The effects of lutein and zeaxanthin on resting state functional connectivity in older Caucasian adults: a randomized controlled trial

  • Cutter A. Lindbergh
  • Jinglei Lv
  • Yu Zhao
  • Catherine M. Mewborn
  • Antonio N. Puente
  • Douglas P. Terry
  • Lisa M. Renzi-Hammond
  • Billy R. Hammond
  • Tianming Liu
  • L. Stephen MillerEmail author


The carotenoids lutein (L) and zeaxanthin (Z) accumulate in retinal regions of the eye and have long been shown to benefit visual health. A growing literature suggests cognitive benefits as well, particularly in older adults. The present randomized controlled trial sought to investigate the effects of L and Z on brain function using resting state functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation would (1) improve intra-network integrity of default mode network (DMN) and (2) reduce inter-network connectivity between DMN and other resting state networks. 48 community-dwelling older adults (mean age = 72 years) were randomly assigned to receive a daily L (10 mg) and Z (2 mg) supplement or a placebo for 1 year. Resting state fMRI data were acquired at baseline and post-intervention. A dictionary learning and sparse coding computational framework, based on machine learning principles, was used to investigate intervention-related changes in functional connectivity. DMN integrity was evaluated by calculating spatial overlap rate with a well-established DMN template provided in the neuroscience literature. Inter-network connectivity was evaluated via time series correlations between DMN and nine other resting state networks. Contrary to expectation, results indicated that L and Z significantly increased rather than decreased inter-network connectivity (Cohen’s d = 0.89). A significant intra-network effect on DMN integrity was not observed. Rather than restoring what has been described in the available literature as a “youth-like” pattern of intrinsic brain activity, L and Z may facilitate the aging brain’s capacity for compensation by enhancing integration between networks that tend to be functionally segregated earlier in the lifespan.


Aging Default mode network Lutein Nutrition Resting state fMRI Sparse representation 



This research project was funded in part by Abbott Nutritional Products (Columbus, OH; research grant to B.R.H., L.M.R., L.S.M.) and the University of Georgia’s Bio-Imaging Research Center (Athens, GA; administrative support to L.S.M.). DSM Nutritional Products (Switzerland) provided the supplements and placebos.

Compliance with ethical standards

Conflict of interest

L.M.R. was an employee of Abbott Nutrition during a portion of the grant period while holding a joint appointment at the University of Georgia. B.R.H. has consulted for Abbott Nutrition. No other potential conflicts of interest exist for any of the study authors, including A.N.P., C.A.L., C.M.M., D.P.T, J.L., T.L., and Y.Z. The study design, the collection, analysis, and interpretation of the data, and the writing of the report were all completed independently of supporting agencies.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11682_2018_34_MOESM1_ESM.pdf (169 kb)
ESM 1 (PDF 169 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Cutter A. Lindbergh
    • 1
  • Jinglei Lv
    • 2
  • Yu Zhao
    • 3
  • Catherine M. Mewborn
    • 1
  • Antonio N. Puente
    • 4
  • Douglas P. Terry
    • 5
  • Lisa M. Renzi-Hammond
    • 1
    • 6
  • Billy R. Hammond
    • 1
  • Tianming Liu
    • 3
  • L. Stephen Miller
    • 1
    • 7
    Email author
  1. 1.Department of PsychologyUniversity of GeorgiaAthensUSA
  2. 2.Department of Psychiatry and Department of Biomedical EngineeringThe University of MelbourneParkvilleAustralia
  3. 3.Department of Computer Science, 420 Boyd Graduate Studies Research CenterUniversity of GeorgiaAthensUSA
  4. 4.Psychiatry and Behavioral SciencesGeorge Washington UniversityWashington D.C.USA
  5. 5.Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Department of Psychiatry, Massachusetts General HospitalHarvard Medical SchoolCharlestownUSA
  6. 6.Institute of GerontologyUniversity of GeorgiaAthensUSA
  7. 7.Bio-Imaging Research Center, Paul D. Coverdell CenterUniversity of GeorgiaAthensUSA

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