Tryptophan-based nutritional interventions and fermented foods as adjuvant therapy in Major Depressive Disorder

Abstract

Major Depressive Disorder is a highly prevalent global mental health disorder that severely compromises well-being and socioeconomic dynamics. Although conventional approaches prioritize pharmacological interventions, high rates of refractoriness and side effects drive the search for adjuvant strategies integrated into the microbiota-gut-brain axis. Given this, the present study aims to analyze the combined use of nutritional interventions based on tryptophan and fermented foods as a coadjutant therapy in Major Depressive Disorder, without the intention of replacing conventional pharmacological treatment and necessary psychotherapeutic interventions. To this end, a qualitative narrative review was conducted based on studies published between 2023 and 2026 in the PubMed, SciELO, and Google Scholar databases. The descriptors Depressive Disorder, Tryptophan, Fermented Foods, and Diet therapy were used, including articles in Portuguese and excluding inconsistent methodologies or conference abstracts. The data demonstrate that approximately 95% of serotonin is synthesized in the gastrointestinal tract. Dietary tryptophan is the essential precursor of this pathway, but intestinal dysbiosis and chronic inflammation, triggered by ultra-processed diets, activate enzymatic mechanisms that divert this amino acid toward a neurotoxic pathway, reducing central serotonin. The introduction of fermented foods, such as kefir and yogurts rich in beneficial bacteria, acts positively on mental regulation. These microorganisms produce short-chain fatty acids that restore the intestinal barrier, block toxin leakage, reduce neuroinflammation, and preserve the production pathway of the well-being neurotransmitter. Thus, the active modulation of the gut-brain axis through tryptophan intake and the consumption of fermented foods constitutes a safe and effective adjuvant strategy, indispensable for mitigating inflammation, optimizing neurotransmission, and pursuing sustained remission of the disorder.