Potential Anti-Inflammatory and Anti-Fatigue Effects of an Oral Food Supplement in Long COVID Patients
Annalisa Noce, Giulia Marrone, Manuela Di Lauro, Chiara Vita, Giulia Montalto, Gloria Giorgino, Carlo Chiaramonte, Cartesio D’agostini, Sergio Bernardini, Massimo Pieri
Pharmaceuticals, doi:10.3390/ph17040463
Long coronavirus disease (COVID) syndrome leads to chronic inflammatory state onset that can have a multisystem impact and compromise organ function. Moreover, long COVID syndrome is often characterized by the presence of chronic fatigue, which affects subjects' daily activities and worsens their quality of life. The aim of our double-blind, placebo-controlled randomized trial (protocol code RS 150.21, approved on 4 November 2021) was to evaluate the beneficial effects of the consumption of 2 cps/day, for two months, of an oral food supplement (OFS), based on Echinacea angustifolia, rosehip, propolis, royal jelly and zinc, in long COVID patients, compared to a two-month placebo period. The OFS's vitamin C content was equal to 22.17 mg/g (8.87 mg/capsule). The OFS's total polyphenol content was 43.98 mg/g gallic acid equivalents. At the end of the in vivo study, we highlighted a significant decrease in the inflammatory parameters in the OFS period, compared to the placebo period (neutrophil-to-lymphocyte ratio, p = 0.0455; monocyte to-lymphocyte ratio, p = 0.0005; C-reactive protein, p = 0.0145). Our study also highlighted a significant increase in vitamin D serum values (p = 0.0005) and, at the same time, an improvement in patients' life quality and a reduction in fatigue, monitored by the fatigue severity scale. This study showed the OFS's beneficial effects on the inflammatory state, fatigue and quality of life in long COVID patients.
Conflicts of Interest: The authors declare no conflicts of interest. Informed Consent Statement: Informed consent was obtained from all subjects involved in the study.
Conflicts of Interest: The authors declare no conflicts of interest.
References
Ahbap, Sakaci, Kara, Sahutoglu, Koc et al., Neutrophilto-lymphocyte ratio and platelet-tolymphocyte ratio in evaluation of inflammation in end-stage renal disease, Clin. Nephrol,
doi:10.5414/CN108584Albanese, Marrone, Paolino, Di Lauro, Di Daniele et al., Effects of Ultramicronized Palmitoylethanolamide (um-PEA) in COVID-19 Early Stages: A Case-Control Study, Pharmaceuticals,
doi:10.3390/ph15020253Bellizzi, Scalfi, Terracciano, De Nicola, Minutolo et al., Early changes in bioelectrical estimates of body composition in chronic kidney disease, J. Am. Soc. Nephrol,
doi:10.1681/ASN.2005070756Bharadwaj, El-Kafrawy, Alandijany, Bajrai, Shah et al., Structure-Based Identification of Natural Products as SARS-CoV-2 M(pro) Antagonist from Echinacea angustifolia Using Computational Approaches, Viruses,
doi:10.3390/v13020305Botezan, Baci, Bagameri, Pasca, Dezmirean, Current Status of the Bioactive Properties of Royal Jelly: A Comprehensive Review with a Focus on Its Anticancer, Anti-Inflammatory, and Antioxidant Effects, Molecules,
doi:10.3390/molecules28031510Bueno-Silva, Kawamoto, Ando-Suguimoto, Casarin, Alencar et al., Brazilian red propolis effects on peritoneal macrophage activity: Nitric oxide, cell viability, pro-inflammatory cytokines and gene expression, J. Ethnopharmacol,
doi:10.1016/j.jep.2017.06.015Burholt, Nash, Short Form 36 (SF-36) Health Survey Questionnaire: Normative data for Wales, J. Public. Health,
doi:10.1093/pubmed/fdr006Chen, Haupert, Zimmermann, Shi, Fritsche et al., Global Prevalence of Post-Coronavirus Disease 2019 (COVID-19) Condition or Long COVID: A Meta-Analysis and Systematic Review, J. Infect. Dis,
doi:10.1093/infdis/jiac136Cho, Park, Kim, Koyanagi, Jacob et al., Immunogenicity of COVID-19 vaccines in patients with diverse health conditions: A comprehensive systematic review, J. Med. Virol,
doi:10.1002/jmv.27828Cho, Park, Koyanagi, Jacob, Yon et al., The effect of pharmacological treatment and lifestyle modification in patients with nonalcoholic fatty liver disease: An umbrella review of meta-analyses of randomized controlled trials, Obes. Rev,
doi:10.1111/obr.13464Cobo, Lindholm, Stenvinkel, Chronic inflammation in end-stage renal disease and dialysis, Nephrol. Dial. Transpl,
doi:10.1093/ndt/gfy175Cornara, Biagi, Xiao, Burlando, Therapeutic Properties of Bioactive Compounds from Different Honeybee Products, Front. Pharmacol,
doi:10.3389/fphar.2017.00412De Rosa, Giampaolino, Lavitola, Morra, Formisano et al., Effect of Immunomodulatory Supplements Based on Echinacea Angustifolia and Echinacea Purpurea on the Posttreatment Relapse Incidence of Genital Condylomatosis: A Prospective Randomized Study, Biomed. Res. Int,
doi:10.1155/2019/3548396Deliorman Orhan, Hartevioglu, Kupeli, Yesilada, In vivo anti-inflammatory and antinociceptive activity of the crude extract and fractions from Rosa canina L. fruits, J. Ethnopharmacol,
doi:10.1016/j.jep.2007.03.029Di Renzo, Gualtieri, Romano, Marrone, Noce et al., Role of Personalized Nutrition in Chronic-Degenerative Diseases, Nutrients,
doi:10.3390/nu11081707Giuliano, Tiple, Agostoni, Armocida, Biardi et al., Italian good practice recommendations on management of persons with Long-COVID, Front. Public. Health,
doi:10.3389/fpubh.2023.1122141Honda, Araki, Hata, Ichihara, Ito et al., 10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling, J. Aging Res,
doi:10.1155/2015/425261Jarosz, Olbert, Wyszogrodzka, Mlyniec, Librowski, Antioxidant and anti-inflammatory effects of zinc. Zincdependent NF-kappaB signaling, Inflammopharmacology,
doi:10.1007/s10787-017-0309-4Kharazmi, Winther, Rose hip inhibits chemotaxis and chemiluminescence of human peripheral blood neutrophils in vitro and reduces certain inflammatory parameters in vivo, Inflammopharmacology,
doi:10.1007/s10787-999-0031-yKim, Kim, Lee, Lee, Stubbs et al., Environmental risk factors, protective factors, and biomarkers for postpartum depressive symptoms: An umbrella review, Neurosci. Biobehav. Rev,
doi:10.1016/j.neubiorev.2022.104761Lohman, Roche, Martorell, Anthropometric Standardization Reference Manual
Mariani, Cattini, Neri, Malavolta, Mocchegiani et al., Simultaneous evaluation of circulating chemokine and cytokine profiles in elderly subjects by multiplex technology: Relationship with zinc status, Biogerontology,
doi:10.1007/s10522-006-9060-8Martinez-Gonzalez, Garcia-Arellano, Toledo, Salas-Salvado, Buil-Cosiales et al., A 14-item Mediterranean diet assessment tool and obesity indexes among high-risk subjects: The PREDIMED trial, PLoS ONE,
doi:10.1371/journal.pone.0043134Melchart, Linde, Fischer, Kaesmayr, Echinacea for preventing and treating the common cold, Cochrane Database Syst. Rev,
doi:10.1002/14651858.CD000530Naik, Shao, Tran, Wong, Russell et al., Evaluating fatigue in patients recovering from COVID-19: Validation of the fatigue severity scale and single item screening questions, Health Qual. Life Outcomes,
doi:10.1186/s12955-022-02082-xNinfali, Mea, Giorgini, Rocchi, Bacchiocca, Antioxidant capacity of vegetables, spices and dressings relevant to nutrition, Br. J. Nutr,
doi:10.1079/BJN20041327Noce, Albanese, Marrone, Di Lauro, Pietroboni Zaitseva et al., Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients, Pharmaceuticals,
doi:10.3390/ph14040336Noce, Bocedi, Campo, Marrone, Di Lauro et al., A Pilot Study of a Natural Food Supplement as New Possible Therapeutic Approach in Chronic Kidney Disease Patients, Pharmaceuticals,
doi:10.3390/ph13070148Nowak, Boesch, Andres, Battegay, Hornemann et al., Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial, Medicine,
doi:10.1097/MD.0000000000005353Patterson, Guevara-Coto, Yogendra, Francisco, Long et al., Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning, Front. Immunol,
doi:10.1016/j.jaut.2020.102433Patterson, Guevara-Coto, Yogendra, Francisco, Long et al., Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning, Front. Immunol,
doi:10.3389/fimmu.2021.700782Ribeiro, Botelho, Pinto, La Torre, Almeida et al., Molecular modeling study of natural products as potential bioactive compounds against SARS-CoV-2, J. Mol. Model,
doi:10.1007/s00894-023-05586-5Riemma, Schettino, Munno, Fasulo, Sandullo et al., Echinacea angustifolia and Echinacea purpurea Supplementation Combined with Vaginal Hyaluronic Acid to Boost the Remission of Cervical Low-Grade Squamous Intraepithelial Lesions (L-SILs): A Randomized Controlled Trial, Medicina,
doi:10.3390/medicina58050646Roman, Stanila, Stanila, Bioactive compounds and antioxidant activity of Rosa canina L. biotypes from spontaneous flora of Transylvania, Chem. Cent. J,
doi:10.1186/1752-153X-7-73Rosenthal, Majeroni, Pretorius, Malik, Fatigue: An overview, Am. Fam. Physician
Roy, Sherman, Monari-Sparks, Schweiker, Hunter, Correction of Low Vitamin D Improves Fatigue: Effect of Correction of Low Vitamin D in Fatigue Study (EViDiF Study), N. Am. J. Med. Sci,
doi:10.4103/1947-2714.139291Ryan, Hope, Masavuli, Lynn, Mekonnen et al., Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection, BMC Med,
doi:10.1186/s12916-021-02228-6Singleton, Orthofer, Lamuela-Raventós, Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent
Taylor, Weber, Standish, Quinn, Goesling et al., Efficacy and safety of echinacea in treating upper respiratory tract infections in children: A randomized controlled trial, JAMA,
doi:10.1001/jama.290.21.2824Terada, Narukawa, Watanabe, Specific hydroxy fatty acids in royal jelly activate TRPA1, J. Agric. Food Chem,
doi:10.1021/jf1041646Turner, Khan, Putrino, Woodcock, Kell et al., Long COVID: Pathophysiological factors and abnormalities of coagulation, Trends Endocrinol. Metab,
doi:10.1016/j.tem.2023.03.002Vajdi, Musazadeh, Khajeh, Safaei, Darzi et al., The effects of royal jelly supplementation on anthropometric indices: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials, Front. Nutr,
doi:10.3389/fnut.2023.1196258Williams, Mancia, Spiering, Agabiti Rosei, Azizi et al., ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension, J. Hypertens,
doi:10.1097/HJH.0000000000001940Winther, Apel, Thamsborg, A powder made from seeds and shells of a rose-hip subspecies (Rosa canina) reduces symptoms of knee and hip osteoarthritis: A randomized, double-blind, placebo-controlled clinical trial, Scand. J. Rheumatol,
doi:10.1080/03009740510018624Yoon, Park, Kim, Kronbichler, Koyanagi et al., National trends in the prevalence of chronic kidney disease among Korean adults, 2007-2020, Sci. Rep,
doi:10.1038/s41598-023-33122-1Yoshida, Hayashi, Watadani, Okano, Tanimura et al., Royal jelly improves hyperglycemia in obese/diabetic KK-Ay mice, J. Vet. Med. Sci,
doi:10.1292/jvms.16-0458Younis, Nafady, Mahmoud, Value of carotid intimal-medial thickness as independent predictor of endothelial dysfunction in uremic patients. Egypt, Heart J,
doi:10.1016/j.ehj.2011.09.008
