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You are here: Anti-Aging Skin Treatments > Topical Actives >

Hyaluronic acid for skin hydration and possibly a lot more

Hyaluronic acid (HA) is a biopolymer naturally occurring is the skin and other tissues. It is an important component of the skin matrix. HA is also a popular skin care ingredient often used topically. To learn what this underappreciated biopolymer is all about we strongly recommend starting with our introductory article on HA. Here we focus on possible skin benefits and limitations of topical hyaluronic acid.

Moisturizing effects of hyaluronic acid

Hyaluronic acid is highly effective humectant, i.e. an ingredient that holds moisture. HA can hold hundreds of times its weight in water and is often used in moisturizing formulas. Indeed it can provide effective skin surface hydration, either alone or in combination with other moisturizing ingredients.

However, there is a controversy whether concentrated HA formulas should be used as a moisturizer in dry climate. When air humidity is very low, HA may preferentially pull water from the skin rather than from the air, thus producing the opposite effect. The optimal use of HA as a moisturizer needs further research. Until then, when trying out HA-based products, it is prudent to be watchful for such an effect, especially in very dry environments. If proper skin hydration is not achieved, you can try adjusting HA concentration and/or combine your HA-based formulation with other skin care products. If you are using a commercial HA product, you can dilute it with a compatible neutral base and/or co-apply with a compatible hydrating product (e.g. a colloidal oatmeal-based moisturizer, such as Aveeno). If you need additional flexibility regarding the concentration of HA and/or combining it with other ingredients, you can easily make an HA-based formulation yourself (see DIY Anti-Aging Skin Care Infopack for practical directions).

Skin irritation and inflammation

Hyaluronic acid is a polymer and the size of its molecules (chains) may vary in a wide range. Depending on the size, HA chains may produce different physiological effects. In particular, relatively large HA chains (molecular weight 500,000 Da or more) appear to reduce inflammatory response. There is some evidence that topically applied HA can reduce skin irritation from various causes (such as retinoids, laser treatments, chemical peels and others). Unfortunately, as of the time of this writing, very few studies investigated HA as a topical anti-irritant. Further research is required to determine optimal HA concentrations and usage patterns for specific conditions. (The concentrations studied so far ranged from 0.1% to 2.5%.)

Actinic keratosis

Actinic keratosis (AKs, solar keratosis) is a premalignant inflammatory skin lesion(s) particularly common in fair skinned people who had substantial cumulative sun exposure. In several studies, a topical formula with 2.5% HA and 3% diclofenac (a non-steroidal anti-inflammatory drug) produced marked improvement or complete clearance of AK lesions in at least half of the patients after 90 days. HA alone also produced improvement in some patients but overall was less effective than the combination.


The content of hyaluronic acid in the skin matrix decreases with age, which may contribute to the development of fine lines, wrinkles and other signs of aging. Hence there is a considerable enthusiasm in the media about topical HA as a potential wrinkle cure.

The problem is that to have an effect on the skin matrix, especially in the dermis (middle layer of the skin) where wrinkles originate, HA needs to penetrate the outer layers of the skin (epidermis and stratum corneum). That is difficult for large biopolymers, including glycosaminoglycans such as HA. In fact, HA variants typically used in skin care (long chain HA with molecular weight 500,000 Da or more) do not appear to penetrate the skin well enough to affect dermal matrix. (To learn more, see our our introductory article on HA.)

Of course, HA chains can be chopped up into the pieces as small as 5000 Da or even less (e.g. by using the enzyme hyaluronidase), which could penetrate into the dermis reasonably well. But there is a catch -- small size HA (molecular weight 5,000 - 20,000 Da) appears to promote certain inflammatory responses, i.e. in that regard it has the opposite effect to large size HA, which is anti-inflammatory. In turn, inflammation increases the production of free radicals, proteolytic enzymes and other entities that damage skin matrix and promote wrinkles. Therefore, even though the small size HA can penetrate the skin, it may not be a good skin rejuvenation agent, especially in regard to preventing or reversing wrinkles.

Fortunately, there appears to be a sweet spot in the HA size range that can deliver anti-wrinkle benefits w/o triggering inflammation and possibly even reducing it. Dr Pavicic and colleagues from the University of Munich studied the efficacy of different formulations of hyaluronic acid as an anti-wrinkle treatment. After sixty days of treatment, they found significant improvement in wrinkle depth and skin roughness in the groups treated with 0.1% HA formulation with molecular weight of 50,000 Da and 130,000 Da. On the other hand, the HA formulations of 300,000 Da or more showed no effect.

Another study, by Dr Poetschke and colleagues (also from the University of Munich) involved various HA creams applied for 3 month. The study showed wrinkle depth reduction by 10-20% and increase in skin tightness by 13-30%.

So far, the evidence for anti-wrinkle effects of HA is encouraging but still relatively limited. The optimum size range for anti-wrinkle effects appears to be about 50,000-150,000 Da (although more research is needed to confirm and work out the best practices). Unfortunately, most skin care companies making topical HA appear to use much larger variant of HA. In fact, as of the time of this writing, I am not aware or any product with HA in the range 50,000-150,000 Da, at least based on the product labels of other available information. However, this variant of HA is available inexpensively as a pure ingredient and can be easily incorporated into a DIY formulation (see DIY Anti-Aging Skin Care Infopack).

Bottom line

Hyaluronic acid (HA) is a natural biopolymer that can be very effective for skin hydration and moisturizing if used properly. Preliminary evidence suggests that medium-to-large size HA may also help combat skin irritation and inflammation. Small-to-medium size HA (50,000-150,000 Da) appears to improve wrinkles, skin roughness and possibly even increase skin tightness. Very small size HA (below 25,000 Da or so) is pro-inflammatory and should be avoided.

There are many commercially available products that contain hyaluronic acid. Unfortunately, most are relatively expensive (at least compared to the cost of ingredients) and may not contain HA concentrations and molecule size that fit your needs. If you cannot find a HA-based product optimal for your skin, you can relatively easily make one yourself. For practical direction on making your own skincare formulations, including those with hyaluronic acid, see DIY Anti-Aging Skin Care Infopack.


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