Methylglyoxal, or MGO, is a reactive chemical compound that forms naturally in all living organisms, including the human body. It is produced during normal metabolic processes and can also be introduced through diet. Its effects depend on its concentration and location. Inside the body, high levels are associated with certain health problems, while in specific foods, it can have other functions entirely.
Formation and Sources of Methylglyoxal
Methylglyoxal (MGO) originates from both internal and external sources. The primary internal, or endogenous, source of MGO is as a natural byproduct of cellular metabolism. Specifically, it forms during glycolysis, the fundamental process cells use to break down glucose for energy.
Exogenous MGO enters the body through the foods and beverages we consume. Significant dietary sources include heat-processed foods where sugars and amino acids have reacted, a process familiar as the Maillard reaction. This means items like coffee, toast, and baked goods contain MGO. Highly processed products with high-fructose corn syrup or caramel coloring also contribute to dietary intake. One of the most concentrated natural sources is Manuka honey, where it develops from a compound in the nectar of the Manuka flower.
The Role of Methylglyoxal in the Body
The primary action of methylglyoxal in the body stems from its high chemical reactivity. It readily binds to biological molecules, including proteins, lipids, and nucleic acids like DNA. This chemical bonding process is a non-enzymatic reaction known as glycation. MGO is a potent glycotoxin because of this ability to modify the structure and function of cellular components.
This process of glycation leads to the formation of complex, stable structures called Advanced Glycation End-products, or AGEs. The creation of AGEs permanently alters the body’s molecular machinery, similar to how heating caramelizes sugar. When MGO reacts with proteins, it can cause them to become cross-linked and dysfunctional. This modification impairs protein function and can trigger inflammation and oxidative stress.
These MGO-derived AGEs disrupt normal cellular behavior in two main ways. First, they can directly damage tissues by altering structural proteins that provide integrity and elasticity, such as collagen in blood vessel walls. Secondly, AGEs can interact with specific receptors on cell surfaces, most notably the Receptor for Advanced Glycation End-products (RAGE), which triggers a cascade of intracellular signals that promote inflammation and further oxidative stress.
Health Implications and Disease Association
The accumulation of AGEs from MGO is linked to several chronic health conditions. This connection is particularly strong in diabetes mellitus, where higher blood glucose concentrations lead to increased MGO production. This leads to diabetic complications, including nerve damage (neuropathy), kidney disease (nephropathy), and eye damage (retinopathy). MGO can directly damage nerve endings, contributing to the chronic pain experienced in diabetic neuropathy.
Beyond diabetes, MGO-driven AGE formation contributes to cardiovascular diseases. When MGO modifies low-density lipoprotein (LDL) cholesterol, it accelerates the process of atherogenesis, the buildup of plaques in arteries. This glycation also affects structural proteins in blood vessel walls, leading to vascular stiffness and increased risk of hypertension.
Emerging research also implicates MGO and AGEs in the aging process and in neurodegenerative disorders. The gradual accumulation of AGE-related damage over a lifetime contributes to the functional decline of tissues associated with aging. In the context of brain health, these compounds have been linked to conditions like Alzheimer’s disease, where they can modify proteins and contribute to the formation of plaques and tangles characteristic of the disease.
The Body’s Detoxification System
The body has an efficient and dedicated system to manage and neutralize methylglyoxal. This detoxification pathway is known as the glyoxalase system, and it acts as a cellular “cleanup crew,” preventing MGO from accumulating to harmful levels. The system relies primarily on two enzymes working in sequence: Glyoxalase I (Glo1) and Glyoxalase II (Glo2).
The detoxification process begins when Glo1 identifies and converts MGO into a less reactive compound. This initial step requires the presence of glutathione, an important antioxidant molecule found in cells. Glo2 then completes the neutralization process, transforming the intermediate into D-lactate, a harmless substance that can be further metabolized or excreted by the body.
This glyoxalase system is active in all cells. Problems arise only when the rate of MGO production surpasses the capacity of this detoxification pathway. This imbalance can occur due to factors like persistently high blood sugar or genetic variations that impair the efficiency of the glyoxalase enzymes.
Methylglyoxal in Manuka Honey
While high levels of methylglyoxal inside the body can be problematic, its presence in Manuka honey is responsible for the honey’s potent antibacterial activity. The MGO in Manuka honey is not derived from the bees themselves but develops after the honey is produced. It forms from a precursor compound called dihydroxyacetone (DHA), which is abundant in the nectar of the Manuka tree flower.
This high MGO concentration gives Manuka honey a non-peroxide antibacterial effect that sets it apart from other types of honey. It is effective against a wide range of bacteria, including antibiotic-resistant strains like Staphylococcus aureus (S. aureus). The MGO works by disrupting bacterial cell walls and inhibiting their ability to function and replicate, which also helps prevent the formation of bacterial biofilms.
Because of this specific action, the MGO level is the primary marker used to grade the potency and quality of medical-grade Manuka honey. This honey is often used topically for applications such as wound dressings and skincare products.