The Circadian Diet in Age-Related Neurodegeneration: Nutrient Timing, Sleep, and Mitochondrial Mechanisms

Abstract

Circadian rhythms coordinate sleep–wake regulation, endocrine secretion, nutrient handling and cellular energy metabolism. Circadian and sleep disturbances are associated with metabolic and cardiovascular morbidity and with neurodegenerative disorders, particularly Alzheimer’s disease (AD) and Parkinson’s disease (PD), although whether restoring circadian alignment modifies neurodegeneration remains uncertain. This narrative review examines chrononutrition within the broader context of sleep regulation, physical activity and circadian care, distinguishing evidence from cellular and animal models, observational studies and clinical trials. Meal timing and dietary composition act as signals to peripheral clocks, while NAD+, sirtuins and AMP-activated protein kinase link nutrient availability with clock regulation and mitochondrial metabolism. We appraise time-restricted eating, protein distribution, NAD+ precursors, tryptophan- and melatonin-containing foods, magnesium, omega-3 fatty acids, polyphenols and fermentable fiber. Experimental findings provide mechanistic plausibility, but metabolic improvements and target engagement have not translated into demonstrated neuroprotection. Clinical application must account for levodopa–protein interactions, undernutrition, frailty and sarcopenia. Adequately powered trials with circadian-phase assessment, controlled energy intake and clinically meaningful neurological outcomes are required before a “circadian diet” can be established as a disease-modifying intervention.

The authors' abstract, as published at the source. Nutrients, 2026 · DOI ↗