Acné

(Versión Completa en Inglés)

According to the Global Burden of Disease Study, acne is the eighth most common skin disease, with an estimated prevalence (amongst all ages) of 9.38%[i]. Among adolescents, the estimated prevalence is 35% to 100%[ii].

The symptoms and impacts of acne

Patients suffering from acne experience comedones, papules and pustules[iii].
Comedones can be subdivided into two types: open comedones (commonly called blackheads), which are clogged follicles whose opening is exposed to air and closed comedones (whiteheads), which are clogged follicles that are not exposed to air[iv].
Papules are raised skin lesions less than 1cm in diameter. Pustules are similar to papules, though present inflammation and are filled with pus. In patients with severe acne, nodules and cysts – inflamed, swollen lesions at least 5 mm in size – may be present. In addition, other symptoms like scarring, erythema, and hyperpigmentation can be seen in acne patients.

In addition to the discomfort of the clinical symptoms of acne, patients can experience other negative impacts. For example, one study observed significantly higher unemployment rates among individuals with acne. Moreover, acne negatively affects individuals’ social life, self-esteem and body image, often comorbid with psychological disorders, including depression and anxiety.

Propionium acne bacterium and acne

The bacterial species, Propionibacterium acnes – now renamed Cutibacterium Acnes – resides in pilosebaceous follicles of individuals both with and without acne, playing a key role in the induction of host inflammatory responses, crucial for the pathogenesis of acne and responsible for the clinical manifestation of the disease. C.acnes contributes to the inflammatory nature of acne by stimulating the release of pro-inflammatory cytokines from innate immune cells, keratinocytes and sebocytes.
Acne is highly correlated with the uncontrolled growth of this gram-positive bacterium, which alters the normal immune response by activating TLR2 factor 31 (Toll-Like 2 receptors). These receptors are part of the innate immune system against the invasion of microorganisms, and their activation alters the expression of cytokine and chemokine responses, which in turn stimulate immune cells.
Inflammation of human monocytes by the C.acnes bacteria results in the activation of TLR2, which consequently stimulates the production of pro-inflammatory cytokines. This activation is down-regulated by CEN1HC-Br (antimicrobial peptide). Depending on the dose, inhibition of the production of cytokines in monocytes is witnessed, and we conclude that this antimicrobial peptide has strong anti-inflammatory properties. CEN1HC-Br also acts by inhibiting the production of IL-12 (3), one of the main pro-inflammatory cytokines, essential in the activation of T cell responses, and involved in the development of tissue injury. Furthermore, this peptide inhibits the production of other cytokines important in the pathogenesis of acne, such as IL-6 and IL1β.

Dietary factors that can influence its severity

The consumption of chocolate and cocoa derivatives has been associated with the severity of the acne: one study showed that when 99% cocoa based-chocolate was consumed by the control group for several weeks, that it did not result in a statistically significant change in acne[v].
We know that oleic acid – found in large amounts in cocoa butter – can affect skin keratinization and promote the development of comedones, contributing to the aggravation of acne[vi].
Milk, however – which is also present in most cocoa derivatives- is also a preponderant factor in this association.
At least three studies and one meta-analysis suggest that milk consumption may increase acne severity,[vii]with milk consumption being significantly associated with the presence of moderate to severe acne. Despite this fact, the consumption of cheeses and yogurts (fermented dairy) has not been shown to worsen the pathology.
The consumption of fiber, fruits, vegetables and fish[viii] has been correlated with a decrease in the risk of severe acne – although it should be noted that processed fruit juices do not provide this protection, and in fact worsen the acneic symptoms[ix].
In general, the indications suggest that the severity of acne can be influenced by diet. A diet with a low nutritional profile, rich in carbonated drinks, processed foods, red meats, deli meats, nuts, eggs, fried foods and foods with a high profile of hydrogenated fats can potentiate acne, whilst the consumption of whole foods that are rich in fiber, lean meats and fish can lessen the incidence and severity.

Personal factors

Body mass index (BMI) and smoking status were correlated with acne severity and presentation.
Individuals with higher BMIs (≥23 kg/m2 and ≥25 kg/m2) are at greater risk compared to individuals with lower BMIs. This is probably due to the fact that the higher the BMI, the higher the glycemic index and androgen levels as well, which in turn increases sebum secretion and consequently promotes the formation of acneic lesions.
Regarding tobacco smoking, despite the data being somewhat controversial and there are those who claim that smoking could reduce the risk of acne[x], in young women. We believe, on the contrary, that smoking tobacco can further expose the individual to inflammatory processes and decrease the immune response, which delays healing. It is a fact that nicotine activates keratinocyte cell receptors, decreasing the healing capacity and speed.
In addition to these issues that negatively affect the severity of acne, other factors include sleep/insomnia, low sun exposure, stress (physical and mental), pressure (whether at home, school, or workplace) and the use of makeup, as well as, residing in areas with a high pollutant level (metropolitan areas and urban environments).
However, there are some factors that can help, such as frequent washing/cleansing of the affected skin and the use of suitable products.

Ozonated oils in the treatment of acne

Ozone is a highly unstable gas that cannot act directly on skin cells, but requires stabilization by first using vegetable oils, which capture the ozone through their PUFAS (polyunsaturated fatty acids) forming ROS (reactive oxygen species) in the form of peroxides. These peroxides increase the activity of redox transcription factors and growth factors, consequently accelerating the cell cycle.
The use of vegetable oils combined with ozone – a process in which ozone gas is combined with vegetable oils, usually olive oil and sunflower oil, thus producing an ozonated oil for topical application and elevated healing potential – has shown enormous success in various skin conditions[xi].

In general, four factors have been identified as playing a decisive role in the pathophysiology of acne:

1. Hair follicle proliferation;
2. Sebum hypersecretion;
3. Inflammation;
4. Cutibacterium acnes hyperactivity/proliferation.

Among these factors, inflammation is a key point in the pathogenesis of acne, being without a doubt the most important at all stages of the formation of acne lesions, even before the formation of comedones.

The simple fact that ozone gas is actually present in the product preparations, supports the potential of ozonated oil use in acne management: showing elevated antimicrobial and antiseptic activity, which promotes elimination of bacteria present in the mucous membranes and the skin. Ozone leads to peroxidation of phospholipids that results in the disruption of the integrity of bacterial membranes[xii].
On the other hand, the inhibitory effect of ozonated oils on nuclear factor -κB makes Ozone a powerful anti-inflammatory agent that can react in an aqueous medium in two ways:

1. Directly: action through molecular reaction;
2. Indirectly: through the formation of free radicals.

in both pathways there is also antimicrobial action.

Moreover, the degradation of the by-products of ozonolysis (the process that occurs during the formation of ozonated vegetable oils) has shown to increase the availability of oxygen in inflamed and ischemic tissues, thus improving topical metabolism and cell proliferation, essential for the rapid and effective healing of damaged/injured tissue.
Topical application of ozonated oils on damaged skin has a rapid antiseptic effect, whilst simultaneously having a very high inhibitory effect on the growth of gram-positive and gram-negative bacteria. Its use for a period of one month, has shown that it can very effectively reduce the number of acne lesions.

A clinical study performed in 2020[xiii], reports that after one month of using ozonated oil, 74% of patients experienced a decrease of more than 50% in the number of lesions (inflammatory and non-inflammatory) and 50% of the participants had a decrease of about 75%, thus concluding that the use of ozonated oil is biocompatible, effective and safe in the treatment of lesions, decreases the appearance of inflammatory and non-inflammatory acne, and is therefore a powerful anti-acne agent.

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[i] Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859):2163-96. doi: 10.1016/S0140-6736(12)61729-2. Erratum in: Lancet. 2013 Feb 23;381(9867):628. AlMazroa, Mohammad A [added]; Memish, Ziad A [added]. PMID: 23245607; PMCID: PMC6350784.

[ii] Stathakis V, Kilkenny M, Marks R. Descriptive epidemiology of acne vulgaris in the community. Australas J Dermatol. 1997 Aug;38(3):115-23. doi: 10.1111/j.1440-0960.1997.tb01126.x. PMID: 9293656.

[iii] Williams HC, Dellavalle RP, Garner S. Acne vulgaris. Lancet. 2012 Jan 28;379(9813):361-72. doi: 10.1016/S0140-6736(11)60321-8. Epub 2011 Aug 29. Erratum in: Lancet. 2012 Jan 28;379(9813):314. PMID: 21880356.

[iv] Mahto A. Acne vulgaris. Medicine. 2017;45(6):386–9. doi: 10.1016/j.mpmed.2017.03.003.

[v] Vongraviopap S, Asawanonda P. Dark chocolate exacerbates acne. Int J Dermatol. 2016 May;55(5):587-91. doi: 10.1111/ijd.13188. Epub 2015 Dec 29. PMID: 26711092.

[vi] Choi EH, Ahn SK, Lee SH. The changes of stratum corneum interstices and calcium distribution of follicular epithelium of experimentally induced comedones (EIC) by oleic acid. Exp Dermatol. 1997 Feb;6(1):29-35. doi: 10.1111/j.1600-0625.1997.tb00142.x. PMID: 9067704.

[vii] Aalemi AK, Anwar I, Chen H. Dairy consumption and acne: a case control study in Kabul, Afghanistan. Clin Cosmet Investig Dermatol. 2019 Jul 1;12:481-487. doi: 10.2147/CCID.S195191. PMID: 31303778; PMCID: PMC6611707.

Di Landro A, Cazzaniga S, Parazzini F, Ingordo V, Cusano F, Atzori L, Cutrì FT, Musumeci ML, Zinetti C, Pezzarossa E, Bettoli V, Caproni M, Lo Scocco G, Bonci A, Bencini P, Naldi L; GISED Acne Study Group. Family history, body mass index, selected dietary factors, menstrual history, and risk of moderate to severe acne in adolescents and young adults. J Am Acad Dermatol. 2012 Dec;67(6):1129-35. doi: 10.1016/j.jaad.2012.02.018. Epub 2012 Mar 3. PMID: 22386050.

Ulvestad M, Bjertness E, Dalgard F, Halvorsen JA. Acne and dairy products in adolescence: results from a Norwegian longitudinal study. J Eur Acad Dermatol Venereol. 2017 Mar;31(3):530-535. doi: 10.1111/jdv.13835. Epub 2016 Jul 16. PMID: 27422392.

Dai R, Hua W, Chen W, Xiong L, Li L. The effect of milk consumption on acne: a meta-analysis of observational studies. J Eur Acad Dermatol Venereol. 2018 Dec;32(12):2244-2253. doi: 10.1111/jdv.15204. Epub 2018 Sep 5. PMID: 30079512.

[viii] Di Landro A, Cazzaniga S, Parazzini F, Ingordo V, Cusano F, Atzori L, Cutrì FT, Musumeci ML, Zinetti C, Pezzarossa E, Bettoli V, Caproni M, Lo Scocco G, Bonci A, Bencini P, Naldi L; GISED Acne Study Group. Family history, body mass index, selected dietary factors, menstrual history, and risk of moderate to severe acne in adolescents and young adults. J Am Acad Dermatol. 2012 Dec;67(6):1129-35. doi: 10.1016/j.jaad.2012.02.018. Epub 2012 Mar 3. PMID: 22386050.

[ix] Karadağ AS, Balta İ, Saricaoğlu H, Kiliç S, Kelekçi KH, Yildirim M, Arica DA, Öztürk S, Karaman G, Çerman AA, Bilgili SG, Turan E, Demirci MM, Uzunçakmak TK, Güvenç SC, Ataseven A, Ferahbaş A, Aksoy B, Çölgeçen E, Ekiz Ö, Demir FT, Bilgiç Ö, Çakmak S, Uçmak D, Özuğuz P, Konkuralp YK, Ermertcan AT, Gökdemir G, Başkan EB, Alyamaç G, Şanli H. The effect of personal, familial, and environmental characteristics on acne vulgaris: a prospective, multicenter, case controlled study. G Ital Dermatol Venereol. 2019 Apr;154(2):177-185. doi: 10.23736/S0392-0488.17.05532-8. Epub 2017 Jul 11. PMID: 28704984.

[x] Rombouts S, Nijsten T, Lambert J. Cigarette smoking and acne in adolescents: results from a cross-sectional study. J Eur Acad Dermatol Venereol. 2007 Mar;21(3):326-33. doi: 10.1111/j.1468-3083.2006.01915.x. PMID: 17309453.

[xi] Travagli V, Zanardi I, Valacchi G, Bocci V. Ozone and ozonated oils in skin diseases: a review. Mediators Inflamm. 2010;2010:610418. doi: 10.1155/2010/610418. Epub 2010 Jul 4. PMID: 20671923; PMCID: PMC2910505.

[xii] Sega A, Zanardi I, Chiasserini L, et al. Properties of sesame oil by detailed 1H and 13C NMR assignments before and after ozonation and their correlation with iodine value, peroxide value, and viscosity measurements. Chemistry and Physics of Lipids. 2010; 163:148-156.

[xiii] Khaoshi, X. and Zhang, C. (2020) Formulation and Clinical Evaluation of Ozonated Olive Oil for the Treatment of Acne Vulgaris Lesions. Stem Cell, 11, 54-60.