The multifactorial nature of acne suggests that there are multiple opportunities to intervene in its development. Several natural compounds have the potential to excel in acne management by targeting various aspects during acne development. For example, some natural compounds possess antimicrobial or bactericidal activity, while others exert powerful anti-inflammatory action.
The rationale for fish-oil supplementation as a treatment for acne stems from the observation that people who habitually consume a diet mainly consisting of oily fish have a lower overall incidence of acne (Khayef 2012; Skroza 2012).
A study of 93 acne patients showed that individuals who consume a Mediterranean diet, which is a plant-based diet rich in omega-3s, are less prone to acne that those who follow other dietary patterns (Skroza 2012).
In a clinical trial, 13 patients with inflammatory acne were given 930 mg of the omega-3 fatty acid eicosapentaenoic acid (EPA) daily for twelve weeks. Some subjects experienced modest improvements in acne severity following treatment (Khayef 2012). A small-scale trial on 5 subjects with mild to moderate acne showed that treatment with 1000 mg EPA daily for two months led to a reduction in inflammation and total number of acne lesions (Rubin 2008).
Zinc is a mineral with several properties that could potentially relieve acne. For example, it exerts anti-inflammatory and antioxidant actions, antibacterial effects against P. acnes, modulates the immune system, and reduces the production of sebum (Brocard 2011; Brandt 2013; Iinuma 2011). Zinc also appears to complement some antibiotics in the treatment of acne (Iinuma 2011). Plasma zinc levels have been found to be significantly reduced in severe acne sufferers compared to those with mild-to-moderate acne in a study on 94 subjects (Ozuguz 2013).
A double-blind trial on 37 subjects with moderate and severe acne compared zinc to a tetracycline antibiotic; both treatments reduced acne severity by about 70% (Michaelsson, Juhlin, Ljunghall 1977). Another placebo-controlled, double-blind trial on 56 acne sufferers demonstrated a significant effect of zinc on acne lesion counts. In this trial, 29 subjects receiving 600 mg zinc sulfate daily achieved significant reductions in acne lesion counts after 12 weeks of treatment compared to 27 subjects taking a placebo (Verma 1980).
In a prospective open-label trial, 48 mild to moderate acne sufferers were given three doses of a 75 mg methionine-bound zinc complex (containing 15 mg of elemental zinc) together with antioxidants for three months. Researchers noted a significant decrease of lesion count in 79% of subjects (Sardana 2010). In another open-label trial, thirty subjects with inflammatory acne took 30 mg of elemental zinc daily for 60 days. Lesions decreased significantly by day 30 of the trial, and this reduction was even more pronounced at the end of the trial. As part of the same study, zinc was found to decrease resistance of P. acnes to erythromycin in cell culture (Dreno 2005).
Zinc is also effective when added to topical solutions for acne. A solution of 1.2% zinc acetate and 4% erythromycin applied twice daily resulted in an over 64% reduction in acne lesion counts after 12 weeks (Langner 2007). In a randomized, observer-blind efficacy trial on 246 mild-to-moderate acne patients, a 1% clindamycin/zinc gel applied once or twice daily was shown to be equally safe and as effective as a 1% clindamycin lotion. Both were applied for 16 weeks (Cunliffe 2005). The addition of zinc to a topical formulation also seems to decrease the systemic absorption of other active compounds that may be included, such as antibiotics. This may lower the risk of systemic side effects and increase the local availability of antibiotic molecules (Chassard 2006).
Lactoferrin, a protein with antimicrobial and anti-inflammatory effects, is a component of the innate immune system and found in natural products such as milk. In a trial of 39 subjects with acne, twice-daily lactoferrin tablets over 8 weeks resulted in a significant decrease in the number of acne lesions in almost 77% of subjects (Mueller 2011). In a placebo-controlled, randomized trial, 18 subjects received 200 mg of lactoferrin daily; acne lesions decreased significantly in the lactoferrin group only. Interestingly, sebum levels also decreased by 31% in the lactoferrin group compared to the placebo group (Kim 2010).
Tea Tree Oil
Tea tree oil is derived from the Melaleuca alternifolia plant and contains terpenoids, which have antimicrobial and anti-inflammatory properties (Pazyar 2013). Terpenoids modulate the signalling of NF-kappaB, a major mediator of inflammatory signalling (de las Heras 2009). In a randomized trial of 60 mild-to-moderate acne sufferers, the treatment group (30 individuals) applied a topical 5% tea tree oil gel for 45 days and experienced a significant reduction in total lesion counts and acne severity compared to the placebo group (Enshaieh 2007). Another single-blind trial in which 124 subjects with mild to moderate acne were randomly assigned to either 5% topical tea tree oil gel or 5% benzoyl peroxide showed that both formulations significantly reduced total lesion count, and the tea tree formulation caused slightly fewer side effects (Bassett 1990).
Niacinamide (also known as nicotinamide) is a compound derived from niacin (vitamin B3) (Surjana 2011). It has been shown to exert anti-inflammatory action within the skin. In a randomized, controlled clinical trial of 65 subjects, 5% nicotinamide performed comparably to 2% clindamycin (both as topical formulations) in reducing acne severity scores (Shahmoradi 2013). As a dietary supplement of 600 mg one to four times daily (in combination with azelaic acid, copper, folic acid, pyridoxine, and zinc), it reduced symptoms by over 80% after 8 weeks of treatment in a clinical trial of 235 subjects. This was an open-label trial in which the nicotinamide supplement was compared to the existing acne medication of the subjects. Nicotinamide succeeded in significantly reducing acne lesion counts and improving appearance as reported by the subjects (Shalita 2012).
In a Japanese double-blind, placebo-controlled trial examining sebum production, fifty subjects received a topical 2% nicotinamide moisturizer daily and fifty subjects received a placebo. After two weeks of treatment, sebum production of the nicotinamide group was reduced significantly in comparison to the placebo group (Draelos 2006). A separate randomized, double-blind multicenter trial compared a 4% nicotinamide emulsion to a 1% clindamycin formulation, both applied daily as topical formulations. The nicotinamide formulation was found to be superior in terms of safety, tolerability, and efficacy (Morganti 2011).
The evidence for vitamin A’s efficacy in acne is mixed (Melnik 2010). In support of vitamin A’s role in treating acne are findings which suggest it can reduce inflammation caused by P. acnes (Agak 2013). Also, vitamin A levels have been found to be significantly lower in the skin (Rollman 1985) and plasma (Labadarios 1987) of acne patients compared to acne-free controls.
Some older evidence suggested efficacy for oral vitamin A in acne, but relied upon very high doses that would not typically be recommended today (Kligman 1981; Labadarios 1987; Michaelsson, Juhlin, Vahlquist 1977). On the other hand, a trial on 211 acne sufferers found that topical vitamin A treatment for 8 weeks led to improvements compared to placebo or standard therapy (Gandola 1976).
Vitamin E (tocopherol) is generally important for skin health, and a deficiency in this antioxidant was correlated with increasing severity of acne (Ozuguz 2013). A side effect of isotretinoin treatment may be a loss of vitamin E; therefore, vitamin E supplementation may be advisable for those receiving this medication (Akturk 2013).
Aloe vera extracts are often used in skin treatments, mainly to relieve minor burns or irritation (Surjushe 2008). In a randomized, double-blind trial of 60 patients with mild to moderate acne, a topical gel with 50% aloe vera and 0.05% tretinoin significantly reduced both comedones and inflammatory lesions more effectively than 0.05% tretinoin alone after eight weeks of treatment. The aloe vera-containing gel also caused significantly less redness as a side effect (Hajheydari 2013).
Barberry has anti-inflammatory and antibacterial properties and can reduce sebum production. Daily oral capsules containing 600 mg of barberry extract were given to 25 patients in a small-scale trial, and changes in their acne symptoms were compared with 24 similarly-afflicted subjects on a placebo pill. The mean number of acne lesion counts and acne severity scores of the subjects taking barberry for four weeks were each reduced by 44% (Fouladi 2012).
Although berberine has been studied in human clinical trials and shown to have several metabolic benefits, concerns about long-term use of berberine have been raised on the basis of certain preclinical studies (Kysenius 2014; Mikes 1985; Mikes 1983). Some evidence suggests that long-term berberine use, especially at high doses, may impair particular aspects of cellular metabolism in specific types of cells. The implications of this preclinical research are yet to be determined by long-term human clinical trials, therefore Life Extension currently recommends short-term use of berberine.
Green tea and its active ingredient, catechins, are associated with inflammatory response regulation through NF-kappaB (Yang 1998; Reuter 2010). Topical applications of green tea extract may have potential in treating acne (Pazyar 2012). In a single-blind, randomized trial of 20 subjects per group comparing 2% tea lotion, the tea preparation significantly reduced inflammatory lesions in subjects with acne (Sharquie 2008). Another one-way trial of 20 subjects applying a 2% green tea lotion twice daily for six weeks demonstrated significant effects of the tea on acne severity and lesion count (Elsaie 2009).
Extracts from various seaweeds have recently attracted interest as a skin treatment. There is evidence that molecules called seaweed oligosaccharides linked to zinc can significantly reduce sebum production (Ruxton 2013). Also, some species have shown anti-inflammatory and antimicrobial activity (Choi 2011). A double-blind trial compared thirty subjects using a topical seaweed-derived oligosaccharide containing 0.1% zinc pyrrolidone with an equal number using a control (non-active) preparation. There was a significant reduction in lesions in the 'seaweed' group only (Capitanio 2012).
Gugulipid, a lipid-based molecule also known as guggulsterone, is understood to regulate the production of other lipid-based substances in the body, which include sebum (Bajor 1997; Ulbricht 2005). In one trial, twenty subjects with acne were allocated to either 25 mg guggulsterone or 500 mg tetracycline. Both were taken twice daily for 3 months, and reductions in acne lesions were comparable in both groups (Thappa 1994).