androgens, mitigating the effects of hormonal dysregulation involvement in AV.
Besides carbohydrates and simple sugar consumption, some key vitamins and minerals may have contributory effects on the clinical manifestations and severity of AV. Zinc is a key cofactor in the regulation of protein and lipid metabolism and, specific to AV, it has been shown to be bacteriostatic against C. acnes, as well as reduce the pro-inflammatory cytokine TNF-alpha.43 Deficiency in selenium has also been reported in AV patients.44 Additionally, selenium supplementation has been shown to play a role in hormone regulation by decreasing the levels of the testosterone precursor dehydroepiandrosterone (DHEA) in female patients with polycystic ovary syndrome (PCOS), an endocrine disorder associated with AV as an established manifestation of androgen excess.45 Additionally, low levels of vitamin D have been correlated with AV severity, predominantly visibly inflammatory AV lesions.46 Supplementing with vitamin D in these patients has been noted to exhibit some improvement in the number of inflammatory AV lesions.47 Finally, low levels of folate have been observed in AV patients.48 Folate has many roles, but one of the most potential links to AV is its inhibitory effects on homocysteine (HCY) levels, which have been documented to be markedly elevated in patients with moderate-to-severe AV.49 HCY degrades structural components of skin, stimulating the production and enzymatic activity of matrix metalloproteases (MMPs); some MMPs function to degrade elastin and collagen and can modulate AV lesion resolution and scarring potential.50,51 Folate also has been hypothesized to play a role in the evolutionary adaptation to ultraviolet (UV) radiation to provide important repair mechanisms to photodamage.52 Although the role of vitamins and minerals in AV warrants additional study, the rationale for proper supplementation based on the collective data reviewed above is well founded and can also provide other positive health benefits beyond just the skin.
The intake of essential vitamins and minerals is vital for good health, including for skin. For example, vitamin A is essential for immune activity, epithelial barrier function, and cell differentiation, but is not synthesized by the human body, so it must be consumed in amounts that are needed physiologically.53 The correlation of oral vitamin A and its therapeutic effects for AV was first shown in a clinical study in 1942.54 This eventually became the basis for the development of tretinoin in the 1960s and isotretinoin in the 1970s.5,54 It has also been observed that low levels of vitamin C are associated with poor wound healing and compensatory thickening of the stratum corneum.53 Taken together, these data suggest that appropriate levels of these and other vitamins and minerals could contribute to improving AV by supporting several of the important physiological mechanisms needed for healthy skin, with some observations more closely related to AV pathophysiology.
Skin and Gut Microbiome
Treatment of AV with systemic antibiotics has been well-established to be effective over several decades of experience and data, suggesting a bacterial component in the pathophysiology of AV.55,56 It remains apparent that colonization with pro-inflammatory strains of C. acnes is a direct contributor to AV pathophysiology and reduction in these strains correlates with improvement in AV.57 However, we recognize that C. acnes does not exist in a vacuum in the skin, and that there is a relationship of microorganisms within the skin microbiome, and even within the gastrointestinal (GI) tract, that can affect AV pathophysiology.16,58 Differences in host response to strains of C. acnes and other microbiome changes that occur in AV may also affect AV severity.12
The top 4 major phyla on the skin are the same for both AV and healthy patients, with differences in diversity of some major microbes shown to correlate with individuals presenting with or without AV.16,58,59 Moreover, the common use of topical and systemic antibiotics contributes to changes in diversity in the gut and skin microflora, allowing resistant bacterial strains to persist often over several months to years after discontinuation of antibiotic therapy.58 The overpopulation of pro-inflammatory strains of C. acnes on the skin triggers several immune responses. These include stimulation of the release of inflammatory mediators (IL-17A and IFN-gamma, IL-1alpha, IL-8, and TNF-alpha) through Toll-like receptors (TLR) on T lymphocytes; secretion of proteases, lipases, and hyaluronidases leading to tissue damage; accumulation of sebum due to lipogenesis by sebocytes; induction of antibacterial resistance to agents and host inflammatory cells; and contribution to AV scar formation through the release and modulation of MMPs.12,58,60
More recently, dysbiosis of the gut microbiome has been associated with many chronic inflammatory conditions, including AV, with 54% of AV patients reported to have marked changes showing dysbiosis in the GI tract microflora; these include a decrease in some organisms known to exhibit positive probiotic effects.16,61,62 With >70% of the immune system reportedly found within the GI tract, the gut is an important location for many inflammatory and potentially pathophysiologic triggers.63,64 Many factors contribute to changes in the gut microbiome, such as host physiology and genetics, antibiotic use, stress, diet, and underlying disease states.65 Participants consuming a Western diet have been shown to often exhibit altered levels of gut microbes, highlighting the potential upstream implications of diet and metabolism on overall health, including AV development.61,66 AV patients have been reported to have a decrease in gut microbial diversity and a loss of commensals such as Faecalibacterium and Clostridiales.61 Dysbiosis of the gut microbiome has been linked to diminished intestinal barrier integrity (increased intestinal permeability) and increased
