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Lutein and age-related macular degeneration

Background
Epidemiology
Nutritional supplements
Scientific sense
Evidence for lutein and zeaxanthin
Comments

Bandolier was first asked about lutein and age-related macular degeneration about a year ago. At the time there was little to find and, we thought, nothing to say. Because there is little effective treatment for age-related macular degeneration, there is much snake oil advice with long lists of supplements to buy. The trouble is that there is little or no evidence they help, or even evidence that they don't help.

A year on, and the situation has changed. The snake oil list gets longer, but for luetin there is emerging what might be a coherent story that includes background science, some epidemiology, and even some small, randomised trials.

Background

At the back of the eye the macula is a tiny area about 5 mm in diameter, with the fovea at its centre. There are no blood vessels, but lots of cells full of photosensitive pigments that allow us to see detail in the centre of vision. As we get older, the cells with retinal pigment become less efficient, the membrane degenerates, some cells atrophy, waste products build up, and central vision is gradually lost. That process is age-related macular degeneration. A good recent review does a better job at covering the whole subject [1].

Epidemiology

There are risk factors for macular degeneration, including hypertension, smoking, and a family history. There are relationships with heart disease, and inflammatory mediators like C-reactive protein found at elevated levels in heart disease are also found in macular degeneration [2].

But the single strongest relationship is with age. A detailed study of visual impairment in UK general practice gives a good insight into how much macular degeneration affects older people [3]. This study was part of an MRC trial of the assessment and management of older people in the community. In 49 general practices, with 14,403 people aged 75 years and older, detailed vision assessments were made.

Binocular visual impairment was present in 1,742 people, a prevalence of 12.5%. In 976 there was pinhole acuity less than 6/18, and with a known cause. Where there was no known cause, it was usually through missing notes (lost, or patient had died), or because there was no cause entered in the notes.

In the 976 with a known cause the main diagnoses for binocular visual impairment excluding a refractive error were age-related macular degeneration (53%) and cataract (36%) (Figure 1). The prevalence of known age-related macular degeneration in people aged 75 years or older was therefore 3.6% (516 out of 14,403). In those with a known cause of binocular visual impairment, macular degeneration rates doubled between 75 and over 90 years (Figure 2).



Figure 1: Cause of binocular vision impairment in 976 over-75s in UK general practice







Figure 2: Age and macular degeneration





Nutritional supplements

In the absence of any physical or medical treatment for age-related macular degeneration, attention has concentrated on nutritional supplements to prevent or slow progress of the condition. A systematic review of randomised controlled trials [4] teases apart the available evidence, and also provides a good background to macular degeneration.

It found seven trials, concerning antioxidants, zinc, vitamin E and lutein, with duration between six months and six years. The detailed critique of the studies is useful and thorough. Three showed some benefit.



Figure 3: Effect of zinc and antioxidant supplementation on progression





Scientific sense

There may be some scientific sense for these results. There seems to be a link between age-related macular degeneration and oxidative stress, some from the actions of light on the retina, and some systemic. As with heart disease, cancer, and other disorders, diets with higher levels of antioxidants, or antioxidant supplements, or both, are associated with less chance of the disease. It is the old healthy living message about eating plenty of fruit and vegetables, getting some exercise, not smoking, and having the odd medicinal glass of what you fancy.

Lutein is a yellowish pigment found in egg yolk, some algae, and in many plants. Zeaxanthin is found in small amounts in most fruits and vegetables. Both are found in the retina, and both are found at relatively high concentration in the macular region of the retina. Zeaxanthin is preferentially found in the foveal region and lutein in the perifoveal region. A systematic review [5] examines how these two pigments might be related to protection against macular degeneration.

Lutein and zeaxanthin may protect the retina in two ways, as antioxidants to oxidative stress from metabolism, and, by filtering short wavelengths of light they also reduce the oxidative effect of blue light.

Evidence for lutein and zeaxanthin

There are a number of studies that indicate a lower risk of macular degeneration associated with consumption of lutein and zeaxanthin, with their levels in diet, or higher levels in the blood. For instance, in a good epidemiological study of 380 people aged 66-75 years in the UK [6], people with lower blood levels of lutein plus zeaxanthin were more likely to have age-related macular degeneration (Figure 4).



Figure 4: Blood lutein and macular degeneration





Supplementing diets with lutein and zeaxanthin raised their levels in blood [7,8] and macular pigment [7], though earlier studies were equivocal. In a small but long randomised and double-blind pilot study [8], luetin supplementation of 15 mg every three days significantly improved visual acuity and glare sensitivity in older people with cataracts. Here patients given lutein had improved macular function.

Comments

All of this has to be interpreted with caution. What we have are straws in the wind. But for those people with macular degeneration, or who want to avoid it, these straws are worth having. A good diet, rich in antioxidants, and perhaps with some antioxidant supplementation, is the first thing to go for. Apart from anything else, it has benefits in terms of hearts, bones, and against cancer.

The second thing is to increase intake of lutein and zeaxanthin. The amount found in a normal western diet is said to be between 1 and 3 mg lutein and zeaxanthin a day. Even those of us with relatively good diets might find that hard to manage, but you can check your intake (www.luteininfo.com/abouthowtake). The recommended amount is 42 mg a week. The strength of that evidence, though, is not known.

The US Department of Agriculture has web pages that tell you the carotenoid content of many foods, (www.nal.usda.gov/fnic/foodcomp/Data/car98/car98.html). Table 1 shows lutein and zeaxanthin content. The message is green, and the greener the better. Until recently lutein supplements in the form of tablets were not available. In the UK at least one high-street chain (Holland and Barrett) stocks 6 mg and 20 mg tablets.



Table 1: Lutein and zeaxanthin content of foods



Source
Lutein and zeaxanthin
(micrograms per 100g)
Kale, raw
40,000
Kale, cooked
16,000
Spinach, raw
11,000
Spinach, cooked
7,000
Broccolli
2,500
Cos lettuce
2,500
Romaine lettuce
2,500
Sweetcorn
1,800
Brussel sprouts
1,500
Peas
1,400
Persimmon
800
Green beans
600
Okra
400
Iceberg lettuce
350
Cabbage
300
Carrots
300
Tangerine
250
Celery
200
Orange
200
Tomato
150
Orange juice
100
Papaya
75
Green peppers
75
Peaches
60
Egg
55
Cantaloupe melon
40
Watermelon
20
Grapefruit
13


There is now at least one British randomised trial of lutein supplementation in the design stage in Birmingham [9]. It will be recruiting about 200 people, and will test lutein plus vitamins AC and E, plus zinc and copper (www.aston.ac.uk/lhs/research/nri/opo/amd).

References:

  1. A Chopdar et al. Age-related macular degeneration. BMJ 2003 326: 485-488.
  2. JM Seddon et al. Association between C-reactive protein and age-related macular degeneration. JAMA 2004 291: 704-710.
  3. JR Evans et al. Causes of visual impairment in people aged 75 years and older in Britain: an add-on study to the MRC trials of assessment and management of older people in the community. British Journal of Ophthalmology 2004 88: 365-370.
  4. H Bartlett, F Eperjesi. Age-related macular degeneration and nutritional supplementation: a review of randomised controlled trials. Ophthal Physiol Opt 2003 23: 383-399.
  5. M Mozaffarieh et al. The role of carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: a review based on controversial evidence. Nutritional Journal 2003 2:20 ( www.nutritionj.com/content/2/1/20)
  6. CR Gale et al. Lutein and zeaxanthin status and risk of age-related macular degeneration. Invest Ophthalmol Vis Sci 2003 44: 2461-2465.
  7. RA Bone et al. Lutein and zeaxanthin dietary supplements raise macular pigment density and serum concentrations of these carotenoids in humans. Journal of Nutrition 2003 133: 992-998.
  8. B Olmedilla et al. Lutein, but not alpha-tocopherol, supplementation improves visual function in patients with age-related cataracts: a 2-y double-blind placebo controlled pilot study. Nutrition 2003 19: 21-24.
  9. H Bartlett, F Eperjesi. A randomised controlled trial investigating the effect of nutritional supplementation on visual function in normal, and age-related macular disease affected eyes: design and methodology. Nutrition Journal 2003 2:12 (www.nutritionj.com/content/2/1/12).

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