Riboflavin, also known as vitamin B2, is a vitamin found in food and used as a dietary supplement. As a supplement it is used to prevent and treat riboflavin deficiency and prevent migraines. It may be given by mouth or injection.
|Synonyms||vactochrome, lactoflavin, vitamin G|
|by mouth, IM, IV|
|E number||E101 (colours)|
|Chemical and physical data|
|Molar mass||376.37 g·mol−1|
|3D model (JSmol)|
It is nearly always well tolerated. Normal doses are safe during pregnancy. Riboflavin is in the vitamin B group. It is required by the body for cellular respiration. Food sources include eggs, green vegetables, milk, and meat.
Riboflavin was discovered in 1920, isolated in 1933, and first made in 1935. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Riboflavin is available as a generic medication and over the counter. In the United States a month of supplements costs less than 25 USD. Some countries require its addition to grains.
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.
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 excess is absorbed is excreted via the kidneys into urine. 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. Although toxic doses can be administered by injection, any excess at nutritionally relevant doses is excreted in the urine, imparting a bright yellow color when in large quantities.
Riboflavin functions as a coenzyme, meaning that it is required for enzymes (proteins) to perform normal physiological actions. Specifically, the active forms of riboflavin flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) function as cofactors for a variety of flavoproteine enzyme reactions:
- Flavoproteins of electron transport chain, including FMN in Complex I and FAD in Complex II
- FAD is required for the production of pyridoxic acid from pyridoxal (vitamin B6) by pyridoxine 5'-phosphate oxidase
- The primary coenzyme form of vitamin B6 (pyridoxal phosphate) is FMN dependent
- Oxidation of pyruvate, α-ketoglutarate, and branched-chain amino acids requires FAD in the shared E3 portion of their respective dehydrogenase complexes
- Fatty acyl CoA dehydrogenase requires FAD in fatty acid oxidation
- FAD is required to convert retinol (vitamin A) to retinoic acid via cytosolic retinal dehydrogenase
- Synthesis of an active form of folate (5-methyltetrahydrofolate) from 5,10-methylenetetrahydrofolate by Methylenetetrahydrofolate reductase is FADH2 dependent
- FAD is required to convert tryptophan to niacin (vitamin B3)
- Reduction of the oxidized form of glutathione (GSSG) to its reduced form (GSH) by Glutathione reductase is FAD dependent
The milling of cereals results in considerable loss (up to 60%) of vitamin B2, so white flour is enriched in some countries such as US 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-consumption 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. 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.
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).
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. The EFSA also reviewed the safety question and like the U.S., decided that there was not sufficient information to set as UL.
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. 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.
Signs and symptomsEdit
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. Anyone choosing a gluten-free or low gluten diet should, however, as a precaution take a multi-vitamin/mineral dietary supplement which provides 100% DV for riboflavin and other B vitamins.[according to whom?]
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. 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). Deficiency of riboflavin during pregnancy can result in birth defects including congenital heart defects and limb deformities.
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.
In other animals, riboflavin deficiency results in lack of growth, 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. 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. Riboflavin deficiency in birds results in low egg hatch rates.
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 erythrocyte. The measurement of the activity coefficient of erythrocyte glutathione reductase (EGR) is the preferred method for assessing riboflavin status. 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. Tillotson and Bashor reported that a decrease in the intakes of riboflavin was associated with increase in EGR AC. In the UK study of Norwich elderly, 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.
- 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. Once intakes of 2.5 mg/d are reached, excretion becomes approximately equal to the rate of absorption (Horwitt et al., 1950) (18). 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.
Riboflavin is continuously excreted in the urine of healthy individuals, making deficiency relatively common when dietary intake is insufficient. 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.
Treatment involves a diet which includes an adequate amount of riboflavin containing foods. 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.
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 to the urine of persons taking a lot of it).
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.)
Various biotechnological processes have been developed for industrial scale riboflavin biosynthesis using different microorganisms, including filamentous fungi such as Ashbya gossypii, Candida famata and Candida flaveri, as well as the bacteria Corynebacterium ammoniagenes and Bacillus subtilis. The latter organism has been genetically modified to both increase the bacteria's production of riboflavin and to introduce an antibiotic (ampicillin) resistance marker, and is now successfully employed at a commercial scale to produce riboflavin for feed and food fortification purposes. 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 certain 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.
Vitamin B was originally considered to have two components, a heat-labile vitamin B1 and a heat-stable vitamin B2. In the 1920s, vitamin B2 was thought to be the factor necessary for preventing pellagra. In 1923[chronology citation needed], Paul Gyorgy in Heidelberg was investigating egg-white injury in rats; 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. In 1933,[chronology citation needed] 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.
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. This observation enabled them to develop a rapid chemical and bioassay to isolate the factor from egg white in 1933[chronology citation needed], they called it Ovoflavin. 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[chronology citation needed] Kuhn’s group identified the structure of so-called flavin and synthesized vitamin B2.
The name "riboflavin" (often abbreviated to Rbf or RBF) 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"). The reduced form, which occurs in metabolism along with the oxidized form, is colorless.
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.
- "riboflavin". The American Society of Health-System Pharmacists. Archived from the original on 30 December 2016. Retrieved 8 December 2016.
- Board, NIIR (2012). The Complete Technology Book on Dairy & Poultry Industries With Farming and Processing (2nd Revised Edition). Niir Project Consultancy Services. p. 412. ISBN 9789381039083. Archived from the original on 2016-12-30.
- "Office of Dietary Supplements - Riboflavin". ods.od.nih.gov. 11 February 2016. Archived from the original on 20 December 2016. Retrieved 30 December 2016.
- Squires, Victor R. (2011). The Role of Food, Agriculture, Forestry and Fisheries in Human Nutrition - Volume IV. EOLSS Publications. p. 121. ISBN 9781848261952. Archived from the original on 2016-12-30.
- "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.
- Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 230. ISBN 9781284057560.
- "Why fortify?". Food Fortification Initiative. 2017. Archived from the original on 4 April 2017. Retrieved 4 April 2017.
- 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 (London, England). 2: 19. doi:10.1186/s40662-015-0030-6. PMC . PMID 26665102.
- 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 . PMID 28665269Note: Authored by Terumo employees
- Gropper, SS; Smith, JL; Groff, JL (2009). "Ch. 9: Riboflavin". Advanced Nutrition and Human Metabolism (5th ed.). Wadsworth: CENGAG Learning. pp. 329–33.
- Unna, K; Greslin, JG (1942). "Studies on the toxicity and pharmacology of riboflavin". J Pharmacol Exp Ther. 76 (1): 75–80.
- Boehnke, C; Reuter, U; Flach, U; Schuh-Hofer, S; et al. (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.
- Zempleni J, Galloway JR, McCormick DB (Jan 1996). "Pharmacokinetics of orally and intravenously administered riboflavin in healthy humans". The American Journal of Clinical Nutrition. The American Society for Nutrition. 63 (1): 54–66. PMID 8604671.
- Higdon, Jane; Victoria J. Drake (2007). "Riboflavin". Micronutrient Information Center. Linus Pauling Institute at Oregon State University. Archived from the original on February 11, 2010. Retrieved December 3, 2009.
- Kanno, C., Kanehara, N., Shirafuji, K., and et al. Binding Form of Vitamin B2 in Bovine Milk: its concentration, distribution, and binding linkage, J. Nutr. Sci. Vitaminol., 37, 15, 1991
- "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.
- 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 0-309-06554-2. Archived from the original on 2015-07-17. Retrieved 2017-08-29.
- "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.
- "Tolerable Upper Intake Levels For Vitamins And Minerals" (PDF). European Food Safety Authority. 2006. Archived (PDF) from the original on 2016-03-16.
- "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.
- "Changes to the Nutrition Facts Panel - Compliance Date" Archived 2017-03-12 at the Wayback Machine.
- Sebrell, W. H.; R. E. Butler (1939). "Riboflavin Deficiency in Man (Ariboflavinosis)". Public Health Reports. 54 (48): 2121–2131. doi:10.2307/4583104. ISSN 0094-6214. JSTOR 4583104.
- Lane M, Alfrey CP (Apr 1965). "THE ANEMIA OF HUMAN RIBOFLAVIN DEFICIENCY". Blood. 25: 432–442. PMID 14284333.
- 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.
- 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.
- Das BS, Das DB, Satpathy RN, Patnaik JK, Bose TK (Apr 1988). "Riboflavin deficiency and severity of malaria". European Journal of Clinical Nutrition. 42 (4): 277–283. PMID 3293996.
- Dutta, Purabi; John Pinto; Richard Rivlin (1985). "ANTIMALARIAL EFFECTS OF RIBOFLAVIN DEFICIENCY". The Lancet. Originally published as Volume 2, Issue 8463. 326 (8463): 1040–1043. doi:10.1016/S0140-6736(85)90909-2. ISSN 0140-6736. Retrieved 2015-02-14.
- 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.
- Sebrell, W. H.; R. H. Onstott (1938). "Riboflavin Deficiency in Dogs". Public Health Reports. 53 (3): 83–94. doi:10.2307/4582435. ISSN 0094-6214. JSTOR 4582435.
- Waisman, Harry A. (1944). "Production of Riboflavin Deficiency in the Monkey". Experimental Biology and Medicine. 55 (1): 69–71. doi:10.3181/00379727-55-14462. ISSN 1535-3702. Retrieved 2015-02-14.
- Romanoff, Alexis L.; J. C. Bauernfeind (1942). "Influence of riboflavin-deficiency in eggs on embryonic development (gallus domesticus)". The Anatomical Record. 82 (1): 11–23. doi:10.1002/ar.1090820103. ISSN 1097-0185. Archived from the original on 2015-04-02. Retrieved 2015-02-14.
- 10. Gibson S. Rosalind, Riboflavin in Principles of Nutritional Assessment, 2nd ed. OXFORD university press, 2005
- Tilloston JA, Bashor EM. An enzymatic measurement of the riboflavin status in man. American J. Of Clin. Nutr., 1972; 72:251-261
- 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.
- Rutishauser IHE, Bates CJ, Paul AA, and et al. Long term vitamin status and dietary intake of health elderly subjects. I. Riboflavin. British J. of Nutr., 1979; 42:33-42
- Gibson S. Rosalind, Riboflavin in Principles of Nutritional Assessment, 2nd ed. OXFORD university press, 2005.
- Brody, Tom (1999). Nutritional Biochemistry. San Diego: Academic Press. ISBN 0-12-134836-9. OCLC 162571066.
- 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.
- 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 . PMID 16348793.
- Handbook of Behavior, Food and Nutrition, edited by Victor R. Preedy, Ronald Ross Watson, Colin R. Martin, Springer Science & Business Media, 15 Apr 2011, Ch.153, p.2428, ISBN 9780387922713
- Shi Z, Zachara JM, Shi L, Wang Z, Moore DA, Kennedy DW, Fredrickson JK. "Redox reactions of reduced flavin mononucleotide (FMN), riboflavin (RBF), and anthraquinone-2,6-disulfonate (AQDS) with ferrihydrite and lepidocrocite". Environ Sci Technol. 46: 11644–52. doi:10.1021/es301544b. PMID 22985396.
- 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.
- National Institutes for Health, Riboflavin Fact Sheet for Health Professionals
- Higdon, Jane, "Riboflavin", Micronutrient Information Center, Linus Pauling Institute, Oregon State University