-
1.
N-Acylphosphatidylethanolamines and N-acylethanolamines increase in saliva upon food mastication: the influence of the individual nutritional status and fat type in food.
De Luca, L, Ferracane, R, Calderón Ramírez, N, Vitaglione, P
Food & function. 2020;(4):3382-3392
Abstract
This study aimed to evaluate the influence of the individual nutritional status on the salivary concentration of N-acylethanolamines (NAEs), including linoleoylethanolamide (LEA), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA), and their precursors N-acylphosphatidylethanolamines (NAPEs) upon mastication of biscuits containing different fats. Three types of biscuits were formulated with 10% extra-virgin olive oil (EVOB), 10% palm oil (PALMB) or 10% paraffin oil (0% lipids, CONB). Twenty-five healthy subjects, 12 normal weight (NW, 9 F, 30.4 ± 8.7 years) and 13 obese (OB, 8 F, 35.5 ± 10.7 years) participated in a randomized crossover study. Fasting subjects collected unstimulated saliva (US) and stimulated saliva by masticating a parafilm piece (PP), and CONB, EVOB and PALMB. NAPEs, LEA, OEA and PEA were quantified in saliva samples by liquid chromatography-high-resolution mass spectrometry. The results showed that salivary NAPE and NAE concentrations in OB were higher than in NW in both US (NAPEs: 280.0 ± 45.4 ng mL-1vs. 121.8 ± 24.4 ng mL-1, p = 0.015; NAEs: 10.8 ± 1.4 ng mL-1vs. 4.8 ± 0.8 ng mL-1, p = 0.002, respectively) and PP (NAPEs: 259.8 ± 47.1 ng mL-1vs. 121.7 ± 16.9 ng mL-1, p = 0.049; NAEs: 6.1 ± 0.8 ng mL-1vs. 3.8 ± 0.4 ng mL-1, p = 0.03, respectively). NAPE and LEA levels were similar in US and PP, while the levels of OEA and PEA were lower in PP vs. US. Compared to PP, biscuit mastication increased the salivary NAPEs, LEA, OEA and overall NAEs in NW and OB. NAPEs increased in the order of EVOB = CONB > PALMB in NW and EVOB > CONB = PALMB in OB. LEA, OEA and overall NAEs increased similarly with all the biscuits in NW and in the order of EVOB > PALMB > CONB in OB. In contrast, the PEA concentration did not vary in saliva upon biscuit mastication in NW and neither with EVOB in OB, while it lowered with CONB and PALMB in OB. In conclusion, OB showed higher salivary levels of NAPEs and NAEs than NW. Mastication itself did not vary salivary NAPEs and LEA but reduced OEA, PEA and overall NAEs. Biscuit mastication increased salivary NAPEs and all NAEs, but PEA. Altogether, the data suggested that NAPEs and NAEs were released in saliva from biscuits at levels influenced by the individual nutritional status and biscuit type. These findings may have implications in molecular mechanisms underpinning gustatory processes in humans.
-
2.
The Effect of Orally Dosed Levagen+™ (palmitoylethanolamide) on Exercise Recovery in Healthy Males-A Double-Blind, Randomized, Placebo-Controlled Study.
Mallard, A, Briskey, D, Richards, A, Mills, D, Rao, A
Nutrients. 2020;(3)
Abstract
The aim of this study was to evaluate the effect of palmitoylethanolamide (PEA), a cannabimimetic compound and lipid messenger, on recovery from muscle damaging exercise. Twenty-eight healthy young male participants attended the laboratory four times on subsequent days. In the first visit, baseline characteristics were recorded before participants were randomized to consume either liquid PEA (167.5 mg Levagen+ with 832.5 mg maltodextrin) or a matched placebo (1 g maltodextrin) drink. Leg press exercise consisted of four sets at 80% of one repetition maximum followed by a performance set. Muscle soreness, thigh circumference, blood lactate concentration, biomarkers of muscle damage and inflammation, and transcription factor pathways were measured pre- and immediately post-exercise and again at 1, 2, 3, 24, 48, and 72 h post-exercise. The leg press exercise increased (p < 0.05) blood lactate concentration and induced muscle damage as evidenced by increased muscle soreness, thigh circumference, biomarkers of muscle damage, and concentrations of tumor necrosis factor-α. PEA reduced (p < 0.05) myoglobin and blood lactate concentrations and increased protein kinase B phosphorylation following exercise. Taken together, these results indicate PEA supplementation may aid in muscle recovery from repeat bouts of exercise performed within a short duration by reducing myoglobin and lactate concentration.
-
3.
The efficacy of an association of palmitoylethanolamide and alpha-lipoic acid in patients with chronic prostatitis/chronic pelvic pain syndrome: A randomized clinical trial.
Giammusso, B, Di Mauro, R, Bernardini, R
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2017;(1):17-21
Abstract
BACKGROUND Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex condition, characterized by uncertain etiology and by limited response to therapy. The definition of CP/CPPS includes genitourinary pain with or without voiding symptoms in the absence of uropathogenic bacteria, as detected by standard microbiological methods, or another identifiable cause such as malignancy. The efficacy of various medical therapies, has been evaluated in clinical studies, but evidence is lacking or conflicting. We compared Serenoa Repens in monotherapy versus Palmitoylethanolamide (PEA) in combination with Alpha-lipoic acid (ALA) and evaluated the efficacy of these treatments in patients with CP/CPPS. METHODS We conducted a randomized, single-blind trial. 44 patients diagnosed with CP/CPPS (mean age 41.32 ± 1.686 years) were randomly assigned to treatment with Palmitoylethanolamide 300 mg plus Alpha-lipoic acid 300 mg (Peanase®), or Serenoa Repens at 320 mg. Three questionnaires (NIH-CPSI, IPSS and IIEF5) were administered at baseline and after 12 weeks of treatment in each group. RESULTS 12 week treatment with Peanase significantly improved the IPSS score compared to the same period of treatment with Serenoa Repens, and significantly reduced NIH-CPSI score. Similar results were observed in the different NIH-CPSI subscores break down. However, the same treatment did not result in significant improvement of the IIEF5 score. Both treatments did not produce undesired effects. CONCLUSIONS The present results document the efficacy of an association of Palmitoylethanolamide (PEA) and Alpha-lipoic acid (ALA) administered for 12 weeks for treating patients with CP/CPPS, compared with Serenoa Repens monotherapy.
-
4.
Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome.
Cremon, C, Stanghellini, V, Barbaro, MR, Cogliandro, RF, Bellacosa, L, Santos, J, Vicario, M, Pigrau, M, Alonso Cotoner, C, Lobo, B, et al
Alimentary pharmacology & therapeutics. 2017;(7):909-922
Abstract
BACKGROUND Intestinal immune activation is involved in irritable bowel syndrome (IBS) pathophysiology. While most dietary approaches in IBS involve food avoidance, there are fewer indications on food supplementation. Palmithoylethanolamide, structurally related to the endocannabinoid anandamide, and polydatin are dietary compounds which act synergistically to reduce mast cell activation. AIM: To assess the effect on mast cell count and the efficacy of palmithoylethanolamide/polydatin in patients with IBS. METHODS We conducted a pilot, 12-week, randomised, double-blind, placebo-controlled, multicentre study assessing the effect of palmithoylethanolamide/polydatin 200 mg/20 mg or placebo b.d. on low-grade immune activation, endocannabinoid system and symptoms in IBS patients. Biopsy samples, obtained at screening visit and at the end of the study, were analysed by immunohistochemistry, enzyme-linked immunoassay, liquid chromatography and Western blot. RESULTS A total of 54 patients with IBS and 12 healthy controls were enrolled from five European centres. Compared with controls, IBS patients showed higher mucosal mast cell counts (3.2 ± 1.3 vs. 5.3 ± 2.7%, P = 0.013), reduced fatty acid amide oleoylethanolamide (12.7 ± 9.8 vs. 45.8 ± 55.6 pmol/mg, P = 0.002) and increased expression of cannabinoid receptor 2 (0.7 ± 0.1 vs. 1.0 ± 0.8, P = 0.012). The treatment did not significantly modify IBS biological profile, including mast cell count. Compared with placebo, palmithoylethanolamide/polydatin markedly improved abdominal pain severity (P < 0.05). CONCLUSIONS The marked effect of the dietary supplement palmithoylethanolamide/polydatin on abdominal pain in patients with IBS suggests that this is a promising natural approach for pain management in this condition. Further studies are now required to elucidate the mechanism of action of palmithoylethanolamide/polydatin in IBS. ClinicalTrials.gov number, NCT01370720.
-
5.
AQ-13, an investigational antimalarial, versus artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria: a randomised, phase 2, non-inferiority clinical trial.
Koita, OA, Sangaré, L, Miller, HD, Sissako, A, Coulibaly, M, Thompson, TA, Fongoro, S, Diarra, Y, Ba, M, Maiga, A, et al
The Lancet. Infectious diseases. 2017;(12):1266-1275
Abstract
BACKGROUND Chloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria. METHODS We did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per μL of blood). Eligible participants were randomly assigned to either the artemether plus lumefantrine group or AQ-13 group by permuting blocks of four with a random number generator. Physicians and others caring for the participants were masked, except for participants who received treatment and the research pharmacist who implemented the randomisation and provided treatment. Participants received either 80 mg of oral artemether and 480 mg of oral lumefantrine twice daily for 3 days or 638·50 mg of AQ-13 base (two oral capsules) on days 1 and 2, and 319·25 mg base (one oral capsule) on day 3. Participants were monitored for parasite clearance (50 μL blood samples twice daily at 12 h intervals until two consecutive negative samples were obtained) and interviewed for adverse events (once every day) as inpatients during week 1. During the 5-week outpatient follow-up, participants were examined for adverse events and recurrent infection twice per week. All participants were included in the intention-to-treat analysis and per-protocol analysis, except for those who dropped out in the per-protocol analysis. The composite primary outcome was clearance of asexual parasites and fever by day 7, and absence of recrudescent infection by parasites with the same molecular markers from days 8 to 42 (defined as cure). Non-inferiority was considered established if the proportion of patients who were cured was higher for artemether plus lumefantrine than for AQ-13 and the upper limit of the 95% CI was less than the non-inferiority margin of 15%. This trial is registered at ClinicalTrials.gov, number NCT01614964. FINDINGS Between Aug 6 and Nov 18, 2013, and between Sept 18 and Nov 20, 2015, 66 Malian men with uncomplicated malaria were enrolled. 33 participants were randomly assigned to each group. There were no serious adverse events (grade 2-4) and asexual parasites were cleared by day 7 in both groups. 453 less-severe adverse events (≤grade 1) were reported: 214 in the combination group and 239 in the AQ-13 group. Two participants withdrew from the AQ-13 group after parasite clearance and three were lost to follow-up. In the artemether plus lumefantrine group, two participants had late treatment failures (same markers as original isolates). On the basis of the per-protocol analysis, the AQ-13 and artemether plus lumefantrine groups had similar proportions cured (28 [100%] of 28 vs 31 [93·9%] of 33; p=0·50) and AQ-13 was not inferior to artemether plus lumefantrine (difference -6·1%, 95% CI -14·7 to 2·4). Proportions cured were also similar between the groups in the intention-to-treat analysis (28 of 33, 84·8% for AQ-13 vs 31 of 33, 93·9% for artemether and lumefantrine; p=0·43) but the upper bound of the 95% CI exceeded the 15% non-inferiority margin (difference 9·1%, 95% CI -5·6 to 23·8). INTERPRETATION The per-protocol analysis suggested non-inferiority of AQ-13 to artemether plus lumefantrine. By contrast, the intention-to-treat analysis, which included two participants who withdrew and three who were lost to follow-up from the AQ-13 group, did not meet the criterion for non-inferiority of AQ-13, although there were no AQ-13 treatment failures. Studies with more participants (and non-immune participants) are needed to decide whether widespread use of modified 4-aminoquinolones should be recommended. FUNDING US Food and Drug Administration Orphan Product Development, National Institutes of Health, US Centers for Disease Control and Prevention, Burroughs-Wellcome Fund, US State Department, and WHO.
-
6.
Effects of mood inductions by meal ambiance and moderate alcohol consumption on endocannabinoids and N-acylethanolamines in humans: a randomized crossover trial.
Schrieks, IC, Ripken, D, Stafleu, A, Witkamp, RF, Hendriks, HF
PloS one. 2015;(5):e0126421
Abstract
BACKGROUND The endocannabinoid system is suggested to play a regulatory role in mood. However, the response of circulating endocannabinoids (ECs) to mood changes has never been tested in humans. In the present study, we examined the effects of mood changes induced by ambiance and moderate alcohol consumption on plasma ECs 2-arachidonoylglycerol (2-AG), anandamide (AEA), and some N-acylethanolamine (NAE) congeners in humans. METHODS Healthy women (n = 28) participated in a randomized cross-over study. They consumed sparkling white wine (340 mL; 30 g alcohol) or alcohol-free sparkling white wine (340 mL; <2 g alcohol) as part of a standard evening meal in a room with either a pleasant or an unpleasant ambiance. RESULTS Plasma concentrations of palmitoylethanolamide (PEA) and stearoylethanolamide (SEA) increased after 30 min in the unpleasant ambiance, while they decreased in the pleasant ambiance. Changes in ECs and their NAE congeners correlated with mood states, such as happiness and fatigue, but in the pleasant ambiance without alcohol only. ECs and their NAE congeners were correlated with serum free fatty acids and cortisol. CONCLUSION This is the first human study to demonstrate that plasma NAEs are responsive to an unpleasant meal ambiance. Furthermore, associations between mood states and ECs and their NAE congeners were observed. TRIAL REGISTRATION Clinicaltrials.gov NCT01426022.
-
7.
N-palmitoylethanolamine and N-acetylethanolamine are effective in asteatotic eczema: results of a randomized, double-blind, controlled study in 60 patients.
Yuan, C, Wang, XM, Guichard, A, Tan, YM, Qian, CY, Yang, LJ, Humbert, P
Clinical interventions in aging. 2014;:1163-9
Abstract
BACKGROUND Asteatotic eczema (AE) is characterized by itchy, dry, rough, and scaling skin. The treatments for AE are mainly emollients, usually containing urea, lactic acid, or a lactate salt. N-palmitoylethanolamine (PEA) and N-acetylethanolamine (AEA) are both endogenous lipids used as novel therapeutic tools in the treatment of many skin diseases. The purpose of this study was to compare a PEA/AEA emollient with a traditional emollient in the treatment of AE. METHODS A monocentric, randomized, double-blind, comparative trial was conducted in 60 AE patients to evaluate and compare the efficacy of the two emollients. The level of skin dryness among the subjects ranged from mild to moderate. The subjects' skin barrier function and the current perception threshold were tested for 28 days by clinical scoring and bioengineering technology. RESULTS The results showed that, although some aspects were improved in both groups, the group using the emollient containing PEA/AEA presented a better skin surface change in capacitance. However, the most impressive finding was the ability of the PEA/AEA emollient to increase the 5 Hz current perception threshold to a normal level after 7 days, with a significant difference between values at baseline and after 14 days. A current perception threshold of 5 Hz was positively and significantly correlated with skin surface hydration and negatively correlated with transepidermal water loss in the PEA/AEA emollient group. CONCLUSION Compared with traditional emollients, regular application of a topical PEA/AEA emollient could improve both passive and active skin functions simultaneously.
-
8.
The effects of vitamin D supplementation on airway functions in mild to moderate persistent asthma.
Arshi, S, Fallahpour, M, Nabavi, M, Bemanian, MH, Javad-Mousavi, SA, Nojomi, M, Esmaeilzadeh, H, Molatefi, R, Rekabi, M, Jalali, F, et al
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2014;(4):404-9
Abstract
BACKGROUND Vitamin D is hypothesized to have some roles in innate and adaptive immunity, inflammation reduction, and remodeling; therefore, it is supposed to affect the asthma phenotype, severity, and response to inhaled corticosteroid (ICS). OBJECTIVE To explore the synergistic effects of vitamin D supplementation in addition to asthma controllers (ICS or ICS plus long-acting β-agonist) on airway functions. METHODS A randomized clinical trial was conducted in 130 individuals aged 10 to 50 years who lived in Tehran during a 24-week period. Data on age, sex, body mass index, stage of asthma, serum total IgE, history of allergic rhinitis, atopic dermatitis, food allergy, and urticaria were collected. Spirometric parameters (forced expiratory volume in 1 second [FEV1] and ratio of FEV1 to forced vital capacity) and serum vitamin D measurement were obtained before and 8 and 24 weeks after the intervention. Patients were divided in 2 groups randomly. Both groups received asthma controllers (budesonide or budesonide plus formoterol) according to their stage, but the intervention group received vitamin D supplementation (100,000-U bolus intramuscularly plus 50,000 U orally weekly) in addition to asthma controllers. RESULTS FEV1 improved significantly in both groups after 8 weeks, but no significant difference was found between the 2 groups at baseline (P = .20) or after 8 weeks (P = .99); however, a significant improvement was seen in the intervention group in the last 16 weeks, and FEV1 was significantly better in the intervention group than the other group after 24 weeks (P < .001). CONCLUSION Vitamin D supplementation associated with asthma controllers could significantly improve FEV1 in mild to moderate persistent asthma after 24 weeks. TRIAL REGISTRATION irct.ir Identifier: IRCT201302079608N1.
-
9.
Singular and combined effects of nebivolol and lifestyle modification on large artery stiffness in hypertensive adults.
Werner, TJ, Boutagy, NE, Osterberg, KL, Rivero, JM, Davy, KP
Therapeutic advances in cardiovascular disease. 2013;(6):285-92
Abstract
BACKGROUND We hypothesized that the combination of nebivolol and lifestyle modification would reduce large artery stiffness in middle-aged and older hypertensive adults more than either intervention alone. METHODS To address this, 45 men and women (age 40-75 years) with stage I hypertension were randomized to receive either nebivolol (NB; forced titration to 10 mg OD; n = 15; age 57.2 ± 11.4 years; body mass index [BMI] 30.8 ± 5.8 kg/m(2)), lifestyle modification (LM; 5-10% weight loss via calorie restriction and physical activity; n = 15; age 52.7 ± 8.5 years; BMI 33.9 ± 7.2 kg/m(2)) or nebivolol plus lifestyle modification (NBLM; n = 15; age 58.9 ± 9.4 years; BMI 32.5 ± 4.9 kg/m(2)) for 12 weeks. β-stiffness index, a blood-pressure-independent measure of arterial stiffness, and arterial compliance were measured via high-resolution ultrasound and tonometry at baseline and after the 12-week intervention. There was no difference between groups in age, body weight or composition, blood pressure, or in β-stiffness index or arterial compliance at baseline (all p > 0.05). RESULTS Following the 12-week intervention, body weight decreased ~5% (p < 0.05) in the LM and NBLM groups but did not change from baseline in the NB group (p > 0.05). Supine brachial and carotid systolic and diastolic blood pressure declined following treatment in each of the groups (p < 0.05). However, the magnitude of reduction was not different (p < 0.05) between groups. β-stiffness index declined (-2.03 ± 0.60, -1.87 ± 0.83 and -2.51 ± 0.90 U) and arterial compliance increased similarly (both p > 0.05) in the NB, LM and NBLM groups, respectively. CONCLUSION In summary, our findings indicate that the combination of nebivolol and lifestyle modification reduced large artery stiffness to a similar degree as either intervention alone in middle-aged and older hypertensive adults.
-
10.
Does nebivolol prevent contrast-induced nephropathy in humans?
Günebakmaz, O, Kaya, MG, Koc, F, Akpek, M, Kasapkara, A, Inanc, MT, Yarlioglues, M, Calapkorur, B, Karadag, Z, Oguzhan, A
Clinical cardiology. 2012;(4):250-4
Abstract
BACKGROUND An experimental study showed that nebivolol is an effective agent in contrast-induced nephropathy (CIN) prophylaxis. HYPOTHESIS We hypothesized that prophylactic nebivolol use had protective effects on renal function in human beings subjected to iodinated contrast agent since it has vasodilatory effect and antioxidant properties. METHODS The present study enrolled 120 patients scheduled for coronary angiography and ventriculography. All patients were hydrated with intravenous isotonic saline. The patients in group I received 600 mg N-acetylcysteine every 12 hours for 4 days. The patients in group II received 5 mg nebivolol every 24 hours for 4 days. The patients in group III were only hydrated. The primary endpoint was the occurrence of CIN. The secondary endpoint was the change in serum creatinine (Cr) levels at 2 days and 5 days after the contrast exposure. RESULTS Nine (22.5%) patients in group I developed CIN, as did 8 patients (20.0%) in group II and 11 patients (27.5%) in group III (P = 0.72). Changes in mean Cr level from baseline to day 2 were not statistically significant in all groups. However, we detected a statistically significant increase in mean Cr levels at day 5 compared with baseline levels in group I and group III (from 1.42 ± 0.13 to 1.52 ± 0.26, p2 = 0.02; and from 1.43 ± 0.14 to 1.55 ± 0.30, p2 = 0.01, respectively). Although an increase was detected in mean Cr level from baseline to the 5-day Cr level in group II, this did not reach statistical significance (from 1.40 ± 0.12 to 1.48 ± 0.23, P = 0.06). CONCLUSIONS Pretreatment with nebivolol is protective against nephrotoxic effects of contrast media.