Lutein Supplementation for Diabetic Macular Edema

Abstract

Lutein is a natural component of the retina that is acquired in the diet; One of its multiple functions is to capture reactive oxygen species and promote their elimination. People with Diabetes Mellitus have a significant increase in oxidative stress due to protein glycation and activation of the polyol pathway; as a result, they develop diabetic retinopathy that can progress to macular edema and cause severe visual disturbances including central blindness. The lack of lutein in people with macular edema is evident, therefore, they require additional consumption to prevent and reduce the complications. We decided to undertake a review in order to learn more about this supplement, its properties and its beneficial effect on the eyesight of individuals with Diabetic Macular Edema.

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Volume 2 | Issue 1 | 1 of 3
Food Sci Nutr Res, 2019
Lutein Supplementation for Diabetic Macular Edema
1Hospital Regional de Alta Especialidad de Ixtapaluca; State of
Mexico, ZIP 56530, Mexico.
2Interdisciplinary Centre of Health Sciences, Milpa Alta Unit;
Instituto Politécnico Nacional, Mexico City, ZIP 12000, Mexico.
3School of Medicine; Instituto Politécnico Nacional, Mexico City,
ZIP 06729, Mexico.
4Salford Royal Hospital, University of Manchester and St. Peter’s
College, Oxford; Manchester City, ZIP M13 9PL, United Kingdom.
*Correspondence:
Gabriela Yanet Cortés Moreno, Hospital Regional de Alta
Especialidad de Ixtapaluca, Mexico-Puebla Federal Highway Km
34.5, Zoquiapan, Ixtapaluca, Estado de México, México, ORCID:
0000-0002-4506-8223, E-mail: medic_gaby@live.com.mx.
Received: 20 March 2019; Accepted: 15 April 2019
Italia A. Rivera1,2, Gustavo A. Altamirano1,3, Eleazar L. Padilla3, Adrian H. Heald4 and Gabriela Y.C.
Moreno1,3,*
Food Science & Nutrition Research
ABSTRACT
Lutein is a natural component of the retina that is acquired in the diet; One of its multiple functions is to capture
reactive oxygen species and promote their elimination. People with Diabetes Mellitus have a signicant increase
in oxidative stress due to protein glycation and activation of the polyol pathway; as a result, they develop diabetic
retinopathy that can progress to macular edema and cause severe visual disturbances including central blindness.
The lack of lutein in people with macular edema is evident, therefore, they require additional consumption to prevent
and reduce the complications. We decided to undertake a review in order to learn more about this supplement, its
properties and its benecial eect on the eyesight of individuals with Diabetic Macular Edema.
ISSN 2641-4295Review Article
Citation: Italia A. Rivera, Gustavo A. Altamirano, Eleazar L. Padilla, et al. Lutein Supplementation for Diabetic Macular Edema. Food
Sci Nutr Res. 2019; 2(1): 1-3.
Keywords
Carotenoids, Diabetes complications, Zeaxanthin.
Introduction
Diabetic Macular Edema (DME) represents the most frequent
cause of blindness in individuals aged 20 to 74 years [1]. is
can start to develop at least 7 years before the diagnosis of Type 2
Diabetes Mellitus [1,2]. Studies in Mexico report a prevalence of
Diabetic Retinopathy of 33.3% (29.9% with Non-Sight reatening
Retinopathy and 3.4% with Sight reatening Retinopathy) of
which, more than half suer from DME [3,4]. Currently, existing
therapies are limited to invasive pharmacological treatments,
however, recent studies have shown ecacy in the treatment of
DME aer the administration of natural supplements derived from
carotenoids. is article provides an overview about Lutein and
evidence of its use as an alternative for the treatment of Diabetic
Retinopathy and DME.
Carotenoids and their Properties
Carotenoids are natural compounds found in dierent plant
structures and in a great variety of animals, algae, fungi and
bacteria. ese pigments are responsible for the coloration of
owers and fruits (in order to favor pollination and the scattering
of seeds), or animal structures such as feathers and the beaks of
certain birds, the exoskeletons of crustaceans and the muscles or
skin of certain types of sh [5].
ese compounds are considered to be essential to life, owing
fundamentally to the functions they carry out in relation to
photosynthesis (harvesting light pigments, photoprotection) [5,6].
ere are two types of carotenoids: carotenes, which contain no
oxygen in their terminal rings (example: β-carotene, lycopene)
and xanthophylls, which contain oxygen in their terminal rings
(example: lutein and zeaxanthin). ese four are the most
abundant in human blood [7,8]. However, the one found in the
greatest proportion in plasma is lutein, which also makes up 90%
of the pigment in the macula (central zone of the retina and area of
greatest ocular vision) [9] (Figure 1).
Carotenoids are isoprenoids (unsaponiable simple lipids) that
have properties of light-absorption through the presence of 7 or
more conjugated double bonds and its principal benet is the
absorption of ultraviolet light (high-energy light, originating from

Volume 2 | Issue 1 | 2 of 3Food Sci Nutr Res, 2019
the sun and electronic appliances that harms the cells of the retina,
causing macular degeneration; this is where its importance to the
visual function is derived from [5,10].
Figure 1: e retinal carotenoids: e 90% of the macular pigment
corresponds to lutein; while the remaining 10% by its precursors:
Zeaxanthin and Meso-zeaxanthin [5].
Lutein and biological functions
Lutein is the most common carotenoid found in nature, as
well as that principal xanthophyll of the protein complex. It is a
dihydroxilated derivative of α-carotene, which, having substituted
beta-rings, has no provitamin A activity. In addition, human beings
cannot synthesize this nutrient, so it must be acquired through the
consumption of foods such as egg yolk, broccoli, orange or chard
spinach [11].
Lutein is a yellowish-orange pigment with a dual mechanism,
inactivating singlet oxygen (energetically excited forms of
molecular oxygen) and trapping free radicals. It also possesses
anti-inammatory and neuroprotective properties [12]. Its
neuroprotective function lies in the preservation of levels of
synaptophysin, a synaptic vesicle protein that is important for the
release of neurotransmitters and activity of the synaptic network.
is protein is abundant in the inner plexiform layer of the retina. In
addition, lutein suppresses the activation of the extracellular signal-
regulated kinases (ERKs), a kinase that degrades Synaptophysin [12].
Anti-inammatory function is achieved through the induction
of changes in the expression of genes related to inammation,
demonstrated in the retinal pigment epithelium (RPE).
Antioxidants inhibit the retinal increase in the redox-sensitive
nuclear transcription factor-B (NF-κB, a transcriptional factor that
controls the expression of many genes involved with inammation)
and what prevents the development of diabetic retinopathy [12].
Its function as an antioxidant in human tissue decreases the risk
of cardiovascular disease and certain kinds of cancer; however, it
presents the greatest benet in ocular problems, especially those
concerning retinal aections, it being a tissue with a high exposure
to oxidative stress [13]. e retina is the neurosensory tissue of
the eye and is extremely rich in membranes with polyunsaturated
lipids, a feature that makes it especially sensitive to the deleterious
action of free radicals derived from oxygen and nitrogen [14]. An
event that lead to the discovery of the eects of this antioxidant on
the human body took place in 1904, when a Japanese bacteriologist,
Inawashiro Noguchi Seisaku, uncovered the causal agent of
trachoma (Chlamydia trachomatis), which causes a contagious
granular conjunctivitis that can lead to blindness. Alongside this
investigation, he studied syphilis; whereby he discovered the
spirochaete Treponema pallidum, which was found in the brain
and in the spinal cord of those aected and came up with a method
of diagnosis that consisted of a modication of the Wassermann
reaction with lutein, a method which was dubbed the Noguchi
reaction with lutein in his honor [15].
From that point on, studies were made on the functions of lutein,
with allowed for its commercialization in powder form and its use
as an additive in certain foods, as well as its use as a supplement in
capsules for eyesight.
Lutein for Diabetic Macular Edema.
Currently, lutein is used to prevent Age-Related Macular
Degeneration (ARMD), however, there is evidence supporting its
ecacy in reducing diabetic macular edema. Bo-Jie Hu, et al. (16)
proved its eects by carrying out an intervention on 30 patients
suering from non-proliferative diabetic retinopathy, to which
they administered 6 mg of lutein and 0.5 mg of zeaxanthin orally
over a span of three months, and made a comparison with a second
group that did not receive lutein, but did have non-proliferative
diabetic retinopathy, and a control group of healthy people; the
results showed that foveal thickness diminished in 83% of patients
aer medication [16].
L. Brazionis et al., reported that people with diabetes have
lower plasma concentrations of α-Carotene β-Carotene, Lutein,
zeaxanthin, Lycopene, compared to control group [17]. M.
Moschos et al, conrms that the Macular Pigment Optical Density
(MPOD) and Contrast Sensitivity (CS) increase aer the carotenoid
supplementation [18].
Likewise, F. Granado et al. tried supplementation with capsules
of α-tocopherol, cis-lutein and trans-lutein in order to nd out if
plasma lutein concentrations are related to oxidative stress, in his
study he reports a non-signicant decrease of plasma lutein levels
in Type 1 diabetics, probably inuenced by the lipid´s metabolism
of each person [19] (Table 1).
Future directions and challenges
is supplement would represent an excellent therapeutic option
for individuals suering from diabetic macular edema, since
treatment for this pathology is currently limited to intravitreal
injections of antiangiogenic pharmaceuticals or corticosteroids
and laser; however, these therapies are only eective in less than a
third of those who undergo them and all this at a high cost [20,21].
Basing ourselves on these investigations, we have decided to
carry out clinical studies in Mexico to compare the eects of this
natural antioxidant to existing therapies for treating Diabetic
Macular Edema. It is necessary that these clinical trials become
the foundation on which to carry out new studies that prove the

Volume 2 | Issue 1 | 3 of 3Food Sci Nutr Res, 2019
© 2019 Italia A. Rivera, et al. is article is distributed under the terms of the Creative Commons Attribution 4.0 International License
Author Year N Population of
study Duration Treatment Results
Plasma Concentrations OCT (μm) BCVA HbA1c (%)
M.
Moschos
et al. [18]
2017 60
Type 2 Diabetes
without diabetic
retinopathy
2 years
One capsule a day
with: -lutein (10 mg)
-zeaxanthin (2 mg) -meso-
zeaxanthin (10 mg)
-------
↑ Macular pigment
density = 157.1 ±
14 to 163.4 ± 13.2
(p≤0.001)
no changes
(≥ 9/10) -------
Hu BJ et
al. [16] 2011 90
Nonproliferative
diabetic
retinopathy
3 months
One capsule a day
with: -Lutein 6mg/d
-Zeaxanthin 0.5mg/d
DR Group: ↑ L/Z
(0.5409 µg/mL and
0.2816 µg/mL).
Control Group: 0.0701
µg/mL and 0.0224 ± µg/
mL (p =0.001)
↓ Foveal thickness=
286.50 ± 134.185
(p=0.05)
Control
Group= 7.9
vs DR= 8.8
(p=0.018)
-------
L.
Brazionis
et al. [17]
2009 111 Type 2 Diabetes
Not taking carotenoid
supplements, only
measurements
↓L/Z (mmol/L) 0.36 vs
DR 0.34 (p=0.736) ------- -------
Control
Group= 7.9
vs DR= 8.8
(p=0.018)
F.
Granado
et al. [19]
2002 18 Type 1 Diabetes 21 days
One capsule a day with:
-12 mg all-trans-lutein - 3
mg of 13/15-cis-lutein -
3.3 mg of α-tocopherol
↑Lutein (nmol/L) 20.76 ±
13.72 vs DM1= 21.29 ±
14.43 (p= NS)
------- -------
Control
Group= 4.8 ±
0.5 vs DM1=
7.7 ± 2
Table 1: Summary of studies investigating the relationships among, Diabetes, Diabetic Retinopathy, supplementation of Lutein/analogs & derivatives.
BCVA: Best corrected Visual Acuity, DR: Diabetic Retinopathy, L/Z: Lutein / Zeaxanthin, DM1: Type 1 Diabetes Mellitus, NS: Non signicant, OCT:
Optical Coherence Tomography.
usefulness of Lutein so it can be opportunely used in cases of
Diabetic Retinopathy and Diabetic Macular Edema.
Acknowledgments
We thank Dr. Tania Villagra Sanjurjo for share her clinical
experience in Diabetic Retinopathy.
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