Benefits
Raises macular pigment when taken with lutein and zeaxanthin
In placebo-controlled trials, daily mixes with about 10 mg meso-zeaxanthin plus lutein and zeaxanthin raised macular pigment optical density in healthy adults and in people with glaucoma. A pooled analysis of 20 trials found larger gains in trials that included meso-zeaxanthin. Macular pigment is a marker in the eye, not a measure of how well you see.
Contrast sensitivity in adults without eye disease
In a 12-month trial of 105 adults with healthy eyes but low macular pigment, 10 mg lutein, 2 mg zeaxanthin and 10 mg meso-zeaxanthin daily improved contrast sensitivity, the ability to make out faint edges, at two of the tested settings versus placebo. All three carotenoids were given together, so the share due to meso-zeaxanthin is unknown.
Contrast sensitivity under glare and in dim light
In a small 6-month study of 36 adults, only the group taking the three-carotenoid mix improved in contrast sensitivity with and without glare. In 62 people with glaucoma, contrast under glare in dim light improved after 18 months on the mix but not on placebo, while no other visual measure changed. Both are small trials from the same research network.
Meso-zeaxanthin added to an AREDS2-type eye formula
The closest test of meso-zeaxanthin itself randomized 121 people with non-advanced age-related macular degeneration to an AREDS2-type formula with or without an extra 10 mg meso-zeaxanthin. Contrast sensitivity and macular pigment improved in both groups, with no significant difference between them, so the added meso-zeaxanthin showed no measurable extra benefit.
Macular pigment across the central retina in early macular changes
In people with early age-related macular degeneration, formulas with 10 or 17 mg meso-zeaxanthin raised macular pigment at every measured point over 12 months, while a lutein-based formula raised it at only one. Over 3 years, all three formulas raised pigment and visual acuity did not change. These studies compared formulas with each other and had no placebo group.
Absorbed into the blood and taken up by the retina
In a 120-day study of 19 adults, a mix that was mostly meso-zeaxanthin appeared in the blood and raised macular pigment versus placebo. In a separate 22-day study, the blood response per mg was 2.5 to 3 times lower for meso-zeaxanthin than for zeaxanthin, suggesting it is less readily absorbed. Both studies were very small.
Mechanism of action
Made in the eye from lutein
In developing chicken eyes and in cell culture, the visual-cycle enzyme RPE65 converts lutein into meso-zeaxanthin. This helps explain why the macula holds meso-zeaxanthin even though it is rare in common foods. The work is laboratory and animal research, not a human supplement study.
Blue light filter at the centre of the macula
Meso-zeaxanthin is the dominant carotenoid at the very centre of the macula, with zeaxanthin and lutein further out. Together they absorb blue light, which is thought to reduce blue haze, veiling glare and colour blur (chromatic aberration). This optical role is the proposed link between macular pigment and contrast or glare measures in trials.
Local antioxidant in retinal tissue
Specific binding proteins hold the macular carotenoids in the retina, where they act as local antioxidants in tissue exposed to light and oxygen. This antioxidant role comes from laboratory and biochemical work; trials of meso-zeaxanthin have not measured it as an outcome in the eye.
Clinical trials
Randomized, placebo-controlled trial of a daily supplement with 10 mg lutein, 2 mg zeaxanthin and 10 mg meso-zeaxanthin for 12 months. Primary outcome: contrast sensitivity at 6 cycles per degree (Nolan et al. 2016, Invest Ophthalmol Vis Sci)
105 adults free of retinal disease with low macular pigment (53 active, 52 placebo).
Versus placebo, contrast sensitivity improved at 6 cycles per degree (P = 0.002) and 1.2 cycles per degree (P = 0.004), and the gains tracked the rise in macular pigment (r = 0.342). Visual acuity, glare disability and photostress recovery were secondary outcomes, and the abstract does not report results for them. All three carotenoids were given together, so the part played by meso-zeaxanthin alone cannot be separated.
Single-masked, placebo-controlled randomized study comparing 20 mg lutein plus 2 mg zeaxanthin, 10 mg lutein plus 2 mg zeaxanthin plus 10 mg meso-zeaxanthin, and placebo for 6 months (Loughman et al. 2012, Invest Ophthalmol Vis Sci)
36 adults (19 men, 17 women), mean age 51, randomly assigned to three groups.
At 3 and 6 months, macular pigment rose at nearly all measured locations only in the meso-zeaxanthin group, and only that group improved in visual acuity and in contrast sensitivity with and without glare. The lutein plus zeaxanthin group improved on one mesopic contrast measure at 6 months; placebo improved on nothing. Only 36 people were split across the three groups, the study was single-masked, and the two active formulas also differed in lutein dose.
Double-masked, randomized, placebo-controlled trial (European Nutrition in Glaucoma Management Study, NCT04460365) of 10 mg lutein, 2 mg zeaxanthin and 10 mg meso-zeaxanthin daily for 18 months. Main outcome: macular pigment (Loughman et al. 2021, Ophthalmol Sci)
62 adults with diagnosed open-angle glaucoma (42 active, 20 placebo).
Macular pigment volume rose at every 6-monthly visit in the active group (P < 0.01) with no change on placebo. Mesopic contrast sensitivity under glare improved at 18 months in the active group but not on placebo. No other visual function or retinal structure measure changed, and no serious adverse events were noted. Glaucoma here is the study population; the trial did not test the supplement as a glaucoma treatment.
Head-to-head randomized clinical trial (ISRCTN13894787) comparing an AREDS2-type formula with 25 mg zinc plus 10 mg meso-zeaxanthin against the same formula without meso-zeaxanthin. Primary outcome: letter contrast sensitivity at 6 cycles per degree (Akuffo et al. 2017, Invest Ophthalmol Vis Sci)
121 people with non-advanced age-related macular degeneration (60 with added meso-zeaxanthin, 61 without).
Contrast sensitivity improved over time (P = 0.013), but the improvement did not differ between the two formulas (P = 0.881). Glare disability, photostress recovery, reading speed and macular pigment also improved over time to a similar degree in both groups. This is the closest test of meso-zeaxanthin itself, and adding it showed no measurable extra benefit. With no placebo arm, the improvements over time cannot be firmly credited to either supplement.
Comparison of three formulas: 20 mg lutein plus 2 mg zeaxanthin; 10 mg meso-zeaxanthin plus 10 mg lutein plus 2 mg zeaxanthin; and 17 mg meso-zeaxanthin plus 3 mg lutein plus 2 mg zeaxanthin, for 12 months. The abstract describes no placebo arm (Sabour-Pickett et al. 2014, Retina)
52 people with early age-related macular degeneration (17, 21 and 14 per group).
Macular pigment rose at every measured location in both meso-zeaxanthin groups but at only one location in the lutein group. Letter contrast sensitivity improved at all spatial frequencies but one in the high meso-zeaxanthin group and at low frequencies in the other two groups. Small groups and no placebo, so the results compare formulas rather than show an effect against nothing.
Randomized comparison of three carotenoid formulas (lutein-based; 10 mg meso-zeaxanthin with 10 mg lutein and 2 mg zeaxanthin; 17 mg meso-zeaxanthin with 3 mg lutein and 2 mg zeaxanthin) over 3 years, without a placebo arm (Akuffo et al. 2015, Eye (Lond))
67 people with early age-related macular degeneration.
At 3 years, macular pigment had risen from baseline in all three groups, except at the outermost measured location in the lutein group. Between years 2 and 3, further increases were seen mainly in the high meso-zeaxanthin group. Contrast sensitivity improved at some spatial frequencies in every group. No significant change in visual acuity or progression to advanced disease was observed. With no placebo arm, the changes cannot be separated from time and retesting effects.
Randomized, placebo-controlled trial (ISRCTN60816411) of one tablet a day with 10.6 mg meso-zeaxanthin, 5.9 mg lutein and 1.2 mg zeaxanthin for 6 months, with clinical blood tests at baseline and 6 months (Connolly et al. 2011, Invest Ophthalmol Vis Sci)
44 healthy adults.
Serum lutein and zeaxanthin rose in the active group (P = 0.001 and P = 0.003) and central macular pigment rose (P = 0.001 at two central locations), with no change on placebo. Clinical pathology tests stayed within normal reference ranges, apart from total cholesterol and LDL values that were already outside the normal range before supplementation. A small, short study, so it can only pick up common problems.
Placebo-controlled 120-day study of gel caps supplying 20 mg/day of a carotenoid mix that was mostly meso-zeaxanthin with smaller amounts of lutein and zeaxanthin (Bone et al. 2007, Nutr Metab (Lond))
19 adults (10 supplemented, 9 placebo).
All three carotenoids appeared in the blood during supplementation. Macular pigment rose at an average 0.59 milli-absorbance units per day in the supplement group versus a fall of 0.17 per day on placebo, a significant difference. This is the nearest any trial here comes to giving meso-zeaxanthin on its own, and it was tiny and measured only blood levels and pigment.