Exploring the Role of Riboflavin: A Comprehensive Review
“Riboflavin fuels energy, cellular metabolism, and fights off diseases, potentially preventing migraines and cardiovascular risks”
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Introduction
Riboflavin, also known as vitamin B2, is an essential vitamin that is required for various physiological functions in the human body[1,2,3,4]. It is one of the eight B vitamins essential for converting food into energy and maintaining overall health[5,6,7].
Riboflavin is commonly found in a variety of foods and riboflavin deficiency is uncommon in most parts of the world, but it remains a global health concern, particularly in regions with limited dietary preferences [8,9]. This article provides a general understanding of riboflavin, including its biochemical properties, dietary sources, metabolic pathways, physiological functions, deficiency consequences, and potential applications.
Science of Vitamin B2 (Riboflavin)
Riboflavin is a water-soluble vitamin. In humans, riboflavin primarily exists in two active forms: flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD)[4,10]. Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) both play vital roles as cofactors in numerous enzymatic reactions involved in cellular metabolism including energy production[3,9].
Humans cannot synthesize riboflavin internally; instead, it must be obtained from external sources such as food or supplements[11,12]. However, a small amount of free riboflavin is produced by bacteria in large intestine[4,13,7].
The absorption of riboflavin primarily occurs in the small intestine, specifically in the jejunum and ileum. Once absorbed, through blood riboflavin is distributed to various tissues and organs throughout the body[14,15].
Riboflavin, being water-soluble, is not extensively stored in significant amounts in the human body. However, the body does store small amount of riboflavin in liver, heart and kidney[4]. The half-life of riboflavin, which is the time it takes for half of the substance to be eliminated from the body, is relatively short, estimated to be 1.4 to 44 hours[16]. This means that within hours to a few days, the majority of riboflavin you consume will have been excreted in urine[17]. Because of its high elimination and low retention, especially at high doses, and no specialized storage organ, a consistent dietary replenishment of Riboflavin is crucial for maintaining sustained levels in the body.
Riboflavin is relatively stable at low to moderate temperatures. However, prolonged exposure to high heat can lead to degradation. Riboflavin is sensitive to light, particularly ultraviolet (UV) light. Foods rich in riboflavin, like milk, when exposed to sunlight or fluorescent light for extended periods, may experience degradation[18].
Health Benefits
Essential for Energy Production (ATP synthesis)
Riboflavin is essential for maintaining optimal energy levels in the body. Riboflavin is an essential component flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), two coenzymes that are particularly related to the production of adenosine triphosphate (ATP), the primary energy molecules required by the body to do work[2,3,7]. Its deficiency can lead to decreased energy production[8]. Ensuring an adequate intake of riboflavin is important for supporting energy synthesis and overall health.
Essential for Metabolism of Carbohydrates and Lipids
Carbohydrates and lipids are the main source of energy for the human body. Riboflavin is involved in the metabolism of carbohydrates and lipids through its role as a precursor FMN and FAD. It helps our bodies to break down these food molecules into a form that can be used for energy synthesis[6,9,14].
Essential for Synthesis Other Vitamins
Riboflavin, as flavin coenzymes, are involved in the synthesis of three different B-vitamins: niacin (B3), pyridoxine (B6), folic acid (B9), and vitamin K, and vitamin D[9,19,20,21,22,23].
Riboflavin has Antioxidant Properties
During the metabolism highly reactive and unstable molecules or atoms, known as free radicals, are generated that have the tendency to interfere in life sustaining reactions, develop oxidative stress and cause harm to the cells[24,25]. Riboflavin is natural antioxidants that play a pivotal role in relieving cells from oxidative stress[26,27].
Riboflavin and Homocysteine
Riboflavin is crucial in the conversion of homocysteine to methionine, a process that helps regulate homocysteine levels in the body[6]. Maintaining adequate riboflavin levels is important for supporting normal homocysteine metabolism and preventing hyperhomocysteinemia (elevated homocysteine levels in the blood), a condition associated with increased risk of cardiovascular disease and other health problems[9,28].
Other Health Effects of Riboflavin
Riboflavin plays a role in hemoglobin synthesis (erythropoiesis), including iron absorption or iron mobilization from iron reserves in human body[6,9]. Research have shown that riboflavin deficiency is associated with increased risk of anemias[7,29].
A National health and nutrition examination survey study suggest that a higher riboflavin intake was associated with lower cardiovascular mortality[30].
Riboflavin has been studied for its potential role in migraine prevention. Some research and clinical trials suggests that riboflavin supplementation may help reduce the frequency and severity of migraine headaches[31,32,33,34].
A number of studies suggest that Riboflavin may have beneficial effect in the case of hypertension[7,19,35], cornea (eye) health[6,19,36], multiple sclerosis[37,38,39], caner[4,6,19,40]. However, data on the relationship between riboflavin and treatment of these conditions are limited and often contradictory with other studies[4,19]. Further research, including clinical trials, are warranted to understand the role of riboflavin supplements in elevating or reducing the risk associated with these conditions.
Riboflavin deficiency can lead to various health consequences, like inflammation and cracking of the corners of the mouth (cheilosis), inflammation or swelling of the tongue (glossitis), and chronic inflammatory skin condition that primarily affects areas rich in sebaceous glands, such as the scalp, and face (seborrheic dermatitis)[41].
Dietary Sources of Riboflavin
Since the human body cannot synthesize Riboflavin in sufficient quantities, it must be obtained through dietary sources. Both plant and animal foods serve as potent sources for replenishing riboflavin levels in our bodies. However, plants-based diet are more potent in providing riboflavin than animals-based diets. FoodData Central of The U.S. Department of Agriculture’s (USDA’s) provides a comprehensive list of foods containing riboflavin[42]. Some of the most common food rich in Vitamin Riboflavin are,
Animal-Based Sources of Riboflavin
Meat: Lean meats such as beef, pork, and lamb are good sources of riboflavin. Organ meats like liver are particularly rich in this vitamin. Chicken and turkey are also good sources of riboflavin. Various types of fish, including salmon, trout, mackerel, and tuna, contain riboflavin[2,16,43].
Dairy Products and eggs: Milk, yogurt, and cheese are excellent sources of riboflavin[18,45]. Both the egg white and yolk contain riboflavin, making eggs a nutritious source of this vitamin[46,47].
Plant-Based Sources of Riboflavin
Leafy Green Vegetables: Spinach, kale, and other leafy greens contain riboflavin, along with other essential nutrients[48,49].
Nuts and Seeds: Almonds, sunflower seeds, and peanuts are examples of nuts and seeds that provide riboflavin along with healthy fats and protein[50].
Fortified Foods: Some processed foods, such as breakfast cereals, energy bars, and nutritional supplements, are fortified with riboflavin to enhance their nutritional value.
Dietary Supplement as Sources of Riboflavin
It's important to note that riboflavin is water-soluble with a very short half-life and its retention if body is limited. Riboflavin supplements are available for those who may have difficulty meeting their requirements through diet alone[7,51].
Recommended Dosage
According to the intake recommendations by Food and Nutrition Board (FNB) at National Academies, the Recommended Dietary Allowance (RDA) for riboflavin varies based on factors such as age, sex, and life stage[4,5]. For most adults (19+), 1.3 and 1.1. milligrams per day is recommended for male and females, respectively. Pregnant and breastfeeding women have slightly higher RDAs (1.4 to 1.6 mg/day)[4,5]. For kids aged 1 to 18 years, the RDA ranges from 0.5 to 0.9 mg/day.
It's important to note that riboflavin is water-soluble and not stored in the body for extended periods. Thus, to prevent ariboflavinosis (riboflavin deficiency), a consistent daily intake is necessary to maintain adequate levels[2,3,4].
Riboflavin supplementation is generally safe and well-tolerated within recommended levels. The maximum daily intake or Upper Tolerable Limit (UL) for riboflavin were not derived[5]. Even at high amount, far above recommended doses, it is considered safe and is unlikely to pose any risk of adverse health effects for almost all individuals in the general population as excess riboflavin is typically excreted in urine[9]. It's advisable to consult with a healthcare provider before initiating high-dose supplementation, particularly if there are concerns about potential interactions with medications or existing health conditions.
Recommendations
In conclusion, riboflavin plays a fundamental role in various physiological processes essential for human health. Adequate intake of riboflavin-rich foods or though supplements is crucial for preventing deficiency and maintaining optimal health. Furthermore, ongoing research continues to uncover the therapeutic potential of riboflavin in preventing and managing various diseases, underscoring its importance in promoting overall well-being.
References
- Massey V (2000) The chemical and biological versatility of riboflavin. Biochem Soc Trans, 28:283-296.
- Said HM, Ross AC (2014) Riboflavin. In AC Ross, B Caballero, RJ Cousins, KL Tucker, TR Ziegler (eds), Modern nutrition in health and disease -11th ed. Lippincott Williams & Wilkins, Baltimore, MD, pp 325-330.
- Rivlin R (2012) Riboflavin. Springer Science & Business Media.
- NIH (2024) U.S. Department of Health and Human Services. Vitamin B2 Fact Sheet for Health Professionals. https://ods.od.nih.gov/factsheets/Riboflavin-HealthProfessional/. Accessed 04/21/2024.
- Institute of Medicine (1998) Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press.
- Powers HJ (2003) Riboflavin (vitamin B-2) and health. Am J Clinic Nutri, 77:1352-1360.
- Thakur K, Tomar SK, Singh AK, Mandal S, Arora S (2017) Riboflavin and health: A review of recent human research. Critical Rev. Food Sci Nutri, 57:3650-3660.
- McNulty H, Pentieva K, Ward M (2023) Causes and Clinical Sequelae of Riboflavin Deficiency. Ann Rev Nutri, 43:101-122.
- Pinto J, Rivlin R (2013) Riboflavin (vitamin B2). Handbook of vitamins, 5:191-266.
- Northrop-Clewes CA, Thurnham DI (2012) The discovery and characterization of riboflavin. Ann Nutri Metab 61:224–230.
- Bacher A, Eberhardt S, Fischer M, Kis K, Richter G (2000) Biosynthesis of vitamin b2 (riboflavin). Ann Rev Nutri, 20:153-167.
- Schwechheimer SK, Park EY, Revuelta JL, Becker J, Wittmann C (2016) Biotechnology of riboflavin. App Microbiol Biotech, 100:2107-2119.
- LeBlanc JG, Milani C, de Giori GS, Sesma F, van Sinderen D, Ventura M (2013) Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotech 24:16-168.
- Barile M, Giancaspero TA, Leone P, Galluccio M, Indiveri C (2016) Riboflavin transport and metabolism in humans. J Inherited Metabol Disease, 39:545-557.
- Merrill Jr AH, McCormick DB (2020) Riboflavin. In Present Knowledge in Nutrition, Academic Press, pp. 189-207
- McCormick DB (2014) Riboflavin. In P Wexler (ed.), Encyclopedia of toxicology-3rd, Academic Press, pp.128-129,
- Chastain JL, McCormick DB (1987) Flavin catabolites: identification and quantitation in human urine. Am J Clinic Nutri, 46:830-834.
- Pinto JT, Zempleni J (2016). Riboflavin. Adv in Nutri, 7:973.
- Higdon J (2024) Riboflavin. https://lpi.oregonstate.edu/mic/vitamins/riboflavin. Accessed on 04/25/2024.
- McCormick DB (1989) Two interconnected B vitamins: riboflavin and pyridoxine. Physiol Rev, 69:1170-1198.
- Jungert A, McNulty H, Hoey L, Ward M, Strain JJ, Hughes CF, ... Pentieva K (2020) Riboflavin is an important determinant of vitamin B-6 status in healthy adults. J Nutri, 150:2699-2706.
- Jarrett H, McNulty H, Hughes CF, Pentieva K, Strain JJ, McCann A, ... Ward M (2022) Vitamin B-6 and riboflavin, their metabolic interaction, and relationship with MTHFR genotype in adults aged 18–102 years. Am J Clinic Nutri, 116:1767-1778.
- Pinto JT, Cooper AJ (2014) From cholesterogenesis to steroidogenesis: role of riboflavin and flavoenzymes in the biosynthesis of vitamin D. Adv Nutri, 5:144-163.
- Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, Squadrito F, Altavilla D, Bitto A (2017) Oxidative Stress: Harms and Benefits for Human Health. Oxi. Med. Cell. Longevity
- Ashoori M, Saedisomeolia A (2014) Riboflavin (vitamin B2) and oxidative stress: a review. Brit J Nutri, 111:1985–1991.
- Olfat N, Ashoori M, Saedisomeolia A (2022) Riboflavin is an antioxidant: A review update. Brit J Nutri, 128:1887-1895.
- Suwannasom N, Kao I, Pruß A, Georgieva R, Bäumler H (2020) Riboflavin: the health benefits of a forgotten natural vitamin. Int J Mol Sci, 21:950.
- Saedisomeolia A, Ashoori M (2018) Riboflavin in human health: a review of current evidences. Adv Food Nutri Res, 83:57-81.
- Shi Z, Zhen S, Wittert GA, Yuan B, Zuo H, Taylor AW (2014) Inadequate Riboflavin Intake and Anemia Risk in a Chinese Population: Five-Year Follow Up of the Jiangsu Nutrition Study. PLoS ONE 9:e88862.
- Li M, Shi Z (2022) Riboflavin Intake Inversely Associated with Cardiovascular-Disease Mortality and Interacting with Folate Intake: Findings from the National Health and Nutrition Examination Survey (NHANES) 2005-2016. Nutrients, 14:5345.
- Holland S, Silberstein SD, Freitag F, Dodick DW, Argoff C, Ashman E (2012) Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology, 78:1346-53.
- Schoenen J, Jacquy J, Lenaerts M (1998) Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology, 50:466-70.
- Pringsheim T, Davenport W, Mackie G, Worthington I, Aube M, Christie SN, …. Becker WJ (2012) Canadian headache society guideline for migraine prophylaxis. Can J Neurol Sci, 39:S1-59.
- Condo M, Posar A, Arbizzani A, Parmeggiani A (2009) Riboflavin prophylaxis in pediatric and adolescent migraine. J Headache Pain, 10:361-5.
- Amenyah SD, Ward M, McMahon A, Deane J, McNulty H, Hughes C, ... Lees-Murdock DJ (2021) DNA methylation of hypertension-related genes and effect of riboflavin supplementation in adults stratified by genotype for the MTHFR C677T polymorphism. Int J Cardiol, 322:233-239.
- Raiskup F, Spoerl E (2013) Corneal crosslinking with riboflavin and ultraviolet A.I. Principles. Ocul Surf, 11:65-74.
- Naghashpour M, Jafarirad S, Amani R, Sarkaki A, Saedisomeolia A (2017) Update on riboflavin and multiple sclerosis: a systematic review. Iranian J Basic Med Sci 20:958.
- Plantone D, Pardini M, Rinaldi G (2021) Riboflavin in neurological diseases: a narrative review. Clinical Drug Investigation, 41:513-527.
- Ghadirian P, Jain M, Ducic S, Shatenstein B, Morisset R (1998) Nutritional factors in the aetiology of multiple sclerosis: a case-control study in Montreal, Canada. Int J Epidemiol, 27:845-852.
- Bassett JK, Hodge AM, English DR, Baglietto L, Hopper JL, Giles GG, Severi G (2012) Dietary intake of B vitamins and methionine and risk of lung cancer. Eur J Clin Nutri, 66:182-187.
- Aşkın Ö, Uzunçakmak TKÜ, Altunkalem N, Tüzün Y (2021) Vitamin deficiencies/ hypervitaminosis and the skin. Clinics Derma, 39:847-857.
- USDA (2023) https://fdc.nal.usda.gov/. Retrieved on 10/21/2023.
- Chungchunlam SM, Moughan PJ (2023) Comparative bioavailability of vitamins in human foods sourced from animals and plants. Critical Reviews Food Sci Nutri, 1-36.
- McCormick DB (2012) Riboflavin. In JW Erdman, IA Macdonald, SH Zeisel (eds.) Present Knowledge in Nutrition. 10th ed. Washington, DC: Wiley-Blackwell; pp 280-292.
- Sunaric S, Denic M, Kocic G (2012) Evaluation of riboflavin content in dairy products and non-dairy substitutes. Italian J Food Sci, 24:352.
- Sunwoo HH, Gujral N (2015) Chemical composition of eggs and egg products. In Handbook of food chemistry, Springer, Berlin, Heidelberg. pp. 331-363.
- Rivlin RS (2007) Riboflavin (Vitamin B2). In J Zempleni, RB Rucker, DB McCormick, JW Suttie (eds.), Handbook of vitamins, CRC Press, Boca Raton, FL, USA, pp. 233-251
- Hodson AZ (1940) Riboflavin content of some common vegetables and fruits. Food Res, 5:395-8.
- Demir B, Gürbüz M, Çatak J, Uğur H, Duman E, Beceren Y, Yaman M (2023) In vitro bioaccessibility of vitamins B1, B2, and B3 from various vegetables. Food Chem, 398:133944.
- Stuetz W, Schlörmann W, Glei M (2017) B-vitamins, carotenoids and α-/γ-tocopherol in raw and roasted nuts. Food Chem, 221:222-227.
- Madigan SM, Tracey F, McNulty H, Eaton-Evans J, Coulter J, McCartney H, Strain JJ (1998) Riboflavin and vitamin B-6 intakes and status and biochemical response to riboflavin supplementation in free-living elderly people. Am J Clinic Nut 68:389-395.