Reference Range
Vitamin B2, or riboflavin, is a water-soluble vitamin most commonly found in the body in the form of the flavocoenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), the latter being most abundant.
Reference ranges are as follows:
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Serum or plasma: 4-24 µg/dL or 106-638 nmol/L
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Urine: >80 µg/dL or >213 nmol/dL
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Erythrocyte: 10-50 µg/dL or 266-1330 nmol/dL [1]
Interpretation
Low test values of vitamin B2 indicate nutritional deficiency or conditions that diminish absorption. Vitamin B2 deficiency usually results from poor dietary intake and often coincides with deficiencies in other vitamins, such as B1 (thiamine) and B3 (niacin). [2, 3] Aside from malnutrition, risk factors for vitamin B2 deficiency include the following [4] :
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Malabsorptive states (eg, celiac disease, small bowel resection, tropical sprue, inflammatory bowel disease)
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Pregnancy and lactation (secreted in milk)
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Inborn errors of riboflavin metabolism
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Anorexia nervosa [5]
Vitamin B2 toxicity has not been described. Upon administration of a large oral dose, absorption of vitamin B2 by the gastrointestinal tract is limited to less than 30 mg. [6]
Collection and Panels
Specimen type and volume: Blood plasma [7]
Specimen container: Green top (heparin), light protective (amber) vial
Specimen volume: 0.50 mL (0.25 mL minimum)
Specimen rejection: Mild hemolysis, lipemia, or icterus is acceptable; reject if gross. Specimen rejected if it is submitted as serum, in a plasma gel tube, or in EDTA.
Special instructions: Specimen should be drawn after overnight (12- to 14-hour) fast. If infant, draw before next meal.
Specimen storage/transport conditions are as follows:
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Must be in light-protective container
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Can be refrigerated for up to 7 days, frozen for up to 14 days
Test method: Liquid chromatography-tandem mass spectrometry
Related tests: Erythrocyte glutathione reductase activity assay, expressed as a ratio of results with and without added flavin adenine dinucleotide. A ratio of 1.3 or more indicates functional vitamin B2 deficiency, while a ratio of less than 1.3 indicates adequate levels. [8]
Urinary riboflavin: Urinary riboflavin can be measured using high-performance liquid chromatography (HPLC) with fluorometry or competitive protein-binding assays. Rapid and sensitive, the protein-binding assays can be used without first treating the urine sample. In HPLC with fluorometry, riboflavin is separated from the other flavins, so this technique tends to produce lower results than does the older fluorometric method alone. [9]
Background
Description
Vitamin B2, or riboflavin, is a water-soluble vitamin most commonly found in the body in the form of the flavocoenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), the latter being most abundant.
These coenzymes play a necessary role in most of the major energy-producing biochemical processes in the body, acting as electron carriers for enzymes in oxidation-reduction reactions. Such dependant enzymes include those of the citric acid cycle, the mitochondrial electron transport chain, and several other pathways in the metabolism of carbohydrates, fats, and proteins. [10] FAD is also a coenzyme needed for the functioning of the antioxidant enzyme glutathione reductase in its protection of cells against oxidative stresses, allowing for the measurement of the enzyme’s activity in red blood cells to be among the methods for the assessment of riboflavin nutritional status. [11]
Vitamin B2 must be obtained from the diet, with notable sources including meat, dairy products, green vegetables, and fortified breads and cereals. [3] It has a characteristically yellow color, which has also prompted its popular use as a food-coloring additive. [10]
It is mostly absorbed in the jejunum [3] through a transport system that becomes saturated beyond the absorption of approximately 30 mg after one oral dose. [6] Once absorbed, most circulating vitamin B2 is weakly bound to albumin, with the remaining largely bound to immunoglobulins.
Entry of the vitamin into cells is mainly facilitated by carrier-mediated transport through a specific riboflavin-binding protein on cell membranes. Passive transport at high concentrations and receptor-mediated transport systems have also been reported. Only small amounts of the vitamin are stored by the body (liver), and it is primarily excreted through the urine. It is also secreted into the milk, therefore increasing the risk of deficiency in the mother during pregnancy and lactation. [4]
The recommended dietary allowance (RDA) of vitamin B2 is 1.3 mg in men and 1.1 mg in women. The recommendation increases during pregnancy and lactation to 1.4 mg and 1.6 mg, respectively. [12]
Indications/Applications
Stand-alone vitamin B2 assessment is unusual since low levels would most likely be found in a setting of multiple other vitamin deficiencies (eg, a known clinical setting of alcoholism or malabsorption). Therefore, it would likely be ordered as one of several tests to assess general nutritional status. Signs and symptoms of potential deficiency (ariboflavinosis), many of which can also occur in frequently coinciding vitamin deficiencies, include the following:
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Cheilosis (cracking and inflammation of lips) [3]
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Angular stomatitis (cracking and inflammation of the angles of the mouth) [3]
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Glossitis (swollen, deep-red tongue) [3]
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Seborrheic dermatitis (greasy, scaled lesions most commonly on the face and scalp) [3]
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Interstitial keratitis with potential opacification and ulceration of the cornea [3]
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Corneal neovascularization [13]
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Night blindness [13]
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Cataracts [13]
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Normocytic normochromic anemia [4]
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Peripheral neuropathy [13]
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Fatigue [13]
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Esophageal and/or cervical dysplasia [13]
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Retarded growth in infants and children [4]
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Birth defect (eg, cleft lip/palate, congenital heart defects) [13]
Evidence indicates that riboflavin can act as a therapeutic agent in the following disorders:
