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Background

Riboflavin is a water-soluble vitamin, which is involved in vital metabolic processes in the body and is necessary for normal cell function, growth, and energy production. Small amounts of riboflavin are present in most animal and plant tissues.

Healthy individuals who eat a balanced diet rarely need riboflavin supplements. Especially good dietary sources of riboflavin are milk (and other dairy products), eggs, enriched cereals/grains, meats, liver, and green vegetables (such as asparagus or broccoli). Intake may be lower in vegetarians compared to non-vegetarians.

Riboflavin is often used as a tracer of medication compliance in the treatment of patients with alcohol dependence, mental disorders, and other conditions. Urinary riboflavin levels may be measured in order to determine the level of compliance.

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Synonyms

7,8-dimethyl-10 (1'-D-ribityl) isoalloxazine, B-complex vitamin, Dolo-Neurotrat, flavin, flavine, lactoflavin, riboflavine, vitamin B2, vitamin G.

Supplements : The most common forms of riboflavin available in supplements are riboflavin and riboflavin 5'-monophosphate. Riboflavin is most commonly found in multivitamin and vitamin B-complex preparations.

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Evidence

Uses based on scientific evidence	Grade*
Neonatal jaundice Riboflavin supplementation is included in the treatment of neonatal jaundice with phototherapy.	A
Riboflavin deficiency (ariboflavinosis) Studies suggest that riboflavin is beneficial in patients with riboflavin deficiency (ariboflavinosis). Ariboflavinosis may cause weakness, throat swelling/soreness, glossitis (tongue swelling), angular stomatitis/cheilosis (skin cracking or sores at the corners of the mouth), dermatitis (skin irritation), or anemia. Particular groups may be especially susceptible to riboflavin deficiency, including the elderly, those with chronic illnesses, the poor, and those with alcohol dependency. Patients with suspected riboflavin deficiency should be evaluated by a qualified healthcare professional.	A
Anemia Some research suggests that riboflavin may play an adjunct role in the treatment of iron deficiency anemia and sickle cell anemia; levels of riboflavin may be low in these conditions. Correction of riboflavin deficiency in individuals who are both riboflavin deficient and iron deficient appears to improve response to iron therapy.	C
Anorexia / bulemia Levels of important nutrients are often low in individuals with anorexia or bulimia, with up to 20-33% of patients deficient in vitamins B2 (riboflavin) and B6 (pyridoxine). Dietary changes alone, without additional supplements, can often bring vitamin B levels back to normal. However, extra B2 and B6 may be required. Nutritional and medical guidance for such patients should be under the direction of a qualified healthcare professional.	C
Cataracts It has been suggested that low riboflavin levels may be a risk factor for developing cataracts or that riboflavin supplementation may be beneficial for prevention. Additional evidence is needed before a clear conclusion can be drawn.	C
Cognitive function Adequate nutrient supplementation with riboflavin may be required for the maintenance of adequate cognitive function. Treatment with B-vitamins including riboflavin has been reported to improve scores of depression and cognitive function in patients taking tricyclic antidepressants. This may be related to tricyclic-caused depletion of riboflavin levels.	C
Depression Adequate nutrient supplementation with riboflavin may be required for the maintenance of adequate cognitive function. Treatment with B-vitamins, including riboflavin, has been reported to improve depression scores in patients taking tricyclic antidepressants. This may be related to tricyclic-caused depletion of riboflavin levels.	C
Esophageal cancer (prevention and treatment) Riboflavin supplementation has been studied in the prevention and treatment of esophageal cancer, mostly in China, with mixed results. No clear conclusion can be drawn at this time.	C
Ethylmalonic encephalopathy Although the exact pathogenesis of this disorder is unknown, some research suggests that riboflavin may lead to slight improvements in motor function, cognitive behavior, and diarrhea.	C
Malaria It remains unclear how riboflavin supplementation may affect malarial infections.	C
Migraine headache prevention Several studies suggest benefits of high-dose riboflavin in preventing migraine headaches.	C
Preeclampsia Limited study has reported an association between low riboflavin levels and an increased risk of preeclampsia (high blood pressure in pregnancy). However, it is not clear if low riboflavin levels are a cause or consequence of this condition, or if additional supplementation is warranted in pregnant women at risk of preeclampsia/eclampsia (beyond the routine use of prenatal vitamins).	C

Key to grades
A Strong scientific evidence for this use
B Good scientific evidence for this use
C Unclear scientific evidence for this use
D Fair scientific evidence against this use (it may not work)
F Strong scientific evidence against this use (it likely does not work)

Grading rationale

Uses based on tradition or theory

Acne, aging, alcohol dependence, ataxia, atherosclerosis, athletic performance, burning eyes, burning feet syndrome, burns, canker sores, carpal tunnel syndrome, cervical cancer, colon cancer, congenital methemoglobinemia, Crohn's disease, excess tearing, dermatitis, dementia, diabetes, digestion disorders, eczema, eye disorders, eye strain/fatigue, fatigue, glaucoma, glossitis (tongue inflammation), growth disorders, healthy hair, HIV, hypertension (high blood pressure), immune system function, lactic acidosis, leg cramps, liver disease, memory loss, mitochondrial disorders, mood disorders, mouth cancer, multiple acylcoenzyme A dehydrogenase deficiency, multiple sclerosis (MS), peptic ulcer disease (PUD), postoperative muscle cramps, neural tube defects, pain, red blood cell aplasia, reproduction disorders, rheumatoid arthritis, skin disorders, stress, stroke, ureteral colic pain, vitality problems.

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Dosing

Riboflavin Deficiency

The U.S. Recommended Dietary Allowance (RDA) for riboflavin was revised in 1998, with the goal to prevent riboflavin deficiency. Clinical signs of deficiency in humans may appear at intakes less than 0.5-0.6 milligram per day and excess urinary excretion of riboflavin can be seen at intake levels of approximately 1 milligram per day. Riboflavin deficiency (ariboflavinosis) can be associated with weakness, throat soreness/swelling, tongue swelling (glossitis), angular stomatitis/cheilosis (skin cracking or sores at the corners of the mouth), dermatitis (skin irritation), and anemia. Good dietary sources of riboflavin are milk (and other dairy products), eggs, enriched cereals/grains, meats, liver, and green vegetables (such as asparagus or broccoli). Riboflavin is easily destroyed by exposure to light (for example, riboflavin in milk stored in clear glass bottles).

Particular groups of people may be particularly susceptible to riboflavin deficiency, including the elderly, those with chronic illnesses, the poor, and those with alcohol dependence.

Adults (over 18 years old)

The U.S. Recommended Dietary Allowance (RDA) for adults (by mouth) is 1 milligram for female adolescents (14-18 years old); 1.3 milligrams for male adolescents (14-18 years old); 1.1 milligrams for female adults (older than 18 years); 1.3 milligrams for male adults (older than 18 years); 1.4 milligrams for pregnant women (any age); and 1.6 milligrams for breastfeeding women (any age).

Children (under 18 years old)

The U.S. Recommended Dietary Allowance (RDA) for infants and children (by mouth) is 0.3 milligram for 0-6 months old; 0.4 milligram for 7-12 months old; 0.5 milligram for 1-3 years old; 0.6 milligram for 4-8 years old; 0.9 milligram for 9-13 years old; 1 milligram for female adolescents (14-18 years old); and 1.3 milligrams for male adolescents (14-18 years old).

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Safety

Allergies

Riboflavin supplementation has been associated with rare reports of allergy/anaphylaxis.

Side Effects and Warnings

In general, the limited capacity of human adults to absorb orally administered riboflavin limits its potential for harm. Riboflavin intake many times higher than the RDA is apparently without demonstrable toxicity. Nevertheless, the photosensitizing (sensitivity to light) properties of riboflavin raise the possibility of some potential risks. Other possible reactions to very high doses include itching, numbness, burning/prickling sensations, and yellow discoloration of the urine.

Very low birth weight infants who receive pre-term infant formulas (PIF) augmented to provide riboflavin at levels five times that in term infant formulas have demonstrated high plasma levels of riboflavin and urinary riboflavin concentrations; lower doses can be considered in this setting.

Pregnancy and Breastfeeding

Riboflavin is generally regarded as being safe during pregnancy and breastfeeding.

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Methodology

This patient information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Monograph methodology

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Selected references

1. Angkatavanich J, Suthutvoravut U, Panijpan B, et al. Effects of multivitamin supplementation for improvement of thiamin, riboflavin, and retinol nutrition in pediatric patients. J Med Assoc Thai 1993;76 Suppl 2:138-145.
2. Breen C, Crowe A, Roelfsema HJ, et al. High-dose riboflavin for prophylaxis of migraine. Can Fam Physician 2003;49:1291-1293.
3. Brivet M, Tardieu M, Khellaf A, et al. Riboflavin responsive ethylmalonic-adipic aciduria in a 9-month-old boy with liver cirrhosis, myopathy and encephalopathy. J Inherit Metab Dis 1991;14(3):333-337.
4. Capo-chichi CD, Gueant JL, Lefebvre E, et al. Riboflavin and riboflavin-derived cofactors in adolescent girls with anorexia nervosa. Am J Clin Nutr 1999;69(4):672-678.
5. Joshi UM, Virkar KD, Amatayakul K, et al. Impact of hormonal contraceptives vis-a-vis non-hormonal factors on the vitamin status of malnourished women in India and Thailand. World Health Organization: Special Programme of Research, Development and Research Training in Human Reproduction. Task Force on Oral Contraceptives. Hum Nutr Clin Nutr 1986;40(3):205-220.
6. Munoz N, Hayashi M, Bang LJ, et al. Effect of riboflavin, retinol, and zinc on micronuclei of buccal mucosa and of esophagus: a randomized double-blind intervention study in China. J Natl Cancer Inst 1987;79(4):687-691.
7. Munoz N, Wahrendorf J, Bang LJ, et al. No effect of riboflavine, retinol, and zinc on prevalence of precancerous lesions of oesophagus. Randomised double-blind intervention study in high-risk population of China. Lancet 1985;2(8447):111-114.
8. Okuda J, Horiguchi N. Nutritional and ariboflavinosis-curing effects of riboflavin-5'-monobutyrate and monopalmitate. Chem Pharm Bull (Tokyo) 1980;28(1):8-13.
9. Rivlin RS. Riboflavin and cancer: a review. Cancer Res 1973;33(9):1977-1986.
10. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998;50(2):466-470.
11. Thorp VJ. Effect of oral contraceptive agents on vitamin and mineral requirements. J Am Diet Assoc 1980;76(6):581-584.
12. Traunmuller F, Ramharter M, Lagler H, et al. Normal riboflavin status in malaria patients in Gabon. Am J Trop Med Hyg 2003;68(2):182-185.
13. Wahrendorf J, Munoz N, Lu JB, et al. Blood, retinol and zinc riboflavin status in relation to precancerous lesions of the esophagus: findings from a vitamin intervention trial in the People's Republic of China. Cancer Res 1988;48(8):2280-2283.
14. Yoon HR, Hahn SH, Ahn YM, et al. Therapeutic trial in the first three Asian cases of ethylmalonic encephalopathy: response to riboflavin. J Inherit Metab Dis 2001;24(8):870-873.
15. Yurdakok M, Erdem G, Tekinalp G. Riboflavin in the treatment of neonatal hyperbilirubinemia. Turk J Pediatr 1988;30(3):159-161.

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