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Open research questions in Diet and metabolism studies

96 unresolved questions extracted from the limitations and future-work sections of 376 Diet and metabolism studies papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • integrate accurate dietary assessment, - objective adherence measures, - metabolic phenotyping, - AD biomarkers, - clinically meaningful outcomes

    Dietary Patterns, Micronutrient Adequacy, and Metabolic Vulnerability in Alzheimer’s Disease: A Critical Narrative Review · 2026 · DOI

  • The current evidence on the relationship between diet and Alzheimer's disease is largely observational. Randomized trials have not consistently demonstrated prevention of cognitive decline. There is a need for more research on the relationship between dietary patterns and Alzheimer's disease.

    Dietary Patterns, Micronutrient Adequacy, and Metabolic Vulnerability in Alzheimer’s Disease: A Critical Narrative Review · 2026 · DOI

  • The study remains limited due to the immune-privileged nature of the retina - The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University - The entire study protocol was conducted in accordance with the guiding principles of the Declaration of Helsinki

    Ketogenic diet attenuates Müller cell activation and retinal neuroinflammation in autoimmune glaucoma through acetylation‑mediated FOXO signalling · 2026 · DOI

  • Further investigation of KD as a potential neuroprotective adjunct therapy for glaucoma - Studies in the area of immune response in glaucomatous optic neuropathy remain limited - Investigation of the differences in ketone body levels between open-angle and angle-closure glaucoma

    Ketogenic diet attenuates Müller cell activation and retinal neuroinflammation in autoimmune glaucoma through acetylation‑mediated FOXO signalling · 2026 · DOI

  • Long-term trials demonstrating that recurrent mild ketosis prevents are needed, - The physiological importance of individual epigenetic effects depends on concentration, cell type and experimental context

    Ketones and brain health: from metabolic rescue to metabolic flexibility · 2026 · DOI

  • The gap in understanding the role of ketones in brain health. The need to explore the concept of intermittent metabolic switching. The lack of understanding of how modern lifestyles affect ketone production.

    Ketones and brain health: from metabolic rescue to metabolic flexibility · 2026 · DOI

  • One challenge is the potential difficulty in maintaining dietary adherence to a ketogenic diet. Another challenge is the need to control for confounding variables, such as caloric intake and weight loss. The study also acknowledges the potential challenge of isolating the specific effects of ketosis.

    Efficacy of ketogenic diet on glycemic-lipid metabolism and menstrual regularity in women with polycystic ovary syndrome: a randomized controlled trial · 2026 · DOI

  • Adverse effects are common with ketogenic diet therapy and can limit its use. There is a need for structured clinical and biochemical monitoring to ensure the safe use of ketogenic diet therapy. The paper notes that tolerability, rather than efficacy, becomes the dominant limitation of KDT over time in some DEE syndromes.

    Ketogenic diet therapy in developmental and epileptic encephalopathies: toward syndrome- and gene-informed precision therapy · 2026 · DOI

  • Comparative-effectiveness data for KDT vs. other antiseizure therapies, - Reporting of nonseizure outcomes across the KDT literature, - Prospective adoption of standardized endpoints to facilitate meaningful cross-study comparisons, - Individual patient data metaanalyses

    Ketogenic diet therapy in developmental and epileptic encephalopathies: toward syndrome- and gene-informed precision therapy · 2026 · DOI

  • Investigating the effects of targeting the gut on reward signals for foods rich in fat or protein, - Examining the relationship between macronutrient composition and depressive symptoms

    Altered food liking in depression is driven by macronutrient composition · 2025 · DOI

  • A fully quantitative and experimental investigation of differences in perceived reward using the macronutrient composition of an extensive set of food items was missing. The relationship between macronutrient composition and food liking in MDD is not well understood.

    Altered food liking in depression is driven by macronutrient composition · 2025 · DOI

  • The lack of standardization in lipidomic techniques can make it difficult to compare results across different studies. The complexity of DE's pathogenesis, involving multiple factors and pathways. The need for a holistic understanding of how cells function and how diseases disrupt these processes.

    Diabetes and brain: omics approaches to study diabetic encephalopathy · 2025 · DOI

  • lack of standardization in lipidomic techniques can make it difficult to compare results across different studies, - omics approaches have been infrequently applied to cellular models of DE, - limited human studies were integrated in the multi-omics approach

    Diabetes and brain: omics approaches to study diabetic encephalopathy · 2025 · DOI

  • inter-individual variability, - need for extensive validation, - poor translatability from research settings to routine clinical practice, - logistical challenges, - recall bias, misreporting, and inter-individual variability in self-reported dietary intake data

    The role of β-hydroxybutyrate testing in ketogenic metabolic therapies · 2025 · DOI

  • The lack of objective biomarkers to accurately monitor dietary adherence and metabolic responses is a major gap in nutrition studies. The limited applicability and reliability of existing biomarkers and testing methods are a significant challenge. The need for further research into the relationship between ketone levels and therapeutic outcomes is a gap in the current literature.

    The role of β-hydroxybutyrate testing in ketogenic metabolic therapies · 2025 · DOI

  • The study is limited by the lack of direct dietary monitoring or ketone blood tests. The study is prone to selection bias. The study highlights the challenge of understanding the interplay between metabolism and mental illness.

    Ketogenic diet as a therapeutic intervention for obsessive-compulsive disorder: a case series of three patients · 2025 · DOI

  • Case series are generally prone to selection bias, - The authors pursued and interviewed individuals who reported improvement in their OCD while on a KD, - The lack of direct dietary monitoring or ketone blood tests prevents definitive confirmation of ketosis

    Ketogenic diet as a therapeutic intervention for obsessive-compulsive disorder: a case series of three patients · 2025 · DOI

  • Further research is needed to evaluate the feasibility, efficacy, and broader applicability of KMT in diverse clinical settings, - Research should investigate the use of KMT in larger populations

    Ketogenic metabolic therapy in the remission of chronic major depressive disorder: a retrospective case study · 2025 · DOI

  • There is limited evidence describing the use of ketogenic metabolic therapy for treatment-resistant major depressive disorder. Current treatments for major depressive disorder have limited effectiveness for some patients. There is a need for alternative, non-pharmacological interventions for treatment-resistant major depressive disorder.

    Ketogenic metabolic therapy in the remission of chronic major depressive disorder: a retrospective case study · 2025 · DOI

  • Future studies should employ matched weight-loss designs, - Future studies should include ketone-supplementation arms to isolate the specific effects of ketosis

    Efficacy of ketogenic diet on glycemic-lipid metabolism and menstrual regularity in women with polycystic ovary syndrome: a randomized controlled trial · 2026 · DOI

  • Dietary supplements that elevate β-HB, such as medium-chain triglycerides and ketone esters, have been proposed as alternatives to the KD, but their sex-specific effects in aging remain poorly defined.

    Ketone ester supplementation in aged mice produces sex-specific cognitive and metabolic effects · 2026 · DOI

  • However, the molecular mechanism by which β-hydroxybutyrate is converted to β-hydroxybutyryl-coenzyme A (BHB-CoA), the cofactor for Kbhb, remains unknown.

    ACSS2 coupled with KAT7 regulates histone β-hydroxybutyrylation to enhance transcription · 2025 · DOI

  • Nevertheless, the mechanisms underlying these effects and their long-term clinical relevance remain incompletely understood.

    A comprehensive overview of the effects of probiotics, prebiotics and synbiotics on the gut-brain axis · 2025 · DOI

  • Particular attention is given to their impact on neurocognitive outcomes and systemic health, highlighting both the therapeutic potential and the existing gaps that warrant further investigation.

    A comprehensive overview of the effects of probiotics, prebiotics and synbiotics on the gut-brain axis · 2025 · DOI

  • Lactobacillus probiotics are commonly used for gut health and immune support, but their mechanism in sarcopenia via the gut-muscle axis remains uncertain.

    Probiotics and muscle health: the impact of Lactobacillus on sarcopenia through the gut-muscle axis · 2025 · DOI

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96 open questions have been extracted from the limitations and future-work passages of 376 Diet and metabolism studies papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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