Dear Colleagues,

1. Introduction and Purpose

Nutritional science is evolving from examining single nutrients to adopting a more integrated view of how dietary components interact to influence human health. Indeed, while reductionist methods have been effective in identifying deficiency diseases, such as linking scurvy to vitamin C deficiency, this type of research is inadequate for addressing modern complex chronic conditions, such as obesity, diabetes, cardiovascular disease, and cancer. Thus, focusing on individual nutrients alone leaves several key challenges unresolved and underscores the need for a more synergistic perspective:

• The “whole food” paradox: Epidemiological studies consistently link diets rich in fruits, vegetables, and whole grains to better health. However, isolating and supplementing specific compounds from these foods often fails to replicate benefits and may even cause harm (e.g., beta-carotene increasing lung cancer risk in smokers). This suggests that health effects arise from synergistic interactions within whole foods rather than from isolated components.
• Individual variability: Since genetics, gut microbiome composition, metabolism, and lifestyle vary in the population, individuals respond differently to the same diet. Thus, no universal “ideal” diet exists, so these interactions should be considered to enable personalized nutrition.
• Dynamic biological networks: Nutrients act through complex networks, including inflammatory pathways, metabolic regulation, and the gut–brain axis, rather than through single, isolated mechanisms. For example, the anti-inflammatory role of omega-3 fatty acids involves multiple cellular and signaling pathways, unlike a single-target drug.

This Special Issue, “Advancements in Synergistic Nutrition: Methodological Innovations and New Perspectives”, aims to highlight research that explores how nutrition interacts with biological, pharmacological, and lifestyle factors to improve health outcomes. We encourage research that extends beyond observation, using advanced methods to uncover the “how” and “why” behind these relationships and to decode the underlying mechanisms involved.

2. Scope and Topics

① Evidence for Synergistic Nutrition

We invite research that showcases how combining nutrition with other factors improves health outcomes, including but not limited to:

• Nutrient–Nutrient Synergy: How vitamins, minerals, and phytonutrients enhance the bioavailability or activity of each other.
• Nutrition–Drug Interactions: How diet can improve drug effectiveness or reduce side effects.
• Nutrition–Toxins Interactions: How foods counteract harmful substances.
• Nutrition–Gene Synergy: How genetics shapes individual responses to dietary components or patterns.
• Nutrition–Microbiome Synergy: How diet affects gut microbiome and systemic health.
• Nutrition–Food Matrix and Processing Synergy: How food structure and preparation alter nutrient availability and health impacts.
• Nutrition–Lifestyle Integration: The combined effects of diet with exercise, sleep, and circadian rhythms.
• Nutrition–Psychological Factors: How nutritional interventions interact with psychological well-being via the gut–brain axis.

② Innovative Methods

We welcome papers that utilize innovative technologies to map synergistic pathways:

• Nutritional Epidemiology: Large-scale data, Mendelian randomization, and clinical randomized control trials (RCTs) that compare combined interventions to single treatments.
• Dietary Indices: Studies that incorporate one or several dietary indices in relation to the observed outcomes, such as the dietary inflammatory index (DII) and others.
• Computational Approaches: Artificial intelligence (AI), machine learning, and network models to predict nutrient interactions and identify targets.
• Chemical Biology Techniques: Application of chemical probes, activity-based protein profiling (ABPP), thermal proteome profiling (TPP), surface plasmon resonance (SPR), biolayer interferometry (BLI), etc., to identify binding sites and mechanisms.
• Multiomics Integration: Genomics, transcriptomics, proteomics, and metabolomics to unravel systemic mechanisms.

Yuxiao Tang, Yu An and Liangkai Chen
Guest Editors