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To determine whether specific dietary interventions increased macular pigment optical density (MPOD) and visual function in patients with atrophic ARMD. The current objective of LAST II is to discern those specific characteristics that increase MPOD that might differentiate a responder from a non-responder.

• Diagnosis of atrophic ARMD (ICD9 362.51) by stereo-bio-ophthalmoscopy
• At least one vision-degrading ARMD-associated visual abnormality associated with ARMD in one or both eyes such as depressed contrast sensitivity, abnormal photostress glare recovery or Amsler grid deficits.

• Recent (within six months) cataract or retinal surgery
• Taking photosensitizing drugs
• Did not meet ophthalmic/visual entrance criteria.

Recruitment

Patients with atrophic ARMD were referred by ophthalmologists at two Chicago-area veterans' medical facilities. 

Design

Randomized controlled trial. Subjects were randomly assigned to one of three groups. 

• Group one (L): Received 10mg lutein per day
• Group two (L/A): Received 10mg lutein per day plus a broad spectrum of antioxidants in a preparation including vitamins, minerals, amino acids and bioflavonoids
• Group three: Received a maltodextrin placebo.

Blinding Used

Double-masked placebo-controlled trial. 

Intervention 

• Lutein supplement
• Lutein plus antioxidant supplement
• Placebo.

Statistical Analysis

• The rate of increase in MPOD was estimated using a longitudinal growth model with random slopes and intercepts
• Special contrast statements were included to compare the intercepts and slopes among the treatment groups
• Three analysis of covariance models were also fit to predict change in MPOD from baseline to 12 months controlling for baseline MPOD density, age and BMI
• A statistically significant difference was defined as P<0.05.

 

Timing of Measurements

August 1999 to May 2001, with measurements at baseline, four months, eight months and 12 months. 

Dependent Variables

Macular pigment optical density (MPOD). 

Independent Variables

• Lutein supplement
• Lutein supplement plus antioxidants
• Placebo.

Control Variables

• Age
• Weight [body mass index (BMI)]
• Initial baseline values of macular pigment
• Inclusion of a mixture of additional carotenoids/antioxidants
• Gender
• Years with ARMD diagnosis
• Cigarette, alcohol, caffeine use
• Nutritional status based on multivitamin use and Harvard School of Public Health Food Frequency Intake Questionnaires
• Ocular data including iris color, lens opacity classification system (LOCS) three cataract grade
• AREDS disease stage
• MOPD at baseline
• Visual data including visual acuity, contrast sensitivity function, glare recovery, Amsler grid defect count.

 

• Initial N: 90 patients (86 males, four females)
• Attrition (final N):  76
• Age: Average age of 74.4 with standard deviation of 7.4 years
• Location: North Chicago, IL.

 

Macular Pigment Optical Density Growth Rates

• Statistically significant differences in intercepts were observed between lutein plus antioxidant and placebo groups (P<0.0384) with lutein plus antioxidant subjects having lower baseline levels of MPOD than placebo subjects
• Statistically significant differences in slopes were also present indicating group differences in MPOD over time. MPOD increased at significantly greater rates in the supplemented groups than in the placebo group (P=0.0007 and P=0.0166 for lutein and lutein plus antioxidant groups, respectively) and these increases in the supplemented groups were significantly different from zero (P<0.0001 and P=0.013, respectively).
•  Differences in the rates of increase in the lutein vs. lutein plus antioxidant groups were not statistically significant (P=0.73)
• At eight and 12 months, the average MPOD for lutein was significantly higher than that for placebo (P=0.0157 and P=0.0010, respectively). 

MPOD Change from Baseline: Controlling for Baseline MPOD Density

• Statistically significant differences in intercepts were observed between supplemented and placebo groups (P=0.013 and P=0.026 for lutein and lutein plus antioxidants, respectively) consistent with the findings that supplements produced greater increases in MPOD over the course of the study than the placebo
• At mean levels of baseline MPOD (0.22 du), statistically significant differences in change from baseline density were observed between lutein and placebo groups (lutein mean, 0.1; placebo mean, -0.004; P=0.0003)
• This change in MPOD for subjects in the lutein group was statistically significantly different from zero (indicating an increase) up to 0.3 du baseline density and was statistically different from placebo up to 0.4 du baseline density
• The change in MPOD for subjects in the lutein plus antioxidant group was not statistically different from zero (indicating an increase) up to 0.2 du baseline density
• The change in MPOD from lutein plus antioxidant subjects was not statistically different from placebo at 0.2 or more du baseline density. These results further support the benefit of supplementation for increasing MPOD and suggest a possible small advantage of supplementing with lutein alone.
• The change in MPOD for subjects in the placebo group differed statistically from zero (indicating a decrease) at 0.35 du baseline MPOD and higher, again consistent with an insufficient washout period between cessation of prestudy supplements and the baseline measures
• Subject eyes in the lower quartile of baseline MPOD in both supplement groups were much more likely to be in the upper quartile for change in density than subjects eyes that were not in the lower quartile at baseline
• None of the 43 subjects eyes in the lowest quartile of baseline MPOD were in the lowest quartile for change in MPOD. There were not statistically significant differences (P=0.5164 between lutein and lutein plus antioxidant groups in the percentage of eyes in the upper quartile for change in MPOD from baseline
• These findings suggest that lutein supplementation (with or without) antioxidants may be most beneficial to patients with low MPOD density; however, there was a statistical trend for subject eyes in the lowest quartile of baseline MPOD to have a greater increase to 12 months on the lutein supplement vs. the lutein plus antioxidant supplement (P=0.077).

MPOD Change from Baseline: Controlling for Age and BMI

• The results of the analysis of the covariance model for change in MPOD from baseline to 12 months controlling for age indicated that change in MPOD did not vary significantly with age.  Also, there were no group differences in the relationship between age and change in MPOD.
• When controlling for BMI, the change in MPOD did not vary significantly. Subjects with higher baseline BMI had greater decreases in MPOD than subjects with lower baseline BMI.
• In both analyses of covariance (for age and BMI), there were statistically significant group differences in mean MPOD change over time in favor of supplementation.

• In this population of a predominantly male pool of ARMD patients from a veterans hospital, it was learned that intervention by dietary supplementation with lutein either alone or in combination with other vitamins, minerals and antioxidants results in continuous increase in MPOD over the course of a year
• The selected method of measurement, heterochromatic flicker photometry (HFP) was capable of providing an adequately accurate and reproducible method for this assessment. Nonetheless, there is a clear need for a less expensive clinical, not research, instrument capable of more facile and accurate evaluations with more rapid and more complete capture of the entire macular profile. 
• The most significant implications from this study are that:
  • Those individuals in greatest need of supplementation, having the lowest levels of measured MPOD, comprised the population with the greatest increase in MPOD
  • It appears macular pigment had not yet reached a plateau for the responding groups within a year, so the level of lutein might be expected to continue to increase beyond a period of one year and, therefore, a continued higher dose of supplementation may be beneficial for the full duration
  • In this study there was no apparent impediment to increasing macular pigment for individuals with two of the purported risk factors for ARMD (BMI and age)
  • As determined by other workers, bioavailability of lutein may in some part be influenced by the nutrients accompanying it at the time of ingestion.

Industry:	Kemin Foods, Inc., Vitacost.com, Nutraceutical Sciences Institute, Alcon Laboratories, Inc. Food Company: Pharmaceutical/Dietary Supplement Company:
Other:	Great Smokies Diagnostic Laboratory

• The authors note the following limitations:
  • The observations that BMI and age did not impede the positive effects of the dietary intervention suggest that future studies may want to expand the population database by investigating broader ranges of age and body mass
  • Because the population of the study was predominantly male, it would be appropriate to assess these influences on macular pigment for a predominantly elderly female population which is reported to be at greater risk of ARMD
• Other limitations of the study include:
  • The distribution of the disease status, prognostic factors and other demographics for the study groups was not provided
  • Co-interventions and extra or unplanned treatments were not described
  • Conflict of interest may exist as one of the study's sponsors, Kemin Foods, Inc., makes the lutein and lutein/antioxidant supplements used in the study.