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Vitamin A toxicity Domina Petric, MD.

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1 Vitamin A toxicity Domina Petric, MD

2 Introduction The hepatic storage of vitamin A tends to mitigate against the development of intoxication due to intakes in excess of physiological needs. Persistent large overdoses (more than 1000 times the nutritionally required amount) can exceed the capacity of the liver to store and catabolize and will thus produce intoxication. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

3 Four aspects of vitamin A metabolism tend to protect against hypervitaminosis:
Relatively inefficient conversion of the provitamins A in the gut. The unidirectional oxidation of the vitamin to a form (retinoic acid) that is rapidly catabolized and excreted. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

4 Four aspects of vitamin A metabolism tend to protect against hypervitaminosis:
The relative excess capacity of CRBP(II) to bind retinol. Accelerated vitamin A catabolism. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

5 Hypervitaminosis A Hypervitaminosis A requires high exposures.
It is manifested after single large doses: >660,000 IU for adults, >330,000 IU for children, or after doses exceeding 100,000 IU/day have been taken for several months. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

6 Children experiencing hypervitaminosis A develop transient (one to two days) signs:
Nausea Vomiting Signs due to increased cerebrospinal fluid pressure: headache, vertigo, blurred or double vision Muscular incoordination 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

7 Chronic hypervitaminosis A
Occurs with recurrent exposures exceeding 12,500 IU in infants to 33,000 IU in adults. It is manifested mainly as changes in the skin and mucous membranes. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

8 Chronic hypervitaminosis A
Dry lips (cheilitis) is a common early sign, often followed by dryness and fragility of the nasal mucosa, leading to dry eyes and conjunctivitis. Skin lesions include dryness, pruritis, erythema, scaling, peeling of the palms and soles, hair loss (alopecia) and nail fragility. Headache, nausea and vomiting (signs of increased intracranial pressure) have also been reported. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

9 Cheilitis HelloMrDoctor.com
9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

10 Vitamin A and bones Hypervitaminosis A can affect bone and may increase risk for bone fracture. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

11 Signs of hypervitaminosis A
General: muscle and joint pain, headache. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

12 Signs of hypervitaminosis A
Skin: erythema, desquamation, alopecia. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

13 Signs of hypervitaminosis A
Mucous membranes: cheilitis, stomatitis, conjunctivitis. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

14 Signs of hypervitaminosis A
Liver dysfunction 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

15 Signs of hypervitaminosis A
Sceletal: thinning and fracture of long bones. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

16 Embryotoxic potential of high levels of vitamin A
Retinoids can be toxic to maternally exposed embryos. 13-cis-retinoic acid is very effective in the treatment of acne, but can cause severe disruption of cephalic neural crest cell activity: birth defects characterized by craniofacial, central nervous system, cardiovascular and thymus malformations. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

17 Embryotoxic potential of high levels of vitamin A
The critical period for fetal exposure to maternally derived retinoids is the time when organogenesis is occurring: before many women suspect they are pregnant. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

18 Embryotoxic potential of high levels of vitamin A
Fetal malformations of cranial– neural crest origin have been reported in cases of oral use of all trans-retinoic acid in treating acne vulgaris and of regular prenatal vitamin A supplements. 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

19 Carotenoid toxicity β-carotene intakes of as much as
30 mg/day are without side effects other than the accumulation of the carotenoid in the skin, with consequent yellowing of the skin (carotenodermia). 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

20 Literature Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc 9/23/2018 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc


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