Q. Vitamins and other supplements are gaining popularity for patients at high risk of progressing to advanced age-related macular degeneration and possibly preventing or treating other ocular disorders. Are there drug interactions or contraindications I need to consider for my patients?

A. Vitamins can be the proverbial double-edged sword. Suboptimal intake of some vitamins is a risk factor for chronic disease, yet overconsumption can also pose a danger.

The Age Related Eye Disease Study found a combination of anti-oxidants and zinc can slow progression for patients with intermediate or monocular advanced AMD.

AREDS forumaltions generally include about 5 times the reccommended daily allowance (RDA) of vitamin C and Zinc (500mg and 80mg, respectively) and 13 times the RDA for vitamin E (400 IU). These doses did not prove beneficial for those with early AMD.

Megadoses of vitamins have well documents health risks, so only recommend AREDS supplements for patients with intermediate to advanced AMD.
That said, heres what we know about some vitamins commonly found in nutritional supplements:

Vitamins A and D. Vitamin A is an atioxidant that helps eyes adjust when adapting from dark to light and is an ingredient in several dry-eye supplements. Vitamin A deficieny can lead to xerophthalmia in children, but the condition is not common in the United States.

High doses of fat-soluble vitamins A and D over a long period can build up in the liver and pose toxicity issues. However, it generally takes about 30,000IU (Inter-national Units) doses daily over years to reach that level, Dr. Abel explains. The Food and Drug Administrations Center for Food Safety and Applied Nutrition suggests 400IU of vitamin D a day.

Long-term consumption of vitamin A stimulates bone resorption and inhibits bone formation, which may contribute to osteoporosis.1 Researchers in the Iowa Womens Health Study followed 34,703 postmenopausal women for a mean 9.5 years to determine whether high levels of vitamin A were associated with an increased risk of fracture.2 Women who took supplements containing vitamin A had a greater incidence of hip fracture than those who did not. Caution older patients on appropriate levels of vitamin A about 5,000IU daily, according to the Center for Food Safety.

Anticoagulant Therapy

Patients who take anticoagulants or platelet inhibitors are monitored regularly by primary-care physicians, taking bleeding and clotting time test periodically to determine the appropriate levels in each patient. However, you can also help steer these patients from medications and supplements that might do more harm than good.

NSAIDS. NSAIDS have an irritative effect on the gastrointestinal mucosa and may increase the risk of serious bleeding in these patients. Therefore, concomitant prescription of the two is not recommended.7 The risk may be lower with Cox-2 inhibitors, but further study is necessary.

Herbs. Ginko biloba extract, taken by some patients to improve cognitive function, has been reported to cause spontaneous bleeding, and may interact with anticoagulants and anti-platelet agents.8 Ginseng, though generally well-tolerated, may decrease a patients response to warfarin.8

A growing number of patients use herbal products for preventative and therapeutic benefits. But, the FDA does not regulate these products before marketing, so adverse effects and potential drug interactions associated with herbal remedies are largely unknown. Its a good rule of thumb to ask all patients about the use of herbal remedies in combination with other medications or symptoms.
Low levels of vitamin D can also put patients at increased risk for osteopenia and fractures.3 However, when taken with calcium, vitamin D can help decrease that risk.4

B Vitamins. B vitamins, often called B complex vitamins, are essential in the breakdown of fats and protein and help maintain a healthy immune system.

Vitamins B-6 and B-12 are important for patients who have cardiovascular disease, neural tube deficits, and colon and breast cancer. Studies have shown that suboptimal levels of B-6, B-12 and folic acid can put patients at increased risk for these conditions.3 These vitamins are also necessary for healthy metabolism.4 The FDA recommends daily doses of 2mg for B-6 and 6mcg of B-12.

Vitamin E and lycopene. Vitamin E, like many vitamins, decreases platelet adhesiveness. For patients on anticoagulants such as Coumadin (warfarin, Bristol Meyers Squibb), taking vitamins will thin their blood even further, says Dr. Abel.

Vitamin E is a powerful antioxidant that can help protect the retina from oxidative damage due to excessive sunlight. And, vitamin E and lycopene may decrease the risk of prostate cancer for men.4 An intake of 30 IU of vitamin E is optimal.

Beta-carotene. An important nutrient in the Age-Related Eye Disease Study formula, beta-carotenes antioxidant properties help combat free radicals. For years, this supplement was thought to be beneficial to smokers. Smoking produces free radicals in the body that damage cells and leads to cancer and heart disease. Beta carotene does deactivate the free radicals from cigarette smoke, but also forms oxidized by-products. This oxidative turnover is believed to put smokers at an increased risk for lung cancer, explains optometrist Mindabeth Greenberg, of Omni Eye Services in Atlanta.

Smokers also tend to have decreased blood levels of vitamins C and E, and cannot combat the oxidative by-products that cause damage to healthy cells, she says.

Vitamin C. Long-term (more than 10 years) supplementation with vitamin C has been shown to reduce a patients risk of cataracts by more than 60%.5 Its also associated with a reduced risk of cortical cataracts in women under age 60.6
Because of its anti-inflammatory and antioxidant properties, Vitamin C is important for patients with rheumatoid arthritis, as it may protect against further damage to inflamed joints, Dr. Greenberg says. Opti-mal intake of vitamin C is 60mg a day, though some research suggests effects occur well above these levels. 

(Next month: Minerals and Herbs.)

1. Genaro Pde S, Martini LA. Vitamin A supplementation and risk of skeletal fracture. Nutr Rev. 2004 Feb;62(2):65-7.
2. Lim LS, Harnack LJ, Lazovich D, Folsom AR. Vitamin A intake and the risk of hip fracture in postmenopausal women: the Iowa Womens Health Study. Osteoporos Int 2004 Feb 3 [ePub ahead of print].
3. Fletcher RH, Fairfield KM. Vitamins for chronic disease prevention in adults: clinical applications. JAMA 2002 Jun 19;287(23):3127-9.
4. Fairfield KM, Fletcher RH. Vitamins for chronic disease prevention in adults: scientific review. JAMA 2002 Jun 19;287(23):3116-26.
5. Taylor A, Jacques PF, Chylack LT Jr, et al. Long-term intake of vitamins and carotenoids and odds for early age-related cortical and posterior subcapsular lens opacities. Am J Clin Nutr. 2002 Mar;75(3):540-9.
6. Mares-Perlman JA, Lyle BJ, Klein R, et al. Vitamin supplement use and incident cataracts in a population-based study. Arch Ophthalmol. 2000 Nov;118(11):1556-63.
7. Avouac B, Combe B, Darne B. [Prescription of NSAIDS in patients treatments with platelet inhibitors or anticoagulants]. Presse Med 2003 Nov 22;32(37 pt 2):S38-43.
8. Cupp MJ. Herbal remedies: adverse effects and drug interactions. Am Fam Physician 1999 Mar 1;59(5):1239-45.

Vol. No: 141:06Issue: 6/15/04