Riboflavin Deficiency


Article Author:
Navid Mahabadi
Aakriti Bhusal


Article Editor:
Stephen Banks


Editors In Chief:
David Wood
Andrew Wilt
Hajira Basit


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
7/3/2019 10:52:11 PM

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 functions as an antioxidant for the proper function of the immune system, 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 maintain 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 by endocrine abnormalities. Riboflavin deficiency also correlates with other vitamin B complexes. Riboflavin naturally occurs in some food such as eggs, dairy products, meats, green vegetables, and grains. The main antioxidant riboflavin works as is glutathione. Glutathione works to destroy free radicals and detox the liver, as free radicals can cause to develop 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 lens, and taking riboflavin supplements can help prevent cataract.

Along with cataract, riboflavin can help other eye disorders such as glaucoma and keratoconus. Riboflavin drops are usually added to the patient’s corneal surface to increase the strength of the cornea. 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% of it 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 supplement. Most of the 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 crack, 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 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 age of 0 to 6 months old is 0.3 mg, 7 to 12 months is 0.4 mg, 1 to 3 years old is 0.5 mg, 4 to 8 years old is 0.6 mg, and 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]

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 the dietitian should regularly encourage patients about eating 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. All this occurs under the guidance of the physician or NP who manages the case. Empirically recommending vitamins for everyone is not recommended.[11][12][13]


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Riboflavin Deficiency - Questions

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A 55-year-old homeless male with a past history of alcohol abuse presents to the clinic complaining of GERD like symptoms. On physical exam, the patient is found to have stomatitis. The patient undergoes endoscopy and the esophagus is biopsied. The patient is diagnosed with esophageal cancer. Deficiency of what vitamin has been linked to esophageal cancer?



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A female from a low socioeconomic background presents with an itchy rash, blurred vision, and cracked and dry lips. She is most likely suffering from deficiency of which vitamin?



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Which of the following is NOT caused by riboflavin deficiency?



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A person with riboflavin deficiency is least likely to present with which symptom?



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Which of the following findings is NOT associated with riboflavin deficiency?



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Which of the following is not commonly seen in riboflavin deficiency?



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A patient presents with a sore throat, skin cracks around the mouth, and inflammation of the tongue. Which of the following vitamins is required for the patient?



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A 32-year-old man visits a primary care provider with complaints of fatigue, scaly skin inflammation, stomatitis, and cheilosis. The patient recently had a job loss and has been drinking every night continuously for the past 2 months. The patient’s red blood count is also low, and he has been having blurry vision. Select which deficiency the patient has.



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In which group of people is riboflavin deficiency most prevalent?



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What is the recommended amount of riboflavin for men to prevent deficiency?



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Riboflavin Deficiency - References

References

Lykstad J,Sharma S, Biochemistry, Water Soluble Vitamins 2019 Jan;     [PubMed]
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 Jan 12;     [PubMed]
Balasubramaniam S,Christodoulou J,Rahman S, Disorders of riboflavin metabolism. Journal of inherited metabolic disease. 2019 Jan 24;     [PubMed]
Finsterer J, An update on diagnosis and therapy of metabolic myopathies. Expert review of neurotherapeutics. 2018 Dec;     [PubMed]
Peechakara BV,Gupta M, Vitamin B2 (Riboflavin) 2019 Jan;     [PubMed]
Cevoli S,Favoni V,Cortelli P, Energy Metabolism Impairment in Migraine. Current medicinal chemistry. 2018 Jun 22;     [PubMed]
Saedisomeolia A,Ashoori M, Riboflavin in Human Health: A Review of Current Evidences. Advances in food and nutrition research. 2018;     [PubMed]
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;     [PubMed]
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;     [PubMed]
Galimberti F,Mesinkovska NA, Skin findings associated with nutritional deficiencies. Cleveland Clinic journal of medicine. 2016 Oct;     [PubMed]
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;     [PubMed]
Lee MS,Wahlqvist ML,Peng CJ, Dairy foods and health in Asians: Taiwanese considerations. Asia Pacific journal of clinical nutrition. 2015;     [PubMed]
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;     [PubMed]

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