Physicians balance benefits of diet, supplements for common ocular conditions

Data are accumulating regarding the ocular benefit of select foods and nutritional supplements on disorders such as cataract, dry eye and macular degeneration, but research results vary, and more than just the eye is affected by nutrition.

According to Allen Taylor, PhD, senior scientist and director of the Laboratory for Nutrition and Vision Research at Tufts University in Boston, the latest nutritional recommendations for age-related macular degeneration are reflected in two double-masked placebo-controlled trials from the National Eye Institute: the Age-Related Eye Disease Study (AREDS) and its follow-up, AREDS2. The studies are the cornerstone for most nutritional recommendations.

“I believe that hydrophilic nutrients such as vitamin C are best for the aqueous environment of the lens and thus for cataract, whereas lipophilic moieties are probably salutary for retina and AMD,” Taylor said. “Carbohydrate intake may also be important. Keeping dietary glycemia low seems to offer protection in all epidemiologic studies published to date. Animal work supports this finding. However, there are no double-blinded placebo-controlled studies to corroborate the findings, and it may be unethical to undertake them. The same holds true for docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).”

Cataract

Consuming diets that deliver glucose into the blood more slowly appears to confer protection against some forms of cataract as well as AMD onset and progress in normal healthy nondiabetic individuals, according to Taylor.

“There are also some benefits to DHA and EPA,” Taylor said. “Clearly, diets that are rich in fruits and vegetables and lower in carbohydrates are salutary.”

In an article on nutritional modulation of cataract that appeared in Nutrition Reviews, epidemiologic literature “suggests that the risk of cataract can be diminished by diets that are optimized for vitamin C, lutein/zeaxanthin, B vitamins, omega-3 fatty acids, multivitamins, and carbohydrates,” co-author Taylor said. In essence, recommended levels of micronutrients are beneficial, he said. The limited data from intervention trials show a positive response for nuclear cataracts; however, adverse effects on risk for posterior subcapsular cataract have also been reported.

Observational data from large cohorts “suggest that maintaining a protein intake of 100 to 150 g/day and a vitamin C intake of approximately 135 mg/day (nearly twice the recommended level), while avoiding frequent large intakes of simple carbohydrates, such as chronic consumption of super-sized sweetened beverages, is prudent,” Taylor said.

In final results from the Physicians’ Health Study II published in Ophthalmology, a randomized double-masked placebo-controlled trial that assessed the effects of multivitamin supplementation in a large cohort of middle-aged and older male physicians, long-term intake of multivitamins had a modest but statistically significant effect in decreasing risk for cataract, particularly nuclear cataract.

AMD and cataract were secondary endpoints in the trial; the primary endpoints were cancer and cardiovascular disease. There was no statistically significant effect on visually significant AMD, however.

“Given that an estimated 10 million adults in the United States have impaired vision due to cataract, even a modest reduction in risk for cataract would have a large public health impact,” the study authors said.

Dry eye

As for the guidelines on ocular nutrition for corneal health and dry eye, Stephen C. Pflugfelder, MD, said: “I do not believe there are any set recommendations; however, there are a few studies that indicate that taking nutritional supplements might decrease irritation symptoms in patients with dry eye and that they also appear to decrease ocular surface inflammation.”

These nutritional supplements consist of fish oil alone or a combination of fish oil and gamma-linoleic acid (GLA).

In a study published in Cornea, Pflugfelder and colleagues conducted a randomized clinical trial that compared vehicle with a nutritional supplement containing fish oil and GLA. Patients took four capsules a day for 6 months and were assessed at baseline and at 4, 12 and 24 weeks.

“There was a statistically significant decrease in irritation symptoms in the patients treated with the supplement compared to the control group,” Pflugfelder said. “There was also a significant decrease in an inflammatory marker called HLA-DR, which is found on some types of inflammatory cells and epithelial cells.”

In addition, the study found a decrease in one topographic surface regularity marker, that is, the surface asymmetry index.

“The bottom line is that the most impressive finding about these supplements is that they decrease irritation symptoms, but they do not decrease clinical signs such as tear breakup time or corneal fluorescein staining,” Pflugfelder said.

AMD

“There are compelling observational data from numerous studies that persons who eat more green leafy vegetables, such as kale, collard greens and spinach, have a lower risk for developing AMD,” Emily Y. Chew, MD, of the National Eye Institute, said. “Cold-water fish — salmon and tuna — that have a lot of long-chain PUFAs (polyunsaturated fatty acids) also seem to provide a protective effect from acquiring AMD.”

However, to Chew’s surprise, omega-3 fatty acids did not have any effect on AMD in the AREDS2, which added omega-3, lutein and zeaxanthin to the original AREDS formulation. Still, secondary exploratory analysis of AREDS2 concluded that “it is worthwhile to substitute beta-carotene, which is in the original formulation, with lutein and zeaxanthin because there is an incremental beneficial effect.”

“In fact, during our first AREDS study, other randomized trials demonstrated that patients who were smokers had an increased risk for lung cancer when assigned to beta-carotene. There was also an increased risk for lung cancer among former smokers who were assigned to beta-carotene in the AREDS2 study. So the idea that beta-carotene is harmful is of some concern. Nearly two-thirds of the AMD patients are either current or former smokers,” she said.

Chew said that it “makes biological sense” that lutein and zeaxanthin would have a beneficial effect because both are found in the eye, whereas beta-carotene is not.

“The final recommendations for AMD are diets [replete] with green leafy vegetables and healthy servings of fish,” Chew said. Her article on the effects of nutrition on ocular diseases in the aging eye was published in Investigative Ophthalmology & Visual Science.

Daily supplementation of B vitamins — B6 and B12 — also seemed to reduce the risk of AMD in the Women’s Antioxidant and Folic Acid Cardiovascular Study.

“But because this was not the primary endpoint, we really cannot make a recommendation,” Chew said. “However, it raises the question whether other nutrients might be important. When people have cardiovascular disease, there is also an elevated level of homocysteine in the blood. When these study patients were given B complex vitamins, the homocysteine decreased, even though it had no effect on cardiovascular disease.”

Night blindness

The most common cause of night blindness worldwide is vitamin A deficiency, primarily in children younger than age 5 years and women during late-stage pregnancy.

“These women on marginal vitamin A diets become deficient because their fetus is drawing down a lot of their vitamin A stores,” Alfred Sommer, MD, a professor of ophthalmology at Johns Hopkins University School of Medicine, said. “In fact, night blindness amongst pregnant women is so prevalent in some areas of the world, foremost in the Indian subcontinent, that it is considered often to be a normal course of pregnancy.”

The reason people with vitamin A deficiency become night blind is because of their inability to generate adequate amounts of the molecule rhodopsin, which is the visual pigment used by photoreceptors in the retina to see under low levels of illumination.

“Night blindness is the earliest ocular manifestation of vitamin A deficiency,” Sommer said.

People are treated for night blindness in the developing world either with daily supplements, which are prohibitively expensive for the most part, or two annual large doses of vitamin A, spaced 6 months apart. For the latter option, the vitamin A is stored in the liver and then slowly released from the liver “for protection against significant deficiency for the next 6 months,” Sommer said.

Sommer said beta-carotene can be converted in the human gut into vitamin A, but the conversion process is inefficient.

“It is almost impossible, particularly for young children — even if they consumed all the green leafy vegetables they possibly could — to attain normal, adequate vitamin A status purely from the beta-carotene that is available in vegetable products,” Sommer said.

Diet vs. supplements

Sommer was the lead author of a global clinical review of vitamin A and carotenoids published in the American Journal of Clinical Nutrition.

“There is no clinically proven nutritional deficiency that causes ocular ill health, at least among a population like Americans who are on a normal diet,” he said.

Taylor said it has been challenging to separate the effects of a single or a few nutrients.

“Hence, there may be synergistic effects from multiple nutrients on ocular health,” he said, noting that adverse reports from micronutrient-rich diets are rare.

“The lack of salutary effects of multivitamins in the relatively short-term trials may imply that only long-term intake from foods or supplementation, like the AREDS Centrum (Pfizer) data, can provide clinical benefit,” Taylor said.

Taylor said that clinicians should cautiously make recommendations based on nutritional data that may improve one ocular condition but compromise another. Each individual’s relative risks should be considered, as should the effects of nutritional supplements on the total body system, not just the eye system.

“For people with poor diets, they offer protection,” Taylor said. “But for people with diets that are rich in fruits and veggies, there is probably limited benefit.”

Pflugfelder said that he is not aware that taking PUFAs from fish oil and GLA for dry eye would worsen any other eye condition. Taking into consideration the total body, though, he said there are some calories associated with those fats, and fish oil can have a thinning effect on the blood.

“So if patients are on blood thinners or if they have problems with bleeding, they should probably check with their physician,” Pflugfelder said. Likewise, certain formulations may be difficult for some patients to digest, possibly causing gastrointestinal upset. “But for the most part, that is not a big issue,” he said.

Pflugfelder said the preliminary evidence suggests that the role of nutritional supplements for corneal health and dry eye is an important area deserving more consideration and rigorous clinical trials. He does not believe that any of the completed studies have established minimum effective dosages.

“Perhaps in some of these trials, more was given than needed,” he said.

Regardless, the typical Western diet “tends to promote inflammation, so people could either take these supplements or they could enrich their diets in foods that have PUFAs, like eating more cold-water fish or eating more nuts that contain PUFAs,” Pflugfelder said. “It certainly points to diet as being a risk factor for dry eye.”

Despite being widely sold and consumed, supplements “make no sense at all,” according to Sommer.

“There can be lots of theoretical bases for thinking that certain nutrients taken as supplements would improve health, particularly eye health … [but] until we have clinical trials that demonstrate that a specific single or group of supplements actually prevents disease or improves vision, there is no basis for recommending additional nutrients at this point in time,” he said.

For example, “People have thought antioxidants could benefit glaucoma, but it has not really been tested,” Chew said.

According to Sommer, it is worrisome that in three large trials using beta-carotene to reduce cancer, the risk for lung cancer increased among prior smokers and did not reduce the risk for cancer in the remaining participants.

“Taking ocular nutrients is not a zero-sum game. It can be harmful to take large doses of nutrients that are otherwise not coming from your normal diet,” Sommer said.

On the other hand, the Physicians’ Health Study found Centrum to have a protective effect against cancer, according to Chew. In addition, the Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract found that patients given Centrum had decreased risk for nuclear cataract but increased risk for posterior subcapsular cataract.

“We still have a great deal to learn about nutrition,” Chew said.

Modifiable factors

Apart from perhaps embracing select foods and nutritional supplements, people can avoid or embrace modifiable personal habits or their environmental settings to improve ocular health.

Smoking, for one, is a modifiable risk factor for dry eye, cataract and AMD.

“We do know that smoking does increase the risk of macular degeneration and probably increases the risk of cataract as well,” Sommer said.

Excessive alcohol consumption is also linked to vitamin A deficiency, but not just because of liver damage. “Alcoholics tend to have very poor diets,” he said.

Maintaining a healthy weight can reduce the risk for diabetes and consequently diabetic retinopathy.

“Obviously, healthy living and keeping your weight and cholesterol in good shape are particularly beneficial for patients with diabetes, whereas hypertension increases the risk of diabetic retinopathy,” Chew said. Furthermore, overexposure to sunlight may predispose a patient to cataract, and wearing sunglasses may be protective.

Manipulation of the indoor environment, too, can help minimize risk for dry eye. People who work in a low-humidity drafty setting can move air ducts to raise the humidity, according to Pflugfelder. Dry eye among office workers who stare at a video monitor for long periods of time can be reduced by positioning the screen at or below eye level to minimize evaporation.

Genetic testing

Regarding the validity of genetic testing to enhance therapeutic response, Taylor thinks the value of such testing is unknown.

“Several prediction models include genetic testing; however, other models that do not include genetic data seem to perform just as well,” he said. “Data over the next few years will better inform us as to the validity of genetic testing.”

Pflugfelder is not aware of any such genetic tests for dry eye. “However, it is conceivable that some people would respond better, based on certain genetic markers,” he said.

“Genetic testing is not terribly valuable as yet, as it relates to nutrition to the eye, because even for those very few diseases for which we can recognize an existing genetic abnormality, like some forms of retinitis pigmentosa, there is not much that we can do about it,” Sommer said. “Other than vitamin A and perhaps Ocuvite (Bausch + Lomb) for people with high risk for macular degeneration, there is no specific need for additional nutrition with an average diet.”

For AMD, genetic testing remains important for research, but there is no evidence that genetic testing at this point helps tailor treatment, according to Chew. – by Bob Kronemyer