How hydrogen work on fat loss?
improving metabolism through regulation of glucagon-like peptide-1 (GLP-1), irisin, and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) It's just a hypothesis! The growing prevalence of obesity and non-communicable diseases has become a major global health problem, resulting in high morbidity and mortality. These diseases not only impose a heavy burden on healthcare systems, but also affect the quality of life of people around the world. As these challenges continue to grow, there is an urgent need to explore effective, economical and accessible treatment options. Although traditional pharmaceutical interventions have shown some efficacy, they often have limitations, including side effects and/or high costs, which highlights the importance of studying alternative or complementary approaches to address these complex health problems. Dietary supplements offer a promising complementary treatment approach by affecting metabolic pathways. Recent advances in the study of metabolic regulation, including the role of gut hormones such as glucagon-like peptide-1 (GLP-1), have opened up new possibilities for innovative treatment approaches. With this goal in mind, we propose hydrogen (H₂) as a potential adjunctive strategy for the management of obesity and related noncommunicable diseases. Hydrogen is a medical gas whose antioxidant, anti-inflammatory, and signaling properties have been extensively demonstrated in more than 1,000 studies in more than 100 disease models. It has shown significant effects in improving clinical endpoints and surrogate markers ranging from metabolic diseases to chronic systemic inflammatory diseases. For example, a 6-month randomized clinical trial involving 1,088 patients with type 2 diabetes (T2DM) receiving standard antidiabetic therapy, some of whom supplemented with inhaled hydrogen and some of whom did not, showed that long-term use of hydrogen significantly improved key metabolic parameters. Specifically, patients in the hydrogen group had reduced levels of glycated hemoglobin, fasting glucose, and total cholesterol, while the homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-β) indices improved, highlighting the potential impact of hydrogen therapy on metabolic health. In a related study, our research team conducted a meta-analysis demonstrating the potential of hydrogen-rich water (HRW) on lipid profiles in clinical populations. Our results showed that total cholesterol, low-density lipoprotein, and triglyceride levels decreased significantly after hydrogen-rich water intervention. These results highlight the key role of hydrogen in metabolic health, indicating that hydrogen can not only regulate lipid profiles, but may also affect insulin and ghrelin, two key hormones that are essential for blood sugar regulation. One of the main mechanisms explaining the effect of hydrogen on insulin involves the regulation of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α). For example, early studies have shown that giving male db/db diabetic mice drinking hydrogen-rich water for two weeks increased the expression of PGC-1α and significantly affected their metabolic profile. In addition, the potential regulatory effect of hydrogen-rich water on PGC-1α expression may also be related to irisin, an actin released into the blood by cleaving fibronectin type III domain-containing protein 5 (FNDC5). The expression of PGC-1α in muscle stimulates increased expression of FNDC5, which in turn directly affects the circulating levels of irisin. Irisin enhances the metabolic activity of adipocytes and myocytes, while also having a protective effect on obesity, insulin resistance, and non-alcoholic fatty liver disease, and these metabolic benefits are associated with inflammatory markers. This suggests that irisin may be involved in regulating inflammatory responses, and it is likely that this irisin-related mechanism partially explains the anti-inflammatory and antioxidant effects of hydrogen. The possible connection between hydrogen and irisin may significantly change the research perspective of hydrogen application. In recent years, therapeutic research on GLP-1 has received widespread attention. Studies have shown that treatment with GLP-1 receptor agonists can bring many benefits, including improved cardiovascular outcomes, reduced mortality, and improved renal function in patients with type 2 diabetes. In addition, GLP-1 receptor agonists can promote weight loss in overweight and obese individuals, regardless of whether they have type 2 diabetes. Therefore, finding treatments or supplements that can regulate GLP-1 secretion has become a focus of metabolic research. Hydrogen may affect GLP-1 secretion through multiple pathways, including those involving PGC-1α and the gut microbiota, potentially enhancing its effects. PGC-1α is primarily known for its involvement in mitochondrial biogenesis, fatty acid oxidation, and energy homeostasis regulation in multiple tissues, including the liver, skeletal muscle, and adipose tissue. Its activation can affect metabolic pathways that may intersect with those regulated by GLP-1. For example, the effects of GLP-1 in improving liver fat accumulation may involve pathways related to mitochondrial function and fat metabolism, which are areas where PGC-1α plays a key role. In addition, studies have shown that GLP-1 can regulate the mitochondrial protective gene PGC-1α. GLP-1 increases PGC-1α expression by downregulating miR-23a, thereby inhibiting hepatocyte apoptosis. Moreover, it also enhances the activity of mitochondrial uncoupling protein 2, which reduces apoptosis by alleviating mitochondrial stress, further emphasizing the interconnected role of these pathways in cell protection. In contrast, hydrogen plays a role in regulating the gut microbiota, thereby indirectly affecting GLP-1 secretion. Studies have shown that short-chain fatty acids (SCFAs) can modulate the release of gut hormones, including triggering the secretion of GLP-1. Certain gut bacteria stimulate the release of GLP-1 by producing short-chain fatty acids such as butyrate, which are known to activate GLP-1-producing L cells in the intestine. A previous study found that hydrogen supplementation for 12 weeks in 10 middle-aged overweight individuals (5 of whom were women) altered their levels of short-chain fatty acids, especially propionate and butyrate. By promoting a healthy intestinal microbial environment, hydrogen may enhance the production of short-chain fatty acids, thereby promoting GLP-1 secretion and improving metabolic regulation. As more and more evidence continues to emerge, the role of hydrogen in regulating GLP-1 secretion through anti-inflammatory effects, regulating the gut microbiota, and enhancing PGC-1α provides a promising direction for metabolic research. In summary, we believe that hydrogen can be a valuable adjunctive treatment for patients with metabolic diseases (see Figure 1). However, further basic and experimental research is needed to elucidate its mechanism of action and expand its therapeutic potential in the management of diseases such as type 2 diabetes, obesity, and metabolic syndrome.
Figure 1: Hydrogen-mediated regulation of PGC-1α, irisin, and GLP-1 expression. The effects of hydrogen gas (H2) on metabolic health are multifaceted. First, H2 enhances the activity of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), which subsequently promotes irisin production through the fibronectin type III domain-containing protein 5 (FNDC5) pathway. In addition, PGC-1α forms a positive feedback loop with glucagon-like peptide-1 (GLP-1), which together have beneficial effects on metabolic health. In addition, H2 has a positive impact on the gut microbiota by promoting the production of short-chain fatty acids (SCFAs), especially butyrate and propionate. These SCFAs have been shown to enhance the secretion of GLP-1, forming a positive feedback loop that further supports metabolic regulation. Created with Adobe Photoshop CS6.