Bye….Bye…Beta-carotene. Say hello to Lutein/zeaxanthine

It’s been a bad year for beta-carotene.

Beta-carotene was part of the AREDS I supplementation along with vitamins C, E, zinc, and copper. This combination reduced the progression to severe AMD by about 25% over five years. The dose of beta-carotene used in AREDS I was a whopping 15mg, about 28,000 IU per day and about six times the daily recommended value. The Physicians’ Health study however showed no difference in AMD between those taking a supplement of 50mg of beta-carotene every other day compared to those who did not.(1) This result was one of the reasons that the AREDS II trial includes a group that is randomized to no beta-carotene (see January 22, 2007 blog on AREDS II).

Now there is concern that extra beta-carotene might actually make AMD worse. Beta-carotene becomes vitamin A, or retinol, which is necessary for sight. In the outer segments of the cones and rods, all trans-retinol is converted to cis-retinol when exposed to light and this starts the electro-chemical process of seeing. If there is no vitamin A, there is no sight. The problem is that the eye doesn’t perfectly recycle the retinol. There are a variety of breakdown products, called retinoids, which accumulate in macular degeneration. One of the breakdown products, called A2E is considered to be especially toxic. There is one study that is testing a drug that binds to the same transport proteins that are used by retinol to get into the eye (see November 19, 2007 blog, Age Related Macular Degeneration: Treatments for Dry AMD). The idea is to prevent an excess of retinol in the eye which will limit the production of A2E and potentially other harmful retinoids. It is hoped that this will reduce the progression of AMD especially the dry or atrophic form. This is analogous to starving the eye a bit from retinol and is the exact opposite idea of supplementing with high doses of beta-carotene!

A recent study from Australia showed that dietary lutein and zeaxanthin reduced the risk of the development of AMD long-term.(2) The same study showed that a high intake of beta-carotene was associated with an increased risk of AMD.

A study from Italy in the same journal showed that short term supplementation with vitamin C, E, copper, zinc, lutein, zeaxanthin, and astaxanthin increased macular function as measured by a special test called a multifocal electroretinogram.(3) Notice that no beta-carotene was used in their patients.

I would recommend an AREDS supplement with lutein especially and also zeaxanthine if you can get it. The doses used in AREDS II are 10 mg lutein and 2mg zexanthine. Don’t take beta-carotene if you’re a smoker since it increases the risk of lung cancer. I would also limit or eliminate the amount of beta-carotene supplements even if you’re not a smoker.

Just eat your vegetables.

References:

1. Christen WG, Glynn RJ, Ajani UA, et al. Age-related maculopathy in a randomized trial of low-dose aspirin among US physicians. Arch Ophthalmol 2001; 119: 1143-9.

2. Tan, JSL, Wang, JJ, “Dietarty Antioxidants and the Long-term Incidence of Age-Related Macular Degeneration.” Ophthalmology 2008;115-334-341.

3. Parisi, V., Tedeschi, M, “Carotenoids and Antioxidants in Age-Related Maculopathy Italian Study.” Ophthalmology 2008;115:324-333.

Possible Treatments for Inflammation in AMD

Two weeks ago, I discussed a study that showed inflammation in the neovascular membranes of patients with wet AMD who had been treated with Avastin.® Inflammation promotes neovascularization so it makes sense to try to limit or even eliminate this inflammation. Eliminating inflammation could make the treatment with Avastin® or Lucentis® more effective or at least perhaps decrease the number of injections needed to control the leakage from the new blood vessels.

Inflammation also occurs in dry AMD. Controlling it may reduce the progression of atrophy which is actually a more common cause of visual loss than new blood vessels in this disease.

The problem is that we don’t know the exact type or mechanism of this inflammation so we don’t know what the best way to control it is. Corticosteroids like prednisone work to control a variety of types of inflammation. The problem with oral prednisone is that only a small part of it gets into the eye and it causes osteoporosis, hypertension, and even diabetes especially when used for long periods. Therefore it’s not a good choice especially in older patients.

A corticosteroid called, Kenalog® is often injected into the eye. It is a depot form of medication that is white and therefore causes dense floaters. Usually though, the floaters sink to the bottom of the vitreous and out of the way of the line of sight. The medication lasts three months. It generally will cause a cataract. It will also cause glaucoma in at least 30% of patients that can be severe.

Dr. Calvin Grant presented a poster at the 2008 annual meeting of the Association for Research in Ophthalmology, (ARVO), in Fort Lauderdale. Dr. Grant placed his wet AMD patients on Xibrom® which is non-steroidal anti-inflammatory in an eyedrop form. It is used twice a day. The company that manufactures Xibrom has evidence that it makes its way through the front of the eye back to the retina. Dr. Grant thinks that the concomitant use of this drop with Avastin® or Lucentis® increases the success rate and decreases the need for re-injections. The advantage of this medicine is that it is easy to use as an eyedrop and has few side-effects. The disadvantage is that Medicare hasn’t reimbursed for it since there are cheaper non-steroidal drops that may be just as good. Dr. Grant used it because he thought it may be better at getting back into the retina.

I also counsel AMD patients to take a full 325mg aspirin a day with the approval of their doctor.