A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis

Steels, Emmanuelle; Venkatesh, Ruchitha; Steels, Eleanor; Vitetta, Gemma; Vitetta, Luis

doi:10.1007/s10787-019-00582-9

Cited by 40 publications

(61 citation statements)

References 48 publications

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“…Locally produced PEA has long been known to participate in the intrinsic control of pain [ 24 ] and to exert a tonic inhibitory control over the induction of nociceptive responses [ 25 ]. Its dietary supplementation was recently proved to relieve pain in natural [ 26 , 27 , 28 ] and experimental OA [ 29 ]. Palmitoyl-glucosamine (PGA)—the amide of palmitic acid and glucosamine—is an ALIAmide particularly suitable for orthopedic use [ 30 ] and it is listed in the EU-Catalogue of feed materials used in animal nutrition.…”

Section: Introductionmentioning

confidence: 99%

Dietary Supplementation with Palmitoyl-Glucosamine Co-Micronized with Curcumin Relieves Osteoarthritis Pain and Benefits Joint Mobility

Gugliandolo

Peritore

Impellizzeri

et al. 2020

Animals

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Chronic mixed pain and orthopedic dysfunction are the most frequently associated consequences of canine osteoarthritis (OA). An unmet need remains for safe and effective therapies for OA. Palmitoyl-glucosamine (PGA) and curcumin are safe and naturally occurring compounds whose use is limited by poor bioavailability. Micronization is an established technique to increase bioavailability. The aim of this study was to investigate if the dietary supplementation with PGA co-micronized with curcumin (PGA-Cur, 2:1 ratio by mass) could limit pathologic process in two well-established rat models of inflammation and OA pain, i.e., subplantar carrageenan (CAR) and knee injection of sodium monoiodoacetate (MIA), respectively. In CAR-injected animals, a single dose of PGA-cur significantly reduced paw edema and hyperalgesia, as well as tissue damage and neutrophil infiltration. The repeated administration of PGA-Cur three times per week for 21 days, starting the third day after MIA injection resulted in a significant anti-allodynic effect. Protection against cartilage damage and recovery of locomotor function by 45% were also recorded. Finally, PGA-cur significantly counteracted MIA-induced increase in serum levels of TNF-α, IL-1β, NGF, as well as metalloproteases 1, 3, and 9. All the effects of PGA-Cur were superior compared to the compounds used singly. PGA-Cur emerged as a useful dietary intervention for OA.

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Section: Introductionmentioning

confidence: 99%

Dietary Supplementation with Palmitoyl-Glucosamine Co-Micronized with Curcumin Relieves Osteoarthritis Pain and Benefits Joint Mobility

Gugliandolo

Peritore

Impellizzeri

et al. 2020

Animals

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“…The main mechanism of action of ALIAmides (i.e., ALIA, autacoid local injury antagonism) mainly relies on the down-modulation of cell hyperactivity following injury [12], as first shown on mast cells by the late Nobel laureate Rita Levi Montalcini [13]. A decrease in PEA levels was reported in the synovial fluid of OA patients [14], and oral treatment with PEA has proved to benefit patients with temporomandibular joint OA and mild to moderate knee OA [15, 16]. N -Palmitoyl- d -glucosamine (PGA, also referred to as Glupamid) is one of the less studied among ALIAmides, and only few reports on this compound have been published so far [17–19].…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of a new micronized formulation of the ALIAmide palmitoylglucosamine in preclinical models of inflammation and osteoarthritis pain

et al. 2019

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BackgroundOsteoarthritis is increasingly recognized as the result of a complex interplay between inflammation, chrondrodegeneration, and pain. Joint mast cells are considered to play a key role in orchestrating this detrimental triad. ALIAmides down-modulate mast cells and more generally hyperactive cells. Here we investigated the safety and effectiveness of the ALIAmide N-palmitoyl-d-glucosamine (PGA) in inflammation and osteoarthritis pain.MethodsAcute toxicity of micronized PGA (m-PGA) was assessed in rats following OECD Guideline No.425. PGA and m-PGA (30 mg/kg and 100 mg/kg) were orally administered to carrageenan (CAR)-injected rats. Dexamethasone 0.1 mg/kg was used as reference. Paw edema and thermal hyperalgesia were measured up to 6 h post-injection, when also myeloperoxidase activity and histological inflammation score were assessed. Rats subjected to intra-articular injection of sodium monoiodoacetate (MIA) were treated three times per week for 21 days with PGA or m-PGA (30 mg/kg). Mechanical allodynia and motor function were evaluated at different post-injection time points. Joint histological and radiographic damage was scored, articular mast cells were counted, and macrophages were immunohistochemically investigated. Levels of TNF-α, IL-1β, NGF, and MMP-1, MMP-3, and MMP-9 were measured in serum using commercial colorimetric ELISA kits. One- or two-way ANOVA followed by a Bonferroni post hoc test for multiple comparisons was used.ResultsAcute oral toxicity of m-PGA resulted in LD50 values in excess of 2000 mg/kg. A single oral administration of PGA and m-PGA significantly reduced CAR-induced inflammatory signs (edema, inflammatory infiltrate, and hyperalgesia), and m-PGA also reduced the histological score. Micronized PGA resulted in a superior activity to PGA on MIA-induced mechanical allodynia, locomotor disability, and histologic and radiographic damage. The MIA-induced increase in mast cell count and serum level of the investigated markers was also counteracted by PGA and to a significantly greater extent by m-PGA.ConclusionsThe results of the present study showed that PGA is endorsed with anti-inflammatory, pain-relieving, and joint-protective effects. Moreover, it proved that particle size reduction greatly enhances the activity of PGA, particularly on joint pain and disability. Given these results, m-PGA could be considered a valuable option in the management of osteoarthritis.

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“…In an experimental model of osteo-arthritis induced by iodium monoiodoacetate (MIA), treatment with PEA has been shown to produce an improvement in locomotor function as well as a protective action on cartilage, in addition to an important anti-inflammatory and pain-relieving action [ 25 ]. The protective action of PEA in joint diseases has been confirmed in human medicine as a potential successful treatment for attenuating pain and reducing other associated symptoms of knee osteoarthritis [ 31 ]. In veterinary medicine, PEA has proven effective in the treatment of atopic dermatitis in dogs and cats [ 8 , 32 ], and has demonstrated potential as an effective treatment for inflammatory processes and pain in veterinary medicine [ 6 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

Oral Supplementation with Ultramicronized Palmitoylethanolamide for Joint Disease and Lameness Management in Four Jumping Horses: A Case Report

Gugliandolo

Barbagallo

Peritore

et al. 2020

Animals

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Background: Four show jumping horses were evaluated for non-responsive lameness, which caused their withdrawal from show jumping competitions. The clinical evaluation was performed by radiographic examination, flexion tests, diagnostic anesthesia and lameness evaluation using the American Association of Equine Practitioners (AAEP) scale. The diagnoses were a case of navicular syndrome, a complicated case of chronic navicular syndrome and arthrosis of the distal interphalangeal joint of the right anterior limb and two cases of distal intertarsal joint arthritis. Nutraceuticals are often an important management strategy or coadjutant of pharmacological therapies in joint disease. Ultramicronized Palmitoylethanolamide (PEA-um) is an endogenous fatty acid amide that is well-known for its anti-inflammatory and analgesic proprieties widely used in human medicine and small animal veterinary medicine. Although it includes a small number of cases, our study describes for the first time the efficacy of the use of PEA-um in horses. The four horses with non-responsive lameness and significant impairment in athletic performance were daily treated with PEA-um into their normal diet. After four months of PEA-um supplementation, all horses showed remissions of lameness that led to their reintroduction into showjumping competitions without disease recurrence. Therefore, despite the small number of cases included in this study, these observations suggest a good prospective for developing a controlled experiment to test PEA in a larger cohort of horses.

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A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis

Cited by 40 publications

References 48 publications

Dietary Supplementation with Palmitoyl-Glucosamine Co-Micronized with Curcumin Relieves Osteoarthritis Pain and Benefits Joint Mobility

Dietary Supplementation with Palmitoyl-Glucosamine Co-Micronized with Curcumin Relieves Osteoarthritis Pain and Benefits Joint Mobility

Safety and efficacy of a new micronized formulation of the ALIAmide palmitoylglucosamine in preclinical models of inflammation and osteoarthritis pain

Oral Supplementation with Ultramicronized Palmitoylethanolamide for Joint Disease and Lameness Management in Four Jumping Horses: A Case Report

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