Chapter 3. Brain Health: Consistently Associated With Metabolic Dysfunction.

We welcome your use of this resource but please cite:

PSGRNZ (2026) Reclaiming Health: Reversal, Remission & Rewiring. Understanding & Addressing the Primary Drivers of New Zealand’s Metabolic & Mental Health Crisis. Bruning, J.R., Physicians & Scientists for Global Responsibility New Zealand. ISBN 978-1-0670678-2-3

An extraordinary amount of scientific research reveals how conditions previously considered exclusively brain-related, commence as metabolic dysfunction. Metabolic dysfunction is inherent to the pathophysiology of mental illness.[1] [2] [3] [4] [5] [6] [7] [8]

The data arises from multiple levels of investigation, including cellular and mechanistic studies, case reports, cohort studies, and population-level (epidemiological) research.

High refined carbohydrate and/or ultraprocessed food diets are conventionally low in bioavailable nutrients, and the relative deficiency in these diets increases risk for cascading and overlapping metabolic, mental and immune system illnesses. Metabolic syndrome is a common correlate when these pressures converge, driving inflammation, and creating feedback loops that can overwhelm the body’s capacity to repair.

The central nervous system and the digestive tract are inter-dependent. A healthy microbiome is essential to optimise bi-directional neuroendocrine signalling, for sensory-motor reflexes, immune activation, gut brain cross-talk and hormonal signalling. [9] [10]

Biomarker studies have tracked relationships between diet quality, metabolic health, and risks for mental disorders including anxiety, depression, addiction and suicidality.[11] Risk factors can overlap, amplifying conditions or increasing the severity of symptoms and diseases.

Inadequate intake, systemic diseases, medical therapies, and genetic conditions can lead to deficiencies of specific nutrients, affecting both the central and peripheral nervous systems.[12]

Figure 4. Mayer EA, Nance K, Chen S. (2022). The Gut–Brain Axis. Annual Review of Medicine.

When these factors overlap and the stressors accrue over years and decades, brain function can be severely impacted. In a book on mental health and mitochondrial function, Harvard-based Chris Palmer has argued that:

mental symptoms are like the canary in the coal mine: they are sometimes the first indication of metabolic and mitochondrial failure.[13]

People with psychiatric diagnoses are rarely diagnosed with a single condition.

Multimorbidity is common in those with mental illness, and further deterioration of mental health, reduced quality of life, and premature mortality have been reported in those with multiple disorders.[14]

Symptoms of mental illnesses can overlap. Therefore, one person may be diagnosed for multiple brain disorders and receive prescriptions for multiple psychiatric medications.[15]

For example, while patients with schizophrenia die 20 years earlier than healthy populations, the mortality risk is predominantly associated with cardiovascular risks. As this paper will discuss below, treatment for individuals with major depressive disorder, bipolar disorder, and schizoaffective disorder can include metabolic and low-carbohydrate approaches.[16] [17] [18] [19] [20] [21]

The under-25 age group may be most severely affected. There is a:

‘greater burden of physical multimorbidity in people with severe mental illness compared with those without is higher for younger cohorts, reflecting a need for earlier intervention.[22]

Once a person is diagnosed with metabolic and psychiatric conditions, they will be prescribed a range of medical drugs for these conditions. The drugs may produce a range of side effects, which can necessitate additive prescriptions for other drugs. The drugs can also deplete the gut microbiome, which can create further disorder. Multiple drug regimens, or polypharmacy has substantially increased in recent decades.

In the US, for example, the prevalence of polypharmacy among adults aged 65 and older increased from 13% in 1998 to 43% in 2014,2425 with the most recent estimates from 2017-2018 at 45%.This increase was driven in particular by the growing use of cardioprotective and antidepressant drug treatments, and the highest prevalence of polypharmacy is seen among populations with heart disease.[23]

The gut-brain connection.

An impaired gut microbiome can produce cascading, interrelated metabolic and mental health outcomes.

Diet is a foundational factor in shaping the gut microbiota, influencing its composition, diversity, and functionality, which in turn affects a wide range of health outcomes through complex microbial-host interactions.[24]

Diet plays a central role in sustaining a healthy gut-brain-axis, the complex neuro-immuno-endocrine signalling pathway[25] that is fundamental for sustaining good mental health.[26]

Communication within this system is nonlinear, is bidirectional with multiple feedback loops, and likely involves interactions between different channels.[27]

Human bodies are complex and there are myriad ways poor diets and insufficient vitamin and mineral levels can affect brain function and mental health over time. Brain fog is associated with elevated glucose levels and gluten sensitivity.[28] Refined food diets and chemical exposures, genetic, and epigenetic stressors can increase risk for digestive disorders and impair nutrient processing and the synthesis of hormones, impair sleep patterns, cortisol regulation and promote fatigue and brain fog.

Key factors which contribute to inflammation and health decline include the following:

Insulin resistance (IR) which plays a crucial role in the development and progression of metabolism-related diseases including diabetes, hypertension, tumours, and non-alcoholic fatty liver disease.[29]
Frequent consumption of ultraprocessed foods that increase risk for insulin resistance.[30]
Gluten-heavy diets that can impair digestive tract function and result in a cascade of events which include symptoms which fit the criteria for many mental illnesses.[31] [32] [33]
Increasing burdens of synthetic chemicals that have toxic effects, which can be at higher levels in refined and ultraprocessed foods, including synthetically refined ingredients and additives, microplastics from packaging, and increasing use of pesticides in staple food crops.[34]
The inflammatory potential of chemically refined vegetable oils.[35] [36]
Suppression of ketone bodies which have anti-oxidative, anti-inflammatory, mitochondrial, neurological and cardio-protective features.[37] [38] [39]
Lower than optimum (insufficient) intakes of micronutrients which are physiologically indispensable for metabolic and/or immunological and/or physiological health, including mental health.

Mitochondria play a central role in metabolic function, and the systematic impact of metabolic stress can be observed at a microscopic level in the mitochondria.[40] Psychiatrists diagnose mental illness based on overactive, underactive or absent brain functions. However, the dysregulation of the mitochondria can drive these symptoms. Five distinct cellular processes are involved, whereby cells can either become overactive, underactive, abnormal, defunct or dead, or unable to function correctly and in disrepair. [41]

A spectrum of related processes such as chronic inflammation, altered gut integrity and dysbiosis, and dysregulation of the HPA axis (the body’s stress response system) can negatively affect metabolic homeostasis and mitochondrial function. They are all associated with risk for a psychiatric diagnosis. This includes impaired sleep and cortisol production.[42] [43] [44]

There is strong evidence that many if not most of the classic symptoms of depression[45] can be associated with a poor diet, metabolic syndrome and poor digestive tract functioning.[46] [47] [48] [49]

PSGRNZ do not downplay or underestimate the role of chronic stress, trauma and grief in driving temporary (ranging from weeks to years) poor mental health but instead draw attention to factors which may lead to a shortening, a reduction or reversal in the symptoms experienced by the person who is suffering. Evaluations of the role of higher-dose nutrients in times of trauma and stress, to identify whether people had improved outcomes, were more resilient and recovered more swiftly have been undertaken.

Following natural disasters of earthquake (Christchurch, Aotearoa/New Zealand, 2010–11) and flood (Calgary, Canada, 2013), controlled research showed statistically and clinically significant reductions in psychological distress for survivors who consumed minerals and vitamins (micronutrients) in the following months.[50]

Accumulation of toxins in the brain may also alter brain function. For example, people with autism spectrum disorder appear to have difficulty regulating mitochondria-related processes of apoptosis, which leads impaired autophagy. This can increase risk for an accumulation of toxic products in the brains of individuals with autism.[51]

Poor sleep can be associated with inadequate nutrition and high intakes of ultraprocessed food is associated with poor sleep-related outcomes.[52] [53] Sleep cycles play a key role in eliminating neurotoxic metabolites, waste products, that without clearing could contribute to dementia and poor brain health. Poor sleep cycles may lead to a reduction in the brain’s capacity to clear toxic waste, creating negative feedback loops that further impair mental health.[54] [55]

New Zealand government officials do not undertake this work that deepens public information and general practitioner knowledge on the relationship between nutrition and brain health. [56] [57] [58] Without an official effort review the scientific literature and update agency staff, nutrients critical for health can be poorly and incorrectly categorised due to out-dated legacy perspectives.

Introducing Nutritional Psychiatry.

Nutritional psychiatry is a growing sub-specialty of psychiatry. Mechanistic, observational and interventional data increasingly demonstrates that diet is a modifiable risk factor for mental illness.[59] Studies researching nutrition and psychiatry have exploded in the past 15 years.[60]

‘nutritional psychiatry encompasses the study of dietary and nutrient-based interventions for the prevention or treatment of mental disorders. The concept of nutraceuticals refers to non-toxic dietary extracts or supplements with scientifically validated benefits for promoting health and aiding in disease management.’[61]

PSGRNZ emphasise that psychotherapy, connection and support play an integral part of healing and management of brain and mind-related challenges. Human connection is central to the healthy functioning of all of us. The greater outcome from psychotherapy, friendship and community engagement includes deeper self-understanding, enhanced self-agency, and greater social engagement. [62]

Nutritional psychiatry which integrates nutritional and dietary changes, complements traditional psychotherapy, may play a key role for people who are treatment resistant and may assist with recovery. Dietary modifications may be an underutilised tool for people diagnosed with a psychiatric condition.[63]

An established and increasing scientific literature demonstrates that metabolic disruption and subclinical nutrient deficiency is a precursor and a companion to a wide range of metabolic and mental illness.[64] [65] [66] Deficiency across a spectrum of micronutrients, can follow months and years of inadequate intakes.[67] Studies consistently show that nutrient insufficiency is common in people with diagnosed with many brain-related conditions including depression and anxiety[68] [69] [70] and ADHD.[71] [72]

It is rarely one nutrient that bodies are missing and treatments with individual nutrients may result in inconsistent trial results. evidence is growing that dietary change and micronutrient supplementation which broadly raises nutrient intake levels may be more effective.[73] [74] [75]

Once ill, people are more likely to be diagnosed with multiple health conditions. Exposure to stressors such as trauma, can further promote systemic inflammation and disease risk, producing cascading harms for an individual.

Dietary shift exerts overlapping complex effects which can improve and repair gut microbiome function, lower the inflammatory burden, and increase nutrient intake. Practitioners in the field of metabolic and psychiatric nutrition, adopt a spectrum of flexible approaches that revolve around reducing carbohydrate intakes to reduce, mitigate and eliminate the markers of poor metabolic health which frequently underlie poor brain health. The approach necessarily involves psychological, behavioural and practical skills coaching.

Therefore, when people reduce ultraprocessed food intakes, glucose and gluten burdens, and shift to wholefood diets that are low in refined and chemically synthesised ingredients, reversal of multiple clinical parameters can occur. Dietary changes can include the elimination of foods that may play a triggering or mediating role in many chronic symptoms and conditions.[76] Biomarker testing, case studies and trials consistently report multiple positive outcomes across multiple clinical parameters.

Low-carbohydrate diets can upregulate endogenous ketone body production by shifting the metabolism toward increased fat oxidation. This may be a key mechanism underpinning many of the observed improvements in metabolic and mental functioning. Ketone bodies are produced when the body shifts from using glucose to mobilising stored fat for energy, have been consistently shown to provide important benefits for brain function and health.

From birth, humans are physiologically adapted to tolerate periods of fasting and food scarcity, and can flexibly transition into a state of nutritional ketosis when carbohydrate availability is low.[77]

Ketone bodies may be produced naturally by the body or provided through external supplements. Growing research is revealing how these molecules influence metabolism and brain function, making their therapeutic potential an exciting and fast-moving area of science. [78] [79] [80] [81] [82]

Ketone bodies not only function as fuel, but also as signalling metabolites with applications in health and disease. Scientists and clinicians are therefore regarding exogenous sources of ketone bodies, such as through infusion of beta-hydroxybutyrate (BHB), as a potential therapeutic treatment to reduce blood glucose, and improve performance, endurance/resilience and health outcomes. [83] A recent review found that dosing regimens of BHB produced more consistent results in healthy than non-healthy populations.[84] [85] [86]

Much of the early work in psychiatric nutrition was undertaken in an effort to improve health outcomes of treatment-resistant patients. For example, psychiatrist Georgia Ede’s approach was adopted after a French colleague, Dr Albert Danan, conducted a trial on 35 treatment resistant patients who were diagnosed with major depression, bipolar disorder (schizoaffective disorder). Patients were placed on a close supervision ketogenic diet. All were on multiple psychiatric medications, and all had been previously hospitalised. Many of the treatment resistant patients had high blood glucose, high blood pressure, high triglycerides and obesity and many could not work due to the psychiatric disability.[87]

By week three the 28 of the original 35 began improving metabolically and psychiatrically.
23 people with depression symptoms experienced substantial improvements in mood.
All 10 people with schizoaffective disorder experienced substantial reduction in psychosis symptoms.
12 people (44%) achieved full clinical remission.
18 people substantially reduced psychiatric medication.
All but one lost weight.

Danan’s diet protocol was adapted from a protocol developed by a Dr Eric Westman at Duke University.[88] [89] The diet consisted almost exclusively of meat, seafood, poultry, eggs, vegetables, nuts and cheese and was well tolerated by the patients.[90]

Multiple disease or symptom parameters (and multimorbidity) can regress, following a dietary shift.[91] [92] In a case of a 38-year-old female diagnosed with post-traumatic stress disorder, ADHD, binge eating disorder, bipolar II disorder, depression, anxiety, and premenstrual dysphoric disorder was placed on an insulin lowering ketogenic diet.:

By week 12, all psychiatric symptoms resolved evidenced by quantitative reductions to 0 across all validated instruments. The patient consistently reported optimal symptom control when blood ketone levels were maintained between 3 and 5 mmol/L. Qualitative reports substantiated marked functional gains, including improved occupational engagement and social functioning.[93]

The case above highlights the complex interplay between trauma, addictive behaviours and eating disorders. Diets high in rapidly absorbed carbohydrates can trigger sharp dopaminergic responses via mesolimbic reward pathways, while simultaneously driving spikes and crashes in blood glucose and insulin. Micronutrient insufficiency may play a significant role, particularly in younger adults.[94] [95] This combination of nutrient insufficiency, transient reward, followed by metabolic depletion and dysphoria, may heighten sensations of emptiness and reinforce repetitive seeking of the same foods. Compounding this, the widespread belief that dietary fat drives body fat can lead to unhealthy suppression of this essential macronutrient class, undermining satiety and further destabilising eating patterns. Vegetarianism may also be more commonly represented in eating disorder groups with the fat and protein intake under-represented.[96] Eating disorder literature rarely addresses the role of healthy saturated fats and proteins in supporting a return to adequate micronutrient status and in cutting short the addictive dopaminergic cycle.

When layered onto sociocultural pressures around body shape and health, pressures that disproportionately affect women, media influence and media, and the expansion of psychiatric categories, these interacting cultural, neurochemical, metabolic and psychosocial mechanisms may contribute meaningfully to the emerging pattern of eating-disorder vulnerability.[97] Low-carbohydrate and ketogenic diet researchers and clinicians have stepped into this field of research, with some success.[98] [99]

A cautionary approach is warranted. The person in the case study above carries a spectrum of risks and could revert to earlier dietary patterns and psychosis, or alternatively, the person may remain stable for the foreseeable future. Care involves navigation over time and people can be medication-supported and nutrition-supported and can taper off to drug-free states.

Nutritional psychiatry is stepping into the treatment void for many people who may choose not to take psychiatric drugs, and can address therapeutic gaps where people have found that conventional medical treatment has not suppressed symptoms (treatment failure), or where they have found adverse effects to be intolerable.

Are Symptoms of Inadequate Nutrition Misclassified as Psychiatric Disorders?

Psychiatric nutrition is a companion partner to conventional psychotherapy because nutrition enhances physiological health. Many of the ‘classic’ symptoms used to diagnose a psychiatric condition may have arisen due to insufficient nutrition or inadequate nutrient absorption over time, and poor mitochondrial (and cellular) health.

Many of the symptoms of depression[100], anxiety[101] and ADHD[102] that are listed in the Diagnostic and Statistical Manual of Mental Disorders[103], and that lead to a diagnosis and subsequent prescription, can be similarly attributable to dietary inadequacy, nutritional deficiencies and poor digestion.

The role of dietary nutrition in protecting from many of the symptoms of depression, including fatigue, insomnia, brain fog, is now well established.

Depressed mood.
Markedly diminished interest or pleasure in most or all activities.
Poor appetite, weight loss, or weight gain.
Insomnia or hypersomnia.
Slowing down of mental or physical activities (for example, sluggishness or diminished hand-eye coordination.
Fatigue or loss of energy.
Feelings of worthlessness or excessive or inappropriate guilt.
Diminished ability to think or concentrate ("brain fog"), or indecisiveness.
Recurrent thoughts of death; thinking about, planning, or attempting suicide.

Many of these categories might simply reflect inadequate nutrient intakes by age and/or gender, a differently functioning brain, a brain where discrete developmental periods mature at different stages (such as due to brain hemisphere differentiation) and/or deficiency in nutrients required for concentration and focus. These factors depend on complex interrelationships between diet, digestion, physical and social environmental exposures, genetics and methylation capacity.

Exercise is critical for optimum health, retention of healthy muscle and is associated with better mental health. However, fatigue, sleep loss, inadequate protein uptake and inadequate nutrition are often not factored in when people are urged to exercise. Over years, inadequate nutrition, although ’healthy’ may result in fatigue in groups that have nutrient requirements that are greater than, or that diverge from, current guideline recommendations.

The pathways, mechanisms and evidence of reversal following dietary shifts provide a compelling body of evidence that nutrition can be, and for some psychiatrists, already is, a first line treatment. [104] [105] [106] Results from trials show that people with major depressive disorder can be helped by making dietary changes, and ketogenic diets may provide one such pathway.[107]

Childhood and adolescent behaviour that is considered non-normative and behaviourally different, when teachers and practitioners clinically diagnose the behaviour of ADHD, sets that child on a path where medical treatment and behavioural strategies are first line treatments, and nutritional status is a minor order issue. The diagnostic criterion for ADHD is difficult to navigate [108] and ambiguous, and the quantity of criteria that are established to confirm an ADHD diagnosis has been arbitrary and flexible.[109]

Proportionately, these issues are not judged as equivalent factors, and there is a knowledge vacuum on the nutrition ‘side’ while the path is smoothed on the ‘medicalisation’ side. I.e. access to prescription drugs following a diagnosis of poor brain/mental health is non-controversial, but dietary changes to reverse or mitigate a brain-related syndrome or diagnosis is much more controversial.

Chapter 4. The Carbohydrate-Dopamine Cycle: Amplified by Ultraprocessed Foods

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