Benfotiamine is a derivative of thiamine, also known as vitamin B1. Benfotiamine was shown to reduce AGE-triggered damage in the retina and throughout the body (Balakumar 2010). In an animal model of diabetes, benfotiamine administration prevented diabetic retinopathy by ameliorating inflammation and mitigating various pathways that facilitate tissue damage due to high blood sugar (Hammes 2003). In a different animal model of diabetes, benfotiamine and thiamine were able to reduce the buildup of AGEs in the retina and other tissues (Karachalias 2010). Supplementation with 300 mg of benfotiamine along with 600 mg of alpha-lipoic acid, both taken twice daily for 28 days, has also been shown to reduce AGE accumulation in people with type 1 diabetes (Du 2008).
Carnosine is a compound primarily produced by skeletal muscle that is made from two amino acids (alanine and histidine). It is able to block the production of AGEs and mitigate oxidative stress and other complications of diabetes (Hipkiss 2009). In an animal model of diabetic retinopathy, carnosine supplements delayed cataract formation and protected retinal capillaries from high blood sugar damage by additional mechanisms aside from AGE inhibition. For example, researchers found that the protective effects of carnosine were associated with the prevention of the high blood sugar induced increase in a growth factor called Ang-2 (Ang-2 in combination with VEGF causes vascular damage and neovascularization) (Pfister 2011; Fagiani 2013). In another model of diabetic retinopathy, carnosine in combination with white willow bark extract, alpha-lipoic acid, and Ginkgo biloba protected retinal cells from damage (Bucolo 2013).
Vitamin B12 may be able to protect against retinopathy by helping to keep homocysteine levels low. Homocysteine is an amino acid that can damage blood vessels. Diabetics are especially sensitive to the vascular damage caused by high homocysteine levels, as diabetes can cause chemical changes in homocysteine that make this molecule more toxic (Rahman 2013). The enzyme that neutralizes homocysteine requires vitamin B12 to function; thus, vitamin B12 deficiency can cause elevated homocysteine levels and contribute to diabetic retinopathy (Satyanarayana 2011).
People suffering from diabetic retinopathy often have higher homocysteine levels and lower levels of vitamin B12, suggesting a link between vitamin B12 deficiency and diabetic retinopathy (Rahman 2013; Satyanarayana 2011). One study found that individuals with proliferative diabetic neuropathy had estimated homocysteine levels about 30% higher than control subjects (Lim 2012). In a similar study conducted on 300 subjects with type 2 diabetes, lower levels of vitamin B12 and folic acid were associated with elevated homocysteine levels, and homocysteine levels were especially high in a subset of the study population who had diabetic retinopathy (Satyanarayana 2011). Another study found that plasma total homocysteine levels were higher among 614 subjects who had retinal vascular disease compared to 762 control subjects (Cahill 2003).
Importantly, homocysteine levels may be increased and vitamin B12 levels depleted by some treatments for diabetes, such as metformin. This treatment-related deficiency in vitamin B12 may increase the risk of diabetic retinopathy, underscoring the importance of supplementation among diabetics (Sato 2013). Other B vitamins may also play a synergistic role in preventing diabetic retinopathy. A study found that a combination of vitamin B12, folic acid, and pyridoxal-5’-phosphate (a form of vitamin B6) had beneficial effects with respect to reducing retinal edema and increasing light sensitivity in individuals with nonproliferative diabetic retinopathy (Smolek 2013).
Green tea powerfully combats oxidative stress, which plays a considerable role in diabetic retinopathy. In an animal model of diabetic retinopathy, administration of green tea for 16 weeks normalized several markers of oxidative stress as well as inflammation. Green tea treatment also preserved the structural integrity of retinal cells (Kumar, Gupta, Nag 2012). Green tea may also be able to help diabetics improve their blood sugar control and may protect against AGEs (Tsuneki 2004; Ho 2010). Some of the compounds in green tea, particularly epigallocatechin gallate (EGCG) may be able to inhibit the abnormal formation of blood vessels that can contribute to retinopathy (Skopinski 2004; Rodriguez 2006).
Vitamin A and Carotenoids
Vitamin A and related compounds called carotenoids are essential for eye health and function. Vitamin A and its precursor, beta-carotene, are needed for cells in the eyes to absorb light. Other carotenoids, including lutein, zeaxanthin, and lycopene are also found in the eye and are essential for normal vision and to protect the eye from potentially damaging light rays and oxidative stress (Brazionis 2009; Hu 2011). Multiple studies have found that people with diabetic retinopathy have lower levels of lycopene, lutein, and other carotenoids compared to diabetics without retinopathy (Li 2010; Brazionis 2009; Hu 2011).
Studies have investigated vitamin A and the other carotenoids as potential retinopathy treatments. A clinical trial found that diabetics with nonproliferative retinopathy had improved vision after daily supplementation with 6 mg of lutein and 0.5 mg of zeaxanthin for three months (Hu 2011). A clinical trial found that intramuscular administration of 10,000 IU of vitamin A for at least two weeks helped improve retinal sensitivity in preterm infants, further supporting the potential protective effects of vitamin A against retinal damage (Mactier 2012).
Bilberry is a fruit related to the blueberry. It contains a variety of beneficial compounds called anthocyanins shown to support eye health (Kemper 1999; Bornsek 2012; Miyake 2012). Historically, bilberry jam was eaten by British pilots in WWII to improve their night vision, but bilberry may also be useful for treating retinopathy (Tracy 2007). Bilberry and bilberry extracts may mitigate neovascularization in the retina, which complicates retinopathy (Tracy 2007; Zafra-Stone 2007; Matsunaga 2010; Kemper 1999).
Zinc is an essential mineral that can help reduce oxidative damage in the eye (Moustafa 2004). People with diabetic retinopathy often have lower zinc levels than healthy individuals (Praveena 2013; Miao 2013). Zinc supplementation may help prevent diabetic retinopathy and delay its progression. Zinc may also help improve glucose control, inhibit the growth of abnormal retinal blood vessels, and keep blood vessels from becoming damaged and leaky (Miao 2013). In a rat model of diabetes, zinc supplementation suppressed levels of VEGF, a chemical involved in neovascularization (Dong 2004; Miao 2013).
Astragalus is a Chinese herb used for many years in traditional Chinese medicine for immune support and for diabetes (Cheng 2013). This herb may be able to prevent diabetic retinopathy, in part by inhibiting the formation of AGEs (Motomura 2009). Clinical studies have suggested that this herb has benefits for improving vision and treating retinopathy in diabetics (Yan 2011; Cheng 2013). In one study, people injected with an extract of astragalus had improved vision and fewer clinical signs of diabetic retinopathy than control subjects (Yan 2011). A comprehensive review of several published studies found that astragalus was able to protect visual acuity and reduce clinical signs of diabetic retinopathy. In all cases, oral preparations of astragalus were used, though doses and supplement forms varied. Some studies used between 60 and 600 mL of an astragalus-containing liquid supplement, while others used between 4.5 and 12 g of astragalus pills (Cheng 2013).
Resveratrol, a chemical thought to have anti-aging properties, can protect nerve cells from damage (Anekonda 2008). Multiple studies on animals have suggested that resveratrol may combat retinopathy. Studies in animal models of diabetes have found that resveratrol reduces oxidative damage and inflammation in retinal cells while also maintaining the health of existing blood vessels and suppressing the growth of new ones (Kim 2012; Yar 2012; Soufi 2012; Losso 2010). Resveratrol has also shown promise in animal models of retinopathy of prematurity (Kim 2010; Li, Jiang 2012). In addition, resveratrol may be effective at treating autoimmune retinopathy (Anekonda 2008).
Alpha-lipoic acid, an antioxidant compound that improves insulin sensitivity in individuals with type 2 diabetes, may prevent diabetic retinopathy (Nebbioso 2013). It can help restore antioxidant defenses within retinal cells (Lin 2006). Studies in animal models of diabetes have found that administration of alpha-lipoic acid reduces the accumulation of molecules damaged by free radicals and helps protect blood vessels in the retina (Kowluru 2004; Roberts 2006). Lipoic acid also appears able to suppress production of growth factors involved in the formation of new blood vessels, which is a major feature involved in the progression of diabetic retinopathy (Nebbioso 2013).
Polyunsaturated Fatty Acids
Polyunsaturated fatty acids, including omega-3 fatty acids, play many roles in the body. There is some evidence that omega-3 fatty acids may play a key role in maintaining the health of the retina (Chew 2011). One omega-3 fatty acid (docosahexaneoic acid [DHA]) is found in very high levels in the retina, and reduced levels of DHA in the retina are associated with altered retinal function. Levels of DHA are conserved in the retina even during periods of low DHA intake, further emphasizing its importance in this tissue (Jeffrey 2001).
DHA has anti-inflammatory properties and may be able to counteract some of the inflammatory changes seen in diabetic retinopathy (Bazan 2011; Chen 2005). In addition, DHA serves as the precursor for a compound called neuroprotectin D1, which protects the eye against inflammatory damage and promotes the survival of cells within the retina (Bazan 2006; Mukherjee 2004). Neuroprotectin D1 also inhibits the growth of new blood vessels (Bazan 2011). DHA itself may combat the growth of abnormal blood vessels in the retina as well (Sapieha 2011). In animal models of diabetes, omega-3 supplementation helped prevent diabetic retinopathy (Tikhonenko 2013; Sapieha 2012).
Omega-3 fatty acids may also play a role in retinopathy of prematurity. During the third trimester of pregnancy, a large amount of long-chain polyunsaturated fatty acids are transferred across the placenta into the fetus. With premature birth, the infant’s reserves may not be sufficient, which could affect retinal development (Hard 2013). In animal models of retinopathy of prematurity, supplementation of the diet with omega-3 fatty acids protected against abnormal blood vessel development and retinopathy (Mantagos 2009; Chen 2011; Chew 2011; Hard 2013; Sapieha 2011). One clinical trial found that premature infants who received intravenous fish oil, which is rich in omega-3 fatty acids, had less laser surgery-requiring retinopathy (Pawlik 2013).
Curcumin is a compound found in turmeric, a spice commonly used in Indian cooking. It may be able to prevent some of the complications of diabetes, including retinopathy (Gupta 2011). Curcumin appears to be able to modulate the activation of multiple proteins involved in inflammation, including tumor necrosis factor-alpha (TNF-α) and COX-2, which play a role in the progression of diabetic retinopathy and other diseases of the eye (Srinivasan 2004). In animal models of diabetic retinopathy, curcumin was able to protect the cells in the retinal capillaries from damage and reduce the levels of VEGF, helping prevent neovascularization (Gupta 2011; Mrudula 2007). Curcumin also reduced markers of retinal inflammation in animal models of diabetic retinopathy (Kowluru 2007). In addition, it may prevent the hyperglycemia-induced proliferation of abnormal blood vessels in the eye (Rema 2007). One clinical trial examined the effects of 200 mg of curcumin daily on people diagnosed with diabetic retinopathy. Subjects receiving the curcumin supplement had less retinal swelling, improved visual acuity, and better blood flow in the retina (Steigerwalt 2012).
Pycnogenol, an extract of bark from the French maritime pine tree, has been studied as a treatment for diabetic retinopathy (Spadea 2001). One benefit of Pycnogenol is that it may help lower blood glucose levels. In addition, Pycnogenol may protect the capillaries in the retina from damage. One clinical trial studying 77 people with type 2 diabetes examined the effects of Pycnogenol on levels of endothelin-1, a marker for blood vessel damage. The 34 subjects given 100 mg of Pycnogenol daily for 12 weeks had reduced levels of endothelin-1 compared to the 43 given placebo (Liu 2004). A comprehensive review of multiple studies totaling 1289 people examining the benefits of Pycnogenol found that it could be useful for treating diabetic retinopathy. This article concluded that doses of Pycnogenol ranging from 60 to 150 mg helped slow progression of diabetic retinopathy, improved visual acuity in people with type 2 diabetes, improved the strength of capillaries, and reduced capillary leakage into the retina (Schonlau 2002). Another study examining the effects of 150 mg of Pycnogenol administered daily to type 2 diabetics over the course of two months found that the 24 subjects receiving Pycnogenol had improved visual acuity as well as less retinal swelling and thickening compared to the 22 people receiving placebo (Steigerwalt 2009). In addition to containing compounds that can neutralize retinal damage due to diabetes, some of the compounds in Pycnogenol may be able to help repair damaged capillaries (Spadea 2001).
Ginkgo biloba extract is derived from the leaves of the Ginkgo biloba tree and contains over 60 bioactive compounds that may help promote human health (Oh 2013). It appears to prevent damage to cells in the retina from toxic chemicals that can damage neurons (Zaghlool 2012; Oh 2013). In addition, Ginkgo biloba extract helps improve circulation by inhibiting blood clots, improving the health of blood vessels, and making red blood cells more pliable, which allows them to circulate more freely (Oh 2013). As a result, Ginkgo biloba may be able to protect against diabetic retinopathy and retinopathy of prematurity. When combined with white willow bark, Ginkgo reduced inflammation and damage to retinal cells in an animal model of diabetes (Bucolo 2013). In a clinical trial, 240 mg of an extract of Ginkgo biloba daily improved retinal blood flow in people with type 2 diabetes when taken for three months (Huang 2004). Ginkgo biloba has also shown promise in preventing damage due to inadequate oxygen delivery (hypoxia), which is involved in retinopathy of prematurity. In both a cell culture and a rat model of retinopathy, a Ginkgo biloba extract prevented hypoxic damage and formation of abnormal blood vessels (Oh 2013; Juarez 2000). Ginkgo biloba should be used with care because its blood thinning capability can lead to an increased risk of bleeding, including retinal bleeding (Fraunfelder 2004).
Rosmarinic acid is a substance that can be isolated from many different plants, including the Chinese medicinal herb Salviae miltiorrhizae, rosemary, and the Lamiaceae family of plants (Kim 2009; al-Sereiti 1999; Huang 2006). In addition to reducing inflammation and cell damage, rosmarinic acid may be able to prevent neovascularization. In a cell culture experiment, addition of rosmarinic acid prevented the formation of new blood vessels (Huang 2006). It also suppressed neovascularization in an animal model of retinopathy of prematurity (Kim 2009). Although more experiments are needed, this represents a promising avenue for further research for treating retinopathy.
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