Quercetin inhibits glycation better in-vitro than aminoguanidine but likely ineffective at realistic dosing

Over the years clear evidence has been established that the accumulation of Advanced Glycation End Products (AGEs) is associated with chronic diseases like diabetes and Parkinson’s disease. In the recent years the role of AGEs is also more broadly discussed as a contributor to aging. Inhibiting AGE formation or breaking down AGEs is therefore desirable. Quercetin, which is a natural occurring compound, has a good safety profile and could be used on a more continuous basis to suppress glycation. The author supplements with Quercetin and wanted to understand possible anti-glycation benefits. The anti-glycation effect by Quercetin is (partly) attributed to its increased antioxidant capacity and maybe effective particularly during the early stage (amadori) of glycation where free radicals are generated . In this study from 2015 researchers compared the effectiveness of Quercetin to aminoguanidine to inhibit formation of AGEs. Aminoguanidine, was an investigational drug for the treatment of diabetic nephropathy but after failing to meet its end point it is seen as a potential anti-glycation drug. Aminoguanidine comes with concerns about toxicity.

Serum albumin is the most abundant protein in plasma (approx. 50 g/L). It has a wide variety of biochemical, physiological, and pharmacological functions. It constitutes about 50% of the proteins present in the plasma of normal healthy individuals. Because of its long half-life (21 days) and high concentration, serum albumin is highly sensitive to glycation. Other proteins including hemoglobin, insulin and immunoglobulins are affected as well. Glycation also affects long half-life proteins of the extracellular matrix such as collagen, laminin and fibronectin. The glycation process is often associated with oxidation (glycoxidation), which occurs when oxidative reactions affect the early stage of glycation products. Glycation processes also occur with highly reactive carbonyl compounds such as oxoaldehydes (glyoxal, methylglyoxal or 3-deoxyglucosone). It is well established that the methylglyoxal (MG) forms AGEs by reacting with bio-macromolecules such as DNA, proteins and lipoproteins.

The study focused on the inhibition of glycation of serum albumin, as described above the most abundant protein in plasma, by use of quercetin and compared to effectiveness of aminoguanidine.

Early glycation inhibition

Hemoglobin-gluconolactone (= an oxidized analogue of glucose), can react rapidly with hemoglobin within red blood cells and significantly increases HbA1C levels. HbA1C is a subset of glycated hemoglobin. Increased levels means poorer control of blood glucose levels and has been associated with cardiovascular disease, nephro-, neuro and retinopathy. The formation of HbA1c proceeds via a so called Schiff base adduct, or aldimine, followed by the Amadori rearrangement. The test results of the assay showed a marked increase of glycated hemoglobin HbA1c after 20 days of incubation without addition of either quercetin or aminoguanidine. At a concentration level of 10 mM aminoguanidine the formation of AGEs was inhibited by 12.5%. Quercetin at concentrations of 10, 20, 50, 100, 200, and 500μM inhibited the formation of HbA1c by 2.1%, 3.1%, 6.3%, 8.1%, 16.6% and 22.6%, respectively.

Intermediate glycation inhibition

The methylglyoxal-HSA assay showed  that quercetin inhibited MG-mediated HSA glycation: at 10, 100, 200 and 500 μM with 14.7%, 41.1%, 54.4% and 72.1%  respectively. Aminoguanidine at 10 mM inhibited 64.7% of MG mediated HSA glycation.

Advanced stage glycation inhibition

Quercetin inhibited almost 75% of the post-Amadori glycation and AGE product formation in the HSA-glyoxal assay at 500μM. At 10 mM, AG inhibited 67.1% of the fluorescence associated with AGE product formation.

The results indicate that quercetin is a potentially better and a more potent antiglycating agent than aminoguanidine at all stages of glycation without its side effects. This study reported similar inhibition results. But unfortunately from this study it can be roughly estimated that, using FDA conversion rules, oral supplementation with 1 gram of Quercetin in humans would lead to a peak plasma level of 3 μM which according to the in-vitro results above is unlikely to have a meaningful impact considering the strong results were seen at concentrations of 500μM.

2 thoughts on “Quercetin inhibits glycation better in-vitro than aminoguanidine but likely ineffective at realistic dosing

  • November 22, 2016 at 3:15 pm

    Because of the extremely low bioavailability of Quercetin, due to digestive processes, it is better to use EMIQ (Enzymatically Modified Iso-Quercetin) that is purported to have better absorption. I use EnduraQ 100mg, for example. According to pharmacokinetic data, the absorption of EMIQ is up to 40 times greater (Cmax) and ~15-17 times greater (AUC) than that of quercetin and reaches peak levels in the bloodstream in just 15 minutes. Therefore, need for high amounts of normal quercetin, as described in this study referenced to obtain sufficient effect, may be greatly reduced by using EMIQ.


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