Response to Keith et al. Re: “Annurca Apple Nutraceutical Formulation Enhances Keratin Expression in a Human Model of Skin and Promotes Hair Growth and Tropism in a Randomized Clinical Trial”

Dear Editor,

Overall, it is evident from the study design and the clinical protocol that the main goal of the article by Tenore et al. ¹ is to provide preliminary data from an original intervention study, which has no precedent in the literature. To this regard, authors are very cautious and state throughout the article that “… represents the first attempt … as potential hair growing nutraceutical agent” (Introduction section) and that “The results of this clinical trial, … provide strong support” (Conclusions section), but not clear evidence, about the effectiveness of the nutraceutical product, object of the article, to promote hair growth and tropism in the human subjects enrolled in this study. Moreover, the Study Strength and Limitations subsection clearly states that “the main limitations of our study include the short-term assessment for the treatment of a chronic condition,” whereas in the Conclusions section is anticipated that “Further studies are ongoing to better clarify the molecular basis….” Actually, this study must be regarded as a pilot study, which reports indicative results to be confirmed by a longer trial, involving a higher number of patients. Nevertheless, despite the short period of time and the limited number of enrolled subjects, our preliminary data have revealed such of interest that we have decided to start communicating our achievement to the scientific community. The authors plan to confirm these results by refining the experimental protocol, also in terms of treatment/placebo duration.

Starting from the aforementioned assumption, authors fully agree with Keith et al. ² as regard with their concern about the correctness of the study design. Of course, there is a lack of official placebo groups, whereas two treatment groups have been directly compared. Nevertheless, each treatment group has accomplished a run-in period during which placebo has been administered to detect false adverse effects as well as possible therapeutic reactions. To this regard, randomization has been performed before placebo (run-in) allocation. Then, results from the two treatment periods have been compared with their respective baseline data, to verify whether the occurrence of biotin, selenium, and zinc, all being recognized as effective on hair growth and tropism, could play a significant role in the bioactive response of the nutraceutical formulation. At that moment, a major interest was to evaluate the different effects of these two samples, whereas in a forthcoming study, we will deepen the efficacy of each sample in a more structurally designed trial, provided with placebo and control groups, and corroborated by a more efficient statistical analysis.

As regard with the concern about the seasonal changes, authors fully agree about the placebo and treatment period have coincided with the peak of anagen step of the year (January–March). Nevertheless, authors are much impressed by the results obtained at the end of the treatment periods, if compared with baseline data, which, in their opinion, are too massive to be imputed to the mere physiological and seasonal hair anagen cycle. In addition, what seems to strongly support authors' thesis is the hair keratin increase at the end of the treatment periods. Undoubtedly, such nonphysiological result should be ascribed to the effect of the nutraceutical formulations.

Authors are confident that the comments from Keith et al. have been properly addressed. Nevertheless, authors remain at full disposal for any further clarification.