Although acne is typically thought of as an ailment of adolescence, millions of adults are also afflicted. In fact, acne among adult females may represent an underappreciated epidemic affecting more than 50% of women aged 20–29 and more than 25% of those aged 40–49. In this population, the presence of acne may indicate underlying hormonal imbalance.

Contrary to popular belief, acne results from multiple processes within the body, the causes of which are known and, most importantly, can be targeted with specific treatments and lifestyle changes.

In this protocol, you will learn how complementing mainstream acne treatments with evidence-based natural interventions, such as zinc and lactoferrin, may improve skin appearance.

Diagnosis

• Acne can usually be diagnosed based on the appearance of the face, back, upper arms, and chest.
• Underlying conditions that could cause acne should be ruled out. For example, polycystic ovary syndrome, a condition in which women develop ovarian cysts and produce excessive testosterone, is associated with acne.

Conventional Medical Treatment Includes:

• Over-the-counter topical agents. These include benzoyl peroxide, azelaic acid, and salicylic acid. They can be used for mild-to-moderate acne and are antimicrobial and anti-inflammatory.
• Antibiotics (topical and oral). These include erythromycin, clindamycin, and nadifloxacin.
• Retinoids (vitamin A-related compounds; topical and oral). Retinoids can be used for mild-to-severe acne and are anti-inflammatory. These include tretinoin, tazarotene, adapalene, and isotretinoin.

Novel and Emerging Strategies Include:

• Hyaluronic acid injections. Microinjections of hyaluronic acid gel into severe acne scars resulted in immediate improvement in a small-scale trial. These injections may be used to improve the appearance of acne scars.
• Light therapy. Evidence shows exposure to blue light suppresses the bacteria Propionibacterium acnes, which plays a major role in acne-related inflammation. Overall, light therapy is a very effective acne treatment option with minimal side effects. A review of published evidence found that as many as 85% of patients who underwent light therapy achieved at least a 50% reduction in acne severity.

Dietary and Lifestyle Considerations Include:

• High intake of fats, sugars, and proteins, which typifies the western dietary pattern, may promote acne in a manner similar to excessive androgen production.
• Gently washing affected areas twice daily with a mild cleanser or gel is suggested for all forms of acne. Excessive scrubbing can make the lesions worse.

Integrative Therapies Include:

• Fish oil. In a clinical trial, 13 patients with inflammatory acne were given 930 mg of the omega-3 fatty acid eicosapentaenoic acid daily for 12 weeks. Some subjects experienced modest improvements in acne severity following treatment.
• Zinc. This mineral exerts anti-inflammatory and antioxidant actions, antibacterial effects against P. acnes, modulates the immune system, and reduces the production of sebum. In an open-label trial, 30 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.
• Lactoferrin. Lactoferrin, a protein with antimicrobial and anti-inflammatory effects, is a component of the innate immune system. In a trial of 39 subjects with acne, twice-daily lactoferrin tablets over eight weeks resulted in a significant decrease in the number of acne lesions in almost 77% of subjects.
• Nicotinamide. As a dietary supplement of 600 mg one to four times daily (in combination with azelaic acid, copper, folic acid, pyridoxine, and zinc), nicotinamide reduced symptoms by over 80% after eight weeks of treatment in a clinical trial of 235 subjects.
• Vitamin E. A deficiency in this antioxidant was correlated with increasing severity of acne. Vitamin E supplementation may also be advisable for those receiving isotretinoin.

Having clear, vibrant skin imparts a considerable boon to self-confidence and promotes psychological well-being. Therefore, the impact of blemishes, blackheads, and scars runs more than skin deep for the millions of people around the world affected by acne (Saitta 2011; Dreno 2007; Behnam 2013; Dunn 2011; Feton-Danou 2010; Cordain 2002; Jansen 2013).

Although acne is typically thought of as an ailment of adolescence, millions of adults are also afflicted. In fact, acne among adult females may represent an underappreciated epidemic affecting more than 50% of women aged 20 – 29 and more than 25% of those aged 40 - 49 (Preneau 2012; Collier 2008). In this population, the presence of acne may indicate underlying hormonal imbalance. Mainstream physicians, however, often fail to recognize this link (Kim, Michaels 2012; Kamangar 2012; James 2012).

Prominent misconceptions about acne, such as it being caused by poor hygiene, make it difficult for those affected to retain a positive outlook regarding the appearance of their skin. Contrary to popular belief, acne results from multiple physiological processes within the body, the causes of which are known and, most importantly, can be targeted with specific treatments and lifestyle changes (Bellew 2011; Beylot 2013; Lee 2013; Rebello 1986; Weldon 1998; Lee, Jung 2010; Dawson 2013).

That being said, combatting acne requires a comprehensive approach. Sadly, many conventional physicians fail to communicate this to their acne patients, instead simply prescribing an antibiotic or topical ointment and sending them on their way. The consequences of this approach are enormous. The over-prescription of powerful systemic antibiotics can lead to the emergence of antibiotic-resistant bacteria that are much more difficult to treat (Tzellos 2011; Luk 2013). Aside from possibly causing treatment-resistant acne, antibiotic-resistant organisms can also cause severe and potentially fatal infections (Diene 2013; Johnson 2013). 

Life Extension’s approach to clear skin is different. In this protocol, you will learn how complementing mainstream acne treatments with evidence-based natural interventions, such as zinc and lactoferrin, may improve skin appearance via multiple mechanisms. You will also learn how novel and innovative acne treatment strategies, such as light therapy, can target several specific factors that compromise skin appearance like inflammation and colonization with bacteria called Propionibacterium acnes (P. acnes). In addition, you will learn about emerging therapies such as hyaluronic acid injections that can help revitalize skin appearance even for those with severe acne scars.

The blemishes and lesions characteristic of acne arise when hair follicles in the skin become blocked with oils and particles such as dead skin cells, bacteria, or occasionally white blood cells (Bellew 2011; Beylot 2013). Sebaceous glands attached to hair follicles secrete an oil-based substance known as sebum. Sebum normally helps moisturize skin and keep it supple. However, if too much sebum is produced, the follicle can become blocked. Testosterone, the characteristic male sex hormone, stimulates sebum production and is a major contributor to the initial formation of acne lesions (Dawson 2013; Lee, Jung 2010; Bhatia 2004). This is a primary reason why acne is more common in adolescence, when sexual maturation coincides with a spike in testosterone production, especially in males.

A clogged pore may form a “blackhead,” which is called an open comedo, or a “whitehead,” known as a closed comedo (Dawson 2013). Sometimes, bacteria called Propionibacterium acnes (P. acnes) that normally reside in the skin interact with the sebum trapped in a clogged follicle and lead to inflammation (Lee 2013; Rebello 1986; Weldon 1998). Inflamed acne lesions, which are more severe than non-inflamed lesions and are more likely to lead to scarring, can be classified as follows (Webster 2002; Mayo Clinic 2011a; Beylot 2013; Hsu 2011):

• Papules - small, raised bumps that are inflamed and may be red and tender.  
• Pustules - small, inflamed, pus-filled bumps that may have a white tip.
• Nodules - solid, irregular or dome-shaped inflamed lesions beneath the skin.
• Cysts - sac-like lesions containing white blood cells, bacteria, and dead cells in a liquid or semi-liquid state.
  • Cysts and nodules often appear in conjunction to form nodulocystic acne, a severe form of the condition which can be very painful and often results in severe inflammation and acne scars.

Acne can be classified based upon the type and number of lesions present. The American Academy of Dermatology has formulated a scheme for the classification of acne; it has three basic levels (Vejjabhinanta 2011):

• Mild acne is characterized by the observation of comedones and few papules and pustules (generally less than 10) and no nodules or cysts.
• Moderate acne includes 10 to approximately 40 papules and/or pustules, with about as many comedones.
• The appearance of less than 40 papules and/or pustules along with as many as 5 large or deep nodules denotes moderate to moderately-severe acne.
• Severe acne is classified as more numerous papules and/or pustules with many nodules and/or cysts.

Acne can usually be diagnosed with a good degree of certainty based upon its outward appearance of characteristic lesions on the face, back, upper arms, and chest (Archer 2012). A health-related quality of life (HRQL) index is also applied in some cases to assess the psychological effects (and possible psychiatric conditions) in patients suffering from acne (Barnes 2012).

Underlying conditions that could cause acne should be ruled out. For example, polycystic ovary syndrome (PCOS), a condition in which women develop ovarian cysts and produce excessive testosterone, is associated with acne (Sam 2007; Kamangar 2012; Rehme 2013). Adrenal hyperplasia can also cause excess androgen production and is sometimes linked with acne (Degitz 2003; Reisch 2013).

Blood tests for dehydroepiandrosterone sulphate (DHEA-S) and testosterone are also sometimes useful in identifying androgen excess as the cause of an acne breakout (First Consult 2013).​

There are a variety of treatment options available for acne. Medications may target one or more of the several underlying causes of acne, such as excessive androgen signalling, overproduction of sebum, bacterial overgrowth, and inflammation (Archer 2012; Dawson 2013; Garner 2012; Simonart 2013; Agak 2013; Tan 2007; Zouboulis 2010; First Consult 2013).

Less severe acne is typically treated with topical preparations, some of which are attainable over-the-counter (OTC) without a prescription, whereas systemic, prescription-only medications may be utilized in addition to topical agents in severe cases. Also, systemic medication may occasionally be employed for less severe acne that has proven resistant to first-line topical agents (First Consult 2013; Garner 2012). For acne scarring, advanced cosmetic procedures such as laser resurfacing, dermabrasion, and chemical peels may be helpful (First Consult 2013; Rai 2013; Khunger 2008). Consulting with a dermatologist is advised since there are so many treatment options available for acne; an experienced physician can help each patient determine the approach that best suits their individual needs.

Over-The-Counter Topical Agents

The following topical agents are often considered “first-line” treatments. They are available in OTC formulations, but some stronger concentrations or preparations in which they are combined with other types of medication may be available by prescription only.

Benzoyl peroxide. Benzoyl peroxide is often used for mild to moderate cases of acne (Sagransky 2009). It is a bactericidal agent, which means it kills bacteria. It is normally prescribed in conjunction with topical antibiotics, but has been shown to be effective against acne when used alone (Kircik 2013; Costa 2013). A combination benzoyl peroxide and antibiotic therapy is typically sold in the form of gels containing up to 10% benzoyl peroxide and often 1% antibiotic (eg, clindamycin) (Baumann 2013; Fluhr 2010). 

Azelaic acid. Azelaic acid is a naturally-occurring compound that has anti-inflammatory and antimicrobial properties (Reis 2013; Mastrofrancesco 2010). It is indicated for mild and moderate acne.

Salicylic acid. Salicylic acid is typically used for non-inflammatory acne. Applied as a 0.5 – 2% lotion, cream, or gel, it helps the outer layer of skin to soften and shed (ie, it is considered keratolytic). Salicylic acid can also be found in some OTC facial washes (First Consult 2013; ePocrates 2013).

Antibiotics

Several antibiotics may be utilized for acne treatment. Both topical and oral formulations of antibiotics are available, with the latter being reserved for more severe cases.

Erythromycin. Erythromycin is an antibiotic that kills P. acnes and has anti-inflammatory activity (Melnik 2013). For treating acne, it is available as a topical formulation at a concentration of 2% typically (Faghihi 2012). It has been found to be most effective when combined with azelaic acid in topical formulations (Pazoki-Toroudi 2010).

Clindamycin. Clindamycin is an antibiotic typically prescribed in a topical formulation for mild to moderate cases of acne. In combination with benzoyl peroxide, it can reduce microorganism counts by just over 99% after one week of treatment (Kircik 2013). 

Nadifloxacin. A 2013 study demonstrated that 76 strains of P. acnes had no resistance to nadifloxacin (Takigawa 2013). In one study, 1% nadifloxacin cream was observed to be as effective as 4% erythromycin gel (43 patients per antibiotic group over twelve weeks) in treating mild to moderate acne (Tunca 2010).

Metronidazole. Metronidazole is used as a topical solution for its antimicrobial and anti-inflammatory properties. Despite its history of use as a medication for moderate acne, there are few studies that have assessed its actual effectiveness in clearing lesions. In one study, there was a slightly greater chance of adverse skin effects caused by 2% metronidazole gel compared to placebo, but 88% of the patients were satisfied with the effects of the treatment (Khodaeiani 2012).

Trimethoprim-sulfamethoxazole. Trimethoprim-sulfamethoxazole is a combination of two separate antibiotics - trimethoprim and sulfamethoxazole - that is more effective than either antibiotic alone (McCarty 2011). It has been used extensively for moderate to severe acne; however, there is evidence that some P. acnes strains are resistant to this treatment (Schafer 2013). Like the other antibiotics prescribed for acne, it is often formulated with benzoyl peroxide or another complementary chemical treatment (McCarty 2011).

Tetracyclines. Tetracyclines are a group of oral antibiotics that were popular for the control of moderate to moderate-severe acne; however, they are becoming less popular for a number of reasons. Tetracyclines are associated with hyperpigmentation of skin that may be irreversible (Garner 2012). They are also often associated with adverse effects such as gastrointestinal disturbances, photosensitivity, headache, and tinnitus (Shalita 2012); and these drugs have a higher-than-average cost (Garner 2012).

Azithromycin. Azithromycin belongs to a group of antibiotics known as macrolides. They have been shown in clinical trials to be as effective as certain tetracyclines for treating acne (Maleszka 2011; Babaeinejad 2011). Azithromycin is often combined with isotretinoin (see next section) to treat moderate to severe acne; after approximately 21 weeks of treatment the combination achieved complete clearance of symptoms in over 90% of subjects in one trial (De 2011).

Retinoids

Tretinoin. Tretinoin (all-trans-retinoic-acid), a retinoid (vitamin A-related compound) usually marketed as a topical cream, has proven effective against mild to moderate acne (Baldwin 2013). It can regulate some aspects of immune response related to the inflammation seen in acne (Agak 2013). In a double-blind, randomized trial, 156 patients were given either a 0.04% or 0.1% tretinoin gel to apply nightly for 12 weeks. Both concentrations achieved significant reductions in total lesion count, though the 0.1% group showed a greater decrease in inflammatory lesions at two weeks (Berger 2007). Another multicenter open-label trial using patients who found their former acne treatments ineffective used these same concentrations and formulations. In this study, 183 patients were assigned to the 0.1% formulation and 361 to the 0.04% gel. Both concentrations produced significant improvements in observer rating scores and Global Acne Grade scores (Eichenfield 2008).

Tazarotene. Tazarotene is another retinoid chemically similar to tretinoin. It is available as a 0.05 - 0.1% foam, gel, or cream for moderate to severe acne (First Consult 2013). Like tretinoin, it normalizes immune response, helping to mitigate inflammation (Duvic 1997; Zheng 2008). Tazarotene, regarded as a teratogen (a compound known to cause fetal abnormalities), carries warning labels directed at women of childbearing age (Epstein 2013).

Adapalene. Adapalene (also a retinoid) is a popular and effective treatment for mild and severe acne. It has an efficacy about equal to that of benzoyl peroxide (Babaeinejad 2013). Adapalene has anti-inflammatory properties and disrupts comedones (Prasad 2012). It appears to act by inhibiting the product of sebum by sebocytes, thus suppressing sebum build-up (Sato 2013). It is available as a topical treatment by itself or in combination with benzoyl peroxide (Kim 2013) or an antibiotic (Prasad 2012).

Isotretinoin. Oral isotretinoin may be prescribed for severe acne after other treatments have failed (Mayo Clinic 2012). It is a form of all-trans-retinoic-acid (Melnik 2010). There is evidence of an association between isotretinoin administration and potentially severe depression (Bremner 2012). Isotretinoin has a variety of immunomodulatory effects; unfortunately, it is also a teratogen (Melnik 2010; Melnik 2011). Female patients of childbearing age are advised to consider fetal risks if a pregnancy occurs and must use two forms of birth control while on isotretinoin (Mayo Clinic 2012). Isotretinoin can also produce other adverse effects, most notably muscle weakness (Georgala 1999).  

Hormonal Modulation

Spironolactone. Spironolactone is a diuretic drug that also disrupts androgen signalling. Due to its activity as an antiandrogen, it may help reduce sebum production in some acne patients (Kim, Del Rosso 2012). It is prescribed to women who are not pregnant and is not typically used in men due to the possibility of feminization (Rathnayake 2010).

Oral contraceptives. Oral contraceptive pills (OCPs) may be prescribed to women with moderate to severe acne. This type of contraceptive contains a progestin (a synthetic progesterone-like drug) alone or in combination with an estrogen. These counteract androgen signalling and thus treat acne caused by androgen excess (Arowojolu 2012). There are many types of OCPs. Some appear to be more effective in treating acne.

• A trial comparing 45 women taking 150 mcg desogestrel + 30 mcg ethinyl estradiol to 46 women taking 150 mcg levonorgestrel + 30 mcg ethinyl estradiol (an older OCP) showed that the decrease in acne was significantly higher in the first group (Sanam 2011).
• Norgestimate, at doses of 0.180 mg, 0.215 mg or 0.250 mg, each with 0.035 mg ethinyl estradiol, was shown to be significantly effective for moderate facial acne in two randomized, placebo-controlled trials in which 324 subjects received 6 treatment cycles (Tan 2007).
• Drospirenone is a spironolactone derivative that acts as a progestin. In two randomized, controlled trials on 889 women, 3 mg of drospirenone along with 0.020 mg ethinyl estradiol achieved total- or near-total clearance of acne scores in 18% of subjects compared to only 6% of subjects receiving a placebo (Tan 2007).

Other Therapies

Dermabrasion. Dermabrasion, which involves removal of the top layers of skin with an abrasive material or tool to allow new, smoother skin to regrow, may be used to reduce the appearance of acne scars (Picosse 2012). Dermabrasion use is decreasing for acne scar treatment in favor of laser resurfacing, but is still a useful treatment option for mild areas of atrophic scarring (ie, scars that form a sunken recess in the skin) that are not likely to worsen (Levy 2012).  

Laser therapy and laser resurfacing. Lasers are very high-intensity light sources. Lasers are produced by shining light through various elements and/or crystals such as erbium, garnet, and yttrium, which causes it to be focused into a concentrated beam of light. Certain lasers such as carbon dioxide (CO2) lasers have shown great efficacy in treating and improving the appearance of acne scars (Shah 2012). These lasers work by removing a thin layer of skin with minimal heat damage (First Consult 2013). Some lasers operate in treating acne by destroying the P. acnes bacteria and damaging the sebaceous glands, causing them to produce less oil (Rai 2013; Mayo Clinic 2011c). Fractional lasers, which are focused on specific affected areas rather than the traditional whole-face approach, are one of the most efficient modern laser therapies (Shah 2012). Laser resurfacing has a longer healing time and higher cost than dermabrasion (First Consult 2013).

Chemical peels. 'Chemical peeling' involves the application of relatively high concentrations of various types of chemicals (usually acids) to affected skin in order to remove the top layers of skin and potentially improve superficial scarring (Bae 2013; Takenaka 2012; Khunger 2011; First Consult 2013). Different strengths of chemical peels are available, ranging from mild to “deep.” Deep chemical peels are done with stronger concentrations of acids at targeted points on the skin.

Alpha hydroxy acids. Alpha hydroxy acids (AHAs) are often used in skin conditions; at high concentrations they act as chemical peels (Takenaka 2012). Examples of AHAs are lactic acid and glycolic acid (Kornhauser 2010). AHAs disrupt both comedone formation and the activity of P. acnes in the skin. A placebo-controlled trial of a 10% glycolic acid wash found that it was significantly effective in reducing mild acne and was well tolerated (Abels 2011). Lactic acid has been shown to give significantly positive results as a chemical peel (92% concentration) for mild acne scarring (Sachdeva 2010). A trial of gluconolactone, another AHA, at 14% concentration in a lotion, was compared to 5% benzoyl peroxide lotion in a double-blind trial of 150 subjects. Both were found to be equally effective in reducing the number of acne lesions (Hunt 1992).​​​​

Hyaluronic Acid Injection

Hyaluronic acid has become very popular in skin treatments and products. It may be effective as an injected treatment for acne scars, as scars are the result of abnormal formation of collagen structures that are associated with skin wound healing. Microinjections of hyaluronic acid gel into severe acne scars resulted in immediate cosmetic improvement in a small-scale trial (Halachmi 2013). Therefore, these injections may be used to "fill out" and thus improve the appearance of acne scars (Lee, Kim 2010).

Light Therapy

The bacteria P. acnes, which play a major role in acne-related inflammation, are sensitive to certain wavelengths of light, especially blue and red light (Gold, Andriessen, Biron, Andriessen 2009). Experimental evidence shows that exposure to blue light suppresses P. acnes, and in one study, blue light therapy reduced acne lesions by 64% after 5 weeks of treatment (Kawada 2002). In a separate study, blue light therapy reduced inflammatory acne lesions by 34%, while topical 1% clindamycin solution achieved only a 14% reduction (Gold 2005).

Blue-light-emitting devices can be used at home (Gold, Andriessen, Biron 2009; Gold, Andriessen, Biron, Andriessen 2009). Studies have shown that self-administered blue light therapy can reduce acne lesions over an 8-week period (Gold, Andriessen, Biron, Andriessen 2009). A study at Cornell University found that blue and red light in combination significantly reduced acne lesion counts following self-administered treatment with a hand-held light-emitting diode (LED) device. The treatment was administered for 4 weeks and acne lesion counts declined during treatment and for 4 weeks following treatment, reaching a final reduction of 69% at 8 weeks (Sadick 2008).

Overall, light therapy is a very effective acne treatment option with minimal side effects. A review of published evidence found that as many as 85% of patients who undergo light therapy achieve at least a 50% reduction in acne severity. Moreover, one-fifth of treated individuals experience a reduction in acne severity of up to 90%. The authors who conducted the review concluded “Amelioration of acne by light therapy, although comparable to the effects of oral antibiotics, offers faster resolution and fewer side effects and leads to patient satisfaction” (Elman 2004).

Dietary Considerations

Evidence suggests that high intake of fats, sugars, and proteins, which typifies the Western dietary pattern, may promote acne in a manner similar to excessive androgen production. This is thought to occur via molecular pathways involving a protein called mTORC1 and insulin-like growth factor-1 (IGF-1), which ultimately increase sebum production in sebaceous glands (Kumari 2013). Therefore, limiting meats and foods high in fats and sugars in favor of low-glycemic, plant-based foods may help alleviate acne for some individuals (Danby 2011; Melnik 2012; Veith 2011; Ismail 2012; Burris 2013; Melnik 2011; Melnik 2010).

Intriguingly, the antidiabetic drug metformin and the natural compounds resveratrol, found in red grapes and Japanese knotweed, as well as epigallocatechin gallate (EGCG) found in green tea, all inhibit mTORC1 signalling. Thus, complementing a healthy, plant-based diet with these agents may confer additional support for healthy skin, although trials are needed to investigate this hypothesis (Melnik 2012).

Lifestyle Considerations

Excess oils on the skin, either naturally-produced or derived from oil-based moisturizers, cosmetics, or hair products can exacerbate acne. Contact irritation from clothing or equipment such as helmet straps can worsen acne (First Consult 2013). Scrubbing or excoriation of acne is not advised, as it could spread P. acnes and increase the probability of more severe symptoms (Mayo Clinic 2011b). There is some evidence that stress and other adverse mental health issues could lead to a breakout or worsening of the condition (Bowe 2011; Saitta 2011).

Gently washing affected areas twice daily with a mild cleanser or gel is suggested for all forms of acne. Many preparations used for cleansing acne-prone skin contain substances that are proven effective in treating acne. Many cleansing products on the market have 'scrubbing' particles incorporated; however, if acne is moderate to severe this may not be a good course of action as it may worsen lesions and increase the risk of scarring (Picosse 2012). Scrubs may be more of a preventative measure to ensure follicles stay free of sebum and dead skin cell debris (Mayo Clinic 2011b).​​

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.

Fish Oil

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

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

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

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).

Vitamin A

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

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

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 Extract

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

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).

Seaweed Extracts

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

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).​​​​​