Riboflavin - Vitamin B2

Riboflavin is one of the B vitamins, which are all water soluble. This riboflavin 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.

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

- Birth to 6 months: 0.3 mg
- Infants 7–12 months: 0.4 mg
- Children 1–3 years: 0.5 mg
- Children 4–8 years: 0.6 mg
- Children 9–13 years: 0.9 mg
- Teen boys 14–18 years: 1.3 mg
- Teen girls 14–18 years: 1.0 mg
- Men: 1.3 mg
- Women: 1.1 mg
- Pregnant teens and women: 1.4 mg
- Breastfeeding teens and women: 1.6 mg

2. Upper Intake Level (UL)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. 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.

How harmful is if excess riboflavin?
A toxic level of riboflavin has not been observed from food sources and supplements. The gut can only absorb a limited amount of riboflavin at one time, and an excess is quickly excreted in the urine. Therefore, a Tolerable Upper Intake Level for riboflavin has not been established.

What happen if deficiency in riboflavin?
Riboflavin deficiency is extremely rare in the United States. In addition to inadequate intake, causes of riboflavin deficiency can include endocrine abnormalities (such as thyroid hormone insufficiency) and some diseases. 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. 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. Anemia and cataracts can develop if riboflavin deficiency is severe and prolonged. The earlier changes associated with riboflavin deficiency are easily reversed. However, riboflavin supplements rarely reverse later anatomical changes (such as formation of cataracts).

Who is at risk of riboflavin deficiency?
The following groups are among those most likely to have inadequate riboflavin status.

1. Vegetarian athletesExercise produces stress in the metabolic pathways that use riboflavin. 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. These associations recommend that vegetarian athletes consult a sports dietitian to avoid this potential problem.

2. Pregnant and lactating women and their infantsPregnant 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. Riboflavin deficiency during pregnancy, for example, can increase the risk of preeclampsia. The limited evidence on the benefits of riboflavin supplements during pregnancy in both developed and developing countries is mixed. Riboflavin intakes during pregnancy have a positive association with infant birth weight and length. 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). However, maternal riboflavin intake has no association with the risk of orofacial clefts in infants. 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. In developing countries, in contrast, riboflavin levels in breast milk range from 160 to 220 mcg/L.

3. People who are vegan and/or consume little milkIn 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. Vegans and those who consume little milk in developed countries are also at risk of riboflavin inadequacy.

4. People with riboflavin transporter deficiencyRiboflavin transporter deficiency (formerly known as Brown-Vialetto-Van Laere or Fazio-Londe syndrome) is a rare neurological disorder. It can begin between infancy and young adulthood and is associated with hearing loss, bulbar palsy (a motor-neuron disease), respiratory difficulties, and other symptoms. The disease is caused by mutations in the SLC52A3 or SLC52A2 genes, which encode riboflavin transporters. As a result, these patients cannot properly absorb and transport riboflavin, so they develop riboflavin deficiency. Although no cure exists for riboflavin transporter deficiency, high-dose riboflavin supplementation can be a life-saving treatment in this population, especially when it is initiated soon after symptom onset.

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

1. Migraine headachesMigraine 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.

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. 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.

2. Cancer preventionExperts 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 [48]. 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 age 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 [50]. 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.

Food Sources
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:

- Almonds
- Dairy milk (low-fat milk), yogurt, cheese.
- Fortified cereals, bread, and grain products.
- Some vegetables (such as mushrooms and spinach)
- Eggs, organ meats (such as kidneys and liver), lean beef and pork, chicken breastand, salmon.

Did you know?
Ever wonder why you don’t usually see milk stored in glass bottles anymore? The reason is due to riboflavin. If the vitamin is exposed to too much light, it can be deactivated from its usable form. Therefore milk is now typically sold in cartons or opaque plastic containers to block light.

Compiled and written by Crocus Media