Effects of Lutein and Zeaxanthin Supplementation on Early Age-related Macular Degeneration: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Lutein and Zeaxanthin Supplementation on Early Age-related Macular Degeneration (NCT01528605), a randomized na study. The primary outcome is Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years.

2. Clinical Question

The clinical question is whether supplementation with lutein, zeaxanthin, or combinations of these carotenoids is associated with changes in macular pigment optical density in people with early age-related macular degeneration. The trial also listed measures of visual acuity, contrast sensitivity, flash recovery time, retinal electrical responses, microperimetry, serum xanthophyll concentrations, and food pattern as secondary outcomes. Those measures provide broader descriptions of visual function, retinal response, circulating compounds, and diet, but their numerical results are not reported in the registry record.

The registry lists six intervention descriptions, including placebo, and reports randomized allocation in a parallel design. The primary outcome is described over multiple measurement times. The record does not supply a single treatment-effect estimate or a clearly specified pairwise comparison for the primary outcome. Consequently, the question can be described from the registered objective and outcome, but the effect of any particular supplement cannot be judged from the information.

3. Trial Design

This was a randomized, quadruple-masked, parallel study sponsored by Peking University. The record lists the phase as NA and the status as completed. Enrollment was 168. The listed start was 2010-06, and primary completion was 2012-09. These registry entries describe the study's broad structure and timeline, but do not establish when every participant was enrolled or followed.

The intervention descriptions include placebo, low lutein, high lutein, lutein plus zeaxanthin, high zeaxanthin, and zeaxanthin plus lutein. The corresponding arm descriptions identify placebo as starch in hard shell gelatine capsules and characterize the other arms by supplement group. Doses, supplement formulations beyond those descriptions, treatment duration, adherence procedures, and the exact allocation ratio are not reported in the registry record.

Randomized allocation means assignment was intended to be determined by a random process, which can help balance measured and unmeasured baseline characteristics across groups. The record does not describe the sequence-generation method or allocation concealment. Quadruple masking indicates that the registry classifies the study as masked at four roles, but the identities of those roles and the practical masking procedures are not reported. The parallel model means participants were assigned to a group rather than described as crossing between interventions; details of participant flow between groups are not given.

The primary outcome was change in macular pigment optical density during 48 weeks and 2 years, with measurements identified at baseline, 24 weeks, 48 weeks, and 2 years. The registry also lists multiple secondary outcomes. It does not report a protocol-based sample-size justification, the planned primary comparison, or the statistical analysis plan. The figures and tables on the page should therefore be read as displays of posted material, not as a substitute for those missing design details.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: We added "High Zeaxanthin" and "High Lutein Zeaxanthin" Arms at the seconde year for additional information on the effect of zeaxanthin on MPOD and visual functions. Therefore, we did not measure the changes of serum concentration, and only measured the change of MOPD and visual functions at baseline and 48 weeks, in the two new groups.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: 4 participants was excluded during the analysis since they did not finish the intervention.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Changes of Macular Pigment Optical Density (MPOD) During 48 Weeks and 2 Years, measured over at baseline and 24 weeks, 48 weeks, 2 years during the intervention.

The primary endpoint is change in macular pigment optical density, or MPOD. The registry describes macular pigment as being located in the center of the retina, the macula, and as consisting of the carotenoids lutein and zeaxanthin. It states that the pigment serves to protect the macula from harmful blue light. MPOD was assessed by analyzing an autofluorescence picture of the participant's macula.

The registry describes MPOD as ranging from 0 to 1, with higher scores corresponding to greater pigment density, described there as greater protection. This gives the endpoint a biological interpretation: it measures the density of macular pigment rather than directly measuring a clinical event or a person's overall visual experience. The measure is relevant to the trial's supplement question because the record connects macular pigment with lutein and zeaxanthin.

Measurements were specified at baseline and at 24 weeks, 48 weeks, and 2 years during the intervention. Repeated measurements can describe how an endpoint changes over time, but interpreting them requires knowing the values, the analysis method, and how missing observations were handled. Numerical MPOD results and uncertainty estimates are not reported in the registry record. Nor does the record describe a minimum change that would be considered important to participants. The endpoint's biological rationale alone cannot establish the size, precision, or clinical importance of any observed change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary measure represent?

MPOD is a continuous measure. The registry describes its values as running from 0 to 1 and says that higher values correspond to greater macular pigment density. The registered measurement used an autofluorescence image of the macula. A continuous endpoint can be summarized with a mean and standard deviation, the parameter and dispersion listed for this outcome. In general, the mean gives a group-level summary, while the standard deviation describes variation among measurements. These summaries do not by themselves show whether groups differ, or quantify uncertainty about a difference.

How should repeated measurements be understood?

The primary outcome covers baseline and follow-up measurements at 24 weeks, 48 weeks, and 2 years. In general, repeated measurements can help describe the course of an outcome, but they also create analytical choices. An analysis might focus on change at a particular visit, compare trajectories across visits, or use a model that accounts for correlations among measurements from the same participant. These are general possibilities, not a description of the method used in this trial. The statistical plan for the repeated MPOD measurements is not reported in the registry record.

Correlated measurements from the same participant are not equivalent to independent observations. A method that treats them as independent when they are correlated can misstate uncertainty. Conversely, a repeated-measures method needs assumptions about the pattern of correlation and how incomplete observations are handled. The record does not identify a model, covariance structure, or other procedure for the primary endpoint, so these details cannot be evaluated.

What can a comparison estimate tell us?

In general, a between-group estimate describes the observed difference in outcome between groups under a specified analysis. A confidence interval communicates uncertainty around that estimate: a narrower interval indicates greater precision under the model, while a wider interval indicates less precision. A p-value addresses compatibility between the data and a stated null hypothesis under the analysis assumptions; it does not give the probability that the null hypothesis is true, nor does it describe the clinical importance of a difference. The registry entries contain no primary comparison estimate, confidence interval, or p-value, and the planned comparison is not reported.

The registry labels the outcome parameter as a mean and the dispersion as a standard deviation. These labels do not establish whether the treatment effect was calculated from raw follow-up values, changes from baseline, or an adjusted model. Such distinctions can affect the estimate and its uncertainty. The analysis method, including any adjustment for baseline measurements, is not reported in the registry record.

Why can dispersion and distribution matter?

General statistical guidance: a mean and standard deviation are most informative when the data and analysis make those summaries appropriate. If observations are strongly skewed, have influential extreme values, or otherwise depart from model assumptions, a mean-based analysis may need additional consideration. Over-dispersion, in general, means that observed variability exceeds what a model assumes; if ignored, uncertainty can be understated. The record does not report distributional diagnostics or over-dispersion, and there is no basis to say that either was present.

What does randomization contribute?

Randomization is intended to make group assignment independent of participant characteristics, reducing systematic differences at baseline on average. It does not guarantee that groups will be identical, particularly in a trial with multiple groups, and it does not prevent bias from missing outcomes, deviations from assigned treatment, or selective reporting. The registry identifies randomized allocation but does not give sequence-generation details, concealment procedures, baseline balance results, or the analysis population. These omissions limit assessment of how the design was implemented and analyzed.

What do the planning illustrations mean?

The page includes a sample-size section based on an illustration using the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. These are planning assumptions for an illustration, not a report of the trial's original design calculation, and the resulting sample sizes are not observed power. The registry does not report the trial's own sample-size justification. Because the primary outcome spans several time points and is not reduced to one comparison, a planning illustration should not be mistaken for the design rationale or a definitive analysis of the trial.

In general, power calculations depend on the assumed effect, variability, analysis, significance threshold, allocation, and target power. Changing assumptions can change a planning result. The illustration is not evidence that the trial had a particular probability of detecting a clinically important effect, and it cannot replace a confidence interval around an observed result. No numerical MPOD effect estimate is reported in the registry record for evaluating such an illustration.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is described at baseline and at 24 weeks, 48 weeks, and 2 years. The record also lists multiple supplement groups and several secondary outcomes. When an analysis involves multiple groups, outcomes, or time points, the chance of at least one apparently notable result can increase if many comparisons are made. General approaches include specifying a primary contrast in advance, using a repeated-measures model, or adjusting for multiple comparisons. These are general options; the registry record does not report which, if any, were used.

The record's analysis note says the primary outcome has several categories or time points and is not reduced to one comparison. It does not identify a primary pairwise contrast, hierarchy among outcomes, multiplicity adjustment, interim analyses, or a prespecified analysis plan. These elements are not reported in the registry record. Without them, readers cannot determine from the record alone how the displayed analyses relate to the planned primary question or whether nominal statistical results account for the range of analyses.

The primary outcome description states that 4 participants were excluded during analysis because they did not finish the intervention; 3 did not finish follow-up, while 1 died from breast cancer. The record does not explain whether these categories overlap, give reasons for the other follow-up losses, or state how missing measurements were handled. It also does not specify whether the analysis followed randomized assignment or included only participants with completed measurements.

In general, excluding participants with incomplete outcomes can introduce bias if the likelihood of missingness is related to treatment or outcome. Methods for handling missing observations rely on assumptions, and sensitivity analyses can explore how conclusions change under alternative assumptions. No missing-data method or sensitivity analysis is reported in the registry record. The analysis population and participant flow by group are also not reported, so the effect of the exclusions cannot be assessed from these details alone.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry's adverse-event entries list serious adverse events and other adverse events separately for each group. The figures show 0 serious adverse events and 0 other adverse events for the participants at risk in each listed group. The numbers at risk are 28 for placebo, 26 for low lutein, 27 for high lutein, 27 for low lutein zeaxanthin, 28 for high zeaxanthin, and 28 for high lutein zeaxanthin. These are the record's group-level counts; they should be read as registry reports, not as a complete account of every possible safety outcome.

The table does not include definitions of serious or other adverse events, the method or period of event collection, or details about event severity beyond the serious-event category. It also does not give a count for deaths: the death entries are null, which is not the same as a reported zero. Separately, the primary outcome description says that 1 participant died from breast cancer. The registry's safety table does not reconcile that statement with its null death entries. Therefore, the adverse-event figures should be interpreted narrowly as the counts displayed, without inferring more about overall safety or the completeness of reporting.

12. What the Result Does, and Does Not, Mean

The record identifies a randomized study of lutein and zeaxanthin supplement groups in people with early age-related macular degeneration, with MPOD as the primary outcome. It also describes the measurement scale, the assessment schedule, and some exclusions during analysis. Those details clarify what the trial set out to measure and how its broad design was organized.

However, the numerical primary outcome results and treatment comparisons are not reported in the registry record. The record therefore does not show whether MPOD increased, decreased, or differed between any particular groups, nor how precise such differences were. The endpoint's connection to macular pigment and the registry's description of higher scores cannot substitute for observed estimates. A biological rationale is not itself a result.

Even if a difference were displayed elsewhere, its interpretation would depend on the comparison, the amount of uncertainty, the analysis of repeated measurements, and the handling of missing outcomes. A statistically detectable difference would not automatically establish that a change is important to patients. Conversely, the absence of a reported estimate is not evidence that groups were the same. No conclusion about treatment benefit or lack of benefit should be drawn from missing numerical results.

The adverse-event entries show zero recorded serious and other adverse events in the listed groups, but the death entries are null and the endpoint description mentions a participant who died from breast cancer. These records do not support a broad safety conclusion. The trial record is informative about its question and structure, but additional outcome and analysis details would be needed to interpret efficacy and safety findings with confidence.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its primary endpoint is measured repeatedly and is described across several follow-up times, while the study includes multiple supplement groups. Those features create questions about which group comparisons and time points should carry the main interpretation. A clear prespecified primary contrast and analysis plan would help readers distinguish the central question from secondary or exploratory comparisons. Such details are not reported in the registry record.

The outcome also illustrates the distinction between a biological measure and a patient-centered conclusion. MPOD is described as a measure of macular pigment density, with higher scores corresponding to greater density. That provides a rationale for the endpoint, but statistical interpretation still depends on the size and precision of observed differences and on how the measure relates to outcomes that matter to participants. The registry entries do not report those numerical comparisons.

Missing observations are another important issue. The record notes exclusions during analysis and incomplete follow-up, including a death from breast cancer. It does not report the analysis population or missing-data method. In repeated-measure studies, these choices can influence both the estimate and its uncertainty, so transparent participant flow and sensitivity analyses are useful for interpretation.

Finally, the posted safety counts and the separate mention of a death show why registry fields need to be read in context. A null entry is not a reported zero, and a table of event counts does not by itself explain collection procedures or completeness. The trial's statistical value for readers depends not only on its randomized design, but also on accessible estimates, uncertainty, and analysis details.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report numerical results for the primary MPOD outcome in the details reviewed. It gives no group-specific means, changes, between-group estimates, confidence intervals, or p-values. This prevents assessment of direction, magnitude, and precision. The record also does not specify a single primary contrast despite describing several groups and time points.

Important design and analysis details are not reported in the registry record, including supplement doses, the randomization procedure, allocation concealment, masking roles, the original sample-size justification, and the statistical analysis plan. The registry does not state whether the analysis adjusted for baseline MPOD or how repeated measurements were modeled. The presence or absence of interim analyses is not reported.

The outcome description reports that 4 participants were excluded during analysis because they did not finish the intervention. It also says 3 did not finish follow-up and 1 died from breast cancer, without clarifying whether these categories overlap. The reasons for other incomplete data, the analysis population, and the missing-data approach are not reported. As a result, the potential influence of incomplete outcomes cannot be assessed.

The adverse-event table lists zero serious and other events by group but gives null entries for deaths, while the outcome description mentions a death. The record does not reconcile these entries or describe event ascertainment. Finally, multiple secondary outcomes are listed, but their numerical results and the approach to multiplicity are not reported. These limitations constrain interpretation of the posted record; they do not establish that a particular bias or analytical problem occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effects of Lutein and Zeaxanthin Supplementation on Early Age-related Macular Degeneration — NCT01528605.
• Registry record last updated 2014-08-29; status last verified 2014-08.
• Results first posted 2014-08-29.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The record describes a completed, randomized, quadruple-masked, parallel trial sponsored by Peking University, with enrollment of 168. It lists early age-related macular degeneration as the study condition and includes placebo and lutein and zeaxanthin supplement groups. The primary outcome was change in macular pigment optical density, measured at baseline, 24 weeks, 48 weeks, and 2 years.

The registry describes the endpoint and lists visual, retinal, serum, and food-pattern measures as secondary outcomes. It reports that 4 participants were excluded during analysis because they did not finish the intervention, including 3 who did not finish follow-up and 1 who died from breast cancer. Numerical primary outcome comparisons and the statistical analysis plan are not reported in the registry record. Adverse-event entries show zero serious and other events in the listed groups, while deaths are recorded as null.