riboflavin

What is Riboflavin

Riboflavin (also called vitamin B2) is one of the B vitamins, which are all water soluble and it’s important for the growth, development, and function of the cells in your body. It also helps turn the food you eat into the energy you need.

More than 90% of dietary riboflavin is in the form of flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN); the remaining 10% is comprised of the free form and glycosides or esters 1), 2). Most riboflavin is absorbed in the proximal small intestine 3). 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 4).

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 5).

Riboflavin is yellow and naturally fluorescent when exposed to ultraviolet light 6). 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 7), 8).

Riboflavin Function

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 9), 10), 11). The conversion of the amino acid tryptophan to niacin (sometimes referred to as vitamin B3) requires FAD 12). 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 13).

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 flavin adenine dinucleotide (FAD) to that without added FAD 14), 15), 16). The most appropriate EGRAC thresholds for indicating normal or abnormal riboflavin status are uncertain 17). 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 18). 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 19).

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) 20). Because the body can store only small amounts of riboflavin, urinary excretion reflects dietary intake until tissues are saturated 21). Total riboflavin excretion in healthy, riboflavin-replete adults is at least 120 mcg/day; a rate of less than 40 mcg/day indicates deficiency 22). This technique is less accurate for reflecting long-term riboflavin status than EGRAC 23), 24). 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 25).

Riboflavin vitamin B2 rich food sources

Riboflavin supplements

Riboflavin is available in many dietary supplements. Multivitamin/multimineral supplements with riboflavin commonly provide 1.7 mg riboflavin (100% of the DV) 26). Supplements containing riboflavin only or B-complex vitamins (that include riboflavin) are also available. In most supplements, riboflavin is in the free form, but some supplements have riboflavin 5’-phosphate.

What are some of the Benefits of Riboflavin on Health

Scientists are studying riboflavin to better understand how it affects health. Here is an example of what this research has shown.

  • Migraine headache

Migraine headaches typically produce intense pulsing or throbbing pain in one area of the head 27). 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 28). Because riboflavin is required for mitochondrial function, researchers are studying the potential use of riboflavin to prevent or treat migraine headaches 29).

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 30). 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 31). 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 32), 33).

The Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society concluded that riboflavin is probably effective for preventing migraine headaches and recommended offering it for this purpose 34). The Canadian Headache Society recommends 400 mg/day riboflavin for migraine headache prevention, noting that although the evidence supporting this recommendation is of low quality, there is some evidence for benefit and side effects (such as discolored urine) are minimal 35).

  • 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 36). 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 37). 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 38). 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 39).

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 40). 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 41).

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.

How much riboflavin do you need ?

The amount of riboflavin you need depends on your age and sex. Average daily recommended amounts are listed below in milligrams (mg).

Intake recommendations for riboflavin and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of the National Academies 42). DRI is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and sex, include:

  • Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals.
  • Adequate Intake (AI): established when evidence is insufficient to develop an RDA; intake at this level is assumed to ensure nutritional adequacy.
  • Estimated Average Requirement (EAR): average daily level of intake estimated to meet the requirements of 50% of healthy individuals. It is usually used to assess the adequacy of nutrient intakes in populations but not individuals.
  • Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects.

Table 1 lists the current RDAs for riboflavin 43). For infants from birth to 12 months, the FNB established an AI for riboflavin that is equivalent to the mean intake of riboflavin in healthy, breastfed infants.

Table 1: Recommended Dietary Allowances (RDAs) for Riboflavin 44)

Life StageRecommended Amount
Birth to 6 months0.3 mg
Infants 7–12 months0.4 mg
Children 1–3 years0.5 mg
Children 4–8 years0.6 mg
Children 9–13 years0.9 mg
Teen boys 14–18 years1.3 mg
Teen girls 14–18 years1.0 mg
Men1.3 mg
Women1.1 mg
Pregnant teens and women1.4 mg
Breastfeeding teens and women1.6 mg

What foods provide riboflavin ?

Foods that are particularly rich in riboflavin include eggs, organ meats (kidneys and liver), lean meats, and milk 45), 46). Green vegetables also contain riboflavin. Grains and cereals are fortified with riboflavin in the United States and many other countries 47). The largest dietary contributors of total riboflavin intake in U.S. men and women are milk and milk drinks, bread and bread products, mixed foods whose main ingredient is meat, ready-to-eat cereals, and mixed foods whose main ingredient is grain 48). The riboflavin in most foods is in the form of FAD, although the main form in eggs and milk is free riboflavin 49).

About 95% of riboflavin in the form of FAD or FMN from food is bioavailable up to a maximum of about 27 mg of riboflavin per meal or dose 50). The bioavailability of free riboflavin is similar to that of FAD and FMN 51), 52). Because riboflavin is soluble in water, about twice as much riboflavin content is lost in cooking water when foods are boiled as when they are prepared in other ways, such as by steaming or microwaving 53).

The U.S. Department of Agriculture’s (USDA’s) Nutrient Database website 54) lists the nutrient content of many foods and provides a comprehensive list of foods containing Riboflavin (vitamin B2) arranged by nutrient content 55) and by food name 56).

Riboflavin is found naturally in some foods and is added to many fortified foods. You can get recommended amounts of riboflavin by eating a variety of foods, including the following:

  • Eggs, organ meats (such as kidneys and liver), lean meats, and low-fat milk
  • Green vegetables (such as asparagus, broccoli, and spinach)
  • Fortified cereals, bread, and grain products

Foods High in Riboflavin (Vitamin B2)

Several food sources of riboflavin are listed in Table 2.

Table 2: Selected Food Sources of Riboflavin

FoodMilligrams
(mg) per
serving
Percent
DV*
Beef liver, pan fried, 3 ounces2.9171
Breakfast cereals, fortified with 100% of the DV for riboflavin, 1 serving1.7100
Oats, instant, fortified, cooked with water, 1 cup1.165
Yogurt, plain, fat free, 1 cup0.635
Milk, 2% fat, 1 cup0.529
Beef, tenderloin steak, boneless, trimmed of fat, grilled, 3 ounces0.424
Clams, mixed species, cooked, moist heat, 3 ounces0.424
Mushrooms, portabella, sliced, grilled, ½ cup0.318
Almonds, dry roasted, 1 ounce0.318
Cheese, Swiss, 3 ounces0.318
Rotisserie chicken, breast meat only, 3 ounces0.212
Egg, whole, scrambled, 1 large0.212
Quinoa, cooked, 1 cup0.212
Bagel, plain, enriched, 1 medium (3½”–4” diameter)0.212
Salmon, pink, canned, 3 ounces0.212
Spinach, raw, 1 cup0.16
Apple, with skin, 1 large0.16
Kidney beans, canned, 1 cup0.16
Macaroni, elbow shaped, whole wheat, cooked, 1 cup0.16
Bread, whole wheat, 1 slice0.16
Cod, Atlantic, cooked, dry heat, 3 ounces0.16
Sunflower seeds, toasted, 1 ounce0.16
Tomatoes, crushed, canned, ½ cup0.16
Rice, white, enriched, long grain, cooked, ½ cup0.16
Rice, brown, long grain, cooked, ½ cup00

*DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration (FDA) to help consumers compare the nutrient contents of products within the context of a total diet. The DV for riboflavin is 1.7 mg for adults and children age 4 and older. Foods providing 20% or more of the DV are considered to be high sources of a nutrient.

[Source 57)]
Foods-Rich-in-Vitamin-B2-Riboflavin

 

Are you getting enough riboflavin ?

Most people in the United States consume the recommended amounts of riboflavin. An analysis of data from the 2003-2006 National Health and Nutrition Examination Survey showed that less than 6% of the U.S. population has an intake of riboflavin from foods and supplements below the Estimated Average Requirement (EAR) 58). An analysis of self-reported data from the 1999–2004 National Health and Nutrition Examination Survey found that intakes of riboflavin were higher in lacto-ovo vegetarians (2.3 mg/day) than nonvegetarians (2.1 mg/day) 59).

Among children and teens, the average daily riboflavin intake from foods is 1.8 mg for ages 2–5 years, 1.9 mg for ages 6–11, and 2.1 mg for ages 12–19 60). In adults, the average daily riboflavin intake from foods is 2.5 mg in men and 1.8 mg in women. The average daily riboflavin intake from foods and supplements in children and teens is 2.1 mg for ages 2–5 years, 2.2 mg for ages 6–11, and 2.3 mg for ages 12–19. In adults aged 20 and older, the average daily riboflavin intake from foods and supplements is 4.5 mg in men and 4.7 mg in women.

Most people in America get enough riboflavin from the foods they eat and deficiencies are very rare. However, certain groups of people are more likely than others to have trouble getting enough riboflavin:

  •  Athletes who are vegetarians (especially strict vegetarians who avoid dairy foods and eggs)
  • Pregnant women and breastfeeding women and their babies
  • People who are vegan
  • People who do not eat dairy foods
  • People with a genetic disorder that causes riboflavin deficiency (such as infantile Brown-Vialetto-Van Laere syndrome)

What happens if you don’t get enough riboflavin ?

You can develop riboflavin deficiency if you don’t get enough riboflavin in the foods you eat, or if you have certain diseases or hormone disorders.

Riboflavin deficiency can cause skin disorders, sores at the corners of your mouth, swollen and cracked lips, hair loss, sore throat, liver disorders, and problems with your reproductive and nervous systems.

Severe, long-term riboflavin deficiency causes a shortage of red blood cells (anemia), which makes you feel weak and tired. It also causes clouding of the lens in your eyes (cataracts), which affects your vision.

Riboflavin Deficiency

Riboflavin deficiency is extremely rare in the United States. Riboflavin deficiency usually occurs with other B vitamin deficiencies. Symptoms and signs include sore throat, lesions of the lips and mucosa of the mouth, glossitis, conjunctivitis, seborrheic dermatitis, and normochromic-normocytic anemia 61).

Causes of Riboflavin Deficiency

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
  • Endocrine abnormalities such as thyroid hormone insufficiency

Symptoms and Signs of Riboflavin Deficiency

People with riboflavin deficiency typically have deficiencies of other nutrients, so some of these signs and symptoms might reflect these other deficiencies. Severe riboflavin deficiency can impair the metabolism of other nutrients, especially other B vitamins, through diminished levels of flavin coenzymes 62). Anemia and cataracts can develop if riboflavin deficiency is severe and prolonged 63).

The signs and symptoms of riboflavin deficiency (also known as ariboflavinosis) include skin disorders, hyperemia (excess blood) and edema of the mouth and throat, angular stomatitis (lesions at the corners of the mouth), cheilosis (swollen, cracked lips), hair loss, reproductive problems, sore throat, itchy and red eyes, and degeneration of the liver and nervous system 64), 65), 66), 67).

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 68).

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.

The earlier changes associated with riboflavin deficiency are easily reversed. However, riboflavin supplements rarely reverse later anatomical changes (such as formation of cataracts) 69).

Diagnosis is usually clinical. Treatment consists of oral or, if needed, IM riboflavin. Riboflavin 5 to 10 mg orally once/day is given until recovery. Other water-soluble vitamins should also be given.

Groups at Risk of Riboflavin Inadequacy

The following groups are among those most likely to have inadequate riboflavin status.

  • Vegetarian athletes

Exercise produces stress in the metabolic pathways that use riboflavin 70). The Academy of Nutrition and Dietetics, Dietitians of Canada, and the American College of Sports Medicine state that vegetarian athletes are at risk of riboflavin deficiency because of their increased need for this nutrient and because some vegetarians exclude all animal products (including milk, yogurt, cheese, and eggs), which tend to be good sources of riboflavin, from their diets 71). These associations recommend that vegetarian athletes consult a sports dietitian to avoid this potential problem.

  • Pregnant and lactating women and their infants

Pregnant or lactating women who rarely consume meats or dairy products (such as those living in developing countries and some vegetarians in the United States) are at risk of riboflavin deficiency, which can have adverse effects on the health of both mothers and their infants 72). Riboflavin deficiency during pregnancy, for example, can increase the risk of preeclampsia (a condition in pregnancy characterized by high blood pressure, sometimes with fluid retention and proteinuria) 73). The limited evidence on the benefits of riboflavin supplements during pregnancy in both developed and developing countries is mixed 74), 75), 76).

Riboflavin intakes during pregnancy have a positive association with infant birth weight and length 77). Infants of mothers with riboflavin deficiency or low dietary intakes (less than 1.2 mg/day) during pregnancy have a higher risk of deficiency and of certain birth defects (such as outflow tract defects of the heart) 78), 79). However, maternal riboflavin intake has no association with the risk of orofacial clefts in infants 80).

In well-nourished women, riboflavin concentrations in breast milk range from 180 to 800 mcg/L and concentrations of riboflavin in breast milk increase over time 81), 82). In developing countries, in contrast, riboflavin levels in breast milk range from 160 to 220 mcg/L 83).

  • People who are vegan and/or consume little milk

In people who eat meat and dairy products, these foods contribute a substantial proportion of riboflavin in the diet. For this reason, people who live in developing countries and have limited intakes of meat and dairy products have an increased risk of riboflavin deficiency 84), 85). Vegans and those who consume little milk in developed countries are also at risk of riboflavin inadequacy 86), 87), 88), 89), 90).

  • People with infantile Brown-Vialetto-Van Laere syndrome

Infantile Brown-Vialetto-Van Laere syndrome is a very rare neurological disorder that can begin at any age and is associated with deafness, bulbar palsy (a motor-neuron disease), and respiratory difficulties 91). The disease is caused by mutations in the SLC52A3 gene, which encodes the intestinal riboflavin transporter. As a result, these patients have riboflavin deficiency. Riboflavin supplementation can be a life-saving treatment in this population.

Health Risks from Excessive Riboflavin

Intakes of riboflavin from food that are many times the RDA have no observable toxicity, possibly because riboflavin’s solubility and capacity to be absorbed in the gastrointestinal tract are limited 92), 93). Because adverse effects from high riboflavin intakes from foods or supplements (400 mg/day for at least 3 months) have not been reported, the FNB did not establish ULs for riboflavin. The limited data available on riboflavin’s adverse effects do not mean, however, that high intakes have no adverse effects, and the FNB urges people to be cautious about consuming excessive amounts of riboflavin 94).

References   [ + ]

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