For years, we have received this question here at FutureDerm.com, and it certainly is a worthy one: of the leading skin care ingredients on the market (AHAs, BHAs, and L-ascorbic acid), which can be used with retinoids?

As renowned dermatologist Dr. Leslie Baumann, M.D., revealed to us in an exclusive interview earlier this year, “You have to also be careful not to use a product that has ingredients that can render the active ingredient useless. Vitamin C (L – Ascorbic Acid), Glycolic (AHA), and salicylic acid and kojic acid can break down retinol and retinoids.” Retinoids and acids simply function better when applied separately. This is because of a two-part enzymatic oxidation process in which retinol is converted within your skin to become active: Ffirst to retinaldehyde, then to all-trans retinoic acid. Retinol oxidation is optimized at a neutral pH (Nature). This is because the enzymes responsible for this oxidation, called retinol and retinal dehydrogenases (DHs), are most active at this pH. So don’t mix retinoids and acids.

[Read more: 11 Things That You Never Knew about Retinol and Retinoids – Until Now

So if you mix retinol with acidic products, there will be suboptimal conversion of retinol to its active form within the skin. Will you still notice some effects? Sure. But for best results, use acidic products during the day, and retinol at night. See below for more.

Aren’t There Multiple Pathways of Conversion?

Retinoids – not retinol – can be activated via a number of pathways. It’s easy to see how this can get confusing. However, as I learned in medical school, no matter which pathway all-trans retinoic acid may undertake, retinol must be converted to retinaldehyde and then retinoic acid within keratinocytes (skin cells) in order to be active (Journal of Biological Chemistry).

The enzymes responsible for the oxidation process – dehydrogenases (DHs) – underlie every pathway of retinol activation within the skin. Don’t be fooled by irrelevant citations: two types of dehydrogenases must convert retinol to retinylaldehyde and then to all-trans retinoic acid within the skin to be activated. This is optimized at a neutral pH (Nature). So for maximal effects for your skin (maximal effects occurring with optimal conversion of retinol to its active form), apply retinol and acidic products at different times of the day.

Retinoids and Vitamin C are NOT Network Antioxidants

Skin care science can be complicated, as can antioxidants. Although there are hundreds of naturally-occurring antioxidants, it is most beneficial to use antioxidants that fight off free radicals in the same pathways together. Why? Just as it’s more effective for policemen to travel in packs of two (or more), antioxidants in the same pathway can enhance the power of each other. Except instead of backup in firearms, network antioxidants work synergistically to donate electrons to depleted others. Retinoids and L-ascorbic acid are both antioxidants, but they do not exist in the same pathways. So when retinol loses its electrons in its pathways, L-ascorbic acid cannot regenerate it, and vice versa. In truth, L-ascorbic acid has been found to regenerate only vitamin E, glutathione, coenzyme Q10, and alpha lipoic acid (Packer et. al., Cosmetic Dermatology).

So these ingredients do not fight off free radicals together as beautifully as vitamin C and E do. They work together, but each ingredient will function suboptimally.

If Nothing Else, Skin Will Be Irritated!

For the sake of argument, let’s say that you don’t care about optimal results from your skin care. Good enough is good enough.

Even so, the pH of your skin care products matter. “Changes in the pH are reported to play a role in the pathogenesis of skin diseases like irritant contact dermatitis, atopic dermatitis, ichthyosis, acne vulgaris and Candida albicans infections” (Skin Pharmacology and Physiology).

What’s more, skin care products do have significant effects on each other. Acidic solutions are associated with increased skin exfoliation (and subsequent sensitivity), so it’s not a great idea to use potent products after sloughing your skin. (If you don’t believe me, make the mistake of applying a concentrated 1.0% retinol treatment after a 10% glycolic acid peel. You will feel the burn!) On the other hand, basic products increase skin swelling and rigidity, because they disrupt the skin’s acid mantle (Dermatologic Therapy).

[Read more: How to Use a Retinoid and AHAs/BHAs Together?

Unless you’re the type of person who diligently waits 30+ minutes between applying each product, chances are that the pH of the skin is still temporarily lowered by the application of the acidic product. We don’t mean to suggest products permanently change the pH of your skin, but after the initial application, you are slightly altering the pH of the skin, albeit temporarily. This alteration is what causes a physical effect or change. For instance, let’s talk about salicyclic acid. According to a 2009 study in the International Journal of Cosmetic Science, 1% salicyclic acid introduced to skin at pH 6.50 produced absolutely no stinging or redness sensation. On the other hand, 1% salicyclic acid introduced at the acidic pH of 3.12 produced redness and stinging.

Keep Retinoids for Night!

Retinol works because it is converted to all-trans retinoic acid in the skin, which can in turn make the skin photosensitive (British Journal of Dermatology). It has been suggested that retinol is anywhere from 5% to 10% as potent as all-trans retinoic acid (Clinics in Dermatology, Journal of Investigative Dermatology). Prescription all-trans retinoic acid at 0.025-0.040% issues warnings all over the bottle to wear sunscreen and avoid daytime use. So why would you apply 0.25-1.0% retinol, not wear sunscreen, and use it in the daytime? It makes no sense. Even if you do apply sunscreen, there is absolutely no additional benefit to using retinol at daytime compared to a nighttime application of retinol; there are only potential drawbacks. With the appropriate retinol strength, vehicle, and complementary skin care routine, daily nighttime applications of a retinol product will be potent enough for any skin type!

Bottom Line

[Read more: Which is Better: Retinoids or Peptides?

If you’re the type of person for whom “good enough” is fine in skin care, then go ahead, keep applying retinoids and acids together. However, for the maximum result from your acidic and retinol products, apply them separately. The class of enzymes necessary for retinol activation – dehydrogenases – function best at a more neutral pH. In addition, acidic products increase skin’s exfoliation (and hence sensitivity). So it’s best for both form and function to apply these products separately. Trust me – I’d love to be able to sell our FutureDerm Time-Release Retinol 0.5 and FutureDerm Vitamin CE Caffeic Silk Serum 16+2 for use together. But I would never want to tell our readers something that could be less than beneficial for their skin, and research shows not only to use these separately for best results, but also that retinoids are best for nighttime use.

*Editor’s Note: The concept discussed does NOT occur between prescription retinoids and acidic products; only retinol and retinal(dehyde) are affected.

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