The oral supplement is from Codex Labs as Antü™ Skin Barrier Support Supplement (San Jose, CA). It contains: L-histidine, Ethnicare M3 Powder Plus consisting of Buddleja globosa, Aristotelia chilensis, and Ugni molinae leaf extracts (M3Complex^TM, San Jose, CA), citric acid, organic and natural flavors, organic rice fiber, sea salt, stevia leaf extract.

The soap is from Codex Labs as Bia™ Unscented Soap (San Jose, CA). It contains sodium olivate, sodium cocoate, sodium shea butterate, aqua, Daucus carota sativa root extract, sodium castorate, sodium sunflowerate, sodium cocoa butterate, and Calendula officinalis.

The moisturizer is available from Codex Labs as Bia Eczema Relief Lotion (San Jose, CA). It contains: aqua, Helianthus annuus seed oil, propanediol, glyceryl stearate, glycerin, Lactobacillus ferment, C13-15 alkane, cetyl alcohol, Calendula officinalis meristem cell extract, Haberlea rhodopensis leaf cell extract, Padina pavonica thallus extract, Symphytum officinale leaf cell extract, Cocos nucifera fruit extract, Butyrospermum parkii butter, Moringa oleifera seed oil, Limnanthes alba seed oil, Macadamia integrifolia seed oil, Cedrus deodara wood oil, hydrogenated lecithin, phytosphingosine, hydrolyzed sodium hyaluronate, ceramide NP, sodium phytate, sclerotium gum, xanthan gum, sodium benzoate, potassium sorbate, citric acid, and 1% colloidal oatmeal to conform with monograph M016.

All investigational products were stored in a secured location at room temperature. Study participants were instructed to use the investigational products as described in Table 1.

The study included participants, ≥18 years old with Fitzpatrick skin phototypes I to III. Subjects had moderate AD defined as a SCORing Atopic Dermatitis (SCORAD) score ranging from 25 to 50 (mean = 34.6). Exclusion criteria included women with childbearing potential, cutaneous pathology other than AD, interfering topical or systemic treatment during the previous weeks liable to interfere with the assessment of the cutaneous efficacy of the study product, surgery under general anesthesia within one-month, excessive exposure to sunlight or UV, and the use of antifungal or antibiotic treatments one month prior to or during the study. Participants were allowed to use their topical corticosteroids during the study if needed and were instructed that they must make note of the topical corticosteroid and number of applications if utilized in a daily log. However, there was no steroid use by the participants during the study duration. Participants were required to maintain their hygiene, cosmetics, and lifestyle habits for the duration of the study.

Participants were provided with products and instructed to use topicals at least once daily and oral supplements once/day. Compliance was documented with a study log and products were weighed before and after dispensation.

This was an eight-week, open-label clinical study conducted in Malbork, Poland, performed by EUROFINS Dermscan/Pharmascan (Gdańsk, Poland). It was conducted according to Helsinki Declaration (1964) and its successive updates. The Internal Bioethics Committee at Dermscan Poland approved the protocol. All participants provided written informed consent prior to enrollment. Individuals were screened for eligibility, and all study procedures were performed in Malbork, Poland. The study is registered on clinicaltrials.gov with identifier NCT06819709.

A wash-out period was implemented for all enrolled subjects using the unscented soap twice/day for 2-3 days prior to baseline (D0). Each participant served as their own control. This was accomplished by using a non-lesional reference site (no moisturizer applied) selected in close proximity to the lesional site for biophysical measurements. There were no changes to the methods or trial outcomes after the initiation of the study, and the study was stopped once enrolled participants completed the study. Study visits occurred at a standard interval (SI) screening, baseline (D0), week 4 (D28), and week 8 (D56).

The primary endpoints of this study included a dermatologist-assessed SCORAD at D0 and D56. Secondary endpoints included the comparative measurements of hydration, trans-epidermal water loss (TEWL), surface area of squamae (SSS), and desquamation index (DI) recorded at the SI.

Antioxidant capacity (ie, thermodynamic conversion efficiency of an oxidant probe) of the M3Complex was assessed using four assays: FRAP (Fluorescence recovery after photobleaching), ABTS((2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid) compound), DPPH((2,2-Diphenyl-1-picrylhydrazyl) compound), and ORAC (Oxygen Radical Absorbance Capacity using peroxyl radicals). Trolox was the reference for all measurements. FRAP, ABTS, and ORAC were performed in an aqueous solvent, while DPPH was performed in 50:50 ethanol:water solvent. Additionally, antioxidant equivalents for M3Complex were measured for flavonoids in quercetin equivalent units and for phenolics in gallic acid equivalent units.

Total and objective SCORAD scores were evaluated by a dermatologist at D0 and D56. The total SCORAD was calculated using the formula: A/5 + 7B/2 + C, where A is the extent score, B is the intensity score, and C is the final symptom score. The objective SCORAD removed the subjective component and was calculated by A/5 + 7B/2.

Pruritis was measured in three ways at D0 and D56. The mean itch intensity was rated by the subjects using the numerical rating scale (NRS) where 0 = minimum and 10 = maximum itch. Pruritus improvement was assessed with the 4-point reduction in NRS, the proportion of subjects that achieved a NRS of 0 or 1 and the proportion that achieved a NRS of 0. The third way used a global assessment of itch scale where 0 = no, 1 = mild, 2 = moderate, and 3 = severe itch.

All biophysical measurements were collected at the SI after acclimation to ambient conditions.²⁴ The biophysical properties of two predetermined areas (treated area with active lesion and non-treated reference area without lesion) were measured: TEWL using a Tewameter® (Courage + Khazaka, Köln, Germany), skin hydration using a Corneometer® (Courage + Khazaka, Köln, Germany), and SSS/DI using D-Squame® (Clinical and Derm LLC, Dallas, TX, USA).

PANAS is a validated, patient-oriented questionnaire that measures positive and negative affect.²⁵ Subjects were asked to report these affects over the past week on a 5-point scale ranging from 1 (very slightly or not at all) to 5 (extremely): Interested, Distressed, Excited, Upset, Strong, Guilty, Scared, Hostile, Enthusiastic, Proud, Irritable, Alert, Ashamed, Inspired, Nervous, Determined, Attentive, Jittery, Active, and Afraid. PANAS was administered on the SI.

Differences in SCORAD, pruritis, TEWL, hydration, SSS, and DI were analyzed using paired student t-tests, while non-parametric data such as patient global assessments and PANAS were analyzed with a Wilcoxon rank-sum analysis. A p-value of < 0.05 was considered statistically significant. All comparisons were within group (baseline data served as controls).

The M3Complex demonstrated higher FRAP (9655.50) and ORAC (8566.00) capacity and comparable ABTS (4371.60) and DPPH (4463.60) to ascorbic acid (vitamin C), curcumin, black tea, and green tea (Figure 1A) and showed the broadest ability to perform in all four assays. M3Complex showed the highest phenolic equivalent at 422.60 (Figure 1B) and comparable flavonoid equivalent to vitamin C at 609.10 vs 645.80 (Figure 1C).

Figure 1.

Thirty-five participants were enrolled into this study, with 86% being female (n = 30) and 14% being male (n = 5). The mean age was 45 years (range, 19-73). Of all participants, 80% (n = 28), 17% (n = 6), and 2.9% (n = 1) had Fitzpatrick skin types II, III, and I, respectively. The average total SCORAD at D0 was 34.6 (range = 26-46). The flow of participants throughout the study is shown in Figure 2. Thirty-three subjects completed the study.

Figure 2.

At D56, there were significant reductions (all p < 0.0001) in scores A (extent), B (intensity), C (subjective scores), and total SCORAD by 94%, 92%, 94%, and 93%, respectively (Figure 3A). The mean SCORAD scores at D0 and D56 were 34.6 and 2.6 (Figure 3B).

Figure 3.

The mean oSCORAD scores at D0 and D56 were 25.9 and 2.0, representing a 92.1% reduction (p < 0.0001, Figure 4A). At D56, 100%, 88%, 64%, and 64% of participants achieved oSCORAD50 (50% reduction in oSCORAD compared to D0), oSCORAD75, oSCORAD90, and oSCORAD100, respectively (Figure 4B).

Figure 4.

The mean pruritus NRS reduced from 5.9 to 0.2 (p < 0.0001) between D0 and D56 (Figure 5A). The proportion of subjects at D56 that achieved a 4-point NRS reduction was 85%, an NRS of 0 or 1 was 94%, and an NRS of 0 was 91% (Figure 5B). The global assessment of their pruritus revealed a reduction at both D28 and D56 (Figure 5C).

Figure 5.

The overall score and individual components of positive affect did not change significantly over the study. However, the overall negative affect score reduced significantly at D56 (p < 0.05). Three components of negative affect improved: scared (p < 0.02), and nervous (p = 0.001) at D56, and ashamed (p = 0.03) at D28. See Figure 7.

Figure 7.

Five participants experienced an adverse event throughout the study. Adverse events included throat infection, headache, and toothache and all these events were self-limiting. None of these adverse events led to an interruption in study protocol or withdrawal. None of these were deemed related to the studied products.

JM reports serving as a consultant for Codex Labs (stockholder). PAL reports being on the speaker’s bureau for AbbVie, Arcutis, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche-Posay/L’Oréal, Pfizer, Pierre-Fabre Dermatologie, Regeneron/Sanofi Genzyme, Verrica; reports consulting/advisory boards for Alphyn Biologics (stock options), AbbVie, Almirall, Amyris, Arcutis, ASLAN, Bristol-Myers Squibb, Burt’s Bees, Castle Biosciences, Codex Labs (stock options), Concerto Biosci (stock options), Dermavant, Eli Lilly, Galderma, Janssen, LEO Pharma, Lipidor, L’Oréal, Merck, Micreos, MyOR Diagnostics, Regeneron/Sanofi Genzyme, Sibel Health, Skinfix, Suneco Technologies (stock options), Soteri Skin (stock options), Theraplex, UCB, Unilever, Verdant Scientific (stock options), Verrica, Yobee Care (stock options). In addition, Dr. Lio has a patent pending for a Theraplex product with royalties paid and is a Board member and Scientific Advisory Committee Member emeritus of the National Eczema Association. RKS reports serving as an advisor for LearnHealth, Arbonne, and Codex Labs, and Trace Minerals and has served as a consultant or speaker for Burt’s Bees, Novozymes, Almirall, Novartis, Incyte, Lilly, Sanofi, Bristol Myers Squibb, Pfizer, Nutrafol, Galderma, Abbvie, Leo, UCB, Sun, and Regeneron Pharmaceuticals.