Matthew Messer
Editor-in-chief
Like other members of the vitamin B group, vitamin B2, also called riboflavin plays an important role in digestion and energy production. Symptoms of vitamin B2 deficiency include fatigue, skin problems, dry throat and lips; growth deceleration can likewise occur in children and teenagers. (1) In general, vitamin B2 deficiency doesn’t lead to such serious complications as low levels of vitamins C or B1, but even a slight deficiency can still negatively affect multiple biological functions.
Vitamin B2’s beneficial qualities are conveyed through two important coenzymes, FMN and FAD. Food tends to contain vitamin B2 in these forms, while vitamin-enriched food, milk, and supplements usually contain free riboflavin. The body must transform all B2 forms into free riboflavin through digestion so it can be absorbed; the body then needs to turn riboflavin back to FMN and FAD.(2)
Riboflavin sources
The best sources of vitamin B2 are liver, almonds, meat, mushrooms, seafish and seafood, dairy products, spinach and eggs.(3) Thankfully, riboflavin is highly heat-resistant, so the thermal treatment of food does not reduce riboflavin content. (6)
Which form is the best?
Food supplements and vitamin enriched food typically contain free riboflavin, which is cheaper and more easily absorbable than more expensive ‘active’ forms.
Active forms are usually marked as riboflavin 5 phosphate on the label, which means FMN. The advantage of plain riboflavin is that unlike FMN, it can be absorbed through passive transport as well, so it can provide sufficient vitamin B2 levels even when one is dealing with digestive issues.(2)
The difference is that riboflavin 5 phosphate needs to be rid of phosphate so it can be absorbed as riboflavin. So its utilisation includes an extra step, even though in the majority of cases it’s not any more effective than plain riboflavin, but it’s much more expensive. (2)
Why else is vitamin B2 important?
Besides supporting metabolism, there’s a good chance that vitamin B2 can render the overly frequent MTHFR mutations irrelevant. (4) MTHFR mutations affect many people; they can increase homocysteine levels in the body, which generates inflammatory processes and an increased risk of cardiovascular problems.(7) This negative effect can only take place if the body’s vitamin B2 supplies are insufficient.
A study found that as little as 1.6 mg of vitamin B2 supplements decreases homocysteine in people with MTHFR polymorphism and vitamin B2 deficiency by a whopping 22%,(5) and those whose riboflavin supply is adequate did not have elevated homocysteine levels, regardless of their MTHFR mutations or folate supply.(13
Vitamin B2 and yellow urine
Many people have noticed that when they start taking a multivitamin or B-complex supplement, the color of their urine changes. This is from riboflavin, which can cause urine to be more yellow than usual. This is completely natural and there is nothing to worry about, as it has no negative effects.
Fun fact
This theory is further supported by the fact that in the United States, where food has been enriched with vitamin B2 for decades, MTHFR mutation does not lead to increased cardiovascular risk, whereas in Europe, where no riboflavin is added to food, the risk is present.(5) Besides folate, supplementing vitamin B2 or consuming vitamin B2 rich food is strongly recommended to people with an MTHFR mutation.
Other beneficial qualities
Insufficient energy producing processes can contribute to the development of migraines. As vitamin B2 has a key role in metabolism, even massive, 400 mg/day doses proved to be a safe and effective treatment for migraines. Several studies proved that this dose can reduce the frequency of migraines by half. (8, 9, 10)
A study published in 2020 discovered that riboflavin supplementation decreases oxidative stress, inflammation in the body, thus, among others, the symptoms of Crohn’s disease. (11) In addition, observational studies took note of a lower risk of colon cancer, which was proportionate to vitamin B2 intake: high dose riboflavin supplements resulted in a 14% risk decrease.
Preventing vitamin B2 deficiency
Vitamin B2 deficiency is easily preventable by consuming the above listed food items several times a week, or taking a daily dose of supplements which contain at least 5 mg of riboflavin. Riboflavin has no documented adverse effects; it’s safe, and, indeed, recommended to use.
[The cover photo of the note shows a champignon. 100 grams contain 0.5 mg of vitamin B2, which provides almost half of the daily requirement.]
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Mosegaard S, Dipace G, Bross P, Carlsen J, Gregersen N, Olsen RKJ. Riboflavin Deficiency-Implications for General Human Health and Inborn Errors of Metabolism. Int J Mol Sci. 2020;21(11):3847. Published 2020 May 28. doi:10.3390/ijms21113847
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Yoshii K, Hosomi K, Sawane K, Kunisawa J. Metabolism of Dietary and Microbial Vitamin B Family in the Regulation of Host Immunity. Front Nutr. 2019;6:48. Published 2019 Apr 17. doi:10.3389/fnut.2019.00048
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https://ods.od.nih.gov/factsheets/Riboflavin-Consumer/
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https://alexleaf.com/supplement-riboflavin-to-fix-the-mthfr-polymorphism/
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McNulty H, Dowey le RC, Strain JJ, Dunne A, Ward M, Molloy AM, McAnena LB, Hughes JP, Hannon-Fletcher M, Scott JM. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation. 2006 Jan 3;113(1):74-80. doi: 10.1161/CIRCULATIONAHA.105.580332. Epub 2005 Dec 27. PMID: 16380544.
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Sheraz MA, Kazi SH, Ahmed S, Anwar Z, Ahmad I. Photo, thermal and chemical degradation of riboflavin. Beilstein J Org Chem. 2014 Aug 26;10:1999-2012. doi: 10.3762/bjoc.10.208. PMID: 25246959; PMCID: PMC4168737.
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Xu B, Kong X, Xu R, Song Y, Liu L, Zhou Z, Gu R, Shi X, Zhao M, Huang X, He M, Fu J, Cai Y, Li P, Cheng X, Wu C, Chen F, Zhang Y, Tang G, Qin X, Wang B, Xue H, Chen Y, Tian Y, Sun N, Cui Y, Hou FF, Li J, Huo Y. Homocysteine and all-cause mortality in hypertensive adults without pre-existing cardiovascular conditions: Effect modification by MTHFR C677T polymorphism. Medicine (Baltimore). 2017 Feb;96(8):e5862. doi: 10.1097/MD.0000000000005862. Erratum in: Medicine (Baltimore). 2017 Jun 02;96(22):e7120. PMID: 28225483; PMCID: PMC5569412.
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Schoenen J, Lenaerts M, Bastings E. High-dose riboflavin as a prophylactic treatment of migraine: results of an open pilot study. Cephalalgia. 1994 Oct;14(5):328-9. doi: 10.1046/j.1468-2982.1994.1405328.x. PMID: 7828189.
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Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology. 1998 Feb;50(2):466-70. doi: 10.1212/wnl.50.2.466. PMID: 9484373.
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Boehnke C, Reuter U, Flach U, Schuh-Hofer S, Einhäupl KM, Arnold G. High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre. Eur J Neurol. 2004 Jul;11(7):475-7. doi: 10.1111/j.1468-1331.2004.00813.x. PMID: 15257686.
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von Martels JZH, Bourgonje AR, Klaassen MAY, Alkhalifah HAA, Sadaghian Sadabad M, Vich Vila A, Gacesa R, Gabriëls RY, Steinert RE, Jansen BH, Bulthuis MLC, van Dullemen HM, Visschedijk MC, Festen EAM, Weersma RK, de Vos P, van Goor H, Faber KN, Harmsen HJM, Dijkstra G. Riboflavin Supplementation in Patients with Crohn's Disease [the RISE-UP study]. J Crohns Colitis. 2020 Jun 19;14(5):595-607. doi: 10.1093/ecco-jcc/jjz208. PMID: 31873717; PMCID: PMC7303596.
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Ben S, Du M, Ma G, Qu J, Zhu L, Chu H, Zhang Z, Wu Y, Gu D, Wang M. Vitamin B2 intake reduces the risk for colorectal cancer: a dose-response analysis. Eur J Nutr. 2019 Jun;58(4):1591-1602. doi: 10.1007/s00394-018-1702-5. Epub 2018 May 9. PMID: 2974460
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García-Minguillán CJ, Fernandez-Ballart JD, Ceruelo S, Ríos L, Bueno O, Berrocal-Zaragoza MI, Molloy AM, Ueland PM, Meyer K, Murphy MM. Riboflavin status modifies the effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms on homocysteine. Genes Nutr. 2014 Nov;9(6):435. doi: 10.1007/s12263-014-0435-1. Epub 2014 Oct 17. PMID: 25322900; PMCID: PMC4235830.