"Honey and the Brain": How a Bee Product Can Protect Against Alzheimer's - What is Already Known and What is Not Yet

Nutrients published a review about honey being not only sweet, but also a potential neuroprotector. According to 27 selected studies (cells, worms, flies, rodents), honey and its phenolic compounds reduce oxidative stress and inflammation, support mitochondria, suppress neuronal apoptosis , and also affect key “nodes” of Alzheimer’s disease: β-amyloid (Aβ), hyperphosphorylated tau, and the enzymes acetyl- and butyrylcholinesterase. There are no clinical RCTs yet, so it’s too early to talk about treatment. But the direction looks promising — especially for “dark” varieties of honey rich in polyphenols (chestnut, heather, buckwheat, etc.).

Background

• Unmet need in AD. Even with the advent of anti-amyloid antibodies, clinical benefit remains modest, treatment is expensive and carries risks. Therefore, complementary, safe nutritional strategies that target the underlying mechanisms of neurodegeneration: oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired protein clearance (Aβ/tau) are actively sought.
• Food patterns as a clue. The Mediterranean and MIND diets are associated with slower cognitive decline. The common denominator of such diets is polyphenols and other phytonutrients. Hence the logic to look at natural products with a rich phenolic profile, in particular honey.
• What is honey from a biochemical point of view? It is not “just sugar”: in addition to glucose and fructose, it contains phenolic acids and flavonoids (e.g. quercetin, luteolin, apigenin, kaempferol, chrysin, pinocembrin), small amounts of vitamins/minerals, enzymes and organic acids. Dark varieties (chestnut, buckwheat, forest honeys; manuka, tualang/kelulut) are usually richer in phenols.
• Current evidence base. Most of the data is preclinical (cell models, C. elegans, Drosophila, rodents). It shows a consistent picture: less oxidative stress/inflammation and improved behavioral memory tests with honey or honey extracts. There are no randomized clinical trials in humans yet, so this is more of a potential than a proven treatment.

Important limitations and pitfalls

• Sugars and metabolism: honey - calories and carbohydrates; people with diabetes/insulin resistance need special calculation and individual approach.
• Composition variability: the phenolic profile is highly dependent on botanical and geographical origin, season and storage; a “spoonful of honey” is not a standard dose of active ingredients.
• Quality and safety: risk of adulteration/overfed syrup batches, trace pesticides/antibiotics from unscrupulous producers; honey is contraindicated for children <1 year due to the risk of botulism.
• Bioavailability: Not all phenols are equally absorbed and cross the BBB; human pharmacokinetics are needed.

What researchers need to do next

1. Standardize the phenolic “passport” of the tested honey (quantitative profile of key molecules), dose by phenolic equivalent, and not by grams of product.
2. Conduct high-quality preclinical work with common endpoints (Aβ/p-Tau, microglia, mitochondria) and realistic doses.
3. Launch pilot RCTs in humans (MCI/early AD): cognitive batteries + neuroimaging and fluids (plasma/CSF Aβ, p-Tau, inflammatory markers), glycemic and weight control.
4. Compare honey with other bee products (propolis/royal jelly) and find out where the effect is stronger/safer.

The practical minimum for the reader today. Honey is not a cure for dementia and is not a substitute for prescribed therapy. It is reasonable to consider it as part of the diet (especially dark varieties with high phenolic content) in the absence of contraindications - taking into account sugars, calories and the quality of the product.

What exactly was dismantled?

The authors systematically searched PubMed, Scopus, and Web of Science and, after filtering, left 27 unique papers on honey/honey extracts in the context of Alzheimer's. The review includes manuka, avocado, acacia, tualang, kelulut (stingless bee honey), chestnut, "coffee" and other varieties. Biological activity strongly depends on the botanical origin and the composition of phenolic compounds: darker honeys usually contain more polyphenols.

How Honey Can “Support” the Brain in AD

• Antioxidant shield. Honey and its extracts reduced excess reactive oxygen species (ROS), increased glutathione levels and SOD/CAT/GPx enzyme activity, and activated the Nrf2 pathway, the main cellular sensor of antioxidant defense. This was demonstrated in cell cultures and in C. elegans/Drosophila and rodent models.
• Mitochondria under protection. Chestnut honey extract prevented the loss of mitochondrial membrane potential in neurons damaged by glutamate - that is, it helped keep the cell's "power plants" working.
• Anti-inflammatory effect. In a number of studies, honey “silenced” the NF-κB signaling pathway and inflammatory molecule derivatives (COX-2, iNOS, TNF-α, IL-6), which is probably also facilitated by Nrf2 activation.
• Antiapoptosis. In rodents, chestnut and kelulut honey reduced the number of apoptotic cells in the cortex, giving shifts in the gene profile: down — FAS-L, P27, BIM, up — Bcl-2; in parallel, the expressed BDNF increased.
• Amyloid and tau. In animal models, honey reduced Aβ1-42 accumulation, shifted the balance toward the “less sticky” Aβ1-40, and reduced p-Tau levels in the rat hippocampus. Certain honey phenols (e.g., rutin, luteolin, 3,4-dicaffeoylquinic acid) showed high affinity for BACE1, a key enzyme in amyloidogenesis.
• Cholinesterases and monoamine oxidase. Several varieties (buckwheat, multiflora, acacia, manuka, etc.) inhibited AChE/BChE in vitro; in rats fed acacia honey, AChE activity decreased in both brain and serum. In tualang, a decrease in AChE was also observed in old rats. Some honeys/bee products inhibited MAO activity in microsome tests.

"How much honey do you need?" - honestly about doses

The authors provide a guideline for converting doses from rats to humans based on surface area: 1 g/kg for a rat ≈ 161 mg/kg for a human, i.e. about 9–10 g of honey per day for a 60-kg adult — a value that is entirely consistent with real life. But this is a rough laboratory estimate, not a recommendation for self-therapy.

Where honey can “go in” stronger

The effects are more noticeable in honeys with a high content of phenols (dark varieties: chestnut, buckwheat, forest honeys; as well as manuka, tualang/kelulut). They contain many phenolic acids and flavonoids - quercetin, luteolin, apigenin, kaempferol, chrysin, pinocembrin, etc. - which "hold" the antioxidant and anti-inflammatory properties.

What does this mean for people?

• It is not a cure for Alzheimer's. The evidence base is still preclinical; there are no randomized clinical trials of honey in AD. We can only talk about a potential complementary effect within the diet.
• Quality is very important. The composition of honey varies by variety, region, harvesting and storage. That is why it is difficult to prescribe a "spoonful dose" without understanding the phenolic profile.
• Sugars and safety. Any honey is carbohydrates. People with diabetes and when monitoring weight should consider the caloric content and glycemic load; choose a diet together with a doctor/nutritionist.

What should scientists do next?

• Conduct well-designed animal studies with consistent endpoints (Aβ/p-Tau, cognitive tests, neuroimaging) and realistic doses/formulations.
• Launch clinical RCTs (e.g. in patients with MSI/early AD) selecting honey with verified phenolic profile; look at biomarkers (CSF/plasma Aβ, p-Tau, inflammation) and cognitive outcome.
• To clarify the bioavailability of key honey phenols and their pharmacokinetics in humans: it is because of this “bottleneck” that beneficial effects from the test tube do not always reach the clinic.

Source: Navarro-Hortal MD et al. Honey as a Neuroprotective Agent: Molecular Perspectives on Its Role in Alzheimer's Disease, Nutrients 17(16):2577, 2025. https://doi.org/10.3390/nu17162577