To the Editor: I read Constable’s article1 on age-related macular degeneration with interest, but was surprised at its somewhat guarded advice on nutritional supplementation and the fact that it gave only passing reference to uncontrolled studies of the carotenoids lutein and zeaxanthin and failed to mention a number of controlled studies that have recently shed light on the potential for these nutrients to influence the progression of age-related macular degeneration (ARMD).

Lutein and its isomer, zeaxanthin, are deposited in the macula, where they make up the macular pigments and act as a blue-light filter to protect the underlying tissues from phototoxic damage, as well as providing antioxidant activity. Lutein was not available in supplement form at the time of conducting the Age-Related Eye Disease Study (AREDS).2 However, the more recent Lutein Antioxidant Supplementation Trial (LAST), a double-masked, placebo-controlled, randomised trial of lutein and antioxidant supplementation in people with ARMD, demonstrated that taking 10 mg lutein daily, with or without additional nutrients, improved visual function.3 Interestingly, lutein supplementation was also found to improve vision in a small, randomised, placebo-controlled study of people with cataracts. It was suggested that these improvements were due to improved macular function and increased macular pigment density.4 Furthermore, a recent study showed that lutein supplementation results in increased macular pigment density in both normal and ARMD patients.5

Lutein occurs naturally in foods such as eggs, spinach, romaine (cos) lettuce, broccoli, zucchini, corn, peas and Brussels sprouts. Although lutein is readily absorbed from foods and dietary supplements, surveys indicate that average lutein intake may be below levels that are associated with disease prevention.6 Toxicology studies have established that lutein is generally safe, with potential for use as a supplement in foods and beverages.6

While advice on smoking cessation and increasing fruit and vegetable intake is useful for a wide range of conditions, including ARMD, Constable’s statement that “antioxidant supplements should be recommended if a fresh diet is impractical and if retinal signs of progression are present”1 appears overly cautious. In light of recent findings on the potential benefits of antioxidants such as lutein, and the low cost and minimal risks associated with supplementation compared with the potentially devastating consequences of blindness from ARMD, it may be prudent to make more general recommendations on nutritional supplements, rather than waiting until signs of retinal progression are evident.

Competing interests: The author has given occasional paid lectures for companies that market carotenoid-containing products.

In reply: While the published literature on dietary supplementation with the antioxidants lutein and zeaxanthin is highly encouraging, it does not yet pass the requisite standards for public endorsement provided by large-scale, independent, evidence-based medical trials. The controlled (“LAST”) trial of lutein1 cited by Cohen consisted of just 91 patients divided into three subgroups including the placebo group, who were followed for only 1 year. The measurement of visual improvement on a Snellen chart would not be accepted as “gold standard” evidence by major granting agencies and regulatory affairs bodies, who demand the higher discrimination of a logarithmic visual acuity chart. Moreover, the data were not derived from multicentre trials and independently assessed.

It is instructive to compare the methodology of the LAST trial with that of the ARED Study,2 which involved 11 centres, 3640 patients and an average follow-up of 6.3 years. For these reasons, although I mentioned lutein in an encouraging fashion, I did not endorse it to the same extent as vitamin C, vitamin E and zinc supplements.

The other reasons for giving limited recommendation of antioxidant supplements at this stage relate to the fact that it is not yet clear to what extent supplements would be beneficial over and above a diet targeted to provide these antioxidants in plentiful supply. It may yet be shown that a nutritious diet — with emphasis on brightly coloured and leafy vegetables, fresh fruits, nuts and fish, coupled with reduced processed vegetable oils (except olive oil) — can, alone, provide substantial protection. While the supplements are generally deemed to be safe, they are not without occasional serious side-effects and have not been followed long term.

Richer, one of the authors of the lutein study, 1 acknowledges commercial relationships with the supplement suppliers, and states that the study requires greater numbers and long-term follow-up to be confirmed.

Cohen cited a second article3 that refers to a 2-year study of cataract, in which a mere 17 patients were allocated to three subgroups including the placebo group. It is not usual practice to quote conclusions from such a small, and therefore potentially unreliable, trial design.

Cohen is right to point to lutein and possibly zeaxanthin supplements as an encouraging possibility for preventing blindness from macular degeneration, and I hope the evident enthusiasm and rapid marketing of lutein proves justified in the long run by forthcoming major trials.