Login Register Cart 0
Current Rheumatology Reviews

Current Rheumatology Reviews

Editor-in-Chief

ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Clinical Trial

Randomised Clinical Trial Study: The Combination of Vitamin D and Curcumin Piperine Attenuates Disease Activity and Pro-inflammatory Cytokines Levels Insystemic Lupus Erythematosus Patients

Author(s): Cesarius Singgih Wahonoorcid of author, Hani Susiantiorcid of author, Arif Luqman Hakim, Firdha Rosita, Mirza Zaka Pratama*orcid of author, Perdana Aditya Rahmanorcid of author and Muhammad Anshoryauthors OrcID

Volume 20, Issue 5, 2024

Published on: 31 January, 2024

Page: [586 - 594] Pages: 9

DOI: 10.2174/0115733971276106231226071002

Price: $65

Become a Editorial Board Member
Become a Reviewer
Become a Editor
Become a Section Editor

Abstract

Background: Curcumin-piperine might synergise with vitamin D to induce clinical remission in patients with systemic lupus erythematosus (SLE).

Objective: To observe the improvement of patients with SLE clinically and the levels of inflammatory cytokines after receiving supplements of curcumin-piperine and cholecalciferol (Vitamin D3).

Methods: Forty-five female SLE patients were included in a three-month double-blind, randomized controlled trial. Participants were classified into: Group I (400 IU cholecalciferol + placebo three times daily, n = 15), Group II (600 mg curcumin + 15,800 m piperine once daily and three times daily placebo, n = 15), and Group III (cholecalciferol 400 IU three times and 600 mg curcumin + 15,800 mg piperine once a day, n = 15). Mexican SLE disease activity score (Mex- SLEDAI), fatigue severity scale (FSS), TGF-β, and IL-6 levels were measured from all patients before and after the treatments.

Results: Mex-SLEDAI, FSS, and IL-6 were reduced significantly, while TGF-β serum levels were increased in all groups after the treatments (p <0.05). Changes in Mex-SLEDAI score (p = 0.003 and p = 0.008), FSS (p = 0.001 and p <0.001), and TGF-β (p = 0.003 and p = 0.004) serum levels were significantly higher in group III compared to the group I or group II. On the other hand, changes in Mex-SLEDAI, FSS, IL-6, and TGF-β serum levels were similar between groups I and II.

Conclusion: Although vitamin D or curcumin-piperine alone could improve the clinical outcome and cytokines levels in SLE, curcumin-piperine combined with vitamin D had the best outcome in improving the disease activity and cytokines levels among patients with SLE. (ClinicalTrials.gov number, NCT05430087).

Keywords: Systemic lupus erythematosus, vitamin D, curcumin, piperine, disease activity, inflammatory cytokines.

« Previous Next »

Graphical Abstract

Graphical abstract illustrating key findings of the study

[1]
Hamijoyo L, Candrianita S, Rahmadi AR, et al. The clinical characteristics of systemic lupus erythematosus patients in Indonesia: a cohort registry from an Indonesia-based tertiary referral hospital. Lupus 2019; 28(13): 1604-9.
[http://dx.doi.org/10.1177/0961203319878499] [PMID: 31566078]
[2]
Handono K, Hasanah D, Kalim H, Mawarti H. The association among serum levels of vitamin D, TGF-β/IL-6 balance and Treg/Th17 balance in systemic lupus erythematosus patients in Indonesia. Int J Biochem Biotechnol 2013; 2(9): 490-6.
[3]
Islam MA, Khandker SS, Alam SS, Kotyla P, Hassan R. Vitamin D status in patients with systemic lupus erythematosus (SLE): A systematic review and meta-analysis. Autoimmun Rev 2019; 18(11): 102392.
[http://dx.doi.org/10.1016/j.autrev.2019.102392] [PMID: 31520805]
[4]
Breslin LC, Magee PJ, Wallace JMW, McSorley EM. An evaluation of vitamin D status in individuals with systemic lupus erythematosus. Proc Nutr Soc 2011; 70(4): 399-407.
[http://dx.doi.org/10.1017/S0029665111001613] [PMID: 21861947]
[5]
Ruiz-Ballesteros AI, Meza-Meza MR, Vizmanos-Lamotte B, Parra-Rojas I, de la Cruz-Mosso U. Association of vitamin D metabolism gene polymorphisms with autoimmunity: evidence in population genetic studies. Int J Mol Sci 2020; 21(24): 9626.
[http://dx.doi.org/10.3390/ijms21249626] [PMID: 33348854]
[6]
Hamza RT, Awwad KS, Ali MK, Hamed AI. Reduced serum concentrations of 25-hydroxy vitamin D in Egyptian patients with systemic lupus erythematosus: Relation to disease activity. Med Sci Monit 2011; 17(12): CR711-8.
[http://dx.doi.org/10.12659/MSM.882131] [PMID: 22129903]
[7]
Terrier B, Derian N, Schoindre Y, et al. Restoration of regulatory and effector T cell balance and B cell homeostasis in systemic lupus erythematosus patients through vitamin D supplementation. Arthritis Res Ther 2012; 14(5): R221.
[http://dx.doi.org/10.1186/ar4060] [PMID: 23075451]
[8]
Aranow C, Kamen DL, Dall’Era M, et al. Randomized, double-blind, placebo-controlled trial of the effect of vitamin D 3 on the interferon signature in patients with systemic lupus erythematosus. Arthritis Rheumatol 2015; 67(7): 1848-57.
[http://dx.doi.org/10.1002/art.39108] [PMID: 25777546]
[9]
Souza VA, Bastos MG, Fernandes NMS, et al. Association of hypovitaminosis D with Systemic Lupus Erythematosus and inflammation. J Bras Nefrol 2014; 36(4): 430-6.
[http://dx.doi.org/10.5935/0101-2800.20140062] [PMID: 25517270]
[10]
Mok CC, Birmingham DJ, Leung HW, Hebert LA, Song H, Rovin BH. Vitamin D levels in Chinese patients with systemic lupus erythematosus: relationship with disease activity, vascular risk factors and atherosclerosis. Rheumatology (Oxford) 2012; 51(4): 644-52.
[http://dx.doi.org/10.1093/rheumatology/ker212] [PMID: 21719424]
[11]
Correa-Rodríguez M, Pocovi-Gerardino G, Callejas-Rubio JL, et al. Vitamin D levels are associated with disease activity and damage accrual in systemic lupus erythematosus patients. Biol Res Nurs 2021; 23(3): 455-63.
[http://dx.doi.org/10.1177/1099800420983596] [PMID: 33380211]
[12]
Zheng R, Gonzalez A, Yue J, et al. Efficacy and Safety of Vitamin D supplementation in patients with systemic lupus erythematosus: A meta-analysis of randomized controlled trials. Am J Med Sci 2019; 358(2): 104-14.
[http://dx.doi.org/10.1016/j.amjms.2019.04.020] [PMID: 31331447]
[13]
Zhao J, Wang J, Zhou M, Li M, Li M, Tan H. Curcumin attenuates murine lupus via inhibiting NLRP3 inflammasome. Int Immunopharmacol 2019; 69: 213-6.
[http://dx.doi.org/10.1016/j.intimp.2019.01.046] [PMID: 30738291]
[14]
Momtazi-Borojeni AA, Haftcheshmeh SM, Esmaeili SA, Johnston TP, Abdollahi E, Sahebkar A. Curcumin: A natural modulator of immune cells in systemic lupus erythematosus. Autoimmun Rev 2018; 17(2): 125-35.
[http://dx.doi.org/10.1016/j.autrev.2017.11.016] [PMID: 29180127]
[15]
Apprato G, Fiz C, Fusano I, Bergandi L, Silvagno F. Natural epigenetic modulators of vitamin D receptor. Appl Sci 2020; 10(12): 4096.
[http://dx.doi.org/10.3390/app10124096]
[16]
Bartik L, Whitfield GK, Kaczmarska M, et al. Curcumin: A novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention. J Nutr Biochem 2010; 21(12): 1153-61.
[http://dx.doi.org/10.1016/j.jnutbio.2009.09.012] [PMID: 20153625]
[17]
Alamro AA, Alsulami EA, Almutlaq M, Alghamedi A, Alokail M, Haq SH. Therapeutic potential of vitamin D and curcumin in an in vitro model of alzheimer disease. J Cent Nerv Syst Dis 2020; 12
[http://dx.doi.org/10.1177/1179573520924311] [PMID: 32528227]
[18]
Arabnezhad L, Mohammadifard M, Rahmani L, Majidi Z, Ferns GA, Bahrami A. Effects of curcumin supplementation on vitamin D levels in women with premenstrual syndrome and dysmenorrhea: A randomized controlled study. BMC Complementary Medicine and Therapies 2022; 22(1): 19.
[http://dx.doi.org/10.1186/s12906-022-03515-2] [PMID: 35065636]
[19]
Wahono C, Setyorini C, Kalim H, Nurdiana N, Handono K. Effect of Curcuma xanthorrhiza supplementation on systemic lupus erythematosus patients with hypovitamin D which were given vitamin D 3 towards disease activity (SLEDAI), IL-6, and TGF- β 1 serum. Int J Rheumatol 2017; 2017: 1-8.
[http://dx.doi.org/10.1155/2017/7687053] [PMID: 29445400]
[20]
Liu W, Zhai Y, Heng X, et al. Oral bioavailability of curcumin: Problems and advancements. J Drug Target 2016; 24(8): 694-702.
[http://dx.doi.org/10.3109/1061186X.2016.1157883] [PMID: 26942997]
[21]
Haq IU, Imran M, Nadeem M, Tufail T, Gondal TA, Mubarak MS. Piperine: A review of its biological effects. Phytother Res 2021; 35(2): 680-700.
[http://dx.doi.org/10.1002/ptr.6855] [PMID: 32929825]
[22]
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas P. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998; 64(4): 353-6.
[http://dx.doi.org/10.1055/s-2006-957450] [PMID: 9619120]
[23]
Wahono CS. Vitamin D and curcumin piperine attenuates disease activity and cytokine levels in systemic lupus erythematosus patients. NCT05430087, 2022.
[24]
Aringer M, Costenbader K, Daikh D, et al. 2019 european league against rheumatism/american college of rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019; 78(9): 1151-9.
[http://dx.doi.org/10.1136/annrheumdis-2018-214819] [PMID: 31383717]
[25]
Uribe AG, Vilá LM, McGwin G Jr, Sanchez ML, Reveille JD, Alarcón GS. The systemic lupus activity measure-revised, the mexican systemic lupus erythematosus disease activity index (SLEDAI), and a modified SLEDAI-2K are adequate instruments to measure disease activity in systemic lupus erythematosus. J Rheumatol 2004; 31(10): 1934-40.
[PMID: 15468356]
[26]
Rifai A, Kalim H, Handono K, Wahono CS. Validity and reliability fatigue severity scale in patients with Systemic Lupus Erythematosus (SLE) in Indonesia. Indonesian Journal of Rheumatology 2016; 8(1)
[27]
Magro R, Saliba C, Camilleri L, Scerri C, Borg AA. Vitamin D supplementation in systemic lupus erythematosus: Relationship to disease activity, fatigue and the interferon signature gene expression. BMC Rheumatol 2021; 5(1): 53.
[http://dx.doi.org/10.1186/s41927-021-00223-1] [PMID: 34857051]
[28]
Pakchotanon R, Lomarat W, Narongroeknawin P, Chaiamnuay S, Asavatanabodee P. Randomized double-blind controlled trial to evaluate efficacy of vitamin d supplementation among patients with systemic lupus erythematosus. J Southeast Asian Med Res 2020; 4(1): 24-32.
[http://dx.doi.org/10.55374/jseamed.v4i1.57]
[29]
Shirzadi M, Karimzadeh H, Karimifar M. The effect of Vitamin D supplementation in disease activity of systemic lupus erythematosus patients with Vitamin D deficiency: A randomized clinical trial. J Res Med Sci 2017; 22(1): 4.
[http://dx.doi.org/10.4103/1735-1995.199089] [PMID: 28400826]
[30]
Xu XY, Meng X, Li S, Gan RY, Li Y, Li HB. Bioactivity, health benefits, and related molecular mechanisms of curcumin: Current progress, challenges, and perspectives. Nutrients 2018; 10(10): 1553.
[http://dx.doi.org/10.3390/nu10101553] [PMID: 30347782]
[31]
Stockton KA, Kandiah DA, Paratz JD, Bennell KL. Fatigue, muscle strength and vitamin D status in women with systemic lupus erythematosus compared with healthy controls. Lupus 2012; 21(3): 271-8.
[http://dx.doi.org/10.1177/0961203311425530] [PMID: 22004972]
[32]
Poster APA. Poster abstract presentation abstracts. Int J Rheum Dis 2023; 26(S1): 89-388.
[http://dx.doi.org/10.1111/1756-185X.14505]
[33]
Lima GL, Paupitz J, Aikawa NE, et al. Vitamin D supplementation in adolescents and young adults with juvenile systemic lupus erythematosus for improvement in disease activity and fatigue scores: A randomized, double-blind, placebo-controlled trial. Arthritis Care Res 2016; 68(1): 91-8.
[http://dx.doi.org/10.1002/acr.22621] [PMID: 25988278]
[34]
Wöbke TK, Sorg BL, Steinhilber D. Vitamin D in inflammatory diseases. Front Physiol 2014; 5: 244.
[PMID: 25071589]
[35]
Peng Y, Ao M, Dong B, et al. Anti-inflammatory effects of curcumin in the inflammatory diseases: Status, limitations and countermeasures. Drug Des Devel Ther 2021; 15: 4503-25.
[http://dx.doi.org/10.2147/DDDT.S327378] [PMID: 34754179]
[36]
Marinho A, Carvalho C, Boleixa D, et al. Vitamin D supplementation effects on FoxP3 expression in T cells and FoxP3+/IL-17A ratio and clinical course in systemic lupus erythematosus patients: a study in a Portuguese cohort. Immunol Res 2017; 65(1): 197-206.
[http://dx.doi.org/10.1007/s12026-016-8829-3] [PMID: 27423437]
[37]
Handono K, Pratama MZ, Endharti AT, Kalim H. Treatment of low doses curcumin could modulate Th17/Treg balance specifically on CD4+ T cell cultures of systemic lupus erythematosus patients. Cent Eur J Immunol 2015; 4(4): 461-9.
[http://dx.doi.org/10.5114/ceji.2015.56970] [PMID: 26862311]
[38]
Kalim H, Handono K, Khalasha T, et al. Immune modulation effects of curcumin in pristane-induced lupus mice. Indian J Rheumatol 2017; 12(2): 86.
[http://dx.doi.org/10.4103/injr.injr_95_16]
[39]
Guimaraes-Stabili MR, de Aquino SG, Curylofo F, et al. Systemic administration of curcumin or piperine enhances the periodontal repair: A preliminary study in rats. Clin Oral Investig 2019; 23(8): 3297-306.
[http://dx.doi.org/10.1007/s00784-018-2755-9] [PMID: 30498979]

Rights & Permissions Print Cite
Article Metrics
Pdf icon 54
Html icon 2
Find your institution