Magnesium, Little Known But Possibly Relevant: A Link between NASH and Related Comorbidities

Abstract

Non-alcoholic steatohepatitis (NASH) is characterized by an abnormal hepatic lipid accumulation accompanied by a necro-inflammatory process and a fibrotic response. It comprises from 10% to 30% of cases of patients with non-alcoholic liver disease, which is a global health problem affecting around a quarter of the worldwide population. Nevertheless, the development of NASH is often surrounded by a pathological context with other comorbidities, such as cardiovascular diseases, obesity, insulin resistance or type 2 diabetes mellitus. Dietary imbalances are increasingly recognized as the root cause of these NASH-related comorbidities. In this context, a growing concern exists about whether magnesium consumption in the general population is sufficient. Hypomagnesemia is a hallmark of the aforementioned NASH comorbidities, and deficiencies in magnesium are also widely related to the triggering of complications that aggravate NASH or derived pathologies. Moreover, the supplementation of this cation has proved to reduce mortality from hepatic complications. In the present review, the role of magnesium in NASH and related comorbidities has been characterized, unraveling the relevance of maintaining the homeostasis of this cation for the correct functioning of the organism.

Protective effects of baicalin magnesium on non-alcoholic steatohepatitis rats are based on inhibiting NLRP3/Caspase-1/IL-1β signaling pathway

“…In addition to, it has been found that reduced levels of magnesium ions in serum and liver lead to reduced mitochondrial function in the body, metabolic disorders, oxidative stress and inflammatory responses thus leading to liver-related diseases [ 29 ]. It was found that magnesium ion deficiency can lead to increased blood lipid levels as well as exacerbate lipid deposition in the liver [ 30 ]. Majid et al revealed that magnesium supplementation had an ameliorating effect on the levels of ALT and AST, etc.…”

Magnesium and Liver Metabolism Through the Lifespan

“…The inefficient hepatic blood transfer that occurs with aging exacerbates the reduction in liver size, and the transport of lipoproteins and carbohydrates has also been reported to be altered. Magnesium has been described to correlate inversely with the quality of circulating carbohydrates [ 98 ], and a relationship between the cation and insulin secretion and insulin resistance (IR) has been recently studied by our group [ 5 ]. Almost 50% of patients with type 2 diabetes mellitus (T2DM) suffer from hypomagnesemia, mainly caused by low intake and increased urinary loss of magnesium [ 99 ].…”

“…Hepatocyte physiology is also altered; polyploidy and accumulation of dense bodies [ 95 ], together with increased lipid content [ 101 ] and impaired metabolic pathways such as glycolysis [ 102 ], β-oxidation [ 103 ], autophagy, energy sensing, and circadian rhythms [ 104 ], are characteristic of aged hepatocytes. In this context, our group has reported that magnesium modulates the lipid content of the liver [ 5 ], and its role as a cofactor in energy-processing enzymes may prevent age-related energetic impairment. Similarly, magnesium plays a role in preventing the activation of KCs [ 105 ] and the production of alpha-smooth muscle actin by hepatic stellate cells (HSC) [ 106 ].…”

“…Maintaining homeostasis is crucial for the correct development of liver functions, with an adequate balance of macro- and micronutrients ensuring the aforementioned processes. In this context, magnesium has appeared as a key compound for such processes, as it has been associated with liver diseases [ 4 ] or related comorbidities [ 5 ]. Magnesium, Mg 2+ in its free form, is the most abundant divalent cation in the cell and the fourth most abundant element in the body, with concentrations ranging from 5 to 20 nM.…”

NASH and Systemic Complications: From Basic to Clinical Research

“…Dietary imbalances are increasingly recognized as the root cause of NASH-related comorbidities and Simón et al [ 10 ] describe in this Special Issue that a deficit in magnesium, a micronutrient found in most green vegetables, legumes, peas, beans and nuts, might aggravate NASH and its related diseases. The authors characterized the potential role that magnesium might play in the development of liver diseases and metabolic syndrome.…”