Healthy diet, depression and quality of life: A narrative review of biological mechanisms and primary prevention opportunities

Table 1 Summary of aetiological hypotheses and nutritional determinants of depression

Aetiological Hypotheses	Main mechanisms	Biological disturbances in UDD	Relationship with Diet	Ref.
Oxidative stress and inflammation	Higher cytokine levels in patients with UDD induce BBB damage and increased permeability to the brain, mainly through claudin 5 dysfunction. Furthermore, oxidative stress and cytokines stimulate the vagal nerve, further promoting a pro-inflammatory in the CNS.	Increased IL-6, TNF-a, C-reactive protein, INT- γ, and other inflammatory cytokines. BBB damage and translocation of cytokines and immune cells into the brain.	Adequate antioxidant intake and lifestyle habits prevent the development of a pro-inflammatory state.	[16,17,19]
Glucocorticoids and HPA-axis	Chronic stress leads to the constant release of cortisol and eventually a down regulation of cortisol receptors in the hypothalamus. In addition, altered immune responses promote further neuronal damage and other metabolic diseases.	Increased basal cortisol and LPS.	Healthy gut microbiomes prevent the release of LPS and other cytokines into the plasma, limiting the potential damage of stress and theoretically decreasing UDD risk.
		Altered cortisol circadian rhythm.
		Secondarily, T-cell differentiation and release of inflammatory cytokines.
Monoamine activity	Inadequate monoamine production and an increased degradation rate, mediated by the MAO enzyme, are related to depressive symptoms. Although current therapy is based on improving monoamine availability in the synapsis, uncertainties remain regarding this hypothesis.	Reduced monoamine formation and activity.	Vit-B12 and folate are necessary for monoamine production.	[28,29,33,34]
		Homocysteine (also homocysteinic acid or cysteine sulfinic acid) has detrimental effects on neurons.	Homocysteine accumulation is a result of Vit-B12 deficiency.
			MAO-B activity has been associated with Vit-B12 levels and dietary practices.
Neuronal development and activity	Altered BDNF function is caused by oxidative stress and inadequate endothelial function. This neurotrophin is essential for neuronal development, synapse formation and cerebral plasticity, in addition to having anti-depressant effects. However, its antidepressant effects are dependent on brain region and therefore not fully understood	Altered BDNF activity and other markers of endothelial function (IL-6, TNF-a, ICAM-1 and VCAM-1).	Antioxidants, MUFA, and PUFA concentrations regulate endothelial function.	[44–46]
		Decreased post-mortem hippocampal and prefrontal cortex volumes.	Vit-B12 promotes the expression of genes that code for BDNF-receptors (Ntrk-2).
The role of Health Related Quality of Life	Lower HRQoL has been associated with depression relapse and increased risk of suicide.	HRQoL is generally lower in patients with depression. Furthermore, pharmacotherapy improves mental components of HRQoL.	Quality of diet has been direct and cross-sectionally associated with HRQoL scores. The effects of diet on homocysteine level influence HRQoL and thus, potentially improve UDD patient status.	[55,57,62,63]

UDD: Unipolar depressive disorder; IL-6: Interleukin 6; TNF-α: Tumoral necrosis factor-α; INT- γ: Interferon- γ; HPA-axis: Hypothalamus-pituitary-adrenal axis; LPS: Lipopolysaccharides; MAO: Monoamine oxidase; BDNF: Brain derived neurotrophic factor; ICAM: Intercellular adhesion molecule; VCAM: Vascular adhesion molecule; MUFA: Monounsaturated fatty acids; PUFA: Polyunsaturated fatty acids; HRQoL: Health related quality of life.