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A Plan for Nutraceutical/Dietary Management of Acne Targeting De Novo Lipogenesis and Inflammation
Abstract
The pathogenesis of acne involves an excess of sebum production. Sebum is a fatty substance produced by de novo lipogenesis (DNL) in sebocytes. A key driver of DNL is the transcription factor steroid response element-binding protein 1-c (SREBP-1c), promoted by insulin-like growth factor-1 (IGF-1)-mediated activation of Akt. Akt disinhibits the LXR-mediated transcription of the SREBP-1c
gene by promoting nuclear exclusion of FOXO1; concurrently, it promotes proteolytic activation SREBP-1c, while enhancing its half-life, via mTORC1-p70 S6 kinase signaling. Adenosine 5′- monophosphate-activated protein kinase (AMPK) can oppose SREBP-1c activity by suppressing LXR expression, while also inhibiting mTORC1; in addition, it also opposes DNL via direct inhibition of acetyl-coA carboxylase 1 (ACC1). Sirtuin 1 (Sirt1) inhibits the transactivational activity of SREBP-1c by deacetylating it, and also boosts AMPK activity. It is proposed that nutraceuticals which activate AMPK (such as berberine) and Sirt1 (such as ferulic acid, methylnicotinamide, and melatonin) thus inhibiting sebocyte DNL. Bacterially driven inflammation may be suppressed with nutraceutical antioxidants such as spirulina, lipoic acid, N-acetylcysteine, and supplemental fish oil. Dietary wise, the plasma free IGF-1 which promotes sebocyte DNL could be reduced with low-protein plant-based diets or low-glycemic-load “Paleolithic” diets – consistent with the observation that acne is a
“disease of civilization”. Practical Applications: The present review is focused on feasible nutraceutical strategies for Acne therapy targeting de novo Lipogenesis and Inflammation. The topic of nutraceuticals that down-regulate those two major pathological pathways in Acne development is a new evolving therapeutical strategy. The mechanisms are reported, and the different nutraceuticals interact in a complementary fashion to reduce risk of Acne, while also helping to prevent it. Additionally, the present review reports practical daily dose ranges for those nutraceuticals that might be expected to have physiological activity. To our knowledge, such an updated manuscript, on
the topic of Acne and nutraceuticals is not available in the food or medical literature.
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