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Vitamin B2
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Vitamin B2

Riboflavin, also known as vitamin B2, is an essential nutrient belonging to the B vitamin family.  B vitamins are crucial for numerous physiological processes in the body. 

Riboflavin’s role as a coenzyme in various metabolic pathways makes it indispensable for energy production, cellular growth, and development. Understanding riboflavin's structure and function is fundamental to understanding its role in maintaining optimal health.  

Moreover, exploring testing options, interpretation of results, and natural strategies to enhance riboflavin status offers valuable insights into promoting overall well-being. In this article, we delve into the multifaceted aspects of riboflavin, providing comprehensive information to aid in a better understanding of its importance and implications for health.

Overview of B Vitamin Family

The B vitamin family comprises a group of water-soluble vitamins that play critical roles in numerous physiological processes essential for human health. 

Comprising eight distinct vitamins, it includes riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folate (B9), and cobalamin (B12), these vitamins are intricately related and often function as coenzymes in various metabolic pathways. 

VItamin B12 is the only B vitamin that can be stored in the body, in the liver.  All other B vitamins are quickly excreted through the urine, therefore they require daily repletion.  

Individually, the B vitamins contribute to energy production, DNA synthesis, nervous system function, and red blood cell formation, among other vital functions. Collectively, the B vitamins are indispensable for maintaining overall health and well-being, underscoring their importance in supporting various physiological systems within the human body.

II. Riboflavin (Vitamin B2)

What is Riboflavin?  [11.]

Riboflavin, also known as vitamin B2, is a water-soluble and heat-stable vitamin with many functions in the body.  It is converted into one of two coenzymes, which provide its functionality: flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).  Many of riboflavin’s actions occur in the mitochondria.  [1.] 

Riboflavin is crucial for metabolizing fats, proteins, and carbohydrates into glucose, providing the body with energy. Riboflavin supports the immune system, promotes healthy skin and hair. 

Without sufficient riboflavin, macronutrients cannot be properly digested and utilized by the body. 

Riboflavin's yellow-green fluorescent pigment gives urine its characteristic yellow color, indicating adequate absorption. 

Riboflavin aids in converting tryptophan to niacin, which in turn activates vitamin B6. 

Adequate riboflavin intake can help prevent anemia, cataracts, migraines, and thyroid dysfunction, while also supporting normal development, lactation, physical performance, and reproduction.

Functions of Riboflavin 

  • Riboflavin participates in the metabolism of macronutrients and contributes to the production of other B-complex vitamins.
  • It is essential for redox reactions in metabolic pathways, facilitated by flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN); FAD and FMN are derived from riboflavin and act as electron carriers.
  • Riboflavin plays a critical role in the electron transport chain, essential for energy production.
  • Inadequate riboflavin intake can disrupt various metabolic processes, affecting the conversion of tryptophan to niacin and vitamin B6 to pyridoxal 5’-phosphate, both of which rely on FAD and FMN, respectively.
  • Riboflavin acts as an antioxidant by regenerating glutathione, a potent free radical scavenger.
  • It is crucial for growth, development, and various physiological processes, especially during fetal development, reproduction, and lactation.

Recommended Daily Allowance (RDA) of Riboflavin

The RDA for adult males is 1.3 mg/day, and 1.1 mg/day for females.  In pregnancy the RDA increases to 1.4 mg/day, and it is set at 1.6 mg/day in lactation.  [4.]  Supplemented doses up to 500 mg a day have shown no adverse effects.  [4.]   

Sources of Riboflavin

Riboflavin is found abundantly in various dietary sources. Common food sources rich in riboflavin include dairy products such as milk, cheese, and yogurt, along with eggs, lean meats like chicken and turkey, and organ meats such as liver and kidneys. 

Additionally, riboflavin can be obtained from plant-based sources like leafy green vegetables, legumes, nuts, and fortified cereals and grains. 

Supplements containing riboflavin are also common, often as part of a B complex supplement or as an individual riboflavin supplement. 

Testing Options for Riboflavin Levels

Blood Tests

Blood tests are commonly used to measure riboflavin levels in the body. These tests typically involve drawing a blood sample from a vein, which is then analyzed in a laboratory to determine the concentration of riboflavin present. 

This test may assess levels of riboflavin in serum, plasma, or red blood cells.

Urine Tests

Less commonly, riboflavin levels may be assessed in the urine.  

Test Procedure and Preparation Guidelines

The procedure for testing riboflavin levels typically involves a blood draw.  Before undergoing a blood test, individuals may be instructed to fast for a certain period and avoid consuming riboflavin-rich foods or supplements to prevent interference with the results. 

It's essential to follow any preparation guidelines provided by the healthcare team to ensure accurate test results and to discuss any medications or supplements being taken that could affect riboflavin levels.

Interpretation of Riboflavin Testing

While individual labs may report different reference ranges, the reference ranges for riboflavin testing are often similar to the following: [16.]

Serum or plasma: 4-24 µg/dL or 106-638 nmol/L

Urine: >80 µg/dL or >213 nmol/dL

Erythrocyte: 10-50 µg/dL or 266-1330 nmol/dL

Clinical Significance of High Riboflavin Levels

High riboflavin levels are extremely rare, and adverse effects from high daily intake have not been reported.  [10.]  However, it could theoretically occur in individuals who excessively consume riboflavin supplements.   

Riboflavin is water-soluble and excess amounts are typically excreted in the urine; additionally, it is poorly absorbed in the gastrointestinal tract.  These mechanisms are thought to be behind the lack of evidence for riboflavin toxicity.  [4.] 

In one study, one individual taking riboflavin and aspirin reported adverse gastrointestinal effects.  [13.]  While they cannot conclusively be attributed to riboflavin intake, excessively high levels may theoretically lead to gastrointestinal disturbances such as nausea, vomiting, and diarrhea. 

Clinical Significance of Low Riboflavin Levels

Riboflavin deficiency, also known as ariboflavinosis, can lead to various health issues due to its essential role in numerous metabolic pathways. 

Common symptoms of riboflavin deficiency include fatigue, weakness, and anemia due to its involvement in energy production and red blood cell formation. 

Additionally, deficiency may manifest as inflammation and soreness of the throat and mouth, known as cheilosis and glossitis, respectively, owing to riboflavin's role in maintaining mucous membranes' health. 

Dermatological manifestations such as a characteristic reddening and scaling of the skin around the nose, mouth, and eyes, called angular stomatitis, can also occur. 

Furthermore, reproductive issues and impaired growth in infants may result from riboflavin deficiency. It is essential to ensure an adequate intake of riboflavin-rich foods to prevent these health complications associated with riboflavin deficiency.

Natural Ways to Optimize B Vitamin Status

Dietary Sources of B Vitamins

Incorporate a variety of foods rich in B vitamins such as:

  • Whole grains like brown rice, oats, quinoa, and barley
  • Leafy greens such as spinach, kale, and Swiss chard
  • Legumes including lentils, chickpeas, and black beans
  • Nuts and seeds like almonds, sunflower seeds, and flaxseeds
  • Lean meats such as chicken, turkey, and beef
  • Dairy products like milk, yogurt, and cheese
  • Eggs, particularly the yolk which contains B vitamins
  • Seafood such as salmon, tuna, and mackerel which are rich in B12
  • Include fortified foods like fortified cereals, bread, and plant-based milk alternatives to increase B vitamin intake.

Lifestyle Strategies to Optimize B Vitamin Status

  • Consume a balanced diet rich in fruits, vegetables, whole grains, and lean proteins to ensure adequate B vitamin intake.
  • Avoid excessive alcohol consumption as it can interfere with the absorption and utilization of B vitamins, particularly B1 (thiamine).  [7.] 
  • Manage stress levels through relaxation techniques such as deep breathing exercises, meditation, yoga, or mindfulness practices, as chronic stress can deplete B vitamin stores.  [18.] 
  • Get regular physical activity, which can help improve overall metabolism and enhance the body's utilization of B vitamins.  Increasing exercise increases vitamin B needs, so supplementing may be desirable in some individuals.  [6.] 

Medications That Lower Vitamin B Levels in the Body

Individuals taking the following medications may want to discuss their B vitamin needs with their healthcare provider:

  • Metformin: Used to treat type 2 diabetes, metformin can reduce vitamin B12 absorption and increase the risk of deficiency over time.  [5., 8.]
  • Proton pump inhibitors (PPIs): These medications, such as omeprazole and esomeprazole, are commonly used to treat acid reflux and peptic ulcers. Long-term use of PPIs can interfere with the absorption of vitamin B12.  [3., 8.]
  • Histamine H2-receptor antagonists: Drugs like ranitidine and cimetidine, used to reduce stomach acid production, may also impair vitamin B12 absorption.  [8.]
  • Anticonvulsants: Some antiepileptic drugs like phenytoin, phenobarbital, and primidone can lower levels of folate and vitamin B12 in the body.  [12.] 
  • Chemotherapy drugs: Chemotherapy medications can affect the body's ability to absorb and utilize B vitamins, leading to deficiencies.  [2.] 
  • Oral contraceptives: Some birth control pills can deplete levels of B vitamins, particularly folate and vitamin B6.  [17.] 
  • Diuretics: Certain diuretic medications, including loop and thiazide diuretics, can increase urinary excretion of B vitamins, particularly vitamin B1 (thiamine) and folate.  [9., 14.]

It's important to consult with a healthcare professional if you're taking any of these medications to discuss potential nutrient deficiencies and appropriate supplementation, if needed.

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What's 
Vitamin B2
?
Vitamin B2, also known as Riboflavin, is an essential nutrient that your body requires but cannot make on its own. It's a water-soluble vitamin, which means it dissolves in water and is transported to your body's tissues but isn't stored, so it needs to be replenished regularly. Riboflavin plays a crucial role in producing energy, working as a helper molecule to break down carbohydrates, proteins, and fats to create energy. It also supports cell function and growth, contributes to healthy skin, and helps maintain proper function of the eyes and nervous system. Additionally, Vitamin B2 is vital in activating and converting other B vitamins, making it an important factor in overall body health.
If Your Levels Are High
Having higher than normal levels of Vitamin B2 might mean that you're consuming more of this nutrient than needed, which could be due to eating lots of B2-rich foods or taking supplements like multivitamins or B-complex vitamins. Some medications might also cause an increase in Vitamin B2 levels. In certain cases, high levels could point to issues with your kidneys, as they play a key role in managing the amount of vitamins in your body. Keep in mind that while Vitamin B2 is important for your health, too much of it can potentially throw off the balance of other essential nutrients in your body.
Symptoms of High Levels
Symptoms of high levels of Vitamin B2 are generally rare due to its water-soluble nature, but in some cases, they could include intense yellowing of the urine.
If Your Levels are Low
Low levels of Vitamin B2 might mean that your body isn't getting enough of this important nutrient. This could be because you're not eating enough foods rich in riboflavin, like dairy products, eggs, lean meats, legumes, nuts, and green leafy vegetables. Lifestyle factors, such as heavy drinking or eating lots of processed foods, could also play a role in lowering your Vitamin B2 levels. Some medications, like certain antidepressants and water pills, might affect how your body absorbs and uses this vitamin. Additionally, health conditions that impact nutrient absorption, like celiac disease or Crohn's disease, could be a reason for low Vitamin B2 levels.
Symptoms of Low Levels
Symptoms of low levels of Vitamin B2 may include fatigue, slowed metabolism, throat swelling or soreness, a swollen tongue, skin inflammation, and changes in mood such as increased anxiety or depression.
See References

[1.] Dmitry P. Perspectives of pharmacological correction and evaluation of mitochondrial dysfunction in neurodegenerative and ischemic brain lesions. Bioactive Natural Products. Published online 2021:65-98. doi:https://doi.org/10.1016/b978-0-12-819487-4.00018-5 

[2.] Dreizen S, McCredie KB, Keating MJ, Andersson BS. Nutritional deficiencies in patients receiving cancer chemotherapy. Postgrad Med. 1990 Jan;87(1):163-7, 170. doi: 10.1080/00325481.1990.11704531. PMID: 2296564. 

[3.] Heidelbaugh JJ. Proton pump inhibitors and risk of vitamin and mineral deficiency: evidence and clinical implications. Ther Adv Drug Saf. 2013 Jun;4(3):125-33. doi: 10.1177/2042098613482484. PMID: 25083257; PMCID: PMC4110863.

[4.] Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academies Press (US); 1998. 5, Riboflavin. Available from: https://www.ncbi.nlm.nih.gov/books/NBK114322/ ‌

[5.] Kim J, Ahn CW, Fang S, Lee HS, Park JS. Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes. Medicine (Baltimore). 2019 Nov;98(46):e17918. doi: 10.1097/MD.0000000000017918. PMID: 31725641; PMCID: PMC6867725.

[6.] Lee MC, Hsu YJ, Shen SY, Ho CS, Huang CC. A functional evaluation of anti-fatigue and exercise performance improvement following vitamin B complex supplementation in healthy humans, a randomized double-blind trial. Int J Med Sci. 2023 Aug 15;20(10):1272-1281. doi: 10.7150/ijms.86738. PMID: 37786445; PMCID: PMC10542023. 

[7.] Mahabadi N, Bhusal A, Banks SW. Riboflavin Deficiency. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470460/ 

[8.] Miller JW. Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. Adv Nutr. 2018 Jul 1;9(4):511S-518S. doi: 10.1093/advances/nmy023. PMID: 30032223; PMCID: PMC6054240. 

[9.] Morrow LE, Grimsley EW. Long-term diuretic therapy in hypertensive patients: effects on serum homocysteine, vitamin B6, vitamin B12, and red blood cell folate concentrations. South Med J. 1999 Sep;92(9):866-70. doi: 10.1097/00007611-199909000-00003. PMID: 10498160. 

[10.] Office of Dietary Supplements - Riboflavin. ods.od.nih.gov. Accessed March 17, 2024. https://ods.od.nih.gov/factsheets/Riboflavin-HealthProfessional/#en3 

[11.] Peechakara BV, Sina RE, Gupta M. Vitamin B2 (Riboflavin) [Updated 2024 Feb 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK525977/ 

[12.] Ray, K. Antiepileptic drugs reduce vitamin B12 and folate levels. Nat Rev Neurol 7, 125 (2011). https://doi.org/10.1038/nrneurol.2011.9

[13.] Schoenen J, Lenaerts M, Bastings E. Rapid communication: High-dose riboflavin as a prophylactic treatment of migraine: Results of an open pilot study. Cephalalgia. 1994;14:328–329. 

[14.] Suter PM, Vetter W. Diuretics and vitamin B1: are diuretics a risk factor for thiamin malnutrition? Nutr Rev. 2000 Oct;58(10):319-23. doi: 10.1111/j.1753-4887.2000.tb01827.x. PMID: 11127971. 

[15.] Talaska Fischbach F, Fischbach MA. Fischbach's A Manual of Laboratory and Diagnostic Tests. 10th ed. Alphen aan den Rijn, The Netherlands: Wolters Kluwer; 2018. 

[16.] Vitamin B2 (Riboflavin): Reference Range, Interpretation, Collection and Panels. eMedicine. Published online June 13, 2023. Accessed March 17, 2024. https://emedicine.medscape.com/article/2088605-overview

[17.] Wilson SM, Bivins BN, Russell KA, Bailey LB. Oral contraceptive use: impact on folate, vitamin B6, and vitamin B12 status. Nutrition Reviews. 2011;69(10):572-583. doi:https://doi.org/10.1111/j.1753-4887.2011.00419.x 

[18.] Young LM, Pipingas A, White DJ, Gauci S, Scholey A. A Systematic Review and Meta-Analysis of B Vitamin Supplementation on Depressive Symptoms, Anxiety, and Stress: Effects on Healthy and 'At-Risk' Individuals. Nutrients. 2019 Sep 16;11(9):2232. doi: 10.3390/nu11092232. PMID: 31527485; PMCID: PMC6770181. 

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