The evidence that the carotenoids are beneficial for the brain is seen (mainly) from the following evidence/studies:
- We know that the amount of carotenoid in the retina (which we can measure) is related to brain concentrations if these nutrients;
- Individuals with high amounts of carotenoids in their blood and retina have enhanced cognitive function compared to individuals with low amounts of carotenoids in their retina;[2, 3]
- Supplementation with the 3 macular carotenoids (Xanthosight) significantly enhances memory in the healthy population; 
- Patients with Alzheimer’s disease have significantly lower amounts of macular pigment compared to age-matched controls;
- Supplementation with the 3 macular carotenoids (Xanthosight) significantly enhances macular pigment in patients with Alzheimer’s disease;
- Supplementation with the 3 macular carotenoids (Xanthosight) plus omega-3 fatty acids significantly enhances macular pigment and improves quality of life in patients with Alzheimer’s disease.
You will see from these studies which represent the main work in brain and carotenoids, that the formulations tested in the clinical studies include the 3 carotenoids and not just lutein.
- Johnson, E.J., et al., Relationship between serum and brain carotenoids,-tocopherol, and retinol concentrations and cognitive performance in the oldest old from the Georgia Centenarian Study. Journal of aging research, 2013. 2013.
- Feeney, J., et al., Low macular pigment optical density is associated with lower cognitive performance in a large, population-based sample of older adults. Neurobiol. Aging, 2013. 34(11): p. 2449-2456.
- Feeney, J., et al., Plasma Lutein and Zeaxanthin Are Associated With Better Cognitive Function Across Multiple Domains in a Large Population-Based Sample of Older Adults: Findings from The Irish Longitudinal Study on Aging. J Gerontol A Biol Sci Med Sci, 2017. 72(10): p. 1431-1436.
- Power, R., et al., Supplemental Retinal Carotenoids Enhance Memory in Healthy Individuals with Low Levels of Macular Pigment in A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. J Alzheimers Dis, 2018. 61(3): p. 947-961.
- Nolan, J., et al., Macular Pigment, Visual Function, and Macular Disease among Subjects with Alzheimer’s Disease: An Exploratory Study. Vol. 42. 2014a.
- Nolan, J.M., et al., The impact of supplemental macular carotenoids in Alzheimer’s disease: a randomized clinical trial. J Alzheimers Dis, 2015. 44(4): p. 1157-69.
- Nolan, J.M., et al., Nutritional Intervention to Prevent Alzheimer’s Disease: Potential Benefits of Xanthophyll Carotenoids and Omega-3 Fatty Acids Combined. J Alzheimers Dis, 2018. 64(2): p. 367-378.
Meso-zeaxanthin is the central carotenoid and dominant at the macula. It is also the carotenoid with strongest antioxidant potential. We know that individuals at risk of AMD have a deficiency in their central macular pigment and that the only way to rebuild the pigment is to supplement with a formulation containing meso-zeaxanthin. The only way to be sure that the individual will respond is to supplement with meso-zeaxanthin. Some individuals are not able to convert lutein to meso-zeaxanthin.
- Kirby, M.L., et al., A Central Dip in the Macular Pigment Spatial Profile is Associated with Age and Smoking. Invest Ophthalmol. Vis. Sci, 2010.
- Nolan, J.M., et al., Macular carotenoid supplementation in subjects with atypical spatial profiles of macular pigment. Exp Eye Res, 2012. 101: p. 9-15.
Meso-zeaxanthin was first identified in 1997. In 2010, the first human studies were published in Waterford Ireland  and since then there have been over 15 head-to-head clinical studies demonstrating the importance and superiority of meso-zeaxanthin in the formulation, including major studies funded by the European Research Council.[3, 4]
- Bone, R.A., et al., Distribution of lutein and zeaxanthin stereoisomers in the human retina. Exp Eye Res, 1997. 64(2): p. 211-8.
- Connolly, E.E., et al., Augmentation of macular pigment following supplementation with all three macular carotenoids: an exploratory study. Curr Eye Res, 2010. 35(4): p. 335-51.
- Nolan, J.M., et al., Enrichment of Macular Pigment Enhances Contrast Sensitivity in Subjects Free of Retinal Disease: Central Retinal Enrichment Supplementation Trials – Report 1. Invest Ophthalmol Vis Sci, 2016. 57(7): p. 3429-39.
- Akuffo, K.O., et al., The Impact of Supplemental Antioxidants on Visual Function in Nonadvanced Age-Related Macular Degeneration: A Head-to-Head Randomized Clinical Trial. Invest Ophthalmol Vis Sci, 2017. 58(12): p. 5347-5360.
It is true that all lutein supplements will contain small (trace) amounts of meso-zeaxanthin as they come from the same source (the Marigold Flower). However, the amounts found in these supplements are not sufficient to optimize circulating levels in blood or tissue levels.
The free from carotenoids or xanthophylls are molecules that have been separated from the fatty acids, such as palmitic, myristic, stearic, etc. Thus, they are in free form and have a smaller molecular weight because they have the esters (fatty acids from the plant) removed. This makes them a more purified compound.
The main differences is in the science! Xanthosight® research studied healthy and diseased populations with a wide age range. AREDS studies were performed only on diseased populations with intermediate AMD. Only Xanthosight, with meso-zeaxanthin shows significant effects for cognition and memory, vision performance, acuity, macular pigment health, glare, and contrast sensitivity. AREDS studies showed limited effects on AMD starting with intermediate progression.
Below is just one animal study that suggests that both Lutein and Zeaxanthin cross the BBB but no mention of MZ. Yes, MZ does cross the BBB. Importantly, all the clinical studies that have used this formulation have proven efficacy and functional benefits (see all the clinical trials on Nolan’s website). We’d be happy to schedule a call to discuss the details of the study below. Also, we see from the studies conducted by Nolan’s team that meso-zeaxanthin is taken up by all major organs following supplementation with this carotenoid.
Meso-zeaxanthin is produced at an industrial level from the lutein obtained from marigold petals. The process involves saponification at high temperatures and high alkaline conditions, and results in isomerization of lutein to Meso-zeaxanthin. Does the industrial process yield a natural product? Yes, the process to concentrate MZ by Industrial Organica is an normal, industry wide process to produce free form carotenioids from marigolds. The results in a natural compound. Meso-zeaxanthin produced from this extraction process is not synthetic. It is the exact same molecular structure as that found in the retina.
The most efficacious and researched form is in oil and softgel delivery. We do have stable beadlets and powder available, these should also be handled carefully with limited exposure to light and oxygen. Oil forms are the most stable and have a longer shelf life. The beadlets, as made by Industrial Orgánica, are also very stable as they have a small surface area. Powders have a lerge surface area and are much more expoed to air, oxygen and heat.
The quick answer is that, in the absence of supplementing, we are all suboptimal in terms of macular pigment levels. In Nolan’s work with Xanthosight, all participants in the study demonstrated a meaningful improvement in macular pigment response. We can all do better with safe and targeted supplementation. 12% of the population have central dips in macular pigment and only meso-zeaxanthin will rebuild the pigment for these individuals. Individuals with a family history of AMD, those who smoke cigarettes, those with high BMI have lower amounts of pigment. Diet is also important, given the dietary origin of these carotenoids.
Meso-zeaxanthin is one of the three stereoisomers found in the eye. With the devolution of our crops, It is not present in plants in significant amounts, but is found in marine species. For this reason, it is crucial that meso-zeaxanthin be a supplemental product to our food supply for global nutrition. Meso-zeaxanthin, lutein, and 3R, 3´R-zeaxanthin are the main carotenoids in the macula lutea, found in a ratio of 1:1:1, and are collectively referred to as macular pigment (MP). Meso-zeaxanthin is concentrated at the epicenter of the macula, where it accounts for around 50% of MP at this location, with lutein dominating the peripheral macula.