Investigation of the Genetic and Environmental Determinants of MP Including Response to Supplementation
Condition: Healthy
Study type: Interventional

Summary: 
      This study aims to investigate genetic and environmental determinants of macular pigment (MP)
      and assess the effects of lutein and zeaxanthin-rich supplements on macular pigment levels.
    

Detailed description: 
      Age-related macular degeneration is the leading cause of blindness in elderly people in
      western countries1. It is a degenerative condition of the macula characterized by the death
      or dysfunction of photoreceptors, leading to the progressive loss of central vision1. Central
      vision is needed for activities requiring fine vision such as reading, driving or recognizing
      faces. With the aging population and increasing expectations in health care it is therefore
      of utmost importance to preserve the quality of life and independence of the elderly through
      prevention of this ocular disease.

      Much interest surrounds macular pigment due to its putative role in protecting the macula
      from oxidative stress and age-related degenerative change2, yet much is still unknown about
      factors that determine its uptake and deposition. Large inter-individual differences in MP
      have been demonstrated with several large population based studies showing that peak macular
      pigment density can vary by over a factor of 10 between individuals3-4. Subsequent studies
      have suggested a number of parameters such as age, diet, percentage body fat, gender and
      tobacco use5-9 as determinants of MP, however these only account for approximately a third of
      the variance leaving a significant proportion unexplained.

      Lutein and Zeaxanthin (L and Z), constituents of MP, cannot be synthesized by the body and so
      are entirely dietary in origin. They are present in foods such as collard greens, spinach and
      Brussels sprouts10. Variation in the bitter-taste receptor gene, TAS2R38 confers the ability
      to taste 6-n-propylthiouracil (PROP) and phenylthiocarbamide (PTC) which is present in many
      of these foods11. People who taste PTC with a greater intensity are more likely to avoid
      these foods and therefore we hypothesize they may have lower levels of macular pigment. Thus,
      this study may help to identify a group at higher risk of macular degeneration.

      Despite MP's dietary origin only modest correlations exist with serum and dietary levels of L
      and Z, and although the level of MP can be augmented in most people by diet or
      supplementation the response is variable and not always correlated with baseline level. Most
      supplementation studies identify a sub-group of "retinal non-responders"12 in which serum
      values of the carotenoids have risen, yet no change is found in macular pigment, the reason
      for this is not clear. The first part of our study will provide a well-phenotyped group in
      which to explore this further. Several studies have also shown that peak macular pigment
      levels are strongly heritable13-14 suggesting genetics may play an important role. Although
      no gene has currently been clearly identified the ApoE gene has been suggested to show an
      association with macular pigment level. A supplementation study in this population will be
      able to determine whether the genes identified on a cross-sectional basis do determine uptake
      of the nutritional supplement. We may also be able to identify specific demographic or
      lifestyle factors of non-responders which may help to explain the phenomenon.

        1. Carpentier S, Knaus M, Suh M. Associations between Lutein, Zeaxanthin, and Age-Related
           Macular Degeneration: An Overview. Clinical Reviews in Food Science and Nutrition. 2009
           49:313-326

        2. Whitehead AJ, Mares J, Danis RP. Macular Pigment: A Review of Current Knowledge. Arch
           Opthamol. July 2006; 124: 1038-1045

        3. Ciulla TA, Curran-Celantano J, Cooper DA, et al. Macular pigment optical density in a
           midwestern sample. Ophthalmology. Apr 2001;108(4):730-737.

        4. Hammond BR, Jr., Caruso-Avery M. Macular pigment optical density in a Southwestern
           sample. Invest Ophthalmol Vis Sci. May 2000;41(6):1492-1497.

        5. Hammond BR, Jr., Curran-Celentano J, Judd S, et al. Sex differences in macular pigment
           optical density: relation to plasma carotenoid concentrations and dietary patterns.
           Vision Res. Jul 1996;36(13):2001-2012.

        6. Hammond BR, Jr., Wooten BR, Snodderly DM. Cigarette smoking and retinal carotenoids:
           implications for age-related macular degeneration. Vision Res. Sep
           1996;36(18):3003-3009.

        7. Ciulla TA, Hammond BR, Jr. Macular pigment density and aging, assessed in the normal
           elderly and those with cataracts and age-related macular degeneration. Am J Ophthalmol.
           Oct 2004;138(4):582-587.

        8. Curran-Celentano J, Hammond BR, Jr., Ciulla TA, Cooper DA, Pratt LM, Danis RB. Relation
           between dietary intake, serum concentrations, and retinal concentrations of lutein and
           zeaxanthin in adults in a Midwest population. Am J Clin Nutr. Dec 2001;74(6):796-802.

        9. Nolan J, O'Donovan O, Kavanagh H, et al. Macular pigment and percentage of body fat.
           Invest Ophthalmol Vis Sci. Nov 2004;45(11):3940-3950.

       10. Carpentier S, Knaus M, Suh M. Associations between Lutein, Zeaxanthin, and Age-Related
           Macular Degeneration: An Overview. Critical Reviews in Food Science and Nutrition. 2009;
           49(4): 313-326

       11. Bachmanov A, Beauchamp G. Taste Receptor Genes. Annual Review of Nutrition.
           2007.27:389-414

       12. Hammond BR, Jr., Johnson EJ, Russell RM, et al. Dietary modification of human macular
           pigment density. Invest Ophthalmol Vis Sci. Aug 1997;38(9):1795-1801.
    

Intervention name(s): Nutrof Total; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Antioxidant and trace element supplement
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Focus; uptake; Lutein; Zeaxanthin; individuals