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Skincare Ingredients: PHAs (Polyhydroxy Acids; Gluconolactone and Lactobionic Acid)

I first read about PHAs a few years back when I was looking for gentler chemical exfoliants for my rosacean skin. As with many people who have atopic dermatitis, acne, or rosacea, traditional glycolic acid (and even the gentler forms of AHA such as lactic acid or mandelic acid) can be rough. It stings, burns, and can cause aggressive flare-ups of redness that domino into other reactions. With rosacean skin specifically, I referred to this as “status cosmeticus” or cosmetic intolerance syndrome. Unfortunately, those with delicate skin still find themselves needing a form of exfoliation. This is where PHAs can be helpful.

There are lots of claims about PHA floating around the Internet, so to break all of the noise down into a short list, the key claims of PHAs are:

  • Less irritating
  • Humectant (water-binding properties)
  • Barrier-strengthening
  • Photoaging benefits comparable to AHAs
  • Not sun sensitizing

Note: Several studies that I found around PHAs were sponsored by Neostrata, a skincare company that uses PHAs as a flagship ingredient. This does not mean that these studies are not valuable, as many studies done by private companies are very useful, but it is worth disclosing.

There are two main types of polyhydroxy acids (PHAs): Gluconolactone and Lactobionic Acid.

Gluconolactone is a derivative of gluconic acid, an organic compound found in mammals that breaks down carbohydrates. It is frequently produced from corn and is most often  used as an exfoliant, though it sometimes moonlights in your ingredient lists as a preservative. It’s sister, lactobionic acid, is a sugar acid and is formed from gluconic acid and galactose, a monosaccharide.

There are several places online that consider PHAs to be just as effective as AHAs but without all of the irritation of AHAs. This is largely due to it’s greater molecular weight.

Molecular weight is a factor that comes up frequently when considering the efficacy and irritation potential of a product. I’ve even mentioned it before when discussing various types of “gentler” AHAs such as mandelic acid and lactic acid.

To be able to determine whether an ingredient or compound can penetrate the skin, the “500 Dalton rule” is referenced most frequently, which states that compounds of molecular weights equal to or below 500 Daltons can pass transcutaneously. The following is a chart of the various weights of the three most popular AHAs against the two most common forms of PHA with water as a point of reference:

Molecular Weight of AHAs vs PHAs
Water 18
Glycolic Acid (AHA) 76
Lactic Acid (AHA) 90
Mandelic Acid (AHA) 152
Gluconolactone (PHA) 178
Lactobionic Acid (PHA) 358

The 500 Dalton rule is why some ingredients – such as the collagen in your anti-aging cream – are more of a marketing ploy than actually beneficial to the “anti-aging” of your skin.

This irritation due to the lower or higher molecular weights can be felt almost immediately by some people, typically in the form of redness or stinging. In such cases, higher molecular weighted ingredients (such as PHAs) are preferable. In one small, twelve-week, controlled-use study, Caucasian women with mild to moderate facial photodamage were enrolled in a study that compared PHAs (n=30) to AHAs (n=27). At the end of the study, “irritation grading and subject self-assessment showed that the PHA regimen was better tolerated than the AHA regimen. Stinging and burning were significantly worse for subjects in the AHA treatment group at both week 6 and week 12, and degree of sensitivity was rated worse for the AHA regimen as well.” (Source)


PHAs are also highly humectant, particularly lactobionic acid, which may be calming to irritated skin and weakened skin barriers. One study that outlined the various types of hydroxy acids states the following about BAs (bionic acids such as lactobionic acid):

BAs are hygroscopic materials that readily attract and retain water, forming a gel matrix when their aqueous solution is evaporated at room temperature. The transparent gel contains certain amounts of water, forming a clear gel matrix. Formation of a gel matrix may add protective and soothing effects for inflamed skin. Indeed, formulations containing BA are well tolerated and help calm skin when applied after cosmetic procedures that weaken the skin’s barrier, including superficial HA peels and microdermabrasion. (Source)

Another study found that this water-loving property may be particularly valuable for those with rosacea who are using azelaic acid (AzA). In a 12-week, single-site, investigator-blinded, randomized, Neostrata-sponsored study of 66 patients with mild-to-moderate type 2 rosacea:

Improvements were seen in skin sensitivity, dryness, texture, smoothness, and overall skin condition with statistical significance (p<0.05) in the patients using the dermatologist-recommended regimen (Group 2) compared to those using their own self-selected regimen (Group 1). … 

Draelos also noted an appreciable clinical improvement in background erythema in patients using the dermatologist-selected regimen and postulates that this improvement in background erythema may be a result of improved SC function from the gluconolactone in the formula. Gluconolactone is a PHA that exhibits humectant properties, which can improve SC barrier function temporarily by inducing a swelling of corneocytes as discussed previously(Source)

As with all things and rosacea, your mileage may vary. Rosacean skin is extremely sensitive and many may find PHAs to still be too irritating for their skin. Patch testing is advised.

In addition to usage with AzA, PHAs can be formulated and used in conjunction with oxidative drugs such as benzoyl peroxide (BP) “to help reduce irritation potential and erythema [redness] caused by the oxidative drug.” (Source)

PHAs have also proven useful at preventing skin irritation and reducing trans-epidermal water loss (TEWL). One study compared four different types of hydroxy acids (glycolic, lactic, tartaric, and gluconolactone) with skin barrier function and irritation. After four weeks, a 5% sodium lauryl sulphate (SLS) patch test was performed. The gluconolactone-treated sites showed “significantly lower TEWL” at both 24 and 48 hours after the patch test was performed. (Source)

The percentage of acid content in PHA products seems to matter little when comparing the hydration levels in the skin. A small study (n=10) compared the effects of a 10% lactobionic acid (LA) peel to 30% LA peel in a split-face test. They concluded no noticeable differences in the participants hydration levels. (Source)

pha_antiagingPHAs are also touted as having “anti-aging” benefits, specifically improving the appearance of the skin. One Neostrata-sponsored study comparing PHAs to AHAs that I referenced above concluded a “relative equivalence of AHAs and PHAs in treating photoaged skin … both regimens provided significant antiaging benefits to skin as measured by clinical evaluations…”

PHAs can also prove valuable in boosting the dermis-thickening benefits of tretinoin, thus reducing fine lines and wrinkles. According to one journal:

In summary, PHA-containing products were used in combination with retinoic acid in treating adult facial acne and were found to be well tolerated. PHAs plus retinyl acetate (pro-vitamin A) in a cream base exhibited significant antiaging skin benefits such as skin smoothing and plumping. … Finally, PHA-containing products were shown to be compatible with African American, Caucasian, and Hispanic/Asian skin and provided significant improvements in photoaging in these populations. (Source)

This is consistent with findings in vitro and in vivo showing the increased production of collagen, hyaluronic acid, and fibroblasts in the dermis due to extended periods of application of glycolic acid.

PHAs may also improve the effects of hydroquinone and assist in reversing hyperpigmentation and photoaging. One example:


Adult man with hyperpigmentation and photoaging at (left) baseline and (right) after twice-daily use of an α-hydroxyacid (AHA)/polyhydroxy acid (PHA)/bionic acid (BA) skin care regimen for 12 weeks. Use of the skin care products resulted in significantly less hyperpigmentation and improved radiance. The product regimen included: 20% AHA/BA cleanser, 10% PHA/BA SPF 15 cream for daytime use, and 15% AHA lotion for nighttime use. (Source)

It is also worth noting that PHAs, particularly gluconolactone, do not increase sun sensitization, making them a good choice for those who are unable to use sunscreen but are still looking for some form of chemical exfoliation.

… an in vitro [test performed outside of the body] cutaneous model of photoaging demonstrated that gluconolactone protects against ultraviolet (UV) radiation. These findings were attributed to the ability of gluconolactone to chelate oxidation-promoting metals and trap free radicals. In addition, pretreatment of skin with gluconolactone does not lead to an increase in sunburn cells after UVB irradiation, as has been shown to occur with glycolic acid; this is thought to be due to its antioxidant effects. (Source)

Just as with AHA, PHA must be formulated at the proper pH in order to be effective. Similar to glycolic acid, the effective pH of PHA is 3.8. The lower the pH value (the more acidic), the more free acid is available to exfoliate the skin, meaning that formulation is important.

When purchasing a PHA, look for a leave-on product as opposed to a wash-off product, which will give it more time to activate on the skin. Products that are already formulated with combination therapies may also be valuable to reduce the number of steps in your routine as well as ensure there are no ingredients that can interfere with the penetration or efficacy of the active ingredients (such as PHA).

If you use tretinoin (Retin-A), adapalene (Differin), or tazarotene (Tazorac), you may also want to space out your product usage, using PHAs during the day and your retinoid at night. As with anything though, do what is best for your unique skin type.

Do you use a PHA product? If so, what are your favorites? Let me know in the comments below!

Skincare Ingredients: Tretinoin, Adapalene, and Tazarotene – part one

Note: This post is meant to discuss topical retinoids as ingredients.  I will be writing an additional post on how to best use Differin .1% (OTC) at a later date, as I am two weeks deep into using it now. In addition, this post only covers the effects of topical retinoids in acne. Please stay tuned for more posts about retinoids and wrinkles and scarring!

Topical retinoids are one of the most common treatments for acne – both during treatment and for maintenance, after the acne is considered to be resolved. During treatment, they are most often prescribed in combination with other products, such as benzoyl peroxide (BPO), where they show the most efficacy.

While the pathogenesis of acne is constantly evolving, it is widely accepted that the key factors that play a role in the development of acne are follicular hyperkeratinization, microbial colonization with p. acnes, sebum production, and inflammation. Additional factors have been suggested by the American Academy of Dermatology (AAD), such as “neuroendocrine regulatory mechanisms, diet, and genetic and nongenetic factors all may contribute to the multifactorial process of acne pathogenesis.” To understand how retinoids can improve acne, you need to first understand some of the mechanisms of acne, particularly follicular hyperkeratinization.

According to William J Cunliffe (Acne: Diagnosis and Management, 2001):

Acne lesions do not usually occur in a follicle bearing a terminal hair [hairs found on the scalp, for example]. The hair acts as a wick allowing sebum to drain from the pilosebaceous canal. In contrast, in the pilosebaceous follicles the hairs are small and vallus in nature and often do not reach the surface. They are ineffective wicks and do not therefore prevent the retention of follicular contents. Histological examination of the pilosebaceous canal reveals that much of the duct comprises an epidermis-like structure undergoing cornification [the final stage of keratinization for the skin cells], the cornified material occupying the more central part of the canal. … The horny cell layers [the stratum corneum is frequently referred to as the horny layer] … soon desquamate [shed] into the central part of the canal to form a heterogeneous [diverse] mass together with sebum and bacteria. … Thus the horny cells distend the pilosebaceous canal, first producing a microcomedone and then a clinical lesion. It is not known why some lesions remain closed comedones (whiteheads) and why other lesions progress to open comedones (blackheads). As the comedones enlarge, the sebaceous gland may atrophy but sebum continues to be produced until the glands are totally replaced. 

In short, the hair of the face is too short and too fine to drain sebum (oil) effectively, which allows the follicles to retain its contents, including skin cells that line the hair follicle that would otherwise be shed normally. This forms a clumpy mass of sebum, bacteria, and shed skin cells, which turns into a microcomedone and from there, a closed or open comedone. Why this occurs is not very well understood, but it is thought to be due to hormones, abnormal lipid compositions, or microbial factors.

In addition to this, it has been found that the follicular cells in patients with acne is more irregular. This favors retention of shed cells. As the lesions mature into a microcomedone, the walls of the follicle become patchy and thin.


However, this has become the basis for retinoid usage, and has placed retinoids at the core of topical therapy for acne due to their comedolytic behavior, which allows them to resolve the precursor to lesions (microcomedones), as well as their mild anti-inflammatory properties.

An Introduction to Retinoids

Retinoids have been used since the 1960s, when they were discovered to have tremendous effects on disorders of keratinization. They work by binding to specific receptors on the cells, and each retinoid binds to a different set of retinoic acid receptors. In tretinoin, they bind to alpha, beta, and gamma receptors, while tazarotene and adapalene selectively bind to beta and gamma receptors. This is what makes each retinoid’s activity on the skin (as well as tolerability) a bit different.

Again, to quote William J Cunliffe:

The activation and inhibition of certain steps of gene transcription results in changes of different pathways. These pathways include proliferation, differentiation, inflammation, and sebum production. … Some retinoids such as tretinoin increases the mitotic activity of the ductal keratinocytes …

In short, these ingredients are cell-communicators that can result in changes to the skin, such as increased cell turnover, reduced sebum production, and more normalized cell shapes.

All retinoids are vitamin A derivatives. There are three major types of topical retinoids available today, which include:

  • Tretinoin (Brand name Retin-A)
    • The first topical retinoid and the gold standard.
    • Available in gels or creams, and is now in less irritating microsphere formulations such as Retin-A Micro.
    • Available in gel and cream .025% and .1% strengths
    • Also available in combinations with topical clindamycin (.025% tretinoin/1.2% clindamycin phosphate)
  • Adapalene (Brand name Differin)
    • One of the best studied retinoids for combination treatments with BPO. Much better tolerated than tretinoin in most cases.
    • Available in .1% gel over-the-counter in the US
    • Available in .1% or .3% creams and .1% lotion
    • Available as combination a with BPO (Epiduo, .1% adapalene, 2.5% BPO)
  • Tazarotene (Brand name Tazorac)
    • Potentially more efficacious than tretinoin at treating papules and open comedones.
    • Stronger than adapalene (Differin)
    • Can be used to treat psoriasis
    • Available in gels, creams, or foams in .05% and .1% strengths

They all carry many of the same side effects of peeling, dryness, erythema (redness), and irritation, and the higher the concentration of the retinoid, the higher the risks of side effects become. In 2016 Guidelines for the Management of Acne, the AAD also notes about combinations with BPO:

Some formulations of tretinoin (primarily generic products) are not photostable and should be applied in the evening. Tretinoin also may be oxidized and inactivated by the coadministration of BP. It is recommended that the 2 agents be applied at different times. Tretinoin microsphere formulation, adapalene, and tazarotene do not have similar restrictions.

Topical retinoids have also been associated with photosensitivity and all people who are using them should use at least SPF 30-50 every day to avoid burns and sun damage, which reverse many of the benefits of retinoids. You should also avoid the eye area, including lids and beneath the eye, as well as the lips and the areas next to the nasal passages. Dr Dray recommends using Vaseline on these areas and calls it “greasing the orifices,” which I quite like.


A Note About Antibiotics and Topical Antibiotic Usage

Since many of the retinoid studies I am about to discuss are those which have been conducted in combination therapies (over 16,000 studies have been published around combination therapies), I think it is both unavoidable to discuss antibiotic resistance and its effects on how doctors are now prescribing topical acne treatments.

As you probably already know, antibiotic resistance is a growing public health concern in virtually all parts of the world. While antibiotics have been considered a fantastic treatment for acne for a long time, primarily due to their anti-inflammatory effects, nonantibiotic agents, particularly BPO, has been advised for combination treatments due to the highly effective nature of BPO to kill p. acnes without creating bacterial resistance.

Antibiotic resistance can change the outcomes of acne treatments, and in a 1998 review, there was a “clear association between poor therapeutic response and antibiotic-resistance propionibacteria [p. acnes].” (Source) The Global Alliance to Improve Outcomes in Acne (which I will be abbreviating to GAIOA from now on) also notes that resident flora has a “memory” “and retains resistance variants long after antibiotic therapy is discontinued.” Worse, this can lead to other complications down the line:

Patients with acne are often treated with multiple antibiotics and their flora is exposed to a significant selective pressure for resistance development. Margolis et al found that patients with acne treated with antibiotics had 2.15 times greater risk of developing an upper respiratory tract infection compared with patients with acne who were not treated with antibiotics. In addition, there have been an increasing number of reports of infections caused by P. acnes, including arthritis, endocarditis, endophthalmitis, and adenitis. … several researched have termed P. acnes infections ‘an emerging clinical entitity’ and ‘an underestimated pathogen.’ 

To put this into perspective, one 12-week study involving 208 patients with acne treated with topical erythromycin showed erythromycin-resistant staph on the face increase from 87% to 98% while the density of the organism increased significantly.

Because of this, it is suggested that most clinicians only prescribe short-round antibiotic usage – 3 to 4 months – and only if absolutely necessary. For the patients who do require antibiotics, especially longer term antibiotic usage, it is very important that your doctor monitor your progress in order to prevent resistances.

Evidence for Combination Therapies

Combination therapies involving retinoids plus an antimicrobial agent have been used since the 1970s, with many early studies showing that retinoids, when used in addition to antimicrobials such as topical BPO, were much more effective than those who were using the antimicrobials alone. While early studies were mostly conducted with topical tretinoin plus oral tetracycline, 67% of patients vs 48% of those treated with tretinoin alone and 41% of those treated with tetracycline alone had “good to excellent” outcomes.

Combination therapies are most broadly recommended for people with mild to moderate acne, as per the AAD:


Most modern combination treatments combine clindamycin and BPO along with a topical retinoid. This combination not only increases the likelihood of a positive outcome, but also decreases the development of resistant strains of bacteria due to topical antibiotics.

Treatment with Combination Therapies

For all of the following therapies, I have included the prescribing information as provided by the American Academy of Dermatology (2016). You should always follow your doctor’s instructions, but I also know some of you may be acquiring these prescription drugs without a doctor for any number of factors, and I feel like you have a right to this information. Please use it responsibly.

Adapalene (Differin and Epiduo)

In 2007, a study of Epiduo (0.1% adapalene and 2.5% BPO) was conducted. According to the GAIOA, “It is thought that adapalene and BPO have synergistic actions, because BPO is the most potent bactericidal agent against p. acnes and adapalene, like other retinoids, is comedolytic and anticomedogenic.” A double-blind study of adapalene/BPO in 517 patients with moderate to moderately severe acne also showed significantly lower lesion counts than patients treated with the vehicle alone (the formula the drug is carried in) or placebo.

The once-daily fixed-dose combination formulation of adapalene/BPO has also been evaluated during 12 months in 452 patients with acne. The fixed-dose combination had good safety with only mild to moderate adverse events that typically occurred in the first 1 to 2 months after initiation of therapy and resolved spontaneously. 

The regimen of adapalene plus BPO and clindamycin products has also been studied, with reduction of lesions apparent as early as week two.


Tazarotene (Tazorac)

While Tazorac (or “Taz”) has not been formulated in a combination product like Adapalene (Epiduo), it has been studied in combination with BPO and 3.0% erythromycin/5% BPO. In a study of 440, investigator-masked, randomized, parallel group study, tazarotene plus erythromycin/BPO was “significantly more effective” than other regimens including tazarotene, such as tazarotene and clindamycin.


Tretinoin (Retin-A, Retin-A Micro, Veltin, Ziana)

Tretinoin is one of the most widely studied of the retinoids, and has significant evidence to back it up in use with combination studies.

Bowman reported the results of a controlled trial comparing three treatments: (1) clindamycin/BPO gel; (2) clindamycin/BPO gel plus tretinoin 0.025% gel; and (3) clindamycin/BPO gel plus tretinoin gel 0.025% plus clindamycin. In this study, the triple combination was most effective in reducing inflammatory lesions (69%) followed by clindamycin/BPO (66%), then tretinoin plus clindamycin (52%); non-inflammatory lesions also were reduced to the greatest extent by the triple combination (61%), then clindamycin (50%). All 3 treatments were well-tolerated, although there were more adverse events in the triple combination group compared with the other groups. (Source, page S15)


Maintenance with Topical Retinoids

At this time, Adapalene is the most well-studied topical retinoid for maintance therapy once the acne has been considered “resolved.” This may be due to its reputation as one of the gentlest of the retinoids. In general though, retinoids are the preferred maintenance therapy due to their ability to prevent development of new acne lesions and resolve existing lesions quickly.

In a study on the efficacy of topical retinoids in the role of maintenance of acne, the following changes were observed:


In a 16-week, randomized, vehicle-controlled maintenance study, patients who enrolled all originally were diagnosed with severe acne and only 28% of patients had moderate acne and 72% had mild or minimal acne or were clear at the time of the maintenance study. By the end of the study, more than 90% of patients were able to maintain their clearing while on adapalene maintenance therapy.

While the following graphs are a bit tough to read, they all should give you a general idea of the efficacy of retinoid maintenance therapies:


The GAIOA concludes that maintenance therapy is an important tool for minimizing the likelihood of relapse, given the chronic nature of acne, with topical retinoids considered the best tool for this. They go on to state:

The majority of studies reported to date have lasted 3 to 4 months and show a trend toward continuing improvement with topical retinoid maintenance therapy and relapse when patients stop treatment. Clinical experience indicates that a longer duration of maintenance therapy is likely to be beneficial for many patients. Ongoing research will help to define the optimal duration of therapy and, perhaps, refine patient selection. Some patients with significant inflammation may need to be treated with a combination of retinoid and antimicrobial agent. This should be further studied.

The fact that microcomedones are subclinical and not apparent to the naked eye underscores the need to apply topical therapies to the entire affected area.
This, in turn, suggests that any agent used for maintenance therapy must be well tolerated. The current studies are well done and interesting; however, future studies should include comparison of several maintenance regimens in different patient populations.

Some Guidelines

Here are some things to conclude from this post:

  • Topical retinoids are very effective for treating acne, especially when used in combination with antimicrobials.
  • Prescription antimicrobials and retinoids need to be used on the entire effected area for efficacy and should not be used as spot treatments.
  • Adapalene is the most gentle of the retinoids.
  • Retinoid use should be maintained after treatment for acne has concluded.
  • Sunscreen should always be used with retinoids.
  • BPO should only be used with microsphere tretinoin, tazarotene, and adapalene.
  • Many generic forms of tretinoin are photo-unstable (break down in UV light) and should be used at night.


Skincare Ingredients: Azelaic Acid

Azelaic acid (AzA) is a very unique ingredient. It is a natural component of the skin as it is a byproduct of malassezia furfur yeast, which lives on everyone’s skin. Not to be confused with hydroxy acids, it is a dicarboxylic acid that can be derived from grains such as barley, wheat, and rye, but is usually lab-engineered due to its stability.

First approved by the FDA in 2002, it comes in multiple prescription topicals, from 20% creams (Azelex) to 15% gels and foams (Finacea), as well as over-the-counter products that I will talk a bit about at the bottom of this post.

AzA is an anti-inflammatory and anti-bacterial, and is frequently used in acne and rosacea treatment, especially with sensitive skin types that are more prone to irritation from ingredients like benzoyl peroxide (BP) and tretinoin (Retin-A). In fact, in one twelve-week study, when 20% AzA was combined with glycolic acid, it showed as being just as efficacious in treating mild-to-moderate acne while offering “superior tolerability and patient approval.”

We conducted a 12-week, multicenter, randomized, double-masked, parallel-group study of the efficacy, safety, and tolerability of azelaic acid 20% cream and glycolic acid lotion compared with tretinoin 0.025% cream and a vehicle lotion to treat mild-to-moderate facial acne vulgaris. Patients treated with azelaic/glycolic acid experienced a significantly greater reduction in the number of papules, as well as a greater reduction in the number of inflammatory lesions, than those treated with tretinoin. Overall global improvement was approximately 25% in both groups. In the physician evaluations, treatment with azelaic/glycolic acid was found to cause significantly less dryness, scaling, and erythema than tretinoin. Patients also reported significantly less dryness, redness, and peeling with azelaic/glycolic acid. Significantly more patients in the azelaic/glycolic acid group than the tretinoin group reported that they felt attractive. (Abstract, source)

It has also shown to be as effective as 5% BP as well as 1% clindamycin in a randomized controlled study with 351 patients (BP gel) and 229 patients (clindamycin), with less irritation than BP (though more than with clindamycin).

Azelaic acid 15% gel proved to be as effective as BPO and clindamycin with median % reduction of the inflamed lesion (papules and pustules) of 70%, and 71% respectively. The azelaic acid gel was well-tolerated, the side effects (local burning and irritation) were distinctly less than with BPO but more pronounced than with clindamycin. Despite these side effects, the treatment was well-accepted by the majority of patients. (Abstract, source)

Due to the bacteriostatic (ability to suppress bacteria from reproduction) is thought to be why it is also anti-inflammatory.

In rosaceans, it has been shown to be potentially as effective as metronidazole (Metro-Gel and Metro-Cream) in treating subtype 2 (Papulopustular Rosacea) in addition to being more tolerable. It also sits at a higher pH range (4.8-5 pH), closer to our skin’s natural pH of 5.5¹, which may be an additional contributing factor to it’s tolerance, though nothing is for certain.

In 2015, it was also been approved for use in a foam vehicle in treatment of mild to moderate rosacea, where it has been shown to be even better tolerated than the cream and gel versions.

It is also a proven suppressant in hyper-proliferation of keratin, which is a factor in conditions such as acne. A small study (45 patients) shows that it may help conditions like keratosis pilaris as well due to it’s ability to reduce inflammation by inhibiting “the reactive oxygen species of neutrophils” (a type of white blood cell), though not enough to be considered significantly better than simply moisturizing.

Results: Of the 45 patients that enrolled in the study, only 24 patients were present at 3 month follow-up. 92% of azelex-treated skin and 83% of [Cetaphil Moisturizing Cream]-treated skin showed improvement in hyperkeratosis and/or erythema after 3 months of therapy. … This small study demonstrates that both azalex and cetaphil is effective in treatment of keratosis pilaris, and that one is not significantly better than the other in reducing the degree of hyperkeratosis or erythema. (Source)

It may also have some benefits for sufferers of perioral dermatitis (or “steroid rosacea,” as it used to be called). A small study of 10 children aged 3-12 suffering from PD were evaluated and treated with 20% azelaic acid cream.

Treatment with 20% azelaic acid cream led to complete resolution of skin lesions after 4 to 8 (mean 5.4) weeks in all patients. Transient exacerbation of skin condition with a peak between the 2nd and 6th day of treatment could be observed in three patients. Side effects of 20% azelaic acid cream were registered in six patients and were predominantly present in the first 2 weeks of treatment. Side effects were minimal and became rarer with ongoing treatment. No recurrences were seen within a follow-up period of 2 to 8 (mean 4.4) months. Treatment with 20% azelaic acid cream could provide an effective and safe alternative therapeutic option in children with nongranulomatous periorificial dermatitis. (Abstract, Source)

It is also a tyrosinase inhibitor, with a special affinity for abnormal melanocytes, making it ideal in treatment of melasma or post-inflammatory hyperpigmentation (PIH). In fact, it is much safer and typically more preferred to hydroquinone, which is a skin lightener that tends to target all skin cells and has created concerns due to potentially causing tumors in mice.² In an open study comparing 20% AzA twice daily to 4% hydroquinone, it showed to be just as effective if not more effective than the hydroquinone in reducing mild melasma.

In conclusion, this study suggests that 20% azelaic acid cream applied twice daily may be more effective than hydroquinone 4% in reducing mild melasma. However, because this was an open trial, it is suggested that further studies involving large groups of

patients be conducted to achieve a more conclusive result. (Conclusion, Source)

In another study involving AzA (15%), waiting until after moisturizing to apply AzA resulted in greater penetration of the AzA. This did not occur with all moisturizers however, and was only seen in moisturizers that lacked large amounts of occlusives. It should also be noted that in a small study, gluconolactone (PHA) was shown to be helpful when combined with Azelaic Acid 15%.³

Unfortunately, it does take time to work and the side-effects when initially starting off can be aggravating. The most common side-effects are itching and stinging as well as mild dryness or peeling. This tends to resolve within 4 weeks. This can be difficult to push through. As someone who uses AzA, I can say that the initial itching upon application can feel very intense and aggravating to deal with, though icing my skin helped me push through the worst days. Your mileage may vary.

It takes about 24 weeks to work in cases of melasma and up to two months in acne cases.

One important note (mentioned by Dr. Dray in her wonderful video on AzA) is that it can lighten and “hide” some forms of melanoma, particularly lentigo maligna melanoma. This does not treat it or cure it, and can in fact hide the melanoma. Please get a skin check before self-treating abnormal dark spots with over-the-counter azelaic acid products.


  1. Disruption of the transmembrane pH gradient–a possible mechanism for the antibacterial action of azelaic acid in Propionibacterium acnes and Staphylococcus epidermidis
  2. Induction of Renal Cell Tumors in Rats and Mice, and Enhancement of Hepatocellular Tumor Development in Mice after Long‐term Hydroquinone Treatment
  3. A Guide to the Ingredients and Potential Benefits of Over-the-Counter Cleansers and Moisturizers for Rosacea Patients
  4. Dr Dray – Azelaic Acid
Skincare Oils: Jojoba Oil

Over the past few weeks, I have credited jojoba oil with the improvements in my skin. It’s softer, smoother, and seems to be more tolerant of products that once irritated it (such as Retin-A .025%). In the process of trying to learn why this may be, I’ve encountered a lot of claims about jojoba oil: it’s anti-aging, it helps heal wounds, it has a smaller molecular size which makes it better absorbed by skin, it heals UV damage, and on and on.

While preparing this post, I went unusually deep. I dug through Google Scholar and sorted through several PDFs, trying to figure out what exactly was so magical about this little oil. It’s recommended everywhere and holds a fair amount of shelf space in natural health food stores like Whole Foods, Sprouts, and Trader Joe’s, and even appears in the acne.org routine.

All About Jojoba Oil

Jojoba oil is produced from the seed of the Jojoba plant, a shrub native to Arizona, southern California, and northwestern Mexico. While frequently called “jojoba oil” due to it’s appearance as a liquidy oil, it is more appropriately described as a wax due to it’s composition, which also accounts for it’s high shelf-life and resistance to high temperatures.


It is also thought to be very similar to our skin’s natural oil, and is even suggested as an ingredient in synthetic lipids when testing how things will interact with human sebum.¹ Some feel like this similarity to our own natural oil can “trick” the skin and help balance it’s own sebum production, though I was unable to find any scientific literature to back up this claim.

Like all oils, jojoba oil is also frequently described and recommended as an occlusive. From HowThingsWork:

“‘Jojoba oil is rich in natural fats that mimic those in the outer layer of the skin,’ explains Joshua Zeichner, M.D., director of cosmetic and clinical research at Mount Sinai Medical Center in New York City. ‘This means it can help the skin retain moisture and heal itself.'”

To learn more, I dug into a study about the TEWL (trans-epidermal water loss) of several oils and popular occlusives, namely jojoba, soybean, almond, avocado, paraffin, as well as petrolatum (control). The study noted that TEWL measurements have become “an important, non-invasive tool in dermatology and cosmetology and is generally associated as a device for the monitoring of changes in the barrier function of the stratum corneum. In intact skin, TEWL values are rather low, as impaired skin provides increased values leading to decreasing value when the barrier recovers.”²


To test the effects on TEWL, two types of measurements were taken on six healthy volunteers, aged between 25-50. Volunteers were instructed to not utilize skincare at least 24 hours before, and not to bathe or shower up to 4 hours prior to the beginning of the measurements. TEWL measurements were taken before and thirty minutes after application as well as after the remaining oil had been wiped off. In vivo (meaning measured on a living being), laser scanning microscopy (LSM) revealed that substance penetration appeared to be limited to the uppermost two layers of corneocytes, meaning that no substance penetrated deeper than the stratum corneum (SC). Surprisingly, soybean and almond oil had the deepest penetration into the SC, down into its third layer, while jojoba, avocado, and paraffin was only detected on the skin’s surface and in lipids around the first few corneocyte layers. Petrolatum, the control, was also not vicisble in upper corneocyte layers. In short, despite quite different oil chemistry, the penetration of the tested vegetable oils vs paraffin oil was comparable.²


TEWL was also measured before the substances were applied as well as after substance application. The results showed that TEWL decreased markedly in all cases, except for jojoba oil.


While this study was very small (only six people), this may be why some people do not find jojoba oil very “moisturizing.”

Jojoba oil is also pretty well-tolerated, which may be due to it’s similarities to human sebum, but it may also be due to it’s composition of only 5-15% oleic acid³, a fatty acid that has garnered a reputation for causing acne, specifically due to it’s ability to increase the growth of P. acnes.⁵ In animal models, oleic acid “and it’s peroxides were able to induce fairly large comedones and there was good correlation between the lipid peroxide levels and the size of the comedones.”⁴ While this does not necessarily speak with absolute certainty to how oleic acid functions in humans, it shouldn’t be discounted and is worth further research.

I’ve also seen two particular studies used to inform whether jojoba has anti-inflammatory and anti-microbial effects. Specifically, one study in rats showed it to be anti-inflammatory by decreasing prostagladin E2 (PGE2) levels, while another (unspecified whether it was animal or human) “demonstrated that exposure of bacteria for 24h to [a jojoba/tea trea mixture] containing an antimicrobial leads to a loss of their culturability.”⁵ While the former may hold merit worth further exploration, as with the oleic acid experiment I noted above, it should be noted that in the latter study, the components in the mixture was not disclosed, and that tea tree was included – a substance that has shown to be as effective (over time) in killing P. acnes as benzoyl peroxide.⁶

An in vitro study (meaning a test taken outside a living organism, such as a tube or culture disc) also showed that jojoba “notably accelerates the wound closure of both keratinocytes and fibroblasts” in scratch wound experiments (“Cells are grown to confluence and a thin “wound” introduced by scratching with a pipette tip”⁷). This study suggests that jojoba could be used in the treatment of wounds in clinical settings, but I could not find any in vivo studies to give certainty to this.

All Tied Together

While I didn’t figure out why this oil has been so magical for me, I do think jojoba is a special oil in it’s unique composition, which makes it worth checking out if you are acne-prone or sensitive.


If buying, look for gold, cold-pressed jojoba, which means that it was extracted mechanically and no extra heat was applied during extraction. This helps the oil retain it’s original properties. Unrefined, cold-pressed jojoba oil should have a very, very faint scent and be gold (but translucent) in color. If your jojoba oil is colorless, it may be refined – a process of bleaching and deodorizing an oil and adding preservatives.

IMG_1874I also suggest buying from a trusted retailer. All oils may vary from retailer to retailer, and from harvest to harvest, as they are collected from a natural source. I purchased my jojoba oil from Trader Joe’s, which while it does not advertise itself as “cold-pressed,” was confirmed to be cold-pressed by a representative for the company.

It should also be noted that it is not a very good occlusive ingredient (like… at all) and is better as an addition to your moisturizer if you need some “slip” or as a stand-alone emollient, filling in the “cracks” of the skin to make it smoother and softer. This lack of occlusivity should also serve in not preventing ingredients on top of it from being absorbed by the skin, such as Retin-A. In fact, it may be an excellent buffering ingredient for this reason.

The only real note is that if you use jojoba oil during the day, beneath sunscreen, make sure to blot your skin of additional oil before applying sunscreen. While sunscreen does not need to be “absorbed” by the skin to be effective (a common myth), it does need to form a film, which can require drying down or settling on the skin. Too much “slip” on the skin, in the form of oil, can prevent this from occurring and render your sunscreen less effective.


  1. Human synthetic sebum formulation and stability under conditions of use and storage
  2. Cosmetic Oils in comparison: penetration and occlusion of paraffin oil and vegetable oils
  3. Jojoba Oil Specifications
  4. Google Books – Acne: Diagnosis and Management
  5. Dermatologia e Venereologia – Warning: Graphic Images
  6. Herbal Therapy in Dermatology
  7. Scratch-wound assay
Skincare Oils: Sea-Buckthorn Oil


Not too long ago, it was thought that oil was bad for skin and the primary cause of acne. Oil-free moisturizers dominated the market, and everyone I knew with acne (myself included) scoured, scrubbed, toned, and moisturized their acne-prone skin with oil-free products and astringents.

Fast-forward to the 2010s and oil-based products and luxury facial oils are everywhere.

Today though, I wanted to talk about an oil that seems to be getting more attention in the skincare world: Sea-Buckthorn Fruit Oil.


Sea-buckthorn oil sounds like it is comes from a creature in the sea, but it is actually derived from the fruit of the sea-buckthorn berry. The oil is typically cold-pressed from the whole berries or the seeds of the berries, and is used in several types of products, from skincare to dietary supplements. [1]


It is advertised as having multiple benefits – from anti-aging to anti-bacterial – and is rich in omega-7 (palmitoleic fatty acid) and omega-3 (oleic fatty acid). It contains a large amount of beta carotene, which gives it the deep reddish-orange hue.

While it varies by distributor, Rose Mountain Herbs gives their sea-buckthorn oil the following analysis:

Odor– Fatty/Characteristic
pH– 3.43

Fatty Acids and Constituents
Beta Carotene– 254 I.U./100 g
Vitamin E– 123 mg/100g
Lycopene– less than 1%
Linoleic– 6.8%
Oleic– 28.4%
Palmitic– 31.3%
Palmitoleic– 29.7%
Stearic– 1.1%


Unfortunately, there aren’t a ton of studies about the benefits of topical sea buckthorn oil, though the studies that do exist show that sea-buckthorn oil is a promising ingredient, with potentially some wound-healing [2] and UV protection [3] properties.

For use, I recommend diluting it with other facial oils or products, as it is indeed a very red/orangey oil and can make fairer skins look very fake-tan orange once applied. Some people also recommend sleeping with a towel on your pillow overnight when using it, though I’ve never noticed long-term staining of fabrics due to sea-buckthorn oil.


I’d recommend it for skin that is acne-prone due to its wound healing properties, though anecdotal evidence seems to point to it having value for rosacean skin types. It may also do well with you if you’ve successfully used macadamia nut oil, as both contain a large amount of palmitoleic fatty acid.

I would also recommend heavy spot testing for people with malessezia folliculitis, fungal acne,  atopic dermatitis, or seborrheic dermatitis, as they are all conditions that can be caused by M. furfur yeast, which oleic and palmitic fatty acid can all cause to grow quickly. [4]

Sea-buckthorn oil can be purchased fairly easily online (it is much more difficult to find in stores) from a variety of retailers, such as The Ordinary, Mountain Rose Herbs, and Amazon.


  1. Wikipedia – Sea-buckthorn oil
  2. Influence of sea buckthorn (Hippophae rhamnoides L.) flavone on dermal wound healing in rats.
  3. Sea buckthorn products: manufacture and composition.
  4. Improved Detection of Malassezia Species in Lipid Supplemented
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