In een muismodel van schade door chemotherapie hebben wetenschappers van de Universiteit of Minnesota, Minneapolis,USA, aangetoond dat de cellen in het weefsel van muizen die met chemotherapie behandeld worden de beschermende stof PEA aanmaken:
Levels of PEA were significantly higher in paw tissue from both cisplatin-treated groups relative to paw tissue from nontreated mice.
In de tabel hieronder is dat in detail goed te zien:
|Treatment||AEA, pmol||PEA, nmol||2-AG, nmol|
|Naïve + vehicle (6)||20.1 ± 1.52*||0.6 [0.34–0.68]||21.4 ± 0.92|
|Cisplatin + vehicle (8)||11.0 ± 1.56||0.9 [0.76–1.17]†||24.5 ± 2.35|
|Cisplatin + URB597 (10)||19.6 ± 1.95*||0.9 [0.72–1.17]†||20.1 ± 1.73|
Opvallend is dat de cellen van onbehandelde muizen 0,6 nmol PEA bevatten, en als de cellen blootgesteld worden aan chemokuur bestanddelen, in dit geval het bekende antikanker middel cisplatin, maken de cellen zelf ongeveer 50% meer PEA. Dat is een significante vermeerdering (Different from vehicle in PEA group at P < 0.05 (one-way ANOVA with Bonferroni t-test).
Inmiddels wordt door steeds meer mensen met kanker die chemotherapie ondergaan PEA gebruikt, om deze beschermende werking nog verder te ondersteunen, met name omdat we weten dat bij chronische belasting (kanker) de eigen synthese van PEA gestoord is.
Aanbeveling: alleen van de PEA capsules met het PEA-opt keurmerk hebben is tot nu toe bewezen ook daadwerkelijk het PEA gehalte in het bloed verhoogd wordt, daarom schrijven artsen ook die capsules voor in dit soort gevallen.
Bovendien bevatten alleen deze PEA capsules het gepatenteerde Micro-PEA (ook te vinden in de Italiaanse Normast PEA tabletten)
Dosis: 3 maal daags een capsule van 400 mg na de maaltijd.
Uhelski ML, Khasabova IA, Simone DA. Inhibition of anandamide hydrolysis attenuates nociceptor sensitization in a murine model of chemotherapy-induced peripheral neuropathy. Neurophysiol. 2015 Mar 1;113(5):1501-10.
Een patient met het chronische vermoeidheidssyndroom (CVS) en fibromyalgie klachten meldde ons: Ik ben een vrouw van 55 jaar en ik heb al geruime tijd veel last van Moeheid en van pijn eigenlijk in…
There currently are only few brands of supplements on the market that contain palmitoylethanolamide (PEA) in a special formulation, called micro-PEA, all based on patented procedures. Most other and recent introduced (cheap) brands contain raw or crushed PEA without any long term safety, nor with demonstrated PEA plasma-levels. It is necessary for a good effect to use only PEA formulations which can increase the PEA levels in our body.
Our choice therefore goes out to PEA formulations that have been clinically proven, are safe and of high quality, and which increase PEA levels in the blood after intake! These are the PEA capsules that carry the PEA Opt label, and the Italian tablets based on PEA-um and PEA-m.
Only these formulations have proven to contain a special PEA formulation, microPEA.
Plasma levels rise after intake of PEA capsules and PEA tablets containing microPEA
PEA levels in the blood have been measured in Italy for the Italian microPEA compositions containing ultramicronized and micronized PEA (as in Normast and Pelvilen), as well as in the Netherlands for the Dutch capsules PEA-opt (as in PeaPure and PeaPlex).
In the above graph, on T0 the baseline concentration of PEA in our blood is depicted. After swallowing a PEA capsule or a PEA tablet the plasma level of PEA clearly rises, at least 2 times, and PEA concentrations stay high in the blood for a period of time. The arrows are the standard deviation of the measurements.
The term microPEA was introduced in 2016 by DR Earle R. Nestmann, and is defined as PEA formulations containing small particles of PEA between 0,5 and 10 micron:
The term microPEA includes both micronized and ultramicronized PEA, as the particle size distribution of 0.5-10 μm includes both fractions.
Only for formulations containing at least relevant amounts of microPEA such rise of PEA in our body (in the plasma) has been measured. For cheap me-too PEA formulations such data are not yet available. Our experience with such formulations is that patients often complain about the absence of efficacy.
Palmitoylethanolamide is a painkilling compound with anti-inflammatory properties that is naturally produced by the body. In 1993, Nobel Prize winner Rita Levi-Montalcini emphasized the significance of this natural substance. She helped create the first PEA tablet, which became available in Italy under the name Normast.
Normast®, PeaPure® and PeaPlex® : a breakthrough in treatment of chronic inflammation and pain.
In 2007 the Italian company Epitech introduced Normast®, which tablets contain 600mg of palmitoylethanolamide along with some other chemical pharmaceutical fillers. A few years later, Normast also became available as a powder (600mg) sweetened with sorbitol.
In 2012 Russell Science Ltd introduced PurePea®, an innovated formula of palmitoylethanolamide in 400mg capsules. PurePea is completely free of chemical fillers, flavoring, coloring and sweeteners. In 2015 a new and optimized PEA formulation became available: PeaPlex: specifically developed for the nervous system, and also containing very fine PEA particles. In the Netherlands these fine PEA particles have been tested and received the PEA-opt quality marker.
PEA-opt stands for patented PEA capsules, with documented safety and efficacy, and resulting in significant rises in plasma levels of PEA after intake.
PeaPure and PeaPlex capsules, as well as Normast tablets, all contain only finely grinded palmitoylethanolamide, based on a special patented method of production, and nothing else. This type of PEA is proven to be effective and safe. This does not count for all other PEA products, which is concerning.
PEA-opt, PEA-um, PEA-m, all containing micro-PEA
For this reason, always choose a PEA capsule with the Pea-Opt label, as in PeaPure and PeaPLex, or a tablet based on PEA-m and PEA-um, as in Normast. The safety and effectiveness (and often the purity) of other preparations have not been proven! The results obtained with Pea-opt certified PEA capsules and Normast containing PEA-um and PEA-m are the only ones described by MDs in international medical literature.
A PEA cream has also been available for several years now. The producer of PeaPure recommends users to strengthen the benefits of PEA capsules with this cream, which works via the thin nerves of the skin.
PEA is produced in our body during chronic inflammation and chronic pain to restore balance. However, during chronic illness this production is often too low. In this case you can take an PEA supplement to restore balance.
Because we received often questions on the details of PeaPure® (produced and available in the Netherlands) and Normast® (produced and available in Italy) this article was written. Also to introduce the terms relevant for good quality PEA products: PEA-um, PEA-m, PEA-opt and microPEA.
PEA: the facts
There are many known facts about the substance Palmitoylethanolamide (PEA):
• PEA has been described in more than 500 scientific publications in 2016.
• The substance PEA and its structure were first described in 1953.
• Normast was the first PEA tablet to be introduced in this century to treat neurogenic inflammation & neuralgic pain.
• PEA has been used by millions of people worldwide.
• PEA can effectively be used for a multitude of chronic pain complaints, including pains due to hernia, diabetes, chemotherapy, nerve pain and arthritis.
• PEA can also be used for chronic inflammation, like inflammation of the prostate, the bladder (if not bacterial) and chronic inflammation of the intestines (colitis ulcerosa).
• PEA can safely be used in combination with other supplements and medication.
• PEA is an all-natural bodily substance.
• PEA is present in all animals to restore balance, except in insects.
• PEA is produced in our bodies and restores balance.
• PEA is also present in foods like meat, eggs, soybeans and peanuts.
• PEA has no side effects and is easily broken down by the body’s own enzymes.
• PEA doesn’t put strain on the kidneys and liver.
• PEA was first mentioned as a natural treatment for advanced disease symptoms by Italian Nobel Prize winner Professor Rita Levi-Montalcini in 1993.
• PEA first became available as a GMP certified capsule in the Netherlands in 2011. Meanwhile there are many copycat remedies on the market of unclear quality and origin, which we don’t recommend, and that have not been clinically tested.
PeaPure is a prescription free food supplement. The benefit of PEA is that it can almost always be used as a natural method to treat chronic pain and inflammation without negative side effects. PEA can also be safely combined with regular medicine, as no negative interactions have been recorded.
Dosage and usage of Normast and PeaPure
The most researched and most effective dosage is 1200 mg of PEA per day. Which means either 600mg of Normast tablets twice daily or 400mg PeaPure capsules three times a day. The PeaPure capsules don’t have to be taken in 3 dosages spread over the day; twice a day is ok as well. For example 2 capsules PeaPure in the morning after breakfast and one PeaPure in the evening after dinner.
Potential indicators or Normast and PeaPure
Below is a detailed piece about the biological meaning of palmitoylethanolamide, as found in PeaPure and Normast.
Palmitoylethanolamide slows the activity of so-called mast cells, certain inflammatory cells, and also contains painkilling and anti-inflammatory properties due to the specific activity on a certain important receptor in the cell nucleus, the PARR-receptor. But PEA, as a biological molecule, has an entire series of natural points of application, which are represented in the model below.
This is why it’s easy to understand why palmitoylethanolamide can be used for so many symptoms. What all these illnesses have in common in chronic pain or inflammation.
Here you find the potential circle of indications for palmitoylethanolamide, based on pharmaceutical studies, pre-clinical studies and clinical studies, as well as our personal experiences at the Institute for neuropathic pain.
This circle of indications was originally designed by the Institute for Neuropathic pain for intercollegiate consult with doctors who turn to the institute concerning treatments of their patients. The circle is not meant as a claim for the effectiveness of Normast or PeaPure in all of these indications.
Circle of Indications for Palmitoylethanolamide
Because palmitoylethanolamide slows the activity of mast cells, on top of that of nerve cells and glia cells that get overworked during chronic pain, the below indications for this substance are understandable based on the pathogenesis. Slowing down the derailing of mast cells and other inflammatory cells happens through the so-called nucleus receptors in the cells.
Chronic pain syndromes
General Chronic pain syndromes     
Pain and spasms due to MS 
Hernia and back pain    
Diabetic neuropathic pains     
Herpes Zoster pain (shingles) 
Neuropathic pain due to different forms of neuropathy, CIAP, CIDP, etc.  
Carpal tunnel syndrome  
Pain due to chemotherapy 
Complex regional pain syndrome, Sudeck  
Pain and painful spasms due to MS      
Central neuropathic pain due to stroke 
Central neuropathic pain due to Syringomyelia and Paraplegia  
Migraine   
Fibromyalgia  
Rheumatoid Arthritis and Bechterew pains  
Psoriatic Arthritis 
Costen Syndrome and Temporomandibulair pain disorder 
Chronic Pruritus, unexplained itch 
Pain and itching after chemotherapy 
Occipital Neuralgia 
Pain in bladder, prostate and vagina
In case of unexplained painful inflammation, when the urologist has ruled out cancer en there is no case of chronic infection due to bacteria, the anti-inflammatory and painkiller PeaPure® or Normast® is a good move. This remedy regulates the excessively active inflammatory cells and reduces pain.
Chronic prostate pain complaints
Chronic prostate pain (prostatodynia) 
When the Gynecologist or urologist ruled out infection and there is unexplained inflammation in the inside of the bladder, with pain, difficulty urinating, urinating small quantities etc, taking Normast® or PeaPure® can be useful.
Chronic pain the bladder
Interstitial cystitis 
Chronic bladder pain 
Ailments of the reproductive organs
Lichen planus with itching and pain 
Vulvar vestibulitis   
Vulvodynia, vestibulodynia  
Perineodynia (unexplained pain in the pelvis) 
Menstruation pains 
Intestinal (and colon) inflammation and pain syndromes   
Ulcerative Colitis   
Crohn’s disease  
Irritable bowel syndrome  
Proctitis  
Chronic unexplained stomach aches  
Chronic unexplained skin inflammation    
Chronic unexplained itching 
Atopic and contact dermatitis   
Psoriasis   
Asthma and COPD  
Hay fever and allergic rhinitis 
Angina pectoris and Kounis syndrome  
Progressive arteriosclerosis 
Ocylar hypertension  
Alzheimer and Parkinson’s disease  
More literature about PEA under this link.
: Esposito E, Paterniti I, Mazzon E, Genovese T, Di Paola R, Galuppo M, Cuzzocrea S. | Effects of palmitoylethanolamide on release of mast cell peptidases and neurotrophic factors after spinal cord injury. | Brain Behav Immun. | 2011 Feb 25.
Migraine: calm the nerve cells by feeding them a body’s own substance: from stress to relax
Standing on shards of glass. Her feet had been extremely painful for almost a year already, as if she was standing on shards of glass. The cause? Diabetes. In case of diabetes, the nerve fibers are so tormented that they almost exclusively give off pain signals, this causes painful and burning sensations in the feet.
The neurologist had tried everything but the pain hardly decreased while the side effects made her very drowsy. She started treatment with a supplement that was quite new in the Netherlands, called PeaPure (400 mg capusles) ( The Italian product Normast (300 and 600 mg tablets contains the same PEA). PeaPure contains palmitoylethanolamide without excipients, which we will elaborate on later.
The fascinating thing is that this substance is produced in our own body by our cells and it is an effective pain reliever. It has been used to treat many thousands of patients successfully. There are no know side effects and the substance can therefore be safely combined with other pain medicine and treatments.
Fortunately this substance was able to finally help her and the pain decreased significantly over the weeks. During her fourth visit she looked particularly happy because something special had happened, het migraines had become less severe as well. For this reason it’s worth it to discuss migraines and how this substance not only helped her get rid of the sharp burning pain but also for the most part rid her of her migraines.
Migraine: unrest in the brain
We all have a friend of family member who regularly suffers from extreme headaches, sometimes even accompanied by nausea that could lead to vomiting. There are remedies against migraines but despite those there’s not much more a migraineur, as people suffering from migraines are called, can do than accept the suffering and hope it passed quickly.
It always passes, but not always as quickly as you’d like. It can take you out for days. For this reason, migraineurs are looking for solutions. As far as medicine is concerned there are only 2 solutions. Either you look for drugs to relieve the attack, like aspirin and more current triptans, or you take chronic measures to prevent the attacks. Unfortunately the ideal remedy has not yet been found.
The general assumption is that the cause of these severe pains lies in the nerve cells within the brain. It is believed these cells become overactive and give off pain signals for hours or days. This is mostly correct, but not entirely, and that’s where an opportunity can be found to develop a new treatment.
It’s not the nerve cells that play the most important role, but a type of connective tissue cell that surrounds and feeds the nerve cell. These cells form a type of lining around the nerve cells. Together these cells form the glia tissue. And in that glia tissue lies a possible new solution for migraine treatment. In case of migraines, the glia tissue is in a constant state of stress and produces all sorts of nervous substances that stimulate the nerves.
The question is, how to we calm the glia tissue?
But before look closer at the glia tissue, let’s go back to the brain and migraine.
Brain in stress
The brains of people with migraines are programmed differently than people without migraines and bursts in to stress easier. In technical terms this is called sensitization. Simple stimuli, that in normal circumstances are hardly noticeable, are amplified with central sensitization. A little bit of light turns in to painfully light, a soft sound turns very loud and a gentle touch can create a severe response. People who experience migraines often prefer to stay alone in a dark place until it passes.
Silence, darkness, the least amount of stimuli possible. Because every stimulus is amplified by the stressed brain, even scents can be too much during an attack. The question is, what is hiding behind this stress? What mechanisms keep the brain in a constant state of amplified stimuli? And how can we bring the brain back in to a relaxed state?
Current insights in to what hides behind the phenomenon of central sensitization, leads to an entirely new approach of migraines. In our practice we have seen some fine examples of this. There is no brake: the cells are on a rampage. In case of migraine there is no brake.
Small stimuli are experienced as strong and during an attack you want to crawl away in a small hole somewhere. Where is the brake? Through current research on brain function we know that this brake is situated somewhere in the brain stem, which is part of what we call the central grey. It is a part of the brain stem that is situated around a channel with cerebrospinal fluid called the aqueduct. Because there is gray matter surrounding the aqueduct we also refer to this part of the brain as the periaqueductal gray, PAG.
Situated in the PAG are the cells that inhibit regular incoming stimuli, so you don’t get stressed about everything. One of the consequences of when the stimuli do rampage freely in to the brain is that the brain swells up a little bit. This swelling is another stimulus that gets amplified so you experience a throbbing headache.
The throbbing is present in everyone’s head, but normally we don’t feel it because the perception of the throbbing is inhibited by the cells in the PAG. The nerve cells become over stimulated and to inhibit that over stimulation substances like triptans were developed.
These substances inhibit a certain neurotransmitter system which is related to serotonin and that’s why the nerve cells calm down a bit and the migraine disappears. But if you think this through you’re only inhibiting the over activity without normalizing the central brake in the PAG.
That brake is made up out of nerve cells that are in a state of central sensitization. To restore that brake we have to focus on calming the lining of the nerve cells, the glia cells.
On every nerve cell ten glia cells: the reason for excitement
Everyone used to think that if you really wanted to understand the working of the nervous system, you specifically have to look at the nerve cells. The other connective tissue cells around the nerve cells were only thought to be a kind of glue to keep the nerve cells in place. However, nothing is further from the truth.
The cells are called glia cells, glia meaning glue, but since several years we have started to understand that these cells are much more important than we thought. Only the fact that there nerve cells are surrounded by 10 glia cells should make us think. And that finally happened. The entire case of central sensitization is maintained by a disturbed metabolism in the glia cells.
During chronic pain, these cells are so hyperactive that they will start to produce and secrete all sorts of substances that agitate the nerve cells. Growth factors is an example of this.
That sounds all right, but due to the work of the Italian professor Rita Levi-Montalcini we understand more about the growth factors. It’s this type of small protein molecule that, together with an army of other substances, is secreted by the glia cells during chronic pain. The nerve cells get aggravated as they are basically bathing in those substances when this happens. When the nerve cells are aggravated they will give off wrong or increased signals, which are pain signals.
This is how both glia cells and nerve cells shoot in to overdrive. On top of that, because of all the growth factors from the glia tissue, the nerve cells will start to produce substances like neurotransmitters, which cause great stress in all the nearby cells. This is called winding up and forms the condition of central sensitization. From a wound up state to a chilled out state: palmitoylethanolamide, the chill molecule.
Professor Montalcini, who got to live to 102 years of age with a clear mind and still active in science, discovered that it’s possible to calm all the stress in the brain due to chronic pain with a natural pain reliever. A simple fatty molecule produced by every cell in our body. It’s a natural bodily substance.
On top of decreasing the pain, this molecule also works as an anti-inflammatory. This is a double benefit, because the molecules that are secreted by the glia cells and irritate the nerve cells are a kind of inflammatory factors, which in turn are inhibited by this substance too.
The substance has a difficult name: palmitoylethanolamide. We will continue to call it PEA. Our own nerve cells and surrounding cells produce this pain relieving and anti-inflammatory substance during chronic pain. It is our own natural painkiller. A small Italian scientific organization followed the directions of professor Montalcini and first developed a tablet containing PEA. Now a supplement is available in capsule form that can be given to patients with severe pain in whose cases no other remedy seems to help. The brand name is PeaPure (capsules) or Normast (tablets).
PEA: who has been treated?
In the mean time thousands of patients have been treated with this substance and often with very impressive results. PEA showed to decrease pain after multiple sclerosis, severe back pains, hernia pain, shingles, pain from pinched nerves like the carpal tunnel syndrome and pain due to diabetes, just to name a few. For this reason we give PEA a green light for the treatment of pain. It looks like this substance can also offer relief for migraines.
PEA is available in the Netherlands as the supplement PeaPure and in Italy as the tablet Normast. Both are made according to the highest quality requirements.
Dosing and the use of PEA for migraines
Start with 1200mg of PEA per day, divided over the morning and evening after meals. PeaPure comes in 400mg capsules. If the pain decreases after 2 months you can change to one capsule twice a day. During a migraine attack, take an extra capsule by opening it and placing the powder under the tongue to let it melt.
In case the pain comes back, increase the dose back to 1200mg per day. If the migraines don’t get less after 2-3 months it makes no sense to keep using this substance.
Jasmin, luc et al. Can satellite glial cells be therapeutic targets for pain control? Neuron gliabiology 2010Dodick D, Silberstein S. Central sensitization theory of migraine: clinical implications. Headache 2006;46(Suppl. 4):S182–91.
Weiller C, May A, Limmroth V, et al. Brain stem activation in human migraine attacks. Nat Med 1995;7:658–60.
Goadsby PJ, Lipton RB, Ferrari MD. Migraine–current understanding and treatment. N Eng J Med 2002;346:257–70.
Watkins LR, Milligan ED, Maier SF. Glial proinflammatory cytokines mediate exaggerated pain states: implications for clinical pain. Adv Exp Med Biol 2003;521:1–21.
Egger J, Carter CM, Wilson J, Turner MW, Soothill JF. Is migraine food allergy? A double blind controlled trial of oligoantigenic diet. Lancet 1983;2:865–9.
Hernia pain en Normast Diabetic neuropathic pain  
Carpale Tunnel Syndrome en Normast 
 G. Guida, A. de Fabiani, F. Lanaia, A. Alexandre, G.M. Vassallo, L. Cantieri, M. de Martino, M. Rogai, S. Petrosino | La palmitoiletanolamida (Normast) en el dolor neuropatico cronico por lumbociatalgia de tipo compresivo: estudio clinico multicentrico. | Dolor | 2010, 25:35-42
 Biasiotta A, La Cesa S, Leone C, Di Stefano G, Truini A, Cruccu G. | Efficacy of palmitoylethanolamide in patients with painful neuropathy. A clincial and neurophysiological open study. Preliminary results. | , Volume 4, Issue 1, May 2010, Page 77.
 Matias I, Wang JW, Moriello AS, Nieves A, Woodward DF, Di Marzo V. | Changes in endocannabinoid and palmitoylethanolamide levels in eye tissues of patients with diabetic retinopathy and age-related macular degeneration. | Prostaglandins Leukot Essent Fatty Acids. |2006 Dec;75(6):413-8. Epub 2006 Oct 2.
 Assini A, Laricchia D, Pizzo R, Pandolfini L, Belletti M, Colucci M, Ratto S. | P1577: The carpal tunnel syndrome in diabetes: clinical and electrophysiological improvement after treatment with palmitoylethanolamide | Eur J Neurol | 2010: 17(S3):295.
 Sarchielli P, Pini LA, Coppola F, Rossi C, Baldi A, Mancini ML, Calabresi P. | Endocannabinoids in chronic migraine: CSF findings suggest a system failure. | Neuropsychopharmacology. | 2007 Jun;32(6):1384-90. Epub 2006 Nov 22.
 Levy D. | Migraine pain, meningeal inflammation, and mast cells. | Curr Pain Headache Rep. |2009 Jun;13(3):237-40.
 Blanco I, Béritze N, Argüelles M, Cárcaba V, Fernández F, Janciauskiene S, Oikonomopoulou K, de Serres FJ, Fernández-Bustillo E, Hollenberg MD. | Abnormal overexpression of mastocytes in skin biopsies of fibromyalgia patients. | Clin Rheumatol. | 2010 Dec;29(12):1403-12. doi: 10.1007/s10067-010-1474-7. Epub 2010 Apr 30.
Palmitoylethanolamide (PEA) has been introduced in the modern world of human pain treatment by two European companies: Epitech Srl., and Russell Science Ltd.
These 2 companies have tested palmitoylethanolamide since many years under the supervision of physicians and specialists. In Italy palmitoylethanolamide has been introduced around 2005, and in the Netherlands around 2010.
For only Normast (Epitech) and PeaPure (Russell Science) data have been generated proving that said formulations create relevant PEA plasmalevels.
Meanwhile many thousands of patients have been treated with these Italian and Dutch formulations, most probably more million patients, including many elderly patients.
Neither Epitech, nor Russell Science ever monitored a serious side effect.
Quality of Palmitoylethanolamide in reliable products
The quality of Epitech products is easy to follow: the products all are produced based on patented procedures leading to micronized palmitoylethanolamide (PEA-m) and ultramicronized palmitoylethanolamide (PEA-um). If one obtains palmitoylethanolamide tablets or palmitoylethanolamide sachets, NOT containing PEA-m or PEA-um, one makes the wrong choice.These are cheap ripp-offs.
The quality of the Russell Science products is also easy to follow: the products all have obtained the quality marker PEA-opt, and the production is also based on a standardized and patented production processes.
Both PEA-m, PEA-um and PEA-opt are all tested for efficacy and safety in the hands of experienced physicians. And for both formulations we know that after oral intake plasma levels of PEA rise. Up to now that has not been proved for any other PEA formulation!
The quality of PEA in the products of both companies has been found to be safe and effective, and the results of clinical testing has been documented in many different scientific journals.
New Palmitoylethanolamide tablets and capsules: warnings
Because of the high sales potential of palmitoylethanolamide, since 2014 we have seen new and cheap palmitoylethanolamide capsules and tablets entering the marketplace. These have been produced by companies without any know how of this special product and no experience in the field of PEA formulations. It was Epitech who first warned on their website for such products:
“Patients buying, via e-commerce, formulations containing highly impure, unmicronized palmitoylethanolamide produced in China, are at serious risk from an unregulated product entirely unsuitable for systemic use in humans…”
In order to bring palmitoylethanolamide formulations to the client, new companies ordered palmitoylethanolamide in the Far East at factories which do not have their own production facility. If these companies get an order from a Western producer of supplements, these Far East companies find a little class B factory to produce only one batch for them, and this of course cannot ensure the quality nor the stability of the product.
Moreover, the production of palmitoylethanolamide in such facilities follows chemical synthesis procedures where solvents are used and residues of these toxic solvents may stay in the final product.
Furthermore, there are companies in the Far East who fill capsules with white powder and bring counterfeit material to the customer.
The quality of most of the palmitoylethanolamide is quite low, as the production of this compound initially was for cosmetic purposes only and not for human consumption. And even these cosmetic products follow a synthesis proces which mostly is quite unfit for human consumption. Low quality of product leads to a low price, and this translates into cheap palmitoylethanolamide products offered to the patient.
There are now to many small producers of palmitoylethanolamide and this makes it not easy for the uninformed customer to decide what product to take.
There are even sellers who copy and paste many text about palmitoylethanolamide, written by clinical experts, and paste in their own brandnames. However, none of the described clinical effects have ever been explored by these sellers for their PEA products! They are just parasites on the back of the initiators of PEA know-how, Epitech and Russell.
Recommendation: PEA products with proven safety and efficacy
We therefore recommend to chose products with a long track of clinical use, and documented safety and efficacy. And products who indeed help raising the PEA levels in our bodies!
These are as far as we know the products containing PEA-m, PEA-um or PEA-opt, produced respectively by Epitech group in Italy and the Russell Science group, produced in the Netherlands.
PEA na Radiotherapie is een aanrader:
Een patient die kanker had, en bestraald was geweest had ernstige bestralingsschade opgelopen. Hij startte met Pea capsules met het PEA-opt keurmerk, maar merkte de eerste weken niets en liet dit op een Forum weten. Echter, hij ging door en uiteindelijk met goed resultaat:
“Een tijdje geleden heb ik hier een negatief berichtje geplaatst over PeaPure. Ik wil mijn mening hierover herzien.
Ik lijd namelijk aan chronische weefselontsteking ten gevolge van radiotherapiebehandeling. Dit zijn langetermijnbijwerkingen die vrijwel nooit meer verdwijnen, integendeel, het ontwikkeld zich chronisch progressief.
Na langdurig gebruik van PeaPure is de chronische pijn sterk verminderd.
Het enige minpunt aan het gebruik van voornoemde voedingssupplement is de kostprijs.”
Advies: neem bij dit soort aandoeningen tenminste 3 maanden Pea (met het PEA-opt keurmerk, omdat we zeker weten dat de PEA dan ook in het bloed komt), en neem de laatste maand in ieder geval de dubbele dosis alvorens te beslissen…
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Case report A 30-year-old woman, suffering from migraine without aura, employee, single, non-smoker, social drinker and regular sleep/wake routine. Comorbidity: ovarian endometriosis surgically treated. The patient reported headaches since the age of 14 at menarche and with episodic attacks (1-2 per month).
Two years ago the patient started an estroprogestinic (etinilestradiolo plus drospirenone) therapy and the headache worsened: the intensity of pain and frequency of attacks increased (about 8 per month) and also the analgesic consumption (about 10 SAID tablets per month).
The pain was throbbing, moderate to severe intensity and unilateral in frontal, temporal and orbital regions and it was associated with autonomic symptoms (photophobia, phonophobia, nausea and sometimes vomit). We suggested changing the type of estroprogestinic drug and prophylactic therapy with amytriptiline (16 mg/day). There were no benefits after three months of the suggested therapy: headache was unchanged and the patient gained weight (5 kg).
In the meanwhile, the gynecologist prescribed a drug to better control pelvic pain: palmitoylethanolamide (PEA), 3 tablets/day for three months.
After three months, the patient returned for a planned control visit and reported great improvement in headache frequency (4-5 attacks per month) and reduction in analgesic drug consumption and pelvic pain.
PEA is an endogenous fatty acid amide analogue of the endocannabinoid anandamide, it is synthesised during inflammation and tissue damage and has been shown to have a number of beneficial effects and to be useful in the control of neurogenic and neuropathic pain. The exact pathophysiogenetic mechanism of migraine and chronic pelvic pain are still unknown, but the role of mast cells is very important in both diseases .
Although its pharmacological efficacy is well known, the mechanism of action of this family of compounds is still unclear. It has been hypothesized that PEA could bind CB2 receptors on mast cells and sensory neurons, according to the ALIA mechanism of PEA (ALIA: Autacoid Local Injury Antagonism) and putative activation of cannabinoids and vanilloid TRPV1 receptors via “entourage” effects.
On PELVIC FLOOR REHABILITATION IN CHRONIC PELVIC PAIN SYNDROME and PEA
Chronic pelvic pain syndrome (CPPS) is used to designate unexplained chronic pelvic pain in men. The management of patients with chronic pelvic and perineal pain requires preliminary clinical analysis designed to identify correlated urological and abdominal dysfunction. Physical evaluation is required to identify trigger points responsible for myofascial pain, pelvic floor muscle tension, and lumbar-pelvic-hip instability.
Physiotherapy is one of the first step therapy suggested in and must be initiated early in the course of the disease by therapists trained in these techniques. These techniques can be supported by use of several drugs.
Palmitoylethanolamide (PEA) is an endogenous fatty acid amide, belonging to the class of nuclear factor agonists. PEA has been demonstrated to bind to a receptor in the cell-nucleus (a nuclear receptor) and exerts a great variety of biological functions related to chronic pain and inflammation.
Aim of the study
Aim of this study is to describe muscle examination in patients with chronic pelvic and perineal pain and to determine the results that can be expected from physiotherapy and use of palmitoylethanolamide.
In the study from January 2014 to April 2015 22 men (average age 37,8 – range 26-62) with Chronic Pelvic Pain Syndrome (CP/CPPS) were selected and enrolled in this study. The pain was associated to irritative voiding symptoms in 12. Preliminary clinical and instrumental evaluation was performed to exclude other pathologies. Physical evaluation was performed to identify trigger points responsible for myofascial pain, pelvic floor muscle tension, and lumbar-pelvic-hip instability. In all patients we administered palmitoylethanolamide, 1200 mg for 15 days and 600 mg for 75 days. Pelvic floor rehabilitation was performed after 15 days of therapy and comprised repeated muscle contractions of the pelvic floor and biofeedback, twice a week for 6 weeks.
All patients were evaluated with Vas pain score and SF 12 score for quality of life before and after therapy. Vas and SF 12 were administrated at three and six months after therapy. We observed a significant decrease of Vas score and increase of SF 12 in 18 of 22 patients ( 81,8%). In 8 of the 12 patients with irritative voiding symptoms we observed significant improvements (66% ). These evaluations were confirmed by the dates at three and six months after therapy ( 16 and 14 of 22 patients). No adverse reactions were recognized during administration of the drug.
Pelvic pain is pain in the area of the pelvis. If the pain lasts for more than six months, it is deemed to be chronic pelvic pain. It can affect both women and men. Chronic pelvic pain in men is often referred to as Chronic Prostatitis / Chronic Pelvic Pain Syndrome (CP/CPPS). This pain is associated with irritative voiding symptoms and/or pain located in the groin, genitalia, or perineum in the absence of pyuria and bacteriuria. The use of the term prostatodynia is not encouraged in current practice. This term carries the negative historical connotation of being a “wastebasket” designation for a melange of psychosomatic symptoms and suggests that the source of the patient’s symptoms invariably lies within the prostate gland itself. Current research has provided evidence of numerous extraprostatic considerations, including neuropathic and other systemic pathologies.
There are no standard diagnostic tests; diagnosis is by exclusion of other disease entities. Multimodal therapy is the most successful treatment option, and includes blockers, phytotherapy, and protocols aimed at quieting the pelvic nerves through myofascial trigger point release with psychological re-training for anxiety control.
Palmitoylethanolamide in pelvic floor problems
Recently some protocols have used Palmitoylethanolamide (PEA). It is an endogenous fatty acid amide, belonging to the class of nuclear factor agonists. PEA, as an N-acylethanolamine, has physico-chemical properties comparable to anandamide, and while it is not strictly an endocannabinoid, it is often studied in conjunction with anandamide because of their overlapping synthetic and metabolic pathways.
The signaling lipid PEA is known to activate intracellular, nuclear and membrane-associated receptors and regulate many physiological functions related to the inflammatory cascade and chronic pain states. PEA’s mechanism of action sometimes is described as Autacoid Local Injury Antagonism (acronym ALIA),and PEA under this nomenclature is an ALIAmide.
Since 1993, many papers have been published on the various effects of PEA on the mast cell. Mast cells are often found in proximity to sensory nerve endings and their degranulation can enhance the nociceptive signal, the reason why peripheral mast cells are considered to be pro-inflammatory and pro-nociceptive and in this work has been used successfully in association with pelvic rehabilitation, in order to emphasize the role of the drug with the use of relaxing exercises understood through biofeedback.
PEA’s activity is currently seen as a new inroad in the treatment of neuropathic pain and related disorders. PEA has been explored in various clinical trials in a variety of pain states, for inflammatory and pain syndrome. From a clinical perspective the most important and promising indications for PEA are linked to neuropathic and chronic pain states, such as diabetic neuropathic pain, sciatic pain, CRPS, pelvic pain and entrapment neuropathic pain states.
Although the limited number of treated patients in this study, Palmitoylethanolamide, in association with pelvic floor rehabilitation, seems to be a useful alternative in the first step of treatment of chronic pelvic pain in men with or without voiding symptoms.
Palmitoylethanolamide is much used in the Netherlands in pet animals, mostly as 400 mg capsules pure PEA. in 2016 2 companies intensified their efforts to bring more PEA products to the market of pet animals:
Premune and Innovet Italia announced that they have expanded their collaboration by signing an exclusive licensing agreement for six additional products, targeting three key areas in companion animal well-being. The extended product range now includes Retopix® Spray, Retopix® Fluid, and Retopix® Oto (skin care), Normalia® (support of gut function) and Oculvet® Wipes and Oculvet® Drops (eye care).
The companies initiated a collaboration in August 2015 with the exclusive licensing agreement for Redonyl® Ultra, a nutritional supplement for support of normal skin function in cats and dogs based on PEA-um® (ultramicronized palmitoylethanolamide). Palmitoylethanolamide is a naturally occurring compound produced on demand by the body in response to inflammation and pain. Retopix®, Normalia® and Oculvet® all contain either PEA-um® or Adelmidrol, an analogue of PEA formulated specifically for topical administration.
The expanded collaboration gives Premune exclusive marketing rights for key European countries, with the option to expand to other geographies including North America. This brings the current Premune portfolio to seven products, all of which will be launched during 2016.
Er zijn veel sceptici die roepen dat PEA niet in het bloed kan komen, dat het in de maag afgebroken wordt, dat het alleen een placebo effect is…. Dat is allemaal onjuist.
Het PEA uit de PeaPure capsule (met het PEA-opt keurmerk) komt namelijk na inname wel degelijk in het bloed. Bij de inname van 800 mg PEA stijgen de plasma waarden ten minste zoveel dat er dubbel zo veel PEA in het bloed zit. We wisten al dat deze PEA capsules uitgebreid gedurende jaren door artsen getest waren op veiligheid en werkzaamheid.
Sinds 2016 weten we ook dat de PEA in de PeaPure capsules na inname inderdaad ook een meetbaar effect heeft op de plasmawaarde van de PEA in het bloed. Die verdubbelde en bij sommige mensen zien we zelfs nog veel grotere toenames.
Deze gegevens ondersteunen nog eens extra dat pure PEA (met het PEA-opt vignet) ook daadwerkelijk het lichaam voorzien van extern PEA.