Can lutein and zeaxanthin reduce the risk of ARMD — maybe even help to slow or halt its progression? Find out what the latest research tell us about vitamins and vision.

By STEVEN D. CANTRELL, O.D.St. Louis, Mo.
RODNEY L. AUSICH, Ph.D.Des Moines, Iowa
Dr. Cantrell has been prescribing supplements containing lutein for the past 18 months and is seeing positive results.
Dr. Ausich is vice president of research and development at Kemin Foods, L.C. He has done extensive research on the role of lutein and zeaxanthin in ARMD.

Lesson

Questions

Today’s optometrist must factor in more than just presbyopia when treating older patients. Take a look at these numbers.

• The U.S. Census Bureau estimates that the number of Americans over 65 years old will more than double by the year 2050, reaching 80 million.

• Prevent Blindness America estimates that 14 million Americans have evidence of age-related macular degeneration (ARMD).

• The Beaver Dam Eye Study reports that 30% of people over age 75 have ARMD and 23% of the remainder will develop ARMD within five years.

Recent advances in our understanding of ARMD reveal that diet can strongly influence the risk of the disease. In particular, lutein and zeaxanthin, specific compounds found in fruits and vegetables, may reduce the risk of ARMD and help slow or halt its progression. This EyeQuest CE Course will focus on the role of dietary supplements in reducing the risk of ARMD.
 

Evidence supports dietary intervention
Diet provides us with an important opportunity to reduce the risk of ARMD. Basic research studies, clinical trials and epidemiologic studies have linked specific dietary components to protection from ARMD.

Goldberg and colleagues (1988) observed a relationship between diet and risk of ARMD when they analyzed results from the first National Health and Nutrition Examination Survey (NHANES I). They studied individuals who were older than 45 years and grouped them on the basis of their dietary intake of certain fruits and vegetables. They then compared people who consumed high quantities of such fruits and vegetables (at least once per day) to those who consumed them rarely (less than once per week). They found that those who ate the greatest quantities of these fruits and vegetables had a significantly lower risk of ARMD.

At the time these results were published, it was suspected that vitamins found in these fruits and vegetables may have been important for reducing the risk of ARMD. However, more recent research suggests that other compounds found in the same foods may be responsible for lowering the risk of ARMD.

A series of studies from the Eye Disease Case-Control have provided insight into how diet can reduce the risk of ARMD. In one study, investigators divided patients into three groups on the basis of their plasma levels of antioxidant micronutrients.

The results indicated that those with higher levels of antioxidants in their plasma had a lower risk of ARMD. The greatest effect was for those with high plasma levels of carotenoids, a family of colored compounds found in fruits and vegetables. Beta-carotene is an example of a carotenoid, and we consume and absorb 14 different carotenoids from our diet.

Investigators also analyzed specific carotenoids and found that patients with high plasma concentrations of two other carotenoids, lutein and zeaxanthin, had lower rates of ARMD. Lutein and zeaxanthin are found in all fruits and vegetables, provide the yellow color to corn kernels and are found in highest concentration in dark green, leafy vegetables. This study concluded that high blood levels of antioxidant carotenoids and vitamins were associated with a reduced risk of ARMD.
 

Carotenoids called lutein and zeaxanthin
The next important question is whether high plasma levels of carotenoids are a result of their consumption in the diet. Indeed, there is a direct relationship between dietary consumption of these compounds and their concentration in plasma — the relationship is strong enough that some researchers have suggested that measurements of such carotenoids in the plasma can be used as an indicator of fruit and vegetable consumption.

Together, these lines of evidence raise a new question: Is there a relationship between diet and a reduced risk of ARMD? To answer this, Eye Disease Case-Control investigators examined whether the consumption of specific vegetables affected a person’s risk of ARMD.

They divided subjects into five groups on the basis of their consumption of various vegetables and vegetable classes. They found that consumption of spinach, in particular, was associated with a significantly reduced risk of ARMD. Subjects in the group with the highest spinach consumption had an 86% lower chance of ARMD as compared to the group with the lowest spinach consumption. It’s interesting to note that this association wasn’t found for consumption of broccoli, cabbage-related vegetables, carrots, sweet potatoes or winter squash — all of which are rich in beta-carotene.
When the investigators analyzed the data a different way to try to determine which nutrients might be responsible for this effect, they found that fruits and vegetables that contained high levels of lutein and zeaxanthin were responsible for this effect.

Biochemical analyses of the nutrient content of specific vegetables have shown that spinach, collard greens and kale are particularly rich sources of lutein and zeaxanthin (the two carotenoids are often grouped together because they are closely related and lutein may be converted to zeaxanthin in the retina).

In the Eye Disease Case-Control studies, other vegetables that are high in beta-carotene, other carotenoids and other antioxidant vitamins (including vitamin C, vitamin E and selenium) weren’t found to be associated with a reduced risk of ARMD. Thus, there is strong clinical evidence that consumption of the carotenoids lutein and zeaxanthin can reduce a person’s risk of ARMD.

How do lutein and zeaxanthin reduce the risk of ARMD?
Lutein and zeaxanthin are absorbed from our diets and circulated in our blood stream. These two compounds are specifically deposited in the macular region of the retina at high concentrations. They are the compounds responsible for the presence of the “macula lutea,” or yellow spot, found in the foveal region. Interestingly, lutein and zeaxanthin are the only carotenoids found in the tissues of the eye, and they are present in virtually all of the different tissues in the eye. The presence of lutein and zeaxanthin in the macular region is often referred to as the macular pigment.

The only source for lutein and zeaxanthin is our diet — our bodies can’t make these compounds. Researchers have demonstrated that consumption of vegetables rich in lutein and zeaxanthin leads to an increase in the level of these carotenoids in our plasma as well as an increase in the level of these compounds in the macular region of the retina. Thus, consumption of dark green, leafy vegetables increases the density of the macular pigment. The study mentioned above demonstrates that the consumption of spinach — and the concomitant consumption of lutein and zeaxanthin — leads to a decrease in the prevalence of ARMD. This is consistent with the hypothesis that high levels of macular pigment are protective against the disease.

Two roles have been proposed to explain how the macular pigment protects the macula.

• Filtering blue light. Because lutein and zeaxanthin are yellow, they efficiently absorb the blue light portion of the visible spectrum. Blue light can damage the retina by inducing photoxidative decay. When sufficient levels of lutein and zeaxanthin are present in the macula, blue light is absorbed and photoxidization is minimized.

• Reducing the damaging effects of free radicals. Lutein and zeaxanthin also are very effective antioxidants and prevent the oxidative damage due to free radicals. The retina is an area of the body that produces among the highest number of free radicals. With sufficient levels of lutein and zeaxanthin in the retina, free radical damage is minimized, including the inhibition of lipid peroxidation (drusen).
One of the most common complaints from patients who have early signs of ARMD is a reduction in visual sensitivity. Hammond and colleagues (1998) studied the change in visual sensitivity that occurs with age and found that a reduction in visual sensitivity is common in certain people, but not in all elderly patients.

Why do some people lose visual sensitivity and others don’t? The researchers found that those elderly patients with a low macular pigment level had a loss of visual sensitivity, whereas those with high macular pigment densities had no loss of visual sensitivity. This finding supports the proposal that the macular pigment serves a protective role.

Additional support for the protective role of the macular pigment comes from studies of other risk factors for ARMD — gender (the disease is more prevalent in women than men), light iris color and smoking. The level of lutein and zeaxanthin have been measured in individuals in each of these risk groups. The amount of lutein and zeaxanthin averaged 50% or less than the level in non-risk groups. These data strongly suggest lutein and zeaxanthin play a protective role in reducing the risk of ARMD.
 

Counseling patients about diet
No evidence exists for adverse effects from dietary consumption of carotenoids in amounts that have been reported to reduce a person’s risk of ARMD. These compounds have no known toxicity, even at high concentrations. Patients may find that increasing their consumption of vegetables high in these nutrients (for example, kale, collard greens and spinach) is a safe, simple and effective way to reduce their risk of ARMD.

As with other risk-reducing measures, increasing dietary consumption of carotenoids is a step that can be implemented early in life to help ward off the risk of ARMD. Furthermore, those with early signs of ARMD may find that increasing their consumption of these foods can stabilize the disease, thereby slowing or halting its progression.

It has been reported that Americans are consuming fewer carotenoid-rich foods, potentially exposing the population to an increased risk of retinal and other diseases. Interestingly, in data just published, two groups at risk for ARMD, women and the elderly, decreased the consumption of lutein and zeaxanthin about 20% from 1988 to 1992. This trend is disturbing. When combined with the aging of the population, this could portend large increases in the prevalence of ARMD in the future.
For patients who find it difficult or inconvenient to prepare foods that provide these important nutrients, supplements are available that provide lutein/zeaxanthin in the optimal dose consistent with those found to be effective in research studies. Such supplements may also help slow progression in those with early signs of ARMD. These supplements have no reported side effects when taken in appropriate quantities.
 

Sunlight: too much of a good thing
Exposure to sunlight has enormous benefits to humans. For example, sunlight is important for synthesis of vitamin D from precursors in the skin and has established psychological benefits. However, we’re all aware of the damaging effects of ultraviolet radiation to vision.
Sunlight exposure has also been linked to ARMD. In several epidemiologic studies, the amount of sunlight to which an individual is exposed during his lifetime was directly related to the chances that he would show signs of ARMD.

While this relationship has not been found in all studies, and the magnitude of the relationship is controversial, it’s very difficult to quantify an individual’s lifetime sunlight exposure. Nevertheless, it’s likely that excessive sunlight exposure accounts for a significant number of cases — preventable cases — of ARMD.

Strong biological evidence supports the role of sunlight exposure in some cases of ARMD. In particular, light in the blue region of the spectrum is known to damage photoreceptors and the retinal pigment epithelium.

As already mentioned, the macular pigment is believed to serve a protective role by filtering blue light and by reducing the potentially damaging effects of free radicals. As the components of the macular pigment, lutein and zeaxanthin are powerful antioxidants and are believed to protect the macular area from free-radical damage induced by light.

We should advise each of our patients about the damaging effects of sunlight exposure. It has been estimated that the average person receives about 80% of his lifetime sunlight exposure during childhood. Thus, even children (and their parents) should take steps to reduce excessive exposure to sunlight, especially if a family history exists.

Simple measures such as wearing a hat and sunglasses can significantly reduce a person’s sunlight exposure to his eyes. Although scientists have had difficulty quantifying the relationship between sunlight exposure and ARMD in formal epidemiologic studies, it’s likely that reducing sunlight exposure is the single most effective measure patients can take to reduce their risk of ARMD.
 

Other risk factors for ARMD
Although the exact mechanisms that cause ARMD aren’t well understood, knowledge about risk factors has given us key insights into preventing the disease.

• Smoking. Smoking is an established risk factor for ARMD. The mechanisms responsible for this effect aren’t clear, but they may be similar to the mechanisms by which smoking increases the risk of cardiovascular disease and stroke. In addition, it’s been shown that smoking depletes the blood of antioxidants, which may counteract the beneficial effects of dietary consumption. Smoking has also been shown to decrease the density of the level of lutein in the macula; this effect may be secondary to reduction in plasma levels of lutein/zeaxanthin. By quenching these antioxidants in the blood, smoking may render them unavailable to accumulate in the macula.

• Alcohol. At least one study has reported a relationship between alcohol consumption and the risk of ARMD. As with smoking, this effect may be related to the effects of alcohol on blood antioxidants. Of course, excessive alcohol consumption is linked to cardiovascular disease and increased risk of death. Make patients aware of alcohol’s potential danger to their vision, as well as the dangers to their overall health.

• Blood lipids. Elevated total cholesterol is also a risk factor for ARMD. Again, it’s not known how the mechanism for this effect relates to the increased risk of cardiovascular disease and stroke associated with elevated total cholesterol. Furthermore, trials of cholesterol-lowering agents haven’t reported rates of ARMD among participants, so it’s unclear whether treatments to lower total cholesterol will reduce the risk of ARMD.

It’s worthwhile reiterating the dangers of elevated cholesterol and alerting patients that elevated cholesterol is a danger to their vision as well as to their cardiovascular system. In general, patients should receive guidance that will bring them into concordance with the guidelines of the National Cholesterol Education Program.

• Drusen. Drusen are deposits in the retina that have been associated with an increased risk of ARMD. These deposits are thought to be oxidized lipid material that accumulate in the foveal region in certain persons during the lifetime. As mentioned earlier, lutein and zeaxanthin inhibit damage to the macula by absorbing blue light, quenching active oxygen and inhibiting lipid peroxidation (drusen). Because patients with drusen are at higher risk for ARMD, you should counsel them on practices that will reduce their risk for ARMD, including eating a diet rich in lutein and zeaxanthin, protecting against sun exposure and refraining from smoking.
 

A safe, nonsurgical treatment alternative
Lutein and zeaxanthin offer your patients new hope in the fight against ARMD in a nonsurgical format. Simple, safe, effective ways patients can reduce their risk of ARMD include wearing sunglasses and hats to reduce sunlight exposure, stopping smoking, moderating alcohol consumption and increasing consumption of foods or supplements that contain lutein and zeaxanthin.