Zinc and Eye Health: Can it Prevent Disease?

Zinc is found throughout the body and takes on an array of roles due to its biochemical versatility. 

Zinc is estimated to be a core feature of around 10% of all proteins, including in some enzymes, meaning it is essential for important reactions to take place in cells. It can also stabilise the structure of some proteins, including many DNA-binding proteins which control which genes get switched on and off, making it an important nutrient in human development. 

It’s also been shown to support the immune system in the development and growth of immune cells, and is essential for antibody production and for signalling between white blood cells.

The average adult needs 9 - 11mg of zinc each day in order for zinc to fulfil each of these roles, with foods such as meat, sea food, and cereals having the highest zinc content. Whilst zinc deficiency is relatively rare in developed countries, 15% of adults in the US don’t meet their daily recommended intake, with certain demographics such as vegetarians, vegans, alcoholics and the elderly being at higher risk of zinc deficiency - we’ll discuss why later. 

Globally, 17% of people are estimated to be zinc deficient. Those suffering with zinc deficiency will experience a range of symptoms which include psychological changes, loss of taste and smell, increased infant mortality in pregnant individuals, and in children can increase the risk of illness and cause developmental issues. 

The majority of zinc is stored in organs, with 86% by mass found in skeletal muscle and bone. Whilst the eyes contain only a small portion of total body zinc (<0.01%), they contain tissues with some of the highest concentrations of zinc. This suggests that zinc is pretty important for eye health, but what does it actually do?

Zinc is an important antioxidant in the eye. Antioxidants protect cells from reactive oxygen species (ROS), which are highly reactive chemicals produced as a byproduct of normal metabolism, and can destructively react with important biological molecules such as DNA, proteins, and cell membranes.

Eyes are unique among our organs in that they are constantly bombarded with electromagnetic radiation (i.e. light). Shorter wavelengths such as blue and UV light can induce ROS formation due to their high energy. Antioxidant concentrations are high in our eyes in order to counteract this process and limit oxidative damage.

Whilst zinc itself protects a select few chemical groups from ROS, it has a more broad antioxidant effect due to forming a core part of the enzyme superoxide dismutase, which converts harmful ROS to less reactive chemicals. Zinc induces the production of antioxidant proteins such as metallothionein, which can bind ROS and reverse their formation. Zinc also induces the production of glutathione, which is required to regenerate antioxidants including metallothionein.

Zinc has other important functions in the eye beyond its role as an antioxidant. Zinc is an essential component of enzymes involved in the production of retinaldehyde, the pigment in receptors in the retina responsible for detecting light. Due to the high amounts of light that the retina is exposed to each day, light receptors are constantly under repair by the retinal pigmented epithelium (RPE). This means the RPE is constantly recycling retinaldehyde back into photoreceptors, which is why the RPE has the highest concentration of zinc anywhere in the body. 

Other parts of the eye, such as the retina, the choroid (which supplies blood to some parts of the eye), the vitreous (a gel which fills the eye), and the iris (the coloured part of eyes which controls how big the pupil is), also have high concentrations of zinc. The lens and cornea, however, have much lower concentrations.

Oxidative damage to the eyes is linked to several eye conditions varying in severity, such as age-related macular degeneration, cataracts, and eye floaters. Many of these diseases are correlated with age, and it has been shown that antioxidant levels decrease in the eye as you age, highlighting the importance of maintaining a healthy intake of zinc. Furthermore, several studies have investigated whether supplementing zinc intake beyond the minimum daily requirements could have a protective or even reversing effect against these diseases. Is there a medical benefit to taking zinc supplements?

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. AMD is often found in patients with damaged retinal pigment epithelium (RPE), meaning photoreceptors cannot be recycled and replaced, so damage accumulates on the retina. 

The retina and RPE are both highly metabolically active, meaning they produce high quantities of ROS which can lead to oxidative damage if there are not sufficient levels of antioxidants. 

UV and other high-energy electromagnetic radiation can induce further ROS production but most harmful radiation is filtered by other structures before reaching the retina. Sufferers of AMD show increased levels of biomarkers of oxidative stress, and AMD is correlated with factors that increase oxidative damage such as ageing, smoking, and poor diet, all showing AMD is linked to oxidative damage. Zinc’s role as an antioxidant and in catalysing the recycling of retinaldehyde has led to investigation into its potential to prevent AMD.

The data on zinc intake and AMD seems pretty convincing. In the Netherlands, one study on over 4,000 adults who self-reported their diet over 8 years found that zinc intake was inversely correlated with risk of AMD. 

A similar Australian study on over 2,000 participants observed across an entire decade found that those consuming 15.6mg of zinc a day decreased the risk of AMD by 44% compared to those who had an average zinc consumption.

Clinical trials have built on these observations. A large-scale study in the US known as the Age-Related Eye Disease Studies (AREDS) observed over 4,000 participants across, on average, 6.3 years. 

The study provided one group of participants with a mixture of antioxidants including 500mg vitamin C, 200IU vitamin E, 15mg beta-carotene, 2mg copper, and 80mg zinc to be taken daily. The study found this decreased the risk of AMD development or progression by 25% compared to those taking a placebo pill. The same researchers developed on their findings over a further 5 years of study with AREDS2, providing some participants with less zinc, and some with no zinc at all. Zinc was found to significantly lower the risk of AMD when compared to the same antioxidant formula lacking zinc, and only 25mg/day was required to see that protection. 

Research has continued to be published supporting this conclusion; a paper evaluating 5 studies on zinc’s effect on AMD found that zinc has consistently been proven to significantly protect eyes against AMD. 

Cataracts is a condition which affects the lens of the eye, and is linked to oxidative damage which causes the lens to become cloudy and opaque. A healthy lens is formed of crystallins, proteins which arrange in a regular pattern at the molecular level so that the lens is transparent. 

Oxidative damage to crystallins is thought to cause them to destabilise and become less regularly arranged, clouding the lens. Unlike in the retina, the main cause of ROS production at the lens is light and UV exposure. A solution called the aqueous humour constantly flows over the lens to supply it with nutrients and antioxidants, including high concentrations of zinc. Because of this, there has been some investigation into whether zinc could provide protection against the development of cataracts.

The AREDS and AREDS2 projects which found zinc could protect against AMD also studied its impact on other eye conditions. They found that zinc supplementation had no significant effect on the risk of developing cataracts. However, some studies have suggested that not getting enough zinc could increase the risk of cataracts. 

One study on trout found that zinc deficiency increased the risk of developing cataracts, and more importantly, humans suffering from acrodermatitis enteropathica, a disease which prevents absorption of zinc from the diet and affects zinc metabolism, have a much higher rate of cataracts. Whilst clinical evidence is lacking, it may be that low zinc levels in your diet could increase your risk of cataracts, even if taking additional zinc beyond the daily minimum requirement won’t protect you further.

In developed countries, diabetic retinopathy is the main cause of vision loss in working-age adults. It is caused by high blood sugar levels resulting from a lack of blood sugar control, which then leads to increased ROS production. 

Sugar molecules when too high a concentration can also react with proteins in a similarly damaging process called glycation. High glucose concentration also activates the polyol pathway, a set of reactions whose products increase glycation and can also cause water to flood into cells, damaging them. Oxidative stress and glycation damage the blood vessels which supply the retina, leading to retinal damage. A protein called protein kinase C is also activated by high blood sugar and can cause weakened blood vessel walls. Zinc not only protects certain chemical groups from ROS, but also from glycation. 

Zinc’s antioxidant and antiglycation effects, and proven role in protecting against retinal damage in AMD has led to some research on whether it could be similarly used to prevent diabetic retinopathy.

One systematic review compiling studies which in total covered over 250,000 participants found that, compared to other antioxidants, zinc was the most strongly correlated with decreased oxidative damage, whilst oxidative damage was closely related to instances of diabetic retinopathy. 

Early clinical data shows some promise. Several small studies have found that supplementation with zinc actually decreases blood sugar levels and increases sensitivity to insulin, a hormone which controls blood sugar levels. Another study on 60 patients with different severities of diabetic retinopathy found that zinc levels were correlated with the progression of retinopathy. 

These results all point to the use of zinc to help protect your eyes against diabetic retinopathy, although this idea has yet to be demonstrated in a full-scale clinical trial over many years, such as the one used in the study of AMD. Such a study would allow a more definitive conclusion as to whether it’s worth increasing zinc intake to help with diabetic retinopathy.

Floaters are dark shapes and lines which float around your vision, and are a less debilitating but still frustrating condition linked to oxidative damage. They are usually more noticeable against bright backgrounds such as digital screens or a clear sky. 

Floaters are thought to be caused by oxidative damage to the vitreous, a gel-like substance made of collagen (a protein) and hyaluronan (a carbohydrate). 

The vitreous fills the centre of the eye and is usually transparent, but when ROS react with collagen they can cause it to dissociate from hyaluronan and clump together in opaque blobs which we see as floaters. In the vitreous, zinc may protect collagen from oxidation and even glycation, and zinc-induced antioxidants such as superoxide dismutase and metallothionein would decrease ROS concentration; together these would protect collagen from dissociation from hyaluronan. 

Zinc is found at a high concentration in the vitreous and so is metallothionein, and so it has been suggested that zinc may protect our eyes from floater formation.

Clinical research into floaters is in its early days. One study in Ireland looked at 61 participants over 6 months, half of them taking a supplement containing several antioxidants, including 5mg zinc. The study used quality of life questionnaires as well as eye scans to determine the amount and severity of floaters in the participants’ eyes and found that 77% of individuals taking the supplement saw a decrease in floaters, compared to just 23% on the placebo pill. With such a small sample size, these results are only preliminary, and because the supplement was a mixture of different antioxidants there is no way of evaluating zinc’s individual contribution to the reduction in floaters. Nevertheless, it’s reason for further study on zinc’s potential to protect against floaters.

So, not getting enough zinc might be an important risk factor for the development of quite a few eye conditions, and increasing zinc intake beyond the minimum requirements has benefits in protecting against some eye conditions. But if you take zinc supplements or increase your dietary intake of zinc, how does it actually end up in your eyes?

Zinc is absorbed into the body through the small intestines and its transport uses two families of proteins: ZIPs, which generally transport zinc into cells, and ZnTs, which generally transport zinc out of cells, although there are exceptions. In the small intestines, enzymes break down proteins associated with zinc so that zinc is free to be taken up by transporter proteins.

ZIPs transport zinc into enterocytes, the cells that line the wall of the intestines, and ZnTs transport zinc from enterocytes into the blood. However, some of these transporters are bidirectional, meaning some zinc is excreted from the blood into the intestines, and some of that reabsorbed. This is an essential part of controlling zinc levels in the body, as excess zinc can be excreted in poo.

Once in the blood, zinc has different methods of reaching different tissues in the eye. In order to reach the retina, zinc crosses the blood-retina barrier, which only allows certain small molecules through. The retinal pigmented epithelium (RPE) has ZIPs to take up zinc from blood and ZnTs to transport zinc to the retina, although much of the zinc taken up by the RPE is incorporated into enzymes used to provide retinaldehyde to the retina.

Evidence from studies on fish shows that increasing dietary zinc intake increase zinc concentration in the retina. It’s less clear how zinc could reach the aqueous and vitreous of the eye, although the ciliary body, a tissue that supplies nutrients to the aqueous and vitreous humours, has ZIPs in its membrane. The rear of the vitreous might also receive some zinc from the retina.

However, there are so far no studies on the relationship between zinc intake and zinc concentration in the aqueous or vitreous, so it’s unclear whether supplementation would even cause more zinc to reach these parts of the eye.

There appear to be benefits for your eyes, especially in protecting against AMD, in ensuring you get enough zinc. How do you know whether you’re already getting adequate zinc?

• Vegetarian/Vegans: Whilst the majority of people in developed countries meet their recommended daily intake, some groups are more susceptible to low zinc intake. For example, vegetarians and vegans consume diets which have lower zinc contents, which is exacerbated by the high phytate content of plants. Phytate binds to zinc and prevents it from being taken up by ZIPs, which can only access free zinc, and even binds to zinc excreted by the body, preventing it from being reabsorbed. This all means that, whilst fruit and vegetables contain many nutrients important for a balanced diet, they put vegetarians and vegans at risk of zinc deficiency. However, certain preparation choices can help those on a plant diet get more zinc. Soaking legumes for several hours before eating them has shown to dramatically reduce their phytate content. Fermented foods also have a decreased phytate content. These will both increase zinc bioavailability, but this doesn’t solve the lack of zinc in a plant-based diet. Taking zinc supplements several hours outside of mealtimes could help provide sufficient zinc intake.

• Pregnant people: Several other groups are vulnerable to low zinc. Pregnant and breast-feeding people have increased zinc demands (3-4mg higher) as they must supply the growing foetus and newborn baby. There is some evidence that low zinc intake increases the risk of birth complications, although there is also conflicting evidence as to whether zinc supplementation can amend this.

• Alcoholics: 30-50% of alcoholics have low zinc levels. This is due to increased urination as a result of alcohol consumption, with zinc being excreted as well. Lowering alcohol consumption may increase zinc levels in the body.

Many other groups of people are susceptible to low zinc. If you are experiencing symptoms that sound like zinc deficiency, or are concerned about your zinc intake, it’s best to speak to a doctor who can advise you on what to do about it.

Although zinc nutrition is not something a lot of people are likely worrying about, evidence has shown that many people might get less zinc than they need without realising. Vegetarianism and veganism are on the rise in developed countries, and have been shown to lead to low zinc levels. Alcoholism is common among adults, with 10.5% of Americans over 12 in 2022 suffering with the disorder, and high alcohol consumption can also lead to low zinc.

Low zinc has been correlated with many eye conditions, such as age-related macular degeneration, cataracts, and diabetic retinopathy. It seems sensible that many different people who could be at risk of low zinc may also be at higher risk of developing these eye conditions. On top of that, consuming more than the average daily requirement for zinc has a protective effect against macular degeneration, and might protect against other eye conditions.

Meat, sea food and cereals have the highest zinc content, and zinc is better absorbed when consumed without plant foods, despite their other nutritional benefits. For vegetarians and vegans, this is obviously not an option, but different preparation methods can increase the ability for zinc to be absorbed. Zinc supplementation may also help people who can’t get enough zinc from their diet, and even in people who can, it can provide additional protection against conditions such as macular degeneration.