Riboflavin: The Health Benefits of a Forgotten Natural Vitamin

Abstract

Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties. Moreover, the combination of RF and other compounds or drugs can have a wide variety of effects and protective properties, and diminish the toxic effect of drugs in several treatments. Research has been done in order to review the latest findings about the link between RF and different clinical aberrations. Since further studies have been published in this field, it is appropriate to consider a re-evaluation of the importance of RF in terms of its beneficial properties.

Keywords: cancer; complementary medicine; functional food; muscular degeneration; neurodegeneration; oxidative stress; riboflavin; vitamin B2.

Figure 1

Structure of (a) Riboflavin (RF), (b) Flavin monophosphate (FMN), and (c) Flavin adenine dinucleotide (FAD). ChemDraw (PerkinElmer Informatics, Inc. MA, USA).

Figure 2

RF is an essential vitamin for multiple physiological aspects in the body.

Figure 3

Flavin adenine dinucleotide (FAD) activates the glutathione reductase (GR) by transferring hydrogen for conversion of glutathione disulfide (GSSG) to glutathione (GSH).

Figure 4

RF is converted by RFK into FMN and FAD, which is essential cofactor the phagocytic NADPH oxidase 2 (Nox2) to generate ROS. Therefore, RF deficiency is incapable of ROS production by the phagocyte Nox2, which is crucial to inactivate phagocytosed microbes and to regulate the inflammatory response in innate immune cells. TNF, tumor necrosis factor; TNFR1, tumor necrosis factor receptor 1.

Figure 5

Activation of NADPH oxidase and microbicidal systems during phagocytosis. Complement and antibody receptors (CRs and FcRs) promote the uptake of micro-organisms by neutrophils, which, in turn, trigger the degranulation and production of ROS.

Figure 6

Role of RF as an adjuvant in cisplatin based chemo radiotherapy [75]. RF stimulates apoptotic factors and downregulates anti-apoptotic factors. Additionally, it activates p53, which also results in an amplification of apoptosis. The inhibitory effects of RF in respect to the deteriorate effect of cisplatin are also shown. On the one hand, it inhibits the downregulation of antioxidant enzymes and proteins; on the other, RF downregulates pro-inflammatory cytokines.

Figure 7

Implications of RF deficiency on health [75].

Figure 8

Conversion oxidized glutathione (GSSG) to the reduced form (GSH) by glutathione reductase requires RF in the FAD co-enzyme form for its activity. G-6P-D, glucose-6-phosphate dehydrogenase [98].

Figure 9

RF in functional food and encapsulation products.