Zeaxanthin

Zeaxanthin is a carotenoid commonly used alongside lutein for preserving retinal health.

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1Sources and Composition

1.1. Sources and Structure

Zeaxanthin is a carotenoid found in the diet. It is commonly discussed alongside lutein as they are both carotenoids found in high levels in dark green vegetables (such as kale or parsley), orange and yellow fruits, and are a major health factor in the yolk of eggs.[4]

Specific foodstuffs that have been shown to contain zeaxanthin include:

  • Eggs at approximately 85 μg per yolk (unenriched[2]) potentially being between 137-487 μg per yolk when intentionally enriched[2]

  • Peaches (Prunus persica)[5]

  • Persimmon (Diospyros kaki L.)[6]

Dark greens actually contain more zeaxanthin than do eggs but the zeaxanthin within eggs have superior absorption, making them a more practical source of zeaxanthin as well as lutein.[7]

Generally speaking, zeaxanthin is found in dark green vegetables and also in yellow-orange fruits and veggies. It can also be found in the yolk of eggs but not the white

When it comes to the structure of zeaxanthin, it is a carotenoid and more specifically in the subgroup of xanthophylls (carotenes, the other subgroup, are non-polar molecules without any oxygen while xanthophylls polar molecules with at least one oxygen molecule[8]); lutein is also a xanthophyll while other supplements that happen to be xanthophylls include both astaxanthin and fucoxanthin.

Zeaxanthin is a carotenoid, and more specifically a xanthophyll, similar to lutein

1.2. Biological Significance

When it comes to the carotenoid class, there are approximately 30-50 that are normally in the human diet with 10-15 of them being able to be detected in serum.[9] These carotenoids are mostly related to lutein and zeaxanthin, being their metabolites or related molecules, and as carotenoids they are able to interact with Vitamin A metabolism to a high degree (as β-carotene is not only the plant form of Vitamin A, but a carotenoid itself). When it comes to zeaxanthin, it only makes up 3% of total human serum carotenoids (in a non-supplemented state) with lutein and lycopene both taking up 20% and β-carotene a mere 10%[10] although it, along with lutein, have more relative importance in the human retina than do the other carotenoids.[9][11]

Xanthophylls in general seem to have more relevance than carotenes in the brain, consisting of 72% total carotenoids[12] whereas the opposite trend seems to exist in the periphery with 57% of total carotenoids being carotenes.[12]

Lutein and zeaxanthin are non-vitamin carotenoids, meaning that they cannot convert into Vitamin A and, alongside their common metabolite (meso-zeaxanthin) they are referred to as the macular pigments.[9]

Zeaxanthin is a naturally occurring carotenoid in not only the diet but also human serum, although it is by no means the major carotenoid in the blood it seems to have more significance in the retina


2Pharmacology

2.1. Absorption

When it comes to lutein, the bioavailability of it seems to be significantly higher when consumed from eggs when compared to either vegetables or dietary supplements even when the amount of dietary fat provided is similar; with 6mg lutein increasing serum lutein 323% with eggs but only 82% and 140% with supplements and spinach respectively.[13] Fat itself is already a major determinant of carotenoid absorption as, without dietary fat, their absorption is greatly hindered[14] but carotenoids seem to also experience better absorption from cholesterol[15] and phospholipids[16] present in eggs. This benefit to absorption applies to more than just the carotenoids within the eggs however, as ingesting cooked eggs alongside vegetables is able to increase how many carotenoids are absorbed from the vegetables.[17]

There is something within eggs that enhances the absorption of carotenoids, and this appears to apply to not only the carotenoids found within the eggs themselves but also coingested carotenoids

2.2. Transportation in Serum

Oral ingestion of food products containing zeaxanthin have been found to increase circulating zeaxanthin[1][2] with one study giving subjects an egg containing 487.31 μg zeaxanthin seeing a 212% increase in serum zeaxanthin when compared to the group given a normal egg (85 μg zeaxanthin)[2] with another study also finding that eggs with high levels of zeaxanthin (213+/-85 μg) can increase serum zeaxanthin 142% higher than control.[18]

The serum concentration of zeaxanthin seen in these studies with eggs (127.5ng/mL from 487.31 μg[2] and 0.105-0.116μM from 213 μg[18]).

2.3. Neurological Distribution

Zeaxanthin and lutein appear to have more relevance in the cerebellum where their concentration is higher than the frontal, occipital, and temporal cortices which seemed to be opposite of α-tocopherol (Vitamin E) which was low in the cerebellum;[12] the occipital cortex seemed to be relatively high in the cryptoxanthin carotenoids[12] while ingestion of pure zeaxanthin in primates appears to increase the amount of zeaxanthin that reaches the cerebellum and frontal cortex.[19]

When zeaxanthin is ingested at 3.9μM/kg in primates for 24-101 weeks (dose estimated to be 15-fold higher than standard lab food) it increases zeaxanthin concentrations in the cerebellum (to the highest degee), occipital and frontal cortices, and pons (to the lowest degree) which differs from isolated lutein that drastically increases lutein concentrations of the occipital cortex;[19] the increases seen in brain tissue are correlated to the changes seen in retinal tissue.[19]

Zeaxanthin is found in the brain, to the highest relative degree in the cerebellum, and oral ingestion of zeaxanthin in primates appears to be able to reach the brain

2.4. Metabolism

β-Carotene oxygenases

Both lutein and zeaxanthin share a common metabolite, called meso-zeaxanthin.


3Neurology

3.1. Neurooxidation

Given how zeaxanthin is a macular carotenoid that accumulates in the retina after consumption and the eyes being intimately connected with the brain, zeaxanthin and other carotenoids have been investigated for their effects on neural tissue. Furthermore, it seems that xanthophylls (lutein and zeaxanthin) are more prominent in the brain relative to carotenes (such as b-carotene and lycopene) while carotenes are more represented in the periphery; this study[12] found that 72% of brain carotenoids (57% of peripheral carotenoids were carotenes) and elsewhere brain xanthophylls have been found to be 66-77% total carotenoids.[20]

In a study on octogenarians and centenarians, lutein and zeaxanthin appeared to have the most significant correlations with cognitive performance when compared to other carotenoids, with higher macular carotenoid concentrations being associated with lower dementia severity[12] and zeaxanthin being positively associated with better overall cognitive performance.[12] There seemed to be a specific relation between zeaxanthin and improved verbal fluency[12] and this association has been found elsewhere where elevated lutein and zeaxanthins are associated with better cognitive function (global cognition, memory, and executive function) while zeaxanthin is further associated with processing speed.[21]

As lutein and zeaxanthin are highly protective in the eye, and the eye is intimately connected to the brain, it is thought that these carotenoids are also protective of the brain. There do appear to be some associations and zeaxanthin may be a relevant protective factor

3.2. Memory and Learning

One study which ingestigated a combination of omega-3 fatty acids (350mg DHA and 650mg EPA), lutein (10mg), and zeaxanthin (2mg) found that, when given to older subjects who were already taking a few antioxidant supplements, that the addition of all three of them or the addition of just the carotenoids failed to exert any cognitive protective effect after one year.[3]


4Interactions with Oxidation

4.1. Hydrogen Peroxide

Zeaxanthin appears to have direct antioxidant potential against peroxyl radicals, being able to scavenge them regardless of whether they are water or lipid soluble.[22]


5Peripheral Organ Systems

5.1. Eyes

Zeaxanthin, along with lutein and their common metabolite meso-zeaxanthin (MZ) are referred to as the macular carotenoids due to their high presence in the human retina.[23][24] The macular carotenoids are the major components of what is known as 'macular pigment' which helps protect the eyes from light-induced damages and is highly protective against age-related macular degeneration;[25] lutein and zeaxanthin are investigated for their effects in the eyes because whether you supplement them[26] or consume them through the diet[27] oral ingestion of these carotenoids increases the level of them inside the retina where they exert protective effects.

A buttermilk drink containing lutein (1.38+/-0.16 mg), zeaxanthin (0.21+/-0.02 mg), and DHA from fish oil (160+/-10 mg) for one year in older adults with suboptimal visual acuity has shown monthly improvements in Macular pigment optical density (MPOD) and visual acuity when compared to control.[1]


6Sexuality and Pregnancy

6.1. Lactation

Lutein and zeaxanthin are both found in breast milk[28][29] where the amount that is detected in breast milk is related to the amount of these two carotenoids in the blood.[29]

Scientific Support & Reference Citations

References

  1. van der Made SM, et al. Increased Macular Pigment Optical Density and Visual Acuity following Consumption of a Buttermilk Drink Containing Lutein-Enriched Egg Yolks: A Randomized, Double-Blind, Placebo-Controlled Trial. J Ophthalmol. (2016)
  2. Kelly ER, et al. The effect of modified eggs and an egg-yolk based beverage on serum lutein and zeaxanthin concentrations and macular pigment optical density: results from a randomized trial. PLoS One. (2014)
  3. Chew EY, et al. Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial. JAMA. (2015)
  4. Nolan JM, et al. Lutein, zeaxanthin and meso-zeaxanthin content of eggs laid by hens supplemented with free and esterified xanthophylls. J Nutr Sci. (2016)
  5. Khachik, F et al.. Separation, identification, and quantification of carotenoids in fruits, vegetables and human plasma by high performance liquid chromatography. Pure Appl Chem. (1991)
  6. Zaghdoudi K, et al. Extraction, Identification and Photo-Physical Characterization of Persimmon (Diospyros kaki L.) Carotenoids. Foods. (2017)
  7. Ribaya-Mercado JD, Blumberg JB. Lutein and zeaxanthin and their potential roles in disease prevention. J Am Coll Nutr. (2004)
  8. Bone RA, et al. Stereochemistry of the human macular carotenoids. Invest Ophthalmol Vis Sci. (1993)
  9. Jia YP, et al. The Pharmacological Effects of Lutein and Zeaxanthin on Visual Disorders and Cognition Diseases. Molecules. (2017)
  10. Khachik F, et al. Identification, quantification, and relative concentrations of carotenoids and their metabolites in human milk and serum. Anal Chem. (1997)
  11. Krinsky NI, Landrum JT, Bone RA. Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu Rev Nutr. (2003)
  12. Johnson EJ, 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)
  13. Chung HY, Rasmussen HM, Johnson EJ. Lutein bioavailability is higher from lutein-enriched eggs than from supplements and spinach in men. J Nutr. (2004)
  14. Brown MJ, et al. Carotenoid bioavailability is higher from salads ingested with full-fat than with fat-reduced salad dressings as measured with electrochemical detection. Am J Clin Nutr. (2004)
  15. Hu X, Jandacek RJ, White WS. Intestinal absorption of beta-carotene ingested with a meal rich in sunflower oil or beef tallow: postprandial appearance in triacylglycerol-rich lipoproteins in women. Am J Clin Nutr. (2000)
  16. Baskaran V, Sugawara T, Nagao A. Phospholipids affect the intestinal absorption of carotenoids in mice. Lipids. (2003)
  17. Kim JE, et al. Effects of egg consumption on carotenoid absorption from co-consumed, raw vegetables. Am J Clin Nutr. (2015)
  18. Handelman GJ, et al. Lutein and zeaxanthin concentrations in plasma after dietary supplementation with egg yolk. Am J Clin Nutr. (1999)
  19. Vishwanathan R, et al. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates. Nutr Neurosci. (2013)
  20. Craft NE, et al. Carotenoid, tocopherol, and retinol concentrations in elderly human brain. J Nutr Health Aging. (2004)
  21. Feeney J, et al. Plasma Lutein and Zeaxanthin Are Associated With Better Cognitive Function Across Multiple Domains in a Large Population-Based Sample of Older Adults: Findings from The Irish Longitudinal Study on Aging. J Gerontol A Biol Sci Med Sci. (2017)
  22. El-Agamey A, et al. Carotenoid radical chemistry and antioxidant/pro-oxidant properties. Arch Biochem Biophys. (2004)
  23. Bone RA, et al. Distribution of lutein and zeaxanthin stereoisomers in the human retina. Exp Eye Res. (1997)
  24. Landrum JT, Bone RA. Lutein, zeaxanthin, and the macular pigment. Arch Biochem Biophys. (2001)
  25. Mozaffarieh M, Sacu S, Wedrich A. The role of the carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: a review based on controversial evidence. Nutr J. (2003)
  26. Thurnham DI, et al. Macular response to supplementation with differing xanthophyll formulations in subjects with and without age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. (2015)
  27. Wenzel AJ, et al. A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women. J Nutr. (2006)
  28. Hanson C, et al. A Comparison of Nutritional Antioxidant Content in Breast Milk, Donor Milk, and Infant Formulas. Nutrients. (2016)
  29. de Azeredo VB, Trugo NM. Retinol, carotenoids, and tocopherols in the milk of lactating adolescents and relationships with plasma concentrations. Nutrition. (2008)

(Common misspellings for Zeaxanthin include zeaxanthine, zexanthin, zexanthine)