The LAST Study (Part II): Lutein Supplementation for ARMD

Introduction:

Observational as well as in vitro and intervention studies suggest that lutein may play a preventive role in age-related macular degeneration (AMD) (1-5). In the Lutein Antioxidant Supplement Trial or LAST, the effects of lutein on macular pigment optical density (MPOD) and objective visual outcomes were evaluated in patients with established atrophic AMD. First reported at an annual meeting of ARVO, the findings were published in the April, 2004 issue of Optometry (6).

Methods:

This study enrolled 90 veterans with atrophic AMD in a prospective, placebo-controlled, double-blind trial that involved repeated visual measures over a 12 month period. Volunteers were randomly assigned to receive 10 mg of lutein alone, 10 mg of lutein along with antioxidants* or a placebo. The investigators used a clinical evaluation protocol that was previously validated in a pilot case series. Several tests were used to detect and follow the disease in a serial manner. One, the contrast sensitivity function (CSF) assessment measures the least amount of contrast needed to detect a visual stimulus. CSF assessment enables the detection of changes in visual processing earlier than visual acuity. The investigators also employed the SKILL Card clinical test to assess visual acuity at low levels of light and contrast, and monocular visual acuity was measured by Snellen letter equivalent. Additional tests included the Amsler grid, the Activities of Daily Vision Scale and Glare Recovery, a test of macular function where the dark adaptation of the eye is measured after a flash of light centered on the macula. MPOD was measured by heterochromic flicker photometer.

Results:

Subjects in the lutein, and lutein/antioxidant groups showed a significant increase in average MOPD (repeated measures ANOVA; p<.05) over 12 months, compared to a slight decline in the placebo group. The increased MPOD was seen across all stages of AMD (II-IV). While the placebo group had no significant changes in any of the measured outcomes, both the lutein and the lutein/antioxidant treatments improved some measures of visual function, including glare recovery, quality of vision reflected by CSF and near visual acuity. For the lutein group, near visual acuity increased by about 1 line, while it decreased for the placebo-takers.

Conclusion:

According to the authors, this modest prospective clinical trial agrees with studies suggesting AMD to be, in part, a nutrition responsive disorder. LAST demonstrated improvements in symptoms of clinical concern to patients, and indicates the need for larger and longer-term trials to confirm these salutary findings.

*A multiple vitamin and mineral supplement including high potency antioxidants such as vitamins C, E and the minerals zinc and copper.

Figure 1. Primary Outcome Intervention Data: change in quality of vision (contrast sensitivity) by intervention group (denoted pictorially as bars of increasing spatial frequency) over 1 year at four spatial frequencies (3, 6, 12, and 18 cc/degree), by eye, with positive numbers denoting improvement between baseline and final visit. Number of eyes in each treatment group (Lutein, Lutein/A, and Placebo) and significance levels are as follows: Lutein (R eyes significant at 3 cc/degree [paired t test; P = 0.04; n = 21 ], 6 cc/degree [P = 0.07;n = 21 ], and 12 cc/degree [P = 0.01,n = 21 ]). In the Lutein/A group, five of eight R eye/L eye spatial frequency combinations were significant at (P < 0.05) and two were near-significant (P < 0.10). In the Placebo group, no statistically significant changes in contrast sensitivity occurred over the 1-year study.

References

1. Seddon JM et al. Dietary carotenoids, vitamins A, C and E, and advanced age-related macular degeneration. JAMA 272:1413-20, 1994.
2. Curran-Celentano J et al. Relation between dietary intake, serum concentrations and retinal concentrations of lutein and zeaxanthin in adults in a Midwest population. Am J Clin Nutr 74:796-802, 2001.
3. Khachik F et al. Identification of lutein and zeaxanthin oxidation products in human and monkey retinas. Invest Ophthalmol Vis Sci. 38 :1802-11, 1997.
4. Bone RA et al. Macular pigment in donor eyes with and without AMD: a case-control study. Invest Ophthalmol Vis Sci; 42:235-40, 2001.
5. Neuringer M et al. Supplementation of carotenoid-deplete rhesus monkeys with lutein or zeaxanthin: Effects on serum and adipose tissue carotenoids and macular pigment. FASEB 42:S224, 2001.
6. Richer S et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry 75:216-30, 2004.