Palmitoylethanolamide (PEA) is a fatty acid and part of endocannabinoids. PEA powder has been utilized in various controlled studies for treating pain in adult patients. It has been proven to have analgesic and anti-inflammatory effects. It is an organic compound and a trace amine, which acts as a central nervous system stimulant in humans. According to preliminary palmitoylethanolamide clinical trial studies, PEA is not an opioid and does not gradually lose its potency over time or acquire pharmacological tolerance, as with opioids. It has been demonstrated to be safe for patients, with no significant side effects reported, and it is believed to have neither acute nor chronic toxicity. Because it has anti-inflammatory properties, it has been studied for many chronic conditions, including knee osteoarthritis.
The key findings
Osteoarthritis is the most common form of arthritis, affecting millions of people worldwide. It happens when the protective cartilage on the ends of your bones decreases over time. Osteoarthritis can damage a joint in your body and commonly affects the joints in your hands, knees, hips, and spine. Although the leading cause of osteoarthritis cannot be cured, the symptoms can be adequately managed. Being physically active, maintaining a healthy weight, and receiving additional therapies can all help to limit the disease’s progression, alleviate the pain, and enhance the overall function of the locomotor system.
The main purpose of this study is to investigate the efficacy and safety of PEA for treating symptoms of knee osteoarthritis. This is a double-blind, randomized, and placebo clinical trial. The participants were questioned in a pre-interview for basic information about their lifestyle, current medication, and medical condition by phone. 111 participants, aged between 38 and 76 years old, were given 300 mg PEA, 600 mg PEA, or a placebo each day for 8 weeks. The participants were with mild to moderate knee osteoarthritis.
All participants were excluded if they had other forms of arthritis such as osteoporosis or rheumatoid arthritis, had a recent injury, had alcohol abuse, had taken any drugs for pain, had high cholesterol, diabetes, and more. They were allowed to administrate only paracetamol to ease the pain.
They administrate the PEA in the form of a capsule in the morning with their breakfast and dinner for eight weeks. The results were obtained using 300mg and 600mg doses compared with the placebo group by the WOMAC. The measurements were taken at the baseline, after two days, after week 1, week 4, and 8 weeks. CRP and other biochemical parameters were measured to evaluate the safety of this study.
The results
There was a significant decrease in the total WOMAC score of the 300mg group and the 600mg group, compared to the placebo group. Also, the pain was reduced in the WOMAC score in the 300mg and 600mg groups after eight weeks.
Steels E, Venkatesh R, Steels E, Vitetta G, Vitetta L. A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis. Inflammopharmacology. 2019 Jun;27(3):475-485. doi: 10.1007/s10787-019-00582-9. Epub 2019 Mar 29. PMID: 30927159.
(A significant reduction in the pain after 8 weeks of PEA.)
There was also a decrease in WOMAC stiffness scores after 8 weeks in both groups compared to the placebo group.
Steels E, Venkatesh R, Steels E, Vitetta G, Vitetta L. A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis. Inflammopharmacology. 2019 Jun;27(3):475-485. doi: 10.1007/s10787-019-00582-9. Epub 2019 Mar 29. PMID: 30927159.
(A significant reduction in the stiffness after 8 weeks of PEA.)
There was a reduction in the WOMAC function at week 4, but not that significant compared to the placebo group. However, by the 8 weeks, there was a significant decrease in the 300mg group compared to the placebo group.
Steels E, Venkatesh R, Steels E, Vitetta G, Vitetta L. A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis. Inflammopharmacology. 2019 Jun;27(3):475-485. doi: 10.1007/s10787-019-00582-9. Epub 2019 Mar 29. PMID: 30927159.
(A significant reduction in the WOMAC function after 8 weeks of PEA in the 300mg group.)
Both the 300 mg PEA group and the 600 mg PEA group significantly decreased the “worst pain” and “least pain” NRS (numerical rating scales) when compared to the placebo. Interestingly, participants who took either dose of PEA also reported less anxiety (DASS) in the 300 mg and 600 mg PEA groups compared to the placebo.
Steels E, Venkatesh R, Steels E, Vitetta G, Vitetta L. A double-blind, randomized placebo-controlled study assessing safety, tolerability, and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis. Inflammopharmacology. 2019 Jun;27(3):475-485. doi: 10.1007/s10787-019-00582-9. Epub 2019 Mar 29. PMID: 30927159.
(Pain scores for PEA at 300mg/day and 600mg/day.)
The hematological and biochemical values were within the reference range. ESR and CRP, two inflammatory indicators, were maintained at comparable values in all therapy groups at baseline and week 8. The trial participants did not report any major adverse effects.
Limitations in the study
Although PEA can be successfully used in the treatment of knee OA, there were some limitations related to this study. The distribution of the male and female populations was not equal, and the time observing the results was very short. Additionally, the study eliminated people with obesity who might influence the final dose needed for therapeutic efficacy.
To sum up
This study is the first human clinical trial of PEA for knee OA pain. The effects demonstrated by using PEA at 300mg/day and 600mg/day showed that PEA could be used in treating knee OA. The participants showed no adverse effects. Furthermore, the anxiety was also reduced after 8 weeks of PEA. According to other animal studies with chronic inflammation, PEA can lower mast cell activation and the production of inflammatory cytokines, thus resulting in reduced pain and inflammation. PEA has the potential to be used as a safe treatment for knee osteoarthritis.
