A comprehensive view of cell metabolism provides a new vision of cancer, conceptualized as tissue with cellular-altered metabolism and energetic dysfunction, which can shed light on pathophysiological mechanisms. Cancer is now considered a heterogeneous ecosystem, formed by tumor cells and the microenvironment, which is molecularly, phenotypically, and metabolically reprogrammable. A wealth of evidence confirms metabolic reprogramming activity as the minimum common denominator of cancer, grouping together a wide variety of aberrations that can affect any of the different metabolic pathways involved in cell physiology. This forms the basis for a new proposed classification of cancer according to the altered metabolic pathway(s) and degree of energy dysfunction. Enhanced understanding of the metabolic reprogramming pathways of fatty acids, amino acids, carbohydrates, hypoxia, and acidosis can bring about new therapeutic intervention possibilities from a metabolic perspective of cancer.

The study of cancer biology should be based around a comprehensive vision of the entire tumor ecosystem, considering the functional, bioenergetic and metabolic state of tumor cells and those of their microenvironment, and placing particular importance on immune system cells. Enhanced understanding of the molecular bases that give rise to alterations of pathways related to tumor development can open up new therapeutic intervention opportunities, such as metabolic regulation applied to immunotherapy. This review outlines the role of various oncometabolites and immunometabolites, such as TCA intermediates, in shaping pro/anti-inflammatory activity of immune cells such as MDSCs, T lymphocytes, TAMs and DCs in cancer. We also discuss the extraordinary plasticity of the immune response and its implication in immunotherapy efficacy, and highlight different therapeutic intervention possibilities based on controlling the balanced systems of specific metabolites with antagonistic functions.

Fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic multisystem disorders characterized by persistent fatigue, pain, cognitive dysfunction, sleep disturbances, and reduced quality of life. Increasing evidence implicates mitochondrial dysfunction, oxidative and nitrosative stress, immune dysregulation, and altered redox and nicotinamide adenine dinucleotide (NAD⁺) metabolism as interconnected mechanisms contributing to fatigue, although the strength of evidence varies across these pathways. Micronutrients are essential components of mitochondrial bioenergetics, antioxidant defense, and immune–metabolic regulation. This narrative review critically examines the mechanistic and clinical evidence supporting mitochondrial-oriented micronutritional interventions in fibromyalgia and ME/CFS, including NAD⁺ precursors, B-complex vitamins, magnesium, coenzyme Q10, alpha-lipoic acid, GlyNAC, L-carnitine, pyrroloquinoline quinone, taurine, and creatine. Mechanistic plausibility is distinguished from clinical efficacy, as disease-specific randomized controlled evidence remains limited for several interventions. We further discuss biomarkers, metabolic phenotyping, and precision nutrition within a systems-based micronutrition framework. Finally, we present the rationale for a future randomized, double-blind, placebo-controlled trial in fibromyalgia patients with clinically significant fatigue, which is planned for 2027, subject to ethics approval and prospective registration, as a strategy for future clinical validation.

Objective: to evaluate the feasibility, safety, and preliminary effectiveness of an integrated nutritional strategy combining a low-protein diet with structured micronutrient supplementation in patients with advanced CKD. Methods: A retrospective observational study was conducted in routine nephrology practice across two centers between January 2021 and June 2022. Seventeen adults aged 40–85 years with CKD stages III–V were included. Participants followed an individualized low-protein diet emphasizing plant-based foods and received a structured supplementation protocol containing vitamins, minerals, essential amino acids, and omega-3 fatty acids. Primary outcomes were feasibility, adherence, retention, safety, and tolerability. Secondary exploratory outcomes included changes in estimated glomerular filtration rate (eGFR), serum creatinine, and KDIGO stage classification. Results: The retention rate was 94% and the adherence rate was 100%. No serious adverse events or clinically significant electrolyte disturbances were reported. After a mean follow-up of 4.88 months, mean eGFR increased significantly from 43.3 to 59.8 mL/min/1.73 m² (p < 0.001), while serum creatinine decreased significantly from 1.70 to 1.25 mg/dL (p < 0.001). All patients demonstrated directional improvement, and 94.1% improved by at least one KDIGO stage. Conclusions: Integrated nutritional guidelines were feasible, well tolerated, and associated with significant short-term improvements in renal function among patients with advanced CKD. These findings support the need for a randomized controlled trial to confirm efficacy and assess long-term clinical benefits.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) involves insulin resistance, altered iron homeostasis, and oxidative stress. We explored changes in hepatic steatosis and cardiometabolic parameters following targeted micronutritional supplementation. Methods: In this prospective, single-center, open-label, single-arm pilot study, 15 adults with ultrasound-confirmed moderate-to-severe hepatic steatosis received two standardized micronutrient formulations for four months, alongside previously established dietary recommendations. No new structured weight-loss program was introduced. The pre-specified primary efficacy target was a ≥10% reduction in Fatty Liver Index (FLI). Secondary outcomes included ultrasound steatosis severity, metabolic and biochemical parameters, quality of life, and safety. Results: The primary efficacy target was not achieved. Mean FLI decreased by 2.55 points (59.18 ± 26.67 to 56.63 ± 27.48), corresponding to a 4.3% relative reduction (p = 0.256). Exploratory analyses showed a shift towards lower ultrasound-defined steatosis grades (nominal p = 0.010), with severe steatosis decreasing from 46.7% to 6.7%. BMI remained unchanged, while waist circumference decreased by 0.89 cm (p = 0.046). Fasting glucose (p = 0.033), insulin (p = 0.025), homocysteine (−23%; p = 0.001), and ferritin (p = 0.007) decreased, while transferrin saturation increased (p = 0.005). No serious adverse events occurred. Conclusions: Although the primary endpoint was not met, micronutritional support was associated with exploratory improvements in ultrasound-defined steatosis and selected cardiometabolic biomarkers. Larger controlled trials are warranted.