Lutein, Zeaxanthin and Meso-Zeaxanthin Across the Lifespan

The idea that a select few dietary nutrients could serve functions as varied as normal brain development, eye protection, skin protection, cardiovascular health, reaction time improvement, cognitive function enhancement, and age-related disease prevention at first seems preposterous. Indeed, any reasonable person approached with such a claim should be highly skeptical, and ask for the evidence. In the following [article], I will provide the evidence for lutein (L), zeaxanthin (Z), and mesozeaxanthin (MZ) as the nutrients described above, and characterize how they play a role in normal development, enhanced function, and health across the lifespan.

L and Z are naturally-occurring carotenoid pigments found primarily in leafy-green vegetables, such as kale.

Lutein and Zeaxanthin are naturally-occurring carotenoid pigments found primarily in leafy-green vegetables, such as spinach and kale (Sommerburg et al. 1998). They are not synthesized by the body, and so must be obtained from dietary sources, or supplements. Those who have diets rich in leafy greens, or supplement with sufficient L and Z, tend to have higher blood and tissue concentrations of these carotenoids (Ciulla et al. 2001; Bone et al. 2003). Although somewhat rare, trace amounts of MZ are present in the diet in various parts of the world – it is found in 21 species of fish, shrimp and sea turtles, as well as eggs (due to supplementation of chicken feed) in California and Mexico (Maoka et al. 1986; Nolan et al. 2013). Importantly, MZ has been shown to be converted from L in the retina; it is found in high densities in the very center of the retina, where it affords protection and performance to the vulnerable neural tissue there. In terms of dietary response, the body appears to recognize MZ, as it has been shown to be readily deposited in the retina when taken in supplement form (Bone et al. 2007; Loughman et al. 2012). L, Z, and MZ serve very important functions in the body. Firstly, they are extremely potent antioxidants. L, Z, and MZ’s antioxidant capability enables them to protect bodily tissues against damaging free-radical oxygen (Krinsky et al. 2003). This is an extremely important function, because if free-radical reactions continue unabated they can lead ultimately to DNA damage, which manifests as tissue degeneration or cancer. We often fail to appreciate the high-energy, somewhat violent nature of the chemistry of our body; for this reason the body builds a defense against oxidation in key areas, such as the retina and brain, where it is most needed. With regard to L, Z, and MZ, this preferential placement in vulnerable tissues starts very early.

The Macular Carotenoids in the Womb / Infancy / Childhood

L and Z have been shown to play a major role in the early development of neural tissue in utero.

Until fairly recently, the role of L, Z, and MZ in health was thought to be limited to helping protect against the development of age-related macular degeneration (AMD; e.g. Seddon et al. 1994). Over the last 6-7 years, however, solid evidence from prenatal and neonatal research indicates an important role for these carotenoids in the very beginning of life. For example, it has been shown that L and Z play a major role in the early development of neural tissue in utero: At about 6 weeks of gestation (before the retina starts to develop), L and Z are transferred via the umbilical cord (Rubin et al. 2012) from the mother to the fetus, and start to accumulate in an ocular reservoir called the vitreous humor. At 20 weeks gestation, as the retina begins to be “built,” L and Z are diverted from the vitreous humor into the now-forming retinal tissue, where they serve as antioxidants during the volatile, extremely high metabolic environment of neurogenesis (Panova et al. 2007). Because oxygen is one of the major building blocks of neural tissue, the potential for free-radical oxidative stress and damage is high; based on the conspicuous timing of passage from the vitreous humor to the retina, coupled with the antioxidant capability of L and Z, it is not unreasonable to suggest that they play a crucial, early role in the development of neural tissues. L in particular is also found in high concentrations in the infant brain (Vishwanathan et al. 2011). This is true of no other carotenoid. The development of the brain occurs so rapidly and with such metabolic intensity that it makes sense the body would put L (a potent antioxidant) in an area of such high oxidative stress. Additionally, because much neurodevelopment in the brain and retina occurs after birth, L no doubt maintains this role well into childhood. In fact, an argument could be made that children, despite their relatively small stature, actually need as much or more daily L (and also Z and MZ) as adults. This is for two reasons: 1) Children are still developing, and are thus using more oxygen to build tissues. More oxygen leads to increased potential for oxidative stress, and L, Z, and MZ can help to reduce it. 2) Tissue stores of L, Z, and MZ (such as the retina, brain, and adipose tissue) are relatively empty. By ensuring that a meaningful amount of these carotenoids is included in a child’s diet, accumulation in these critical areas of the body is promoted. This would ultimately lead to enhanced protection into adulthood and beyond.

Lutein, Zeaxanthin, and Mesozeaxanthin in Adulthood / Old Age

Excitingly, new research direction for L, Z, and MZ involves their potential role in preventing the onset, or slowing the progression, of cognitive decline.

In adults, L, Z, and MZ in the retina (where they are collectively referred to as the “macular carotenoids”) have been shown to be positively associated with a number of important functions related to both health and performance. There are several visual performance advantages, including increasing visual processing speed (Hammond & Wooten, 2005), and many parameters of visual performance in bright light environments. On average, subjects with higher concentrations of the macular carotenoids are able to maintain visibility of a flickering light at higher frequencies than those with lower retinal lutein (who see the light as a stable, solid disc of light). In other words, those subjects with higher concentrations of L, Z, and MZ in their retinas have faster visual systems; this manifests as faster reaction time performance. High macular carotenoid concentration has also been shown to substantially improve visual performance in bright light environments (i.e. glare). These effects include reduced visual discomfort in bright light (Stringham et al. 2003; 2004; 2011), increased ability to see through glare (Stringham and Hammond, 2007; 2008), and decreased photostress recovery time (recovering a visual target after exposure to an extremely bright light; Stringham and Hammond, 2007; 2008; Stringham et al. 2011). More recently, the macular carotenoids have been shown to be associated with better cognitive function in people over 50 – subjects with higher macular carotenoid concentrations (which have been shown to be correlated to brain levels of L and Z – Vishwanathan et al. 2013) perform better on cognitive tasks related long-term memory and decision-making (Feeney et al. 2013). Additionally, in a recent study of deceased centenarians (those who had lived to over 100 years of age), Johnson et al. (2013) found that brain concentrations of L were significantly higher than any other carotenoid, especially in areas that serve cognitive function, such as the frontal and temporal lobes. This suggests not only that L appears to be very important to brain function well into old age, but also (based on the areas into which it is deposited) that L is important in preserving high-level cognitive function. L also appears to play a protective role in cardiovascular health, in that it inhibits vascular cell adhesion molecules from accumulating atherosclerotic plaques (Kailora et al. 2006). Over time, this function leads to a greatly reduced risk for developing atherosclerosis, and cardiovascular disease. Interestingly, L and Z (by virtue of their deposition throughout the layers of the skin) also appear to provide protection from UVB-induced erythema (i.e. sunburn; Heinrich et al. 2003). Moreover, L and Z were shown to help manage and limit damage already caused by UVB light. Perhaps the most exciting new research direction for L, Z, and MZ involves their potential role in preventing the onset, or slowing the progression, of cognitive decline. As noted above, in several studies, people over 50 years of age performed significantly better on cognitive tasks as a function of their macular carotenoid concentration. This idea was recently investigated by Nolan et al. (2014) in a study of early-stage Alzheimer’s disease patients versus normal, age-matched controls. The Alzheimer’s patients were shown to have significantly lower macular carotenoid concentrations than the control subjects. This finding suggests that, as in AMD, perhaps the macular carotenoids are preventing cumulative damage over the lifespan that can, if left unchecked, produce neural damage that ultimately lead to cognitive impairment. In a follow-up study (Nolan et al. 2015), Alzheimer’s disease patients were found to respond positively in the retina to macular carotenoid supplementation, which suggests that the body maintains the ability to absorb and use these carotenoids in neural tissue, and that they may offer some potential benefit in increased concentrations. Lastly, as noted earlier, there is a well-established relationship between high concentrations of macular carotenoids and a reduced risk for developing AMD, the leading cause of blindness in people over 60 in the United States (National Eye Institute). Importantly, there is evidence that even after the onset of AMD symptoms (e.g. mild distortions of central vision), macular carotenoid supplementation can slow down, or even perhaps stop the progression of the disease (Richer et al. 2004). It appears therefore that the macular carotenoids have not only long-term protective effects on tissues, but also can have acute beneficial effects as well.

In summary, L, Z, and MZ appear to provide meaningful, significant benefits across the lifespan. The more we learn about these carotenoids, the more it becomes apparent that they are crucial to normal development, health, and performance. From their involvement very early in protecting developing neural tissues, to reducing cumulative damage that results in age-related disease, it is clear that L, Z, and MZ are meant to play a significant role in human development, performance, and aging. Although L, Z, and MZ are not considered essential nutrients (i.e., vitamins), based on the available scientific evidence, they may certainly be considered essential for optimal health and performance. Lastly, given our ever-increasing lifespan, any factor that can plausibly extend to us a benefit that can ensure more healthful years of life is always welcome. L, Z, and MZ appear to be such factors.

JAMES STRINGHAMAbout the author: James Stringham, Ph.D.

Dr. Stringham earned his doctoral degree in experimental psychology from the University of New Hampshire in 2003. During postdoctoral appointments at the Schepens Eye Research Institute at Harvard Medical School and the Medical College of Georgia, he conducted research on ocular lutein, age‐related macular degeneration, the effects of intense light on visual performance, and plasticity of the visual system. Dr. Stringham then took a position as a visiting assistant professor at the University of Georgia, where he continued and extended a research program involving lutein and many facets of visual performance. In 2007, he became a senior vision scientist in the Air Force Research Laboratory (AFRL), where he was involved in extensive testing of the effects of lutein and zeaxanthin on human visual performance. Currently he is a research scientist at the University of Georgia, where his research includes studying the effects of lutein, zeaxanthin, and mesozeaxanthin on a variety of human physiological, health, and performance parameters.

 

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