Retinoids: The gold standard for anti-aging

By Alpana Mohta, MD, DNB, FEADV, FIADVL, IFAAD | Fact-checked by Barbara Bekiesz
Published July 10, 2024

Key Takeaways

  • Retinoids have cemented their place as a cornerstone in dermatological anti-aging treatments with proven efficacy in reducing fine lines, wrinkles, and hyperpigmentation. 

  • Despite their impressive properties, the use of retinol and other retinoids can be limited by adverse effects such as dryness, peeling, photosensitivity, and pruritus.

  • Alternatives like bakuchiol are available for patients who cannot tolerate retinoids, but their efficacy remains in question due to limited scientific evidence.

When it comes to anti-aging, everyone’s talking about retinoids—the general population and the medical community alike. You can't walk into a dermatologist's office or a skincare seminar without hearing about them. 

But is it really possible to “reverse” the signs of aging with a topical ointment?

Behind skin aging

As detailed in a 2023 review from Biomolecules, skin aging is driven by intrinsic factors like genomic instability, telomere shortening, and cellular senescence, and by extrinsic factors such as UV radiation, pollution, and lifestyle choices.[]

These processes cause collagen breakdown, reduced cellular turnover, oxidative stress, and inflammation (aka, inflammaging), leading to visible changes like wrinkles, pigmentation issues, and thinning skin, affecting its integrity and barrier function. 

Related: How to protect your youthful glow against ‘inflammaging’

While no topical therapy can fully reverse the signs of skin aging, topical retinoids have the most robust evidence for mitigating these effects.

Retinoids defined

This class of compounds, derived from vitamin A, includes all-trans retinoic acid (tretinoin), retinaldehyde, synthetic retinoids (adapalene, tazarotene, and trifarotene), retinol, and its metabolites, such as retinaldehyde/retinal and retinoic acid.[]

Pharmacologically, retinoids bind to retinoic acid receptors (RARs) and retinoid X receptors in skin cells, modulating gene expression. This process promotes skin cell turnover, reduces corneocyte cohesion (leading to desquamation), prevents collagen breakdown by inhibiting matrix metalloproteinases activity, and stimulates collagen production—improving skin texture and reducing fine lines and wrinkles. 

Behind the hype

Tretinoin was the first retinoid approved in 1995 for treating fine wrinkles, photoaging, and hyperpigmentation.[] Subsequently, similar anti-aging benefits were identified in other topical retinoids. However, apart from retinol and adapalene, most retinoids are available only by prescription.

Consider the research: 

  • In a split-face trial, both 0.15% and 0.30% retinol improved skin discoloration and facial wrinkles and increased skin smoothness after 8 weeks of daily usage in 20 women aged 34–65.[]

  • A study comparing retinol and retinoic acid showed that after 4 weeks, both treatments increased epidermal thickness and upregulated genes for type 1 and type 3 collagen, with retinol achieving more than half the effect of retinoic acid. After 3 months, retinol use showed a clinically significant reduction in facial wrinkles.[]


Dose-dependent side effects frequently limit retinoids’ use. The most common adverse effects are localized dryness, peeling, photosensitivity, and pruritus. Even though retinol is generally milder and better tolerated than prescription retinoids, it can still cause irritation, especially in patients with sensitive skin.

Retinoids are also contraindicated in pregnant and lactating women due to potential teratogenic effects. In fact, by November 1, 2025, the European Union (EU) will restrict the amount of retinol permissible in skincare and body care products due to concerns about skin irritation and systemic absorption. Face and hand products will be limited to a maximum of 0.30% pure retinol, while body lotions will be restricted to 0.05% retinol.[]

Owing to the above factors, researchers are increasingly exploring viable retinol alternatives.

Natural retinol alternatives


Derived from the Psoralea corylifolia plant, bakuchiol works by modulating some retinoid-responsive genes in the skin responsible for collagen production, hyaluronic acid synthesis, and skin hydration. Furthermore, it doesn’t affect the genes encoding RARs (responsible for the irritant potential of retinoids).[]

Other noteworthy benefits include antioxidative, anti-inflammatory, and antimicrobial properties.[] One small study of 44 participants found bakuchiol as effective as retinol for fine lines and skin tone but with less irritation.[] Another trial observed significant improvement in fine lines, wrinkles, firmness, elasticity, pigmentation, and photodamage with 12 weeks of bakuchiol therapy.[]

Most other studies on bakuchiol have been done on skin cells or substitutes, not on humans, limiting the evidence for its efficacy. 

A review from Skin Health and Disease spotlights some retinoic acid alternatives from the plant kingdom that have shown efficacy in in-vitro studies.[] Top contenders include squalene (derived from olive oil and marine microalgae) and phytol (from the South American herb Bidens pilosa). 

Other options include pimaric acid, pimaradienoic acid, and abietic acid, found in the rhizome of Aralia cordata, which grows in Korea, Japan, and eastern China. The best part of these natural, plant-based retinol alternatives? All of these agents are available over-the-counter.[]

Rosehip oil

Rosehip is a natural source of trans-retinoic acid, along with vitamin B complex and vitamin C. Although it has less retinoic acid than prescription products, evidence suggests it can reduce collagen breakdown. A randomized control trial found that oral consumption of 45 g of rosehip powder daily for 8 weeks significantly reduced crow’s feet and improved skin elasticity and hydration.[]

Research on oral alternatives

Oral retinol

Some retinoids, such as the aforementioned rosehip powder, can be taken in supplement form. While oral retinol (vitamin A1) has been found to provide similar anti-aging benefits as topical retinoids, topical versions remain the gold standard for reliable anti-aging benefits—due, at least in part, to the fact that oral vitamin A and natural alternatives are not as well-researched. 

However, certain patients can see great benefit in oral retinoids.

In a 12-week randomized trial from Cosmetics, patients with moderate to severe facial skin aging saw greater improvements when combining topical retinoic acid gel with oral vitamin supplements (50,000 IU vitamin A and 50 mg vitamin E daily) compared with using either just the topical product or oral supplements alone, without any overt adverse events.[]

Other oral retinoids, such as isotretinoin, acitretin, and bexarotene, have limited evidence for anti-aging benefits. One study found that low-dose isotretinoin was not superior to 0.05% retinoic acid for advanced photoaged skin.[]

Additionally, due to their teratogenic risk (category X) and impact on the musculoskeletal system, hepatic, and lipid profiles, their use is discouraged unless treating systemic conditions such as severe acne, hidradenitis suppurative, psoriasis, or mycosis fungoides.

How to advise your patients on using retinol

Topical retinoids are a great option for patients interested in anti-aging. Physicians can consider the following before prescribing or advising retinoids:

  • Evaluate your patient’s skin type, sensitivity, and pregnancy or lactation status before recommending retinol. 

  • Patients with sensitive skin or those new to retinol should start with lower concentrations, typically between 0.01% and 0.05%, once or twice a week. Gradually increase the concentration and frequency as tolerance builds. 

  • Monitor for signs of irritation and adjust accordingly.

  • Combining retinol with hydrating and soothing agents, such as hyaluronic acid and ceramides, can mitigate irritation and enhance the skin barrier function. 

  • Advise patients to apply retinol only at night and avoid mixing it with other active ingredients like AHAs or BHAs. However, retinol can be combined with azelaic acid for patients with acne or hyperpigmentation.

  • Retinol increases photosensitivity and runs the risk of retinoid dermatitis, so consistent photoprotection during the day is a must. 

  • For patients sensitive to retinol or contraindicated for retinoids, you can consider bakuchiol due to its gentle nature and pregnancy safety.

For patients interested in oral supplements, you can advise incorporating milk, eggs, and liver into their diets, as these are rich sources of retinol and dehydroretinol (vitamin A2).

What this means for you

Treating aging skin is more about improvement than complete reversal. As the skincare industry evolves, staying informed about emerging research and new ingredients is increasingly important. Retinoids remain the gold standard in anti-aging due to their proven efficacy, but no anti-aging skincare routine is complete without photoprotection (daily sunscreen) followed up with moisturizer, as these steps not only reverse but also prevent premature skin aging.

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