Nutraceuticals in Psychiatric Disorders: A Systematic Review.

Correct nutrition and diet are directly correlated with mental health, functions of the immune system, and gut microbiota composition. Diets with a high content of some nutrients, such as fibers, phytochemicals, and short-chain fatty acids (omega-3 fatty acids), seem to have an anti-inflammatory and protective action on the nervous system. Among nutraceuticals, supplementation of probiotics and omega-3 fatty acids plays a role in improving symptoms of several mental disorders. In this review, we collect data on the efficacy of nutraceuticals in patients with schizophrenia, autism spectrum disorders, major depression, bipolar disorder, and personality disorders. This narrative review aims to provide an overview of recent evidence obtained on this topic, pointing out the direction for future research.

Metabolic Insights into Neuropsychiatric Illnesses and Ketogenic Therapies: A Transcriptomic View.

The disruption of brain energy metabolism, leading to alterations in synaptic signaling, neural circuitry, and neuroplasticity, has been implicated in severe mental illnesses such as schizophrenia, bipolar disorder, and major depressive disorder. The therapeutic potential of ketogenic interventions in these disorders suggests a link between metabolic disturbances and disease pathology; however, the precise mechanisms underlying these metabolic disturbances, and the therapeutic effects of metabolic ketogenic therapy, remain poorly understood. In this study, we conducted an in silico analysis of transcriptomic data to investigate perturbations in metabolic pathways in the brain across severe mental illnesses via gene expression profiling. We also examined dysregulation of the same pathways in rodent or cell culture models of ketosis, comparing these expression profiles to those observed in the disease states. Our analysis revealed significant perturbations across all metabolic pathways, with the greatest perturbations in glycolysis, the tricarboxylic acid (TCA) cycle, and the electron transport chain (ETC) across all three disorders. Additionally, we observed some discordant gene expression patterns between disease states and ketogenic intervention studies, suggesting a potential role for ketone bodies in modulating pathogenic metabolic changes. Our findings highlight the importance of understanding metabolic dysregulation in severe mental illnesses and the potential therapeutic benefits of ketogenic interventions in restoring metabolic homeostasis. This study provides insights into the complex relationship between metabolism and neuropsychiatric disorders and lays the foundation for further experimental investigations aimed at appreciating the implications of the present transcriptomic findings as well as developing targeted therapeutic strategies.

[The basics of metabolic psychiatry].

The stability of brain functions is mainly determined by the energy management of the cells, and mental health is, therefore, profoundly affected by metabolic dysfunctions and immune and inflammatory processes. Research sheds light on more and more details and connections about the efficacy of diet and exercise, based on which we can develop effective metabolic interventions. The roots of this discipline, which is emerging today, go back to thousands of years of traditions and hundreds of years of documented observations. This paper reviews the role of mitochondria in healthy cell functions, in the distress cascade, and in the neurobiology of mental illnesses, as well as the modern knowledge related to metabolic interventions that support mitochondrial function, the therapeutic fasting, the ketogenic diet therapy, the regular exercise, and the use of nutritional supplements, and finally discusses the role of metabolic interventions in curing psychiatric diseases and improving mental health. The purpose of metabolic psychiatric interventions is to prevent neuroprogression in the broad sense, if it is already developing, to stop it, to break it, to restore the degraded functions, as a supplement to the usual psychosocial, pharmacological, somatic and neuromodulation treatments.

Induced Ketosis as a Treatment for Neuroprogressive Disorders: Food for Thought?

Induced ketosis (or ketone body ingestion) can ameliorate several changes associated with neuroprogressive disorders, including schizophrenia, bipolar disorder, and major depressive disorder. Thus, the effects of glucose hypometabolism can be bypassed through the entry of beta-hydroxybutyrate, providing an alternative source of energy to glucose. The weight of evidence suggests that induced ketosis reduces levels of oxidative stress, mitochondrial dysfunction, and inflammation-core features of the above disorders. There are also data to suggest that induced ketosis may be able to target other molecules and signaling pathways whose levels and/or activity are also known to be abnormal in at least some patients suffering from these illnesses such as peroxisome proliferator-activated receptors, increased activity of the Kelch-like ECH-associated protein/nuclear factor erythroid 2-related factor 2, Sirtuin-1 nuclear factor-κB p65, and nicotinamide adenine dinucleotide (NAD). This review explains the mechanisms by which induced ketosis might reduce mitochondrial dysfunction, inflammation, and oxidative stress in neuropsychiatric disorders and ameliorate abnormal levels of molecules and signaling pathways that also appear to contribute to the pathophysiology of these illnesses. This review also examines safety data relating to induced ketosis over the long term and discusses the design of future studies.

Feeding-produced subchronic high plasma levels of uric acid improve behavioral dysfunction in 6-hydroxydopamine-induced mouse model of Parkinson's disease.

The development of Parkinson's disease (PD) involves the degeneration of dopaminergic neurons caused by oxidative stress. Accumulating clinical evidence indicates that high blood levels of uric acid (UA), an intrinsic antioxidative substance, are associated with reduced risk of PD. However, this hypothesis has not been confirmed by in-vivo experiments. The present study investigated the effects of UA on behavioral abnormalities in the development of PD. We used unilateral 6-hydroxydopamine-lesioned mice, which were fed on a diet containing 1% UA and 2.5% potassium oxonate (an uricase inhibitor) to induce hyperuricemia. A significant elevation in UA levels was found in groups that were fed a UA diet. The 6-hydroxydopamine-lesioned mice showed impaired rotarod performance and increased apomorphine-induced contralateral rotations. These behavioral abnormalities were significantly reversed by feeding a UA diet for 1 week before and 5 weeks after surgery (subchronic hyperuricemia). These behavioral improvements occurred in parallel with recovery of tyrosine hydroxylase protein levels in the lesioned striatal side. The present study with a dietary hyperuricemia mice model confirms that UA exerts a neuroprotective effect on dopaminergic neuronal loss, improving motor dysfunction and ameliorating PD development.

Man and the Microbiome: A New Theory of Everything?

The gut microbiome is implicated in the pathophysiology of a wide range of psychological disorders. Preclinical studies have provided us with key insights into the mechanisms by which the microbiome influences bidirectional gut-brain communication. There are many signaling pathways involved, including the hypothalamic-pituitary-adrenal axis, immune modulation, tryptophan and serotonin metabolism, bile acid transformation, microbial production of neuroactive compounds, and regulation of the endocannabinoid system. The complex and widespread influence of the microbiome on many physiological and psychological processes has generated a keen interest in its therapeutic potential for depression, anxiety, autism, and other psychiatric disorders. It has been shown that the microbiome composition of people suffering with such conditions differs significantly from that of healthy controls, and although the area is in its infancy, interventional studies that alter a person's microbiome through the use of probiotics, prebiotics, or dietary change can alleviate psychopathological symptoms.

The impact of neuropsychiatric disease on fetal growth: a case-control study.

PURPOSE: To determine the impact of depression, epilepsy and drug abuse during pregnancy on delivery and fetal outcome. Due to the worldwide increasing prevalence of neurological and psychiatric diseases and drug abuse, the number of affected pregnant women is increasing. METHODS: A large-scale retrospective case-control analysis of pregnancies affected by depression, epilepsy or drug abuse with and without medication was conducted in two German perinatal centres between 2013 and 2017. The case group consisted of 706 pregnant women who had a diagnosis of depression, epilepsy or drug abuse vs. 12,574 pregnant women without neuropsychiatric diagnosis (control group). The analysis included the rate of intrauterine growth restriction, birth weight and length, neonatal head circumference. RESULTS: Significant differences in the subgroups were found in the parameters intrauterine growth restriction, birth weight, length and head circumference. Women with epilepsy were affected less often than women with depression and substance abuse. Major differences were found in the group of women with substance abuse. Negative associations were found within the non-pharmacologically managed disease group itself compared to women exposed to medication. CONCLUSION: The present results demonstrated a negative association between maternal neurological or psychiatric disease and pregnancy outcome in the examined parameters. However, the non-pharmacologically treated maternal disease was identified as a risk factor itself.

Epigenetics, nutrition and mental health. Is there a relationship?

Many aspects of human development and disease are influenced by the interaction between genetic and environmental factors. Understanding how our genes respond to the environment is central to managing health and disease, and is one of the major contemporary challenges in human genetics. Various epigenetic processes affect chromosome structure and accessibility of deoxyribonucleic acid (DNA) to the enzymatic machinery that leads to expression of genes. One important epigenetic mechanism that appears to underlie the interaction between environmental factors, including diet, and our genome, is chemical modification of the DNA. The best understood of these modifications is methylation of cytosine residues in DNA. It is now recognized that the pattern of methylated cytosines throughout our genomes (the 'methylome') can change during development and in response to environmental cues, often with profound effects on gene expression. Many dietary constituents may indirectly influence genomic pathways that methylate DNA, and there is evidence for biochemical links between nutritional quality and mental health. Deficiency of both macro- and micronutrients has been associated with increased behavioural problems, and nutritional supplementation has proven efficacious in treatment of certain neuropsychiatric disorders. In this review we examine evidence from the fields of nutrition, developmental biology, and mental health that supports dietary impacts on epigenetic processes, particularly DNA methylation. We then consider whether such processes could underlie the demonstrated efficacy of dietary supplementation in treatment of mental disorders, and whether targeted manipulation of DNA methylation patterns using controlled dietary supplementation may be of wider clinical value.

Expanding collaborative care: integrating the role of dietitians and nutrition interventions in services for people with mental illness.

OBJECTIVE: This article aims to draw mental health clinicians' attention to the connections between nutrition and mental health, and the roles that Accredited Practising Dietitians play in improving mental and physical health through dietary change. METHODS: Selective narrative review. RESULTS: Unhealthy dietary practices are common in high prevalence and severe mental illness. Epidemiological evidence demonstrates that nutrients and dietary patterns impact on mental health. In addition, poor physical health is well documented in people with mental illness and the greatest contributor to the mortality gap. Dietary intervention studies demonstrate improved mental and physical health outcomes. Accredited Practising Dietitians translate nutrition science into practical advice to improve the nutritional status of patients with mental illness, and prevent and manage comorbidities in a variety of care settings. CONCLUSIONS: Medical Nutrition Therapy offers opportunities to improve the physical and mental health of people living with mental illness.

Promising evidence for nutrition interventions in people with serious mental illness.

People with serious mental illness (SMI) are more likely to engage in health risk behaviours such as unhealthy eating, physical inactivity and smoking. The review by Teasdale et al in this issue shows the potential for nutrition interventions to help people with SMI to manage their weight.

Solving a weighty problem: systematic review and meta-analysis of nutrition interventions in severe mental illness.

BACKGROUND: Nutrition interventions would appear fundamental for weight management and cardiometabolic risk reduction in people experiencing severe mental illness (SMI). Comprehensive evaluation of nutrition interventions is lacking. AIMS: To subject randomised controlled trials of nutrition interventions in people with SMI to systematic review and meta-analysis, and to measure anthropometric and biochemical parameters and nutritional intake. METHOD: An electronic database search identified trials with nutrition intervention components. Trials were pooled for meta-analysis. Meta-regression analyses were performed on anthropometric moderators. RESULTS: Interventions led to significant weight loss (19 studies), reduced body mass index (17 studies), decreased waist circumference (10 studies) and lower blood glucose levels (5 studies). Dietitian-led interventions (6 studies) and studies delivered at antipsychotic initiation (4 studies) had larger effect sizes. CONCLUSIONS: Evidence supports nutrition interventions as standard care in preventing and treating weight gain among people experiencing SMI.

[Iron deficiency: A diagnostic and therapeutic perspective in psychiatry]. / Carence en fer : une perspective diagnostique et thérapeutique en psychiatrie.

BACKGROUND: Iron plays an essential role in balancing the various metabolism in the body. It is also involved in the synthesis of several neurotransmitters. Nutritional iron deficiency is one of the most widespread worldwide; it poses a great health challenge due to the consequences it entails. OBJECTIVES: The aim of this research study is to explore the percentage of psychiatric patients who have a deficiency in iron. In addition, the study investigates the efficacy of iron administered by oral treatment on psychiatric symptomatology among iron deficient patients. The research study utilized the martial biological results, which involved the observation of the level of iron deficiency among the outpatients of a local psychiatrist and assessor from the period of January 2012 until December 2013. METHODS: Out of 412 patients, 295 were women and 117 men. The age of the participants ranged from 16 to 89years, with an average age of 45years. The only exclusion criterion was a patient's refusal or inability to take the prescribed iron assessment test. We considered a transferrin saturation coefficient (TSC)<30% and/or a serum ferritin level≤50ng/mL to be "indicative" of obvious iron deficiency, and a ferritin level between 51 and 100ng/mL to be "suggestive" of iron deficiency. A plasma ferritin assay was performed at least once on all of the participants prior to any proposed iron treatment. A calculation of the TSC in 138 patients was requested due to suspected iron deficiency despite a blood ferritin level of>100ng/ml. A single method was utilized in the various laboratories to analyse the blood samples to determine whether there was a deficiency in iron. Only those patients with blood ferritin levels ≤100ng/mL and/or a TSC of<30% (335 patients) were subsequently given exclusively an oral iron treatment prescribed on its own or as a supplement or simultaneously with psychotropic treatment. The daily administered dose of elemental iron varied between 50 and 200mg a day. RESULTS: About half of the women - 145 (35.19% of the subjects) - and 15 men (3.64% of the subjects) certainly had a deficiency in iron (blood ferritin level≤50ng/mL). Ninety women and 24 men (27.6% of the subjects) had blood ferritin levels between 51 and 100ng/mL indicating iron deficiency, and 28 women and 33 men (14.8% of the subjects) had a TSC of<30% despite a blood ferritin level of>100ng/mL. Overall, 335 patients (81.3% of the subjects) showed an iron deficiency based on the criteria we set. In the remaining 77 patients (18.7% of the subjects), all of them had blood ferritin levels>100ng/mL and some had TSC≤30%, while the remaining patients' TSC was unknown because it was not measured. The results indicated that there is an iron deficiency in 198 out of 240 patients suffering mostly from mood and behavioural disorders, in 101 out of 126 patients suffering mostly from anxiety disorders, in 18 out of 27 patients suffering mostly from sleep disorders, in 14 out of 15 patients suffering mostly from delusions of persecution, and in the 4 patients suffering mostly from burn out. There was evidence of regression/remission of psychiatric symptoms in 193 responsive patients whereas the remaining 142 patients were considered non-responsive. In the responsive patient category, 37 participants were treated with just iron, 52 received iron supplemented to the initial psychotropic treatment which was not fully effective, and 104 patients were treated with iron and prescribed psychotropic drugs simultaneously. The iron treatment seems to bring about a reduction - particularly through its mono-aminergic neurotransmitter synthesis-promoting action - in hyperemotivity, anxiety, irritability, aggressiveness, sadness, anhedonia, apathy, asthenia, sleep disorders, dysautonomia symptoms, eating disorders, restless-leg syndrome, cognitive performance and the likelihood of resorting to psychiatric admission. A daily elemental iron dose intake between 50 and 200mg/day by deficient patients appears to likely enhance the effects of the psychotropic drugs and even to act as an actual antidepressant. Many patients who received a prescription for iron and antidepressants showed few side effects related to antidepressants and a small number required psychiatric hospitalization. Patients considered unresponsive to iron therapy were those who left the study, were not assessed because the study's timeframe ended, still had an iron deficiency because they did not continuously take the medication, or suffered from somatic diseases which explains their resistance to treat the low iron level (nutritional imbalance, digestive or urinary or gynecological or iatrogenic diseases, sleep apnea). CONCLUSION: Our clinical observation of two years in a local psychiatrist's clinic revealed that over 80% of patients had iron deficiency. Although the low iron level cannot explain all physical and psychiatric symptoms in patients, it is useful to note that more than half of the iron deficient patients responded favorably after an oral treatment of iron. This result leads to further investigation of the level of iron in psychiatric patients and to reconsider the iron range placed by the laboratories. In addition, it is crucial not to eliminate the possibility of iron deficiency in psychiatric patients. Further research studies are needed to set more specific and detailed criteria to determine the range of iron deficiency in order to support the findings of this study and optimize the care given to patients suffering from various disorders and psychiatric syndromes.

Dietary supplements in child and adolescent psychiatry.

Complementary and alternative treatments, including dietary supplements, are very popular and increasingly used in developed countries. Some features such as accessibility, ease of use, the possibility of self-administration and the belief they are safe without side effects, have led to an increase in their consumption. However, there is limited evidence of the effectiveness and safety of these treatments because of methodological issues. The level of scientific evidence is particularly low and weak in the field of child and adolescent Psychiatry. The purpose of this article is to give an updated overview of dietary treatments in this area. We make a brief introduction about general questions, including legal aspects, and propose general practical recommendations for a proper management by the families that choose these treatments. We focus on reviewing the current state of research into dietary treatments in some childhood and juvenile psychiatric disorders, highlighting current evidence of specific treatments. The final purpose of this article is to describe the level of current evidence on dietary treatments and to provide professionals involved in the care of children and adolescents with a useful tool to help, guide and educate families about their use in order to achieve the greatest benefit to patients.

The Role of Omega-3 Fatty Acids in Diets.

The article is a summary of Dra. Carmen Gómez Candela's presentation at the Science in Nutrition 3rd International Congress in Milan, March 2014. The article covers omega-3 fatty acids use in different medical areas and several institutions' opinions in relation to the topic. Omega-3 acids are essential fatty acids. A certain amount of omega-3 is needed in our daily diet; however, the usual consumption is generally less than the recommended amount. Changes in dietary patterns in the course of history have led to deficit levels of omega-3 in the human body. Currently, there is increasing evidence of the benefits of omega-3 in different medical specialities. There are still some gaps regarding its role in illnesses such as dementia, psychiatric disorders, and inflammatory diseases. Nevertheless, stronger evidence is being proved in cardiovascular diseases and cancer. This article provides a reflection on possible ways to increase omega-3 daily consumption and the constraints associated with food with high contents of heavy metals, which, in turn, are also rich in omega-3s.

The "psychomicrobiotic": Targeting microbiota in major psychiatric disorders: A systematic review.

The gut microbiota is increasingly considered as a symbiotic partner in the maintenance of good health. Metagenomic approaches could help to discover how the complex gut microbial ecosystem participates in the control of the host's brain development and function, and could be relevant for future therapeutic developments, such as probiotics, prebiotics and nutritional approaches for psychiatric disorders. Previous reviews focused on the effects of microbiota on the central nervous system in in vitro and animal studies. The aim of the present review is to synthetize the current data on the association between microbiota dysbiosis and onset and/or maintenance of major psychiatric disorders, and to explore potential therapeutic opportunities targeting microbiota dysbiosis in psychiatric patients.

[Nutrition and dietary supplements in psychiatric diseases]. / Ernährung und Nahrungsergänzungsmittel bei psychiatrischen Erkrankungen.

Nutrition and specific nutritional supplements can have prophylactic or therapeutic properties with respect to certain psychiatric disorders. A traditional Mediterranean diet, for example, seems to have prophylactic benefits against depression and dementia, whereas overeating and obesity increase the risk for both.Although evidence for nutritional supplements in the treatment of psychiatric disorders is not sufficient for general recommendations, data from observational studies and randomized controlled trials (RCT) seem to point to their use for specific indications. Folate, S-adenosylmethionine (SAM) and eicosapentaenoic acid (EPA), for instance, seem to have antidepressant properties, zinc may be beneficial in attention deficit hyperactivity disorder (ADHD), vitamin B6 (pyridoxine) could reduce extrapyramidal side effects of antipsychotics and N-acetylcysteine (NAC) seems to be effective against negative symptoms, abnormal movements and akathisia in schizophrenia.Psychiatric disorders, in turn, may lead to deficiency of mineral nutrients and vitamins. For instance, vitamin B1 (thiamine) deficiency is common in alcohol-dependent patients and should therefore be considered during withdrawal treatment. Although vitamin malnutrition is uncommon in developed countries, vitamin deficiency syndromes, such as pernicious anemia or Wernicke's encephalopathy are still relevant differential diagnoses.Some psychopharmacological drugs may additionally change the nutritional habits of the patients in an unfavorable way leading to weight gain and obesity and the risk for further psychiatric problems.

An Anti-Inflammatory Diet and Its Potential Benefit for Individuals with Mental Disorders and Neurodegenerative Diseases-A Narrative Review.

This narrative review synthesizes current evidence regarding anti-inflammatory dietary patterns and their potential benefits for individuals with mental disorders and neurodegenerative diseases. Chronic low-grade inflammation is increasingly recognized as a key factor in the etiology and progression of these conditions. The review examines the evidence for the anti-inflammatory and neuroprotective properties of dietary components and food groups, focusing on whole foods rather than specific nutrients or supplements. Key dietary components showing potential benefits include fruits and vegetables (especially berries and leafy greens), whole grains, legumes, fatty fish rich in omega-3, nuts (particularly walnuts), olive oil, and fermented foods. These foods are generally rich in antioxidants, dietary fiber, and bioactive compounds that may help modulate inflammation, support gut health, and promote neuroprotection. Conversely, ultra-processed foods, red meat, and sugary beverages may be harmful. Based on this evidence, we designed the Brain Anti-Inflammatory Nutrition (BrAIN) diet. The mechanisms of this diet include the modulation of the gut microbiota and the gut-brain axis, the regulation of inflammatory pathways, a reduction in oxidative stress, and the promotion of neuroplasticity. The BrAIN diet shows promise as an aid to manage mental and neurodegenerative disorders.