Background: Sickle cell disease remains a hereditary condition for which there is no widely accessible curative treatment in sub-Saharan Africa. Growing interest in nutrition as a means of reducing morbidity has led to the development of adapted local nutritional alternatives. The Objective of this study was to evaluate the impact of consuming an enriched flour with anti-inflammatory and antioxidant properties among undernourished patients with sickle cell disease. Methods: This was a prospective interventional study conducted from July 1, 2024, to July 31, 2025, at the National Center for Sickle Cell Disease Reference and Follow-up in Togo. Of the 233 patients recruited, 154 were identified as undernourished; 75 of them were enrolled in the intervention phase, and 57 completed the 6-month follow-up period while consuming the enriched flour porridge. Results: The prevalence of malnutrition was 66.1%. After 6 months of intervention, vaso-occlusive crises decreased by 86% (from 1.46 to 0.20 episodes/month, p < 0.001), and quantitative CRP levels decreased by 64%. Paired analysis (McNemar’s test) showed a significant improvement in CRP levels (OR = 7.33; 95% CI 2.20 - 24.50; p < 0.001) and albumin levels (OR = 7.00; 95% CI 1.59 - 30.80; p = 0.004), with no significant paired change for alpha-1-glycoprotein (OR = 1.08; 95% CI 0.51 - 2.29; p = 1.000), alpha-2-glycoprotein (OR = 0.22; 95% CI 0.05 - 1.03; p = 0.065), or beta-2-glycoprotein (OR = 2.40; 95% CI 0.85 - 6.81; p = 0.143). The proportion of patients with normal muscle mass increased by 21%. Conclusion: Enriched flour made from local products showed a positive and clinically significant impact on nutritional status, inflammatory status, the incidence of vaso-occlusive crises, and quality of life in undernourished patients with sickle cell disease, although this effect was not consistent across the inflammatory markers studied. Systematic integration of nutritional management into the overall care of sickle cell patients is recommended.
References
[1]
Pauling, L., Itano, H.A., Singer, S.J. and Wells, I.C. (1949) Sickle Cell Anemia, a Molecular Disease. Science, 110, 543-548. https://doi.org/10.1126/science.110.2865.543
[2]
Ware, R.E., de Montalembert, M., Tshilolo, L. and Abboud, M.R. (2017) Sickle Cell Disease. The Lancet, 390, 311-323. https://doi.org/10.1016/s0140-6736(17)30193-9
[3]
Jonani, B., Kasule, E.C., Herman, B.R., Arturo, J.F., Mugambwa, M.C., Stephen, S., et al. (2025) Burden of Sickle Cell Anemia in Africa: A Systematic Review and Meta-Analysis. PLOS ONE, 20, e0337090. https://doi.org/10.1371/journal.pone.0337090
[4]
Esoh, K., Wonkam-Tingang, E. and Wonkam, A. (2021) Sickle Cell Disease in Sub-Saharan Africa: Transferable Strategies for Prevention and Care. The Lancet Haematology, 8, e744-e755. https://doi.org/10.1016/s2352-3026(21)00191-5
[5]
Sundd, P., Gladwin, M.T. and Novelli, E.M. (2019) Pathophysiology of Sickle Cell Disease. Annual Review of Pathology: Mechanisms of Disease, 14, 263-292. https://doi.org/10.1146/annurev-pathmechdis-012418-012838
[6]
Manwani, D. and Frenette, P.S. (2013) Vaso-Occlusion in Sickle Cell Disease: Pathophysiology and Novel Targeted Therapies. Blood, 122, 3892-3898. https://doi.org/10.1182/blood-2013-05-498311
[7]
Silva-Junior, A.L., Garcia, N.P., Cardoso, E.C., Dias, S., Tarrag？, A.M., Fraiji, N.A., et al. (2021) Immunological Hallmarks of Inflammatory Status in Vaso-Occlusive Crisis of Sickle Cell Anemia Patients. Frontiers in Immunology, 12, Article ID: 559925. https://doi.org/10.3389/fimmu.2021.559925
[8]
Obeagu, E.I. and Obeagu, G.U. (2024) Malnutrition in Sickle Cell Anemia: Prevalence, Impact, and Interventions: A Review. Medicine, 103, e38164. https://doi.org/10.1097/md.0000000000038164
[9]
Nartey, E.B., Spector, J., Adu-Afarwuah, S., Jones, C.L., Jackson, A., Ohemeng, A., et al. (2021) Nutritional Perspectives on Sickle Cell Disease in Africa: A Systematic Review. BMC Nutrition, 7, Article No. 9. https://doi.org/10.1186/s40795-021-00410-w
[10]
Williams, T.N. (2021) Undernutrition: A Major but Potentially Preventable Cause of Poor Outcomes in Children Living with Sickle Cell Disease in Africa. BMC Medicine, 19, Article No. 17. https://doi.org/10.1186/s12916-020-01892-4
[11]
Kaponda, A., Muya, K., Panda, J., Koto, K.K. and Bonnechère, B. (2024) Unraveling the Complexity of Vaso-Occlusive Crises in Sickle Cell Disease: Insights from a Resource-Limited Setting. Journal of Clinical Medicine, 13, Article 2528. https://doi.org/10.3390/jcm13092528
[12]
Kim, I.S. (2021) Current Perspectives on the Beneficial Effects of Soybean Isoflavones and Their Metabolites for Humans. Antioxidants, 10, Article 1064. https://doi.org/10.3390/antiox10071064
[13]
Pareek, A., Pant, M., Gupta, M.M., Kashania, P., Ratan, Y., Jain, V., et al. (2023) Moringa Oleifera: An Updated Comprehensive Review of Its Pharmacological Activities, Ethnomedicinal, Phytopharmaceutical Formulation, Clinical, Phytochemical, and Toxicological Aspects. International Journal of Molecular Sciences, 24, Article 2098. https://doi.org/10.3390/ijms24032098
[14]
Silva, M.L., Rita, K., Bernardo, M.A., Mesquita, M.F.d., Pint？o, A.M. and Moncada, M. (2023) Adansonia Digitata L. (Baobab) Bioactive Compounds, Biological Activities, and the Potential Effect on Glycemia: A Narrative Review. Nutrients, 15, Article 2170. https://doi.org/10.3390/nu15092170
[15]
Tchagbele, O., Codjo, K., Chantal, B., Essodolom, P., Mouawiyatou, B. and Moudassirou, B. (2025) Physical, Chemical, and Microbiological Characterization of a Flour with Antioxidant and Anti-Inflammatory Properties for Patients with Sickle Cell Anemia in Togo. International Journal of Nutrition and Food Sciences, 14, 383-394. https://doi.org/10.11648/j.ijnfs.20251406.13
[16]
Layibo, Y., Kuéviakoé, I.M., Padaro, E., Magnang, H., Vovor, A. and Agbonon, A. (2019) Prévalence de l’albuminurie chez les drépanocytaires au centre hospitalier universitaire campus de lomé au togo. Annales de Biologie Clinique, 77, 79-86. https://doi.org/10.1684/abc.2018.1404
[17]
Farrell, A.T., Panepinto, J., Carroll, C.P., Darbari, D.S., Desai, A.A., King, A.A., et al. (2019) End Points for Sickle Cell Disease Clinical Trials: Patient-Reported Outcomes, Pain, and the Brain. Blood Advances, 3, 3982-4001. https://doi.org/10.1182/bloodadvances.2019000882
[18]
Cashin, K. and Oot, L. (2018) Guide to Anthropometry: A Practical Tool for Pro-gram Planners, Managers, and Implementers. Food and Nutrition Technical Assistance III Project (FANTA)/FHI 360. https://www.fantaproject.org/tools/anthropometry-guide
[19]
Soylu, M., ？ensoy, N., Do？an, ？., Do？an, N., Maz？c？o？lu, M.M. and ？ztürk, A. (2021) Four-Site Skinfolds Thickness Percentiles of Schoolchildren and Adolescents in Turkey. Public Health Nutrition, 24, 5414-5425. https://doi.org/10.1017/s1368980021003323
[20]
Hasselmann, M. and Alix, E. (2003) Outils et procédures de dépistage de la dénutrition et de son risque en milieu hospitalier. Nutrition Clinique et Métabolisme, 17, 218-226. https://doi.org/10.1016/j.nupar.2003.09.004
[21]
Kouassi, K., Bagny, A., Kaaga, L., Bouglouga, O., Lawson Anani-Soh, L., Lamboni, C., and Redah, D. (2014). Prevalence of Protein-Energy Undernutrition Evaluated by the Measurement of Triceps Skinfold Thickness and Mid-Arm Muscle Circumference of 103 Adults with Cirrhosis of the Liver Hospitalized in the Department of Hepatology and Gastroenterology of the Lomé Campus University Hospital (Togo). Médecine et Santé Tropicales, 24, 208？213. https://doi.org/10.1684/mst.2014.0334
[22]
Caquet, R. (2015) 250 Examens de laboratoire. 12th Edition, Elsevier-Masson.
[23]
Durand, G. and Beaudeux, J.L. (2011) Biochimie Médicale. 2nd Edition, Lavoisier.
[24]
Doumas, B.T., Ard Watson, W. and Biggs, H.G. (1971) Albumin Standards and the Measurement of Serum Albumin with Bromcresol Green. Clinica Chimica Acta, 31, 87-96. https://doi.org/10.1016/0009-8981(71)90365-2
[25]
Mann, C.K. and Yoe, J.H. (1956) Spectrophotometric Determination of Magnesium with Sodium 1-Azo-2-Hydroxy-3-(2,4-Dimethylcarboxanilido)-Naphthalene-1’-(2-Hydroxybenzene-5-Sulfonate). Analytical Chemistry, 28, 202-205. https://doi.org/10.1021/ac60110a016
[26]
Henry, R. (1974) Clinical Chemistry. 2nd Edition, Harper & Row, 723 p.
[27]
Eda, S., Kaufmann, J., Roos, W. and Pohl, S. (1998) Development of a New Microparticle-Enhanced Turbidimetric Assay for C-Reactive Protein with Superior Features in Analytical Sensitivity and Dynamic Range. Journal of Clinical Laboratory Analysis, 12, 137-144. https://doi.org/10.1002/(sici)1098-2825(1998)12:3<137::aid-jcla2>3.0.co;2-6
[28]
Price, C.P., Trull, A.K., Berry, D. and Gorman, E.G. (1987) Development and Validation of a Particle-Enhanced Turbidimetric Immunoassay for C-Reactive Protein. Journal of Immunological Methods, 99, 205-211. https://doi.org/10.1016/0022-1759(87)90129-3
[29]
Dubois, S., McGovern, M. and Ehrhardt, V. (1988) Eisenstoffwechsel-Diagnostik mit Boehringer Mannheim/Hitachi-Analysensystemen: Ferritin, Transferrin und Eisen. GIT Labor-Medizin, 9, 468-471.
[30]
Hartman, K., Luterotti, S., Osswald, H.F., Oehme, M., Meier, P.C., Ammann, D., et al. (1978) Chloride-Selective Liquid-Membrane Electrodes Based on Lipophilic Methyl-Tri-N-Alkyl-Ammonium Compounds and Their Applicability to Blood Serum Measurements. Mikrochimica Acta, 70, 235-246. https://doi.org/10.1007/bf01201614
[31]
Shibata, Y., Maruizumi, T., & Miyagi, H. (1992) Characteristics of Sodium Ion-Selective Electrodes Based on Neutral Carriers and Their Application to Analysis of Physiological Fluids. NIPPON KAGAKU KAISHI, 961？967. https://doi.org/10.1246/nikkashi.1992.961
[32]
Shono, T., Okahara, M., Ikeda, I., Kimura, K. and Tamura, H. (1982) Sodium-Selective PVC Membrane Electrodes Based on Bis(12-Crowns-4)S. Journal of Electroanalytical Chemistry and Interfacial Electrochemistry, 132, 99-105. https://doi.org/10.1016/0022-0728(82)85009-2
[33]
Pioda, L.A.R., Stankova, V. and Simon, W. (1969) Highly Selective Potassium Ion Responsive Liquid-Membrane Electrode. Analytical Letters, 2, 665-674. https://doi.org/10.1080/00032716908051343
[34]
Adom, K.K. and Liu, R.H. (2002) Antioxidant Activity of Grains. Journal of Agricultural and Food Chemistry, 50, 6182-6187. https://doi.org/10.1021/jf0205099
Messina, M. (2010) Insights Gained from 20 Years of Soy Research. The Journal of Nutrition, 140, 2289S-2295S. https://doi.org/10.3945/jn.110.124107
[37]
Bhagwat, S., Haytowitz, D. and Holden, J. (2008) USDA Database for the Isoflavone Content of Selected Foods, Release 2.0. U.S. Department of Agriculture, Agricultural Research Service, Nutrient Data Laboratory.
[38]
Chadare, F.J., Linnemann, A.R., Hounhouigan, J.D., Nout, M.J.R. and Van Boekel, M.A.J.S. (2008) Baobab Food Products: A Review on Their Composition and Nutritional Value. Critical Reviews in Food Science and Nutrition, 49, 254-274. https://doi.org/10.1080/10408390701856330
[39]
Cisse, M., Sakho, M., Dornier, M., Diop, C.M., Reynes, M. and Sock, O. (2009) Caractérisation du fruit du baobab et étude de sa transformation en nectar. Fruits, 64, 19-34. https://doi.org/10.1051/fruits/2008052
[40]
Fahey, J.W. (2005) Moringa Oleifera: A Review of the Medical Evidence for Its Nutritional, Therapeutic, and Prophylactic Properties. Part 1. Trees for Life Journal, 1, 1-15.
[41]
Nouman, W., Basra, S.M.A., Siddiqui, M.T., Yasmeen, A., Gull, T. and Alcayde, M.A.C. (2014) Potential of Moringa oleifera L. as Livestock Fodder Crop: A Review. Turkish Journal of Agriculture and Forestry, 38, 1-14. https://doi.org/10.3906/tar-1211-66
[42]
Aggarwal, B.B. and Harikumar, K.B. (2009) Potential Therapeutic Effects of Curcumin, the Anti-Inflammatory Agent, against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases. The International Journal of Biochemistry & Cell Biology, 41, 40-59. https://doi.org/10.1016/j.biocel.2008.06.010
[43]
Gupta, S.C., Sung, B., Kim, J.H., Prasad, S., Li, S. and Aggarwal, B.B. (2012) Multitargeting by Turmeric, the Golden Spice: From Kitchen to Clinic. Molecular Nutrition & Food Research, 57, 1510-1528. https://doi.org/10.1002/mnfr.201100741
[44]
Bhat, K.V., Kumari, R., Pathak, N. and Rai, A.K. (2014) Value Addition in Sesame: A Perspective on Bioactive Components for Enhancing Utility and Profitability. Pharmacognosy Reviews, 8, 147-155. https://doi.org/10.4103/0973-7847.134249
[45]
Suja, K.P., Jayalekshmy, A. and Arumughan, C. (2005) Antioxidant Activity of Sesame Cake Extract. Food Chemistry, 91, 213-219. https://doi.org/10.1016/j.foodchem.2003.09.001
[46]
Barden, E.M., Kawchak, D.A., Ohene-Frempong, K., Stallings, V.A. and Zemel, B.S. (2002) Body Composition in Children with Sickle Cell Disease. The American Journal of Clinical Nutrition, 76, 218-225. https://doi.org/10.1093/ajcn/76.1.218
[47]
Salman, E.K., Haymond, M.W., Bayne, E., Sager, B.K., Wiisanen, A., Pitel, P., et al. (1996) Protein and Energy Metabolism in Prepubertal Children with Sickle Cell Anemia. Pediatric Research, 40, 34-40. https://doi.org/10.1203/00006450-199607000-00007
[48]
Chawla, A., Sprinz, P.G., Welch, J., Heeney, M., Usmani, N., Pashankar, F., et al. (2013) Weight Status of Children with Sickle Cell Disease. Pediatrics, 131, e1168-e1173. https://doi.org/10.1542/peds.2012-2225
[49]
Gabay, C. and Kushner, I. (1999) Acute-Phase Proteins and Other Systemic Responses to Inflammation. New England Journal of Medicine, 340, 448-454. https://doi.org/10.1056/nejm199902113400607
[50]
Cui, J., Li, H., Zhang, T., Lin, F., Chen, M., Zhang, G., et al. (2025) Research Progress on the Mechanism of Curcumin Anti-Oxidative Stress Based on Signaling Pathway. Frontiers in Pharmacology, 16, Article ID: 1548073. https://doi.org/10.3389/fphar.2025.1548073
[51]
Liu, M., Wang, J., Song, Z. and Pei, Y. (2025) Regulation Mechanism of Curcumin Mediated Inflammatory Pathway and Its Clinical Application: A Review. Frontiers in Pharmacology, 16, Article ID: 1642248. https://doi.org/10.3389/fphar.2025.1642248
[52]
Villegas-Vazquez, E.Y., Gómez-Cansino, R., Marcelino-Pérez, G., Jiménez-López, D. and Quintas-Granados, L.I. (2025) Unveiling the Miracle Tree: Therapeutic Potential of Moringa Oleifera in Chronic Disease Management and Beyond. Biomedicines, 13, Article 634. https://doi.org/10.3390/biomedicines13030634
[53]
da Silva Parente, T.S.J., Sarandy, M.M., de Araújo, E.R.D., Gon？alves, R.V. and Zucolotto, S.M. (2025) Effect of Moringa Oleifera on Inflammatory Diseases: An Umbrella Review of 26 Systematic Reviews. Frontiers in Pharmacology, 16, Article ID: 1572337. https://doi.org/10.3389/fphar.2025.1572337
[54]
Obiekwe, C.L., Ibegbulem, C.O., Ujowundu, C.O., Igwe, C.U. and Nwaoguikpe, R. (2025) Proximate Analysis, Phytochemical Content and the Antioxidant Effect of Moringa Oleifera Leaf Methanol Extract in Sickle Cell Disease Management. International Journal of Science and Research Archive, 16, 334-348. https://doi.org/10.30574/ijsra.2025.16.1.1963
[55]
Abdulwaliyu, I., Arekemase, S.O., Batari, M.L., Oshodin, J.O., Mustapha, R.A., Ibrahim, D., et al. (2024) Nutritional and Pharmacological Attributes of Baobab Fruit Pulp. Food Production, Processing and Nutrition, 6, Article 98. https://doi.org/10.1186/s43014-024-00283-z
[56]
Monteiro, S., Reboredo, F.H., Lageiro, M.M., Louren？o, V.M., Dias, J., Lidon, F., et al. (2022) Nutritional Properties of Baobab Pulp from Different Angolan Origins. Plants, 11, Article 2272. https://doi.org/10.3390/plants11172272
[57]
Goh, Y.X., Jalil, J., Lam, K.W., Husain, K. and Premakumar, C.M. (2022) Genistein: A Review on Its Anti-Inflammatory Properties. Frontiers in Pharmacology, 13, Article ID: 820969. https://doi.org/10.3389/fphar.2022.820969
[58]
Omoni, A.O. and Aluko, R.E. (2005) Soybean Foods and Their Benefits: Potential Mechanisms of Action. Nutrition Reviews, 63, 272-283. https://doi.org/10.1111/j.1753-4887.2005.tb00141.x
[59]
Wu, Z. and Liu, L. (2022) The Protective Activity of Genistein against Bone and Cartilage Diseases. Frontiers in Pharmacology, 13, Article ID: 1016981. https://doi.org/10.3389/fphar.2022.1016981
[60]
Goel, Y., Arellano, M.A., Fouda, R.T., Kerr, D., Jana, S., Lomeli, R.A., et al. (2023) Mechanism-Based Targeting of Sickle Cell Pathobiology and Pain with Novel Transdermal Curcumin. Blood, 142, 2490-2490. https://doi.org/10.1182/blood-2023-182512
[61]
Wood, K.C., Hsu, L.L. and Gladwin, M.T. (2008) Sickle Cell Disease Vasculopathy: A State of Nitric Oxide Resistance. Free Radical Biology and Medicine, 44, 1506-1528. https://doi.org/10.1016/j.freeradbiomed.2008.01.008
[62]
Stevens, M.C.G., Hayes, R.J. and Serjeant, G.R. (1983) Body Shape in Young Children with Homozygous Sickle Cell Disease. Pediatrics, 71, 610-614. https://doi.org/10.1542/peds.71.4.610
[63]
Orsi, B.C., Gorski, D., Krul, N.E., Wiens, A., Brito, M., Tonin, F.S., et al. (2025) The Effects of Nutritional Supplementation for Children and Adolescents with Sickle Cell Disease: A Systematic Review and Meta-Analyses. Clinical Nutrition, 47, 157-168. https://doi.org/10.1016/j.clnu.2025.02.016
