PRODUCTS

VITAMIN B2

CAS No: 83-88-5
Empirical Formula (Hill Notation): C17H20N4O6
Molecular Weight:376.36
Density:1.7±0.1 g/cm3
Boiling Point:715.6±70.0 °C at 760 mmHg
Melting Point:290 °C
EC Number:201-507-1

Riboflavin, also known as vitamin B2, is a water-soluble vitamin and is one of the B vitamins.
Unlike folate and vitamin B6, which occur in several chemically related forms known as vitamers, Vitamin B2 is only one chemical compound.
Vitamin B2 is a starting compound in the synthesis of the coenzymes flavin mononucleotide (FMN, also known as riboflavin-5'-phosphate) and flavin adenine dinucleotide (FAD).
FAD is the more abundant form of flavin, reported to bind to 75% of the number of flavin-dependent protein encoded genes in the all-species genome (the flavoproteome) and serves as a co-enzyme for 84% of human-encoded flavoproteins.

In Vitamin B2s purified, solid form, riboflavin is a yellow-orange crystalline powder with a slight odor and bitter taste.
Vitamin B2 is soluble in polar solvents, such as water and aqueous sodium chloride solutions, and slightly soluble in alcohols.
Vitamin B2 is not soluble in non-polar or weakly polar organic solvents such as chloroform, benzene or acetone.
In solution or during dry storage as a powder, Vitamin B2 is heat stable if not exposed to light.
When heated to decompose, Vitamin B2 releases toxic fumes containing nitric oxide

Riboflavin, also known as vitamin B2, is a vitamin found in food and sold as a dietary supplement.
It is essential to the formation of two major coenzymes, flavin mononucleotide and flavin adenine dinucleotide.
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. Riboflavin is prescribed to treat corneal thinning, and taken orally, may reduce the incidence of migraine headaches in adults.
Riboflavin deficiency is rare and is usually accompanied by deficiencies of other vitamins and nutrients.

Vitamin B2 may be prevented or treated by oral supplements or by injections.
As a water-soluble vitamin, any riboflavin consumed in excess of nutritional requirements is not stored; vitamin B2 is either not absorbed or is absorbed and quickly excreted in urine, causing the urine to have a bright yellow tint.
Natural sources of vitamin B2 include meat, fish and fowl, eggs, dairy products, green vegetables, mushrooms, and almonds.
Some countries require vitamin B2s addition to grains.

Vitamin B2 was discovered in 1920, isolated in 1933, and first synthesized in 1935.
In vitamin B2s purified, solid form, vitamin B2 is a water-soluble yellow-orange crystalline powder.
In addition to vitamin B2s function as a vitamin, vitamin B2 is used as a food coloring agent.
Biosynthesis takes place in bacteria, fungi and plants, but not animals.
Industrial synthesis of riboflavin was initially achieved using a chemical process, but current commercial manufacturing relies on fermentation methods using strains of fungi and genetically modified bacteria.

Riboflavin (7,8-dimethyl-10-ribityl-isoalloxazine) is a water-soluble vitamin present in a wide variety of foods.
Riboflavin was initially isolated, although not purified, from milk whey in 1879 and given the name lactochrome.
Riboflavin can be crystallized as orange-yellow crystals and in its pure form is poorly soluble in water.
Riboflavins most important biologically active forms, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), participate in a range of redox reactions, some of which are absolutely key to the function of aerobic cells.
Despite this and the facts that riboflavin deficiency is endemic in many regions of the world and that certain sections of populations in affluent societies have low intakes, studies of effects of inadequate riboflavin intakes have attracted limited interest.
In light of the recent interest in the putative role of riboflavin in protecting against cancer and cardiovascular disease, it is appropriate to reevaluate the metabolic roles of this vitamin and the public health relevance of low intakes.

Food sources of riboflavin
Milk and dairy products make the greatest contribution to riboflavin intake in Western diets, making riboflavin exceptional among the water-soluble vitamins.
National dietary surveys in the United Kingdom report that, on average, milk and dairy products contribute 51% of intake in preschool children, 35% in schoolchildren, 27% in adults, and 36% in the elderly.
Cereals, meats (especially offal), and fatty fish are also good sources of riboflavin, and certain fruit and vegetables, especially dark-green vegetables, contain reasonably high concentrations.

Riboflavin deficiency is endemic in populations who exist on diets lacking dairy products and meat (1–5).
In Guatemala, the riboflavin status of elderly persons was highly correlated with the frequency of consumption of fresh or reconstituted milk (2).
The National Diet and Nutrition Survey of young people aged 4–18 y (6) reported a high prevalence of poor riboflavin status, determined biochemically, among adolescent girls in the United Kingdom.

A clear age-related decrease in the habitual consumption of whole milk was reported for both girls and boys.
The most recent National Food Consumption Survey in the United Kingdom (7) confirmed a continuing trend toward lower household consumption of liquid whole milk (47% decrease since 1990).
This is partly offset by an increase in the household consumption of semi-skim and other skimmed milks, although not fully skimmed milk.

Grain products contain low natural amounts of riboflavin, but fortification practices have led to certain breads and cereals being very good sources of riboflavin.
Cereals now contribute > 20% to the household consumption of riboflavin in the United Kingdom.
Daily consumption of breakfast cereal with milk would be expected to maintain an adequate intake of riboflavin.
Thus, it is not surprising that various studies from different countries have shown a higher riboflavin intake or better riboflavin status among those who consume cereal at breakfast than among those who do not, irrespective of age (8–10).

Vegetarians with access to a diversity of fruit and vegetables can avoid deficiency, although intakes in vegetarians may be lower than in omnivores (11), and elderly vegetarians may be at higher risk (12).
Although relatively heat-stable, riboflavin is readily degraded by light. Milk kept in glass bottles and delivered to the doorstep might be particularly susceptible to loss through this route, which is also associated with flavor changes, because the oxidative products of photolysis can damage milk lipids.
This light sensitivity of riboflavin has led to loss of riboflavin from banked breast milk used in the parenteral nutrition of newborns.

Riboflavin is essential to the formation of two major coenzymes, FMN and FAD.
These coenzymes are involved in energy metabolism, cell respiration, antibody production, growth and development.
Riboflavin is essential for the metabolism of carbohydrates, protein and fats.
FAD contributes to conversion of 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; in riboflavin deficiency, homocysteine levels increase, elevating the risk of cardiovascular diseases.

Redox reactions of Vitamin B2
Redox reactions are processes that involve the transfer of electrons.
The flavin coenzymes support the function of roughly 70-80 flavoenzymes in humans (and hundreds more across all organisms, including those encoded by archeal, bacterial and fungal genomes) 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 endogenous antioxidant, glutathione.

Micronutrient metabolism of Vitamin B2
Vitamin B2, 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 the FAD-dependent enzyme, kynurenine 3-monooxygenase.
Dietary deficiency of riboflavin can decrease the production of NAD and NADP, thereby promoting niacin deficiency.

Conversion of vitamin B6 to its coenzyme, pyridoxal 5'-phosphate synthase, involves the enzyme, pyridoxine 5'-phosphate oxidase, which requires FMN.
An enzyme involved in folate metabolism, 5,10 methylenetetrahydrofolate reductase, requires FAD to form the amino acid, methionine, from homocysteine.
Vitamin B2 deficiency appears to impair the metabolism of the dietary mineral, iron, which is essential to the production of hemoglobin and red blood cells.
Alleviating riboflavin deficiency in people who are deficient in both riboflavin and iron improves the effectiveness of iron supplementation for treating iron-deficiency anemia.

Absorption, metabolism, excretion of Vitamin B2
More than 90% of Vitamin B2 in the diet is in the form of protein-bound FMN and FAD.
Exposure to gastric acid in the stomach releases the coenzymes, which are subsequently enzymatically hydrolyzed in the proximal small intestine to release free riboflavin.
Absorption occurs via a rapid active transport system, with some additional passive diffusion occurring at high concentrations.
Bile salts facilitate uptake, so absorption is improved when the vitamin is consumed with a meal.

One small clinical trial in adults reported that the maximum amount of Vitamin B2 that can be absorbed from a single dose is 27 mg.
The majority of newly absorbed Vitamin B2 is taken up by the liver on the first pass, indicating that postprandial appearance of Vitamin B2 in blood plasma may underestimate absorption.
Three Vitamin B2 transporter proteins have been identified: RFVT1 is present in the small intestine and also in the placenta; RFVT2 is highly expressed in brain and salivary glands; and RFVT3 is most highly expressed in the small intestine, testes, and prostate.
Infants with mutations in the genes encoding these transport proteins can be treated with riboflavin administered orally.

Vitamin B2 is reversibly converted to FMN and then FAD.
From Vitamin B2 to FMN is the function of zinc-requiring riboflavin kinase; the reverse is accomplished by a phosphatase.
From FMN to FAD is the function of magnesium-requiring FAD synthase; the reverse is accomplished by a pyrophosphatase.
FAD appears to be an inhibitory end-product that down-regulates its own formation.

When excess Vitamin B2 is absorbed by the small intestine, it is quickly removed from the blood and excreted in urine.
Urine color is used as a hydration status biomarker and, under normal conditions, correlates with urine specific gravity and urine osmolality.
However, Vitamin B2 supplementation in large excess of requirements causes urine to appear more yellow than normal.

With normal dietary intake, about two-thirds of urinary output is riboflavin, the remainder having been partially metabolized to hydroxymethylriboflavin from oxidation within cells, and as other metabolites.
When consumption exceeds the ability to absorb, Vitamin B2 passes into the large intestine, where it is catabolized by bacteria to various metabolites that can be detected in feces.
There is speculation that unabsorbed riboflavin could affect the large intestine microbiome.

Prevalence of Vitamin B2
Vitamin B2 deficiency is uncommon in the United States and in other countries with wheat flour or corn meal fortification programs.
From data collected in biannual surveys of the U.S. population, for ages 20 and over, 22% of females and 19% of men reported consuming a supplement that contained riboflavin, typically a vitamin-mineral multi-supplement.

For the non-supplement users, the dietary intake of adult women averaged 1.74 mg/day and men 2.44 mg/day.
These amounts exceed the RDAs for riboflavin of 1.1 and 1.3 mg/day respectively.
For all age groups, on average, consumption from food exceeded the RDAs.
A 2001-02 U.S. survey reported that less than 3% of the population consumed less than the Estimated Average Requirement of riboflavin.

Signs and symptoms of Vitamin B2
Vitamin B2 deficiency (also called ariboflavinosis) results in stomatitis, symptoms of which include chapped and fissured lips, inflammation of the corners of the mouth (angular stomatitis), sore throat, painful red tongue, and hair loss.
The eyes can become itchy, watery, bloodshot, and sensitive to light.

Riboflavin deficiency is associated with anemia.
Prolonged riboflavin insufficiency may cause degeneration of the liver and nervous system.
Riboflavin deficiency may increase the risk of preeclampsia in pregnant women.

Deficiency of riboflavin during pregnancy can result in fetal birth defects, including heart and limb deformities.
Vitamin B2 deficiency is a significant risk when diet is poor, because the human body excretes the vitamin continuously, so it is not stored. A person who has a B2 deficiency normally lacks other vitamins too.
People who drink excessive amounts of alcohol are at greater risk of vitamin B deficiency.

There are two types of riboflavin deficiency:
Primary riboflavin deficiency happens when the person’s diet is poor in vitamin B2
Secondary riboflavin deficiency happens for another reason, maybe because the intestines cannot absorb the vitamin properly, or the body cannot use it, or because it is being excreted too rapidly
Riboflavin deficiency is also known as ariboflavinosis.

Signs and symptoms of deficiency include:
-A lack of vitamin B2 can lead to mouth ulcers and other complaints.
-Angular cheilitis, or cracks at the corners of the mouth
-Cracked lips
-Dry skin
-Inflammation of the lining of the mouth
-Inflammation of the tongue
-Mouth ulcers
-Red lips
-Sore throat
-Scrotal dermatitis
-Fluid in mucous membranes
-Iron-deficiency anemia
-Eyes may be sensitive to bright light, and they may be itchy, watery, or bloodshot

Risk factors of Vitamin B2 deficiency
People at risk of having low Vitamin B2 levels include alcoholics, vegetarian athletes, and practitioners of veganism.
Pregnant or lactating women and their infants may also be at risk, if the mother avoids meat and dairy products.

Anorexia and lactose intolerance increase the risk of riboflavin deficiency.
People with physically demanding lives, such as athletes and laborers, may require higher riboflavin intake.
The conversion of riboflavin into FAD and FMN is impaired in people with hypothyroidism, adrenal insufficiency, and riboflavin transporter deficiency.

Vitamin B2, also called riboflavin, is one of 8 B vitamins.
All B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which is used to produce energy.
These B vitamins, often referred to as B-complex vitamins, also help the body metabolize fats and protein.

B complex vitamins are necessary for a healthy liver, skin, hair, and eyes.
B complex vitamins also help the nervous system function properly.
All B vitamins are water soluble, meaning the body does not store them.

In addition to producing energy for the body, riboflavin works as an antioxidant, fighting damaging particles in the body known as free radicals.
Free radicals can damage cells and DNA, and may contribute to the aging process, as well as the development of a number of health conditions, such as heart disease and cancer.
Antioxidants, such as riboflavin, can fight free radicals and may reduce or help prevent some of the damage they cause.

Riboflavin is also needed to help the body change vitamin B6 and folate into forms it can use.
Riboflavin is also important for growth and red blood cell production.
Most healthy people who eat a well-balanced diet get enough riboflavin.
However, elderly people and alcoholics may be at risk for riboflavin deficiency because of poor diet.

Symptoms of riboflavin deficiency include:
-Fatigue
-Slowed growth
-Digestive problems
-Cracks and sores around the corners of the mouth
-Swollen magenta-colored tongue
-Eye fatigue
-Swelling and soreness of the throat
-Sensitivity to light

Vitamin B2 deficiency Causes
Vitamin B2 deficiency is usually found together with other nutrient deficiencies, particularly of other water-soluble vitamins.
A deficiency of riboflavin can be primary (i.e. 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 that increase risk of deficiency include veganism and low-dairy vegetarianism.
Diseases such as cancer, heart disease and diabetes may cause or exacerbate riboflavin deficiency.

There are rare genetic defects that compromise Vitamin B2 absorption, transport, metabolism or use by flavoproteins.
One of these is Vitamin B2 transporter deficiency, previously known as Brown-Vialetto-Van Laere syndrome.
Variants of the genes SLC52A2 and SLC52A3 which code for transporter proteins RDVT2 and RDVT3, respectively, are defective.

Infants and young children 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.
When untreated, infants with riboflavin transporter deficiency have labored breathing and are at risk of dying in the first decade of life. Treatment with oral supplementation of high amounts of Vitamin B2 is lifesaving.
Other inborn errors of metabolism include riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency, also known as a subset of glutaric acidemia type 2, and the C677T variant of the methylenetetrahydrofolate reductase enzyme, which in adults has been associated with risk of high blood pressure.

Diagnosis and assessment
The assessment of Vitamin B2 status is essential for confirming cases with non-specific symptoms whenever deficiency is suspected.
Total Vitamin B2 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.
Vitamin B2 excretion rates decrease as a person ages, but increase during periods of chronic stress and the use of some prescription drugs.

Indicators used in humans are erythrocyte glutathione reductase (EGR), erythrocyte flavin concentration and urinary excretion.
The erythrocyte glutathione reductase activity coefficient (EGRAC) provides a measure of tissue saturation and long-term riboflavin status.
Results are expressed as an activity coefficient ratio, determined by enzyme activity with and without the addition of FAD to the culture medium.

An EGRAC of 1.0 to 1.2 indicates that adequate amounts of riboflavin are present; 1.2 to 1.4 is considered low, greater than 1.4 indicates deficient.
For the less sensitive "erythrocyte flavin method", values greater than 400 nmol/L are considered adequate and values below 270 nmol/L are considered deficient.
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 is below 50 nmol/g.
Urinary excretion load tests have been used to determine dietary requirements.
For adult men, as oral doses were increased from 0.5 mg to 1.1 mg, there was a modest linear increase in urinary riboflavin, reaching 100 micrograms for a subsequent 24-hour urine collection.
Beyond a load dose of 1.1 mg, urinary excretion increased rapidly, so that with a dose of 2.5 mg, urinary output was 800 micrograms for a 24-hour urine collection.

Vitamin B-2, or riboflavin, is naturally in some foods. It’s present in other foods in synthetic form.
Vitamin B-2 and the other B vitamins help your body build red blood cells and support other cellular functions that give you energy.
You’ll get the most out of the B vitamins if you take supplements or eat foods that contain all of them.

These functions include the breakdown of fats, proteins, and carbohydrates.
You may have experienced an energy boost from taking supplements containing B vitamins.
Vitamin B2 helps break down proteins, fats, and carbohydrates. It plays a vital role in maintaining the body’s energy supply.

Riboflavin helps convert carbohydrates into adenosine triphosphate (ATP).
The human body produces ATP from food, and ATP produces energy as the body requires it.
The compound ATP is vital for storing energy in muscles.

Cataracts
Vitamin B2, along with other nutrients, is important for normal vision.
Early studies suggest that riboflavin might help prevent cataracts, damage to the lens of the eye, which can lead to cloudy vision. In one double-blind, placebo-controlled study, people who took a niacin and riboflavin supplement had fewer cataracts than people who took other vitamins and nutrients.
However, researchers do not know whether that was due to riboflavin, niacin, or the combination of the two.
More research is needed to see if riboflavin can really help prevent cataracts.

Migraine headache
Several studies suggest that people who get migraines may reduce how often they get migraines and how long the migraines last by taking riboflavin.
One double-blind, placebo-controlled study showed that taking 400 mg of riboflavin a day cut the number of migraine attacks in half.
However, the study did not compare riboflavin to conventional medications used to prevent migraines. More research is needed.

Autism
Preliminary research suggests that supplementation with vitamin B2, along with vitamin B6, and magnesium reduces the level of dicarboxylic acids (abnormal organic acids) in the urine of autistic children.

Dietary Sources
The best sources of riboflavin include:
-Brewer's yeast
-Almonds
-Organ meats
-Whole grains
-Wheat germ
-Wild rice
-Mushrooms
-Soybeans
-Milk
-Yogurt
-Eggs
-Broccoli
-Brussels sprouts
-Spinach
-Flours and cereals are often fortified with riboflavin.

Riboflavin is destroyed by light.
So food should be stored away from light to protect its riboflavin content.
While riboflavin is not destroyed by heat, it can be lost in water when foods are boiled or soaked.
Roasting and steaming foods preserves more riboflavin than frying or scalding your foods.

Riboflavin is vitamin B2.
Riboflavin is widely found in both plant- and animal-based foods, including milk, meat, eggs, nuts, enriched flour, and green vegetables.
Riboflavin is involved in many body processes.

Riboflavin's required for the proper development of the skin, lining of the digestive tract, blood cells, and brain function.
People most commonly use riboflavin to prevent riboflavin deficiency, for migraine, and for high levels of homocysteine in the blood.
Riboflavin's also used for acne, muscle cramps, and many other conditions, but there is no good scientific evidence to support these other uses.

Effective for
Riboflavin deficiency (ariboflavinosis).
Taking riboflavin by mouth can increase levels of riboflavin in the body, helping to treat and prevent riboflavin deficiency.

Possibly Effective for
High levels of homocysteine in the blood (hyperhomocysteinemia). Taking riboflavin by mouth for 12 weeks decreases levels of homocysteine by up to 40% in some people with a specific gene type.

Migraine.
Taking high-dose riboflavin by mouth seems to modestly reduce the number and severity of migraine headaches in adults.
It's unclear if it helps children.
There is interest in using riboflavin for a number of other purposes, but there isn't enough reliable information to say whether it might be helpful.

Vitamin B2 helps convert food into energy.
Vitamin B2 is necessary for healthy skin, hair, circulatory system, brain and nervous system.
Dryness around the mouth and lips, dermatitis, conjunctivitis, photophobia, tongue inflammation, anxiety, loss of appetite and fatigue may occur in vitamin B2 deficiency.
Milk, eggs, yogurt, cheese, meat, green leafy vegetables, mushrooms, almonds and cereals contain vitamin B2.

Riboflavin (Vitamin B2) contributes to normal energy-yielding metabolism.”
Riboflavin (Vitamin B2) contributes to the maintenance of normal mucosa, normal red blood cells, normal skin and normal vision.”
Riboflavin (Vitamin B2) contributes to the normal metabolism of iron.”
Riboflavin (Vitamin B2) contributes to the reduction of tiredness and fatigue.

Vitamin B2, also known as riboflavin, is one of the eight B-complex vitamins.
Like other B vitamins, Vitamin B2 plays a role in energy production in the body, but also has many other important uses.
Vitamin B2 is a water-soluble vitamin that is flushed out of the body daily, so it must be restored each day.
The best way to get this vitamin is by eating foods that are rich in riboflavin.
Vitamin B2 is found in eggs, nuts, dairy products, meats, broccoli, brewer's yeast, Brussel sprouts, wheat germ, wild rice, mushrooms, soybeans, green leafy vegetables and whole grain and enriched cereals and bread, according to the UK's NHS website.

Vitamin B2 Roles and Benefits
Vitamin B2 has an important role in the healthy functioning of many functions of the body.
Vitamin B2, which is involved in the production of energy from food, is also a necessary vitamin for the regular functioning of the nervous system.
It also supports the use of oxygen by tissues such as skin, hair and nails.

Vitamin B2 plays an important role in growth and development, reduces the aging process and provides protection against the risk of cancer.
It is also a vitamin that is beneficial for asthma and bronchitis disease.
Vitamin B2 should also be taken for antibody and red blood cell production. It is an effective vitamin in the prevention of many diseases such as thyroid, headache, cataract, eczema, dermatitis, rheumatoid arthritis.

In Vitamin B2 Deficiency…
- Problems occur in the absorption of protein, fat and carbohydrates.
- Digestive problems may occur.
- Dullness of hair color, wrinkles on the skin may occur.
- Sores may occur in the mouth and tongue.
- Loss of appetite can be seen.
- It can cause complaints such as eye fatigue, bloodshot eyes, and visual disturbances.
- Increases the risk of cataracts.
- It can lead to mental depression and forgetfulness.

Which Foods Have Vitamin B2?
Vitamin B2 is one of the rare vitamins found in many foods. Below are the richest food sources of vitamin B2:
- Cheese
- Almond
- Red meat
- Oily fish
- Egg (boiled)
- Mushrooms
- Sesame
- Green leafy vegetables (spinach, broccoli)

What is the Daily Vitamin B2 Requirement?
It varies between 1 mg – 2 mg in adults.
In cases of pregnancy and breastfeeding, the need for vitamin B2 can increase up to 15 mg.

RIBOFLAVIN BENEFITS
Vitamin B2 is a vitamin that is needed for growth and overall good health.
Vitamin B2 helps the body break down carbohydrates, proteins and fats to produce energy, and it allows oxygen to be used by the body.
Vitamin B2 is also important for eye health.

According to the National Center for Biotechnology Information, this vitamin is needed to protect glutathione, which is an important antioxidant in the eye.
The U.S. National Library of Medicine (NLM) reports that eating a diet rich in riboflavin can lower the risk of developing cataracts.
Taking supplements containing riboflavin and niacin may also be helpful in preventing cataracts.

Levels of certain vitamins, chemicals and minerals in the bloodstream seem to be dependent on healthy levels of B2, as well.
For example, riboflavin changes vitamin B6 and folate (vitamin B9) into forms that the body can use.
According to the American Journal of Clinical Nutrition, riboflavin is important to how the body processes iron.

Without it, research shows that the body is more likely to develop anemia.
Taking riboflavin can also reduce homocysteine levels in the blood by 26 to 40 percent, according to the NLM.
B2 may be important to maintaining a healthy pregnancy diet, as well.

According to a study by the University Women's Hospital in Heidelberg, Germany, riboflavin deficiency may be a factor in causing preeclampsia, a condition that causes high blood pressure in late pregnancy.
Those suffering from migraines may find that taking doses of B2 may help.
A study by the department of neurology of Humboldt University of Berlin found that those taking high doses of riboflavin had significantly fewer migraines.

Riboflavin (also known as vitamin B2) is one of the B vitamins, which are all water soluble.
Riboflavin is naturally present in some foods, added to some food products, and available as a dietary supplement.
This vitamin is an essential component of two major coenzymes, flavin mononucleotide (FMN; also known as riboflavin-5’-phosphate) and flavin adenine dinucleotide (FAD).

These coenzymes play major roles in energy production; cellular function, growth, and development; and metabolism of fats, drugs, and steroids .
The conversion of the amino acid tryptophan to niacin (sometimes referred to as vitamin B3) requires FAD.
Similarly, the conversion of vitamin B6 to the coenzyme pyridoxal 5’-phosphate needs FMN.
In addition, riboflavin helps maintain normal levels of homocysteine, an amino acid in the blood.

More than 90% of dietary riboflavin is in the form of FAD or FMN; the remaining 10% is comprised of the free form and glycosides or esters.
Most riboflavin is absorbed in the proximal small intestine.
The body absorbs little riboflavin from single doses beyond 27 mg and stores only small amounts of riboflavin in the liver, heart, and kidneys.
When excess amounts are consumed, they are either not absorbed or the small amount that is absorbed is excreted in urine.

Bacteria in the large intestine produce free riboflavin that can be absorbed by the large intestine in amounts that depend on the diet.
More riboflavin is produced after ingestion of vegetable-based than meat-based foods.

Riboflavin is yellow and naturally fluorescent when exposed to ultraviolet light.
Moreover, ultraviolet and visible light can rapidly inactivate riboflavin and its derivatives.
Because of this sensitivity, lengthy light therapy to treat jaundice in newborns or skin disorders can lead to riboflavin deficiency.
The risk of riboflavin loss from exposure to light is the reason why milk is not typically stored in glass containers.

Riboflavin status is not routinely measured in healthy people.
A stable and sensitive measure of riboflavin deficiency is the erythrocyte glutathione reductase activity coefficient (EGRAC), which is based on the ratio between this enzyme’s in vitro activity in the presence of FAD to that without added FAD.
The most appropriate EGRAC thresholds for indicating normal or abnormal riboflavin status are uncertain.

An EGRAC of 1.2 or less is usually used to indicate adequate riboflavin status, 1.2–1.4 to indicate marginal deficiency, and greater than 1.4 to indicate riboflavin deficiency.
However, a higher EGRAC does not necessarily correlate with degree of riboflavin deficiency.
Furthermore, the EGRAC cannot be used in people with glucose-6-phosphate dehydrogenase deficiency, which is present in about 10% of African Americans.

Another widely used measure of riboflavin status is fluorometric measurement of urinary excretion over 24 hours (expressed as total amount of riboflavin excreted or in relation to the amount of creatinine excreted).
Because the body can store only small amounts of riboflavin, urinary excretion reflects dietary intake until tissues are saturated.
Total riboflavin excretion in healthy, riboflavin-replete adults is at least 120 mcg/day; a rate of less than 40 mcg/day indicates deficiency.

This technique is less accurate for reflecting long-term riboflavin status than EGRAC.
Also, urinary excretion levels can decrease with age and increase with exposure to stress and certain drugs, and the amount excreted strongly reflects recent intake.

Riboflavin and Health
This section focuses on two conditions in which riboflavin might play a role: migraine headaches and cancer.

Migraine headaches
Migraine headaches typically produce intense pulsing or throbbing pain in one area of the head.
These headaches are sometimes preceded or accompanied by aura (transient focal neurological symptoms before or during the headaches).

Mitochondrial dysfunction is thought to play a causal role in some types of migraine.
Because riboflavin is required for mitochondrial function, researchers are studying the potential use of riboflavin to prevent or treat migraine headaches.
Some, but not all, of the few small studies conducted to date have found evidence of a beneficial effect of riboflavin supplements on migraine headaches in adults and children.

In a randomized trial in 55 adults with migraine, 400 mg/day riboflavin reduced the frequency of migraine attacks by two per month compared to placebo.
In a retrospective study in 41 children (mean age 13 years) in Italy, 200 or 400 mg/day riboflavin for 3 to 6 months significantly reduced the frequency (from 21.7 ± 13.7 to 13.2 ± 11.8 migraine attacks over a 3-month period) and intensity of migraine headaches during treatment.
The beneficial effects lasted throughout the 1.5-year follow-up period after treatment ended.
However, two small randomized studies in children found that 50 to 200 mg/day riboflavin did not reduce the number of migraine headaches or headache severity compared to placebo.

Cancer prevention
Experts have theorized that riboflavin might help prevent the DNA damage caused by many carcinogens by acting as a coenzyme with several different cytochrome P450 enzymes.
However, data on the relationship between riboflavin and cancer prevention or treatment are limited and study findings are mixed.

A few large observational studies have produced conflicting results on the relationship between riboflavin intakes and lung cancer risk.
A prospective study followed 41,514 current, former, and never smokers in the Melbourne Collaborative Cohort Study for 15 years, on average.
The average riboflavin intake among all participants was 2.5 mg/day. The results showed a significant inverse association between dietary riboflavin intake and lung cancer risk in current smokers (fifth versus first quintile) but not former or never smokers.

However, another cohort study in 385,747 current, former, and never smokers who were followed for up to 12 years in the European Prospective Investigation into Cancer and Nutrition found no association between riboflavin intakes and colorectal cancer risk in any of the three groups.
Moreover, the prospective Canadian National Breast Screening Study showed no association between dietary intakes or serum levels of riboflavin and lung cancer risk in 89,835 women aged 40-59 from the general population over 16.3 years, on average.
Observational studies on the relationship between riboflavin intakes and colorectal cancer risk have not yielded conclusive results either.

An analysis of data on 88,045 postmenopausal women in the Women’s Health Initiative Observational Study showed that total intakes of riboflavin from both foods and supplements were associated with a lower risk of colorectal cancer.
A study that followed 2,349 individuals with cancer and 4,168 individuals without cancer participating in the Netherlands Cohort Study on Diet and Cancer for 13 years found no significant association between riboflavin and proximal colon cancer risk among women.
Future studies, including clinical trials, are needed to clarify the relationship between riboflavin intakes and various types of cancer and determine whether riboflavin supplements might reduce cancer risk.

Riboflavin or vitamin B2 is a member of the group of vitamins referred to as vitamin B complex, which is a water-soluble vitamin.
As a drug, healthcare providers often prescribe it in a combined formulation consisting of other B complex vitamins as a prophylactic supplement to prevent the development of deficiency.

Riboflavin deficiency is rare as it is ubiquitous in a variety of food choices.
However, individuals following a diet scarce in milk and meat, which are one of the best sources of riboflavin, and some specific groups of individuals, as discussed below, may be prone to its deficiency.

Milk and dairy products have very high riboflavin content; dairy intake is the most significant contributor of the vitamin in Western diets, making riboflavin deficiency uncommon among water-soluble vitamins.
However, in developed countries, there is an increased intake of semi-skimmed milk, depleting milk of its riboflavin content.
Although relatively stable, it easily degrades by light exposure.
Milk kept in a glass bottle may be susceptible to degradation through this route.

Grain products possess low natural amounts, but fortification practices ensure that certain breads and cereals have become sources of riboflavin.
Therefore, according to an article by Morgan KJ et al., high riboflavin levels were found in those having cereals for breakfast.
Fatty fish are also excellent sources of riboflavin, and certain fruits and vegetables, especially dark green vegetables, contain reasonably high concentrations.
Vegetarians with access to a variety of fruit and vegetables can avoid deficiency, although intake may be lower than omnivores, and elderly vegetarians are at a higher risk.

Primary riboflavin deficiency results from inadequate intake of the following:
-Fortified cereals
-Milk
-Other animal products

Secondary riboflavin deficiency is most commonly caused by the following:
-Chronic diarrhea
-Malabsorption syndromes
-Liver disorders
-Hemodialysis
-Peritoneal dialysis
-Long-term use of barbiturates
-Chronic alcoholism
-Symptoms and Signs of Riboflavin Deficiency

The most common signs of riboflavin deficiency are pallor and maceration of the mucosa at the angles of the mouth (angular stomatitis) and vermilion surfaces of the lips (cheilosis), eventually replaced by superficial linear fissures. The fissures can become infected with Candida albicans, causing grayish white lesions (perlèche).
The tongue may appear magenta.
Seborrheic dermatitis develops, usually affecting the nasolabial folds, ears, eyelids, and scrotum or labia majora.
These areas become red, scaly, and greasy.
Rarely, neovascularization and keratitis of the cornea occur, causing lacrimation and photophobia.

Diagnosis of Riboflavin Deficiency
-Therapeutic trial
-Urinary excretion of riboflavin
-The lesions characteristic of riboflavin deficiency are nonspecific. -

Riboflavin deficiency should be suspected if characteristic signs develop in a patient with other B vitamin deficiencies.
Diagnosis of riboflavin deficiency can be confirmed by a therapeutic trial or laboratory testing, usually by measuring urinary excretion of riboflavin.

Treatment of Riboflavin Deficiency
-Oral riboflavin and other water-soluble vitamins
-Riboflavin 5 to 10 mg orally once a day is given until recovery.
Other water-soluble vitamins should also be given.

Key Points
Riboflavin deficiency causes various nonspecific skin and mucosal lesions, including maceration of mucosa at the angles of the mouth (angular stomatitis) and surfaces of the lips (cheilosis).
Suspect riboflavin deficiency in patients with characteristic symptoms and other B vitamin deficiencies; confirm it with a therapeutic trial of riboflavin supplements or measurement of urinary excretion of riboflavin.
Treat with supplement of riboflavin and other water-soluble vitamins.

Does riboflavin interact with other nutrients?
Riboflavin, alongside niacin and zinc, helps our bodies convert vitamin B6 to its active (functional) forms in our bodies.
Having good amounts of these micronutrients in our diets, particularly riboflavin, is important to ensure that our bodies can use vitamin B6 in its functions.

What happens if I have too little riboflavin?
Riboflavin deficiency is rare in developed countries since most people get the recommended amounts for this vitamin from a varied diet.
When it does happen, it often comes alongside other nutrient deficiencies, caused by malnutrition or specific health conditions that prevent our bodies from absorbing nutrients from foods.

Because of this, it’s hard to link a deficiency in riboflavin with specific health effects.
Nevertheless, a lack of riboflavin can cause skin inflammation, a sore throat, sores at the corners of the mouth, swollen and cracked lips and anaemia.
However, these can also be signs of problems other than a riboflavin deficiency.

Digestion and absorption
Riboflavin is present in foods mostly (80–90%) as FAD and FMN cofactors of proteins.
Hydrochloric acid from the stomach readily releases the flavins that are only loosely bound to their proteins.
A small percentage of food flavin is bound to a histidyl-nitrogen or cysteinyl-sulfur and proteolysis results in the release of amino acid-linked 8-alpha-FAD which is biologically inactive.

FMN is dephosphorylated to riboflavin by alkaline phosphatase (EC3.1.3.I) in the small intestine.
FAD is broken up by nucleotide pyrophosphatase (EC3.6.1.9) at the brush border of villous tip cells into AMP and FMN from which riboflavin can then be released.
Some of the riboflavin in plant-derived foods is present as beta-glucoside, which has to be cleaved by a beta-glucosidase (possibly lactase) prior to absorption.

Fractional intestinal absorption of riboflavin and related compounds is high over a large range of intakes (75% of a 20 mg dose) and declines with intakes beyond that.
Riboflavin is absorbed mainly from the jejunum, and only to a much lesser degree from the large intestine.
Uptake proceeds by a rapid process dependent on energy, but not on sodium or proton flux.

At higher concentrations passive diffusion into the enterocyte becomes increasingly relevant.
Retention in the enterocyte does not entail metabolic modification of free riboflavin.
The maximal amount that can be absorbed from a single dose appears to be about 27 mg.

Phosphorylation of free riboflavin by riboflavin kinase (flavokinase, EC2.7.1.26; zinc) to FMN is critical for retaining riboflavin in the enterocyte.
FMN can then be converted to FAD by ATP:FMN adenylyltransferase (FAD synthetase; EC2.7.7.2).
About 60% of absorbed riboflavin is exported as FMN or FAD .
Absorbed riboflavin is not clear whether riboflavin and its metabolites leave the enterocyte by simple diffusion or by another process.

Mechanism of Action
Riboflavin is involved in the metabolism of macronutrients and the production of some other B complex vitamins.
Riboflavin is known to participate in redox reactions in the metabolic pathways through cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), derived from riboflavin, by acting as electron carriers.
Inadequate riboflavin intake would be expected to lead to a disturbance in the intermediate steps of metabolism, with specific functional implications.

Riboflavin is also known for its role as an antioxidant due to its involvement in the regeneration of glutathione, a free radical scavenger.
Additionally, it is involved in growth and development, especially during fetal life, reproduction, and lactation.

Administration
A small amount of riboflavin is present in foods as free riboflavin, a majority as its derivative flavin adenine dinucleotide (FAD), and a smaller amount as flavin mononucleotide (FMN).
A small amount, however, is also produced by the intestinal bacteria.
For the absorption of dietary riboflavin, a prerequisite is converting FAD and FMN to free riboflavin, catalyzed by enzymes called phosphatases in the enterocyte.
Absorption of the vitamin takes place predominantly in the proximal small intestine through a saturable, active, carrier-mediated transport process.

Riboflavin, also known as vitamin B2, is a vitamin found in food and used as a dietary supplement.
As a supplement it is used to prevent and treat riboflavin deficiency and prevent migraines.
Riboflavin may be given by mouth or injection.

Riboflavin is nearly always well tolerated. Normal doses are safe during pregnancy.
Riboflavin is in the vitamin B group. It is required by the body for cellular respiration.
Food sources include eggs, green vegetables, milk, and meat.

Functions and Applications
1. Stimulate growth and cell regeneration;
2. The skin, nails, hair, normal growth;
3. To help eliminate the mouth, lips, tongue inflammation;
4. To enhance visual acuity and reduce eye fatigue;
5. The interaction with other substances to help the carbohydrates, fats, protein metabolism

Bioavailability
A small amount of riboflavin is present in foods as free riboflavin, which is an isoalloxazine ring bound to a ribitol side chain; most is present as the derivative FAD, and a smaller amount occurs as the monophosphorylated form, FMN. FAD and FMN occur predominantly in a non-covalently-bound form to enzymes; flavins that are covalently bound do not appear to be available for absorption.
In contrast with most foodstuffs, milk and eggs contain appreciable quantities of free riboflavin bound to specific binding proteins.
A prerequisite for the absorption of dietary riboflavin is the hydrolysis of FAD and FMN to riboflavin, catalyzed by nonspecific phosphatases in the brush border membranes of enterocytes.
Absorption takes place predominantly in the proximal small intestine through an active, carrier-mediated, saturable transport process that is reported to be linear up to ≈30 mg riboflavin given in a meal .

There is little additional absorption of riboflavin in amounts greater than this.
Urinary excretion increases linearly with increasing intakes in riboflavin-replete subjects, with an absorption half-life of 1.1 h. Initially, free riboflavin is taken up into enterocytes and undergoes ATP-dependent phosphorylation catalyzed by cytosolic flavokinase (EC 2.7.1.26) to form FMN; most of this is further converted to FAD by the FAD-dependent FAD synthetase (EC 2.7.7.2).

Nonspecific phosphatases act on intracellular flavins to permit transport across the basolateral membrane.
Riboflavin may enter the plasma from the small intestine as the free form or as FMN.
Research has indicated that carrier-mediated absorption of riboflavin in the colon might be more important than previously thought.
Riboflavin synthesized by bacterial metabolism in the colon might therefore be a more important source of this vitamin than previously recognized.

Little information is available regarding the relative bioavailability of riboflavin from different food sources.
However, no reports have suggested that the efficiency of absorption of dietary riboflavin is a limiting factor in determining riboflavin status.
The upper limit of the uptake process greatly exceeds usual daily intakes (see the section “Dietary requirements for riboflavin”).

Transport and metabolism
Free riboflavin is transported in the plasma bound both to albumin and to certain immunoglobulins, which will also bind flavin coenzymes.
Other riboflavin binding proteins are specific to pregnancy. Riboflavin binding proteins expressed in fetuses of different species are evidently essential to normal fetal development.
Early classic studies identified a riboflavin binding protein in chicken egg white that is induced by estrogen and is essential to fetal survival.

Further studies in various other species confirmed the presence of similar riboflavin binding proteins in the circulation, which have been ascribed various functions, including placental transport.
Elevated plasma binding of riboflavin has been reported in patients with malignancies, attributable to an elevation in specific immunoglobulins, which may contribute to riboflavin retention in such patients.

Almost all riboflavin in tissues is enzyme bound, such as FAD covalently bound to succinic dehydrogenase (EC 1.3.5.1).
Unbound flavins are relatively labile and are rapidly hydrolyzed to free riboflavin, which diffuses from cells and is excreted.
The intracellular phosphorylation of riboflavin is therefore a form of metabolic trapping key to riboflavin homeostasis.

Intakes of riboflavin in excess of tissue requirements are excreted in the urine as riboflavin or other metabolites, such as 7-hydroxymethylriboflavin (7-α-hydroxyriboflavin) and lumiflavin.
Some urinary metabolites reflect bacterial activity in the gastrointestinal tract as well.

DIETARY REQUIREMENTS FOR RIBOFLAVIN
Balance studies in humans show a clear increase in the urinary excretion of riboflavin as riboflavin intakes increase, with a sharp and continuous rise in excretion at intakes above ≈1 mg/d.
Elderly subjects consuming a riboflavin supplement of 1.7 mg above their habitual intake of 1.8 mg showed a urinary excretion of riboflavin that was twice that of unsupplemented subjects consuming 1.8 mg from the diet alone.
The inflection of the urinary excretion curve is considered to reflect tissue saturation.

Urinary excretion of riboflavin is, however, not a sensitive marker of very low riboflavin intakes, and the preferred method for assessing riboflavin status is stimulation of the FAD-dependent erythrocyte glutathione reductase (EC 1.6.4.2) in vitro.
The results are expressed as an activation coefficient (EGRAC), such that the poorer the riboflavin status the higher the activation coefficient.
Numerous studies have shown the sensitivity of this measurement to riboflavin intakes, especially at daily intakes ≤ 1.0 mg (2, 5).
Such studies have also highlighted the speed with which tissue riboflavin depletion and repletion occur.

Although in experimental riboflavin deficiency FAD is conserved at the expense of free riboflavin, there is no store of riboflavin or its metabolites (ie, no site from which riboflavin can be mobilized in times of low dietary intake).
There is only a small difference between intakes associated with biochemical deficiency (< 0.5 mg) and those associated with tissue saturation (> 1.0 mg) in adults (30).
Current recommended nutrient intakes in the United Kingdom range from 0.4 mg/d in infancy to 1.3 mg/d in adult females.

An increment has been set of 0.3 mg in pregnancy and 0.5 mg during lactation to cover increased tissue synthesis for fetal and maternal development and riboflavin secretion in milk.
These values are similar to recommendations made by the World Health Organization in 1974, the European population reference intake , and the US recommended dietary allowance.

Riboflavin in intermediary metabolism
It is well established that riboflavin participates in a diversity of redox reactions central to human metabolism, through the cofactors FMN and FAD, which act as electron carriers.
Most flavoproteins use FAD as a cofactor. Inadequate intake of riboflavin would therefore be expected to lead to disturbances in steps in intermediary metabolism, with functional implications.
In fact, it is sometimes difficult to trace physiologic and clinical effects of riboflavin deficiency to specific metabolic “blocks.”

Riboflavin deficiency in rats was associated with a dose-response, tissue-specific reduction in succinate oxidoreductase (EC 1.3.99.1; succinate dehydrogenase) activity.
Such an effect may have implications for energy production via oxidative phosphorylation of the electron transport chain.

Steps in the cyclical β oxidation of fatty acids are also dependent on flavins as electron acceptors.
An effect on the β oxidation of fatty acids is thought to be responsible for the altered fatty acid profile in hepatic lipids in severely riboflavin-deficient rats (69, 70), which seems to be independent of the dietary source of lipid.
The most marked effect was an increase in 18:2n−6 and a lowering of 20:4n−6. Similar but less striking differences were observed in plasma, erythrocyte membranes, and kidney.

The influence of riboflavin deficiency on fatty acid profiles may reflect an overall reduction in the β oxidation of fatty acids, while essential fatty acids present in the diet accumulate.
Weanling rats fed a riboflavin-deficient diet rapidly showed impaired oxidation of palmitoyl CoA and stearic, oleic, and linoleic acids (71, 72).
Associated with this is the excretion of various dicarboxylic acids,resulting from microsomal and peroxisomal handling of the fatty acids (73–75).

This scenario has its counterpart in humans with inborn errors of lipid metabolism leading to organic aciduria that is responsive to pharmacologic doses of riboflavin.
Transient riboflavin depletion associated with phototherapy in full-term neonates was not associated with any measurable change in long-chain fatty acid β oxidation.
An elegant stable-isotope approach to measuring fatty acid oxidation in premature infants with riboflavin deficiency also failed to detect any effects of riboflavin supplementation.
It is unknown whether riboflavin deficiency in other human groups is associated with impaired fatty acid oxidation.

Riboflavin deficiency and developmental abnormalities
Early studies of riboflavin deficiency in pregnant animals documented abnormal fetal development with a variety of characteristics.
Diverse skeletal and soft tissue abnormalities are well described in the offspring of rats and mice fed riboflavin-deficient diets.
The importance of riboflavin carrier protein to fetal development has been documented in mice (79) and chickens (21).

Riboflavin deficiency, along with deficiency of other vitamins, has been implicated in the etiology of cleft lip-palate abnormalities in 2 infants born to a woman with malabsorption syndrome (41), although no measurement of riboflavin status was made, so the association remains unconfirmed.
The role of riboflavin in gastrointestinal development is discussed in the section “Riboflavin and gastrointestinal development.”

Riboflavin and hematologic status
Very early studies of riboflavin deficiency in human populations (in which it almost certainly coexisted with other deficiencies) and animals indicated effects of riboflavin on aspects of the hemopoietic system.
Riboflavin-responsive anemia in humans was described by Foy and Kondi (80, 81) in the 1950s, the characteristic features being erythroid hypoplasia and reticulocytopenia.
Further studies in subhuman primates fed a riboflavin-deficient diet showed marked disturbances in the production of red blood cells in the bone marrow and in the kinetics of iron handling (82, 83).

Some of the effects of riboflavin deficiency on the activity of the bone marrow may be mediated by the adrenal cortex, which is both structurally and functionally impaired by riboflavin deficiency (84).
More recent work, however, suggests other mechanisms whereby riboflavin deficiency might interfere with iron handling and thereby influence hematologic status.

Riboflavin, neurodegeneration, and peripheral neuropathy
Symptoms of neurodegeneration and peripheral neuropathy have been documented in several studies of riboflavin deficiency in different species.
Young, rapidly growing chickens fed a riboflavin-depleted diet developed peripheral nerve demyelation (102, 103).

Peripheral nerve demyelination has also been documented in racing pigeons (104) and riboflavin-deficient rats (105). Little information is available regarding the relevance of these observations to humans, although an interesting case of a 2.5-y-old girl with biochemical evidence of moderate riboflavin deficiency has been described.
The child had a range of neurologic abnormalities, with anemia and visual impairment.
With high-dose riboflavin supplementation, the anemia resolved quickly and the neurologic and visual abnormalities resolved over several months.

Riboflavin plays a role in thyroxine metabolism, and riboflavin deficiency may contribute to the pathophysiology of some mental illness via this route.
An early report of personality changes in riboflavin deficiency has not been substantiated .

Riboflavin and cancer
The literature relating riboflavin with cancer is complex.
Some studies indicate that riboflavin deficiency increases the risk of cancer at certain sites, whereas others point to a possible attenuating effect of riboflavin in the presence of some carcinogens and a protective effect of deficiency.

Some carcinogens are metabolized by flavin-dependent enzymes, and in these instances riboflavin may enhance or ameliorate the effects of the carcinogen.
Studies in various animal species have shown that riboflavin deficiency can lead to disruption of the integrity of the epithelium of the esophagus, similar to precancerous lesions in humans (84). Some epidemiologic studies have identified a relation between esophageal cancer and diets low in riboflavin, although not all studies support such a relation.
Combined daily supplements of riboflavin and niacin over 5 y were effective in reducing the incidence of esophageal cancer in Linxian, China, an area with a high prevalence of this type of cancer (116).

Recent work has shown that riboflavin deficiency in rats exposed to hepatocarcinogens leads to increased DNA strand breakage. Induction of repair enzymes, which contribute to the resistance to malignant transformations, was also enhanced in the riboflavin-deficient animals.
High-dose riboflavin supplementation reversed both effects to near-normal values.
Also supportive of a protective role of riboflavin in carcinogenesis is the observation that carcinogen binding to DNA is increased in riboflavin-deficient rats.

Poor riboflavin status has also been implicated as a risk factor for cervical dysplasia, a precursor condition for invasive cervical cancer.
A case-control study of 257 cases of cervical dysplasia and 133 controls showed an increased risk of cervical dysplasia at a riboflavin intake of < 1.2 mg/d, after correction for known risk factors and total energy intake.
There was a significant trend effect.

Riboflavin and cardiovascular diseases
Flavin reductase and dihydroriboflavin
Dihydroriboflavin, produced from riboflavin by NADPH-dependent flavin reductase (EC 1.5.1.30), has been shown to be an efficient reducing agent for heme proteins containing ferric iron and therefore a potential antioxidant.
Interesting work has emerged to indicate that riboflavin might have protective effects against the tissue damage associated with ischemia-reperfusion, probably mediated by flavin reductase and the reduction by dihydroriboflavin of oxidized heme proteins.

All studies so far have been conducted in animal models.
Riboflavin, administered in low concentrations in vivo or to tissues ex vivo, reduced cellular injury in 3 models: ischemia-reperfusion injury in isolated hearts, activated complement-induced lung injury, and brain edema after hypoxia-reoxygenation.
Because of its nontoxicity, riboflavin is an attractive candidate as a reductant of iron in heme proteins for the protection of tissues from oxidative injury.

The potential therapeutic role for this vitamin in this context should be the subject of intense investigation.
Whether riboflavin status might influence recovery from oxidative injury associated with stroke, for example, remains to be established.

Riboflavin as a modulator of homocysteine concentrations
In recent years there has been much interest in the importance of plasma homocysteine as a graded risk factor for cardiovascular disease.
Homocysteine is a thiol-containing amino acid that arises as a product of the metabolism of the essential amino acid methionine.
Homocysteine is not incorporated into protein and therefore its concentration is regulated by the rate of its synthesis and metabolism.
The main determinants of the homocysteine concentration in tissues and consequently in the circulation are genotype and diet.

Homocysteine is metabolized through 2 main routes, transsulfuration, which is vitamin B-6 dependent, and remethylation to methionine, which is folate, vitamin B-12, and riboflavin dependent.
Most attention has been directed toward the importance of folate, which is a strong independent predictor of plasma homocysteine and which has homocysteine-lowering activity.
Supplementary vitamin B-12 has modest homocysteine-lowering effects under certain circumstances (124), whereas reports of the effects of supplementary vitamin B-6 are inconsistent.

Riboflavin has been largely ignored, despite the fact that FAD is a cofactor for methylenetetrahydrofolate reductase (EC 1.7.99.5), which metabolizes folate to the form used in homocysteine methylation.
A common mutation of methylenetetrahydrofolate reductase, (the 677C→T thermolabile variant), for which 5–30% of different populations are reported to be homozygous, is associated with increased plasma homocysteine concentrations (127).
Further evidence for a role of riboflavin in homocysteine homeostasis comes from a report of elevated homocysteine in the skin of riboflavin-deficient rats (128).

Riboflavin status was reported as being a modulator of plasma homocysteine concentrations in healthy adults, especially among subjects homozygous for the common 677C→T mutation.
Riboflavin intake also emerged as a factor influencing plasma total homocysteine in men and women from the Framingham Offspring Cohort.
We recently confirmed a folate-riboflavin interaction in determining plasma homocysteine that is unrelated to genotype.

Riboflavin in vision
Corneal vascularization and corneal opacity have been described in animals fed diets low in riboflavin.
Cataracts have also been described in animals fed riboflavin-deficient diets.
The importance of riboflavin deficiency in the etiology of cataracts in elderly humans is not fully understood.

More recently, it was hypothesized that riboflavin deficiency may be associated with night blindness in some communities and that improving riboflavin status might enhance the improvement in night blindness evoked by vitamin A.
Venkataswamy reported riboflavin-responsive night blindness in India.
Riboflavin-dependent photoreceptors (cryptochromes) identified in the retina are thought to play a role in the process of dark adaptation.

Dietary riboflavin might influence dark adaptation through these photoreceptors, through interaction with vitamin A, or independently.
This is an area that deserves further attention.

Riboflavin is part of the structure of the coenzymes flavin adenine dinucleotide (FAD) and flavin mononucleotide, which participate in oxidation-reduction (redox) reactions in numerous metabolic pathways and in energy production via the mitochondrial respiratory chain.
Riboflavin is stable to heat but is destroyed by light.
Milk, eggs, organ meats, legumes, and mushrooms are rich dietary sources of riboflavin.
Most commercial cereals, flours, and breads are enriched with riboflavin.

Riboflavin Deficiency
The causes of riboflavin deficiency (ariboflavinosis) are mainly related to malnourished and malabsorptive states, including GI infections.
Treatment with some drugs, such as probenecid, phenothiazine, or oral contraceptives (OCs), can also cause the deficiency.
The side chain of the vitamin is photochemically destroyed during phototherapy for hyperbilirubinemia, since it is involved in the photosensitized oxidation of bilirubin to more polar excretable compounds.

Riboflavin (vitamin B2) is a water-soluble vitamin that plays a key role in several important functions of the body.
Among other things, it helps metabolize glucose—the form of sugar that the body uses for energy—and supports the production of healthy red blood cells.
Riboflavin also serves as an antioxidant, preventing free radicals from damaging cells and increasing the risk of many aging-related diseases.

Vitamin B2 is found naturally in many different foods, most of which are common in the American diet.
Because of this, riboflavin deficiency is infrequently seen in the United States.
If riboflavin deficiency does occur, it is usually a result of severe malnutrition or conditions that impair vitamin absorption.

History of a Riboflavin
The name "riboflavin" comes from "ribose" (the sugar whose reduced form, ribitol, forms part of its structure) and "flavin", the ring-moiety which imparts the yellow color to the oxidized molecule (from Latin flavus, "yellow").
The reduced form, which occurs in metabolism along with the oxidized form, appears as orange-yellow needles or crystals.
The earliest reported identification, predating any concept of vitamins as essential nutrients, was by Alexander Wynter Blyth.
In 1897, Blyth isolated a water-soluble component of cows' milk whey, which he named "lactochrome", that fluoresced yellow-green when exposed to light.

In the early 1900s, several research laboratories were investigating constituents of foods, essential to maintain growth in rats. These constituents were initially divided into fat-soluble "vitamine" A and water-soluble "vitamine" B. (The "e" was dropped in 1920.)
Vitamin B was further thought to have two components, a heat-labile substance called B1 and a heat-stable substance called B2.
Vitamin B2 was tentatively identified to be the factor necessary for preventing pellagra, but that was later confirmed to be due to niacin (vitamin B3) deficiency.

The confusion was due to the fact that riboflavin (B2) deficiency causes stomatitis symptoms similar to those seen in pellagra, but without the widespread peripheral skin lesions.
For this reason, early in the history of identifying riboflavin deficiency in humans the condition was sometimes called "pellagra sine pellagra" (pellagra without pellagra).
In 1935, Paul Gyorgy, in collaboration with chemist Richard Kuhn and physician T. Wagner-Jauregg, reported that rats kept on a B2-free diet were unable to gain weight.
Isolation of B2 from yeast revealed the presence of a bright yellow-green fluorescent product that restored normal growth when fed to rats.

The growth restored was directly proportional to the intensity of the fluorescence.
This observation enabled the researchers to develop a rapid chemical bioassay in 1933, and then isolate the factor from egg white, calling it ovoflavin.
The same group then isolated the a similar preparation from whey and called it lactoflavin.
In 1934, Kuhn's group identified the chemical structure of these flavins as identical, settled on "riboflavin" as a name, and were also able to synthesize the vitamin.

Circa 1937, riboflavin was also referred to as "Vitamin G".
In 1938, Richard Kuhn was awarded the Nobel Prize in Chemistry for his work on vitamins, which had included B2 and B6.
In 1939, it was confirmed that riboflavin is essential for human health through a clinical trial conducted by William H. Sebrell and Roy E. Butler.
Women fed a diet low in riboflavin developed stomatitis and other signs of deficiency, which were reversed when treated with synthetic riboflavin.
The symptoms returned when the supplements were stopped.

Synonms:
-Riboflavin
- CAS 83-88-5
- Calbiochem
7,8-dimethyl-10-[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]-2H,3H,4H,10H-benzo[g]pteridine-2,4-dione
-lactoflavin
-ovoflavin
-hepatoflavin
-B-complex vitamin
-vitamin B complex