Retinitis pigmentosa in Herbs, Foods and antioxidants Points of View

 By Kyle J. Norton(Draft Article)

Retinitis pigmentosa is a genetic degenerative of eye diseases characteristic of slowly progressive damage of the retina, affecting about 1 in 4,000 people in the United States(1) and about 1in 3500 Canadians.(2).
Epidemiological studies, linking certain herbs, foods and vitamins in delay and alleviation of symptoms of the disease have produced certain success, but large sample size and multi centers studies are necessary to improve the validation of the claims.

A. The herbs
Limitation of research in finding the natural treatment for Retinitis pigmentosa, may be due to its genetically mutative nature.
Bilberry is low-growing shrubs in the genus Vaccinium, belonging to the family Ericaceae, native to
the temperate and subarctic regions of the world(3). The herb has been used in folk medicine for its astringent action, an antihistamine effect, and it is also believe to posses anti-microbial as well as anti-diarrheal effects(4), due to its antioxidants effects of delphinidin, cyanidin, petunidin, peonidin, malvidin, etc.(5). According to epidemiological studies. although with limitation, bilberry may be beneficiary in delayed progression and alleviated symptoms of Retinitis pigmentosa due to its effectiveness in protection of vision against many forms of eye diseases.(6)(7)(8)(9). According to ¹Johns Hopkins University, in Ninety-six Retinitis pigmentosa (RP) patients with any level of vision completed an anonymous internet survey. bilberry supplement was used in 32% of the correspondents, who were experiencing some impact on vision and physical/emotional well-being(10). In a blue light, a high-energy or short-wavelength visible light induced retinal diseases such as age-related macular degeneration and genetic related retinitis pigmentosa, bilberry extract (B-ext), containing high amounts of polyphenols (anthocyanins, resveratrol, and proanthocyanidins) exhibited its effects in improved the viability of 661 W cells and inhibited the generation of intracellular ROS induced by blue LED light irradiation, probably through inhibited the activation of p38 MAPK and NF-kappaB and caspase-3/7 activation and autophagy(11). Other herbs may also contain similar effects as bilberry such as lingo berry or cowberry(11).

B. The foods
1. The fatty fish and fish oil
Linseed oil or fish oil  may have a potential in delay the progression in genetic eye disorder of Retinitis pigmentosa, In retinas of RP rat model, the combination of linseed and fish oil exhibited lower-than-normal levels of ROS DHA may reflect an adaptive, possibly protective, mechanism in the P23H(12). In the University of Ottawa study, Onega 3 fatty acid found abundantly in fish oil showed in improvement of some retinitis pigmentosa outcomes in Clinical preliminary  research in this field, further studies are necessary(13). Docosahexaenoic acid (DHA), an other chemical derived from Omega 3 fatty acid, found abundantly in cold water fatty fish, such as salmon, in the study by the Harvard Medical School, showed a positive effect in among patients who were not taking vitamin A prior to entry, those in the DHA + A group had a slower decline in field sensitivity and electroretinogram amplitude than those in the control + A group over the first 2 years(14). Due to the influences of membrane phospholipid fatty acid abnormalities(15), some researchers suggested Fatty acid content alterations in membrane phospholipids of red blood cells of patients with Retinitis pigmentosa may be considered as markers for abnormalities in the lipid metabolism which disturb the retina integrity(16). Unfortunately, according to Johns Hopkins Bloomberg School of Public Health, in the review of the existent data of  394 titles and abstracts and nine ClinicalTrials.gov records and included three RCTs that met eligibility criteria, indicated a no clear evidence for benefit of treatment with DHA for people with RP(13).

2. The coffee
Chlorogenic acid, found in green coffee extract or Coffee, in this prospective, non-comparative, single-arm study, showed a beneficial effect on the peripheral area at the margins of retinal degeneration, and should be considered as an anti-oxidant for the management of retinitis pigmentosa(17)

C. The antioxidants
Antioxidants, may be potential in delay the progression and management of retinitis pigmentosa, according to aster University, when initial signs of vision health deterioration are observed, the appropriate nutritional supplement products may be recommended but only to augment the primary medical treatments(18). Dr. Baumgartner WA and Dr. Baumgartner AM. in one patient study to test  a developed and tested a treatment regimen with a range of antioxidants in combination with the off-label use of deprenyl (1 mg/day), a safe antiapoptotic agent, for 140 months indicated a significant improvement as patient's right eye visual field showed 0% decline and left eye 13.3% decline of which defianted  to the rate constants for logarithmic decline of visual field measured prior to treatment as visual fields would have decreased by 64% and 70%, respectively by month 140 in the absence of treatment(19).

1. Vitamin A
Vitamin A is a general term of Vitamin A Retinol, retinal, beta-carotene, alpha-carotene, gamma-carotene, and beta-cryptoxanthin best known for its functions for vision health and antioxidant scavenger and essential for growth and differentiation of a number of cells and tissues.
Recommended intakes of vitamin A, according to  the Institute of Medicine of the National Academies (formerly National Academy of Sciences) is 600 µg daily as extremely high doses (>9000 mg) can be toxicity as causes of dry, scaly skin, fatigue, nausea, loss of appetite, bone and joint pains, headaches, etc.
Suggestion of the pathology of 11-cis-retinal deficiency caused by gene mutations may result in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP)(20) due to  involvement in the interaction of light with rhodopsin rather than with free chromophore or bleached rhodopsin(21). In autosomal dominant retinitis pigmentosa patients, vitamin A supplements may be beneficiary for some patients with retinitis pigmentosa, especiallt in patients with autosomal dominant, according to Dr. Roberts L and research team(22). In the regard of Vitamin A's effectiveness in delaying progression of the disease, researchers at the ¹Centro di Ricerca in Nutrizione suggested " a lifetime generous supplementation of retinol is advisable, together with a vitamin A-rich diet and/or a dietary supplement (e.g. carrot flour) or pharmacologic supplement of vitamin A. Supply of vitamin A in doses up to 25000 IU (7500 igr/day), even for several years, has so far proved safe from risk of occurrence of liver disease"(23). Although it is controversial, some researchers suggested 15,000 IU of vitamin A palmitate per day may slow the progression,  Low vision rehabilitation, long wavelength pass filters, and pedigree counseling remain the mainstay of management(24).

2. Vitamin E
 Vitamin E,  a fat soluble vitamin, consisting eight different variants (alpha-, beta-, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-tocotrienol) with varying levels of biological activity(2), found abundantly in corn oil, soybean oil, margarine, wheat germ oil, sunflower,safflower oils, etc. plays an important role in neurological functions and inhibition of platelet aggregation, regulation of enzymatic activity, free radical scavenger, etc..
Vitamin E supplementation may improve symptoms and prevent the progression of Retinitis pigmentosa as its variant  alpha-tocopherol (vitamin E) inhibited proliferation of human RPE in culture without exerting cytotoxic effects.(25). According to the National University of Mexico, in the study of the formula taurine/diltiazem/vitamin E on the progression of visual field loss in retinitis pigmentosa indicated a improving changes in the, slope values with decreasing the rate of visual field loss, likely through a protective action from free radical reactions in affected photoreceptors(26). Unfortunately, the study of supplements of vitamin A or vitamin E alone or in combination in the affect of  the course of retinitis pigmentosa, suggested a positive effect in delay and progress of the diseases with 15,000 IU/d of vitamin A but an adverse effect of 400 IU/d of vitamin E on the course of retinitis pigmentosa(27) and vitamin E should be avoided(28).

3. Lutein
Lutien a xanthophyll, belonging to the family of carotenoids, found abundantly in green leafy vegetables such as spinach, kale, yellow carrots, etc., plays an important role in modulation of light energy and protection of retina against damage of free radicals produced by blue light. lutein supplementation may be effective in slowing visual function decline in patients with retinitis pigmentosa receiving vitamin A, according to the Harvard Medical School, dietary intake of Lutein supplementation of 12 mg/d slowed loss of midperipheral visual field on average among nonsmoking adults with retinitis pigmentosa taking vitamin A(29). The randomized double-masked placebo-controlled clinical trial [NCT00029289] conducted by the Johns Hopkins University, suggested that lutein supplementation improves visual field and also might improve visual acuity slightly, although these results should be interpreted cautiously(30). The study at the University of Pennsylvania showed no change no in central vision after 6 months of lutein supplementation, but suggested that a long-term influences on the natural history of these retinal degenerations require further study(31).
Other study also showed the potential effect in the combination application of Lutein and vitamin A in patient of Retinitis pigmentosa, as lutein improved short-term vision improvements in age-related macular degeneration--also occur in RP, especially in blue-eyed individuals; vitamin A may also increase visual field benefits(32).

Taken altogether, excluding vitamin E, even with limitation of data, herbal bilberry, fatty fish and fish oil and antioxidants vitamin A and Lutein may be effective in delay the progression of genetic degenerative eye disease,  retinitis pigmentosa, but larger sample size and multi centers studies to improve their validation are necessary. Please make sure you follow the guideline of the Institute of Medicine of the National Academies. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying

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References
(1) Retinitis pigmentosa (PubMed)
(2) Retinitis Pigmentosa ~ Overview(The foundation fighting blindness)
(3) Bilberry(Wikipedia)
(4) Bilberry(Herbs2000.com)
(5) Bilberry and its Constituents(MDidea)
(6) Effect of fermented bilberry extracts on visual outcomes in eyes with myopia: a prospective, randomized, placebo-controlled study by Kamiya K¹, Kobashi H, Fujiwara K, Ando W, Shimizu K.(PubMed)
(7) Bilberry (Vaccinium myrtillus L.) by Chu W, Cheung SCM, Lau RAW, Benzie IFF.(PubMed)
(8) Vision preservation during retinal inflammation by anthocyanin-rich bilberry extract: cellular and molecular mechanism by Miyake S¹, Takahashi N, Sasaki M, Kobayashi S, Tsubota K, Ozawa Y.(PubMed)
(9) Protective effect of bilberry (Vaccinium myrtillus L.) extracts on cultured human corneal limbal epithelial cells (HCLEC) by Song J¹, Li Y, Ge J, Duan Y, Sze SC, Tong Y, Shaw PC, Ng TB, Tsui KC, Zhuo Y, Zhang KY.(PubMed)
(10) Reported effects of non-traditional treatments and complementary and alternative medicine by retinitis pigmentosa patients by Kiser AK¹, Dagnelie G.(PubMed)
(11) Protective effects of bilberry and lingonberry extracts against blue light-emitting diode light-induced retinal photoreceptor cell damage in vitro by Ogawa K, Kuse Y, Tsuruma K, Kobayashi S, Shimazawa M, Hara H.(PubMed)
(12) Alterations in retinal rod outer segment fatty acids and light-damage susceptibility in P23H rats by Bicknell IR¹, Darrow R, Barsalou L, Fliesler SJ, Organisciak DT.(PubMed)
(13) The evidence for efficacy of omega-3 fatty acids in preventing or slowing the progression of retinitis pigmentosa: a systematic review, by Hodge WG¹, Barnes D, Schachter HM, Pan YI, Lowcock EC, Zhang L, Sampson M, Morrison A, Tran K, Miguelez M, Lewin G.(PubMed)
(14) Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses by Berson EL¹, Rosner B, Sandberg MA, Weigel-DiFranco C, Moser A, Brockhurst RJ, Hayes KC, Johnson CA, Anderson EJ, Gaudio AR, Willett WC, Schaefer EJ.(PubMed)
(15) Red blood cell membrane phosphatidylethanolamine fatty acid content in various forms of retinitis pigmentosa by Schaefer EJ¹, Robins SJ, Patton GM, Sandberg MA, Weigel-DiFranco CA, Rosner B, Berson EL.(PubMed)
(16) Evaluation of fatty acids in membrane phospholipids of erythrocytes in retinitis pigmentosa patients by Simonelli F¹, Manna C, Romano N, Nunziata G, Voto O, Rinaldi E.(PubMed)
(17) Vitamin A and fish oils for retinitis pigmentosa by Rayapudi S¹, Schwartz SG, Wang X, Chavis P.(PubMed)
(18) Antioxidants and vision health: facts and fiction by Grover AK¹, Samson SE.(PubMed)
(19) Rationale for an experimental treatment of retinitis pigmentosa: 140-month test of hypothesis with one patient by Baumgartner WA¹, Baumgartner AM(PubMed)
(20) Vitamin A derivatives as treatment options for retinal degenerative diseases by Perusek L¹, Maeda T.(PubMed)
(21) The dependence of retinal degeneration caused by the rhodopsin P23H mutation on light exposure and vitamin a deprivation by Tam BM¹, Qazalbash A, Lee HC, Moritz OL.(PubMed)
(22) Management of a South African family with retinitis pigmentosa-should potential therapy influence translational research protocols? by Roberts L, Rebello G, Ramesar R, Greenberg J.(PubMed)
(23) [Diet and management of degenerative diseases of the retina (retinitis pigmentosa)].[Article in Italian] by Miggiano GA¹, Falsini B(PubMed)
(24) Sector retinitis pigmentosa by Van Woerkom C¹, Ferrucci S.(PubMed)
(25) Vitamin E inhibits retinal pigment epithelium cell proliferation in vitro by Mojon D¹, Boscoboinik D, Haas A, Bohnke M, Azzi A(PubMed)
(26) Treatment with taurine, diltiazem, and vitamin E retards the progressive visual field reduction in retinitis pigmentosa: a 3-year follow-up study by Pasantes-Morales H¹, Quiroz H, Quesada O.(PubMed)
(27) A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa by Berson EL¹, Rosner B, Sandberg MA, Hayes KC, Nicholson BW, Weigel-DiFranco C, Willett W.(PubMed)
(28) Antioxidants and vision health: facts and fiction by Grover AK¹, Samson SE.(PubMed)
(29) Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A by Berson EL¹, Rosner B, Sandberg MA, Weigel-DiFranco C, Brockhurst RJ, Hayes KC, Johnson EJ, Anderson EJ, Johnson CA, Gaudio AR, Willett WC, Schaefer EJ.(PubMed)
(30) Lutein supplementation in retinitis pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial [NCT00029289] by Bahrami H¹, Melia M, Dagnelie G.(PubMed)
(31) Macular pigment and lutein supplementation in retinitis pigmentosa and Usher syndrome by Aleman TS¹, Duncan JL, Bieber ML, de Castro E, Marks DA, Gardner LM, Steinberg JD, Cideciyan AV, Maguire MG, Jacobson SG.(PubMed)
(32) Lutein improves visual function in some patients with retinal degeneration: a pilot study via the Internet by Dagnelie G¹, Zorge IS, McDonald TM.(PubMed)