syndrome or insulin resistance with AV may also benefit from metformin treatment.23 Beyond this, there are traditional botanicals that have been shown to help with balancing the negative effects of glucose and insulin fluctuations, such as berberine and ginger, which also may improve clinical manifestations of AV.
Berberine (Berberis aristate, Indian barberry) is a botanical that has been used in Chinese traditional medicine for hypercholesterolemia, diabetes type 2, and to fight infections.24 Recent research suggests that it does so in part by improving blood glucose and insulin sensitivity through direct effects on LDL receptors and glucose absorption and uptake.25-27 Berberine is now being tested for the management of dyslipidemia, diabetes, and obesity.25-27 In fact, the effects of berberine on plasma lipids are recognized in The European guidelines for the management of dyslipidemias.28 Now, evidence-based studies have linked potential therapeutically beneficial properties of berberine in AV patients. A 2002 comparative study of a tablet containing berberine vs minocycline in acne patients saw no difference between the 2 groups.29 Another study in PCOS women with moderate acne reported a 61% decrease in Global Acne Grading System (GAGS) and 71% decrease in Cardiff Acne Disability Index (CADI).24 Moreover, the relatively minor side effect profile of berberine has seen success when used in patient populations such as those with PCOS or dyslipidemia, where long-term modern therapies were not tolerated.24 In this sense, berberine could provide a powerful tool against a novel target for patients with AV.
Ginger (Zingier officinale), has also been used in traditional medicine for its numerous benefits not only for addressing metabolic disorders, but also for its anti-inflammatory and anti-oxidative properties.30,31 A meta-analysis examining the benefits of ginger on type II diabetes and the associated hyperglycemia found that HbA1c levels and fasting serum glucose levels improved with the consumption of ginger.32 On a larger scale, the benefits of ginger were studied in a meta-analysis including patients with type 2 diabetes, non-alcoholic fatty liver disease, and osteoarthritis. They found that the intake of ginger significantly decreased circulating levels of CRP and tumor necrosis factor-alpha (TNF-alpha).30
Another important aspect of the patient's metabolic profile is their consumption of key vitamins and minerals, and as dermatologists, we have been trained to assess this. In patients with AV, low levels of vitamin A, D, and selenium have been reported and there is growing evidence that once corrected, AV may improve.33-35 Placebo-controlled clinical studies show that supplementing with zinc significantly decreases inflammatory acne scores and improves AV severity in patients.36,37 Niacinamide (vitamin B3) is a key precursor to the coenzymes NAD/NADP/NADH/NADPH, critical for reduction-oxidation reactions throughout the body.38 Niacinamide has been shown to have a wide range of purported benefits in the skin: it has antioxidant effects, improves epidermal barrier function, increases dermal collagen and protein production, and reduces hyperpigmentation.39 Specific to AV, in a formula combined with other ingredients including azelaic acid, zinc, copper, pyridoxine, and folic acid; ingestible niacinamide has been shown to reduce inflammatory papules.40 Indications suggest that vitamin D may be a potent immune modulator with endocrine, paracrine, and autocrine functions.38 Finally, women with PCOS who received selenium in a double-blind, placebo-controlled trial had significantly decreased DHEA levels.41 All of this evidence suggests there may be an overlap of underlying whole-body drivers of AV and a necessity to balance them to manage AV and promote general skin health.
Gut and Skin Microbiome
Antibiotics are a mainstay of acne treatment due to the role of C. acnes in the pathogenesis of AV.42 Both oral and topical antibiotics are commonly prescribed, although short-course therapy is now favored due to the potential for developing antibiotic resistance.43 Along with this, research suggests that the gut microbiome in patients with AV may be less diverse and has a higher ratio of Bacteroides to Firmicutes.42,44 The gut microbiome has been shown to interact with the nutrient-sensitive kinase mammalian target of rapamycin (mTORC), known to play a role in the pathogenesis of AV.45 Oral antibiotics also contribute to gut dysbiosis in patients with moderate-to-severe AV.42,46
Along the same lines, using milk cultures with bacteria topically to treat AV dates back to the 1930s, showing the use of natural remedies to manage the microbiome and thus the underlying pathogenesis of AV.47 Current findings now indicate that improved biodiversity of the skin and gut microbiome is essential for epithelial health.48,49 Clinical studies suggest that supplementing with probiotics may improve symptoms of AV, in part by decreasing sebum production, which could reduce follicular colonization of C. acnes and the associated inflammation.47 It also may have immunomodulatory properties through the inhibition of cytokines in epithelial cells and keratinocytes.47 Supplementing with commensals has also been suggested to aid in the remediation of leaky gut, leading to an improved inflammatory profile systemically.50 The daily intake of the heat-killed postbiotic L-137 has been linked to improved skin parameters such as improved TEWL and improved dermatology life quality index in participants with dry skin.51
The gut microbes may also interact directly with the intestinal lumen cells by promoting immune responses. Short-chain fatty acids (SCFA) such as butyrate, are synthesized and released in the colon by bacterial fermentation of starches and fibers.52 Clinical data suggests that patients
