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Background and Aims: Growing evidence suggests nutritional intervention may influence the development and progression of Alzheimer's Disease (AD). Choline, an essential dietary nutrient plays a critical role in neurological development and brain function, however, its effects on AD in humans is unclear. The research aims to investigate mechanistic links between dietary choline intake and cognitive functioning, focusing on the role of phosphatidylcholine (PC) in neuroplasticity and its interaction with amyloid beta (Aβ) peptides in neuron membranes. Additionally, human evidence on the potential benefits of PC interventions on AD, cognition, and proposed mechanisms are evaluated., Methods: A reproducible systematic literature search was performed using a three-tranche strategy, consisting of a review, mechanism, and intervention search. Using PubMed as the main database, 1254 titles and abstracts were screened, 149 papers were read in full and 65 peer-reviewed papers were accepted, critically appraised, and analysed in a narrative review., Results: Predominantly preclinical evidence demonstrated that PC enhances neuroplasticity, a key biological substrate for cognition, by activating intracellular neuronal signalling pathways or through neuron membrane function. Molecular dynamic simulation methods provided a mechanistic understanding of the interconnection between neuronal PC content and the potential behaviour and trajectory of Aβ peptide aggregation. The results indicate that the neuronal membrane composition of PC is critical to inhibiting Aβ aggregation and neuronal damage, protecting the neuron from Aβ toxicity. This might provide a foundation for optimising cellular PC which may prove beneficial in the treatment or prevention of neurodegenerative disease. Altered PC metabolism in AD was evidenced in observational studies; however, whether this relationship represents a cause or consequence of AD remains to be determined. Human intervention studies did not produce conclusive evidence supporting its effectiveness in enhancing cognitive function. This lack of consistency primarily stems from methodological constraints within the conducted studies. Human observational research provided the most compelling evidence linking a higher dietary PC intake to a reduced risk of dementia and significant improvements in cognitive testing., Conclusion: Despite the lack of randomised control trials (RCTs) assessing the efficacy of lecithin/PC to improve cognition in AD patients, there exists promising evidence supporting its neuroprotective and neurotrophic role. This review establishes an evidence-based framework through chains of mechanistic evidence, that may provide potential strategies for enhanced neuroprotection and reduced neurodegeneration caused by AD. Considering the escalating global burden of AD and the current shortcomings in effective treatments, this review together with the limitations and gaps identified in the existing research presents valuable insights that emphasise the urgency of more comprehensive research into the relationship between PC and AD., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Epidemiological studies have associated reduced bacterial diversity and abundance and food allergy. This mechanistic review investigated the link between gut dysbiosis and food allergy with a focus on the role of short-chain fatty acids (SCFAs) in modulating T-cells. T-cell differentiation poses an opportunity to direct the immune cells towards an anergic regulatory T cell (Treg) or allergic T helper 2 (Th2) response. Probiotic intervention to prevent and/or treat atopic disease symptoms through this mechanistic pathway was explored., Methodology: A narrative review was conducted following a three-stage systematic literature search of EMBASE and Medline databases. Ninety-six of 571 papers were accepted and critically appraised using ARRIVE and SIGN50 forms. Thematic analysis identified key pathophysiological mechanisms within the narrative of included papers., Results: Preclinical studies provided compelling evidence for SCFAs' modulation of T-cell differentiation, which may act through G-protein coupled receptors 41, 43 and 109a and histone deacetylase inhibition. Foxp3 transcription factor was implicated in the upregulation of Tregs. Human probiotic intervention studies aimed at increasing SCFAs and Tregs and preventing atopic disease showed inconclusive results. However, evidence for probiotic intervention in children with cow's milk protein allergy (CMPA) was more promising and warrants further investigation., Conclusion: Preclinical evidence suggests that the mechanism of gut dysbiosis and reduced SCFAs may skew T-cell differentiation towards a Th2 response, thus inducing allergy symptoms. Probiotic trials were inconclusive: probiotics were predominantly unsuccessful in the prevention of allergic disease, however, may be able to modulate food allergy symptoms in infants with CMPA., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: The epidemic of obesity is associated with a substantial, complex and escalating burden of disease. Dietary and lifestyle interventions provide the mainstay of management; however, obesity is multifactorial and challenging to address clinically. Disrupted circadian behaviours, including late eating, are associated with obesity. Time-restricted feeding (TRF), the confinement of calorie intake to a temporal 'eating window', has received growing interest as a weight-loss intervention. Benefits are purported to arise from the fasting period and strengthened circadian metabolism. However, the current evidence-base for TRF is small-scale, limited, and there has been little evaluation of circadian schedule. This research aims to enable evidence-based conclusions regarding circadian-aligned TRF as a weight-loss intervention in obesity., Methods: A systematic three-tranche search strategy was conducted within PubMed. Included studies were critically evaluated. Search tranches scoped: interventional evidence for TRF; evidence linking meal timing, obesity and metabolic function; and evidence linking circadian function, obesity, and dysmetabolism. Results were summarised in a narrative analysis., Results: A total of 30 studies were included. From small-scale and short-term evidence, TRF was consistently associated with improved weight, glycaemic and anthropometric outcomes versus baseline or control. Good adherence and safety, and consistency of results between studies, were notable. Earlier ('circadian-aligned') eating was associated with greater diet-induced thermogenesis, and improved weight loss and glycaemic outcomes. Limited evidence suggested meaningful correlations between circadian clock function and obesity/metabolic risk., Conclusions: Circadian-aligned TRF may present a promising intervention for weight loss and metabolic benefits in obese/overweight individuals., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: The rising prevalence of obesity is a major international concern and is associated with a substantial burden of disease. Disrupted circadian behaviours, including late and extended eating patterns, are identified as risk factors for obesity. The circadian rhythm synchronises metabolic functions between and within tissues, optimising physiology to integrate with environmental and behavioural cycles. Cellular circadian rhythms also separate poorly compatible processes and enable adaptive integration of energy metabolism with autophagy. The timing of nutritional input is a key and easily controllable variable that influences circadian function. Misalignment of nutritional input with the centrally generated circadian rhythm may dampen and disrupt circadian metabolic function. This review seeks to provide a mechanistic overview of nutritional circadian entrainment and its downstream metabolic effects. The aims are: to characterise the key cellular and physiological mechanisms involved in the nutritional entrainment of circadian rhythms; and to explore the perturbation of these pathways by misaligned nutritional inputs, with relevance to obesity-associated dysmetabolism., Methods: A systematic two-tranche search strategy was employed. Searches were conducted within PubMed between March and December 2020. Included studies were formally evaluated for quality. Evidence was extracted and coded into key themes., Results: 142 records were screened and 50 accepted. The evidence analysed was moderate-to-high quality and enabled the detailed characterisation of cellular pathways involved in nutritional circadian entrainment. Results indicated that diverse nutritional input pathways converge upon key nutrient/redox sensors and nutritionally sensitive core clock genes, which integrate with circadian metabolic pathways, allowing bidirectional communication between circadian clock function and metabolism. Versus alignment, nutritional misalignment was causally associated with dampening and alteration of core clock rhythms, between-tissue rhythmic decoupling, dysmetabolism, and obesity. Signalling through key circadian nodes, such as NAD + /SIRT, was indicated to have importance in these metabolic changes. Misaligned nutritional inputs were associated with altered core circadian temporal dynamics of metabolism and autophagy, and different time division between insulin-sensitive and insulin-resistant metabolic states. Time-restricted feeding protocols aligned with the natural circadian rhythm (light-dark cycle) relatively strengthened circadian oscillatory patterns and protected against diet-induced obesity., Conclusions: This review suggests potential value in further investigating circadian-normalising nutritional interventions for obesity, such as circadian-aligned time-restricted feeding., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)