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Characteristics of patients with wet age-related macular degeneration and low intake of lutein and zeaxanthin
a r c h s o c e s p o f t a l m o l . 2 0 1 2;8 7(4):112–118
ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia
Original article
Characteristics of patients with wet age-related macular degeneration and low intake of lutein and zeaxanthin夽 J.L. Olea a,∗ , J.A. Aragón a , M.E. Zapata b , J.A. Tur b a
Sección de Vítreo-Retina, Servicio de Oftalmología, Hospital Son Espases, Islas Baleares, Spain Facultad de Ciencias, Departamento de Biología Fundamental y Ciencias de la Salud, Universidad de las Islas Baleares (Grupo investigación nutrición comunitaria y estrés oxidativo), Palma, Spain
b
a r t i c l e
i n f o
a b s t r a c t
Article history:
Objective: To assess the characteristics of patients with wet AMD and low intake of lutein
Received 15 February 2011
and zeaxanthin in our population.
Accepted 10 October 2011
Methods: A prospective, observational, cross-sectional study was conducted on patients with
Available online 23 July 2012
active wet AMD. A full blood count, a lipid and liver profile, a dietary interview (24-h recall), and an anthropometric study were performed. Lutein–zeaxanthin (LZ) intake results split
Keywords: Lutein Zeaxanthin Age-related macular degeneration Retinal carotenoids
the patents in two groups. Group 1 (“sufficient” intake): patients with ≥1400 mg/day intake in women and 1700 mg/day in men (2/3 of the average daily intake in a normal population). Group 2: patients with daily intakes below that of group 1. A descriptive and comparative statistical study was performed.
Antioxidants
Results: Fifty-two patients with a mean age of 78.9 years. Group 1: eleven patients (21% of
Mediterranean diet
the sample). Group 2: forty-one patients. The subjects with adequate intake of LZ had higher a body mass index (BMI) and waist circumference. Between 70 and 80% of patients in group 1 had inadequate intake of vitamins A, C, E and zinc. Conclusions: Seventy-nine percent of the patients with wet AMD have a deficient daily intake in LZ. The population with adequate intake is associated with an increased BMI and waist circumference, and in addition, most of them have an insufficient intake of vitamins A, C, E and zinc. © 2011 Sociedad Española de Oftalmología. Published by Elsevier España, S.L. All rights reserved.
Características de la población con ingesta baja en luteína y zeaxantina en pacientes con degeneración macular asociada a la edad variante húmeda r e s u m e n Palabras clave:
Objetivo: Averiguar las características de los pacientes con DMAE húmeda que ingieren sufi-
Luteína
ciente luteína y zeaxantina en nuestra población.
夽
Please cite this article as: Olea JL, et al. Características de la población con ingesta baja en luteína y zeaxantina en pacientes con degeneración macular asociada a la edad variante húmeda. Arch Soc Esp Oftalmol. 2012;87:112–8. ∗ Corresponding author. E-mail address: [email protected] (J.L. Olea). 2173-5794/$ – see front matter © 2011 Sociedad Española de Oftalmología. Published by Elsevier España, S.L. All rights reserved.
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Zeaxantina
Métodos: Estudio protocolizado, prospectivo, observacional, transversal, en pacientes diag-
Degeneración macular asociada
nosticados de DMAE húmeda activa. Se efectúa hemograma, perfil lipídico, y perfil hepático;
a la edad
una entrevista dietética sobre los hábitos alimentarios a partir de la realización de un
Carotenoides retinianos
recordatorio de 24 h y estudio antropométrico. Se dividen en dos grupos en función de
Dieta mediterránea
la ingesta de luteína-zeaxantina (L-Z). Grupo 1 (ingesta «suficiente»): pacientes con ingesta diaria ≥ 1.400 mg/día en mujeres y 1.700 mg/día en hombres (2/3 de la ingesta media diaria en población normal). Grupo 2: pacientes con ingesta diaria inferior a las del grupo 1. Se efectúa un estudio estadístico descriptivo y comparativo entre ambos grupos. ˜ Resultado: Un total de 52 pacientes, con una edad media de 78,9 anos. Grupo 1: 11 pacientes (21% de la muestra). Grupo 2: 41. Los pacientes con ingesta suficiente de L-Z tienen mayor índice de masa corporal y perímetro de cintura. El 70-80% de los pacientes del grupo 1 presentan ingesta insuficiente de vitaminas A, C y E, y zinc. Conclusiones: El 79% de los pacientes tienen ingesta diaria de L-Z baja. Los pacientes con aporte suficiente tienen un aumento en el índice de masa corporal y perímetro de cintura, y además la mayoría tienen una ingesta insuficiente de vitaminas A, C y E, y zinc. © 2011 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L. Todos los derechos reservados.
Introduction
Table 1 – Epidemiological and ophthalmological characteristics of patients.
Age-related macular degeneration (ARMD) is the main cause of blindness among the elderly population in civilized countries.1 In Spain, with 13% of the population over 65 years of age, the prevalence of advanced ARMD varies from 0.5% at 55 up to 7% above 65. About 25,000 new cases of the wet variety are expected each year. Lutein and zeaxanthin are almost exclusively the only carotenoids present in the macula,2 and are defined as the macular pigments. They act to improve visual function, protecting visual structures from oxidative damage which is very high at this level.3–6 Said carotenoids neutralize free radicals7–9 and filter the blue component of the visible spectrum.9,10 In 2001, report number 8 of AREDS demonstrated a statistically significant reduction of 25% of the possibilities of developing advanced ARMD and loss of vision against placebo with the addition of a fixed association of antioxidants and zinc.11 Many studies have found an association between the levels of lutein and zeaxanthin in plasma and retina, with a possible reduction of the risk of severe ARMD forms. It would be important to identify patients with a deficiency of said nutrients either through a nutrition habits survey or plasmatic assessments. However, both options are laborious and unavailable in routine clinic. Even so, we can try to determine the existence of a clinical profile differentiating said patients in order to establish the characteristics of the population with a normal intake of lutein–zeaxanthin and those under 2/3 of the daily recommended intake (DRI) which in this case is theoretical. The final objective of the research line which this paper endorses is the identification in the clinical practice of patients exhibiting deficit of antioxidants, particularly lutein and zeaxanthin and to identify the solution either with customized dietary recommendations or, if that is not possible, pharmacological supplements.
Patients: 52 Male 21 (40.4%) Female 31 (59.6%) Mean age: 78.9 (SD 6.5)
Eyes involved: 59 Right 21 Left 24 Bilateral 7 Mean Snellen VA 0.21 (SD 0.1)
Subretinal neovascular membrane Type: Classic 17 (28.8%) Hidden 26 (44.2%) RAP 15 (25.4%) Polypoid 1 (1.6%)
Location: Subfoveal 41 (69.5%) Juxtafoveal 16 (27.1%) Extrafoveal 2 (3.4%)
Snellen VA: visual acuity in decimal scale with Snellen optotypes; SD: standard deviation; RAP: retinal angiomatous proliferation.
Subjects, material and methods A protocolized, prospective, observational and transversal study in patients diagnosed with active wet ARMD in the Retina and Vitreous Section of the Ophthalmology Service in the Son Dureta University Hospital (Palma de Mallorca, Spain). The patient diagnosis and assessment was formed after a full ophthalmology history comprising fluorescein angiography and optic coherence tomography. The ophthalmological assessment data are summarized in Table 1. Together with the clinical diagnosis, the patients were requested to accept inclusion in the study (this project had already been approved by the Ethics Committee of the Balearic Islands). The analytical data were obtained from recent analysis (under 3 months). Optionally, we requested a new analysis comprising hemogram, urea, creatinine, glucose, uric acid, hepatic transaminases (ALT, AST, GGT) overall bilirubin, overall cholesterol, HDL and LDL and triglycerides. One month later, at the time of the second intravitreal injection, the patients were interviewed and asked about their
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eating habits on the basis of a 24-h reminder by a qualified nutritionist researcher of the Community Nutrition And Oxidative Stress Research Group of the Balearic Islands University (UIB). Subsequently, the anthropometric study was performed, comprising size, weight, brachial circumference, waist and hips, thickness of the tricipital skinfold, fatty mass and arterial pressure. The BMI and the waist–hip ratio, fatty and muscle area of the arm were calculated. The conversion of food into nutrients was carried out with a computerized application of the UIB nutrition expert group, based on the American, European and Spanish tables of nutritional contents in food.12–15 In many cases, lutein and zeaxanthin do not appear separated in the content of various foods and therefore were analyzed jointly in the intake calculations. In addition, the analysis included vitamins A, C and E, zinc and copper. All the data were compared between the 2 groups established on the basis of the daily lutein and zeaxanthin intake according to the data obtained in the 24-h reminder survey results. Group 1: patients with a daily intake exceeding 1700 mg/day in males and 1400 mg/day in females. This is the group having a “sufficient” intake of lutein–zeaxanthin. This cut-off line was established arbitrarily, taking into account the average daily intake of lutein and zeaxanthin in the American population indicated in the Food and Nutrition Board 2001 table, which establishes a mean intake of 2.0–2.3 mg/day for males and 1.7–2.0 mg/day for females.16 No additional references of said nutrients were found and there is no DRI. In other series for other nutrients it was considered that 2/3 below the DRI involves a moderate risk of associated problems, and said cut-off line is close to that ratio. It would be the group with an “insufficient” intake. Group 2: patients with an intake below the group 1 data. This is the group with the “insufficient” intake. The statistical data were analyzed with the SPSS 13.0 software (SPSS Inc.; Chicago, IL, USA), including descriptive statistics of the different variables. For the comparative study of the qualitative variables, a 2 value was utilized and for the quantitative variables a t for student value was applied, establishing statistical significance for values of p ≤ 0.05.
Results The study comprised 52 patients. In some samples it was not possible to determine some components and for this reason in some variables the n value is under 52.
General epidemiologic data Group 1: only 25% of patients were above the established cutoff line. The group comprised 11 patients, 7 females (64%) and 4 males (37%), with a mean age of 78.3 years (SD 3.7). Group 2 comprised 42 patients, 24 females (59%) and 17 males (41.5%), with a mean age of 79.1 (SD 7.1) years. These would be the patients with an intake below the recommended values and therefore theoretically insufficient. No significant differences
were found in the distribution for gender or mean age between both samples. The data for the variables are grouped on the basis of the factors that can influence the metabolism of the distribution of lutein–zeaxanthin in order to facilitate the interpretation thereof.
Data related to body fat and serum lipids (Table 2) Seventy-three percent of group 1 had a history of dyslipidemia against 46% of group 2, without significant differences. These differences were smaller when including in the dyslipidemia group the patients with analyses exhibiting values above 220 mg/dL overall cholesterol or 200 mg/dL triglycerides. Eighty percent of group 1 and 73% of group 2 had dyslipidemia. When analyzing cholesterol as a quantitative variable, group 2 exhibited a mean value of 11.5% higher than group 1, with a p value of 0.08, almost reaching statistical significance. The cholesterol type distribution was somewhat different between the groups: group 1 exhibited lower values both for HDL and LDL cholesterol, reaching statistical significance (p = 0.01) in HDL cholesterol, which was 21% lower than in group 2. Triglycerides did not exhibit differences between both groups. The anthropometric parameter analysis shows that group 1 had a greater tendency to overweight: in group 1, with the same height, weight is higher (p = 0.08); BMI is significantly higher. Eighty percent of this group is overweight (BMI > 27%), the waist perimeter with high risk gender-corrected values (males > 88 cm and females > 102 cm) and percentage of fatty mass excess (males > 25 and females > 33), in group 2 this value goes down to 50% (p = 0.1 and 0.09 respectively). These differences are not found in the last parameter. Finally, the liver plays a crucial role in the metabolism of lutein and zeaxanthin and the absorption of fats. There are no differences between groups in the transaminases while the overall bilirubin is at the statistical significance limit, and is higher in group 2.
Data related to cardiovascular risk factors and diseases The dyslipidemia history and cholesterol levels in serum described in the previous section are an important cardiovascular risk factor (CVRF). The remaining CVRFs are summarized in Table 3. The prevalence of diabetes mellitus is high in both groups (25 and 27%, respectively). If we add patients with baseline glycemia > 115 mg/dL, the percentage reaches 50% and 60%, respectively. No significant differences were found between the 2 groups. The prevalence of AHT was of 82% in group 1 and 51% in group 2, with p = 0.09. It is frequent to find high values in measurements taken at the practice. As it was impossible to eliminate the emotional component of the active disease, the numbers obtained in the practice in many cases were pathological (SAT > 140 mmHg; DAT > 90 mmHg) even though they did not involve diagnostic value. The number of active smokers was very low: only 3 of the 52 patients included in the study were smokers. Three patients exhibited history of myocardium infarct and 5 had stable or unstable angor. In addition, one
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Table 2 – Parameters related to body fat and serum lipids. Group 1, n = 11
History: dyslipidemia Dis. + Chol > 220/T > 200 Overweight BMI AR waist perimeter % fatty mass excess
Group 2 (<2/3 IDR) n = 41
Yes (%)
No (%)
Yes (%)
8 (73) 8 (80) 9 (82) 9 (82) 9 (82)
3 (27) 2 (20) 2 (18) 2 (18) 2 (18)
19 (46) 30 (73) 19 (46) 21 (51) 34 (83)
Size (cm) Weight (kg) BMI Brachial perimeter (cm) AMA (mm2 ) AFA (mm2 ) Waist perimeter (cm) Hip perimeter (cm) Overall cholesterol (mg/dL) HDL cholesterol (mg/dL) LDL cholesterol (mg/dL) Triglycerides (mg/dL) ALT AST GGT Overall bilirubin (mg/dL)
p
No (%) 22 (54) 11 (27) 22 (54) 20 (49) 7 (17)
Mean
SD
Mean
SD
159.6 75.2 29.8 31.4 47.8 31.3 102.1 110.1 186.6 46.3 117.5 113.5 15.8 20.1 32.3 0.45
7.9 9.3 3.1 3.3 8.1 14.1 12.9 7.8 36.9 11.1 35.3 31.3 6.9 6.8 18.3 0.1
159.4 68.3 27.1 29.0 41.3 26.9 94.5 105.2 211.5 58.8 129.3 117.7 17.7 20.4 38.5 0.66
9.4 11.9 4.1 3.8 12.3 13.5 10.9 8.7 41.1 14.3 35.4 41.6 5.6 4.9 60.4 0.3
0.1 1.0 0.1 0.09 1.0
0.9 0.08 0.05 0.07 0.1 0.3 0.05 0.09 0.08 0.01 0.3 0.7 0.3 0.8 0.3 0.3
% fatty mass excess: above 33% in females and 25% in males; AFA (mm2 ): arm fatty area ([arm circumference2 /4] − AMA); ALT, AST, GGT: hepatic transaminases in U/L; AMA (mm2 ): arm muscle area (arm circumference in mm − tricipital skinfold size2 /4); Dis. + Col > 220/T > 200: history of dyslipidemia or analysis alterations (overall cholesterol > 220 or triglycerides > 200 mg/dL); overweight BMI: body mass index above 27%; BMI: body mass index (weight in kg/height in meters2 ); AR waist perimeter: waist perimeter above the high risk values (females > 88 cm; males > 102 cm).
had suffered an ictus and 3 peripheral arterial disease. Due to the low number of cases, it was decided to take this variable as a whole, as cardiovascular disease (CVD) history. In group 1, the prevalence was of 33% and in group 2 of 12% with p = 0.08. No differences were found in the serial levels of glucose, urea, creatinine or uric acid.
Data related to the intake of other antioxidants and micronutrients Table 4 illustrates the mean daily intake of other antioxidants such as vitamins A, C and E, together with zinc and copper (micronutrients). No significant differences were found in the daily intake of said elements.
Table 3 – Parameters related to cardiovascular risk factors and diseases. Group 1 (n = 11) Yes (%) DM history DM + glucose > 115 mg/dL AHT history AHT + SAT > 140 or DAT > 90 mmHg Active smoker Cardiovascular disease
Glucose (mg/dL) Urea (mg/dL) Creatinine (mg/dL) Uric acid (mg/dL)
3 (27) 5 (50) 9 (82) 11 (100) 2 (18) 4 (36)
Group 2 (<2/3 IDR) (n = 41) No (%)
Yes (%)
No (%)
8 (73) 5 (50) 2 (18) 0 (0) 9 (82) 7 (64)
10 (25) 27 (66) 21 (51) 34 (83) 1 (3) 5 (12)
31 (75) 14 (34) 20 (49) 7 (17) 40 (97) 36 (88)
Mean
SD
Mean
SD
110.4 46.1 1.0 5.4
17.1 15.7 0.3 1.8
111.1 42.2 0.9 5.2
44.4 12.6 0.3 1.1
p
1.0 0.4 0.09 0.3 0.6 0.08
0.9 0.4 0.1 0.7
DM: diabetes mellitus; cardiovascular disease: patients with ictus or infarct history, angor or peripheral arterial disease; AHT: arterial hypertension; DAT: diastolic arterial tension; SAT: systolic arterial tension.
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Table 4 – Mean daily intake and low intake of antioxidants and micronutrients. Group 1 (n = 11) Yes (%) *
Vitamin A Vitamin C* Vitamin E* Zinc* Copper*
Vitamin A (gRE) Vitamin C (mg) Vitamin E (mg) Zinc (mg) Copper (mg) ∗
8 (73) 9 (82) 8 (73) 9 (82) 0 (100)
Group 2 (<2/3 IDR) (n = 41) No (%) 3 (27) 2 (18) 3 (27) 2 (18) 11 (100)
p
Yes (%)
No (%)
24 (58) 33 (80) 28 (68) 36 (88) 1 (3)
17 (42) 8 (20) 13 (32) 5 (12) 40 (97)
Mean
SD
Mean
SD
1082.5 241.9 7.9 10.6 2.1
1146.7 172.9 3.5 7.1 0.5
1583.4 152.4 8.7 10.4 2.4
3389.9 100.8 3.9 7.7 1.0
0.5 1.0 1.0 0.6 1.0
0.6 0.03 0.6 0.9 0.3
Daily intake below: copper: < 900 mg. Vitamin A: male 60–69 < 1.000. + 70 < 900; female 60–69 < 800. + 70 < 700 gRE (retinol equivalent micrograms). Vitamin C: male < 80; female < 70 mg. Vitamin E: male 60–69 < 10 + 70 < 12; female 60–69 < 8 + 70 < 10 mg. Zinc: male < 15; female < 12 mg.
The vitamin C intake was of 241.9 mg in group 1 and of 152.4 mg in group 2 (36.9% less). This difference is significant from the statistical viewpoint (p = 0.03).
Discussion Lutein and zeaxanthin are xanthophile carotenoids.17,18 They cannot be synthesized by the body and must be supplied by diet. They are found in green leaf vegetables such as spinach as well as in corn, lettuce and egg yolk. There is no DRI and the only known data is the mean daily intake in the USA population, which was of 2.0–2.3 mg/day for males and 1.7–2 mg/day for females.16 These values were used in this study as DRI. In small series, it has been demonstrated that the intake of lutein and zeaxanthin through enriched diets (2.4–30 mg/day) have improved visual function in the short term and the optic density of macular pigments both in healthy patients as well as in ARMD patients.3,9,19–21 In patients with atrophic ARMD, in the Lutein Antioxidant Suplementation Trial (LAST), lutein increased 40% the optic density of macular pigments and improved several visual functional tests.6 The Third National Health and Nutrition Examination Survey assessed 8222 subjects and found a protective effect in the group between 40 and 59 years of age with a high intake of lutein and zeaxanthin (progression to retinal pigmentary alterations).22 An additional study published in 2009 which surveyed the eating habits of 7934 patients (belonging to the AREDS study) concluded that subjects with a higher intake of antioxidants have reduced risk of drusen and the advanced forms of ARMD.23 AREDS 2 has implemented a multicenter prospective study to assess the influence of lutein, zeaxhantin and Omega-3 fatty acids in the progression to the advanced forms of ARMD. The evidence found to date reveals that intermediate (10–15 mg/day) or high (>30 mg/day) levels of pharmacological or dietary supplementation could be beneficial.
It would be important to identify ARMD patients with insufficient intake of lutein and zeaxhantin, as well as quantifying said intake in order to correct through dietary recommendations or pharmacological supplements. A complete survey on eating habits or plasmatic assessments is not available in usual clinical practice although we can try to determine differences in the characteristics of patients with abnormal intake of lutein–zeaxhantin and those below 2/3 of the DRI (which in this case is theoretical). The most detailed tables that illustrate the content of nutrients in various foods show the content of lutein and zeaxhantin together and therefore this value had to be applied jointly. In our series, the patients with a normal intake (group 1) exhibited greater tendency towards overweight and hyperlipidemia. As the sample is small, some of the variables having a patient value between 0.05 and 0.1 could achieve statistical significance by increasing the n value. For this reason, this will have to be taken into account in future studies. The same occurred with the dyslipidemia history (73 vs 46%), with BMI above 27% (82 vs 46%), a high risk value in waist perimeter (82 vs 51%), mean weight with equivalent sizes and genders, and brachial perimeter. Significant differences were found in the mean BMI. In summary, antropomorphic parameters exhibit rates of overweight among patients with sufficient lutein and zeaxhantin intake. The assessment of serum lipids shows that group 1 patients have a lower mean cholesterol level. Seventy-three percent of these were diagnosed with dyslipidemia and were probably in dietary and pharmacological treatment, and this accounts for the lower overall cholesterol figures. HDL cholesterol, the socalled “good” cholesterol, has a higher value in patients with lower lutein and zeaxhantin intake (21%). CVRFs illustrate a higher prevalence of AHT (82 vs 51%) in group 1, bordering statistical significance, with lower HDL cholesterol. In addition, group 1 exhibited a higher number of CVD (36 vs 12%), bordering statistical significance. Increased lutein and zeaxhantin intake is carried out through hyperlypemiating and hypercaloric diet which involves weight increases.
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The Mediterranean diet is rich in antioxidants and, in contrast with what occurs in North America and northern European countries, it includes a high proportion of vegetables (cereals, fruit, greens, dried fruits, wine and olive oil).24 Even so, dietary habits are changing towards lower antioxidant intakes.25 A study carried out by Romaguera et al. in 200426 with 396 elderly subjects in the Balearic Islands revealed a deficit in antioxidants supply (vitamins A, C, E and zinc), with levels increasing in parallel to the increase of energy intake, simple sugars and saturated fats. The same occurs in our wet ARMD sample of patients: the increased intake of lutein and zeaxhantin is at the cost of a diet that increases the prevalence of overweight, CVRF and CVD. Group 1 exhibited a deficit in the intake of vitamins A, C, E and zinc in 70–80% of patients. Therefore, the diet with sufficient amounts of lutein–zeaxhantin does not allow patients to reach normal levels of other antioxidants. This means that dietary recommendations or supplements should also increase the levels of vitamins A, C, E and zinc. This study has several limitations, i.e., it is a small sample and only assessed the 24-h intake which is much more demanding as it involves taking every day sufficient levels of lutein and zeaxhantin. However, its main advantage is that it was carried out in patients with wet ARMD and there are no specific studies for this group of patients. It is essential to change the eating habits of wet ARMD patients due to high deficit of antioxidants, even when they have a normal intake of lutein and zeaxhantin. The objective would be to raise the levels of these 2 nutrients together with other antioxidants with a normal or hypo-calorie diet to avoid overweight and the CVD this involves.
Funding This project was subsidized by the Dirección General d’Avaluació i Acreditació, Conselleria de Salut i Consum. Govern Balear. DGAVAL PI 033/09 (IB 1148/09).
Conflict of interests No conflict of interest has been declared by the authors.
references
1. Chopdar A, Chakravarthy U, Verma D. Age-related macular degeneration. BMJ. 2003;326:485–8. 2. Yeum KJ, Russell RM. Carotenoid bioavailability and bioconversion. Ann Rev Nutr. 2002;22:483–504. 3. Richer S. ARMD—pilot (case series) environmental intervention data. J Am Optom Assoc. 1999;70: 24–36. 4. Falsini B, Piccardi M, Iarossi G, Fadda A, Merendino E, Valentini P. Influence of short-term antioxidant supplementation onmacular function in age-related macuolpathy: a pilot study including electrophysiologic assessment. Ophthalmology. 2003;110:51–60.
117
5. Dagnelie G, Zorge IS, McDonald TM. Lutein improves visual function in some patients with retinal degeneration: a pilot study via the internet. Optometry. 2000;71: 147–64. 6. Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D, et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry. 2004;75:216–30. 7. Davies NP, Morland AB. Macular pigments: their characteristics and putative role. Prog Retin Eye Res. 2004;23:533–59. 8. Sujak A, Gabrielska J, Grudzinski W, Borc R, Mazurek P, Gruszecki WI. Lutein and zeaxanthin as protectors of lipid membranes against oxidative damage: the structural aspects. Arch Biochem Biophys. 1999;371:301–7. 9. Bone RA, Landrum JT, Guerra LH, Ruiz CA. Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans. J Nut. 2003;133:992–8. 10. Junghans A, Sies H, Stahl W. Macular pigments lutein and zeaxanthin as blue light filters studied in liposomes. Arch Biochem Biophys. 2001;391:160–4. 11. Age-Related Eye Disease Study Group (AREDS). A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C ans E, beta carotene, and Zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119: 1417–36. ˜ 12. Mataix J, Manas M, Llopis J, Martinez de Victoria E, Juan J, ˜ Borregon A. Tablas de composición de alimentos espanoles (Spanish Food Composition Tables) 2004. Granada: INTA, Universidad de Granada; 2004. 13. Ortega RM, Lopez A, Requejo AM, Marcos AM, Carvajales PA. La composición de los alimentos. Herramienta básica de valoración nutricional. Madrid: Departamento de Nutrición, Facultad de Farmacia, Universidad Complutense; 2004. 14. U.S. Department of Agriculture, Agricultural Research Service (2009) USDA National Nutrient Database for Standard Reference, Release 22. Nutrient Data Laboratory Home Page. Available from: http://www.ars.usda.gov/ba/bhnrc/ndl [accessed 20.06.10]. 15. Olmedilla B, Granado F, Blanco I, Gil-Martinez E, Rojas-Hidalgo E. Contenido de carotenoides de verduras ˜ Madrid: Instituto y frutas de mayor consumo en Espana. Nacional de Salud; 1996. 16. Johnson EJ. The role of carotenoids in human health. Nutr Clin Care. 2002;5:56–65. 17. Bone RA, Landrum JT, Hime GW, Cains A, Zamor J. Stereochemistry of the macular carotenoids. Invest Ophthamol Vis Sci. 1993;34:2033–40. 18. Carpentier S, Knaus M, Suh M. Associations between lutein, zeaxanthin, and age-related macular degeneration: an overview. Crit Rev Food Sci Nutr. 2009;49:313–26. 19. Hammond Jr BR, Johnson EJ, Russell EJ, Krinsky NI, Yeum KJ, Edwards RB, et al. Dietary modification of human macular pigment density. Invest Ophthamol Vis Sci. 1997;38: 1795–801. 20. Johnson EJ, Hammond RB, Yeum KJ, Qin J, Wang XD, Wang XD, et al. Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density. Am Clin Nutr. 2000;71:1555–62. 21. Cardinault N, Gorrand JM, Tyssandier V, Grolier P, Rock E, Borel P, et al. Short-term supplementation with lutein affects biomarkers of lutein status similarly in young and elderly subjects. Exp Gerontol. 2003;38:573–82.
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22. Mares-Perlman JA, Fisher A, Klein R, Palta M, Block G, Millen AE, et al. Lutein and zeaxanthin in the diet and serum and their relation to age-related maculopathy in the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 2001;153:424–32. 23. Chiu CJ, Milton RC, Klein R, Gensler G, Taylor A. Dietary compound Score and risk of age-related macular degeneration in the Age-Related Eye Disease Study. Ophthalmology. 2009;116:939–46.
24. Tur JA. Los antioxidantes en la dieta mediterránea. Rev Esp Nutr Comunitaria. 2004;10:198–207. 25. Tur JA, Serra-Majem L. Does the diet of the Balearic population, a Mediterranean type diet, still provide adequate antioxidant nutriet intakes? Eur J Nutr. 2005;44:204–13. 26. Romaguera D, Llompart I, Bonnin T, Pons A, Tur JA. Análisis de la ingesta dietética y calidad nutricional en ancianos no institucionalizados de las Islas Baleares. Rev Esp Nutr Comunitaria. 2004;10:168–77.
ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia
Original article
Characteristics of patients with wet age-related macular degeneration and low intake of lutein and zeaxanthin夽 J.L. Olea a,∗ , J.A. Aragón a , M.E. Zapata b , J.A. Tur b a
Sección de Vítreo-Retina, Servicio de Oftalmología, Hospital Son Espases, Islas Baleares, Spain Facultad de Ciencias, Departamento de Biología Fundamental y Ciencias de la Salud, Universidad de las Islas Baleares (Grupo investigación nutrición comunitaria y estrés oxidativo), Palma, Spain
b
a r t i c l e
i n f o
a b s t r a c t
Article history:
Objective: To assess the characteristics of patients with wet AMD and low intake of lutein
Received 15 February 2011
and zeaxanthin in our population.
Accepted 10 October 2011
Methods: A prospective, observational, cross-sectional study was conducted on patients with
Available online 23 July 2012
active wet AMD. A full blood count, a lipid and liver profile, a dietary interview (24-h recall), and an anthropometric study were performed. Lutein–zeaxanthin (LZ) intake results split
Keywords: Lutein Zeaxanthin Age-related macular degeneration Retinal carotenoids
the patents in two groups. Group 1 (“sufficient” intake): patients with ≥1400 mg/day intake in women and 1700 mg/day in men (2/3 of the average daily intake in a normal population). Group 2: patients with daily intakes below that of group 1. A descriptive and comparative statistical study was performed.
Antioxidants
Results: Fifty-two patients with a mean age of 78.9 years. Group 1: eleven patients (21% of
Mediterranean diet
the sample). Group 2: forty-one patients. The subjects with adequate intake of LZ had higher a body mass index (BMI) and waist circumference. Between 70 and 80% of patients in group 1 had inadequate intake of vitamins A, C, E and zinc. Conclusions: Seventy-nine percent of the patients with wet AMD have a deficient daily intake in LZ. The population with adequate intake is associated with an increased BMI and waist circumference, and in addition, most of them have an insufficient intake of vitamins A, C, E and zinc. © 2011 Sociedad Española de Oftalmología. Published by Elsevier España, S.L. All rights reserved.
Características de la población con ingesta baja en luteína y zeaxantina en pacientes con degeneración macular asociada a la edad variante húmeda r e s u m e n Palabras clave:
Objetivo: Averiguar las características de los pacientes con DMAE húmeda que ingieren sufi-
Luteína
ciente luteína y zeaxantina en nuestra población.
夽
Please cite this article as: Olea JL, et al. Características de la población con ingesta baja en luteína y zeaxantina en pacientes con degeneración macular asociada a la edad variante húmeda. Arch Soc Esp Oftalmol. 2012;87:112–8. ∗ Corresponding author. E-mail address: [email protected] (J.L. Olea). 2173-5794/$ – see front matter © 2011 Sociedad Española de Oftalmología. Published by Elsevier España, S.L. All rights reserved.
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Zeaxantina
Métodos: Estudio protocolizado, prospectivo, observacional, transversal, en pacientes diag-
Degeneración macular asociada
nosticados de DMAE húmeda activa. Se efectúa hemograma, perfil lipídico, y perfil hepático;
a la edad
una entrevista dietética sobre los hábitos alimentarios a partir de la realización de un
Carotenoides retinianos
recordatorio de 24 h y estudio antropométrico. Se dividen en dos grupos en función de
Dieta mediterránea
la ingesta de luteína-zeaxantina (L-Z). Grupo 1 (ingesta «suficiente»): pacientes con ingesta diaria ≥ 1.400 mg/día en mujeres y 1.700 mg/día en hombres (2/3 de la ingesta media diaria en población normal). Grupo 2: pacientes con ingesta diaria inferior a las del grupo 1. Se efectúa un estudio estadístico descriptivo y comparativo entre ambos grupos. ˜ Resultado: Un total de 52 pacientes, con una edad media de 78,9 anos. Grupo 1: 11 pacientes (21% de la muestra). Grupo 2: 41. Los pacientes con ingesta suficiente de L-Z tienen mayor índice de masa corporal y perímetro de cintura. El 70-80% de los pacientes del grupo 1 presentan ingesta insuficiente de vitaminas A, C y E, y zinc. Conclusiones: El 79% de los pacientes tienen ingesta diaria de L-Z baja. Los pacientes con aporte suficiente tienen un aumento en el índice de masa corporal y perímetro de cintura, y además la mayoría tienen una ingesta insuficiente de vitaminas A, C y E, y zinc. © 2011 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L. Todos los derechos reservados.
Introduction
Table 1 – Epidemiological and ophthalmological characteristics of patients.
Age-related macular degeneration (ARMD) is the main cause of blindness among the elderly population in civilized countries.1 In Spain, with 13% of the population over 65 years of age, the prevalence of advanced ARMD varies from 0.5% at 55 up to 7% above 65. About 25,000 new cases of the wet variety are expected each year. Lutein and zeaxanthin are almost exclusively the only carotenoids present in the macula,2 and are defined as the macular pigments. They act to improve visual function, protecting visual structures from oxidative damage which is very high at this level.3–6 Said carotenoids neutralize free radicals7–9 and filter the blue component of the visible spectrum.9,10 In 2001, report number 8 of AREDS demonstrated a statistically significant reduction of 25% of the possibilities of developing advanced ARMD and loss of vision against placebo with the addition of a fixed association of antioxidants and zinc.11 Many studies have found an association between the levels of lutein and zeaxanthin in plasma and retina, with a possible reduction of the risk of severe ARMD forms. It would be important to identify patients with a deficiency of said nutrients either through a nutrition habits survey or plasmatic assessments. However, both options are laborious and unavailable in routine clinic. Even so, we can try to determine the existence of a clinical profile differentiating said patients in order to establish the characteristics of the population with a normal intake of lutein–zeaxanthin and those under 2/3 of the daily recommended intake (DRI) which in this case is theoretical. The final objective of the research line which this paper endorses is the identification in the clinical practice of patients exhibiting deficit of antioxidants, particularly lutein and zeaxanthin and to identify the solution either with customized dietary recommendations or, if that is not possible, pharmacological supplements.
Patients: 52 Male 21 (40.4%) Female 31 (59.6%) Mean age: 78.9 (SD 6.5)
Eyes involved: 59 Right 21 Left 24 Bilateral 7 Mean Snellen VA 0.21 (SD 0.1)
Subretinal neovascular membrane Type: Classic 17 (28.8%) Hidden 26 (44.2%) RAP 15 (25.4%) Polypoid 1 (1.6%)
Location: Subfoveal 41 (69.5%) Juxtafoveal 16 (27.1%) Extrafoveal 2 (3.4%)
Snellen VA: visual acuity in decimal scale with Snellen optotypes; SD: standard deviation; RAP: retinal angiomatous proliferation.
Subjects, material and methods A protocolized, prospective, observational and transversal study in patients diagnosed with active wet ARMD in the Retina and Vitreous Section of the Ophthalmology Service in the Son Dureta University Hospital (Palma de Mallorca, Spain). The patient diagnosis and assessment was formed after a full ophthalmology history comprising fluorescein angiography and optic coherence tomography. The ophthalmological assessment data are summarized in Table 1. Together with the clinical diagnosis, the patients were requested to accept inclusion in the study (this project had already been approved by the Ethics Committee of the Balearic Islands). The analytical data were obtained from recent analysis (under 3 months). Optionally, we requested a new analysis comprising hemogram, urea, creatinine, glucose, uric acid, hepatic transaminases (ALT, AST, GGT) overall bilirubin, overall cholesterol, HDL and LDL and triglycerides. One month later, at the time of the second intravitreal injection, the patients were interviewed and asked about their
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eating habits on the basis of a 24-h reminder by a qualified nutritionist researcher of the Community Nutrition And Oxidative Stress Research Group of the Balearic Islands University (UIB). Subsequently, the anthropometric study was performed, comprising size, weight, brachial circumference, waist and hips, thickness of the tricipital skinfold, fatty mass and arterial pressure. The BMI and the waist–hip ratio, fatty and muscle area of the arm were calculated. The conversion of food into nutrients was carried out with a computerized application of the UIB nutrition expert group, based on the American, European and Spanish tables of nutritional contents in food.12–15 In many cases, lutein and zeaxanthin do not appear separated in the content of various foods and therefore were analyzed jointly in the intake calculations. In addition, the analysis included vitamins A, C and E, zinc and copper. All the data were compared between the 2 groups established on the basis of the daily lutein and zeaxanthin intake according to the data obtained in the 24-h reminder survey results. Group 1: patients with a daily intake exceeding 1700 mg/day in males and 1400 mg/day in females. This is the group having a “sufficient” intake of lutein–zeaxanthin. This cut-off line was established arbitrarily, taking into account the average daily intake of lutein and zeaxanthin in the American population indicated in the Food and Nutrition Board 2001 table, which establishes a mean intake of 2.0–2.3 mg/day for males and 1.7–2.0 mg/day for females.16 No additional references of said nutrients were found and there is no DRI. In other series for other nutrients it was considered that 2/3 below the DRI involves a moderate risk of associated problems, and said cut-off line is close to that ratio. It would be the group with an “insufficient” intake. Group 2: patients with an intake below the group 1 data. This is the group with the “insufficient” intake. The statistical data were analyzed with the SPSS 13.0 software (SPSS Inc.; Chicago, IL, USA), including descriptive statistics of the different variables. For the comparative study of the qualitative variables, a 2 value was utilized and for the quantitative variables a t for student value was applied, establishing statistical significance for values of p ≤ 0.05.
Results The study comprised 52 patients. In some samples it was not possible to determine some components and for this reason in some variables the n value is under 52.
General epidemiologic data Group 1: only 25% of patients were above the established cutoff line. The group comprised 11 patients, 7 females (64%) and 4 males (37%), with a mean age of 78.3 years (SD 3.7). Group 2 comprised 42 patients, 24 females (59%) and 17 males (41.5%), with a mean age of 79.1 (SD 7.1) years. These would be the patients with an intake below the recommended values and therefore theoretically insufficient. No significant differences
were found in the distribution for gender or mean age between both samples. The data for the variables are grouped on the basis of the factors that can influence the metabolism of the distribution of lutein–zeaxanthin in order to facilitate the interpretation thereof.
Data related to body fat and serum lipids (Table 2) Seventy-three percent of group 1 had a history of dyslipidemia against 46% of group 2, without significant differences. These differences were smaller when including in the dyslipidemia group the patients with analyses exhibiting values above 220 mg/dL overall cholesterol or 200 mg/dL triglycerides. Eighty percent of group 1 and 73% of group 2 had dyslipidemia. When analyzing cholesterol as a quantitative variable, group 2 exhibited a mean value of 11.5% higher than group 1, with a p value of 0.08, almost reaching statistical significance. The cholesterol type distribution was somewhat different between the groups: group 1 exhibited lower values both for HDL and LDL cholesterol, reaching statistical significance (p = 0.01) in HDL cholesterol, which was 21% lower than in group 2. Triglycerides did not exhibit differences between both groups. The anthropometric parameter analysis shows that group 1 had a greater tendency to overweight: in group 1, with the same height, weight is higher (p = 0.08); BMI is significantly higher. Eighty percent of this group is overweight (BMI > 27%), the waist perimeter with high risk gender-corrected values (males > 88 cm and females > 102 cm) and percentage of fatty mass excess (males > 25 and females > 33), in group 2 this value goes down to 50% (p = 0.1 and 0.09 respectively). These differences are not found in the last parameter. Finally, the liver plays a crucial role in the metabolism of lutein and zeaxanthin and the absorption of fats. There are no differences between groups in the transaminases while the overall bilirubin is at the statistical significance limit, and is higher in group 2.
Data related to cardiovascular risk factors and diseases The dyslipidemia history and cholesterol levels in serum described in the previous section are an important cardiovascular risk factor (CVRF). The remaining CVRFs are summarized in Table 3. The prevalence of diabetes mellitus is high in both groups (25 and 27%, respectively). If we add patients with baseline glycemia > 115 mg/dL, the percentage reaches 50% and 60%, respectively. No significant differences were found between the 2 groups. The prevalence of AHT was of 82% in group 1 and 51% in group 2, with p = 0.09. It is frequent to find high values in measurements taken at the practice. As it was impossible to eliminate the emotional component of the active disease, the numbers obtained in the practice in many cases were pathological (SAT > 140 mmHg; DAT > 90 mmHg) even though they did not involve diagnostic value. The number of active smokers was very low: only 3 of the 52 patients included in the study were smokers. Three patients exhibited history of myocardium infarct and 5 had stable or unstable angor. In addition, one
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Table 2 – Parameters related to body fat and serum lipids. Group 1, n = 11
History: dyslipidemia Dis. + Chol > 220/T > 200 Overweight BMI AR waist perimeter % fatty mass excess
Group 2 (<2/3 IDR) n = 41
Yes (%)
No (%)
Yes (%)
8 (73) 8 (80) 9 (82) 9 (82) 9 (82)
3 (27) 2 (20) 2 (18) 2 (18) 2 (18)
19 (46) 30 (73) 19 (46) 21 (51) 34 (83)
Size (cm) Weight (kg) BMI Brachial perimeter (cm) AMA (mm2 ) AFA (mm2 ) Waist perimeter (cm) Hip perimeter (cm) Overall cholesterol (mg/dL) HDL cholesterol (mg/dL) LDL cholesterol (mg/dL) Triglycerides (mg/dL) ALT AST GGT Overall bilirubin (mg/dL)
p
No (%) 22 (54) 11 (27) 22 (54) 20 (49) 7 (17)
Mean
SD
Mean
SD
159.6 75.2 29.8 31.4 47.8 31.3 102.1 110.1 186.6 46.3 117.5 113.5 15.8 20.1 32.3 0.45
7.9 9.3 3.1 3.3 8.1 14.1 12.9 7.8 36.9 11.1 35.3 31.3 6.9 6.8 18.3 0.1
159.4 68.3 27.1 29.0 41.3 26.9 94.5 105.2 211.5 58.8 129.3 117.7 17.7 20.4 38.5 0.66
9.4 11.9 4.1 3.8 12.3 13.5 10.9 8.7 41.1 14.3 35.4 41.6 5.6 4.9 60.4 0.3
0.1 1.0 0.1 0.09 1.0
0.9 0.08 0.05 0.07 0.1 0.3 0.05 0.09 0.08 0.01 0.3 0.7 0.3 0.8 0.3 0.3
% fatty mass excess: above 33% in females and 25% in males; AFA (mm2 ): arm fatty area ([arm circumference2 /4] − AMA); ALT, AST, GGT: hepatic transaminases in U/L; AMA (mm2 ): arm muscle area (arm circumference in mm − tricipital skinfold size2 /4); Dis. + Col > 220/T > 200: history of dyslipidemia or analysis alterations (overall cholesterol > 220 or triglycerides > 200 mg/dL); overweight BMI: body mass index above 27%; BMI: body mass index (weight in kg/height in meters2 ); AR waist perimeter: waist perimeter above the high risk values (females > 88 cm; males > 102 cm).
had suffered an ictus and 3 peripheral arterial disease. Due to the low number of cases, it was decided to take this variable as a whole, as cardiovascular disease (CVD) history. In group 1, the prevalence was of 33% and in group 2 of 12% with p = 0.08. No differences were found in the serial levels of glucose, urea, creatinine or uric acid.
Data related to the intake of other antioxidants and micronutrients Table 4 illustrates the mean daily intake of other antioxidants such as vitamins A, C and E, together with zinc and copper (micronutrients). No significant differences were found in the daily intake of said elements.
Table 3 – Parameters related to cardiovascular risk factors and diseases. Group 1 (n = 11) Yes (%) DM history DM + glucose > 115 mg/dL AHT history AHT + SAT > 140 or DAT > 90 mmHg Active smoker Cardiovascular disease
Glucose (mg/dL) Urea (mg/dL) Creatinine (mg/dL) Uric acid (mg/dL)
3 (27) 5 (50) 9 (82) 11 (100) 2 (18) 4 (36)
Group 2 (<2/3 IDR) (n = 41) No (%)
Yes (%)
No (%)
8 (73) 5 (50) 2 (18) 0 (0) 9 (82) 7 (64)
10 (25) 27 (66) 21 (51) 34 (83) 1 (3) 5 (12)
31 (75) 14 (34) 20 (49) 7 (17) 40 (97) 36 (88)
Mean
SD
Mean
SD
110.4 46.1 1.0 5.4
17.1 15.7 0.3 1.8
111.1 42.2 0.9 5.2
44.4 12.6 0.3 1.1
p
1.0 0.4 0.09 0.3 0.6 0.08
0.9 0.4 0.1 0.7
DM: diabetes mellitus; cardiovascular disease: patients with ictus or infarct history, angor or peripheral arterial disease; AHT: arterial hypertension; DAT: diastolic arterial tension; SAT: systolic arterial tension.
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Table 4 – Mean daily intake and low intake of antioxidants and micronutrients. Group 1 (n = 11) Yes (%) *
Vitamin A Vitamin C* Vitamin E* Zinc* Copper*
Vitamin A (gRE) Vitamin C (mg) Vitamin E (mg) Zinc (mg) Copper (mg) ∗
8 (73) 9 (82) 8 (73) 9 (82) 0 (100)
Group 2 (<2/3 IDR) (n = 41) No (%) 3 (27) 2 (18) 3 (27) 2 (18) 11 (100)
p
Yes (%)
No (%)
24 (58) 33 (80) 28 (68) 36 (88) 1 (3)
17 (42) 8 (20) 13 (32) 5 (12) 40 (97)
Mean
SD
Mean
SD
1082.5 241.9 7.9 10.6 2.1
1146.7 172.9 3.5 7.1 0.5
1583.4 152.4 8.7 10.4 2.4
3389.9 100.8 3.9 7.7 1.0
0.5 1.0 1.0 0.6 1.0
0.6 0.03 0.6 0.9 0.3
Daily intake below: copper: < 900 mg. Vitamin A: male 60–69 < 1.000. + 70 < 900; female 60–69 < 800. + 70 < 700 gRE (retinol equivalent micrograms). Vitamin C: male < 80; female < 70 mg. Vitamin E: male 60–69 < 10 + 70 < 12; female 60–69 < 8 + 70 < 10 mg. Zinc: male < 15; female < 12 mg.
The vitamin C intake was of 241.9 mg in group 1 and of 152.4 mg in group 2 (36.9% less). This difference is significant from the statistical viewpoint (p = 0.03).
Discussion Lutein and zeaxanthin are xanthophile carotenoids.17,18 They cannot be synthesized by the body and must be supplied by diet. They are found in green leaf vegetables such as spinach as well as in corn, lettuce and egg yolk. There is no DRI and the only known data is the mean daily intake in the USA population, which was of 2.0–2.3 mg/day for males and 1.7–2 mg/day for females.16 These values were used in this study as DRI. In small series, it has been demonstrated that the intake of lutein and zeaxanthin through enriched diets (2.4–30 mg/day) have improved visual function in the short term and the optic density of macular pigments both in healthy patients as well as in ARMD patients.3,9,19–21 In patients with atrophic ARMD, in the Lutein Antioxidant Suplementation Trial (LAST), lutein increased 40% the optic density of macular pigments and improved several visual functional tests.6 The Third National Health and Nutrition Examination Survey assessed 8222 subjects and found a protective effect in the group between 40 and 59 years of age with a high intake of lutein and zeaxanthin (progression to retinal pigmentary alterations).22 An additional study published in 2009 which surveyed the eating habits of 7934 patients (belonging to the AREDS study) concluded that subjects with a higher intake of antioxidants have reduced risk of drusen and the advanced forms of ARMD.23 AREDS 2 has implemented a multicenter prospective study to assess the influence of lutein, zeaxhantin and Omega-3 fatty acids in the progression to the advanced forms of ARMD. The evidence found to date reveals that intermediate (10–15 mg/day) or high (>30 mg/day) levels of pharmacological or dietary supplementation could be beneficial.
It would be important to identify ARMD patients with insufficient intake of lutein and zeaxhantin, as well as quantifying said intake in order to correct through dietary recommendations or pharmacological supplements. A complete survey on eating habits or plasmatic assessments is not available in usual clinical practice although we can try to determine differences in the characteristics of patients with abnormal intake of lutein–zeaxhantin and those below 2/3 of the DRI (which in this case is theoretical). The most detailed tables that illustrate the content of nutrients in various foods show the content of lutein and zeaxhantin together and therefore this value had to be applied jointly. In our series, the patients with a normal intake (group 1) exhibited greater tendency towards overweight and hyperlipidemia. As the sample is small, some of the variables having a patient value between 0.05 and 0.1 could achieve statistical significance by increasing the n value. For this reason, this will have to be taken into account in future studies. The same occurred with the dyslipidemia history (73 vs 46%), with BMI above 27% (82 vs 46%), a high risk value in waist perimeter (82 vs 51%), mean weight with equivalent sizes and genders, and brachial perimeter. Significant differences were found in the mean BMI. In summary, antropomorphic parameters exhibit rates of overweight among patients with sufficient lutein and zeaxhantin intake. The assessment of serum lipids shows that group 1 patients have a lower mean cholesterol level. Seventy-three percent of these were diagnosed with dyslipidemia and were probably in dietary and pharmacological treatment, and this accounts for the lower overall cholesterol figures. HDL cholesterol, the socalled “good” cholesterol, has a higher value in patients with lower lutein and zeaxhantin intake (21%). CVRFs illustrate a higher prevalence of AHT (82 vs 51%) in group 1, bordering statistical significance, with lower HDL cholesterol. In addition, group 1 exhibited a higher number of CVD (36 vs 12%), bordering statistical significance. Increased lutein and zeaxhantin intake is carried out through hyperlypemiating and hypercaloric diet which involves weight increases.
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The Mediterranean diet is rich in antioxidants and, in contrast with what occurs in North America and northern European countries, it includes a high proportion of vegetables (cereals, fruit, greens, dried fruits, wine and olive oil).24 Even so, dietary habits are changing towards lower antioxidant intakes.25 A study carried out by Romaguera et al. in 200426 with 396 elderly subjects in the Balearic Islands revealed a deficit in antioxidants supply (vitamins A, C, E and zinc), with levels increasing in parallel to the increase of energy intake, simple sugars and saturated fats. The same occurs in our wet ARMD sample of patients: the increased intake of lutein and zeaxhantin is at the cost of a diet that increases the prevalence of overweight, CVRF and CVD. Group 1 exhibited a deficit in the intake of vitamins A, C, E and zinc in 70–80% of patients. Therefore, the diet with sufficient amounts of lutein–zeaxhantin does not allow patients to reach normal levels of other antioxidants. This means that dietary recommendations or supplements should also increase the levels of vitamins A, C, E and zinc. This study has several limitations, i.e., it is a small sample and only assessed the 24-h intake which is much more demanding as it involves taking every day sufficient levels of lutein and zeaxhantin. However, its main advantage is that it was carried out in patients with wet ARMD and there are no specific studies for this group of patients. It is essential to change the eating habits of wet ARMD patients due to high deficit of antioxidants, even when they have a normal intake of lutein and zeaxhantin. The objective would be to raise the levels of these 2 nutrients together with other antioxidants with a normal or hypo-calorie diet to avoid overweight and the CVD this involves.
Funding This project was subsidized by the Dirección General d’Avaluació i Acreditació, Conselleria de Salut i Consum. Govern Balear. DGAVAL PI 033/09 (IB 1148/09).
Conflict of interests No conflict of interest has been declared by the authors.
references
1. Chopdar A, Chakravarthy U, Verma D. Age-related macular degeneration. BMJ. 2003;326:485–8. 2. Yeum KJ, Russell RM. Carotenoid bioavailability and bioconversion. Ann Rev Nutr. 2002;22:483–504. 3. Richer S. ARMD—pilot (case series) environmental intervention data. J Am Optom Assoc. 1999;70: 24–36. 4. Falsini B, Piccardi M, Iarossi G, Fadda A, Merendino E, Valentini P. Influence of short-term antioxidant supplementation onmacular function in age-related macuolpathy: a pilot study including electrophysiologic assessment. Ophthalmology. 2003;110:51–60.
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5. Dagnelie G, Zorge IS, McDonald TM. Lutein improves visual function in some patients with retinal degeneration: a pilot study via the internet. Optometry. 2000;71: 147–64. 6. Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D, et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry. 2004;75:216–30. 7. Davies NP, Morland AB. Macular pigments: their characteristics and putative role. Prog Retin Eye Res. 2004;23:533–59. 8. Sujak A, Gabrielska J, Grudzinski W, Borc R, Mazurek P, Gruszecki WI. Lutein and zeaxanthin as protectors of lipid membranes against oxidative damage: the structural aspects. Arch Biochem Biophys. 1999;371:301–7. 9. Bone RA, Landrum JT, Guerra LH, Ruiz CA. Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans. J Nut. 2003;133:992–8. 10. Junghans A, Sies H, Stahl W. Macular pigments lutein and zeaxanthin as blue light filters studied in liposomes. Arch Biochem Biophys. 2001;391:160–4. 11. Age-Related Eye Disease Study Group (AREDS). A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C ans E, beta carotene, and Zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119: 1417–36. ˜ 12. Mataix J, Manas M, Llopis J, Martinez de Victoria E, Juan J, ˜ Borregon A. Tablas de composición de alimentos espanoles (Spanish Food Composition Tables) 2004. Granada: INTA, Universidad de Granada; 2004. 13. Ortega RM, Lopez A, Requejo AM, Marcos AM, Carvajales PA. La composición de los alimentos. Herramienta básica de valoración nutricional. Madrid: Departamento de Nutrición, Facultad de Farmacia, Universidad Complutense; 2004. 14. U.S. Department of Agriculture, Agricultural Research Service (2009) USDA National Nutrient Database for Standard Reference, Release 22. Nutrient Data Laboratory Home Page. Available from: http://www.ars.usda.gov/ba/bhnrc/ndl [accessed 20.06.10]. 15. Olmedilla B, Granado F, Blanco I, Gil-Martinez E, Rojas-Hidalgo E. Contenido de carotenoides de verduras ˜ Madrid: Instituto y frutas de mayor consumo en Espana. Nacional de Salud; 1996. 16. Johnson EJ. The role of carotenoids in human health. Nutr Clin Care. 2002;5:56–65. 17. Bone RA, Landrum JT, Hime GW, Cains A, Zamor J. Stereochemistry of the macular carotenoids. Invest Ophthamol Vis Sci. 1993;34:2033–40. 18. Carpentier S, Knaus M, Suh M. Associations between lutein, zeaxanthin, and age-related macular degeneration: an overview. Crit Rev Food Sci Nutr. 2009;49:313–26. 19. Hammond Jr BR, Johnson EJ, Russell EJ, Krinsky NI, Yeum KJ, Edwards RB, et al. Dietary modification of human macular pigment density. Invest Ophthamol Vis Sci. 1997;38: 1795–801. 20. Johnson EJ, Hammond RB, Yeum KJ, Qin J, Wang XD, Wang XD, et al. Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density. Am Clin Nutr. 2000;71:1555–62. 21. Cardinault N, Gorrand JM, Tyssandier V, Grolier P, Rock E, Borel P, et al. Short-term supplementation with lutein affects biomarkers of lutein status similarly in young and elderly subjects. Exp Gerontol. 2003;38:573–82.
118
a r c h s o c e s p o f t a l m o l . 2 0 1 2;8 7(4):112–118
22. Mares-Perlman JA, Fisher A, Klein R, Palta M, Block G, Millen AE, et al. Lutein and zeaxanthin in the diet and serum and their relation to age-related maculopathy in the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 2001;153:424–32. 23. Chiu CJ, Milton RC, Klein R, Gensler G, Taylor A. Dietary compound Score and risk of age-related macular degeneration in the Age-Related Eye Disease Study. Ophthalmology. 2009;116:939–46.
24. Tur JA. Los antioxidantes en la dieta mediterránea. Rev Esp Nutr Comunitaria. 2004;10:198–207. 25. Tur JA, Serra-Majem L. Does the diet of the Balearic population, a Mediterranean type diet, still provide adequate antioxidant nutriet intakes? Eur J Nutr. 2005;44:204–13. 26. Romaguera D, Llompart I, Bonnin T, Pons A, Tur JA. Análisis de la ingesta dietética y calidad nutricional en ancianos no institucionalizados de las Islas Baleares. Rev Esp Nutr Comunitaria. 2004;10:168–77.