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Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa

Purpose | Background | Description | Patient Eligibility | Recruitment Status | Current Status | Results | Publications | Resource Centers | NEI Representative

Purpose

To determine whether supplements of vitamin A or vitamin E alone or in combination affect the course of retinitis pigmentosa.

Background

Retinitis pigmentosa (RP) is a group of inherited retinal degenerations with a worldwide prevalence of about 1 in 4,000. Patients typically report night blindness in adolescence and lose vision in the midperipheral followed by far-peripheral visual field in adulthood due to progressive loss of both rod and cone function. Most patients have reductions in central vision by age 50 to 80 years. Modern-day electroretinograms (ERGs) make it possible to record retinal responses from most patients with remaining vision and thereby monitor objectively the course of their disease.

While the natural course of retinal degeneration in the common forms of RP was being studied, it was noted that a subgroup of patients aged 18 through 49 who were treating themselves with both vitamin A and vitamin E and other nutritional supplements exhibited less decline in ERG amplitude over a 2-year period. These preliminary findings, as well as the known roles of vitamins A and E in maintaining normal photoreceptor function and structure, prompted this randomized, controlled trial to determine whether these vitamins alone or in combination would halt or slow the progression of the common forms of RP.

Description

This study was a randomized, controlled double-masked trial with 2 x 2 factorial design and duration of 4 to 6 years. Patients were assigned to one of four treatment groups:

The main outcome measure was the 30-Hz cone ERG amplitude. In addition, visual field and visual acuity were measured annually.

Patient Eligibility

Men and nonpregnant women between ages 18 and 49 years with common forms of RP were included. All eligible patients had retinal arteriolar attenuation, elevated dark adaptation thresholds, and reduced ERGs. Patients had best corrected Snellen visual acuity of 20/100 or better, central visual field diameter on the Goldman perimeter with V4e white test light of 8° or greater, and ERG amplitude of 2.5 µV or greater in response to 0.5-Hz white light or of 0.12 µV or greater in response to 30-Hz white flickering light in at least one eye. In addition, patients had normal fasting serum retinol and serum liver function profile and weight above the lower fifth percentile for age, sex, and height. All patients had a total estimated pre-trial intake of vitamins A and E from diet plus pills not greater than 11,500 IU/day and 40 IU/day, respectively.

Patient Recruitment Status

Completed. From May 1984 to June 1987, 1,051 patients from across the United States and Canada were examined to identify 601 study participants with common forms of RP who met all eligibility criteria.

Current Status of Study

Completed.

Results

Ninety-five percent of patients completed the study. Rates of decline for remaining ERG per year for all randomized patients were:

The two groups on 15,000 IU of vitamin A lost on average less retinal function than those not on this dose. Among 354 patients with initially higher 30-Hz amplitudes, the two groups on 15,000 IU of vitamin A were 32 percent less likely to decline greater than or equal to 50 percent from baseline in a given year than those not on this dose. While not statistically significant, similar trends were observed for rates of field area decline. Acuity declined about one letter per year in all groups.

The study supports the hypothesis that a 15,000-IU supplement of vitamin A taken daily will slow the progression of the common forms of RP as monitored by ERG testing. The findings also suggest that a 400-IU supplement of vitamin E taken daily may have an adverse effect on the course of common forms of RP.

Based on this randomized trial, it is recommended that most adult patients with the common forms of RP take a supplement of 15,000 IU of vitamin A palmitate daily under the supervision of their ophthalmologist and avoid high-dose supplements of vitamin E such as the 400 IU used in this study. Although no toxic side effects were observed in this trial, patients should have a fasting serum vitamin A and liver function profile prior to treatment and annually thereafter as a precaution. In the context of this treatment, a beta carotene supplement is not a suitable substitute for vitamin A in the palmitate form.

Optimal benefit occurred among patients with a total daily intake (diet + capsules) of 18,000 IU of vitamin A daily, and a higher intake provided no greater benefit. Therefore, patients should not take vitamin A supplements greater than the 15,000 IU used in this study or modify their diet to select foods with high levels of vitamin A. Because of the potential for birth defects, women who become pregnant or who are planning to become pregnant should be advised to discontinue this dose of vitamin A. Since patients younger than age 18 were not evaluated in this study, no formal recommendations can be made for patients with RP younger than this age.

Vitamin A supplementation has been estimated to provide 7 additional years of useful vision for the average patient with RP who starts this supplement at age 32. Patients should be encouraged to have a computer-averaged ERG taken before the start of treatment and every 2 years thereafter to help determine the course of their condition.

Publications

Sandberg MA, Weigel-DiFranco C, Rosner B, Berson EL: The relationship between visual field size and electroretinogram amplitude in retinitis pigmentosa. Invest Ophthalmol Vis Sci 37: 1693-1698, 1996.

Berson EL, Rosner B, Sandberg MA, Hayes KC, Nicholson BW, Weigel-DiFranco C, Willett W: A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol 111: 761-772, 1993.

Resource Centers

Chairman's Office
Eliot L. Berson, Ophthalmologist
Britain W Nicholson, Internist
Berman-Gund Laboratory for the Study of Retinal Degenerations
Harvard Medical School
Massachusetts Eye and Ear Infirmary
243 Charles Street
Boston, MA 02114
Telephone: (617) 573-3600

Data Coordinating Center
Bernard Rosner, Ph.D., Statistician
Michael A Sandberg, Ph.D.
K.C. Hayes, D.V.M., Ph.D., Nutritional Biochemist
Carol Weigel-DiFranco, Data Manager
Walter Willett, M.D., Nutritional Epidemiologist
Berman-Gund Laboratory for the Study of Retinal Degenerations
Harvard Medical School
Massachusetts Eye and Ear Infirmary
243 Charles Street
Boston, MA 02114
Telephone: (617) 573-3600

NEI Representative

Natalie Kurinij, Ph.D.
National Eye Institute
National Institutes of Health
Executive Plaza South, Suite 350
6120 Executive Boulevard, MSC 7164
Bethesda, MD 20892-7164
Telephone: (301) 496-5983
Fax: (301) 402-0528

Last Updated: 9/21/99



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