Vitamin B2, or riboflavin, is an essential nutrient and plays a key role in energy production.1
Free riboflavin is found in milk, beef liver, and in enriched breads and cereals. In most foods, riboflavin occurs as one of its coenzyme derivatives, flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD). FMN is metabolized in the body to form FAD.
Most dietary riboflavin is efficiently absorbed by a saturable carrier mechanism primarily in the proximal small intestine. A small amount of FAD is unavailable for absorption as it is covalently bound to certain tissue enzymes.1,2
A small amount of riboflavin is lost during heating; in alkaline solution more riboflavin is destroyed during cooking than in acidic solution. Riboflavin is easily destroyed by light. Foods rich in riboflavin should be stored in opaque containers and foods should be covered when cooking.
FAD and FMN act as intermediate hydrogen acceptors in the mitochondrial electron transport chain and pass on electrons to the cytochrome system in cellular respiration.1
Riboflavin has antioxidant activity which is derived from its role as a precursor to FAD and as a cofactor in the production of glutathione. Riboflavin deficiency increases lipid peroxidation and decreases the regeneration of reduced glutathione, which is necessary for the function of the antioxidant glutathione peroxidases.1
The most common signs of riboflavin deficiency are pallor and cracking of the mucosa at the corners of the mouth and surfaces of the lips, followed by linear fissures. Lesions may become infected and the tongue may have a magenta hue. Areas of the body including the nasolabial folds, alae nasi, ears, eyelids, scrotum, and labia major may become red, scaly, and greasy. Sebaceous material accumulates in the hair follicles which produces dyssebacea or shark skin.1
Riboflavin deficiency may cause neovascularization of the cornea and epithelial kerititis that can result in tearing and photophobia.1
Urinary excretion of more than 30 mcg of riboflavin/g creatinine is associated with clinical signs of riboflavin deficiency.
Increased activation of red blood cell glutathione reductase by riboflavin is an early sign of riboflavin deficiency.
No danger of toxicity appears to be associated with large doses of oral riboflavin. Riboflavin is readily excreted in the urine and absorption by the digestive tract may be less than 20 mg for one dose.1
Riboflavin sources include beef, liver, lean meat, kidney, non-fat milk, oysters. Other good sources include dark green leafy vegetables, mushrooms, asparagus, broccoli, salmon, and enriched cereal products.
Primary riboflavin deficiency is associated with inadequate milk, egg, and animal protein consumption.
One study found that 10% of omnivores and vegetarians had low riboflavin levels. However, 30% of vegans were riboflavin deficient. These results indicate that vegans are at an increased risk for riboflavin deficiency. 3
Deficiency frequently occurs in people with chronic diarrhea, alcoholism, or liver disease. Lack of supplemental nutrients in post-operative nutrient infusions also increases the risk of riboflavin deficiency.
Consumption of propantheline bromide (Pro-Banthine), a proton pump inhibitor (PPI) for ulcers, causes a delay in the rate of absorption of riboflavin but the total amount of absorption is increased due to an increased residence time of riboflavin at gastrointestinal (GI) absorption sites. It is advisable to take riboflavin 1 to 2 hours before or 3 to 4 hours after drug administration.
Riboflavin and all other B vitamins interfere with absorption of the antibiotic tetracycline. Doses of tetracycline and riboflavin or B vitamin supplements should be seperated by at least 2 hours.
Tricyclic antidepressants including imipramine, desimpramine, amitriptyline, and nortriptyline reduce circulating amounts of riboflavin. Riboflavin supplements or increasing dietary riboflavin can increase circulating riboflavin and may even improve the efficacy of the drug.
Phenothiazines, antipsychotic drugs, may reduce circulating amounts of riboflavin. Supplemental riboflavin can correct any deficiency.
Methotrexate is used to treat certain cancers and rheumatoid arthritis. This drug can prevent the body from using riboflavin.
Probenecid is a drug used to treat gout. Probenecid can prevent absorption of riboflavin and may also increase excretion of riboflavin.
Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature. In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship.
Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM).
A randomized, placebo-controlled, double-blind trial investigated the effects of vitamin B2 supplements on hematologic status. One-hundred-nineteen women aged 19 to 25 years who had evidence of riboflavin deficiency completed the eight week study. Evidence of vitamin B2 deficiency was erythrocyte glutathione reductase activation coefficient greater than 1.40. Participants were randomly assigned to receive 2 mg vitamin B2 daily, 4 mg vitamin B2 daily, or a placebo daily. As expected, eight weeks of riboflavin supplement improved vitamin B2 status in a dose response relationship (P<0.0001). Improvement in hemoglobin status was found for those assigned to supplemental vitamin B2; increase in hemoglobin status correlated with increased riboflavin status (P<0.02). Compared to the first and second tertiles of riboflavin status, women in the lowest tertile (EGRAC>1.65) had a significantly greater increase in hemoglobin status (P<0.01). The results of this study suggest that improvement of riboflavin status positively affects iron status for women initially biochemically riboflavin deficient. Larger studies to evaluate this relationship will be useful to understand the mechanisms of iron and riboflavin balance.7
A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial.
A trial investigated the effect of two riboflavin-containing treatments on migraine incidence. Forty-nine participants completed the three month trial. Subjects were randomized to receive either a so-called placebo containing 25 mg riboflavin or a supplement containing 400 mg riboflavin, 300 mg magnesium, and 100 mg feverfew. No difference between groups was detected for migraine incidence, migraine days, or migraine severity. Compared with baseline, both treatment groups demonstrated significant reductions in number of migraines, migraine days, and migraine index. These results suggest that a supplement of 25 mg riboflavin is sufficient to improve migraine symptoms.8
High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre.
An open label study investigated the efficacy of riboflavin for migraine prevention. Subjects consumed 400 mg riboflavin daily during the six month trial. After six months, headache frequency was significantly reduced from 4 days/month to 2 days/month (P<0.05). The use of abortive drugs was also significantly reduced (P<0.05). Headache hours and intensity did not change during the trial. The results of this trial indicate that 400 mg riboflavin daily significantly improved migraine frequency and the necessity of drugs for treatment.9
A recent study investigated riboflavin levels and the effect of short-term supplementation on people with acute ischemic stroke. Ninety-six people presenting with acute ischemic stroke participated in the study. Riboflavin status was measured at baseline, after 7 days, and after 14 days. Participants were randomized to receive 5 mg riboflavin plus other B vitamins daily for 14 days or a placebo. The first dose of riboflavin plus B vitamins or placebo was given within 12 hours of the stroke onset. At baseline, 51% of participants were riboflavin deficient. Riboflavin supplements significantly improved riboflavin status. After supplementation, 19% of the riboflavin plus B vitamin group participants remained riboflavin deficient; in the placebo group, 56% of participants were riboflavin deficient at the end of the trial (P=0.035 for the differences in cumulative changes between groups). These results suggest that improving riboflavin status may be beneficial for those at risk for stroke.10
Riboflavin supplementation and biomarkers of cardiovascular disease in the elderly.
A randomized, double-blind, placebo-controlled trial investigated the effects of riboflavin supplements on cardiovascular disease markers in elderly people in Portugal. Forty-two men and women participated in the trial (aged 60 to 94 years, 66.7% female). Participants had erythrocyte glutathione reductase activation coefficients (EGRAC) of at least 1.2. Participants were randomly assigned to 10 mg vitamin B2 or a placebo once daily for 28 days. Riboflavin supplements were associated with significant decreases in EGRAC (P=0.014). Plasma total homocysteine was also decreased in the riboflavin supplemented group (P=0.005). Plasma ferritin, uric acid, and C-reactive protein were not altered in either group. The results of this small study indicate that riboflavin supplements can reduce certain biomarkers for cardiovascular disease. Further studies are needed to determine whether these results can be achieved in other populations.11
Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort.
Relationships between plasma total homocysteine and other parameters were evaluated using the Framingham Offspring Study participants, an observational, population-based study. The Framingham Offspring Study includes 1,960 men and women aged 28 to 82 years during the fifth examination cycle (1991 to 1994). Total plasma homocysteine was found to be 11% higher in men than in women (P<0.001). Total plasma homocysteine was positively associated with alcohol intake (P for trend=0.004), caffeine intake (P for trend <0.001), serum creatinine (P for trend <0.001), number of cigarettes smoked (P for trend <0.001), and antihypertensive medication use (P<0.001). Total plasma homocysteine was also found to be 23% higher in people over the age of 65 years than those less than 45 years (P<0.001). Total homocysteine was associated with plasma folate, vitamin B12, and pyridoxal phosphate (P for trend <0.001); dietary folate, vitamin B6, and riboflavin were associated with total homocysteine for people not taking supplements (P for trend <0.01). People who used vitamin B supplements had 18% lower total plasma homocysteine concentrations than those who did not (P<0.001). These results suggest that additional factors, beyond those already known, influence total plasma homocysteine concentrations.12
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