EFFECT OF LUTEIN AND ZEAXANTHIN ON AGE RELATED MACULAR DEGENERATION (AMD) By Dr Venket Rao, PhD, Professor Emeritus

There is convincing scientific evidence to support the association between oxidative stress and chronic diseases including cancer, cardiovascular diseases, diabetes, osteoporosis, and macular diseases. During the course of the last two decades, there has been great interest in the use of antioxidants in the prevention and management of chronic diseases. Dietary guidelines around the globe have recommended increased consumption of plant foods including fruits and vegetables to reduce their risk. Fruits and vegetables are good sources of several beneficial phytochemicals. Antioxidant phytochemicals, in particular, constitute an important component of plant phytochemicals. Carotenoids are among the most important antioxidant phytochemicals present in plants. Considerable research work has been done, over the past two decades, on the beneficial role of carotenoids in human health.

Carotenoids are synthesized by plants giving them yellow, orange and red colors. They are lipid soluble compounds. More than 600 carotenoids have so far been identified. However, the important ones are β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin. β-carotene, α-carotene, β-cryptoxanthin are provitamin A carotenoids that can be covered by the body to retinol. On the other hand, lycopene, lutein, and zeaxanthin do not posses any vitamin A activity but are strong naturally occurring antioxidants. Studies have shown that dietary lutein and zeaxanthin are absorbed selectively into the macula of the eye contributing to visual function by absorbing a major portion of the blue light. The antioxidant properties of these carotenoids are due to the presence of several double bonds in their chemical structures.

One of the major health disorders associated with aging is the loss of vision referred to as age related macular degeneration (AMD). The loss of vision that takes place is caused by the death of visual cells due to the degeneration of retinal pigment epithelial cells (RPE cells) in the eye as well as membrane leakage. Although the etiological factors responsible for AMD are not fully understood, it is known that many factors including age, genetic history, environmental factors such as exposure to sunlight, diet, smoking, and obesity, are among the more important risk factors. Several studies have now demonstrated that oxidative damage caused by the absorption of blue light by the macula plays an important role in the damage of the visual cells leading to AMD. The recognition of this association initiated several observational studies investigating dietary intakes and a few intervention trials assessing the efficacy of lutein and zeaxanthin supplementation on AMD. The two main reasons for this interest being the selective accumulation of these carotenoids in the macula of the eye as well as their potent antioxidant properties.

A review article published by Buscemi S in 2018 investigated the effect of lutein on Eye and extra-eye health.⁽¹⁾ They reviewed 28 studies that were published on this topic between 2013 to 2016.  They concluded that:

• Lutein qualifies as a powerful antioxidant
• It has favorable effects on eye health
• In addition to eye, lutein has beneficial effects on other tissues especially the brain, where it was associated with improved cognitive performance

Based on these observations the authors suggest that a “high lutein intake with a diet rich in fruit and vegetables and also its supplementation might be encouraged, particularly in the elderly and in individuals at high risk of different clinical conditions”. However, they caution that there are still some conflicting results that need to be clarified by undertaking long term randomized trials with large cohorts of general population to demonstrate the beneficial effects of lutein on eye health.

In another recent randomized clinical trial, Korobelnik JF et al investigated the efficiency of dietary supplementation containing lutein, zeaxanthin, ω-3 polyunsaturated fatty acids, and vitamins to increase the density of macular pigment in first-generation offspring of parents with neovascular AMD.⁽²⁾ A total of 120 subjects free of any retinal ocular disease participated in the study. The subjects were randomised in a 1:1 ratio to receive either 2 daily dietary supplementation capsules or placebo for 6 months. The primary assessment criterion was the measurement of macular pigment optical density (MPOD) after 3 and 6 months of supplementation. Results showed a statistically significant increase in plasma lutein and zeaxanthin in the supplemented group compared to the placebo group. However, they did not observe any significant differences in the MPOD. Based on the results obtained they concluded that MPOD was not modified after 6 months of lutein and zeaxanthin dietary supplementation, although the plasma levels of these carotenoids showed continuous exposure to the carotenoids. They suggest further studies to better understand the mechanism of absorption and metabolism of the carotenoids in the macula and their clinical benefits to the patients.

During the course of the past 15 years, several observational and intervention studies have been reported relating to the role of carotenoids and in particular the role of lutein and zeaxanthin in AMD. The following conclusions can be drawn from these publications:

1. AMD is an important condition affecting the elderly populations
2. Oxidative damage caused due to the exposure to blue light is an important contributor to AMD
3. Lutine and zeaxanthin are strong antioxidants that are selectively absorbed into the macular tissue
4. Observational studies have provided good evidence in support of the relationship between the consumption of lutein and zeaxanthin and reduced risk of AMD
5. Dietary and supplementary intervention studies, in general, have shown the benefits of lutein and zeaxanthin in elderly and at-risk patients. Further well-designed fully randomized intervention studies taking into consideration the type of subjects, length of the study, dosage levels and the nature of outcome measurements are needed to confirm the positive role that lutein and zeaxanthin can play in the prevention and management of AMD.

Although, more information is needed to better understand the effect of lutein and zeaxanthin on AMD, based on the evidence that we have so far, it is safe to conclude that dietary or supplemental lutein and zeaxanthin will be beneficial in the management of AMD and improving the quality of life in the elderly population.

References:

1. Buscemi, S., et al, 2018. Nutrients. 2018 18;10(9)
2. Korobelnik J-F et al. 2017. JAMA Ophthalmology, 135, (11): 1259 – 1266

Additional References:

• Carpentier, S., et al. 2009. Critical Reviews in Food Science and Nutrition 49: 313 – 326

• Eisenhauer, R., et al. 2017.  Nutrients: 9:120

• Khoo HE et al. 2019. Nutrients for Prevention of Macular Degeneration and Eye-Related Diseases. Antioxidants (Basel): 8: 85.

• Krinsky, N.I., et al. 2003. Annual Review of Nutrition 23:171 – 201

• Mares-Perlman, J.A., et al. 2002. Overview. Journal of Nutrition 132: 518S – 524S

• Mares, J., 2016. Annual Review of Nutrition 36: 571 – 602

• Rao, A.V., and Rao, L.G. 2007. Pharmacological Research 55: 207–216

• Tang, D., et al. 2019. BMJ Open: 9(2): e024774.

• Seydou, A., et al.  2016. Investigative Ophthalmology and Visual Science 57: 1160 – 1167