When it comes to anti-ageing, 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 ageing with a topical ointment?

Behind skin ageing

As detailed in a 2023 review from Biomolecules, skin ageing 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.

Quan T. Human skin ageing and the anti-ageing properties of retinol. Biomolecules. 2023;13(11):1614.

While no topical therapy can fully reverse the signs of skin ageing, 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.

Motamedi M, Chehade A, Sanghera R, et al. A clinician's guide to topical retinoids. J Cutan Med Surg. 2022;26(1):71–78.

Behind the hype

Tretinoin was the first retinoid approved in 1995 for treating fine wrinkles, photoaging, and hyperpigmentation.

Baldwin HE, Nighland M, Kendall C, et al. 40 years of topical tretinoin use in review. J Drugs Dermatol. 2013;12(6):638–642, e94–e105.

Subsequently, similar anti-ageing 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 discolouration and facial wrinkles and increased skin smoothness after 8 weeks of daily usage in 20 women aged 34–65.

  Zasada M, Budzisz E. Randomized parallel control trial checking the efficacy and impact of two concentrations of retinol in the original formula on the ageing skin condition: pilot study. J Cosmet Dermatol. 2020;19(2):437–443.

   

• 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.

  Kong R, Cui Y, Fisher GJ, et al. A comparative study of the effects of retinol and retinoic acid on histological, molecular, and clinical properties of human skin. J Cosmet Dermatol. 2016;15(1):49–57.

   

Challenges

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.

European Commission. Commission Regulation (EU) 2024/996 of 3 April 2024.

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

Natural retinol alternatives

Bakuchiol 

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).

Brown A, Furmanczyk M, Ramos D, et al. Natural retinol analogs potentiate the effects of retinal on aged and photodamaged skin: results from in vitro to clinical studies. Dermatol Ther (Heidelb). 2023;13(10):2299–2317.

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.

Sadgrove NJ, Oblong JE, Simmonds MSJ. Inspired by vitamin A for anti-ageing: searching for plant-derived functional retinoid analogues. Skin Health Dis. 2021;1(3):e36.

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.

Sadgrove NJ, Oblong JE, Simmonds MSJ. Inspired by vitamin A for anti-ageing: searching for plant-derived functional retinoid analogues. Skin Health Dis. 2021;1(3):e36.

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.

Oargă Porumb DP, Cornea-Cipcigan M, Cordea MI. Unveiling the mechanisms for the development of rosehip-based dermatological products: an updated review. Front Pharmacol. 2024;15:1390419.

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.

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.

Bagatin E, Guadanhim LR, Enokihara MM, et al. Low-dose oral isotretinoin versus topical retinoic acid for photoaging: a randomized, comparative study. Int J Dermatol. 2014;53(1):114-22.

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).