ZEAXANTHIN

BACKGROUND

Ingredient Type: Constituent, Substance to supplement the diet

Also Known As: Anchovyxanthin, Zeaxanthol, Xanthophyll 3

Zeaxanthin cannot be produced by the human body and is primarily a dietary supplement. It can be found in green leafy vegetables, brightly colored orange and yellow fruits, egg yolks, corn, and herbs (1,2,3,4). While green vegetables have the highest natural concentration, it can also be produced in a highly pure form synthetically (5).

Zeaxanthin’s name comes from Zea mays, or common yellow maize corn, and Xanthos, the Greek word for “yellow.”

Zeaxanthin is usually discussed together with a similar carotenoid called lutein. Most studies do not separate the two because they are usually coexistent and are understood to serve the same purpose.

TRADITIONAL USES:

Traditional Chinese medicine used plants high in zeaxanthin, like wolfberry and seaberry, to help improve eye function and jing, the basic elements that make the body and support life (6).

WHAT DOES SCIENCE TELL US?

Zeaxanthin Might Enhance Visual Function:

A study that tested older male patients with AMD tested zeaxanthin’s effects for one year. This study reported that zeaxanthin induced foveal MPOD and provided complementary distinct visual benefits by improving foveal cone-based visual parameters.  Additionally, a larger percentage of zeaxanthin patients experienced a clearing of their kinetic visual fields central scotomas than other trials (7).

A double-blind, placebo-controlled study reported that daily supplementation of zeaxanthin (2 mg/day) and lutein (10 mg/day) for a year significantly increased serum levels and MPOD, causing an improvement in the contrast in the eyes and stimulating a faster recovery process from light damage. The participants of this study included 115 healthy, university students who were asked to take one tablet every morning with breakfast for a year. 109 participants returned for at least one follow-up visit. The researchers reported a statistically significant increase in plasma lutein and zeaxanthin that were obtained over the course of the study period in the LZ-supplemented group versus placebo (P < 0.001 for both lutein and zeaxanthin). There was also a significant correlation between MPOD levels over time and visual performance (8).

Similarly, another study tested visual processing speed in healthy individuals aged 18–32 years, who were at their peak efficiency.  It reported increased macular pigment density through zeaxanthin supplementation and resulted in significant improvements in visual processing speed.  Participants were tested over a four-month period with either placebo, zeaxanthin only (20 mg/day) or a mixed formulation containing 26 mg/day zeaxanthin, 8 mg/day lutein, and 190 mg/day mixed omega-3 fatty acids. This double-blind study reported significant correlations between MP and CFF thresholds (p<0.01) and visual-motor performance (overall p<0.01). Additionally, supplementation with zeaxanthin and the mixed formulation (considered together) produced significant (p<0.01) increases in CFF thresholds (12%) and visual-motor reaction time (10%) compared to placebo (9).

Zeaxanthin Possibly Helps Support Aging Eyes:

Uncertainty is apparent in the research as most of the studies report that their findings are inconclusive and that further research is needed.  Some studies only hypothesized that zeaxanthin can protect the retina and lens against AMD because the results linking AMD to MPOD have been inconsistent across populations (10). Other studies have described zeaxanthin (and lutein) as having an alleged role in protecting against retinal degeneration and that there has been an association between zeaxanthin intake with beneficial results in people with early to intermediate AMD, but results are inconclusive (11).

It should also be noted that in a study designed to evaluate the relationship between zeaxanthin/lutein and AMD, zeaxanthin/lutein intake was inversely associated with prevalent neovascular AMD.  Study participants reported the highest dietary intake of zeaxanthin/lutein were statistically less likely to have advanced AMD. However, the authors disclaimed that there might be confounding variables, like the other nutritional supplements, interfering with zeaxanthin/lutein intake with AMD. Therefore, while zeaxanthin may be considered useful in reducing the risk of AMD, further evidence is needed to confirm that people who report a higher intake of zeaxanthin have a reduced likelihood of having NV AMD (12).

On the other hand, a large, placebo-controlled, clinical trial for people at high risk to advanced AMD, showed that the effect zeaxanthin had on AMD was not statistically significant. Researchers administered daily supplementation of L (10 mg) and zeaxanthin (2 mg), DHA (350 mg) and EPA (650 mg), zeaxanthin/lutein and DHA and EPA, or placebo to 4203 participants aged 50 to 85 years old and discovered that there was no statistically significant overall effect on progression to advanced AMD or changes in visual acuity (13). In sum, the research linking zeaxanthin to reducing the risk of AMD or improving vision within people with early to intermediate AMD might have some validity but additional studies are needed to solidify the link.

Zeaxanthin Possibly Helps Support Healthy Skin Growth:

Because zeaxanthin is usually studied in relation to ocular health, there are limited studies that would inform us of zeaxanthin’s effect on skin health. However, there were 2 studies reviewed that spoke specifically to zeaxanthin’s relationship skin cancer. The first was an experimental study, conducted in duplicate, where results were repeated at least three times.  These results showed that zeaxanthin not only intervenes in the interaction between fibroblasts and melanoma cells (notorious for metastases in skin cancer) but also inhibits the migration of fibroblasts and melanoma cells suggesting anti‐tumor activity (1).

The other study included a review of 26 epidemiological studies reporting that high intake and high blood levels of zeaxanthin (alone or with lutein) might impede cell growth and apparently lowers the occurrence of various tumors including “Non-Hodgkin lymphoma, cervical, esophagus, stomach, lung breast, kidney, head and neck, colon, and pancreas cancers”. Additionally, zeaxanthin might induce apoptosis of lymphoma, breast cancer, colon cancer, and neuroblastoma cells in vitro (2).  Clinical trials are needed to explore zeaxanthin in relation to treatment for melanoma, and cancer in general (1,2).

Zeaxanthin Possibly Helps Increase Skin Protection:

Zeaxanthin is an antioxidant that not only acts as a yellow filter protecting the macula from the blue light (2), but also has the possibility to reduce skin damage by blocking the formation of melanin pathways, decrease cytokines, and increase other antioxidants in the skin. One randomized, double-blind, placebo-controlled clinical trial containing 46 healthy males and females (18–45 years old) with mild-to-moderate dry skin, reported that zeaxanthin and lutein may perform the aforementioned duties as well as lighten and improve skin conditions. Participants were given an oral dietary supplement daily that contained either 10 mg of lutein and 2 mg of zeaxanthin or a placebo over a 12-week period. Results showed that overall skin tone was significantly improved in the zeaxanthin/lutein group compared to the placebo (P<0.0237) (14).

Zeaxanthin Might Improve Cognitive Functioning:

There were no studies on zeaxanthin alone, but the literature reviewed was consistent in reporting zeaxanthin and lutein has a positive effect on various cognitive domains. Zeaxanthin/lutein supplementation was related to improved CFF thresholds, reaction time, and coincidence anticipation errors at high speeds. Nevertheless, it is important to note that their subjects were healthy affluent university students and some of the variables might not have been sufficiently taxing to the nervous system, suggesting differing results across populations (9).  In one study with 62 participants being randomized into either the active supplement group or the placebo group, the researchers reported that zeaxanthin and lutein supplementation improved cognitive function. More specifically, participants that received the active zeaxanthin/lutein supplement had statistically significant increases in MPOD (p < 0.03) and improvements in complex attention (p < 0.02) and cognitive flexibility domains (p < 0.04), relative to participants taking the placebo. They also noted a trend for executive functioning (p = 0.073). Additionally, supplementation yielded improved composite memory (p = 0.04) but only in their male participants (15).

Similarly, a randomized, double-blind placebo-controlled trial of 51 young, healthy adults showed an improvement in visual memory and other cognitive domains like complex attention and reasoning ability with zeaxanthin/lutein supplementation. The results showed that zeaxanthin/lutein supplementation increased MPOD significantly over the course of the year vs. the placebo (p < 0.001), which resulted in significant improvements in spatial memory (p < 0.04), reasoning ability (p < 0.05) and complex attention (p < 0.04), above and beyond improvements due to practice effects (16). Generally, data that suggests that increasing zeaxanthin and lutein levels has a positive effect on brain functioning, are consistent (17).

Zeaxanthin Possibly Supports Brain Health in Older Adults:

In a double-blind study with sixty-nine participants, researchers found that MPOD did not change in the placebo group but did increase significantly in both supplement conditions. Participants received either a placebo, a pure zeaxanthin supplement (20 mg/day) or a xanthophyll combination (26 mg zeaxanthin + 8mg lutein + 190 mg mixed n-s fatty acids/day) for 4 months. In general, both conditions increased MPOD by nearly 0.10 log units suggesting that increasing zeaxanthin levels has a positive effect on the brain and its processing speed.  However, it must be noted that the improvement in processing speed was seen in young, healthy subjects and not older participants with cognitive deficits (17).  Thus, leaving an opportunity for future studies to test if zeaxanthin can improve processing speed in people with degenerative diseases that tend to slow temporal processing.

Similarly, epidemiologic evidence to date suggests that dietary carotenoids like zeaxanthin may be beneficial in cognitive health because of their properties. For example, damage and inflammation are known to cause cognitive decline in the elderly but zeaxanthin (and lutein) has antioxidant and anti-inflammatory roles that can serve to prevent deteriorations.

Nevertheless, while these assumptions might hold validity, zeaxanthin’s definite role in cognitive health requires longitudinal epidemiologic studies and clinical trials of supplementation in order to have conclusive and consistent results (18,19).

A small randomized clinical trial of lutein combined with zeaxanthin and omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) in 49 women with a limited follow-up showed a possible role for zeaxanthin/lutein in the treatment of cognitive impairment. However, a follow-up, randomized, double-masked, placebo-controlled, 2 × 2 factorial trial evaluating cognitive function and the risks and benefits of adding lutein (10mg) and zeaxanthin(2mg), among omega-3 fatty acids and other nutrient supplementations, showed no statistically significant effect on cognitive function. This 5-year study of 82 participants revealed that among older persons with AMD, oral supplementation caused no significant difference between the intervention groups. However, even though the randomized controlled clinical trials have failed to show beneficial effects, observational data suggest strong inverse associations with dementia (9).

SAFETY

Interactions & Side-Effects:

As mentioned, there are no known toxic side effects of taking higher doses of zeaxanthin.  In fact, there have never been any adverse reports filed since its inception as a dietary supplement in 1994.  In one instance, a loose bowel movement occurred on the day the test article was administered and resolved the following day without the need for medication. As it pertains to zeaxanthin, a comprehensive battery of in vitro and in vivo tests for genotoxicity showed there was no evidence for mutagenicity or clastogenicity under appropriate conditions of use (20).

REFERENCES

1. Wu NL, Chiang YC, Huang CC, Fang JY, Chen DF, Hung CF. Zeaxanthin inhibits PDGF-BB-induced migration in human dermal fibroblasts. Exp Dermatol. 2010;19(8):173-181. doi:10.1111/j.1600-0625.2009.01036.x
2. Bi M-C, Rosen R, Zha R-Y, McCormick SA, Song E, Hu D-N. Zeaxanthin Induces Apoptosis in Human Uveal Melanoma Cells through Bcl-2 Family Proteins and Intrinsic Apoptosis Pathway. Evid Based Complement Alternat Med. 2013;2013:205082. doi:10.1155/2013/205082
3. Jia YP, Sun L, Yu HS, et al. The pharmacological effects of lutein and zeaxanthin on visual disorders and cognition diseases. Molecules. 2017;22(4):1-22. doi:10.3390/molecules22040610
4. Nolan JM, Meagher KA, Howard AN, Moran R, Thurnham DI, Beatty S. Lutein, zeaxanthin and meso-zeaxanthin content of eggs laid by hens supplemented with free and esterified xanthophylls. J Nutr Sci. 2016;5:e1. doi:10.1017/jns.2015.35
5. Edwards JA. Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake. J Ophthalmol. 2016;2016. doi:10.1155/2016/3690140
6. Bucheli P, Gao Q, Redgwell R, et al. Biomolecular and Clinical Aspects of Chinese Wolfberry. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis; 2011. Chapter 14. https://www.ncbi.nlm.nih.gov/books/NBK92756/
7. Richer SP, Stiles W, Graham-Hoffman K, et al. Randomized, double-blind, placebo-controlled study of zeaxanthin and visual function in patients with atrophic age-related macular degeneration: the Zeaxanthin and Visual Function Study (ZVF) FDA IND #78, 973. Optometry. 2011;82(11):667-680.e6. doi:10.1016/j.optm.2011.08.008
8. Hammond BR, Fletcher LM, Roos F, Wittwer J, Schalch W. A double-blind, placebo-controlled study on the effects of lutein and zeaxanthin on photostress recovery, glare disability, and chromatic contrast. Investig Ophthalmol Vis Sci. 2014;55(12):8583-8589. doi:10.1167/iovs.14-15573
9. Bovier ER, Renzi LM, Hammond BR. A Double-Blind, Placebo-Controlled Study on the Effects of Lutein and Zeaxanthin on Neural Processing Speed and Efficiency. PLoS One. 2014;9(9):e108178.
10. Trieschmann M, Beatty S, Nolan JM, et al. Changes in macular pigment optical density and serum concentrations of its constituent carotenoids following supplemental lutein and zeaxanthin: The LUNA study. Exp Eye Res. 2007;84(4):718-728. doi:10.1016/j.exer.2006.12.010
11. Bernstein PS, Li B, Vachali PP, et al. Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease. Prog Retin Eye Res. 2016;50:34-66. doi:10.1016/j.preteyeres.2015.10.003
12. Group A-REDSR. The relationship of dietary carotenoid and vitamin a, e, and c intake with age-related macular degeneration in a case-control study: Areds report no. 22. Arch Ophthalmol. 2007;125(9):1225-1232.
13. Eye TA, Study D. Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration. Jama. 2013;309(19):2005. doi:10.1001/jama.2013.4997
14. Juturu V, Bowman JP, Deshpande J. Overall skin tone and skin-lightening-improving effects with oral supplementation of lutein and zeaxanthin isomers: A double-blind, placebo‑controlled clinical trial. Clin Cosmet Investig Dermatol. 2016;9:325-332. doi:10.2147/CCID.S115519
15. Hammond BR, Stephen Miller L, Bello MO, Lindbergh CA, Mewborn C, Renzi-Hammond LM. Effects of lutein/zeaxanthin supplementation on the cognitive function of community dwelling older adults: A randomized, double-masked, placebo-controlled trial. Front Aging Neurosci. 2017;9(AUG):1-9. doi:10.3389/fnagi.2017.00254
16. Renzi-Hammond LM, Bovier ER, Fletcher LM, et al. Effects of a lutein and zeaxanthin intervention on cognitive function: A randomized, double-masked, placebo-controlled trial of younger healthy adults. Nutrients. 2017;9(11):1-13. doi:10.3390/nu9111246
17. Bovier ER, Hammond BR. A randomized placebo-controlled study on the effects of lutein and zeaxanthin on visual processing speed in young healthy subjects. Arch Biochem Biophys. 2015;572:54-57. doi:10.1016/j.abb.2014.11.012
18. Johnson EJ. A possible role for lutein and zeaxanthin in cognitive function in the elderly. Am J Clin Nutr. 2012;96(5):1161S-1165S. doi:10.3945/ajcn.112.034611.
19. 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;2013(Mci). doi:10.1155/2013/951786
20. Evans M, Beck M, Elliott J, Etheve S, Roberts R, Schalch W. Effects of formulation on the bioavailability of lutein and zeaxanthin: A randomized, double-blind, cross-over, comparative, single-dose study in healthy subjects. Eur J Nutr. 2013;52(4):1381-1391. doi:10.1007/s00394-012-0447-9

See the Examine.com entry for zeaxanthin, this WebMD article about lutein and zeaxanthin for vision, or this National Eye Institute article about the Age-Related Eye Disease Studies for more information.