It is a water-soluble, yellow pigment with green flourescence which is widely distributed in foods of both plant and animal origin. While relatively stable to heat, it is destroyed on exposure to light, hence consider-able loss can occur in some foods such as milk. The minimal daily requirement appears to be about 0.6-0.7 mg. in the adult, 0.4-0.5 mg. in the infant. The recommended intake is considerably higher than this, 1.4 to 1.6 mg. for the adult (Table 3), in order to supply adequate tissue reserves. Flavoproteins function in a number of important enzyme systems in tissue respiration.
There is a close relationship between the retention of riboflavin and the retention of protein. It seems likely, therefore, that abnormalities of riboflavin metabolism may be associated with severe injuries, burns, hemorrhage and infection. Riboflavin deficiency often occurs in association with lack of niacin and signs of an inadequate supply of riboflavin have been confused with those of pellagra.
Manifestations of riboflavin deficiency have been observed in prolonged febrile illnesses, such as rheumatic fever, tuberculosis and sub-acute bacterial endocarditis, in malignancy, hyperthyroidism, cardiac failure, diabetes mellitus and diseases of the gastrointestinal tract. Deficiency occurs with greater frequency in older than in younger age groups.
Symptoms of riboflavin deficiency are photophobia, burning of the eyes, lacrimation, soreness of the lips and tongue and cracks at the corners of the mouth. Charactertistic physical findings are cheilosis, angular stomatitus, glossitis, a seborrheic type of dermatitis and superficial vascularization of the cornea (91). The lips may be swollen, red at the line of closure and denuded; maceration, crusts and fissures are present at the angles of the mouth. Common sites of seborrheic dermatitis are the nasolabial and nasomalar folds, the outer canthi of the eyes and the ears. Scrotal dermatitis was a frequent finding in experimentally induced riboflavin deficiency (92). The tongue may be magenta in color, with papillary atrophy or hypertrophy, and fissures may be present. None of these lesions is pathognomonic of riboflavin deficiency although all of them have been induced in human subjects receiving diets inadequate in riboflavin. Cheilosis and angular stomatitis have been observed in experimental niacin deficiency and following the administration of desoxypyridoxine (93). Lesions of the lips may be the result of exposure to weather, while angular fissures occur in association with malocclusion and poorly fitting dentures. Vascularization of the cornea may be due to trauma or infection and seborrheic dermatitis may be related to lack of vitamin B0 or be unassociated with malnutrition.
Glossitis is common in deficiency of many of the B-complex vitamins.
In animals, the ability of the liver to inactivate estradiol is reduced in riboflavin deficiency. It has been suggested that a similar change may occur in man. In animals, also, riboflavin deficiency during pregnancy has resulted in abortion and in abnormalities of the embryo. The relationship of riboflavin deficiency to congenital defects in man remains unknown.
Diagnosis of riboflavin deficiency is dependent on a history of low dietary intake, the presence of several of the lesions mentioned above and, at times, association with some disease which influences riboflavin metabolism. Laboratory studies may be of assistance in diagnosis. The concentrations of free riboflavin and flavin mononucleotide in plasma have been found to decrease in many, but not in all, subjects when the intake of riboflavin is restricted, while plasma flavin dinucleotide and total white blood cell riboflavin show little change. The concentration of riboflavin in red blood cells decreases significantly during periods of restricted intake. Bessey has suggested that “red blood cell contrations below 14 ,ug/100 ml. can be interpreted as meaning a level of intake that, if continued,_ will lead to clinical manifestations of deficiency.” Concentrations above 20 ug/100 ml. indicate an adequate riboflavin intake. While analysis of riboflavin in plasma is useful in determining nutritional status, it may be that determination of riboflavin in erythrocytes will prove to be a better measure of tissue stores. The latter test requires further study.
Measurement of the urinary excretion of riboflavin is of limited value in assessment of nutritional status (17). An excretion of more than 200 ug of riboflavin in 24 hours is seldom associated with significant tissue depletion, and an excretion of more than 150 µg per gram of creatinine in a random specimen of urine is usually indicative of tissue saturation . However, excretions of this order of magnitude do not necessarily indicate normalcy. The output of riboflavin is increased in acute but not in chronic starvation, in diabetes mellitus, in conditions in which nitrogen balance is negative and after the administration of certain antibiotics. Physical activity also influences excretion.
In subjects receiving constant diets, excretion following small test doses (less than 2 mg.) has been found to reflect dietary intake. Estimation of excretion for four hours following parenteral administration of 1.0 mg. of riboflavin is a procedure which seems to merit further study in the evaluation of riboflavin nutrition.
A controlled therapeutic test is valuable in corroborating the diagnosis of riboflavin deficiency; lesions due to an inadequate supply of riboflavin heal rapidly when the vitamin is administered.