Riboflavin (Vitamin B2)


Vitamin B2 is Riboflavin, a precursor of coenzymes called FAD and FMN, which are needed for flavoprotein enzyme reactions, including activation of other vitamins.

Required for the flavoenzymes of the respiratory chain and supports energy metabolism involving fats, carbohydrates, and proteins.

Riboflavin, also known as vitamin B2, is a vitamin found in food.

It is a water-soluble vitamin and is one of the B vitamin complex.

It is sold as a dietary supplement.

It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide. 

It is a starting compound in the synthesis of the coenzymes flavin mononucleotide (FMN) , also known as riboflavin-5′-phosphate) and flavin adenine dinucleotide (FAD). 

Riboflavin is the biosynthetic precursor of FMN and FAD

These coenzymes are involved in energy metabolism, cellular respiration, and antibody production, as well as normal growth and development. 

The coenzymes are also required for the metabolism of niacin, vitamin B6, and folate. 

It is prescribed to treat corneal thinning, and may reduce the incidence of migraine headaches in adults.

Routes of administration-oral, 

intramuscular, intravenous.

A dietary supplement

Elimination half-life 66 to 84 minutes

Excretion Urine

Riboflavin deficiency is rare.

Riboflavin deficiency is usually accompanied by deficiencies of other vitamins and nutrients. 

As a water-soluble vitamin, riboflavin consumed in excess of nutritional requirements is not stored.

Excess riboflavin is either not absorbed or is absorbed and quickly excreted in urine.

It can cause the urine to have a bright yellow tint. 

Riboflavin natural sources include meat, fish, fowl, eggs, dairy products, green vegetables, mushrooms, and almonds. 

In addition to its functions as a vitamin, it is used as a food coloring agent. 

Its biosynthesis takes place in bacteria, fungi and plants.

Commercial manufacturing uses fermentation of strains of fungi and genetically modified bacteria.

FAD is the more abundant form of flavin, reported to bind to 75% of the number of flavin-dependent protein encoded genes.

FAD serves as a co-enzyme for 84% of human-encoded flavoproteins.

In its purified, solid form, riboflavin is a yellow-orange crystalline powder with a slight odor and bitter taste. 

Riboflavin is essential to the formation of two major coenzymes, FMN and FAD, which are involved in energy metabolism, cell respiration, antibody production, growth and development.

It  is essential for the metabolism of carbohydrates, protein and fats.

FAD helps to convert tryptophan to niacin (vitamin B3) and the conversion of vitamin B6 to the coenzyme pyridoxal 5′-phosphate requires FMN.

Riboflavin is involved in maintaining normal circulating levels of homocysteine

Riboflavin deficiency associated with increased homocysteine levels, elevating the risk of cardiovascular diseases.

The flavin coenzymes support the function of roughly 70-80 flavoenzymes that are responsible for one- or two-electron redox reactions which capitalize on the ability of flavins to be converted between oxidized, half-reduced and fully reduced forms.

FAD is also required for the activity of glutathione reductase, an essential enzyme in formation of the antioxidant, glutathione.

Riboflavin, FMN, and FAD are involved in the metabolism of niacin, vitamin B6, and folate.

The synthesis of the niacin-containing coenzymes, NAD and NADP, from tryptophan involves a  FAD-dependent enzyme.

Dietary deficiency of riboflavin decreases production of NAD and NADP, promoting niacin deficiency.

The conversion of vitamin B6 to its coenzyme, pyridoxal 5′-phosphate synthase requires FMN that involves the enzyme pyridoxine 5′-phosphate oxidase.

FAD is required to metabolize 5,10-methylenetetrahydrofolate reductase (folate) to form the amino acid, methionine, from homocysteine.

A deficiency of riboflavin impairs the metabolism of the dietary mineral, iron, which is essential to the production of hemoglobin and red blood cells. 

Alleviating riboflavin deficiency improves the effectiveness of iron supplementation for treating iron-deficiency anemia.

The biosynthetic precursors to riboflavin are ribulose 5-phosphate and guanosine triphosphate.

These two compounds are then the substrates for the penultimate step in the pathway, catalyzed by the enzyme lumazine synthase.

Conversions of riboflavin to the cofactors FMN and FAD are carried out by the enzymes riboflavin kinase and FAD synthetase acting sequentially.

The industrial-scale production of riboflavin uses various microorganisms.

Keratoconus is the most common form of corneal ectasia, a progressive thinning of the cornea, and  is treated by corneal collagen cross-linking, which increases corneal stiffness. 

Cross-linking is achieved by applying a topical riboflavin solution to the cornea, which is then exposed to ultraviolet A light.

High-dose riboflavin (400 mg) taken at 400 mg per day for at least three months may reduce the frequency of migraine headaches in adults and should be considered for migraine prevention.

Research on high-dose riboflavin for migraine prevention or treatment in children and adolescents is inconclusive, and so supplements are not recommended.

Riboflavin is used as a food coloring-yellow-orange.

The requirement for riboflavin for women and men aged 14 and over are 0.9 mg/day and 1.1 mg/day, respectively.

The RDAs are 1.1 and 1.3 mg/day, respectively. 

The RDA during pregnancy is 1.4 mg/day and the RDA for lactating females is 1.6 mg/day. 

For infants up to the age of 12 months, the Adequate Intake (AI) is 0.3–0.4 mg/day and for children aged 1–13 years the RDA increases with age from 0.5 to 0.9 mg/day. 

For riboflavin there is no upper limit as there is no human data for adverse effects from high doses.

Any excess riboflavin is excreted via the kidneys into urine, resulting in a bright yellow color known as flavinuria.

Recommended Dietary Allowances

0–6 months 0.3mg/d

6–12 months 0.4mg/d

1–3 0.5mg/d

4–8 0.6 mg/d

9–13 0.9 mg/d

Females 14–18 1.0mg/d

Males 14–18 1.3y mg/d

Females 19+ 1.1 mg/d

Males 19+ 1.3 mg/d

Pregnant females 1.4 mg/d

Lactating females 1.6 mg/d

During a clinical trial on the effectiveness of riboflavin for treating the frequency and severity of migraines, abdominal pains and diarrhea were among the side effects reported.

Source. Amount (mg)

Beef liver, pan-fried 3.42 per 100 grams

Chicken liver, pan-fried 2.31 per 100 grams

Whey protein powder 2.02 per 100 grams

Salmon, cooked, wild/farmed 0.49/0.14 per 100 grams

Cows’ milk, whole 0.41 (one cup) per 100 grams

Turkey, cooked, dark/breast 0.38/0.21 per 100 grams

Pork, cooked, chop 0.23 per 100 grams

Chicken eggs, fried 0.23 (one, large) per 100 grams

Chicken, cooked, thigh/breast 0.19/0.11 per 100 grams

Beef, ground, cooked 0.18 per 100 grams

Cheese, cheddar 0.43 per 100 grams

Yogurt, whole milk 0.25 (one cup) per 100 grams

Almonds 1.14 per 100 grams

Mushrooms, white, raw 0.40 per 100 grams

Spinach, boiled 0.24 per 100 grams

Bread, baked, fortified 0.25 per 100 gram

Pasta, cooked, fortified 0.14 per 100 grams

Corn grits 0.06 per 100 grams

Rice, cooked, brown/white 0.05/0.00 per 100 grams

Avocado 0.14 per 100 grams

Kale, boiled 0.14 per 100 grams

Sweet potato baked 0.11 per 100 grams

Peanuts, roasted 0.11 per 100 grams

Tofu, firm 0.10 per 100 grams

Beans, green 0.10 per 100 grams

Brussels sprouts, boiled 0.08 per 100 grams

Romaine lettuce 0.07 per 100 grams

Potato, baked, with skin 0.05 per 100 grams

Beans, baked 0.04 per 100 grams

The milling of wheat results in an 85% loss of riboflavin, so white flour is enriched in some countries, as are baby foods, breakfast cereals, pastas and vitamin-enriched meal replacement products.

Riboflavin enrichment of bread and ready-to-eat breakfast cereals contributes significantly to the dietary supply of the vitamin. 

Free riboflavin is naturally present in animal-sourced foods along with protein-bound FMN and FAD. 

Cows’ milk contains mainly free riboflavin, while FMN and FAD are present at low concentrations.

Some countries require or recommend fortification of grain foods.

More than 90% of riboflavin in the diet is in the form of protein-bound FMN and FAD.

In the stomach gastric acid releases the coenzymes, which are subsequently enzymatically hydrolyzed in the proximal small intestine to release free riboflavin.

Absorption of FAD and FMN flavins occur via a rapid active transport system, with some additional passive diffusion at high concentrations.

Bile salts facilitate uptake, so absorption is improved when the vitamin is consumed with a meal.

The  maximum amount of riboflavin that can be absorbed from a single dose is 27 mg.

Three riboflavin transporter proteins have been identified: small intestine, placenta, brain and salivary glands, testes, and prostate.

Riboflavin is reversibly converted to FMN and then FAD. 

Excess riboflavin is absorbed by the small intestine, and is excreted in urine.

Riboflavin supplementation in large excess of requirements causes urine to appear more yellow than normal.

About two-thirds of urinary output is riboflavin, the remainder is partially metabolized to hydroxymethylriboflavin from oxidation within cells, and as other metabolites. 

When consumption exceeds the ability to absorb, riboflavin passes into the large intestine.

It is catabolized in the large intestine by bacteria to various metabolites that can be detected in feces, and could affect the large intestine microbiome.

Riboflavin deficiency is rare in the United States and in other countries with wheat flour or corn meal fortification programs.

A 2001-02 U.S. survey reported that less than 3% of the population consumed less than the Estimated Average Requirement of riboflavin.

Riboflavin deficiency results in stomatitis, chapped and fissured lips, angular stomatitis, sore throat, painful red tongue, and hair loss, and 

eyes that can become itchy, watery, bloodshot, and sensitive to light.

Riboflavin deficiency is associated with anemia, and prolonged riboflavin insufficiency may cause degeneration of the liver and nervous system.

Riboflavin deficiency may increase the risk of preeclampsia in pregnant women, cause fetal birth defects, including heart and limb deformities.

People at risk of having low riboflavin levels: alcoholics, vegetarian athletes, 

lactose intolerant, anorexants, and practitioners of veganism, pregnant or lactating women and their infants may also be at risk, if the mother avoids meat and dairy products.

Athletes and laborers, may require higher riboflavin intake.

People with hypothyroidism, adrenal insufficiency, and riboflavin transporter deficiency have decreased conversion of riboflavin into FAD and FMN 

Riboflavin deficiency is usually associated with other nutrient deficiencies, particularly of other water-soluble vitamins.

A deficiency of riboflavin can be primary, caused by poor vitamin sources in the regular diet, or secondary, which may be a result of conditions that affect absorption in the intestine. 

Secondary deficiencies are typically caused by the body not being able to use the vitamin, or by an increased rate of excretion of the vitamin.

Diet patterns associated with risk of deficiency include veganism and low-dairy vegetarianism.

Cancer, heart disease and diabetes may cause or exacerbate riboflavin deficiency.

Genetic defects that compromise riboflavin absorption, transport, metabolism or use by flavoproteins: riboflavin transporter deficiency; gene variants of the genes SLC52A2 and SLC52A3 are defective.

Infants and young children with congenital riboflavin deficiency due to absorption abnormality present with muscle weakness, cranial nerve deficits including hearing loss, sensory symptoms including sensory ataxia, feeding difficulties, and respiratory distress caused by a sensorimotor axonal neuropathy and cranial nerve pathology. 

Such infants with riboflavin transporter deficiency have labored breathing and are at risk of dying in the first decade of life if untreated: oral supplementation of high amounts of riboflavin is lifesaving.

Total riboflavin excretion in healthy adults with normal riboflavin intake is about 120 micrograms per day, while excretion of less than 40 micrograms per day indicates deficiency.

Riboflavin excretion rates decrease as a person ages.

Riboflavin excretion rates increase during periods of chronic stress and the use of some prescription drugs.

The erythrocyte glutathione reductase activity coefficient provides a measure of tissue saturation and long-term riboflavin status.

Urinary excretion is expressed as nmol of riboflavin per gram of creatinine: Low is defined as in the range of 50 to 72 nmol/g. 

Deficient riboflavin is below 50 nmol/g. 

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