Emerging Skin Lightening Ingredients

 

While hyperpigmentation isn’t easy to treat, there seems to be almost a horde of topical options to choose. The most documented and used ones include: hydroquinone, its glycosylated cousin arbutin, mequinol, retinoids, hydroxy acids, azelaic acid, kojic acid, vitamins B3 (amide) and C, licorice, soy, and N-acetyl glucosamine. And because hyperpigmentation is such a common problem, more and more “options” are discovered every few years.

Therefore, as we prepare for New Year’s Eve and look towards the future with personal resolutions and whatnot, it seems germane to discuss some topical emerging therapies that have the potential to become a more standard component of one’s skin care arsenal or armamentarium when it comes to dealing with hyperpigmentary conditions in the future.

So without further ado, here are three ingredients that show varying degrees of promise.

Methimazole

Methimazole

This ingredient has the distinct advantage of already being approved by the FDA for use on humans. Therefore, most of the mechanisms of action, drug interactions, side effects, and toxicity, etc., have already been discovered and enumerated. However, this drug has only been approved to be used as an oral antithyroid medication. Very little of the data has any relevance to skin lightening.

However, in a case study on a 27-year-old male with postinflammatory hyperpigmentation (due to an acid burn), it was shown that 5% methimazole provoked a “moderate to marked improvement of the hyperpigmentation lesions within 6 weeks of once-daily application.” Furthermore, as someone with an impaired epidermis (due to the acid burn), the patient was able to tolerate this novel therapy very well (Dermatology2005).

Now, when taken orally, among the major side effects is agranulocytosis, which is when a person’s white blood count drastically drops to life-threatening levels. This acute (meaning temporary as opposed to chronic) condition is dangerous because it suppresses an individual’s ability to fight off infections. Therefore, it is vital to assess the pharmacokinetics of topical methimazole (Drugs.com).

While the above-cited case study indicated that after 6 weeks of once-daily topical application, no methimazole or any of the thyroid hormones (free thyroxin, free triiodothyronine, and the thyroid-stimulating hormone) were detected in the serum of the patient, a larger test (population) sample is needed to substantiate these initial findings.

This was done at the Department of Dermatology at the Geneva University Hospital, which performed an enhanced version of the case study with 26 patients. 6 volunteers took a 5-mg tablet of methimazole, while the other 20 applied 5% methimazole for 6 weeks (once per day) to the skin. “From 15 min up to 24 h after application, methimazole was undetectable in the serum of the individuals receiving single topical methimazole dosing. Methimazole, however, was detected in serum after 15 min of oral administration and remained detectable in serum up to 24 h after administration.” Furthermore, after 6 weeks, none of the serum levels of the thyroid hormones (free thyroxin, free triiodothyronine, and TSH) exhibited statistically significant changes. Adverse cutaneous side effects were also not apparent. The study concluded that “present data together with the previously shown non-cytotoxic and non-mutagenic characteristics of methimazole indicate that this agent could be considered as a safe skin-depigmenting compound for topical treatment of skin hyperpigmentary disorders in humans” (Skin Pharmacology and Physiology2008).

Conclusion:

Overall, I agree with these two studies that methimazole represents an exciting new tributary to the main course of skin lightening ingredients. Unfortunately, as this is a prescription-only product, I can’t see this ever being introduced into the skin care industry en masse. And of course larger, longer, and more relevant studies need to be done before any physician would ever consider prescribing this for off-label use.     

Dioic Acid

Probably the best advantage of dioic acid is that it inhibits the tyrosinase enzyme via a different mechanism than hydroquinone and its derivatives. Dioic acid appears to modulate tyrosinase activity by binding to three types of peroxisome proliferator-activated receptors (PPARs), which mediate melanogenesis. By binding to PPARgamma, PPARalpha, and PPARdelta, the levels of tyrosinase and its corresponding mRNA were reduced, leading to decreased melanogenesis (the production of melanin) (International Journal of Cosmetic Science, 2005).

Its in vivo efficacy was demonstrated in a study done on 96 female patients, which compared the effectiveness of 1% dioic acid against that of 2% hydroquinone. After 12 weeks of twice-daily application, hydroquinone was shown to be only marginally more effective than dioic acid, though the difference was not statistically significant. Furthermore, irritation was present less evidently with those that applied dioic acid (International Journal of Dermatology2009).

Conclusion:

While this product is innovative, there’s too much alcohol present.

If I were a dermatologist, would I recommend dioic acid over hydroquinone? No. But, I wouldn’t deny that dioic acid shows quite a bit of potential. Unfortunately, there are very few products that contain this ingredient in “efficacious” amounts, so there’s nothing for me to recommend. One reader did mention the Skinceuticals Blemish and Age Defense ($61.99, amazon.com). However, I can’t wholeheartedly recommend this product because of the inclusion of so much alcohol. Usually, I’m okay with alcohol so long as it isn’t present in high amounts. However, seeing as there’s more ethanol than water… Anyways, as with most things, all we can do is wait.

[Related: Is Ethanol in Skin Care Products Safe?]

Undecylenoyl Phenylalanine

The biggest advantage of undecylenoyl phenylalanine (UP) is that there are already products on the market containing this ingredient. But before we get into recommendations, let’s discuss the evidence.

Like with dioic acid, UP (allegedly) represents a novel mechanism by which to inhibit melanogenesis. It has been postulated and suggested that it does this by acting as an antagonist to alpha-melanocyte-stimulating hormone (MSH), which is an important component of the melanogenesis process. In the same double-blind, vehicle-controlled study, 2% UP was shown to have a moderate to marked improvement in the treatment of solar lentigines (Clinical and Experimental Dermatology2010).

In another (open-label) study done by Procter & Gamble, 1% UP with 5% niacinamide was shown to be more effective than both the vehicle and the 5% niacinamide formulation alone (Journal of Cosmetic Dermatology2009). And that makes sense, since niacinamide inhibits melanogenesis via a different mechanism (by inhibiting melanosome transfer) than UP.

Conclusion (and Product Recommendations!):

While it’s likely that no existing product contains anywhere near 1-2% undecylenoyl phenylalanine, it may be worthwhile to introduce this ingredient into you routine if you’ve had unsatisfactory results with established protocols; or are simply curious to see how it performs.

This is an excellent product for dry to combination oily skin types!

For drier skin types, the Philosophy Miracle Worker Dark Spot Corrector ($57.99, amazon.com) is an excellent option. Besides the good amounts of niacinamide and UP, this product contains good to decent amounts of three vitamin C esters (tetrahexyldecyl ascorbate, ascorbyl linoleate, and ascorbyl palmitate), as well as moderate amounts of resveratrol and a vitamin E ester, and dashes of green tea; all of which have evidence supporting the ability to lighten the skin. Everything is embedded in a silky lotion-like texture comprised of glycerin, several fatty alcohols, and two coconut oil fatty acids.

Note that phenylethyl resorcinol is NOT the same compound as resorcinol. It is unreasonable and inaccurate to claim that the former ingredient carries all of the positive and negative characteristics surrounding the latter, considering that only a single study establishes SOME potential for efficacy (Journal of Cosmetic Dermatology, 2011). Originally, I didn’t think that this ingredient was particularly worth mentioning. However, after reading another product review on this site, I wanted to clarify that the two compounds should not be treated equally. The same concept applies to hexylresorcinol.

[Related: Philosophy Miracle Worker Dark Spot Corrector Review]

Ingredients:
Water, Glycerin, Cetyl Alcohol, Behenyl Alcohol, Niacinamide, Caprylic/Capric Triglyceride, Cetearyl Olivate, Hexyldecanol, Sorbitan Olivate, Butylene Glycol, Tetrahexyldecyl Ascorbate, Ascorbyl Linoleate, Undecylenoyl Phenylalanine, Hexylresorcinol, Phenylethyl Resorcinol, Resveratrol, Tocopheryl Ferulate, Ethyl Linoleate, Cyclopentasiloxane, Cychohexasiloxane, Ethylhexylglycerin, Glycine Soja (Soybean) Sterols, Safflower Glyceride, Potassium Cetyl Phosphate, Sodium Hyaluronate, Hydrogenated Palm Glycerides, Camellia Sinensis Leaf Extract, Rumex Occidentalis Extract, Brassica Campestris (Rapeseed) Sterols, Tocopheryl Acetate, Ascorbyl Palmitate, Linoleic Acid, Phospholipids, Bisabolol, Cetylhydroxyproline Palmitamide, Arginine, Heptapeptide-12, Beta-Glucan, Retinyl Palmitate, Lysolecithin, Methyl Dihydroxybenzoate, Disodium EDTA, Stearic Acid, Xanthan Gum, Chlorphenesin, Phenoxyethanol

This is a great product for normal to oily skin types!

For oilier skin types, the Mary Kay TimeWise Even Complexion Essence ($16.99, amazon.com) is also a very good option. Besides good amounts of niacinamide and UP, this product contains two vitamin C derivatives (ascorbyl glucoside and magnesium ascorbyl phosphate), two peptides, a vitamin E ester, as well as moderate amounts of the licorice, green tea, ginseng, and mulberry extracts; all of which have evidence supporting the ability to lighten the skin.  Everything is embedded in a watery serum comprised of propylene glycol, dimethicone, and glycerin. Note that this does contain very faint shimmer particles.

Ingredients:
Water, Propylene Glycol, Dimethicone, Isododecane, Glycerin, Niacinamide, Ascorbyl Glucoside, Triethanolamine, Betaine, Magnesium Ascorbyl Phosphate, 1-Methylhydantoin-2-Imide, Undecylenoyl Phenylalanine, Palmitoyl Oligopeptide, Palmitoyl Tetrapeptide, Tocopheryl Acetate, Dipotassium Glycyrrhizate, Citrus Medica Limonum Fruit Extract, Cucumis Sativus Fruit Extract, Camellia Oleifera Leaf Extract, Panax Ginseng Root Extract, Thymus Extract, Sanguisorba Root Extract, Morus Alba Bark Extract, Oenothera Biennis Seed Extract, Serine, Threonine, Proline, Arginine, Glycine, Alanine, Lysine, Glutamic Acid, Sodium PCA, Sorbitol, Polysorbate 20, Butylene Glycol, Laurenth-7, C13-14 Isoparaffin, PEG-12 Dimethicone, Polyacrylamide, Boron Nitride, Carbomer, Sodium Citrate, Disodium EDTA, Phenoxyethanol, Methylparaben, Ethylparaben, Propylparaben, Butylparaben, Isobutylparaben, Mica, Titanium Dioxide

Bottom Line

In the paradoxically adamant yet ever-changing world of skin care, my approach has always been to support the documented, the chronicled, and the corroborated. However, it would be rather parochial of me to reject emerging remedies. I may never be ruled by the newest vicissitude, but, with caution, I do gradually consider and implement them into my knowledge base and perception.

 

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25 thoughts on “Emerging Skin Lightening Ingredients

  1. simona says:

    Nice ! Thanks for all the information!

    Just wondering if, in those 2 products, the niacinamide% could be greater than 3? I have made for myself a cream with 5% niacinamide and I wonder if there really are products on the market using it at this % :))

  2. Eileen says:

    Thank you for the informative post, John. Even though many of us have found skin care routines that work well, our skin is constantly changing as we age and so are our skincare needs. It’s important to be informed so that we can make good decisions as we seek products that keep our skin in good condition. Thanks again.

  3. RAFAEL says:

    Here in Brazil it is possible to find this product from Mary Kay.
    formulation has a really interesting, I’ll look

    and a happy new year with lots of happiness and reviews so interesting as intelligent, the way you always do :D

  4. JennB says:

    Thanks for the great post! I almost fell off the sofa when I read Methimazole! I have a cat with hyperthyroidism that I used a compounded cream on him twice a say. The Vet was very serious that I use finger cots and wash my hands thoroughly after I dose the cat. Because he really is concerned that it may mess up my thyroid.

  5. John Su says:

    @simona

    You know, I cannot tell you the % of NCA. :( It’s literally impossible without formulary testing. But the strengths of these two products are that they contain multiple lightening ingredients to compound the effect of NCA. But, if you’re happy with you DIY cream, then more power to ya.

    Happy New Year!

  6. John Su says:

    @RAFAEL

    Thank you for your support! I’m not sure if Mary Kay is available in Brazil. :( Perhaps you should consider calling their toll free number to ask? I’m pretty sure a company as large as Mary Kay has international branches.

    Happy New Year!

  7. John Su says:

    @JennB

    Hmm what you’re saying is very interesting. Could you maybe provide a reference for why MMI shouldn’t be used on humans topically? Because the studies I cited seem to support that topical use of MMI on humans is safe.

    I think the vet just gav that warning with a “better safe than sorry” attitude. Because while the education pathway for a vet is very similar to a human doctor’s, the content is vastly different. So perhaps the vet isn’t as knowledgeable? And since cat skin isn’t very similar to human skin, the same rules may not apply to both parties when it comes to MMI. But yeah, I’d be happy to change this article if I see some reference or a warning from a dermatologist or something, because the safety of everyone is what’s important!

    Anyways, thanks for the heads up and have a Happy New Year!

  8. Matheus F. says:

    Hey John, I’m really happy you researched about dioic acid, as I asked you.

    As I told you, I’m using Blemish+Age Defense and a Niacinamide, green tea and panthenol cream, under sunscreen. This calming cream makes a big difference between tolerating or not the routine.
    Before bedtime, Retin-A Micro .1%.

    Well, what can I say? I stop on the mirror to take a look in my gorgeous skin. I never did this before. But it’s a heavy routine.

    Thank you very much and happy 2013.

  9. John Su says:

    @Matheus F.

    I’m glad that you got around to reading this article! And green tea, niacinamide, and panthenol can definitely help people tolerate Retin-A and things like hydroxy acids.

    Like I said last time, keep up the routine!

  10. charu alwani says:

    Hey John! From the looks of it the Mary Kay product seems good. However I am not sure whether I can use this in conjunction with the products I use in the morning and evening. So I will just like what I use at morning and night and maybe you ca help me figure out when to use this?

    Morning: 15% vit c serum+hylauronic (b5 hydrationg css)+sunscreen
    Evening : Tretinoin 0.025%(alternate nights)+melaglow cream + hydra b5.
    Melaglow is an indian cream . Here are its ingredients:
    Soy isoflavones 0.20%, w/w, Licorice Extract 40% CA 0.10% w/w, Tetrahydrocurcumin CG 0.10% w/w, Zinc Oxide 1% w/w Niacinamide 4% w/w, Kojic acid 2% w/w

    As you can see I am not using a moisturizer currently . and considering I have oily dehydrated skin(no breakouts though only slightly acne prone on chin blackheads on nose) ,without a moisturizer my foundation doesnt spread well and does not last well. The hydra b5 i have just started i feel has helped my skin not be so dehydrated+no flakes but, does not really help my makeup as well as with other moisturizers. plus wud luv my skin to look more ‘soft and fresh’(for lack of a better word but being a skin care expert I am sure you know what i mean..hehe :=)) . I was using clinique extended moisture surge for about 1.5 year however recently stopped ; the jar packaging , and urea in it made me not want to put this in my skin, however it did work well under my foundation and has some gr8 antioixdants(but the jar packaging degrades these anyway :(. )
    so now I am on the hunt for a good moisturizer for my skin, but most moisturizers on the market I have been seeing are loaded with alcohols(as you know i try to avoid this as much as i can!), sillicones, and have urea .Since I am trying to avoid these ingredients ( to a certain extent I know cannot fully avoid as these are present in most products even if only a little bit), it has been difficult to find a good moisturizer.
    Now stumbling upon this post the mary kay product seems great, no alcohol,no urea , only 1 sillicone: dimethicone, and from the reviews i read good under foundation, plus the skin lightening ingredients seem wonderful for my melasma prone skin. So my question(FINALLY hehe) is can i combine this with my skincare routine?
    Here r my doubts :
    -in the morning cannot combine this with my vit c serum coz of the niacinamide,
    - in the evening while i am not using a vit c serum, the melaglow cream has niacinamide and the mary kay product has niacinamide. so can this double dose of niacinamide not interact with the vit c derivatives in the mary kay product and the two cancel each other out? cud i apply this on alternate nights with tretinoin, and then skip the melaglow on these days?
    - if i cannot use this what moisturizer wud u suggest ? and if it has some skin lightening botanicals that wud b evn better?hav been looking into mac prep and prime skin visage.whts your opinion?

    PS: Just in case u r wondering why I am bombarding you with my whole skin care routine ,i am getting products ordered from the US by friends who are visiting , ( germany (where i stay) is vry limited in terms of skin care products! ),and have to order by tomorrow morning! trying to figure out which best ones to buy that vl hv maximum benefit!:-)
    Thanks:-))

  11. John Su says:

    @charu alwani

    Sure, I’ll do my best!

    Actually, almost every leave-on product that people use are “moisturizers,” because if any product reduces the amount of water loss of the skin and increases moisturization, it’s a moisturizer. Please see this post for more information: http://www.futurederm.com/2012/11/01/common-misconceptions-of-skin-care-terminology/

    I personally don’t think you need the Mary Kay product because you’ve already got a majority of the “active” ingredients in your current routine. You wouldn’t really be getting much additional benefit from it. You can really just focus on aesthetics when looking for a good product to enhance makeup application. If you like the effect of the Skin Visage, then go ahead and use it. It’s ingredients aren’t bad by any means either.

    Also, it seems like you have something against urea, silicones, and alcohols. Why is that? Which ones specifically?

    And you don’t have to worry about niacinamide interacting with vitamin C derivatives; only Vitamin C itself (L-ascorbic acid). Please see this post for more information: http://www.futurederm.com/2012/10/25/should-niacinamide-and-l-ascorbic-acid-be-used-together/

    Sorry I couldn’t be of more help, but I really don’t think you need the Mary Kay product, which is a good thing! You can just focus on aesthetics now. :)

  12. charu alwani says:

    hey john! Thanks for answering immediately, just read your recent post and realized how busy you are! Really appreciate you taking the time out and responding to everyones post! Thankyou!

    So I read your post on moisturizers, and from what I gather the c serum and hydra b5 qualify as nmoisturizers. However now after a week of using them both together I realize the alcohol content in both the products is drying out my skin too much, at least it feels dry to touch after I apply these two . Now I realize alcohol allows for better penetration of active ingredients, so I am happy to use the vit ce serum but definitely not in conjunction with hydra b5 which is also alcohol based. So hence is there any other good moisturizer to apply to the skin after applying the vitamin ce serum when my skin ‘feels’ very dry? I have oily dehydrated skin so it is difficult to find a good moisturizer! The ingredient list of clinique moisture surge is very nice, but the jar packaging really puts me off it. Also over a long time of using it I felt my skin was drying out slightly more, I dont know maybe because of the butylene glycol?? Also immediately after applying it I always felt my face would look slightly more ‘yellow# or darker (skin felt slightly more sensitive also) if you will , washing me out.I dont know why that is. So any good hydrating additional moisturizer without alcohol but good occlusive agent, humectant and emolient,antioxidant you would suggest?

    In regards to ur question I avoid alcohol , since it dries out my skin a lot, and urea and sillicones I read were toxic, specifically on http://www.orestra.com skin toxins.

    Sorry it may seem like i am asking the same question but i really feel like i need an additional product to compensate for the dryness the alcohol in my serum causes! Thanks again john! I completely understand if u r very busy so take ur time to answer this whenever you can !:-)

  13. John Su says:

    @charu alwani

    Assuming that the alcohol content is actually the drying ethanol, than you can certainly add another product. Hmm, since it’s during the daytime, I’d consider something that contains some well-documented antioxidants. Based on your routine, it would appear that you’re missing some polyphenolic action. Well, specifically ingredients like green tea, resveratrol, pomegranate, and the like.

    You can give either the Replenix Power of Three or CF Cream a try. The Estee Lauder Nutritious Lotion is also a good bet. Note that these three products are a bit more on the emollient side. But since you said your skin is pretty dehydrated from the alcohol content, these may be suitable. Finally, while the Paula’s Choice Skin Balancing Gel does contain a small amount of niacinamide, it is nevertheless an affordable option for oily skin.

    If you would like more anti-inflammatory action to soothe irritation, the Estee Lauder Perfectionist and the First Aid Beauty Aloe + Plus Soothing Gel are two products to consider.

    Keep in mind that there are quite a few good moisturizers out there. I’m just naming a handful. But just because I do so, doesn’t mean these are the “best” or anything.

    Finally, while I can’t see that site you linked, I can assure you that both urea and silicones are NOT toxic on the skin.

    Does that make sense?

  14. John Su says:

    @Charu

    You’re welcome! And I glanced over at that list, and it’s just a bunch of scare-mongering and inaccurately interpreted science data. It’s just that “all-natural” BS again. The only things that warrant conditional caution are: dioxane, dioxin, formaldehyde, nitrosating agents, phthalates, toluene, and certain formaldehyde releasing preservatives.

    The biggest thing that these “sites” fail to recognize is concentration. Almost all of these ingredient encountered in cosmetics (if at all; I mean, who includes formaldehyde these days?) are present at concentrations way below the minimum threshold of toxicity. Obviously, you’ll want to avoid some of the more potent ones. But I mean, so many people are frightened to death of these ingredients, when the sun is far more carcinogenic. That’s right, the sun causes cancer! People seem to forget that and insist on going the “all-natural” route, while wearing little or impotent sunscreens that don’t provide good amounts of protection and UVA and UVB rays. It’s absolutely infuriating!

    I mean, there are carcinogenic compounds all around. Ever hear of processed and fast food? Yep, these all-natural beauty people will eat those without fail… God, sorry I’m going on a little rant here, but the hypocrisy is appalling. I understand that you should do whatever you can in whatever way you want to, in terms of reducing the amount of carcinogenic compounds that you come into contact, but still it’s just such a blatant display of ignorance.

    But ANYWAYS, keep me updated on how these products work out for you, if you decide to try one!

  15. Charu Alwani says:

    Hey John! So the only thing that was available to me here was the Estee Lauder nutritious lotion. However trying a sample of that it seems it made me break out, i think it was the jojoba oil in it. Do you have any other suggestions? I have recently come across the sebamed oil free face care gel(havent tried it yet) . What do you think of that? Here are he ingredients :Aqua, Aloe barbadensis leaf gel, Propylene Glycol, Glycerin, Sorbitol, Panthenol, Sodium Hyaluronate, Allantoin, Sodium Carbomer, Sodium Citrate, Phenoxyethanol, Sorbic Acid

  16. John Su says:

    @Charu Alwani

    Sorry to hear that. Yeah, you can use the other product, but it doesn’t contain any particularly good or notable ingredient. But it may be an acceptable moisturizer, since you did say that your skin needed more moisture.

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