Corneal Clarity

Making sense of AREDS, vitamins and beyond…

Nutritional supplements — to consume or avoid is the question.

By Thomas John, MD

Nutritional supplements continue to gain in popularity, but with so many different nutrients and supplements, making sense of them all can be difficult. Added to all the media hype, we often hear the term “AREDS,” which may further confuse our patients, since they are not likely to know it’s an acronym for Age-Related Eye Disease Study. In this article, I will review antioxidants, AREDS and then move on to other areas to increase understanding when it comes to nutrients and the eye.

SUPPLEMENT JARGON

Antioxidants

When stimulated by light, oxygen molecules can form toxic molecules referred to as reactive oxygen species. These can react with lipids in cell membranes and lead to their demise. We know macrophages that are part of the immune system utilize reactive oxygen species to kill bacterial cells that invade the human body.

The body’s antioxidants tend to destroy the invading reactive oxygen species before causing tissue damage. A relative lack of antioxidants or an excess of reactive oxygen species can contribute to retinal cell damage. The main antioxidants are vitamins A, C, and E, which were used in AREDS (Table, page 20). While the recommended dietary allowance for beta-carotene is about 3 mg/day, for vitamin C it is about 80 mg/day and for vitamin E about 15 mg/day, AREDS used high levels of these antioxidants.

AREDS

Sponsored by the National Eye Institute, AREDS comprises two studies: The first, AREDS 1¹ and later, AREDS 2.^2,3 The table compares the nutritional supplements the two studies used.

Currently, no study supports the use of supplements to prevent AMD. However, individuals “at risk” should consider them. AREDS showed the use of high levels of antioxidants and zinc had no benefit in healthy subjects, but did have a benefit in those with AMD — specifically, a 25% reduction of developing advanced AMD only in subjects with intermediate and advanced AMD. However, the high levels of antioxidants and zinc had no effect on cataract development or progression.

AREDS 2 showed the addition of omega 3 fatty acids, lutein or zeaxanthin derived no benefit. Lutein and zeaxanthin are xanthophylls ­— yellow pigments. The term arises from the Greek word xanthos, yellow, and phyllon, referring to leaf.

The yellow color of the macula is secondary to the lutein and zeaxanthin it contains. They absorb ionizing blue light and appear to play a role in protecting the eye. Foods that are good sources of lutein and zeaxanthin include eggs, kiwi, Swiss chard, spinach, kale, broccoli, zucchini, corn, Brussels sprouts, goji berry (wolfberries), mustard greens and romaine lettuce.

AREDS2 associated the use of β carotene in the formula to an increased risk of lung cancer in smokers. The first study used copper to prevent copper deficiency anemia that occurs with increased zinc intake.

AREDS formulation vs. multivitamins

Many patients wonder if the AREDS formulation is the same, or as beneficial, as a multivitamin. The answer is no. The AREDS formulation contains levels of antioxidants and zinc that are much higher than in multivitamins. Hence, a person can take a multivitamin even if she or he is already on an AREDS formulation supplement, which is not a substitute for a multivitamin.

THE BUILDING BLOCKS

Let’s take a closer look at the nutritional components used in both AREDS studies.

Omega 3 vs. omega 6 fatty acids

Omega 3 polyunsaturated fatty acids are found mainly in fish and nuts. They have anti-inflammatory and possibly antiangiogenic properties. They are present in high concentration in the outer retina and choroidal capillaries.

In contrast, omega 6 fatty acids are found in red meat, and act as pro-inflammatory mediators. Because inflammation plays a role in numerous diseases, including AMD, cardiovascular disease, type 2 diabetes and rheumatoid arthritis, a lower intake of omega 6 and a higher intake of omega 3 is beneficial.

Studies have indicated that humans largely evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids of about 1:1, whereas in current Western diets the ratio is 15:1 to 16.7:1.⁴ This disproportionate increase in omega-6 promotes pathogenesis of many diseases including cardiovascular disease, cancer, osteoporosis, inflammatory and autoimmune diseases.⁴

Metals — zinc and potassium

Zinc is an essential trace mineral critical to the immune system and the brain. It also plays a role in wound healing and is an integral part of enzymes that play a role in various bodily functions. The macula has high levels of zinc and zinc assists vitamin A to create melanin pigment that protects the eye. The recommended dietary allowance of zinc is about 10 mg/day, while both AREDS and AREDS2 utilized higher levels.

As for potassium, low levels have been associated with dry eyes. Potassium is an important part of the tear film.

VITAMINS

Water- and fat-soluble

All vitamins are not the same. The broad groups are fat-soluble and water-soluble, with most vitamins being the former. These include vitamins A, D, E, and K, while B and C are water-soluble.

The body absorbs fat-soluble vitamins in lipids as chylomicrons, which travel into the blood circulation and are stored in body tissues. Excessive intake can result in hypervitaminosis; lower levels, due to either low fat intake or decreased fat absorption due to drugs or diseases, can lead to hypovitaminosis. In the lab, vitamin E can be altered to a water-solubilized vitamin that research indicates offers enhanced absorption.

As for ocular health, a recent study of 14,641 U.S. male physicians age 50 and older who consumed a daily multivitamin or placebo over an average treatment period of 11.2 years, showed that long-term daily multivitamin use modestly and significantly reduced cataract risk, but had no significant effect on visually significant AMD.⁵

Individual vitamins

Now let’s look at some individual vitamins and their health benefits.

• Vitamin E 400 IU, same as in AREDS and AREDS2, under the selenium and vitamin E cancer prevention trial (SELECT),⁶ showed that it significantly increased the risk of prostate cancer among healthy men compared to placebo. However, AREDS failed to show a similar effect. Also, Alpha-the Tocopherol, Beta Carotene (ATBC) Trial, which used vitamin E 50 mg daily, showed a 35% decline in the risk of prostate cancer.⁷

• Vitamin D. Recent evidence has indicated vitamin D may play a role in ocular health,⁵ as well as an important part in immune regulation that may protect against the aging process.⁵ Older mice treated with vitamin D3 showed decreased retinal inflammation, decreased amyloid beta accumulation, and a decrease in the numbers of retinal macrophages.⁵ Amyloid beta accumulation is considered a hallmark of biological aging. Vitamin D3 improved visual function in the treated older mice. AMD is associated with retinal inflammation and amyloid beta accumulation. Thus, early evidence has indicated that vitamin D3 may offer a damper on age-related visual decline.

• Vitamin B complex. Vitamin B6 aids absorption of magnesium, which helps in the production of prostaglandin E-7 necessary to produce tears. Hence vitamin B6 may be beneficial in the treatment of dry eyes.

Important role of diet

Nutritional experts agree that it is best for people to get their nutrients from foods, however, rather than supplements. So let’s review some information on diet.

• Fats. Fats fall into two main categories, unsaturated and saturated. Saturated fats are triglycerides with only saturated fatty acids, meaning they have no double bonds between the carbon atoms of the fatty acid chain; it is fully saturated with hydrogen atoms. Examples of food with high saturated fat include animal products such as cream, butter, cheese, ghee, and vegetable products such as coconut oil and chocolate. The unsaturated fats are comprised of mono- and poly-unsaturated fats, trans fat, and omega fatty acids,

• Green leafy vegetables. Some studies have indicated that diets rich in green leafy vegetables are linked to a lower risk of developing AMD. About 1,000 species of plants have edible leaves, such as spinach and lettuce. Leaf vegetables are low in calories and fat, while high in fiber, calcium, iron and phytochemicals, including vitamin C, vitamin K, carotenoids, folate, lutein and magnesium.

Phylloquinone, the most common form of vitamin K, is directly involved in photosynthesis. Hence, leaf vegetables have high levels of vitamin K and can interact with vitamin K antagonist medications such as the anticoagulant warfarin. Individuals on warfarin should avoid leaf vegetables entirely.

A matter of choice

Use of supplements seems to have some beneficial effects both in the front and back of the eye in a select subset of patients. These include some patients with dry eye, cataract and AMD. For instance, use of fish oil or combined fish oil and gamma-linoleic acid (GLA) might decrease symptoms of ocular irritation, HLA-DR (an inflammatory marker) and surface asymmetry index in corneal topography evaluations in some dry eye patients.

At this time, the decision to take nutritional supplements is a personal choice due to the absence of hard scientific data to consistently support either side of the aisle. A well-balanced diet favoring omega 3 over omega 6 fatty acids, along with nutritional supplements, regular exercise with cardiovascular emphasis, adequate sleep, no smoking, decreased alcohol consumption, wearing of sunglasses and a hat in the sun, the reduction of stress by yoga or other means, embracing laughter and a compatible partner, can contribute to an overall fruitful life here on earth. Some might call it “wishful thinking.” OM

REFERENCES

Thomas John, MD, a world leader in lamellar corneal surgery, is a clinical associate professor at Loyola University at Chicago, and in private practice in Oak Brook, Tinley Park and Oak Lawn, Ill. His e-mail is tjcornea@gmail.com. Disclosure: Dr. John has financial relationships with Bausch + Lomb, Bio-Tissue and iScience Corp., and is a speaker for Allergan.