The brain is the complex organ responsible for controlling most of the body's functions and processes. It is the center of the nervous system and plays a vital role in cognition, emotion, memory, sensory processing, motor control, and coordination. Comprising billions of neurons and glial cells, the brain consists of various interconnected regions, each with specific functions and responsibilities. The cerebral cortex, divided into four lobes (frontal, parietal, temporal, and occipital), is responsible for higher-level cognitive functions, such as reasoning, language, and perception. The brainstem regulates essential functions such as heart rate, breathing, and sleep-wake cycles. The cerebellum coordinates movement and balance, while the limbic system is involved in emotions and memory. Despite its relatively small size compared to the rest of the body, the brain is incredibly complex and remains one of the least understood organs in the human body.

The brain can be affected by various disorders, including:

1. Alzheimer's Disease: A      progressive neurodegenerative disorder characterized by cognitive decline,      memory loss, and changes in behavior and personality, typically seen in      older adults.
2. Stroke: Occurs when blood flow to a part of the      brain is interrupted, leading to brain tissue damage and neurological      deficits, such as paralysis, speech impairment, or cognitive impairment.
3. Traumatic Brain Injury (TBI):      Resulting from external trauma to the head, TBIs can range from mild      concussions to severe brain damage, leading to a range of physical,      cognitive, and emotional symptoms.
4. Parkinson's Disease: A      neurodegenerative disorder characterized by tremors, rigidity,      bradykinesia (slowed movement), and postural instability, due to the loss      of dopamine-producing neurons in the brain.
5. Epilepsy: A neurological disorder characterized      by recurrent seizures, resulting from abnormal electrical activity in the      brain.
6. Multiple Sclerosis (MS): An      autoimmune disease that affects the central nervous system, leading to      demyelination of nerve fibers, inflammation, and neurological symptoms      such as weakness, numbness, and impaired coordination.
7. Migraine: A neurological condition characterized      by recurrent headaches, often accompanied by sensory disturbances, nausea,      and sensitivity to light and sound.
8. Brain Tumors:      Abnormal growths of cells in the brain, which can be benign or malignant      and may cause symptoms such as headaches, seizures, cognitive changes, and      motor deficits.

These disorders can significantly impact a person's quality of life and may require various treatments, including medications, physical therapy, surgery, and lifestyle modifications, depending on the severity and underlying causes.

1. Alzheimer's Disease:      Insulin resistance in the brain may contribute to the development of      Alzheimer's disease, as impaired insulin signaling can affect glucose      metabolism, increase oxidative stress, and promote the accumulation of      amyloid-beta plaques and tau tangles, characteristic features of      Alzheimer's pathology.
2. Stroke: Insulin resistance and metabolic      syndrome are associated with an increased risk of stroke due to their      effects on cardiovascular health, including hypertension, dyslipidemia,      and atherosclerosis.
3. Traumatic Brain Injury (TBI):      Insulin resistance and metabolic dysfunction may exacerbate the secondary      injury cascade following TBI, leading to increased inflammation, oxidative      stress, and neuronal damage.
4. Parkinson's Disease: Some      studies suggest a potential link between insulin resistance and      Parkinson's disease, although the mechanisms are not fully understood.      Insulin resistance may contribute to neuroinflammation and mitochondrial      dysfunction, processes implicated in Parkinson's pathology.
5. Epilepsy: Insulin resistance and metabolic      syndrome may influence epilepsy risk and seizure frequency through their      effects on neuronal excitability, neurotransmitter function, and energy      metabolism in the brain.
6. Multiple Sclerosis (MS):      Insulin resistance and metabolic dysfunction may exacerbate      neuroinflammation and demyelination in MS, although further research is      needed to understand the precise mechanisms involved.
7. Migraine: Insulin resistance and metabolic      abnormalities may contribute to migraine susceptibility and severity      through their effects on vascular function, neurotransmitter regulation,      and inflammatory pathways in the brain.
8. Brain Tumors:      Insulin resistance and metabolic dysregulation may promote tumor growth      and progression in the brain by providing cancer cells with a metabolic      advantage, supporting angiogenesis, and modulating the tumor      microenvironment.

Overall, the dysregulation of insulin and metabolic processes seen in hyperinsulinemia, insulin resistance, and metabolic syndrome can impact brain health and contribute to the development or exacerbation of various neurological disorders.We are prepared to provide grants for online attendance at a range of conferences/courses. 

Many of those conferences will also supply CME for professionals (paid for by you). 

  Associated with cognitive decline, neuroinflammation, and an increased risk of stroke. 

  Increases the risk of vascular dementia, Alzheimer's disease, and  cognitive impairment due to impaired cerebral blood flow and insulin  resistance. 

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental  disorder characterized by persistent patterns of inattention,  hyperactivity, and impulsivity that significantly impact functioning and  development. ADHD symptoms typically manifest in childhood and may  persist into adolescence and adulthood. 

1. Neurological Manifestations: ADHD primarily affects brain function and development, characterized by difficulties with attention, hyperactivity, and impulsivity. While metabolic factors such as insulin resistance, hyperinsulinemia, and metabolic syndrome are not direct causes of ADHD, they may influence neurotransmitter systems implicated in the disorder. For instance, insulin resistance has been associated with alterations in dopamine signaling, which plays a key role in attention regulation and reward processing, potentially contributing to ADHD symptoms.
2. Inflammation and Immune Dysregulation: Metabolic syndrome is associated with chronic low-grade inflammation and immune dysregulation, which have been implicated in the pathogenesis of neurodevelopmental disorders, including ADHD. Inflammatory cytokines and immune dysregulation can disrupt neural development and neurotransmitter function, potentially contributing to the development or exacerbation of ADHD symptoms. Additionally, elevated inflammatory markers have been reported in individuals with ADHD, suggesting a link between metabolic abnormalities and neuroinflammatory processes in the disorder.
3. Hormonal Dysregulation: Hormonal abnormalities, including alterations in the hypothalamic-pituitary-adrenal (HPA) axis and dysregulation of stress response systems, have been observed in individuals with ADHD. Metabolic factors such as insulin resistance and metabolic syndrome may exacerbate hormonal dysregulation by disrupting cortisol metabolism and increasing stress reactivity, potentially contributing to symptom exacerbation and behavioral dysfunction in ADHD.
4. Treatment Considerations: Addressing underlying metabolic abnormalities such as insulin resistance and metabolic syndrome may be important for optimizing treatment outcomes in individuals with ADHD. Lifestyle modifications such as regular physical activity, weight management, and dietary changes may help improve metabolic health and reduce the severity of ADHD symptoms. Additionally, some medications used to manage metabolic syndrome, such as certain antipsychotics or mood stabilizers, may have adjunctive benefits in ADHD treatment by targeting neurochemical pathways or modulating neuroinflammatory processes.

In summary, while ADHD primarily affects brain function and is considered a neurodevelopmental disorder, metabolic factors such as insulin resistance, hyperinsulinemia, and metabolic syndrome can potentially influence disease presentation and management. Understanding the interactions between ADHD and metabolic abnormalities is important for developing comprehensive treatment strategies that address both the neurodevelopmental and metabolic aspects of the condition, ultimately improving outcomes and quality of life for individuals affected by ADHD.

The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder 

https://pubmed.ncbi.nlm.nih.gov/33549739/

"People with ADHD are at increased risk for obesity, asthma, allergies, diabetes mellitus, hypertension, sleep problems, psoriasis, epilepsy, sexually transmitted infections, abnormalities of the eye, immune disorders, 

and metabolic disorders"

August 2023

 In conclusion, KD improved typical behavioral performance of ADHD with  hyperactivity and impulsivity in SHR. Additionally, KD significantly  activated the DRD1/cAMP/PKA/DARPP32 pathway in SHR. The richness and  diversity of gut microbiota were altered in SHR after KD treatment, with  significant changes in Ruminococcus_gauvreauii_group, Bacteroides, Bifidobacterium, and Blautia at the genus level. KD-induced gut microbiota were enriched in amino  acid metabolism- and sugar-related pathways. These results give novel  insights into the mechanism of KD in ADHD treatment. 

  Alzheimer's disease is a progressive neurodegenerative disorder  characterized by cognitive decline, memory loss, and eventual loss of  ability to perform daily 

1. Neurological Manifestations: Alzheimer's disease primarily affects brain function and structure, making it a neurodegenerative disorder. Metabolic factors such as insulin resistance, hyperinsulinemia, and metabolic syndrome have been implicated in the pathogenesis of Alzheimer's disease. Insulin resistance, for example, may impair insulin signaling in the brain, leading to reduced glucose uptake and metabolism, synaptic dysfunction, and neuronal death. Hyperinsulinemia may exacerbate these effects by promoting neuroinflammation and oxidative stress, contributing to neurodegeneration in Alzheimer's disease.
2. Amyloid Beta and Tau Pathology: Alzheimer's disease is characterized by the accumulation of abnormal protein aggregates in the brain, including beta-amyloid plaques and tau tangles. Metabolic factors such as insulin resistance and metabolic syndrome may influence the processing and clearance of amyloid beta protein, leading to its accumulation and aggregation in the brain. Additionally, insulin resistance has been associated with increased tau phosphorylation, a key pathological feature of Alzheimer's disease, further exacerbating neurodegeneration and cognitive decline.
3. Inflammation and Oxidative Stress: Metabolic syndrome is associated with chronic low-grade inflammation and oxidative stress, which have been implicated in the pathogenesis of Alzheimer's disease. Inflammatory cytokines and oxidative damage can disrupt neuronal function, exacerbate amyloid beta and tau pathology, and contribute to neuroinflammation and neurodegeneration. Additionally, elevated inflammatory markers have been reported in individuals with Alzheimer's disease, suggesting a link between metabolic abnormalities and neuroinflammatory processes in the disorder.
4. Hormonal Dysregulation: Hormonal abnormalities, including alterations in insulin-like growth factor (IGF) signaling, have been implicated in the pathogenesis of Alzheimer's disease. Insulin resistance and hyperinsulinemia may disrupt IGF signaling pathways, impairing neuronal survival and synaptic function in the brain. Additionally, dysregulation of insulin and IGF signaling has been associated with increased amyloid beta production and tau phosphorylation, further contributing to neurodegeneration and cognitive decline in Alzheimer's disease.
5. Treatment Considerations: Addressing underlying metabolic abnormalities such as insulin resistance and metabolic syndrome may be important for optimizing treatment outcomes in individuals with Alzheimer's disease. Lifestyle modifications such as regular physical activity, weight management, and dietary changes may help improve metabolic health and reduce the risk or severity of Alzheimer's disease. Additionally, some medications used to manage metabolic syndrome, such as certain antidiabetic agents or anti-inflammatory drugs, may have adjunctive benefits in Alzheimer's disease treatment by targeting neurodegenerative pathways or modulating neuroinflammatory processes.

In summary, while Alzheimer's disease primarily affects brain function and is considered a neurodegenerative disorder, metabolic factors such as insulin resistance, hyperinsulinemia, and metabolic syndrome can potentially influence disease progression and management. Understanding the interactions between Alzheimer's disease and metabolic abnormalities is important for developing comprehensive treatment strategies that address both the neurodegenerative and metabolic aspects of the condition, ultimately improving outcomes and quality of life for individuals affected by Alzheimer's disease.

"There are no cures for Alzheimers' disease and Parkinson's Disease and current treatments are limited to symptom management.  "

" Given the link between metabolic dysfunction in obesity and neurodegeneration, dietary interventions are a logical approach 

" In a single-phase, assessor-blinded, two-period randomized crossover  trial, participants diagnosed with AD (n=26) were randomized into a  ketogenic diet (29% protein, 6% carbohydrates and 58% fat) or a low fat  diet (19% protein, 62% carbohydrates and 11% fat) for 12 weeks."  

" lthough motor and nonmotor symptoms were improved in both diet groups,  the ketogenic urinary problems, pain, fatigue, daytime sleepiness, and  cognitive impairment were lower in the ketogenic group. "

 
Multiple pieces of evidence here for seed oils in AD progression.
Oxidized LA is a primary source of the DNA damage measure used. HNE is a toxin from seed oils that induces mitochondrial dysfunction, reduced ATP, and beta-amyloid production. RLIP and glutathione are both part of HNE detoxifying system, both are impaired by high levels of HNE.
H/T @tuckergoodrich on X

*
The role of RLIP76 in oxidative stress and mitochondrial dysfunction:
Evidence based on autopsy brains from Alzheimer's disease patients

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and interaction, as well as restricted, repetitive patterns of behavior, interests, or activities. While the exact causes of autism are not fully understood, a combination of genetic, environmental, and neurobiological factors is believed to contribute to its development.

Here's how autism spectrum disorder relates to metabolic factors:

1. Neurological Manifestations: Autism primarily affects brain development and function, making it a neurodevelopmental disorder. While metabolic factors such as insulin resistance, hyperinsulinemia, and metabolic syndrome are not direct causes of autism, they may influence brain development and neurotransmitter systems implicated in the disorder. For example, insulin resistance has been associated with alterations in brain insulin signaling and synaptic function, which may impact neural circuitry involved in social cognition and communication.
2. Inflammation and Immune Dysregulation: Metabolic syndrome is associated with chronic low-grade inflammation and immune dysregulation, which have been implicated in the pathogenesis of neurodevelopmental disorders, including autism. Inflammatory cytokines and immune dysregulation can disrupt neural development and synaptic plasticity, potentially contributing to the development or exacerbation of autism symptoms. Additionally, elevated inflammatory markers have been reported in individuals with autism, suggesting a link between metabolic abnormalities and neuroinflammation in the disorder.
3. Gut-Brain Axis Dysfunction: Emerging evidence suggests a link between gastrointestinal (GI) disturbances and autism, leading to the concept of the gut-brain axis. Metabolic factors such as insulin resistance and metabolic syndrome may contribute to GI dysfunction, altering the gut microbiota composition and increasing intestinal permeability. Dysregulation of the gut-brain axis may impact neurodevelopment and behavior in individuals with autism, potentially exacerbating symptoms and impairing cognitive function.
4. Treatment Considerations: Addressing underlying metabolic abnormalities such as insulin resistance and metabolic syndrome may be important for optimizing treatment outcomes in individuals with autism. Lifestyle modifications such as regular physical activity, weight management, and dietary changes may help improve metabolic health and reduce the severity of autism symptoms. Additionally, some medications used to manage metabolic syndrome, such as certain antioxidants or anti-inflammatory agents, may have adjunctive benefits in autism treatment by targeting neuroinflammatory pathways or modulating gut-brain axis function.

In summary, while autism primarily affects brain development and function and is considered a neurodevelopmental disorder, metabolic factors such as insulin resistance, hyperinsulinemia, and metabolic syndrome can potentially influence disease progression and management. Understanding the interactions between autism spectrum disorder and metabolic abnormalities is important for developing comprehensive treatment strategies that address both the neurodevelopmental and metabolic aspects of the condition, ultimately improving outcomes and quality of life for individuals affected by autism.

 "She's lost weight, cleared her head, and feels more stable”. She also uses these ketogenic metabolic therapies with kids with ADHD and Autism to normalize their blood sugar and mood and stabilize them so they can improve in other ways as well. 

The mission of The Johnson Center for Child Health and Development is  to advance the understanding of childhood development through clinical  care, research, and education.

http://www.johnson-center.org/

Part one of this webinar is in the heading 

The mission of The Johnson Center for Child Health and Development is  to advance the understanding of childhood development through clinical  care, research, and education.

http://www.johnson-center.org/

   Behavioral disorders encompass conditions affecting behavior, emotions,  and social interactions, including ADHD, ODD, and conduct disorder.  While their causes vary, genetic, environmental, and neurobiological  factors play significant roles. Metabolic factors like insulin  resistance and metabolic syndrome, though not direct causes, may  influence brain function and neurotransmitter systems involved in these  disorders. Additionally, they are associated with inflammation,  oxidative stress, and hormonal dysregulation, which can exacerbate  symptoms. Addressing metabolic abnormalities through lifestyle changes  and medications may improve treatment outcomes for behavioral disorders,  necessitating comprehensive strategies considering both neurological  and metabolic aspects. 

  "Behavioural inflexibility is a symptom of neuropsychiatric and  neurodegenerative disorders such as Obsessive-Compulsive Disorder,  Autism Spectrum Disorder and Alzheimer's Disease, encompassing the  maintenance of a behaviour even when no longer appropriate. Recent  evidence suggests that insulin signalling has roles apart from its  regulation of peripheral metabolism and mediates behaviourally-relevant  central nervous system (CNS) functions including behavioural  flexibility. Indeed, insulin resistance is reported to generate anxious,  perseverative phenotypes in animal models, with the Type 2 diabetes  medication metformin proving to be beneficial for disorders including  Alzheimer's Disease. Structural and functional neuroimaging studies of  Type 2 diabetes patients have highlighted aberrant connectivity in  regions governing salience detection, attention, inhibition and memory "

   Food addiction (FA) is loosely defined as hedonic eating behavior  involving the consumption of highly palatable foods (ie, foods high in  salt, fat, and sugar) in quantities beyond homeostatic energy  requirements. FA shares some common symptomology with other pathological  eating disorders, such as binge eating. Current theories suggest that  FA shares both behavioral similarities and overlapping neural correlates  to other substance addictions. Although preliminary, neuroimaging  studies in response to food cues and the consumption of highly palatable  food in individuals with FA compared to healthy controls have shown  differing activation patterns and connectivity in brain reward circuits  including regions such as the striatum, amygdala, orbitofrontal cortex,  insula, and nucleus accumbens. Additional effects have been noted in the  hypothalamus, a brain area responsible for regulating eating behaviors  and peripheral satiety networks. FA is highly impacted by impulsivity  and mood. Chronic stress can negatively affect  hypothalamic–pituitary–adrenal axis functioning, thus influencing eating  behavior and increasing desirability of highly palatable foods. Future  work will require clearly defining FA as a distinct diagnosis from other  eating disorders. 

Bipolar disorder is a mood disorder characterized by manic and depressive episodes. While its precise causes are complex, metabolic factors like insulin resistance and metabolic syndrome may influence its development and severity:

Neurological Manifestations:Bipolar disorder involves disruptions in neurotransmitter systems. Metabolic factors like insulin resistance may affect neurotransmitter balance, potentially contributing to bipolar symptoms.

Inflammation and Oxidative Stress:Metabolic syndrome is linked to inflammation and oxidative stress, implicated in bipolar disorder. These factors can disrupt neuronal function and exacerbate mood dysregulation.

Hormonal Dysregulation: Bipolar disorder involves hormonal abnormalities, and metabolic factors may exacerbate this dysregulation, contributing to mood instability.

Addressing metabolic abnormalities through lifestyle changes and medications may improve treatment outcomes for bipolar disorder, considering its interactions with metabolic factors. Understanding these connections is crucial for comprehensive treatment strategies and better outcomes.

Bipolar disorder is a mood disorder characterized by manic and depressive episodes. While its precise causes are complex, metabolic factors like insulin resistance and metabolic syndrome may influence its development and severity:

Neurological Manifestations:Bipolar disorder involves disruptions in neurotransmitter systems. Metabolic factors like insulin resistance may affect neurotransmitter balance, potentially contributing to bipolar symptoms.

Inflammation and Oxidative Stress:Metabolic syndrome is linked to inflammation and oxidative stress, implicated in bipolar disorder. These factors can disrupt neuronal function and exacerbate mood dysregulation.

Hormonal Dysregulation: Bipolar disorder involves hormonal abnormalities, and metabolic factors may exacerbate this dysregulation, contributing to mood instability.

Addressing metabolic abnormalities through lifestyle changes and medications may improve treatment outcomes for bipolar disorder, considering its interactions with metabolic factors. Understanding these connections is crucial for comprehensive treatment strategies and better outcomes.

Cognitive decline refers to a gradual worsening of cognitive abilities, often associated with aging or neurodegenerative disorders like Alzheimer's disease. Metabolic factors, including insulin resistance, hyperinsulinemia, and metabolic syndrome, play a role in cognitive decline:

Neurological Manifestations: Metabolic factors are implicated in the pathogenesis of cognitive decline, affecting brain function and contributing to neurodegeneration, particularly in Alzheimer's disease and vascular dementia.

Vascular Dysfunction: Metabolic syndrome increases the risk of cerebrovascular disease, damaging brain blood vessels and leading to reduced blood flow and cognitive impairment.

Inflammation and Oxidative Stress: Metabolic syndrome is linked to inflammation and oxidative stress, which contribute to neuroinflammation, synaptic dysfunction, and neurodegeneration in cognitive decline.

Treatment Considerations: Addressing metabolic abnormalities like insulin resistance and metabolic syndrome may improve treatment outcomes for cognitive decline. Lifestyle changes and medications targeting metabolic syndrome can help manage cognitive decline by addressing vascular risk factors and reducing inflammation.

Understanding the relationship between metabolic factors and cognitive decline is crucial for developing effective treatment strategies that address both cognitive and metabolic aspects of the condition, ultimately improving outcomes and quality of life for affected individuals.

"The peri-menopausal transition is a  tipping point for female brain aging. From the metabolic perspective,  the process begins with decline in glucose metabolism and increase in  insulin resistance, followed by a compensatory mechanism to use fatty  acids and ketone bodies as an auxiliary fuel source’ Wang et al

TCR  reduces brain insulin resistance and inflammation. If carbohydrate  intake is sufficiently reduced ketone bodies can provide an alternative  fuel source for the brain, further supporting cognitive function. 

1. Cunnane  SC, Trushina E, Morland C, et al. Brain energy rescue: an emerging  therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020;19(9):609-633. doi:10.1038/s41573-020-0072-x 
2. Yang  H, Shan W, Zhu F, Wu J, Wang Q. Ketone Bodies in Neurological Diseases:  Focus on Neuroprotection and Underlying Mechanisms. Front Neurol. 2019;10. doi:10.3389/fneur.2019.00585 
3. Mishra, A. et al. (2021) ‘A Tale of Two Systems: Lessons Learned from Female Mid-Life  Aging with Implications for Alzheimer’s Prevention & Treatment’, Ageing Research Reviews, p. 101542. doi:10.1016/j.arr.2021.101542.
4. Phillips MCL, Deprez LM, Mortimer GMN, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimer’s Research & Therapy. 2021;13(1):51. doi:10.1186/s13195-021-00783-x
5. Taylor  MK, Sullivan DK, Mahnken JD, Burns JM, Swerdlow RH. Feasibility and  efficacy data from a ketogenic diet intervention in Alzheimer’s disease.  Alzheimers Dement (N Y). 2017;4:28-36. doi:10.1016/j.trci.2017.11.002 

 82-Year-Old woman reverse cognitive decline with keto. 

She has seen amazing benefits to her cognitive function once starting a keto diet. Her brain function has improved tremendously using diet alone ! This is just emerging in the scientific literature and was previously thought to be impossible using diet alone.

 Ketogenic protocols are unequal in regard to ketosis. KD and IF require  constant adherence to establish ketosis as opposed to MCT, which can  trigger ketosis in a matter of minutes [41].  Future research should determine the ideal feasible method and  sub-method (e.g., time-restricted IF vs. alternate-day IF), or  minimum-effective-dose of MCT and composition (i.e., C8 vs. C10) that  can produce cognitive advantages. Novel methods, such as  MCT-supplemented IF or KD-combined IF [39],  are worth examining. Moreover, the identification of the minimum  ketosis threshold that can produce favorable cognitive outcomes,  regardless of method, is essential for clinical relevance. We wish to  emphasize that molecular and neurophysiological explanations are highly  valued at this point with respect to their research potential, and  acknowledge that mechanistic research may have promise in bolstering the  evidence within this context and is needed to advance ketogenic use to  manage cognitive decrements. 

Dementia is a broad term used to describe a decline in cognitive function severe enough to interfere with daily life. It is characterized by memory loss, impaired judgment, difficulty communicating, and other cognitive deficits. Alzheimer's disease is the most common cause of dementia, accounting for approximately 60-70% of cases, followed by vascular dementia, Lewy body dementia, and other less common types. 

Neurological Manifestations: Dementia primarily affects brain function and is characterized by the progressive loss of neurons and synaptic connections. While the exact mechanisms underlying dementia vary depending on the specific type, metabolic factors have been implicated in the pathogenesis of certain types of dementia, including Alzheimer's disease and vascular dementia.  Insulin resistance, for example, may impair neuronal insulin signalling and contribute to neurodegeneration and cognitive decline. 

Vascular Dysfunction: Metabolic factors are associated with vascular dysfunction and an increased risk of cerebrovascular disease, including stroke and small vessel disease. Vascular risk factors can damage blood vessels in the brain, leading to reduced cerebral blood flow, hypoperfusion, and ischemia, which may contribute to the development or exacerbation of vascular dementia. Additionally, metabolic abnormalities associated with insulin resistance and hyperinsulinemia may exacerbate vascular dysfunction and increase the risk of cerebrovascular events in individuals with dementia.

Inflammation and Oxidative Stress: Metabolic factors are  associated with chronic low-grade inflammation and oxidative stress, which have been implicated in the pathogenesis of dementia. Inflammatory cytokines and oxidative damage can contribute to neuroinflammation, synaptic dysfunction, and neurodegeneration in dementia. Additionally, inflammatory markers may be elevated in individuals with dementia, suggesting a link between metabolic abnormalities and neuroinflammatory processes in the disorder.

Developing  comprehensive treatment strategies that address both the cognitive and metabolic aspects of the condition, ultimately improving outcomes and quality of life for individuals affected by dementia.

Management of cardiometabolic health may be a key  component of dementia prevention. Yet, with metabolic changes owing to  both aging and potential underlying chronic diseases, including  dementia, studies in older persons have been discordant, and there is no  clear consensus on the strategy to use for their management in late  adulthood for the purpose of delaying or preventing dementia onset. Most  previous studies have examined risk factors individually and did not  formally model trajectories over a long time prior to dementia. By  modeling concurrently the trajectories of main cardiometabolic risk  factors in prodromal dementia in a large prospective cohort, we provide  evidence that BMI declines several years before dementia diagnosis and  might indicate preclinical disease, whereas BP, specifically DBP, is  consistently lower among future dementia cases, which may reflect both  underlying disease and a causal association between low BP and dementia.  Finally, elevated glucose levels over the course of older adulthood  were higher among those who eventually developed dementia and may thus  represent a risk factor for dementia.

Whether  confirmed and extended to other populations, these findings emphasizing  blood glucose control, low BP, and weight loss as key components of  cardiovascular health management for primary and secondary prevention of  dementia in older persons may have important implications for  preventive care practice in geriatric populations.

Glioblastoma is an aggressive type of brain cancer that originates in the glial cells, which are supportive cells in the brain. It is the most common and deadliest form of primary brain tumor in adults. Glioblastomas are highly malignant and infiltrative, making complete surgical removal challenging and leading to a high rate of recurrence.

Here's how glioblastoma relates to metabolic factors:

Tumor Metabolism: Glioblastoma cells exhibit altered metabolism compared to normal brain cells, a phenomenon known as the Warburg effect. This metabolic shift involves increased glucose uptake and glycolysis, even in the presence of oxygen (aerobic glycolysis), leading to the generation of energy and metabolic intermediates necessary for rapid tumor growth and proliferation. Insulin resistance and hyperinsulinemia may influence tumor metabolism by providing additional glucose and growth-promoting signals to glioblastoma cells, potentially exacerbating tumor progression.

Inflammation and Immune Dysregulation: Metabolic syndrome is associated with chronic low-grade inflammation and immune dysregulation, which may contribute to tumor growth and progression in glioblastoma. Inflammatory mediators released from adipose tissue in metabolic syndrome can create a pro-inflammatory microenvironment that promotes tumor cell proliferation, angiogenesis (formation of new blood vessels), and metastasis. Additionally, immune dysfunction associated with metabolic syndrome may impair the anti-tumor immune response, allowing glioblastoma cells to evade immune surveillance and promote tumor progression.

Treatment Implications: While surgical resection, radiation therapy, and chemotherapy are standard treatments for glioblastoma, addressing underlying metabolic abnormalities such as insulin resistance and metabolic syndrome may be important for optimizing treatment outcomes. Some medications used to manage metabolic syndrome, such as certain antidiabetic agents or anti-inflammatory drugs, may have adjunctive benefits in glioblastoma treatment by targeting metabolic pathways or modulating the tumor microenvironment. Additionally, lifestyle modifications such as regular physical activity, weight management, and dietary changes may help improve metabolic health and potentially enhance the effectiveness of conventional glioblastoma therapies.

1. Winter  SF, Loebel F, Dietrich J. Role of ketogenic metabolic therapy in  malignant glioma: A systematic review. Crit Rev Oncol Hematol.  2017;112:41-58. doi:10.1016/j.critrevonc.2017.02.016 ABSTRACT
2. Amaral, L. et al. (2023) ‘The ketogenic diet plus standard of care for adults with  recently diagnosed glioblastoma: Results from a phase 1 trial.’, Journal of Clinical Oncology, 41(16_suppl), pp. 2076–2076. Available at: https://doi.org/10.1200/JCO.2023.41.16_suppl.2076. ABSTRACT
3. Voss  M, Wenger KJ, von Mettenheim N, et al. Short-term fasting in glioma  patients: analysis of diet diaries and metabolic parameters of the ERGO2  trial. Eur J Nutr. Published online September 6, 2021. doi:10.1007/s00394-021-02666-1
4. Smith,  K.A., Hendricks, B.K., DiDomenico, J.D., Conway, B.N., Smith, T.L.,  Azadi, A., Fonkem, E., n.d. Ketogenic Metabolic Therapy for Glioma. Cureus 14, e26457. doi.org/10.7759/cureus.26457
5. Panhans  CM, Gresham G, Amaral JL, Hu J. Exploring the Feasibility and Effects  of a Ketogenic Diet in Patients With CNS Malignancies: A Retrospective  Case Series. Front Neurosci. 2020;14. doi:10.3389/fnins.2020.00390
6. Woodhouse  C, Ward T, Gaskill-Shipley M, Chaudhary R. Feasibility of a modified  Atkins diet in glioma patients during radiation and its effect on  radiation sensitization. Current Oncology. 2019;26(4). doi:10.3747/co.26.4889
7. Santos  J G, Faria G, Da Cruz Souza Da Cruz W, Fontes C A, Schönthal A H,  Quirico-Santos T, da Fonseca C O. Adjuvant effect of low-carbohydrate  diet on outcomes of patients with recurrent glioblastoma under  intranasal perillyl alcohol therapy. 11-Nov-2020;11:389. doi:10.25259/SNI_445_2020
8. Schwartz  KA, Noel M, Nikolai M, Chang HT. Investigating the Ketogenic Diet As  Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons  Learned. Front Nutr. 2018;5. doi:10.3389/fnut.2018.00011
9. Elsakka  AMA, Bary MA, Abdelzaher E, et al. Management of Glioblastoma  Multiforme in a Patient Treated With Ketogenic Metabolic Therapy and  Modified Standard of Care: A 24-Month Follow-Up. Front Nutr. 2018;5.  doi:10.3389/fnut.2018.00020
10. Woolf  EC, Syed N, Scheck AC. Tumor Metabolism, the Ketogenic Diet and  β-Hydroxybutyrate: Novel Approaches to Adjuvant Brain Tumor Therapy.  Front Mol Neurosci. 2016;9:122. doi:10.3389/fnmol.2016.00122
11. Varshneya  K, Carico C, Ortega A, Patil CG. The Efficacy of Ketogenic Diet and  Associated Hypoglycemia as an Adjuvant Therapy for High-Grade Gliomas: A  Review of the Literature. Cureus. 2015;7(2). doi:10.7759/cureus.251 
12. Abdelwahab  MG, Fenton KE, Preul MC, et al. The Ketogenic Diet Is an Effective  Adjuvant to Radiation Therapy for the Treatment of Malignant Glioma.  PLOS ONE. 2012;7(5):e36197. doi:10.1371/journal.pone.0036197
13. Rieger  J, Bähr O, Maurer GD, et al. ERGO: A pilot study of ketogenic diet in  recurrent glioblastoma.  INTERNATIONAL JOURNAL OF ONCOLOGY 44:   1843-1852, 201. doi: 10.3892/ijo.2014.2382 PDF
14. van  der Louw EJTM, Olieman JF, van den Bemt PMLA, et al. Ketogenic diet  treatment as adjuvant to standard treatment of glioblastoma multiforme: a  feasibility and safety study. Ther Adv Med Oncol.  2019;11:1758835919853958. doi:10.1177/1758835919853958  
15. Seyfried  TN, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Is the restricted  ketogenic diet a viable alternative to the standard of care for  managing malignant brain cancer? 2012;100(3):310-326. doi:10.1016/j.eplepsyres.2011.06.017  PDF
16. Meidenbaueret  al. The glucose ketone index calculator: a simple tool to monitor  therapeutic efficacy for metabolic management of brain cancer. Nutrition  & Metabolism (2015) 12:12 doi:10.1186/s12986-015-0009-2 

Case Reports

1. Seyfried  TN, Shivane AG, Kalamian M, Maroon JC, Mukherjee P, Zuccoli G.  Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the  Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up  Case Report. Front Nutr. 2021;8. doi:10.3389/fnut.2021.682243
2. Tóth  C, Dabóczi A, Chanrai M, Schimmer M, Horváth K, Clemens Z. 4-Year Long  Progression-Free and Symptom-Free Survival of a Patient with Recurrent  Glioblastoma Multiforme: A Case Report of the Paleolithic Ketogenic Diet  (PKD) Used as a Stand-Alone Treatment After Failed Standard  Oncotherapy. Published online November 9, 2020. doi:10.20944/preprints201912.0264.v2   (Alternative version with additional details)
3. Tóth  C, Dabóczi A, Chanrai M, Schimmer M, Clemens Z. 38-Month Long  Progression-Free and Symptom-Free Survival of a Patient with Recurrent  Glioblastoma Multiforme: A Case Report of the Paleolithic Ketogenic Diet  (PKD) Used as a Stand-Alone Treatment after Failed Standard  Oncotherapy.; 2019. doi:10.13140/RG.2.2.29464.55047
4. Schwartz  K, Chang HT, Nikolai M, et al. Treatment of glioma patients with  ketogenic diets: report of two cases treated with an IRB-approved  energy-restricted ketogenic diet protocol and review of the literature.  Cancer & Metabolism. 2015;3(1):3. doi:10.1186/s40170-015-0129-1 
5. Zuccoli  G, Marcello N, Pisanello A, et al. Metabolic management of glioblastoma  multiforme using standard therapy together with a restricted ketogenic  diet: Case Report. Nutr Metab (Lond). 2010;7:33. doi:10.1186/1743-7075-7-33

 Logan Sneed had a glioblastoma removed and turned to a ketogenic diet to keep it from growing back. Even though doctors said he only had 1-10 years to live, he's seen the exact opposite. The tumor hasn't grown back at all and he is thriving more than ever. He's building muscle and becoming a huge influencer in the space ! 

" I am a Brain Cancer survivor that was diagnosed with a stage 4  Glioblastoma Brain Tumor March 26th, 2016. I have been through brain  surgery, radiation, and chemotherapy. I have grown in numerous ways  mentally, physically, and emotionally. The day my life changed was the  day that I began the Ketogenic diet. Doctors told me nothing would help  this. Might as well give up. "

https://www.logansneed.com/

 Huntington's disease (HD) is a progressive neurodegenerative disorder  caused by a genetic mutation in the huntingtin gene. While it primarily  affects the central nervous system, metabolic factors like insulin  resistance and metabolic syndrome can exacerbate disease progression  through various pathways. Metabolic abnormalities such as alterations in  glucose metabolism and inflammation have been observed in HD patients,  contributing to neurodegeneration. Addressing underlying metabolic  abnormalities through lifestyle changes and medications may optimize  treatment outcomes and improve quality of life for individuals with HD.  Understanding the interplay between HD and metabolic factors is crucial  for developing comprehensive treatment strategies to manage the  condition effectively. 

  Huntington's disease (HD) is a progressive, fatal neurodegenerative  disorder with limited treatment options. Substantial evidence implicates  mitochondria dysfunction in brain and skeletal muscle in the  pathogenesis of HD. Metabolic strategies, such as fasting and ketogenic  diets, theoretically enhance brain and muscle metabolism and  mitochondria function, which may improve the clinical symptoms of HD. We  report the case of a 41-year-old man with progressive, deteriorating HD  who pursued a time-restricted ketogenic diet (TRKD) for 48 weeks.  Improvements were measured in his motor symptoms (52% improvement from  baseline), activities of daily living (28% improvement), composite  Unified HD Rating Scale (cUHDRS) score (20% improvement), HD-related  behavior problems (apathy, disorientation, anger, and irritability  improved by 50-100%), and mood-related quality of life (25%  improvement). Cognition did not improve. Weight remained stable and  there were no significant adverse effects. This case study is unique in  that a patient with progressive, deteriorating HD was managed with a  TRKD, with subsequent improvements in his motor symptoms, activities of  daily living, cUHDRS score, most major HD-related behavior problems, and  quality of life. Our patient remains dedicated to his TRKD, which  continues to provide benefit for him and his family.      . 

  Insomnia, a sleep disorder characterized by difficulty falling or  staying asleep, is influenced by metabolic factors such as insulin  resistance, hyperinsulinemia, and metabolic syndrome. These factors  disrupt circadian rhythms, hormone balance, and may contribute to  sleep-disordered breathing. Psychological factors like stress and  depression, often linked to metabolic abnormalities, can also exacerbate  insomnia. Treatment involves addressing metabolic issues through  lifestyle changes and cognitive-behavioral therapy for insomnia (CBT-I)  alongside conventional approaches. Understanding the interplay between  metabolic factors and insomnia is crucial for effective treatment and  improved sleep outcomes. 

 The prevalence of insomnia (symptoms) is 39% (95% confidence interval,  34-44) in the T2D population and may be associated with deleterious  glycemic control.      

1. Gangitano, E. et al. (2023) ‘Comparison of the Effects of a Ketogenic Diet and an Isocaloric  Balanced Diet administered to Obese patients on Quality of Life and  Sleep: a Randomized Clinical Trial’, in Endocrine Abstracts. ECE 2023, Bioscientifica. Available at: https://doi.org/10.1530/endoabs.90.P626.
2. Siegmann  MJ, Athinarayanan SJ, Hallberg SJ, et al. Improvement in  patient-reported sleep in type 2 diabetes and prediabetes participants  receiving a continuous care intervention with nutritional ketosis. Sleep  Med. 2019;55:92-99. doi:10.1016/j.sleep.2018.12.014
3. Barrea, L. et al. (2023) ‘Can the ketogenic diet improve our dreams? Effect of very low-calorie ketogenic diet (VLCKD) on sleep quality’, Journal of Translational Medicine, 21(1), p. 479. Available at: https://doi.org/10.1186/s12967-023-04280-7.
4. Merlino, G. et al. (2023) ‘Sleep of migraine patients is ameliorated by ketogenic diet, independently of pain control’, Sleep Medicine [Preprint]. Available at: https://doi.org/10.1016/j.sleep.2023.05.006.
5. Castro  AI, Gomez-Arbelaez D, Crujeiras AB, et al. Effect of A Very Low-Calorie  Ketogenic Diet on Food and Alcohol Cravings, Physical and Sexual  Activity, Sleep Disturbances, and Quality of Life in Obese Patients.  Nutrients. 2018;10(10). doi:10.3390/nu10101348
6. Osman, A. et al. (2023) ‘Ketogenic diet acutely improves gas exchange and sleep apnoea  in obesity hypoventilation syndrome: A non-randomized crossover study’, Respirology (Carlton, Vic.) [Preprint]. Available at: https://doi.org/10.1111/resp.14526.
7. Robberechts, R. et al. (no date) ‘Exogenous Ketosis Improves Sleep Efficiency and Counteracts the Decline in REM Sleep Following Strenuous Exercise’, Medicine & Science in Sports & Exercise, p. 10.1249/MSS.0000000000003231. Available at: https://doi.org/10.1249/MSS.0000000000003231.
8. O’Hearn LA. The therapeutic properties of ketogenic diets, slow-wave sleep, and circadian synchrony. Current Opinion in Endocrinology, Diabetes and Obesity. Published online July 23, 2021. doi:10.1097/MED.000000000000066
9. Tokuchi  Y, Nakamura Y, Munekata Y, Tokuchi F. Low carbohydrate diet-based  intervention for obstructive sleep apnea and primary hypothyroidism in  an obese Japanese man. Asia Pac Fam Med. 2016;15. doi:10.1186/s12930-016-0029-8
10. Kalam  F, Gabel K, Cienfuegos S, Ezpeleta M, Wiseman E, Varady KA. Alternate  Day Fasting Combined with a Low Carbohydrate Diet: Effect on Sleep  Quality, Duration, Insomnia Severity and Risk of Obstructive Sleep Apnea  in Adults with Obesity. Nutrients. 2021;13(1):211. doi:10.3390/nu13010211
11. Benton D, Bloxham A, Gaylor C, Young H. Influence of Carbohydrate on the Stages of Sleep – A Meta-Analysis. Current Developments in Nutrition. 2021;5(Supplement_2):896-896. doi:10.1093/cdn/nzab049_009
12. McStay M, Gabel K, Cienfuegos S, Ezpeleta M, Lin S, Varady KA. Intermittent Fasting and Sleep: A Review of Human Trials. Nutrients. 2021;13(10):3489. doi:10.3390/nu13103489 
13. Tavakoli  A, Mirzababaei A, Mirzaei K. Association between low carbohydrate diet  (LCD) and sleep quality by mediating role of inflammatory factors in  women with overweight and obesity: A cross-sectional study. Food Science & Nutrition. n/a(n/a). doi:10.1002/fsn3.2584
14. Barrea L, Pugliese G, Frias-Toral E, et al. Is there a relationship between the ketogenic diet and sleep disorders? International Journal of Food Sciences and Nutrition. 2021;0(0):1-11. doi:10.1080/09637486.2021.1993154 ABSTRACT
15. Ünalp  A, Baysal BT, Sarıtaş S, et al. Evaluation of the effects of ketogenic  diet therapy on sleep quality in children with drug-resistant epilepsy  and their mothers. Epilepsy Behav. 2021;124:108327. doi:10.1016/j.yebeh.2021.108327 ABSTRACT
16. Makowski, M.S. et al. (2021) ‘Performance Nutrition for Physician Trainees Working Overnight Shifts: A Randomized Controlled Trial’, Academic Medicine [Preprint]. doi:10.1097/ACM.0000000000004509

Metabolic factors like insulin resistance, hyperinsulinemia, and metabolic syndrome can influence migraine susceptibility, severity, and management:

Neurological Manifestations:Metabolic abnormalities may affect neuronal excitability and neurotransmitter signalling pathways involved in migraine pathogenesis.

Inflammatory and Vascular Mechanisms:Metabolic syndrome is associated with inflammation and endothelial dysfunction, exacerbating vascular abnormalities and neuroinflammation linked to migraine attacks.

Hormonal Influence: Insulin resistance and metabolic syndrome can impact oestrogen metabolism and hormone signalling, potentially affecting migraine susceptibility, especially in women.

Addressing metabolic abnormalities through lifestyle changes and medications may optimize migraine management, reducing attack frequency and severity.

Understanding the interplay between metabolic factors and migraine is crucial for developing tailored treatment approaches, improving outcomes, and enhancing quality of life for migraine sufferers.

Helping those suffering from migraines with nutrition 

 "The problem can be resolved by avoiding a high carbohydrate diet and by  adding a sufficiently increased amount of salt to consumed water to  increase blood volume, to provide enough sodium for the brain under any  circumstance, so it can continuously support those important action  potentials. "

  Dr. Palmer’s clinical practice has focused on helping people suffering from treatment-resistant mental illnesses, including mood disorders, psychotic disorders, and personality disorders. Most recently, his research interests have turned to the areas of metabolism, metabolic disorders, and their connection to mental disorders. He is focused on combining and understanding epidemiological data, basic science research, and clinical studies in order to better understand what role metabolism plays in mental illness.  Dr. Palmer has been pioneering the use of the ketogenic diet and its applications in psychiatry. He has published case studies, pilot clinical trials, and is actively conducting research in this area. He is also working with researchers from around the world to further explore this treatment in clinical populations as well as pursuing more basic science research.

   Changes in eating habits can have a beneficial effect on the condition  of our body, but also on the development and course of many diseases.  This review provides evidence that the ketogenic diet may provide  therapeutic benefits in patients with neurological problems associated  with increased oxidative stress and neuro-inflammation or disruption in  brain energy metabolism. The review of the scientific literature shows  that KD could affect not only the progression of neurological disorders  but also the course and outcome of their treatment. The effectiveness of  KD has been proven in epilepsy and in other neurological diseases, such  as depression, migraine, or neurodegenerative diseases e.g., AD and PD.  KD should be also considered as an adjuvant therapeutic option in other  neurological diseases. 

Schizophrenia is a complex mental disorder characterized by disruptions in thought processes, perceptions, emotions, and behaviour, with genetic, environmental, and neurobiological factors believed to be involved. Metabolic factors, such as insulin resistance and metabolic syndrome, relate to schizophrenia in several ways:

Neurological Manifestations: Schizophrenia affects brain function and neurotransmitter systems like dopamine and glutamate. Metabolic factors can influence neurotransmitter balance and synaptic transmission, potentially contributing to psychotic symptoms.

Inflammation and Oxidative Stress: Metabolic syndrome is linked to chronic inflammation and oxidative stress, implicated in schizophrenia's pathogenesis. Inflammatory cytokines and oxidative damage may disrupt neuronal function, contributing to neuroinflammation and neurodegeneration.

Hormonal Dysregulation: Hormonal abnormalities, including alterations in stress response systems, are observed in schizophrenia. Metabolic factors may exacerbate hormonal dysregulation, potentially worsening symptoms and cognitive impairment.

Treatment Considerations: Addressing metabolic abnormalities is crucial for optimizing schizophrenia treatment outcomes. Lifestyle changes and medications targeting metabolic syndrome may help improve metabolic health and reduce psychotic symptoms, although medication side effects should be monitored.

Understanding the interaction between schizophrenia and metabolic factors is essential for developing comprehensive treatment strategies, ultimately improving outcomes for affected individuals.

 Purpose of review:                      The aim of this article is to review recent findings on the  efficacy of ketogenic diet in preclinical models and in patients with  schizophrenia. This review will also highlight emerging evidence for  compromised glucose and energy metabolism in schizophrenia, which  provides a strong rationale and a potential mechanism of action for  ketogenic diet.     

Recent findings:                      Recent transcriptomic, proteomic and metabolomic evidence from  postmortem prefrontal cortical samples and in-vivo NMR spectroscopy  results support the hypothesis that there is a bioenergetics dysfunction  characterized by abnormal glucose handling and mitochondrial  dysfunctions resulting in impaired synaptic communication in the brain  of people with schizophrenia. Ketogenic diet, which provides alternative  fuel to glucose for bioenergetic processes in the brain, normalizes  schizophrenia-like behaviours in translationally relevant  pharmacological and genetic mouse models. Furthermore, recent case  studies demonstrate that ketogenic diet produces improvement in  psychiatric symptoms as well as metabolic dysfunctions and body  composition in patients with schizophrenia.     

 Summary:                      These results support that 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 inherent to the  disease and resulted by antipsychotic treatment.