Riboflavin for women's health and emerging microbiome strategies

Abstract

Riboflavin (vitamin B2) is an essential water-soluble vitamin that serves as a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). FMN and FAD are coenzymes involved in key enzymatic reactions in energy metabolism, biosynthesis, detoxification and electron scavenging pathways. Riboflavin deficiency is prevalent worldwide and impacts women's health due to riboflavin demands linked to urogenital and reproductive health, hormonal fluctuations during the menstrual cycle, pregnancy, and breastfeeding. Innovative functional foods and nutraceuticals are increasingly developed to meet women's riboflavin needs to supplement dietary sources. An emerging and particularly promising strategy is the administration of riboflavin-producing lactic acid bacteria, combining the health benefits of riboflavin with those of probiotics and in situ riboflavin production. Specific taxa of lactobacilli are of particular interest for women, because of the crucial role of Lactobacillus species in the vagina and the documented health effects of other Lactobacillaceae taxa in the gut and on the skin. In this narrative review, we synthesize the underlying molecular mechanisms and clinical benefits of riboflavin intake for women's health, and evaluate the synergistic potential of riboflavin-producing lactobacilli and other microbiota.

Fig. 1. Impact of riboflavin deficiency on various aspects of women’s health.

The different body sites where riboflavin is crucial are indicated. The evidence is categorized based on the available documentation on associations between (1) riboflavin deficiency and specific health problems, (2) riboflavin supplementation and how it improves specific health outcomes and (3) how normal riboflavin levels support and maintain physiological processes. EFSA-approved health claims are indicated in bold. This figure was created with Biorender.com and based on the following key refs. ^{–,,,,,,,,,,}.

Fig. 2. Riboflavin mechanisms of action with a focus on women’s health (overview).

On the left part of the figure, a female’s life trajectory is depicted according to five different stages based on associated estrogen levels. Riboflavin’s interference in these life stages is indicated, and the involved modes of action of riboflavin (right) are highlighted via colored dots. Starred items are strongly influenced by the female hormonal cycle. Mechanisms affecting each other/acting together are connected with gray arrows. FMN flavin mononucleotide, FAD flavin adenine dinucleotide, IL interleukin, IFN-γ interferon gamma, NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells, NO nitric oxide, TNFα tumor necrosis factor alpha, COX2 cyclooxygenase 2, ROS reactive oxygen species, RfBP riboflavin binding protein, RFT riboflavin transporter, FSH follicle stimulating hormone, LH luteinizing hormone. This figure was created with Biorender.com and based on the following key refs. ^{,,–,–,,,,,,,,,,}.

Fig. 3. The postulated synergistic effects of riboflavin-producing microbiota members such as probiotic lactobacilli and riboflavin.

The beneficial properties consist of riboflavin-mediated effects (as previously described in Fig. 2), probiotic and microbiome-promoting effects such as modulation of immune responses, microbe-microbe interactions and enhancement of the epithelial barrier function and effects mediated by unstable riboflavin intermediates/derivatives leading to MR1-dependent activation of Mucosal Associated Invariant T cells (MR1 = Major Histocompatibility complex class 1 related protein). This figure was created with Biorender.com.