Anti-Skin-Aging Effect Of A Treatment With A Cosmetic Product And A Food Supplement Based On A New Hyaluronan: A Randomized Clinical Study in Healthy Women Part 2

3.5. Skin Firmness

Glycoside of cistanche can also increase the activity of SOD in heart and liver tissues, and significantly reduce the content of lipofuscin and MDA in each tissue, effectively scavenging various reactive oxygen radicals (OH-, H₂O₂, etc.) and protecting against DNA damage caused by OH-radicals. Cistanche phenylethanoid glycosides have a strong scavenging ability of free radicals, a higher reducing ability than vitamin C, improve the activity of SOD in sperm suspension, reduce the content of MDA, and have a certain protective effect on sperm membrane function. Cistanche polysaccharides can enhance the activity of SOD and GSH-Px in erythrocytes and lung tissues of experimentally senescent mice caused by D-galactose, as well as reduce the content of MDA and collagen in lung and plasma, and increase the content of elastin, have a good scavenging effect on DPPH, prolong the time of hypoxia in senescent mice, improve the activity of SOD in serum, and delay the physiological degeneration of lung in experimentally senescent mice With cellular morphological degeneration, experiments have shown that Cistanche has the good antioxidant ability and has the potential to be a drug to prevent and treat skin aging diseases. At the same time, echinacoside in Cistanche has a significant ability to scavenge DPPH free radicals and has the ability to scavenge reactive oxygen species and prevent free radical-induced collagen degradation, and also has a good repair effect on thymine free radical anion damage.

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The R0 parameter did not show any significant intergroup difference at T0 (Figure 5a),  and all treatments resulted in a significant reduction of the R0 parameter at T28 concerning its basal values (p < 0.05 for G1, p < 0.001 for G2 and G3). The R0 values at T42 were almost the same as those at T28. No intergroup significant differences were observed during the treatment period. In terms of mean percentage variation of R0, the G3  treatment induced a higher decrement (−9.5%) concerning G1 and G2 at T28, as shown in Figure 5b; then, the G3 treatment showed a further decrement of such value (−11.1%) at T42. Percentage variations in G1 and G2 subjects were almost similar to the T28 values and to levels that still were higher compared to those at T14.

3.6. Skin Profilometry

Skin profilometry was evaluated in terms of wrinkle depth and skin smoothness (expressed as the Ra value): both parameters showed a similar profile throughout the study. The basal levels of wrinkle depth and Ra value did not show any significant differences between the groups (Figure 6a,c). A progressive and significant decrease in the mean wrinkle depth and the Ra value was observed throughout the treatment period for all three groups, showing a peak at T28, (p < 0.001). At T42, the wrinkle depth values and Ra values showed a slight increase compared to their previous values at T28, but their levels were still statistically lower compared to those at T0, respectively, p < 0.001 for wrinkle depth for all groups, p < 0.05 for G2 and p < 0.001 for G1 and G3 for the Ra values. No significant intergroup differences throughout the whole study period were observed. The highest mean percentage variation of wrinkle depth and Ra value concerning their T0 values (Figure 6b,d) was achieved at T28 for all treatments; then, the percentage variation decreased at T42, but to levels that were still higher concerning those at T14 for G1 and G3, and lower for G2 at T42.

The skin profilometry of a G3 subject throughout the study period is shown in Figure 7.

3.7. Self-Assessment Questionnaire 

The subjects reported almost 100% positive answers on the tolerability of the products and their peculiar characteristics.

The cut-off was satisfied for 8 out of 10 questions relating to the product’s performance. The visibility of deep wrinkles in general resulted in less than 80% of the answer; only G1 reached the goal at T28. A rejuvenated skin appearance was perceived only by G3  participants, who gave more than 80% of positive answers both at T28 and at T42 (Table 1).

4. Discussion

The efficacy of HA, a well-known group of ingredients widely used in health and personal care [29,30], administered as ingredients of cosmetic formulations or as food supplements, in amelioration aging clinical signs by enhancing skin moisturization, elasticity, and roughness, has been largely reported in the last decades [8,9,21,24]. However, a full characterization of the polymer size of hyaluronans was not reported in the majority of studies. Indeed, it is generally recognized that the biological effects of HA are dependent on the polymer size [27,31], which leads to differentiated performances [25–28]. The Full Spectrum HA obtained by this novel technology [32] can mimic the human skin's physiological composition and, consequently, the synergy naturally occurring in the skin.

The novelty of this clinical study also relies on the In&Out approach, i.e., a concomitant supply of the same active ingredient, hyaluronic acid, through two different routes: topical and oral.

This approach of using both a cosmetic product and a food supplement aims at two main goals: the first one is to achieve a prompt anti-aging effect due to the direct application of hyaluronan onto the skin, which, according to its physicochemical properties, replenishes its content in the ECM, improves skin hydration level, and ameliorates the aging signs;  the second aims at a long-lasting effect on skin regeneration through the physiological responses elicited by signaling fragments generated from the metabolism of oral HA.

Indeed, both G1 and G2 treatments, containing a single active product, resulted effective in ameliorating the skin aging signs in a mature female population at the end of the product treatment, confirming the usefulness of the administration of the Full Spectrum HA either in a cosmetic product or as a food supplement, in an anti-skin-aging approach. In terms of mean percentage variation, the active cosmetic treatment resulted in a greater improvement of skin parameters concerning oral administration, according to the prompt availability of HA into the skin obtained through this route. The effect of cosmetic supplementation with the Full Spectrum HA lasted also after its substitution with the placebo cream, as measured after the follow-up period. G1 showed a similar/slightly higher effect concerning G2 in skin hydration distribution, skin firmness, and skin profilometry (wrinkle depth and skin smoothness) after the follow-up period, suggesting a  different kinetics of activity for the oral treatment.

Accordingly, subjects receiving the combination of ExceptionHYAL® Star and PrincipHYAL® lasting showed, at T28, a significative improvement in all parameters concerning the basal levels, and the mean percentage variation resulted higher concerning the treatments based on a single active product; such levels remained higher after the followup period as far as skin moisturization, hydration distribution, elasticity, and firmness were concerned.

Wrinkle depth and skin smoothness resulted to be positively affected by the oral treatment, as the percentage variation recorded for G1 at T28 was similar to that for G2 and G3, and, after the follow-up, both parameters for G1 showed a lower decrement at T42 concerning the levels recorded for the other two treatments, resulting similar to those in G3.

5. Conclusions

Administration of Full Spectrum Hyaluronan, in a cosmetic product or a food supplement, resulted in a significant improvement in the skin aging signs of a mature female population; a further amelioration of the skin conditions was achieved by using concomitantly the topical and oral administration routes, i.e., the In&Out treatment. Results recorded after the follow-up period suggest that such an approach could also have a  lasting effect on skin aging conditions by replenishing the HA content through different routes and, therefore, mechanisms.

Although the study aimed to evaluate the efficacy of the In&Out treatment, i.e.,  administering the same active ingredient by two different routes, a limitation of the study could be seen in the lack of “true” placebo treatment, that, in the first instance, could affect the effective instrumental as well perceptive results mainly concerning the treatment with ACP. The treatment period could also appear too short, mainly concerning the oral treatment; in fact, a longer-term study would be appropriate to further elucidate the maximal effects on elasticity and profilometric parameters, but the protocol was developed according to the general acceptance of skin treatment by consumers, who seek products that give immediate benefits and that demonstrate efficacy in a short period of treatment.

Author Contributions: F.C., A.M., and F.T. designed the study; G.R. enrolled volunteers and carried out the clinical evaluations and determination of the skin parameters; A.M and F.R. analyzed the data and carried out the statistical analysis; F.T. and A.M wrote the draft; all authors took part to the discussion for the final version of the paper and agreed to the published version of the manuscript. F.C. did not influence data interpretation. All authors have read and agreed to the published version of the manuscript.

Funding: This research was sponsored by Roelmi HPC SRL. 

Institutional Review Board Statement: The study was conducted by the Declaration of Helsinki and approved by the Independent Ethical Committee for Non-Pharmacological Clinical Studies” Genova, Italy (Ref: 2019/09, approved on 4 September 2019).

Data Availability Statement: Data supporting the findings of this study are available from the corresponding author upon reasonable request.

Conflicts of Interest: Roelmi HPC sells ExceptionHYAL® Star and PrincipHYAL® Difference. Roelmi HPC did not influence data collection or interpretation nor the paper writing.

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