Lutein

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Description

Lutein is a naturally occurring carotenoid used to improve eye health, especially in people with age-related macular degeneration (ARMD) and cataracts. Studies show that the retina selectively accumulates two carotenoids, lutein and its chemical cousin zeaxanthin. Within the central macula, zeaxanthin is the dominant component (up to 75%), whereas in the peripheral retina, lutein predominates (greater than 67%). The macular concentration of lutein and zeaxanthin is so high that they are visible as a dark yellow spot called the macular pigment. Because these carotenoids are powerful antioxidants and absorb blue light, researchers have hypothesized that they protect the retina. While both are abundant in green and yellow fruits and vegetables, lutein is the carotenoid most often used as a supplement. Dietary intake of lutein and zeaxanthin is estimated at 1 to 3 mg daily (Landrum et al 2001). Sources include spinach, collard greens, corn, kiwis, zucchini, pumpkins, squash, peas, cucumbers, green peppers, and egg yolks.

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Actions & Pharmacology

Effects

Lutein is an antioxidant that has immunostimulant and photoprotectant properties.

Immunomodulatory Effects

Animal studies show that lutein appears to modulate cellular and humoral-mediated immune responses. Cats supplemented with 10 mg of lutein daily for 12 weeks had significantly increased peripheral blood CD4+T and CD21+B lymphocytes compared to controls, suggesting that lutein affects cell surface marker expression (Kim et al 2000). Similar effects were found in a study of dogs treated for 12 weeks (Kim et al 2000). Lutein also stimulated phytohemagglutinin-induced lymphocyte proliferation in a small study of mice fed a semipurified diet with 0.1% and 0.4% lutein for 2 or 4 weeks (Chew et al 1996).

Photoprotective Effects

Lutein may protect against photo-oxidation because of its ability to absorb light, especially blue light. It may also provide photoprotection through its antioxidant effects, including the ability to scavenge free radicals/reactive oxygen species and reduce peroxidation of membrane phospholipids (Beatty et al 2001; Landrum et al 2001; Mares-Perlman et al 2001).

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Clinical Trials

Cancer Prevention

Daily dietary intake of lutein (5,921 mcg to more than 7,300 mcg) appears to be protective against various types of cancer. As revealed by logistic regression analysis, lutein/zeaxanthin intake of more than 7,300 mcg daily was associated with a 70% reduction in the risk for developing endometrial cancer compared with consumption of less than 3,501 mcg daily in a case-controlled study (McCann et al 2000). A multivariate risk analysis showed that the highest quintile intake of lutein (>5,921 mcg of lutein daily for women and 6,701 mcg daily for men) was associated with a nonsignificant 19% reduction in lung cancer risk compared with the lowest quintile intake, based on pooled results from two prospective United States cohort studies (Michaud et al 2000). In addition, lutein/zeaxanthin intake of >7,162 mcg daily was associated with a 53% reduction (p=0.001) in the risk of developing breast cancer compared with consumption of <3,652 mcg daily in a population-based case-controlled study of premenopausal women over age 40 (Freudenheim et al 1996).

Cataracts

Consumption of more than 2.4 mg of lutein/zeaxanthin daily from foods and supplements was significantly correlated with reduced incidence of nuclear lens opacities, as revealed from data collected during a 13- to 15-year period in the Nutrition and Vision Project (NVP). However, these results were insignificant after adjustment for other nutrients. The authors state that due to study limitations, an inverse relationship between lutein/zeaxanthin intake and nuclear lens opacities cannot be ruled out with certainty (Jacques et al 2001).

In a prospective cohort study of male healthcare professionals aged 45 to 75 years (n=36,664), men consuming the highest amounts of lutein and zeaxanthin had a 19% reduction in cataract development risk requiring extraction compared with men who had the lowest consumption. Subjects were followed from 1986 to 1994 or until cataract extraction, cancer, or death occurred. Eating vegetables high in lutein (broccoli and spinach) was also associated with reduced cataract development risk, but increased consumption of fruits and vegetables was not associated with a risk reduction, suggesting that the effect is specific to lutein (Brown et al 1999).

Macular Degeneration, Age-Related

The Lutein Antioxidant Supplementation Trial (LAST) examined the effect of lutein alone or in combination with antioxidants, vitamins and minerals on atrophic age-related macular degeneration (ARMD). This 12-month, randomized, double-masked, placebo-controlled trial enrolled 90 veterans from two veterans' medical facilities. Patients were randomized to three groups: Group 1 (n=29) received lutein 10 mg; Group 2 (n=30) received the combination of lutein 10 mg plus antioxidants/vitamins/minerals in a broad-spectrum formulation; Group 3 (n=31) received placebo. The objective was to note any improvements in visual function and symptoms related to supplementation with lutein.

Ophthalmic testing occurred at baseline and at 4, 8, and 12 months in all subjects. Measures included macular pigment optical density (MPOD), monocular visual acuity at distance, and contrast sensitivity function (CSF). By treatment end, improvements were noted in MPOD for both Groups 1 and 2: mean eye MPOD increased approximately 0.09 log units from baseline measures. Specifically, mean eye MPOD improved 36% in Group 1 and 43% in Group 2. MPOD was mildly decreased in the placebo group. Snellen equivalent visual acuity improved 5.4 letters for Group 1 and 3.5 for group 2; contrast sensitivity was improved in both groups. Subjects receiving placebo (Group 3) had no significant changes in any of the measured findings.

The investigators concluded that, in this study, lutein supplementation improved visual function. The authors point out that the sample included in the study was comprised mostly of male subjects (n=86), although the prevalence of ARMD is generally higher among older women. Therefore, larger studies with more female subjects are required to assess the long-term beneficial effects of lutein supplementation for the treatment of atrophic ARMD (Richer et al 2004).

On average, lutein and zeaxanthin concentrations in donor eyes from individuals with AMD were lower in the inner, medial, and outer areas of the retina than levels found in control eyes (n=112). Using the outer portion of the retina (considered a more reliable predictor of AMD), the risk of developing AMD after logistic regression analysis was 82% less in those with the highest concentrations of lutein/zeaxanthin compared to donors with the lowest concentrations (Bone et al 2001).

Intake of food high in carotenoids decreased neovascular AMD in a multicenter study of individuals with advanced AMD (n=356; aged 55 to 80 years) compared with matched controls (n=520). The researchers also controlled for smoking and other risk factors using multiple logistic regression analysis. Individuals with the highest intake of carotenoids had a 43% lower risk of developing AMD compared to individuals who consumed the lowest amount (p = 0.02). The strongest association was found between increased intake of lutein/zeaxanthin and reduced risk for AMD (p=0.001) (Seddon et al 1994).

However, in the third National Health and Nutrition Examination Survey of individuals over 40 years of age (n=8,222), dietary intake and serum levels of lutein/zeaxanthin were not inversely correlated with early or late AMD diagnosed by photographic evidence. Inverse relationships were noted in certain subgroups of the overall study group. Intake of lutein/zeaxanthin were inversely correlated with pigment abnormalities in at-risk individuals aged 40 to 59 and late AMD in at-risk individuals aged 60 to 79. A direct correlation was reported between intake of lutein/zeaxanthin and soft drusen (the most common type of early AMD). This finding was inconsistent with other evidence and may be due to increases in intake of fruits and vegetables as a result of diagnosed retinal abnormalities (Mares-Perlman et al 2001).

Retinitis Pigmentosa

A double-masked, randomized, placebo-controlled phase I/II clinical trial examined the effect of lutein supplementation in patients with retinitis pigmentosa (RP). The primary objective was to observe the effect of lutein in preserving visual function. The study employed a crossover design: 34 adult subjects with RP were randomized to two groups. One group (n=16) was randomized to treatment with lutein for the first 24 weeks (10 mg/day for 12 weeks followed by 30 mg/day for 12 weeks) before switching to placebo for another 24 weeks. The other group (n=18) was randomized to placebo for the initial 24 weeks prior to receiving the lutein regimen for the remaining 24 weeks. By treatment end, the investigators observed a statistically significant effect of lutein on visual field (p = 0.038); this effect increased in a model assuming a 6-week delay in the effect of lutein supplementation. These results suggest that lutein supplementation in patients with RP improves visual field and may lead to slight improvements in visual acuity (Bahrami et al 2006).

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Indications & Usage

Unproven Uses

Increased consumption of lutein may prevent, delay, or modify the course of age-related macular degeneration, although conclusive evidence is not available. Lutein has also been used to help prevent or treat various cancers, including breast, ovarian, endometrial, lung, and prostate. Some advocates have promoted lutein as a general antiaging supplement.

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Precautions & Adverse Reactions

No data on side effects is available.

Scientific evidence for the safe use of Lutein during pregnancy and breast-feeding is not available.

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Drug Interactions

No human drug interaction information is available.

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Dosage

Mode of Administration

Oral

How Supplied

Capsule

Daily Dosage

For prevention of macular degeneration, the standard supplemental dose is 10 mg daily (Berendschot et al 2000). For cancer prevention, a daily dietary intake of 5,921 mcg to more than 7,300 mcg appears to be protective against various types of cancer (McCann et al 2000, Michaud et al 2000; Freudenheim et al 1996).

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Literature

Bahrami H, Melia M, Dagnelie G: Lutein supplementation in retinits pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial [NCT000299289]. BMC Ophthalmol; 6:23. 2006Beatty S, Murray IJ, Henson DB et al: Macular pigment and risk for age-related macular degeneration in subjects from a northern European population. Invest Ophthalmol Vis Sci; 42(2):439-446. 2001Berendschot TTJM, Goldbohm RA, Klopping WAA et al: Influence of lutein supplementation on macular pigment, assessed with two objective techniques. Invest Ophthalmol Vis Sci; 41(11):439-446. 2000Bone RA, Landrum JT, Dixon Z et al: Lutein and zeaxanthin in the eyes, serum and diet of human subjects. Exp Eye Res; 71(3):239-245. 2000Bone RA, Landrum JT, Mayne ST et al: Macular pigment in donor eyes with and without AMD: a case-control study. Invest Ophthalmol Vis Sci; 42(1):235-240. 2001Brown L, Rimm EB, Seddon JM et al: A prospective study of carotenoid intake and risk of cataract extraction in US men. Am J Clin Nutr; 70(4):517-524. 1999Chew BP, Wong MW, Wong TS: Effects of lutein from marigold extract on immunity and growth of mammary tumors in mice. Anticancer Res; 16(6B):3689-3694. 1996Freudenheim JL, Marshall JR, Vena JE et al: Premenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients. J Natl Cancer Inst; 88(6):340-348. 1996Hammond BR, Johnson EJ, Russell RM et al: Dietary modification of human macular pigment density. Invest Ophthalmol Vis Sci; 38(9):1795-1801. 1997Hankinson SE, Stampfer MJ, Seddon JM et al: Nutrient intake and cataract extraction in women: a prospective study. BMJ; 305(6849):335-339. 1992Jacques PF, Chylack LT, Hankinson SE et al: Long-term nutrient intake and early age-related nuclear lens opacities. Arch Ophthalmol; 119(7):1009-1019. 2001Johnson EJ, Hammond BR, Yeum KJ et al: Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density. Am J Clin Nutr; 71(6):1555-1562. 2000Kim HW, Chew BP, Wong TS et al: Dietary lutein stimulates immune response in the canine. Vet Immunol Immunopathol; 74(3-4):315-327. 2000Kim HW, Chew BP, Wong TS et al: Modulation of humoral and cell-mediated immune responses by dietary lutein in cats. Vet Immunol Immunopathol; 73(3-4):331-341. 2000Landrum JT, Bone RA: Lutein, zeaxanthin, and the macular pigment. Arch Biochem Biophysc; 385(1):28-40. 2001Mares-Perlman JA, Brady WE, Klein R et al: Serum antioxidants and age-related macular degeneration in a population-based case-control study. Arch Ophthalmol; 113(12):1518-1523. 1995Mares-Perlman JA, Fisher AI, Klein R 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; 153(5):424-432. 2001McCann SE, Freudenheim JL, Marshall JR et al: Diet in the epidemiology of endometrial cancer in western New York (United States). Cancer Causes Control; 11(10):965-974. 2000Michaud DS, Feskanich D, Rimm EB et al: Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts. Am J Clin Nutr; 72(4):990-997. 2000Olmedilla B, Granado F, Gil-Martinez E et al: Supplementation with lutein (4 months) and alpha-tocopherol (2 months), in separate or combined oral doses, in control men. Cancer Lett; 114(1-2):179-181. 1998Richer S, Stiles W, Statkute L, 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; 75:216-230. 2004Seddon JM, Ajani UA, Sperduto RD et al: Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA; 272(18):1413-1420. 1994Sommerburg O, Keunen JEE, Bird AC et al: Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes. Br J Ophthalmol; 82(8):907-910. 1998van het Hof KH, West CE, Weststrate JA et al: Dietary factors that affect the bioavailability of carotenoids. J Nutr; 130(3):503-506. 2000

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Lutein

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