Methyl-donor Nutrient Supplementation and Methylation Profile in Lupus Patients With Obesity

Official title

Effect of Methyl-donor Nutrient Supplementation on Methylation Profile of Inflammatory-related Genes in Lupus Patients With Obesity: a Clinical Trial

Overview

Dietary supplementation with methyl donors has been demonstrated to increase DNA methylation in leucocytes whereas a limited dietary intake of methyl donors was associated with DNA hypomethylation. Considering SLE disease, previously study showed that high doses of vitamin B6 and folate were associated with less severe SLE. Furthermore, some evidences reported a relatively high incidence of decreased serum B12 levels in rheumatic patients. This led to the suggestion that diets rich in methyl group donors could have beneficial effects on SLE.

Interventions

• Dietary supplement Vitamin B12 + folic acid supplementation
  A 12 weeks parallel-group randomised controlled trial will be performed, in which erythematous lupus patients will complete a vitamin B12 and folic acid supplementation, in addition to the usual therapy. The dietary supplementation will be by capsules, which will content 400 mcg of folic acid and 2000 mcg of vitamin B12 each.
• Dietary supplement Placebo supplementation
  A 12 weeks parallel-group randomised controlled trial will be performed, in which erythematous lupus patients will complete a placebo supplementation.The placebo and vitamin B12 + folic acid supplement will be indistinguishable in terms of taste, smell, and appearance.

Primary outcome measures

• Change from baseline on DNA methylation profile at 12 weeks [Time frame: Baseline and 12 weeks]
• Change from baseline on weight at 12 weeks [Time frame: Baseline and 12 weeks]
• Change from baseline on serum vitamin B12 concentrations at 12 weeks [Time frame: Baseline and 12 weeks]
• Change from baseline on serum folic acid concentrations at 12 weeks [Time frame: Baseline and 12 weeks]

Secondary outcome measures (12)

• Age of onset [Time frame: Baseline]
• Duration of disease since diagnosis [Time frame: Baseline]
• Change from baseline on miR-146 expression at 12 weeks [Time frame: Baseline and 12 weeks]
• Change from baseline on miR-181 expression at 12 weeks [Time frame: Baseline and 12 weeks]
• Change from baseline on miR-21 expression at 12 weeks [Time frame: Baseline and 12 weeks]
• Change from baseline on miR-126 expression at 12 weeks [Time frame: Baseline and 12 weeks]
• Change from baseline on TNF-a gene expression at 12 weeks [Time frame: Baseline and 12 weeks]
• Change from baseline on LEP gene expression at 12 weeks [Time frame: Baseline and 12 weeks]
• Change from baseline on ADIPOQ gene expression at 12 weeks [Time frame: Baseline and 12 weeks]
• Change from baseline on MTHFR gene expression at 12 weeks [Time frame: Baseline and 12 weeks]
• Change from baseline on STAT3 gene expression at 12 weeks [Time frame: Baseline and 12 weeks]
• Change from baseline on IL-6 gene expression at 12 weeks [Time frame: Baseline and 12 weeks]

Eligibility criteria

Inclusion criteria

• SLE diagnosis
• Female
• In pre-menopausal period
• Aged between 18 to 45 years
• Patients that meet the classification criteria according to Systemic Lupus International Collaborating Clinics classification criteria (SLICC)
• Patients with SLEDAI score ≤ 4 on Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
• Under prednisone treatment at a dosage <10 mg/day
• Under treatment with chloroquine at a stable dose
• BMI > 18,5 kg/m2

Exclusion criteria

• Current infection
• Diabetes
• Arterial hypertension
• Smokers
• Pregnancy
• Anticoagulants use
• Methotrexate use
• Other autoimmune diseases
• Current vitamin B12 or/and folic acid supplementation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Basic science

Study locations

Brazil · 1 center

• Univsersity of Sao Paulo — São Paulo

Publications

• Carvalho LM, da Mota JCNL, Ribeiro AA, Souza LL, Sposeto RB, Pinhel MAS, Nonino CB, Costa-Fraga N, Crujeiras AB, Izquierdo AG, Diaz-Lagares A, Hounkpe BW, Borba EF, Gualano B, Nicoletti CF. Epigenetic and metabolic signatures in systemic lupus erythematous: The impact of excess body weight on adipose tissue DNA methylation profile. Genomics. 2026 Mar;118(2):111217. doi: 10.1016/j.ygeno.2026.111217 PMID 41666998
• da Mota JCNL, Carvalho LM, Souza LL, Ribeiro AA, Pinhel MAS, Nonino CB, Godoy AL, Borba EF, Hounkpe BW, Gualano B, Nicoletti CF. Nutritional status-dependent DNA methylation modifications on adipose tissue in systemic lupus erythematosus women following folic acid and vitamin B12 supplementation: a randomized double-blind placebo-controlled trial. Clin Epigenetics. 2026 Jan 3;18(1):21. doi: 10.118 PMID 41484640
• da Mota JCNL, Carvalho LM, Ribeiro AA, Souza LL, Borba EF, Roschel H, Gualano B, Nicoletti CF. Methyl-donor supplementation in women with systemic lupus erythematosus with different nutritional status: the protocol for a randomised, double-blind, placebo-controlled trial. Lupus Sci Med. 2024 Oct 7;11(2):e001279. doi: 10.1136/lupus-2024-001279. PMID 39375179

Identifiers

NCT: NCT05097365 · SLE and DNA methylation

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗