Research
We delve into groundbreaking scientific research to uncover the complex connections between metabolic health and various mental health illnesses including ADHD, bipolar disorder, schizophrenia, anxiety, depression, addiction, eating disorders, and obesity.
Through a comprehensive coverage of international scientific publications, we strive to provide insights, stimulate discussions, and contribute to a deeper understanding of how metabolic processes influence mental well-being.
Biopolar Disorder
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Shebani Sethi, Diane Wakeham, Terence Ketter, Farnaz Hooshmand, Julia Bjornstad, Blair Richards, Eric Westman, Ronald M Krauss, Laura Saslow
To initiate a low-carbohydrate, high-fat (LCHF) or ketogenic dietary (KD) intervention among a cohort of outpatients with either schizophrenia or bipolar illness who also have metabolic abnormalities, overweight/obesity, and/or are currently taking psychotropic medications experiencing metabolic side effects.
Stanford-affiliated
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Nicole Needham, Iain H Campbell, Helen Grossi, Ivana Kamenska, Benjamin P Rigby, Sharon A Simpson, Emma McIntosh, Pankaj Bahuguna, Ben Meadowcroft, Frances Creasy, Maja Mitchell-Grigorjeva, John Norrie, Gerard Thompson, Melissa C Gibbs, Ailsa McLellan, Cheryl Fisher, Tessa Moses, Karl Burgess, Rachel Brown, Michael J Thrippleton, Harry Campbell, Daniel J Smith
Bipolar disorder (BD) is a mental health condition that affects your moods, which can swing from one extreme to another. It is a major lifelong mental health condition that significantly impacts the quality of life of those who live with it. Our current understanding of how it develops is poor, and as such treatments are not always effective. There is some evidence that the ketogenic diet (KD), which is low in carbohydrate and high in fat, may be an effective treatment for BD, and some patients already follow this diet. To date there has been no clinical trial of the KD in BD.This study will pilot the introduction of a KD for 8 weeks in patients with BD. The aim is to find out how easy it is to do this, the main challenges, and how to address these.
Externally-conducted
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Norwitz, Nicholas G, Shebani Sethi, Palmer, Christopher M.
It is critical that researchers and clinicians are made aware of the trajectory of evidence for the implementation of ketogenic diets in mental illnesses. Metabolic intervention provides not only a novel form of symptomatic treatment, but one that may be able to directly address the underlying disease mechanisms and, in so doing, treat burdensome comorbidities.
Stanford-affiliated
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Prof Daniel Smith
Two women with type II bipolar disorder were able to maintain ketosis for prolonged periods of time... Both experienced mood stabilization that exceeded that achieved with medication and experienced a significant subjective improvement that was distinctly related to ketosis... These cases demonstrate that the ketogenic diet is a potentially sustainable option for mood stabilization in type II bipolar illness.
Externally-conducted
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Benjamin Goldstein, David E Kemp, Joanna K Soczynska, Roger S McIntyre
Bipolar disorder and inflammation are linked through shared genetic polymorphisms and gene expression as well as altered cytokine levels...Several conventional mood stabilizers have anti-inflammatory properties...Inflammation is closely linked with behavioral parameters such as exercise, sleep, alcohol abuse, and smoking, as well as with medical comorbidities including coronary artery disease, obesity and insulin resistance, osteoporosis, and pain.
Externally-conducted
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Elisabeth A. Frazier, Mary A. Fristad, L. Eugene Arnold
This article examines a case study of a 12-year-old boy with bipolar disorder and co-morbid diagnoses treated for 6 years with conventional medication and a multinutrient supplement. After 6 years of conventional treatment, he received 14 months of EMPowerplus (EMP+) which resulted in outcomes superior to conventional treatment.
Externally-conducted
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Iain H Campbell, Harry Campbell
Researchers conducted an observational analytic study of free-text comments in online forums about mood effects of dietary interventions (ketogenic, omega-3 enriched or vegetarian) classified by a priori categories of change in mood stabilization in 274 people with bipolar disorder. Reports of significant mood stabilization or remission of symptoms over a period were substantially higher for a ketogenic diet than for other diets.
Externally-conducted
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Elisa Brietzke, Rodrigo B Mansur, Mehala Subramaniapillai, Vicent Balanzá-Martínez, Maj Vinberg, Ana González-Pinto, Joshua D Rosenblat, Roger Ho, Roger S McIntyre
Preclinical studies, case reports, and case series have demonstrated antidepressant and mood-stabilizing effects of ketogenic diet (KD), however, to date, no clinical trials for depression or bipolar disorder have been conducted. Due to potential pleiotropic benefits, KD should be considered as a promising intervention in mood disorder therapeutics, particularly in treatment-resistant presentations.
Externally-conducted
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R S El-Mallakh, M E Paskitti
The ketogenic diet may stabilize mood in bipolar illness. Several anticonvulsant interventions may improve outcome in mood disorders. Furthermore, beneficial changes in brain-energy profile are noted in subjects on the ketogenic diet. Finally, the extracellular changes that occur in ketosis would be expected to decrease intracellular sodium concentrations, a common property of all effective mood stabilizers.
Externally-conducted
ADHD
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Rowena M A Packer, Tsz Hong Law, Emma Davies, Brian Zanghi, Yuanlong Pan, Holger A Volk
Dogs with idiopathic epilepsy may exhibit behaviors that resemble ADHD symptoms seen in humans and rodent models of epilepsy. A ketogenic diet may be able to improve some of these behaviors, along with potentially anxiolytic effects.
Externally-conducted
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Jane Pei-Chen Chang, Li Jingling, Ya-Ting Huang
Children with ADHD had a higher deficiency of essential fatty acids, and a deficiency in essential fatty acids had a positive association with ADHD severity.
Externally-conducted
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Donna McCann, PhD, Angelina Barrett, BSc, Alison Cooper, MSc, Debbie Crumpler, BSc, Lindy Dalen, PhD
Researchers found that artificial colors, a sodium benzoate preservative, or the combination of the two in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population.
Externally-conducted
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K S Rowe, K J Rowe
Behavioral changes in irritability, restlessness, and sleep disturbance are associated with the ingestion of tartrazine (synthetic food coloring) in some children. A dose response effect was observed in children who were identified as "reactors."
Externally-conducted
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Laura J Stevens, Thomas Kuczek, John R Burgess, Elizabeth Hurt, L Eugene Arnold
Evidence suggests that a subgroup of ADHD patients improve on an artificial color-free diet. Studies suggest that some children, in addition to being sensitive to AFCs, are also sensitive to common nonsalicylate foods (milk, chocolate, soy, eggs, wheat, corn, legumes) as well as salicylate-containing grapes, tomatoes, and oranges.
Externally-conducted
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Annelies A J Verlaet, Daniela Briceno Noriega, Nina Hermans, Huub F J Savelkoul
This review paper explores the relationship between immune imbalances, nutrition, and ADHD.
Externally-conducted
Schizophrenia
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Shebani Sethi, Diane Wakeham, Terence Ketter, Farnaz Hooshmand, Julia Bjornstad, Blair Richards, Eric Westman, Ronald M Krauss, Laura Saslow
To initiate a low-carbohydrate, high-fat (LCHF) or ketogenic dietary (KD) intervention among a cohort of outpatients with either schizophrenia or bipolar illness who also have metabolic abnormalities, overweight/obesity, and/or are currently taking psychotropic medications experiencing metabolic side effects.
Stanford-affiliated
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Norwitz, Nicholas G.a; Sethi, Shebani Sethi; Palmer, Christopher M.c
It is important that researchers and clinicians are made aware of the trajectory of evidence for the implementation of ketogenic diets in mental illnesses. Metabolic intervention provides not only a novel form of symptomatic treatment, but one that may be able to directly address the underlying disease mechanisms and, in so doing, also treat burdensome comorbidities.
Stanford-affiliated
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F. J. BRACELAND, L. J. MEDUNA, J. A. VAICHULIS
3 out of 4 patients with schizophrenia exhibited a delayed response to intravenous insulin. This may be attributed to the anti-insulin factor that has been found to be present in the blood of many patients with schizophrenia.
Externally-conducted
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Özge Küçükerdönmez, Murat Urhan, Merve Altın, Özge Hacıraifoğlu, Burak Yıldız
This study aimed to determine the prevalence of food addiction among patients with schizophrenia and to examine the relationship between food addiction, anthropometric measurements, and dietary nutrient intake. It was observed that the development of food addiction in patients with schizophrenia increased the risk of obesity and cardiovascular diseases, which were found at higher levels in these patients.
Externally-conducted
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Zoltán Sarnyai, Ann-Katrin Kraeuter, Christopher M Palmer
Recent findings support that the ketogenic diet may present a novel therapeutic approach through restoring brain energy metabolism in schizophrenia. Randomized controlled clinical trials are needed to further show the efficacy of ketogenic diet as a co-treatment to manage both clinical symptoms and metabolic abnormalities.
Externally-conducted
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Elisa Brietzke, Rodrigo B Mansur, Mehala Subramaniapillai, Vicent Balanzá-Martínez
Preclinical studies, case reports, and case series have demonstrated antidepressant and mood stabilizing effects of ketogenic diet (KD), however, to date (2018), no clinical trials for depression or bipolar disorder have been conducted. Because of its potential pleiotropic benefits, KD should be considered as a promising intervention in mood disorder therapeutics, particularly in treatment resistant presentations.
Externally-conducted
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Ann Katrin, Kraeutera Heather, Loxtona, Bruna Costa, Limaa, Donna Rudd, Zoltán Sarnyai
3 weeks of ketogenic diet regulated induced schizophrenia symptoms in mice (psychomotor hyperactivity, stereotyped behavior, social withdrawal, and working memory deficits). Elevated ketone levels were also observed.
Externally-conducted
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This pilot study found that removal of gluten from the diet is associated with improvement in psychiatric and gastrointestinal symptoms in people with schizophrenia or schizoaffective disorder.
Externally-conducted
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MAN MOHAN SINGH AND STANLEY R. KAY
Patients with schizophrenia maintained on a cereal grain-free and milk-free diet and receiving optimal treatment with neuroleptics showed improved symptoms. After reintroducing gluten, the improvement was reinstated. The observed effects seemed to be due to a primary schizophrenia-promoting effect of wheat gluten.
Externally-conducted
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Malcolm Peet
After statistical analysis of the national general population cohort, researchers found that individuals with Celiac Disease may be at increased risk of non-affective psychosis.
Externally-conducted
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Norbert Müller, Elif Weidinger, Bianka Leitner, and Markus J. Schwarz
Increasing evidence for a role of proinflammatory cytokines in schizophrenia, the strong influence of pro- and anti-inflammatory cytokines on tryptophan/kynurenine metabolism, the related influence of cytokines on glutamatergic neurotransmission, the results of imaging studies, genetic findings and the therapeutic effect of anti-inflammatory drugs all support the view that the recent increased focus of schizophrenia research on psychoneuroimmunology and inflammation is justified.
Externally-conducted
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Martina C.M. Ryan, M.B., M.R.C.Psych., Patrick Collins, M.Sc., Ph.D., and Jogin H. Thakore M.B., Ph.D., M.R.C.Psych., M.R.C.P.I.
First-episode, drug-naive patients with schizophrenia have impaired fasting glucose tolerance, are more insulin resistant, and have higher levels of plasma glucose, insulin, and cortisol than healthy comparison subjects.
Externally-conducted
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Martina C.M. Ryan Jogin H. Thakore
There is evidence of overactivity of the HPA axis in schizophrenia, a cause of increased visceral fat. This obesity is associated with glucose intolerance and insulin resistance. Future studies are needed to further examine drug-naive patients for a prolonged period of time.
Externally-conducted
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JH Thakore, JN Mann, I Vlahos, A Martin & R Reznek
In comparison to controls, patients with schizophrenia had higher levels of central obesity and plasma cortisol. Central obesity is a well-recognized risk factor in developing certain general medical conditions. This study shows that patients with schizophrenia have increased intra-abdominal fat which may provide one explanation for premature death in these populations.
Externally-conducted
Depression and Anxiety
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MetS and its components significantly increased the risk of anxiety, which increased with the number of components. This association may be partially mediated by serum inflammatory indicators, suggesting that MetS may increase the risk of anxiety by elevating the level of chronic inflammation.
Externally-conducted
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Rats on a ketogenic diet spent less time immobile, suggesting that rats on a ketogenic diet, like rats treated with antidepressants, are less likely to exhibit 'behavioral despair.'
Externally-conducted
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Rats on a ketogenic diet spent less time immobile, suggesting that rats on the ketogenic diet, like rats treated with antidepressants, are less likely to exhibit 'behavioral despair.'
Externally-conducted
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The adult ketogenic diet (KD) offspring exhibit reduced susceptibility to anxiety and depression, and elevated physical activity level when compared with controls exposed to the Standard Diet both in utero and postnatally. Many neuro‐anatomical differences exist between the KD offspring and controls, including, for example, a cerebellar volumetric enlargement.
Externally-conducted
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In middle-aged participants, a processed food dietary pattern is a risk factor for depression 5 years later, whereas a whole food pattern is protective.
Externally-conducted
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Findings implicate a Western dietary pattern in poorer behavioral outcomes for adolescents. Improved behavioral outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.
Externally-conducted
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A detrimental relationship was found between trans unsaturated fat intake and depression risk, whereas weak inverse associations were found for MUFA, PUFA and olive oil. These findings suggest that cardiovascular disease and depression may share some common nutritional determinants related to subtypes of fat intake.
Externally-conducted
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Consumption of a 'Mediterranean-style' dietary pattern by mid-aged women may have a protective influence against the onset of depressive symptoms.
Externally-conducted
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The aim of this study was to investigate associations between sweet food and beverage intake, common mental disorders and depression, and to examine the role of reverse causation (influence of mood on intake) as potential explanation for the observed linkage. This study confirms an adverse effect of sugar intake on long-term psychological health.
Externally-conducted
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Researchers conducted meta-analysis of double-blind randomized placebo-controlled trials to estimate the efficacy of omega-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in the improvement of depression...Current evidence supports the finding that omega-3 PUFAs with EPA ≥ 60% at a dosage of ≤1 g/d would have beneficial effects on depression.
Externally-conducted
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'SMILES’ was a 12-week, parallel-group, single blind, randomized controlled trial of an adjunctive dietary intervention in the treatment of moderate to severe depression...Results indicate that dietary improvement may provide an efficacious and accessible treatment strategy for the management of this highly prevalent mental disorder.
Externally-conducted
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This study examined the extent to which the high-prevalence mental disorders are related to habitual diet in women. A 'traditional' dietary pattern characterized by vegetables, fruit, meat, fish, and whole grains was associated with lower odds for major depression or dysthymia and for anxiety disorders. A 'western' diet of processed or fried foods, refined grains, sugary products, and beer was associated with greater psychological symptoms.
Externally-conducted
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This study investigated whether low fish consumption is associated with increased risk of developing depression. A low frequency of fish consumption was statistically significantly associated with depression in women, but not in men.
Externally-conducted
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Self-reported data indicates vegetarian men have more depressive symptoms after adjustment for socio-demographic factors. Nutritional deficiencies (e.g. in cobalamin or iron) are a possible explanation for these findings.
Externally-conducted
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In this study, we report that women habitually consuming less than the recommended intake of red meat were more likely to have a diagnosed depressive or anxiety disorder than those consuming the recommended amount. Moreover, those consuming more than the recommended amount of red meat were also more likely to have a depressive disorder once overall diet quality was taken into account.
Externally-conducted
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This is a prospective analysis of the relationship of this pattern and depression risk among participants in the Nurses’ Health Study...The inflammatory dietary pattern is associated with a higher depression risk. This finding suggests that chronic inflammation may underlie the association between diet and depression.
Externally-conducted
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This study aimed to assess the magnitude and direction of associations of depression with C-reactive protein (CRP), interleukin (IL)-1, and IL-6 in community and clinical samples. Researchers found that depression and CRP, IL-1, and IL-6 are positively associated and BMI is a mediating/moderating factor. A dose-response relationship between depression and these inflammatory markers may exist.
Externally-conducted
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The promotion of a healthy diet with anti-inflammatory properties may help to prevent depressive symptoms, particularly among men, smokers, or physically inactive individuals.
Externally-conducted
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This review examines the relationship between the consumption or avoidance of meat and psychological health and well-being.
Externally-conducted
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The relationship between inflammation and depression is less defined among perinatal women. Perinatal depression may be a heterogeneous construct, and that inflammation may be relevant to it in the context of other inflammatory morbidities of pregnancy.
Externally-conducted
Eating Disorders
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This paper explores proposed mechanisms of why a diet low in refined carbohydrates, processed sugar and higher fat content may be helpful in alleviating symptoms of binge eating disorder.
Stanford-affiliated
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This is the first report to demonstrate the feasibility of prescribing a ketogenic diet for patients with obesity who report binge eating and food addiction symptoms.
Stanford-affiliated
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This first randomized control trial evaluated the efficacy and safety of PHEN/TPM‐ER for BED/BN. It was found that this drug combination was significantly more effective at reducing binge eating than placebo and was well-tolerated.
Externally-conducted
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Findings implicate a Western dietary pattern in poorer behavioral outcomes for adolescents.Improved behavioral outcomes were associated with a higher intake of fresh fruit and leafy green vegetables.
Externally-conducted
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Despite abnormally low BMI, Anorexia Nervosa (AN) seems to be associated with increased inflammatory cytokines. Whether specific elevated cytokines represent trait or state markers of AN, and whether they could be treatment targets requires further study.
Externally-conducted
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Research suggests increased levels of various pro-inflammatory cytokines as well as the spontaneous production of tumor necrosis factor in anorexia nervosa; genetic studies further support a dysregulated immune system in this disorder.
Externally-conducted
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For the first time, IL-1α, IL-10, EGF, and IFN-γ were shown to differ between patients with anorexia nervosa and healthy controls, and between patients with anorexia nervosa and individuals with obesity, with or without binge-eating disorder.
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The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder.
Obesity
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This review examines the overlap between mental illness and comorbid obesity highlighting clinical and biological factors that have been linked to this association in order to improve our understanding and help elucidate potential therapeutic avenues.
Externally-conducted
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This cross-sectional study provides preliminary evidence that not all foods are equally implicated in addictive-like eating behavior, and highly processed foods, which may share characteristics with drugs of abuse (e.g. high dose, rapid rate of absorption) appear to be particularly associated with food addiction.
Externally-conducted
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This review proposes that food addiction is a plausible etiological factor contributing to the heterogeneous condition and phenotype of obesity. In at least one subset of vulnerable individuals, high-glycemic-index carbohydrates trigger addiction-like neurochemical and behavioral responses.
Externally-conducted
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This study compared effect of interdisciplinary therapy on the physical and metabolic profiles, including body composition, insulin resistance and sensitivity as well as adiponectin and leptin concentrations, of obese adolescents with and without eating disorder symptoms.
Externally-conducted
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There is increasing evidence of the impact of ultra-processed foods on multiple metabolic and neurobiological pathways, including those involved in eating behaviors, both in animals and in humans. This study explored ultra-processed foods and their link with disordered eating in a clinical sample.
Addiction
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This paper explores proposed mechanisms behind why a diet low in refined carbohydrates, processed sugar and higher fat content may be helpful in alleviating symptoms.
Stanford-affiliated
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To better understand how diet influences brain aging, this paper focuses on the presymptomatic period during which prevention may be most effective. Findings show brain network destabilization may reflect early signs of hypometabolism, associated with dementia. Dietary interventions resulting in ketone utilization increase available energy and thus may show potential in protecting the aging brain.
Externally-conducted
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This review examines the potential therapeutic benefits of a ketogenic diet on neurodegenerative and psychiatric disorders in humans and animal models.
Externally-conducted
General
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This study focused on metabolic changes in the medial prefrontal region, which shows a decline years before documented cognitive changes, relative to high or low insulin-resistance status in postmenopausal women at risk for dementia who were randomized to continue or discontinue existing stable hormone therapy for 2 years.
Stanford-affiliated
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To better understand how diet influences brain aging, this paper focuses on the presymptomatic period during which prevention may be most effective. Findings show brain network destabilization may reflect early signs of hypometabolism, associated with dementia. Dietary interventions resulting in ketone utilization increase available energy and thus may show potential in protecting the aging brain.
Externally-conducted
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This review examines the potential therapeutic benefits of ketogenic diet on neurodegenerative and psychiatric disorders in humans and animal models.
Externally-conducted