Supplements for Glaucoma

Supplements: IOP and Glaucoma

Despite reports of certain supplements being able to lower eye pressure, none that have been tested in the FitEyes tonometry community have demonstrated any consistency in lowering intraocular pressure (IOP) on their own. Even one of the newly touted supplements with the brand name Mirtogenol, consisting of bilberry and pycnogenol (which supposedly was backed by clinical tests), failed to signficantly lower eye pressure in any of those in the FitEyes tonometry group that tested it.

However, in 2014, after more than eight years of research, we are finding that a program that involves synergies between several supplements is finally demonstrating some real life efficacy in lowing our eye pressure. FitEyes founder David wrote a comprehensive report about the supplements he is using with success now.

However, our experience is that supplements alone are not enough to overcome glaucoma. As a community, we are intently interested in healthy lifestyle factors such as meditation. The most useful protocol we have found is based on Serene Impulse meditation. Serene Impulse isn't a medical treatment, but we have found that reducing stress can indirectly help many of us manage our eye pressure.

Amongst some of the supplements and substances historically reporting to have a lowering effect are: Vitamin C, rutin, forskolin, fish oil and a few others. The most well studied has been vitamin C, but when it did have an effect, it was via large intravenous dosages, and the effect is believed to have been because of fluid or osmotic changes. However in spite of the above, we include here a few substances which because of scientific studies, may prove to have some benefit to the physiology of the Trabecular meshwork (drain of the eye), and therefore, may help regulate eye pressure. It is also quite possible that some see an effect on eye pressures even though others may not. You might also find two blog posts by Dr Robert Ritch  Non-pharmaceutical medications and approaches to glaucoma and Complementary Therapy for the Treatment of Glaucoma informative.

Possible beneficial long term IOP effects: Substances found in foods 

• Forskolin - Probably one of the most promising natural substances which can have a direct effect on lowering eye pressure is Forskolin. It was originally publicized for its IOP lowering effect via a topical ocular application, but certain problems were encountered in this approach. However, there are newer studies showing a noticeable effect with an oral extract. See these new studies to learn more: 1) Forskolin and rutin prevent intraocular pressure spikes after Nd:YAG laser iridotomy. 2) Oral administration of forskolin and rutin contributes to intraocular pressure control in primary open angle glaucoma. 3) Forskolin: Upcoming antiglaucoma molecule. We hope to do our own experiments with forskolin soon via our FitEyes community to determine the possible effects on eye pressure. You may also wish to read one installment of Dave's personal experience with forskolin here.

• ACE inhibitors-  These work on the Renin Agiotensin system, and as follows, show potential for a role in glaucoma; ACE inhibitors in the treatment of glaucoma. We can also deduce the potential for ACE inhibition via the noted Effect of oral losartan potassium administration on intraocular pressure in normotensive and glaucomatous human subjects. There are natural substances which will have a mild ACE effect, and so please read ACE inhibitors found in plants. It is also worth mentioning that the 'natto' enzyme known as nattokinase has natural ACE inhibiting properties;  Inhibition of angiotensin I converting enzyme by subtilisin NAT (nattokinase) in natto.

• 11betaHSD1 or 11 beta-hydroxysteroid dehydrogenase, is an enzyme which catalyzes conversion of inactive cortisone into active cortisol and is found in the eye. The authors also did a pilot uncontrolled study in which IOP fell by 17.5% following the administration of oral carbonoxonole, an inhibitor of 11betaHSD1. Please also read Inhibition of 11β-hydroxysteroid dehydrogenase type 1 lowers intraocular pressure in patients with ocular hypertension. You can find a discussion listing natural sources for 11betaHSD1 inhibitors on the FitEyes site Here. Additionally, glycyrrhizic acid found in licorice can inhibit this enzyme.

• Fish Oil omega 3's. Increasing dietary omega-3 in mice reduces IOP by increasing outflow facility and diets with increased omega-3 and decreased omega-6 PUFA’s may favor increased synthesis of PG-F2. In rabbits, intramuscular cod liver oil lowered IOP by 3mmHg at 0.2 ml/day, and 6.5mmHg at 1 ml/day. When treatment with cod liver oil was  topped, IOP rose to baseline levels. However, human studies investigating dietary fat consumption and primary open-angle glaucoma (POAG) showed that a high ratio of dietary omega-3 to omega-6 polyunsaturated fat consumption appears to increase the risk of POAG.

• Ginkgo Biloba In one study, a topical ginkgo compound reduced steroid induced IOP and demonstrated a favorable effect on extracellular matrix deposition. Effect of topical Ginkgo Biloba extract on steroid-induced changes in the TM and IOP

• Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells. Found in Red wine, grapes, blueberries and other berries. In a peer reviewed study, administration of resveratrol was associated with a significant lowering of inflammatory indicators, oxidative damage and age-related degenerative markers in trabecular meshwork cells. The experimental findings at Duke Eye Center led investigators to consider a possible role for resveratrol or other similar dietary agents to prevent changes associated with the development or progression of open-angle glaucoma, a leading cause of blindness.

• Quercetin- has been shown to upregulate the expression of certain peroxiredoxins in the trabecula. Glaucotamous eyes have been shown to have lower levels of peroxiredoxins, and thus may have more oxidative damage to the TM.  See Quercetin, peroxedoxins and the TM. Quercitin containing foods include onions, apples, green tea.

• Tyrosine kinase inhibitors (TKI) and protein kinase C inhibitors (PKCI) – relaxes trabecular meshwork without tightening the ciliary muscle: These substances are found in high amounts in beans, including yellow split pea, black turtle beans, baby lima beans, large lima beans, anasazi beans, red kidney beans, red lentils, soybeans, black eyed peas, pinto beans, mung beans, adzuki beans, etc. Quercetin is also a TKI, so eat lots of yellow skinned onions, drink some green tea, and eat garlic and broccoli. 

Diet, Supplements and Glaucoma (benefits beyond IOP)

The foods and/or substances which may yield possible benefit to glaucoma is too vast to cover in great detail. Therefore, an attempt will be made to present the highlights. Dr. Robert Ritch, renowned Glaucoma specialist with the New York Eye and Ear Infirmary, has recommended the following (amongst many others he has studied) as having potential benefits with glaucoma, and the following therefore, represents summaries he has graciously shared with the FitEyes community.

Ginkgo Biloba Extract (GBE)

• Exerts significant protective effects against free radical damage and lipid peroxidation in various tissues. The antioxidant properties are due to its direct free radical scavenging activity. Proteasome inhibitory properties of anthocyanins may contribute to their antioxidative, anti-inflammatory and neuroprotective  activities, rationalizing their use in neurodegenerative disorders.
• GBE preserves mitochondrial metabolism and ATP production in various tissues. In contrast to other antioxidants, gingko has the capacity to enter the inner mitochondrial membrane, thus making it an effective antioxidant at the mitochondrial level. It can scavenge nitric oxide and possibly inhibit its production. Substantial experimental evidence exists to support the view that GBE has neuroprotective properties in conditions such as hypoxia/ischemia, seizure activity, cerebral edema, and peripheral nerve damage. GBE protects against glutamate toxicity and it can reduce glutamate-induced elevation of calcium concentrations and oxidative metabolism in both resting and calcium-loaded neurons. 
• GBE improves both peripheral and cerebral blood flow. It is effective in treating Raynaud’s disease, which is strongly associated with normal-tension glaucoma. It has been reported to protect myocardium against hypoxia and ischemia-reperfusion injury and to relax blood vessel walls. It has been suggested that alterations in systemic  endothelial dysfunction are involved in vascular dysregulation in glaucoma.
• GBE reportedly attenuates endothelial dysfunction and improvement of peripheral circulation by GBE is at least partly attributable to its effects on the NO-pathway or endothelium-dependent vasodilation. In the eye, GBE may have a protective effect against the progression of diabetic retinopathy and it reduces ischemia-reperfusion injury in rat retina.(Szabo et al. 1993).
• GBE protects retinal photoreceptors against light-induced damage by preventing oxidative stress in the retina. 
• Jia et al found that GBE suppressed dexamethasone-induced IOP elevation in rabbits. It reduced certain accumulation of extracellular materials within layers of the trabecular meshwork and achieved better meshwork cellularity. In cultured human trabecular cells, GBE substantially reduced dexamethasone-induced myocilin expression. 
• GBE has been reported to improve automated visual field indices.

Curcumin –  Found in Turmeric

• The antioxidant activity of curcumin reportedly includes up-regulation of defensive genes and proteins, inhibition of heavy metal-catalyzed lipid, peroxidation by chelating toxic metals, and reduction of nitrite levels attenuates mitochondrial dysfunction by reducing reactive oxygen species. Curcumin was reported to be effective protecting against hippocampal cell death in mice and in the NMDA-induced damage of cultured retinal cells. Curcumin was also reported to be effective against glutamate toxicity in rat cerebral cortical neurons
• Effects of curcumin on pro-inflammatory cytokines have been well documented. (2) Curcumin reportedly inhibits effects of high glucose on lipid peroxication and secretion of cytokines such as TNF-a, IL-6, IL-8 or MCP-1 by cultured monocytes
• Curcumin affects b-amyloid peptide, suppressing oxidative damage and inflammatory signaling pathways.
• Curcumin was reported to ameliorate cataract formation in rats caused by selenium-induced oxidative stress, probably by preventing free-radical-induced accumulation of Ca2+ in the lens
• A diet supplemented with curcumin was also reported effective in ameliorating retinal damage caused by diabetes.
• It protected cells of retina-derived cell lines from H2O2-induced damage by up-regulating cellular protective mechanisms.

Resveratrol – See above for IOP, but resveratrol also has additional neuroprotective effects that may be beneficial to glaucoma beyond the benefits to the Trabecular meshwork.

Fish oil (omega 3 fatty acids)

• Omega-3 fatty acids, found most notably in fish oil, include docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). DHA has many diverse functions at the cellular  level including enzyme regulation, membrane fluidity, regulation of ion channels and signal transduction. Increasing dietary omega-3 in mice reduces IOP by increasing outflow facility.
• Diets with increased omega-3 and decreased omega-6 PUFA’s may favor increased synthesis of PG-F2. In rabbits, intramuscular cod liver oil lowered IOP by 3mmHg at 0.2 ml/day, and 6.5mmHg at 1ml/day. When treatment with cod liver oil was stopped, IOP rose to baseline levels. However, human studies investigating dietary fat consumption and primary open-angle glaucoma (POAG) showed that a high ratio of dietary omega-3 to omega-6 polyunsaturated fat consumption appears to increase the risk of POAG.
• Decreased retinal DHA content affects visual function in monkeys, and a combination of DHA, vitamin E, and vitamin B were reported to improve contrast sensitivity and  isual field indices. In addition, DHA protects cells from oxidative stress by modulating levels of pro-and anti-apoptotic proteins of the Bcl-2 family, which protects photoreceptors from oxidative stress.
• In conclusion, omega-3 fatty acids play an important role in reducing oxidative damage in the retina, improving ocular blood flow and protecting against retinal ischemia induced by increased IOP.

Magnesium

Fifteen patients with NTG (study group) received 300 mg oral magnesium citrate for 1 month, while 15 patients with NTG (control group) received no treatment. Blood magnesium level measurement,visual field analysis, and color Doppler imaging of the orbital vessels were done before treatment and at 1 month. Color Doppler imaging indices did not change after magnesium therapy. Conclusions: Oral magnesium therapy may provide improvement in the visual field, but does not seem to affect ocular blood flow in patients with NTG. Other mechanism than increased ocular blood flow may be responsible for the improvement in the visual field with oral magnesium therapy. (Eur J Ophthalmol2010; 20: 131-5) 

Melatonin

• Because of the continuous and large-scale retinal ganglion cell degeneration in glaucoma, recent literature emphasizes that glaucoma may be the main ophthalmologic disease affecting the photic input to the circadian system. Among its features is the neuroprotective role of melatonin. Melatonin and its metabolites are potent protectors against oxidative stress in neurons and have been considered candidate substances for the treatment of neurodegenerative diseases of the central nervous system.

• Melatonin is also an effective antioxidant in the retina, acting as a scavenger of light-induced free radicals and inhibiting the nitridergic pathway having a protective effect on the photoreceptors outer membranes and reversing the effect of ocular hypertension on retinal function.

• Indeed, in an experimental animal model, the concentration of melatonin in the retina of glaucomatous rats with high IOP was significantly reduced. Melatonin not only protects ocular tissue against free radicals, but also it has a direct effect on the IOP. Several studies have shown circadian changes of the IOP and in particular an effective reduction in the IOP via melatonin, mediated principally by the MT3 receptor. In this context, the circadian (physiological reduction during the night) and seasonal rhythmicity of IOP as well as the influences of nocturnal ocular blood flow and sleep on the IOP could be phenomena associated with the timing of melatonin release.

• Melatonin has been proven to directly reduce IOP significantly through the putative MT3 receptor and, thus, may have clinical potential for treating elevated IOP.

• Furthermore, the antioxidant potency of melatonin in ocular tissue and the neuroprotective role of melatonin in glaucoma could be of use in the management of the disease

Additional supplements and substances for glaucoma

• Vitamin B12 - for five years in an open-label study to evaluate the vitamin's influence on vision. The patients receiving B12 experienced less measurable loss of peripheral vision, more stable visual acuity, and better control of eye fluid pressure compared to a group that did not take B12. The effects of vitamin B12 are attributed to the preservation of myelin, which insulates nerve cells. Results of this study were achieved with methylcobalamin, a readily absorbable form of vitamin B12

• Astaxanthin - ASX treatment significantly decreased the percent of apoptotic cells when compared to non treated ocular hypertensive controls. The presented data confirm the role of oxidative injury in EIOP and highlight the protective effect of ASX in ocular hypertension. Suppressive effect of astaxanthin on retinal injury induced by elevated intraocular pressure.

• Green Tea - Orally administered EGCG attenuates retinal neuronal death . Significantly, EGCG statistically blunted many of the effects induced by ischemia/reperfusion which included the activation of caspases. These studies demonstrate conclusively that orally administered EGCG attenuates injury to the retina caused by ischemia/reperfusion where caspases were activated. Also see, New Evidence That Green Tea May Help Fight Glaucoma and Other Eye Diseases

• Wolfberry-Goji Berry Also mentioned in Dr. Ritch's paper. Wolfberry on the survival of retinal ganglion cells in a rat ocular hypertension model

• Alpha Lipoic Acid exerts potent antioxidant effects in the lens and retina. In the lens, lipoic acid reduces the iron pool from the cytoplasm of lens cells, which increases the cells’  defense against oxidative damage. It also may prevent or slow progression of cataract through mechanisms such as decreasing lens aldose reductase activity and increasing lens glutathione levels. Agents such as ALA that specifically enhance ganglion cell mitochondrial energy production and decrease oxidative stress should theoretically be beneficial in a disease such as glaucoma. Alpha lipoic acid improved visual function in 45% of glaucoma patients supplemented with lipoic acid and two months of alpha lipoic acid supplementation was found to increase aqueous glutathione levels in POAG patients. In addition, a-lipoic acid supplementation with vitamin C is believed to increase aqueous humor drainage by  reducing the viscosity of trabecular meshwork hyaluronic acid properties which could be protective against glaucoma. This protection possibly includes the trabecular meshwork, which is also thought to be effected by oxidative stress in glaucoma. 

• Luteolin (found in celery, parsley, and other foods). Luteolin triggers global changes in the microglial transcriptome. A unique anti-inflammatory and neuroprotective phenotype. From the studies: Our findings confirm the inhibitory effects of luteolin on pro-inflammatory cytokine expression in microglia. Moreover, our transcriptomic data suggest that this flavonoid is a potent modulator of microglial activation and affects several signaling pathways leading to a unique phenotype with anti-inflammatory, anti-oxidative, and neuroprotective characteristics. With the identification of several novel luteolin-regulated genes, our findings provide a molecular basis to understand the versatile effects of luteolin on microglial homeostasis. The data also suggest that luteolin could be a promising candidate to develop immuno-modulatory and neuroprotective therapies for the treatment of neurodegenerative disorders.

• Quercetin Is demonstrated in the following (and other studies) to have antioxidant properties which could be protective against glaucoma. This protection possibly includes the Trabecular meshwork, which is also thought to be effected by oxidative stress in glaucoma. Quercetin Induces the Expression of Peroxiredoxins 3and 5 via the Nrf2/NRF1 Transcription Pathway. Citrus fruits, apples, onions, parsley, sage, tea, and red wine -- are the primary dietary sources of quercetin. Olive oil, grapes, dark cherries, and dark berries -- such as blueberries, blackberries, and bilberries -- are also high in flavonoids, including quercetin. 

Substances noted in visual field improvements:

Magnesium, B12, ginkgo, Alpha lipoic acid

Overall diet and Glaucoma guidelines

There are many types of glaucoma, and this means there are different possible paths leading to the ultimate deterioration of the optic nerve, supporting structures, and retinal nerve fiber layers. However, the final result is basically the same for all types – which culminates in nerve cell loss via oxidative stress, and inflammatory processes (such as TNF alpha). Therefore, it makes sense to us at FitEyes, that the aim of  a diet should primarily be geared toward neuroprotection, reducing inflammation and oxidative damage/stress. This means primarily an anti-inflammatory and high anti-oxidant diet.  Therefore,  in the approach above, it is equally helpful to consider what things should be eliminated from the diet, vs the things which should be added to achieve this end. In the first case, all or most processed and sugary foods should be eliminated and substituted with natural foods. It is a recognized fact that processed foods and over consumption of sugar can have an inflammatory effect – and are largely devoid of nutrients. It is probably also a good idea to reduce the consumption of 'factory farm' meats. An exhaustive list of all the possible foods and substances which  would achieve the above goals is beyond the scope of this article.

However, a good place to start would be foods that include the substances listed above which were elucidated in light of glaucoma benefits. Whenever possible, substances should be consumed in natural and whole foods, but when it is not possible to consume sufficient quantities of a given substance, supplements should be considered. Some basic guidelines are as follows for an anti-oxidant and anti-inflammatory diet:

• Eliminate processed foods, trans fatty acids, and hydrogenated foods from your diet. Cut down or eliminate sugars and simple carbohydrates. The corresponding release of insulin has been shown to produce inflammation.

• Increase your intake of leafy greens, other vegetables and superfoods. Strive to eat foods with a variety of colors, as this variety corresponds to different phytochemicals, carotenoids, anthocyanadins- which have antioxidant and anti-inflammatory properties – they work best in synergy.

• Pick from a broad range of whole foods such as fish (especially omega 3 rich), poultry, dairy, fruits, nuts, berries, vegetables, and herbs. Keep abreast of the latest research and try to include foods which contain substances of possible benefit.

• Consider studying the principles of Ayurveda and diet which emphasize eating according to body type, time of year, and other factors. This branch of ancient medicine and lifestyle has a long history behind it.

Note: All of the above guidelines for supplements and foods assume that your particular medical or health conditions are taken into consideration – ask your doctor if you don't know. Finally, try to eat organic, or locally grown whenever possible. Otherwise, be diligent to avoid as much pesticide and harmful residues as possible in food.

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