Critique 021 25 October 2010
Kanthan GL, Mitchell P, Burlutsky G, Wang JJ. Alcohol Consumption and the Long-Term Incidence of Cataract and Cataract Surgery: The Blue Mountains Eye Study. Am J Ophthalmol 2010;150:434–440.
● PURPOSE: To assess whether alcohol consumption is associated with the long-term incidence of cataract or cataract surgery.
● DESIGN: Population-based prospective cohort study.
● METHODS: A total of 3,654 persons aged 49+ years were examined at baseline and 2,564 were re-examined after 5 and/or 10 years. Lens photographs were taken at each visit and assessed using the Wisconsin Cataract Grading System by masked graders. An interviewer-administered questionnaire was used to collect information on alcohol consumption.
● RESULTS: No significant associations were observed between alcohol consumption and long-term risk of nuclear, cortical, and posterior subcapsular cataract. However, after adjusting for age, gender, smoking, diabetes, myopia, socioeconomic status, and steroid use, total alcohol consumption of over 2 standard drinks per day was associated with a significantly increased likelihood of cataract surgery, when compared to total daily alcohol consumption of 1 to 2 standard drinks (adjusted odds ratio [OR] 2.10, 95% confidence interval [CI] 1.16-3.81). Abstinence from alcohol was also associated with increased likelihood of cataract surgery when compared to a total alcohol consumption of 1 to 2 standard drinks per day (adjusted OR 2.36, 95% CI 1.25–4.46).
● CONCLUSION: A U-shaped association of alcohol consumption with the long-term risk of cataract surgery was found in this older cohort: moderate consumption was associated with 50% lower cataract surgery incidence, compared either to abstinence or heavy alcohol consumption.
This is an interesting paper that deals with a common medical condition that will continue to be of great importance with the ageing of the population.
Background: Few longitudinal studies have dealt with cataracts, with the Beaver Dam Eye Study (BDES)1 the only one prior to the present one that has been population based. BDES found little relationship between alcohol and cataracts, although there was some evidence for a U-shaped curve with posterior subcapsular cataracts.
Among other cohort studies, the Nurses’ Health Study2 found little evidence of an effect of alcohol intake on the risk of surgery for cataracts. Their data are compatible with a slight decrease in risk of total cataracts with light drinking (up to 14.9 g/day) and an increased risk for certain types of cataract with greater amounts of alcohol. An earlier report from the Physician’s Health Study3 reported no significant effect of alcohol, although there was a trend towards increased risk of certain types of cataracts with greater alcohol intake.
Comments on the Present Study: The strengths include the analyses being based on a population-based cohort with excellent recruitment and good retention of subjects, and repeated eye examinations with excellent ascertainment of cataracts. The investigators had blinded assessments of lens photographs for the objective diagnosis of cataracts. Weaknesses that limit the information presented relate to the choice of the category with 1-2 drinks/day as the referent group, as there were very few subjects reporting consumption at this level. (For example, there were only 4 subjects with posterior subcapsular cataracts in the referent group consuming wine and 8 in the referent group for beer.) The paper does include in the text the associations between alcohol and cataract surgery using nondrinkers as the referent group, and state that “persons reporting moderate alcohol consumption (1-2 drinks/day) had a significantly reduced incidence of cataract surgery (OR 0.47, 95% CI 0.26-0.85),” but data are not presented for the lighter drinkers.
One would assume that data on the development of cataracts would be more objective and informative than on the occurrence of cataract surgery, as the latter may be related to many other socio-economic factors. (On the other hand, the associations generally changed very little when the age-gender-adjusted rates are compared with the fully adjusted models that included socio-economic status.)
It is unfortunate that the authors chose to not include in their paper the results of multivariable-adjusted analyses for many categories, since the “dose-response” pattern is often more informative than the statistical significance of any one cell. In other words, if odds ratios of cataracts are lower in both the non-drinkers and the heavier drinkers than among the moderate drinkers, it would suggest a “U-shaped” association. The conclusions of the authors are apparently based exclusively on statistical results and tend to not describe the pattern of effect for each beverage and total alcohol
Of the results in the categories of alcohol intake reported, there was a clear pattern suggesting a U-shaped relation only for cortical cataracts for beer and red wine intake, and suggestions of an increase in risk with spirits intake. Also, the shape of the relation suggested a potential increase in risk of posterior subcapsular cataracts for beer and spirits. For cataract surgery, there was a step-wise decrease (not statistically significant) for red wine going from no alcohol to >2 drinks/day, but there was a suggestion of a U-shaped curve for other beverages and total alcohol. (The total alcohol category is difficult to interpret due to different patterns of effect with different beverages).
Potential mechanisms of an effect of alcohol on risk of cataracts: Potential mechanisms for both beneficial and adverse effects of alcohol on cataract formation have been identified, making the effects of alcohol, and especially wine, on the risk of developing cataracts biologically plausible. As stated by the authors, “Alcohol has been shown to disrupt calcium homeostasis in the lens, augment processes such as membrane damage, alter protein-protein interactions, and produce pro-oxidant molecules when metabolized in the liver.”
Forum members state that cataracts in diabetics can be due to an oxidative process; polyphenols in wine and certain other beverages may play a role in decreasing risk of cataracts. There are a number of studies showing that cataract and macular degeneration appear when the diet is low in antioxidants. Vitamin C (highly concentrated in the crystalline lens) seems to have a protective effect4,5. Some antioxidants have been explored with this disease, from melatonin (able to reduce oxidative markers), to vitamin C or quercetin, that have been found to be protective with enzymatic markers in crystalline lens. Possibly the phenolics and metabolites (from wine) could play a role in the economy of vitamin C in the crystalline lens or act directly as protective compounds against the oxidative process, as has been demonstrated by Yamakoshi et al6. Red wine procyanidins and their antioxidative metabolites can prevent the progression of cataract formation by their antioxidative action against NADPH oxidase and other oxidative enzymes. The larger molecular procyanidins in wine might contribute to this anti-cataract activity.
Pathophysiological mechanisms of cataract formation may also include deficient glutathione levels contributing to a faulty antioxidant defense system within the lens of the eye. Moreover, diabetic cataracts are mainly caused by an elevation of polyols within the lens of the eye catalyzed by the enzyme aldose reductase. Flavonoids, quercetin and its derivatives for example, are potent inhibitors of aldose reductase.
However, one should be aware that from a drug-delivery perspective, ocular bioavailability depends on the physicochemical and biopharmaceutical characteristics of the selected compound and more importantly the route of administration. Indeed, in order to trigger an effect, bioactive compounds should be found at the site of the problem (i.e., the eye) and therefore need to cross the blood brain barrier. This is possible as several line of evidence place some polyphenols and their metabolite within the brain.
It is also important to stress that upon consumption, bioactives will undergo metabolism by phase 1 and 2 enzymes, therefore decreasing their antioxidant potential. Thus, it is more likely that the bioactive compounds may induce xeno-hormetic actions leading to increases in GSH though the Keap1-Nrf2-ARE pathway, for example. Another possible mechanism is the direct inhibition of some enzymes responsible for increased levels of free radicals such as the NADPH oxidase (act as apocynin-like inhibitors) or the decrease of the plasma glucose level as observed in a study dealing with the impact of astaxanthin on cataract in salmon7.
Increased risk of cataracts with heavy alcohol consumption: One Forum member emphasizes that excessive alcohol intake may be associated with an increase in some types of cataracts. He states that in his practice in Scandinavia, about 25% of patients younger than age 65 years who present with cataract are found to be heavy alcohol consumers. He adds: “It has been my experience that if the opacities are incipient and if the consumption of alcohol is stopped completely, the posterior subcapsular changes may reverse and even disappear.”
References from Forum Comments
1. Klein BE, Klein R, Lee KE, Meuer SM. Socioeconomic and lifestyle factors and the 10-year incidence of age-related cataracts. Am J Ophthalmol 2003;136(3):506 –512.
2. Chasan-Taber L, Willett WC, Seddon JM, et al. A prospective study of alcohol consumption and cataract extraction among U.S. women. Ann Epidemiol 2000;10(6):347–353.
3. Manson JE, Christen WG, Seddon JM, Glynn RJ, Hennekens CH. A prospective study of alcohol consumption and risk of cataract. Am J Prev Med 1994;10(3):156 –161.
4. Simon JA, Hudes ED. Serum ascorbic acid and other correlates of self-reported cataract among older Americans. J Clin Epidemiol 1999;52:1207-1211.
5. Mares-Perlman JA, Lyle BJ, Klein R, et al. Vitamin supplement use and incident cataracts in a population-based study. Arch Ophthalmol 2000;118:1556-1563.
6. Yamakoshi J, Saito M, Kataoka S, Tokutake S. Procyanidin-rich extract from grape seeds prevents cataract formation in hereditary cataractous (ICR/f) rats. J Agric Food Chem 2002;50:4983–4988.
7. Waagbø R, Hamre K, Bjerkås E, Berge R, Wathne E, Lie O, Torstensen B. Cataract formation in Atlantic salmon, Salmo salar L., smolt relative to dietary pro- and antioxidants and lipid level. J Fish Dis 2003;26:213-229.
This population-based prospective study from Australia utilized repeated lens photographs over a period of 5 to 10 years to diagnose cataracts, relating their development to the reported alcohol intake of subjects. They also related alcohol to the occurrence of surgery for cataracts. Previous research has provided some biological mechanisms that make an association between alcohol and cataracts plausible.
Overall, the present study showed little relation between alcohol and cataracts, although adjusted results suggested a “U-shaped” association between total alcohol intake and development of cataract and especially with cataract surgery. These results are consistent with previous cohort studies. On inspection of the data presented, the potential reduction in risk of cataract was primarily for wine and beer. Larger intake of alcohol may be associated with an increased risk of some types of cataracts.
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Comments included in this critique by the International Scientific Forum on Alcohol Research were provided by the following:
Andrew L. Waterhouse, PhD, Marvin Sands Professor, Department of Viticulture and Enology, University of California, Davis.
David Vauzour, PhD, Dept. of Food and Nutritional Sciences, The University of Reading, UK.
Pierre-Louis Teissedre, PhD, Faculty of Oenology – ISVV, University Victor Segalen Bordeaux 2, Bordeaux, France.
Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark.
Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA.
R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA.