Riboflavin

BACKGROUND

Riboflavin is a water-soluble vitamin. The bioactive forms of riboflavin are the oxidised and reduced forms of flavin adenine dinucleotide (FAD and FADH 2 , respectively) and flavin mononucleotide (FMN and FMNH 2 , respectively) (FNB:IOM 1998, McCormick 2000, Thurnham 2000). They function as coenzymes for key reactions in the catabolism of fuel molecules (eg β-oxidation of fatty acids, Krebs cycle), and in certain biosynthetic pathways (eg fatty acid synthesis). Riboflavin and its derivatives are important for the body's handling of some other nutrients including conversion of vitamin B-6 to its bioactive form, pyridoxal phosphate; conversion of tryptophan to niacin and conversion of methylenetet rahydrofolate (MTHF) to methylTHF by the enzyme methyleneTHF reductase (MTHFR).

As methylTHF is essential for the conversion of homocysteine to methionine, riboflavin deficiency can result in raised plasma levels of homocysteine that are associated with increased cardiovascular risk. A cross-sectional study (McNulty et al 2002) suggested that this association is much more likely to occur in individuals with the TT genetic variant of MTHFR (ie homozygous for the C677T polymorphism), which is found in about 12% of humans, than those with the CT or CC variants. Powers (2003) also noted that riboflavin deficiency is often associated with anaemia, which may result from problems in the body's handling of iron.

The metabolism of riboflavin is tightly controlled and depends on the riboflavin status of the individual (Lee & McCormick 1983). Riboflavin is converted to coenzymes mostly in the small intestine, liver, heart and kidney (Brown 1990, Darby 1981). Surplus riboflavin is excreted in urine, either as riboflavin itself (about two-thirds of total excretion) or as a range of metabolites. In deficiency, only small amounts are excreted.

Most of the riboflavin in our foods occurs as the nucleotides FAD/FADH 2 and FMN/FMNH 2 in a complex of food protein (Merrill et al 1981, Nicholalds 1981). This is released as free riboflavin by digestive enzymes in the small intestine and absorbed into the bloodstream. The major sources are milk and milk products and fortified breads and cereals. The bioavailability of riboflavin is high, probably about 95% (Zempleni et al 1996), but our capacity to absorb riboflavin from the small intestine is only moderate. The classic disease of riboflavin deficiency is ariboflavinosis, which manifests in growth disturbances, seborrhaeic dermatitis, inflammation of the oral mucosa and tongue, cracks at the corner of the mouth and normocytic anaemia (Wilson 1983).

A range of indicators has been used to assess riboflavin status. These include clinical assessment of the classic physical symptoms of deficiency indicating severe deficiency, urinary excretion of riboflavin, erythrocyte flavin levels and determination of the erythrocyte glutathione reductase activity coefficient (EGRAC) in which erythrocyte glutathione reductase is assayed in the presence and absence of added FAD to establish an in vitro activity coefficient. This value provides an indirect indicator of cellular FAD levels and, by extrapolation, an indicator of whole body riboflavin status. Unfortunately, different studies have used different reference ranges for EGRAC. All of these methods are reasonably satisfactory indicators (Hustad et al 2002), however erythrocyte flavin has not been widely used.