Can diet influence the progress of degenerative eye diseases? The impact of diet on eye health has recently become of rapidly increasing interest to researchers studying a variety of ophthalmic disorders including among others, cataract, macular degeneration and glaucoma. There is a high incidence of these chronic conditions, particularly in the elderly and each can severely affect quality of life and are expensive disabilities to manage often because of the external care required. Prevention is better than cure. Some think we are not genetically and biochemically adapted to survive past middle age, but even so, many also believe these age-related illnesses are not an inevitable consequence of growing old and the disease process might be intercepted, particularly by diet. Postponement, even prevention, of onset of each of these conditions offers enormous clinical and cost-effectiveness benefits both to patients and to healthcare budgets.
In each case, evidence is mounting that nutrition, particularly antioxidant therapy, influences disease progression. Of the several hundred peer-reviewed articles written since 1980 on diet and eye health, some 15% (cataract) and 30% (macular degeneration) have been published in the last two years. This article reviews the latest scientific and medical research into how nutrition and nutritional supplements may influence eye health and discusses the April 2000 dietary reference recommendations by the U.S. National Academies of Science and the considerable quantity of nutritional research to be reported at the Association for Research in Vision and Ophthalmology (ARVO) conference during May. ARVO is the main annual worldwide forum for eye research.
Cataract
Cataract is the leading cause of blindness in the world. Surgery offers adequate and cost-effective treatment, although considerable long term complications may ensue. While unoperated cataract represents a massive and poorly addressed problem in the Third World (approximately 50 million), it was reported earlier this year that even in the U.K. there are 700,000 patients who will never receive surgery and similar shortfalls in provision of treatment persist in the U.S. and other Western countries. There are more than one million cataract operations performed in the U.S. each year, with an overall cost of more than $4 billion. Population analysis shows that if diet could delay onset of cataract by 10 years, the overall need for surgery would be halved, but even a slight improvement would be hugely cost effective.
The potentially beneficial effects of antioxidants in cataract are being heavily researched. Many feel the eye is well able to cope with the considerable free radical exposure it naturally suffers; others disagree and say it can be compromised or become deficient. Furthermore, exposure to UV light and the accumulation of nitrite ions and/or cadmium in the eye due to smoking, offer additional insults. The audience at ARVO will hear evidence from three separate groups that antioxidants in the lens and aqueous humor are "surprisingly effective" in protecting the lens against UV, and even X-ray, damage.
Body mass correlates with incidence of cataract. Very recent research links cataract with blood lipid and fibrinogen levels, clotting disorders and an increased risk of heart attack. While not yet mainstream ophthalmology, these connections would not astonish cardiovascular researchers who are much further ahead in understanding how and why polar oxidized molecules, particularly degraded lipids, activate the immune and clotting systems to cause diverse damage depending on location.
A 1999 study showed how systemic inflammation may cause cataract, emphasizing the need for adequate antioxidant protection and perhaps explained why low-dose aspirin taken for cardiovascular reasons may also protect against some forms of cataract. Direct protein damage by free radicals is particularly relevant in the lens where conformational integrity of crystallin proteins is required to maintain transparency.
Following a series of studies throughout the 1990's (especially during 1998-99), several antioxidants, all found in the lens, are now currently thought by researchers to be protective, particularly vitamins C and E, taurine, glutathione, pyruvate, carotenoids, beta-carbolines, curcumin, even cholesterol itself. However, there are enough conflicting findings that, on April 10, the National Academies of Science (while increasing recommended daily intake levels) could not yet be definitive about declaring clinical benefits for antioxidants. There is an urgent need both for definitive clinical trials and a thorough Cochrane Collaboration meta-analysis (the clinical research gold standard) in order to be able to clarify whether and which antioxidants are protective of cataract. On theoretical terms, the somewhat disregarded ubiquinone (Coenzyme Q10), also an antioxidant and present in every cell in the body, seems worthy of research too. A report at ARVO will suggest that the blood levels of the enzyme co-factors copper, zinc and selenium are severely depleted in cataract patients.
The U.S. National Academy and some research studies have just recommended daily intake of vitamin C be increased to approximately 100mg/day (twice the previous anti-scurvy level). However, blood levels of Vitamin C fall precipitously at all times of stress (infection, surgery etc.), when its requirement by the body soars (reason unknown). During stress, even more than five grams per day may be insufficient to find it appearing in the urine! So perhaps it is at times of stress when the body, particularly the lens, is most susceptible to oxidative damage because of reduced free radical protection. Harvard University will present to ARVO its findings of a 15 year study that vitamin C up to 360mg per day is substantially protective against the development of cataract.
Last year saw several clinical studies demonstrating that the carotenoids lutein and zeaxanthin could lower the proportion of cataracts that required surgery. It was reported last December that the localized deposition of these carotenoids, and of vitamin E, within the human lens actually changes as we get older, suggesting mechanisms to trigger cataract formation, but also possibilities for preemptive nutritional strategies.
Gauging worldwide epidemiological evidence of the non-genetic (i.e. sporadic, environmental) cases of congenital cataract, we suspect a maternal nutritional argument could also eventually emerge, such as with folic acid and spina bifida. If so, as with national folic acid wheat programs there might develop a strong cost effectiveness argument for food supplementation, especially since clinically important and costly complications (reoperations, glaucoma) are common in this group.
Macular Degeneration
In the U.S., age related macular degeneration is the main cause of blindness and low vision among the elderly. Looking at the incidence of all disorders affecting those over 70, only heart disease and arthritis have greater national impact for impaired function and patient quality of life. Smokers have a higher incidence of the disease. An important difference between cataract and macular degeneration is that there is effective treatment for the former but much less available for the latter, making any reduction of disease progression that might be identified an extremely clinically and cost-effective strategy. As a result there is considerable current research towards prevention.
As with cataract, there is compelling epidemiological and experimental evidence for a long-term protective role of several antioxidants, but too few large and prolonged clinical studies to be definitive. While brain cells are the most active source of free radicals in the body, these highly reactive molecular fragments are also formed abundantly in the macula, which protects itself by a range of effective natural antioxidant mechanisms. Recently published research following more than 21,000 U.S. physicians over 12 years suggested vitamin E or multivitamins might reduce the incidence of macular degeneration by about 13%; several other studies published in good journals during 1999, and upcoming ARVO presentations, provide even more compelling evidence for protection. If proved true, taking extra vitamin E may offer a profound improvement in patient quality of life years and create a huge financial impact.
As well as the antioxidants mentioned earlier, current research is also focused on selenium, copper and zinc (which is important in retinal metabolism) studies. As with protection against coronary heart disease, omega 3 fatty acids seem important in maintaining retinal integrity and could theoretically prove relevant here too. Recently, a large study suggested wine consumption was protective of macular degeneration, again probably through lipid oxidization pathways. A recent Cochrane report on ginkgo biloba extract, which acts by increasing local blood flow and also quenches free radicals, was encouraging, but limited.
Glaucoma
Nutritional research into glaucoma is in its infancy. Some researchers feel that glaucoma in the elderly may occasionally be caused by a nutritional deficit, whether secondary to poor blood flow or a direct metabolic deficiency or imbalance (there are several candidates). Recent findings that antioxidant activity of the lacrimal fluid may decrease as glaucoma develops could reasonably be juxtaposed with experimental research showing that direct vitamin E treatment can reduce ocular pressure. Two papers at the current ARVO meeting state that the total antioxidant capacity of the aqueous humor is reduced by 75% in patients with glaucoma and that this is likely to be a local phenomena within the eye, as it is not systemic.
Conclusions
Arguments for the beneficial effects in eye disease of several antioxidants seem compelling on theoretical grounds and are partially backed up by many diverse lines of investigation (embracing not just ophthalmology, but a wealth of cardiovascular, immunological, hematological, metabolic and lipid research as well). Doses required will probably be higher than government recommendations and will have to be weighed up against recent conjecture about possible toxicities. In terms of both cost-effectiveness and long term quality of life, taking antioxidants daily is probably more important for maintaining eye health than for influencing cardiovascular risk. Certainly an intriguing area to watch, it will be surprising if nutritional-based strategies for delaying, or preventing, these important eye diseases do not have a major impact over the next few years.
NW
