Pea by Orthoplex White

POSSIBLY EFFECTIVE

• Osteoarthritis. Oral PEA seems to reduce pain and improve function in patients with osteoarthritis. Details: Clinical research in patients with osteoarthritis shows that taking PEA (Levagen, Gencor Pacific) 300 mg or 600 mg daily in two divided doses for 8 weeks modestly improves function and reduces pain, stiffness, and the need for rescue analgesics when compared with placebo. The worst reported pain from the day prior was reduced by 40% to 50% in patients taking PEA, compared with no improvement in those taking placebo. Also, the number of patients reporting no pain in the previous 24 hours was more than doubled in those taking PEA when compared with placebo (106274).
• Pain (chronic). Oral PEA seems to reduce pain in patients with chronic pain due to various causes. Details: A meta-analysis of the available clinical research, as well as one observational study, shows that taking micronized or ultramicronized PEA (Normast, Epitech Group) 300-1200 mg daily for up to 60 days reduces pain in people with chronic pain due to various causes, regardless of the use of other analgesics. The meta-analysis estimated a five-fold reduction in pain every two weeks in patients using PEA when compared to control. Estimates also suggest that pain reduction to a score of less than or equal to 3 is approximately twice as likely to occur in patients using PEA when compared to control (93314,93320). A more recent meta-analysis of small clinical studies in patients with pain of various etiologies taking PEA 300-1200 mg for 10-180 days did not find any further pain reduction with the use of higher doses or longer durations. There was also no difference in pain reduction when compared with either a placebo control or a non-placebo control (101327). The validity of these findings is limited by the variability of the studies in the analysis and the lack of differentiation between patients with neuropathic and non-neuropathic pain.

POSSIBLY INEFFECTIVE

• Spinal cord injury. Oral PEA does not seem to reduce pain or spasticity associated with spinal cord injury. Details: Clinical research shows that taking ultramicronized PEA (Normast, Epitech Group SpA) 600 mg sublingually twice daily for 12 weeks as add-on pain therapy does not reduce neuropathic pain, spasticity, or insomnia in patients with pain and spasticity associated with spinal cord injury when compared with using conventional pain treatments (93370).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). It is unclear if oral PEA is beneficial for ALS. Details: Preliminary clinical research in adults with ALS shows that taking ultramicronized PEA 600 mg twice daily for 6 months, in addition to riluzole 50 mg, slows the decline of pulmonary function when compared with a control group taking riluzole alone. Taking PEA also attenuates the reduction in forced vital capacity, with a 4% decrease in the treatment group compared to a 15% decrease in the control group (93369).
• Atopic dermatitis (eczema). Topical PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with atopic dermatitis shows that using an emollient containing PEA 0.3% and N-acetylethanolamine 0.21% (Stiefel Laboratories Ltd) twice daily for 28 days modestly improves skin hydration, scaling, dryness, and itching when compared with a control emollient. There was no effect on skin redness or integrity (106271).
• Autism spectrum disorder. It is unclear if oral PEA is beneficial for autism. Details: A small clinical study in children aged 4-12 years with autism and moderate to severe irritability shows that taking PEA 600 mg twice daily for 10 weeks as an adjunct to treatment with risperidone improves irritability and hyperactivity, but does not seem to affect lethargy/social withdrawal, inappropriate speech, or stereotypic behavior, when compared with placebo and risperidone (101338).
• Cannabis use disorder. Although there is interest in using oral PEA for cannabis withdrawal, there is insufficient reliable information about the clinical effects of PEA for this condition.
• Carpal tunnel syndrome. It is unclear if oral PEA is beneficial for carpal tunnel syndrome. Details: Preliminary clinical research in patients with moderate severity carpal tunnel syndrome shows that taking PEA 600 or 1200 mg daily in divided doses for 30 days reduces or delays discomfort when compared to no treatment (93377). The validity of these findings is limited by the lack of an adequate comparator group. Another small preliminary clinical trial in patients with moderate to severe carpal tunnel syndrome shows that taking ultra-micronized PEA (Normast, Epitech Group S.p.A) 1200 mg daily prior to carpal tunnel surgery improves sleep disturbance and pain when compared with control. Two 600 mg sachets of the product were used daily for 10 days, followed by two 600 mg tablets daily for 50 days. The treatment regimen was then continued for another 90 days, but there was no difference between groups with regard to sleep and pain outcomes during this period (101333). PEA might not work as well in patients with milder carpal tunnel syndrome. A clinical study in patients with low to moderate severity carpal tunnel syndrome shows that taking PEA 300 mg twice daily for 60 days does not improve symptoms when compared with placebo (101334).
• Chronic kidney disease (CKD). Although there is interest in using oral PEA for CKD, there is insufficient reliable information about the clinical effects of PEA for this condition.
• Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small preliminary clinical study in patients with CP/CPPS shows that taking a specific combination product containing PEA 300 mg with alpha-lipoic acid 300 mg (Peanase) daily for 12 weeks improves lower urinary tract symptoms, pain, and quality of life, but does not improve erectile function, when compared with taking saw palmetto 320 mg (101336). It is not clear if these effects are due to PEA, other ingredients, or the combination.
• Circadian rhythm sleep disorders. It is unclear if oral PEA is beneficial in patients with disturbed sleep patterns. Details: A clinical study in healthy adults with disturbed sleep patterns shows that taking a specific formulation of oral PEA (Levagen+) 350 mg nightly, one hour prior to sleep, for 8 weeks does not improve the quality of sleep when compared with placebo. However, treatment with PEA shortens the time needed to fall asleep at weeks 4 and 8 when compared with placebo (107807). This study may have been inadequately powered to detect a difference between groups.
• Cognitive impairment. Although there is interest in using oral PEA for cognitive impairment, there is insufficient reliable information about the clinical effects of PEA for this condition.
• Complex regional pain syndrome. Although there is interest in using topical PEA for complex regional pain syndrome, there is insufficient reliable information about the clinical effects of PEA for this condition.
• Coronavirus disease 2019 (COVID-19). It is unclear if oral PEA is beneficial for recovery of smell following COVID-19 infection. Details: COVID-19 infection has been associated with persistent smell or taste disorder. In patients with olfactory impairment lasting at least 90 days after a confirmed negative COVID-19 test, a small preliminary clinical trial shows that taking PEA 700 mg plus luteolin 70 mg (Glialia, Epitech pharmaceutical) daily for 30 days in combination with olfactory rehabilitation modestly improves olfactory recovery, based on threshold, discrimination, and identification, when compared with olfactory rehabilitation alone. However, patients randomized to PEA plus luteolin had worse olfactory status at baseline and had experienced olfactory impairment for about twice the duration as those in the control group. These baseline differences may have confounded any findings (106270).
• Depression. It is unclear if oral PEA is beneficial for depression when used in combination with citalopram. Details: A small clinical trial in patients with major depressive disorder shows that, in addition to citalopram, taking ultra-micronized PEA 600 mg twice daily for 6 weeks results in at least a 50% improvement on the Hamilton Depression Rating Scale (HAM-D) in all patients, compared to about 75% of patients in the group receiving placebo and citalopram. However, there was no between-group difference in complete remission rates (101335).
• Diabetic neuropathy. It is unclear if oral PEA is beneficial for diabetic neuropathy. Details: Preliminary clinical research in adults with diabetic neuropathy shows that taking a specific type of micronized PEA (Normast, Epitech Group srl) 300 mg twice daily for 60 days reduces neuropathic pain when compared with baseline (93335). The validity of this finding is limited by the lack of a comparator group.
• Dry eye. It is unclear if eye drops containing PEA are beneficial for dry eye. Details: Observational research in patients with glaucoma and dry eye has found that applying specific PEA eye drops (Defluxaa), one drop in each eye twice daily for 30 days, is linked to improved tear stability and tear production (101332).
• Dry skin. It is unclear if topical PEA is beneficial for dry skin. Details: Preliminary clinical research in patients with pruritus related to dry skin shows that applying a lotion containing PEA (Physiogel Calming Relief) twice daily for 14 days does not reduce itchiness, roughness, or scaling when compared with applying the vehicle alone (106272).
• Dysmenorrhea. Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adolescents and young adults with primary dysmenorrhea shows that taking a combination of PEA 400 mg plus trans-polydatin 40 mg daily for 10 days, starting on the 24th day of the cycle, modestly reduces pelvic pain when compared with placebo. Also, approximately 98% of patients taking PEA had some pain reduction, compared with 56% of those taking placebo (106273).
• Endometriosis. Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of clinical and observational research in patients with endometriosis-related pain shows that taking micronized PEA 400 mg and trans-polydatin 40 mg twice daily for 3 months moderately improves pelvic pain and dysmenorrhea and modestly improves pain with intercourse when compared with placebo (101337). However, taking the same specific combination of PEA 400 mg plus polydatin 40 mg (Pelvilen, Epitech Group Srl) daily for 3 months was not as effective as taking celecoxib 200 mg twice daily for 7 days. Satisfaction with treatment is comparable between PEA and celecoxib (101407). Limited research has also assessed PEA in combination with alpha-lipoic acid. Preliminary clinical research shows that taking a combination of PEA 300 mg and alpha-lipoic acid 300 mg twice daily for 6-9 months reduces endometriosis-associated pelvic pain and improves quality of life and sexual function when compared to baseline (93379). The validity of this finding is limited by the lack of a comparator group.
• Exercise-induced muscle damage. It is unclear if oral PEA is beneficial for the prevention or treatment of exercise-induced muscle damage. Details: A small clinical study in young males shows that taking a drink containing PEA 150 mg (as Levagen+) plus maltodextrin 832.5 mg before, immediately after, and 3 hours, 24 hours, and 48 hours after an exercise session designed to cause muscle damage modestly reduces myoglobin levels, a marker of muscle damage, in the 3-hour post-exercise period when compared with taking maltodextrin 1 gram. However, there were no effects on levels of creatine kinase or inflammatory cytokines over 72 hours (106267).
• Exercise-induced muscle soreness. It is unclear if oral PEA is beneficial for the prevention or treatment of exercise-induced muscle soreness. Details: A small clinical study in young males shows that taking a drink containing PEA 150 mg (as Levagen+) plus maltodextrin 832.5 mg before, immediately after, and 3 hours, 24 hours, and 48 hours after an exercise session designed to cause muscle soreness does not reduce muscle soreness in the 72-hour post-exercise period when compared with taking maltodextrin 1 gram (106267).
• Fibromyalgia. It is unclear if oral PEA is beneficial for fibromyalgia. Details: Retrospective and prospective observational research in patients with fibromyalgia who are taking duloxetine and pregabalin shows that taking micronized or ultramicronized PEA (PEA-m or PEA-um, Epitech Group) 600-1200 mg daily for 3 months reduces pain and tender points when compared with duloxetine and pregabalin alone (93338). The validity of these findings is limited by poor study design and the lack of a placebo control.
• Glaucoma. Taking oral PEA seems to have a small beneficial effect on intraocular pressure. However, it is unclear if oral PEA is beneficial for glaucoma. Details: In patients with normal-tension glaucoma, preliminary clinical research shows that taking ultramicronized PEA 600 mg in divided doses for 6 months reduces intraocular pressure by 3.3 mmHg and improves visual field indices without impacting visual acuity when compared to baseline (93378). Other preliminary clinical research in patients with stable open-angle or normal tension glaucoma already using standard topical therapy shows that taking PEA (Visimast) 600 mg daily for 4 months modestly improves the function of retinal ganglion cells, intraocular pressure, and quality of life when compared with not taking PEA. However, in this study there was no effect on the visual field (106268). PEA has also been evaluated for the general reduction of intraocular pressure. In patients undergoing bilateral laser iridotomy for the prevention of primary closed-angle glaucoma, a small clinical study shows that taking a specific PEA product (Visimast, Epitech Group Srl) 300 mg twice daily for 15 days prior to surgery prevents a rise in intraocular pressure within 2 hours of surgery when compared with placebo (93323). In patients with ocular hypertension but without other symptoms of glaucoma, preliminary clinical research shows that taking PEA 300 mg twice daily for 90 days reduces levels of intraocular pressure by approximately 3% when compared to baseline (93326). The validity of these findings is limited by the lack of a comparator group.
• Inflammatory bowel disease (IBD). Although there is interest in using oral PEA for IBD, including Crohn disease and ulcerative colitis, there is insufficient reliable information about the clinical effects of PEA for these conditions.
• Interstitial cystitis. Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in males and females with interstitial cystitis and chronic bladder pain shows that taking a product containing micronized PEA 400 mg plus polydatin 40 mg (Pelvilen Forte, Epitech Group SpA) twice daily for 3 months, and then once daily for an additional 3 months, modestly reduces pain intensity, urgency, and frequency when compared with baseline. The pain reduction was maintained for at least an additional 2 months (106269). The validity of these findings is limited by the lack of a comparator group.
• Irritable bowel syndrome (IBS). Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with IBS shows that taking PEA 200 mg and polydatin 20 mg (EP1844784, Epitech group Srl) twice daily for 12 weeks reduces abdominal pain severity but does not affect other gastrointestinal symptoms when compared with placebo (101331). It is not clear if these effects are due to PEA, other ingredients, or the combination.
• Migraine headache. It is unclear if oral PEA is beneficial for reducing the frequency and severity of migraines in children. Details: Preliminary clinical research in children and adolescents aged 5-17 years with migraine without aura shows that taking ultra-micronized PEA 300 mg twice daily for 3 months reduces the frequency of migraine attacks by at least 50% in about 64% of patients when compared with baseline. The intensity of migraine attacks was reduced by approximately 30%, with an 80% reduction in the number of patients experiencing a severe migraine attack (106266). The validity of these findings is limited by the lack of a comparator group.
• Multiple sclerosis (MS). It is unclear if oral PEA is beneficial for MS. Details: Anecdotal evidence from case reports has suggested that PEA can reduce MS-related pain (93319,93321). Preliminary clinical research in patients with relapsing-remitting MS being treated with subcutaneous interferon-beta1a shows that taking ultra-micronized PEA (Normast, Epitech Group SpA) 600 mg daily for 12 months improves some, but not all, symptoms of MS, as well as adverse effects from interferon treatment. However, taking PEA does not seem to improve physical or emotional well-being or overall quality of life (93368).
• Neuropathic pain. It is unclear if oral PEA is beneficial for improving neuropathic pain. Details: Small, low-quality clinical studies and case series suggest that taking PEA 600-1200 mg daily in divided doses reduces neuropathic pain from various causes, including chemotherapy and trauma. Pain reduction has been reported to occur even if patients are using other treatments or receiving acupuncture (93333,93336,93376). The validity of these findings is limited by small study size, poor study design, and the lack of a comparator group.
• Obesity. Although there is interest in using oral PEA for weight loss, there is insufficient reliable information about the clinical effects of PEA for this use.
• Parkinson disease. It is unclear if oral PEA is beneficial for patients with Parkinson disease using levodopa. Details: Observational research in patients with Parkinson disease using levodopa found that taking a specific ultra-micronized PEA product (Normast, Epitech Group SpA) 600 mg twice daily for 3 months, followed by 600 mg once daily for up to one year, is associated with improved symptoms when compared to baseline, such as mood, sleep disturbances, and tremor, and improved activities such as getting out of bed and walking (101328). The validity of these findings is limited by the observational nature of the study and the lack of a comparator group.
• Postoperative pain. It is unclear if oral PEA is beneficial for reducing postoperative pain. Details: Preliminary clinical research in adults undergoing impacted third molar extraction shows that taking a specific type of micronized PEA (Normast, Epitech Group SpA) 300 mg twice daily for 15 days reduces postoperative pain when compared with a control group. PEA reduces pain by 36% and 33% at 3 and 7 days, respectively, when compared with control (93322).
• Prurigo nodularis. Topical PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in elderly individuals with chronic pruritus or prurigo nodularis shows that topical application with a cream containing 10% omental lipids and 'anti-itching' agents, including PEA, twice daily for 4 weeks reduces itching severity by 86% when compared with baseline. Skin barrier function was also improved. Other 'anti-itching agents' included polidocanol and stimutex made up of spent grain wax, shea extract, and Argania spinosa kernel oil (106275). The validity of these findings is limited by the lack of a comparator group.
• Respiratory tract infections. It is unclear if oral PEA is beneficial for preventing respiratory tract infections. Details: Some low-quality, clinical studies in adults and children shows that taking a specific type of PEA (Impulsin) up to 1800 mg daily in divided doses for at least 12 days reduces the risk of developing an acute respiratory infection by 32% to 59% (93372,101412). Retrospective, observational research in children with recurrent respiratory infections shows taking a specific product (Sinerga) containing PEA, bovine colostrum, and phenylethylamine, as one sachet daily for 10-20 consecutive days each month for 4 months, reduces the need for antibiotics. The combination product reduced the need for antibiotic treatment to only 52% of children, compared to 95% of the children taking a probiotic extract (93337). It is not clear if these effects are due to PEA, other ingredients, or the combination.
• Sciatica. Small clinical studies suggest that oral PEA may be beneficial for reducing pain associated with sciatica. Details: Some small clinical studies in patients with sciatica shows that taking PEA 300 mg twice daily for 30 days in conjunction with standard treatment reduces pain and physical aspects of quality of life when compared with standard treatment alone (93374,93375). Some higher quality clinical research in adults with sciatica and low back pain also shows that taking a specific type of PEA (Normast, Epitech Group srl) 300 mg or 600 mg daily for 21 days reduces pain by 45% to 70% in patients with lumbosciatica, compared to a 30% reduction with placebo (101408,101409).
• Shigellosis. Although there is interest in using oral PEA for shigellosis, there is insufficient reliable information about the clinical effects of PEA for this use.
• Stroke. Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in stabilized, conventionally-treated adults undergoing rehabilitative treatment for a recent stroke shows that taking a specific product (Glialia, Epitech Group SpA) containing ultra-micronized PEA 700 mg and luteolin 70 mg twice daily sublingually for 60 days improves spasticity, pain, and activities of daily living when compared to baseline (93339). The validity of these findings is limited by the lack of a comparator group.
• Temporomandibular disorders (TMD). It is unclear if oral PEA is beneficial for TMD. Details: Preliminary clinical research shows that taking PEA 600-900 mg in divided doses for 14 days improves pain associated with temporomandibular arthritis by 89%, compared to only 46% in patients taking ibuprofen 600 mg three times daily for 14 days. PEA also increased mouth opening by 11.5%, compared to an increase of 5.5% with ibuprofen (93373).
• Tourette syndrome. Although there is interest in using oral PEA for Tourette syndrome, there is insufficient reliable information about the clinical effects of PEA for this use.
• Vulvar pain. Oral PEA has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with vestibulodynia shows that taking PEA 400 mg plus polydatin 40 mg daily, in conjunction with intravaginal transcutaneous electrical nerve stimulation (TENS) therapy, does not reduce pain more than the use of TENS therapy and placebo (93327). More evidence is needed to rate PEA for these uses.

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POSSIBLY SAFE ...when used orally and appropriately, short-term. PEA has been used with apparent safety in doses of up to 1400 mg daily for up to 3 months (93314,93326,93327,93333,93335,93338,93339,93369,93373,101333)(101335,106269,106274). ...when used topically and appropriately, short-term. An emollient containing PEA 0.3% and N-acetylethanolamine 0.21% (Stiefel Laboratories Ltd) had been used with apparent safety twice daily for up to 28 days (106271). There is insufficient reliable information available about the safety of PEA when applied topically or when used orally, long-term.

CHILDREN:
. ..when used orally and appropriately, short-term. PEA 300-600 mg twice daily for 10-12 weeks has been used with apparent safety in children 4-17 years old (101338,106266).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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General ...Orally and topically, PEA seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Nausea.

Cardiovascular ...Orally, PEA has been reported to cause palpitations in one patient (93322).

Dermatologic ...Topically, applying a lotion containing PEA twice daily worsened pruritus and caused stinging, scaling, or reddening in 13% of patients with dry skin. However, these adverse effects did not occur more frequently than in patients applying the vehicle alone (106272).

Gastrointestinal ...Orally, PEA has been rarely reported to cause mild and transient gastrointestinal symptoms, such as nausea (93325,93327,106266).

Genitourinary ...Orally, PEA has been rarely reported to cause spotting when used in combination with polydatin. However, it is unclear whether this adverse effect is due to PEA, polydatin, or the combination (93325).

Neurologic/CNS ...Orally, PEA has been reported to cause drowsiness or a sensation of floating in one patient each (93322,106266).

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