Updated Data Regarding Pathogenesis and Implications for Natural Therapeutics
Paul S. Anderson, ND
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders that are characterized by progressive degeneration of the photoreceptors and the underlying retinal pigment epithelium.1 Given its prevalence of 1 case among 3000 to 5000 individuals, RP is the most common group of inherited retinal diseases.2,3 Signs and symptoms often include slowly progressive bilateral loss of night vision. A ring scotoma is often present on perimetry, which tends to widen the decreasing central vision. Dark “bone spicule” pigment changes are frequently seen in the retina. Diagnostic investigations include perimetry, dark adaptation testing, and electroretinographic studies.
Natural therapeutic interventions have been limited, but popular inclusion of retinol in complementary and alternative medicine (CAM) therapies followed original work by Berson et al4 in 1993. Natural therapeutics, including retinol, lutein, and docosahexaenoic acid have shown promise in slowing the progression of RP.5-9 In the past, conflicting and unclear data have been reported that seemed to point to a negative sensitivity of patients with RP to vitamin E supplementation4 and some derangement of amino metabolism in patients with RP,10 which led to no new biochemical conclusions or novel medical interventions. These limited and inconclusive data resulted in no new clear treatment directions for natural therapeutics to treat RP.
More recent data regarding the biochemical pathogenesis of RP is leading to a better understanding of the disease, and interventional investigations have broadened the therapeutic options for patients with RP. In a mouse model of RP, an imbalance between the superoxide dismutase and glutathione peroxidase 4 antioxidant systems was identified in RP.11,12 It has been known for more than a decade that an association between glutathione synthase deficiency and RP exists as well.13 Mitochondrial DNA dysfunction has also been documented in RP, with the following conclusion: “Antioxidant therapies hold promise for improving mitochondrial performance; however, medicine still has large gaps in its knowledge of which types and ratios of antioxidants, and in which forms, will result in the best outcomes. However, physicians seeking systematic treatments for their patients might consider testing urinary organic acids to determine how best to treat them.”14(p90) Given the known imbalance between superoxide dismutase and glutathione peroxidase 4, the low levels of glutathione synthase, and the reported negative effect to vitamin E supplementation, patients with RP may benefit from an approach to balance glutathione production and activity, along with protection of mitochondria.
Therapeutic Interventions to Treat RP
Table 1 lists natural therapeutics to treat RP. Data sources for the research on these agents are also given.
Table 1. Therapeutic Interventions to Treat Retinitis Pigmentosa
|Retinol (as vitamin A palmitate)||10 000-15 000 IU/d||Berson et al,4 1993; Berson,5 2000; Aleman et al,6 2001; Berson,7 2004; Gong et al,8 1992; Bazan et al,9 1986; Berson et al,15 2010|
|Lutein||10-20 mg/d||Berson et al,4 1993; Berson,5 2000; Aleman et al,6 2001; Berson,7 2004; Gong et al,8 1992; Bazan et al,9 1986; Berson et al,15 2010|
|Zeaxanthin||10-20 mg/d||Miranda et al,16 2010|
|Docosahexaenoic acid||200 mg/d or a diet integrating a mean of 200 mg/d of omega-3–containing fish||Berson et al,4 1993; Berson,5 2000; Aleman et al,6 2001; Berson,7 2004; Gong et al,8 1992; Bazan et al,9 1986; Berson et al,17 2012|
|N-acetylcysteine||500-600 mg twice daily||Lee et al,18 2011; Gibson et al,19 2011|
|Alpha lipoic acid||200-300 mg twice daily||Komeima et al,20 2006; Miranda et al,16 2010; Bunin et al,21 1992|
|Magnesium, pantothenic acid, selenium, riboflavin, niacinamide||Support nutrients to balance glutathione cycling and improve intracellular glutathione activity||Barbagallo et al,22 1999; Bede et al,23 2008; Zhu et al,24 1993|
Intravenous glutathione can be of incredible benefit to patients in need of this support and has been shown to increase intercellular magnesium,22 in addition to bolstering circulating glutathione levels. If trained to perform intravenous therapy, physicians can administer intravenous glutathione 1 to 3 times weekly until levels are restored or therapeutic benefit is achieved. An ongoing investigational trial25 at the Bastyr Integrative Oncology Research Center (Bastyr University, Kenmore, Washington) and at Anderson Medical Specialty Associates (Seattle, Washington) is evaluating the administration of intravenous glutathione and support nutrients to optimize glutathione activity in patients with nerve injury. The glutathione preload has a total volume of 635 mL and an osmolarity of 615 mOsm/L; the prescription formula is listed in Table 2. Preliminary data show benefit in the resolution of radiation therapy–induced and chemotherapy-induced neuropathy, likely rendering this formula beneficial in the improvement of glutathione function and activity in nervous system tissues.
Table 2. Glutathione Preload Intravenous Formulaa
|Therapeutic Agent||Dosage||Volume, mL|
|Sterile water||For infusion||500|
|Vitamin C-500||25 g||50|
|Calcium gluconateb||1 g||10|
|Magnesium sulfatec||2 g||4|
|Zinc chloride||25 mg||5|
|Vitamin B-100||Multiple-component additivee||3|
|Vitamin B5||500 mg||2|
|Vitamin B6||100 mg||2|
aFrom Anderson and Standish.25 For additions and subtractions, follow with 2 to 4 g of glutathione in 100 mL of normal saline.
bMay substitute 3 mL of calcium chloride.
cMay substitute 10 mL of magnesium chloride.
dMay add 5 to10 mg of methyl vitamin B12.
eVitamin B-100 contains thiamine hydrochloride (100 mg), dexpanthenol (2 mg), riboflavin 5′-phosphate sodium (2 mg), niacinamide (100 mg), and pyridoxine hydrochloride (2 mg).
fOmit in central line.
Safe and Efficacious Level of Intervention
While RP has no known cure, data and clinical practice support the use of certain nutrient therapies that enhance the retina and the nervous system. A focus on correcting endogenous imbalance in antioxidant function by maximizing glutathione activity, providing retinal flavonoid support, and enhancing the balance of retinol and omega-3 can provide a safe and efficacious level of intervention.
Paul S. Anderson, ND is a graduate of National College of Natural Medicine, Portland, Oregon, and practices in Seattle, Washington, at Anderson Medical Specialty Associates and the Bastyr Clinical Research Center. He is a cancer researcher at Bastyr University, and his investigations concentrate on intravenous therapies and their influences on cancer and chronic disease. Dr Anderson also teaches board reviews for the Naturopathic Physicians Licensing Examinations, as well as many continuing medical education classes for physicians, including some courses offered through International IV Nutritional Therapy for Professionals, Cedar Ridge, California.
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13. MedLink. Glutathione synthetase deficiency. http://www.medlink.com/medlinkcontent.asp. Accessed July 15, 2012.
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15. Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2010;128(4):403-495.
16. Miranda M, Alvarez-Nölting R, Araiz J, Romero Gómez FJ. Antioxidant therapy in retinitis pigmentosa. In: Romero Gómez FJ, Miranda M, Soria JM, eds. Novel Aspects of Neuroprotection, 2010. http://www.ehu.es/OftalmoBiologiaExperimental/documentos/antioxidant-therapy-in-retinitis-pigmentosa.pdf. Accessed July 28, 2012.
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18. Lee SY, Usui S, Zafar AB, et al. N-acetylcysteine promotes long-term survival of cones in a model of retinitis pigmentosa. J Cell Physiol. 2011;226(7):1843-1849.
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20. Komeima K, Rogers BS, Lu L, Campochiaro PA. Antioxidants reduce cone cell death in a model of retinitis pigmentosa. Proc Natl Acad Sci U S A. 2006;103(30):11300-11305.
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24. Zhu Z, Kimura M, Itokawa Y. Selenium concentration and glutathione peroxidase activity in selenium and magnesium deficient rats. Biol Trace Elem Res. 1993;37(2-3):209-217.
25. Anderson P, Standish L. IV therapy experience at Bastyr Integrative Oncology Research Center: ongoing clinical trial involving intravenous therapeutics in cancer and chronic disease; 2012; Seattle, Washington.