Although a 1930s study of Scottish schoolchildren had observed that ‘poor nutrition has undoubtedly an effect on mental capacity …’ (Riddell, 1932), Grajek et al (2022) report that ‘the relationship between nutrition and patients’ mental status has been underappreciated, as evidenced by the lack of research conducted before the 21st century …’ with Adana et al (2019) predicting that Europe in coming decades will see an increased burden of psychiatric disorders, mood disorders and stress-induced cognitive vulnerabilities, and they advocate continued research on the role of diet in mental health.
Nutrition and the brain
The body's microbiome comprises some 200 trillion (2 x 1014) organisms and Hoffmann (2023) explains that it is adversely affected by the consumption of ultra-processed foods (UPFs) which lower the population of beneficial versus harmful gut bacteria that can promote ‘increased intestinal mucosal permeability, which in turn triggers an augmented immune response, cytokine production, and chronic neuroinflammation, a significant cause of mental illness.’ Expanding on this, Mörkla et al (2020) highlight the importance of the gut-brain axis, a bidirectional communication pathway between the intestine and brain, connecting the enteric nervous system to the central nervous system. For example, evidence cited by Mörkla et al (2020) shows a reduction in the number of bacterial species in a range of mental disorders and demonstrates how intestinal bacteria intervene directly in our neurotransmitter metabolism, especially serotonin metabolism, which is significant from a psychiatric perspective.
Anxiety and altered mood
Dietch et al (2023) acknowledge a growing public interest in the use of low carbohydrate (LC) and/or ketogenic diets (KDs) to address mood and anxiety disorders. AKD is a high-fat, low-carbohydrate diet where the main metabolic fuel source for cellular mitochondrial adenosine triphosphate production – the body's energy source – switches from glucose to ketone bodies produced in the liver and derived from the breakdown of fatty acids (Campbell and Campbell, 2019).
Dietch et al (2023) cite a self-report uncontrolled survey of LC diets in 1580 patients with diverse conditions like obesity and type 2 diabetes (T2D) that found significant improvements in mood, anxiety and energy and less antidepressant use (although psychiatric diagnoses were not provided). But while several uncontrolled studies suggest possible beneficial effects, Dietch et al (2023) found no high-quality evidence of LC/KD efficacy in mood or anxiety disorders, and they recommend that ‘[r]obust studies are now needed to demonstrate efficacy, to identify clinical groups who may benefit …’
Nevertheless, Childers (2023) notes that the effects of high glycaemic index (GI) carbohydrates on mood have been investigated, citing a 2015 report based on the Women's Health Initiative study which ‘found that in postmenopausal women, a high GI diet was associated with depression.’ Childers (2023) further cites a 2019 systematic review and meta-analysis whose findings ‘suggest a possible causal relationship between dietary GI, glycaemic load and depression.’
Depression
Danan et al (2022) point out that globally at least 280 million are thought to be afflicted with depressive illness, and across Europe around 19% of those with depression are ‘treatment-resistant’. Explaining that depressive symptoms are prevalent among those with T2D, Adams et al (2022) reported the results of their two-year study of 262 patients with T2D, finding that participants’ depressive symptoms ‘consistently improved over 2 years of a digital T2D treatment emphasizing a carbohydraterestricted eating plan. Additionally, greater adherence to low carbohydrate eating predicted decreased depressive symptoms.’
Danan et al (2022) also speculate that the apparent separation between neurological and psychiatric illness may be more rhetorical than biological, given their common origin in the brain; shared biochemical similarities like dysfunctional neurotransmitter systems; unstable neural networks; neuroinflammation; excessive oxidative stress; aberrant neuroplasticity; mitochondrial dysfunction; and disturbed cerebral glucose metabolism.
Danan et al (2022) investigated 31 adult treatment-resistant patients with severe persistent mental illness like major depressive disorder, bipolar disorder, and schizoaffective disorder who were given a KD allied to conventional inpatient care, with the intervention lasting from 6 to 248 days. Their study found that this approach was ‘feasible, well-tolerated, and associated with significant and substantial improvements in depression and psychosis symptoms and multiple markers of metabolic health’ (Danan et al, 2022).
Bipolar disorder
Bipolar disorder (BD) is characterised by manic and depressive episodes, and the World Health Organisation cites BD as the sixth commonest cause of disability worldwide, affecting around 5% of the population (Lam et al, 2023). El-Mallakh and Paskitti (2001) hypothesise that ‘[t]here are several reasons to suspect that the KD may … have utility as a mood stabilizer in BD’, and impaired mitochondrial energy metabolism is closely related to BD. Further, ‘[c]ompared with the general population, the prevalence of mitochondrial dysfunction is higher in people with BD’ (Lam et al, 2023).
Acknowledging that BD individuals with insulin resistance or T2D are more susceptible to rapid mood cycling and prone to a more progressive disease course, Danan et al (2022) adduce evidence that glucose and insulin dysregulation may adversely affect mood and that a KD can increase brain concentrations of glutathione, an antioxidant that helps to buffer oxidative stress.
And when Campbell and Campbell (2019) considered associations between a KD and mood stabilisation among 274 individuals with BD, they found that notwithstanding the limitations of their observational data based on online self-reports, and acknowledging the need for controlled trials, ‘the association strength and reports of sustained benefit support a hypothesis of a KD diet being associated with beneficial effects on mood stabilisation.’
No full-scale clinical trials have yet been conducted, but in June 2023 a multi-disciplinary team at the University of Edinburgh reported preliminary results (not yet peer-reviewed at the time of writing) of a pilot study funded by the Baszucki Brain Research Fund (Needham et al, 2023). To assess the feasibility of a KD intervention in BD, 27 euthymic (neutral or tranquil mood) individuals with BD were recruited to a 6–8-week trial of a modified KD, with 20 completing the study. Needham et al (2023) established the feasibility of a 6–8-week KD, with high outcome measure completion rates: ‘The majority of participants reached and maintained ketosis and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.’
Alzheimer's disease
Bikman (2020, p 27) asserts that a new understanding of Alzheimer's disease (AD) is emerging, recognising the contribution of insulin resistance.. Insulin resistance is a reduced response to insulin, with a key feature being that blood concentrations of insulin are higher than they used to be, and the insulin often works less effectively (Bikman,(2020, p 6).
Might diet have a role in provoking – and perhaps even preventing – AD? As Steen et al (2005) explain, in 2005, neuroscientist Dr Suzanne de la Monte published a groundbreaking paper that suggested a new theory about AD's origins: ‘AD may represent a neuro-endocrine disorder that resembles, yet is distinct from, diabetes mellitus. Therefore, we propose the term, “Type 3 Diabetes” to reflect this newly identified pathogenic mechanism of neurodegeneration’ (Steen et al, 2005).
Some evidence of a different approach as to how AD might be influenced by diet was provided when Seneff et al (2011) reported that researchers had identified cell mitochondrial dysfunction and brain insulin resistance as early indicators of AD; that the cerebrospinal fluid of AD brains is deficient in fats and cholesterol; that synthesis of the neurotransmitter, glutamate – a potent oxidising agent – increases when cholesterol is deficient; and that dietary modification ‘towards fewer highly-processed carbohydrates and relatively more fats and cholesterol, is likely a protective measure against AD.’
In addition, Berger (2016) suggests that excessive consumption of refined carbohydrates, insufficient exercise, and poor sleep hygiene could contribute to insulin resistance, which would promote glycation and oxidative stress in the brain. With specific neurons losing the ability to metabolise and derive energy from glucose, neuronal degeneration and death result, and ‘[s]imultaneously, chronic peripheral hyperinsulinaemia prevents ketogenesis, thus depriving struggling neurons of a highly efficient alternative fuel substrate’ (Berger, 2016).
Given that one of the features of AD is the production of intracellular neurofibrillary tangles and the accumulation of amyloid β peptide (Aβ) plaques, Versele et al (2020) have demonstrated that the rise of ketone body concentrations through a KD promotes ‘Aβ clearance from the brain to blood in addition to exciting perspectives for studying the use of ketone bodies in therapeutic approaches.’
Food addiction
With more research in recent years turning to relatively new areas like psychodietetics and nutripsychiatry, the role of nutrient-poor calorie-enriched UPFs in physical and mental wellbeing is coming under increasing critical scrutiny. And as Hoffmann (2023) makes clear, the rise of UPFs ‘is widely considered an important factor in the approximately 700% increase in T2D, vascular disease, obesity and a range of mental disorders.’ In this context, the mental health challenges posed by the consumption of UPFs in terms of their addictive nature are now being explored. For example, noting that the concept of food addiction (FA) was first described in 1956, Unwin et al (2022) explain that despite extensive debate, the question of whether FA represents a distinct disorder meriting official recognition remains unresolved and, to date ‘FA has not been classified in the Diagnostic and Statistical Manual of Mental Disorders or in the International Classification of Diseases. However, using the term FA to mean dependency behaviours relating to sugar and processed foods (although often referred to as UPF addiction), Unwin et al (2022) have demonstrated for the first time ‘the short-term clinical effectiveness of a low carbohydrate “real food” intervention delivered in an online group format with education and social support for individuals with FA symptoms.’
Finally
It appears that as the interface between nutrition, neuroscience and psychology/psychiatry becomes more porous, the evidence that the consumption of real, unprocessed, low-carbohydrate food confers distinct physical and mental health benefits will become even more compelling.