{ "abstract": "Background/Objectives: Long-term treatment options for fibromyalgia syndrome (FMS) remain limited and there is a lack of real-world data on the extended use of nutraceutical formulations containing palmitoylethanolamide (PEA) and acetyl-L-carnitine (ALC). This study describes a cohort treated for 12 months with a fixed multicomponent formulation containing PEA and ALC, followed by an additional visit three months post-treatment. Methods: This retrospective, uncontrolled single-cohort study involved 150 consecutive adults diagnosed with fibromyalgia syndrome (FMS). Participants received a fixed oral formulation comprising palmitoylethanolamide (PEA) 600 mg, acetyl-L-carnitine (ALC) 500 mg, Boswellia serrata 100 mg, vitamin B6 and vitamin E, administered twice daily as an adjunct to stable background therapy. Pain levels were assessed using the Visual Analogue Scale (VAS), and the impact of the disease was evaluated with the revised Fibromyalgia Impact Questionnaire (FIQR) over a period of up to 15 months. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI) for up to 6 months. Missing data were addressed through various methods, including a mixed model, last observation carried forward, delta-adjusted and baseline-carried-forward scenarios, as well as non-responder imputation. Results: Sixty-four patients completed the 12-month course, 45 discontinued (36 for perceived lack of efficacy) and 41 were lost to follow-up. Estimated mean VAS fell from 76.3 to 52.3 at 12 months and FIQR from 73.6 to 56.1; under the worst-case assumption that every non-completer returned to baseline, the mean 12-month change in VAS was −13.0 points (95% CI −15.9 to −10.2). At 6 months, 78.1% of completers reached the FIQR minimal clinically important difference and 59.4% the IMMPACT 30% pain threshold, corresponding to 37.3% and 28.7% of all 150 patients with non-responder imputation; only 20.3% of completers (10.0% of all patients) improved by ≥3 PSQI points. Recorded adverse events occurred in 10.0% of patients. Retention at 12 months was 60.6% (42.7% if patients lost to follow-up were counted as discontinuations). In completers, pain and FIQR three months after the end of treatment were within one point of the 12-month values. Conclusions: In this uncontrolled cohort, 12 months of add-on treatment with a multicomponent formulation containing PEA and ALC was associated with reductions in pain and disease impact, whereas sleep outcomes changed minimally. However, attrition was substantial and partially response-dependent; therefore, the observed changes cannot be attributed to the formulation or its individual components. These descriptive findings support the need for a controlled trial with a duration of at least 12 months.", "abstract_shown": true, "affiliations": [ "Department of Surgery, Dentistry, Gynecology and Pediatrics, Section of Anaesthesia, Intensive Care and Pain Therapy, University of Verona, 37129 Verona, Italy", "Department of Interdisciplinary Medicine–Pain and ICU Section, University of Bari Aldo Moro, 70121 Bari, Italy", "Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy", "Department of Diagnostics and Public Health, Section of Forensic Medicine, University of Verona, 37129 Verona, Italy" ], "article_type": null, "arxiv": null, "author_total": 14, "authors": [ { "affs": [ 0 ], "name": "Enrico Polati", "orcid": "0000-0001-5628-184X" }, { "affs": [ 0 ], "name": "Marco Anderloni", "orcid": "0000-0002-2949-541X" }, { "affs": [ 0 ], "name": "Leonardo Gottin" }, { "affs": [ 0 ], "name": "Katia Donadello", "orcid": "0000-0002-7053-8434" }, { "affs": [ 0 ], "name": "Lorenzo Peluso" }, { "affs": [ 0 ], "name": "Alvise Martini", "orcid": "0000-0002-7280-5356" }, { "affs": [ 0 ], "name": "Luca Polati" }, { "affs": [ 0 ], "name": "Vincenzo Di Maria", "orcid": "0009-0006-5499-4778" }, { "affs": [ 0 ], "name": "Libera Villagrossi" }, { "affs": [ 0 ], "name": "Alex Patton" }, { "affs": [ 1 ], "name": "Filomena Puntillo", "orcid": "0000-0001-7274-6467" }, { "affs": [ 2 ], "name": "Gabriele Finco", "orcid": "0000-0002-3059-9865" }, { "affs": [ 3 ], "name": "Giovanna Del Balzo", "orcid": "0000-0002-9147-9373" }, { "affs": [ 0 ], "name": "Vittorio Schweiger", "orcid": "0000-0001-9833-4997" } ], "bibtex": "https://research.draconitic.com/paper/agzmyq1y7nrp7.bib", "cited_by": 0, "doi": "10.3390/nu18213693", "fulltext_url": null, "id": "agzmyq1y7nrp7", "issns": [ "2072-6643" ], "landing_url": "https://www.mdpi.com/2072-6643/18/21/3693", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [], "openalex": null, "pdf_url": null, "pmcid": null, "pmid": null, "published": "2026-11-07", "publisher": "MDPI AG", "ris": "https://research.draconitic.com/paper/agzmyq1y7nrp7.ris", "sources": [ { "first_seen": "2026-11-10T00:21:40Z", "native_id": "10.3390/nu18213693", "source": "crossref", "url": "https://www.mdpi.com/2072-6643/18/21/3693" } ], "subjects": [ { "field": "medicine", "origin": "issn:2072-6643", "subfield": "nutrition" } ], "title": "Long-Term Add-On Use of a Fixed Multicomponent Formulation Containing Palmitoylethanolamide and Acetyl-L-Carnitine in Fibromyalgia Syndrome: A 15-Month Retrospective Single-Cohort Study of 150 Patients", "title_text": "Long-Term Add-On Use of a Fixed Multicomponent Formulation Containing Palmitoylethanolamide and Acetyl-L-Carnitine in Fibromyalgia Syndrome: A 15-Month Retrospective Single-Cohort Study of 150 Patients", "type": "peer-reviewed", "updated_at": "2026-11-10T00:21:40Z", "url": "https://research.draconitic.com/paper/agzmyq1y7nrp7", "venue": "Nutrients", "versions": [] }