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Riboflavin Deficiency

Riboflavin Deficiency Disease

Riboflavin (vitamin B2) deficiency is caused by inadequate dietary intake, malabsorption, and impaired metabolism. Its manifestations are glossitis, angular stomatitis, cheilosis, anemia, and peripheral neuropathy.


Presentation

Isolated riboflavin deficiency rarely occurs, it usually occurs in conjunction with other micronutrient deficiencies. However, isolated vitamin B6, C, and D deficiencies have been documented.

Riboflavin deficiency is mostly seen in people with poor intake of milk and dairy products, chronic alcoholics, patients with chronic diarrhea or chronic malabsorption syndromes and the elderly [9].

Clinical presentation of riboflavin deficiency includes cheilosis and angular stomtitis. Cheilosis presents as fissuring and swelling of the lips and angular stomatitis refers to fissuring and ulceration of the angular sides of the mouth. Other common indications of riboflavin deficiency include seborrheic dermatitis affecting the scrotum, vulva, and the area between nose and lips, conjunctivitis, and anemia [14]. Riboflavin deficiency also commonly causes peripheral neuropathy which presents as numbness in the hands and feet and dysesthesias presenting as reduced sensitivity to temperature, pressure, and vibration.

Maternal riboflavin deficiency may result in several congenital anomalies including cleft lip and palate, congenital heart defects and transverse limb deficiency. A study in the Netherlands provided evidence that a maternal diet low in riboflavin and high in saturated fats may increase the risk of congenital heart defects [15]. Findings from a study carried out to prevent birth defects indicated that pregnant mothers' diet found low in riboflavin is associated with an increased risk of transverse limb deficiency.

Anemia
  • Severity of anemia was no different between the two anemic groups either.[ncbi.nlm.nih.gov]
  • Riboflavin deficiency also alters your iron balance, and can contribute to iron deficiency anemia – so symptoms associated with anemia are often signs that you might also be suffering from a lack of B2.[stop-being-tired.com]
  • A dietary deficiency of riboflavin causing a syndrome chiefly marked by cheilitis, angular stomatitis, glossitis associated with a purplish red or magenta-colored tongue that may show fissures, corneal vascularization, dyssebacia, and anemia.[profiles.umassmed.edu]
  • […] and sickle cell anemia 11. important in maintaining levels of other B vitamins; needed for the conversion of tryptophan to niacin (vitamin B3) in the body 12. helps to treat carpal tunnel syndrome when used with vitamin B6 13. important during pregnancy[healthsupplementsnutritionalguide.com]
Cheilitis
  • Cellulitis of lips Cheilitis NOS Cheilodynia Cheilosis Exfoliative cheilitis Fistula of lips Glandular cheilitis Hypertrophy of lips Perlèche NEC Type 1 Excludes ariboflavinosis ( E53.0 ) cheilitis due to radiation-related disorders ( L55-L59 ) congenital[icd10data.com]
  • A dietary deficiency of riboflavin causing a syndrome chiefly marked by cheilitis, angular stomatitis, glossitis associated with a purplish red or magenta-colored tongue that may show fissures, corneal vascularization, dyssebacia, and anemia.[profiles.umassmed.edu]
  • Showing it to your doctor, he would certainly tell you point blank – Angular Cheilitis! This would be followed by you asking, “What is Angular Cheilitis?” To learn specific details of angular cheilitis in an informative video, Click Here.[web.archive.org]
Sore Mouth
  • mouth Pyridoxine (B6) or vitamin B12 deficiency Muscles Muscle spasms Calcium, magnesium or vitamin D deficiency Nails Brittle, thin nails Iron deficiency Saliva Sticky saliva / dry mouth Under-hydrated Skin Moist skin Over-hydrated Dry, scaly, pale[precisionnutrition.com]
Pruritus
  • The mother usually presents hyperemesis gravidarum in the absence of other features of riboflavin deficiency, such as skin lesions, jaundice, pruritus, sore mucous membranes, visual disturbances.[orpha.net]
Photophobia
  • Rarely, neovascularization and keratitis of the cornea occur, causing lacrimation and photophobia. Diagnosis Therapeutic trial Urinary excretion of riboflavin The lesions characteristic of riboflavin deficiency are nonspecific.[msdmanuals.com]
  • Rarely, neovascularization and keratitis of the cornea occur, causing lacrimation and photophobia. Therapeutic trial Urinary excretion of riboflavin The lesions characteristic of riboflavin deficiency are nonspecific.[merckmanuals.com]
  • […] cervix (cervical dysplasia) Esophageal dysplasia Deformed palate Growth retardation in infants and children Absence of parts of the lower limb (transverse limb deficiency) Congenital (by birth) heart defects Magenta-colored tongue Intolerance to light or photophobia[healthhype.com]
  • Signs & Symptoms of Vitamin B2 Deficiency: Cheilosis (chapping of the lips) Angular Stomatitis (cracking in the corners of the lips) Photophobia (sensitivity to light) Dry itchy eyes Depression Anxiety Memory loss Neuropathy Fatigue Vitamin B2 has been[towncenterwellness.com]
Dry Eyes
  • Specifically to superficial epithelium of the conjunctiva where conjunctivitis occurs as well as a decrease in the number of goblet cells on the epithelium surface (a decrease in goblet cells are associated with a condition known as Dry Eye .)[onlineholistichealth.com]
  • eyes Vitamin A or zinc deficiency; under-hydration Dry eyes with gray spots Vitamin A deficiency Red or difficult-to-control eyes Riboflavin (B2), pyridoxine (B6), thiamine (B1) or phosphorus deficiency Face Acne Vitamin C deficiency Feet Tingling feet[precisionnutrition.com]
Burning Eyes
  • . • Lack of vitality Just Get Enough Riboflavin In Your Diet The fact is that riboflavin is very important for your vision and here’s the proof: In one study, 47 patients who had light sensitivity, eyestrain, burning eyes, eyes that watered easily, and[webeyeclinic.com]
  • It seems to help with burning eyes, excess tearing, and decreased vision resulting from eye strain. Riboflavin is also used for many kinds of stress conditions, fatigue, and vitality or growth problems.[healthy.net]
Corneal Opacity
  • Other signs include corneal opacity, lenticular cataracts, hemorrhagic adrenals, fatty degeneration of the kidney and liver, and inflammation of the mucous membrane of the gastrointestinal tract.[en.wikipedia.org]
Red Eye
  • Other symptoms include red eyes, oily skin rashes on the face and around the scrotum and vulva. Riboflavin deficiency also causes numbness and heaviness of the hands and feet.[symptoma.com]
Numbness of the Hand
  • […] of the hands decreased sensitivity to touch, temperature, and vibration Diagnosis Riboflavin status is diagnosed using a test conducted on red blood cells that measures the activity of an enzyme called glutathione reductase.[medical-dictionary.thefreedictionary.com]
  • Riboflavin deficiency also commonly causes peripheral neuropathy which presents as numbness in the hands and feet and dysesthesias presenting as reduced sensitivity to temperature, pressure, and vibration.[symptoma.com]
Dysesthesia
  • Riboflavin deficiency also commonly causes peripheral neuropathy which presents as numbness in the hands and feet and dysesthesias presenting as reduced sensitivity to temperature, pressure, and vibration.[symptoma.com]

Workup

Diagnosis of riboflavin deficiency is made on clinical grounds from history and physical examination, however, the diagnosis is confirmed by assessing an individual's riboflavin status. The riboflavin status is assessed by measuring the activity of glutathione reductase in the erythrocytes [16].

This assessment is conducted by placing extracts of red blood cells in two test tubes. In one of the tubes, FAD is added, while the other tube contains none. The added riboflavin derivative causes insignificant enzyme stimulation in the red blood cells of individuals having normal riboflavin levels. When stimulation is 20% and less, riboflavin content is considered as normal; stimulation above 20% indicates that the patient has riboflavin deficiency.

Treatment

The treatment of riboflavin deficiency and conditions related to it comprises of riboflavin supplementation at the right dosage. Riboflavin supplement should also be initiated with correction of other co-existing B-vitamin deficiencies. Administration of multivitamins has not been proven to be effective, as each vitamin deficiency must be corrected adequately.

Riboflavin is one of water-soluble vitamins with no side effects. Riboflavin should be administered with food due to the significantly low absorption if taken without food; only 15% of riboflavin is absorbed if taken alone. The absorption rate of riboflavin is also reduced in conditions such as hepatitis, malabsorption syndromes, biliary obstruction, and cirrhosis. However, riboflavin is generally well absorbed by the GI tract. 

Riboflavin should be administered in divided doses in adults and children above 12 years, and in children of 3-10 years: 6-30 mg orally for adults and 3 -10 mg for children. The safety of administration of riboflavin for children below the age of 3 years has not been established.

The biological half-life of this vitamin is 66-84 minutes after a single oral or intramuscular dose. Excess serum riboflavin is excreted unchanged or as its metabolites by the kidneys, these give the urine a characteristic fluorescent yellow-green color [17]. A significant percentage (91%) of the vitamin is excreted after metabolism, 9% is excreted unchanged. Excretion occurs mostly by tubular secretion and glomerular filtration.

Riboflavin is denatured by light. If riboflavin is exposed to light and oxygen, it may be metabolized into free radicals which may worsen certain diseases, such as cataracts. Therefore, patients having cataract are advised to take riboflavin at a maximum daily dose of 10 mg.

Prognosis

Riboflavin deficiency is rarely associated with mortality or significant morbidity.

Etiology

A major cause of riboflavin deficiency is chronic alcoholism. Chronic alcohol consumption causes poor intestinal absorption, intake, and utilization of riboflavin. Additionally, the elevated homocysteine level which occurs in riboflavin deficiency reduces with alcohol withdrawal [4]. Poor intake of riboflavin is also seen in anorexic and lactose-intolerant individuals. Milk and other dairy products which are avoided by lactose-intolerant patients are rich sources of riboflavin.

Sun exposure and food processing including heating denatures riboflavin in riboflavin-rich foods, for example, keeping a bottle of milk under the direct sunlight for periods exceeding 3 hours may lead to destruction causing a loss of above 70% of riboflavin content. This is because combination of light and riboflavin produces toxic peroxides.

Gastrointestinal (GI) disorders such as chronic diarrhea, malabsorption syndromes, and hepatic diseases are common causes of riboflavin deficiency. These may alter the absorption or metabolism of the vitamin. Certain GI surgical procedures may also impair adequate absorption of the vitamin. Impairment of riboflavin function is found in patients affected by hypothyroidism open link and adrenal insufficiency due to impairment of riboflavin conversion to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) [5].

Physically active individuals especially athletes usually have an increase riboflavin requirements. However, there is no proof that riboflavin supplementation boosts their exercise performance [6]. 

Clinical riboflavin deficiency is a rare occurrence in the developed world; however, reports have suggested that subclinical riboflavin deficiency may be very common in the developed countries. Findings in the national survey data, by using EGRac as a functional biomarker, have reported the incidence of riboflavin deficiency in many otherwise healthy British adults.

Epidemiology

Studies on riboflavin deficiency in the United States revealed an incidence rate of 10% among the elderly. This value was based on biochemical analysis. However, on the basis of dietary intake, an incidence rate of 27% was reported [7] [8]. The prevalence estimated in Europe ranges from 7% to 20%. 

Sex distribution
Age distribution

Pathophysiology

Riboflavin occurs in the plasma bound to albumin, certain immunoglobulins, and flavin coenzymes [10]. There are other riboflavin-binding proteins, but these are specific to pregnancy. Several studies have suggested that these riboflavin-binding proteins may perform various functions necessary for fetal development and survival. These proteins have been found in different species where they serve similar functions. Increased riboflavin binding occurs in patients with malignancies, this is attributable to the increased expression of immunoglobulins associated with malignancies [11].

Almost all tissue riboflavin is bound to an enzyme called FAD which is bound by covalent bond to succinic dehydrogenase. Unbound flavins are unstable and are rapidly broken down by hydrolysis to riboflavin which diffuses from the tissues and excreted. This intracellular riboflavin phosphorylation is a way of trapping riboflavin [12].

Excess riboflavin in plasma is excreted in the urine. It may be excreted unaltered or as its metabolites including lumiflavin and 7-hydroxymethylriboflavin. Some urinary metabolites are useful in assessing gastrointestinal bacterial activity [13].

Prevention

Prevention of riboflavin deficiency entails increased consumption of foods rich in riboflavin contents such as eggs, vegetables, dairy products, milk, and carrots.

Summary

Riboflavin is also known as Vitamin B2 and is an important antioxidant in the body. It is essential for maintaining red blood cell levels, boosting energy levels, proper digestion of nutrients, scavenging free radicals, and maintaining healthy skin and eyes [1].

A water soluble vitamin, riboflavin is found in high levels in certain foods including brewer's yeast, liver, organ meats, oily fish, nori seaweed, milk products, shellfish, eggs, beans, whole grain products, avocados, mushrooms and dark leafy vegetables such as broccoli and spinach. Brewer's yeast is the most abundant of natural sources of vitamin B2. Less rich sources of vitamin B2 include tropical fruits, carrots, cabbage, cucumbers, grapes, berries, apples, and figs.

Riboflavin deficiency usually occurs along with the deficiency of other B-vitamins. The proper functioning of other B-vitamins is tied to a high level of vitamin B2 [2]. The daily requirement of riboflavin is 1.3 mg/day for adult male and 1.1 mg/day for female. Children and infants require much lower amounts of riboflavin.

Riboflavin functions in a lot of metabolic pathways via various enzyme systems. The two main functional derivatives of Riboflavin are: riboflavin 5' phosphate, which is a flavin mononucleotide, and riboflavin 5' adenosine diphosphate, a flavin adenine dinucleotide derivative. These derivatives act as coenzymes which combine with certain apoenzyme proteins to form flavin-based enzymes. The flavin coenzymes play essential roles in carbohydrate, amino acids, and cellular metabolism. Riboflavin may also play a crucial function in fat metabolism [3].

Gastrointestinal diseases which may impair riboflavin absorption include malabsorption syndromes, inflammatory bowel disease, and chronic diarrheal infections. Impaired function and metabolism of riboflavin occurs in cases of hypothyroidism and adrenal insufficiency.

Riboflavin deficiency presents with angular stomatitis, cheilosis, anemia, peripheral neuropathy, and seborrheic dermatitis. Low maternal intake of riboflavin may be associated with the development of certain congenital birth defects in the babies.

Diagnosis of riboflavin deficiency can be made on clinical grounds; however, it can be confirmed by analyzing erythrocyte glutathione reductase activity.

Treatment of riboflavin deficiency involves replenishment of the vitamin and other deficient vitamins, and correction of the underlying disease.

Patient Information

Riboflavin is vitamin B2 and is one of the water-soluble vitamins. Riboflavin is essential for energy production, protection from diseases, boosting red blood cell levels, and iron metabolism.

Riboflavin deficiency may be caused by reduced intake of riboflavin-rich foods, poor absorption of the vitamin, and impaired function and availability of the vitamin in the body.

Examples of Riboflavin-rich foods include root vegetables, dairy products, milk, leafy dark green vegetables such as spinach and broccoli, shellfish, beans, avocados, whole grains, mushrooms, nori seaweed, organ meats, and eggs. Less rich sources of riboflavin include cabbage, carrots, cucumbers, grapes, and berries.

Generally, there are three factors that can lead to deficiency of this vitamin in the body: reduced intake, poor absorption, and impaired function.

Dietary deficiency of riboflavin may not be from an overt lack of intake of riboflavin-rich foods, but may also be from environmental factors such as heat and sunlight. Heating and evaporation of milk causes up to 20% loss of riboflavin. Riboflavin loss also occurs with use of soda. Direct exposure to sunlight causes destruction and inactivation of riboflavin in riboflavin-containing foods, for example, a bottle of milk kept under direct sunlight for over 3 hours causes loss of over 70% of the riboflavin content.

Diseases of the gut which cause chronic diarrhea and vomiting may impair intake and absorption of riboflavin. Certain surgeries of the gut may also impair absorption of riboflavin. Other diseases such as low thyroid and adrenal function may also cause impaired function of the vitamin. Liver diseases are also characterized by poor metabolism of riboflavin making it unavailable for use in the body.

Some factors are associated with increased excretion of riboflavin. These include drugs and diseases such as diabetes which cause increased urination. This can also be caused by antibiotic use.

Certain states which put a higher demand of nutrients on the body, such as pregnancy and stress, may also trigger riboflavin deficiency.

Riboflavin has a wider role in the metabolism and utilization of all basic elements of food, the carbohydrates, fats and protein. A deficiency of riboflavin therefore adversely affects body's vital functions. 

Riboflavin deficiency concurrently occurs with the deficiency of other vitamins. Riboflavin deficiency typically presents with cracking of the lips, redness of the tongue, and the presence of cracks and ulcers at the angle of the mouth.

Other symptoms include red eyes, oily skin rashes on the face and around the scrotum and vulva. Riboflavin deficiency also causes numbness and heaviness of the hands and feet.

Studies have revealed that pregnant women who do not ingest adequate riboflavin-rich foods may give birth to children with certain birth defects including cleft lips and palate.

Riboflavin deficiency is suspected when a patient presents with the above characteristic symptoms. However, the condition can be diagnosed by a laboratory investigation of the red blood cells.

Treatment of riboflavin deficiency is not done in isolation. The other deficient vitamins must be supplemented concomitantly until the symptoms resolve. The riboflavin supplements should be taken with food, as they are poorly absorbed if they are taken alone. Consumption of riboflavin-rich foods may help prevent riboflavin deficiency. 

References

Article

  1. Henriques BJ, Olsen RK, Bross P, et al. Emerging roles for riboflavin in functional rescue of mitochondrial β-oxidation flavoenzymes. Curr Med Chem. 2010;17(32):3842-3854.
  2. Ma AG, Schouten EG, Zhang FZ, et al. Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplements. J Nutr. 2008; 138(10):1946-1950.
  3. Powers HJ. Riboflavin (vitamin B-2) and health. Am J Clin Nutr. 2003; 77(6):1352-1360.
  4. Heese P, Linnebank M, Semmler A, et al. Alterations of homocysteine serum levels during alcohol withdrawal are influenced by folate and riboflavin: results from the German Investigation on Neurobiology in Alcoholism (GINA). Alcohol Alcohol. 2012; 47(5):497-500.
  5. Powers HJ. Current knowledge concerning optimum nutritional status of riboflavin, niacin and pyridoxine. Proc Nutr Soc. 1999;58(2):435-440.
  6. Soares MJ, Satyanarayana K, Bamji MS, Jacob CM, Ramana YV, Rao SS. The effect of exercise on the riboflavin status of adult men. Br J Nutr. 1993; 69(2):541-551.
  7. Guthrie HA, Guthrie GM. Factor analysis of nutritional status data from Ten State Nutrition Surveys. Am J Clin Nutr. 1976;29:1238–1241.
  8. Fanelli MT, Woteki CE. Nutrition intakes and health status of older Americans. Data from the NHANES II. Ann New York Acad Sci. 1989;561:94–103.
  9. Suboticanec K, Stavljenic A, Bilic-Pesic L, et al. Nutritional status, grip strength and immune function in institutionalised elderly. Int J Vitam Nutr Res. 1989;59:20–28.
  10. Innis WS, McCormick DB, Merrill AH Jr. Variations in riboflavin binding by human plasma: identification of immunoglobulins as the major proteins responsible. Biochem Med. 1986;34:151–165.
  11. Innis WS, Nixon DW, Murray DR, McCormick DB, Merrill AH Jr. Immunoglobulins associated with elevated riboflavin binding by plasma from cancer patients. Proc Soc Exp Biol Med. 1986;181:237–241.
  12. Gastaldi G, Ferrari G, Verri A, Casirola D, Orsenigo MN, Laforenza U. Riboflavin phosphorylation is the crucial event in riboflavin transport by isolated rate enterocytes. J Nutr 2000;130:2556–2561.
  13. Chastain JL, McCormick DB. Flavin catabolites: identification and quantitation in human urine. Am J Clin Nutr. 1987;46:830–834.
  14. Food and Nutrition Board, Institute of Medicine. Riboflavin. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington D.C.: National Academy Press; 1998:87-122.
  15. Smedts HP, Rakhshandehroo M, Verkleij-Hagoort AC, et al. Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects. Eur J Nutr. 2008; 47(7):357-65.
  16. Hoey L, McNulty H, Strain J. Studies of biomarker responses to intervention with riboflavin: a systematic review. Am J Clin Nutr. 2009; 89(6):1960S-1980S.
  17. Moriyama Y. Riboflavin transporter is finally identified. J Biochem. 2011; 150 (4):341-3.

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Last updated: 2018-06-22 01:59