Riboflavin Deficiency

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Continuing Education Activity

Riboflavin, vitamin B2, is a heat-stable, water-soluble vitamin that the body uses to metabolize carbohydrates, fats, and protein into glucose for energy. In addition to boosting energy, this vitamin functions as an antioxidant for the proper functioning of the immune system, healthy skin, and hair. In riboflavin deficiency, macronutrients like fats, carbohydrates, and proteins cannot be digested to maintain the body. Riboflavin is necessary for normal development, lactation, physical performance, and reproduction. This activity illustrates the evaluation and management of riboflavin deficiency and reviews the role of the interprofessional team in improving care for patients with this condition.

Objectives:

  • Review the causes of riboflavin deficiency.

  • Describe the workup of a patient with riboflavin deficiency.

  • Summarize the treatment options for riboflavin deficiency.

  • Explain the importance of improving care coordination among the interprofessional team members to educate the patients on the importance of riboflavin for normal development, lactation, physical performance, and reproduction to enhance the delivery of care for those with riboflavin deficiency.

Introduction

Riboflavin, vitamin B2, is a water-soluble and heat-stable vitamin that the body uses to metabolize fats, protein, and carbohydrates into glucose for energy. In addition to boosting energy, riboflavin is an antioxidant for the proper immune system function and healthy skin and hair. These effects occur with the help of two coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Without an adequate amount of riboflavin, macronutrients like carbohydrates, fats, and proteins cannot be digested and maintained by the body. With a healthy digestive system, the body can absorb most of the nutrients from the diet, so it is important to get most of the riboflavin from dietary sources. Riboflavin has a yellow-green fluorescent pigment, which causes urine to turn yellow, indicating the body is absorbing riboflavin. Riboflavin also helps convert tryptophan to niacin, which activates vitamin B6. Some preventable diseases manageable with adequate riboflavin are anemia, cataracts, migraines, and thyroid dysfunction. Riboflavin is necessary for normal development, lactation, physical performance, and reproduction.[1][2]

Etiology

Riboflavin deficiency can result from inadequate dietary intake or endocrine abnormalities. Riboflavin deficiency also correlates with other vitamin B complexes. Riboflavin naturally occurs in foods such as eggs, dairy products, meats, green vegetables, and grains. Riboflavin works as an antioxidant via the glutathione redox cycle. Glutathione works to destroy free radicals and detox the liver, as free radicals can cause to development of several diseases. Riboflavin deficiency can also result from chronic diarrhea, liver disorder, alcoholism, and hemodialysis.[3][4][5] 

Epidemiology

Riboflavin deficiency is extremely rare in the United States. Riboflavin deficiency is most common in developing countries in Asia and Africa. Older adults, alcoholics, and women who take birth control pills are most likely to suffer from riboflavin deficiency since the body cannot absorb much riboflavin when on birth control pills. Riboflavin deficiency can be related to many developmental abnormalities, such as cleft lip and palate, growth retardation, and cardiac disease. Pregnant and lactating women, people with Brown-Vialetto-Van Laere syndrome (BVVL), and vegan people are also at risk of riboflavin deficiency.

Pathophysiology

Research has shown that riboflavin deficiency can alter iron absorption and cause anemia, which leads to fatigue. Riboflavin is involved in red blood cell production and transportation of oxygen to the cells. Improving the amount of riboflavin in the body can increase circulating hemoglobin levels and increase red cell production. Collagen is a protein found in most skin and hair, so riboflavin is necessary to maintain an adequate collagen level. Taking supplements of riboflavin is also a cure for migraines. Research showed that 400 mg of riboflavin a day had demonstrated efficacy in the prevention of migraine headaches in adults, but dosing must be for a minimum of 3 months for good results. This finding is most likely because mitochondrial dysfunction has been shown to play a role in migraines, and riboflavin is a precursor of flavin cofactors of the electron transport chain. According to research, riboflavin supplements can help with mitochondrial complex I deficiency by improving muscle strength, cardiomyopathy, and encephalopathy. A cataract is an eye disorder causing blurry lenses, and taking riboflavin supplements can help prevent cataracts.

Along with cataracts, riboflavin can help other eye disorders such as glaucoma and keratoconus. Riboflavin drops are usually added to the patient’s corneal surface to increase its strength. Taking riboflavin supplements can also reduce homocysteine levels and blood pressure. According to research, lowering homocysteine by 25% can lower the risk of coronary heart disease and stroke. Homocysteine is an amino acid that the body manufactures from methionine, obtained through nutritional factors.

Toxicokinetics

Severe riboflavin deficiency can diminish levels of FAD and FMN and affect the metabolism of other nutrients, especially other B vitamins. Riboflavin is excreted from the body, while only 15% is absorbed. Carbohydrates received from food convert to ATP, which is then used to produce energy in the body. It is essential to consume riboflavin every day, either by food or with supplements. Most riboflavin is absorbed in the small intestine, and excess passes out of the body as urine. Urinary excretion can also decrease with age and stress. Hydrolysis of FAD and FMN to riboflavin done by pyrophosphates and phosphatase must occur in the upper intestine for dietary riboflavin absorption. Individuals who eat nutritional diets may not need supplements; therefore, it is necessary that they consume foods rich in B vitamins along with others. Also, foods provide better absorption of riboflavin when compared to supplements.

History and Physical

Riboflavin deficiency can cause fatigue, swollen throat, blurred vision, and depression. It can affect the skin by causing skin cracks, itching, and dermatitis around the mouth. Hyperemia and edema around the throat, liver degeneration, and hair loss can also occur along with reproductive issues. Usually, people with riboflavin deficiency also have deficiencies of other nutrients. In most cases, riboflavin deficiency is reversible unless it is anatomical changes such as cataracts.

Evaluation

A therapeutic trial confirmed riboflavin deficiency by measuring the rate of urinary excretion of riboflavin. Urinary excretion increases when consuming riboflavin supplements. If urinary riboflavin excretion is lower than 40 micrograms per day, then riboflavin deficiency can occur. Measuring erythrocyte glutathione reductase can aid in detecting riboflavin deficiency. When the enzyme activity coefficient with FAD is 1.4 or higher, it indicates riboflavin deficiency.[6][7][8]

Treatment / Management

Riboflavin supplements come in 25 mg, 50 mg, and 100 mg tablets. According to the National Institutes of Health, the recommended daily nutrient intake of riboflavin is 1.3 mg for men, 1.1 mg for women, 1.3 mg for male adolescents (age 14 to 18), and 1.0 mg for female adolescents (age 14 to 18). Recommendations are that pregnant women take 1.4 mg and breastfeeding women take 1.6 mg. For infants 0 to 6 months old, the dose is 0.3 mg; for 7 to 12 months, it is 0.4 mg; for 1 to 3 years, it is 0.5 mg; for 4 to 8 years old is 0.6 mg; and for 9 to 13 years is 0.9 mg. It is important to take riboflavin supplements with meals because absorption levels increase with food. If oral supplementation is not possible, then injections are an option.[9][10]

Differential Diagnosis

  • Anaemia
  • Cataracts
  • Cleft lip and palate deformities
  • Fatigue
  • Migraines
  • Malignancies
  • Night blindness
  • Peripheral neuropathy
  • Red, itchy eyes

Pearls and Other Issues

Taking certain medications such as anticholinergic, anticonvulsants, phenothiazines, and phenytoin can reduce the level of riboflavin by not being able to be absorbed effectively into the body. Riboflavin can also interfere with some medications, such as tetracycline, which is an antibiotic, and doxorubicin, a chemotherapy drug.

Enhancing Healthcare Team Outcomes

Riboflavin deficiency is not common in the USA. The best way to prevent it is to educate the patient on a healthy diet. The primary care provider, nurse practitioner, pharmacist, and dietitian, working cohesively as an interprofessional team, should regularly encourage patients to eat fruits and vegetables. Also, most cereals are fortified with multivitamins. These disciplines need to communicate across interprofessional boundaries to guide patient outcomes optimally. The pharmacist can indicate optimal supplemental dosing along with the dietician, who can monitor dietary sources and recommendations for riboflavin-rich foods. The pharmacist can recommend particular supplements, and the nurse can track therapeutic progress on follow-up visits before the clinician sees the patient, charting all pertinent data regarding changes in status. All this occurs under the guidance of the physician or NP who manages the case. Empirically recommending vitamins for everyone is not recommended, which is why an interprofessional team approach is more beneficial to patient outcomes.[11][12][13]


Details

Updated:

7/17/2023 9:03:12 PM

References


[1]

Lykstad J, Sharma S. Biochemistry, Water Soluble Vitamins. StatPearls. 2024 Jan:():     [PubMed PMID: 30860745]


[2]

O'Callaghan B, Bosch AM, Houlden H. An update on the genetics, clinical presentation, and pathomechanisms of human riboflavin transporter deficiency. Journal of inherited metabolic disease. 2019 Jul:42(4):598-607. doi: 10.1002/jimd.12053. Epub 2019 Feb 21     [PubMed PMID: 30793323]


[3]

Balasubramaniam S, Christodoulou J, Rahman S. Disorders of riboflavin metabolism. Journal of inherited metabolic disease. 2019 Jul:42(4):608-619. doi: 10.1002/jimd.12058. Epub 2019 Mar 11     [PubMed PMID: 30680745]


[4]

Finsterer J. An update on diagnosis and therapy of metabolic myopathies. Expert review of neurotherapeutics. 2018 Dec:18(12):933-943. doi: 10.1080/14737175.2018.1550360. Epub 2018 Nov 27     [PubMed PMID: 30479175]


[5]

Peechakara BV, Sina RE, Gupta M. Vitamin B2 (Riboflavin). StatPearls. 2024 Jan:():     [PubMed PMID: 30247852]


[6]

Cevoli S, Favoni V, Cortelli P. Energy Metabolism Impairment in Migraine. Current medicinal chemistry. 2019:26(34):6253-6260. doi: 10.2174/0929867325666180622154411. Epub     [PubMed PMID: 29932030]


[7]

Saedisomeolia A, Ashoori M. Riboflavin in Human Health: A Review of Current Evidences. Advances in food and nutrition research. 2018:83():57-81. doi: 10.1016/bs.afnr.2017.11.002. Epub 2018 Feb 2     [PubMed PMID: 29477226]

Level 3 (low-level) evidence

[8]

Naghashpour M, Jafarirad S, Amani R, Sarkaki A, Saedisomeolia A. Update on riboflavin and multiple sclerosis: a systematic review. Iranian journal of basic medical sciences. 2017 Sep:20(9):958-966. doi: 10.22038/IJBMS.2017.9257. Epub     [PubMed PMID: 29085589]

Level 1 (high-level) evidence

[9]

Udhayabanu T, Manole A, Rajeshwari M, Varalakshmi P, Houlden H, Ashokkumar B. Riboflavin Responsive Mitochondrial Dysfunction in Neurodegenerative Diseases. Journal of clinical medicine. 2017 May 5:6(5):. doi: 10.3390/jcm6050052. Epub 2017 May 5     [PubMed PMID: 28475111]


[10]

Galimberti F, Mesinkovska NA. Skin findings associated with nutritional deficiencies. Cleveland Clinic journal of medicine. 2016 Oct:83(10):731-739. doi: 10.3949/ccjm.83a.15061. Epub     [PubMed PMID: 27726828]


[11]

Kozlowska A, Jagielska AM, Okreglicka KM, Dabrowski F, Kanecki K, Nitsch-Osuch A, Wielgos M, Bomba-Opon D. Dietary vitamin and mineral intakes in a sample of pregnant women with either gestational diabetes or type 1 diabetes mellitus, assessed in comparison with Polish nutritional guidelines. Ginekologia polska. 2018:89(11):581-586. doi: 10.5603/GP.a2018.0100. Epub     [PubMed PMID: 30508208]


[12]

Lee MS, Wahlqvist ML, Peng CJ. Dairy foods and health in Asians: Taiwanese considerations. Asia Pacific journal of clinical nutrition. 2015:24 Suppl 1():S14-20. doi: 10.6133/apjcn.2015.24.s1.03. Epub     [PubMed PMID: 26715079]


[13]

Nichols EK, Talley LE, Birungi N, McClelland A, Madraa E, Chandia AB, Nivet J, Flores-Ayala R, Serdula MK. Suspected outbreak of riboflavin deficiency among populations reliant on food assistance: a case study of drought-stricken Karamoja, Uganda, 2009-2010. PloS one. 2013:8(5):e62976. doi: 10.1371/journal.pone.0062976. Epub 2013 May 2     [PubMed PMID: 23658790]

Level 3 (low-level) evidence