What are Lutein, Zeaxanthin, and Meso-Zeaxanthin?

Lutein, zeaxanthin, and meso-zeaxanthin belong to the family of vitamins referred to as carotenoids. Other notable members of this same family include beta-carotene (a precursor to vitamin A) and lycopene. Carotenoids are responsible for pigments (i.e., red, orange, yellow, and green) widely found in vegetables, fruits, and other plants. As a result, lutein, zeaxanthin, and meso-zeaxanthin are classified as phytochemicals and non-provitamin A carotenoids, which means they are unable to be converted into vitamin A. In general, carotenoids are lipophilic or hydrophobic, which means they are soluble in fat and insoluble in aqueous media. The human body is unable to produce endogenous carotenoids. Therefore, they must be obtained from exogenous sources, mainly diet and/or supplementation. Carotenoids are coveted for their anti-inflammatory and antioxidant (and even anti-cancer) properties. Close to 700 carotenoids have been isolated and characterized in nature, yet roughly 40 carotenoids have been detected in human milk, serum, and tissues.

In addition to being found in many dark-green leafy vegetables and colorful fruits, both lutein and zeaxanthin are found in high concentrations in the macula of the human eye. Zeaxanthin is the dominant carotenoid in the macula. The macula, a small (5.5 mm in size) area in the central portion of the retina, is a very important region of the eye and contains the largest concentration of photoreceptor cells (i.e., rods and cones) in the retina. As a result, the macula provides the sharpest vision needed for precise activities such as reading and writing, and the ability to perceive colors. In fact, both lutein and zeaxanthin contribute to the yellow hue of the macula. Remember, macula is short for “macula lutea” (from the Latin macula, meaning “spot,” and lutea, meaning “yellow”). Again, this fact speaks to the uniqueness of lutein and zeaxanthin being the marquis carotenoids concentrated in the macula, out of roughly 40 carotenoids currently identified in the serum of humans.

The macula can be subdivided into the following areas: umbo, foveola, foveal avascular zone (FAZ), fovea, parafovea, and perifovea. The fovea, a depression in the center of the macula, may be the most important part of the eye. It is responsible for the sharp central vision required for essential daily activities such as reading, writing, driving, and recognizing faces. The fovea only contains cone photoreceptors, which are tightly packed into this tiny area, and is devoid of any rod receptors. For reference, the carotenoid concentration in the fovea approximates 1 mM, and the ratio of lutein to zeaxanthin to meso-zeaxanthin is 1:1:1. In contrast, this concentration declines over 100-fold just a few millimeters from the center of the fovea.

Recent research has discovered a third carotenoid in the macula called meso-zeaxanthin. Unlike lutein and zeaxanthin, meso-zeaxanthin is a non-dietary carotenoid that is not found in the serum of humans, but only in the retina (specifically the macula). Scientists have found evidence that suggests meso-zeaxanthin is produced in the retina from lutein via an isomerization process. It is believed that lutein and zeaxanthin are transported from the serum to the retina in equal ratios, and then transferred into the macula where lutein is preferentially converted into meso-zeaxanthin. In fact, a simple shift of a double bond produces meso-zeaxanthin from dietary lutein, and it is this conformational similarity that makes it more likely that lutein rather than zeaxanthin is the immediate precursor to meso-zeaxanthin. In summary, the macular carotenoids (also known as the macular xanthophylls) are dietary lutein and zeaxanthin, and their conversion isomer meso-zeaxanthin. These macular carotenoids comprise the macular pigment that is charged with protecting the retina from harmful influences.

Why are They Important for Your Eyes?

Voluminous information has been gleaned from numerous studies that identify lutein and zeaxanthin as vital components for eye health. In nature, lutein and zeaxanthin work to absorb excess light energy, which prevents damage to plants from excess sunlight (especially from high-energy light rays such blue light [400–500 nm on the electromagnetic light spectrum] and ultraviolet [UV] light [up to approximately 380 nm on the electromagnetic light spectrum]). Similar to their functions in plants, lutein and zeaxanthin (and meso-zeaxanthin) act as protective antioxidants in the eye. The retina is the most metabolically active tissue in the body, and this exceptionally high metabolic rate results in a large quantity of potentially damaging oxidative by-products. The macular carotenoids protect the eye from oxidative stress/damage by scavenging harmful oxygen free radical species.

Lutein, zeaxanthin, and meso-zeaxanthin in the macular pigment also specifically targets the oxidative stress-induced damage to the retina caused by blue light. In other words, the macular pigment protects the retina by absorbing blue light, which protects the underlying layer of photoreceptor cells. Blue light is emitted into the environment from screens (e.g., television and computer) and various other forms of artificial lighting. If the concentrations of the macular carotenoids are low, blue light has the potential to cause significant damage to the retina. In addition, blue light scatters more easily due to its shorter wavelengths (compared to other forms of visible light), contributing to glare and reducing contrast sensitivity and visual acuity. The macular pigment selectively filters harmful blue light, which is image-degrading, for sharper vision.

Food Sources for Carotenoids

There are only 2 ways to increase the density of the protective macular pigment—diet or supplementation. What are some foods that are sources of these macular carotenoids? As mentioned previously, dark-green leafy vegetables (e.g., kale, spinach, broccoli, Swiss chard, and greens [collard, turnip, and mustard]) are excellent dietary sources of lutein and zeaxanthin. Kale and spinach top the list providing 18,250 and 12,200 mcg lutein/zeaxanthin per 100 g of food, respectively. Other dietary sources of lutein and zeaxanthin may include the following:

• Eggs
• Carrots
• Sweet potatoes
• Dried fruit (especially apricots, peaches, and prunes)
• Citrus fruit (e.g., lemons, oranges, kiwis, and grapefruits)
• Green peas and green beans
• Romaine lettuce
• Brussel sprouts
• Bell peppers (regardless of color)
• Grapes
• Zucchini and squash
• Corn products

It is worth noting that the bioaccessibility of lutein and zeaxanthin from dark-green leafy vegetables is low, and various dietary factors affect their bioavailability. Given the lipophilic/hydrophobic nature of these vitamins, there is evidence that consuming carotenoid-rich foods in the presence of oils or cholesterol may increase their uptake. In addition to vegetables and fruits, which are less bioavailable, egg yolks and fortified milk are also good dietary and bioavailable sources of lutein and zeaxanthin.

Carotenoid Supplementation and MPOD

How does one determine that a patient needs carotenoid supplementation? The volume of lutein and zeaxanthin in the macular region of the retina is measured as macular pigment optical density (MPOD). The thickness, or optical density, of macular pigment varies from individual to individual and can be affected by factors such as aging, lifestyle, and dietary choices. Despite this, MPOD testing has been shown to be accurate and repeatable. As a result, norms amongst patients have been established. MPOD scores ranges from 0 to 1. A “low” MPOD score is in the range of 0 to 0.21, while a “high” score is in the range of 0.45 to 1.0.  To put this into perspective, the average MPOD in the United States is 0.35. Currently, there are no formal guidelines for the recommended daily intake of carotenoid supplements (i.e., lutein, zeaxanthin, and meso-zeaxanthin), but recent studies have shown health benefits after supplementation consisting of 10 mg/day of lutein and 2 mg/day of zeaxanthin. It should be noted that taking carotenoid supplements with a source of fat or oil helps to increase absorption of the macular carotenoids.

There are several high-quality carotenoid-providing products available in the United States. One such product is Lumega-Z®, a medical food manufactured by Guardion Health Sciences of San Diego, CA. According to Guardion, “Lumega-Z is the only vision-specific medical food created to restore and maintain the macular pigment.” This medical food is composed of the 3 critical carotenoids (lutein, zeaxanthin, and meso-zeaxanthin) that comprise the macular pigment along with 35 other micronutrients possessing antioxidant and anti-inflammatory properties.

MPOD can be retested after interventions such as dietary modifications and/or carotenoid supplementation to gauge an individual’s response to risk factor reduction. Of course, an increase in the thickness of macular pigment would signal a favorable response to risk factor reduction. Recently, MPOD has become a useful biomarker for predicting ophthalmic disease and visual function. Indeed, a low MPOD score is a key risk factor for age-related macular degeneration (AMD), while a high MPOD score not only reduces the risk of AMD but also improves visual performance.

Carotenoids and Risk Factor Reduction

As previously mentioned, epidemiological, clinical and interventional studies have concluded that carotenoids reduce the risk of chronic eye diseases, including AMD and cataracts. AMD and cataracts are the leading causes of visual impairment and acquired blindness in the United States. In fact, AMD is the leading cause of legal blindness with limited treatment options in people over 65 years of age in industrialized countries. Oxidative stress (mentioned earlier), aging, and smoking are key risk factors for the development of AMD and cataracts. As of late, nutrition has emerged as a potentially promising method of risk factor reduction in the development and progression of chronic eye diseases such as AMD and cataracts.