KEYWORDS
Lutein
Zeaxanthin
Eye-Brain Axis
Eye Health
Cognitive Health
Macular Pigment Optical Density
Abstract
The eye is an extension of the central nervous system, forming the eye–brain axis that integrates visual signals with cognition, memory, and executive function. Lutein and zeaxanthin, natural carotenoids concentrated in the macula, also accumulate in brain regions essential for learning and memory. Higher macular pigment optical density (MPOD), a marker of carotenoid status, is linked with better cognitive performance across age groups. This article will outline the evidence linking the eye–brain axis with cognition and highlight the potential of lutein and zeaxanthin as supporting nutrients.
The eye-brain axis: A new frontier in visual health
The eye represents more than a visual organ; it is an anatomical and functional extension of the central nervous system. During gestation the eye develops from the forebrain and this developmental connection links the eye to specific brain regions (1). This bi-directional pathway, referred to as the eye–brain axis, integrates visual input with higher-order processes including cognition, memory and executive function. Each ocular signal is transmitted through a complex neural and biochemical network that directly influences central processing (2). Increasing evidence indicates that aspects of eye health, particularly retinal function, offer insights into brain function and overall neurological health (1,3). Recognition of this interconnection is critical for developing strategies that simultaneously support both ocular and cognitive health, particularly in the context of healthy ageing.
Lutein and zeaxanthin: Nutrients at the crossroads of vision and cognition
Through the eye-brain axis, nutrients that support vision may also benefit cognitive function. Lutein and zeaxanthin are natural carotenoids that accumulate in the lens and macula lutea of the eye, passing through the blood-retinal and blood-brain barriers. Within the eye, they dominate the macular pigment, while in the brain they account for up to 77% of total carotenoids, concentrated in regions critical for memory, learning and visual processing, including the hippocampus, cerebellum and cortical areas (4).
Macular pigment optical density (MPOD) is largely determined by the concentration of lutein and zeaxanthin in the macula and is a non-invasive measure of brain concentration of these carotenoids (4,5,6). In the eye, higher MPOD is associated with improvements in several aspects of visual health (7). Higher MPOD has also been linked with better cognitive performance and lower risk of cognitive decline in adults (6). In studies involving older adults, higher MPOD and plasma levels of lutein and zeaxanthin were associated with improved global cognition, processing speed, memory and visual learning (8,9).
The primary functions of lutein and zeaxanthin are to absorb damaging short-wave light and act as fat-soluble antioxidants, helping to neutralise free radicals, modulate oxidative stress and protect both retinal and neuronal cells from damage (4,10). They act as optical filters, with a broad absorption band peaking around 450nm, making them highly effective at absorbing blue light (typically 400nm-500nm) before it reaches macular photoreceptors.
As antioxidants, lutein and zeaxanthin help protect neural tissues and retinal phospholipids, mitochondrial DNA, and photoreceptor proteins from oxidative damage caused by free radicals (4,11). The retina and brain exhibit high metabolic activity and as a byproduct generate reactive oxygen species (ROS), which can drive oxidative stress and inflammation (11). Consequently, these dietary carotenoids have gained increasing interest as potential agents associated with improved visual and cognitive function, and markers relevant to healthy ageing.
Clinical evidence of lutein and zeaxanthin supporting the eye-brain axis
The benefits of lutein and zeaxanthin for both visual and cognitive health have been evaluated in multiple high-quality, randomised, double-blind, placebo-controlled clinical trials.
Most recently, a randomised, double-blind, placebo-controlled study investigated a standardised proprietary complex of lutein (10 mg) and zeaxanthin (2 mg) in adults, 40-75 years, with self-reported cognitive complaints for six months. Supplementation indicated improvements in visual learning and visual episodic memory (9). Similarly, other studies have shown that lutein and zeaxanthin intake may benefit aspects of cognitive function, which may be due to their effects on vision, cerebral perfusion, as well as direct antioxidant and anti-inflammatory activity in the brain (5,8). An in vitro study demonstrated reduced telomere shortening with lutein and zeaxanthin supplementation under conditions of oxidative stress, indicating this could be a further mechanism of supporting ocular and neurological health (12).
Systematic review and meta-analyses support lutein and zeaxanthin’s role in improving MPOD (13,14). A randomised, double-blind, placebo-controlled study investigating the same standardised proprietary lutein (10 mg) and zeaxanthin (2 mg) complex, indicated increases in MPOD after 6 months of supplementation in healthy adults (15). Dose-response studies indicate daily intakes over 5 mg of lutein and zeaxanthin combined, for three months, are sufficient to increase MPOD, with optimal doses >10 mg per day (7). MPOD has been found to be significantly related to visual health and cognitive function. A recent systematic review involving 1371 individuals reported that lutein and zeaxanthin supplementation may increase serum levels and demonstrated a link between MPOD and improved cognitive function - including memory, processing speed, attention and reasoning in adults (8).

A digital illustration of the Eye-Brain Axis, showing how visual signals travel from the eye to the brain for processing.
Understanding lutein and zeaxanthin bioavailability: The marigold advantage
Lutein and zeaxanthin are not synthesised in the body and must therefore be obtained through diet or supplementation. Natural dietary sources include yellow fruit and vegetables, spinach, kale and egg yolks however, they can have low concentration, as well as bioavailability (10,16). On average, it is estimated diet only provides approximately 1-2 mg combined lutein and zeaxanthin per day which is below what studies have found to be protective (7,10).
The bioavailability of lutein and zeaxanthin is limited by poor intestinal absorption and stability in dietary sources. As lipid soluble carotenoids, their absorption is increased with inclusion of fat such as oil or eggs with dietary sources. Fat stimulates bile flow which facilitates micelle formation for absorption in the small intestine. Conversely, competition with other carotenoids and dietary fibre can reduce absorption from food sources (10,17).
Marigold flowers are a rich natural source of lutein and zeaxanthin. In marigolds, carotenoids are mainly in the ester form, whereas most foods contain the free form. Ester forms of carotenoids are more stable with comparable bioavailability to the free form (18). Supplemental preparations oflutein, zeaxanthin and meso-zeaxanthin can be processed into micromicelles to enhance absorption and bioavailability. Meso-zeaxanthin is the carotenoid that is concentrated mostly in the epicentre of the macula and is derived from lutein in the retina (17). Supplementation that includes meso-zeaxanthin, alongside lutein and zeaxanthin, bypasses the reliance on in vivo conversion and ensures direct availability of this important carotenoid. The 5:1 ratio of lutein to zeaxanthin reflects the natural dietary ratio, supports absorption and has been clinically studied for eye health and cognitive benefits (9,16,15).

Marigolds are a rich natural source of lutein and zeaxanthin, nutrients to support eye and brain health.
A pharmacist’s perspective: Integrating evidence-based nutraceuticals in eye-care
Pharmacists can play a pivotal role in guiding interventions for this important and growing area of healthcare. Moreover, combining lifestyle adjustments with targeted nutritional support can help protect vision, support cognition and optimise general health and wellbeing.
- Supplement with lutein and zeaxanthin, clinical studies indicate that 10 mg of lutein and 2 mg of zeaxanthin (including meso-zeaxanthin) may support eye and cognitive function (9,15)
- Increase dietary carotenoid and antioxidants by consuming a wide variety of colourful fruit and vegetables and foods rich in lutein (asparagus, spinach, kale, lettuce, parsley, corn, pistachio, eggs) and zeaxanthin (orange capsicum, corn, eggs, squash, pumpkin, orange) (17)
- Consider additional supplementation with antioxidants such as vitamin C, E and zinc to further support eye health (19).
- Schedule regular eye examinations to identify and correct visual concerns (20).
Conclusion
The eye–brain axis represents a compelling frontier in both visual and cognitive health, highlighting the interconnectedness of ocular and neural function. Evidence from clinical studies underscores the role of lutein and zeaxanthin in supporting macular pigment density, while also helping to enhance cognitive performance. For pharmacists and healthcare professionals, integrating evidence-based nutraceuticals alongside lifestyle strategies offers a practical approach to support eye and brain health across the lifespan. As research continues to expand, leveraging the eye–brain axis provides a promising pathway for optimising long-term wellbeing, emphasising that supporting vision is intrinsically linked to supporting cognitive health.
References and notes
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- Lindbergh CA, Renzi-Hammond LM, Hammond BR, Terry DP, Mewborn CM, Puente AN, Miller LS. Lutein and Zeaxanthin Influence Brain Function in Older Adults: A Randomized Controlled Trial. J Int Neuropsychol Soc. 2018;24(1):77-90.
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- Lopresti AL, et al. The Effects of Lutein and Zeaxanthin Supplementation on Cognitive Function in Adults With Self-Reported Mild Cognitive Complaints: A Randomized, Double-Blind, Placebo-Controlled Study. Front Nutr. 2022;9:843512(supported and funded by Bio-gen Extracts).
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