Nutrition, nutritional deficiencies, and schizophrenia: An association worthy of constant reassessment

Table 1 Diet and Nutritional supplements as therapeutic targets

Item	Subject	Model	Outcome	Ref.
DASH diet	Human	Randomised controlled study	No difference in the prevalence of metabolic syndrome between groups	[131]
		Interventional study	Reduced sodium load and caloric intake compared to baseline	[14]
Gluten-free diet	Human	Double-blind gluten-free vs gluten-rich diet study	Improved functioning or decreased symptoms severity	[118-121]
		Clinical study	Improvements in symptoms of schizophrenia and extrapyramidal side-effects	[124]
		Clinical study	no significant effect of gluten-free diet	[122,123]
Ketogenic diet	Human	Case report	Complete amelioration of schizophrenia symptom	[130]
Omega-3 fatty acid	Rodents	Ketamine model of schizophrenia	Was protective against the development of behavioural changes	[134]
			Protective against decreased inhibition of the startle reflex, lipid peroxidation, and decreased antioxidant status in different brain regions	[139]
	Human	Clinical study	Decrease in the rate of transition to full-threshold psychosis and a decrease in the positive and negative symptoms, compared to those administered placebo	[95]
		Randomised, double-blind, placebo-controlled clinical trials	Omega-3 fatty acid PUFA supplementation was effective in reducing clinical symptoms in persons with prodrome and/or first episode schizophrenia; mixed results were observed in persons with chronic schizophrenia	[140]
		Clinical study amongst hospitalised persons with acute violent schizophrenia	No significant effect of adjunctive omega-3 fatty acid supplementation on symptoms, when compared to conventional therapy alone	[141]
Eicosapentaenoic acid (EPA)	Human	Clinical study	Improvements in symptoms were observed in persons with early schizophrenia	[136,142]
			No benefits were observed in persons with chronic forms of schizophrenia	[143,144]
Zinc	Rodent	Ketamine model of schizophrenia	Reversal of schizophrenia-like behaviours	[107]
			Age-related decrease in ketamine-induced alterations in behaviours (open field memory and anxiety) acetylcholinesterase activity, and oxidative stress parameters	[92]
Melatonin	Rodent	Ketamine model of schizophrenia	Reversal of schizophrenia-like symptoms, with benefits comparable to standard medications	[29]

DASH: Dietary approaches to stop hypertension; PUFA: Polyunsaturated fatty acid.