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Vitamin B2 (riboflavin)

Riboflavin has important roles in metabolism and as an antioxidant.

Vitamin B2, or riboflavin, is the key building block for its co-enzymatic forms Flavin adenine dinucleotide (FAD) and Flavin mononucleotide (FMN). These serve as electron carriers in various redox reactions in energy production and metabolic pathways, including carbohydrate, lipid, and protein metabolism; the electron transport chain and various antioxidant functions.Date of preparation: December 2018

Contribution:

 


 

Importance of riboflavin for health

 

Riboflavin (vitamin B2) is the key building block for its co-enzymatic forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which serve as electron carriers in various redox reactions in energy production and metabolic pathways (1, 2):

 

  • Carbohydrate, lipids, and protein metabolism
  • Electron transport (respiratory) chain
  • Metabolism of drugs and toxins (in conjunction with cytochrome P-450)
  • Antioxidant functions (glutathione reductase, glutathione peroxidase, xanthine oxidase)

 

Humans are neither capable of in vivo riboflavin synthesis nor efficient in riboflavin storage, requiring a steady supply through dietary intake (3).

 

Absorption is mainly occurring in the proximal small intestine by an active, carrier-mediated, saturable transport process (2). Riboflavin metabolism is closely regulated by riboflavin status of the individual. Conversion of riboflavin to its co-enzymatic forms occurs within the cellular cytoplasm of many tissues, but mostly in the small intestine, liver, heart, and kidney (4). An ATP-dependent phosphorylation transform riboflavin into FMN, which subsequently is complexed with certain apoenzymes to various flavoproteins. However, most FMN is phosphorylated to FAD, which is therefore the main form of vitamin B2 in body tissue (2, 4). In plasma, riboflavin, FMN, and FAD are found, all associated with plasma proteins such as albumin (5).

 

Milk, dairy products, eggs, and (organ) meat are a major source of dietary riboflavin, but most plant- and animal derived foods contain at least small amounts of this vitamin (1, 6). Approximately 95% of riboflavin in foods is present as FAD and FMN. Its bioavailability (for all vitamers) is estimated to a maximum of 27mg per meal or dose (6). Being a water-soluble vitamin, riboflavin losses are about twice as high when foods are boiled in water compared to other food processing such as steaming or microwaving (6).

 

Nutrient Interactions

 

Vitamin B2 as flavoproteins are involved in the metabolism of several other vitamins, such as niacin, vitamin B6, and folate, but also other nutrients, as listed in Table 1.

 

Table 1: Interactions of riboflavin with other nutrients (1, 2)
 Nutrient Function of riboflavin
 Niacin/Tryptophan  Kynurenine mono-oxygenase (NAD, NADP synthesis from tryptophan)
 Vitamin B6  Pyridoxine 5'-phosphate oxidase (PPO; converts the most naturally available vitamin B6 into its co-enzymatic form, PLP)
 Folate  MTHFR (FAD-dependent enzyme for maintaining a specific folate co-enzyme required for methionine formation from homocysteine)
 Vitamin B12  Methionine synthase (FAD-dependent; synthesis of methyl-cobalamin)
 Iron  Riboflavin may impait iron absorption, increase intestinal loss of iron, or impair iron utilization for haemoglobin sythesis

MTHFR: 5,10-methylene-tetrahydrofolate reductase; PLP: pyridoxal 5’-phosphate;

 

Risks

Clinical riboflavin deficiency is called ariboflavinosis and is usually found in combination with other deficiencies of other water-soluble vitamins due to decreasing levels of flavin co-enzymes. Signs of deficiency include endocrine abnormalities, skin disorders, hyperaemia and oedema of the mouth and throat, angular stomatitis, cheilosis, hair loss, reproductive problems, sore throat, itchy and red eyes, and degeneration of liver and nervous system. In severe and prolonged states of deficiency, anaemia and cataracts can occur. Riboflavin deficiency has also been associated with preeclampsia in pregnant women (1, 4, 6).

Groups at particular risk for riboflavin deficiency include vegetarian athletes due to increased stress in the riboflavin-dependent metabolic pathways, pregnant and lactation women and their infants, vegans, alcoholics or anorexic individuals (1, 6). However, riboflavin supplementation may positively affect migraine headaches and may aid in the prevention of DNA damage caused by carcinogens (6).

There is no evidence of adverse effects of excess riboflavin intake. However, given the little data available, the Food and Nutrition Board advises to be cautious about excess riboflavin consumption since adverse effects may still occur. High-dose riboflavin therapy can intensify the yellow colour of urine, which is a harmless side-effect (1, 6).

Key info

Keywords: riboflavin, flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), redox reactions, energy production, cellular function, erythrocyte glutathione reductase activity, ariboflavinosis

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