Last week the French Directorate General of Competition, Consumer Affairs and Fraud Prevention (DGCCRF) published the findings of a two-year investigation into the mislabelling of eye health supplements.
The report said: “50% of products [analysed on the French market] were contaminated by meso-zeaxanthin, an unrated isomer of zeaxanthin. The ingredient present in this molecule is the result of a manufacturing process not authorised at European level that could cause adverse effects.”
Responding to the findings, Professor John Nolan, principal investigator for the macular pigment research group at Waterford Institute of Technology in Ireland, told NutraIngredients it was unsurprising that MZ was being fraudulently sold on the market as zeaxanthin by some firms since it was cheaper to produce.
Professor John Nolan
“If there were adverse effects, A. this would have been identified by now in the well conducted clinical trials of which there have been many and B. if it was happening with MZ, it would be happening with zeaxanthin and lutein too.”
But professor Nolan, who has worked on 72 peer-reviewed research papers on the macular carotenoids, said the allegations of adverse effects were unfounded.
MZ is one of three carotenoids found in the macular pigment of the eye, along with lutein and zeaxanthin, leading researchers to look into the use of plant-based forms extracted from marigold (Tagetes erecta) in the management of eye conditions like Age-Related Macular Degeneration (AMD).
Nolan favours a three-caratanoid approach to AMD and said doubts raised over meso-zeaxanthin's safety were being fuelled by the commercial interests of companies that did not hold patents for MZ production. He said he had no commercial link with these companies, with the majority of his research being supported by the European Research Council via, "competitive and peer-reviewed research grants”.
Novel?
Nolan also questioned accusations around the legality of the compound as a novel food ingredient. The report stated that MZ’s “harmlessness” had never been evaluated, meaning it was not permitted for use as an ingredient in the European Union as it did not have novel foods approval.
But Nolan suggested this may not be necessary under EU law since the compound existed within the food chain before 1997 (when novel foods laws kicked into life) through its inclusion in chicken feed.
Aikaterini Apostola, spokesperson at the European Commission's Health directorate in Brussels, did not engage this exemption theory, but told us: “Regarding the use of substances other than vitamins/minerals in food supplements, the general rule is that either such a substance is novel and an authorisation is required under the novel food regulation, or it is not novel and it may be used unless it is unsafe.”
Aikaterini Apostola, European Commission
“Regarding the use of substances other than vitamins/minerals in food supplements, the general rule is that either such a substance is novel and an authorisation is required under the novel food regulation, or it is not novel and it may be used unless it is unsafe.”
She added: “As all substances other than vitamins and minerals, the use of those substances in food including in food supplement is not harmonised at EU level, and therefore, member states are allowed to maintain or adopt national rules governing such use, in accordance with Articles 34 to 36 TFEU [Treaty on the Functioning of the European Union].”
The Finnish food safety authority (EVIRA) told us it had no information about the use of MZ in foods and food supplements prior to May 1997, and said the substance had not been discussed in the novel food forum of EU member state authorities.
Meanwhile, the American Food and Drug Administration (FDA) has ruled that meso-zeaxanthin-rich extract is Generally Recognized as Safe (GRAS) as a food ingredient in selected food products at prescribed levels.
Eye health combination
Professor Nolan said his research had shown MZ was key in AMD treatment, particularly in its ability to filter blue light. He said that those at risk of AMD were found to be lacking MZ, adding macular pigment was more powerful when MZ was included.
He said he was due to publish a paper next month in the journal Retina that showed the benefits of having the three carotenoids in a supplement for patients with AMD.
“My message is clear – all three carotenoids together are far superior than anything else. Focused macular carotenoid intervention, including MZ, is helping patients with AMD.”
Professor John Nolan
“My message is clear – all three carotenoids together are far superior than anything else. Focused macular carotenoid intervention, including MZ, is helping patients with AMD.”
Meanwhile, in the past lutein and zeaxanthin firm Kemin has said such claims were "premature".
On the claims front, none of the carotenoids have been approved for eye health in the EU, with six nutrition and health claim regulation (NHCR) rejections for zeaxanthin/lutein and one for MZ.
Safety allegations
Last week’s report raised questions about the safety of MZ, which it said had been broadly linked to some cases of toxidermia. “The occurrence of toxidermia may potentially be explained by the presence of byproducts produced as a result of the manufacturing process used to produce MZ, which have never been identified or evaluated. Similarly, they may be explained by other solvent residues found in the finished product.”
However Nolan said that of all the trials he had conducted, with thousands of patients sometimes taking doses of MZ as high as 20 mg over periods of up to five years, he had not seen adverse effects. He added that if these effects were true of MZ, they would be true also of lutein and zeaxanthin.
He was concerned the report could put a brake on important eye health research and that certain organisations were using it to gain competitive advantage.
More investigations to come?
Nolan did however say that he was unsurprised by the report's findings around mislabelling. The report said: "MZ is not actively included as an ingredient but rather comes as a result of the process used for the esterification of lutein, which is performed under conditions that favour the formation of this isomer over its naturally occurring counterpart (90% meso-zeaxanthin, against 10% zeaxanthin).
"Five suppliers of zeaxanthin were identified as the source of the adulterations that were found in the inspected products. For one of the extracts (manufactured by a French company), evidence was uncovered that an unauthorized solvent, DMSO, had been used by the company."
DGCCRF report
"Five suppliers of zeaxanthin were identified as the source of the adulterations that were found in the inspected products."
Kemin, a supplier of lutein and zeaxanthin, said it welcomed the exposure of this practice and it anticipated other EU member states would undertake similar investigations to ensure, “food supplement safety and truth in labelling”.
The firm said: "The same type of misleading practices with respect to meso-zeaxanthin is also occurring in the U.S. For example, some U.S. eye health supplements labeled to contain zeaxanthin, upon laboratory analysis, have been determined to contain instead meso-zeaxanthin as the predominant ingredient."
Kemin, a lutein and zeaxanthin company
"The same type of misleading practices with respect to meso-zeaxanthin is also occurring in the U.S. For example, some U.S. eye health supplements labeled to contain zeaxanthin, upon laboratory analysis, have been determined to contain instead meso-zeaxanthin as the predominant ingredient."
The EC’s Apostola said that while food business operators are primarily responsible for ensuring compliance of their products with food law, EU member states are responsible for ensuring that food products on the European market are safe.
She said therefore: “We would not have anything to comment on the fact that, further to investigations by a member state on the possible use of an unauthorised substance, such investigations should be done in other member states. RASFF [Rapid Alert System for Food and Feed] procedures are in place for such situation and should be used by member states where they deem it necessary.”
Meanwhile EVIRA said it had only received one unconfirmed food supplement notification of a product containing MZ and was not aware if the product was still on the market. A spokesperson said: "We haven’t received any reports of adverse reactions related to eye health food supplements either. Therefore, we haven’t found further investigations necessary. However, the French report is interesting and will be taken in further consideration."
The UK Foods Standards Agency (FSA) said it had not been consulted on the report but would review the findings in due course.