Inflammation, oxidative stress, and vitamin D play pivotal roles in the pathogenesis and progression of both type 2 diabetes (T2D) and depression through several interconnected biochemical mechanisms. In T2D, chronic inflammation is driven by an excess of pro-inflammatory cytokines like TNF-α, which impairs insulin signaling by activating serine kinases that phosphorylate insulin receptor substrate-1. Oxidative stress further exacerbates this condition by generating reactive oxygen species (ROS), which damage cellular proteins, lipids, and DNA, thereby promoting β-cell apoptosis and worsening insulin resistance.

In depression, neuroinflammation and oxidative stress disrupt neurotransmitter homeostasis, particularly serotonin, by increasing the production of inflammatory cytokines which activate the enzyme indoleamine 2,3-dioxygenase (IDO), diverting tryptophan metabolism from serotonin production towards kynurenine pathway metabolites that are neurotoxic, contributing to depressive symptoms. Vitamin D modulates these pathways by exerting anti-inflammatory and antioxidant effects.

Polyunsaturated fatty acids (PUFAs), particularly omega-3s, ameliorate these conditions by penetrating cell membranes, where they reduce the production of pro-inflammatory eicosanoids from arachidonic acid and enhance mitochondrial function, reducing oxidative stress by improving electron transport chain efficiency and decreasing ROS production. Consequently, PUFA supplementation may restore insulin sensitivity in T2D and reduce neuroinflammation in depression, offering a targeted approach to managing these complex conditions.

This study investigates the biochemical changes that occurred over a 6-month period induced by omega-3 polyunsaturated fatty acid supplementation. We examined oxidative stress and inflammation biomarkers, alongside 25 OH vitamin D levels, in several patient groups: depressive, diabetic, and patients with both conditions. The findings were further analyzed in relation to cortisol and serotonin levels to elucidate the impact of omega-3 PUFAs on molecular homeostasis. The interesting beneficial effects observed can be attributed to the PUFAs' ability to stabilize and structurally integrate into cell membranes, thereby normalizing fluidity and enhancing the cellular resilience against oxidative stress and inflammation.