RESUMO
This narrative review provides an overview of current knowledge on the impact of nutritional strategies on chronic craniofacial pain associated with temporomandibular disorders (TMDs). Individuals experiencing painful TMDs alter their dietary habits, avoiding certain foods, possibly due to chewing difficulties, which might lead to nutrient deficiencies. Our literature investigation revealed that the causal links between nutritional changes and craniofacial pain remain unclear. However, clinical and preclinical studies suggest that nutraceuticals, including vitamins, minerals, polyphenols, omega-3 fatty acids, isoprenoids, carotenoids, lectins, polysaccharides, glucosamines, and palmitoylethanolamides, could have beneficial effects on managing TMDs. This is described in 12 clinical and 38 preclinical articles since 2000. Clinical articles discussed the roles of vitamins, minerals, glucosamine, and palmitoylethanolamides. The other nutraceuticals were assessed solely in preclinical studies, using TMD models, mostly craniofacial inflammatory rodents, with 36 of the 38 articles published since 2013. Our investigation indicates that current evidence is insufficient to assess the efficacy of these nutraceuticals. However, the existing data suggest potential for therapeutic intervention in TMDs. Further support from longitudinal and randomized controlled studies and well-designed preclinical investigations is necessary to evaluate the efficacy of each nutraceutical intervention and understand their underlying mechanisms in TMDs.
Assuntos
Dor Crônica , Suplementos Nutricionais , Dor Facial , Transtornos da Articulação Temporomandibular , Transtornos da Articulação Temporomandibular/dietoterapia , Humanos , Dor Facial/dietoterapia , Dor Facial/etiologia , Dor Crônica/dietoterapia , Dor Crônica/terapia , Animais , Ácidos Graxos Ômega-3/administração & dosagem , Glucosamina/administração & dosagem , Vitaminas/administração & dosagem , Amidas , Etanolaminas , Ácidos PalmíticosRESUMO
AIM: To investigate the efficacy of Palmitoylethanolamide (PEA, 300 mg), Superoxide Dismutase (SOD, 70 UI), Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), nicotinamide (9 mg), and minerals (Mg 30 mg, Zn 2.5 mg) in one tablet in people with Diabetic Neuropathy (DN). PATIENTS-METHODS: In the present pilot study, 73 people (age 63.0 ± 9.9 years, 37 women) with type 2 Diabetes Mellitus (DMT2) (duration 17.5 ± 7.3 years) and DN were randomly assigned to receive either the combination of ten elements (2 tablets/24 h) in the active group (n = 36) or the placebo (n = 37) for 6 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured vibration perception threshold (VPT) with biothesiometer, and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Sudomotor function was assessed with SUDOSCAN, which measures electrochemical skin conductance in hands and feet (ESCH and ESCF). Pain score (PS) was assessed with Pain DETECT questionnaire. Quality of life was assessed by questionnaire. RESULTS: In the active group, there was a large improvement of pain (PS from 20.9 to 13.9, p < 0.001). There was also a significant improvement of vitamin B12 (B12) levels, MNSIQ, SNCV, VPT, and ESCF (222.1 vs. 576.3 pg/ mL, p < 0.001; 6.1 vs. 5.9, p = 0.017; 28.8 vs. 30.4, p = 0.001; 32.1 vs. 26.7, p = 0.001; and 72.2 vs. 74.8, p < 0.001 respectively). In the placebo group, neither pain (21.6 vs. 21.7, p = 0.870) or any other aforementioned parameters changed significantly, and MNSIE worsened (2.9 vs. 3.4, p < 0.001). As a result, changes from baseline to follow-up in pain, B12 levels, VPT, and MNSIQ differed significantly between the two groups (p < 0.001, 0.025, 0.009, and <0.001, respectively). CARTs, SNAP, ESCH did not significantly change in either of the two groups. CONCLUSIONS: The combination of the ten elements in one tablet for 6 months at a daily dose of two tablets in people with DN significantly improves pain, vibration perception threshold, and B12 levels.
Assuntos
Amidas , Neuropatias Diabéticas , Etanolaminas , Niacinamida , Ácidos Palmíticos , Superóxido Dismutase , Ácido Tióctico , Vitamina B 12 , Vitamina B 6 , Humanos , Pessoa de Meia-Idade , Feminino , Neuropatias Diabéticas/tratamento farmacológico , Masculino , Idoso , Vitamina B 12/administração & dosagem , Ácido Tióctico/administração & dosagem , Projetos Piloto , Vitamina B 6/administração & dosagem , Ácidos Palmíticos/administração & dosagem , Etanolaminas/administração & dosagem , Niacinamida/administração & dosagem , Niacinamida/uso terapêutico , Amidas/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Zinco/administração & dosagem , Vitamina E/administração & dosagem , Método Duplo-Cego , Tiamina/administração & dosagem , Resultado do Tratamento , Suplementos NutricionaisRESUMO
Palmitoylethanolamide (PEA) is a highly lipophilic molecule with low solubility, making absorption difficult. Recent techniques like micronisation, ultra-micronisation and combining PEA with solvents have improved their bioavailability and stability. Our study analysed particle size differences and absorption kinetics using specific solvents (PEAΩ and PEA DynoΩ) over time (0.5 h-6 h) in a dose-dependent manner (200 mg-1800 mg). The results showed that PEAΩ and PEA DynoΩ achieved 82-63% absorption at 3 h, compared to 30-60% for micronised, ultra-micronised PEA and a commercial product, highlighting the optimal dose range of 300 mg-600 mg. In addition, a 3D model of the peripheral nerve was utilised to explain the efficacy after gut passage and support the most effective dose (300 mg or 600 mg) achieved at the gut level. PEAΩ and PEA DynoΩ, which are associated with better intestinal bioavailability compared to PEA-micronised, PEA ultra-micronised and a commercial product, have allowed not only a reduction in the inflammatory context but also an improvement of peripheral nerve well-being by increasing specific markers like MPZ (26-36% vs. 8-15%), p75 (25-32% vs. 13-16%) and NRG1 (22-29.5% vs. 11-14%). These results highlight the potential of advanced PEA formulations to overcome solubility challenges and maintain in vitro efficacy, modulating peripheral nerve well-being.
Assuntos
Amidas , Etanolaminas , Ácidos Palmíticos , Ácidos Palmíticos/química , Ácidos Palmíticos/farmacologia , Etanolaminas/química , Amidas/química , Humanos , Disponibilidade Biológica , Relação Dose-Resposta a Droga , Suplementos Nutricionais , Animais , Nervos Periféricos/efeitos dos fármacos , Tamanho da PartículaRESUMO
Plasma levels of endocannabinoids (eCBs) are very dynamic and variable in different circumstances and pathologies. The aim of the study was to determine the levels of the main eCBs and N-acylethanolamines (NAEs) in COVID-19 patients during the acute and post-acute phase of SARS-CoV-2 infection. Samples collected before December 31, 2020 were used for the determination of circulating eCB levels by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The association between plasma eCB measurements and biochemical and hematological parameters, as well as serum IL-6 levels, was evaluated. Samples of 64 individuals were analysed, n = 18 healthy donors, n = 30 acute, and n = 16 post-acute patients. Plasma levels of 2-arachidonoylglycerol (2-AG), were significantly elevated in COVID-19 patients when compared to healthy individuals. Plasma N-palmitoylethanolamide (PEA) and N-arachidonoylethanolamide (AEA) levels were found to be decreased in post-acute patient samples. These results suggest that 2-AG plays an important role in the inflammatory cascade in COVID-19 disease; in addition, eCBs might be involved in the post-acute pathogenesis of COVID-19. This study provides evidence of altered levels of circulating eCBs as a consequence of SARS-CoV-2 infection.
Assuntos
Ácidos Araquidônicos , COVID-19 , Endocanabinoides , Glicerídeos , Inflamação , SARS-CoV-2 , Humanos , Endocanabinoides/sangue , COVID-19/sangue , COVID-19/virologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Ácidos Araquidônicos/sangue , Inflamação/sangue , Glicerídeos/sangue , Alcamidas Poli-Insaturadas/sangue , Etanolaminas/sangue , Idoso , Interleucina-6/sangue , Ácidos Palmíticos/sangue , Espectrometria de Massas em Tandem , Amidas , Cromatografia LíquidaRESUMO
Depression and anxiety are prominent symptoms of withdrawal syndrome, often caused by the abuse of addictive drugs like morphine. N-palmitoylethanolamide (PEA), a biologically active lipid, is utilized as an anti-inflammatory and analgesic medication. Recent studies have highlighted PEA's role in mitigating cognitive decline and easing depression resulting from chronic pain. However, it remains unknown whether PEA can influence negative emotions triggered by morphine withdrawal. This study seeks to explore the impact of PEA on such emotions and investigate the underlying mechanisms. Mice subjected to morphine treatment underwent a 10-day withdrawal period, followed by assessments of the effect of PEA on anxiety- and depression-like behaviors using various tests. Enzyme-linked immunosorbent assay was conducted to measure levels of monoamine neurotransmitters in specific brain regions. The findings indicate that PEA mitigated anxiety and depression symptoms and reduced 5-hydroxytryptamine, noradrenaline, and dopamine levels in the hippocampus and prefrontal cortex. In summary, PEA demonstrates a significant positive effect on negative emotions associated with morphine withdrawal, accompanied with the reduction in levels of monoamine neurotransmitters in key brain regions. These insights could be valuable for managing negative emotions arising from morphine withdrawal.
Assuntos
Amidas , Ansiedade , Depressão , Etanolaminas , Morfina , Ácidos Palmíticos , Síndrome de Abstinência a Substâncias , Animais , Síndrome de Abstinência a Substâncias/psicologia , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Etanolaminas/farmacologia , Ácidos Palmíticos/farmacologia , Camundongos , Masculino , Morfina/farmacologia , Depressão/metabolismo , Depressão/tratamento farmacológico , Depressão/psicologia , Depressão/etiologia , Amidas/farmacologia , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Ansiedade/metabolismo , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Emoções/efeitos dos fármacos , Serotonina/metabolismo , Dependência de Morfina/metabolismo , Dependência de Morfina/psicologia , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Norepinefrina/metabolismo , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacosRESUMO
BACKGROUND: The mental health benefits of cannabidiol (CBD) are promising but can be inconsistent, in part due to challenges in defining an individual's effective dosage. In schizophrenia, alterations in anandamide (AEA) concentrations, an endocannabinoid (eCB) agonist of the eCB system, reflect positively on treatment with CBD. Here, we expanded this assessment to include eCBs alongside AEA congeners, comparing phytocannabinoids and dosage in a clinical setting. METHODS: Liquid chromatography-tandem mass spectrometry quantified changes in serum levels of AEA, 2-arachidonoylglycerol (2-AG), alongside AEA-related compounds oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which were attained from two independent, parallel-designed, clinical trials investigating single, oral CBD (600 or 800 mg), delta-9-tetrahydrocannabinol (Δ9-THC, 10 or 20 mg) and combination administration (CBD|800 mg+Δ9-THC|20 mg) in healthy volunteers (HVs, n=75). Concentrations were measured at baseline (t=0), 65 and 160 min post administration. RESULTS: CBD-led increases in AEA (1.6-fold), OEA and PEA (1.4-fold) were observed following a single 800 mg (pcorr<0.05) but not 600 mg dosage. Declining AEA was observed with Δ9-THC at 10 mg (-1.3-fold) and 20 mg (-1.4-fold) but restored to baseline levels by 160 min. CBD+Δ9-THC yielded the highest increases in AEA (2.1-fold), OEA (1.9-fold) and PEA (1.8-fold) without reaching a maximal response. CONCLUSION: CBD-administered effects towards AEA, OEA and PEA are consistent with phase II trials reporting clinical improvement for acute schizophrenia (CBD≥800 mg). Including Δ9-THC appears to enhance the CBD-induced response towards AEA and its congeners. Our results warrant further investigations into the potential of these lipid-derived mediators as metabolic measures for CBD dose prescription and co-cannabinoid administration.
Assuntos
Ácidos Araquidônicos , Canabidiol , Relação Dose-Resposta a Droga , Dronabinol , Endocanabinoides , Etanolaminas , Voluntários Saudáveis , Alcamidas Poli-Insaturadas , Humanos , Endocanabinoides/sangue , Ácidos Araquidônicos/sangue , Ácidos Araquidônicos/administração & dosagem , Canabidiol/administração & dosagem , Canabidiol/sangue , Adulto , Masculino , Alcamidas Poli-Insaturadas/sangue , Alcamidas Poli-Insaturadas/administração & dosagem , Etanolaminas/administração & dosagem , Etanolaminas/sangue , Dronabinol/sangue , Dronabinol/administração & dosagem , Dronabinol/farmacocinética , Feminino , Adulto Jovem , Administração Oral , Pessoa de Meia-Idade , Amidas , Ácidos PalmíticosRESUMO
Fibromyalgia is characterized by chronic widespread pain, fatigue, and sleep disturbances. Recent theories attribute fibromyalgia to central sensitization syndromes, suggesting altered nociceptive processing leads to hyperalgesia and allodynia. Standardized effective treatments are currently lacking. Palmitoylethanolamide and melatonin have shown pain-relieving effects in chronic pain conditions, including fibromyalgia, with excellent safety. Our open-label study assessed the impact of a daily combination of 1200 mg of palmitoylethanolamide and 0.2 mg of melatonin on pain, sleep, and quality of life in fibromyalgia patients. Between June 2023 and March 2024, 50 patients (2016 ACR criteria) were treated and evaluated at baseline, 1 month, 3 months, and 4 months (1 month discontinuation). The assessments included VAS for pain, ISI for insomnia, HAQ for health assessments, and a tender points evaluation. The patients, averaging 54.12 years old with a 3:1 female-to-male ratio, showed significant improvements in VAS, ISI, and HAQ scores relative to their own baselines and a reduction in tender points at 1 and 3 months, which was maintained at 4 months. No adverse events were reported. This study is the first to demonstrate the efficacy of a palmitoylethanolamide and melatonin combination as an adjunct therapy in fibromyalgia, highlighting its potential to reduce pain and improve sleep and quality of life.
Assuntos
Amidas , Combinação de Medicamentos , Etanolaminas , Fibromialgia , Melatonina , Ácidos Palmíticos , Qualidade de Vida , Humanos , Melatonina/administração & dosagem , Fibromialgia/tratamento farmacológico , Feminino , Ácidos Palmíticos/administração & dosagem , Ácidos Palmíticos/uso terapêutico , Pessoa de Meia-Idade , Projetos Piloto , Masculino , Etanolaminas/administração & dosagem , Amidas/administração & dosagem , Adulto , Idoso , Sono/efeitos dos fármacos , Resultado do Tratamento , Medição da Dor , Manejo da Dor/métodos , Dor Crônica/tratamento farmacológicoRESUMO
This study details trends in direct alcohol biomarker concentrations from civil cases within the United Kingdom (UK). Our subject cohort in this study related to family law litigation, where an individual was subject to an alcohol monitoring order by the court. This monitoring was conducted by quantification of alcohol biomarkers Phosphatidlyethanol (PEth) in dried blood spots (DBS) and Ethyl Glucuronide (EtG) and Ethyl Palmitate (EtPa) from hair segments. In total 298 PEth cases predominantly from the South East of England during the period July 2022 to August 2023 were analysed for alcohol biomarkers in DBS and hair. Subjects alcohol intake was classified as abstinence/low alcohol consumption, moderate or excessive alcohol consumption, based on a combination of Society for Hair Testing and PEth Net guidelines. Our results indicate that 33â¯% of PEth concentrations were consistent with excessive alcohol use (>200â¯ng/mL DBS), with 36â¯% consistent with social or moderate alcohol use (20-200â¯ng/mL DBS). In relation to EtG and EtPa 23â¯% and 31â¯% of subjects were classified as excessive alcohol users respectively. This study indicates that DBS sampling of PEth is a more sensitive predictor of alcohol use, in particular, at differentiating between moderate and excessive alcohol use compared to EtG and EtPa testing in hair. The authors suggest that increased frequency in the sampling of PEth in DBS (multiple occasions per month) may provide a more accurate assessment and simplification of the interpretation criteria of alcohol patterns rather than the combined hair testing and DBS sampling that are typically requested by UK courts.
Assuntos
Consumo de Bebidas Alcoólicas , Biomarcadores , Glucuronatos , Glicerofosfolipídeos , Cabelo , Humanos , Glucuronatos/análise , Cabelo/química , Biomarcadores/sangue , Biomarcadores/análise , Masculino , Feminino , Inglaterra , Adulto , Consumo de Bebidas Alcoólicas/legislação & jurisprudência , Glicerofosfolipídeos/sangue , Teste em Amostras de Sangue Seco , Pessoa de Meia-Idade , Adulto Jovem , Detecção do Abuso de Substâncias/métodos , Adolescente , Ácidos PalmíticosRESUMO
BACKGROUND: The Mediterranean diet (MedDiet) has demonstrated efficacy in preventing age-related cognitive decline and modulating plasma concentrations of endocannabinoids (eCBs) and N-acylethanolamines (NAEs, or eCB-like compounds), which are lipid mediators involved in multiple neurological disorders and metabolic processes. Hypothesizing that eCBs and NAEs will be biomarkers of a MedDiet intervention and will be related to the cognitive response, we investigated this relationship according to sex and apolipoprotein E (APOE) genotype, which may affect eCBs and cognitive performance. METHODS: This was a prospective cohort study of 102 participants (53.9% women, 18.8% APOE-É4 carriers, aged 65.6 ± 4.5 years) from the PREDIMED-Plus-Cognition substudy, who were recruited at the Hospital del Mar Research Institute (Barcelona). All of them presented metabolic syndrome plus overweight/obesity (inclusion criteria of the PREDIMED-Plus) and normal cognitive performance at baseline (inclusion criteria of this substudy). A comprehensive battery of neuropsychological tests was administered at baseline and after 1 and 3 years. Plasma concentrations of eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and N-docosahexaenoylethanolamine (DHEA), were also monitored. Baseline cognition, cognitive changes, and the association between eCBs/NAEs and cognition were evaluated according to gender (crude models), sex (adjusted models), and APOE genotype. RESULTS: At baseline, men had better executive function and global cognition than women (the effect size of gender differences was - 0.49, p = 0.015; and - 0.42, p = 0.036); however, these differences became nonsignificant in models of sex differences. After 3 years of MedDiet intervention, participants exhibited modest improvements in memory and global cognition. However, greater memory changes were observed in men than in women (Cohen's d of 0.40 vs. 0.25; p = 0.017). In men and APOE-ε4 carriers, 2-AG concentrations were inversely associated with baseline cognition and cognitive changes, while in women, cognitive changes were positively linked to changes in DHEA and the DHEA/AEA ratio. In men, changes in the OEA/AEA and OEA/PEA ratios were positively associated with cognitive changes. CONCLUSIONS: The MedDiet improved participants' cognitive performance but the effect size was small and negatively influenced by female sex. Changes in 2-AG, DHEA, the OEA/AEA, the OEA/PEA and the DHEA/AEA ratios were associated with cognitive changes in a sex- and APOE-dependent fashion. These results support the modulation of the endocannabinoid system as a potential therapeutic approach to prevent cognitive decline in at-risk populations. TRIAL REGISTRATION: ISRCTN89898870.
Assuntos
Cognição , Dieta Mediterrânea , Endocanabinoides , Genótipo , Síndrome Metabólica , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amidas , Apolipoproteínas E/genética , Ácidos Araquidônicos/sangue , Biomarcadores/sangue , Cognição/fisiologia , Dieta Mediterrânea/estatística & dados numéricos , Endocanabinoides/sangue , Etanolaminas/sangue , Glicerídeos/sangue , Síndrome Metabólica/genética , Ácidos Oleicos/sangue , Ácidos Palmíticos/sangue , Alcamidas Poli-Insaturadas/sangue , Estudos Prospectivos , Fatores SexuaisRESUMO
Palmitoylethanolamide (PEA) emerged over the years as a promising approach in the management of chronic pain. Despite the fact that the efficacy of micron-size PEA formulations appears to be time-dependent, the optimal timing has not yet been elucidated. This systematic review and meta-analysis aim to estimate the possible advantage of an extended treatment in the relief of chronic pain. The literature search was conducted consulting scientific databases, to identify clinical trials in which micron-size PEA was administered for at least 60 days, and pain assessed by the Visual Analogue Scale (VAS) or Numeric Rating Scale (NRS). Nine studies matched the required criteria, for a total of 742 patients involved. The meta-analysis showed a statistically and clinically significant pain intensity reduction after 60 days of micron-size PEA supplementation, compared to 30 days (1.36 points, p < 0.01). The secondary analysis revealed a weighted NRS/VAS score decrease of 2.08 points within the first month of treatment. These two obtained scores corresponded to a 35.1% pain intensity reduction within the first month, followed by a further 35.4% during the second month. Overall, these results confirm the clinically relevant and time-depended pain-relieving effect of micron-size PEA and therefore the advantage of an extended treatment, especially in patient with incomplete pain management.
Assuntos
Amidas , Dor Crônica , Etanolaminas , Ácidos Palmíticos , Ácidos Palmíticos/administração & dosagem , Ácidos Palmíticos/uso terapêutico , Humanos , Amidas/administração & dosagem , Etanolaminas/administração & dosagem , Dor Crônica/tratamento farmacológico , Medição da Dor , Administração Oral , Resultado do Tratamento , Analgésicos/administração & dosagemRESUMO
OBJECTIVE: The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underlying the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Palmitoylethanolamide, Epilobium and Calendula extract in patients with CP/CPPS III. MATERIALS AND METHODS: From June 2023 to July 2023, we enrolled 45 consecutive patients affected by CP/CPPS type III in three different institution. We included patients aged between 18 and 75 years with symptoms of pelvic pain for 3 months or more before the study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 12 point and diagnosed with NIH category III, according to 4-glass test Meares-Stamey test. Patients were then allocated to receive rectal suppositories of PEA, Epilobium and Calendula, 1 suppository/ die for 1 month. All patients have been tested with standard urinalysis in order to assess urinary leukocytes (U-WBC). The primary endpoint of the study was the reduction of NIHCPSI. The secondary outcomes were the change of peak flow, post-void residual (PVR), IIEF-5, VAS score, PSA and decrease of U-WBC. RESULTS: A total of 45 patients concluded the study protocol. At baseline, the median age of all the patients included in the cohort was 49 years, the median PSA was 2.81 ng/ml, the median NIH-CPSI was 18.55, the median IIEF-5 was 18.27, the median U-WBC was 485.3/mmc, the median VAS score was 6.49, the median PVR was 26.5 ml and the median peak flow was 16.3 ml/s. After 1 month of therapy we observed a statistically significant improvement of NIH-CPSI, U-WBC, PSA, IIEF-5, peak flow, PVR and VAS. CONCLUSIONS: In this observational study, we showed the clinical efficacy of the treatment with PEA, Epilobium and Calendula, 1 suppository/die for 1 month, in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cells in the urine that could imply a reduction of inflammatory cytokines. These results should be confirmed in further studies with greater sample size.
Assuntos
Amidas , Calendula , Epilobium , Etanolaminas , Ácidos Palmíticos , Extratos Vegetais , Prostatite , Humanos , Masculino , Pessoa de Meia-Idade , Adulto , Prostatite/tratamento farmacológico , Supositórios , Amidas/administração & dosagem , Amidas/uso terapêutico , Idoso , Ácidos Palmíticos/administração & dosagem , Ácidos Palmíticos/uso terapêutico , Resultado do Tratamento , Adulto Jovem , Etanolaminas/administração & dosagem , Etanolaminas/uso terapêutico , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Adolescente , Doença Crônica , Dor Pélvica/tratamento farmacológico , Dor Pélvica/etiologiaRESUMO
Opioid-related overdose deaths are still on the rise in North America, emphasizing the need to better understand the underlying neurobiological mechanisms regarding the development of opioid use disorder (OUD). Recent evidence from preclinical and clinical studies indicate that the endocannabinoid system (ECS) may play a crucial role in stress and reward, both involved in the development and maintenance of substance use disorders. Animal models demonstrate a specific crosstalk between the ECS and the endogenous opioid system. However, translational studies in humans are scarce. Here, we investigated basal plasma levels of the endocannabinoids anandamide (AEA) and 2-arachidonoyglycerol (2-AG), and eight endocannabinoid-related lipids, including oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), as well as whole blood fatty acid amide hydrolase (FAAH) activity in chronic non-medical prescription opioid users (NMPOU; n = 21) compared to opioid-naïve healthy controls (n = 29) considering age, sex, and cannabis use as potential confounders. Additionally, the association of endocannabinoids and related lipids with the participants' response to experimentally induced social exclusion was examined. We found significantly elevated basal AEA, OEA, and PEA levels in NMPOU compared to controls, but no differences in FAAH activity, 2-AG, or other endocannabinoid-related lipids. Within NMPOU, higher AEA levels were associated with lower perception of social exclusion. Robust positive correlations within N-acylethanolamines (i.e., AEA, OEA, and PEA) indicate strong metabolic associations. Together with our recent findings of elevated basal 2-AG levels in dependent cocaine users, present results indicate substance-specific alterations of the ECS that may have implications in the search for novel therapeutic interventions for these populations.
Assuntos
Amidoidrolases , Endocanabinoides , Transtornos Relacionados ao Uso de Opioides , Endocanabinoides/sangue , Endocanabinoides/metabolismo , Humanos , Masculino , Feminino , Adulto , Transtornos Relacionados ao Uso de Opioides/sangue , Amidoidrolases/sangue , Glicerídeos/sangue , Etanolaminas/sangue , Alcamidas Poli-Insaturadas/sangue , Isolamento Social/psicologia , Adulto Jovem , Ácidos Palmíticos/sangue , Ácidos Oleicos/sangue , Amidas/sangue , Pessoa de Meia-Idade , Ácidos Araquidônicos/sangue , Analgésicos Opioides/sangueRESUMO
Neuropathy affects 7-10% of the general population and is caused by a lesion or disease of the somatosensory system. The limitations of current therapies highlight the necessity of a new innovative approach to treating neuropathic pain (NP) based on the close correlation between oxidative stress, inflammatory process, and antioxidant action. The advantageous outcomes of a novel combination composed of Hop extract, Propolis, Ginkgo Biloba, Vitamin B, and palmitoylethanolamide (PEA) used as a treatment was evaluated in this study. To assess the absorption and biodistribution of the combination, its bioavailability was first examined in a 3D intestinal barrier model that replicated intestinal absorption. Further, a 3D nerve tissue model was developed to study the biological impacts of the combination during the essential pathways involved in NP. Our findings show that the combination could cross the intestinal barrier and reach the peripheral nervous system, where it modulates the oxidative stress, inflammation levels, and myelination mechanism (increased NRG, MPZ, ERB, and p75 levels) under Schwann cells damaging. This study proves the effectiveness of Ginkgo Biloba, Propolis, Hop extract, Vitamin B, and PEA in avoiding nerve damage and suggests a potential alternative nutraceutical treatment for NP and neuropathies.
Assuntos
Amidas , Suplementos Nutricionais , Etanolaminas , Neuralgia , Ácidos Palmíticos , Plantas Medicinais , Etanolaminas/farmacologia , Ácidos Palmíticos/farmacologia , Ácidos Palmíticos/administração & dosagem , Animais , Neuralgia/tratamento farmacológico , Amidas/farmacologia , Amidas/química , Plantas Medicinais/química , Polifenóis/farmacologia , Polifenóis/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ratos , Masculino , Antioxidantes/farmacologia , Ginkgo biloba/química , HumanosRESUMO
Current epidemiological data estimate that one in five people suffers from chronic pain with considerable impairment of health-related quality of life. The pharmacological treatment is based on first- and second-line analgesic drugs, including COX-2 selective and nonselective nonsteroidal anti-inflammatory drugs, paracetamol, antidepressants, anti-seizure drugs and opioids, that are characterized by important side effects. N-palmitoylethanolamine (PEA) is a body's own fatty-acid ethanolamide belonging to the family of autacoid local injury antagonist amides. The anti-inflammatory and pain-relieving properties of PEA have been recognized for decades and prompted to depict its role in the endogenous mechanisms of pain control. Together with its relative abundance in food sources, this opened the way to the use of PEA as a pain-relieving nutritional intervention. Naïve PEA is a large particle size lipid molecule with low solubility and bioavailability. Reducing particle size is a useful method to increase surface area, thereby improving dissolution rate and bioavailability accordingly. Micron-size formulations of PEA (e.g., ultramicronized and co-(ultra)micronized) have shown higher oral efficacy compared to naïve PEA. In particular, ultramicronized PEA has been shown to efficiently cross the intestinal wall and, more importantly, the blood-brain and blood-spinal cord barrier. Several preclinical and clinical studies have shown the efficacy, safety and tolerability of ultramicronized PEA. This narrative review summarizes the available pharmacokinetic/pharmacodynamic data on ultramicronized PEA and focuses to its contribution to pain control, in particular as 'add-on' nutritional intervention. Data showing the ability of ultramicronized PEA to limit opioid side effects, including the development of tolerance, have also been reviewed.
Assuntos
Analgésicos , Dor Crônica , Etanolaminas , Ácidos Palmíticos , Etanolaminas/efeitos adversos , Etanolaminas/uso terapêutico , Ácidos Palmíticos/uso terapêutico , Ácidos Palmíticos/farmacologia , Ácidos Palmíticos/efeitos adversos , Humanos , Analgésicos/efeitos adversos , Analgésicos/farmacologia , Dor Crônica/tratamento farmacológico , Animais , Amidas , Tamanho da Partícula , Disponibilidade BiológicaRESUMO
Oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) are endogenous lipids that act as agonists of the peroxisome proliferator-activated receptor α (PPARα). Recently, an interest in the role of these lipids in malignant tumors has emerged. Nevertheless, the effects of OEA and PEA on human neuroblastoma cells are still not documented. Type I interferons (IFNs) are immunomodulatory cytokines endowed with antiviral and anti-proliferative actions and are used in the treatment of various pathologies such as different cancer forms (i.e., non-Hodgkin's lymphoma, melanoma, leukemia), hepatitis B, hepatitis C, multiple sclerosis, and many others. In this study, we investigated the effect of OEA and PEA on human neuroblastoma SH-SY5Y cells treated with IFNß. We focused on evaluating cell viability, cell proliferation, and cell signaling. Co-exposure to either OEA or PEA along with IFNß leads to increased apoptotic cell death marked by the cleavage of caspase 3 and poly-(ADP ribose) polymerase (PARP) alongside a decrease in survivin and IKBα levels. Moreover, we found that OEA and PEA did not affect IFNß signaling through the JAK-STAT pathway and the STAT1-inducible protein kinase R (PKR). OEA and PEA also increased the phosphorylation of p38 MAP kinase and programmed death-ligand 1 (PD-L1) expression both in full cell lysate and surface membranes. Furthermore, GW6471, a PPARα inhibitor, and the genetic silencing of the receptor were shown to lower PD-L1 and cleaved PARP levels. These results reveal the presence of a novel mechanism, independent of the IFNß-prompted pathway, by which OEA and PEA can directly impair cell survival, proliferation, and clonogenicity through modulating and potentiating the intrinsic apoptotic pathway in human SH-SY5Y cells.
Assuntos
Amidas , Endocanabinoides , Etanolaminas , Neuroblastoma , Ácidos Oleicos , Humanos , Neuroblastoma/tratamento farmacológico , Antígeno B7-H1 , Janus Quinases , PPAR alfa , Inibidores de Poli(ADP-Ribose) Polimerases , Fatores de Transcrição STAT , Transdução de Sinais , Apoptose , Ácidos Palmíticos/farmacologiaRESUMO
OBJECTIVE: This study aimed to evaluate the efficacy and safety of co-micronized palmitoylethanolamide (PEA)/polydatin (PD) in the treatment of abdominal pain symptoms in pediatric patients with irritable bowel syndrome (IBS). METHODS: This was a multicenter trial conducted at three Italian pediatric gastroenterology centers, employing a double-blind, placebo-controlled, parallel-arm design. Participants were ages 10 to 17 y and met Rome IV criteria for pediatric IBS. They were randomly allocated to receive either co-micronized PEA/PD or placebo, administered three times daily in a 1:1 ratio, over a 12-wk period. The study assessed baseline severity using the IBS-Severity Scoring System (IBS-SSS) at enrollment and after 4, 8, and 12 wk of treatment. Abdominal pain frequency was assessed on a scale from 1 to 7 d/wk, while stool consistency was classified using the Bristol Stool Scale (BSS) to categorize various IBS subtypes. The primary outcome was the percentage of patients who achieved complete remission, defined as IBS-SSS score <75 points after 12 wk of therapy. RESULTS: The study involved 70 children with IBS. Of the participants, 34 received co-micronized PEA/PD, and 36 received a placebo. As compared with the placebo group, the co-micronized therapy group had significantly more patients achieving complete remission after 12 wk (P = 0.015), with particular benefit in the IBS-diarrhea subtype (P = 0.01). The treatment group also experienced a significant reduction in abdominal pain intensity and frequency compared with the placebo group. No adverse events were recorded during the study period. CONCLUSIONS: Co-micronized PEA/PD is a safe and effective treatment to treat abdominal pain symptoms in pediatric IBS.
Assuntos
Amidas , Etanolaminas , Glucosídeos , Síndrome do Intestino Irritável , Ácidos Palmíticos , Estilbenos , Humanos , Criança , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/tratamento farmacológico , Diarreia/tratamento farmacológico , Resultado do Tratamento , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Resposta Patológica Completa , Método Duplo-CegoRESUMO
PURPOSE: Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment. METHODS: After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T0) and 6 months (T1) using a parosmia questionnaire and Sniffin' Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia. RESULTS: The umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p < 0.001). Rates of parosmia resolution after 6 months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated. CONCLUSIONS: umPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit.
Assuntos
COVID-19 , Transtornos do Olfato , Ácido Tióctico , Humanos , Feminino , COVID-19/complicações , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/etiologia , Transtornos do Olfato/terapia , Transtornos do Olfato/reabilitação , Ácido Tióctico/uso terapêutico , Ácido Tióctico/administração & dosagem , Etanolaminas/uso terapêutico , Ácidos Palmíticos/uso terapêutico , Ácidos Palmíticos/administração & dosagem , Amidas/uso terapêutico , Adulto , SARS-CoV-2 , Resultado do Tratamento , Idoso , Anosmia/etiologia , Anosmia/terapia , Olfato/fisiologia , Terapia Combinada , Treinamento OlfativoRESUMO
Coronavirus disease 2019 (COVID-19) may lead to neuropsychiatric sequelae. Palmitoylethanolamide (PEA) is an anti-inflammatory and neuroprotective amide used in depressive syndromes. Here we investigate whether micronized/ultramicronized (m/um) PEA improves neuropsychiatric sequelae in COVID-19 survivors. Patients evaluated at our post-COVID-19 outpatient clinic between February and August 2021 and presenting neuropsychiatric manifestations ( n â =â 98) were offered treatment with m/umPEA 600â mg twice daily for 3 months. Those accepting m/umPEA therapy ( n â =â 57) were compared with those who did not ( n â =â 41), in terms of depression, fatigue, chronic pain and subjective well-being, through validated scales administered pre- and posttreatment. The two groups did not differ in terms of demographics, comorbidities, psychiatric history, antidepressant therapy, acute COVID-19 severity and baseline neuropsychiatric status. Patients receiving m/umPEA showed a greater improvement in depression and fatigue (both P â <â 0.05). Conversely, no association was found with changes in chronic pain or subjective well-being. At multivariable logistic regression, m/umPEA predicted neuropsychiatric improvement independently of age, sex and baseline neuropsychiatric status. Worse pretreatment fatigue and subjective well-being identified those who most likely benefited from treatment. In conclusion, despite its retrospective nature, our study suggests that m/umPEA may improve depression and fatigue in COVID-19 survivors, justifying future research in this setting.
Assuntos
Amidas , Tratamento Farmacológico da COVID-19 , COVID-19 , Depressão , Etanolaminas , Fadiga , Ácidos Palmíticos , Humanos , Ácidos Palmíticos/uso terapêutico , Ácidos Palmíticos/administração & dosagem , Feminino , Masculino , Amidas/uso terapêutico , Etanolaminas/uso terapêutico , Etanolaminas/administração & dosagem , Pessoa de Meia-Idade , Fadiga/tratamento farmacológico , Depressão/tratamento farmacológico , COVID-19/complicações , COVID-19/psicologia , Idoso , Adulto , Sobreviventes , Resultado do Tratamento , SARS-CoV-2/efeitos dos fármacosRESUMO
The pathogenesis of renal calcium-oxalate (CaOx) stones is complex and influenced by various metabolic factors. In parallel, palmitic acid (PA) has been identified as an upregulated lipid metabolite in the urine and serum of patients with renal CaOx stones via untargeted metabolomics. Thus, this study aimed to mechanistically assess whether PA is involved in stone formation. Lipidomics analysis of PA-treated renal tubular epithelial cells compared with the control samples revealed that α-linoleic acid and α-linolenic acid were desaturated and elongated, resulting in the formation of downstream polyunsaturated fatty acids (PUFAs). In correlation, the levels of fatty acid desaturase 1 and 2 (FADS1 and FADS2) and peroxisome proliferator-activated receptor α (PPARα) in these cells treated with PA were increased relative to the control levels, suggesting that PA-induced upregulation of PPARα, which in turn upregulated these two enzymes, forming the observed PUFAs. Lipid peroxidation occurred in these downstream PUFAs under oxidative stress and Fenton Reaction. Furthermore, transcriptomics analysis revealed significant changes in the expression levels of ferroptosis-related genes in PA-treated renal tubular epithelial cells, induced by PUFA peroxides. In addition, phosphatidyl ethanolamine binding protein 1 (PEBP1) formed a complex with 15-lipoxygenase (15-LO) to exacerbate PUFA peroxidation under protein kinase C ζ (PKC ζ) phosphorylation, and PKC ζ was activated by phosphatidic acid derived from PA. In conclusion, this study found that the formation of renal CaOx stones is promoted by ferroptosis of renal tubular epithelial cells resulting from PA-induced dysregulation of PUFA and phosphatidic acid metabolism, and PA can promote the renal adhesion and deposition of CaOx crystals by injuring renal tubular epithelial cells, consequently upregulating adhesion molecules. Accordingly, this study provides a new theoretical basis for understanding the correlation between fatty acid metabolism and the formation of renal CaOx stones, offering potential targets for clinical applications.
Assuntos
Cálcio , Ferroptose , Humanos , Oxalato de Cálcio/química , PPAR alfa , Ácidos Graxos Insaturados , Ácidos PalmíticosRESUMO
BACKGROUND: Palmitoylethanolamide (PEA) is an endocannabinoid-like lipid mediator which is naturally produced in the body and found in certain foods. The aim of this study was to assess the effect of a bioavailable formulated form of PEA (Levagen+®) on serum BDNF levels and parameters of cognitive function in healthy adults. METHODS: A randomised double-blinded placebo-controlled cross-over trial was implemented to measure the effects of a 6-week 700 mg/day course of formulated PEA supplementation versus a placebo. Participants (n = 39) completed pre- and post-assessments of a lab-based cognitive test. Serum samples were collected to measure BDNF concentrations using an immunoassay. RESULTS: A significant increase in serum BDNF levels was found following PEA supplementation compared with the placebo (p = 0. 0057, d = 0.62). The cognition test battery demonstrated improved memory with PEA supplementation through better first success (p = 0.142, d = 0.54) and fewer errors (p = 0.0287; d = -0.47) on the Paired Associates Learning test. CONCLUSION: This was the first study to report a direct beneficial effect of Levagen+® PEA supplementation on memory improvement as well as corresponding increases in circulating neurotrophic marker levels. This suggests that formulated PEA holds promise as an innovative and practical intervention for cognitive health enhancement.