Lutein and Zeaxanthin: 2020 and Beyond

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luteinIn Addition to Keeping Our Vision 20/20, These Nutrients Are Important for Brain and Skin Health, as Recent Research Highlights

If a multiple-choice test asked which organ the carotenoid lutein helps protect, and gave the options of the brain, eyes, or skin, many would select the eyes. Given lutein’s accumulation in the retina and other structures of the eye,[1] we do see a preponderance of research related to this organ. However, high levels of lutein are also found in the brain and skin.[2],[3] Correspondingly, there has been substantial investigation into its impact on these organs, with many benefits being demonstrated.[4],[5] So, technically, the correct answer would be all of the above. Zeaxanthin, a carotenoid very similar in structure to lutein, also accumulates in the eye, brain, and skin;2,3 thus, it also offers these organs protection. With age and habits like smoking,3,[6] levels of lutein and zeaxanthin (L/Z) decline, leaving the eyes, brain, and skin more susceptible to damage.

One reason that these molecules help protect the eyes is because they absorb light.1 In particular, they absorb light on the violet to blue end of the spectrum (~400 to 500 nm),[7] which, incidentally, leads to their orangish-yellow appearance. Blue light damages the retina through a photo-oxidation reaction with lipofuscin, a mixture of lipids, proteins, and fluorescent compounds that are a byproduct of incompletely digested phagocytosed photoreceptor cells.7

With our digital technology–related increase in exposure to blue light that computer screens, digital devices, energy-efficient indoor lighting, and television screens emit, we see an increase in problems related to blue light exposure.

This includes dry eyes,[8] eye strain, and eye fatigue,[9] and, long term, can contribute to a gradual loss of visual function and conditions such as age-related macular degeneration.[10]

Lutein and zeaxanthin also quench singlet molecular oxygen, prevent lipid peroxidation, and induce nuclear factor erythroid 2-related factor 2 (Nrf2)–dependent antioxidant transcription.[11],[12],[13],[14] They act as anti-inflammatories as well,[15] and thus may be helpful in conditions such as uveitis,[16] traumatic brain injury,[17] or ischaemic stroke,[18] in which substantial damage is also caused by inflammation. In acute settings such as these, higher levels of lutein prior to the event and administration afterwards may both be protective.[19],[20]

Dietarily, we can increase our intake of L/Z by consuming dark green, leafy vegetables, with cooked kale and spinach both delivering more than 10 mg/100 g; eggs, with the yolk having the highest amounts of these nutrients; and pistachio nuts, which also deliver more than 1 mg/100 g.[21] Other foods high in L/Z include orange peppers, squash, parsley, and romaine lettuce. Absorption of these carotenoids, which are fat-soluble nutrients, may be enhanced by the consumption with other fats, much like it is for other fat-soluble nutrients. For example, the consumption of a salad with fat-free dressing negligibly increases plasma carotenoid content, while consumption with 6 or 28 g of canola oil dose-dependently increases carotenoid content of the plasma.[22] There is not a dietary guideline for lutein and/or zeaxanthin intake; however, research suggests that, to prevent macular degeneration, one should consume 6 mg of lutein and zeaxanthin a day.[23] Yet dietary studies have shown that U.S. adults only consume 1 to 2 mg/day.[24]

Herein, we take a look at the clinical studies using lutein, zeaxanthin, or a combination thereof, and the protection they offer for the eyes, brain, and skin.

Eye Health

As noted, one of the primary mechanisms by which L/Z help protect the eyes is by the absorption of blue light. Concentrated in the fovea, the central region of the macula where the density of cones is the greatest, the concentration of zeaxanthin is about 1,000 times higher than other tissues.[25] Meso-zeaxanthin, a stereoisomer of zeaxanthin, is actually most central, being found at highest density in the epicenter of the macula. The highest concentration of zeaxanthin borders this, with lutein being highest more peripherally.[26],[27] Data suggests that a small amount of lutein is converted into meso-zeaxanthin in the macula;[28],[29] however, it also may be present at low levels in supplements containing zeaxanthin.27

Dietary supplementation of lutein or L/Z has been shown to increase their levels not only in the serum but also in the macula, typically evaluated by assessment of macular pigment optical density (MPOD).[30],[31],[32] Interestingly, in one study looking at L/Z in combination or both as monotherapies, it was shown that zeaxanthin, as a monotherapy, did not significantly impact macular levels.30 Increases in MPOD may depend on levels at baseline, with one study showing improvements only in the individuals having lower levels at baseline.[33]

Because L/Z are fat-soluble antioxidants that gradually accumulate in their destination tissues, the duration of intervention prior to outcome evaluation is usually a minimum of two to six months;

however, residual effects have also been seen up to four months after cessation of the therapies.[34] Increases in macular L/Z concentration correspond with a reduction in transmitted blue light.

Multiple studies have assessed how L/Z supplementation affects the vision of healthy individuals, typically evaluating the effect on visual acuity or symptoms related to intense light exposure (referred to as glare). With visual stressors such as the intense light of a camera flash, it takes some time for the eye to recover and there are aspects of discomfort. A higher MPOD is correlated with faster photostress recovery and reduced glare discomfort and disability.[35],[36] A correlation has been shown between low macular levels of L/Z and the development of age-related macular degeneration (AMD).6,[37] Dietary intake studies also suggest this relationship, particularly in those with a high genetic risk of the condition.[38],[39],[40]

In one randomised, double-blind, placebo-controlled trial, healthy subjects were supplemented with a combination of 10 mg of lutein and 2 mg of zeaxanthin or placebo daily for one year.[41] Significant improvements in photostress recovery as well as chromatic contrast were seen with time, paralleling the time-related increase in MPOD. In another study in which participants received 10.5 mg of lutein and 0.96 mg of zeaxanthin daily for six months, those who had lower MPOD levels at baseline were more likely to respond to supplementation and experience a reduction in glare sensitivity.34 In a single-arm study, supplementation of 10 mg of lutein and 2 mg of zeaxanthin daily for six months also was shown to significantly improve visual performance under glare conditions.[42]

Numerous additional studies have shown that supplementation with lutein, usually accompanied by a small amount of zeaxanthin at a 10:1 to 10:2 ratio, improves these and other aspects of vision in healthy adults. At doses of L/Z ranging from as little as 6 mg/day to 22 mg/day, improvements in vision have been seen as early as 45 days, although typically, assessment occurred after six months of supplementation.[43],[44],[45],[46] Improvements in parameters related to night vision,44 contrast sensitivity,45,46 and global visual function46 were seen with regular, daily supplementation of L/Z.

The impact of L/Z supplementation on ocular disease has also been extensively evaluated. From complaints as simple as dry eye to serious conditions like diabetic retinopathy,

Not surprisingly, the majority of human studies have looked at the effect that L/Z supplementation has on vision in individuals with AMD. In individuals with early AMD, supplementation of 20 mg lutein with 2 mg zeaxanthin for 12 months improved letter contrast sensitivity.[49] In a longer, five-year study of patients with AMD, supplementation of L/Z (10 and 2 mg/day) significantly reduced the risk of progression to late AMD.[50] It also reduced the risk of development of neovascular AMD in individuals with large drusen bilaterally, but not those who already had late AMD in one eye. In an additional assessment of the same population, it was found that L/Z supplementation significantly reduced the risk of needing cataract surgery in individuals in the lowest quintile of dietary L/Z intake.[51] Three additional studies, having a duration of six months to two years, found that daily supplementation of 10 mg of lutein, with zeaxanthin ranging from 1 to 2 mg, significantly improved contrast sensitivity[52],[53] and visual acuity.53,[54]

It should be noted that in one of the studies finding improved contrast sensitivity,52 supplementation also included small amounts of vitamins B3, C, and E (as α-tocopherol); zinc; and copper, while in one of the studies showing improved visual acuity,54 supplementation included vitamins E and C; zinc; copper; and astaxanthin. Studies suggest there may be synergistic effects of the antioxidant vitamins with L/Z while astaxanthin, another member of the carotenoid family, also is known to benefit vision.7,[55],[56]

Brain Health

Several studies have established that central nervous system (CNS) levels of lutein and zeaxanthin are related to brain function.[57],[58],[59] Because the CNS levels of lutein and zeaxanthin can only be determined post mortem, this research primarily relies on evaluation of MPOD, which is correlated with L/Z levels in the brain (in humans and nonhuman primates) and can be measured noninvasively.2 In various populations, associations have been shown between MPOD or serum lutein levels and hippocampal function, visual-spatial and construction abilities, language ability, attention, processing speed, accuracy, mini-mental state examination scores, and general and fluid intelligence.[60],[61],[62],[63]

In the fatty tissues of the CNS, the antioxidant protection that lutein and zeaxanthin offer to membranes is important for the health and function of neural plasma membranes, axonal projections, mitochondria, nuclear membranes, and myelin.12,[64],[65] Levels of L/Z have been shown to be correlated with white matter integrity in several regions of the brain, including those that are vulnerable to cognitive decline.[66] The cognitive impact of lutein has also been suggested to be related to docosahexaenoic acid (DHA) levels due to their colocalisation in several regions of the brain.[67] In both the prefrontal cortex and striatum, mitochondrial lutein levels have been shown to be inversely related to DHA oxidation products, further pointing toward the interdependence of these nutrients.[68]

In research pertaining to CNS function, supplementation of lutein and zeaxanthin is also implemented for a fairly long period prior to assessment, commonly with a ratio of 10:2 of lutein:zeaxanthin. In aging adults (with an average age of approximately 74), after supplementing with 12 mg of L/Z for a period of a year, significant improvements were seen in complex attention, cognitive flexibility, and composite memory (males only), with trends toward improvement in executive function domain.[69]

In a study employing functional magnetic resonance imaging (fMRI) in aging individuals, after supplementation with 12 mg of L/Z for one year, fMRI showed increased internetwork connectivity, suggesting that rather than restoring brain function to a more youth-like state, capabilities may be enhanced by increased integration.[70] A study of a similar population (using the same supplementation regime) found that those receiving L/Z had increased electroencephalogram (EEG) signal power when subject to a visual stimuli (steady-state visual evoked potential[71]) at various flicker frequencies, suggesting that L/Z improved visual processing.[72] Additionally, in individuals having a higher MPOD, increased EEG activation was seen at the highest frequencies.

One additional study in an aging population looked at the effects of a combination of L/Z with DHA. In this double-blind, placebo-controlled, multiple-arm study, women (from 60 to 80 years of age) were randomised to receive the combination of 12 mg of L/Z and 800 mg of DHA, 800 mg of DHA, 12 mg of L/Z, or placebo for a period of four months.[73] Although all groups except placebo had significant improvements in verbal fluency, only those receiving the combination had significant improvements in memory scores and rate of learning, with trends toward more efficient learning also being seen.

Skin Health

Lutein and zeaxanthin are also important for the health of the skin. Here, they help protect against the damaging effects of another portion of the electromagnetic spectrum: ultraviolet (UV) light. Animal studies have shown that supplementation of lutein or L/Z reduces inflammation and edema, reactive oxygen species production, and epidermal hyperproliferation with exposure to UV-B radiation.[74],[75] When subject to routine exposure with UV-B light for 16 weeks, feed supplementation of L/Z significantly attenuated multiple parameters of photoaging as well as UV exposure–related tumour burden.75

But perhaps more interesting regarding L/Z and skin health is the protection they provide against the damaging effects of blue light as well. Although the damaging effects of the UV portion of the spectrum are well known, many people are less aware of the oxidative and DNA-damaging effects that blue light exposure also has on the skin.[76],[77],[78] Blue light exposure even increases our production of melanin[79]—which also suggests our body inherently knows to do the things that help protect us from it.

The magnitude of blue light damage to skin is less than what UV rays impart, but because of the regular exposure we have to blue light, and the lack of protection that sunscreen provides,5 blue light exposure not only causes its own damage, it renders us more susceptible to damage from the intense UV-A and UV-B rays as well. Damage from each of these forms of light is cumulative—which is why we see more signs of skin aging and skin cancer on light-exposed regions of our skin with increasing age.

Clinical studies have looked at the impact that oral, as well as topical, use of L/Z has on various parameters related to skin health. In one such randomized, double-blind, placebo-controlled study, healthy individuals with fair to olive skin that had mild to moderately dryness were supplemented with 12 mg of L/Z or placebo for a period of 12 weeks.[80] The skin tone of individuals taking L/Z was significantly lightened and overall skin tone improved, perhaps indicative of the absorption of blue light and subsequent reduction of melanin production. In those taking L/Z, the minimal erythema dose (when subject to UV-A/UV-B light) and elastic recovery were significantly increased relative to baseline, and higher than those receiving placebo; however, the difference was not significant.

In another study, healthy women, age 25 to 50 years, were instructed to administer L/Z orally (10.5 mg), topically (a standardised dilution in butylene glycol), or topically and orally for a period of 12 weeks.[81] Although the combination of topical and oral treatment typically had the greatest effects, both topical and oral treatment with L/Z led to a significant increase in skin lipids, hydration, elasticity, and minimal erythema dose, and a reduction in lipid peroxidation. Although there was an increase in skin lipids, questionnaires did not indicate subjects found their skin to be too oily, suggesting the increase may be attributable to things other than just sebaceous secretions, which often lead to such complaints.

Clearly, the benefits of supplementation with lutein and zeaxanthin cover more than just vision, giving many reasons for these carotenoids to be included in supplement protocols to support not just ocular function, but also brain and skin health, in 2020 and beyond.

 References

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