Current state of nutritional psychiatry: A scoping review of randomized controlled trials

Table 1 List of articles included in the analysis

Ref.	Sample size	Study design	Outcome assessment	Conclusions
Rudzki et al[8], 2019	Patients with depression were randomized to receive either the probiotic Lactobacillus Plantarum 299v plus an SSRI (n = 30) or placebo plus an SSRI (n = 30) for 8 weeks	Psychiatric symptoms were assessed using the Hamilton Depression Rating Scale, Symptom Checklist and Perceived Stress Scale. Cognitive function was assessed using the Attention and Perceptivity Test, Stroop Test. Biochemical markers measured included tryptophan, kynurenine	There was a significant decrease in kynurenine concentration in the Lactobacillus Plantarum 299v group compared to the placebo group. Results of post hoc analysis did not reach statistical significance in neither probiotic nor placebo group. There were no significant changes of TNF-α, IL-6, and IL-1β and cortisol concentrations in neither probiotic nor placebo groups	Augmentation of SSRI treatment with probiotic bacteria Lactobacillus Plantarum 299v improved cognitive performance and decreased kynurenine concentration
Lee et al[14], 2022	The study involved 17 subjects with major depressive disorder (aged 60 years or older, 41.2% female) and received levomirasipran or placebo for 12 weeks	To determine if changes in gut microbiota occur with remission in geriatric depression	Baseline enrichment of Faecalibacterium, Agathobacter, and Roseburia relative to a reference frame was associated with treatment outcome of remission	Fecal microbiota as a potential predictor of treatment response in geriatric depression
Vaghef-Mehrabani et al[13], 2023	45 women with obesity and major depression	Patients were assigned to consume either inulin or maltodextrin at a dose of 10 g per day for 8 weeks. All patients also consumed a healthy calorie-restricted diet. Anthropometric measurements, food intake, depression, lipopolysaccharide, inflammatory biomarkers (TNF-α, IL-10, monocyte chemoattractant protein-1, Toll-like receptor-4, high-sensitivity C-reactive protein), and BDNF were measured	Weight loss and Hamilton Depression Rating Scale scores decreased in both groups, with non-significant between-group differences at the end of the study	In a short-term study, prebiotic supplementation had no significant beneficial effects on depressive symptoms, intestinal permeability, or inflammatory biomarkers in obese and depressed women
Badrfam et al[11], 2024	60 hospitalized patients with a history of methamphetamine use for 3 years or more	Brief Psychiatric Rating Scale, Beck Anxiety Inventory, Pittsburgh Sleep Quality Index were evaluated under treatment with Probiotic Lactobacillus acidophilus with risperidone	Patients who took probiotics had better quality sleep, increased appetite, and a higher BMI, but there were no statistically significant differences between the two groups when it came to improvement in psychiatric and anxiety symptoms	The use of probiotics was associated with improved sleep quality, increased appetite, and increased BMI in patients with chronic methamphetamine use
Sevillano-Jiménez et al[39], 2022	A randomized clinical trial of a group of 50 people diagnosed with schizophrenia spectrum disorder during the severe acute respiratory syndrome-coronavirus 2 restriction period	Assessment of cardiovascular event risk factors in a personalized nutrition education program rich in prebiotics and probiotics (e.g., dairy products, fermented foods, green leafy vegetables, high-fiber fruits, and whole grains)	A 27.4% reduction in the prevalence of metabolic syndrome risk factors in all its components was evidenced, leading to a clinically significant improvement (decrease in cardiovascular risk) in the intervention group at 6 months	The development of a nutritional program focused on increasing the dietary content of prebiotics and probiotics effectively improves the cardio-metabolic profile in schizophrenia spectrum disorders
Hwang et al[10], 2019	A 12-week intervention for 100 patients with mild cognitive impairment	Lactobacillus plantarum C29 fermented soy (DW2009) was administered as a dietary supplement for cognitive enhancement, and the composite score of cognitive function related to memory and attention measured by computerized neurocognitive testing and BDNF levels were measured	DW2009 group showed greater improvements in the combined cognitive functions, especially in the attention domain. Cognitive improvement was associated with increased serum BDNF levels	DW2009 can be safely administered to enhance cognitive function in individuals with MCI. Increased serum BDNF levels after administering DW2009 may provide preliminary insight into the underlying effects of cognitive improvement, which suggests the importance of the gut-brain axis in ameliorating cognitive deficits in MCI
Freijy et al[12], 2024	An 8-week trial of probiotics and prebiotics in 118 depressed adults	At baseline and 8 weeks, the Cogstate Brief Battery was administered, testing processing speed, attention, visual learning, and working memory. Data were analyzed using Bayesian linear regression	Weak evidence that the probiotic improved working memory. For the other treatments, there was little or no evidence of cognitive improvement. Weak evidence that the prebiotic diet impaired processing speed	A probiotic-induced improvement in working memory, and prebiotic-induced impairment in processing speed. However, the evidence remains inconclusive regarding any cognitive benefit or harm induced by the probiotic, prebiotic diet, or synbiotic treatments

BDNF: Brain-derived neurotrophic factor; BMI: Body mass index; IL: Interleukin; MCI: Mild cognitive impairment; SSRI: Selective serotonin reuptake inhibitor; TNF-α: Tumor necrosis factor alpha.