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Vitamin B2 Riboflavin

Vitamin B-2 Vitamin
Alternative names

Deficiency - vitamin B-2 (riboflavin); Vitamin B-2 (riboflavin) deficiency; Diet - riboflavin; Vitamin B-2
Definition

Riboflavin is a water-soluble vitamin in the B-complex group.

Function

Riboflavin (vitamin B-2) works with the other B vitamins. It is important for body growth and red blood cell production and helps in releasing energy from carbohydrates.

Food Sources

Lean meats, eggs, legumes, nuts, green leafy vegetables, dairy products, and milk provide riboflavin in the diet. Breads and cereals are often fortified with riboflavin.

Because riboflavin is destroyed by exposure to light, foods with riboflavin should not be stored in glass containers that are exposed to light.

Side Effects

Deficiency of riboflavin is not common in the U.S. because this vitamin is plentiful in the food supply. Significant deficiency syndromes are characterized by sore throat, swelling of mucous membranes, mouth and/or lip sores, anemia, and skin disorders.

There is no known toxicity to riboflavin. Because riboflavin is a water-soluble vitamin, excess amounts are easily excreted by the body in the urine.

Recommendations

Recommended daily allowances (RDAs) are defined as the levels of intake of essential nutrients that the Food and Nutrition Board judges to be adequate to meet the known nutrient needs of almost all healthy people.

The best way to get the daily requirement of essential vitamins is to eat a balanced diet that contains a variety of foods from the food guide pyramid.

Specific recommendations for each nutrient depend on age, gender, and other factors (such as pregnancy). The U.S. Department of Agriculture has a PDF file that lists these recommendations.

Background

Riboflavin is a water-soluble vitamin which is involved in vital metabolic processes in the body, and is necessary for normal cell function, growth, and energy production. Small amounts of riboflavin are present in most animal and plant tissues.

Healthy individuals who eat a balanced diet rarely need riboflavin supplements. Especially good dietary sources of riboflavin are milk (and other dairy products), eggs, enriched cereals/grains, meats, liver, and green vegetables (such as asparagus or broccoli). Intake may be lower in vegetarians compared to non-vegetarians (1).

Riboflavin is often used as a tracer of medication compliance in the treatment of patients with alcohol dependence, mental disorders, and other conditions. Urinary riboflavin levels may be measured in order to determine level of compliance (2;3;4;5;6;7;8)

Synonyms

7,8-dimethyl-10 (1'-D-ribityl) isoalloxazine, B-complex vitamin, Dolo-Neurotrat , flavin, flavine, lactoflavin, riboflavine, vitamin B2, Vitamin G.

Supplements: The most common forms of riboflavin available in supplements are riboflavin and riboflavin 5'-monophosphate. Riboflavin is most commonly found in multivitamin and vitamin B-complex preparations.

Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Acne, aging, alcohol dependence, ataxia, atherosclerosis, athletic performance, burning eyes, burning feet syndrome, burns, canker sores (113), carpal tunnel syndrome, cervical cancer (114), colon cancer, congenital methemoglobinemia, Crohn's disease, excess tearing, dermatitis, dementia, diabetes, digestion disorders, eczema, eye strain/fatigue, fatigue, glaucoma, glossitis (31), growth disorders, healthy hair, HIV, hypertension, immune system function, keratoconus (115;116;117;118), lactic acidosis, leg cramps, liver disease, memory loss, mitochondrial disorders (119;120;121;122;123), mood disorders, mouth cancer, multiple acylcoenzyme A dehydrogenase deficiency, multiple sclerosis, peptic ulcer disease, postoperative muscle cramps, neural tube defects, pain, red blood cell aplasia, reproduction disorders, rheumatoid arthritis, skin disorders, stress, stroke, ureteral colic pain, vitality problems.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Riboflavin Deficiency:
The U.S. Recommended Dietary Allowance (RDA) for riboflavin was revised in 1998, with the goal to prevent riboflavin deficiency. Clinical signs of deficiency in humans may appear at intakes less than 0.5-0.6 mg/day, and excess urinary excretion of riboflavin can be seen at intake levels of approximately 1 mg/day. Riboflavin deficiency (ariboflavinosis) can be associated with weakness, throat soreness/swelling, tongue swelling (glossitis), angular stomatitis/cheilosis (skin cracking or sores at the corners of the mouth), dermatitis (skin irritation), and anemia. Good dietary sources of riboflavin are milk (and other dairy products), eggs, enriched cereals/grains, meats, liver, and green vegetables (such as asparagus or broccoli). Riboflavin is easily destroyed by exposure to light (for example, riboflavin in milk stored in clear glass bottles).

Particular groups of people may be particularly susceptible to riboflavin deficiency, including the elderly, those with chronic illnesses, the poor, and those with alcohol dependence (32;33;34;35;36). Riboflavin depletion may be measured by decreased urinary excretion of riboflavin or increased erythrocyte reductase activity coefficients (37;38;39). Capillary electrophoresis with laser-induced fluorescence detection may be a useful tool for the assessment of riboflavin status in humans, allowing detection of all riboflavin vitamers below physiological concentrations (124). Dosage forms and formulation factors affect bioavailability of riboflavin, and riboflavin is sensitive to light. Aquabiosorb soft elastic capsule formulations may enhance bioavailability of riboflavin (125).

Adult Dosing (18 years and older):
U.S. Recommended Dietary Allowance (RDA) for adults (oral): 1.0mg for female adolescents (14-18 years old); 1.3mg for male adolescents (14-18 years old); 1.1mg for female adults (older than 18 years); 1.3mg for male adults (older than 18 years); 1.4mg for pregnant women (any age); 1.6mg for breastfeeding women (any age).

Children (younger than 18 years):
U.S. Recommended Dietary Allowance (RDA) for infants and children (oral): 0.3mg for 0-6 months old; 0.4mg for 7-12 months old; 0.5mg for 1-3 years old; 0.6mg for 4-8 years old; 0.9mg for 9-13 years old; 1.0mg for female adolescents (14-18 years old); 1.3mg for male adolescents (14-18 years old).

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies
Riboflavin supplementation has been associated with rare reports of allergy/anaphylaxis (126;127).

Side Effects and Warnings
Toxicity: In general, the limited capacity of human adults to absorb orally administered riboflavin limits its potential for harm. Riboflavin intake many times higher than the RDA is apparently without demonstrable toxicity. Nevertheless, the photosensitizing (sensitivity to light) properties of riboflavin raise the possibility of some potential risks. Other possible reactions to very high doses include itching, numbness, burning/prickling sensations, and yellow discoloration of the urine.

Infants: Very low birth weight infants who receive pre-term infant formulas (PIF) augmented to provide riboflavin at levels 5 times that in term infant formulas, have demonstrated high plasma levels of riboflavin and urinary riboflavin concentrations, and lower doses can be considered in this setting (128).

Pregnancy and Breastfeeding
Riboflavin is generally regarded as being safe during pregnancy and breastfeeding. The U.S. Recommended Daily Allowance (RDA) for riboflavin in pregnant women is higher than for non-pregnant women, and is 1.4mg daily (1.6mg for breastfeeding women).

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs:
Anticholinergics: Anticholinergic drugs may affect riboflavin absorption (129;130;131;132).

Anti-malarial drugs: Low riboflavin levels have been associated with anti-malarial effects, and anti-riboflavin therapies were proposed in the 1980s (88;89;90;91;92;93;94;95;96;97;98;99;100;101;102), although more recent evidence has challenged this proposed association (102). The anti-malarial medication quinacrine inhibits the incorporation of riboflavin into FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide).

Doxorubicin (Adriamycin): Doxorubicininhibits the incorporation of riboflavin into FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide) and may deplete riboflavin levels (133;134;135).

Methotrexate: Methotrexate may inhibit the effects of riboflavin in the body (136;137).

Oral contraceptives: Early reports suggested that women taking high-dose oral contraceptives developed diminished riboflavin nutritional status, but when investigators controlled for dietary riboflavin intake, no impact was found (138;139;140;141;142;143;144;138;145;146;147).

Phenobarbitol: based on animal research, long-time use of phenobarbitol may increase destruction of riboflavin by liver enzymes, increasing the risk of deficiency (148;149;150;151).

Phenothiazine antipsychotic medications (e.g., chlorpromazine): These drugs may lower riboflavin levels. Phenothiazines inhibit the incorporation of riboflavin into FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide).

Phenytoin (DIlantin): Phenytoin may alter riboflavin levels (152).

Probenecid: Probenecid may decrease the absorption of riboflavin from the digestive tract and increase excretion in the urine (153;154).

Tamoxifen: There is preliminary evidence suggesting that postmenopausal breast cancer patients with low riboflavin levels will normalize their levels following treatment with tamoxifen (155). However, the cause of their baseline low riboflavin is unclear, and may be related to prior treatment with doxorubicin chemotherapy, a suspected cause of low riboflavin levels (which would likely recover with or without tamoxifen).

Tetracycline: Riboflavin either alone or in combination with other B-vitamins should be taken at different times from tetracycline (156;157). In addition, long-term use of antibiotics can deplete vitamin B levels in the body (particularly B2, B9, B12, and biotin).

Thiazide diuretics: These drugs may increase the loss of riboflavin in the urine (158).

Tricyclic antidepressants (e.g., imipramine, desimpramine, amitriptyline, and nortriptyline): Tricyclic antidepressantsmay reduce levels of riboflavin in the body, meriting supplementation. Treatment with B-vitamins, including riboflavin, has been reported to improve scores of depression and cognitive function in patients taking tricyclic antidepressants (76).

Interactions with Herbs and Dietary Supplements:
B-complex vitamins: Severe riboflavin deficiency may impact multiple enzyme systems in the body, because riboflavin-dependent flavoproteins are involved in the metabolism of other vitamins including B6 (pyridoxine), B3 (niacin), and folate (159;160;161;162). The synthesis of the niacin-containing coenzymes, NAD and NADP, from the amino acid tryptophan, requires the FAD-dependent enzyme kynurenine mono-oxygenase (severe riboflavin deficiency can decrease the conversion of tryptophan to NAD and NADP, increasing the risk of niacin deficiency) (159;163;164;165;166;167;168).

Interactions with Laboratory Assays:
Homocysteine: Intake of riboflavin may be associated with decreased plasma homocysteine levels, and has been attributed to the riboflavin/FAD (flavin adenine dinucleotide)-dependent enzyme methylene tetrahydrofolate reductase (MTHFR) which plays an important role in maintaining the specific folate coenzyme required to form methionine from homocysteine (169;170;171). This phenomenon may be particularly relevant in individuals with a genetic mutation found only in some individuals: those who are homozygous for the C677T polymorphism of the MTHFR gene and whose folate intake is low (169;172;173;174;175;170). However, other research has found no effects of riboflavin on homocysteine levels in normal individuals (compared to folic acid which yields significant reductions of homocysteine levels) (171). Conversely, elevated homocysteine levels have been associated with low riboflavin levels (169) and may lead to decreased FMN or FAD activity.

Iron: Riboflavin deficiency appears to alter iron metabolism, although the mechanism is not clear. Animal and human research suggests that riboflavin deficiency may impair iron absorption, increase intestinal loss of iron, and/or impair iron utilization for the synthesis of hemoglobin (58;59;60;57;61;62;63;64;65;66;67;68;69). Riboflavin nutritional status may affect circulating hemoglobin levels (70;57;61;71). Correction of riboflavin deficiency in individuals who are both riboflavin deficient and iron deficient appears to improve response to iron therapy (56;57;62;72;53;54;55).

Mechanism of Action (Pharmacodynamics/Kinetics):
Absorption:Oral doses of riboflavin (20mg, 40mg, 60mg) and IV bolus injections (11.6mg) appear to have a maximal absorption of 27mg per adult (176;177;178). Aquabiosorb soft elastic capsule formulations may enhance bioavailability of riboflavin (125).

Half-life: Oral doses of riboflavin (20mg, 40mg, 60mg) and IV bolus injections (11.6mg) are reported to have a 1.1 hour half-life (176;177;178).

Distribution/Elimination: Oral doses of riboflavin (20mg, 40mg, 60mg) and IV bolus injections (11.6mg) are significantly higher after intravenous administration than after oral dosing (176;177;178).


Other useful Vitamin information: Vitamin B-6 | Vitamin C | Choline

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