Palmitoylethanolamide (PEA) in Glaucoma: A Review of Clinical Evidence
Glaucoma is an eye disease marked by optic nerve damage, often linked to high intraocular pressure (IOP). Standard glaucoma treatments focus on lowering IOP, but researchers are exploring neuroprotective supplements as add-ons. One promising compound is palmitoylethanolamide (PEA), a naturally occurring fatty acid amide with anti-inflammatory and neuroprotective effects (pmc.ncbi.nlm.nih.gov). PEA is found in foods (egg, soy, peanuts) and made in our bodies; it interacts with the endocannabinoid system and PPAR-α receptors to calm nerve inflammation. In Italy and parts of Europe, PEA is even sold as a medical food (e.g. “PeaPure,” Normast) for eye health (pmc.ncbi.nlm.nih.gov). Importantly, a recent analysis found that PEA treatment significantly lowers IOP in glaucoma and ocular hypertension patients (pubmed.ncbi.nlm.nih.gov). In practice, PEA is usually given orally (often 600 mg per day in divided doses) alongside regular eye drops. This article reviews human trials of PEA in glaucoma, focusing on IOP reduction, nerve protection, dosing, and safety.
PEA and Intraocular Pressure
Several clinical trials have tested whether oral PEA can help lower IOP in glaucoma or ocular hypertension. In these studies, patients usually continued their usual eye drops and added PEA tablets. A key finding is that PEA tends to produce a modest but statistically significant drop in IOP compared to control. For example, one randomized crossover trial added PEA (300 mg twice daily) to glaucoma therapy (timolol drops) in patients with open-angle glaucoma or ocular hypertension (pubmed.ncbi.nlm.nih.gov). After two months on PEA, mean IOP fell by about 3.5 mmHg (15%) from baseline, versus only ~0.3 mmHg with placebo (pubmed.ncbi.nlm.nih.gov). No changes in vision or side effects were seen. In practical terms, that 3.5 mmHg drop can be meaningful toward preventing nerve damage.
Another well-designed study looked at ocular hypertensive patients (IOP above normal but no optic nerve damage) in a placebo-controlled crossover design (pubmed.ncbi.nlm.nih.gov). Participants took 300 mg PEA twice a day for 3 months (with a 2-month washout then switch). The PEA period showed significantly lower IOP (around 22.2 mmHg) compared to placebo (23.0 mmHg) (pubmed.ncbi.nlm.nih.gov) – a reduction of about 0.8 mmHg. More strikingly, vascular function (flow-mediated dilation of the brachial artery) improved significantly on PEA and stayed better even after stopping PEA (pubmed.ncbi.nlm.nih.gov). This suggests PEA not only lowers eye pressure slightly, but also boosts blood vessel health, which may benefit glaucoma.
A meta-analysis of these trials confirms PEA’s pressure effect. Daily PEA intake (typically 600 mg total) was associated with about a 1.3 mmHg greater IOP reduction than placebo on average (pmc.ncbi.nlm.nih.gov). In plain terms, patients on PEA consistently saw small, statistically significant drops in IOP beyond what standard drops achieved (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Even if 1–3 mmHg sounds minor, every bit helps protect glaucoma nerves. For example, one review concluded: “PEA showed significant efficacy in reducing IOP in patients…encouraging its clinical use in glaucoma” (pubmed.ncbi.nlm.nih.gov).
Some trials focused on specific situations. After laser iridotomy (a YAG laser opening in the iris, which can cause a temporary pressure spike), patients were pretreated with PEA or placebo for 2 weeks (2 tablets/day). The PEA group did not experience the usual IOP jump seen in the placebo group (pubmed.ncbi.nlm.nih.gov). In other words, PEA “counteracted” the post-laser pressure rise, likely by reducing inflammation in the eye (pubmed.ncbi.nlm.nih.gov).
In summary, PEA taken orally (usually 300 mg twice daily, or 600 mg total) for weeks to months has lowered IOP in multiple small trials. The average IOP drop with PEA has been on the order of 1–3 mmHg relative to placebo (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). That effect size, while modest, is consistent and statistically significant in analyses of the data (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Notably, PEA was studied in different glaucoma subtypes: primary open-angle glaucoma (POAG), ocular hypertension (OH), and normal-tension glaucoma (NTG) (see below) (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). It appears to have pressure-lowering action across these groups.
PEA’s Effects on the Retina and Neuroinflammation
Glaucoma involves chronic neuroinflammation and damage to retinal ganglion cells (RGCs). PEA’s known anti-inflammatory and neuroprotective actions make it an attractive adjunct for this aspect of glaucoma. One way to study retinal nerve function is the pattern electroretinogram (PERG), which measures electrical responses of RGCs. In a randomized crossover trial (40 patients, mostly POAG) PEA 600 mg once daily (one tablet) was added to ongoing drops for four months (pubmed.ncbi.nlm.nih.gov). Compared to the untreated period, PEA significantly increased the PERG P50 amplitude (improved nerve signal strength) and lowered IOP by about 1.6 mmHg (pubmed.ncbi.nlm.nih.gov). Patients also reported better quality-of-life scores. This suggests PEA may enhance retinal function and patient well-being in glaucoma (pubmed.ncbi.nlm.nih.gov).
Similarly, the NTG trial found that PEA slowed visual field loss: after 6 months on 300 mg twice daily, visual field mean deviation and pattern standard deviation improved significantly from baseline (while the untreated group worsened) (pubmed.ncbi.nlm.nih.gov). This trial supports the idea that PEA’s benefit extends beyond just pressure – it may protect nerve fibers and vision.
Mechanistically, PEA is believed to dampen harmful glial activity and inflammatory mediators in the eye (pmc.ncbi.nlm.nih.gov). A 2015 review called PEA an “endogenous cell-protective lipid” and noted its “anti-inflammatory and neuroprotective” properties in retinal diseases (pmc.ncbi.nlm.nih.gov). In animal models, PEA has been shown to reduce inflammatory cytokines and retinal cell damage. While human trials haven’t directly measured eye inflammation markers, the improved retinal electrophysiology and visual fields seen with PEA suggest it may be mitigating the chronic low-grade inflammation that contributes to glaucoma progression.
Dosing Regimens and Treatment Duration
Across studies, the dosing of PEA has been fairly consistent. Most trials used 300 mg tablets twice daily (total 600 mg/day). For example, the POAG/OH trial used 300 mg BID for 2 months (pubmed.ncbi.nlm.nih.gov), the ocular hypertensive study 300 mg BID for 3 months (pubmed.ncbi.nlm.nih.gov), and the NTG study 300 mg BID for 6 months (pubmed.ncbi.nlm.nih.gov). The PERG trial used one 600 mg tablet once daily for 4 months (pubmed.ncbi.nlm.nih.gov). Many studies specifically used ultramicronized or micronized PEA, which improves absorption (pubmed.ncbi.nlm.nih.gov).
Treatment durations varied from 2 weeks (laser iridotomy pre-treatment) up to 6 months (NTG study). In the crossover PERG trial, one 4-month PEA period showed effects, and longer follow-up was implied. In general, benefits were seen within a few months. Clinicians considering PEA often start with at least a month-long trial.
While most trials stuck to 600 mg/day, note that PEA has been safely used at higher doses in other contexts. For instance, studies in pain and neurological conditions have tested up to 1.8 grams per day without serious issues (pmc.ncbi.nlm.nih.gov). However, in glaucoma the standard supplements and trials have used the 600 mg/day regimen. Potential side effects are minimal, so dosing can be adjusted under medical advice.
Safety and Product Quality
PEA safety in these trials was excellent. None of the glaucoma studies reported serious adverse effects. For example, the ocular hypertension trial explicitly noted “No side effects were observed” on PEA (pubmed.ncbi.nlm.nih.gov), and the NTG study likewise found “neither ocular nor systemic side effects” after 6 months (pubmed.ncbi.nlm.nih.gov). The PERG study did not report any dropouts or drug-related problems. These findings are consistent with broader safety data: one review noted that PEA (in ultramicronized form) was “found to be safe and effective up to 1.8 g/day, with excellent tolerability” in various trials (pmc.ncbi.nlm.nih.gov).
In practice, PEA is classified as a dietary supplement or medical food in many countries. Quality can vary between products, so patients should use reputable brands. In Italy, PEA supplements like Normast and PeaVera are regulated as diet foods for medical purposes (particularly for glaucoma and neuroinflammation) (pmc.ncbi.nlm.nih.gov). These formulations are typically ultramicronized to enhance bioavailability. Patients should look for pharmaceutical-grade or medical-grade PEA preparations if using it as a glaucoma supplement.
Minor tolerability issues are rare. Some people might feel slight digestive upset or drowsiness, but none of the trials reported significant complaints or lab abnormalities on PEA. Since no drug interactions specific to glaucoma medications have emerged, PEA can generally be added to a patient’s regimen without affecting standard treatments. As always, patients should discuss any supplement use with their doctor.
Who Might Benefit Most?
PEA appears to help across glaucoma types, but normal-tension glaucoma (NTG) is a particularly interesting case. In NTG, IOP is in the normal range, so non-pressure factors (like blood flow and inflammation) are thought to drive damage. PEA’s vasodilatory and anti-inflammatory effects may be especially useful here. Indeed, the NTG trial showed both lower IOP (even from a normal baseline) and improved visual field indices with PEA (pubmed.ncbi.nlm.nih.gov). Moreover, the ocular hypertensive trial found improved systemic endothelial function on PEA (pubmed.ncbi.nlm.nih.gov), suggesting it helps blood vessels – a key issue in NTG.
While more research is needed, these findings hint that NTG patients could derive extra benefit from PEA’s neuroprotective actions. That said, PEA helped pressure even in high-pressure glaucoma, and helped retinal signaling in the mostly high-pressure cohort. Thus, PEA may be broadly useful as an adjunct therapy. Clinics might prioritize PEA for patients who have progression despite controlled IOP or who exhibit vascular risk (like NTG or glaucoma with poor blood pressure control).
Conclusion
In summary, clinical trials indicate that oral PEA supplements can modestly lower intraocular pressure and may improve retinal nerve function in glaucoma patients. Typical effective doses have been around 300 mg twice daily for months, with benefits seen as small additional IOP drops (on the order of 1–3 mmHg) and signs of neuroprotection. Importantly, PEA was well-tolerated in all studies, with no serious side effects reported (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). While PEA is not a substitute for proven treatments, it appears to be a safe adjunct that could help some patients, especially those with normal-tension glaucoma or ongoing progression. Further larger trials will clarify which patients gain the most. For now, PEA represents a promising nutraceutical for glaucoma care.
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