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Italian-American Trial of Multi Use & Cataract

A recent prospective cohort analysis of the National Eye Institute (NEI)-supported Age-Related Eye Disease Study (AREDS) reported that consistent use of a multi-vitamin and mineral supplement may delay the progression of lens opacities [See EduFacts Vol. 8 No. 4]. That analysis found a 25% reduction in risk of nuclear cataract, a similar - though non-significant - risk reduction for cortical cataract, and no beneficial effect for posterior subcapsular opacity.

The NEI has also supported The Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract (CTNS), a 13-year, single-center clinical trial designed to evaluate whether multi use can affect the development or progression of lens opacities in a well-nourished Western population.

Results from the CTNS trial (1), published in the April issue of the journal Ophthalmology, support multivitamin supplementation for preventing or delaying the more common nuclear, and perhaps cortical opacities as well.

Study Design and Methods

In this double-blind, placebo-controlled trial, a total of 1,020 subjects aged 55-70 with early or no cataract were randomized to receive a multivitamin/mineral supplement or placebo daily, and were followed for an average of 9 years. Baseline and annual lens photographs were graded for severity of lens opacities according to a modification of the Age-Related Eye Disease Study system for classifying cataracts.

The primary outcome was a pre-specified increase from baseline in nuclear, cortical, or posterior subcapsular cataract (PSC) opacity grades or cataract surgery. Secondary outcomes included an increase in type-specific opacity grades, cataract surgery, and visual acuity loss from baseline > or = to 15 letters. The statistical analyses yield estimates of hazard ratios (HRs) that can be interpreted as relative risks.

Results

There was an overall benefit and a decrease in total lens events in participants assigned to the multivitamin and mineral formulation compared with those assigned to the placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.68 - 0.98; P= 0.03). Participants assigned to the multi were 34% less likely to experience a nuclear opacity event than participants assigned to a placebo (HR, 0.66; 95% CI, 0.50-0.88; P= 0.004). Multi users were also 22% less likely to experience a cortical event, although the difference did not reach statistical significance (HR, 0.78; 95% CI, 0.60 -1.02; P= 0.07).

Comments

First, there was no significant decrease in cataract removal or benefit for visual acuity. Is a larger or longer trial necessary for an adequate evaluation of the effects of multivitamins on visual acuity and/or cataract surgery rates? It should also be noted, however, that the multi tested in the CTNS trial did not contain lutein or zeaxanthin. These carotenoids are being examined in AREDS 2, and have been consistently linked to lower cataract risk, particularly nuclear opacity, and reduced risk for cataract surgery in observational studies.

Secondly, the benefits seen for the most common types of cataract, nuclear and cortical, are consistent with the findings from a number of observational trials, and the Linxian, China randomized trial, which reported a 36% reduction in the risk of nuclear cataract with multivitamin supplements. This implies that supplementation could help delay cataract and result in public health savings.

Lastly, the increased risk for PSC is puzzling, as most studies to date have shown no benefit but also no higher risk for PSC from supplemental antioxidants or multis. PSCs are less common than cortical or nuclear, and are often associated with eye trauma and steroid use. It is possible that the mechanisms involved in nuclear or cortical cataract formation are more susceptible to the level of oxidative stress than are PSC. Further research is needed.