https://www.jstage.jst.go.jp/article/bpb/38/12/38_b15-00387/_html - link to the study
Clinical research on topical alopecia treatments included clinical studies of procyanidin B-222) and minoxidil.4,23) After 48 weeks of male pattern hair loss treatment, the parameter known as non-vellus hair count (mean change from baseline) in the 5% minoxidil, 2% minoxidil, and placebo groups measured 18.6, 12.7, and 3.9 strands/cm2, respectively.4) The change from baseline in the non-vellus hair count was significantly superior with 5% topical minoxidil compared to 2% topical minoxidil and placebo. After 48 weeks of female pattern hair loss treatment, the non-vellus hair count (mean change from baseline) in the 5% minoxidil, 2% minoxidil, and placebo groups measured 24.5, 20.7, and 9.4 strands/cm2, respectively.23) As in the male patients, 5% topical minoxidil was significantly superior to 2% topical minoxidil and placebo in the female patients. To investigate the effects of topical procyanidin B-2 (1%), which is purified from apples, on the scalp and hair, a placebo controlled clinical trial was performed in male pattern baldness.22) After 16 weeks, a significantly greater increase in the total number of hairs in the designated scalp area (1.0 cm2) was observed in subjects receiving procyanidin B-2 than in those receiving placebo (procyanidin B-2, 14.68 strands/cm2; placebo, −10.16 strands/cm2). In our study, the non-vellus hair counts (mean change from week 0) were 9.72 and 2.69 strands/cm2 in male subjects in the RB-SCE and placebo groups, respectively, showing a statistically significant difference between the groups (p=0.034; Table 3). In female subjects, the hair counts were 13.63 and 10.39 strands/cm2 in the RB-SCE and placebo groups, respectively. However, there was no statistically significant difference between the groups (p=0.198; Table 3). Although study duration, race, gender, drug administration protocol, and other factors differ between our study and the prior studies, the increase in hair count in the 0.5% RB-SCE group after 16 weeks in our study (9.72 strands/cm2 in male subjects) is similar to or slightly lower than that reported for 2% minoxidil after 48 weeks of treatment in men (12.7 strands/cm2)4) or for 1% procyanidin B-2 after 16 weeks of treatment in men (14.68 strands/cm2).22)
In terms of hair diameter, it was reported that 78.9% of subjects treated with 1% procyanidin B-2 showed an increased mean hair diameter, whereas only 30.0% in the placebo group showed any increase. The change in hair diameter after 16 weeks was 2.68 and −1.08 µm, respectively, in the 1% procyanidin B-2 and placebo groups. The increased ratio (8.04%) of hairs measuring more than 40 µm in diameter after 16 weeks of procyanidin B-2 treatment was significantly higher than that in controls (−4.32%). In our study, the hair diameter (mean change from week 8) after 16 weeks was 8.8 µm (from 66 to 75 µm) and 2.8 µm (from 66 to 69 µm) in male subjects with RB-SCE and placebo, respectively, showing a significant increase (p=0.001; Table 4). The hair diameter (mean change from week 8) after 16 weeks was 8.6 µm (from 80 to 89 µm) and 0.5 µm (from 73 to 74 µm) in female subjects with RB-SCE and placebo, respectively, showing a significant increase (p=0.004; Table 4). The increase in hair diameter in the RB-SCE group after 16 weeks (17.3 and 16.6 µm in male and female subjects, respectively) was higher than that reported for 1% procyanidin B-2 after 16 weeks (8.04 µm).
Regarding the expert panel assessment of global photographs in male subjects, at 16 weeks of treatment, the average score in the RB-SCE group (0.89±0.601) was clearly higher than that in the placebo group (0.08±0.862), and the difference was statistically significant (p=0.024) (Table 5). In female subjects at 16 weeks of treatment, the average score in the RB-SCE group (1.25±0.452) and in the placebo group (1.11±0.601) and the difference were not statistically significant (p=0.552) (Table 5).
Self-questionnaires have been reported useful for the evaluation of new potential hair growth-promoting candidates or medicines.4,17,23) In the study of Olsen et al. in male patients,4) patient questionnaire hair growth composite scores at week 48 (efficacy-evaluable population) for 5% minoxidil, 2% minoxidil, and placebo were 60.4, 56.8, and 50.7, respectively. In the study of Lucky et al. in female patients,23) patient questionnaire hair growth composite scores at week 48 (efficacy-evaluable population) for 5% minoxidil, 2% minoxidil, and placebo were 64.5, 60.5, and 56.4, respectively. In our study, the population with improvement in bitemporal recession and hair shedding in the RB-SCE group of male subjects was significantly larger than that in the placebo group at 16 weeks based on the chi-square test for uniformity of groups (p=0.003, p=0.011, respectively; Table 6), but it otherwise was not in female subjects (Table 7). Although comparison with previous results is difficult because of the use of different questionnaire items,4,23) we confirmed that 2 items in questionnaire analysis results in the RB-SCE group were significantly increased compared to those in the placebo group after 16 weeks, especially in male subjects.
Overall, the significant differences in hair density, hair diameter, and expert panel assessment of global photographs were shown in male subjects after 16 weeks of treatment with RB-SCE. In addition, the significant differences between the RB-SCE and placebo groups after 16 weeks showed in hair density, expert panel assessment of global photographs, and questionnaire analysis in male subjects. In female subjects after 16 weeks of treatment with RB-SCE, the significant differences in hair density, hair diameter, and expert panel assessment of global photographs were shown but not significantly different from those of the placebo group.
In a previous study,11) to examine the hair growth-promoting activity of RB-SCE, we selected linoleic acid (LA), oryzanol (OZ), policosanol (PS), and tocotrienol (TT) as the main components of RB-SCE. In particular, the unsaturated fatty acids such as γ-LA, LA, and oleic acid as well as RB-SCE have been shown to have anti-hair loss activity by inhibiting the 5-α-reductase enzyme in androgen-responsive organs.12,24) In this study, RB-SCE had a significant hair growth-promoting effect in male subjects but not in female subjects, meaning that RB-SCE may have an effect in androgen-dependent hair loss. Recently, female patients with alopecia were reported to be divided by androgen-dependent female pattern hair loss (FPHL) and androgen-independent FPHL according to the serum androgen levels of the female patients.25,26) The analyses of blood chemistry tests including hormonal levels for female patients are needed in further study.
Previous researchers have confirmed the toxicological safety of RB-SCE in RAW264.7 cells. Additional safety evaluations included single oral dose toxicity in rats,13) an acute dermal and ocular irritation test,14) a single dose and 4-week repeated dose dermal toxicity study,15) and a genotoxicity assessment.16) As urinalysis, hematological tests, clinical biochemistry tests, necropsies, and histopathological examinations were performed in male and female rats after 4-week repeated-dose dermal administration of RB-SCE, no liver or kidney damage was observed.15) In addition, in this study, no specific side effects such as irritant contact dermatitis, allergic contact dermatitis, itching, pricking, burning, erythema, oozing, vesicles, skin rashes, and so on were observed in patients receiving RB-SCE. Therefore, RB-SCE is thought to be safe for topical application in humans.