{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T05:23:16Z","timestamp":1763788996919,"version":"3.45.0"},"reference-count":91,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Cancer patients often use natural health products (NHPs) during chemotherapy without medical supervision. We have previously described the clinical cases of two patients taking capecitabine in combination with folate supplements who suffered from severe diarrhoea and hand-foot syndrome, emphasising that the combination of NHPs with chemotherapeutic agents such as fluoropyrimidines (FPs) can lead to life-threatening events. Although the potential harmful interaction between folate supplements and capecitabine is reported in the summary of product characteristics for this FP, it remains unclear, and evidence regarding interactions with other NHPs is even more limited. Objectives\/Methods: This narrative review aimed to provide an update on the literature regarding the effects of combining NHPs and FPs, describing the results of randomised clinical trials and observational studies to provide a critical analysis of the factors influencing the clinical outcomes of cancer patients following this therapeutic approach. Results: Herbal supplements belonging to traditional Chinese medicine and other NHPs, including polyunsaturated fatty acids and probiotics, may reduce the incidence and severity of gastrointestinal, haematological, and skin toxicities related to FPs. In addition to potential safety benefits, NHPs may improve the efficacy of FP-based therapy. Folate supplements appear to improve efficacy outcomes, such as disease-free survival and overall survival, but have also been associated with serious FP-related adverse events. However, the results are mixed, partly because they are influenced by the patient\u2019s genetic background. Conclusions: Overall, the available data are inconclusive and do not support the introduction of natural products as complementary therapy in cancer patients undergoing FP-based chemotherapy, highlighting the need for further investigation.<\/jats:p>","DOI":"10.3390\/ph18111767","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T14:21:54Z","timestamp":1763648514000},"page":"1767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Natural Health Products in Combination with FP-Based Chemotherapy"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6964-2739","authenticated-orcid":false,"given":"Valeria","family":"Conti","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, 84081 Baronissi, Italy"},{"name":"Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, 84131 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-8704","authenticated-orcid":false,"given":"Berenice","family":"Stefanelli","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, 84131 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmineantonio","family":"Romeo","sequence":"additional","affiliation":[{"name":"Postgraduate School of Clinical Pharmacology and Toxicology, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Postgraduate School of Clinical Pharmacology and Toxicology, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominga","family":"Valentino","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, 84131 Salerno, Italy"},{"name":"Postgraduate School in Clinical Pharmacology and Toxicology, Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3441-889X","authenticated-orcid":false,"given":"Graziamaria","family":"Corbi","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples \u201cFederico II\u201d, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6431-8278","authenticated-orcid":false,"given":"Francesco","family":"Sabbatino","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, 84081 Baronissi, Italy"},{"name":"Oncology Unit, University Hospital \u201cSan Giovanni di Dio e Ruggi D\u2019Aragona\u201d, 84131 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8543-5462","authenticated-orcid":false,"given":"Emanuela","family":"De Bellis","sequence":"additional","affiliation":[{"name":"PhD School \u201cClinical and Translational Oncology (CTO)\u201d, Scuola Superiore Meridionale, University of Naples \u201cFederico II\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8235-9118","authenticated-orcid":false,"given":"Amelia","family":"Filippelli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, 84081 Baronissi, Italy"},{"name":"Clinical Pharmacology Unit, San Giovanni di Dio e Ruggi d\u2019Aragona University Hospital, 84131 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrc1074","article-title":"5-Fluorouracil: Mechanisms of Action and Clinical Strategies","volume":"3","author":"Longley","year":"2003","journal-title":"Nat. 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