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

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.

Mucosal-Associated Invariant T Cells as a Possible Target to Suppress Secondary Infections at COVID-19

“…A strategy of the oral supplementation with riboflavin may be proposed, given that some bacteria can switch from biosynthesis to uptake of riboflavin when it is environmentally available. It should be noted that riboflavin supplementation (100 mg daily for 3 weeks) in patients with Crohn's disease, a type of inflammatory bowel disease, led to anti-inflammatory effects (20). Activation of innate MAIT cells in inflammatory bowel diseases resulted in a switch in the pattern of cytokine secretion was previously demonstrated (21).…”

Systemic Oxidative Stress, Aging and the Risk of Cardiovascular Events in the General Female Population

“…The results of this study confirm what research has been increasingly showing for the past years; serum free thiols prove to be a reliable biomarker for oxidative stress, a major effector mechanism in many diseases and conditions ( 4 , 8 ). Thiols are particularly interesting for research due to their susceptibility to therapeutic modulation, for example administering antioxidants ( 43 ). For instance, within the context of the present study, extracellular free thiols could theoretically be enhanced by hormone replacement therapy among postmenopausal women.…”

Oxidative stress is associated with suspected non‐alcoholic fatty liver disease and all‐cause mortality in the general population

“…Since systemic free thiols (R‐SH) are considered to be amenable to therapeutic manipulation, it could also become a beneficial treatment target in NAFLD. In this regard, hydrogen sulphide (H 2 S) or precursors like N‐acetylcysteine (NAC) and glutathione as low molecular weight thiol‐containing compounds (and many other antioxidant supplementations) are considered to be potential treatment options to correct an imbalanced redox status in diseases like NAFLD 43,44 . Endogenous production of H 2 S is reduced in the cirrhotic liver, while exogenous H 2 S supplementation prevents NASH in an animal experimental model via abating oxidative stress and suppressing inflammation 45 .…”

“…Endogenous production of H 2 S is reduced in the cirrhotic liver, while exogenous H 2 S supplementation prevents NASH in an animal experimental model via abating oxidative stress and suppressing inflammation 45 . In addition, antioxidant supplementation with riboflavin (vitamin B 2 ) significantly decreased inflammatory markers, while it increased systemic levels of free thiols in patients with Crohn's disease, demonstrating that antioxidant therapy holds promise in diseases which are characterized by overproduction of reactive species 44 …”