The science behind what we do

This systematic review and meta-analysis found that antipsychotic-naive patients with first-episode psychosis show higher rates of insulin resistance and impaired glucose tolerance than healthy controls, suggesting early metabolic dysfunction may accompany schizophrenia development and help explain its strong association with type 2 diabetes.

This Ethiopian case–control study found dyslipidemia was twice as common in patients with severe mental illness compared to controls. Urban residence, physical inactivity, and higher BMI significantly increased risk, highlighting the need for routine lipid screening and metabolic risk management in psychiatric care.

About 20–30% of people with depression show an immuno-metabolic subtype marked by chronic low-grade inflammation, with elevated CRP and cytokines. This inflammatory profile clusters with energy-related symptoms and metabolic dysfunction, increases cardiometabolic risk, and may explain poor response to standard antidepressants, supporting inflammation-targeted treatments.

Psychiatric, metabolic, and immune disorders often co-occur because stress increases the body’s energy demands. The Allostatic Triage Model proposes that chronic stress disrupts brain and mitochondrial energy balance, prioritizing short-term survival over long-term health, leading to persistent emotional dysregulation and transdiagnostic mental and physical illness.

Obesity is recognized by the American Medical Association as a serious disease and a leading cause of preventable illness and death, and it is closely linked with mental illness. When obesity and severe mental illness co-occur, health outcomes are significantly worse, highlighting shared clinical and biological mechanisms that may inform more effective treatments.

This review explains how ketogenic diets may help improve mental illnesses and summarizes recent clinical studies. Conditions like schizophrenia, depression, and bipolar disorder share problems with brain energy use, hormones, stress and inflammation; and strong evidence suggests ketogenic diets can address these issues and improve symptoms.

This study compared 58 people with newly diagnosed schizophrenia (not yet on medication) to 58 healthy individuals and found that those with schizophrenia had higher insulin resistance, even before treatment. Higher insulin resistance was linked to genetic risk for schizophrenia and poorer response to antipsychotic medications, suggesting metabolic problems are part of the illness itself, not just a side effect of treatment.

This study examined 447 hospitalized adults with schizophrenia and found that over 80% showed some level of cognitive impairment based on memory and thinking tests. Higher levels of certain blood fats, especially apolipoprotein B, were linked to better cognitive function, suggesting that altered lipid metabolism may play a role in thinking difficulties in schizophrenia.

This review summarizes findings from many human and animal studies showing that inflammation is common in people with schizophrenia and may disrupt brain cells that help keep thinking and behavior organized. Inflammation-related changes in these brain circuits may explain cognitive symptoms and why current treatments help only about half of patients, highlighting new targets for better therapies.

The study involved people with schizophrenia who were stable on medication and following a diet without grains or milk. When wheat gluten was added back without their knowledge, their symptoms worsened, and after gluten was removed, their clinical improvement returned.

This review draws on evidence from genetic, protein, and brain imaging studies showing that people with schizophrenia often have impaired mitochondrial function, leading to low energy production and increased inflammation in the brain. These mitochondrial problems may trigger long-term inflammatory and oxidative stress responses during brain development, contributing to the onset and progression of schizophrenia.

The ketogenic diet shifts brain fuel from sugar to ketones, which can improve brain energy use, mitochondrial function, and reduce oxidative stress, problems often seen in schizophrenia. Ketones make more energy with less damage and help remove faulty mitochondria. The diet may also calm brain signaling and inflammation by increasing calming chemicals like GABA, reducing excess glutamate and dopamine activity, and lowering inflammatory markers such as IL-6 and TNF-α, which are commonly elevated in schizophrenia.

Research shows that people with schizophrenia have early insulin resistance and brain glucose problems, even before medication, raising diabetes and heart disease risk. For example, first-episode patients show disrupted brain energy use. A ketogenic diet provides ketones, a more efficient brain fuel, improving mitochondria, brain signaling, inflammation, and cognition, while also supporting overall metabolic and heart health.

People with schizophrenia often have weight and metabolic problems, partly due to medication side effects and unhealthy diets. Medicines like metformin and newer GLP-1 drugs, along with diet changes such as ketogenic diets, may help improve both physical health and mental well-being when used together.

A 32 year old male with schizophrenia followed a strict meat-based ketogenic diet with professional support and experienced remission of symptoms, even in challenging financial and social conditions. The case shows how carefully monitored ketogenic diets may help mental health and highlights the value of teamwork between nutrition and mental health professionals.

The ketogenic diet is already known to help with obesity, diabetes, and epilepsy, and this pilot 4-month study tested it in 23 people with schizophrenia or bipolar disorder. Adherent participants lost significant weight, improved blood sugar and cholesterol, and also showed better mental health, sleep, and quality of life, suggesting the diet may be a helpful added treatment.

Adults with severe mental illness who had not improved with standard treatments showed large improvements in depression and psychosis after following a very low-carbohydrate ketogenic diet in hospital care. Along with mental health gains, patients also improved in weight, blood sugar, blood pressure, and cholesterol, showing the diet was doable and well tolerated.

This review explains how ketogenic diets may help improve mental illnesses and summarizes recent clinical studies. Conditions like schizophrenia, depression, and bipolar disorder share problems with brain energy use, hormones, stress and inflammation; and strong evidence suggests ketogenic diets can address these issues and improve symptoms.

Metformin improved brain energy metabolism in schizophrenia by reducing excess lactate and pyruvate while boosting downstream TCA cycle activity, indicating more efficient mitochondrial energy use. These metabolic shifts were linked to improved hippocampal connectivity and better working memory and verbal learning, suggesting cognition benefits through restored cellular energy pathways.

Genetic studies suggest activating the GLP-1 receptor lowers schizophrenia risk, mainly through effects on body weight rather than blood sugar control. GLP-1 drugs may also protect the brain by reducing inflammation, improving insulin signaling, supporting neuron growth and connections, and lowering oxidative stress, which could help cognition in schizophrenia beyond weight loss alone.

Pioglitazone activates PPAR-γ, which suppresses NF-κB–driven neuroinflammation by lowering pro-inflammatory cytokines and regulating immune signaling in the brain. Because inflammation and PPAR signaling are disrupted in schizophrenia, pioglitazone may improve symptoms by reducing brain inflammation, protecting neurons, and enhancing neurotransmission, especially when added to antipsychotic treatment.

A review of 19 randomized control trials looked at metformin in people with schizophrenia taking antipsychotics. Beyond helping with weight gain, metformin showed modest benefits for thinking and symptoms, with mostly mild side effects, suggesting it may support both metabolic and mental health, though more long-term studies are needed.

A review of seven studies found that GLP-1 medications helped people with schizophrenia on antipsychotics lose weight and improve waist size, BMI, and blood pressure compared to placebo. These drugs appeared generally safe, but more research is needed to confirm effects on insulin levels and breathing-related side effects.

In people with schizophrenia taking clozapine or olanzapine, adding liraglutide for 16 weeks improved blood sugar control, with many returning to normal glucose levels. It also led to meaningful weight loss and better heart-health markers, with mainly mild stomach-related side effects.

In a small 24-week study, people with schizophrenia taking clozapine who received weekly exenatide lost significantly more weight and had better blood sugar control than those receiving usual care. These results suggest exenatide may help reduce clozapine-related weight gain and diabetes risk.

A study of 40 patients with chronic schizophrenia found that adding pioglitazone to risperidone significantly improved negative symptoms and overall schizophrenia scores compared with placebo. These results suggest pioglitazone may be an effective add-on therapy to help reduce negative symptoms in schizophrenia.

70 studies with 240,704 participants show that insulin resistance rises during active depression, especially atypical depression with symptoms like sleeping too much and weight gain, but returns to normal when depression improves. This suggests a metabolic subtype of depression, where simple blood tests (insulin, HOMA-IR) could help identify people who may benefit from metabolism-focused treatments, even though antidepressants alone don’t change insulin levels.

Depression is linked to abnormal blood fats, which can trigger brain inflammation, damage energy-producing cells, and worsen mood through stress hormones and insulin problems, creating a vicious body–brain cycle. Researchers suggest using advanced blood tests to track lipid-related inflammation and treating it with diet, lifestyle changes, and medications.

Depression affects about 8.4% of people in the U.S. and ~280 million worldwide, yet around one-third of patients do not improve with common serotonin-based antidepressants. This shows depression is more complex than a single “chemical imbalance,” involving stress, inflammation, immune signals, and multiple brain pathways beyond serotonin alone.

Major depressive disorder is highly disabling and usually diagnosed by symptoms, but studies suggest mitochondrial dysfunctions may play a key role, making diagnosis difficult without biological tests. This review highlights mitochondrial markers as potential objective tools and discusses newer treatments, including ketamine, brain stimulation, and anti-inflammatory approaches, beyond standard antidepressants.

Low-carbohydrate and ketogenic diets may improve depression by lowering sugar intake, stabilizing brain energy use, and increasing BDNF, a key molecule that supports brain plasticity and mood regulation. By improving metabolic signaling and neural resilience, these diets may help reduce symptoms and relapse risk in treatment-resistant depression.

The ketogenic diet may improve depression by changing brain energy use, boosting mitochondrial function, reducing oxidative stress, and shifting neurotransmitters toward calming signals (more GABA, less excitation). It also lowers inflammatory cytokines (like TNF-α and IL-1) and alters gut bacteria, which together may stabilize brain circuits and improve mood.

This review analyzed 50 studies including 41,718 adults on ketogenic diets. In 10 randomized trials, ketogenic diets led to modest improvements in depression symptoms, especially when ketosis was confirmed, but showed no clear benefit for anxiety. Overall, ketogenic diets may help some adults with depression, but results vary and stronger, longer human trials are needed to confirm benefits and understand who responds best.

Young adults with depression followed a ketogenic diet for 10–12 weeks alongside usual care and most were able to maintain ketosis. Participants saw large improvements in mood and well-being, along with weight and fat loss, better metabolic markers, and some cognitive gains, suggesting the diet may help support depression treatment.

Adults with severe mental illness who had not improved with standard treatments showed large improvements in depression and psychosis after following a very low-carbohydrate ketogenic diet in hospital care. Along with mental health gains, patients also improved in weight, blood sugar, blood pressure, and cholesterol, showing the diet was doable and well tolerated.

This review explains how ketogenic diets may help improve mental illnesses and summarizes recent clinical studies. Conditions like schizophrenia, depression, and bipolar disorder share problems with brain energy use, hormones, stress and inflammation; and strong evidence suggests ketogenic diets can address these issues and improve symptoms.

Metformin shows antidepressant-like effects by protecting hippocampal neurons, improving brain plasticity, and boosting the effects of standard antidepressants. Mechanistically, it may reduce depression by regulating neurotransmitters, increasing neurogenesis, lowering inflammation, and altering gut microbiota, though exact pathways are still being studied.

Depression is linked to metabolic problems like high blood sugar, abnormal fats, and insulin resistance, which may also contribute to memory loss and mood symptoms. GLP-1, a hormone that regulates glucose and insulin, affects multiple brain pathways and may help improve depression by targeting these underlying metabolic and brain changes.

This open-label study treated 34 depressed bipolar patients with insulin resistance, most treatment resistant, with pioglitazone for 8 weeks to improve insulin sensitivity. Depression, anxiety, and daily functioning improved significantly as metabolic health improved. Mechanistically, pioglitazone likely reduced bipolar depression by improving insulin sensitivity and lowering inflammation, with higher baseline IL-6 predicting greater symptom improvement.

A meta-analysis of 80 randomized clinical trials involving 107,860 patients found that GLP-1 receptor agonists (GLP1-RAs) do not increase the risk of depression or other psychiatric problems compared with placebo. Across these trials, GLP1-RAs improved quality of life, emotional and restrained eating, and overall mental and physical well-being in patients with obesity or diabetes.

A review of clinical trials found mixed results for metformin on mood but clearer benefits for thinking and memory. Overall, metformin improved cognitive function compared to placebo in some conditions, while evidence for treating depression was limited, suggesting metformin may be useful mainly for cognitive problems rather than mood symptoms.

This study tested metformin in people with hard-to-treat bipolar depression who also had insulin resistance. Those whose insulin resistance improved, mostly on metformin, showed lasting improvements in depression, anxiety, daily functioning, and overall illness severity, suggesting metformin may help some patients when standard treatments fail.

In this study, people with major depression who took metformin along with an antidepressant improved more than those taking the antidepressant alone. They had greater symptom relief, higher recovery rates, and healthier inflammation and brain-related markers, suggesting metformin may safely boost depression treatment even in people without diabetes.

A meta-analysis of four trials (161 patients) found that pioglitazone, alone or added to standard antidepressants, led to higher remission rates in major depressive episodes (27% vs 10%), especially in patients without metabolic issues. About six patients need treatment for one additional remission, suggesting pioglitazone may be a clinically effective antidepressant.

In this 8-week study of people with bipolar depression, pioglitazone was safe but did not improve depression more than a placebo; in fact, the placebo group improved slightly more. Although pioglitazone affected some metabolic markers, the small study size means it does not support pioglitazone as an effective antidepressant for bipolar depression.

In adults with depression or bipolar disorder and cognitive difficulties, adding liraglutide for 4 weeks improved memory, attention, and problem-solving skills. The benefits were greater in those with higher body weight or insulin resistance, and the treatment was generally safe and well tolerated, though larger controlled studies are needed.

The ketogenic diet may improve depression by changing brain energy use, boosting mitochondrial function, reducing oxidative stress, and shifting neurotransmitters toward calming signals (more GABA, less excitation). It also lowers inflammatory cytokines (like TNF-α and IL-1) and alters gut bacteria, which together may stabilize brain circuits and improve mood.

This review combined 24 studies and found that people with anxiety had a slightly higher chance of having metabolic syndrome (about 7–14% higher risk), based mainly on cross-sectional data. Anxiety may raise stress hormones and inflammation, increasing blood sugar and weight, while metabolic problems and insulin resistance can also affect brain areas that control mood, suggesting both mental and physical health should be treated together.

In a Greek primary-care study of 181 adults (average age ~62, 68% women), with 20% of them having significant depression or anxiety, their low HDL-C (good-cholesterol) and high LDL-C (bad-cholesterol) were associated with both depression and anxiety symptoms, including worse mood, sleep, energy, and cognitive symptoms, showing different biological patterns behind depression and anxiety.

A review of 14 studies compared 1,188 people with generalized anxiety disorder (GAD) to 10,623 controls and found higher levels of inflammation markers, especially C-reactive protein, in people with GAD. Overall, this suggests anxiety may be linked to low-grade inflammation, but results were mixed and more long-term studies are needed to understand cause and effect.

Using UK Biobank data from 72,000–80,000 adults, researchers found that specific mitochondrial DNA variants were linked to anxiety and depression scores (GAD-7, PHQ-9). Several mitochondrial genes also interacted with the inflammation marker CRP, suggesting that combined mitochondrial dysfunction and inflammation increase anxiety and depression risk.

Low-carbohydrate and ketogenic diets induce ketosis, shifting brain fuel use to ketones, which increases GABA signaling, reduces glutamate-driven excitability, lowers mTOR activity, and decreases oxidative stress and inflammation. These diets also reshape gut microbiota and neurosteroid pathways, enhancing GABA-A receptor function and anti-inflammatory omega-3 effects, potentially reducing anxiety through improved neural inhibition and immune balance.

Anxiety disorders are linked to unhealthy diets and increased risk of chronic disease, partly through inflammatory pathways. The ketogenic diet may reduce neuroinflammation and improve anxiety by shifting GABA–glutamate balance and stabilizing metabolism, potentially supporting remission and relapse prevention, though stronger evidence is still needed.

This article describes three adults with depression and anxiety who followed a personalized ketogenic diet along with regular support for 3–4 months. All showed major improvements in mood and anxiety, lost significant weight, and improved metabolic health, with some reaching full remission and overall better well-being.

Anxiety disorders carry high global burden and may involve inflammatory and metabolic dysregulation. Nutritional strategies such as low-carbohydrate, high-fat diets may help reduce inflammation and support metabolic stability, potentially improving anxiety outcomes and relapse prevention when used alongside standard treatments, though further research is needed.

This study shows that anxiety is linked to reduced AMPK activity in the medial prefrontal cortex, causing impaired GABAergic inhibition and neural imbalance. Metformin restores AMPK function, normalizes inhibitory signaling, and reduces anxiety-like behaviors, suggesting AMPK activation as a potential therapeutic target for anxiety disorders.

Metabolic disorders can drive depression through inflammation, insulin resistance, and brain dysfunction, making diabetes drugs like GLP-1 analogs potential treatments. In diabetic mice, semaglutide reduced inflammation, improved insulin signaling, neurotransmitters, synaptic plasticity, and gut–brain balance, leading to better mood, cognition, and anxiety-like behavior.

This study tested metformin in people with hard-to-treat bipolar depression who also had insulin resistance. Those whose insulin resistance improved—mostly on metformin—showed lasting improvements in depression, anxiety, daily functioning, and overall illness severity, suggesting metformin may help some patients when standard treatments fail.

In patients with PCOS and psychological distress, pioglitazone–metformin significantly reduced anxiety and depression symptoms. These improvements were accompanied by inhibition of the NLRP3 inflammasome and reductions in proinflammatory cytokines (IL-1β, IL-6, TNF-α), suggesting symptom relief is mediated through anti-inflammatory mechanisms.

This genetic study compared very large samples (over 1.2 million participants combined) and found that ADHD and type 2 diabetes share many risk genes, with a moderate genetic overlap. People with genetic risk for ADHD were about 30% more likely to develop type 2 diabetes, and diabetes genes also slightly increased ADHD risk, possibly through shared inflammation pathways.

This review suggests that trans fats from hydrogenated oils may increase ADHD risk, especially when exposure occurs during pregnancy, by harming brain development. Trans fats may also disrupt gut bacteria and brain signaling (gut–brain axis), affecting attention and behavior; reducing trans-fat intake during early life may help prevent ADHD.

This review of 14 human studies found that people with ADHD often show changes in inflammation markers, such as altered cytokine genes or higher blood cytokine levels, compared with controls. Although results were mixed, findings from blood and spinal fluid studies suggest inflammation may play a role in ADHD, highlighting the need for larger, clearer studies.

Research suggests that in ADHD, brain cells may not work properly due to factors like oxidative stress, inflammation, metabolic problems, and genetics. Studies link mitochondrial problems in ADHD to changes in dopamine and serotonin genes, suggesting energy and cleanup defects in brain cells may contribute to attention and behavior symptoms.

This randomized trial included 153 three-year-old children and 144 children aged 8–9 years from the general population. Both age groups were tested with drinks containing artificial food colors and additives or placebo to compare behavior and attention outcomes.

ADHD involves brain network changes, excess glutamate, low dopamine and GABA, and increased oxidative stress. A ketogenic diet may help by improving brain energy use, increasing GABA, stabilizing dopamine signaling, lowering glutamate-driven excitability, and reducing oxidative stress, supporting healthier neural network function.

Most evidence for ketogenic diets helping ADHD comes from case reports where ADHD changes were not the main focus. In one small study of children with epilepsy, two children on a ketogenic diet had fewer seizures and improved attention-related symptoms, suggesting possible benefits that need further research.

The study included 21 drug-naïve children with ADHD and 21 children without ADHD, comparing their omega-3 intake and fatty acid deficiency. Children with ADHD had more fatty acid deficiency and performed worse on attention and waiting tasks, with more severe symptoms linked to lower omega-3 intake.

This case-study describes a 9-year-old boy with Fragile X syndrome, autism, epilepsy, and severe behavioral dysregulation including ADHD. Despite persistent seizures and significant aggression on antiepileptic therapy, initiation of metformin at age 7 was followed by complete seizure cessation, marked behavioral and anxiety improvement, normalized eating patterns, and substantial gains in communication and school functioning, with only mild gastrointestinal side effects.

This review analyzed 13 adult studies and found PTSD raises the risk of type 2 diabetes and worsens blood sugar control, while people with diabetes, especially women, veterans, and refugees, have higher PTSD rates (up to 30–50%). Shared stress hormones, inflammation, and lifestyle factors link both conditions, supporting integrated mental and metabolic care.

This meta-analysis of 17 studies found that people with PTSD have higher “bad” fats in the blood, like total cholesterol, LDL, and triglycerides, and lower “good” fat like HDL compared with healthy people. These lipid changes may act as warning signs for heart disease risk, suggesting routine cholesterol checks could help improve long-term health in PTSD patients.

This review of 50 studies found that people with PTSD often have higher inflammation markers in their blood, such as cytokines, across many trauma types. Brain scans also show inflammation-related changes in stress and emotion areas like the amygdala, hippocampus, and frontal cortex, suggesting inflammation affects both the body and brain in PTSD.

This review analyzed 43 studies (29 animal, 15 human) and found that human studies involving about 1,100 people with PTSD and 300 with partial PTSD found changes in how brain cells produce energy, including altered mitochondrial DNA levels and higher oxidative stress. These findings suggest that problems in cell energy systems may be linked to PTSD in people and could become useful biomarkers or treatment targets, though it is still unclear if they are a cause or an effect of the disorder.

A ketogenic diet reduces oxidative stress by increasing antioxidants (like SOD and NQO1) and preserving mitochondrial enzyme function, helping prevent energy failure and brain damage after injury.

This case report describes a 38 years-old female patient with severe, treatment-resistant PTSD, ADHD, BED, bipolar II disorder, depression, anxiety, and premenstrual dysphoric disorder who achieved complete symptom remission following ketogenic metabolic therapy. Sustained nutritional ketosis correlated with optimal symptom control and major functional improvements, highlighting KMT’s potential as a transdiagnostic metabolic intervention warranting further controlled trials.

This feasibility study tested a 4-week ketogenic diet with added ketones in adults with PTSD to see if it was safe and manageable. Most participants completed the program, reached ketosis safely, and showed clear improvements in PTSD symptoms and quality of life, suggesting larger studies are worthwhile.

In a PTSD rat model, stress caused mitochondrial damage and neuron death in the hippocampus through oxidative stress and disrupted energy signaling. Metformin activated the AMPK pathway, reduced oxidative stress, and protected hippocampal neurons from apoptosis, suggesting that improving brain energy metabolism may help treat PTSD.

In a large Veterans Health Administration cohort, veterans with PTSD who used metformin were significantly more likely to experience clinically meaningful symptom improvement than matched controls. Longer metformin exposure further increased benefit, suggesting this common antidiabetic drug may have therapeutic potential for PTSD symptom reduction.

Genetic studies in children found that OCD and everyday obsessive-compulsive symptoms (like repeated checking, cleaning, or counting) share genes linked to brain insulin signaling. Some OCD-related thoughts also share genetic risk with insulin problems like high fasting insulin or type 2 diabetes, suggesting metabolism and mental health may be biologically connected.

This review suggests that OCD may be linked to problems in brain fats (lipids) that help brain cells communicate and stay healthy. Human studies show stronger evidence for oxidative fat damage and phospholipid changes, while cholesterol and fatty acids show mixed results, suggesting brain lipid markers may help future OCD diagnosis and treatment.

This review of eight studies involving over 31,000 people with OCD found higher levels of inflammation markers like TNF-α, interleukins, and the neutrophil-to-lymphocyte ratio. These findings suggest inflammation may play a role in OCD, and early use of anti-inflammatory treatments could be worth studying.

This study analyzed blood gene data from OCD patients and healthy controls and identified eight possible biomarkers, with two mitochondrial genes (NDUFA1 and COX7C) consistently lower in OCD across datasets and lab validation. These genes are linked to energy production pathways and immune changes (e.g., higher CD8 T cells), suggesting mitochondrial dysfunction may help diagnose and target OCD.

The ketogenic diet shifts the brain’s fuel from glucose to ketones, which produce more energy, improve mitochondrial function, reduce oxidative stress, and increase antioxidant defenses. Ketones also rebalance brain chemicals by lowering glutamate, increasing GABA, and suppressing inflammatory pathways (AMPK, NF-κB, NLRP3), helping stabilize brain networks and reduce neuropsychiatric symptoms.

This case series followed three people with OCD who adopted a ketogenic diet, with symptoms measured using the Yale-Brown Obsessive Compulsive Scale. All three became medication-free and achieved remission, with an average 21-point (about 90%) drop in Y-BOCS scores, and symptoms returned when the diet was stopped.

This case followed a 26-year-old man with treatment-resistant OCD who used a ketogenic diet alongside exposure and response prevention (ERP) for 12 weeks. His compulsions dropped from 3–8 hours daily to under one hour within weeks, with symptom remission and improved mood, sleep, and quality of life lasting nearly two years.

This case followed a 37-year-old obese woman with long-standing OCD and ulcerative colitis who used a personalized whole-food ketogenic diet for 12 weeks. Her UC went into remission within 3 weeks, OCD fully remitted by 12 weeks, body weight dropped 12%, and metabolic health and quality of life markedly improved.

This randomized crossover fMRI study included 20 adults with type 2 diabetes and 20 lean healthy controls aged 40–65 years. Blocking endogenous GLP-1 prevented meal-related reductions in brain reward and satiety signals, showing that GLP-1 normally suppresses food-cue–driven brain activity to promote satiety, especially in type 2 diabetes.

Repetitive, compulsive-like behaviors in ASD often respond poorly to behavioral therapy and SSRIs, prompting exploration of novel treatments. In an adolescent with severe autism, liraglutide reduced obsessive food cravings, binge eating, weight gain, and behavioral problems, suggesting GLP-1 signaling as a promising therapeutic target for obsessive behaviour.

This review highlights that many people with autism show insulin resistance, which may affect brain development through disrupted insulin signaling, inflammation, and altered energy use in the brain. Across ASD studies, insulin resistance is linked to gut dysbiosis and inflammatory pathways (e.g., PI3K/Akt/mTOR), suggesting that improving insulin sensitivity through diet or metabolic treatments may benefit a subset of individuals.

This review analyzed 9 human cohort studies measuring lipids in pregnancy, after birth, or in cord blood, linking low omega-3 levels, low DHA, and low maternal LDL with higher autism risk in children. Studies also found altered newborn lipids tied to brain energy and inflammation, predicting later autism symptoms with moderate accuracy, suggesting early metabolic biomarkers.

This review of 41 studies, including data from Saudi Arabia, found that people with autism show higher oxidative stress, mitochondrial problems, and abnormal lipids and neurotransmitters, increasing brain, gut, and metabolic risks. These changes disrupt brain signaling and cause chronic inflammation, supporting the use of blood-based biomarkers for earlier diagnosis and personalized autism care.

In a study of 60 children with autism and 28 typically developing children, blood testing found 18 inflammation-related proteins were higher in autism, showing immune system activation. Three markers (IL-17C, CCL19, CCL20) strongly distinguished autism (AUC > 0.75), suggesting blood inflammation markers may help diagnose autism and relate to social behavior.

A review of 204 studies found that many people with autism show signs of mitochondrial problems, such as higher blood lactate, pyruvate, and creatine kinase, and changes in mitochondrial DNA compared with controls. These mitochondrial markers were linked to autism severity, developmental delays, and gut symptoms, suggesting energy problems affect a subgroup of individuals with autism and may be useful targets for early diagnosis and treatment.

The ketogenic diet shifts the body from glucose to ketones, improving brain energy metabolism and reducing inflammation and oxidative stress. In autism, KD may rebalance neurotransmitters, influence gene expression, and reshape gut microbiota, mechanisms that together may improve behavior and brain function.

Autism involves brain energy, signaling, and inflammatory imbalances. The ketogenic diet shifts the brain to ketones, improving energy production, lowering oxidative stress, and rebalancing neurotransmitters. It may also reduce mTOR overactivity and reshape gut microbiota, mechanisms that together could improve behavior and brain function in ASD.

A 3-month trial tested a modified gluten-free ketogenic diet with MCTs in 15 children with autism. Many showed improvement in core autism symptoms, especially in imitation, body use, and fear, with benefits linked to changes in cholesterol and albumin. Improvements persisted in most children after 6 months.

In a study of 100 children with autism, half received a 10-week intermittent ketogenic diet alongside special education, while the other half received only education. Children on the ketogenic diet showed greater improvements in autism symptoms and abnormal behaviors, with lower scores on standard autism rating scales compared to the control group.

A study of 45 children with autism tested three diets: ketogenic (modified Atkins), gluten-free casein-free, and a regular diet. Both special diets improved autism symptoms, but the ketogenic diet showed the best results for thinking and social skills, suggesting these diets can safely help children with ASD.

In a study of 187 children with autism, 6 with metabolic issues tried a ketogenic diet. 1 child showed major improvement in social communication and could stop medications, while all 6 experienced reduced ADHD, compulsive behaviors, unusual fixations, and sleep problems, showing KD may help manage autism-related symptoms.

A child with autism and epilepsy, unresponsive to medications, improved on a gluten-free, casein-free ketogenic diet with MCTs. The diet greatly reduced seizures, resolved obesity, improved behavior and thinking, and over several years lowered autism severity scores dramatically while increasing IQ by 70 points, showing lasting physical and cognitive benefits.

A 6-year-old with high-functioning autism and mild epileptic activity showed little improvement with usual treatments. After starting a ketogenic diet, the child’s behavior, attention, communication, and emotional responses improved within a month, with continued progress over 16 months, alongside changes in brain glucose metabolism seen on PET scans.

A 6-month pilot study tested a ketogenic diet in 30 children with autism, using cycles of diet and breaks. Eighteen children (60%) who followed the diet showed improvements in autism symptoms, with two showing major, eight moderate, and eight minor improvements, while others could not tolerate or discontinued the diet early.

This mouse study used C57BL/6 mice fed a high-fat diet for 10 weeks, with or without metformin treatment. High-fat diet worsened repetitive behavior, anxiety, and hyperactivity, while metformin improved these behaviors by altering gut bacteria and increasing gut serotonin (5-HT), suggesting a gut–brain mechanism linking metabolism, microbiota, and autism-like behaviors.

This study used BTBR autistic mice treated repeatedly with semaglutide to assess behavior and DNA repair. Semaglutide reduced autism-like behaviors, improved antioxidant balance, and enhanced DNA repair by lowering DNA damage signals and increasing repair enzymes, suggesting GLP-1 signaling may improve neurodevelopmental and cellular stress mechanisms in ASD.

This study used juvenile rats exposed prenatally to LPS to model autism-like behaviors, then treated them daily with pioglitazone. Pioglitazone reversed social and communication deficits and lowered IL-6 levels, suggesting it improves autism-like symptoms by reducing inflammation rather than through its glucose-lowering effects.

A 10-week randomized, double-blind trial evaluated metformin (500 mg/day) added to risperidone for irritability in children with ASD. Metformin significantly reduced irritability and improved hyperactivity and inappropriate speech versus placebo, with good safety, supporting further investigation before routine clinical use.

Repetitive, compulsive-like behaviors in ASD often respond poorly to behavioral therapy and SSRIs, prompting exploration of novel treatments. In an adolescent with severe autism, liraglutide reduced obsessive food cravings, binge eating, weight gain, and behavioral problems, suggesting GLP-1 signaling as a promising therapeutic target for obsessive behaviour.

This 16-week pilot dose-finding study in autistic children found pioglitazone safe and well tolerated, with a maximum tolerated dose of 0.75 mg/kg/day and no serious adverse events. Preliminary efficacy signals showed significant improvements in social withdrawal, repetitive, and externalizing behaviors, supporting the need for randomized controlled trials.

This review analyzed 22 studies (12 in meta-analysis) and found different insulin responses across eating disorders. People with anorexia nervosa (about 340 participants) showed higher insulin sensitivity, while those with bulimia or binge-eating disorder (over 3,300 participants) showed reduced insulin sensitivity. These results suggest eating disorder subtypes affect metabolism differently, highlighting insulin sensitivity as a possible biological link needing further study.

This review explains that binge eating disorder (BED), marked by repeated loss-of-control eating, is common in people with obesity and linked to serious health risks. Studies show BED is strongly associated with metabolic syndrome features such as high blood sugar, high cholesterol, high blood pressure, obesity, and type 2 diabetes. The link is driven not only by weight, but also by shared biological, genetic, and behavioral factors, highlighting the need for early screening and combined mental–metabolic care.

This randomized study followed women with bulimia nervosa or binge-eating disorder for one year during exercise-diet therapy or CBT, tracking blood sugar, cholesterol, and thyroid hormones. While averages were normal, 33% had high total cholesterol and 39% had high LDL. Women with binge-eating disorder more often had low “good” HDL cholesterol and rising cholesterol and TSH over time. Results were similar across treatments, suggesting regular metabolic monitoring is important for these patients.

This case–control study compared 76 Iranian adults with bulimia nervosa seeking bariatric surgery to 42 healthy controls. Bulimia patients more often used caffeine, tobacco, alcohol, and had depression, and showed higher blood sugar, HbA1c, cholesterol, triglycerides, and kidney markers. They also had higher inflammatory cytokines (IL-1β, IL-6, TNF-α), suggesting bulimia in this group is linked to metabolic problems and chronic inflammation.

In a study of 39 adults with obesity, those with binge eating disorder (BED) showed more bingeing, emotional eating, and higher depression scores than those without BED. Blood tests also showed higher inflammation (CRP, TNF-α) and leptin, a hunger-related hormone. BED was independently linked to depression and inflammation, suggesting it marks a more severe metabolic and mental health risk in obesity.

Ketosis from ketogenic diets or ketone esters suppresses appetite by preventing the usual rise in the hunger hormone ghrelin that follows weight loss, helping reduce hunger and weight regain. Mechanistically, ketones directly signal satiety pathways, with appetite suppression appearing only above a certain ketone level, shown in rodents and humans.

3 adults with obesity and binge-eating/food addiction tried a low-carb ketogenic diet for 6–7 months. All tolerated the diet well, lost 10–24% of their weight, and reported big reductions in binge eating and cravings, with benefits maintained for up to 17 months while continuing the diet.

5 women with binge eating or food addiction followed a very-low-calorie ketogenic diet (VLCKD) for 5–7 weeks, then a low-calorie diet for 11–21 weeks, while keeping protein intake sufficient. All participants lost weight, preserved muscle, and reported complete remission of binge eating or food addiction symptoms, showing the diet is feasible and potentially therapeutic.

A telemedicine program using therapeutic carbohydrate reduction (TCR) helped employees with food addiction and binge eating. Participants saw a 40.7% drop in food addiction symptoms and a 34.7% drop in binge eating, along with weight loss, reduced medication needs, and improved mental health, showing TCR can support overall wellness.

Research suggests binge eating and addiction to ultraprocessed foods may be linked to metabolism. High-sugar, refined carbs can spike blood sugar and insulin, triggering brain changes that increase hunger and overeating, unlike healthy fats, which don’t cause these spikes or addictive eating behaviors.

Metformin suppresses appetite by activating GIP receptors specifically in the brainstem NTS, repairing gut–brain satiety signaling independently of GLP-1 or PYY.

This review explains how ketogenic diets may help treat mental illnesses like schizophrenia, depression, bipolar disorder, and binge eating. These conditions share problems with brain energy use, chemical balance, and inflammation, and evidence shows ketogenic diets can target these issues and improve patients’ symptoms.

A review of five studies with 182 participants found that GLP-1 agonists may influence central and peripheral pathways, improving satiety and reducing binge-eating episodes through brain–gut interactions and modulation of reward systems. GLP-1 agonists also help people with binge eating disorder (BED) lose weight, reduce BMI and waist size, and lower binge eating scores compared to controls. These findings suggest GLP-1 agonists may be a promising treatment for BED.

A study tested phentermine/topiramate ER in 22 adults with binge-eating or bulimia. The medication reduced binge-eating days, helped more people stop binge episodes, and caused an average weight loss of 5.8 kg, with few side effects, showing it’s effective and safe for binge-eating disorder, though evidence for bulimia is limited.

In a 17-week trial of 27 adults with binge eating disorder, both liraglutide 3 mg/day and placebo reduced binge episodes, but remission rates were similar (44% vs 36%). Liraglutide led to significantly greater weight loss (5.2% vs 0.9%), showing promise for weight management in BED, though further research is needed.

In a 12-week study of type 2 diabetes patients with binge eating disorder, dulaglutide reduced binge eating, body weight, BMI, body fat, and blood sugar more effectively than gliclazide. Improvements in binge eating were closely linked to weight loss and better blood sugar control, highlighting dulaglutide’s potential benefits for both behavior and metabolism.

In a 12-week study of non-diabetic obese adults with subclinical binge eating, liraglutide significantly reduced binge eating, body weight, BMI, waist size, blood pressure, blood sugar, and cholesterol compared with controls. Ghrelin, an appetite hormone, increased, which could limit further weight loss despite these benefits.

A study tested phentermine/topiramate ER in 22 adults with binge-eating or bulimia. The medication reduced binge-eating days, helped more people stop binge episodes, and led to an average 5.8 kg weight loss, with few side effects, showing it’s effective and safe for binge-eating disorder, though evidence for bulimia is limited.

In a 26 years old female patient with PCOS, bulimia nervosa, and depression, adding liraglutide to metformin led to rapid satiety and complete remission of bulimic behaviors within two weeks, with sustained remission for over 5 years. Stopping either liraglutide or metformin caused recurrent hunger and weight gain, while resolution of bulimia was associated with remission of depression and discontinuation of psychiatric treatment.

This was a single-patient case study of a 26-year-old woman with PCOS, bulimia nervosa, reactive hypoglycemia, and depression that did not improve with antidepressants or therapy. After adding liraglutide 1.2 mg daily to long-term metformin, her binge–purge behavior resolved within two weeks and remained absent for five years, with remission of depression.