Riboflavin toxicity

Like thiamine, there is no known toxicity associated with ingestion of riboflavin and there is no established UL. At the same time, there is no known benefit to ingesting industrial quantities of riboflavin. 

Including in the medication a biological marker that is non-toxic, inert, chemically stable and easily detectable in biological fluids (such markers include riboflavin, phenol red and small quantities of digoxin). 

Several mechanisms have been postulated to account for thallium s toxicity, including ligand formation with sulfhydryl groups of enzymes and transport proteins, inhibition of cellular respiration, interaction with riboflavin and riboflavin-based cofactors, alteration of the activity of K -dependent proteins, and disruption of intracellular calcium homeostasis. ... 

In foods vitamin B2 occurs free or combined both as FAD and FMN and complexed with proteins. Riboflavin is widely distributed in foodstnffs, but there are very few rich sources. Only yeast and liver contain more than 2mg/100g. Other good sources are milk, the white of eggs, fish roe, kidney, and leafy vegetables. Since riboflavin is continuously excreted in the urine, deficiency is qnite common when dietary intake is insufficient. The symptoms of deficiency are cracked and red lips, inflammation of the lining of the month and tongue, mouth ulcers, cracks at the comer of the mouth, and sore throat. Overdose of oral intake present low toxicity, probably explained by the limited capacity of the intestinal absorption mechanism [417]. 

Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans and, therefore, must must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble (Figure 28.1). Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in Die liver and adipose tissue. In fact, consumption of vitamins A and D in exoess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds. 

Vitamin B2 (riboflavin) has the active forms FAD and FMN. It functions in electron trans fer. A deficiency of riboflavin is rare, but it causes dermatitis and angular stomatitis. There is no known toxicity. 

Lactic acidosis is a severe and potentially fatal form of mitochondrial toxicity. Metabolic stress or vitamin deficiencies (riboflavin, carnitine) might provoke it. There is suggestive evidence of clinical benefit with riboflavin therapy (846). 

Carbohydrate metabolism provides the main energy source in coccidia. Diets deficient in thiamin, riboflavin, or nicotinic acid—all cofactors in carbohydrate metabolism—result in suppression of parasitic infestation of chickens by E tenella and E acervulina. A thiamin analog, amprolium—1-[(4-amino-2-propyl-5-pyrimidinyl)-methyl]-2-picolinium chloride—has long been used as an effective anticoccidial agent in chickens and cattle with relatively low host toxicity. The antiparasitic activity of amprolium is reversible by thiamin and is recognized to involve inhibition of thiamin transport in the parasite. Unfortunately, amprolium has a rather narrow spectrum of antiparasitic activity it has poor activity against toxoplasmosis, a closely related parasitic infection. 

Because of its intense yeUow color and low toxicity, riboflavin is widely used as a food color (E-fOf). It is also used in relatively high doses in the treatment of recessive famUial methemoglobinemia and some organic acidurias. 

Because of its low solubility and limited absorption from the gastrointestinal tract, riboflavin has no significant or measurable toxicity by mouth. At extremely high parenteral doses (300 to 400 mg per kg of body weight), there may be crystallization of riboflavin in the kidney because of its low solubility. 

When amino acids in parenteral solutions are exposed to relatively intense illumination for 24 hours, simulating phototherapy in neonatal nurseries, most individual amino acids decrease only slightly. Decreases in the concentrations of methionine, proline, tryptophan, and tyrosine are significantly greater in the presence of riboflavine. The observed decreases in amino acid concentrations are unlikely to be nutritionally important. However, in view of the possibility that photooxidation products may exert toxic effects, it is best to shield amino acid solutions containing vitamins from strong sources of UV-VIS irradiation (86). 

Two HIV-1-positive women, both of whom had taken regimens containing stavudine and didanosine for at least 2 years, presented in the third trimester of pregnancy, one with acute lactic acidosis and one with acute pancreatitis and lactic acidosis (32). In the first case both mother and baby died. It is not known whether pregnancy is a risk factor for NRTI-induced lactic acidosis, perhaps in combination with riboflavin deficiency or a metabolic defect in the fetus, or whether NRTIs independently cause lactic acidosis through mitochondrial toxicity. 

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