‘Ground-breaking research’: Micromicellar formulation boosts carotenoid bioavailability in RCT

By Stephen Daniells

- Last updated on GMT

© monkeybusinessimages / Getty Images
© monkeybusinessimages / Getty Images

Related tags Lutein Zeaxanthin meso-zeaxanthin Carotenoids Eye health Amd Cognitive function Bioavailability Dietary supplements

Using a micromicellar formulation of lutein, zeaxanthin, and meso-zeaxanthin led to significantly higher increases in serum levels of the carotenoids, compared to other formulations, says a new study from Ireland.

Data published in Antioxidants indicated that six months of supplementation with the micromicellar formulation led to significant greater bioavailability of zeaxanthin and meso-zeaxanthin compared to when the carotenoids were formulated in sunflower or omega-3 oil.

The micromicellar formulation is made by esterified with acetate or propionate to form diacetates of lutein, zeaxanthin, and meso-zeaxanthin. These are then homogenized in their natural original flower matrix in the presence of lipids, phospholipids, fatty acids, and emulsifiers to keep the carotenoid soluble.

“This ground-breaking research really is disruptive science in the best sense where emerging technology and new knowledge are applied to boost the effectiveness of proven supplements,” ​said Prof John Nolan, founder of the Nutrition Research Centre Ireland (NRCI) at Waterford Institute of Technology and senior author on the paper.

“The real-world impact of this research is underlined by how the new formulation is being commercialised in the US by MacuHealth and in Europe by MacuPrime.”

Carotenoids and 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.

Data collected over two decades from 102,046 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study showed that increased levels of lutein and zeaxanthin are associated with a 40% reduction in the risk of advanced age-related macular degeneration (AMD). Scientists from Harvard and Brown Universities published their data in JAMA Ophthalmology​ in 2015.

Study details

The new study looked at whether the micromicellar could enhance bioavailability of lutein, zeaxanthin, and meso-zeaxanthin from a dietary supplement. In order to test this, the Ireland-based researchers recruited 81 healthy volunteers to participate in Carotenoid-Omega Availability Study (COAST).

Participants were randomly assigned to one of five groups: Group 1 received lutein (10 mg) plus, zeaxanthin (2 mg) plus meso-zeaxanthin (10 mg) in sunflower oil as one capsule; Group 2 was the same doses of the carotenoids in sunflower oil as two capsules; Group 3 was the same doses in DHA (430 mg) and EPA (90 mg) in two capsules; Group 4 was the same doses in the micromicelle formulation (one capsule); while Group 5 was placebo (sunflower oil).

After six months of supplementation the results showed that all of the interventions increased serum levels of the three carotenoids, compared to placebo, while “the diacetate micromicelle formulation exhibited a significantly higher mean response in serum concentrations of [zeaxanthin and meso-zeaxanthin] compared to the other active interventions,”​ wrote the scientists.

Lutein vs zeaxanthin and meso-zeaxanthin

John Nolan Waterford
Prof John Nolan and Dr Marina Green-Gomez are pictured at Carriganore House on WIT’s West Campus where the NRCI is based (Pic: Shane O’Neill, Aspect Photography).

“A finding that merits discussion is the impact of the diacetate micromicelle formulation on the absorption of the ingested carotenoids,”​ they added. “In the present study, the serum response to [zeaxanthin diacetate and meso-zeaxanthin diacetate] (Group 4) was significantly greater compared to the formulations containing free carotenoids.

“However, it was striking to see that the serum response to [lutein diacetate] remained similar to that of free [lutein]. This, however, is consistent with a previous clinical trial performed by Landrum et al., which reported that serum response to [lutein diacetate] was slightly higher but not statistically different when compared to the group supplemented with free [lutein] provided as microcrystals in oil.”

The researchers added that there this may be explained by multiple mechanisms, one of which may focus on the chemical structure of lutein, compared to zeaxanthin and meso-zeaxanthin. Specifically, lutein contains what is called an epsilon-ring, which is oriented differently from the beta-ring seen in zeaxanthin and meso-zeaxanthin, and this may affect the position that lutein occupies in lipid membranes.

“[Lutein diacetate], with an acetate group added to the epsilon-ring, could be positioned less favorably than [zeaxanthin diacetate and meso-zeaxanthin diacetate] in nascent micelles,” ​they explained.

“On the other hand, to explain the different behavior of [lutein diacetate] we also suggest an alternative hypothesis: L microcrystals could be sufficiently solubilized in the digestive tract, thus efficiently yielding soluble free lutein for micelle formation. In this way, [lutein diacetate] would not offer any advantage over [lutein] microcrystals, unlike what we have seen with [zeaxanthin diacetate and meso-zeaxanthin diacetate].”

To conclude, the researchers stated: “[Zeaxanthin and meso-zeaxanthin] diacetates in a micromicellar formulation presented an increased bioavailability, most likely due to improved micellarization and absorption efficiency.

“This formulation is a promising technology advancement that enhances the bioavailability of [zeaxanthin and meso-zeaxanthin] when compared to traditional carotenoid formulations.”

Alongside Prof Nolan, the research team included by Dr Marina Green-Gomez, Dr Alfonso Prado-Cabreror; Dr Rachel Moran, Tommy Power and Jim Stack from NRCI and Dr Laura Gómez-Mascaraque from the Teagasc Food Research Centre in Fermoy, Co Cork.

Source: Antioxidants
2020, 9​(8), 767; doi: https://doi.org/10.3390/antiox9080767
“The Impact of Formulation on Lutein, Zeaxanthin, and meso-Zeaxanthin Bioavailability: A Randomised Double-Blind Placebo-Controlled Study”
Authors: M. Green-Gomez et al.

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