Riboflavin

Riboflavin, also known as vitamin B2, is a vitamin found in food and used as a dietary supplement.[1][3] Food sources include eggs, green vegetables, milk and other dairy product, meat, mushrooms, and almonds.[3] Some countries require its addition to grains.[3][4] As a supplement it is used to prevent and treat riboflavin deficiency and prevent migraines.[1][3] It may be given by mouth or injection.[1]

It is nearly always well tolerated.[1] Normal doses are safe during pregnancy.[1] Riboflavin is in the vitamin B group.[1] It is required by the body for cellular respiration.[1]

Riboflavin was discovered in 1920, isolated in 1933, and first made in 1935.[5] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[6] Riboflavin is available as a generic medication and over the counter.[7] In the United States a month of supplements costs less than 25 USD.[7]

Riboflavin
Riboflavin
Riboflavin-3d-balls
Chemical structure
Clinical data
Trade namesmany
Synonymsvactochrome, lactoflavin, vitamin G[2]
AHFS/Drugs.comMonograph
Pregnancy
category
  • US: A (No risk in human studies) and C[1]
Routes of
administration
by mouth, IM, IV
ATC code
Legal status
Legal status
Pharmacokinetic data
ExcretionUrine
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC17H20N4O6
Molar mass376.369 g·mol−1
3D model (JSmol)

Medical uses

Riboflavin solution
A solution of riboflavin.

Corneal ectasia is a progressive thinning of the cornea; the most common form of this condition is keratoconus. Collagen cross-linking by applying riboflavin topically then shining UV light is a method to slow progression of corneal ectasia by strengthening corneal tissue.[8]

As of 2017 a system is marketed by Terumo in Europe that is used to remove pathogens from blood; donated blood is treated with riboflavin and then with ultraviolet light.[9]

A 2017 review found that riboflavin may be useful to prevent migraines in adults, but found that clinical trials in adolescents and children had produced mixed outcomes.[10]

Side effects

In humans, there is no evidence for riboflavin toxicity produced by excessive intakes, in part because it has lower water solubility than other B vitamins, because absorption becomes less efficient as doses increase, and because what exceeds the absorption is excreted via the kidneys into urine.[11][12] Even when 400 mg of riboflavin per day was given orally to subjects in one study for three months to investigate the efficacy of riboflavin in the prevention of migraine headache, no short-term side effects were reported.[13] Although toxic doses can be administered by injection,[12] any excess at nutritionally relevant doses is excreted in the urine,[14] imparting a bright yellow color when in large quantities. The limited data available on riboflavin’s adverse effects do not mean, however, that high intakes have no adverse effects, and the Food and Nutrition Board urges people to be cautious about consuming excessive amounts of riboflavin.[15]

Function

Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) function as cofactors for a variety of flavoprotein enzyme reactions:

For the molecular mechanism of action see main articles Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD)

Other Flavin derivatives such as N(5)-ethylflavinium ion, Et-Fl+, can oxidize water and produce O2.[16]

Nutrition

United States
Age group (years) RDA for riboflavin (mg/d)[17] Tolerable upper intake level[17]
Infants 0–6 months 0.3* ND
Infants 6–12 months 0.4*
1–3 0.5
4–8 0.6
9–13 0.9
Females 14–18 1.0
Males 14–18 1.3
Females 19+ 1.1
Males 19+ 1.3
Pregnant females 14–50 1.4
Lactating females 14–50 1.6
European Food Safety Authority
Age group (years) Adequate Intake of riboflavin (mg/d)[18] Tolerable upper limit[18]
7–11 months 0.4 ND
1–3 0.6
4–6 0.7
7–10 1.0
11–14 1.4
15–17 1.6
18+
Australia and New Zealand
Age group (years) Adequate Intake of riboflavin (mg/d)[19] Upper level of intake[19]
0–6 months 0.3* ND
7–12 months 0.4*
1–3 0.5
4–8 0.6
9–13 0.9
Females 14–70 1.1
Males 14–70 1.3
Females >70 1.3
Males >70 1.6
Pregnant females 14–50 1.4
Lactating females 14–50 1.6
* Adequate intake for infants, no RDA/RDI yet established[17]

Food sources

Food and beverages that provide riboflavin without fortification are milk, cheese, eggs, leaf vegetables, liver, kidneys, lean meats, legumes, mushrooms, and almonds.[20][15]

The milling of cereals results in considerable loss (up to 60%) of vitamin B2, so white flour is enriched in some countries by addition of the vitamin. The enrichment of bread and ready-to-eat breakfast cereals contributes significantly to the dietary supply of vitamin B2. Polished rice is not usually enriched, because the vitamin’s yellow color would make the rice visually unacceptable to the major rice-consuming populations. However, most of the flavin content of whole brown rice is retained if the rice is steamed (parboiled) prior to milling. This process drives the flavins in the germ and aleurone layers into the endosperm. Free riboflavin is naturally present in foods along with protein-bound FMN and FAD. Bovine milk contains mainly free riboflavin, with a minor contribution from FMN and FAD. In whole milk, 14% of the flavins are bound noncovalently to specific proteins.[21] Milk and yogurt contain some of the highest riboflavin content.[3] Egg white and egg yolk contain specialized riboflavin-binding proteins, which are required for storage of free riboflavin in the egg for use by the developing embryo.

Riboflavin is added to baby foods, breakfast cereals, pastas and vitamin-enriched meal replacement products. It is difficult to incorporate riboflavin into liquid products because it has poor solubility in water, hence the requirement for riboflavin-5'-phosphate (E101a), a more soluble form of riboflavin. Riboflavin is also used as a food coloring and as such is designated in Europe as the E number E101.[22]

Dietary recommendations

The National Academy of Medicine (then the U.S. Institute of Medicine [IOM]) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for riboflavin in 1998. The current EARs for riboflavin for women and men ages 14 and up are 0.9 mg/day and 1.1 mg/day, respectively; the RDAs are 1.1 and 1.3 mg/day, respectively. RDAs are higher than EARs so as to identify amounts that will cover people with higher than average requirements. RDA for pregnancy is 1.4 mg/day. RDA for lactation is 1.6 mg/day. For infants up to 12 months the Adequate Intake (AI) is 0.3–0.4 mg/day. and for children ages 1–13 years the RDA increases with age from 0.5 to 0.9 mg/day. As for safety, the IOM sets Tolerable upper intake levels (ULs) for vitamins and minerals when evidence is sufficient. In the case of riboflavin there is no UL, as there is no human data for adverse effects from high doses. Collectively the EARs, RDAs, AIs and ULs are referred to as Dietary Reference Intakes (DRIs).[11][17]

The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL defined the same as in United States. For women and men ages 15 and older the PRI is set at 1.6 mg/day. PRI for pregnancy is 1.9 mg/day, for lactation 2.0 mg/day. For children ages 1–14 years the PRIs increase with age from 0.6 to 1.4 mg/day. These PRIs are higher than the U.S. RDAs.[23] The EFSA also reviewed the safety question and like the U.S., decided that there was not sufficient information to set an UL.[24]

For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For riboflavin labeling purposes 100% of the Daily Value was 1.7 mg, but as of May 27, 2016 it was revised to 1.3 mg to bring it into agreement with the RDA.[25] A table of the old and new adult Daily Values is provided at Reference Daily Intake. The original deadline to be in compliance was July 28, 2018, but on September 29, 2017 the FDA released a proposed rule that extended the deadline to January 1, 2020 for large companies and January 1, 2021 for small companies.[26]

Deficiency

Signs and symptoms

Mild deficiencies can exceed 50% of the population in Third World countries and in refugee situations. Deficiency is uncommon in the United States and in other countries that have wheat flour, bread, pasta, corn meal or rice enrichment regulations. In the U.S., starting in the 1940s, flour, corn meal and rice have been fortified with B vitamins as a means of restoring some of what is lost in milling, bleaching and other processing. For adults 20 and older, average intake from food and beverages is 1.8 mg/day for women and 2.5 mg/day for men. An estimated 23% consume a riboflavin-containing dietary supplement that provides on average 10 mg. The U.S. Department of Health and Human Services conducts National Health and Nutrition Examination Survey every two years and reports food results in a series of reports referred to as "What We Eat In America." From NHANES 2011–2012, estimates were that 8% of women and 3% of men consumed less than the RDA. When compared to the lower Estimated Average Requirements, fewer than 3% did not achieve the EAR level.

Riboflavin deficiency (also called ariboflavinosis) results in stomatitis including painful red tongue with sore throat, chapped and fissured lips (cheilosis), and inflammation of the corners of the mouth (angular stomatitis). There can be oily scaly skin rashes on the scrotum, vulva, philtrum of the lip, or the nasolabial folds. The eyes can become itchy, watery, bloodshot and sensitive to light.[27] Due to interference with iron absorption, even mild to moderate riboflavin deficiency results in an anemia with normal cell size and normal hemoglobin content (i.e. normochromic normocytic anemia). This is distinct from anemia caused by deficiency of folic acid (B9) or cyanocobalamin (B12), which causes anemia with large blood cells (megaloblastic anemia).[28] Deficiency of riboflavin during pregnancy can result in birth defects including congenital heart defects[29] and limb deformities.[30] Prolonged riboflavin insufficiency is also known to cause degeneration of the liver and nervous system.[15]

The stomatitis symptoms are similar to those seen in pellagra, which is caused by niacin (B3) deficiency. Therefore, riboflavin deficiency is sometimes called "pellagra sine pellagra" (pellagra without pellagra), because it causes stomatitis but not widespread peripheral skin lesions characteristic of niacin deficiency.[27]

Riboflavin deficiency prolongs recovery from malaria,[31] despite preventing growth of plasmodium (the malaria parasite).[32]

Causes

Riboflavin is continuously excreted in the urine of healthy individuals,[33] making deficiency relatively common when dietary intake is insufficient.[33] Riboflavin deficiency is usually found together with other nutrient deficiencies, particularly of other water-soluble vitamins. A deficiency of riboflavin can be primary – poor vitamin sources in one's daily diet – or secondary, which may be a result of conditions that affect absorption in the intestine, the body not being able to use the vitamin, or an increase in the excretion of the vitamin from the body. Subclinical deficiency has also been observed in women taking oral contraceptives, in the elderly, in people with eating disorders, chronic alcoholism and in diseases such as HIV, inflammatory bowel disease, diabetes and chronic heart disease. The Celiac Disease Foundation points out that a gluten-free diet may be low in riboflavin (and other nutrients) as enriched wheat flour and wheat foods (bread, pasta, cereals, etc.) is a major dietary contribution to total riboflavin intake. Phototherapy to treat jaundice in infants can cause increased degradation of riboflavin, leading to deficiency if not monitored closely.

Diagnosis

Overt clinical signs are rarely seen among inhabitants of the developed countries. The assessment of riboflavin status is essential for confirming cases with unspecific symptoms where deficiency is suspected.

  • Glutathione reductase is a nicotinamide adenine dinucleotide phosphate (NADPH) and FAD-dependent enzyme, and the major flavoprotein in erythrocytes. The measurement of the activity coefficient of erythrocyte glutathione reductase (EGR) is the preferred method for assessing riboflavin status.[34] It provides a measure of tissue saturation and long-term riboflavin status. In vitro enzyme activity in terms of activity coefficients (AC) is determined both with and without the addition of FAD to the medium. ACs represent a ratio of the enzyme’s activity with FAD to the enzyme’s activity without FAD. An AC of 1.2 to 1.4, riboflavin status is considered low when FAD is added to stimulate enzyme activity. An AC > 1.4 suggests riboflavin deficiency. On the other hand, if FAD is added and AC is < 1.2, then riboflavin status is considered acceptable.[11] Tillotson and Bashor[35] reported that a decrease in the intakes of riboflavin was associated with increase in EGR AC. In the UK study of Norwich elderly,[36] initial EGR AC values for both males and females were significantly correlated with those measured 2 years later, suggesting that EGR AC may be a reliable measure of long-term biochemical riboflavin status of individuals. These findings are consistent with earlier studies.[37]
  • Experimental balance studies indicate that urinary riboflavin excretion rates increase slowly with increasing intakes, until intake level approach 1.0 mg/d, when tissue saturation occurs. At higher intakes, the rate of excretion increases dramatically.[34] Once intakes of 2.5 mg/d are reached, excretion becomes approximately equal to the rate of absorption[38] At such high intake a significant proportion of the riboflavin intake is not absorbed. If urinary riboflavin excretion is <19 µg/g creatinine (without recent riboflavin intake) or < 40 µg per day are indicative of deficiency.

Treatment

Treatment involves a diet which includes an adequate amount of riboflavin containing foods.[1] Multi-vitamin and mineral dietary supplements often contain 100% of the Daily Value (1.3 mg) for riboflavin, and can be used by persons concerned about an inadequate diet. Over-the-counter dietary supplements are available in the United States with doses as high as 100 mg, but there is no evidence that these high doses have any additional benefit for healthy people.

Other animals

In other animals, riboflavin deficiency results in lack of growth,[39] failure to thrive, and eventual death. Experimental riboflavin deficiency in dogs results in growth failure, weakness, ataxia, and inability to stand. The animals collapse, become comatose, and die. During the deficiency state, dermatitis develops together with hair loss. Other signs include corneal opacity, lenticular cataracts, hemorrhagic adrenals, fatty degeneration of the kidney and liver, and inflammation of the mucous membrane of the gastrointestinal tract.[40] Post-mortem studies in rhesus monkeys fed a riboflavin-deficient diet revealed about one-third the normal amount of riboflavin was present in the liver, which is the main storage organ for riboflavin in mammals.[41] Riboflavin deficiency in birds results in low egg hatch rates.[42]

Chemistry

As a chemical compound, riboflavin is a yellow-orange solid substance with poor solubility in water compared to other B vitamins. Visually, it imparts color to vitamin supplements (and bright yellow color of urine in persons taking it).[1]

Industrial uses

Riboflavinspectra
Fluorescent spectra of riboflavin
RiboflavinSolution
A solution of riboflavin in water (right) is yellow with chartreuse fluorescence under fluorescent room lighting. The beaker prepared at left holds a detergent in water, forming micelles that will show the passage of a visible laser beam.
RiboflavinSolutionAndBlueLaser
A 473 nm 200 mW blue laser beam is directed into the two beakers from the left. The detergent shows the path of the beam by blue scattered light. The light from the riboflavin solution is intense green fluorescence showing along the path of this laser beam.

Because riboflavin is fluorescent under UV light, dilute solutions (0.015–0.025% w/w) are often used to detect leaks or to demonstrate coverage in an industrial system such a chemical blend tank or bioreactor. (See the ASME BPE section on Testing and Inspection for additional details.)

Industrial synthesis

Micrococcus riboflavin
Large cultures of Micrococcus luteus growing on pyridine (left) and succinic acid (right). The yellow pigment being produced in the presence of pyridine is riboflavin.

The industrial scale production of riboflavin using diverse microorganisms, including filamentous fungi such as Ashbya gossypii, Candida famata and Candida flaveri, as well as the bacteria Corynebacterium ammoniagenes and Bacillus subtilis.[43] The latter organism, genetically modified to both increase the production of riboflavin and to introduce an antibiotic (ampicillin) resistance marker, is employed at a commercial scale to produce riboflavin for feed and food fortification. The chemical company BASF has installed a plant in South Korea, which is specialized on riboflavin production using Ashbya gossypii. The concentrations of riboflavin in their modified strain are so high that the mycelium has a reddish/brownish color and accumulates riboflavin crystals in the vacuoles, which will eventually burst the mycelium. Riboflavin is sometimes overproduced, possibly as a protective mechanism, by some bacteria in the presence of high concentrations of hydrocarbons or aromatic compounds. One such organism is Micrococcus luteus (American Type Culture Collection strain number ATCC 49442), which develops a yellow color due to production of riboflavin while growing on pyridine, but not when grown on other substrates, such as succinic acid.[44]

History

Vitamin B was originally considered to have two components, a heat-labile vitamin B1 and a heat-stable vitamin B2.[45] In the 1920s, vitamin B2 was thought to be the factor necessary for preventing pellagra.[45] In 1923, Paul Gyorgy in Heidelberg was investigating egg-white injury in rats;[45] the curative factor for this condition was called vitamin H (which is now called biotin or vitamin B7). Since both pellagra and vitamin H deficiency were associated with dermatitis, Gyorgy decided to test the effect of vitamin B2 on vitamin H deficiency in rats. He enlisted the service of Wagner-Jauregg in Kuhn’s laboratory.[45] In 1933, Kuhn, Gyorgy, and Wagner found that thiamin-free extracts of yeast, liver, or rice bran prevented the growth failure of rats fed a thiamin-supplemented diet.[45]

Further, the researchers noted that a yellow-green fluorescence in each extract promoted rat growth, and that the intensity of fluorescence was proportional to the effect on growth.[45] This observation enabled them to develop a rapid chemical and bioassay to isolate the factor from egg white in 1933.[45] The same group then isolated the same preparation (a growth-promoting compound with yellow-green fluorescence) from whey using the same procedure (lactoflavin). In 1934, Kuhn’s group identified the structure of so-called flavin and synthesized vitamin B2, leading to evidence in 1939 that riboflavin was essential for human health.[45]

Etymology

The name "riboflavin" (often abbreviated to Rbf or RBF)[46][47] comes from "ribose" (the sugar whose reduced form, ribitol, forms part of its structure) and "flavin", the ring-moiety which imparts the yellow color to the oxidized molecule (from Latin flavus, "yellow").[48] The reduced form, which occurs in metabolism along with the oxidized form, is colorless.

See also

References

  1. ^ a b c d e f g h i j "Riboflavin". Drugs.com, The American Society of Health-System Pharmacists. 1 August 2018. Archived from the original on 30 December 2016. Retrieved 7 November 2018.
  2. ^ NIIR Board (2012). The Complete Technology Book on Dairy & Poultry Industries With Farming and Processing (2nd Revised Edition). Niir Project Consultancy Services. p. 412. ISBN 9789381039083.
  3. ^ a b c d e "Riboflavin: Fact Sheet for Health Professionals". Office of Dietary Supplements, US National Institutes of Health. 20 August 2018. Retrieved 7 November 2018.
  4. ^ "Why fortify?". Food Fortification Initiative. 2017. Archived from the original on 4 April 2017. Retrieved 4 April 2017.
  5. ^ Squires, Victor R. (2011). The Role of Food, Agriculture, Forestry and Fisheries in Human Nutrition – Volume IV. EOLSS Publications. p. 121. ISBN 9781848261952.
  6. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
  7. ^ a b Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 230. ISBN 9781284057560.
  8. ^ Mastropasqua L (2015). "Collagen cross-linking: when and how? A review of the state of the art of the technique and new perspectives". Eye and Vision. 2: 19. doi:10.1186/s40662-015-0030-6. PMC 4675057. PMID 26665102.
  9. ^ Yonemura S, Doane S, Keil S, Goodrich R, Pidcoke H, Cardoso M (July 2017). "Improving the safety of whole blood-derived transfusion products with a riboflavin-based pathogen reduction technology". Blood Transfusion = Trasfusione del Sangue. 15 (4): 357–364. doi:10.2450/2017.0320-16. PMC 5490732. PMID 28665269Note: Authored by Terumo employees
  10. ^ Thompson DF, Saluja HS (August 2017). "Prophylaxis of migraine headaches with riboflavin: A systematic review". Journal of Clinical Pharmacy and Therapeutics. 42 (4): 394–403. doi:10.1111/jcpt.12548. PMID 28485121.
  11. ^ a b c Gropper SS, Smith JL, Groff JL (2009). "Ch. 9: Riboflavin". Advanced Nutrition and Human Metabolism (5th ed.). Wadsworth: CENGAG Learning. pp. 329–33. ISBN 9780495116578.
  12. ^ a b Unna K, Greslin JG (1942). "Studies on the toxicity and pharmacology of riboflavin". J Pharmacol Exp Ther. 76 (1): 75–80.
  13. ^ Boehnke C, Reuter U, Flach U, Schuh-Hofer S, Einhäupl KM, Arnold G (July 2004). "High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre". European Journal of Neurology. 11 (7): 475–7. doi:10.1111/j.1468-1331.2004.00813.x. PMID 15257686.
  14. ^ Zempleni J, Galloway JR, McCormick DB (January 1996). "Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans". The American Journal of Clinical Nutrition. 63 (1): 54–66. doi:10.1093/ajcn/63.1.54. PMID 8604671.
  15. ^ a b c Institute of Medicine (1998). Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: The National Academies Press. pp. 35–48. ISBN 978-0-309-06554-2.
  16. ^ Mirzakulova E, Khatmullin R, Walpita J, Corrigan T, Vargas-Barbosa NM, Vyas S, Oottikkal S, Manzer SF, Hadad CM, Glusac KD (October 2012). "Electrode-assisted catalytic water oxidation by a flavin derivative". Nature Chemistry. 4 (10): 794–801. Bibcode:2012NatCh...4..794M. doi:10.1038/nchem.1439. PMID 23000992.
  17. ^ a b c d Institute of Medicine (1998). "Riboflavin". Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: The National Academies Press. pp. 87–122. ISBN 978-0-309-06554-2. Archived from the original on 2015-07-17. Retrieved 2017-08-29.
  18. ^ a b European Food Safety Authority (February 2006). "Tolerable Upper Intake Levels for Vitamins and Minerals" (PDF). EFSA. Retrieved June 18, 2018.
  19. ^ a b "Nutrient reference values for Australia and New Zealand" (PDF). National Health and Medical Research Council. September 9, 2005. Retrieved June 19, 2018.
  20. ^ Higdon J, Drake VJ (2007). "Riboflavin". Micronutrient Information Center. Linus Pauling Institute at Oregon State University. Archived from the original on February 11, 2010. Retrieved December 3, 2009.
  21. ^ Kanno C, Kanehara N, Shirafuji K, Tanji R, Imai T (February 1991). "Binding form of vitamin B2 in bovine milk: its concentration, distribution and binding linkage". Journal of Nutritional Science and Vitaminology. 37 (1): 15–27. doi:10.3177/jnsv.37.15. PMID 1880629.
  22. ^ "Current EU approved additives and their E Numbers". UK Food Standards Agency. July 27, 2007. Archived from the original on October 7, 2010. Retrieved December 3, 2009.
  23. ^ "Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products, Nutrition and Allergies" (PDF). 2017. Archived (PDF) from the original on 2017-08-28.
  24. ^ "Tolerable Upper Intake Levels For Vitamins And Minerals" (PDF). European Food Safety Authority. 2006. Archived (PDF) from the original on 2016-03-16.
  25. ^ "Federal Register May 27, 2016 Food Labeling: Revision of the Nutrition and Supplement Facts Labels. FR page 33982" (PDF). Archived (PDF) from the original on August 8, 2016.
  26. ^ "Changes to the Nutrition Facts Panel – Compliance Date" Archived 2017-03-12 at the Wayback Machine
  27. ^ a b Sebrell WH, Butler RE (1939). "Riboflavin Deficiency in Man (Ariboflavinosis)". Public Health Reports. 54 (48): 2121–2131. doi:10.2307/4583104. JSTOR 4583104.
  28. ^ Lane M, Alfrey CP (Apr 1965). "The Anemia of Human Riboflavin Deficiency". Blood. 25: 432–442. PMID 14284333.
  29. ^ Smedts HP, Rakhshandehroo M, Verkleij-Hagoort AC, de Vries JH, Ottenkamp J, Steegers EA, Steegers-Theunissen RP (Oct 2008). "Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects". European Journal of Nutrition. 47 (7): 357–365. doi:10.1007/s00394-008-0735-6. PMID 18779918.
  30. ^ Robitaille J, Carmichael SL, Shaw GM, Olney RS (Sep 2009). "Maternal nutrient intake and risks for transverse and longitudinal limb deficiencies: data from the National Birth Defects Prevention Study, 1997–2003". Birth Defects Research. Part A, Clinical and Molecular Teratology. 85 (9): 773–779. doi:10.1002/bdra.20587. PMID 19350655.
  31. ^ Das BS, Das DB, Satpathy RN, Patnaik JK, Bose TK (April 1988). "Riboflavin deficiency and severity of malaria". European Journal of Clinical Nutrition. 42 (4): 277–83. PMID 3293996.
  32. ^ Dutta P, Pinto J, Rivlin R (November 1985). "Antimalarial effects of riboflavin deficiency". Lancet. 2 (8463): 1040–3. doi:10.1016/S0140-6736(85)90909-2. PMID 2865519.
  33. ^ a b Brody T (1999). Nutritional Biochemistry. San Diego: Academic Press. ISBN 978-0-12-134836-6. OCLC 162571066.
  34. ^ a b Rosalind, Gibson S. (2005) "Riboflavin" in Principles of Nutritional Assessment, 2nd ed. Oxford University Press.
  35. ^ Tillotson, J. A.; Baker, E. M. (1972). "An enzymatic measurement of the riboflavin status in man". The American Journal of Clinical Nutrition. 25 (4): 425–31. doi:10.1093/ajcn/25.4.425. PMID 4400882.
  36. ^ Bailey AL, Maisey S, Southon S, Wright AJ, Finglas PM, Fulcher RA (Feb 1997). "Relationships between micronutrient intake and biochemical indicators of nutrient adequacy in a "free-living' elderly UK population". The British Journal of Nutrition. 77 (2): 225–42. doi:10.1079/BJN19970026. PMID 9135369.
  37. ^ Rutishauser, I. H.; Bates, C. J.; Paul, A. A.; Black, A. E.; Mandal, A. R.; Patnaik, B. K. (1979). "Long-term vitamin status and dietary intake of healthy elderly subjects. 1. Riboflavin". The British Journal of Nutrition. 42 (1): 33–42. doi:10.1079/BJN19790087. PMID 486392.
  38. ^ Horwitt MK, Harvey CC, Hills OW, Liebert E (June 1950). "Correlation of urinary excretion of riboflavin with dietary intake and symptoms of ariboflavinosis". The Journal of Nutrition. 41 (2): 247–64. doi:10.1093/jn/41.2.247. PMID 15422413.
  39. ^ Patterson BE, Bates CJ (May 1989). "Riboflavin deficiency, metabolic rate and brown adipose tissue function in sucking and weanling rats". The British Journal of Nutrition. 61 (3): 475–483. doi:10.1079/bjn19890137. PMID 2547428.
  40. ^ Sebrell WH, Onstott RH (1938). "Riboflavin Deficiency in Dogs". Public Health Reports. 53 (3): 83–94. doi:10.2307/4582435. JSTOR 4582435.
  41. ^ Waisman HA (1944). "Production of Riboflavin Deficiency in the Monkey". Experimental Biology and Medicine. 55 (1): 69–71. doi:10.3181/00379727-55-14462. Retrieved 2015-02-14.
  42. ^ Romanoff AL, Bauernfeind JC (1942). "Influence of riboflavin-deficiency in eggs on embryonic development (Gallus domesticus)". The Anatomical Record. 82 (1): 11–23. doi:10.1002/ar.1090820103.
  43. ^ Stahmann KP, Revuelta JL, Seulberger H (May 2000). "Three biotechnical processes using Ashbya gossypii, Candida famata, or Bacillus subtilis compete with chemical riboflavin production". Applied Microbiology and Biotechnology. 53 (5): 509–516. doi:10.1007/s002530051649. PMID 10855708.
  44. ^ Sims GK, O'loughlin EJ (Oct 1992). "Riboflavin Production during Growth of Micrococcus luteus on Pyridine". Applied and Environmental Microbiology. 58 (10): 3423–3425. PMC 183117. PMID 16348793.
  45. ^ a b c d e f g h Northrop-Clewes CA, Thurnham DI (2012). "The discovery and characterization of riboflavin". Annals of Nutrition & Metabolism. 61 (3): 224–30. doi:10.1159/000343111. PMID 23183293.
  46. ^ Preedy, Victor R.; Watson, Ronald Ross and Martin, Colin R. eds. (2011) Handbook of Behavior, Food and Nutrition, Springer Science & Business Media. Ch.153, p. 2428, ISBN 9780387922713
  47. ^ Shi Z, Zachara JM, Shi L, Wang Z, Moore DA, Kennedy DW, Fredrickson JK (2012). "Redox reactions of reduced flavin mononucleotide (FMN), riboflavin (RBF), and anthraquinone-2,6-disulfonate (AQDS) with ferrihydrite and lepidocrocite". Environ Sci Technol. 46 (21): 11644–52. Bibcode:2012EnST...4611644S. doi:10.1021/es301544b. PMID 22985396.
  48. ^ "Riboflavin". Online Etymology Dictionary, Douglas Harper. 2018. Retrieved 7 November 2018.

External links

B vitamins

B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism. Though these vitamins share similar names, they are chemically distinct compounds that often coexist in the same foods. In general, dietary supplements containing all eight are referred to as a vitamin B complex. Individual B vitamin supplements are referred to by the specific number or name of each vitamin: B1 = thiamine, B2 = riboflavin, B3 = niacin, etc. Some are better known by name than number: niacin, pantothenic acid, biotin and folate.

Each B vitamin is either a cofactor (generally a coenzyme) for key metabolic processes or is a precursor needed to make one.

Corneal collagen cross-linking

Corneal collagen cross-linking with riboflavin (vitamin B2) and UV-A light is a surgical treatment for corneal ectasia such as keratoconus, PMD, and post-LASIK ectasia.

It is used in an attempt to make the cornea stronger. According to a 2015 Cochrane review, there is insufficient evidence to determine if it is useful in keratoconus. In 2016, the US Food and Drug Administration approved riboflavin ophthalmic solution crosslinking based on three 12-month clinical trials.

FAD-AMP lyase (cyclizing)

In enzymology, a FAD-AMP lyase (cyclizing) (EC 4.6.1.15) is an enzyme that catalyzes the chemical reaction

FAD AMP + riboflavin cyclic-4',5'-phosphate

Hence, this enzyme has one substrate, FAD, and two products, AMP and riboflavin cyclic-4',5'-phosphate.

This enzyme belongs to the family of lyases, specifically the class of phosphorus-oxygen lyases. The systematic name of this enzyme class is FAD AMP-lyase (riboflavin-cyclic-4',5'-phosphate-forming). Other names in common use include FMN cyclase, and FAD AMP-lyase (cyclic-FMN-forming).

Flavin adenine dinucleotide

In biochemistry, flavin adenine dinucleotide (FAD) is a redox-active coenzyme associated with various proteins, which is involved with several important enzymatic reactions in metabolism. A flavoprotein is a protein that contains a flavin group, this may be in the form of FAD or flavin mononucleotide (FMN). There are many flavoproteins besides components of the succinate dehydrogenase complex, including α-ketoglutarate dehydrogenase and a component of the pyruvate dehydrogenase complex; some examples are shown in section 6.

FAD can exist in four different redox states, which are the flavin-N(5)-oxide, quinone, semiquinone, and hydroquinone. FAD is converted between these states by accepting or donating electrons. FAD, in its fully oxidized form, or quinone form, accepts two electrons and two protons to become FADH2 (hydroquinone form). The semiquinone (FADH·) can be formed by either reduction of FAD or oxidation of FADH2 by accepting or donating one electron and one proton, respectively. Some proteins, however, generate and maintain a superoxidized form of the flavin cofactor, the flavin-N(5)-oxide.

Flavin group

Flavin (from Latin flavus, "yellow") is the common name for a group of organic compounds based on pteridine, formed by the tricyclic heterocycle isoalloxazine. The biochemical source is the vitamin riboflavin. The flavin moiety is often attached with an adenosine diphosphate to form flavin adenine dinucleotide (FAD), and, in other circumstances, is found as flavin mononucleotide (or FMN), a phosphorylated form of riboflavin. It is in one or the other of these forms that flavin is present as a prosthetic group in flavoproteins.

The flavin group is capable of undergoing oxidation-reduction reactions, and can accept either one electron in a two-step process or two electrons at once. Reduction is made with the addition of hydrogen atoms to specific nitrogen atoms on the isoalloxazine ring system:

In aqueous solution, flavins are yellow-coloured when oxidized, taking a red colour in the semi-reduced anionic state or blue in the neutral (semiquinone) state, and colourless when totally reduced. The oxidized and reduced forms are in fast equilibrium with the semiquinone (radical) form, shifted against the formation of the radical:

Flox + FlredH2 ⇌ FlH•where Flox is the oxidized flavin, FlredH2 the reduced flavin (upon addition of two hydrogen atoms) and FlH• the semiquinone form (addition of one hydrogen atom).

In the form of FADH2, it is one of the cofactors that can transfer electrons to the electron transfer chain.

Flavin mononucleotide

Flavin mononucleotide (FMN), or riboflavin-5′-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as prosthetic group of various oxidoreductases including NADH dehydrogenase as well as cofactor in biological blue-light photo receptors. During the catalytic cycle, a reversible interconversion of the oxidized (FMN), semiquinone (FMNH•) and reduced (FMNH2) forms occurs in the various oxidoreductases. FMN is a stronger oxidizing agent than NAD and is particularly useful because it can take part in both one- and two-electron transfers. In its role as blue-light photo receptor, (oxidized) FMN stands out from the 'conventional' photo receptors as the signaling state and not an E/Z isomerization.

It is the principal form in which riboflavin is found in cells and tissues. It requires more energy to produce, but is more soluble than riboflavin.

Flavoprotein

Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin: the flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN).

Flavoproteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repair. The flavoproteins are some of the most-studied families of enzymes.

Flavoproteins have either FMN or FAD as a prosthetic group or as a cofactor. The flavin is generally tightly bound (see example adrenodoxin reductase wherein the FAD is deeply buried in the enzyme).

About 5-10% of flavoproteins have a covalently linked FAD. Based on the available structural data, FAD-binding sites can be divided into more than 200 different types.90 flavoproteins are encoded in the human genome; about 84% require FAD, and around 16% require FMN, whereas 5 proteins require both. Flavoproteins are mainly located in the mitochondria. Of all flavoproteins, 90% perform redox reactions and the other 10% are transferases, lyases, isomerases, ligases.

Hoşmerim

Höşmerim is a Turkish dessert popular in the Aegean, Marmara, Trakya and Central Anatolia regions of Turkey. It is sometimes called peynir helva or "cheese halva". It is generally consumed after a meal as a light dessert and may be topped with ice cream, honey or nuts.

Höşmerim has been served for 50–55 years as a commercial product in the markets and pastry shops. However, most of its manufacture occurs on a small scale. Recipes and methods may differ from one region to another. Traditional recipes include fresh unsalted cheese, semolina and powdered sugar. Commercially produced höşmerim may include cream, egg and riboflavin in addition to the traditional ingredients for the homemade varieties.

Kinase

In biochemistry, a kinase is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the substrate gains a phosphate group and the high-energy ATP molecule donates a phosphate group. This transesterification produces a phosphorylated substrate and ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and ADP gains a phosphate group (producing a dephosphorylated substrate and the high energy molecule of ATP). These two processes, phosphorylation and dephosphorylation, occur four times during glycolysis. Kinases are part of the larger family of phosphotransferases. Kinases should not be confused with phosphorylases, which catalyze the addition of inorganic phosphate groups to an acceptor, nor with phosphatases, which remove phosphate groups. The phosphorylation state of a molecule, whether it be a protein, lipid, or carbohydrate, can affect its activity, reactivity, and its ability to bind other molecules. Therefore, kinases are critical in metabolism, cell signalling, protein regulation, cellular transport, secretory processes, and many other cellular pathways, which makes them very important to human physiology.

Max Tishler

Max Tishler (October 30, 1906 – March 18, 1989) was president of Merck Sharp and Dohme Research Laboratories where he led the research teams that synthesized ascorbic acid, riboflavin, cortisone, pyridoxine, pantothenic acid, nicotinamide, methionine, threonine, and tryptophan. He also developed the fermentation processes for actinomycin, vitamin B12, streptomycin, and penicillin. Tishler invented sulfaquinoxaline for the treatment for coccidiosis.

Pathogen reduction using riboflavin and UV light

Pathogen reduction using riboflavin and UV light is a method by which infectious pathogens in blood for transfusion are inactivated by adding riboflavin and irradiating with UV light. This method reduces the infectious levels of disease-causing agents that may be found in donated blood components, while still maintaining good quality blood components for transfusion. This type of approach to increase blood safety is also known as “pathogen inactivation” in the industry.

Despite measures that are in place in the developed world to ensure the safety of blood products for transfusion, a risk of disease transmission still exists. Consequently, the development of pathogen inactivation/reduction technologies for blood products has been an ongoing effort in the field of transfusion medicine. A new procedure for the treatment of individual units of single-donor (apheresis) or whole blood–derived, pooled, platelets has recently been introduced. This technology uses riboflavin and light for the treatment of platelets and plasma.

Paul Gyorgy

Paul György (April 7, 1893 – March 1, 1976) was a Hungarian-born American biochemist, nutritionist, and pediatrician best known for his discovery of three B vitamins: riboflavin, B6, and biotin. Gyorgy was also well known for his research into the protective factors of human breast milk, particularly for his discoveries of Lactobacillus bifidus growth factor activity in human milk and its anti-staphylococcal properties. He was a recipient of the National Medal of Science in 1975 from President Gerald Ford.

Refined grains

Refined grains, in contrast to whole grains, refers to grain products consisting of grains or grain flours that have been significantly modified from their natural composition. The modification process generally involves the mechanical removal of bran and germ, either through grinding or selective sifting. Further refining includes mixing, bleaching, and brominating; additionally, thiamin, riboflavin, niacin, and iron are often added back in to nutritionally enrich the product. Because the added nutrients represent a fraction of the nutrients removed, refined grains are considered nutritionally inferior to whole grains. However, for some grains the removal of fiber coupled with fine grinding results in a slightly higher availability of grain energy for use by the body. Furthermore, in the special case of maize, the process of nixtamalization (a chemical form of refinement) yields a considerable improvement in the bioavailability of niacin, thereby preventing pellagra in diets consisting largely of maize products.

Riboflavin kinase

In enzymology, a riboflavin kinase (EC 2.7.1.26) is an enzyme that catalyzes the chemical reaction

ATP + riboflavin ADP + FMN

Thus, the two substrates of this enzyme are ATP and riboflavin, whereas its two products are ADP and FMN.

Riboflavin is converted into catalytically active cofactors (FAD and FMN) by the actions of riboflavin kinase (EC 2.7.1.26), which converts it into FMN, and FAD synthetase (EC 2.7.7.2), which adenylates FMN to FAD. Eukaryotes usually have two separate enzymes, while most prokaryotes have a single bifunctional protein that can carry out both catalyses, although exceptions occur in both cases. While eukaryotic monofunctional riboflavin kinase is orthologous to the bifunctional prokaryotic enzyme, the monofunctional FAD synthetase differs from its prokaryotic counterpart, and is instead related to the PAPS-reductase family. The bacterial FAD synthetase that is part of the bifunctional enzyme has remote similarity to nucleotidyl transferases and, hence, it may be involved in the adenylylation reaction of FAD synthetases.

This enzyme belongs to the family of transferases, to be specific, those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. The systematic name of this enzyme class is ATP:riboflavin 5'-phosphotransferase. This enzyme is also called flavokinase. This enzyme participates in riboflavin metabolism.

However, archaeal riboflavin kinases (EC 2.7.1.161) in general utilize CTP rather than ATP as the donor nucleotide, catalyzing the reaction

CTP + riboflavin CDP + FMN

Riboflavin kinase can also be isolated from other types of bacteria, all with similar function but a different number of amino acids.

Riboflavin synthase

Riboflavin synthase is an enzyme that catalyzes the final reaction of riboflavin biosynthesis:

(2) 6,7-dimethyl-8-ribityllumazine → riboflavin + 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione

Riboflavinase

In enzymology, a riboflavinase (EC 3.5.99.1) is an enzyme that catalyzes the chemical reaction

riboflavin + H2O ribitol + lumichrome

Thus, the two substrates of this enzyme are riboflavin and H2O, whereas its two products are ribitol and lumichrome.

This enzyme belongs to the family of hydrolases, those acting on carbon-nitrogen bonds other than peptide bonds, specifically in compounds that have not been otherwise categorized within EC number 3.5. The systematic name of this enzyme class is riboflavin hydrolase. This enzyme participates in riboflavin metabolism.

Vitamin

A vitamin is an organic molecule (or related set of molecules) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nutrients cannot be synthesized in the organism, either at all or not in sufficient quantities, and therefore must be obtained through the diet. Vitamin C can be synthesized by some species but not by others; it is not a vitamin in the first instance but is in the second. The term vitamin does not include the three other groups of essential nutrients: minerals, essential fatty acids, and essential amino acids. Most vitamins are not single molecules, but groups of related molecules called vitamers. For example, vitamin E consists of four tocopherols and four tocotrienols. The thirteen vitamins required by human metabolism are: vitamin A (retinols and carotenoids), vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B7 (biotin), vitamin B9 (folic acid or folate), vitamin B12 (cobalamins), vitamin C (ascorbic acid), vitamin D (calciferols), vitamin E (tocopherols and tocotrienols), and vitamin K (quinones).

Vitamins have diverse biochemical functions. Some forms of vitamin A function as regulators of cell and tissue growth and differentiation. The B complex vitamins function as enzyme cofactors (coenzymes) or the precursors for them. Vitamin D has a hormone-like function as a regulator of mineral metabolism for bones and other organs. Vitamins C and E function as antioxidants. Both deficient and excess intake of a vitamin can potentially cause clinically significant illness, although excess intake of water-soluble vitamins is less likely to do so.

Before 1935, the only source of vitamins was from food. If intake of vitamins was lacking, the result was vitamin deficiency and consequent deficiency diseases. Then, commercially produced tablets of yeast-extract vitamin B complex and semi-synthetic vitamin C became available. This was followed in the 1950s by the mass production and marketing of vitamin supplements, including multivitamins, to prevent vitamin deficiencies in the general population. Governments mandated addition of vitamins to staple foods such as flour or milk, referred to as food fortification, to prevent deficiencies. Recommendations for folic acid supplementation during pregnancy reduced risk of infant neural tube defects. Although reducing incidence of vitamin deficiencies clearly has benefits, supplementation is thought to be of little value for healthy people who are consuming a vitamin-adequate diet.The term vitamin is derived from the word vitamine, coined in 1912 by Polish biochemist Casimir Funk, who isolated a complex of micronutrients essential to life, all of which he presumed to be amines. When this presumption was later determined not to be true, the "e" was dropped from the name. All vitamins were discovered (identified) between 1913 and 1948.

Vitamin deficiency

Vitamin deficiency is the condition of a long-term lack of a vitamin. When caused by not enough vitamin intake, it can be classified as a primary deficiency, whereas when due to an underlying disorder such as malabsorption, it is called a secondary deficiency. An underlying disorder may be metabolic – as in a genetic defect for converting tryptophan to niacin – or from lifestyle choices that increase vitamin needs, such as smoking or drinking alcohol. Governments guidelines on vitamin deficiencies advise certain intakes for healthy people, with specific values for women, men, babies, the elderly, and during pregnancy or breastfeeding. Many countries have mandated vitamin food fortification programs to prevent commonly occurring vitamin deficiencies.Conversely hypervitaminosis refers to symptoms caused by vitamin intakes in excess of needs, especially for fat-soluble vitamins that can accumulate in body tissues.The history of the discovery of vitamin deficiencies progressed over centuries from observations that certain conditions – for example, scurvy – could be prevented or treated with certain foods having high content of a necessary vitamin, to the identification and description of specific molecules essential for life and health. During the 20th century, several scientists were awarded the Nobel Prize in Physiology or Medicine or the Nobel Prize in Chemistry for their roles in the discovery of vitamins.

Yam khai dao

Yam khai dao (Thai: ยำไข่ดาว, pronounced [jām kʰàj dāːw], "fried-egg spicy salad") is a Thai dish made out of fried chicken or duck eggs. It is an easy-to-prepare food, but it cannot usually be purchased in restaurants. It is easy to find ingredients which are nutritious that are beneficial to health. It contains many vitamins, such as vitamin B2 (Riboflavin), vitamin B12 and vitamin D.

Fat soluble
Water soluble
Combinations

This page is based on a Wikipedia article written by authors (here).
Text is available under the CC BY-SA 3.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.