KOREAN FOUNDATION FIGHTING BLINDNESS

비타민 A와 DHA를 복용하는 아래 글대로 시도해 보신분계세요?
행복은마음	2007/02/05	1,282
New Findings Lead to Revised Therapeutic Regimen to Slow RP The Berman-Gund Laboratory for the Study of Retinal Degenerations, at Harvard Medical School, has just completed the second in an ongoing series of clinical trials testing nutritional or other supplements as potential therapies for retinitis pigmentosa (RP). The first clinical trial completed in 1993 demonstrated a beneficial effect on visual function of Vitamin A and a deleterious effect of Vitamin E. As a result, the Foundation Fighting Blindness and the National Eye Institute jointly recommended for most adults the daily administration of 15,000 units of Vitamin A palmitate. Not fully understood, either then or now, the beneficial effect of Vitamin A was slow to take effect, becoming evident in the original clinical trial only after several years of administration. Just completed, a second study was designed to test whether a lipid of special relevance to vision, DHA, taken as a dietary supplement would enhance the already recognized sight-saving benefit of Vitamin A. The results of the second trial are published in two reports in the September 2004 issue of the American Medical Association’s Archives of Ophthalmology. The lead author of the report, Eliot L. Berson, M.D., is a member of the Scientific Advisory Board of The Foundation Fighting Blindness. The results are complex and are best understood when it is kept in mind that the benefit to vision observed in the original trial took several years to become evident. In fact, some wondered at the announcement of the results of the first clinical trial if treatment effects so delayed were indeed valid. The second trial sheds light on the question of validity as it demonstrates an interaction between Vitamin A and DHA such that DHA apparently foreshortens the time for Vitamin A to become effective. This became evident when it was recognized that two groups of participants took part in the second clinical trial: subjects already taking Vitamin A and subjects not taking Vitamin A. Among many other considerations, this distinction was not recognized in the original study design and, hence, no notice of it was taken in the original randomization. However, early in the course of the just reported clinical trial an interaction was recognized. Thereafter, the clinical course of the two categories of participants was followed annually. At the conclusion of the clinical trial, subgroup analyses clearly documented that DHA accelerated the onset of visual benefit for those who were newly started on Vitamin A. But in participants who had already taken Vitamin A for a period of time long enough to achieve its full benefit, DHA did not add to that benefit. The second clinical trial included a careful survey of dietary practices of all participants. When these were analyzed, it was discovered that intake once or twice a week of fish with a high fat content (such as tuna, mackerel, sardines, salmon or herring) conferred an additional visual benefit. The study from the Berman-Gund Laboratory also showed that patients with higher red blood cell levels of DHA experienced a substantially slower loss of vision field sensitivity than did patients with lower levels. These results are consistent with findings from a previous FFB-sponsored trial by Dr. Dennis Hoffman of the University of Texas Southwestern Medical Center and colleagues in subjects with X-linked RP showing that increased DHA levels in the blood were associated with a decreased rate of decline in visual function. Based on the findings of these clinical trials, Dr. Berson and his colleagues have issued an advisory letter. The letter follows and is also available on the Foundation Fighting Blindness web site (FightBlindness.org). It contains specific recommendations and cautions. These include obtaining blood tests periodically as well as information on sources of appropriate Vitamin A and DHA supplements. The research was supported by grants from The Foundation Fighting Blindness and the National Eye Institute. -------------------------------------------------------------------------------- HARVARD MEDICAL SCHOOL * MASSACHUSETTS EYE AND EAR INFIRMARY BERMAN-GUND LABORATORY FOR THE STUDY OF RETINAL DEGENERATIONS 243 Charles Street Boston Massachusetts 02114 September 23, 2004 New Treatment Regimen for Patients with Retinitis Pigmentosa 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 above letterhead address. Eliot L. Berson, M.D. ELB/jbq -------------------------------------------------------------------------------- Known Sources of Vitamin A Palmitate Vitamin A palmitate 15,000 IU/day has been recommended for most adults with typical forms of retinitis pigmentosa (see Berson et al; Archives of Ophthalmology 111:761-772, 1993). Patients with retinitis pigmentosa should consult with their doctor concerning whether vitamin A is appropriate for them before ordering this supplement. Adults planning to take vitamin A palmitate should have a normal fasting serum vitamin A and liver function profile before starting this treatment and annually thereafter. It is important to note that beta-carotene (the precursor of vitamin A) 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. The recommended dose of vitamin A palmitate is not available in most food stores. Some known sources are listed below. Sources of 15,000 IU of vitamin A palmitate FREEDA VITAMINS, INC. 36 East 41st Street New York, NY 10017 1–800–777–3737 (outside NY) or 1–212–685–4980; FAX 1-212-685–7297 AKORN OPHTHALMICS 2500 Millbrook Drive Buffalo Grove, IL 60089 1–800–932–5676 A–Palmitate–15 100 Tablets $5.90/bottle 250 Tablets $11.65/bottle Shipping & Handling $4.95 Will ship outside USA for extra postage Palmitate–A 15000 100 Tablets/Bottle $7.50/bottle (minimum order of two bottles) Shipping & Handling included J.R. CARLSON LABORATORIES, INC. 15 College Drive Arlington Heights, IL 60004–1985 1–888–234–5656 (outside Chicago) or 1–847–255–1600 Products #1101 and 1102 120 Gel-caps $6.90/bottle 240 Gel-caps 12.90/bottle Shipping & Handling 4.50 Will ship outside USA for extra postage Precautions: Women who are pregnant or planning to be pregnant should not take this dose of vitamin A because of the increased risk of birth defects among women on high-dose vitamin A supplements. Because of a slight increase (1% or less) in the risk of developing a hip fracture noted in post-menopausal women not on hormones but taking vitamin A supplements (Feskanich et al: JAMA 287:47-54, 2002) and in men age 49 or older with high serum vitamin A levels (Michaelsson et al: NEJM 348:287-294, 2003), such patients should have a periodic evaluation of bone health with their physician. This dose should not be used in children or young adolescents with RP because of a potential for toxicity. Disclaimer: The listing of these suppliers and their products should not be misinterpreted as a recommendation or indication of proprietary interest in any of these companies. -------------------------------------------------------------------------------- Known Sources of Neuromins® DHA 200mg DHA in a dose of 600 mg twice a day has been recommended for most adult patients with typical retinitis pigmentosa who are starting vitamin A palmitate 15,000 IU/day for the first time (see Berson et al; Archives of Ophthalmology 122: 1306-1314, 2004). Patients with retinitis pigmentosa should consult with their doctor concerning whether DHA is appropriate for them before ordering this supplement. Neuromins® DHA 200 was the form of DHA used in this study. Neuromins® DHA 200 is available in many health food stores across the country. Brands of Neuromins® DHA 200 include Nature’s Way, Source Naturals, Solaray, Natrol, and Solgar. The above brands are sold directly to retail stores and clearing houses (two listed below) rather than to individual consumers. However, both Nature’s Way (1-800-962-8873 or www.naturesway.com) and Natrol (1-800-262-8765 or www.natrol.com) will help you locate a local supplier. The dose recommended is 600 mg twice each day (3 in the AM and 3 in the PM with meals) only for 2 years. Therefore, patients ordering Neuromins® DHA 200 will be taking six softgels per day. For example, a one-month supply would be 180 softgels and patients should plan accordingly. The following are sources of Neuromins® DHA 200 readily accessible by toll-free phone or via their websites. SWANSON HEALTH PRODUCTS P.O. Box 6003 Fargo, ND 58108-6003 1–800–437-4148 www.swansonvitamins.com (search Neuromins® on the homepage) 30 softgels (SWU092) 200mg 12.49/bottle Shipping & Handling 4.95 Ship abroad for additional fee. THE VITAMIN SHOPPE Customer Care Department 2101 91st Street North Bergen, NJ 07047 1-800-223-1216 www.vitaminshoppe.com (search Neuromins® on the homepage) 60 softgels (SR-5558) 200mg 30.80/bottle 120 softgels (SR-5559) 200mg 59.98/bottle Shipping & Handling 4.99 Ship abroad with restrictions for added fee Precautions: Please be reminded that DHA supplementation in a dose of 600 mg twice a day for adults with typical retinitis pigmentosa (RP) on vitamin A palmitate was reported to be effective for only two years and only in patients starting vitamin A for the first time. The products described above in this dose have not been tested or evaluated to determine their safety or effectiveness in children or adolescents with RP. Stopping instructions: This dose of DHA should not be continued beyond two years because no evidence was found of a continued benefit and also because a slight tendency toward adversity on ocular function was observed over the longer term among patients on vitamin A palmitate 15,000 IU/day (see Archives of Ophthalmology, Volume 122, pages 1306-1314, 2004). This supplement in combination with vitamin A palmitate should not be taken by women who are pregnant or planning to become pregnant because of an increased risk of birth defects among women on high dose vitamin A intake. Disclaimer: The listing of these suppliers and their products should not be misinterpreted as a recommendation or indication of proprietary interest in any of these companies. -------------------------------------------------------------------------------- September 23, 2004 PROCEDURE FOR OBTAINING A RED BLOOD CELL DOCOSAHEXAENOIC ACID (DHA) LEVEL 1. Patients should fast overnight. If not feasible, fast at least 4 hours prior to the blood draw. 2. Use a 5 ml EDTA - Lavender top vacutainer tub (Becton Dickenson Catalog #DB366452 or #DB367863). Collect about 3 ml of blood in an EDTA tube. The tube should be labeled with the PATIENT'S NAME and the DATE THE BLOOD WAS DRAWN. 3. The patient's blood should be packaged in a Specimen Collection Kit provided by the laboratories below only on request from your physician. Your physician should fill in the required information on a Test Requisition Form, available at the websites of the laboratories listed below, and request a RBC DHA level which is part of a RBC total lipid fatty acid profile. 4. Send the lavender EDTA tube of whole blood at room temperature by same day courier on the day collected (Mondays through Thursdays only) in a Specimen Collection Kit following kit instructions for packaging and shipping along with the Test Requisition Form to either one of the three laboratories listed below to arrive within 24 hours after the specimen was drawn via DHL or Federal Express: Peroxisomal Diseases Laboratory Kennedy Krieger Institute 707 North Broadway, Room 530 Baltimore, MD 21205 Tel # 443-923-2788 Fax# 443-923-2755 www.genetics.kennedykrieger.org $150.00 with specimen (pre-pay) Great Smokies Diagnostic Laboratory 63 Zillicoa Street Asheville, NC 28801 Tel# 800-522-4762 Fax# 828-252-9303 www.gsdl.com $150.00 with specimen (pre-pay) Metametrix Clinical Laboratory 4855 Peachtree Ind. Blvd Norcross, GA 30092 Tel# 800-221-4640 Fax#770-441-2237 www.metametrix.com $150.00 with specimen (pre-pay) A report will be sent within about 1 month. Adults with typical retinitis pigmentosa on vitamin A palmitate 15,000 IU/day and an omega-3 rich diet should strive to have a RBC DHA level of 4% or greater of total RBC fatty acids. If the level is 4% or greater, the level could be rechecked annually. Patients who have not achieved this level should consult with their physician on ways to increase their RBC DHA level through food intake and then recheck their level about 3 months after changing their food intake (See Archives of Ophthalmology 122:1306-1314, 2004). Disclaimer: The listing of these suppliers and their tests should not be misinterpreted as a recommendation or indication of proprietary interest in any of these companies. http://www.blindness.org/rp-nutrition/index.asp