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Complementary and Alternative Medicines for Glaucoma

Oral Supplements I Currently Recommend for Patients with Glaucoma

Based on the limited evidence available, there are a few supplements that I recommend to my patients with glaucoma. These recommendations are accompanied by two significant caveats:

  1. Supplement treatment for glaucoma should be done in combination with already prescribed medical therapy. In other words, and with rare exception, these supplements should not be taken instead of prescription medical or surgical therapy. There simply is not enough evidence to risk permanent loss of vision when well-established medical or surgical glaucoma therapies are available.
  2. The main purpose of using supplements in the treatment of glaucoma is to provide protection of the optic nerve (neuroprotection). A reduction in IOP is not expected with the use of most supplements. Therefore, periodic testing of the structure and function of the optic nerve is necessary in order to confirm the benefit of taking these
    supplements.

Recommended Oral Supplements for Glaucoma:

NOTE: The contents on this website are intended for educational purposes only and should in no way be viewed as medical advice. No treatment mentioned on this site is effective for everyone with glaucoma and it would be unwise to modify one’s own treatment without consultation and examination by a medical doctor properly trained in the diagnosis and treatment of glaucoma.

Alpha-Lipoic Acid for Glaucoma

Alpha-Lipoic Acid for GlaucomaEach cell in our body has a number of bean-shaped power generators called mitochondria. Without them we wouldn’t survive but a few seconds. But power generation at the microscopic level is messy in that it produces a lot of free-radicals. Left unchecked these could destroy the cell via oxidative damage. A powerhouse that destroys the very cell it is trying to power isn’t much good to the cell. So the cell produces a powerful antioxidant to protect it from these damaging mitochondrial byproducts. Alpha-lipoic acid is the name of this naturally occurring substance. Not only does it scavenge free radicals, but it can actually regenerate other antioxidants.

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.

Citicoline

Citicoline for GlaucomaCiticoline is naturally made within our own bodies. When taken orally it is broken down in the gut into smaller molecules that can be easily absorbed into the bloodstream. From the bloodstream these molecules can enter the brain where they are used to create phosphatidylcholine. The nerve cells in our brains need phosphatidylcholine to function properly. Additionally Citicoline may decrease the production of free radicals which would otherwise damage nerve cells. [9] In general Citicoline can be considered a neuroprotective drug. [10]

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.

Forskolin (Coleus)

Forskolin (Coleus) is an extract from the roots of the plant Plectranthus barbatus (Coleus forskohlii). It has traditionally been used in ayurvedic medicine. [18] Although commonly available as an eyedrop it is also available as an oral supplement.

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

Forskolin (Coleus) for GlaucomaEye 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 ing

Ginkgo Biloba

Ginkgo Biloba for GlaucomaGinkgo biloba is a tree that grows wild in China and is known for its distinctly shaped “duck feet” leaves. The extract from this tree is known to contain two active chemicals: flavonoids, which act as antioxidants [30]; and terpenoids, which have a blood thinning [31]effect. There is evidence that Ginkgo biloba extract can act as a neuroprotective agent. Exactly how it does this is not known. However, it is thought to work through a combination of vasodilation (possibly increasing the blood supply to the optic nerve), antiplatelet action (blood thinning), and antioxidant effect. [32]

Additionally, Ginkgo biloba is a natural source of Quercetin. [33] Quercetin is a member of the flavonoid family of naturally occurring compounds. There is laboratory evidence that Quercetin has antioxidant [34]and anti-inflammatory [35] properties. At higher doses, however, it may also increase oxidative damage. [36] Additionally, the anti-inflammatory properties noted in the laboratory may not be active in the body. [37]

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.

Melatonin

Melatonin (scientific name: N-acetyl-5-methoxytryptamine) is ahormone naturally produced in the brain and retina. [47] It can also befound in a number of plant-based foods such as cherries, [48] walnuts, [49]tomatoes, and strawberries. [50] It has a number of functions, the best known of which is to regulate sleep.

Evidence That Melatonin Can Be Effective in the Treatment of Glaucoma

Melatonin for GlaucomaAs 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.

Mirtogenol®

Mirtogenol® is composed of extracts from bilberry (Mirtoselect®)and French maritime pine bark (Pycnogenol®). These extracts have been shown to increase the blood flow to the eye.

Additionally, there is evidence that bilberry may be a neuroprotective agent.

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

Mirtogenol for GlaucomaInitial 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.

Omega-3 Fatty Acids

Omega-3 fatty acidsOmega-3 fatty acids, commonly found in fish oil, have been shown to benefit conditions ranging from heart disease to dry eye. Two of the most frequently studied omega-3 fatty acids are docosahexaenoicacid (DHA) and eicosapentaenoic acid (EPA). Animal experiments support a role of DHA in retinal health. What about its role in glaucoma?

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.

Palmitoylethanolamide (PEA)

PEA is an endocannabinoid. [90] Our bodies naturally produce endocannabinoids such as PEA. [91] Certain foods such as peanut oil, egg yolk, and soybean lecithin also contain PEA. [92] If the term“endocannabinoid” sounds familiar it is because “cannabis” is the term used to describe plants that produce delta-9-tetrahydrocannabinol(the main active ingredient in marijuana). There is evidence that cannabinoids can be used to treat glaucoma [93] What about PEA?

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.

Resveratrol

Resveratrol for GlaucomaResveratrol is naturally found in the skin of grapes and the wine made from those grapes. [85] It can also be found in Açai berries, [86] grape tomatoes, peanuts, [87] plums, and raspberries. It is most well-known for its possible role in extending lifespan. The evidence supporting this benefit, however, is based on fruit fly (not mammalian) research. Thus, it’s a stretch to believe that humans could derive the same life extending benefit from Resveratrol as do fruit flies.

Although Resveratrol is well absorbed from the gut, very little of it makes it into the general bloodstream. This is because the liver inactivates the vast majority of what is absorbed. [88] Once past the liver, however, Resveratrol appears to be able to pass the blood-brain barrier and enter brain tissue. [89]

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.

Rutin

Rutin is a flavonoid naturally found in apples, buckwheat, elderflowers, eucalyptus, Ginkgo biloba, hawthorn leaves and flowers, Japanese pagoda tree, lime tree flowers, rue, St. John’s Wort, among other fruits and vegetables. It is most concentrated in Ziziphus Jujuba(Chinese/Korean Date). It appears to have antioxidant properties. [102] Rutin is converted in the gastrointestinal tract to quercetin, which is believed to be responsible for many of the touted benefits of Rutin.

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). 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.

Saffron

Saffron is the term used to describe the highly valued spice extracted from the plant Crocus sativus. This spice is rich in the carotenoid derivatives crocin and crocetin. There is evidence that these active compound scan function as powerful antioxidants [108] and neuroprotectants. [109]

Evidence That Saffron Can Be Effective in the Treatment of Glaucoma

Saffron for GlaucomaIn 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.

Tumeric (Curcumin)

Curcumin (chemical name: diferuloylmethane) is an extract of Tumeric, a common spice used throughout India and Asia. [117]

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

Tumeric (Curcumin) for GlaucomaOf 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.

B Vitamins

B vitamins are a group of chemically varied water-soluble vitamins that are often naturally found together in food. There are eight distinct vitamins that are often packaged together in supplements termed “Vitamin B Complex”:ƒƒ Vitamin B1 (thiamin)ƒƒ

  • Vitamin B2 (riboflavin)ƒƒ
  • Vitamin B3 (niacin or niacinamide)ƒƒ
  • Vitamin B5 (pantothenic acid)ƒƒ
  • Vitamin B6 (pyridoxine, pyridoxal, pyridoxamine, orpyridoxine hydrochloride)ƒƒ
  • Vitamin B7 (biotin)ƒƒ
  • Vitamin B9 (folate)ƒƒ
  • Vitamin B12 (various cobalamins such as Methylcobalamin)

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.

Vitamin D

Vitamin D for GlaucomaVitamin D is a fat-soluble chemical naturally produced by our bodies during exposure to the sun. That’s a good thing as there are very few natural dietary sources of Vitamin D other than fatty fish such as herrings, mackerel, sardines, and tuna. Vitamin D helps our bodies absorb critical minerals such as calcium from our gut. Calcium is needed for bone health. As such, Vitamin D supplements are commonly recommended to treat disorders of the bones such as osteoporosis.

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.

Vitamin E

Vitamin E for GlaucomaAlpha-tocopherol is a fat-soluble substance commonly known as“Vitamin E.” As it is naturally found in both vegetable oils and animal fats it is rare to find someone with Vitamin E deficiency. Diet alone appears to adequately provide our daily requirement of Vitamin E.Its primary health benefit appears to be related to its antioxidant properties. [139]

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.

References

[1] Filina A. A., Davydova N. G., Endrikhovskii S. N., Shamshinova A. M. Lipoic acid as a means of metabolic therapy of open-angle glaucoma. Vestn Oftalmol 1995;111(4):6-8.

[2] Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant alphalipoic acid. Free Radic Biol Med.1997;22(1-2):359-78.

[3] Ziegler D, Reljanovic M, Mehnert H, Gries FA. Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials. Exp Clin Endocrinol Diabetes. 1999;107(7):421-30.

[4] Vincent HK, Bourguignon CM, Vincent KR, Taylor AG. Effects of alpha-lipoic acid supplementation in peripheral arterial disease: a pilot study. J Alt Complement Med 2007;13:577-84.

[5] Packer L, Witt EH, Tritschler HJ. Alpha-Lipoic acid as a biological antioxidant. Free Radic Biol Med 1995;19:227-50.

[6] Jacob S, Henriksen EJ, Schiemann AL, et al. Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Arzneimittelforschung 1995;45:872-4.

Jacob S, Ruus P, Hermann R, et al. Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo controlled, pilot trial. Free Rad Biol Med 1999;27:309-14.

Ansar H., Mazloom Z., Kazemi F., Hejazi N. Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients. Saudi Med J 2011;32(6):584-588.

Porasuphatana S, Suddee S, Nartnampong A, et al. Glycemic and oxidative status of patients with type 2 diabetes mellitus following oral administration of alpha-lipoic acid: a randomized double-blinded placebo-controlled study. Asia Pac J Clin Nutr 2012;21(1):12-21.

[7] Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.

[8] Segermann J, Hotze A, Ulrich H, Rao GS. Effect of alpha-lipoic acid on the peripheral conversion of thyroxine to triiodothyronine and on serum lipid-, protein- and glucose levels. Arzneimittelforschung 1991;41:1294-8.

[9] Weiss GB. Metabolism and actions of CDP-choline as an endogenous compound and administered exogenously as citicoline. Life Sci 1995;56:637-60

Adibhatla RM, Hatcher JF. Citicoline decreases phospholipase A2 stimulation and hydroxyl radical generation in transient cerebral ischemia. J Neurosci Res 2003;73:308-15.

[10] Grieb P, Rejdak R: Pharmacodynamics of citicoline relevant to the treatment of glaucoma. J Neurosci Res, 2002; 67:143-8.

[11] 27 Conant R, Schauss AG. Therapeutic applications of citicoline for stroke and cognitive function in the elderly: A review of the literature. Altern Med Rev 2004;9:17-31.

[12] Rejdak R, Toczolowski J, Krukowski J, et al. Oral citicoline treatment improves visual pathway function in glaucoma. Med Sci Monit 2003;9:PI24-8.

Parisi, V., Coppola, G., Centofanti, M., Oddone, F., Angrisani, A. M., Ziccardi, L., Ricci, B., Quaranta, L., and Manni, G. Evidence of the neuroprotective role of citicoline in glaucoma patients. Prog.Brain.Res 2008;173:541-554.

[13] Parisi, V., Manni, G., Colacino, G., and Bucci, M. G. Cytidine-5’-diphosphocholine (citicoline) improves retinal and cortical responses in patients with glaucoma. Ophthalmology. 1999;106(6):1126-1134.

[14] Pecori-Giraldi J, Virno M, Covelli G et al: Therapeutic value of citicoline in the treatment of glaucoma (computerized and automated perimetric investigation). Int Ophthalmol, 1989; 13: 109-12

[15] Ottobelli L, Manni GL, Centofanti M, Iester M, Allevena F, Rossetti L. Citicoline oral solution in glaucoma: Is there a role in slowing disease progression? Ophthalmologica 2013;229:219-26.

[16] Fioravanti M, Yanagi M. Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database Syst Rev 2005;(2):CD000269.

[17] Spiers PA, Myers D, Hochanadel GS, et al. Citicoline improves verbal memory in aging. Arch Neurol 1996;53:441-8.

[18] Ammon HP, Muller AB. Forskolin: From a ayurvedic remedy to a modern agent. Planta Med 1985;6:473-7.

[19] Caprioli J, Sears M, Bausher L, et al. Forskolin lowers intraocular pressure by reducing aqueous inflow. Invest Ophthalmol Vis Sci 1984;25:268-77.

Burstein NL, Sears ML, Mead A. Aqueous flow in human eyes is reduced by forskolin, a potent adenylate cyclase activator. Exp Eye Res 1984;39:745-9.

Brubaker RF, Carlson KH, Kullerstrand LJ, et al. Topical forskolin (colforsin) and aqueous flow in humans. Arch Ophthalmol 1987;105:637-41.

[20] Seto C, Eguchi S, Araie M, et al. Acute effects of topical forskolin on aqueous humor dynamics in man. Jpn J Ophthalmol 1986;30:238-44.

[21] Pescosolido N, Librando A. Oral administration of an asociation of forskolin, rutin and vitamins B1 and B2 potentiates the hypotonising effects of pharmacologic treatments in POAG patients. Clin Ter 2010;161(3):e81-5.

[22] Vetrugno M, Uva M, Russo V, et al. Oral administration of forskolin and rutin contributes to Intraocular Pressure Control in Primary Open Angle Glaucoma 2012;28(5):536-41.

[23] Nebbioso M, Rusciano D, Pucci B, et al. Treatment of glaucomatous patients by means of food supplement to reduce the ocular discomfort: a double blind randomized trial. Eur Rev Med Pharmacol Sci 2013;17(8):1117-1122.

[24] Brubaker RF, Carlson KH, Kullerstrand LJ, et al. Topical forskolin (colforsin) and aqueous flow in humans. Arch Ophthalmol 1987;105:637-41.

[25] Agarwal KC, Zielinski BA, Maitra RS. Significance of plasma adenosine in the antiplatelet activity of forskolin: potentiation by dipyridamole and dilazep. Thromb Haemost 1989;61:106-10. Haemost 1989;61:106-10.

Christenson JT, Thulesius O, Nazzal MM. The effect of forskolin on blood flow, platelet metabolism, aggregation and ATP release. Vasa 1995;24:56-61.

[26] Lindner E, Dohadwalla AN, Bhattacharya BK. Positive inotropic and blood pressure lowering activity of a diterpene derivative isolated from Coleus forskohli: Forskolin. Arzneimittelforschung 1978;28(2):284-289.

Schlepper M, Thormann J, Mitrovic V. Cardiovascular effects of forskolin and phosphodiesterase-III inhibitors. Basic Res Cardiol 1989;84 Suppl 1:197-212.

[27] Lindner E, Metzger H. The action of forskolin on muscle cells is modified by hormones, calcium ions and calcium antagonists. Arzneimittelforschung 1983;33:1436-41.

[28] Kramer W, Thormann J, Kindler M, Schlepper M. Effects of forskolin on left ventricular function in dilated cardiomyopathy. Arzneimittelforschung 1987;37:364-7.

Baumann G, Felix S, Sattelberger U, Klein G. Cardiovascular effects of forskolin (HL- 362) in patients with idiopathic congestiv cardiomyopathy. A comparative study with dobutamine and sodium nitroprusside. J Cardiovasc Pharmacol 1990;16:93-100.

[29] Caprioli J, Sears M. Forskolin lowers intraocular pressure in rabbits, monkeys, and man. Lancet 1983;1:958-60.

Seto C, Eguchi S, Araie M, et al. Acute effects of topical forskolin on aqueous humor dynamics in man. Jpn J Ophthalmol 1986;30:238-44.

Meyer BH, Stulting AA, Muller FO, et al. The effects of forskolin eye drops on intraocular pressure. S Afr Med J 1987;71:570-1.

[30] Marcocci L, Packer L, Droy-Lefaix MT, et al: Antioxidant action of Ginkgo biloba extract EGb 761. Methods Enzymol 234:462–75, 1994

Ko¨se K, Dogˇan P: Lipoperoxidation induced by hydrogen peroxide in human erythrocyte membranes. 1. Protective effect of Ginkgo biloba extract (EGb 761). J Int Med Res 23:1–8, 1995

[31] Braquet P: Proofs of involvement of PAF-acether in various immune disorders using BN 52021 (ginkgolide B): a powerful PAF-acether antagonist isolated from ginkgo biloba L. Adv Prostaglandin Thromboxane Leukot Res 16:179–98, 1986

[32] Kleijnen J, Knipschild P. Ginkgo biloba for cerebral insufficiency. Br J Clin Pharmacol 1992;34:352–8.

Ritch R. A potential role for Ginkgo biloba extract in the treatment of glaucoma. Med Hypotheses 2000;54:221–35.

Heinrich AK, Mozaffarieh M, Flammer J. Ginkgo biloba: An adjuvant therapy for progressive normal and high tension glaucoma. Molecular Vision 2012; 18:390-402.

Kubota Y, Tanaka N, Kagota S, Nakamura K, Kunitomo M, Umegaki K, Shinozuka K. Effects of Ginkgo biloba extract on blood pressure and vascular endothelial response by acetylcholine in spontaneously hypertensive rats. J Pharm Pharmacol. 2006 Feb;58(2):243-9.

Maltas E, Yildiz S. Evaluation of Phytochemicals and Antioxidant Activity of Ginkgo biloba from Turkey. Pharmacologia 2012;3: 113-120

[33] Wang FM, Yao TW, Zeng S. Determination of quercetin and kaempferol in human urine after orally administrated tablet of ginkgo biloba extract by HPLC. J Pharm Biomed Anal. (2003)

[34] Lean ME, Noroozi M, Kelly I. Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. Diabetes 1999;48:176-81.

[35] Anon. Quercetin. Alt Med Rev 1998;3:140-3. Nieman DC, Henson DA, Davis JM, et al. Quercetin’s influence on exercise-induced changes in plasma cytokines and muscle and leukocyte cytokine mRNA. J Appl Physiol 2007;103:1728-35.

[36] Harwood M, Danielewska-Nikiel B, Borzelleca JF, et al. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic / carcinogenic properties. Food Chem Toxicol 2007;45:2179-205.

[37] de Pascual-Teresa S, Johnston KL, DuPont MS, et al. Quercetin metabolites downregulate cyclooxygenase-2 transcription in human lymphocytes ex vivo but not in vivo. J Nutr 2004;134:552-7.

[38] Quaranta L, Bettelli S, Uva MG, Semeraro F, Turano R, Gandolfo E. Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma. Ophthalmology 2003;110:359-62.

[39] Lee J, Sohn S, Kee C. Effect of Ginkgo biloba Extract on Visual Field Progression in Normal Tension Glaucoma. Journal of Glaucoma. 2013; 22:780-784.

[40] Le Bars PL, Katz MM, Berman N, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American Study EGb Group. JAMA 1997;278:1327–32.

[41] Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with Ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med 2005;20;657-61.

[42] Kudolo GB. The effect of 3-month ingestion of Ginkgo biloba extract (EGb 761) on pancreatic beta-cell function in response to glucose loading in individuals with noninsulindependent diabetes mellitus. J Clin Pharmacol 2001;41:600-11.

[43] Miwa H, Iijima M, Tanaka S, Mizuno Y. Generalized convulsions after consuming a large amount of gingko nuts. Epilepsia 2001;42:280-1.

[44] Arenz A, Kelin M, Flehe K, et al. Occurrence of neurotoxic 4’-O-methylpyridoxine in ginkgo biloba leaves, ginkgo medications and Japanese ginkgo food. Planta Med 1996;62:548-51.

[45] Gregory PJ. Seizure associated with Ginkgo biloba? Ann Intern Med 2001;134:344. Granger AS. Ginkgo biloba precipitating epileptic seizures. Age Ageing 2001;30:523-5.

[46] Galluzzi S, Zanetti O, Binetti G, et al. Coma in a patient with Alzheimer’s disease taking low dose trazodone and Ginkgo biloba. J Neurol Neurosurg Psychiatry 2000;68:679-80.

[47] Bernard M, et al. Melatonin synthesis pathway: circadian regulation of the genes encoding the key enzymes in the chicken pineal gland and retina. Reprod Nutr Dev. -1999

[48] Burkhardt S, et al. Detection and quantification of the antioxidant melatonin in Montmorency and Balaton tart cherries (Prunus cerasus). J Agric Food Chem. (2001)

[49] Reiter RJ, Manchester LC, Tan DX. Melatonin in walnuts: influence on levels of melatonin and total antioxidant capacity of blood. Nutrition. (2005)

[50] Iriti M, Varoni EM, Vitalini S. Melatonin in traditional Mediterranean diets. J Pineal Res. (2010)

[51] Samples JR, Krause G, Lewy AJ. Effect of melatonin on intraocular pressure. Curr Eye Res. (1988)

[52] Ismail SA, Mowafi HA. Melatonin provides anxiolysis, enhances analgesia, decreases intraocular pressure, and promotes better operating conditions during cataract surgery under topical anesthesia. Anesth Analg. (2009)

[53] Crooke A, et al. Regulation of ocular adrenoceptor genes expression by 5-MCA-NAT: implications for glaucoma treatment. Pharmacogenet Genomics. (2011)

Crooke A, et al. Involvement of carbonic anhydrases in the ocular hypotensive effect of melatonin analogue 5-MCA-NAT. J Pineal Res. (2012)

[54] Zwirska-Korczala K, et al. Influence of melatonin on cell proliferation, antioxidative enzyme activities and lipid peroxidation in 3T3-L1 preadipocytes–an in vitro study. J Physiol Pharmacol. (2005)

Allegra M, et al. The chemistry of melatonin’s interaction with reactive species. J Pineal Res. (2003)

Reiter RJ, et al. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem Biophys. (2001)

Poeggeler B, et al. Melatonin–a highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci. (1994)

Noda Y, et al. Melatonin and its precursors scavenge nitric oxide. J Pineal Res. (1999)

Zhang H, Squadrito GL, Pryor WA. The reaction of melatonin with peroxynitrite: formation of melatonin radical cation and absence of stable nitrated products. Biochem Biophys Res Commun. (1998)

[55] Wang JZ, Wang ZF. Role of melatonin in Alzheimer-like neurodegeneration. Acta Pharmacol Sin. (2006)

[56] Kwon KJ, et al. Melatonin Potentiates the Neuroprotective Properties of Resveratrol Against Beta-Amyloid-Induced Neurodegeneration by Modulating AMP-Activated Protein Kinase Pathways. J Clin Neurol. (2010)

Kwon KJ, et al. Melatonin synergistically increases resveratrol-induced heme oxygenase-1 expression through the inhibition of ubiquitin-dependent proteasome pathway: a possible role in neuroprotection. J Pineal Res. (2011)

[57] Valcavi R, et al. Effect of oral administration of melatonin on GH responses to GRF 1-44 in normal subjects. Clin Endocrinol (Oxf). (1987)

[58] Carr R, et al. Long-term effectiveness outcome of melatonin therapy in children with treatment-resistant circadian rhythm sleep disorders. J Pineal Res. (2007)

[59] Arangino S, et al. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol. (1999)

Nishiyama K, et al. Acute effects of melatonin administration on cardiovascular autonomic regulation in healthy men. Am Heart J. (2001) Cagnacci A, et al. Influences of melatonin administration on the circulation of women. Am J Physiol. (1998)

References

”]

[60] Steigerwalt RD, Belcaro G, Paolo M, Bombardelli E, Burki C, Schönlau F. Effects of Mirtogenol on ocular blood flow and intraocular hypertension in asymptomatic subjects. Mol Vis. 2008;14:1288–1292.

[61] Steigerwalt RD, Belcaro G, Paolo M, Bombardelli E, Burki C, Schönlau F. Mirtogenol potentiates latanoprost in lowering intraocular pressure and improves ocular blood flow in asymptomatic subjects. Clinical Ophthalmology 2010; 4: 471-476.

[62] Shim SH. Kim JM, Choi CY, Kim CY, Park KH. Ginkgo biloba extract and bilberry anthocyanins improve visual function in patients with normal tension glaucoma. J Med Food 2012;15(9):818-823.

[63] Putter M, Grotemeyer KH, Wurthwein G, et al. Inhibition of smoking-induced platelet aggregation by aspirin and pycnogenol. Thromb Res 1999;95:155-61.

Araghi-Niknam, M., Hosseini, S., Larson, D., Rohdewald, P., and Watson, R. R. Pine bark extract reduces platelet aggregation. Integr.Med. 3-21-2000;2(2):73-77.

Wang S, Tan D Zhao Y et al. The effect of pycnogenol on the microcirculation, platelet function and ischemic myocardium in patients with coronary artery diseases. Eur Bull Drug Res 1999;7:19-25.

[64] Lankinen, M., Schwab, U., Kolehmainen, M., Paananen, J., Poutanen, K., Mykkanen, H., Seppanen-Laakso, T., Gylling, H., Uusitupa, M., and Oresic, M. Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the Sysdimet study. PLoS One 2011;6(8).

Liu X, Wei J, Tan F, et al. Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II. Life Sci 2004;75:2505-13.

[65] Rice-Evans CA, Packer L, eds. Flavonoids in Health and Disease. Manhattan, NY: Marcel Dekker, Inc., 1998.

Liu FJ, Zhang YX, Lau BH. Pycnogenol enhances immune and haemopoietic functions in senescence-accelerated mice. Cell Mol Life Sci 1998;54:1168-72.

[66] Rice-Evans CA, Packer L, eds. Flavonoids in Health and Disease. Manhattan, NY: Marcel Dekker, Inc., 1998.

Liu FJ, Zhang YX, Lau BH. Pycnogenol enhances immune and haemopoietic functions in senescence-accelerated mice. Cell Mol Life Sci 1998;54:1168-72.

[67] Mancino M, Ohia E, Kulkarni P. A comparative study between cod liver oil and liquid lard intake on IOP in rabbits. Prostaglandins Leukot Essent Fatty Acids . 1992;45:239– 243

[68] Nguyen CTO, Bui BV, Sinclair AJ, et al. Dietary omega 3 fatty acids decrease intraocular pressure with age by increasing aqueous outflow facility. Invest Opthalmol Vis Sci . 2007;48:756–762.

[69] Cellini M, Caramazza N, Mangiafi co P, et al. Fatty acid use in glaucomatous optic neuropathy treatment. Acta Ophthalmol Scand . 1998;227(suppl):41–42.

[70] Galbis-Estrada C, Pinazo-Durán MD, Cantú-Dibildox J, Marco-Ramírez C, Díaz- Llopis M, Benítez-del-Castillo J. Patients undergoing long-term treatment with antihypertensive eye drops responded positively with respect to their ocular surface disorder to oral supplementation with antioxidants and essential fatty acids. Clin Interv Aging. 2013;8:711–719.

[71] Terano T, Hirai A, Hamazaki T, et al. Effect of oral administration of highly purified eicosapentaenoic acid on platelet function, blood viscosity and red cell deformability in healthy human subjects. Atherosclerosis 1983;46:321-31

[72] Woodman RJ, Mori TA, Burke V, et al. Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr 2002;76:1007-15.

[73] Prisco D, Paniccia R, Bandinelli B, et al. Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients. Thromb Res 1998;1:105-12.

Toft I, Bonaa KH, Ingebretsen OC, et al. Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial. Ann Intern Med 1995;123:911-8.

Sacks FM, Hebert P, Appel LJ, et al. Short report: the effect of fish oil on blood pressure and high-density lipoprotein-cholesterol levels in phase I of the trials of hypertension prevention. J Hypertens 1994;12:209-13.

Vandongen R, Mori TA, Burke V, et al. Effects on blood pressure of omega 3 fats in subjects at increased risk of cardiovascular disease. Hypertension 1993;22:371-9.

References

”]

[74] Lambert DM, Di Marzo V. The palmitoylethanolamide and oleamide enigmas: are these two fatty acid amides cannabimimetic? Curr Med Chem. 1999;6:757–773.

[75] Bachur NR, Masek K, Melmon KL, Udenfriend S. Fatty acid amides of ethanolamine in mammalian tissues. J Biol Chem. 1965;240:1019–1024.

[76] Kuehl FA, Jacob TA, Ganley OH, Ormond RE, Meisinger MAP. The identification of N-(2-hydroxyethyl)-palmitamide as a naturally occurring anti-inflammatory agent. J Am Chem Soc. 1957;79:5577–5578.

[77] Buchwald A, Browne CE, Wu WM, Ji F, Bodor N. Soft cannabinoid analogues as potential anti-glaucoma agents. Pharmazie. 2000;55:196–201.

[78] Kumar A, Qiao Z, Kumar P, Song ZH. Effects of palmitoylethanolamide on aqueous humor outflow. Invest Ophthalmol Vis Sci. 2012 Jul 3;53(8):4416-25.

[79] Chen J, Matias I, Dinh T, et al. Finding of endocannabinoids in human eye tissues: implications for glaucoma. Biochem Biophys Res Commun. 2005;330:1062–1067.

[80] Gagliano C, Ortisi E, Pulvirenti L, et al. Ocular hypotensive effect of oral palmitoylethanolamide: a clinical trial. Invest Ophthalmol Vis Sci. 2011;52:6096–6100.

[81] Strobbe E, Cellini M, Campos EC. Effectiveness of palmitoylethanolamide on endothelial dysfunction in ocular hypertensive patients: a randomized, placebo controlled cross-over study. Invest Ophthalmol Vis Sci. 2013 Feb 1;54(2):968-73.

[82] Gagliano C, Longo A, Uva MG, Reibaldi M, Amato R, Russo V, Biondi P, Avitabile T. Clinical trial for the evaluation of neuroprotective effects of palmitoylethanolamide: Visual Field and Pattern-ERG. Paper presented at: EVER 2012. 2013 Oct 10-13; Nice, France.

[83] Costagliola C, Romano MR, dell’Omo R, Russo A, Mastropasqua R, Semeraro F. Effect of palmitoylethanolamide on visual field damage progression in normal tension glaucoma patients: results of an open-label six-month follow-up. J Med Food. 2014 Sep;17(9):949-54.

[84] Keppel Hesselink JM. New targets in pain, non-neuronal cells, and the role of palmitoylethanolamide. Open Pain J. 2012;5:12–23.

[85] Huang X, Mazza G. Simultaneous analysis of serotonin, melatonin, piceid and resveratrol in fruits using liquid chromatography tandem mass spectrometry. J Chromatogr A. (2011)

[86] Poulose SM, et al. Anthocyanin-rich açai (Euterpe oleracea Mart.) fruit pulp fractions attenuate inflammatory stress signaling in mouse brain BV-2 microglial cells. J Agric Food Chem. (2012)

[87] Sobolev VS, Cole RJ. trans-resveratrol content in commercial peanuts and peanut products. J Agric Food Chem. (1999)

[88] Cottart CH, et al. Resveratrol bioavailability and toxicity in humans. Mol Nutr Food Res. (2010)

[89] Wang Q, et al. Resveratrol protects against global cerebral ischemic injury in gerbils. Brain Res. (2002)

[90] Bureau G, Longpré F, Martinoli MG. Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J Neurosci Res. (2008)

[91] Wang Q, et al. Resveratrol protects against global cerebral ischemic injury in gerbils. Brain Res. (2002)

Moldzio R, et al. Protective effects of resveratrol on glutamate-induced damages in murine brain cultures. J Neural Transm. (2013).

Lee JG, et al. Combined treatment with capsaicin and resveratrol enhances neuroprotection against glutamate-induced toxicity in mouse cerebral cortical neurons. Food Chem Toxicol. (2012)

[92] Kwon KJ, et al. Melatonin Potentiates the Neuroprotective Properties of Resveratrol Against Beta-Amyloid-Induced Neurodegeneration by Modulating AMP-Activated Protein Kinase Pathways. J Clin Neurol. (2010)

Kwon KJ, et al. Melatonin synergistically increases resveratrol-induced heme oxygenase-1 expression through the inhibition of ubiquitin-dependent proteasome pathway: a possible role in neuroprotection. J Pineal Res. (2011)

[93] Murias M, Handler N, Erker T, et al. Resveratrol analogues as selective cyclooxygenase-2 inhibitors: synthesis and structure-activity relationship. Bioorg Med Chem 2004;12:5571-8.

[94] Wang N, Chintala SK, Fini ME, Schuman JS. Activation of a tissue-specific stress response in the aqueous outflow pathway of the eye defines the glaucoma disease phenotype. Nat Med 2001;7:304–309.

[95] Alvarado J, Murphy C, Polansky J, Juster R. Age-related changes in trabecular meshwork cellularity. Invest Ophthalmol Vis Sci 1981;21:714–727.

Alvarado J, Murphy C, Juster R. Trabecular meshwork cellularity in primary openangle glaucoma and nonglaucomatous normals. Ophthalmology 1984;91:564–579.

[96] Luna C, Li G, Liton PB, et al. Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells. Food Chem Toxicol. 2009;47(1):dse198–204. doi:10.1016/j.fct.2008.10.029.

[98] Howells LM, et al. Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases–safety, pharmacokinetics, and pharmacodynamics. Cancer Prev Res (Phila). (2011)

[99] Gehm BD, McAndrews JM, Chien PY, Jameson JL. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci U S A 1997;94:14138-43.

Basly, J. P., Marre-Fournier, F., Le Bail, J. C., Habrioux, G., and Chulia, A. J. Estrogenic/ antiestrogenic and scavenging properties of (E)- and (Z)-resveratrol. Life Sci. 1-21- 2000;66(9):769-777.

Levenson, A. S., Gehm, B. D., Pearce, S. T., Horiguchi, J., Simons, L. A., Ward, J. E., III, Jameson, J. L., and Jordan, V. C. Resveratrol acts as an estrogen receptor (ER) agonist in breast cancer cells stably transfected with ER alpha. Int.J.Cancer 5-1- 2003;104(5):587- 596.

[100] Pace-Asciak CR, Hahn S, Diamandis EP, et al. The red wine phenolics transresveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta 1995;235:207-19.

Bertelli AA, Giovannini L, Giannessi D, et al. Antiplatelet activity of synthetic and natural resveratrol in red wine. Int J Tissue React 1995;17:1-3.

Pace-Asciak CR, Rounova O, Hahn SE, et al. Wines and grape juices as modulators of platelet aggregation in healthy human subjects. Clin Chim Acta 1996;246:163-82.

Bertelli AA, Giovannini L, Bernini W, et al. Antiplatelet activity of cis-resveratrol. Drugs Exp Clin Res 1996;22:61-3.

[101] Timmers S, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. (2011)

[102] Kostyuk VA, Potapovich AI. Antiradical and chelating effects in flavonoid protection against silica-induced cell injury. Arch Biochem Biophys 1998;355:43-8.

[103] Pescosolido N, Librando A. Oral administration of an asociation of forskolin, rutin and vitamins B1 and B2 potentiates the hypotonising effects of pharmacologic treatments in POAG patients. Clin Ter 2010;161(3):e81-5.

[104] Vetrugno M, Uva M, Russo V, et al. Oral administration of forskolin and rutin contributes to Intraocular Pressure Control in Primary Open Angle Glaucoma Patients Under Maximum Tolerated Medical Therapy. J ocul Pharmacol Ther 2012;28(5):536-41.

[105] Nebbioso M, Rusciano D, Pucci B, et al. Treatment of glaucomatous patients by means of food supplement to reduce the ocular discomfort: a double blind randomized trial. Eur Rev Med Pharmacol Sci 2013;17(8):1117-1122.

[106] Mehta DK (Ex Ed). British National Formulary, Number 37. British Medical Association and Royal Pharmaceutical Society of Great Britain: London, England, March 1999.

[107] Miksicek RJ. Commonly occurring plant flavonoids have estrogenic activity. Mol Pharmacol. 1993 Jul;44(1):37-43.

[108] Assimopoulou AN, Sinakos Z, Papageorgiou VP. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res 2005;19(11):997–1000.

[109] Ochiai T, Shimeno H, Mi shima K, Iwasaki K, Fujiwara M, Tanaka H, Shoyama Y, Toda A, Eyanagi R, Soeda S. Protective effects of carotenoids from saffronon neuronal injury invitro and invivo. Biochim Biophys Acta 2007;1770(4):578–584.

[110] Jabbarpo, Bonyadi, et al. The ocular hypotensive effect of saffron extract in primary open angle glaucoma: a pilot study. BMC Complementary and Alternative Medicine 2014;14:399.

[111] Electronic Code of Federal Regulations. Title 21. Part 182 — Substances Generally Recognized As Safe. Available at: http://ecfr.gpoaccess.gov/cgi/t/text/ text-idx?c=ecfr&sid= 786bafc6f6343634fbf79fcdca7061e1&rgn=div5&view= text&node=21:3.0.1.1.13&idno=21

[112] Akhondzadeh S, Tahmacebi-Pour N, Noorbala AA, et al. Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebocontrolled trial. Phytother Res 2005;19:148-51.

Safarinejad MR, Shafiei N, Safarinejad S. A prospective double-blind randomized placebo-controlled study of the effect of saffron (Crocus sativus Linn.) on semen parameters and seminal plasma antioxidant capacity in infertile men with idiopathic oligoasthenoteratozoospermia. Phytother Res 2011;25:508-16.

[113] Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.

[114] McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association’s Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical Economics Company, Inc., 1998.

[115] Imenshahidi M, Hosseinzadeh H, Javadpour Y. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother.Res 12-9-2009.

Fatehi M, Rashidabady T, Fatehi-Hassanabad Z. Effects of Crocus sativus petals’ extract on rat blood pressure and on responses induced by electrical field stimulation in the rat isolated vas deferens and guinea-pig ileum. J Ethnopharmacol. 2003;84(2-3):199- 203.

[116] Boskabady MH, Shafei MN, Shakiba A, Sefidi HS. Effect of aqueous-ethanol extract from Crocus sativus (saffron) on guinea-pig isolated heart. Phytother Res 2008;22(3):330-334.

[117] Goel A, et al., Curcumin as ‘‘Curecumin’’: From kitchen to clinic, Biochem Pharmacol (2007), doi:10.1016/j.bcp.2007.08.016

[118] Cole GM, Teter B, Grautschy SA. Neuroprotective effects of curcumin. Adv Exp Med Biol 2007;595:197-212.

[119] Deshpande S, et al. Subchronic oral toxicity of turmeric and ethanolic turmeric extract in female mice and rats. Toxicology Letters. 1998;95:183-193.

Kandarkar SV, Sawant SS, Ingle AD, et al. Subchronic oral hepatotoxicity of turmeric in mice–histopathological and ultrastructural studies. Indian J Exp Biol. 1998;36:675- 679

[120] Kiso Y, Suzuki Y, Watanabe N, Oshima Y, Hikino H. Antihepatotoxic principles of Curcuma longa rhizomes. Planta Med 1983;49:185–7.

[121] Lao CD, Ruffin MTt, Normolle D, Heath DD, Murray SI, Bailey JM, et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 2006;6:10.

[122] Srivastava, R., Dikshit, M., Srimal, R. C., and Dhawan, B. N. Anti-thrombotic effect of curcumin. Thromb Res 11-1-1985;40(3):413-417.

Srivastava, R., Puri, V., Srimal, R. C., and Dhawan, B. N. Effect of curcumin on platelet aggregation and vascular prostacyclin synthesis. Arzneimittelforschung. 1986;36(4):715-717.

Srivastava, K. C., Bordia, A., and Verma, S. K. Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins Leukot.Essent.Fatty Acids 1995;52(4):223- 227.

Shah BH, Nawaz Z, Pertani SA. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol 1999;58:1167-72.

[123] Arun, N. and Nalini, N. Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats. Plant Foods Hum.Nutr. 2002;57(1):41-52.

Nishiyama, T., Mae, T., Kishida, H., Tsukagawa, M., Mimaki, Y., Kuroda, M., Sashida, Y., Takahashi, K., Kawada, T., Nakagawa, K., and Kitahara, M. Curcuminoids and sesquiterpenoids in turmeric (Curcuma longa L.) suppress an increase in blood glucose level in type 2 diabetic KK-Ay mice. J Agric Food Chem. 2005;53(4):959-963.

Seo, K. I., Choi, M. S., Jung, U. J., Kim, H. J., Yeo, J., Jeon, S. M., and Lee, M. K. Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Mol Nutr Food Res 2008;52(9):995-1004.

Weisberg, S. P., Leibel, R., and Tortoriello, D. V. Dietary curcumin significantly improves obesity-associated inflammation and diabetes in mouse models of diabesity. Endocrinology 2008;149(7):3549-3558.

Yu, Y., Hu, S. K., and Yan, H. The study of insulin resistance and leptin resistance on the model of simplicity obesity rats by curcumin Zhonghua Yu Fang Yi.Xue.Za Zhi. 2008;42(11):818-822.

Madkor, H. R., Mansour, S. W., and Ramadan, G. Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats. Br J Nutr 2011;105(8):1210-1217.

Srinivasan, M. Effect of curcumin on blood sugar as seen in a diabetic subject. Indian J Med Sci 1972;26(4):269-270.

[124] Rasyid A, Rahman AR, Jaalam K, Lelo A. Effect of different curcumin dosages on human gall bladder. Asia Pac J Clin Nutr 2002;11:314-8

[125] Thamlikitkul V, Bunyapraphatsara N, Dechatiwongse T, et al. Randomized double blind study of Curcuma domestica Val. for dyspepsia. J Med Assoc Thai 1989;72:613- 20

[126] Carroll RE, Benya RV, Turgeon DK, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 2011;4:354-64

[127] Ashok, P. and Meenakshi, B. Contraceptive effect of Curcuma longa (L.) in male albino rat. Asian J Androl 2004;6(1):71-74.

Mishra, R. K. and Singh, S. K. Reversible antifertility effect of aqueous rhizome extract of Curcuma longa L. in male laboratory mice. Contraception 2009;79(6):479-487.

Hu, G. X., Liang, G., Chu, Y., Li, X., Lian, Q. Q., Lin, H., He, Y., Huang, Y., Hardy, D. O., and Ge, R. S. Curcumin derivatives inhibit testicular 17beta-hydroxysteroid dehydrogenase 3. Bioorg.Med.Chem.Lett. 4-15-2010;20(8):2549-2551.

Naz, R. K. Can curcumin provide an ideal contraceptive? Mol.Reprod.Dev 2011;78(2):116-123.

[128] Tuntipopipat, S., Judprasong, K., Zeder, C., Wasantwisut, E., Winichagoon, P., Charoenkiatkul, S., Hurrell, R., and Walczyk, T. Chili, but not turmeric, inhibits iron absorption in young women from an iron-fortified composite meal. J Nutr. 2006;136(12):2970-2974.

[129] Srichairatanakool, S., Thephinlap, C., Phisalaphong, C., Porter, J. B., and Fucharoen, S. Curcumin contributes to in vitro removal of non-transferrin bound iron by deferiprone and desferrioxamine in thalassemic plasma. Med.Chem. 2007;3(5):469- 474

Jiao, Y., Wilkinson, J., Christine, Pietsch E., Buss, J. L., Wang, W., Planalp, R., Torti, F. M., and Torti, S. V. Iron chelation in the biological activity of curcumin. Free Radic.Biol. Med. 4-1-2006;40(7):1152-1160.

Tuntipopipat, S., Zeder, C., Siriprapa, P., and Charoenkiatkul, S. Inhibitory effects of spices and herbs on iron availability. Int.J Food Sci.Nutr. 2009;60 Suppl 1:43-55.

[130] Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001;21:2895–900.

Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998;64:353–6.

[131] Sharma RA, McLelland HR, Hill KA, et al. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res 2001;7:1894-900.

Baum L, Lam CW, Cheung SK, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease (letter). J Clin Psychopharmacol 2008;28:110-3.

Carroll RE, Benya RV, Turgeon DK, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 2011;4:354-64.

[132] Baum L, Lam CW, Cheung SK, et al. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease (letter). J Clin Psychopharmacol 2008;28:110-3.

[133] Cellini M, Caramazza N, Mangiafico P, et al. Fatty acid use in glaucomatous optic neuropathy treatment. Acta Ophthalmol Scand. 1998;227(suppl):41–42.

[134] Azumi I, Kosaki H, Nakatani H. Effects of metcobalamin (Methylcobal) on the visual field of chronic glaucoma – a multi-center open study. Folia Ophthalmol Jpn. 1983;34:873–878.

Ichikawa H, Shiose Y, Tanabe Y, et al. Effect of Methycobal for visual field change of glaucoma – multicenter clinical trial by controlled study. Journal of the Eye. 1988;5:617- 624.

Kojima Y, Futa R, Furuyoshi N, et al. The long-term effect of mecobalamine on visual function in glaucomatous eyes. Folia Ophthalmol Jpn. 1990;41:1314-1318.

Sasaki T, Murata M, Amemiya T. Effect of long-term treatment of glaucoma with vitamin B12. Glaucoma. 1992;14:167-170.

[135] Shiose Y. The efficacy of methylcobalamine against low-tension glaucoma. Folia Ophthalmol Jpn. 1988;39:750-756.

Yamazaki Y, Hayamizu F, Nakagami T, et al. Effect of peroral mecobalamine on the visual field defect in normal-tension glaucoma. Jpn J Clin Ophthalmol. 1998;52:915- 919

Yamazaki Y, Hayamizu F, Tanaka C. Effects of long-term methylcobalamin treatment on the progression of visual fi eld defects in normal-tension glaucoma. Curr Ther Res. 2000;61:443–451.

[136] Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999

[137] Yamazaki Y, Hayamizu F, Tanaka C. Effects of long-term methylcobalamin treatment on the progression of visual fi eld defects in normal-tension glaucoma. Curr Ther Res. 2000;61:443–451.

Yoo TK, Oh E, Hong S. Is vitamin D status associated with open-angle glaucoma? A cross-sectional study from South Korea. Public Health Nutr. 2014 Apr;17(4):833-43.

[139] Jiang Q, Christen S, Shigenaga MK, Ames BN. gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am J Clin Nutr 2001;74:714-22.

[140] Cellini M, Caramazza N, Mangiafico P, et al. Fatty acid use in glaucomatous optic neuropathy treatment. Acta Ophthalmol Scand. 1998;227(suppl):41–42.

[141] Haas AL, Boscoboinik D, Mojon DS, et al. Vitamin E inhibits proliferation of human Tenon’s capsule fi broblasts in vitro. Ophthalmic Res. 1996;28:171–175.

[142] Pinilla I, Larrosa JM, Polo V, et al. Alpha-tocopherol derivatives in an experimental model of fi ltering surgery. Ophthalmic Res. 1999;31:440–445.

[143] Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/

[144] Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: High-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005;142:60520- 53

Lonn E, Bosch J, Yusuf S, et al. HOPE and HOPE-TOO Trial Investigators. Effects of longterm vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005;293:1338-47.

Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and metaanalysis. JAMA 2007;297:842-57.

Hayden KM, Welsh-Bohmer KA, Wengreen HJ, et al; Cache County Investigators. Risk of mortality with vitamin E supplements: the Cache County study. Am L Med 2007;120:180-4.

[145] Celestini A, Pulcinelli FM, Pignatelli P, et al. Vitamin E potentiates the antiplatelet activity of aspirin in collagen-stimulated platelets. Haematologica 2002;87:420-6.

Freedman JE, Farhat JH, Loscalzo J, Keaney JF. Alpha-tocopherol inhibits aggregation of human platelets by a protein kinase C-dependent mechanism. Circulation 1996;94:2434-40.

Stampfer MJ, Jakubowski JA, Faigel D, et al. Vitamin E supplementation effect on human platelet function, arachidonic acid metabolism, and plasma prostacyclin levels. Am J Clin Nutr 1988;47:700-6.

[146] Lonn E, Bosch J, Yusuf S, et al. HOPE and HOPE-TOO Trial Investigators. Effects of long – term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005;293:1338-47.

[147] Hayden KM, Welsh-Bohmer KA, Wengreen HJ, et al; Cache County Investigators. Risk of mortality with vitamin E supplements: the Cache County study. Am L Med 2007;120:180-4.

[148] Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst 2007;99:754-64.

Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011;306:1549- 56

[149] Berson EL, Rosner B, Sandberg MA, et al. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol 1993;111:761-72.

[150] Hayden KM, Welsh-Bohmer KA, Wengreen HJ, et al; Cache County Investigators. Risk of mortality with vitamin E supplements: the Cache County study. Am L Med 2007;120:180-4.

[151] Booth SL, Golly I, Sacheck JM, et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr 2004;80:143-8.

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