What is Palmitoylethanolamide?
Palmitoylethanolamide is a natural pain killer ingredient in the fatty acid amide category and synthesized within your own body, we call it endogenous. It is widely used in sports nutrition supplements and joint health formulas worldwide, especially in the United States, Australia, UK, Canada and EU countries like the Netherlands, Belgium, and Italy.
Palmitoylethanolamide is a pretty long word, if it is your first time to come across it, you may wonder how to memorize or pronounce it. Well, palmitoylethanolamide is a word consists of three words:
Palmitoyl / pɑːmɪ’tɔɪl/ +Ethanol / ‘eθənɔːl/ +Amide / ‘æmɪd/
In our daily life, PEA (the first letter of each of the three words) is to refer to palmitoylethanolamide for short. However, PEA itself is a plant, and PEA protein is also applied in bodybuilding supplements as a vegetarian source of protein content. Don’t get them wrong.
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.
Palmitoylethanolamide chemical properties
The IUPAC name of PEA is N-(2-Hydroxyethyl) hexadecanamide. Raw Palmitoylethanolamide is usually in the powder form, with molecule formula and weight as C18H37NO2 and 299.49 respectively. 544-31-0 is Palmitoylethanolamide’s CAS Registry Number and unique chemical identity.
Palmitoylethanolamide is practically insoluble in water and poorly soluble in most other aqueous solvents. Therefore, you may find that almost 99% fished dosage formulations of palmitoylethanolamide are in capsules or soft gels.
Palmitoylethanolamide VS Phenylethylamine
In fact, they are two completely different ingredients. No relationship is between them. Phenylethylamine or Phenylethylamine HCl is most known as a mood and weight loss ingredient in many sports nutrition. While Palmitoylethanolamide is popularly known as a painkiller. The connection is that both compounds are abbreviated as PEA, and called by PEA powder. So don’t get them wrong.
Palmitoylethanolamide vs anandamide
Many of our clients who buy bulk Palmitoylethanolamide powder are also interested in Bulk anandamide powder and anandamide oil from us. Therefore, what’s the relation between them?
Both palmitoylethanolamide and anandamide are endogenous fatty acid amide in our human bodies.
According to Wikipedia, PEA and related compounds such as anandamide seem to have synergistic effects in models of pain and analgesia.
Gas-chromatography/mass-spectrometry measurements indicate that the levels of anandamide and PEA in the skin are enough to cause a tonic activation of local cannabinoid receptors.
In one study, the data shows that anandamide and PEA activate pharmacologically distinct receptors and that these two substances can be produced simultaneously in tissues. When injected together in equal amounts, anandamide and PEA inhibited the early phase of formalin-evoked pain behavior with a potency that was approximately 100-fold greater than each of the compounds separately (Fig. 3a). A similar synergistic potentiation occurred in the late phase, on which anandamide had no effect when given alone (Figs 1a and 3b). Earlier administration of either CB1 or CB2 antagonists entirely blocked the response.
Anandamide and PEA synergistically inhibit formalin-evoked nociception.
a, Early phase.
b, Late phase (open squares, anandamide; filled diamonds, PEA; filled circles, anandamide plus PEA). Equal amounts of anandamide and PEA were administered by i.pl. Injection at the doses indicated on the abscissa.
In addition, the FAAH enzyme is able to break down both anandamide and palmitoylethanolamide in the body. If more PEA and AEA powder are added, it will take more time for FAAH to work and thus lasts longer positive effects.
Palmitoylethanolamide food sources
Some natural sources are found to contain Palmitoylethanolamide.
You may notice that soy lecithin, soybean, peanut (Arachis hypogaea), and Medicago sativa are among the top food sources. However, the calculating weight unit is ng/g (nanogram/gram). 6700 ng/g is equal to 6.7mg/kilo, meaning that only 6.7mg PEA is in 1 kilo of soybean. The concentration of palmitoylethanolamide in natural foods are too low to meet our daily need. All the market need is bulk Palmitoylethanolamide, high in concentration and low in manufacturing cost. Cima science is a bulk supplier of palmitoylethanolamide raw powder. If you have any question regarding PEA, just feel free to contact us.
Palmitoylethanolamide safety status
When we talk about ingredient safety, you need to check about how Drug Administration (FDA) and European Medicines Agency (EMA) regulate it.
Palmitoylethanolamide and FDA
Palmitoylethanolamide is marked as a dietary supplement ingredient in the United States. FDA has a flexible policy upon dietary ingredient. Federal law does not require dietary supplements to be proven safe to FDA’s satisfaction before they are marketed. As long as the ingredient can be found in the human body metabolic process, it is regarded as safe to be used.
Palmitoylethanolamide is naturally occurring in your body, and can also be found in many food sources. It is safe to be supplemented to the body. More than 400 studies and clinical trials are conducted; no serious side effects have been reported yet.
Moreover, there are hundreds of palmitoylethanolamide supplements on sales on supplement stores Amazon, Vitamin Shoppe, iHerb, GNC, etc.
Although there is no GRAS notice for palmitoylethanolamide ingredient, for the time being, it is still safe to use PEA in your supplement formula. And there is nothing to worry about.
European Medicines Agency (EMA) regulation
In some European countries like Italy, Germany, and Spain, palmitoylethanolamide is commercially advertised as dietary food for special medical purposes (AFMS). Just name some trademarks for your reference, such as PeaVera™ from JP Russell Science), Normast® of Epitech and Visimast® from Medivis.
In Italy, The Italian Ministry of Health has recently revised its two food supplement guidelines on permitted daily levels of vitamins and minerals and nutrients and other substances with a nutritional or physiological effect.
It is also interesting to note that Palmitoylethanolamide has been proved to be devoid of side effects, even if used for prolonged periods and/or administered to fragile subjects. That’s why Palmitoylethanolamide (PEA) is added to the list of substances for use in food supplements without defined maximum limits.
Palmitoylethanolamide clinical trials
More than 500 clinical studies on Palmitoylethanolamide has been extensively carried out in the past decades. These studies demonstrate objective improvements in nerve function, chronic pain, neuropathic pain, and chronic inflammation, etc.
In one paper, it recorded 21 clinical studies, of which 16 were clinical trials enrolling a range of 20 to 636 patients and five were case/pilot studies. In the clinical trials, Palmitoylethanolamide was used for periods ranging from 14 days to 120 days, and the doses ranged from 300 mg to 1200 mg daily. The administration form of PEA was in most cases oral tablets except some occasional use of sublingual formulations (sachets), and the commonest form of evaluation was the visual analog scale (VAS), where the patient makes a subjective assessment of her/his pain level on a 10 cm line where the left side represents no pain, and the right side represents the worst imaginable pain. With one exception, possibly a ‘floor effect’), all available clinical trials reported significantly reduced pain intensity and an almost complete absence of unwanted effects, the latter confirming early field studies of Palmitoylethanolamide in healthy individuals.
The literature is listed as below:
- The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review
- Efficacy of ultra-micronized palmitoylethanolamide (um-PEA) in geriatric patients with chronic pain: study protocol for a series of N-of-1 randomized trials
- Palmitoylethanolamide in the Treatment of Chronic Pain Caused by Different Etiopathogenesis
- Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy
There are various PEA specifications available, such as powder form, topical cream, capsule, tablet, etc.
Our popular specs are powder forms. Well, there are two main sub-categories: normal PEA powder and micronized or ultra-micronized palmitoylethanolamide.
Both are food grade and pharmaceutical grade ingredients that can be used in supplement and medicines directly. The difference lies in the particle size.
Micronized Palmitoylethanolamide powder has a particle size ranges from 2 to 6 micron (or μm). The normal PEA powder is about 80 mesh(which is equal to 180 microns. The micronized PEA is about 100 times smaller the non-micronized PEA. The benefits of being micronized are that it has much better bioavailability and gastroenteric absorption, and the micronized PEA has the anti-caking property and maintains stable at room temperature. That’s why so many clients prefer to use micronized Palmitoylethanolamide.
Mechanism of action of Palmitoylethanolamide
Palmitoylethanolamide works by affecting various receptors directly or indirectly, such as PPAR-a, CB1, CB2, GPR119, GPR55, etc.
Palmitoylethanolamide increases the endogenous levels of AEA (anandamide) and 2-AG(2-arachidonoyl-glycerol) through the inhibition of the activity or expression of FAAH, or via additional unknown mechanisms, which directly activate CB2 and TRPV1 receptors (transient receptor potential vanilloid type-1 channel). PEA, possibly through allosteric modulation of TRPV1 receptors, potentiates the actions of AEA and 2-AG at TRPV1 receptors.
PPAR-α and GPR55 are direct receptors. The PPAR-a receptor mediates mood, pain, and neuroinflammation. PEA bound to PPAR-a receptors forms heterodimers with retinoic acid receptors. The dimer acts as a transcription factor promoter of peroxisome proliferator response elements.
Activation of PPAR-a increases the production of intracellular neurosteroids, which alters calcium channels and big conductance potassium channels leading to hyperpolarized neurons. This accounts for the antiseizure activity of PEA in animal models.
Palmitoylethanolamide blocks the excessive activity of mast cells and glial cells and restores their normal activity. By the way, Palmitoylethanolamide also cuts down the activity of the pro-inflammatory enzyme COX. There are more mechanisms showing how palmitoylethanolamide works (listed in the very bottom of this page.)
Relieving pain and fighting against inflammation are the two main benefits.
PEA for Neuropathic Pain
In one pivotal, double-blind, placebo-controlled trial in 636 sciatic pain patients, pain intensity is strongly reduced by 50% after 3 weeks of treatment.
Furthermore, no drug interactions or troublesome side effects have been described so far.
PEA for anti-Inflammation
Inflammation means pain. The inflammatory process is of great significance in the development of Neuropathic Pain.
Palmitoylethanolamide is an anti-inflammatory and pro-resolving lipid mediator that turns down mast cell activation and regulates glial cell behaviors. The sustained imbalance between pro-inflammatory and pro-resolving mediators shows that chronic neuroinflammation is happening.
The FAAH enzyme further degrades the available amide in the body, further reducing its quantity and effectiveness. Palmitoylethanolamide functions to counter the action of the FAAH enzyme, thereby improving the condition of aggravated inflammation, which is the root cause of neuropathic pain.
Supplements containing Palmitoylethanolamide
If you check all the supplement markets, you’ll find various PEA supplement forms available, some in capsules, some in tablets, some even in powder forms; some are used in a single ingredient formula, some are blended with other joint health compounds. Below are some typical examples of PEA forms and their respective dosage information:
PEA Discomfort Relief
This Palmitoylethanolamide is in chewable tablet form. One tablet contains 600mg PEA, and the dosage is one to two tablets a day, that’s 600mg to 1200mg daily.
This PEA formula is Palmitoylethanolamide 600mg with 300mg Turmeric Root Extract (95% curcuminoids) per serving. (per day)
Joint Formula Powder
Methylsulfonylmethane (MSM), Turmeric Extract (Root), Hyaluronic Acid and Palmitoylethanolamide are the four main active ingredients in this joint health powder formula. The daily intake of PEA is 600mg as well.
Mirica Natural Pain Relief Formula
Palmitoylethanolamide Side effects
Palmitoylethanolamide is naturally occurring and is one part of our body. The EU has no limit on the dosage of Palmitoylethanolamide every day. No serious adverse effects have been reported yet.
Where to buy Palmitoylethanolamide powder?
Cima Science is the professional manufacturer of bulk palmitoylethanolamide powder, and able to ship to every country by courier, by air, by sea or other means.
Our PEA powder has been tested by trusted and authoritative Third-Party Testing labs and organizations on purity, Heavy Metals, Residual Solvents, NMR spectrum, microorganism testing (Microbiology testing) and Oral Acute Toxicity Study of Palmitoylethanolamide
The purity (assay) of Palmitoylethanolamide tested by Advanced Botanical Consulting & Testing Inc.(ABC Testing. Inc) is 99.18%
The tested metals include Mercury (Hg), Lead (Pb), Arsenic (As) and Cadmium (Cd). Each content tested in the Eurofins confirms to the standard of below 0.005 g/kg and 0.001g/kg, low than the standard requirement. According to Pony Testing International Group, none of the heavy metals is detected.
Palmitoylethanolamide Microbiology testing tested aerobic plate count and moulds & Yeast. Eurofins analytical report results are both less than 10 CFU/g.
The detailed testing reports in downloadable PDF forms are as below:
- Palmitoylethanolamide purity testing report by Advanced Botanical Consulting & Testing Inc
- Palmitoylethanolamide NMR spectrum
- Palmitoylethanolamide Powder Residual Solvents Pony Testing result
- Palmitoylethanolamide Microbiology testing Eurofins analytical report
- Palmitoylethanolamide heavy metals testing by Pony
- Palmitoylethanolamide heavy metals Eurofins analytical report
- Oral Acute Toxicity Study of Palmitoylethanolamide (SLX1253)+in+Rats(R)
What are our advantages of Cima PEA?
- Palmitoylethanolamide, a Special Food for Medical Purposes, in the Treatment of Chronic Pain: A Pooled Data Meta-analysis
- The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations
- Micronized ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain
- Therapeutic benefit of palmitoylethanolamide in the management of neuropathic pain