EVIDENCE- Riboflavin

BASED CARE
SHEET What We Know
› Riboflavin (also known as vitamin B2, lactoflavin, and vitamin G) is a water-soluble,
B-complex vitamin. Riboflavin is an essential micronutrient that should be replenished
daily to avoid depletion; which is not difficult because it is present in a wide variety
of foods, is included in fortified food programs, and is easily absorbed from the
upper gastrointestinal tract (GI) tract. As a result, riboflavin deficiency is rare for
uncompromised individuals in Western countries(5,6,10,11,13,14,18)
• Although a small amount of riboflavin in food occurs in the free form, about 90% is
present in the noncovalently-bound forms of flavin mononucleotide (FMN) and flavin
adenine dinucleotide (FAD)(2,6,10,11,13,14)
› Actions of riboflavin(2,5,6,10,11,12,13,14,18)
• The coenzymes FMN and FAD are biologically active forms of riboflavin
• FMD and FAD function as electron carriers
• Riboflavin catalyzes proteins involved in respiratory reactions to produce energy
• The coenzymes contribute to the formation of vitamins B6, B12, and niacin (also called
vitamin B3) and their coenzymes
• FAD is required for the conversion of retinol to retinoic acid, which is essential for
normal vision
• FAD also plays a role in fatty acid oxidation
› Riboflavin is unstable in light and food sources of riboflavin should be
stored in light-resistant containers. Dietary sources of riboflavin include the
following:(2,5,6,7,10,12,18)
• Milk and milk products
• Vitamin A-enriched breakfast cereals
• Fatty fish, beef, and pork, including organ meats such as liver, kidney, and heart
• Eggs
• Dark green vegetables
• Mushrooms
› Recommended daily intake of riboflavin(2,7,10,13,18)
Author
Cherie Marcel, BS
• Pediatric requirements
Cinahl Information Systems, Glendale, CA –Adequate intake (AI) for infants < 6 months of age: 0.3 mg (based on 0.04 mg/kg)
–AI for infants 6–12 months: 0.4 mg (based on 0.04 mg/kg)
Reviewers –Recommended dietary allowance (RDA) for children 1–3 years: 0.5 mg
Sharon Richman, MSPT
Cinahl Information Systems, Glendale, CA
–RDA for children 4–8 years: 0.6 mg
Nursing Executive Practice Council
–RDA for children 9–13 years: 0.9 mg
Glendale Adventist Medical Center, –RDA for females 14–19 years: 1 mg
Glendale, CA –RDA for males 14–19 years: 1.3 mg
• Adult RDA
Editor
Diane Pravikoff, RN, PhD, FAAN
–Women ≥ 19 years: 1.1 mg
Cinahl Information Systems, Glendale, CA –Pregnant women > 19 years: 1.4 mg
–Lactating women ≥ 19 years: 1.6 mg
–Men ≥ 19 years: 1.3 mg
September 28, 2018

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› Riboflavin deficiency(2,10,11,12,18)
• Ariboflavinosis (i.e., riboflavin deficiency) is relatively rare in Western countries due to food and fortification
programs. When ariboflavinosis occur, it is usually associated with malabsorption and accompanied by other nutrient
deficiencies(2,5,7,10,18)
• The normal range for riboflavin level is 3–15 mcg/L. Patients with a value of < 2 mcg/L are considered to have riboflavin
deficiency
• Risk factors for ariboflavinosis include(10)
–alcoholism
–anorexia nervosa or malnutrition
–diabetes mellitus, cardiac or liver disease, or malignancy
–chronic infections
–taking the drug probenecid
–being pregnant or lactating
–infants
–older adults
–athletes
–failure to consume adequate food sources of riboflavin; vegan vegetarians (i.e., following a diet with no dairy or meat) are
at increased risk
• Signs and symptoms of ariboflavinosis include(10,18)
–sore throat and glossitis
–cheilosis (also called angular stomatitis), which is the development of cracks in the lips and the corners of the mouth
–neuropathy, frequently on the feet
–seborrheic dermatitis and other skin lesions
–digestive disturbances
–headache
–depression
–corneal vascularization, which can manifest as photophobia and itchy eyes(10)
› Riboflavin Toxicity(7,10)
• Riboflavin toxicity is not a major concern because it is not stored in the body. Although taking large doses can cause the
urine to become bright yellow because of the yellow color of riboflavin,
› Risk of the interaction of riboflavin with medications(13)
• Probenecid can interfere with the absorption of riboflavin
• Riboflavin decreases the action of tetracycline
› Recent research findings on riboflavin
• The effect of riboflavin on cardiovascular health has been of particular interest in research since riboflavin deficiency is
associated with elevated blood levels of homocysteine, a putative cardiovascular disease (CVD) risk factor(2)
–Scientist have identified polymorphism region near the gene that encodes methylenetetrahydrofolate reductase (MTHFR),
the folate metabolizing enzyme, as one of 8 genomic loci linked to hypertension and CVD. Studies of this relationship
have revealed that a significant gene-environmentinteraction exists, which increases the risk of hypertension and CVD.
There is evidence that riboflavin could be the influencing environmental factor. Researchers suggest that improving
riboflavin status via targeted riboflavin treatment in individuals with this genotype could prevent the development of
hypertension in those individuals(8)
–Results of a randomized controlled study analyzing the effect of riboflavin supplementation on the blood levels
of homocysteine in 88 older adults found that oral supplementation at the rate of 10 mg/day significantly lowered
homocysteine blood concentration in subjects with low riboflavin levels(14)
• Elevated blood levels of homocysteine have been associated with brain atrophy, which can lead to cognitive decline,
dementia,and Alzheimer’s disease. Low vitamin B status has also been documented in persons with dementia and
Alzheimer’s disease. While researchers have shown that vitamin B (including riboflavin) supplementation reduces
homocysteine levels,study results have been conflicting on the efficacy of vitamin B supplementation for improving
cognitive function(9,17)
 –Authors of a meta-analysis of 11 studies, which compared treatment with B vitamins to placebo for cognitive function and
aging, concluded that lowering homocysteine via vitamin B supplementation had no effect on cognitive performance(1)
• Riboflavin has been used for migraine prophylaxis based on findings of decreased levels of the vitamin in the blood
and brain of patients with migraine and the idea that the pathology of migraine headaches might involve impaired
mitochondrial oxygen metabolism in the brain. Authors of a systematic review of the effectiveness and safety of riboflavin
supplementation for the prevention of migraine report that riboflavin is inexpensive, well tolerated, and effective for
reducing the frequency of migraine headaches in adults(16)
–According to the results of a study including 130 adult migraine patients in Germany, a proprietary supplement containing
riboflavin, magnesium, and coenzyme Q10 significantly decreased the intensity of migraine pain and although statistically
non-significant decreased the frequency of migraines when compared to placebo(4)
• In a study investigating the effect of riboflavin supplementation on riboflavin levels in acutely ill older patients, researchers
concluded that supplementation significantly improved riboflavin levels in the subjects, although the benefit diminished
when supplementation ceased. Authors of another study reported that older patients with higher riboflavin intake had a
lower risk of all-causemortality(3,7)
• Scientists have studied the ability of lactic acid bacteria to synthesize riboflavin and have also developed genetically
modified strains of lactic acid bacteria to enhance the biosynthesis of riboflavin. This fermentation-based approach is
relevant in the production of functional foods that are riboflavin-enriched without the need for vitamin fortification. Lactic
acid fermentation provides an environmentally friendly alternative to the traditional chemical synthesis of riboflavin and
reduces the food production cost(15)

What We Can Do
› Become knowledgeable about the physiologic effects of riboflavin so you can accurately assess your patient’s characteristics
and health education needs; share this information with your colleagues
› Assess your patients’ health and diet history and risk factors for ariboflavinosis
› Request that the treating clinician order riboflavin supplementation if beneficial to your patient
› Educate your patients about the importance of eating a balanced diet that includes good sources of riboflavin (e.g., milk,
yogurt, and green, leafy vegetables)
› Educate your patients about all potential interactions between riboflavin-rich foods or supplements and any medications they
may be receiving
› Assess your patients and their family members for knowledge deficits about the prescribed treatment regimen, and
emphasize the importance of strict treatment regimen adherence and continued medical surveillance to monitor health status

Related Guidelines
› Patients with a serum riboflavin value of < 2 mcg/L are considered to have riboflavin deficiency. For guidelines on the
recommended daily intake of riboflavin, see What We Know, above

Coding Matrix
References are rated using the following codes, listed in order of strength:

M Published meta-analysis RV Published review of the literature PP Policies, procedures, protocols

SR Published systematic or integrative literature review
RCT Published research (randomized controlled trial)
R Published research (not randomized controlled trial)
C Case histories, case studies
G Published guidelines
RU Published research utilization report
QI Published quality improvement report
L Legislation
PGR Published government report
PFR Published funded report
X Practice exemplars, stories, opinions
GI General or background information/texts/reports
U Unpublished research, reviews, poster presentations or
other such materials
CP Conference proceedings, abstracts, presentation

References
1. Clark, R., Bennett, D., Parsh, S., Lewington, S., Skeaff, M., Eussen, S. J., ... Grodstein, F. (2014). Effects of homocysteine lowering with B vitamins on cognitive aging:
Meta-analysis of 11 trials with cognitive data on 22,000 individuals. American Journal of Clinical Nutrition, 100(2), 657-666. doi:10.3945/ajcn.113.076349 (M)
2. Delage, B., Drake, V. J., & Higdon, J. (2013). Riboflavin. Linus Pauling Institute Micronutrient Information Center. Retrieved June 22, 2018, from http://lpi.oregonstate.edu/mic/
vitamins/riboflavin#reference35 (GI)
3. Gariballa, S., Forster, S., & Powers, H. (2009). Riboflavin status in acutely ill patients and response to dietary supplements. Journal of Parenteral & Enteral Nutrition, 33(6),
656-661. doi:10.1177/0148607109336602 (RCT)
4. Gaul, C., Diener, H.-C., & Danesch, U. (2015). Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium, and Q10: A randomized,
placebo-controlled, double-blind, multicenter trial. The Journal of Headache and Pain, 16, 32. doi:10.1186/s10194-015-0516-6 (RCT)
 5. The George Mateljan Foundation editorial team. (n.d.). The world's healthiest foods: Vitamin B2 – riboflavin. Retrieved June 22, 2018, from http://www.whfoods.com/
genpage.php?tname=nutrient&dbid=93 (GI)
6. Hoey, L., McNulty, H., & Strain, J. J. (2009). Studies of biomarker responses to intervention with riboflavin: A systematic review. American Journal of Clinical Nutrition, 89(6S),
1960S-1980S. doi:10.3945/ajcn.2009.27230B (SR)
7. Huang, Y., Lee, M., & Wahlqvist, M. L. (2011). Prediction of all-cause mortality by B group vitamin status in the elderly. Clinical Nutrition, 31(2), 191-198. doi:10.1016/
j.clnu.2011.10.010 (RCT)
8. McNulty, H., Strain, J. J., Hughes, C. F., & Ward, M. (2016). Riboflavin, MTHFR genotype and blood pressure: A personalized approach to prevention and treatment of
hypertension. Molecular Aspects of Medicine, 53, 2-9. doi:10.1016/j.mam.2016.10.002 (R)
9. Mikkelson, K., Stojanovska, L., Tangalakis, K., Bosevski, M., & Apostolopoulos, V. (2016). Cognitive decline: A vitamin B perspective. Maturitas, 93, 108-113. doi:10.1016/
j.maturitas.2016.08.001 (RU)
10. National Institutes of Health. Office of Dietary Supplements. (2018). Riboflavin. U.S. Department of Health & Human Services. Retrieved June 22, 2018, from
https://ods.od.nih.gov/factsheets/Riboflavin-HealthProfessional/ (GI)
11. Northrop-Clewes, C. A., & Thurnham, D. I. (2012). The discovery and characterization of riboflavin. Annals of Nutrition & Metabolism, 61(3), 224-230. doi:10.1159/000343111
(GI)
12. Shields, K. M., Fox, K. L., & Liebrecht, C. (2018). Riboflavin (vitamin B2). In Pearson nurse's drug guide 2018 (pp. 1401-1402). Hoboken, NJ: Pearson Education. (GI)
13. Skidmore-Roth, L. (2017). Riboflavin (vitamin B2). In Mosby's 2017 nursing drug reference (30th ed., p. 1027). St. Louis, MO: Elsevier. (GI)
14. Tavares, N. R., Moreira, P. A., & Amaral, T. F. (2009). Riboflavin supplementation and biomarkers of cardiovascular disease in the elderly. Journal of Nutrition, Health and
Aging, 13(5), 441-446. doi:10.1007/s12603-009-0081-2 (RCT)
15. Thakur, K., Tomar, S. K., & De, S. (2015). Lactic acid bacteria as a cell factory for riboflavin production. Microbial Biotechnology, 9(4), 441-451. doi:10.1111/1751-7915.12335
(R)
16. Thomposon, D. F., & Salujan, H. S. (2017). Prophylaxis of migraine headaches with riboflavin: A systemtic review. Journal of Clinical Pharmacy & Therapeutics, 42(4), 394-403.
doi:10.1111/jcpt.12548 (SR)
17. Tucker, K. L. (2016). Nutrient intake, nutritional status, and cognitive function with aging. Annals of the New York Academy of Sciences, 1367, 38-49. (RV)
18. Wax, E. (2017). Riboflavin. MedlinePlus. Retrieved June 22, 2018, from https://www.nlm.nih.gov/medlineplus/ency/article/002411.htm (GI)