Eye health supplements may contain undeclared meso-zeaxanthin, say researchers. Nothing to see here, says supplier

By Stephen Daniells contact

- Last updated on GMT

Image © iStockPhoto / malivoja
Image © iStockPhoto / malivoja

Related tags: Lutein, Eye, Zeaxanthin

Commercial lutein and zeaxanthin supplements for eye health may contain undeclared meso-zeaxathin, say researchers from Ireland, which may challenge a long-held hypothesis in the eye health sector.

However, a leading lutein producer has said that the process of producing lutein ‘unavoidably’ creates tiny amounts of meso-zeaxanthin, and that these levels “are unlikely to affect the safety or efficacy” ​of its ingredient.

Questioning a major hypothesis

Prof John Nolan from the Macular Pigment Research Group at the Waterford Institute of Technology in Ireland told NutraIngredients-USA that a major hypothesis in the eye health community is that meso-zeaxanthin is derived from lutein in the retina, and that commercial lutein is all you need.

“I used to stand up and say that meso-zeaxanthin comes from lutein,”​ he said. This hypothesis is supported by two key studies, explained Prof Nolan: One is a study by Neuringer et al. supported by DSM, which fed monkeys lutein and zeaxanthin (Invest Ophthalmol Vis Sci​., 2004, Vol 45, pp. 3234-43). The other study was done with quail by Paul Bernstein’s group at the University of Utah (Biochemistry​, 2007, Vol. 46, pp. 9050-7), which found that meso-zeaxanthin is generated by lutein.

“The science shows that meso-zeaxanthin is about 33% of the macula pigment, so what’s the enzyme that converts lutein to meso-zeaxanthin?” ​asked Prof Nolan.  

“Our new study is the result of finding something we didn’t expect to find: We were testing the blood of people fed lutein and found that meso-zeaxanthin was there, so we thought we’d better test the supplements. We found meso-zeaxanthin in there,” ​he said.

Lutein & eye health

The link between lutein and eye health was first reported in 1994 by Dr Johanna Seddon and her co-workers at Harvard University, who found a link between the intake of carotenoid-rich food, particularly dark green leafy vegetables like spinach, and a significant reduction in AMD (JAMA​, Vol. 272, pp. 1413-1420). The burden of AMD falls on 25 to 30 million people worldwide, according to AMD Alliance International.

The macula is a yellow spot of about five millimeters diameter on the retina. The yellow color is due to the content of the carotenoids lutein and zeaxanthin, which we derive from the diet. These compounds are the only carotenoids capable of filtering the harmful blue light than can damage cells in the eye, the rods and the cones.

A thin macular pigment can allow the blue light through and destroy the cells. Maintaining high levels of the macular carotenoids, and therefore the macular pigment, is seen by many eye health experts as a valid approach to maintaining eye health and reducing the risk of AMD.

“I want to understand the absolute origins of these nutrients. The origin of meso-zeaxanthin needs to be confirmed. It is not exclusively from lutein. I want openness and transparency.”

Study details

The Waterford-based scientists, working with scientists from The Howard Foundation at the University of Cambridge (UK) and the University of Greifswald (Germany), purchased commercial supplements in the US and in Europe. Dr Nolan and his co-workers tested three batches of nine products for lutein, zeaxanthin, and meso-zeaxanthin content.

“In every product tested, actual lutein concentration was close to target, but zeaxanthin concentration varied greatly (47–248 % of declared concentration), and the lutein:zeaxanthin ratio within some supplements was adversely affected in consequence,” ​they wrote in the European Food Research and Technology​.

In addition, they found meso-zeaxathin in six of the seven products that did not declare this carotenoid, they said.

Four of these products used the commercial FloraGLO Lutein ingredient, said the researchers.

“This indicates that a greater degree of regulation is required for the use of commercially available supplements containing the macular carotenoids, and greater transparency by producers with respect to the source of the respective carotenoids is advised,” ​they concluded.

Kemin: De minimis​ quantities of meso-zeaxanthin are an unavoidable by-product of the saponification process

In response to the study’s findings, Dick Roberts, PhD, principal manager; scientific affairs & technical services for Kemin Human Nutrition and Health Division, told NutraIngredients-USA that tiny amounts of meso-zeaxathin are “unavoidably”​ produced during the production of FloraGLO Lutein from marigolds, and that Kemin and DSM have been “transparent with regulatory bodies around the world acknowledging this fact”.

“Lutein has been the topic of scientific investigation for more than 20 years, particularly as it pertains to human eye health, and FloraGLO Lutein is the most researched brand of lutein available on the market today with more than 70 human clinical studies including the landmark ARED2 trial, more than all its competitors combined,” ​said Dr Roberts. 

Marigold
Image: iStockPhoto

“The recent article by Prado-Cabrero, et al. from the Macular Pigment Research Group in Ireland reports the results of a chiral high-performance liquid chromatography analysis of commercial eye health products made with FloraGLO Lutein in which varying amounts of meso-zeaxanthin were found ranging from 0.04 to 0.18 mg per capsule,”​ said Dr Roberts.

“Based upon this data, the authors speculate that these small amounts of meso-zeaxanthin are a result of the using FloraGLO Lutein as source of lutein. Furthermore, the authors use these results to call for more transparency in the labeling of vitamin/dietary supplement products intended for use in eye health that would include the labeling of the lutein, zeaxanthin, and meso-zeaxanthin of such products.

“First, it needs to be understood that Kemin and DSM have been transparent with regulatory bodies around the world acknowledging the fact that the saponification process involved in converting the oleoresin obtained from marigold flowers to crystalline lutein and crystalline zeaxanthin as used in the manufacture of FloraGLO Lutein produces small, ​de minimis quantities of meso-zeaxanthin. This xanthophyll is an unavoidable by-product of the saponification process,”​ said Dr Roberts.

“The ​de minimis amounts of meso-zeaxanthin eventually present in FloraGLO Lutein are unlikely to affect the safety or efficacy that has been repeatedly shown for this material.”

The company monitors the meso​-zeaxanthin content of the FloraGLO Lutein product, he added.

“In the results of testing for the three products that were labeled as containing only FloraGLO Lutein and that had assay results consistent with its composition, the meso-zeaxanthin content was less than 0.11 mg per capsule (less than 1% of the total amount of lutein present),”​ noted Dr Roberts. “Furthermore, there was one product tested containing FloraGLO Lutein in which no meso-zeaxanthin could be found (non-detectable). Kemin and DSM maintain that the overwhelming scientific support for the eye health benefits of products with FloraGLO Lutein result from the lutein and zeaxanthin content.” 

Transparency

Macula
The macula is a yellow spot of about five millimeters diameter on the retina. Image: iStockPhoto

Dr Roberts said that Kemin and DSM welcome and support the authors’ call for greater transparency in the labeling of eye health products containing lutein and zeaxanthin.

“The use of terms like ‘zeaxanthin isomers’ has been used to describe mixtures of zeaxanthin and meso-zeaxanthin and create more confusion in the mind of consumers than they provide benefit,” ​he said. “Furthermore, the intentional substitution of meso-zeaxanthin in place of any or all of the zeaxanthin in any product and labeling it as containing zeaxanthin is an unacceptable and illegal practice that should not be tolerated in an industry that values high quality standards and transparency. 

“However, this issue is one for the regulatory bodies in the various countries in which eye health products are being marketed, as demonstrated recently by some European Member States (France and Poland) where controls of mislabeled food supplements has become a priority.”  

Current scientific understanding

“The current scientific understanding is that the human body has the ability to convert lutein to meso-zeaxanthin in appropriate amounts in the eye where it is needed,” ​stressed Dr Roberts. “To date, no research has shown that this conversion capacity is altered in human eyes either through disease or aging. 

“Although research conducted by the Macular Pigment Research group in Ireland has shown that there may be benefits to supplementation with a combination of lutein, zeaxanthin and meso-zeaxanthin in individuals with low central macular pigment optical density, this benefit has never been demonstrated to be attributable to meso-zeaxanthin alone since no clinical study has been conducted on meso-zeaxanthin by itself to support such efficacy. 

“Furthermore, the effects of meso-zeaxanthin have not been demonstrated to prevent or reduce the progress of any age-related ocular condition.  Indeed, the importance of these findings has yet to be identified.”

Source: European Food Research and Technology
Published online ahead of print, doi: 10.1007/s00217-015-2569-9
“Assessment of lutein, zeaxanthin and meso-zeaxanthin concentrations in dietary supplements by chiral high-performance liquid chromatography”
Authors: A. Prado-Cabrero, S. Beatty, A. Howard, J. Stack, P. Bettin, J.M. Nolan

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1 comment

A response to Kemin from Drs Nolan & Beatty

Posted by Dr John Nolan,

Dear Editor,
We appreciate the kind acknowledgment by Dick Roberts of our recently published work, demonstrating the presence of undeclared meso-zeaxanthin (MZ) in many commercially available products aimed at eye health, and we would like to take this opportunity to address and add to a few points raised by Dr. Roberts.
First, we agree entirely that the efficacy of pure MZ has not been tested, but it would be remiss of any commentator if he/she omitted to mention that the efficacy of pure lutein (L) or pure zeaxanthin (Z) has also never been studied.
Second, we are somewhat surprised that Dr. Roberts asserts that “…the current scientific understanding is that the human body has the ability to convert lutein to MZ in appropriate amounts..” when this has simply never been studied in humans.1
Third, Dr. Roberts’ statement that "This xanthophyll [MZ] is an unavoidable by product of saponification process" is not true, as pure L can be generated2 (but the process is difficult and costly).
Fourth, Dr. Roberts says that the amounts of undeclared MZ in the formulations tested is “de minimis”, but this statement should be interpreted with full appreciation of the fact that the patient is consuming one table daily, indefinitely, and that studies have shown that consumption of daily “de minimis” concentrations of MZ results in detectable changes in circulating levels of this carotenoid.3
Finally, and given that the aim of supplementation is to augment macular pigment and to optimize vision, it should be noted that several head-to-head trials have demonstrated that a formulation containing all three macular carotenoids (in a MZ:L:Z [mg] ratio of 10:10:2) is superior in these endeavors than formulations lacking MZ.3-8
We hope our comments add to this emerging debate,
Kind Regards,
Stephen Beatty and John Nolan
Reference List

(1) Nolan JM, Meagher K, Kashani S, Beatty S. What is meso-zeaxanthin, and where does it come from? Eye (Lond) 2013.
(2) Akuffo KO, Beatty S, Stack J, Dennison J, O'Regan S, Meagher KA et al. Central Retinal Enrichment Supplementation Trials (CREST): design and methodology of the CREST randomized controlled trials. Ophthalmic Epidemiol 2014; 21(2):111-123.
(3) Meagher KA, Thurnham DI, Beatty S, Howard AN, Connolly E, Cummins W et al. Serum response to supplemental macular carotenoids in subjects with and without age-related macular degeneration. Br J Nutr 2013; 110(2):289-300.
(4) Nolan JM, Akkali MC, Loughman J, Howard AN, Beatty S. Macular carotenoid supplementation in subjects with atypical spatial profiles of macular pigment. Exp Eye Res 2012; 101:9-15.
(5) Sabour-Pickett S, Beatty S, Connolly E, Loughman J, Stack J, Howard A et al. Supplementation with three different macular carotenoid formulations in patients with early age-related macular degeneration. Retina 2014; 34:1757-1766.
(6) Akuffo KO, Nolan JM, Howard AN, Moran R, Stack J, Klein R et al. Sustained supplementation and monitored response with differing carotenoid formulations in early age-related macular degeneration. Eye (Lond) 2015; 29(7):902-912.
(7) Thurnham DI, Nolan JM, Howard AN, Beatty S. Macular response to supplementation with differing xanthophyll formulations in subjects with and without age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2015; 253(8):1231-1243.
(8) Loughman J, Nolan JM, Howard AN, Connolly E, Meagher K, Beatty S. The impact of macular pigment augmentation on visual performance using different carotenoid formulations. Invest Ophthalmol Vis Sci 2012; 53:7871-7880.

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