Potential Applications and Risks of Supranutritional Selenium Supplementation in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Critical Review

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most prevalent chronic diseases in the world, lacking specific pharmacological interventions or well-established treatments. MASLD involves intricate pathological mechanisms characterized by oxidative stress and robust inflammatory responses. Selenium, an essential trace element, plays a critical role in antioxidation, regulation of inflammation, anticancer activity, and so on. Recent studies have reported that supplementation with selenium could alleviate MASLD and associated hepatic disorders, while excessive consumption may result in insulin resistance or even selenosis. Therefore, supranutritional selenium supplementation can be more suitable for the therapy and prevention of MASLD. This paper comprehensively reviews research about selenium and MASLD to highlight the potential applications and risks of supranutritional selenium supplementation in MASLD, following three steps: conducting a search, reviewing research articles and reviews, and discussing results. The keywords for the search include but are not limited to selenium, MASLD, supranutritional, hepatic diseases, selenoproteions, and selenium nanoparticles (SeNPs). We have reached the following conclusions: supranutritional selenium supplementation exhibits promising potential as a strategy to treat MASLD, but there are still some risks, depending on the dose and form of selenium; evaluating MASLD severity and selenium nutritional status accurately, as well as supplementing with superior forms of selenium (e.g., organic selenium and SeNPs), can further ensure the safety and efficacy of selenium supplementation. However, relationships between selenium homeostasis disorders and the occurrence and development of MASLD have not been fully elucidated. Methods for comprehensively assessing selenium status and mechanisms of selenosis require further investigation and research.

Keywords: metabolic dysfunction-associated steatotic liver disease; non-alcoholic fatty liver disease; selenium; selenium nanoparticles; selenoproteins; supranutritional.

Figure 1

The pathological progression and risk factors for MASLD. Abbreviations: HCC, hepatocellular carcinoma; MASH, metabolic dysfunction-associated steatohepatitis; TG, triglyceride.

Figure 2

Schematic diagram for the metabolism of selenium. Selenate, selenite, SeMet, SeCys, MeSeCys, and other common dietary forms of selenium gradually transform to selenide (red), which is a precursor for the synthesis of selenoproteins upon intake. Then the central metabolite selenide is used in three major ways: incorporation into selenoproteins (orange), methylation and excretion (green), and conversion to selenosugars (blue). Figure adapted from previous references [41,58,59]. Abbreviations: CH3-SeGalNac, 1β-methylseleno-N-acetyl-D-galactosamine; GS-SeGalNac, 1β-glutathionylseleno-N-acetyl-D-galactosamine; GSSeSG, selenodiglutathione; SeCys, selenocysteine.

Figure 3

Potential mechanisms of selenium intake in MASLD-associated hepatic metabolism. Abbreviations: Akt, protein kinase B; AMPK, adenosine monophosphate-activated protein kinase; ATP, adenosine triphosphate; ECM, extracellular matrix; GPX, glutathione peroxidase; GST, glutathione-S-transferase; KEAP1, Kelch-like ECH-associated protein 1; mTOR, mammalian target of rapamycin; NF-κB, nuclear factor kappa B; NRF2, nuclear factor erythroid 2-related factor 2; PI3K, phosphatidylinositol 3-kinase; ROS, reactive oxygen species; SAM, S-adenosylmethionine; SELENOP, selenoprotein P; TCA, tricarboxylic acid; TLR4, toll-like receptor 4; TXNRD, thioredoxin reductase.