Natural Glaucoma Treatments

Evidence That Alpha-Lipoic Acid Can Be Effective in the Treatment of Glaucoma:

One small Russian study comparing standard glaucoma treatment to standard treatment plus Alpha-Lipoic acid in patients with open angle glaucoma reported a benefit in those patients who took 150mg per day. ^[1]As my knowledge of Russian is limited to names of vodkas, I can’t vouch for the quality of this study. Nevertheless, there is good evidence that Alpha-lipoic acid can provide a neuroprotective effect. ^[2] It’s one thing to show that a chemical can protect a cell in a petri dish, quite another to show that something taken by mouth could actually be absorbed into the bloodstream and then pass the bloodbrain barrier. It turns out that Alpha-Lipoic acid, unlike many other antioxidants, easily crosses the blood-brain barrier and therefore should be available to protect central nerves such as the optic nerve from oxidative damage.

Potential Risks and Side Effects of Alpha-Lipoic Acid

In general Alpha-Lipoic acid is well tolerated at doses of up to 600mg per day. ^[3] However, both skin rash and nausea have been reported with oral use of Alpha-Lipoic acid. ^[4] Additionally, Alpha-Lipoic acid can be toxic in those who are thiamine deficient. People who may be thiamine deficient (such as those who consume large amounts of alcohol) should only take Alpha-Lipoic acid with thiamine or not take Alpha-Lipoic acid at all. ^[5]

Potential Drug Interactions

Anti-Diabetes Drugs

Alpha-Lipoic acid may lower blood sugar. ^[6] In those whose blood sugar is not well-controlled this could be a good thing. However, care should be taken when used along with other antidiabetes drugs such as glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, metformin (Glucophage), pioglitazone (Actos), and rosiglitazone (Avandia).

Chemotherapy

Although unproven, antioxidant use may decrease the effectiveness of chemotherapy. ^[17]

Anyone undergoing chemotherapy should consult with their oncologist prior to initiating antioxidant therapy.

Thyroid Hormone

Animal studies suggest that Alpha-Lipoic acid may decrease the effectiveness of thyroid hormone therapy. ^[8] As such it should be used with caution in people who are also taking thyroid hormone medications.

Recommended Dosage

Based only upon the results of the Russian study, it would seem reasonable to dose Alpha-Lipoic acid in the range of 150-250mg per day. To put this in perspective, 150mg is only one fourth the dose used in a number of studies that have looked at Alpha-Lipoic acid in the treatment of diabetic neuropathy (600mg/day). Alpha-Lipoic acid can be found at most health food stores as well as online. Take note, however, that the quality can vary greatly. To be certain you are getting a high quality product that is formulated for maximum benefit I would recommend you only purchase supplements from well-respected brands such as Life Extension or Doctor’s Optimal Formula.

Evidence That Citicoline Can Be Effective in the Treatment of Glaucoma:

The role of Citicoline as a glaucoma treatment has been studied with intramuscular^[11], oral^[12], and topical administration.

Intramuscular

Although not practical for most glaucoma patients, intramuscular injections (IM) of 1,000mg of Citicoline were compared to IM injections of placebo given over a course of 60 days.^[13] Retinal and visual pathway functions were evaluated by visual evoked potentials (VEPs) and pattern-electroretinograms (PERGs). There was a significant improvement in test results noted in the IM Citicoline group compared to the group who received the placebo.

In another study, visual field improvement was noted after only a 10 day course of 1,000mg of intramuscular Citicoline.^[14]

Oral

Because Citicoline is so well absorbed by the gut oral intake should have a similar benefit compared to intramuscular administration. There is one published study evaluating a small group of glaucoma patients who took an oral dose of 1,000mg of Citicoline daily. In most, but not all, of these patients the visual evoked potential (VEP) results improved after four weeks of treatment. Unfortunately there was no placebo control group in this study.

A separate study evaluated a proprietary oral solution of Citicoline. In this study 500mg per day appeared to slow the progression of glaucomatous loss of vision^[15] over a period of 60 days.

Eye Drops

A preliminary study was published using an experimental eye drop solution of 2% Citicoline, 0.2% high molecular weight hyaluronic acid, and 0.01% BAK (OMK1, Omikron Italia s.r.l.). This study demonstrated that Citicoline is absorbed into the eye. Additionally, after 60 days of use in patients with glaucoma the retinal ganglion cell function improved.

Potential Side Effects and Risks of Citicoline

Citicoline appears to be safe and well-tolerated when taken by mouth^[16] The most common side effects are nausea and diarrhea.

Potential Drug Interactions

None known.

Recommended Dosage

Citicoline appears to be safe in doses ranging from 1,000-2,000mg per day for short periods of time ranging up to three months.^[17] It is not known whether it is safe to use over a gram a day of Citicoline for longer periods of time. Based on the limited available research, 500-1,000mg per day of Citicoline would appear to be necessary in order to achieve improvement in retinal and visual pathway function.

Citicoline can be found at most health food stores as well as online. Take note, however, that the quality can vary greatly. To be certain you are getting a high quality product that is formulated for maximum benefit I would recommend you only purchase supplements that contain the Cognizin(R) brand of Citicoline. Manufacturers that use Cognizin(R) Citicoline include Healthy Origins, Life Extension, Swanson, and Vitacost.

Evidence That Forskolin (Coleus) Can Be Effective in the Treatment of Glaucoma

Eye Drop

There are no studies that have evaluated the effectiveness of Forskolin (Coleus) eye drops in the treatment of glaucoma. There are multiple studies, however, that have evaluated its effect on aqueous flow and intraocular pressure (IOP) in animals and humans without glaucoma. Forskolin (Coleus) appears to reduce the production of aqueous fluid with little or no impact on aqueous outflow.^[19] In one Japanese human study a single drop of Forskolin (Coleus) had no effect on IOP whereas a second drop placed five minutes after the first drop resulted in a decrease of IOP by 1.1-3.7mmHg one hour after instillation.^[20]

Oral

There are no studies evaluating the effect of Forskolin (Coleus) alone as a treatment of glaucoma. However, two studies have evaluated the effect of Forskolin (Coleus) combined with Rutin on IOP in patients with glaucoma. The specific product studied was Kronek® (SOOFT Italia, Montegiorgio, Italy) which contains Forskolin (Coleus) 15mg, Rutin 200mg, Vitamin B1 0.7mg, and Vitamin B2 0.8mg. The first study evaluated the use of Kronek® in patients with medically controlled primary open angle glaucoma. It was a small study (only 16 patients) and without the benefit of a placebo control. Despite these severe limitations, the IOP decreased by an average of 20% after 40 days of use.^[21]

The most impressive study evaluated Forskolin (Coleus) and Rutin in patients awaiting glaucoma surgery. These patients had uncontrolled IOP on maximum tolerated medical therapy (MTMT). Patients in the study treatment arm were instructed to take the supplement twice daily.

In those patients taking the supplement IOP dropped by an average of 10% after one to three weeks of treatment. The IOP lowering effect appeared to be dependent upon the initial pretreatment IOP. In other words, the higher the initial IOP, the greater the IOP lowering effect of the supplement.^[22] In addition to the IOP lowering potential, there is evidence that Kronek® may also improve the symptoms of ocular surface disease related to the use of BAK-containing glaucoma drops.^[23]

Potential Side Effects and Risks of Forskolin (Coleus)

Use of Forskolin (Coleus) eyedrops have been associated with redness of the eye (hyperemia) and irritation^[24]

Potential Drug Interactions

Blood Thinners

Forskolin (Coleus) may have an antiplatelet (blood-thinning) effect.^[25] As such, it should be avoided or used only with extreme caution in those who are already taking oral blood thinning medications. An incomplete list of blood thinners with which Forskolin (Coleus) should be avoided would include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), and warfarin (Coumadin).

Anti-Hypertensive Medications

Forskolin (Coleus) may lower blood pressure.^[26] In those whose blood pressure is not well-controlled this could be a good thing. However, care should be taken when used along with other bloodpressure lowering medications such as captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), amlodipine (Norvasc), hydrochlorothiazide (HydroDIURIL), furosemide (Lasix), as well as many others.

Calcium Channel Blockers

Forskolin (Coleus) appears to work on the Calcium channels in heart and blood vessel cells.^[27] As such, it should be taken with extreme caution in those already using calcium channel blockers. Some commonly prescribed calcium channel blockers include nifedipine (Adalat, Procardia), nicardipine (Cardene), isradipine (DynaCirc), and amlodipine (Norvasc).

Nitrates

Forskolin (Coleus) has blood vessel dilating properties.^[28] In theory this could result in a dangerously low blood pressure in someone who is also using nitrate medications. As such Forskolin (Coleus) should not be used in those who are also taking nitrates such as nitroglycerin (Nitro-Bid, Nitro-Dur, Nitrostat) and isosorbide (Imdur, Isordil, Sorbitrate).

Recommended Dosage

Eye Drop

As there have been no studies evaluating Forskolin (Coleus) eye drops in patients with glaucoma it is not possible to know what dosing amount or frequency would be effective (if any). The studies that evaluated use in humans without glaucoma used eye drops with a Forskolin (Coleus) concentration of 1%.^[29]

A study published in The Lancet documented the greatest IOP lowering effect one hour after placement of the eye drop. IOP remained reduced (though less so) five hours later. No dosing studies have been published. However, from The Lancet study alone it would be reasonable to conclude that four times daily dosing would likely be required in order to achieve a sustained reduction in IOP.

The likely need for frequent dosing throughout the day makes Forskolin (Coleus) a poor choice for glaucoma therapy. There are at least two reasons for this:

1) Multiple studies have confirmed that adherence to glaucoma therapy worsens as the number of daily drops increase. In other words, the more drops one has to use each day the less likely it is that all of them will be instilled.

2) Mounting evidence suggests that IOP fluctuation may also be a contributor to worsening glaucoma. Missing scheduled drops would allow the IOP to rise. It is likely that drops will be forgotten when using a medication that must be dosed multiple times a day. Thus, use of a drop that must be taken four times each day is essentially ensuring fluctuating IOP (and possible worsening of glaucoma) in all but the most obsessive-compulsive people.

Finally, based on the Japanese study a single drop is unlikely to have any beneficial effect. In order to achieve any benefit a second drop would need to be placed in the eye five minutes after the initial drop. This would make it quite impractical as a treatment option for most people with glaucoma.

Oral

Based on the studies evaluating the effect of combined Forskolin (Coleus) and Rutin on IOP, it would be reasonable to use 30mg of Forskolin (Coleus) and 400mg of Rutin per day (divided into two or three doses). Because supplements can vary widely in quality and concentration of the active ingredients, I recommend use of the actual studied brand, Kronek®, if available locally or online.

Evidence That Ginkgo Biloba Can Be Effective in the Treatment of Glaucoma

As far back as 2003 there has been evidence that Ginkgo biloba may have a benefit in the treatment of glaucoma.^[38] Patients with Normal Tension Glaucoma (NGT) who were given 40mg of Ginkgo biloba extract three times a day (120mg total daily dose) showed a short term improvement on their visual fields compared to those who took placebo. No difference in IOP was noted, but the fact that pre-existing visual field defects got better is impressive.

I never tell my patients to expect visual field improvement from any standard medical or surgical therapy, so this finding was quite surprising.

In late 2013 a study was published in the Journal of Glaucoma evaluating the effect of Ginkgo biloba extract on visual field loss inpatients with Normal Tension Glaucoma. These patients were studied for an average of 12 years and were using Ginkgo biloba extract for at least four years. Although there was no effect on intraocular pressure(IOP), there was a significant reduction in the rate of visual field loss in those patients taking Ginkgo biloba extract.^[39] These results are quite impressive as most studies only look at IOP, whereas what we are really interested in is saving vision. This study is unique in that it is (to the best of my knowledge) the only study that has shown that an over-the-counter supplement can effectively reduce the rate of long term vision loss in patients with glaucoma.

Potential Side Effects and Risks of Ginkgo Biloba

In a long-term study comparing Ginkgo biloba extract to placebo in the treatment of dementia there were no significant differences inside effects between the two groups.^[40] Other studies, however, have noted an association with mild irritability, nausea or diarrhea.

Potential Drug Interactions

Blood Thinners

Ginkgo biloba is known to have anticoagulant properties which can result in undesirable bleeding.^[41] This is even more concerning in those who are already taking anticoagulant medications suchas apixaban (Eliquis), clopidogrel (Plavix), dabigatran (Pradaxa),rivaroxaban (Xarelto)and warfarin (Coumadin).

Therefore, I generally do not recommend use of Ginkgo Biloba in my patients who are already taking blood thinners.

It is important to let all your doctors know if you are taking this supplement. It is also important to discontinue Ginkgo biloba extract prior to any planned surgery.

Anti-Diabetes Medications

Ginkgo biloba may alter insulin levels as well as blood sugar^[42] in diabetics taking oral anti-diabetes medications. As such, Ginkgo biloba should be used with caution or not at all in those who are also taking anti-diabetes medications. An incomplete list of such medications would include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), and rosiglitazone (Avandia).

Anti-Seizure Medications

Ginkgo seeds contain a chemical called Ginkgo toxin. Risk of seizure is increased when large amounts of the roasted seed are eaten.^[43] High quality ginkgo leaf extracts, however, should have very little ginkgotoxin.^[44]

Nevertheless, ginkgo extracts should be taken only under the supervision of a physician or not at all in those who have a history of epilepsy or are already taking anti-seizure medications such as carbamazepine (Tegretol), gabapentin (Neurontin), phenobarbital, phenytoin (Dilantin), primidone (Mysoline), and valproic acid (Depakene).^[45] Trazodone (Desyrel).

There is a single published report of a patient who became comatose while taking both Ginkgo biloba and trazodone.^[46] Therefore use of Ginkgo biloba should be avoided in anyone taking trazodone (Desyrel).

Possible Interactions with Diseases or Conditions

Surgery

Due to its antiplatelet (blood clotting) effect, Ginkgo biloba should be discontinued two weeks prior to anticipated surgery.

Recommended Dosage

Ginkgo biloba extract may be found in many dosages. The dosage used in the aforementioned studies ranged from 40mg taken three times daily (120mg total daily dose) to 80mg twice daily (160mg total daily dose).

Where to Buy

Ginkgo Biloba can be found online, as well as at most pharmacies and health food stores. Take note, however, that the quality can vary greatly. To be certain you are getting a high quality product I would recommend you only purchase Ginkgo biloba or other supplements from a trusted brand such as Life Extension.

Evidence That Melatonin Can Be Effective in the Treatment of Glaucoma

As little as 500mcg (0.5mg) of Melatonin has been shown to lower intraocular pressure (IOP) in healthy men. ^[51] A larger dose (10mg) was demonstrated to lower IOP when taken prior to cataract surgery.^[52] This effect appears to be due to Melatonin’s actions on both the alpha and beta adrenergic receptors as well as carbonic anhydrase.^[53]

In essence, Melatonin acts on three of the four IOP lowering pathways currently targeted with modern prescription ocular therapy (beta blockers,alpha-agonists, and carbonic anhydrase inhibitors).

Melatonin has other potential benefits to those with glaucoma. For example, it is a powerful antioxidant.^[54] Melatonin has also been shown to provide a neuroprotective effect.^[55] This neuroprotective effect appears to be enhanced when both Resveratrol and Melatonin are present.^[56]

Potential Side Effects and Risks of Melatonin

Melatonin has been taken in single doses as high as 500mg without notable side effects. ^[57] Long term, taking up to 5mg per day of Melatonin appears to be safe.^[58]

Potential Drug Interactions

Anti-Hypertensive Medications

Melatonin may lower blood pressure.^[59] In those whose blood pressure is not well-controlled this could be a good thing. However, care should be taken when used along with other blood pressure lowering medications such as captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), amlodipine (Norvasc), hydrochlorothiazide (HydroDIURIL), furosemide (Lasix), as well as many others.

Recommended Dosage

I recommend that my patients begin taking a minimum of 500mcg(0.5mg) of Melatonin thirty minutes prior to going to bed at night. If they are also having difficulty falling asleep then I will instruct them to slowly increase the dose until they have reached a maximum dose of 5mg per night. As both glaucoma and sleep disturbance are more common as we age, supplementing with Melatonin provides a dual benefit.

Evidence That Mirtogenol® Can Be Effective in the Treatment of Glaucoma

Initial evidence that Mirtogenol® could lower IOP was published in 2008^[60]. Although the study size was small (20 patients treated with Mirtogenol®, 18 patients untreated) Mirtogenol® taken orally twice daily was shown to decrease IOP by 3mmHg after two months of therapy. Additionally, 95% of the patients who took Mirtogenol® experienced a reduction in IOP.

In a study published in 2010^[61] Mirtogenol® (120mg taken once daily) was shown to lower IOP almost as much as prostaglandin analog eyedrops (one of the more effective classes of glaucoma medications). In addition, when Mirtogenol® was combined with the use of a prostaglandin analog the IOP was reduced even further. The amount of additional IOP reduction was similar to what I generally expect from adding another class of prescription eye drop.

One limitation of Mirtogenol® is that its effect on IOP is not immediate. It took six times as long as latanoprost (24 vs 4 weeks) for the full effect of Mirtogenol® (120mg taken once daily) to appear.

Based on the 2008 study, however, it may be possible to speed up the response by taking a larger initial dose (120mg taken twice daily). In addition to its IOP lowering effect, the bilberry extract portion of Mirtogenol® (Mirtoselect®) may help to stabilize visual function and visual fields. Bilberry extract contains anthocyanins which are believed to be responsible for many of bilberry’s beneficial health effects. In one study of patients with Normal Tension Glaucoma who were taking anthocyanins, visual fields appeared to actually improve over the two year study period.^[62]

Potential Side Effects and Risks of Mirtogenol®

No serious side effects from Mirtogenol® were noted in the above studies. Indeed, according to the authors of the 2010 study, “serious side-effects have never been reported for Mirtoselect® and Pycnogenol®, despite their decades-old use in ophthalmology”. Mild side effects such as gastrointestinal upset and dizziness, however,have been reported.

Potential Drug Interactions

Blood Thinners

Research suggests that both bilberry extract and Pycnogenol® may limit the ability of platelets to clump^[63] This could increase the risk of bleeding when used with ”blood thinning” medications. As such, Mirtogenol® should be used with caution in those who are also taking blood thinners such as aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, indomethacin (Indocin), ticlopidine (Ticlid), and warfarin(Coumadin).

Anti-Diabetes Medications

Bilberries and Pycnogenol® may have an effect on blood glucose.^[64] Indeed, whole bilberries, bilberry extract, and Pycnogenol® are commonly used alternative medicine treatments for diabetes. Thus, Mirtogenol® should be used with caution in those who are also taking anti-diabetes medications such as glimepiride(Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, metformin (Glucophage), pioglitazone (Actos), androsiglitazone (Avandia).

Immunosuppressant Medications

Pycnogenol® appears to have an immune stimulating effect^[65] which may interfere with immuno suppressant medications. Therefore Pycnogenol® should not be used when also taking immuno suppressant drugs such as azathioprine (Imuran), basiliximab (Simulect), cyclosporine (Neoral, Sandimmune), dacliximab (Zenapax), muromonab-CD3 (OKT3, OrthocloneOKT3), mycophenolate (CellCept), tacrolimus (FK506, Prograf), sirolimus (Rapamune), prednisone (Deltasone, Orasone), and other corticosteroids (glucocorticoids).

Possible Interactions with Diseases or Conditions

Autoimmune Diseases

Pycnogenol® may have an immune stimulating effect.^[66] As such,patients with autoimmune disorders such as multiple sclerosis, systemic lupus erythematosus (SLE), rheumatoid arthritis and other less common autoimmune conditions should avoid use ofsupplements such as Mirtogenol® that contain Pycnogenol®.

Surgery

Due to its potential antiplatelet (blood thinning) effect, Mirtogenol® should be discontinued two weeks prior to anticipated surgery.

Recommended Dosage

Mirtogenol® tablets contain 80mg of Mirtoselect® bilberry extract and 40mg of Pycnogenol® French maritime pine bark extract. The above studies instructed their patients to take one (2010 study) or two (2008 study) tablets of Mirtogenol® each day.

Where to Buy

Mirtogenol can be found at Life Extension or Doctor’s Optimal Formula. Both of these suppliers obtain their product from the same manufacturer so you can be assured of the quality of their supplements.

Evidence That Omega-3 Fatty Acids Can Be Effective in the Treatment of Glaucoma

When injected into the muscles of rabbits, fish oil (DHA and EPA) was shown to reduce intraocular pressure (IOP).^[67] As we wouldn’t likely be injecting omega-3 fatty acids into our muscles, other studies have looked at dietary intake of omega-3 fatty acids in laboratory animals. In mice, at least, a diet rich in omega-3 fatty acids was shown to lower IOP by making it easier for fluid to exit the eye.^[68]

In humans, the benefit of omega-3 fatty acids is less clear. At least in combination with Vitamins B and E, DHA has been shown to improve visual fields and retinal sensitivity in patients with glaucoma^[69]

There may bean additional benefit to using omega-3 fatty acids for those who are already taking drops to treat their eye pressure. There is growing evidence that long-term use of topical glaucoma medication scan result in or worsen dry eye disease. Oral omega-3 fatty acid supplementation appears to protect the surface of the eye.^[70]

Potential Side Effects and Risks of Omega-3 Fatty Acids

The most commonly experienced side effects of oral supplementation with omega-3 fatty acids are “fishy burps”, gastrointestinal distress (stomach upset), and blood thinning. Many omega-3 supplements are now “enteric coated” in order to decrease the risk of the first two annoying side effects. Taking these supplements with meals or storing them in the freezer also helps. With regard to blood thinning, it is important to consult one’s primary doctor (internist or family physician) if already taking blood thinners. For those who are not already taking blood thinners there is very little risk of excess bleeding associated with oral doses of 4,000mg or less per day.

Potential Drug Interactions

Blood Thinners

Docosahexaenoic acid (DHA) alone does not appear to have a significant effect on platelet aggregation (blood clotting). However, when combined with eicosapentaenoic acid (EPA) blood thinning is, at least in theory, possible. ^[71] As most over the-counter (OTC) supplements include a combination of DHA and EPA they should be used with caution in those who are also taking known blood thinners such as aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), and warfarin (Coumadin).

Anti-Diabetes Medications

DHA may increase fasting blood glucose.^[72] As such, it could interfere with the effect of anti diabetes drugs such as glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase),insulin, metformin (Glucophage), pioglitazone (Actos), androsiglitazone (Avandia).

Anti-Hypertensive Medications

Both DHA and EPA appear to lower blood pressure.^[73] In those whose blood pressure is not well-controlled this could be a good thing. However, care should be taken when used along with other blood-pressure lowering medications such as captopril (Capoten),enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan),diltiazem (Cardizem), amlodipine (Norvasc), hydrochlorothiazide (HydroDIURIL), furosemide (Lasix), as well as many others.

Possible Interactions with Diseases or Conditions

Surgery

Due to its blood thinning effect, EPA should be discontinued two weeks prior to anticipated surgery.

Recommended Dosage

Although laboratory animal studies seem to imply a role of omega-3 fatty acids in lowering IOP, there is little evidence in humans that oral supplementation with omega-3 fatty acids could benefit those with glaucoma. Nevertheless, there are many other well documented health benefits of omega-3 fatty acids and the risks of taking them are small.

In my patients who tolerate it I recommend oral supplementation of omega-3 fatty acids in the range of 1,000-4,000 mg per day (divided into 2-3 doses if needed to avoid side effects).

Where to Buy

The price of omega-3 fatty acid supplementation can vary from $5-70 per month depending upon the source, brand and whether or not they are enteric coated. Take note, however, that the quality can vary greatly. To be certain you are getting a high quality product I would recommend you only purchase supplements such as Omega-3 fatty acids from a trusted brand such as Eye Science or Nordic Naturals.

Evidence That Palmitoylethanolamide (PEA) Can Be Effective in the Treatment of Glaucoma

PEA has been shown to increase the flow of aqueous fluid out of the eye.^[94] Additionally, PEA is naturally found in the ciliary body (the eye tissue that produces aqueous fluid). In patients with glaucoma there is a reduced amount of PEA in the ciliary body.^[95] If patients with glaucoma have less PEA in their eyes could increasing the amount of PEA treat glaucoma?

There are now multiple studies in which PEA has been shown to lower the intraocular pressure (IOP). Studies published in 2011^[96] and 2013^[97] comparing PEA against placebo demonstrated a statistically significant reduction in IOP with the use of PEA (which was not seen with the placebo). In addition to IOP reduction, visual field and pattern-ERG results in glaucoma patients treated with PEA over a two year period was presented by Dr. Gagliano at the 2012 meeting of the European Association for Vision and Eye Research. Those taking 300mg of PEA twice daily experienced a significant benefit in all three metrics compared to those taking placebo.^[98]

The most recent study was published in 2014. In this study patients who received 300mg of PEA twice daily for six months were compared to those who did not take PEA. Those in the PEA arm experienced both lower IOP and visual field improvement.^[99]

Potential Side Effects and Risks of Palmitoylethanolamide (PEA)

As reported in the most recent study, “neither ocular nor systemic side effects were recorded during the study period.” Earlier studies have also noted the lack of significant side effects.

Potential Drug Interactions

No known drug interactions.^[100]

Recommended Dosage

In the most recent study, patients were instructed to take 300mg of PEA by mouth twice daily.

Where to Buy

PEA is not cheap. The commercially available form (PeaPure™) is $30-50 for a package of 30 (thirty) 400mg capsules. As the study evaluated patients who took a total of 600mg a day the monthly cost of this treatment would be $45-100/month.

Evidence That Palmitoylethanolamide (PEA) Can Be Effective in the Treatment of Glaucoma

PEA has been shown to increase the flow of aqueous fluid out of the eye.^[94] Additionally, PEA is naturally found in the ciliary body (the eye tissue that produces aqueous fluid). In patients with glaucoma there is a reduced amount of PEA in the ciliary body.^[95] If patients with glaucoma have less PEA in their eyes could increasing the amount of PEA treat glaucoma?

There are now multiple studies in which PEA has been shown to lower the intraocular pressure (IOP). Studies published in 2011^[96] and 2013^[97] comparing PEA against placebo demonstrated a statistically significant reduction in IOP with the use of PEA (which was not seen with the placebo). In addition to IOP reduction, visual field and pattern-ERG results in glaucoma patients treated with PEA over a two year period was presented by Dr. Gagliano at the 2012 meeting of the European Association for Vision and Eye Research. Those taking 300mg of PEA twice daily experienced a significant benefit in all three metrics compared to those taking placebo.^[98]

The most recent study was published in 2014. In this study patients who received 300mg of PEA twice daily for six months were compared to those who did not take PEA. Those in the PEA arm experienced both lower IOP and visual field improvement.^[99]

Potential Side Effects and Risks of Palmitoylethanolamide (PEA)

As reported in the most recent study, “neither ocular nor systemic side effects were recorded during the study period.” Earlier studies have also noted the lack of significant side effects.

Potential Drug Interactions

No known drug interactions.^[100]

Recommended Dosage

In the most recent study, patients were instructed to take 300mg of PEA by mouth twice daily.

Where to Buy

PEA is not cheap. The commercially available form (PeaPure™) is $30-50 for a package of 30 (thirty) 400mg capsules. As the study evaluated patients who took a total of 600mg a day the monthly cost of this treatment would be $45-100/month.

Evidence That Resveratrol Can Be Effective in the Treatment of Glaucoma

Laboratory evidence suggests that Resveratrol can protect neurons from the toxic effects of inflammation.^[90] It has also been shown to increase cerebral blood flow as well as provide a neuroprotective effect.^[91]This neuroprotective benefit appears to be enhanced when both Resveratrol and Melatonin are present.^[92] Resveratrol also appears to have antioxidant properties.^[93]

Intraocular pressure (IOP) elevation in the most common form of open angle glaucoma is thought to be due to malfunction of the eye’s drainage grate (trabecular meshwork). This malfunction is known to be associated with certain biochemical markers of inflammation[94] and oxidative cellular damage^[95] One laboratory study demonstrated that Resveratrol was able to decrease these markers in trabecular meshwork cell culture models of oxidative damage.^[96]

Potential Side Effects and Risks of Resveratrol

Resveratrol appears to be safe when taken in doses commonly available in over-the-counter supplements. Indeed, when taken in amounts up to 5,000mg per day the only observable side effects were gastrointestinal upset^[97] and nausea.^[98]

A Caution for those with Hormone Sensitive Cancers or Conditions

Resveratrol has a structure that is similar to estrogen. As such,it may alter estrogen metabolism^[99] Women with the following conditions should in general avoid use of Resveratrol: breast,uterine, and ovarian cancer, as well as endometriosis and uterine fibroids.

Potential Drug Interactions

Blood Thinners

Resveratrol is known to have anti-platelet properties^[100] which can result in undesirable bleeding in those who are already taking anticoagulant medications such as aspirin, apixaban (Eliquis), clopidogrel (Plavix), dabigatran (Pradaxa), rivaroxaban (Xarelto) and warfarin (Coumadin).

It is important to let all your doctors know if you are taking this supplement. It is also prudent to discontinue Resveratrol prior to any planned surgery.

Anti-Diabetes Medications

Resveratrol increases the body’s sensitivity to insulin.^[101] As such,it may have an effect on blood glucose. For those whose blood sugar is not well controlled this could be a good thing. This effect can be seen with oral doses as low as 5-10mg per day.

However,if one’s blood sugar is well-controlled then Resveratrol should be used with caution and only with the knowledge of the physician who is monitoring one’s blood sugar. Resveratrol may enhance the blood sugar lowering effect of medications including glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase),insulin, metformin (Glucophage), pioglitazone (Actos), androsiglitazone (Avandia), among others.

Recommended Dosage

As no human glaucoma studies have been done looking at the role of Resveratrol in the treatment of glaucoma, it is not possible to recommend a proper dosage. However, it appears that Resveratrol’s benefit on cerebral (brain) blood flow occurs with daily dosages in the range of 250-500mg per day. Morning dosing may result in better bioavailability.

Evidence That Rutin Can Be Effective in the Treatment of Glaucoma

There is no direct evidence that Rutin could have an IOP lowering effect on the eye. However, two studies have evaluated the effect of Rutin combined with Forskolin (Coleus) on IOP in patients with glaucoma.

The specific product studied was Kronek® (SOOFT Italia, Montegiorgio, Italy) which contains Rutin 200mg, Forskolin (Coleus) 15mg, Vitamin B1 0.7mg, and Vitamin B2 0.8mg. The first study evaluated the use of Kronek® in patients with medically controlled primary open angle glaucoma. It was a small study (only 16 patients) and without the benefit of a placebo control. Despite these severe limitations, the IOP appeared to decrease by an average of 20% after 40 days of use.^[103]

The most impressive study evaluated Rutin and Forskolin (Coleus) inpatients awaiting glaucoma surgery. These patients had uncontrolled IOP on maximum tolerated medical therapy (MTMT). Patients in the study treatment arm were instructed to take the supplement twice daily. In those patients taking the supplement, IOP dropped by an average of 10% after one to three weeks of treatment. The IOP lowering effect appeared to be dependent upon the initial pre-treatment IOP.

In other words, the higher the initial IOP, the greater the IOP lowering effect of the supplement.^[104] In addition to the IOP lowering potential, there is evidence that Kronek® may also improve the symptoms of ocular surface disease related to the use of BAK-containing glaucoma drops.^[105]

Potential Side Effects and Risks of Rutin

Use of Rutin has been associated with flushing, headache, mild gastrointestinal distress, and skin rashes.^[106]

Hormone Sensitive Cancers or Conditions

Rutin is a flavonoid. Flavonoids have a structure that is similar to estrogen.^[107] As such, Rutin may alter estrogen metabolism. Women with breast, uterine, and ovarian cancer, as well as endometriosis and uterine fibroids should avoid use of flavonoid containing supplements.

Potential Drug Interactions

None known.

Recommended Dosage

Based on the studies evaluating the effect of combined Rutin and Forskolin (Coleus) on IOP, it would be reasonable to use 400mg of Rutin and 30mg of Forskolin (Coleus) per day (divided into two or three doses).

Where to Buy

Because supplements can vary widely in quality and concentration of the active ingredients, I recommend use of the actual studied brand, Kronek®, if available locally or online.

Evidence That Saffron Can Be Effective in the Treatment of Glaucoma

In 2014 a study was published comparing oral saffron against placebo in patients with stable glaucoma who were already treated with topical glaucoma medications.^[110] Although the study was small (only 34 patients completed the study) the results were impressive. After only 3 weeks of using 30mg of “Sargol” grade saffron the intraocular pressure (IOP) dropped by 2mmHg. This effect, which was statistically significant, persisted at the 4 week visit. No such effect was noted in the placebo group.

Potential Side Effects and Risks of Saffron

Saffron is generally recognized as safe^[111] at 30mg per day. At 60mg per day the following has been reported: anxiety, change in appetite,drowsiness, nausea, vomiting, headache, sedation, and hypomania.^[112] Severe side effects have been reported with oral intake of 5,000mg.^[113] Saffron can even be fatal when taken in amounts as high as 12,000mg.^[114] Of note is that supplementation with the carotenoid beta-carotene has been associated with an increased risk of lung cancer. As saffron is high in carotenoid compounds it should probably not be used by those who are active or have been active smokers.

Potential Drug Interactions

Antihypertensive Medications

At least in rats (and possibly guinea-pigs), Saffron appears to lower blood pressure.^[115] In those whose blood pressure is not well-controlled this could be a good thing. However, care should be taken when used along with other blood-pressure lowering medications such as captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), amlodipine (Norvasc), hydrochlorothiazide (HydroDIURIL), furosemide (Lasix), as well as many others.

Calcium Channel Blockers

Saffron extract has been shown in the laboratory to affect the action of the heart muscle.^[116] As such, use of Saffron should be avoided (or only done with great caution and with the knowledge of one’s physician) in those who are already taking calcium channel blockers or other medications which affect the action of the heart muscle. Examples of Calcium channel blockers include verapamil (Calan, Covera-HS, Verelan), nifedipine (Procardia),and diltiazem (Cardizem, Dilacor, Tiazac).

Recommended Dosage

The dosage of saffron used in the 2014 study was 30mg per day. It is important to note, however, that this was “Sargol” grade saffron. Sargol grade is comprised of only the red stigma tips. It is considered to be the purest and most expensive saffron available.

Very few commercially available saffron products use such a high grade and it is simply not known whether or how much of a lower grade would have the same IOP lowering effect noted in the 2014 study.

It should also be noted that pure saffron ranks as one of the 20 most valuable materials by weight (valued at roughly $5,000 USD per pound). As such, it’s not going to be cheap. Inexpensive “saffron”products most likely are either made up of lower grades of saffron(such as “Pushal”, “Pushali”, or “Bunch”) or are not pure saffron.

Expect to pay $20-50 for a one month supply. The brand of saffron I currently recommend is Paradise Herbs Saffr-Tone. Each capsule contains 15mg of saffron stigma tips. In order to achieve the equivalent dosage as that used in the 2014 study one capsule should be taken twice daily.

Evidence That Tumeric (Curcumin) Can Be Effective in the Treatment of Glaucoma

Of the supplements I recommend for my patients with glaucoma, this one has the least evidence supporting its use. Although it has been shown to have a neuroprotective^[118] effect, it has not specifically been shown to either reduce IOP or slow the progression of glaucoma. In other words, because glaucoma is a disease of the optic nerve, and Curcumin has been shown to protect nerves from damage, it is thought that Curcumin may also benefit those with glaucoma.

Potential Side Effects and Risks of Tumeric (Curcumin)

The FDA reports that Curcumin is “generally recognized as safe”. The most commonly reported side effect is stomach upset. There is, however, laboratory evidence that Curcumin could be toxic to the liver when large doses are used over a long period of time.^[119] Such toxicity has not been shown to occur in humans taking Curcumin by mouth. Indeed, there is even evidence that Curcumin could protect the liver from damage.^[120] In general there is very little evidence that oral supplementation with Curcumin could result in serious side effects even in doses as high as 12,000mg/day.^[121]

Minor side effects may include “GI distress” (stomach upset) when taken in the capsule form. If this is the case it can often be alleviated by simply opening the capsule and pouring the Curcumin powder over soft food (such as soup or mashed potatoes).

Potential Drug Interactions

Blood Thinners

Curcumin has been reported to affect the ability of platelets to aggregate (blood clotting).^[122] In theory this could increase the risk of unwanted bleeding when combined with other blood thinners. As such Curcumin should be used with caution or not at all in those who are also taking known blood thinners such as aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), and warfarin (Coumadin).

Anti-Diabetes Medications

Curcumin appears to reduce blood glucose in both laboratory animals and humans.^[123] In those whose blood sugar is not well controlled this could be a good thing. However, care should be taken when used along with antidiabetes drugs such as glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, metformin (Glucophage), pioglitazone (Actos), and rosiglitazone (Avandia).

Possible Interactions with Diseases or Conditions

Gall Bladder Disease

There is evidence that Curcumin may increases gall bladder contractions.^[124] As such, it should not be taken by those with gallstones or other gall bladder disease.

Gastroesophageal Reflux (GERD)

Although Curcumin has been used to treat indigestion,^[125] it may also cause it.^[126] Thus it would be prudent for those with GERD to use Curcumin with caution.

Infertility

Curcumin appears to reduce the production of sperm.^[127] Its use should therefore be avoided in anyone actively trying to have children or who is undergoing fertility treatments.

Iron Deficiency

At relatively low doses, Curcumin does not appear to affect the absorption of iron.^[128] However, laboratory evidence suggests that at higher doses Curcumin may prevent iron from being absorbed into the bloodstream.^[129] As such, anyone who is anemic or iron deficient should likely avoid use of Curcumin.

Surgery

Due to its antiplatelet (blood clotting) effect, Curcumin should be discontinued two weeks prior to anticipated surgery.

Recommended Dosage

As there are no published studies that have evaluated the effect of Curcumin on IOP or glaucoma progression, it is not possible to recommend a glaucoma-specific dose. In the studies that have evaluated the effect of Curcumin on other diseases the dosages ranged from 20mg to 12,000mg/day^[130] As many of these studies evaluated the effect of doses around 500-1,000mg/day this is most likely a reasonable range to consider and is what I generally recommend to my patients with glaucoma who are interested in adding oral supplements to their treatment.

Where to Buy

Curcumin can be found at most health food stores as well as online for as little as $0.17 per 500mg capsule. Take note, however, that the quality can vary greatly. Additionally, Curcumin is very poorly absorbed through the gastrointestinal tract.^[131] Absorption may be improved if it is taken with food^[132] To be certain you are getting a high quality product that is formulated for maximum absorption I would recommend you only purchase supplements such as Curcumin from a trusted brand such as Life Extension.

Evidence That B Vitamins Can Be Effective in the Treatment of Glaucoma

At least in combination with Vitamin E and DHA, Vitamin B has been shown to improve visual fields and retinal sensitivity in patients with glaucoma.^[133] Of the B vitamins, Vitamin B12 (Methylcobalamin) has the most support for its role in glaucoma treatment. Multiple studies have looked into it’s effect on both chronic open angle glaucoma^[134] as well as normal tension glaucoma^[135] The evidence suggests that its use may slow visual field loss.

Potential Side Effects and Risks of B Vitamins

In the dosages available in most over-the-counter multivitamins the most common side effect is a change in the color and odor of one’s urine. Thiamine, Riboflavin, Pantothenic acid, and biotin are essentially without other significant side effects when taken orally. However, high concentrations achieved from intravenous or intramuscular injection of B vitamins can be associated with significant side effects.

Additionally, the following B vitamins can have significant side effects when taken orally in large doses: VitaminB3 (nicotinamide >3000 mg/day or nicotinic acid >1500 mg/day),Vitamin B6 (pyridoxine >200mg/day), Vitamin B9, Vitamin B12.

Potential Drug Interactions

Chloramphenicol

Vitamin B12 should not be taken along with Chloramphenicol as this combination can have a detrimental effect on red blood cells.^[136]

Recommended Dosage

As there are only a few studies that have looked at treating glaucoma with Vitamin B complex, the optimal dosage is not known. At least with Vitamin B12 (methylcobalamin) we have one study that demonstrated a benefit on visual field defect progression in patients with normal tension glaucoma using a daily dose of 1,500mcg (1.5mg).^[137] Thus, I now recommend that my patients with glaucoma take a Vitamin B Complex as well as 1,500mcg (1.5mg) of VitaminB12 (methylcobalamin) each day.

Where to Buy

Vitamin quality can vary greatly. To be certain you are getting a high quality product I would recommend you only purchase supplements such as B vitamins from a trusted brand such as Life Extension.

Evidence That Vitamin D Can Be Effective in the Treatment of Glaucoma

In early 2014 a study was published that supported the association of Vitamin D deficiency with the presence of glaucoma.^[138] Vitamin D deficiency is relatively common among adults in industrialized countries (especially in urban environments). Thus, it makes sense for those at risk for glaucoma to get tested for Vitamin D deficiency. If deficient then supplementation would be advisable.

Potential Side Effects and Risks of Vitamin D

Vitamin D is generally well tolerated in the doses used to treat Vitamin D deficiency. When taken in excessive doses, however, it can result in too much calcium in the blood (hypercalcemia) or a decrease in blood cells (anemia). Both of these conditions are associated with a long list of vague symptoms (such as fatigue) but can be easily diagnosed with a simple blood test.

Potential Drug Interactions

Certain Cardiac Medications

The risk of developing life-threatening abnormal heart rhythms (arrhythmias) is increased in patients with abnormally high levels of blood calcium (hypercalcemia) who are also taking medications to control the heart rhythm. Patients who are taking Digoxin or Calcium Channel Blockers (diltiazem, verapamil) should limit on going Vitamin D supplementation to 2,000 IU or less per day. Regular blood monitoring of Vitamin D levels is also advised.

Thiazide Diuretics

These include chlorothiazide (Diuril), hydrochlorothiazide (HydroDIURIL, Esidrix), indapamide (Lozol), metolazone (Zaroxolyn), and chlorthalidone (Hygroton). Thiazide diuretics limit the body’s ability to remove calcium through the kidneys. This could result in hypercalcemia in those who are also taking Vitamin D and/or calcium supplements. Regular blood monitoring of Vitamin D levels is advised in those who are taking both thiazide diuretics and Vitamin D supplements.

Recommended Dosage

The association with glaucoma is relative to the Vitamin D deficiency: the more deficient, the higher the association. Thus, dosage will depend upon the results of an individual’s blood testing. Initial recommended dosages can be as high as 50,000 IU per week followed by much lower maintenance doses in the range of 400-2,000 IU per day. If you are Vitamin D deficient you should follow your family physician’s or internist’s advice regarding dosage and frequency of Vitamin D supplementation.

Evidence That Vitamin E Can Be Effective in the Treatment of Glaucoma

At least in combination with Vitamin B and DHA, Vitamin E has been shown to improve visual fields and retinal sensitivity in patients with glaucoma.^[140] It may also have a role in preventing bleb failure after trabeculectomy or glaucoma drainage device surgery. In the laboratory Vitamin E has been shown to limit the proliferation of human Tenon’s capsule fibroblasts.^[141] These cells are largely responsible for the scarring and failure of blebs. Additionally, Vitamin E was shown to limit bleb failure in rabbit models of trabeculectomy.^[142]

Potential Side Effects and Risks of Vitamin E

Vitamin E is well-tolerated with rare side effects in doses up to 1,000 IU per day.[143] However, there is some concern that taking more than 400 IU per day over long periods of time may increase the risk of death.^[144]

Potential Drug Interactions

Blood Thinners

When Vitamin E is taken in doses of 800 IU or more per day it appears to inhibit blood clotting.^[145] Thus, a lower daily dose of Vitamin E is recommended for those who are taking blood thinners. Drugs that might interact with vitamin E include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), and warfarin (Coumadin).

Possible Interactions with Diseases or Conditions

Diabetes

High doses (400 IU or more) of Vitamin E increases the risk of developing life-threatening heart disease in patients with diabetes.^[146]

Cardiovascular (Heart) Disease

High doses (400 IU or more) of Vitamin E are associated with a greater risk of death in those with pre-existing heart disease.^[147]

Prostate Cancer

Vitamin E may increase the risk of developing prostate cancer^[148]

Retinitis Pigmentosa

Synthetic Vitamin E appears to worsen the progressive loss of vision associated with Retinitis Pigmentosa (RP).^[149] Small doses of naturally derived Vitamin E in the range of 3 IU per day may,however, be safe even for those with RP.

Stroke (Cerebrovascular Accident)

Vitamin E should not be taken by those with a history of stroke or with a high risk of developing a stroke.^[150]

Surgery

Due to its antiplatelet (blood clotting) effect, Vitamin E should be discontinued two weeks prior to anticipated surgery.

Vitamin K Deficiency

Vitamin E should not be taken by those with Vitamin K deficiency^[151]

Recommended Dosage

Due to the limited evidence of benefit in patients with glaucoma I do not recommend doses greater than that found in common over the-counter supplements. In general I recommend limiting Vitamin E supplementation to no more than 400 IU per day.

Where to Buy

Vitamin E can be found in nearly every drug, grocery, or health food store. It’s worth noting that the natural form (d-alpha tocopherol) is better absorbed than the more commonly found synthetic form (dlalphatocopherol). As with most supplements, cost can vary widely.