New Findings Lead to Revised Therapeutic Regimen to Slow RP
Harvard Medical School - Massachusetts Eye and Ear Infirmary
Berman-Gund Laboratory for the Study of Retinal Degenerations
In June 1993, we reported in the Archives of Ophthalmology that vitamin A palmitate 15,000 IU/day helped to preserve retinal function while vitamin E 400 IU/day appeared to hasten the loss of retinal function among patients with retinitis pigmentosa (RP). This led to the recommendation that most adults with the typical forms of RP should take vitamin A palmitate 15,000 IU/day and avoid high dose vitamin E supplements such as the 400 IU/day used in this study. This recommendation remains the same today.
In September 2004, the Archives of Ophthalmology has just published two reports that summarize the results of 8 years of work to evaluate the effects of docosahexaenoic acid (DHA) for adults with typical RP also receiving vitamin A palmitate 15,000 IU/day. The results are complex.
The first new report on all participants taken together showed that DHA supplementation by capsules (600 mg twice each day) did not, on average, slow the course of RP over a four-year interval. Therefore, we cannot make any general recommendation for DHA supplementation by capsules for patients already taking vitamin A palmitate.
The second new report describes the results in subgroups of the participants. Here we observed that DHA supplementation did provide a benefit. However, the benefit was limited to the subgroup of patients starting vitamin A palmitate for the first time. In a comparison among randomized patients in this subgroup, DHA supplementation by capsules slowed the course of RP for two years.
In addition, a dietary benefit of omega-3 rich food became evident as stated in the second report. We observed that patients taking vitamin A palmitate (but not on DHA capsules) with a higher omega-3 rich diet intake (i.e., equivalent to eating 1-2 three-ounce servings per week of omega-3 rich fish, such as salmon, tuna, mackerel, herring, or sardines, which contain among other constituents considerable DHA) had, on average, a 40 - 50% slower annual rate of loss of visual field than patients with a lower omega-3 rich diet intake.
The results in the second report lead us to offer the following general recommendations:
(1) For adults with typical RP already on vitamin A palmitate 15,000 IU/day, we advise that they continue vitamin A palmitate and eat 1-2 three-ounce servings per week of omega-3 rich fish. Including this amount of fish in the diet is consistent with current American Heart Association recommendations. About three months after starting omega-3 rich fish, we advise a measurement of fasting red blood cell (RBC) DHA through their physician to confirm that the RBC DHA level is at least 4% of total RBC fatty acids, as we reported that such patients have, on average, a slower rate of decline of visual field than patients with lower levels. If the RBC DHA level is not at least 4%, we advise patients to consult with their physician on how best to reach this level through food. If the level is 4% or greater, this test could be repeated annually thereafter.
(2) For adults with typical RP who plan to start vitamin A palmitate 15,000 IU/day for the first time, the results support the following. If fasting serum vitamin A and liver function profile are normal, we advise that they take this dose of vitamin A palmitate and also supplement with DHA capsules 600 mg twice each day (i.e., three 200 mg capsules in both the AM and PM with meals) for two years. After two years patients should discontinue DHA supplementation by capsules because no evidence was found for continued benefit and because a slight tendency toward adversity on ocular function was observed over the longer term among patients concurrently on vitamin A palmitate. After stopping DHA capsules after two years, patients should continue vitamin A palmitate 15,000 IU/day and also eat 1-2 three-ounce servings of omega-3 rich fish each week. Then, about three months after starting omega-3 rich fish, we advise measurement of fasting RBC DHA as described above. It should be noted that combining an omega-3 rich fish diet with DHA capsules did not provide any additional benefit.
The study results reported in the second paper show that the potential benefit of combining vitamin A palmitate with dietary intake of 1-2 servings of omega-3 rich fish per week is substantial: the rate of decline of loss of visual field sensitivity was reduced by 40 - 50% per year. Therefore, combining vitamin A palmitate with this diet regimen could achieve a gain of almost two decades of visual preservation. For example, we have estimated that an average patient age 37 with typical RP already on vitamin A palmitate 15,000 IU/day who maintains an omega-3 fatty acid food intake of at least 0.2 grams per day (i.e., equivalent to eating 1-2 three ounce servings of omega-3 rich fish per week) would be expected to lose virtually all central visual field sensitivity by age 78, whereas an average patient who eats less than 0.2 grams per day would be expected to lose all central visual field sensitivity by age 59.
It should be noted that beta-carotene is not vitamin A. It is the precursor of vitamin A, but it is not predictably converted into vitamin A. Therefore beta-carotene is not a suitable substitute for vitamin A palmitate in the context of this treatment regimen. Although no toxic side effects have been observed among adults with RP in good general health on vitamin A palmitate 15,000 IU per day (Sibulesky et al., Safety of Less Than 25,000 IU Vitamin A Daily in Adults with Retinitis Pigmentosa, Am J Clin Nutr 69:656-663 1999), we continue to advise that patients obtain a fasting serum vitamin A and liver function profile annually and continue vitamin A palmitate only if these tests are normal. We have observed no toxic side effects among adults with RP in good general health on DHA supplementation by capsules.
The results apply to most adult patients with typical RP including those with partial hearing loss. The results do not apply to patients with RP and profound congenital deafness, RP as part of the Bardet-Biedl syndrome, or atypical or rare forms of RP as such patients were not included in this study. Women with RP who are pregnant or planning to be pregnant should not take the combination of vitamin A palmitate and DHA by capsules because high vitamin A intake has been associated with an increased risk of birth defects. We did not study patients under age 18 or patients with best-corrected visual acuity of less than 20/100 in both eyes; therefore, we cannot make any formal recommendation for such patients.
Our conclusions are based on group averages and, therefore, we cannot provide assurance that this regimen will benefit a specific patient or that it is appropriate for any particular patient.
Sources of vitamin A palmitate 15,000 IU as well as DHA in 200 mg gelcaps and the procedure for obtaining a RBC DHA level are attached. Please share this information with your ophthalmologist and family physician to determine if this regimen is appropriate for you. This treatment regimen should be done only under medical supervision. You are referred to the Archives of Ophthalmology Volume 122, pages 1297-1305 and pages 1306-1314, 2004 if you or your doctors wish to review the details of our research. If you still have questions, please write to us at the Berman-Gund Laboratory, Mass. Eye and Ear, 243 Charles Street, Boston, MA 02114.