Glycation and your eye health: How sugar could be damaging your vision

Glycation is a non-enzymatic chemical reaction, meaning it occurs spontaneously without the help of proteins. These reactions lead to the linking of proteins, lipids, or DNA with free sugar molecules such as glucose or fructose, which produces glycation intermediates chemically known as Amadori products. These intermediates can then undergo further irreversible modifications to form advanced glycation end products (AGEs).     

There are two types of AGEs: endogenous and exogenous. 

• Endogenous AGEs are produced within our bodies, with the glycation of long-lasting proteins such as collagen coming into contact with free sugars contributing to this.
• Exogenous AGEs are AGEs which we take in from external sources, principally coming from food, and can contribute significantly to the AGE pool.

The levels of AGEs present in food is dependent on both the type of food and the methods of preparation used. Animal-derived foods that are high in fat and protein (e.g., red meat, eggs, and cheeses) are generally AGE-rich compared to carbohydrate-rich foods such as vegetables and whole grains. 

As our lifestyles have evolved to suit modern life, the way we prepare food has changed, and our reliance on pre-prepared, processed food has increased. These processed foods contain much higher levels of AGEs compared to freshly home-cooked meals. 

AGE-rich foods are also prone to the formation of new AGEs during cooking. Food cooked with dry, high heat tends to contain more AGEs as these conditions promote glycation reactions to a greater extent than methods such as boiling or stewing. 

Environmental factors, such as UV irradiation of skin cells  or smoking, can also contribute to glycation and the accumulation of AGEs. Tobacco smoke contains compounds which can react with proteins to form AGEs, while both UV exposure and smoking can promote conditions which increase AGE formation.

So now we know what glycation and AGEs are, how exactly do they affect our health?

There are three main ways the process of glycation can affect our bodies:

• It can impair the elasticity of tissues such as blood vessels, skin, and tendons
• Lead to a loss of protein function within cells 
• Accumulation of AGEs can trigger oxidative stress and inflammation

The formation of AGEs is promoted by elevated oxidative stress, which is when there is an imbalance between the formation of reactive oxygen species and antioxidant defences. However, AGEs themselves exacerbate further oxidative stress and also induce inflammation. 

This occurs due to the interaction of AGEs with their receptors (RAGE), which activates pro-inflammatory signalling pathways. The excessive oxidative and inflammatory stress caused by AGEs can contribute to the exacerbation of AGE-related illnesses such as Alzheimer’s Disease. To learn more about oxidative stress and its impact on our health and eyes, check out this article. 

Ageing of tissues can occur due to glycation. In the skin, the accumulation of AGEs results in wrinkles, loss of elasticity, and dullness, some of the main mechanisms of skin ageing. This primarily occurs as a result of cross-linking of the proteins in the skin such as collagen and elastin, as well as AGE-induced oxidative stress. 

Unfortunately, our eyes are not excluded from the effects of glycation. In fact, the relatively low occurrence of cell proliferation in tissues in the eye can make them more susceptible to AGE-associated damage, as there are fewer opportunities for the dilution of AGEs or damage repair. 

The vitreous humour is a clear, gel-like substance that fills the space between the retina and the lens in the eye. Collagen and hyaluronic acid are the major structural molecules of the vitreous. The glycation and subsequent crosslinking of collagen fibrils causes collagen to dissociate from hyaluronic acid, which destabilises the vitreous gel structure and can cause eye floaters. 

Similar to the vitreous, the glycation and crosslinking of collagen in the cornea can lead to the thickening of the cornea and contribute to keratopathy (corneal disease), particularly in diabetics. 

In the lens, extensive research has shown that glycation can result in the formation of cataracts. The glycation and crosslinking of lens crystallin proteins results in their aggregation and insolubility, clouding the lens and blocking light.

The accumulation of AGEs in parts of the retina has also been associated with the development and progression of conditions such as diabetic retinopathy and age-related macular degradation, which can significantly impair an individual’s sight, and in the case of retinopathy lead to complete loss of vision.

The above information suggests we should look for ways to minimise the amount of glycation and AGEs we encounter. There has been extensive research and clinical trials into AGE inhibitors and AGE “breakers” (compounds which can reverse glycation reactions) as potential therapeutics, but at this stage there are no approved drugs to treat AGE-induced conditions. 

The compound carnosine has gained particular attention for its anti-glycating properties and has even been used as an ingredient in skin care products to help combat ageing. However, there are still few human studies to support the effectiveness of this.

Theia Bio’s supplement Clearer contains carefully selected micronutrients which have specific antioxidative and antiglycation activities, so can be an effective way to reduce glycation. For example, lysine has been shown to prevent collagen glycation by combining with free sugars thus preventing them from reacting with various proteins. Zinc too can prevent glycation and AGE-induced oxidative stress, and has been hypothesised to also combine with either reacting sugars or potential glycation sites on proteins to prevent glycation reactions from occurring. Grape seed extracts which contain proanthocyanidins are also used. These are potent antioxidants that can modulate oxidative stress induced by AGEs and their receptors. 

Other than supplementation, simple lifestyle changes are arguably the easiest and most effective way to protect ourselves from glycation, so here are 7 lifestyle tips which can help us to reduce it:

Using methods such as stewing, boiling, and steaming rather than dry, high heat can significantly reduce the amount of glycation during cooking and AGEs in your meals. 

Cooking at lower temperatures, with moist heat, for shorter periods of time all reduce AGE formation during cooking. Slow cookers are also a very healthy way of preparing your meals.

As well as limiting the amount of sugar we take in, we can also reduce the amount of dietary AGEs we consume.

Animal and human studies have suggested that limiting dietary AGEs helps protect against many diseases and premature ageing. In a 1-year trial which investigated the effects of a low-AGE diet in 138 people with obesity, the researchers saw an increase in insulin sensitivity, a modest decrease in body weight, and lower levels of AGEs, oxidative stress, and inflammation.

While there are no current guidelines on optimal intake of AGEs, you can use useful guides such as this blog, which details the levels of AGEs in common foods, as well as comparing AGE levels in foods across different cooking methods, to allow you to make appropriate changes to reduce AGEs.

Choosing whole grains, vegetables, and fruits more regularly over foods such as red meat, fried eggs and butter will help make a significant reduction in your dietary AGEs.

A particular consideration for new parents is that depending on the type of formula, baby formula milk can have up to 670-fold greater AGE content compared to human breast milk.  Therefore, breast-feeding, with either the mother’s own milk or donor milk, is recommended.

Studies have shown that natural antioxidants can reduce AGE formation. 

For example, curcumin which is an antioxidant compound found in turmeric can inhibit AGE formation, while vitamins A, C and E have all been shown to have anti-glycation properties.

Therefore, incorporating more types of fruit and veg, as well as some herbs and spices can help to combat the harmful effects of AGEs and glycation.

Regular exercise is extremely important for your health in general but has also been shown to reduce the level of AGEs in the body. Physical activity also lowers your blood sugar levels and improves your glycaemic control, which will also help reduce the amount of glycation occurring in your body. 

Tobacco smoke has been identified as an exogenous source of AGEs, so quitting smoking can help to reduce your AGE intake, as well as benefiting your cardiovascular health. Speaking to your doctor can help you start your journey to becoming smoke free.    

Modern diets, high in sugars and processed foods, have contributed significantly to higher levels of AGEs in our bodies. 

Glycation and high amounts of AGEs have been linked to many different chronic diseases, affecting organs throughout the body. Our eyes in particular are especially vulnerable to the damage which can occur as a result of glycation. 

All of this means it’s extremely important that we consider ways we can reduce glycation. While there are yet to be any approved medicines, simply making adjustments to our lifestyles can be an effective way to minimise glycation and its effects.

By altering the food choices we make, the methods we use to prepare our meals, and maintaining an active lifestyle - among other changes - we can protect our health and effectively combat the damaging effects glycation can have on our bodies.