The document discusses riboflavin deficiency and toxicity. Riboflavin deficiency can result in a variety of signs and symptoms affecting multiple organ systems. Inadequate dietary intake, enhanced catabolism during illness or exercise, alcohol consumption, phototherapy, and certain medications can contribute to riboflavin deficiency. Subclinical deficiency has been associated with increased carcinogenesis and oxidative DNA damage. Riboflavin deficiency may also provide some protection against malaria infection and tryptophan deficiency-induced cataracts. Riboflavin toxicity is very low due to poor absorption, with high oral doses being essentially nontoxic.

1. Domina Petric, MD
Riboflavin deficiency and
toxicity

2. Riboflavin deficiency
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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3. Signs of riboflavin deficiency overview
Organ system/function Signs
Appetite Decreased
Growth Decreased
Dermatologic Cheilitis, stomatitis
Muscular Weakness
Gastrointestinal Inflammation, ulcer
Skeletal Deformities
Vital organs Hepatic steatosis
Erythrocytes Anemia
Nervous Ataxia, paralysis
Males Sterility
Females Decreased fertility
Fetal Malformations, death
Retinal Photophobia
Corneal Decreased vascularization 3

4. Factors contributing to
riboflavin deficiency
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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5. Inadequate diet
• Inadequate diet is the most important cause
of riboflavin deficiency.
• This involves the low consumption of
milk, which is the most important source of
the vitamin available in most diets.
• In industrialized countries, riboflavin
deficiency occurs most frequently among
alcoholics, whose dietary practices are often
faulty, leading to this and other deficiencies.
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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6. Enhanced catabolism
Catabolic conditions
associated with illness or
vigorous physical exercise
and involving nitrogen loss
increase riboflavin losses.
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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7. Alcohol
High intakes of alcohol
appear to antagonize
the utilization of FAD
from foods.
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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8. Phototherapy
Phototherapy of infants with
hyperbilirubinemia often leads to
riboflavin deficiency (by
photodestruction of the vitamin)
if such therapy does not also
include the administration of
riboflavin.
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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9. Exercise
• Physical exercise can produce
abnormalities in a variety of biochemical
markers of riboflavin status such as
increased erythrocyte glutathione
reductase activity coefficient and
reduced urinary riboflavin.
• There is no evidence that such
abnormalities lead to impairments in
physiological performance.
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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10. Other
• Reduced riboflavin status among
some women using oral
contraceptive agents.
• Patients receiving diuretics or
undergoing hemodialysis
experience enhanced loss of
riboflavin (as well as other water-
soluble vitamins).
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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11. Deficiency signs
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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12. Deficiency signs
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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13. Deficiency signs
cheilosis/cheilitis angular stomatitis glossitis
hyperemia and
edema of the oral
mucosa
seborrheic dermatitis
around the nose and
mouth and
scrotum/vulva
normocytic,
normochromic anemia
with reticulocytopenia,
leukopenia and
thrombocytopenia
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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14. Cheilosis
Sabkadentist.com
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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15. Seborrheic dermatitis
Noskinproblems.com
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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16. Deficiency signs
Riboflavin-deficient patients also
experience neurological dysfunction:
• Peripheral neuropathy of the
extremities characterized by
hyperesthesia, coldness and pain, as
well as decreased sensitivity to
touch, temperature, vibration and
position.
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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17. Subclinical deficiency
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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18. Subclinical deficiency
• Riboflavin deficiency has been reported
to enhance carcinogenesis.
• This effect is thought to be due to
diminished antioxidant protection,
increasing the activation of carcinogens
and oxidative damage to DNA, and/or
diminished folate metabolism, reducing
DNA synthesis, repair and methylation.
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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19. Subclinical deficiency
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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20. Protection against malaria
Because growth of the
malarial parasite
(Plasmodium spp.) in
the erythrocytes of
infected hosts causes
oxidative stress in those
cells, riboflavin
deficiency is protective
against propagation of
the infection.
4/16/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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21. Protection against tryptophan
deficiency-induced cataract
• Riboflavin deficiency has been shown
to protect the rat from the
cataractogenic effect of a low-
tryptophan diet.
• The metabolic basis of this effect may
involve the lack of formation of a
riboflavinyl tryptophan adduct that
accelerates the photo-oxidation of the
amino acid to a prooxidative form.
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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22. Riboflavin toxicity
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Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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23. Riboflavin toxicity
The toxicity of riboflavin is very low
and problems of hypervitaminosis
are not expected.
Probably because it is not well
absorbed, high oral doses of
riboflavin are essentially nontoxic.
4/16/2018
Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
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24. • Combs GF. The Vitamins. Fundamental Aspects
in Nutrition and Health. Elsevier Inc. 2008.
Literature
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