Macular Pigment Density Increased by Dietary Supplements

Linda Roach

March 21, 2013

Adults with "dry" age-related macular degeneration (AMD) developed a denser macular pigment layer after taking a daily oral supplement of carotenoid compounds and omega-3 long-chain polyunsaturated fatty acids, a German research group has found.

However, the clinical importance of this is unknown, Christin Arnold, Dipl-Troph, and colleagues from Friedrich Schiller University, in Jena, Germany, report in a paper published March 21 in JAMA Ophthalmology.

The randomized, double-blind, placebo-controlled, parallel clinical trial compared outcomes in 145 participants, aged 50 to 93 years, divided into 3 groups. All patients had nonexudative AMD. The trial was conducted for 12 months.

One group (n = 55) took a capsule containing 10 mg lutein, 1 mg zeaxanthin, 100 mg docosahexaenoic acid (DHA), and 30 mg eicosapentaenoic acid (EPA); another took a capsule containing twice those doses (n = 50); and the placebo group (n = 40) took an identical-looking dummy capsule.

The researchers report that after 1 month, plasma concentrations of the 2 carotenoids increased significantly in the treated groups and this level was maintained throughout the trial. In addition, optical density of the macular pigment increased significantly (P < .05) in the treated groups, rising slowly through 12 months, but was nearly unchanged in the placebo group.

The pigment's density was slightly higher in the double-dose group than in the other treated group, but the difference was insufficient to support use of the higher doses of these nutritional supplements.

In an interview with Medscape Medical News, Arnold, who is a doctoral-degree candidate in nutritional sciences, pointed to the latter finding as most clinically relevant to physicians whose patients with dry AMD ask about taking supplements.

"Our patients responded to the supplementation in both groups, but we found that you did not need 20 mg of lutein. As a nutritionist I feel better about the lower dose, because I prefer for people to get their nutrients from food as much as possible," Arnold explained. "There are toxicological studies showing that 20 mg is safe. But now that we know 10 mg is effective, we can say that patients should not be using the higher dose."

Clinically Useful?

Retinal researchers generally regard the macular pigment, which contains lutein, zeaxanthin, and their isomer, meso-zeaxanthin, as a defense against oxidative damage to the retina. But the biological and clinical connections — if any — between the density of the macular pigment and AMD development or progression remain murky.

Emily Y. Chew, MD, PhD, deputy director of the Division of Epidemiology and Clinical Applications at the National Eye Institute, Bethesda, Maryland, told Medscape Medical News that the German group's study was small, had limited follow-up, and had no way to determine what the elevated pigment density means functionally for a patient with AMD.

"It's interesting data but it doesn't prove anything. It's awfully small numbers. It would be hard to come up with anything other than the fact that the macular pigment levels are different," Dr. Chew, who is an ophthalmologist and an epidemiologist, explained.

"They report that the optical density of the macular pigment increases, but so what? Does that improve your vision? Does that mean it's good? We don't know. So it's interesting but what does it mean?" she added.

Rather than looking at structural changes after supplementation, it is more important to determine whether the right nutritional supplements, in the right doses, prevent development and/or progression of AMD, Dr. Chew said.

She is chair of the second Age-Related Eye Diseases Study (AREDS2), the National Eye Institute's large randomized, controlled, multicenter clinical trial that is expected to report results this spring. AREDS2 tested the same supplements as were used in the German study, but at different doses and in different combinations. The AREDS2 dosing was 10 mg lutein, 2 mg zeaxanthin, 650 mg EPA, and 350 mg DHA.

The average follow-up in approximately 4000 participants was nearly 5 years, giving AREDS2 the statistical power to detect changes in clinical outcomes of a slow-moving disease, Dr. Chew noted.

"Our ultimate goal is to look at whether we can prevent progression to advanced disease, something that is very important to the patient," she said. "That's why we followed so many patients for so long."

The study was supported by Novartis GmbH and Carl Zeiss Meditec. The authors and Dr. Chew have disclosed no relevant financial relationships.

JAMA Ophthalmol. Published online March 21, 2013.