New Trend: Methionine Restriction and Dietary Change

Hundreds of years ago, sailors from small European cities, risking their lives, rounded the Cape of Good Hope at the tip of the African continent, entered the Indian Ocean, and reached the Indian subcontinent and the islands of South Asia. They then turned westward, first reaching a place called "India." Magellan and his companions continued westward, finally proving that the Earth we inhabit is truly a sphere, not a flat, flat Earth.

They suddenly discovered that the world was far beyond their imagination. The vast oceans and lands held a dazzling array of people, animals, trees, flowers, and even food. Food was redefined and reinterpreted by humanity. Curiosity and wonder attracted a large number of sailors, adventurers, merchants, and travelers. Differences in food led to price differentials, and trade began. Porcelain, silk, and tea from the mysterious East, and tomatoes, potatoes, and corn from America became items of exchange. Spices were also part of this triangular trade, linking four geographically distant continents economically. This, along with the infamous slave trade, also led to it.

For centuries, Europeans' thirst for pepper, cinnamon, and cloves enriched merchants, who amassed vast fortunes from the spice trade from Malacca to Marseille. Monarchs profited from the pepper trade to fund their armies. Once-small European cities like Venice, Lisbon, and Amsterdam, resource-poor places, had no choice but to seek livelihoods abroad. Asian spices played a leading role in the flourishing of urban trading centers. These cities rose to become among the world's greatest, ruling a spice empire (Krondl, The Taste of Conquest, 2008). 

Spices weren't nutritional ingredients, but they enhanced the flavor of food and prolonged its shelf life, preserving meat for months before refrigeration. Transport and exchange, by breaking down the constraints of origin, allowed people throughout Europe to enjoy the flavors of distant lands, from Turkey, Jerusalem, India, China, and the Americas. 

Textbooks teach that history moves on a giant wheel, encompassing world wars, Napoleonic upsoaring, popular revolutions, economic upheavals, and technological changes. Yet, seemingly insignificant details of everyday life can transform the world order. Searching for a modern commodity comparable to the transformative role played by spices in Europe's expansion, historians have sought analogies with today's dependence on Middle Eastern oil. However, it is precisely this very non-essentiality that makes them a useful lens for examining humanity's relationship with food. Once people no longer fear starvation, their reasons for eating become diverse. Food is more than just fuel; it carries profound logic and symbolic meaning.

People are often perceived as having conservative taste preferences. While this may be true for specific individuals, societal dietary habits often shift within a generation or two, just as Italians generally didn't develop a love for pasta until after World War II. Today, culinary styles across countries are constantly evolving and converging. It's fair to say that McDonald's, Coca-Cola, and their imitators are ubiquitous worldwide. Fast food culture, the processing and preparation of food, the use of spices and additives, combined with convenient logistics and the growth of tourism, have resulted in globalization, leading to the most dramatic culinary transformations in the world's major cities. Cuisine from around the world has converged, making it easy to sample and imitate.

Food isn't just about satisfying hunger; it's also about nutrition and health. Disease is humanity's greatest threat. Diabetes, cardiovascular disease, cognitive impairment in the elderly, cancer, and aging are all surging, becoming the next most pressing concern. A low-methionine diet is gaining increasing acceptance.

Methionine is an essential sulfur-containing amino acid that cannot be synthesized by the human body and must be obtained through diet. It plays a central role in protein synthesis, methylation reactions (DNA methylation and protein modification), and glutathione synthesis (antioxidant defense). Major sources include meat, fish, eggs, dairy products, and some nuts and seeds. Plant proteins (especially legumes and grains) are generally low in methionine.

Low-methionine diets initially attracted attention in animal studies due to their association with lifespan extension, tumor suppression, and improved metabolic health (Orentreich et al., 1993; Richie et al., 2004). The main mechanisms include: inhibition of the mTOR signaling pathway, accompanied by slowed cell proliferation and aging, reduced IGF-1 levels, reduced cancer cell growth signals, altered mitochondrial metabolism, reduced oxidative stress, impacted DNA methylation patterns, and delayed epigenetic aging. Although long-term, systematic clinical studies in humans are limited, its health effects can be inferred from multiple perspectives. A low-methionine diet has been shown to significantly extend lifespan (10–40%) in models such as mice and fruit flies. It is speculated that it may also delay age-related diseases (cardiovascular disease, diabetes, and neurodegenerative diseases) in humans, with potential benefits in slowing aging. The mechanism is similar to caloric restriction (CR), but may have fewer side effects because it does not require a total reduction in energy intake.

Many tumors (breast cancer, gastric cancer, and glioma) are highly dependent on methionine. Methionine restriction can metabolically "starve" cancer cells, potentially enhancing the efficacy of chemotherapy or radiotherapy when combined with chemotherapy (Gao et al., 2019). By improving metabolism, a low-methionine diet can lower blood sugar, improve insulin sensitivity, and reduce hepatic fat accumulation, potentially providing a therapeutic benefit for type 2 diabetes and fatty liver disease.

However, inherent potential risks include impaired immune function. T cells require methionine to synthesize SAM (S-adenosylmethionine) and maintain DNA and histone methylation; deficiency may weaken immune responses (Bian et al., 2020). In cancer patients, excessive methionine restriction may actually reduce anti-tumor immunity. Inadequate protein synthesis. Long-term extremely low methionine intake may impair muscle synthesis, leading to sarcopenia or decreased physical strength, a risk particularly high in the elderly. Developmental risks: Children, pregnant women, and lactating women have a higher methionine requirement. Long-term methionine restriction may affect nervous system development and the establishment of methylation imprints.

Low-methionine foods are not naturally rare. Future technological approaches include protein reconstruction and plant-based protein formulations. Leveraging the low methionine content of legumes, grains, and potatoes, precise formulations can be used to create low-methionine but high-nutrient foods. Alternatively, precision fermentation can be employed to produce proteins with specific amino acid ratios through microbial production, eliminating or reducing methionine. CRISPR technology can edit the relevant enzymes in high-methionine crops (such as corn and soybeans) to create low-methionine varieties suitable for specific populations. Combining genomics and metabolomics can assess individual methionine metabolism and tailor protein ratios and sources to achieve a precisely tailored low-methionine diet.

The global popularity of modern fast food (McDonald's, KFC, Starbucks) is the result of an industrialized food system, standardized flavors, and efficient distribution. For low-methionine health foods to gain global appeal, they must find a similar opportunity to fuse East and West, focusing on grains, legumes, and vegetables that are inherently low in methionine, and emphasizing the medicinal and edible properties of foods like soybeans, mung beans, and Job's tears. This integration with Western diets, coupled with advanced industrialization and increased health awareness, has led to a willingness to try plant-based alternatives, gradually addressing the prevalence of high-protein diets and excessive animal protein intake. Low-methionine foods can be marketed as a scientifically advanced vegetarian diet in the East and as a future food for anti-aging and cancer prevention in the West. Examples include low-methionine burgers (plant-based protein meat with a low-methionine sauce), Eastern-style low-methionine bento boxes (multi-grain rice with tofu and seasonal vegetables), and functional low-methionine meal replacement shakes (with added polyphenols and prebiotics).

The next question is whether low-methionine foods will become as popular as fast food. To become popular, large-scale clinical data must support the safety and benefits of a low-methionine diet. The taste and price competitiveness must be comparable to regular foods at an affordable price. Brands and culture must associate low-methionine foods with health and longevity, personalized nutrition, and sustainable development, forming a dietary habit. In the short term (5-10 years), it is expected to first gain popularity among high-income, health-conscious individuals, similar to the current ketogenic and vegan diets. In the medium term (10-20 years), the functional food industry chain will mature, and low-methionine products will enter mainstream supermarket shelves. In the long term (20+ years), if sufficient scientific evidence is available, they could become a public health recommendation, similar to low-sugar diets, driving a global restructuring of dining culture. If these conditions are met, it may promote the integration of Eastern and Western diets, combining the traditional low-methionine grain vegetarian diet of the East with the modern food industry of the West to create a group of new global functional food brands. 

Imagine a female office worker in Shibuya buying an "M-Lite Low-Methionine Sushi Roll" at a subway station convenience store one morning. The rice is a mix of low-methionine brown rice and quinoa, and the filling is "vegetarian tuna" made from fermented soy, topped with a small amount of nori powder, rich in iodine and polyphenols. As she eats, she scrolls through the news on her phone, reading about new research suggesting a low-methionine diet may slow skin aging. To her, it's just as natural a habit as drinking more water and walking more. A Wall Street financial analyst walks into a PlantFusion fast food restaurant in Manhattan and orders an "Anti-Cancer Energy Bowl" of low-methionine mung bean noodles topped with roasted broccoli, shredded carrots, a sprinkling of almonds, and seasoned with sesame paste and turmeric juice. A QR code is placed on the bottom of the bowl, allowing users to scan it and see their daily methionine intake and blood sugar response forecast. In Paris in the year 2045, a French restaurant called Cuisine Longévité is serving dinner. The appetizer is low-methionine pumpkin puree, the main course is a "vegetarian steak" made from fermented soy protein with a red wine sauce, and the dessert is a "longevity mousse" made with oat milk and berries. Low-methionine cuisine in France has not lost its sophistication, but has become a symbol of elegant and healthy living. The chef tells diners that this is more than just a diet; it's an investment in one's future.

Perhaps by 2050, the global integration of low-methionine foods will have matured. Japanese convenience store sushi will use low-methionine soybeans from Brazil. American burger chains will offer "Oriental Veggie Burgers" with low-methionine rice crackers and spicy tofu. Chinese food delivery platforms offer "low-methionine hot pot combos" with a broth containing goji berries, reishi mushrooms, and porcini mushrooms, emphasizing both the medicinal and edible qualities and molecular nutrition. European restaurants are offering "Mediterranean low-methionine menus" featuring olive oil, beans, and whole-wheat bread. This integration is not only happening in high-end restaurants but also in home kitchens and street food stalls. Low methionine is no longer a strange nutritional term; it's become an everyday concept, like sugar-free or high-fiber. The adoption of low-methionine foods bears similarities to that of fast food: a global supply chain, with core ingredients (beans, grains, and vegetables) sourced from diverse regions around the world. Standardized production processes ensure precise nutritional ratios and consistent taste, representing a healthy, long-lived, and environmentally friendly lifestyle. However, unlike fast food, it relies on scientific evidence and personalized nutrition technology, rather than simply stimulating taste. It pursues long-term health benefits rather than instant gratification.

Even so, the adoption process is not without challenges. Consumers in some regions may not be accustomed to the taste of plant-based and low-methionine foods, requiring time to adapt. Early technology costs were high, and prices were relatively high, requiring reliance on policy subsidies and high-end consumer groups to drive the market. There are also cultural and psychological factors: some may view a low-methionine diet as "restrictive" rather than "free," requiring cultural remediation to change perceptions. The turning point could come with a global health initiative, such as the WHO or national health ministries incorporating a low methionine intake limit into dietary guidelines. Scientific evidence shows it significantly reduces cancer incidence and prolongs lifespan, and major food companies (Nestlé, Coca-Cola, PepsiCo) roll out a comprehensive line of low-methionine products.

In this scenario, low-methionine foods could become truly global, like modern fast food, but representing not fast and cheap but slow and long-term, a global dietary revolution grounded in nutritional science and transcending cultural boundaries. By then, dishes might include Chinese tofu casserole, French sauces, Spanish olives, American salads, and Japanese miso soup—all with the common characteristic that they gently control methionine levels, silently safeguarding everyone's health and longevity.

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Written by  Dr. Haining Jin ，and  Dr. Bin Xu