Introduction & Objectives: Benzoyl peroxide (BPO) is commonly used alone or in combination with retinoids or antibiotics as
first line treatment in acne vulgaris (AV). BPO-based topical anti-AV products are effective however, often, the skin tolerability
profile is not optimal due to skin irritation and skin dryness commonly observed during treatment. It is frequently needed to
combine an appropriate dermo cosmetic approach to restore the function of the skin barrier. The fixed-dose combination of
BPO with clindamycin (BPO-Cli) has demonstrated to be very effective and well tolerated in the treatment of AV. Oral vitamin
A (retinol) has shown to improve AV lesions mainly in non-controlled observational studies with a good skin tolerability. Some
data suggest that oral Vitamin A could also have beneficial effects on gut microbiome. So far, no controlled data regarding an
“In&Out” strategy using BPO-Cli topical product and oral Vitamin A have been conducted in AV treatment. We evaluated
and compared the efficacy and tolerability of BPO-Cli gel alone or in combination with oral Vitamin A in subjects with mild
to-moderate AV. In addition, as secondary endpoint, we evaluated the effect of combination therapy on gut microbiome by
mean of Trimethylamine N-Oxide (TMAO) serum measurements.
Materials & Methods: In a randomised, prospective, assessor-blinded trial a total of sixty subjects (10 men and 50 women,
mean age: 24 years) with AV were enrolled in an 8-week trial, after their informed written consent. Thirty subjects were
allocated to BPO-Cli gel treatment (one application per day in the morning) (Group A) and thirty subjects were allocated to BPO-Cli gel and Vitamin A oral supplementation (50.000 IU) once daily (Group B). The primary endpoint was the evolution
of Global Acne Grading System (GAGS) assessing AV lesions number and type (with a score of 0 representing no lesions, 1-18
mild, 19-30 moderate, and >31 severe and very severe acne). GAGS score was evaluated at baseline and after 8 weeks by an
investigator unaware of treatment allocation. As indirect parameter of gut microbiota we also measured serum TMAO level
in group B subjects at baseline and after treatment.
Results: All subjects concluded the 8-week treatment period. No severe adverse events were registered in both groups. At
baseline the GAGS score was 26.2 ± 3.0 in Group A and 25.9 ± 2.6 in Group B. After 8-week of treatment Group A shown a
percentage reduction of GAGS in comparison with baseline values of -40%. In the Group B the percentage reduction was
56%. At week 8, the GAGS values were significantly lower (p=0.0001) in Group B (11.4 ± 2.8) in comparison with Group A
(15.8 ± 3.0) with an absolute difference of -4.37 points (95% CI: -5.9 to -2.8). At week 8, the percentage of subjects with a GAGS
score <18 was 66.7% (20 out 30) in Group A and 96.7% in Group B (29 out of 30) (P=0.0056; Fisher exact test). At baseline
TMAO serum levels were 3 ± 2. The treatment with oral vitamin A reduced TMAO serum level to 1.9 ± 1.8 (representing a
37% reduction) (P=0.024; paired t-test).
Conclusion: The combination of BPO-Cli with oral Vitamin A has shown to be more effective in comparison with the topical
treatment alone in the treatment of mild-moderate AV. Oral vitamin A seems also able to positively modulate in acne subjects
gut microbiome, probably trough a decrease of TMA producing bacteria (i.e. Proteobacteria). The combination was also very
well tolerated.