My Thoughts On The Drunk Elephant A-passioni Retinol Controversy

This morning I received a DM from @daniellelouisehay regarding a retinol product she had used from Drunk Elephant that she had quite a strong reaction to. She contacted the manufacturer to ask How is this causing dryness and peeling when prescription strength doesn’t?” She used this cosmetic retinol product for 2 days after having used prescription tretinoin 0.05% from @Dermatica.skin for a few months. Danielle never experienced irritation or peeling with the Dermatica tretinoin product. 

According to Danielle, irritation from this cosmetic product is quite common. She queried this directly with the manufacturer and received a response. Danielle asked me my opinion on this response. There are 3 issues the manufacturer raised and I have commented on each one: they relate to silicone in skincare and its effect on the efficacy of actives, why their retinol is supposedly ‘stronger’ than tretinoin, and the concept that a retinol is ‘equivalent’ to tretinoin. 

I go into detailed discussion of all three of these topics, including the exact statements made by the manufacturer in their response to Danielle, in my blog – click on the link in my bio. 

And, btw, she was probably reacting to the chlorhexidine in the product, not the retinol. Or perhaps it was the broccoli extract ;) maybe that should be a new addition to the ‘suspicious 6’?

Check out @carolinehirons for a detailed, unbiased overview of this DE product.

@drunkelephant @rivas_nathan @dermatica.skin 

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Statement made by manufacturer:

‘The retinol in [the product] is 100% bioavailable to skin because we don’t use any ingredients that would slow or prevent absorption (like siliciones or waxes). Silicones…reduce the amount of actives that are available to skin…the fact that [the product] lacks silicones makes it a much faster penetrating formula + you’re getting the full dose is 1% without any loss (re: due to silicones)…’ (note from NS: quote taken verbatim, grammatical errors by quoted author)


The product in question has 61 ingredients. Though none of these are silicone-based, chlorhexidine is one of the ingredients and this is known to be a strong irritant to skin. 


Can the manufacturer please provide the trial data supporting the statement that the retinol in their product is ‘100% bioavailable to skin’?

The statement that silicone slows or prevents absorption of actives like retinol is incorrect. Indeed, silicones have been used for over 60 years to enhance the drug delivery and efficacy of topical and transdermal products. I can provide a review article of the use of silicone in skincare with 76 referenced research articles investigating the successful and efficient use of silicones in topical drug delivery systems. 

Statement made by the manufacturer:

‘We can’t really say why you 0.5% (note from NS: Danielle was using 0.05%, factual error by quoted author) wasn’t as strong, because we don’t know the particulars of the formula.’

The tretinoin used in the prescription Dermatica product is a pharmaceutical grade tretinoin that comes as tretinoin powder and is added in the compounding lab to a vehicle for application to the skin. The vehicle has to be inert while also allowing the medication to impart its effect on the skin. The compounding vehicle is thus designed to allow penetration of the drug it is mixed with. 

The vehicle used to deliver the tretinoin in the compounded prescription Dermatica product has the following ingredients:

Purified water, humectants, O/W emulsifier, lubricants, silicone, rheology enhancer, preservative, vitamin E

Silicone is one of the key ingredients in this particular vehicle for tretinoin and it does not cause any problems with efficacy or tolerability. Please see some of our patient before and afters on Instagram or contact us for more information. 

This leads onto a separate yet very important question: Is the level of irritation you get from a topical retinoid a reflection of its ‘strength’? 

‘Potency’ or ‘efficacy’ are probably more appropriate words to use in this context. We do not fully understand how or why retinoid dermatitis occurs (see below for a more thorough explanation of this) but we do know that irritation is not a requirement for a topical retinoid to be efficacious; in other words, irritation is not a reflection of the ‘strength’ or ‘potency’ of the retinoid. Most patients do get some level of irritation at the beginning of treatment with a topical retinoid but it is not an indicator of efficacy or potency of the product. That being said, it is widely acknowledged that, especially in relation to the treatment of acne, increasing the concentration of the retinoid increase efficacy but may reduce tolerability.

Statement made by manufacturer:

‘1% retinol is equivalent to prescription tretinoin….Also, to be clear, research has long confirmed that 1% retinol is absolutely equivalent to prescription retinoids (i.e. tretinoin)…So retinol works very similarly to prescription retinoids – the results just take longer to see – but nonetheless the fact remains 1% retinol has been established as providing the same end results as prescription retinoids.’

There are hundreds of clinical trials investigating the anti-aging effects of topical retinoic acid (tretinoin); it is considered one of the most effective and well-substantiated compounds for treating the signs and symptoms of photodamage and aging skin. However, very few studies have been performed on OTC retinol products. Of the limited data available, retinaldehyde appears to be the most efficacious (which can also be hypothesised from the metabolism of vitamin A as shown below). 

Retinol has been used in OTC cosmetic products since 1984. In 1995, Kang et al show that application of retinol onto normal human skin induced epidermal thickening via the same mechanism as retinoic acid while also observing that retinol showed only minimal signs of erythema and irritation unlike tretinoin. Since then there have been at least 5 well controlled human studies indicating that 1% retinol should be effective in the treatment of aging and photoaging. However, every study has noted that the vehicle used for retinol delivery is of crucial importance in eliciting its efficacy as retinol is extremely unstable and easily gets degraded to biologically inactive forms on exposure to light and air (Mukherjee et al. Review: retinoids in the treatment of skin aging: an overview of safety and efficacy. Clin Inter Aging 2006:1(4) 327-348.) Thus, retinol derivatives like retinyl acetate and palmitate are widely used in cosmetic products instead of retinol. 

There is some evidence that retinaldehyde 0.05% induces effects similar to those of tretinoin 0.025% (Sorg O, Didierjean L, Saurat JH. Metabolism of topical retinaldehyde. Dermatology 1999;199*suppl 1):13-7.)

Babcock et al (2015) have published a reasonably well-powered split face study in 65 subjects comparing retinol with tretinoin in various concentrations and found that the sustained release retinol complex used in the study was comparable to the tretinoin in producing the desired improvement on photodamaged skin of humans (J Drugs Dermatol. 2015;14(1):24-30.)


The bottom line is that, as yet, there is not sufficient evidence to state categorically that 1% retinol is equivalent to tretinoin. The research is absolutely NOT longstanding or confirmatory. Indeed, the fact that the manufacturers of the cosmetic product state that it takes longer to see a result from the use of retinol in itself is evidence that the two are far from equivalent. 

More worrying perhaps is the fact that the manufacturer of this cosmetic product is saying that the cosmetic ingredient (retinol) is equivalent to a medicine; By definition a cosmetic product cannot be equivalent to a medicine.

EXTRA INFO:


Why do retinoids cause irritation?

Since the early 1980s, up to 92% of subjects using tretinoin in various studies report what has been coined ‘retinoid dermatitis’ – the development of red, itchy, flaky skin at the site of application. In some patients, this is a serious limitation to the use of topical tretinoin and it has also raised the questions as to whether ‘irritation’ is the mechanism underlying the long-term positive repairing effects of treatment. In order to answer this question, a study was performed comparing the efficacy and irritation of two concentrations of tretinoin cream, 0.1% and 0.025%. The treatments were used once daily for 48 weeks and there was no significant difference in the overall improvement in photoaging produced by the two concentrations but 0.1% tretinoin was significantly more irritating (reference: Griffiths CEM, Kang S, Ellis CN et al. Two concentrations of topical tretinoin (retinoic acid) cause similar improvement of photoaging but different degree of irritation. Arch Dermatol 1995: 131; 1037-44).


So why does the irritation occur and what can you do about it?

No one really knows what the mechanism is for retinoid dermatitis. One study suggests that it might be due, at least partially, to an ‘overload’ of the retinoic acid-dependent pathway with non-physiologic amounts of exogenous retinoic acid in the skin. (reference: Didierjean L, Carraux P, Grand D, et al. Topical retinaldehyde increases skin content of retinoic acid and exerts biologic activity in mouse skin. J Invest Dermatol 1996;107:714-9.) This is potentially how using pre-cursor retinoids like retinaldehyde can prevent this ‘overload’ and thus reduce the irritation. However, the debate is still ongoing about whether or not these ‘downstream’ retinoids are as effective as the gold standard retinoic acid (tretinoin). 

I generally start my patients on the lowest possible concentration of tretinoin – 0.012% or 0.025% - and start by using it three times a week only for the first 4 weeks. If irritation occurs, I advise patients to stop using it until their skin is back to normal and then start again. It is important to apply the tretinoin to thoroughly dry skin to minimise the irritation. I also suggest applying a bland emollient before the tretinoin at bedtime in order to further minimise irritation at the beginning of treatment. Studies show that doing this does not reduce the efficacy of the tretinoin, even in acne patients, but it does minimise the irritation. 

Retinoic Acid: The Facts

The word ‘retinoid’ is an umbrella term for any product that has an active form of vitamin A in it; it refers to a class of chemical compounds that either contain vitamin A or are chemically related to it. The retinoid that actually acts on the skin cells to cause a change is retinoic acid. In the cell, retinoic acid regulates and alters gene expression via binding to Retinoic Acid Response Elements (RARE) which are critical DNA sequences in the promoter regions of select genes. Retinoic acid binds to Retinoic acid Receptors (RAR) and Retinoic acid X Receptors (RXR). 


Retinol is actually just vitamin A. It is formed from the breakdown of beta-carotene. Retinol has to undergo oxidisation into the active molecule retinoic acid and this is the rate-limiting step in the generation of active retinoic acid in the cell from any type of retinoid pre-cursor, 

This picture illustrates the steps required for different types of retinoids to convert into the active form of retinoic acid. Simply stated, the less steps required to get to the active form the more effective the topical treatment will be. That’s why tretinoin is the gold standard retinoid for a myriad of both cosmetic and medical dermatological conditions. 

The known benefits of topical retinoids are numerous and include renewing of epidermal cells, acting as UV filters, preventing oxidative stress, controlling cutaneous bacterial flora and improving the signs of skin aging and photo aging. Topical tretinoin was first licensed and used to treat actinic keratoses (sun damage) and acne in 1971. It was found to have potent anti-aging effects when a number of women who had used it for facial acne reported an improvement in fine periorbital wrinkling. The first human study of tretinoin on facial wrinkling did not happen until 1983 and every study since has shown similar results – once daily use of tretinoin cream produces significant improvement in fine facial wrinkling associated with chronic sun exposure and biopsy studies confirm an increase in collagen and other positive changes in the dermis. However, we still do not understand the precise mechanism by which topical retinoids work to improve skin wrinkling with photoaging. Since retinoids are the only topical treatment that are known to have this type of effect, research into understanding how and why and therefore finding innovative ways to improve the way we use retinoids is a top priority. 


Sammi Scotto