Methionine restriction diets: Unravelling biological mechanisms and enhancing brain health

Background: Methionine (Met) uptake and metabolism are integral to various cellular functions. Excessive intake of Met from human diets can lead to numerous health issues. Conversely, methionine restriction (MR) diets have recently gained considerable attention due to their diverse bioactivities. These include anti-cancer, anti-aging and anti-inflammatory, anti-obesity, cardiovascular protection, intestinal improvement, liver protection, brain health improvement, and other effects. The effectiveness of MR in exerting these bioactivities is closely linked to the modulation of critical molecular targets. Scope and approach: This review offers a thorough and current examination of Met food sources, Met metabolism, the beneficial functions, particularly in brain health, and potential adverse effects of MR diets, along with their underlying molecular mechanisms. Specifically, the impact of MR diets on homocysteine (Hcy) metabolism. Key findings and conclusions: In addition to plant-based and animal-based foods, Met can also be obtained from microbe-based foods. MR may be more easily adopted by humans without the need to restrict energy intake. MR offers multiple health benefits, including anti-obesity, anti-diabetic, anti-cancer, cardiovascular protective, and neuroprotective effects. These benefits stem from its impact on various regulatory mechanisms, such as onecarbon metabolism, oxidative stress, mTOR signaling, IGF-I signaling, FGF21 and H2S production, epigenetics, and regulation of short-chain fatty acids (SCFAs). N-Hcy-protein is associated with various Hcy pathologies, and MR may effectively block its formation. Clinical trials have demonstrated the efficacy of MR in treating obesity and cancer, highlighting the need for further exploration of its therapeutic potential. Overall, MR diets show promise for the preventing of certain chronic human diseases.