Riboflavin Supplementation in Patients with Crohn's Disease [the RISE-UP study]

J Crohns Colitis. 2020 Jun 19;14(5):595-607. doi: 10.1093/ecco-jcc/jjz208.

Abstract

Background and aims: Crohn's disease [CD] is characterised by chronic intestinal inflammation and dysbiosis in the gut. Riboflavin [vitamin B2] has anti-inflammatory, antioxidant and microbiome-modulatory properties. Here, we analysed the effect of riboflavin on oxidative stress, markers of inflammation, clinical symptoms, and faecal microbiome in patients with CD.

Methods: In this prospective clinical intervention study, patients received 100 mg riboflavin [DSM, Nutritional Products Ltd] daily for 3 weeks. Clinical disease activity [Harvey-Bradshaw Index: HBI], serum biomarkers of inflammation and redox status [plasma free thiols], and faecal microbiome taxonomical composition and functionality [fluorescent in situ hybridisation: FISH; and metagenomic shotgun sequencing: MGS], were analysed before and after riboflavin intervention.

Results: In total, 70 patients with CD with varying disease activity were included. Riboflavin supplementation significantly decreased serum levels of inflammatory markers. In patients with low faecal calprotectin [FC] levels, IL-2 decreased, and in patients with high FC levels, C-reactive protein [CRP] was reduced and free thiols significantly increased after supplementation. Moreover, HBI was significantly decreased by riboflavin supplementation. Riboflavin supplementation led to decreased Enterobacteriaceae in patients with low FC levels as determined by FISH; however, MGS analysis showed no effects on diversity, taxonomy, or metabolic pathways of the faecal microbiome.

Conclusions: Three weeks of riboflavin supplementation resulted in a reduction in systemic oxidative stress, mixed anti-inflammatory effects, and a reduction in clinical symptoms [HBI]. FISH analysis showed decreased Enterobacteriaceae in patients with CD with low FC levels, though this was not observed in MGS analysis. Our data demonstrate that riboflavin supplementation has a number of anti-inflammatory and anti-oxidant effects in CD.

Keywords: Crohn’s disease; clinical intervention study; riboflavin [vitamin B2].

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Biomarkers / blood
  • Blood Sedimentation
  • C-Reactive Protein / metabolism
  • Crohn Disease / blood
  • Crohn Disease / drug therapy*
  • Dietary Supplements
  • Enterobacteriaceae / isolation & purification
  • Fatty Acids, Volatile / analysis
  • Feces / chemistry
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Humans
  • Interleukin-2 / blood
  • Leukocyte L1 Antigen Complex / analysis
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects*
  • Platelet Count
  • Prospective Studies
  • Quality of Life
  • Riboflavin / pharmacology
  • Riboflavin / therapeutic use*
  • Severity of Illness Index
  • Sulfhydryl Compounds / blood
  • Vitamin B Complex / pharmacology
  • Vitamin B Complex / therapeutic use*

Substances

  • Biomarkers
  • Fatty Acids, Volatile
  • IL2 protein, human
  • Interleukin-2
  • Leukocyte L1 Antigen Complex
  • Sulfhydryl Compounds
  • Vitamin B Complex
  • C-Reactive Protein
  • Riboflavin