Grape seed extract and your eyes: What does the research say?

Finlay Yates

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Grapes are a nutritious and delicious treat option for part of a balanced diet. Their seeds are high in antioxidants, and recent research suggests supplements formulated from grape seeds might help protect eyes from conditions related to ageing, UV damage, and pollutant exposure. With the research in its infancy, it’s easy to be sceptical of these claims. We’ve analysed the latest research on grape seed extract so you can decide whether it could make a difference to your eye health. 

Introduction

Grapes are a commonly consumed fruit in much of the world, but if you take a grape seed and purify it to a high concentration, you end up with a mixture of powerful antioxidants. Recently, grape seed extract has been investigated for its potential to prevent an array of oxidative damage-related health conditions, often chronic diseases that become debilitating with age. Research is in its infancy, but there’s some claims that grape seed extract could help protect against eye diseases. We’ve picked out the key scientific papers on the topic to analyse these claims.

What is grape seed extract?


Grape seed extract is the concentrated contents of grape seed, and is rich in antioxidants . When people talk about grape seed extract, they’re usually referring to proanthocyanidins, a class of chemical which is abundant in several kinds of plants. Proanthocyanidins are polymers - molecular chains containing repeating units - of flavonoids, a group of powerful antioxidants which includes vitamin B2.


Proanthocyanidins are metabolised in the body but only around 5-10% of proanthocyanidins in grape seed extract can be absorbed. This is because most proanthocyanidins are too long, and only chains of 2-4 flavonoids can be absorbed. Nevertheless, these proanthocyanidins have been shown to be better antioxidants than compounds like vitamin C and vitamin E


This has led to a lot of excitement surrounding grape seed extract, with claims including the ability to improve atherosclerosis, high cholesterol, prevent cognitive decline, and protect eyes from several age-related diseases .


How can so many different claims be made? It’s due to the broad effect oxidative stress has on your entire body, and therefore the important role antioxidants have in regards to your health. 

Why do we need antioxidants like proanthocyanidins?

The body’s cells are constantly producing highly reactive chemicals called reactive oxygen species (ROS) as a byproduct of normal metabolism. Antioxidants keep ROS levels low by neutralising them in a controlled manner. When ROS levels get too high to be managed by antioxidants, they cause oxidative stress, which is when ROS start to react with and damage important cellular structures such as DNA, proteins and cell membranes, eventually leading to apoptosis, which is controlled cell death. This process also leads to inflammation in the affected area.


Lifestyle choices impact the amount of oxidative stress in the body. Smoking and alcohol consumption, as well as a high-fat diet, all increase ROS production in cells and studies have measured higher markers of oxidative stress all over the body as a result. Antioxidant consumption is correlated with reduced oxidative stress markers.


In our eyes, antioxidants are even more important, since constant exposure to electromagnetic radiation, particularly higher energy forms such as blue light and UV, can also induce ROS production. 


Several eye conditions have been shown to be correlated with oxidative stress, including glaucoma, macular degeneration, cataracts, floaters, among many others. The risk of these diseases also increases with age, reflecting an accumulation of oxidative damage due to constant UV and blue light exposure throughout a lifetime, alongside a gradual decline in antioxidants in the eye with age.


Increasing antioxidant intake through diet or supplementation has been suggested to protect against these diseases. Proanthocyanidins directly react with ROS to neutralise them, and have been shown to be better ROS scavengers than well-known antioxidants such as vitamin C


They also have been shown to induce the production of antioxidant proteins and signals that prevent cell death such as the MAP kinase pathway or the Nrf2 pathway, both of which are present in cells and induce the production of antioxidant proteins as well as proteins that repair oxidative damage (e.g. by repairing damage to DNA). 


However, this doesn’t necessarily mean that proanthocyanidins have a protective effect against these diseases. Before looking at the existing studies on its potential as a preventative antioxidant in the eye, we need to understand how proanthocyanidins are absorbed and whether they reach the eye at all.



How is Grape Seed Extract Absorbed From Your Diet?

Not that much is known about how proanthocyanidins are absorbed from the diet. We know that only around 5-10% of proanthocyanidins from plant extracts can be absorbed in the gut, since most are too long. 


The specific transporters haven’t been identified, but the transport is thought to be passive (i.e. no energy is used to transport proanthocyanidins into the body), meaning absorption efficiency can only reach a maximum of 50%. Once inside the body, proanthocyanidins are often metabolised into various molecules. There is no direct evidence that proanthocyanidins are transported to the eye, and little is understood about its distribution throughout the body. 


Transport to the eye is not like other organs in the body, since a selective barrier called the blood-retina barrier prevents larger molecules from getting in. However, studies on rats have found that the proanthocyanidins and their metabolites can pass through the blood-brain barrier, which has similar permeability to the blood-retina barrier. Because of this, some studies should be taken with a grain of salt, as the question remains whether proanthocyanidins can make it to the eyes in the first place.

Does it Really Work?

Although there is a breadth of research regarding grape seed extract’s potential benefits all over the body, most of this research targeting the eye is still in its early stages with very few studies beyond cells and animal models. Because of this, it’s impossible to confidently assess whether proanthocyanidins have any benefits for your eyes. However, we can still examine the existing evidence and you can decide for yourself whether you are convinced. We’ll look at studies on glaucoma, diabetic retinopathy, macular degeneration, cataracts, and floaters.

Glaucoma

Glaucoma is the most  common cause of irreversible blindness worldwide. It is caused by oxidative damage to the trabecular meshwork, a filter of collagen towards the front of the eye through which liquid inside the eye (called aqueous humour) drains. ROS react with the meshwork and the cells that produce it, causing the collagen fibres to become too dense, limiting aqueous humour outflow. Pressure builds up inside the eye causing cells in the optic nerve to die


It’s this damage that is irreversible as the optic nerve cannot regenerate. The risk of glaucoma increases with age, consistent with the accumulation of oxidative stress over time, and the reduced antioxidant capacity as we get older. But could proanthocyanidins help prevent this damage accumulating?


Tests on cell lines of retinal ganglions (i.e. cells in the optic nerve) have shown a potential of proanthocyanidins to  reduce oxidative stress. These cells in isolation were exposed to ROS and subsequently treated with proanthocyanidins. Not only was there a decrease in oxidative stress in the cells treated, but they also saw decreases in proteins that signal to the cell to self-destruct, and an increase in signals that prolong cell lifespan. 


These results suggest proanthocyanidins could prevent retinal ganglion death that would otherwise arise from oxidative damage to the trabecular meshwork, reducing the risk of glaucoma. However, without any studies on whether proanthocyanidins reach the optic nerve in the first place, it’s difficult to assess the value of studies on cells in isolation.


Studies on animal models have also been carried out. Mice with glaucoma were fed with grape seed extract and compared to a regular diet, with those fed grape seed extract showing reduced pressure in the eye and increased retinal ganglion survival. 


These are more promising results as they demonstrate the ability for proanthocyanidins in diet (rather than direct application to cells) to slow glaucoma progression. However, these were carried out in mice and the same results might not necessarily be seen in humans, since our metabolism differs. It’s also difficult to assess an effective dose from animal trials alone


Supplements often vary in dosage, but doses as high as 2,500mg/day for four weeks have been tested without showing toxicity, and lower doses have been confirmed safe for as long as 11 months . Without clinical trials in humans, we still can’t be certain of the impact proanthocyanidins would have on glaucoma. These results are promising nevertheless.

Diabetic Retinopathy

In developed countries, diabetic retinopathy is the main cause of vision loss in working-age adults. It results from uncontrolled blood sugar levels as a result of diabetes, which then increases ROS production in the eye. Increased glucose has further impacts, as free glucose molecules can react with and damage proteins in a process called glycation. 


Glycation and oxidative damage to blood vessels supplying the retina deprives the retina of nutrients, leading to retinal cell death. High glucose levels are also a signal to generate new blood vessels, but in diabetes this leads to overproduction of small, fragile blood vessels that leak solid lipid and protein fragments in the eye which can sometimes obstruct vision. In theory, antioxidants can help protect against diabetic retinopathy.


Studies on diabetic rats have been promising. One experiment found that rats with diabetic retinopathy treated with grape seed extract had reduced oxidative damage and increased retinal cell survival. This wasn’t strictly due to its antioxidant activity - the researchers found proanthocyanidins activated a protein called Nrf2, which leads to several antioxidant proteins being synthesised. 


Another study found that diabetic rats treated with grape seed extract saw lower levels of Muller cells in the optic nerve. Muller cells are responsible for increasing blood vessel synthesis in response to glucose and causing inflammation, so proanthocyanidins could prevent overproduction of blood vessels, and therefore help sustain blood supply to the retina.


An early clinical trial has been carried out on humans. 124 participants with non-proliferative diabetic retinopathy were included, with the trial group receiving 150mg grape seed extract daily. The study found grape seed extract more effective than both a placebo and calcium dobesilate (the current drug for treating diabetic retinopathy) at reducing solid lipid and protein which leaks from blood vessels. 


However, there was no significant conclusion regarding the progression of diabetic retinopathy, which is more important to eye health than the presence of solids in vision. It’s nevertheless a promising early trial, and studies on patients with proliferative (i.e. worsening) diabetic retinopathy could determine whether grape seed extract could replace calcium dobesilate.

Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of vision loss in developed countries and results from permanent damage to photoreceptor cells at the centre of the retina. Photoreceptors are constantly being replaced and recycled due to the amount of high-energy radiation they receive, and this is carried out by the retinal pigmented epithelium (RPE)


AMD is often found in patients with a damaged RPE, which means photoreceptors cannot be recycled, so the retina deteriorates. Both the retina and RPE have high metabolic activity, meaning they are prone to high ROS levels and oxidative damage, with sufferers of AMD showing increased levels of biomarkers of oxidative stress; AMD is correlated with factors that increase oxidative damage such as ageing, smoking, and poor diet.


Several antioxidants have been investigated for their potential in preventing AMD, but proanthocyanidins are only just starting to be examined. In isolated RPE cell lines, treatment with proanthocyanidins have been shown to reduce cell senescence, which is when the cells can no longer reproduce. 


Avoiding senescence means the RPE can regenerate, and in mice, AMD has been improved by targeting and removing senescent RPE cells. As before, these data are very limited in not being reproduced in human trials, but they suggest potential for further study.

Cataracts

Cataracts is the clouding of the lens so that it becomes opaque, and is the leading cause of blindness in low and middle income countries, with an estimated 95 million people affected by the condition. 


Cataracts are caused by crystallins, proteins that normally have a specific arrangement that makes the lens transparent, become damaged and clump together irregularly. This can occur when ROS (primarily generated by UV, blue light and pollutant exposure) react with crystallins and disrupt them. Antioxidants have been investigated for the potential to mitigate damage to crystallins and prevent cataracts.


Again, studies are limited to cells and animal models. In isolated lens epithelial cells exposed to high levels of ROS, proanthocyanidins have been shown to reduce oxidative damage, not only by reacting with ROS but by suppressing oxidative and inflammatory signals. Rats have also been injected with grape seed extract and found to have lower rates and severity of cataracts. Injection rather than receiving proanthocyanidins through diet might make these results less likely to transfer to humans, since injection can achieve much higher concentrations than consumption. 


In any case, human clinical trials are necessary to conclude whether proanthocyanidins can protect against cataracts in humans.

Floaters

Floaters are dark squiggly lines and dots that float in your vision, and whilst they are not as serious as the previously discussed diseases, they are still a common condition that can have detrimental effects to wellbeing


Floaters are thought to mainly be caused by oxidative damage to the vitreous, a gel-like structure that fills the eye. The vitreous consists of a network of collagen (a fibrous protein) and hyaluronan (a fibrous carbohydrate), and when these react with ROS they can clump together into opaque blobs that we see as floaters. The vitreous is full of antioxidants that help protect against this process, but the levels of these antioxidants decreases as we age .


Floaters are a fairly neglected area of research, but one early clinical trial on 61 patients over 6 months provided one group of participants with a supplement containing several antioxidants, including grape seed extract. 


Quality of life questionnaires as well as scans on the eyes of participants found a significant improvement for those taking the supplement. 77% of participants in the trial group said they were happy with the supplement as a treatment for floaters, compared to just 22% on the placebo. 


Whilst promising, this is a small sample size that looked at several antioxidants at once, so it cannot be concluded whether grape seed extract was making the difference. Nevertheless, it supports the idea that dietary supplementation with antioxidants might prevent the development of floaters.

Who Shouldn't Take Grape Seed Extract?


If the above evidence has made you want to try proanthocyanidins supplements, you should consider whether any of the following applies to you. If so, taking grape seed extract may be dangerous:

  • Currently taking blood-thinning medication, such as aspirin and warfarin , or are prone to bleeding, or are going into surgery, since grape seed extract may also be blood-thinning. Taking with other blood-thinners could lead to complications with bleeding.

  • Have high blood pressure and are already taking vitamin C, since vitamin C can increase blood pressure further. Taking both may lead to dangerously high blood pressure.

  • Pregnant, since no trials have been performed on pregnant individuals, and drugs can interact quite differently with pregnant people.


Otherwise, daily grape seed extract supplementation has been tested for up to 11 months and has been tolerated well, so general consensus is that it’s safe. However, you should always consult your doctor before taking a new supplement, particularly if you are on any medication or have any health condition.

Conclusion

Grape seed extract is a naturally sourced, antioxidant rich supplement that is generally considered safe for human consumption, at least below 2,500mg / day


The active ingredients are proanthocyanidins, which are chains of molecules broken down into smaller chains before being absorbed in the gut. From here they are thought to travel all over the body, although it’s unclear to what extent they are deposited in the eye, if they are at all. They may also be metabolised into other active compounds which may have other beneficial effects across the body.


Once they reach their destination, proanthocyanidins work by directly neutralising ROS, highly reactive chemicals produced as a byproduct of cellular metabolism, or as a product of high energy radiation (e.g. UV). 


Proanathocyanidins also activate signalling pathways that further protect against oxidative damage and repair cellular machinery affected by ROS.


Grape seed extract might protect against eye conditions that are attributed to oxidative damage. Proanthocyanidins have been shown to protect retinal ganglions in the optic nerve, both in isolated cell lines and in rodents. Optic nerve health is vital to preventing glaucoma, a major cause of irreversible blindness. 


Similar trials have shown the potential for proanthocyanidins to protect against diabetic retinopathy and cataracts. However, no human trials have repeated these findings.


The only human trial using grape seed extract to treat any eye condition was a small preliminary trial on individuals with floaters. The supplement was shown to be effective in reducing a small sample size’s severity of floaters, but this supplement also contained other antioxidants, so it’s difficult to be confident in proanthocyanidins contribution to these results.


Research is still in its early days, but these trials suggest a potential for protection against oxidative stress in the eyes that warrants further investigation with human trials. 


Other human trials have demonstrated a broad benefit to grape seed extract, although there is the question of whether equally effective antioxidants could be obtained through a balanced diet. It’s up to you to decide whether supplementation is right for you, and you should always consult a doctor before taking a new supplement.

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