hyaluronic acid and your skin

Skin hydration, anti-ageing, wound healing, water retention, cellulite

Hyaluronic acid (also known as hyaluronate or hyaluronan) is the most important moisturising molecule in the human body, an essential component of skin and connective tissue, and an invaluable anti-ageing and connective tissue restructuring active ingredient. Hyaluronic acid comes in various sizes (molecular weights), with the higher sizes forming a film on the skin and the smaller ones penetrating in the deeper dermal layers.

Low molecular weight (LMW) hyaluronic acid comprises small size hyaluronic acid molecules and can penetrate deeper than normal hyaluronate. In addition, LMW hyaluronan itself is also a penetration absorber for other active ingredients in body / face creams. 


Which molecular weights of hyaluronic acid penetrate the skin better?

This question has been answered by the 2016 study titled: Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy. The results of the study are quite clear and quite enlightening: anything up to 300 kDa offers a food degree of penetration, with 50-300 kDa being ideal for anti-ageing and lower molecular weights (800-10k Da) being ideal for cellulite and water retention. On the other hand, anything above 1000 kDa stays on the surface of the epidermis, with the body's native 2000 kDa hyaluronan being totally unable to penetrate the epidermis.

"Our results show a difference of skin permeation of the three HA. Indeed, HA with low molecular weight (20-300 kDa) passes through the stratum corneum in contrast of the impermeability of high molecular weight HA (1000-1400 kDa)"



For all these reasons, LMW hyaluronic acid is of great importance as an active ingredient in anti-cellulite, leg wellness, anti-ageing and under-eye creams. Hyaluronic acid creams are now popular for dry, aged skin and to fill wrinkles and fine lines [the Celluence® cellulite and leg wellness creams are the only creams in the world with 99% pure LMW hyaluronic acid - less than 10 kDa - plus 39x other natural anti-cellulite actives].


10+ of the many ways hyaluronic acid...

...can help boost skin healing and fight skin aging, water retention and cellulite



10/ Fifty-kDa hyaluronic acid upregulates some epidermal genes without changing TNF-alpha expression in reconstituted epidermis

Abstract: BACKGROUND: Due to its strong water binding potential, hyaluronic acid (HA) is a well-known active ingredient for cosmetic applications. However, based on its varying molecular size, skin penetration of HA may be limited. Recent studies have demonstrated that low-molecular-weight HA (LMW HA) may show a certain proinflammatory activity. We thus aimed to characterize an LMW-sized HA molecule that combines strong anti-aging abilities with efficient skin penetration but lacks potential proinflammatory effects. METHODS: Total RNA and total protein were isolated from reconstituted human epidermis following incubation with HAs of various molecular weights (20, 50, 130, 300, 800 and 1,500 kDa). Tumor necrosis factor-α expression was determined using quantitative PCR. Genomic and proteomic expression of various junctional proteins was determined using Affymetrix and common Western blotting techniques. RESULTS:
LMWHA of approximately 50 kDa did not significantly alter tumor necrosis factor-α expression compared to 20-kDa HA, but revealed significantly higher skin penetration rates than larger sized HA associated with increased expression of genes and proteins known to be involved in tight junction formation and keratinocyte cohesion. CONCLUSION:
LMW HA of approximately 50 kDa shows better penetration abilities than larger-sized HA. In addition, LMW HA influences the expression of various genes including those contributing to keratinocyte differentiation and formation of intercellular tight junction complexes without showing proinflammatory activity. These observations contribute to current knowledge on the effects of LMW HA on keratinocyte biology and cutaneous physiology.



9/ Hyaluronic acid fights aging / delays cellular aging...

...by maintaining the replicative ability of stem cells (Source: Hyaluronan keeps mesenchymal stem cells quiescent and maintains the differentiation potential over time)



8/ Oral hyaluronic acid significantly increases skin elasticity...

...skin hydration, and to a significant decrease in skin roughness and wrinkle depths (Source: Ingestion of an Oral Hyaluronan Solution Improves Skin Hydration, Wrinkle Reduction, Elasticity, and Skin Roughness: Results of a Clinical Study)



7/ Enzymatic fragments of hyaluronan inhibit adipocyte differentiation in 3T3-L1 pre-adipocytes

Hyaluronan has diverse biological activities depending on its molecular size. High molecular weight hyaluronan (2000 kDa) is a major component of extracellular matrix, and has been used in wounding healing, extracellular matrix regeneration, and in the treatment of osteoarthritis. Hyaluronan fragments can stimulate inflammation or induce loss of extracellular matrix. Hyaluronan is expressed during adipocyte differentiation, and down regulation of hyaluronan synthesis can reduce adipogenic differentiation. However, the direct effects of hyaluronan fragments on adipocyte differentiation have not been elucidated. Therefore, we prepared hyaluronan fragments by enzymatic digestion, and examined the inhibitory effects of these hyaluronan fragments on the accumulation of lipid droplets and on adipogenic gene mRNA expression in differentiating 3T3-L1 pre-adipocytes. Medium sized hyaluronan fragments (50 kDa) decreased lipid droplet accumulation in a dose-dependent manner. However, high molecular weight hyaluronan did not inhibit lipid droplet accumulation when used at a concentration of 600 μg/ml. Two or 4 day treatments with medium molecular weight of hyaluronan resulted in similar inhibitory levels of lipid accumulation as did treatment for 8 days. Medium sized hyaluronan inhibited the differentiation of 3T3-L1 pre-adipocytes during the early stages of adipogenesis. When 3T3-L1 cells were treated with 180 μg/ml of medium sized hyaluronan, the mRNAs for the master adipogenic transcription factors PPAR-γ and C/EBP-α were inhibited. Additionally, medium molecular weight hyaluronan suppressed mRNA expression of PPAR-γ target genes, including aP2 and FAS. This study is the first to report that medium molecular weight hyaluronan fragments can inhibit adipocyte differentiation.



6/ Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period.

Abstract: BACKGROUND: Hyaluronan (HA) has critical moisturizing property and high water retention capacity especially for human skin. This study aimed to evaluate the effect of oral intake of HA. METHODS: The mean molecular weight (MW) of HA is 2 k and 300 k. Sixty Japanese male and female subjects aged 22-59 years who presented with crow's feet wrinkles were randomly assigned to the HA 2 k or HA 300 k at 120 mg/day or the placebo group. The subjects were administered HA at a rate of 120 mg/day or a placebo for 12 weeks. The skin wrinkles were evaluated by image analysis of skin wrinkle replicas, and their skin condition was evaluated using a questionnaire survey. RESULTS: During the study period, the HA groups showed better level of the whole sulcus volume ratio, wrinkle area ratio, and wrinkle volume ratio than the placebo group. After 8 weeks of ingestion, the HA 300 k group showed significantly diminished wrinkles compared with the placebo group. Skin luster and suppleness significantly improved after 12 weeks in all groups compared with the baseline. CONCLUSION:
The results suggest that oral HA (both HA 2 k and HA 300 k) inhibits skin wrinkles and improves skin condition.



5/ Noninvasive penetration of 5 nm hyaluronic acid molecules across the epidermal barrier (in vitro) and its interaction with human skin cells

Abstract: OBJECTIVE: Hyaluronic acid represents one of the major components of the extracellular environment. The main challenge remains in the ability to deliver these molecules noninvasively across the skin barrier, which can be overcome by the reduction in size to an extent that allows these molecules to pass across the skin barrier. The aim of this study was to measure the penetration and bioavailability of low molecular weight hyaluronic acid to cross an epidermal barrier model. METHODS: Determining the quantity of hyaluronic acid in the test solutions was carried with method of photocolorimetry analysis. Investigation of the interaction of cells with LMWHA was studied with a confocal microscope. RESULTS:
The study showed that LMWHA is able to cross the epidermis. Most effective penetration level is during the first 6 hours reaching 75%, and then the concentration started to decline and reached the equilibrium state within the following 2 hours. Confocal laser microscopy demonstrated different distribution and behavior of these molecules among the keratinocytes and fibroblasts. CONCLUSION: Reducing the size of hyaluronic acid to 5 nm enhance their transport across the epidermal layer. The concentration of hyaluronic acid molecules was higher on the fibroblast surface in comparison to their extracellular environment.



4/ Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy.

Abstract: BACKGROUND: Topical delivery of molecules into the human skin is one of the main issues in dermatology and cosmetology. Several techniques were developed to study molecules penetration into the human skin. Although widely accepted, the conventional methods such as Franz diffusion cells are unable to provide the accurate localization of actives in the skin layers. A different approach based on Raman spectroscopy has been proposed to follow-up the permeation of actives. It presents a high molecular specificity to distinguish exogenous molecules from skin constituents. METHODS:
Raman micro-imaging was applied to monitor the skin penetration of hyaluronic acids (HA) of different molecular weights. The first step, was the spectral characterization of these HA. After, we have determined spectral features of HA by which they can be detected in the skin. In the second part, transverse skin sections were realized and spectral images were recorded. RESULTS:
Our results show a difference of skin permeation of the three HA. Indeed, HA with low molecular weight (20-300 kDa) passes through the stratum corneum in contrast of the impermeability of high molecular weight HA (1000-1400 kDa). CONCLUSION:
Raman spectroscopy represents an analytical, non-destructive, and dynamic method to evaluate the permeation of actives in the skin layers.



3/ Novel curcumin - hyaluronic acid conjugate improves curcumin's wound healing and antioxidant activity

Curcumin is a promising wound healing agent but its clinical application is limited due to being undiluted to water and lack of stability. However, curcumin conjugated to hyaluronic acid, has been found to be better than curcumin for fighting free radical damage and wound healing than plain curcumin. (Source: Wound healing activity of curcumin conjugated to hyaluronic acid: in vitro and in vivo evaluation)



2/ Phlebitis ulcers heal with the aid of herbal cream consisting of horse chestnut, butcher's broom, allantoin and hyaluronic acid

This herbal compound, in combination with compression garments, significantly improved inflammation, healing time and pain in phlebitis, in relation to compression garments alone. Ivy extract in the cream contributed to pain reduction; horse chestnut, butcher's broom and grape seed extract reduced inflammation; and allantoin, gotu kola and hyaluronic acid aided sore healing. In patients who applied both the cream and the compression garment pain stopped in 72 hours, inflammation disappeared in one week, tissue swelling stopped in one week and healing was complete in 4 weeks. (Source: Multicentric study on a topical compound with lymph-draining action in the treatment of the phlebostatic ulcer of the inferior limbs)



1/ 50 kDa hyaluronic acid reduces fat and fights obesity...

...by decreasing adipose tissue hypertrophy, inhibiting adipogenic differentiation, enhancing PPAR-α and suppressing PPAR-γ expression (Source: Anti-obesity potential of enzymatic fragments of hyaluronan on high-fat diet-induced obesity in C57BL/6 mice)