While Chemically Similar, They Have Differences: Retinol Is Over-the-counter, Weaker, and Comes with Less Side Effects, Whereas Retinoids Are Prescription, Stronger, and Come with More Side Effects

The Essential Info
You have probably heard commercials for anti-aging creams touting the benefits of retinol. You may also have heard about prescription anti-acne gels/creams that contain retinoids (tretinoin, adapalene, tazarotene).
The names “retinol” and “retinoids” sound similar, and that’s because they are chemically similar compounds that are derived from vitamin A. However, they have subtle yet important differences that result in unique therapeutic effects.
Retinol:
- Available over-the-counter
- Weaker than retinoids
- Work on mild-to-moderate acne to some degree
- Mainly used for cosmetic purposes, particularly anti-aging
Retinoids:
- Available only as a prescription (except for 0.1% adapalene)
- Stronger than retinol
- Work on mild-to-moderate acne to some degree (more than retinol)
- Mainly used as anti-acne treatments, but often prescribed for cosmetic purposes as well, particularly anti-aging

The Science
Retinol and retinoids are compounds derived from vitamin A that are often confused with one another because they sound similar and are frequently used to treat the same skin conditions. Both retinol and retinoids are usually formulated into topical products, so for the purposes of this article, I’ll discuss the topical versions of these compounds.
Research investigating the effectiveness of retinol and retinoids has shown that both are effective for treating skin ailments like mild-to-moderate acne, rosacea, psoriasis, and skin cancers, as well as helping fade stretch marks, aiding in wound healing, and combating aging.1-9 However, retinol and retinoids come from different sources, have distinct chemical structures, and work differently in the skin, and ultimately, even though both work, retinol is weaker. Let’s have a look at how they differ.
Retinol (over-the-counter): An inactive form of vitamin A. The body must convert retinol into its active form after it is applied to the skin. It is available in many over-the-counter anti-aging creams and some over-the-counter acne treatments.
Retinoids (prescription): An active form of vitamin A. It is available in the prescription medications tretinoin, adapalene, and tazarotene. (One exception–the lowest 0.1% strength form of adapalene is now available in over-the-counter products as well.)
Expand to learn about sources of retinol & retinoids
Retinol: Retinol is a type of vitamin A that living organisms create through eating fruits, vegetables, and certain animal proteins. Scientists can also create retinol in a laboratory setting.
Retinoids: Specific derivatives of vitamin A that are created in a laboratory setting.
However, classification of retinol and retinoids leads to confusion because both have similar chemical structures, and are therefore grouped into a large family of chemical compounds termed retinoids. Consequently, scientists classify retinol as a retinoid because its chemical structure is similar to that of other substances in the retinoid family. However, retinol is a unique member of the retinoid family because it is naturally created.10-13 For the purposes of clarity, this article defines retinol as the vitamin A substance that is produced naturally and retinoids as all members of the retinoid family that scientists synthesize in a laboratory.

Expand to learn about creation and synthesis of retinol & retinoids
Retinol: Creation occurs in the body when the liver converts beta-carotene, or other similar chemicals found in colorful fruits and vegetables, into retinol after consumption. The liver can also convert animal sources of retinol, including organ meat like the kidney or liver, and also eggs, which contain chemicals like retinyl ester, into retinol.13
Retinoids: For retinoids, scientists begin synthesis with a glucuronidation molecule isolated from animal liver. After isolation, scientists then chemically modify and convert glucuronidation into the desired retinoid chemical compound.14,15 After the chemical modification process is complete, pharmaceutical companies add the synthesized retinoid to creams, gels, or other solutions which doctors can then prescribe to patients to treat various skin conditions.

Expand to learn how retinol & retinoids work inside skin cells
In order to treat skin conditions, both retinol and retinoids must be introduced into skin cells. How retinol or retinoids enter skin cells depends on its source.
Retinol: In response to bodily signals, retinol synthesized and stored in the liver is released into the bloodstream in order to travel to skin cells. Skin proteins on the surface of the cell absorb retinol once it arrives. If a person applies topical skincare products containing retinol, skin proteins on the surface of the cell absorb the substance. Once inside the cell, retinol signals for and alters the expression of certain genes, which provides the associated therapeutic effects.
Retinoids: When a person applies topical skincare products containing retinoids, skin cells absorb the retinoids. Once inside the cell, much like retinol, retinoids signal for and alter the expression of certain genes, which provides the associated therapeutic effects. The difference in the mechanism of action between retinol and retinoids is largely due to the specificity of each for a different set of skin proteins, which triggers difference in skin gene expression.1,13,16-26

Expand to learn about the chemical structural differences of retinol & retinoids
Like all other organic (carbon-containing) molecules, the chemical structure of the family of retinoids–including retinol–contains a foundation of carbon atoms. To form organic chemicals, multiple carbon atoms are bonded together to form linear strings or circular rings, which provide the molecule with different functions.4,27,28
Retinol: Contains four specific molecular structural features. However, it lacks a single oxygen atom on the structural feature known as the polar end group, which is present in all other retinoids.
Retinoids: Contain the same four specific molecular structural features which, when altered, allow for the creation of new retinoid derivatives. Over time, scientists have slightly altered these foundational elements in order to create new laboratory-synthesized retinoids with improved efficacy. Four generations of retinoids have been created based on their molecular structure and time of discovery.4,12,13,29,30 Each generation differs slightly in structural changes within one or more of the foundational elements that provide it with an altered mechanism of action and therapeutic effect.2 For example, when scientists altered the positions of the single and double bonds within the polyene side chain, it allowed for retinoids to bind to a more diverse set of skin proteins and differentially affect skin gene expression.4,27,28 The chemical structures and therapeutic effects of different synthesized retinoids are summarized below.

Side Effects of Retinol & Retinoids
As with any medication, patients using retinol or retinoids to treat various skin conditions can develop side effects.
Retinol: People using topical retinol treatments can develop skin irritation like itching, burning, and rashes.
Retinoids: Patients applying topical retinoid treatments can develop irritation, scaling, and redness on the skin. For retinoid therapy, a medical professional monitors patients, and therefore controls or prevents side effects by altering the type or dosage of the retinoid therapy.4,31-34

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