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Complementary and Alternative Methods for Treatment of Acne Vulgaris: a Systematic Review

  • Molly R. Marous
  • Hania K. Flaten
  • Brigitte Sledge
  • Hope Rietcheck
  • Robert P. Dellavalle
  • Tina Suneja
  • Cory A. Dunnick
Invited Commentary
  • 17 Downloads

Abstract

Purpose of Review

To review the current literature regarding complementary and alternative treatment options for acne vulgaris.

Recent Findings

Acne vulgaris is an increasingly prevalent disease worldwide. While conventional methods of treatment are still primarily used to treat acne, complementary and alternative methods of treatment are becoming utilized in conjunction or in place of prescription medications.

Summary

Studies have shown comparable benefit of Complementary and Alternative Medicine (CAM) therapies to conventional treatment. Oral green tea extract was a moderately effective treatment of inflammatory acne without significant side effects. Nicotinamide oral and topical preparations demonstrated efficacy in the treatment of moderate inflammatory acne without significant side effects. Oral zinc gluconate was not as effective as oral minocycline in the treatment of inflammatory acne. CAM therapy has relatively few reported side effects for acne vulgaris, and is mildly effective in treatment of inflammatory and comedonal acne. More studies are needed for further comparison of CAM modalities with each other as well as with conventional treatment.

Keywords

Acne vulgaris Complementary treatment Alternative treatment 

Introduction

Complementary and alternative medicine (CAM) is defined as interventions neither taught widely in medical schools nor generally available in US hospitals [1]. Complementary medicine in general uses natural, less invasive interventions before costly, invasive ones [2]. CAM is used by one-third (33.2%) of US adults. Fifty-nine million of Americans spend money out of pocket on complementary health care per year. Total spending on CAM in the USA is estimated to be $30.2 billion per year [3].

Patients with chronic medical conditions often seek out CAM therapy when conventional medication treatments are unsuccessful at controlling their disease. Individuals also use CAM therapy due to the perception that these treatments are more natural compared to conventional treatment. Adverse effects of CAM nonetheless may be significant [4].

Many dermatologic conditions including acne, psoriasis, and atopic dermatitis are common chronic conditions. Thus, there is a wide body of literature supporting and exploring various CAM treatments of these conditions [5]. In the 1990s, 6.7% of the US population reported having skin diseases in the last 12 months had used alternative therapy and 2.2% had seen an alternative medicine practitioner which include massage therapists, chiropractors, acupuncturists, and practitioners offering hypnosis for their condition [1]. Multiple factors have been identified which motivate patients to try CAM therapies. Factors include cultural determinants, dissatisfaction with conventional medicine, desire for natural therapies, skepticism regarding efficacy of conventional medicine, perception that conventional medicine is unsafe and that CAM is less toxic, and failure of conventional medicine leading to trying any possible therapy [4, 6, 7, 8, 9].

Another reason for the growth of CAM treatment includes formularies which limit drugs available to patients. In addition, 27 million Americans under age 65 (10% of the population in this age group) are uninsured and as a result have limited access to prescription drugs (https://www.cbo.gov/publication/51385). These patients may seek out over-the-counter treatments for acne rather than prescription since their access to physicians is limited. Over-the-counter treatments include salicylic acid or benzyl peroxide topical agents commonly used in Western medicine, as well as alternative treatments such as tea tree oil.

Due to its high prevalence, acne constitutes the most disabling skin diseases in the world and comprises approximately 0.6% of all disability from all diseases [10]. The objective of this review is to evaluate the current literature detailing CAM treatments of acne.

Methods

A literature search was performed in September of 2017 using the databases PubMed, Ovid, Embase, and Scopus. Search terms were “Complementary OR Alternative AND Therapy AND Acne vulgaris”. Inclusion criteria included English language, human subjects, date range of January 1, 1990 to October 1, 2017, and evidence level 1A-4 according to level of evidence guidelines [11]. One thousand twelve hundred and sixty articles met inclusion criteria and were reviewed by investigators. Further articles excluded consisted of nonhuman in vitro studies, review articles, and non-CAM articles. After correcting for duplicates, a total of 30 studies were included in this review.

Results

Green Tea Extract

Four studies have reported successful treatment of mild-to-moderate acne using green tea extract. Mahmood et al. looked at 3% green tea in water combined with oil emulsion and found significant reduction in sebum in participants (p < 0.5%). Significant difference of skin sebum production was measured using Sebumeter MPA 5 [12]. Forest et al. compared a 500-mg tablet of green tea extract to placebo tablets and found a significant decrease in inflammatory acne lesions in the treatment cohort Forest et al. compared 50 cc of Aloe vera juice to 50 cc of water with artificial Aloe vera flavor administered orally once daily for 30 days and although oral Aloe vera juice was effective in diminishing inflamed and total acne lesions, this effect was not statistically significant [13•]. Lu et al. compared 1500 mg green tea extract to placebo tablet composed of cellulose and reported a significant decrease in total acne lesions in the treatment group. Inflammatory lesion counts (papules, pustules, nodules, and cysts) were used as the major outcome measurement [14]. Yoon et al. examined the effects of Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, and found a reduction in sebum and inflammation as well as an induction of sebocyte apoptosis and decreased viability of P. acnes, thus targeting almost all pathogenic features of acne. In an 8-week clinical trial, EGCG, in 1 and 5% solutions, significantly improved both inflammatory and non-inflammatory acne lesions when compared to a vehicle control (p < 0.05). Revised Leeds grading and acne lesion counts were performed to measure significant difference, and a visual analogue scale (VAS) was also measured to assess subjective assessment of patients with time [15]. Adverse event rates were not significantly found in any of these three studies (Tables 1, 2 and 3). Table 2 shows the levels of evidence for therapeutic studies.
Table 1

Demographic information of reviewed articles

 

Author/year

Patient population

Number of subjects

Patient acne type

Geographic location

Green tea extract

Forest et al., 2014

Male and female age 12–17 with mean of 14

34

Mild-moderate

Iran

Mahmood et al., 2010 [12]

Male age 25–40

10

Mild-moderate

Pakistan

Lu et al., 2015

Female age 25–45 with mean 28

64

Moderate-severe

Taiwan

Nicotinamide

Weltert et al., 2004 [16•]

Males and females

158

Moderate inflammatory

Unspecified

Shalita et al., 1995 [17]

Male and female age 15–25

76

Moderate inflammatory

USA

Niren et al., 2006

Male and female age 12+

159

Mild-moderate

USA

Zinc

Dreno et al., 2001 [18•]

Male and female age 12+ with mean of 19

332

Mild-moderate Inflammatory only

France

Sharquie et al., 2008 [19]

Male and female age 12–27 with mean 19

40

Mild-moderate

Iraq

Other

Aloe vera

Orafidiya et al., 2014

Male and female age 20–25

84

Mild-severe

Nigeria

Bukachiol/Gingko biloba

Polokova et al., 2015

Age 12–25

111

Mild-moderate

France

Cannabis seed

Ali et al., 2015

Asian male age 20–35

Unspecified

Unspecified

USA

Casuarina equisetifolia bark

Shafiq et al., 2014 [20]

Male and female age 17–34

50

Unspecified

Pakistan

Cedarwood oil

Hassoun et al., 2016 [21]

Female age 35

1

Mild-moderate

USA

Clay jojoba

Meier et al., 2012 [22]

Mean age 32

194

Mild-moderate

Germany

Copaiba essential oil

Da Silva et al., 2012 [23]

Unspecified

Unspecified

Mild

Brazil

Eladi Karem

Appiah et al., 2017 [24]

Male and female mean age 30

21

Mild-moderate

UK

Zingiber officinale—ginger

Miglani et al., 2014

Male and female age 12–25 with mean 18

31

Mild-severe

India

Granulysin-derived Peptide-20

Lim et al., 2015 [25]

Male and female age 19+ with mean 22

30

Mild - Severe

South Korea

Hippophae rhamnoides/Cassia fistula extract

Khan et al., 2014

Age 18–37

25

Mild-moderate

Pakistan

Honeybee venom

Han et al., 2013 [26]

Unspecified

12

Unspecified

South Korea

Kanuka honey

Semprini et al., 2017

Age 16–40

Unspecified

Mild-moderate

New Zealand

Keigai-rengyo-to

Kim et al., 2012

Males age 13–35 with mean 22

44

Mild-severe

Seoul, Republic of Korea

Lemon juice

Bilgili et al., 2014 [27]

Unspecified

123

Unspecified

Turkey

Omega-3 fatty acids

Ruben et al., 2008

Male and female age 18–23

5

Unspecified

USA

Pentothenic acid

Yang 2014

Male and female

51

Mild-moderate

USA

Polyherbal Unani

Lone et al., 2012 [387]

Male and female age 12–30

25

Mild-severe

India

Green algae

Bartenjev et al., 2011 [28]

Females Age 18–35

50

Mild

France

Tea tree oil

Malhi et al., 2017 [29]

Male and female age 14–45

14

Mild-moderate

Australia

Vitamin A

Dreno et al., 2009 [30]

Female age 30–40

397

Mild-moderate

France

CAM therapies for acne vulgaris. Table 1 describes demographic information of patient populations studied in reviewed articles

Table 2

Levels of Evidence for Therapeutic Studies

Level

Type of Evidence

1A

Systematic Review (with homogeneity) of RCTs

1B

Individual RCT (with narrow confidence interval)

1C

All or none study

2A

Systematic Review (with homogeneity) of cohort studies

2B

Individual cohort study (including low quality RCT, e.g. <80% follow up)

2C

“Outcomes” research, Ecological studies

3A

Systematic Review (with homogeneity) of case control studies

3B

Individual case control study

4

Case series (and poor quality case control and cohort studies)

5

Expert opinion without explicit critical appraisal or based on physiology bench research or “first principles”

Table 3

Results of reviewed articles

 

Compound

Outcomes

Results

Side effects

Author/year

Evidence level

Formulation

Comparison arm

Lesion count

Subjective grading scale

Sebum production

Green tea extract

Three capsules of 500 mg green tea extract three times for 30 days

Three capsules of 500 mg of placebo 3 times a day for 30 days

Total acne lesions and inflamed acne lesions decreased significantly in green tea extract group. No significant difference in the reduction of non-inflammatory acne lesions between treatment and control groups

N/A

N/A

Aqueous green tea extract could be an effective alternative treatment for inflammatory acne.

Not significant

Forest et al., 2014

1B

3% green tea in water combined with oil emulsion applied for 8 weeks

N/A

N/A

N/A

Statistically significant reduction in sebum production of cohort following 3% green tea application

3% green tea emulsion could be an effective treatment for acne vulgaris

Not significant

Mahmood et al. 2010 [12]

2B

1500 mg decaffeinated green tea extract daily for 4 weeks

1500 mg of placebo (cellulose) daily for 4 weeks

Green tea extract showed statistically significant reduction in lesion counts from baseline compared to placebo cellulose

N/A

N/A

Oral green tea extract could be an effective alternative treatment for acne vulgaris.

Not significant

Lu et al., 2015

1B

Epigallocatechin-3-gallate (EGCG), a green tea extract, in 1 and 5% solutions for 8 weeks

Vehicle control

EGCG improved both inflammatory and non-inflammatory lesion counts compared to control (p < 0.05)

Visual analogue scale (VAS) score decreased significantly from baseline after 2 weeks (p < 0.05)

 

Therapeutic rational for use of EGCG in acne.

Not significant

Yoon et al., 2012

1B

Nicotinamide

4% nicotinamide gel twice daily for 8 weeks

4% erythromycin gel twice daily for 8 weeks

4% nicotinamide gel (52.4%) and 4% erythromycin (53.8%) gel produced no statistically significant reduction in total acne lesions

N/A

N/A

4% Nicotinamide gel could be a comparably effective treatment for moderate inflammatory acne.

Not significant

Weltert et al., 2004 [16•]

1B

4% nicotinamide gel twice daily for 8 weeks

1% clindamycin gel twice daily for 8 weeks

4% nicotinamide gel and 1% clindamycin gel produced similar reduction in total acne lesions.

After 8 weeks, both treatments produced comparable (p = 0.19) beneficial results in the Physician’s Global Evaluation of Inflammatory Acne

N/A

4% nicotinamide gel could be a comparably effective treatment for moderate inflammatory acne. Power of the study was inadequate to detect treatment differences, with sample sizes of only n = 38 for each comparison arm.

Not significant

Shalita et al., 1995 [17]

1B

Nicotinamide 750 mg, zinc 25 mg, copper 1.5 mg, folic acid 500 μg daily for 8 weeks OR twice daily OR undisclosed frequency

None

63% of patients had a significant decrease in lesion count at the end of 8 weeks. Lesion counts in the treatment group compared with those taking oral antibiotics or using topical retinoids alone decreased with no significant difference between the groups.

Using the Patient Global Evaluation tool, there was a significant decrease in acne severity; moderately better or much better acne improvement was reported in 79% after 4 weeks and 88% at 8 weeks; 21% (at 4 weeks) and 12% (at 8 weeks) rated no change, slightly worse, or much worse. This was a significant difference (p < .0001).

N/A

The nicotinamide combination therapy could be an effective alternative or additive, with oral antibiotics or topical therapies, in the treatment for mild to moderate acne.

Not significant

Niren et al., 2006

2B

Zinc

30 mg zinc gluconate daily for 3 months

100 mg minocycline daily for 3 months

Clinical success, defined as more than 2/3 decrease in inflammatory lesions found significant difference (p < 0.001) for zinc gluconate and minocycline hydrochloride was 31.2 and 63.4% respectively.

N/A

N/A

Minocycline hydrochloride showed 9% superiority in action at 1 month and 17% superiority at 3 months. After 90 days of treatment, MD − 16.42, (RR 2.03, 95% CI 1.56 to 2.63). Zinc gluconate is not as effective as minocycline hydrochloride in the treatment of acne vulgaris.

Unspecified

Dreno et al., 2001 [18•]

1B

Topical 2% tea lotion daily for 2 months

Topical 5% zinc sulfate lotion daily for 2 months

2% tea lotion had a statistically significant clinical improvement, scored by counting the number of inflammatory acne lesions before and after treatment, 5% zinc sulfate solution was beneficial but did not reach statistical significance for clinical improvement.

N/A

N/A

2% tea lotion is more effective for treating mild to moderate acne compared with 5% zinc sulfate.

Mild self-resolving itching was reported for 2% tea lotion and mild self-resolving itching and burning was reported for 5% zinc sulfate.

Sharquie et al., 2008 [19]

2B

Other

Aloe vera

100% Aloe vera gel OR 50% Aloe vera gel OR Aloe vera gel combined with 2% Ocimum gratissimum

Placebo gel 1% clindamycin gel

Activity of pure Ocimum gel and 25% Aloe vera in Ocimum had similar results of 1% clindamycin. 50% Aloe vera in Ocimum and 100% Aloe vera in Ocimum showed significantly greater lesion reduction compared to negative control. Neither preparations of Ocimum oil and aloe gel nor 1% clindamycin significantly decreased nodulocystic lesions. Nodulocystic lesions were found to be more resistant to treatments than papulopustular lesions

N/A

N/A

Ocimum oil lotion formulated with 50% or 100% aloe gel proved to be the most active gel for treating papulopustular acne (p < 0.05).

Not Significant

Orafidiya et al. 2014

1B

Bukachiol/Gingko biloba

Unspecified dose of Bukachiol/Gingko biloba extract added to 0.1% adapalene gel; applied twice daily for 2 months

Control arm consisted of adapalene 0.1% and vehicle cream.

56% reduction in inflammatory and non-inflammatory lesions in treatment group compared to 50% in control

N/A

N/A

Bukachiol/Gingko biloba/mannitol addition to 0.1% adapalene provides an additive effect for treatment of acne vulgaris

Not significant

Polakova et al. 2015

1B

Cannabis seed

3% cannabis seed cream; applied twice daily to cheeks for 12 weeks

None

N/A

Erythema content significantly decreased with treatment

Skin sebum significantly decreased with treatment cream.

3% cannabis seed is an effective treatment for acne vulgaris

Not significant

Ali et al. 2015

2B

Casuarina equisetifolia bark

5% Casuarina equisetifolia bark extract applied twice daily then washed with water for 45 days

Unspecified concentration of benzoyl peroxide wash applied once daily for 45 days

N/A

Patient grading on 5-point scale (excellent response, good response, poor response, no response, no comment); the 5% cream had a significant improvement in acne from baseline compared with the benzoyl peroxide group.

N/A

5% Casuarina equisetifolia bark extract is an effective treatment for acne vulgaris.

No side effects noted in 5% cream group; side effects of irritation, redness, and swelling of skin noted in benzoyl peroxide group.

Shafiq et al., 2014 [20]

2B

Cedarwood oil

2–3 drops of cedarwood oil combined with pea-sized amount of 1% adapalene

None

N/A

After 4 weeks of treatment, patient and physician noted significant improvement of face, chest, and upper back acne.

N/A

Cedarwood oil could be an effective additive treatment for mild to moderate acne.

Not significant

Hassoun et al., 2016 [21]

4

Clay Jojoba

Unknown concentration of clay Jojoba oil applied to face 2–3 times/week for a total of 15–20 min per treatment; trial period of 6 weeks

None

54% reduction in total lesion count

80% of patients rated skin sensation and effectiveness of the mas as good or very good.

N/A

Clay jojoba masks can be an effective alternative treatment for acne vulgaris

Not significant

Meier et al., 2012 [22]

2C

Copaiba essential oil

100 mL of neutral liquid soap for facial cleansing followed by copaiba essential oil in gel form; applied twice daily for 21 days

Placebo gel

Calculated by percent of total facial area with acne lesions: decreased in acne severity (69% total variance within data set) compared with placebo (26.8% of total variance in dataset)

N/A

N/A

Copaiba essential oil had a significant decrease in percent of facial area affected with acne lesions and can be an effective alternative for acne vulgaris.

Not significant

Da Silva et al., 2012 [23]

1B

Eladi Karem

Eladi Karem in coconut oil; 5 mL applied daily

Coconut oil; 5 mL applied daily

Treatment group showed a 59% reduction in total lesion count, 60% reduction in inflammatory lesions, and 59% reduction in non-inflammatory lesions

N/A

N/A

Eladi Karem in coconut oil showed significant improvement in acne lesions and could be a good alternative treatment for acne vulgaris

Not significant

Appiah et al., 2017 [24]

1B

Zingiber officinale—ginger

Zingiber officinale—ginger 6C potency in four pills four times a day for 1 week, if improvement then dosage increased to 30C, 200C, and 1 M in sequential fashion; 1 week on and 1 week off for 6 months

None

Lesion counts decreased in patients with mild and moderate acne. No significant decrease in lesion count for patients with severe acne.

Significant improvement in Global Acne Grading Scale score in subjects

N/A

Zingiber officinale can be an effective treatment for acne vulgaris.

Not significant

Miglani et al., 2014

2B

Granulysin-derived peptide-20

Granulysin-derived peptide 20 Granulysin-derived peptide 20 (GDP20) which is the concentration at which they found most antibacterial efficacy, in water-soluble cream formulation applied to acne lesions twice a day for 12 weeks.

None

Comedonal and papular lesions increased significantly in the GDP20 group; pustular lesions in the GDP20 group decreased significantly compared to baseline; a decrease in nodular lesions was consistently seen although the difference was not statistically significant compared to baseline

N/A

N/A

Granulysin-derived peptide 20 could be an effective treatment for pustular and nodular acne.

Not significant

Lim et al., 2015 [25]

1B

Hippophae rhamnoides/Cassia fistula

Hippophae rhamnoides/Cassia fistula 500 mg topical solution applied twice daily for 12 weeks extract

Placebo formulation (vehicle) administered on opposite cheek of active formulation.

N/A

N/A

21.13% sebum reduction with 5% max concentration of extract

Hippophae rhamnoides and Cassia fistula plant extract could be an effective treatment for mild to moderate acne.

Not significant

Khan et al., 2014

1B

Honeybee venom

Honeybee venom unknown formulation of honeybee venom applied to unknown area of skin for 2 weeks

Cosmetics without purified bee venom (PBV)

Significant reduction in inflammatory and non-inflammatory lesion counts in treatment group

N/A

N/A

Honeybee venom could be an effective treatment for inflammatory and non-inflammatory acne vulgaris.

Not significant

Han et al., 2013 [26]

1B

Kanuka honey

Kanuka honey topical 90% medical grade kanuka honey with 10% glycerine base was applied twice daily for a 30–60 min time period per treatment for a total of 12 weeks

Antibacterial soap twice daily for 12 weeks

N/A

7.6% of treatment group had a 2+ improvement based on Investigative Global Assessment (IGA) criteria; however, there was no statistical significance

N/A

Kanuka honey could be a comparable treatment alternative for acne vulgaris.

Not significant

Semprini et al., 2017

1B

Keigai-rengyo-to

Keigai-rengyo-to Keigai-rengyo-to extract (KRTE) 7.4 g three times a day after meals for 4 weeks

Three additional study arms: waiting list, acupuncture only and acupuncture combined with KRTE

Statistically significant mean percent reduction in total acne lesions

N/A

N/A

Keigai-rengyo-to extract could be an effective alternative therapy for acne vulgaris.

Not significant

Kim et al., 2012

1B

Lemon juice

Lemon juice unspecified amount

None

N/A

Patients reported improvement with daily use of lemon juice on acne lesions

N/A

Lemon juice could be a beneficial additive treatment for acne vulgaris.

Not significant

Bilgili et al., 2014 [27]

2C

Omega-3 fatty acids

Omega 3 fatty acids eicosapentaenoic acid 100 mg, EGCG 200 mg, zinc glucontae 15 mg, selenium 200 μg, and chromium 200 μg for 2 months

None

4 out of 5 subjects had reduced total lesion count

Marked decrease in inflammation and redness of acne lesions.

N/A

Addition of Omega 3 fatty acids could be beneficial in the treatment of acne vulgaris.

Not significant

Ruben et al., 2008

4

Pentothenic acid

Pentothenic acid; two tablets of 2.2 g pentothenic acid or twice daily with food for 12 weeks.

Two tablets of placebo twice daily with food for 12 weeks

Lesion count in the treatment group versus placebo was decreased by 68.1% and was statistically significant after 12 weeks.

N/A

N/A

Pentothenic acid could be an effective alternative therapy for mild to moderate acne.

Not significant

Yang 2014

1B

Polyherbal Unani

Polyherbal Unani Unani 6–10 g applied to face nightly and then washed with lukewarm water in the morning for 45 days

None

Significant reduction in lesion count at end of 45 day trial

Reduction in acne severity using Cook’s acne grading system at the end of 45-day trial

N/A

Polyherbal Unani could be an effective alternative therapy for acne vulgaris.

Not significant

Lone et al., 2012

2B

Green algae

Green algae moisturizer with unknown dosage of green algae with salicylic acid applied twice daily for 2 months

None

Number of inflammatory and retentional lesions on the forehead, cheeks, and chin decreased after 2 months of use

N/A

Level of sebum secretion decreased 33.4%, and level of scaling decreased by 38.5%

The addition of green algae in cosmetic creams could be a beneficial prevention measure for acne vulgaris.

Not significant

Bartenjev et al., 2011 [28]

2B

Tea tree oil

Tea tree oil 7 mg/g tea tree face wash followed by 200 mg/g tea tree medicated gel applied twice daily for 12 weeks

None

Total acne lesion counts compared with baseline were significantly reduced (from 25 at baseline to 10 at 12 weeks)

Significant improvement in Investigative Grading Assessment (IGA) acne score by patients.

N/A

Tea tree oil could be an effective alternative therapy for mild to moderate acne vulgaris.

Self-resolving local peeling, dryness, and scaling.

Malhi et al., 2017 [29]

2B

Vitamin A

Vitamin A oil in water mattifying emulsion with all-trans retinaldehyde 0.1% and glycolic acid 6% for application to facial acne daily for 90 days

None

Retentional and inflammatory acne lesions decreased significantly over the 90-day period

N/A

N/A

Retinaldehyde and glycolic acid could be an effective alternative therapy for acne vulgaris.

Mild self-resolving irritation, skin tightening, and pruritis.

Dreno et al., 2009 [30]

2B

Table 3 reviews the results and conclusions of each article reviewed along with corresponding level of evidence

Nicotinamide

Three studies have shown improvement in acne vulgaris with the use of nicotinamide formulations. Niren et al. showed nicotinamide/zinc/copper/folic acid regimen significantly reduced acne lesions compared with placebo group and performed similarly to oral antibiotic or topical retinoid regimens [31]. Shalita et al. reported 4% nicotinamide gel performed similarly to 1% clindamycin gel in both decreasing total acne lesions and in the Patient Global Evaluation Scale [17]. Power of this study was inadequate to detect treatment differences, with sample sizes of only n = 38 for each comparison arm. Weltert et al. showed clinically similar results in acne lesion counts with 4% nicotinamide gel and 4% erythromycin gel [16•]. Adverse event rates were not significantly found in any of these three studies. The alternative treatments avoid emergence of resistant microorganisms, an adverse event associated with use of antimicrobials.

Zinc

Two studies reported on the use of zinc as a treatment for acne vulgaris. Dreno et al. found that an oral suspension of zinc gluconate had a significant inferior performance (31.2% clinical success rate) when compared with oral minocycline (63.4% clinical success rate) [18•]. Patients received either 30 mg elemental zinc or 100 mg minocycline over 3 months. Minocycline had a superior effect with respect to mean change in lesion count, evaluated to be 17%. The majority of adverse events for both arms concerned the gastrointestinal system and was moderate. Sharquie et al. showed that topical 2% tea lotion is more effective in treating mild-to-moderate acne when compared with topical 5% zinc sulfate [19].

Other CAM Treatments

Multiple studies were found reporting success of individual CAM therapies in treating acne vulgaris. We have reported effect size when it was noted in the following studies. Orafidiya et al. showed Ocimum gratissimum (leaf) essential oil with and without Aloe vera gel was beneficial in treatment of papulopustular acne when compared to 1% clindamycin. Application occurred twice daily for 4 weeks. The activity of 0 and 25% aloe gel-content Ocimum oil preparations was similar to that of 1% clindamycin (control), while the preparations containing 50 or 100% aloe gel exhibited significantly better effects (p < 0.05) than the control [32]. Polakova et al. found an additive benefit when Bukachiol/Gingko biloba/Mannitol was added to 0.1% adapalene gel. Application occurred once a day for 2 months and measurements were recorded at baseline, day 28, and day 56. At the end of the trial, the percent decrease from D0 was 62.7% for the active association group and 41.5% for the vehicle association group; the difference between both groups was statistically significant (P < 0.05) and in favor of the active association group [33]. Ali et al. discussed the use of 3% Cannabis seed extract cream versus vehicle in reducing erythema content and skin sebum in patients with acne vulgaris. Application occurred twice a day for 12 days and measurements were recorded at baseline and every 2 weeks thereafter. Measurements demonstrated that skin sebum and erythema content of base plus 3% Cannabis seeds extract treated side showed significant decrease (p < 0.05) compared with base-treated side [34]. Shafiq et al. showed the benefit of 5% Casuarina equisetifolia bark extract compared to topical benzoyl peroxide based on a patient feedback scale. Application of the herbal cream occurred twice daily for 45 days after which there was a significant difference (p < 0.001) compared to baseline assessed by Cook’s acne grading scale [20]. Hassoun et al. presented a case report showing the effectiveness of cedarwood oil in treating mild-to-moderate acne; after 4 weeks of adding several drops of cedarwood oil to tretinoin cream, there were significant improvements in acne lesion counts [21]. Meier et al. reported a significant reduction in papulopustular acne lesions with the use of clay jojoba facial masks comparing difference at baseline versus after 6 weeks of applying masks two to three times per week. This was an open, prospective, observational pilot study and lacked vehicle control as well as blinding. Both inflammatory and non-inflammatory skin lesions were reduced significantly after treatment compared to baseline [22]. Da Silva et al. showed the effectiveness of Copaiba essential oil versus vehicle in reducing facial acne lesions. Application occurred twice daily for 21 days. There was a highly significant decrease in the surface affected with acne in the areas treated with the 1.0% copaiba essential oil preparation (F = 86.494, p = 0.000, r = 0.834; r2 = 0.695), while apparent decrease in the surface affected with acne subsequent to placebo application was not accepted, since at least 73% of the effect could not be explained [23]. Appiah et al. reported the use of Eladi Karem in coconut oil and its success in improving mild and moderate acne versus vehicle control. Application occurred daily for 28 days. There was a significant improvement in the treatment group (p < 0.005) measured by reduction in both inflammatory and non-inflammatory lesions while the control group had no significant changes [24]. A report from Miglani et al. showed significant improvement (p < 0.001) in mild-to-moderate acne lesion counts and Global Acne Grading Scale score with the use of Zingiber officinale (ginger) over a period of 6 months [35]. Lim et al. studied Granulysin-derived peptide 20 and found it to be beneficial in treating cystic and pustular acne compared to baseline over 12 weeks (p < 0.05) while concomitantly increasing the severity of comedonal and papular acne [25]. Khan et al. shared data revealing Hippophae rhamnoides and Cassia fistula plant extract significantly reducing sebum production in the skin versus vehicle application (p < 0.05) following application twice daily for 12 weeks [36]. Han et al. discussed the success of honeybee venom in the treatment of both non-inflammatory and inflammatory acne compared to use of vehicle cosmetics without bee venom. Significant difference (p = 0.027) was observed in lesion counts of the treatment group versus control after 2 weeks [26]. Semprini et al. showed a mild subjective improvement in acne following use of topical 90% medical-grade kanuka honey with 10% glycerine base applied twice daily for a 30–60-min time period per treatment for a total of 12 weeks but did not reach statistical significance when compared to antibacterial soap (p = 0.17) [37]. Kim et al. showed oral Keigai-rengyo-to extract (KRTE) dosed at 7.4 g three times a day after meals for 4 weeks to be effective in treating non-inflammatory and inflammatory acne lesions compared to no treatment, acupuncture only, and acupuncture combined with KRTE. KRTE only showed a statistically significant difference in both mean percent change of inflammatory and non-inflammatory acne lesions [38]. Bilgili et al. reported an additive subjectively measured benefit of topical lemon juice for treating acne vulgaris [27]. Rubin at el. showed five cases of a reduction in acne lesion count and facial inflammation and erythema with the self-administration of oral omega-3 fatty acids after 2 months [39]. Yang et al. demonstrated the effectiveness of oral pentothenic acid versus placebo in the treatment of mild-to-moderate acne. Measurements of total lesion count showed significant reduction in the pantothenic acid group versus placebo after 12 weeks (p = 0.0197) [40]. Lone et al. showed a significant reduction (p < 0.01) in mild, moderate, and severe acne lesion counts and positive subjective grading criteria with the use of topical polyherbal unani compared to baseline. Administration occurred once a night for 45 days [41]. Bartenjev et al. revealed the effectiveness of combining salicylic acid with green algae in preventing acne vulgaris lesions. After 2 months of use, the number of inflammatory and retentional lesions on the forehead, cheeks, and chin decreased significantly [28]. Malhi et al. reported successful acne lesion reduction with the use of topical tea tree oil compared to baseline (p < 0.0001). Application occurred twice daily for 12 weeks [29]. Dreno et al. discussed the success of a retinaldehyde and glycolic acid topical solution in reducing mild-to-moderate acne with significant decrease in both inflammatory and retentional lesions from baseline to 90 days (P < 0.0001). Application occurred with continued use of previous acne treatments [30].

Discussion

Complementary and alternative treatments for acne vulgaris is an emerging field of investigation and one that shows increasing promise. As the popularity of CAM increases throughout the USA, so do research studies investigating single treatment therapies or comparing CAM to conventional medicines. This systematic review focused on treatments that can be attained without prescriptions. The studies evaluated in this review demonstrate the variety of treatments, ranging from plant-based to vitamin derivatives, which have equal or greater efficacy with minimal side effects compared with standard prescription treatments.

Significant results were found in many randomized control trials presented. However, a meaningful comparison between CAM treatments is difficult to perform due to differing analysis modalities used in each study. Twenty-two (76%) studies included used number of acne lesions as the primary endpoint; however, there were others that based results solely on the opinion of subjects and investigators. Several subjective criteria were used in these studies, including Global Severity Assessment and Global Acne Grading Scale, which are not comparable to one another. Although this review cannot compare CAM treatments directly, the evidence presented indicates a significant efficacy and safety profile although the CAM treatments were not studied in the rigorous manner of conventional therapies which require two large randomized control trials verse vehicle achieving statistical significance.

Complementary and alternative medicine is a promising avenue for treatment of a variety of illnesses, including acne vulgaris. An increasing amount of evidence has demonstrated that natural plant-based and vitamin-derived compounds are legitimate therapeutic options for treating acne vulgaris. The global burden of acne has been increasing in recent years proving CAM more relevant than ever as viable treatment options for patients in diverse cultures and environments. With the growth in popularity, more studies are needed to compare both individual CAM modalities and CAM with conventional medicine.

Prospero listing: CRD42017077524

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Supplementary material

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ESM 1 (DOCX 15 kb)
13671_2018_230_MOESM2_ESM.docx (42 kb)
ESM 2 (DOCX 41 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Molly R. Marous
    • 1
  • Hania K. Flaten
    • 2
  • Brigitte Sledge
    • 3
  • Hope Rietcheck
    • 2
  • Robert P. Dellavalle
    • 2
    • 4
  • Tina Suneja
    • 5
  • Cory A. Dunnick
    • 2
    • 6
  1. 1.Geisinger Commonwealth School of MedicineScrantonUSA
  2. 2.Department of DermatologyUniversity of Colorado School of MedicineAuroraUSA
  3. 3.Texas College of Osteopathic MedicineFort WorthUSA
  4. 4.Department of Veteran Affairs Medical Center, Department of Veterans Affairs Rocky Mountain Regional Medical Center, Dermatology ServiceAuroraUSA
  5. 5.Department of EpidemiologyColorado School of Public HealthAuroraUSA
  6. 6.Department of DermatologyColorado Permanente Medical GroupCentennialUSA

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