Key Takeaways (expand)
- Riboflavin, or vitamin B2, is a B-complex vitamin essential for human health.
- Riboflavin is needed for forming two major coenzymes involved in oxidation-reduction reactions: flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD).
- These coenzymes play important roles in antibody production, skin health, nail health, hair health, and growth and development.
- The enzymes that use FMN or FAD are called flavoproteins, and some of the most important are glutathione peroxidases, xanthine oxidase, and glutathione reductase (which helps protect cells from reactive oxygen species by assisting in the redox cycle of glutathione).
- Like other B vitamins, riboflavin plays a role in energy production: specifically, it serves as a cofactor for enzymes used in the Krebs cycle, including succinate dehydrogenase (which allows for the oxidation of succinate into fumarate in this cycle).
- Through its coenzyme role, riboflavin assists in the metabolism of several other nutrients—including vitamin B6, folate, niacin, and iron.
- Research shows that riboflavin could help prevent cardiovascular disease, due to acting as a cofactor for the MTHFR enzyme; this gives it a role in lowering homocysteine levels and reducing high blood pressure in people with genetically reduced MTHFR activity.
- Riboflavin supplementation could help reduce the severity and frequency of migraine headaches, especially in adults.
- Riboflavin could also have a protective effect against cancer (including colorectal cancer, lung cancer, and breast cancer), due to its impact on MTHFR activity and folate metabolism—both of which play roles in cancer development.
- Some research suggests riboflavin could help prevent the formation of cataracts, though more trials in humans are needed.
- The technical term for riboflavin deficiency is ariboflavinosis, though it rarely happens as an isolated nutrient deficiency; when it does occur, it can produce cracks or sores in the corners of the mouth, an inflamed or red tongue, swelling and redness in the mouth and throat, and reduced red blood cell count.
- During pregnancy, riboflavin deficiency can increase the risk of preeclampsia up to five-fold.
- Great sources of riboflavin include organ meats, leafy green vegetables, mushrooms, eggs, milk, almonds, squash, legumes, and yeast.
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Riboflavin, also known as vitamin B2, was the second vitamin to ever be isolated—although its first observation traces back to 1872, when the English chemist Alexander Wynter Blythe discovered a pigment in milk with a yellow-green fluorescence and named it lactochrome. The word riboflavin comes from a combination of its two component molecules: ribose, a type of sugar, and ‘flavin,’ derived from the Latin word for yellow (flavus). Due to its bright yellow-orange color, riboflavin is sometimes used as a coloring additive in beverages and sweets.
Like other B vitamins, it plays an important role in energy metabolism—breaking down the carbohydrates, fat, and protein we eat for use as fuel (hence why B-complex vitamins are often nicknamed the “energy vitamins!”), as well as neurotransmitter production, cellular function, and a wide variety of organ functions.
Rich sources of riboflavin include organ meat, mushrooms, leafy green vegetables, eggs, milk and other dairy products, almonds, yeast, legumes, and squash. Some foods, like breakfast cereals, are also fortified with riboflavin.
The Biological Roles of Vitamin B2 (Riboflavin)
Riboflavin is essential for forming two major coenzymes that act as electron carriers for oxidation-reduction reactions: flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These coenzymes, in turn, play a huge number of roles within the body, including antibody production, growth and development, skin health, hair health, nail health, and the metabolism of vitamin B6, niacin, and folate. Riboflavin is also essential for the metabolism of steroids, protein, fat, carbohydrates, drugs, and circulating toxins.
Other FAD-dependent enzymes include glutathione reductase (which participates in the redox cycle of glutathione, ultimately playing a role in protecting cells from reactive oxygen species), glutathione peroxidases (which require reduced glutathione in order to break down hydroperoxides), and xanthine oxidase (which catalyzes hypoxanthine and xanthine oxidation to form uric acid—a very effective water-soluble antioxidant in the blood). But, there are a huge number of additional FAD- and FMN-dependent enzymes as well! The enzymes that use FAD or FMN are collectively called flavoproteins.
Like other B vitamins, it also plays an important role in energy metabolism—particularly the second stage of cellular respiration, called the Krebs cycle or citric acid cycle. The Krebs cycle is an incredibly important series of chemical reactions that all aerobic organisms use to generate energy, through an eight-step process taking place in a cell’s mitochondria. During this cycle, acetate (in the form of acetyl CoA) derived from carbohydrates, fat, or protein undergoes a series of redox, dehydration, hydration, and decarboxylation reactions to produce adenosine triphosphate (ATP), the energy currency for all cells—as well as the waste product carbon dioxide, and reduced forms of NADH and FADH2 (which can then be converted into yet more ATP in the last step of the Krebs cycle: oxidative phosphorylation in the electron transport chain). This is complex biochemistry, but the important part here is that there are a whole lot of chemical reactions required to produce energy for our cells, and B vitamins are essential for that process!
Riboflavin’s specific role in energy production is in acting as a cofactor for enzymes used in the Krebs cycle. In particular, FAD is a cofactor for the enzyme succinate dehydrogenase, which catalyzes the oxidation of succinate into fumarate in this cycle.
Interactions with Other Nutrients
Riboflavin also has some important interactions with other micronutrients, due to serving as a precursor for coenzymes that ultimately assist in nutrient metabolism.
For example, the conversion of vitamin B6 to its active form (pyridoxal 5’-phosphate) requires a FMN-dependent enzyme called pyridoxine 5’-phosphate oxidase—making vitamin B6 status somewhat dependent on riboflavin levels in the body. In fact, studies in the elderly have shown that supplementing with riboflavin can help correct low blood levels of vitamin B6, and observationally, indicators of riboflavin status and levels of vitamin B6 are interlinked in the context of normal dietary intake.
On top of that, a FAD-dependent enzyme called kynurenine 3-monooxygenase is required for synthesizing two niacin-containing coenzymes, NAD and NADP; as a result, riboflavin deficiency can decrease the conversion process and ultimately increase the risk of niacin deficiency. FAD is also particularly important for folate metabolism, due to serving as a cofactor for the methylenetetrahydrofolate reductase (MTHFR) enzyme, which is needed for converting folate into its active form—and which, in turn, plays a major role in other processes in the body, including breaking down the cardiovascular disease-associated amino acid homocysteine! (In fact, higher blood levels of riboflavin have been linked to lower blood levels of homocysteine.)
Riboflavin can also alter iron metabolism, likely by reducing iron absorption, impairing iron utilization for hemoglobin synthesis, or increasing the loss of iron in the intestines. Although the exact mechanisms aren’t totally clear, human studies have shown that improving riboflavin status can increase circulating hemoglobin levels, and correcting riboflavin deficiency in people who are also deficient in iron makes their iron-deficiency anemia more responsive to iron therapy.
Vitamin B2 (Riboflavin) in Health and Disease
Riboflavin (vitamin B2) has some promising potential for helping treat or reduce the risk of a number of health conditions. Studies suggest that riboflavin could help protect against cardiovascular disease, particularly in people with impaired MTHFR activity: via its coenzyme role, it can reduce homocysteine levels and lower high blood pressure in these individuals. Some evidence suggests riboflavin could also help treat migraine headaches, protect against the formation of cataracts, and help prevent preeclampsia during pregnancy. Through its involvement in regulating MTHFR activity and folate metabolism, riboflavin may also have some cancer-protective effects, particularly against lung cancer, breast cancer, and colorectal cancer.
Riboflavin and Migraine Headaches
In some studies, riboflavin has been shown to decrease the severity and frequency of migraine headaches in adults—possibly due to the role of impaired mitochondrial oxygen metabolism in migraine development, and riboflavin serving as a precursor to FAD and FMN, which are used by enzymes in the mitochondrial electron transport chain. Riboflavin is also sometimes used for preventing pediatric migraines, although not all trials have confirmed its effectiveness here.
Riboflavin and Cardiovascular Disease
Likewise, riboflavin may have a role in preventing cardiovascular disease (as well as its risk factors): riboflavin can help lower homocysteine levels, due to acting as a cofactor for the MTHFR enzyme, and can also help reduce high blood pressure in people homozygous for the C667T polymorphism of the MTHFR gene (this polymorphism ultimately leads to reduced MTHFR activity). Multiple randomized, placebo-controlled trials have shown that riboflavin supplementation is able to improve hypertension in MTHFR 677T homozygotes, including among people with premature cardiovascular disease and those who had failed to achieve target blood pressure levels despite taking three or more antihypertensive medications.
Riboflavin and Cancer
Via its relationship with MTHFR activity and folate metabolism, riboflavin may also have a protective effect against cancer. Folate deficiency is associated with greater cancer risk, and the MTHFR-mediated conversion of homocysteine to methionine is important for the production of S-adenosylmethionine (SAM), which has been shown to inhibit the growth, invasion, and metastasis of various cancer cells (in part through its role as a methyl donor for transmethylation events). And, in people with colorectal polyps (small clumps of cells that can sometimes progress to colon cancer), combining riboflavin with folic acid supplementation was able to enhance the effect of the folic acid supplement on circulating levels of 5-methyl tetrahydrafolate (5-MeTH4), particularly in C667T carriers—suggesting that in riboflavin can improve the response to folic acid supplementation in people with genetically reduced MTHFR activity.
Additional research in postmenopausal women has shown that individuals in the highest quartile of riboflavin intake (greater than 3.97 mg daily) versus the lowest quartile of intake (less than 1.8 mg daily) had significantly lower risk of developing colorectal cancer; this is particularly interesting, because even the lowest quartile of intake was well above the current RDA for this nutrient! In observational studies, riboflavin also appears weakly protective against lung cancer and breast cancer.
And, riboflavin may be helpful in conjunction with anti-cancer agents: when combined with niacin and coenzyme Q10, riboflavin (at 10 mg per day) was able to prevent the oxidative stress associated with tamoxifen treatment, and in mouse models, combining riboflavin with cisplatin (one of the most effective chemotherapy drugs) led to lower cisplatin-induced DNA damage in the kidneys and liver. More studies, especially in humans, are needed to further understand the interactive effects between riboflavin and anti-cancer drugs.
Riboflavin and Eye Health
Some research suggests that riboflavin could help prevent the formation of cataracts. In multiple case-control observational studies, adults in the highest quintile of riboflavin intake—compared to those in the lowest quintile of intake—were up to 50% less likely to develop age-related cataracts. But, randomized trials are needed to confirm the cause-and-effect component of this relationship!
Riboflavin and Genetic Disorders
Riboflavin supplementation also appears to help patients with metabolic disorders caused by defective FAD-dependent enzymes. For example, a fatty acid metabolism disorder called multiple acyl-CoA dehydrogenase deficiency (or MADD) involves a deficiency of FAD-dependent electron transfer enzymes, and riboflavin supplementation can support clinical improvements in people with this condition. Riboflavin also helps reduce symptoms of acyl-CoA dehydrogenase 9 deficiency (or ACAD9), defective riboflavin transport-associated disorders (which can cause a rare neurodegenerative disorder called Brown-Vialetto-Van Laere syndrome), and riboflavin-responsive trimethylaminuria or “fish odor syndrome” (caused by defective oxidation of trimethylamine, due to deficiency of a liver enzyme called FMO3).
Health Effects of Vitamin B2 (Riboflavin) Deficiency
Riboflavin deficiency is called ariboflavinosis—though due to the way B vitamins naturally cluster together in foods, it’s rare to be riboflavin deficient without also being deficient in other water-soluble vitamins. And while true riboflavin deficiency is uncommon, it can occur during times of malnutrition or malabsorption. Alcoholics are at a higher risk of riboflavin deficiency due to a combination of reduced dietary intake, lower intestinal absorption, and impaired riboflavin utilization within the body, and anorexic patients are also more susceptible to riboflavin (and other B vitamin) deficiencies due to low dietary intake. Hypothyroidism and adrenal insufficiency are known to impair the conversion of riboflavin into its coenzymes, and people with high levels of physical activity (like athletes and laborers) have higher riboflavin requirements that could make them slightly more susceptible to deficiency than people with lower activity levels.
Symptoms of riboflavin deficiency include cracks or sores on the corners of the mouth (called angular cheilitis or angular stomatitis), inflammation or redness of the tongue (called magenta tongue), sore throat, swelling and redness of the mouth and throat, decreased red blood cell count alongside normal hemoglobin levels and normal red blood cell size (called normochromic normocytic anemia), blood vessel formation in the eye’s cornea, and inflamed, scaly skin (called seborrheic dermatitis). Prolonged riboflavin deficiency can also cause more severe symptoms, including the degeneration of the nervous system and liver.
In pregnant people, riboflavin deficiency can increase the risk of preeclampsia—a condition consisting of elevated blood pressure, swelling, and protein in the urine, and which can sometimes progress to eclampsia (characterized by seizures, high risk of bleeding, and potentially death). In fact, one study found that women who were riboflavin deficient were nearly five times more likely to develop preeclampsia than women who had normal riboflavin status. Although the mechanisms linking riboflavin and preeclampsia aren’t fully known, it’s possible that lower intracellular levels of FAD and FMN could lead to mitochondrial dysfunction, cause greater oxidative stress, impair nitric oxide release, and interfere with blood vessel dilation, all contributing to the development of preeclampsia. In addition, carrying the C677T variant of the gene coding for the MTHFR enzyme (which is FAD-dependent) has been linked to a higher risk of preeclampsia, though the link seems to vary amongst different ethnic groups—suggesting that the risks associated with this variant could be modified by dietary factors like riboflavin. In addition, riboflavin deficiency during pregnancy can result in birth defects, such as limb deformities and congenital heart defects.
Riboflavin insufficiency is also linked to increased oxidative stress, and due to its role (via FAD) in helping the enzyme xanthine oxidase form uric acid, can result in reduced xanthine oxidase activity and subsequently lower levels of uric acid in the blood.
How Much Vitamin B2 (Riboflavin) Do We Need?
The recommended dietary allowance (RDA) for riboflavin is based on avoiding deficiency, and is 1.1 mg daily for adult women (1.4 mg daily during pregnancy and 1.6 mg when breastfeeding) and 1.3 mg of riboflavin daily for adult men. No tolerable upper intake level has been determined for riboflavin, and there’s no apparent toxicity even from longer-term high-dose supplementation.
Riboflavin from multivitamins or other dietary supplements is unlikely to cause side effects, due to this nutrient being water-soluble (excess undergoes excretion rather than storage in the body). However, large amounts of riboflavin can cause urine to have an abnormally bright yellow color!
Best Food Sources of Vitamin B2 (Riboflavin)
The following foods have high concentrations of riboflavin, containing at least 50% of the recommended dietary allowance per serving, making them our best food sources of this valuable B-vitamin!
Good Food Sources of Vitamin B2 (Riboflavin)
The following foods are also excellent or good sources of riboflavin, containing at least 10% (and up to 50%) of the daily value per serving.
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