Tretinoin and Other Retinoids: What Are the Scientific Facts on Skin Rejuvenation?


Skin aging is a natural process manifested by wrinkles, loss of elasticity, and blemishes. Retinoids are one of the most researched and used ingredients in the dermatology world to slow this process and rejuvenate the skin. Retinoids are molecules derived from vitamin A and are found in various forms in both pharmaceuticals and cosmetic products.

In this article, we will discuss the anti-aging effects and clinically proven properties of different retinoids, including tretinoin, isotretinoin, alitretinoin, retinol, retinaldehyde, and retinyl esters.

Tretinoin: The Gold Standard Retinoid
Tretinoin (all-trans-retinoic acid) is the most potent and well-researched retinoid for skin rejuvenation. It is considered the clinical gold standard.

Approved Uses: It is available as a prescription drug for the treatment of acne, wrinkles, and hyperpigmentation.

Concentration range: 0.01%–0.1%, most commonly 0.025%, 0.05%, and 0.1%.

Evidence: In a 2-year clinical study with 204 participants, 0.05% tretinoin cream was found to be effective and safe for long-term use.

Lower concentrations are better tolerated, while higher concentrations provide stronger effects but increase the risk of irritation. Therefore, treatment is generally started with a low dose and increased as the skin tolerates it, supplemented with moisturizer.

In recent years, nanoformulations of tretinoin have been developed. This preserves its instability to light and oxygen, slows its release, and reduces skin irritation. Experimental studies show that nanoformulations provide better results than traditional tretinoin. However, there is currently no approved tretinoin nanoformulation on the market.

Isotretinoin: From Acne Treatment to Anti-Aging Use
Isotretinoin is the cis-isomer of tretinoin. Although it is primarily used in capsule form for acne treatment, topical creams have also been studied.

0.05%–0.1% isotretinoin cream has been found effective in reducing wrinkles and blemishes in photoaged skin.

In a large-scale study involving 800 patients, isotretinoin cream yielded significantly better results than carrier cream.

However, conventional forms are prone to irritation and instability.

Therefore, research is currently underway on isotretinoin nanoformulations. Experiments in mice show that nanoformulations are more effective and less irritating.

Alitretinoin: Strong Effects, High Side Effects
Alitretinoin is a potent retinoid that binds to both RAR and RXR receptors. It is originally approved for the treatment of Kaposi's sarcoma.

However, it has also been tested on photoaged skin in small-scale studies. Despite effective results, it has not found widespread use for anti-aging purposes due to its frequent side effects.

Retinol: The Most Popular Retinoid
The most common retinoid in cosmetic products is retinol.

Effectiveness: It is approximately 10 times weaker than tretinoin. However, it has fewer side effects.

Usage: It is typically used at up to 0.3% in creams, serums, and lotions.

Clinical evidence: 0.25% retinol has been found to be as effective as 0.025% tretinoin.

Comparative studies: Some studies have shown that retinol provides similar results to tretinoin, while others show no difference.

Another problem with retinol is its instability. It is unstable to light, oxygen, and heat. Therefore, when used in cosmetics, the formulation must be carefully designed. Nanoformulations have been developed for retinol in recent years, but sufficient clinical evidence is not yet available.

Retinaldehyde: The Balanced Option
Retinaldehyde is a natural precursor that can be converted to tretinoin.

Effectiveness: Stronger than retinol and retinyl esters, but less potent than tretinoin.

Advantage: Less irritating, therefore well tolerated.

Clinical study: 0.05% retinaldehyde cream was found to be as effective as tretinoin but caused significantly less irritation.

In recent years, nanotechnological solutions have been developed for retinaldehyde. This increases its stability and ensures a more even release into the skin.

Retinyl Esters: The Weakest and Most Popular Retinoids
The most commonly used forms of retinoids in cosmetics are esters such as retinyl palmitate, retinyl propionate, retinyl acetate, and retinyl retinoate.

Retinyl Palmitate: This is the most abundant form found in the skin. However, it is unstable to UV rays, and some studies have suggested it may be harmful.

Retinyl Propionate: Laboratory studies have shown it to be more potent than retinol and RP, but clinical results are poor.

Retinyl Acetate: Widely used in cosmetics, but clinical evidence for its anti-aging effectiveness is lacking.

Retinyl Retinoate: A more stable derivative, it has shown promising results in reducing wrinkles in small studies.

While these esters are generally less irritating, they lag behind tretinoin, retinol, and retinaldehyde in effectiveness. Furthermore, the amount used in cosmetics