E101 (i): Riboflavin
E101 (ii): Riboflavin-5-sodium phosphate (sometimes called E106)
Vitamin B2, lactoflavin
Foods and beverages that provide unfortified riboflavin include milk, cheese, eggs, leafy vegetables, liver, kidney, lean meat, beans, mushrooms, and almonds.
The milling of grains can cause a large loss of vitamin B 2 (up to 60%), so in some countries, vitamins are added to enrich white flour. Abundant bread and instant breakfast cereals make a significant contribution to the dietary supply of vitamin B 2. Polished rice is usually not rich in vitamins, because the yellow color of vitamins will make the rice visually unacceptable by major rice consumers. However, if the rice is steamed (semi-cooked) before the rice is milled, most of the flavin content of the whole grain of brown rice will be retained. This process drives the flavin in the germ and aleurone layer into the endosperm. Free riboflavin is naturally present in food together with protein-bound FMN and FAD. Milk mainly contains free riboflavin, and a small amount comes from FMN and FAD. In whole milk, 14% of flavin is non-covalently bound to specific proteins. Some riboflavins are highest in milk and yogurt. Egg white and yolk contain special riboflavin binding protein, which is necessary for storing free riboflavin in eggs for use by developing embryos.
Riboflavin is added to baby food, breakfast cereals, pasta, and vitamin-rich meal replacement products. Due to the poor solubility of riboflavin in water, it is difficult to add riboflavin to liquid products, so riboflavin-5'-phosphate (E101a), a more soluble form of riboflavin, is needed. Riboflavin is also used as a food coloring, so it is designated as E number E101 in Europe.
Functions and features:
Yellow food coloring. Not very soluble in water.
Many different products.
Up to 0.5 mg/kg body weight.
In humans, there is no evidence that excessive intake of riboflavin will cause riboflavin toxicity, partly because its water solubility is lower than other B vitamins, because the absorption efficiency decreases with increasing doses, and substances exceeding the absorbed amount are excreted through the kidneys In the urine. Even in a three-month study in which 400 mg of riboflavin was orally administered to subjects every day to study the efficacy of riboflavin in preventing migraines, no short-term side effects were reported. Any excess of nutrition-related doses will be excreted in the urine and will appear bright yellow when used in large quantities. However, the limited data on the adverse effects of riboflavin does not mean that high intakes have no adverse effects. The Food and Nutrition Commission urges people to be cautious about consuming excessive amounts of riboflavin.
None; E101 can be consumed by all religious groups, vegans and vegetarians. Although it can be produced from milk, it is not commercialized.
Signs and symptoms
Mild riboflavin deficiency can exceed 50% of the population in developing countries and in refugee situations. Deficiencies are not common in the United States and other countries with wheat flour, bread, pasta, corn flour or rice enrichment regulations. In the United States, since the 1940s, B vitamins have been added to flour, corn flour and rice to restore some of the vitamins lost during milling, bleaching, and other processing. For adults 20 years and older, the average food and beverage intake for women is 1.8 mg/day, and for men 2.5 mg/day. It is estimated that 23% of people consume dietary supplements that provide an average of 10 mg of riboflavin. The U.S. Department of Health and Human Services conducts a National Health and Nutrition Examination Survey every two years and reports food results in a series of reports entitled "What Do We Eat in the United States". From NHANES 2011-2012, it is estimated that 8% of women and 3% of men consumed less than RDA. Compared to the lower estimated average requirements, less than 3% of people did not reach the EAR level.
Riboflavin deficiency (also called riboflavin disease) can cause stomatitis, including sore throat, chapped and cracked lips (cleft lip), and inflammation of the corners of the mouth (angular stomatitis). An oily scaly rash may appear on the scrotum, vulva, lip or nasolabial fold. The eyes can become itchy, watery, bloodshot and sensitive to light. Due to interference with iron absorption, even mild to moderate riboflavin deficiency can cause anemia with normal cell size and hemoglobin (ie, orthochromatic normocytic anemia). This is different from anemia caused by folic acid (B 9) or cyanocobalamin (B 12) deficiency, which can lead to macrocytic anemia (megaloblastic anemia). Lack of riboflavin during pregnancy can cause birth defects, including congenital heart defects and limb deformities. Long-term riboflavin deficiency is also known to cause liver and nervous system degeneration.
The symptoms of stomatitis are similar to pellagra, and both are caused by niacin (B 3) deficiency. Therefore, riboflavin deficiency is sometimes called "pellagra" (pellagra without pellagra) because it causes stomatitis but does not cause the extensive peripheral skin lesions that are characteristic of niacin deficiency. .
Prolonged recovery from riboflavin deficiency in malaria, despite preventing the growth of Plasmodium (malaria parasite) .
Riboflavin is continuously excreted in the urine of healthy individuals, and deficiency is relatively common when dietary intake is insufficient. Riboflavin deficiency is usually found together with other nutritional deficiencies, especially other water-soluble vitamins. The lack of riboflavin may be the main factor-insufficient vitamin sources in the daily diet-or secondary, which may be due to conditions that affect intestinal absorption, the body's inability to use vitamins, or increased excretion of vitamins from the body.
Subclinical defects have also been observed in women taking oral contraceptives, the elderly, those with eating disorders, chronic alcoholism, and diseases such as HIV, inflammatory bowel disease, diabetes, and chronic heart disease. The Celiac Disease Foundation pointed out that the content of riboflavin (and other nutrients) in a gluten-free diet may be lower because foods rich in wheat flour and wheat (bread, pasta, grains, etc.) are for total riboflavin intake The main dietary contribution of the amount.
Obvious clinical symptoms are rarely seen in residents of developed countries. The assessment of riboflavin status is essential to confirm cases with non-specific symptoms suspected of deficiency.
Glutathione reductase is a nicotinamide adenine dinucleotide phosphate (NADPH) and FAD-dependent enzyme, and is the main flavoprotein in red blood cells. The measurement of erythrocyte glutathione reductase (EGR) activity coefficient is the preferred method for assessing riboflavin status. It provides a measure of tissue saturation and long-term riboflavin status. The in vitro enzyme activity expressed as activity coefficient (AC) is measured with and without FAD added to the medium. ACs represents the ratio of the enzyme activity to the enzyme activity of FAD and the enzyme activity without FAD. When FAD is added to stimulate enzyme activity, AC is 1.2 to 1.4, and the riboflavin state is considered low. AC> 1.4 indicates riboflavin deficiency. On the other hand, if FAD is added and AC <1.2, the riboflavin status is considered acceptable. Tillotson and Bashor reported that the decrease in riboflavin intake was related to the increase in EGR AC. In a British study of the Norwich elderly,  the initial EGR AC values of men and women were significantly correlated with the values measured after 2 years, indicating that EGR AC may be a reliable measure of the individual's long-term biochemical riboflavin status. These findings are consistent with earlier studies.
Experimental balance studies have shown that with the increase in intake, the excretion rate of riboflavin in urine slowly increases until the intake is close to 1.0 mg/d, at which time the tissue is saturated. At higher intakes, the excretion rate increases sharply. Once the intake of 2.5 mg/day is reached, the excretion is approximately equal to the absorption rate. With such a high intake, a large part of the intake of riboflavin is not absorbed. If the excretion of riboflavin in the urine is less than 19 µg/g creatinine (no recent intake of riboflavin) or less than 40 µg/day, a deficiency is indicated.
Multivitamin dietary supplements usually contain 100% of the U.S. daily intake of riboflavin (1.3 mg) and can be used by people who are concerned about dietary insufficiency. Over-the-counter dietary supplements in doses up to 100 mg are available in the United States, but there is no evidence that these high doses have any additional benefits for healthy people .
Corneal dilatation is the gradual thinning of the cornea; the most common form of this condition is keratoconus. Cross-linking of collagen by topical application of riboflavin and then irradiating ultraviolet rays is a way to slow the progression of corneal dilation by strengthening the corneal tissue.
A 2017 review found that taking about 200 to 400 times the recommended dietary intake (RDA) of riboflavin per day may help prevent migraines in adults, but found mixed results in clinical trials in adolescents and children. A hypothesis has been proposed that riboflavin can increase mitochondrial energy production.
The maximum amount of riboflavin that an adult can usually absorb in a single dose is 27 mg. When ingested in excess, they are either not absorbed, or the small amount absorbed is excreted in the urine. After a single oral administration, the biological half-life of a healthy person is approximately 66 to 84 minutes.
Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) act as cofactors for a variety of flavin protease reactions:
- The electron transport chain of flavoprotein, which is included in FMN complex I and FAD in complex II
- FAD is necessary for the production of pyridoxine from pyridoxal (vitamin B 6) by pyridoxine 5'-phosphate oxidase
- The main coenzyme form of vitamin B 6 (pyridoxal phosphate) is FMN dependent
- Oxidized pyruvate, alpha ketoglutarate, and branched chain amino acids are required to share part of the FAD E3 dehydrogenase complex
- Fatty acyl-CoA dehydrogenase requires FAD for fatty acid oxidation
- FAD is required for the conversion of retinol (vitamin A) to retinoic acid by cytosolic retinal dehydrogenase.
- The synthesis of active form of folic acid (5-methyltetrahydrofolate) from 5,10-methylenetetrahydrofolate by methylenetetrahydrofolate reductase is FADH 2-dependent
- Kynurenine 3-monooxygenase requires FAD to convert tryptophan to niacin (vitamin B 3)
- The reduction of oxidized form of glutathione (GSSG) to its reduced form (GSH) by glutathione reductase is FAD-dependent
The National Academy of Medicine (then the Institute of Medicine [IOM]) updated the estimated average requirement (EAR) and recommended dietary intake (RDA) for riboflavin in 1998. The current riboflavin EAR for women and men 14 years and older is 0.9 mg/day and 1.1 mg/day; RDA is 1.1 and 1.3 mg/day, respectively. The RDA is higher than the EAR in order to determine the amount that can cover people above the average requirement. The RDA for pregnancy is 1.4 mg/day. The RDA during lactation is 1.6 mg/day. For infants under 12 months, the Adequate Intake (AI) is 0.3-0.4 mg/day. For children aged 1-13, the RDA increases with age from 0.5 to 0.9 mg/day. As for safety, the IOM sets a tolerable upper limit intake (UL) of vitamins and minerals when the evidence is sufficient. In the case of riboflavin, there is no UL because there are no human data on high-dose side effects. EAR, RDA, AI and UL are collectively referred to as Dietary Reference Intake (DRI).
In the European Food Safety Agency (EFSA), it refers to the collective group for the information of the dietary nutrient reference value of the residents, and the population reference intake (PRI) instead of RDA and average requirement, not EAR. The definitions of AI and UL are the same as in the United States. For women and men 15 years and older, the PRI is set at 1.6 mg/day. The PRI is 1.9 mg/day for pregnancy and 2.0 mg/day during lactation. For children aged 1-14, PRIs increase from 0.6 to 1.4 mg/day with age. These PRIs are higher than the US RDA. EFSA also reviewed safety issues and, like the United States, decided that there was not enough information to set up UL.
For US food and dietary supplement labeling purposes, the quantity in a serving is expressed as a percentage of daily value (%DV). For riboflavin labeling purposes, 100% of the daily value is 1.7 mg, but as of May 27, 2016, it was revised to 1.3 mg to make it consistent with the RDA. Manufacturers with annual food sales of US$10 million or more must comply with the updated labeling regulations by January 1, 2020, and manufacturers with lower food sales must comply by January 1, 2021. The reference daily intake provides a table of old and new adult daily values.
As a compound, riboflavin is an orange-yellow solid substance. Compared with other B vitamins, it has poor solubility in water. Visually, it imparts color to vitamin supplements.