Background/Objectives: Chronic severe neuropathic pain (NP) affects one in 10 individuals over the age of 30 in North America. Standard pharmacological interventions are associated with significant side effects and have limited effectiveness. Diets seeking to improve physiological health, support gut barrier integrity, and decrease systemic inflammation have recently emerged as powerful tools conferring neuroprotective and anti-inflammatory effects, potentially reducing the overall morbidity and mortality of multiple neurological and metabolic diseases. This systematic review aimed to synthesize the literature around NP outcomes following dietary interventions compared to routine standard of care. Methods: Following PRISMA guidelines, an initial search yielded 15,387 records after deduplication. Six interventional trials specifically assessing dietary interventions for neuropathic pain were included and analyzed. The dietary lifestyle interventions included low-fat plant-based, plant-based fasting-mimicking, low-calorie, potassium-reduced, gluten-free, and intermittent high-protein/Mediterranean diets. Results: The included studies described some statistically significant improvements in pain severity on objective quantitative sensory testing, electrophysiology, imaging, and subjective questionnaires. The overall risk of bias was moderate, with only one trial demonstrating a low risk of bias across all assessed domains. No serious adverse events were identified, and dietary interventions were generally well tolerated. Conclusions: The data collected and synthesized in this systematic review indicate that dietary lifestyle interventions may offer a low-risk, low-cost, low-tech option for chronic neuropathic pain management, potentially improving quality of life and reducing overall morbidity. However, given substantial variability across studies and a moderate risk of bias, further research is warranted to substantiate these findings.
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