Retinoids — The Gold Standard Face Cream That Nothing Has Yet Replaced

Decades of use, an evidence base, and a of effect that no newer has come close to replicating. Here is an honest account of what retinoids actually do, how the different forms compare, and why the gentlest option is not always the wisest choice.

A five-decade head start

The story of retinoids in dermatology begins not with anti-ageing but with acne. Tretinoin (all-trans acid) was first for acne in the 1960s. Its properties were identified almost by accident, as patients and clinicians observed that skin treated with tretinoin looked not just clearer but structurally improved, smoother, firmer, more evenly pigmented, with a quality of that went well beyond what acne treatment alone could explain.

The subsequent of research into that observation have one of the most robust bases in all of dermatology. No topical skincare ingredient has been as thoroughly, over as long a period, or with as consistently positive results as retinoic acid and its derivatives.

That head start matters . When a patient asks a new ingredient might be as effective as their retinoid, the honest answer almost always begins with an that nothing has had the time, the research investment, or the clinical to make that confidently. The newer ingredients may be promising. The retinoid evidence is established.

What is a retinoid?

The term "retinoid" refers to the entire family of A derivatives, both and synthetic, that share the ability to bind to retinoic acid receptors in the skin and gene . The family several that are in clinical and practice, and their relationship to one is essential for that follows.

At the top of the sits tretinoin, all-trans retinoic acid, the fully active form that binds directly to receptors any conversion.

One step removed is retinaldehyde (also called retinal), which requires a single enzymatic conversion to become acid.

Two steps removed is retinol — the form most found in over-the-counter — which must be converted first to and then to acid before it can exert any effect.

Further still are the esters, retinyl palmitate & retinyl acetate, which require an additional step before the pathway.

Beyond these occurring forms sit the synthetic retinoids: adapalene, tazarotene, and the newer retinoate (HPR), each designed to with specific or bypass the pathway in different ways.

What retinoids actually do

The breadth of effect at the cellular and molecular level is, genuinely, remarkable. include keratolytic activity, of proliferation and of cells, of fibroblasts, of synthesis and collagen recycling, prevention of collagen loss, in matrix metalloproteinases MMP-1 and MMP-8, and a decrease in epidermal through of kinase.

Retinoids accelerate the of the epidermal surface, a in skin texture and tone.

They stimulate dermal to new while the enzymes responsible for collagen degradation — a dual action that is particularly valuable in Ageing Skin & Wrinkles skin where both are .

They normalise the disordered that accumulates with sun exposure.

They the organisation of the stratum corneum.

And they do all of this through a single, elegantly coherent mechanism: binding to nuclear retinoic acid receptors (RARs) in keratinocytes, triggering a of gene changes that affect every aspect of skin simultaneously.

Retinoids are central of skin biology, influencing proliferation, differentiation, immune modulation, and barrier .

Their therapeutic has long been attributed to retinoic acid receptor-mediated transcriptional activity; however, recent studies have layers of regulation, epigenetic modifications, kinase signalling networks, and interactions with the skin . The more closely the mechanism is examined, the more sophisticated it .

The sebum question

A word about sebum (natural skin oils) — because it is cited as one of retinoids' beneficial effects and the evidence deserves honest .

Oral retinoids, such as Roaccutane used systemically for severe acne, produce a and in gland and sebum . The same effect in application is less certain.

The that skin treated with topical retinoids becomes less oily may reflect improved and rather than a direct in sebum output. The distinction is worth making; not to diminish the value of retinoids, whose are and well-documented in other respects, but because accuracy matters more than a .

The conversion pathway — and why it matters

Every over-the-counter retinoid must be converted, in the skin, to acid before it can bind to the receptors that drive its biological effects. The skin can only use one form of vitamin A: retinoic acid. Everything else is a precursor.

The conversion pathway is sequential and each step introduces . of the first-generation representatives decreases in the following order, from most potent down to weakest:

Retinoic acid (Tretinoin)

Retinaldehyde

Retinol

Retinyl esters

Whilst and hence side effects are the reverse. With Retinyl esters being the gentlest through to Retinoic Acid being the .

In terms: esters, the gentlest and most commonly found form in moisturisers, must undergo two enzymatic steps before becoming active. requires two steps. Retinaldehyde requires one. is already in its active form and requires no conversion at all. The further from acid a sits in this pathway, the less efficiently it the active to the tissue but the less irritating it is in the .

This is the chemical basis for Dr Forrester’s clinical suspicion that retinoids are less effective and the evidence it directly. can take twice as long as to begin showing results.

The newer retinoids — genuine advance or elegant marketing?

Hydroxypinacolone (HPR), commercially known as granactive retinoid, has attention as a retinoid that supposedly bypasses the conversion pathway by to retinoic acid receptors without conversion.

The elegance is real. The clinical is thinner. In vitro data comparable collagen-stimulating to tretinoin is not the same as in vivo data in humans over meaningful timeframes — and the latter remains sparse. in with newer are biologically plausible, yet they have not been proven against active retinoid comparators in randomised .

Retinaldehyde a more interesting position. As the immediate to retinoic acid, it requires only a single step and a more controlled of active retinoic acid than direct .

Metabolism of retinaldehyde to retinoic acid occurs only by keratinocytes at a pertinent stage of differentiation, leading to a more controlled delivery of retinoic acid and weaker effects to tretinoin. It is, in our view, the most clinically credible of the retinoids though it suffers from significant instability challenges that have historically its in reliably products.

The adaptation strategy — getting patients to the effective dose

The most practically important insight about is one that is frequently omitted from prescribing and practice: the period is manageable, and managing it well is the difference between a who the full benefit of retinoid and one who abandons it after a few weeks of .

In terms: start at the lowest available concentration, apply every third night initially, and the barrier aggressively throughout with ceramide-containing moisturisers and niacinamide.

Increase and concentration only when the skin has demonstrated tolerance at the current level. The goal is to work up to the most potent form the skin can comfortably sustain — not to to the gentlest option because it requires the least clinical .

A on tretinoin is receiving demonstrably more effect than a on a retinol at the same comfort level. Getting the first patient to the second is a skill worth investing in.

The conclusion that the evidence supports

Retinoids remain the topical ingredient in dermatology. The of their biological effect — stimulation, renewal, normalisation, improvement — has not been replicated by any newer ingredient in the same depth or over the same . The from to prescription strength is a gradient of both efficacy and tolerability, and the clinical art lies in managing that in the interest rather than defaulting to the most comfortable or the most commercially convenient option.

The newest ingredients in the skincare landscape — polynucleotides, growth factors, exosomes, — are interesting, and some of them are genuinely promising. We examine them in the companion piece to this one. None of them has yet earned the right to displace retinoids from their position at the foundation of evidence-based topical . That position has been built over five of clinical research, and it is not easily challenged.

The views in are the Dr Forrester’s own and his and professional experience in aesthetic medicine.

References

1.     Cosmetic use in photoaged skin: A review of the compounds, their use and mechanisms of action.  Journal of . 2025. 

2.     A Review of the Strategies to Reduce Retinoid-Induced Skin in Formulation. Dermatology Research and . 2024. 

3.     The Next of Skin Care: Retinoid Therapeutics. PMC. 2025. 

4.     An Updated Review of Tretinoin in . Journal of Clinical Medicine. 2025;14(22):7958. 

5.     Use of in Topical Antiaging Treatments: A Focused Review. PMC. 2022. 

6.      in the treatment of skin aging: an overview of efficacy and safety. PMC. 2006. 

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