The third carotenoid-mesozeaxanthin (Z -RS) and who needs to consume it

We all need it. Beyond this simple statement is a mile of commercial controversy with some prominent optometrists declaring that we must choose eye supplements containing all three carotenoids, including the two isomers of zeaxanthin-namely zeaxanthin (Z) and mesozeaxanthin (MZ). On face value, this seems reasonable. But has it been scientifically proven? No. 

There are 600 carotenoids in nature-50 commonly found in fruits and vegetables and 20 in the human blood stream. Of these 20, the retina specifically selects two to comprise the macular pigment. This process actually begins when a fetus is still in the womb. Thus, only two dietary carotenoids make up the macular pigment of the human retina: lutein (L) from leafy greens like spinach, kale, and collard greens, and Z (specifically the RR isomer) from orange peppers, paprika, and corn. The ratio of carotenoids in the blood serum is approximately 4 L/1 Z/0 MZ. Notice that there is no MZ in blood. That is, there is no MZ in the U.S. diet unless one happens to eat an egg originating from Mexico, where MZ originated as an egg yolk colorant added to chicken feed. One could also consume several hundred pounds of fish skin to achieve a physiologically significant dietary dose.  

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The MZ found in eye health supplements is a chemical synthetic derivative produced from a heat-induced, base-catalyzed conversion of L. It is important to note that this is a synthetic process, not simply an extraction of a material from a natural source. While formulas with MZ have been shown to raise macular pigment and improve vision,¹ the MZ naturally occurring in the human eye is derived from L metabolically within the retina without MZ supplementation.^2,3 MZ has not been found in other non-retinal human tissues, especially in brain tissue where L and Z are believed to play important, but as yet undefined, roles. In the center of the fovea, there are equal concentrations of L, Z, and MZ. There is no question that MZ is important.

These are the scientific concerns:

• There is a competition in absorption among L, Z, and MZ that is well recognized. This reduces serum levels of L and Z. This is important because L, especially, is the major carotenoid in the human brain. Universally better brain function has been recently associated with higher L cerebral concentrations in infants and centenarians.^4,5 Thus, by taking eye health supplements containing all three macular carotenoids, we could theoretically increase the amount of macular pigment in the eye only to find cerebral function is compromised.

• MZ has been studied only in combination with L and Z-never alone. Therefore, it is impossible to attribute any of the activity seen in trials employing the combination of L, Z, and MZ to the activity of MZ itself since it is impossible to separate the functionality of these three macular pigments. 

When a consumer buys an AREDS 2-type of supplement from a big box store labeled as containing “zeaxanthin isomers” (i.e. a combination of Z and MZ,) there is no assurance that the product contains significant amounts of Z-the component used in the AREDS 2 supplement. Furthermore, some products labeled as containing Z may actually contain little-instead they contain MZ in place of Z. Doctors and consumers both deserve clear labeling of products in order to ensure they are getting what they expect in an eye health supplement. There is a distinct need for forthright discussion of the scientific issues associated with MZ. Simple proclamations suggesting three pigments are better than two are misleading.ODT

Disclosure: Dr. Richer is the International Scientific Director for the Zeaxanthin Trade Association (ZTA).

References

1. Sabour-Pickett S, Beatty S, Connolly E, et al. Supplementation with three different macular carotenoids in patients with early age related macular degeneration. Retina. 2014 May 30.

2. Johnson EJ, Neuringer M, Russell RM, et al. Nutritional manipulation of primate retinas, III: Effects of lutein or zeaxanthin supplementation on adipose tissue and retina of xanthophyll-free monkeys. Invest Ophthalmol Vis Sci. 2005 Feb; 46(2):692-702.

3. Widomska J, Subczynski WK. Why has Nature Chosen Lutein and Zeaxanthin to Protect the Retina? J Clin Exp Ophthalmol. 2014 Feb 21;5(1):326.

4. Vishwanathan R, Kuchan MJ, Sen S, Johnson EJ. Lutein is the Predominant Carotenoid in Infant Brain: Preterm Infants Have Decreased Concentrations of Brain Carotenoids. J Pediatr Gastroenterol Nutr. 2014 Mar 31.

5. Johnson EJ, Vishwanathan R, Johnson MA, et al. Relationship between Serum and Brain Carotenoids, α-Tocopherol, and Retinol Concentrations and Cognitive Performance in the Oldest Old from the Georgia Centenarian Study. J Aging Res. 2013.