat Photodamage?

English: 1BKV Collagen triple helix
This pretty molecule is collagen. Regular tretinoin use helps to prevent collagen loss. How? Tretinoin essentially gets rid of the enzymes that degrade collagen.

UV-induced damage results in dramatic decreases in collagen production, specifically collagen types I (makes up 80% of the dermis matrix), III (10%), and VII (1%) (3).

Furthermore, UV damage massively increases the production of several enzymes that break down collagen, called matrix metalloproteinases (4).  These enzymes result in the production of collagenase, gelatinase, and stromelysin.  Tretinoin inhibits the creation of all three of these collagen-degrading enzymes (5)!

For the Ultra Scientific

This happens because two transcription factors, c-Jun and c-Fos, combine to produce activator protein-1 (AP-1).  In turn, this activates the MMP genes.

By inactivating one of the transcription factors, the MMPs never come into play – resulting in preserved collagen.  Tretinoin specifically inactivates the c-Jun protein by stimulating its breakdown through a chemical pathway known as the ubiquitin-proteasome pathway.

Bottom Line

Women who are pregnant or nursing should not use tretinoin, as vitamin A toxicity has been shown to result in birth defects and to be harmful for infants. [Read more:  FutureDerm – Skin Care Ingredients and Supplements Pregnant or Nursing Women Should Not Use]

Now, I know that this only beings to scratch the surface of what tretinoin, the most studied topical treatment used in dermatology, can do. But I hope it gives you all the appropriate mindset to better understand the upcoming retinol metabolism post! Stay tuned!


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