Alzheimer’s disease (AD) is a progressive neurological disease. It causes memory loss, behavioral disturbance, and cognitive decline. Many factors contribute to the pathology of AD, like chronic neuroinflammation, oxidative stress, accumulation of pathological proteins like hyperphosphorylated tau tangle and amyloid-beta (Aβ) plaques, and apoptosis. Current therapeutic methods are symptomatic, and there is an urgent need to investigate the natural products with neuroprotective properties. Honey is a natural substance rich in flavonoids, polyphenols, and other bioactive components. It has received attention as a potential neuroprotective agent. The anti-inflammatory, antioxidant, and anti-apoptotic properties suggest a possible therapeutic effect in slowing or preventing AD progression.
This review aims to examine the available evidence on honey and honey-derived extracts in relation to their neuroprotective potential in AD with a focus on mechanistic insights, therapeutic implications, and limitations that restrict their translation to human applications.
Several studies demonstrate that honey can mitigate key mechanisms involved in AD pathogenesis. Preclinical evidence consistently highlights honey’s capacity to reduce oxidative stress by lowering malondialdehyde (MDA) levels while simultaneously enhancing antioxidant defenses, such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase activities. For instance, animal studies have shown that daily supplementation of honey at doses as high as 1 g/kg/day reduces oxidative biomarkers and improves memory function in experimental AD models. Honey also modulates inflammatory pathways by reducing the levels of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, while promoting anti-inflammatory mediators. Furthermore, honey regulates cholinergic transmission by inhibiting acetylcholinesterase (AChE), thereby prolonging acetylcholine activity, a neurotransmitter critical for memory and learning that is severely depleted in AD.
Another mechanistic aspect involves honey’s modulation of apoptotic pathways. Evidence suggests that honey-derived polyphenols reduce neuronal apoptosis by modulating pro-apoptotic proteins, such as Bax and caspase-3, while upregulating anti-apoptotic proteins, including Bcl-2. Honey also attenuates mitochondrial dysfunction, although data remain sparse. Importantly, honey has shown potential to interfere with the pathological accumulation of amyloid-beta plaques and tau protein hyperphosphorylation, two hallmark features of AD. This positions honey as a candidate for targeting both upstream and downstream processes in AD progression.
Among the different varieties, avocado, manuka, chestnut, kelulut, and tualang honeys have been studied most extensively. Each type contains unique phytochemical signatures. Manuka honey is rich in methylglyoxal, while chestnut honey contains a high phenolic content, both of which contribute to distinctive biological effects. However, it is essential to note that even within the same variety, the phytochemical composition can vary significantly depending on the botanical source, geographic region, harvest season, and processing method. This variability complicates the ability to generalize findings or propose standardized therapeutic protocols.
This study has significant limitations, including the absence of human trials and the use of unrealistically high doses in animal models. These studies do not replicate the complexity of AD and do not accurately address pharmacokinetic considerations, such as oral bioavailability.
While honey has neuroprotective properties in a preclinical setting, it decreases oxidative stress and neuroinflammation, increases antioxidant defense, modulates cholinergic activity, and interferes with tau and Aβ pathology. Methodological biases and weaknesses, high heterogeneity in studies, lack of clinical trials, and unrealistic dosage limit the human translation. Further randomized clinical trials, standard dosage protocol, and evaluation of pharmacokinetics are required before honey is suggested as a preventive or therapeutic intervention for AD’s management.
References: Navarro-Hortal MD, Romero-Márquez JM, Ansary J, et al. Honey as a Neuroprotective Agent: Molecular Perspectives on Its Role in Alzheimer’s Disease. Nutrients. 2025; 17(16):2577. doi:10.3390/nu17162577
