Interpretation
Low test values for Vitamin B2 are indicative of nutritional deficiency or conditions that diminish absorption.
Vitamin B2 deficiency is usually due to poor dietary intake and often coincides with deficiencies in other vitamins such as B1 (thiamine) and B3 (niacin). [2, 3, 4] Aside from malnutrition, risk factors for vitamin B2 deficiency include: [5]
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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
Vitamin B2 toxicity has not been described. If given a large oral dose, absorption of vitamin B2 by the gastrointestinal tract is limited to less than 30 mg. [6]
Collection and Panels
Collection and panel details are as follows:
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Specimen type and volume: Blood plasma
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Specimen container: Green top (heparin), light protective (amber) vial
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Specimen volume: 0.50 mL (0.25 mL minimum)
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Specimen rejection: Mild hemolysis, lipemia, or icterus is acceptable, reject if gross. Specimen rejected if submitted as serum, in plasma gel tube, or in EDTA.
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Special instructions: Specimen should be drawn after overnight (12-14 hours) fast. If infant, draw before next meal.
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Specimen storage/transport conditions:
Must be in light protective container
Can be refrigerated for up to 7 days, frozen for up to 14 days
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Test method: Liquid chromatography-tandem mass spectrometry
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Related tests: Erythrocyte glutathione reductase activity assay, expressed using a ratio of tests performed with and without added flavin adenine dinucleotide. A ratio greater than or equal to 1.3 is indicative of functional vitamin B2 deficiency, while a ratio of less than 1.3 indicates adequate levels. [7]
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, as well as several other pathways in the metabolism of carbohydrates, fats, and proteins. [8] 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. [9]
Vitamin B2 must be obtained from the diet, with notable sources including meat, dairy products, green vegetables, and fortified breads and cereals. [3] It also has a characteristically yellow color, which has prompted its popular use as a food coloring additive. [8] 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 as well as 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 riskofdeficiencyinthemother during pregnancy and lactation. [5]
Recommended Dietary Allowance (RDA) of vitamin B2 for adult males is 1.3 mg, and 1.1 mg for adult females. The recommendation increases during pregnancy and lactation to 1.4 mg and 1.6 mg, respectively. [10, 11]
Indications/Applications
It would be unusual for a physician to order an assessment of vitamin B2 levels as a stand-alone test due to the fact that low levels would most likely be found in a setting of multiple other vitamin defiencies (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:
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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 [12]
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Night blindness [12]
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Cataracts [12]
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Peripheral neuropathy [12]
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Fatigue [12]
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Esophageal and/or cervical dysplasia [12]
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Retarded growth in infants and children [5]
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Birth defect (eg, cleft lip/palate, congenital heart defects) [12]
The impairment of vitamin B2 metabolism in association with mutations in the genes SLC52A2 and AIMF1 has been linked to auditory neuropathy spectrum disorder (ANSD). Consequently, James et al suggested that ANSD in neonates may also result from other causes of vitamin B2 deficiency, proposing that the association found between hyperbilirubinemia and ANSD may be related to vitamin B2 depletion by bilirubin metabolism and by phototherapy for hyperbilirubinemia. [14]
