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The least explored vitamin- Riboflavin (Vitamin B2)

The article below appeared in the November 22  issue of Health with Perdana, a regular column in The Star by Perdana University faculty members. This week’s article is contributed by Dr. Lee Tze Yan, Lecturer, Perdana University School of Liberal Arts, Science and Technology, and Dr. Chin Voon Ki, former Research Assistant at Department of Medical Microbiology, Universiti Putra Malaysia.

 

What are Vitamins?  

Vitamins are essential micronutrients that are required in small quantities for all living cells to perform biochemical processes. Vitamins are often used as precursors for enzymes (biological catalysts that speed up the chemical reaction). Unfortunately, humans are incapable of synthesizing vitamins and have to consume them externally. Classification of all the 13 vitamins are based on their solubility in fat and water. Vitamin A, D, E, and K are fat soluble vitamins which metabolize in the same manner as fats while water soluble vitamins are B and C .The large vitamin B family consists of thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate (B9), and cobalamin (B12).

 

What is Riboflavin?

Among the B vitamins, riboflavin is non-toxic and is naturally found at the area of the skin, eye, red blood cells, brain, muscles and aortic tissues in the human body. Also, there are little amounts of riboflavin found in plants and animals. Physically, the odorless riboflavin are orange-yellow crystals with a bitter taste without an acute melting point. These specific crystals darken at 240°C and melt in temperatures ranging from 274-282°C. Besides, riboflavin is sparingly soluble in water at room temperature and its water solubility increases with higher temperature. This vitamin is quite stable with a low pH (acidic environment) whereas at a higher pH (alkaline environment), riboflavin is easily decomposed into photoproducts (product which is produced by a chemical reaction that uses light or other electromagnetic radiation to increase energy of particles) in the presence of UV light. Riboflavin contains two important co-factors namely flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) which participate in numerous oxidation-reduction reactions and also energy metabolism. Both flavins are light- sensitive and are rapidly photodegraded into inactivated forms of the vitamin, wherein some of these photodegraded products are toxic to human tissues. Riboflavin, when exposed to visible lights, can form adduct (a chemical addition product) with tryptophan (an essential amino acid in humans) that causes structural damage in cells and elevates the rate of mutagenicity in cells. Therefore, extra precautions are vital and needed when handling riboflavin, especially for experimental purposes.

 

What are the main sources of Riboflavin?

Due to the absence of an intrinsic system to produce riboflavin endogenously, humans acquire exogenous riboflavin through microbial sources such as intestinal microbiota and/or daily consumption of food including fish, dairy products (milk and cheese), breads, dark-green vegetables, fruits, cereals and grain products that are rich in riboflavin. Conversely, riboflavin can be produced de novo by several fungi, bacteria and plants. Commercial riboflavin is often used in the pharmaceutical, food and feed industries. The industrial production of riboflavin has shifted from chemical synthesis to microbial fermentation which comprises of mutagenesis and genetic engineering. The microbial fermentation process utilizes microbial strains, such as Bacillus subtilis and Ashbya gossypii, which are considered as riboflavin overproducing strains. Unlike in humans, some pathogenic bacteria such as Escherichia coli (diarrhea, urinary tract infections and pneumonia), Salmonella typhimurium (typhoid fever and gastroenteritis) and Mycobacterium tuberculosis (tuberculosis infection) are highly dependant on the endogenous source of riboflavin since these pathogens lack of an effective riboflavin uptake system. Different sources have demonstrated that the riboflavin biosynthesis pathway appears to be a promising druggable (a biological target (such as a protein) that is known to or is predicted to bind with high affinity to a drug) target to tackle pathogenic microorganisms that rely on the endogenous supply of riboflavin for survival and growth in humans, which could be a probable alternative in resolving the emerging antimicrobial resistance scenario globally.

 

What happens after Riboflavin is ingested into body?

Once consumed, riboflavin is absorbed in the stomach and small intestine after it is released from protein in food through the action of hydrochloric acid. The absorption is mainly carried out by diffusion. In the intestine, riboflavin is converted into its active form FMN and FAD and is transported in enterocytes via translocators (transport of proteins across the membrane of an organelle). The level of riboflavin acquired through oral consumption from daily diets or via multivitamin supplements are unlikely to cause any side effects or to develop toxicity in humans based on its physiologic nature and rapid excretion from human body when in excess. Excess riboflavin that is not converted into FMN and FAD will be excreted by kidney, causing a normal urine discoloration (yellow-coloured urine), or it can be secreted into extracellular fluids through the ABCG2 transporter. Numerous toxicity studies using different experimental models on riboflavin have been performed and via different routes of administration, including oral, intraperitoneal, subcutaneous and intravenous injection. These findings support the use of riboflavin in total parenteral nutrition because it has minimal to no adverse effects.

 

What are some of the biological functions of Riboflavin?

Riboflavin, Vitamin B2 (a micronutrient) plays an indispensable role in producing energy by metabolizing macronutrients, like carbohydrates, fats and proteins into glucose together with flavocoenzymes (coenzymes derived from riboflavin). The metabolism of macronutrients involves the biological oxidation-reduction reactions (redox reactions) to mediate the electron transfer participating in numerous key metabolic pathways of mitochondria, such as energy metabolism, vitamin B6 metabolism, purine catabolism, fatty acid oxidation, Krebs cycle and respiratory chain. These metabolic pathways are mediated by an electron transport chain to ensure normal cellular growth and development.

Riboflavin possesses antioxidant properties within cell systems to scavenge free radicals to alleviate oxidative injuries caused by several diseases. Glutathione reductase is the most famous natural antioxidant that uses FAD to generate two reduced glutathione molecules from oxidized glutathione. Subsequently, these molecules function as an endogenous antioxidant by breaking down hydrogen peroxide to water in the presence of glutathione peroxidases. This is known as the glutathione oxidation-reduction cycle to maintain cellular redox status. Another FAD-dependent enzyme, xanthine oxidase catalyzes the oxidation of hypoxanthine and xanthine to uric acid, which functions as a water-soluble antioxidant in the bloodstream. Due to a vast amount of riboflavin-dependent enzymes, riboflavin deficiency is correlated with an increased oxidative stress leading to aging and degenerative diseases.

 

What happens if there is a deficiency of Riboflavin?

Riboflavin deficiency, also called ariboflavinosis is commonly found in developing countries such as Asia and Africa. In the event of riboflavin deficiency, macronutrients cannot be digested to function in the human body. Reasons underlying riboflavin deficiency are inadequate dietary intake with riboflavin (e.g. dairy products, meats, eggs and green vegetables), endocrine abnormalities, due to deficiency of other vitamin B complexes and/or mutations in riboflavin transporters. Riboflavin deficiency frequently occurs in people with liver disease, alcoholism, chronic diarrhea and hemodialysis as well as people with an increased need of riboflavin due to physiological conditions such as athletes, childhood, elderly, pregnant and breastfeeding women.

Riboflavin deficiency leads to an array of implications on human systems, such as circulatory and bone (leads to anemia, erythroid hypoplasia), endocrine system (disturbs overall growth) and digestive system (disrupts metabolism of carbohydrates, fats and proteins and inflamed mucous membrane). Riboflavin deficiency affects organs as well, such as head (migraine, hair loss), eyes (corneal vascularisation, cataract development) and mouth and neck (cheilosis, glossitis, angular stomatitis and sore throat). In other words, anemia, cataracts, migraines, thyroid dysfunction and other preventable diseases are both manageable and preventable with sufficient riboflavin.

 

What happens if there is a deficiency of Riboflavin?

Riboflavin deficiency, also called ariboflavinosis is commonly found in developing countries such as Asia and Africa. In the event of riboflavin deficiency, macronutrients cannot be digested to function in the human body. Reasons underlying riboflavin deficiency are inadequate dietary intake with riboflavin (e.g. dairy products, meats, eggs and green vegetables), endocrine abnormalities, due to deficiency of other vitamin B complexes and/or mutations in riboflavin transporters. Riboflavin deficiency frequently occurs in people with liver disease, alcoholism, chronic diarrhea and hemodialysis as well as people with an increased need of riboflavin due to physiological conditions such as athletes, childhood, elderly, pregnant and breastfeeding women.

Riboflavin deficiency leads to an array of implications on human systems, such as circulatory and bone (leads to anemia, erythroid hypoplasia), endocrine system (disturbs overall growth) and digestive system (disrupts metabolism of carbohydrates, fats and proteins and inflamed mucous membrane). Riboflavin deficiency affects organs as well, such as head (migraine, hair loss), eyes (corneal vascularisation, cataract development) and mouth and neck (cheilosis, glossitis, angular stomatitis and sore throat). In other words, anemia, cataracts, migraines, thyroid dysfunction and other preventable diseases are both manageable and preventable with sufficient riboflavin.

 

What are some of the antimicrobial activities of Riboflavin?

Antibiotics and/or antimicrobial agents are undoubtedly amongst the most prominent discoveries in medicine. The steady use of antimicrobial drugs enable the effective treatment of complicated and life-threatening microbial infections and have become a fundamental instrument in modern medicine, facilitating a broad range of medical procedures including cancer chemotherapy, orthopedic surgery and transplantation. This eventually will reduce microbial-related infections and improve the quality of human life. However, currently, we are facing the emergence of antimicrobial resistance (AMR) and multidrug-resistance (MDR) to the clinical available antimicrobial drugs attributed by misuse and/or intensive use in agriculture and/or health sectors, which pose a serious challenge and threat to the community and healthcare systems globally. Indeed, the World Health Organization (WHO) has declared AMR as one of the most serious threats to animal and human health. With fewer new antimicrobial agents with resistance- breaking features being in the progress of development and/or even less successfully marketed; it is unlikely that we will see significant improvements in AMR and MDR scenarios in the near future. This scenario presumably will cause a high fatality rate and huge economic burden on both individuals and countries.

 

Conclusion

In consideration of the multiple roles of riboflavin in humans, it is appropriate to re-assess the importance of riboflavin in the context of its beneficial properties in humans and create public awareness on the forgotten health benefits of vitamins, not only of riboflavin but also the other essential vitamins in maintaining human health. Further scientific research related to riboflavin particularly in the hot fields such as medical microbiology and infectious diseases is indeed important to further unlock the hidden potential and explore the unknown benefits of riboflavin. Lastly, the next time you buy any food product or supplements for you and your family, do check out the nutrition information labelling. You will be surprised to see the amount of vitamins in it especially vitamin B2!

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