Lutein and Zeaxanthin: Clinical Use. Dosage
AGE-RELATED MACULAR DEGENERATION
The evidence that lifetime oxidative stress plays an important role in the development of ARMD is now compelling. ARMD is thought to be the result of free radical damage to photoreceptors within the macula, and therefore it is suspected that inefficient macular antioxidant systems play a role in disease development. Low levels of lutein and zeaxanthin in the diet, serum or retina, as well as excessive exposure to blue light and cigarette smoking, are therefore considered to increase the risk of ARMD. People with cystic fibrosis are theoretically at increased risk of ARMD because they have reduced lutein in the macular pigment.
Epidemiological and autopsy studies have found an inverse relationship between lutein and zeaxanthin intake and macular pigment density. Plasma lutein and macular pigment density have also been demonstrated to increase with lutein supplementation in ARMD patients and healthy controls, suggesting that ARMD is not associated with intestinal malabsorption of carotenoids and that a diseased macula can accumulate and stabilise lutein and/or zeaxanthin. Conclusive evidence as to whether increased intake of lutein or zeaxanthin will reduce the incidence of ARMD is still unavailable.
Interestingly, two case-controlled studies have found that lycopene, rather than lutein or zeaxanthin, was reduced in the serum of ARMD patients. It was suggested that this result could be due to antioxidant protection of lutein and zeaxanthin by lycopene or different dietary habits.
Recent studies have produced encouraging results for people with pre-existing ARMD. Improvements of up to 92% in visual acuity tests were observed when subjects consumed a diet designed to contain approximately 1 50 g of spinach 4-7 times a week, and in 30 patients with early ARMD and visual acuity of 6/9 or better daily supplementation with lutein, vitamin E and nicotinamide for 180 days improved macular function. The results from the Lutein Antioxidant Supplementation Trial provide further support for lutein supplementation in ARMD. This was a double-blind, randomised, placebo-controlled study involving 90 subjects with atrophic ARMD who were given 10 mg lutein, 10 mg lutein plus broad spectrum antioxidants/vitamins/minerals, or placebo for 1 year. At baseline and every 4 months during the study period, subjects were examined for changes in macular pigment density (MPD), photostress recovery, contrast sensitivity, and visual acuity. Both the lutein and lutein + antioxidant groups achieved an increase of 36% and 43%, respectively, in MPD, whereas the placebo group experienced a slight decrease. Significant improvements in visual acuity, objective visual function parameters, photostress recovery, and contrast sensitivity were also observed with lutein therapy.
Clinical note — ARMD
ARMD is the leading cause of blindness in people over 65 years of age. Its exact aetiology is unknown; however, several risk factors have been established such as lighter iris colour, positive family history, lifestyle factors (e.g. cigarette smoking), hypertension, female gender and low serum concentrations of carotenoids. The disease causes a loss of central vision and can impair most activities essential for independent living, such as reading, driving and writing. The prevalence of ARMD and its social and economic consequences are increasing in line with the ageing population.
CATARACTS
Lens density has been found to inversely correlate to macular lutein and zeaxanthin levels and numerous observational studies have found that increased consumption of foods high in lutein and zeaxanthin is associated with a decreased risk for cataracts. In one study involving 77,466 female nurses from the Nurses Health Study, those with the highest quintile for consumption of zeaxanthin and lutein were found to have a 22% reduction in the risk of cataract extraction. These results contrast with those from a cohort study of 478 women without previously diagnosed cataracts, which failed to detect a significant inverse relationship between lutein intake and lens opacities over a 13-1 5-year follow-up period.
The link between lutein and cataracts is supported by a small randomised placebo-controlled trial of 17 patients with clinically diagnosed age-related cataracts that found that supplementation with lutein 1 5 mg three times weekly for up to 2 years resulted in improved visual performance (visual acuity and glare sensitivity) compared with placebo.
RETINITIS PIGMENTOSA
Daily supplementation with 40 mg of lutein over 9 weeks followed by 20 mg for a further 16 weeks was found to significantly improve visual acuity in a 26-week trial involving 16 subjects with retinitis pigmentosa, many of whom were also taking other supplements.
ATHEROSCLEROSIS
Oxidative modification of LDL in the vascular wall seems to be a key factor in atherosclerosis development and thus lipid-soluble antioxidants that can protect LDLs may have a role in atherosclerosis prevention; however, the relationship between lutein and zeaxanthin status and atherosclerosis is unclear.
Plasma levels of lutein, beta-cryptoxanthin and zeaxanthin were correlated to carotid intima-media thickness in a 3-year case-controlled study of 231 subjects, as well as in an 18-month epidemiological study of 573 subjects, suggesting that these carotenoids may be protective against early atherosclerosis. Lutein intake has also been found inversely associated with the risk of ischaemic stroke in an observational study involving 43,738 males, as well as being inversely associated with the risk of subarachnoid haemorrhage in a cohort study of 26,593 male smokers. Serum levels of lutein and zeaxanthin, however, were not associated with atherosclerosis risk in a case-control study involving 108 cases of aortic atherosclerosis in an elderly population.
The foregoing findings contrast with those from two case-controlled studies that found a positive correlation between lutein and zeaxanthin levels and cardiovascular risk. A nested, case-control study of 499 cases of cardiovascular disease with matched controls taken from the Physicians’ Health Study found that concentrations of plasma lutein, zeaxanthin and retinol corresponded to a moderate increase in cardiovascular disease. Similarly, myocardial infarction risk was positively associated with lutein and zeaxanthin levels in adipose tissue and the diet in a case-controlled study of 1456 cases of first acute myocardial infarction and matched controls. The clinical significance of these findings is unclear and requires further investigation.
ALZHEIMER’S DEMENTIA
Dementia has been found to be associated with increased protein oxidative modification and the depletion of a large spectrum of antioxidant micronutrients, including lutein and zeaxanthin. A clinical study of 25 subjects with mild cognitive impairment, 63 subjects with AD and 56 healthy individuals found that serum lutein levels were lowest in the first two groups, particularly those with AD.
CANCER PREVENTION
High dietary intake of lutein has been associated with reduced risk of some cancers, most notably endometrial and ovarian cancer, but not all cancers, according to epidemiological evidence.
Lung cancer
The link between carotenoid intake and lung cancer has undergone extensive scrutiny and extensive epidemiological evidence suggests a reduction in lung cancer risk with high dietary intake of carotenoids. Initial research used food composition tables and therefore focused on beta-carotene, for which data was available; however, the dietary intake of beta-carotene and other carotenoids such as lutein and zeaxanthin are highly correlated and as food composition data for these nutrients has become available studies have suggested a link between dietary lutein intake and reduced lung cancer risk.
Three large population studies of diet and lung cancer have revealed a nonsignificant association between high lutein intake and lower risk of lung cancer, and a significant trend was observed in another population-based case-control study. A nested case control study also found that serum lutein and zeaxanthin were lower in those with lung cancer than in controls. These results are contrasted with those from a case-control study of 108 cases of lung cancer in a Chinese occupational cohort that found that higher serum carotenoid levels, including lutein and zeaxanthin, were significantly associated with increased lung cancer risk among alcohol drinkers, while having a possible protective association among non-drinkers.
Cervical cancer
A recent systematic review suggests that lutein/zeaxanthin is likely to have a protective effect for cervical neoplasia and possibly for human papilloma virus persistence.
Endometrial cancer
An epidemiological study involving 232 patients with endometrial cancer and 639 controls found that an intake of more than 7.3 mg/day of lutein was associated with a 70% reduced risk of endometrial cancer.
Ovarian cancer
A case-control study found that weekly intake of lutein of more than 24 mg was associated with a 40% reduction in the risk for developing ovarian cancer compared with weekly consumption of less than 3.8 µg.
Breast cancer
High lutein and zeaxanthin intake has been related to reduced risk of breast cancer. High lutein intake (>7 mg/day) was associated with a 53% reduction in the risk of developing breast cancer compared with low consumption (<3.7 mg/day) in a population-based case-control study of 608 premenopausal women over age 40. Similar risk reductions were found in a nested case-control study of 540 New York women and another nested case-control study of 969 cases of breast cancer and matched controls from the Nurses’ Health Study found that the risk of breast cancer was 25-35% less for women with the highest quintile compared with that for women with the lowest quintile of lutein/zeaxanthin and total carotenoid intake. Although this association is encouraging, another study of 4697 women followed over 25 years found no significant relationships between lutein intake and breast cancer risk. Gastric cancer High serum lutein levels have been associated with a higher incidence of gastric carcinoma, according to a cohort study of 29,584 patients with oesophageal and stomach cancer; however, this association requires further investigation.
Bowel cancer
The relationship between lutein and zeaxanthin intake and colon cancer is uncertain. A case-control study involving 1993 cases of colon cancer and 2410 controls found that lutein intake, as measured by a food frequency score, was inversely associated with colon cancer and another case-control study of 223 subjects with histologically confirmed colon or rectal cancer identified a non-significant inverse association with lutein. A cohort analysis of 5629 women, however, found no such association. More recently, a case-controlled study found that women with high intakes of long-chain polyunsaturated fatty acids had an inverse association between lutein and zeaxanthin intake and the risk of colon cancer risk. Further investigation is required to clarify these findings because animal studies suggest low doses of lutein inhibit aberrant crypt foci formation, whereas high doses may increase the risk by 9-59%. Prostate cancer Overall, epidemiological evidence suggests that lutein and zeaxanthin intake has no influence over the risk of prostate cancer. However, when lutein was included as part of a mixed carotenoid and tocopherol extract, the combination was effective in an in vitro study of prostate cancer cell lines and a case-controlled study of 130 patients with adenocarcinoma of the prostate found that prostate cancer risk was seen to decline with increasing consumption of carotenoids, including lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin.
Laryngeal cancer A case-control study involving 537 subjects identified an inverse relationship between dietary lutein and zeaxanthin intake, together with the intake of other carotenoids, and the risk of laryngeal cancer.
Lutein and Zeaxanthin: Other Uses
Lutein and zeaxanthin may be used as part of a general antioxidant supplement, often taken in conjunction with other carotenoids in cases where there is known or suspected increased oxidative load.
Lutein and Zeaxanthin: Dosage Range
ACCORDING TO CLINICAL STUDIES
• Macular protection: lutein 5-20 mg/day; zeaxanthin 2-5 mg/day.
• Cataracts — improving visual performance: lutein 15 mg three times weekly.
