Acne Relief

Acne is a common condition that usually occurs during puberty but can persist into adulthood. Acne vulgaris (AV) commonly known as ‘acne’ is a disease of the pilosebaceous unit that causes non-inflammatory lesions (open and closed comedones), inflammatory lesions (papules, pustules, and nodules), and various degree of scars (1).
What is the Pilosebaceous Unit?
The hair follicle, hair shaft and sebaceous gland in the skin are collectively known as the pilosebaceous unit. The pilosebaceous unit is a complex, dynamic, 3-D structure, which is the site of unique biochemical, metabolical and immunological events (17).

The first factor in acne pathogenesis is the androgen-induced enlargement of sebaceous glands with the overproduction of sebum.
The sebaceous glands have steroid-metabolizing enzymes that convert dehydroepiandrosterone (DHEAS) to dihydrotestosterone (DHT).
Furthermore, two subtypes of 5-α-reductase isozymes, that is, type 1 and type 2, expressed in the scalp, chest, sebaceous glands, genitourinary tissue, dermal papillae, and hair follicles, convert testosterone to the more active hormone DHT. DHT stimulates the sebaceous gland to produce excess sebum. Excess sebum production causes blockage in the pilosebaceous unit and increases cell turnover in the follicular canal thus leading to acne (2).

The second factor of pathogenesis is pilosebaceous follicles are surrounded by macrophages and inflammatory mediators that express Toll-like receptors (TLR2) on their surface.
TLR2 activation leads to transcription of nuclear factor triggering and thus heading towards the expression of cytokines
Activation of TLR-2 initiates a sequence of inflammatory responses where cytokines are released inducing keratinocyte hyperproliferation (a rapid division of cells).
Desquamated (Shedding of an outer layer of the skin) keratinocytes within the pilosebaceous unit initiate follicular plugging which disturbs the normal architecture of the follicle and leads to the formation of a thin-walled cystic lesion- comedo. As the keratinocytes and sebum continue to accumulate, the microcomedo wall eventually ruptures & leads to inflammation (2).

Developing comedone contains a mixture of keratin, sebum, bacteria, and the superficial layer of melanin which may appear as a blackhead or a whitehead. Depending upon the severity of pathologic conditions, these lesions can further develop into a papule, pustule, nodule, or cyst (2).

Open comedones or Blackheads

Comedones when outburst through the skin surface having a central black appearance (due to the oxidation of tyrosine to melanin by tyrosinase) are called “blackheads” or open comedones.

Closed Comedones or Whiteheads

Enlargement of the follicle with improperly desquamated keratinocytes and sebum results in the development of “whiteheads” or closed comedones which remain underneath the skin surface as closed follicles.

Propionibacterium acnes is an anaerobic Gram-positive bacterium that is primarily known to be present as a skin commensal (Present on the skin without being harmful) but under favourable conditions, it becomes an opportunistic pathogen.  

A large number of P.acnes are found in comedones as they are filled with sebum- a lipid substrate that is a rich nutrient source for this organism to thrive as well as provides an anaerobic environment which will allow P.acnes to proliferate (2).  

• P. acnes is involved in the development of inflammatory acne by activating inflammatory response and metabolizing triglycerides present in the sebum to fatty acids that irritate the surrounding skin.  
• P. acnes produces lipases, proteases, and hydrolases, which contribute to inflammation and tissue destruction, comedonal rupture, and also stimulate a cascade of inflammatory responses by acting on TLR-2. This stimulates the expression of cytokines by follicular keratinocytes and macrophages, which in turn activates hyperkeratinization and inflammation.  

The sequential phenomena lead to an inflammatory response and cause follicular disruption giving rise to lesions in the form of papules, pustules, and nodules (2). 

Altered lipogenesis, sebum production, hyperkeratinization, proliferation/differentiation of sebocytes, and cytokine expression can be a reason for the formation of acne lesions. Acne management can be done efficiently only when the exact mechanism involved in the pathogenesis gets attention. These mechanisms play direct & indirect roles in acne pathogenesis (2) 

• There is no universal standard grade for acne grading but acne severity is classified in a more or less similar manner. Acne lesions occur primarily on the face, neck, upper back, and chest. When assessing the severity of the acne, one needs to consider:  
• • The distribution of acne (back, chest, and upper arms)  
  • Type and number of lesions (comedones, papules, pustules, nodules) 
• • The presence or absence of scarring (4). 

• Zinc  
  • Zinc possesses anti-androgen activity as it inhibits 5α-reductase type 1 and type 2 activity thus inhibiting the conversion of testosterone to DHT. This prevents excess sebum production under the influence of DHT which controls acne breakouts (5).  
  • Zinc also targets another mode of action of acne breakouts by its antimicrobial activity against P.acne. (6) 
  • A study carried out by Sahib et a., concluded that administration of antioxidants to patients with acne vulgaris significantly reduced serum Malondialdehyde level; and increased serum level of Glutathione after eight weeks compared to pre-treatment value, also significantly reduced Interleukine-8 serum levels and the number of inflammatory lesions in patients with acne compared to placebo (3).  

  Acne Relief also contains vitamins A, D, E, B3 i.e. niacinamide and vitamin B5 i.e. pantothenic acid; and selenium and chromium among the minerals.  

  • Vitamin A helps reduce excess sebum production and its deficiency is linked to acne severity.  
  • Supplementation with vitamin A may help reduce the plugging of pores in individuals with a deficiency (17).  

  Niacinamide helps in managing inflammatory response & to reduce sebum production.  

  • IGF-1 triggers androgen production which will in turn trigger the proliferation of sebocytes. This leads to excess sebum production and the pathogenesis of acne. Chromium picolinate is involved in lowering the IGF-1 & insulin levels.  
• Vitamin D plays an important role in the immune system, and its deficiency has been implicated in various skin diseases.  The highest incidences of acne have been noticed to occur when Insulin-like growth factor- 1 (IGF-1) levels peak. High levels of IGF are often seen during puberty however, adult women with acne also show increased levels of IGF-1.   
• Chromium: 
• • A study concluded that Vitamin D deficiency is more frequent in patients with acne, which is inversely correlated with disease severity, indicating a potential role of vitamin D deficiency in acne pathogenesis (16).  
  • It has a role in the proliferation and differentiation of keratinocytes and sebocytes. Moreover, it has an anti-comedogenic and antioxidant effect. Therefore, vitamin D deficiency may facilitate the pathogenesis of Acne (16).   
• • Open-label, multicentre, prospective cohort study investigated the use of oral nicotinamide alongside zinc, copper and folic acid in patients and found that 79% reported improvement in acne condition as better (14). 
• Niacinamide: 
• Pantothenic Acid: Coenzyme A increases the breakdown of excess sebum from the skin & this in turn reduces the clogging of pores as well as acne breakouts.  
• Vitamin D:  
• • It has been shown that pantothenic acid may regulate epidermal barrier function through the proliferation and differentiation of keratinocytes via CoA metabolism (15). 
• Pantothenic acid regulates epidermal barrier function and keratinocyte differentiation via CoA (Co-enzyme A) metabolism. CoA is a critical agent important in lipid metabolism and other cellular processes.  
• Vitamin E & Selenium 
• • Combined treatment of acne with oral vitamins A and E were reported to have a synergistic effect by regulating keratinization (13). 
• Vitamins & Minerals:  
• Research reveals that lower levels of vitamin E & Selenium are generally found in acne patients.  Vitamin A is necessary for epithelial cell differentiation.  
• • It helps to regulate keratinocyte differentiation.  
• Vitamin A: 
• • Excessive generation of ROS by the immune system could result in an inflammatory response. Selenium & Vitamin E are antioxidants that play a role in managing these inflammatory responses (3).  
• • Research suggests that tea polyphenols (EGCG) exert their effect on sebum production and acne via various mechanisms, including acting as anti-microbial, anti-lipogenic, and anti-inflammatory molecules (10).  
  • In the study, 80 subjects were randomly assigned to receive either decaffeinated green tea extract (providing EGCG) or placebo (cellulose), once daily for 4 weeks. The results showed that green tea extract intake resulted in a significant reduction in inflammatory lesions on the forehead and cheek as compared with the placebo. The green tea extract-treated group also showed decreased total blood cholesterol. However, the non-inflammatory acne lesions were not reduced by the treatment (11). 

  Oxidative stress & inflammation are associated with the pathogenesis of acne. Silymarin, an active component of milk thistle acts as a free radical scavenger, stabilizes the plasma membrane, and protects the cell against the free radicals generated by radiation or chemical reactions.  

• • It also reduces the production of inflammatory mediators produced by P. acnes and scavenges free radicals (12).  
• Milk Thistle (Silybum marianum Extract):  
• Dihydrotestosterone (DHT) is a more potent androgen than testosterone. DHT is generally considered responsible for the stimulation of the sebaceous gland and increased local formation of DHT has been documented in acne outbreaks. The reduction of testosterone to dihydrotestosterone (DHT) by the enzyme 5α-reductase is an important enzymatic process involved in androgen activity.  
• Zinc is a micronutrient that is essential for the development and functioning of the skin. Acne Relief uses zinc for its antimicrobial properties and its ability to block DHT.  
• • Zinc was compared to minocycline in a multicenter randomized double-blind trial. Patients received either 30 mg elemental zinc or 100 mg minocycline for 3 months. The clinical success rate was 31.2% for zinc and 63.4% for minocycline. Minocycline and zinc gluconate are both found to be effective in the treatment of inflammatory acne (7). 
  • In a double-blind study, the effects of oral zinc and tetracyclines were compared in patients with moderate and severe acne. No difference in effect between the treatments was seen. After 12 weeks of treatment, the average decrease in the acne score was about 70% in both groups (8). 
  • A study was carried out to estimate serum zinc levels in acne patients and their correlation to the improvement of acne. Oral zinc sulphate 220 mg twice a day, raised serum level. Oral zinc treatment can increase serum zinc levels and raised serum zinc levels cause a response in acne severity. Oral zinc has a role in the treatment of acne (9).  

  Polyphenols are the active components of green tea which exhibit antimicrobial and anti-inflammatory properties. Studies have suggested that tea polyphenols may be used for reducing sebum production in the skin and for acne vulgaris.  

• Green Tea Extract (EGCG):