How does methylglyoxal (MGO) in Manuka honey influence systemic metabolism and are there measured effects on insulin signaling in humans?
Executive summary
Methylglyoxal (MGO) is the reactive dicarbonyl largely responsible for Manuka honey’s antibacterial reputation, and biochemically it is a potent glycating agent that can form advanced glycation end‑products (AGEs) which plausibly perturb insulin signaling and vascular function; however, direct, well‑controlled evidence that dietary MGO from Manuka honey measurably impairs insulin signaling in humans is lacking [1]. Experimental and animal studies point to mechanisms by which MGO could contribute to insulin resistance, while small, heterogeneous human observations are inconsistent and do not prove a causal systemic metabolic effect of Manuka honey’s MGO content .
1. What MGO is and why it matters to metabolism
Methylglyoxal is a small, highly reactive α‑dicarbonyl compound produced endogenously during glycolysis and by sugar autoxidation, and it is one of the most potent glycating agents known — meaning it reacts with proteins, lipids and nucleic acids to create AGEs that alter molecular function and signaling pathways relevant to metabolism . Accumulations of endogenous MGO have been implicated in diabetic complications and vascular dysfunction in experimental literature, and mechanistic reviews link MGO to processes—protein glycation, oxidative stress, inflammation—that can impair insulin action at the cellular level [1].
2. Manuka honey: a unique dietary source of exogenous MGO
Manuka honey concentrates MGO through conversion of nectar dihydroxyacetone during honey maturation, and antibacterial activity is associated with MGO levels above reported thresholds (~150 mg/kg), which is why commercial Manuka products advertise MGO content . This makes Manuka honey an unusual dietary source of an otherwise primarily endogenous reactive aldehyde, raising theoretical questions about whether consuming high‑MGO honey meaningfully increases systemic MGO exposure beyond normal metabolic production .
3. Mechanisms linking MGO to insulin signaling — plausible, documented in vitro and in animals
Mechanistic studies show MGO can form AGEs and trigger oxidative stress and inflammatory signaling that interfere with insulin receptor downstream pathways such as PI3K/Akt, a central axis for glucose uptake and metabolic regulation; these pathways are proposed targets by which honey or its components might modulate glycemia . Animal and cell studies occasionally report that MGO exposure worsens insulin resistance and β‑cell dysfunction, while other reports show antioxidant components of honey may mitigate oxidative damage and improve pancreatic markers in rodent diabetes models — an internally inconsistent preclinical picture [1].
4. Human evidence: scant, inconsistent, and methodologically weak
Clinical data directly tying dietary MGO from Manuka honey to impaired insulin signaling or new insulin resistance in humans are essentially absent: authoritative reviews and commentaries call for randomized controlled trials to assess safety in diabetic populations, and available human reports are small, heterogeneous, or indirect . One small, uncontrolled study reported transient reductions in blood glucose and increased insulin after aerosolized honey exposure in healthy volunteers, but this does not isolate MGO’s role, was not a metabolic challenge trial, and cannot be generalized to oral consumption of high‑MGO Manuka honey . Systematic human measurements of plasma MGO after eating Manuka honey, or insulin signaling assays in people exposed to quantified MGO doses, are not reported in the provided literature .
5. Practical interpretation and research gaps
Taken together, the biochemical plausibility that MGO can perturb insulin signaling is strong based on molecular and animal work, and Manuka honey is a concentrated dietary source of MGO that has raised caution for wound care in diabetics, but there is no robust human evidence that typical dietary Manuka honey consumption produces clinically meaningful insulin resistance or alters insulin signaling pathways systemically [1]. The available sources call explicitly for randomized clinical studies measuring systemic MGO exposure, AGE formation, insulin signaling biomarkers and clinical glycemic endpoints after controlled Manuka honey intake to resolve this question .