A 12-week, Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of a Nutraceutical Supplement for Mild to Moderate Non-cystic Acne in Young Adults

J Clin Aesthet Dermatol. 2024;17(11):24–30.

by Glynis Ablon, MD, FAAD

Dr. Ablon is with the Ablon Skin Institute and Research Center in Manhattan Beach, California.

FUNDING: This study was sponsored by VitaMedica, the manufacturer of the study product. 

DISCLOSURES: The author reports no conflicts of interest relevant to the content of this article.

Abstract: Background: Acne vulgaris is a chronic, inflammatory skin disease of the pilosebaceous unit frequently cited as the most common condition diagnosed and treated by dermatologists. Among the many therapies developed for treating acne, none are effective for all patients and new treatments are always being sought. A commercial nutraceutical formulated with vitamins, minerals and a proprietary blend of botanicals has been used as a safe and effective adjunctive therapy for non-cystic acne (Clear Skin Formula; VitaMedica®).

Objective: The objective of this study was to evaluate the safety and efficacy of this nutraceutical for treating non-cystic acne.

Methods: Subjects randomly received study product (n=26) or placebo capsules (n=14) which were taken daily for 84 days.

Results: Treatment with the nutraceutical supplement decreased mean (SD) inflammatory lesions counts from 21.4 (9.3) to 10.4 (8.1) (p=0.0001), decreased non-inflammatory lesion counts from 35.0 (17.1) to 19.5 (13.2) (p<0.0001) versus nonsignificant changes for placebo-treated subjects. Mean baseline IGA scores improved by nearly 1 grade from 2.3 (0.5) to 1.4 (0.6) after 84 days of treatment (p<0.0001) versus no change for subjects treated with placebo. The clinical improvements corresponded with significant improvements in acne-related quality of life measures. The nutraceutical supplement was well-tolerated.

Conclusion: These results demonstrate this nutraceutical to be safe and effective adjunctive therapy for patients with non-cystic acne. ClinicalTrial.gov Identifier NCT05879406.

Keywords: Acne vulgaris, nutraceutical, nutritional therapy, vitamins and minerals, clinical trial

Introduction

Acne vulgaris is a chronic, inflammatory skin disease of the pilosebaceous unit¹ and commonly cited as one of the most common conditions diagnosed and treated by dermatologists.² A recent global study conducted on 50,552 individuals older than 16 years in 20 countries revealed an overall acne prevalence of 20.5 percent, reaching 28.3 percent among those aged 16 to 24 years.³ It has been estimated that this represents 231.2 million cases, an approximately 48-percent increase since 1990.⁴ The negative impact of acne on the quality of life of impacted individuals has been well described and has even been associated with serious psychiatric symptoms.^5,6

The pathogenesis of acne is complex and involves four primary features: 1) enhanced sebum gland activity and sebum production; 2) follicular hyperkeratinization and sebaceous follicle obstruction; 3) increased Cutibacterium acnes proliferation; and 4) release of mediators of inflammation. As the causes of acne are multifactorial, numerous therapies have been used to treat the different characteristics of acne. Depending on severity, these include but are not limited to various topical agents (eg, benzoyl peroxide, retinoids, antibiotics), systemic antibiotics (eg, minocycline, doxycycline), hormonal agents (eg, oral contraceptives, spironolactone), and systemic isotretinoin^2,7 although antibiotic resistance due to overprescribing has become problematic.⁸ In addition, there are numerous energy-based devices available for treating acne, such as ablative fractional lasers.⁹ All of these therapies are effective for some patients, but none of them are effective for all patients. In addition, many of these therapies are associated with adverse events, and in some instances, are poorly tolerated by patients, leading to discontinued treatment.² 

In addition to the four primary causes of acne, it has also been suggested that other factors, such as emotional stress, diet, hormonal changes, and immune function may also play a role.¹⁰ There is accumulating evidence that vitamins, minerals, and botanicals may mitigate some of the pro-inflammatory effects from the activation of these underlying factors.¹¹

The objective of this study was to assess the safety and efficacy of a commercial nutraceutical product (Clear Skin Formula; VitaMedica®) for the treatment of non-cystic acne. Ingredients found in this nutraceutical with previously demonstrated benefits for acne include methylsulfonylmethane,^13,14 bromelain,^15–17 burdock root (Arctium lappa),¹⁸ dandelion root (Taraxacum officinale),¹⁹ yellow dock extract root (Rumex crispus),¹⁹ and Oregon grape root (Mahonia aquifolium),²⁰ the vitamins A,^21,22 C,²³ and E,²⁴ and the minerals chromium,²⁵ selenium,²⁶ and zinc.^27,28 Here, the author has evaluated efficacy as measured by the change in baseline inflammatory and non-inflammatory lesion counts, the proportion of subjects who achieve ≥1-grade reduction in baseline Modified Investigator Global Assessment Scores, and improvement in subject non-cystic acne quality of life and self-assessment questionnaires.

Methods

Subjects. Forty (N=40) healthy male and female subjects aged 18 to 40 years with any Fitzpatrick Skin Type were enrolled. Subjects were required to have baseline Modified Investigator Global Assessment (IGA) scores of 2 (mild) or 3 (moderate) (Table 1), a facial non-cystic acne inflammatory lesion (ie, papules and pustules) count greater than 10 but 50 or fewer, and a facial non-cystic acne non-inflammatory lesion (ie, open and closed comedones) count greater than 10 but 100 or fewer. Each subject expressed their willingness to comply with the requirements of the study, such as avoiding tanning booths or sunbathing. Female subjects of childbearing potential agreed to practice effective contraception for the duration of the study and provide a negative urine pregnancy test at the baseline visit.

Exclusion criteria. Reasons for exclusion from study participation included the use of an investigational drug or device within 30 days of enrollment or participation in a concurrent research study; a facial dermatological condition that could interfere with clinical study evaluations such as acne conglobata, acne fulminans, secondary acne, perioral dermatitis, clinically significant rosacea, gram-negative folliculitis, dermatitis, or eczema; facial acne cysts; a facial beard or mustache that could interfere with the study assessments; female subjects with a history of hirsutism, polycystic ovarian disease, or clinically significant menstrual irregularities; regional enteritis, ulcerative colitis, inflammatory bowel disease, pseudomembranous colitis, chronic or recurrent diarrhea, or antibiotic-associated colitis; treatment of any form of cancer within the last six months except complete surgical excision of skin cancer outside the planned treatment area; subjects who received the following topical treatments within the specified washout periods: topical facial astringents and abrasives, prohibited facial moisturizers or sunscreens, or non-cystic acne surgery (1 week); facial antibiotics, other topical facial non-cystic acne drugs, antimicrobial soap, or facial light therapy (eg, LED, PDT) (2 weeks); facial anti-inflammatories and corticosteroids, retinoids, facial chemical peels or microdermabrasion, facial laser therapy (4 weeks); subjects who received the following systemic treatments within the specified washout periods: high-dose vitamin A and beta-carotene supplements (2 weeks), corticosteroids including intramuscular injections (inhaled corticosteroids permitted), antibiotics, other systemic treatments (4 weeks), and systemic retinoids (6 months); female subjects who were pregnant, nursing, or planning to become pregnant during the study; presence of an uncontrolled underlying disease or condition that places the subject’s safety at risk.

Study product. Each capsule contained vitamin A, vitamin C, vitamin E, zinc, selenium, chromium and a proprietary blend of methylsulfonylmethane, bromelain, burdock root, dandelion root, yellow dock root, and Oregon grape root (Table 2).¹² The placebo was a similar-appearing inert capsule. Each subject was also provided with a supply of skin cleanser, moisturizing lotion, and SPF 30 sunscreen to use as instructed during the study (Cetaphil® Gentle Skin Cleanser, Cetaphil® Moisturizing Lotion, and Cetaphil® SPF 30; Galderma Laboratories, Fort Worth, TX).

Study procedures. Subjects were randomized to receive the study product or placebo capsules and instructed to take two capsules of their assigned treatment with food daily. Subjects were instructed to cleanse their face each morning with the gentle skin cleanser provided followed by facial application of the SPF 30 lotion. Subjects were to cleanse their face each evening with the gentle skin cleanser followed by facial application of the moisturizing lotion provided. Subjects returned to the study site on Days 14, 28, 56, 84 for blinded assessments. 

Efficacy assessments. The primary efficacy endpoints on Day 84 were the change in baseline inflammatory lesion counts, change in baseline non-inflammatory lesion counts, and the proportion of subjects who achieve at least a 1-grade reduction in mean baseline Modified IGA Scale scores. 

The secondary efficacy endpoints on Day 84 were change in baseline Non-Cystic Acne Quality of Life Questionnaire scores, change in baseline Non-Cystic Acne Self-Assessment Questionnaire scores, and a favorable analysis of the Clear Skin Formula Supplement Subject Satisfaction Questionnaire. 

The tertiary efficacy endpoints on Day 84 were change in baseline VISIA photography imaging of the left, right and front views of the face to include the Percentile Rating, Score Rating, and Feature Count Rating for wrinkles, texture, pores, red areas, and porphyrins.

Safety assessments. Study safety assessments included the nature, severity, and frequency of adverse events (AEs) associated with the study versus placebo. Safety assessments included the frequency of local and systemic AEs, Investigator Tolerability Assessment, and Subject Tolerability Self-Assessment. A complete blood count (CBC) and comprehensive chemistry panel was performed at baseline and Week 12.

Statistical analysis. The per-protocol (PP) population was the primary population for all statistical analyses. The PP population will include all subjects who randomized and received at least one treatment. For continuous variables, descriptive statistics included the number of subjects (N), mean, median, standard deviation (SD), minimum (min) and maximum (max) values. Categorical variables included the frequency and percentage of each category.

Ethics. Each subject provided written informed consent prior to participating in any study-related activities. Subjects also provided a signed HIPAA form, photography release, and confirmed their willingness to submit to facial imaging. This study protocol and related materials were approved by a commercial Institutional Review Board (Advarra® IRB Services; Columbia, MD). The conduct of this study followed guidelines for the protection of human subjects for research as outlined in the United States FDA 21 CFR Part 50, in accordance with the accepted standards for Good Clinical Practices (GCPs) and the standard practices of the Ablon Skin Institute and Research Center. ClinicalTrial.gov Identifier NCT05879406.

Results

Subjects were randomized to receive the study product (n=26) or placebo capsules (n=14). Demographics and baseline clinical characteristics are summarized in Table 3 by treatment group. There were no significant between-group differences. Acne had been a preexisting condition for 2 to 19 years (mean, 12.1 years).

Efficacy. The results of the primary efficacy endpoints are summarized in Table 4. Among subjects who received active treatment, there were significant improvements in inflammatory and non-inflammatory acne lesions and modified IGA scores. Treatment with the nutraceutical supplement decreased mean (SD) inflammatory lesions counts from 21.4 (9.3) to 10.4 (8.1) (p=0.0001) versus a change from 20.8 (9.3) to 17.9 (7.4) among placebo treated subjects (p=NS). Similarly, subjects receiving active treatment achieved a decrease in non-inflammatory lesion counts from 35.0 (17.1) to 19.5 (13.2) (p<0.0001) versus 34.0 (13.1) to 30.1 (8.3) for placebo-treated subjects. (p=NS). Mean (SD) baseline IGA scores improved by nearly 1 grade from 2.3 (0.5) to 1.4 (0.6) after 84 days of treatment (p<0.0001). In contrast, the mean baseline IGA of 2.2 (0.4) remained essentially unchanged in the placebo group after 84 days at 2.1 (0.4) (p=NS).

The improvement in baseline Non-Cystic Acne Quality of Life Questionnaire scores (Table 5), a secondary endpoint, was significantly greater among subjects receiving active treatment compared to placebo-treated subjects (p<0.05) except for Questions 10 (I avoid going out in public because of my facial non-cystic acne) and Question 13 (Because of my facial non-cystic acne, I feel less attractive to my significant other). The change in baseline Non-Cystic Acne Self-Assessment Questionnaire scores is summarized in Table 6. Here again, the improvement among subjects treated with the nutraceutical supplement was significantly greater than subjects who received placebo except Question 2 (How would you rate your current level of non-cystic acne on your back, chest, and other body areas?). There were no significant between-group differences in the responses to the Clear Skin Formula Supplement Subject Satisfaction Questionnaire (Table 7).

The changes in baseline VISIA photography imaging, a tertiary efficacy endpoint, included a percentile rating, a score rating, and a feature count rating for wrinkles, texture, pores, red areas, and porphyrins; however, there were no significant between-group differences. As an example, the score ratings are summarized in Table 8.

Safety. The Investigator Tolerability Assessment tool and results of the assessment are shown in Table 9 and Table 10. Erythema was significantly higher among placebo-treated subjects at Day 84 while itching was significantly greater among active treatment subjects (for each, p<0.05); however, both were mild. Subject Tolerability Self-Assessment is shown in Table 11. At Day 84, there was one report of mild stinging and one report of moderate itching among the active treatment subjects. There was one unrelated subject-reported adverse event of a minor bruise following an accident in the active treatment group. There were no significant changes in clinical chemistry or hematology parameters.

Discussion

Despite the high global prevalence of acne and the numerous available therapies, the treatment of acne remains far from ideal. Shortcomings of existing therapies include treatment compliance, tolerability and adverse events, cost, and lack of efficacy.²⁹ Due to years of overprescribing, antibiotic resistance of Cutibacterium acnes has reached over 50% in some countries, requiring coadministration of topical retinoids or benzoyl peroxide to maintain effectiveness.³⁰ It is therefore essential to advance new potential acne treatments as much as possible.

The objective of the present study was to assess the safety and efficacy of a novel commercial nutraceutical product for treating non-cystic acne (Clear Skin Formula; VitaMedica®).¹² Although this product has long been available and widely used for the treatment of non-cystic acne, to-date, its efficacy has not been evaluated in a randomized trial. 

A primary measure of efficacy was a comparison of the change in baseline inflammatory and non-inflammatory lesion count achieved by both treatment groups. Based on these measures, subjects in the active treatment group attained significantly better treatment outcomes than placebo-treated subjects (Table 4). Similarly, subjects who received the nutraceutical supplement achieved a nearly ≥1-grade reduction in baseline Modified Investigator Global Assessment Scores compared to those receiving placebo supplement (0.9 versus 0.1, p<0.0001). As the study was conducted for only 84 days, it is possible the continued improvement in each measure of efficacy might be achieved with ongoing use of the product. 

These improvements corresponded with improvements in subject responses to the Non-cystic Acne Quality of Life (Table 5) and Non-Cystic Acne Self-assessment Questionnaire (Table 6); however, there were no between-group differences in the Clear Skin Formula Supplement Subject Satisfaction Questionnaire (Table 7). The nutraceutical supplement was well-tolerated, with only mild itching reported.

Conclusion

A novel nutraceutical product formulated with select vitamins, minerals and a proprietary blend of botanicals with demonstrated efficacy for treating non-cystic acne is a safe and effective adjunctive therapy for patients with non-cystic acne.¹² The results of the current randomized study demonstrate the product is effective for reducing the number of inflammatory and non-inflammatory acne lesions and physician assessments of acne severity. These clinical improvements correspond with overall improvements in acne-related quality of life. 

Acknowledgement 

This study was sponsored by VitaMedica Corporation, Henderson, NV. The author acknowledges the assistance of Dr. Carl S. Hornfeldt, Apothekon, Inc., during the preparation of this manuscript.

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