What does excess glucose do in our blood that we aren’t really aware about? Do feel free to check out my other article on 10 Nutrients That Support A Healthy Heart while you're at it!
The Maillard reaction is a classic example of what happens when a sugar reacts with a protein. It is purportedly so that:
The Maillard reaction has three stages. First, the carbonyl group of a sugar reacts with an amino group on a protein or amino acid to produce water and an unstable glycosylamine. Then, the glycosylamine undergoes Amadori rearrangements to produce a series of aminoketose compounds. Last, a multitude of molecules, including some with flavor, aroma, and color, are created when the aminoketose compounds undergo a host of further rearrangements, conversions, additions, and polymerizations.
This Maillard reaction is one of the factors that is responsible for the non-enzymatic browning of foods. The slightly browned potato chip that comes out of a freshly opened pack of potato chips? That’s the Maillard reaction right there. Freshly baked brown bread? Roasted brown coffee? Grilled brown steaks? All that browning comes from the Maillard reaction.
The initial step that sets off the Maillard reaction chain is the reaction of a carbonyl group on a sugar molecule reacting with an amino group on a protein or amino acid.
Glucose, for instance, exists as 3 different anomers in equilibrium at pH 7 — α-glucose (37%), β-glucose (0.003%), and γ-glucose (63%). The β-glucose anomer contains the reactive carbonyl group that can react with the amino groups on the protein, which we can also term as an aldehyde.
As these 3 anomers exist in equilibrium, any β-glucose that has reacted with the protein will be replaced by more β-glucose that is converted from α-glucose and γ-glucose. This aldehyde group on glucose can be shown from a simple test involving Fehling’s solution, as shown in the video below:
In the presence of an aldehyde, Fehling’s solution will form a visible brown precipitate (copper metal) from a previously deep blue solution (dissolved copper ions). While fructose is chemically identical to glucose, its structure is different from glucose. It will not be able to cause color changes to Fehling’s solution.
Great. What does this all mean?
It means that glucose can react with other biological agents in our body. As I have explained previously in Type 2 Diabetes — A Case of The Immune System Gone Bad, Too?:
Worse still, this glucose is reactive and can react with other biochemicals in the body in this chemical reaction known as glycation. Glycation is a common thing — most diabetics would have heard of the blood test that measures their HbA1c levels, for instance. What the HbA1c test does is that it determines how much haemoglobin (Hb) protein in our blood has been glycated by glucose into HbA1c. Hb is necessary for transporting oxygen through our blood to our cells — HbA1c cannot do that as effectively.
Essentially, this glycation reaction is a reflection of our body undergoing the Maillard reaction internally. Would it be surprising if diabetics were to develop brown spots on their skin, then? (It could also be a melanin issue related to the tyrosinase enzyme, as I explore in The Science Behind Banana Browning And Parkinson’s Disease.)
The problem is, it doesn’t stop there!
Because while fructose isn’t directly a reducing agent, enzymatic activity in the body will convert it into glyceraldehyde. In any case, glucose can also be converted into glyceraldehyde. Too much glyceraldehyde, if not disposed of via the glycolysis pathway for energy generation, can also be bad for health because of all them reactive aldehyde groups, and more of these aldehyde groups in the body can react with more different biomolecules in the body as well, which results in the development of more advanced Glycation End-products (or AGEs).
There’s your Maillard reaction happening internally.
Therefore, an overconsumption of sugar isn’t really the biggest thing that one ought to be worrying about — it’s about what the sugar actually does in the body that is worrying. More sugar in the blood leads to a greater occurrence of the glycation reaction in our body — and that’s a worrying thing.
The development of these AGEs parallels the damaging activity of 4-hydroxynonenal (4-HNE) that we can see in lipid peroxidation (Lipid Peroxidation and the Omega-3 Fatty Acid). Unfortunately, though, some of these AGEs aren’t just going to stop at being AGEs. Some of them are still reactive and biologically active.
AGEs can bind to AGE Receptors (RAGEs).
Our body also contains RAGEs, or Receptors of AGEs. As it is mentioned in this article, RAGE was discovered as a receptor for advanced glycation endproducts (AGEs), such as carboxymethyl lysine (CML). AGEs, the products of nonenzymatic glycation and oxidation of proteins, form to an accelerated degree in hyperglycemia. AGEs, largely via RAGE, activate signaling mechanisms that cause cell stress, contribute to cellular dysfunction, and damage target organs, leading to complications.
In addition, the
hearts of diabetic mice subjected to ischemia/reperfusion in the isolated perfused mode displayed increased damage as assessed by release of higher levels of lactic dehydrogenase (LDH), reduced ATP levels in the heart, and higher left ventricular developed pressure (LVDP), the latter a marker of cardiac dysfunction, compared to nondiabetic mice, and that in the presence of soluble RAGE or by RAGE deletion, these parameters were greatly improved.
Therefore, the activation of RAGEs by AGEs can directly influence heart issues among diabetics. With reduced ATP levels in the heart, the heart muscle’s ability to generate energy is reduced… wouldn’t that lead to diabetics feeling fatigued more easily, and having much less stamina than a healthy person?
Long term AGE effects in the body
The deleterious effects of AGEs and RAGE activation are highlighted here. The AGEs that accumulate in the body are reactive and will also have the propensity to alter the structure of our extracellular matrices via crosslinking, which makes them stiffer and affects their mechanical properties and functions.
The skin won’t be that supple any more, for instance.
The activation of the RAGEs would also result in the upregulation of pro-inflammatory pathways such as the nuclear factor kappa B (NF-κB) pathway and trigger premature cell apoptosis.
In men, an accumulation of excessive AGEs will also have a negative impact on their sperm and fertility.
The upregulation of pro-inflammatory pathways in the body would also put people at higher risk of health problems such as osteoporosis, osteoarthritis, heart disease, and neurodegenerative disorders.
Should there not be a justified RAGE about AGEs?
Worse still, we are facing a deluge of processed and refined carbohydrate products in the markets today, which further exacerbates the problem of AGEs and RAGEs (The Problem With Excess Sugar Consumption In Our Lives).
But yet most doctors wouldn’t explain glycation to their diabetic patients, most of whom still wouldn’t have a basic understanding of what HbA1c is, let alone an advanced understanding of AGEs and RAGEs!
Do feel free to check out my Patreon article on 10 Nutrients That Support A Healthy Heart too.
This article was originally published on Medium.
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