Vitamin A Toxicity and Overdose

Vitamin A Toxicity Definition

Vitamin A toxicity, also known as hypervitaminosis A, is a state arising from excessive vitamin A in the body. Normally, sufficient quantities of vitamin A can be acquired from a balanced diet. No additional supplementation is necessary. Consuming large amounts of foods containing vitamin A is a common cause of vitamin A toxicity.  Overzealous use of vitamins, usually multi-vitamins, and drugs that are precursors of active vitamin A can lead to toxicity. This can lead to severe symptoms which may not cause any permanent damage if the source of high doses of vitamin A is discontinued. However, in pregnant women there is the risk of defects in fetal development which is permanent.

Vitamin A Functions and Absorption

Vitamins are vital nutrients required for proper growth, health, and development. Most of the vitamins are obtained from the diet. Taking too much of any vitamin can result in vitamin toxicity or hypervitaminosis. Vitamin A (retinol) is required for good vision and repair of the epithelial tissue that lines the cavities in the human body.

Green leafy vegetables, yellow vegetables (like carrots), meats (like liver, kidney, milk, and fish oil), drug supplements and bright-colored fruits contain substances called ?-carotene and carotenoids. These substances change into retinol in the body. After absorption, retinol binds to proteins called chylomicrons and is sent to the liver. The liver stores 80 to 90% of the body’s retinol.

There is no proper mechanism to eliminate excess vitamin A. Therefore an overdose of vitamin A can cause vitamin A toxicity.

Vitamin A Toxicity Maximum Dosage

To avoid the risk of vitamin A toxicity, the intake should not cross the daily tolerable upper levels in healthy individuals. These levels are:

  • 0.6 mg or 2000 IU (international units) for 0 to 3 years of age
  • 0.9 mg or 3000 IU for 4 to 8 years of age
  • 1.7 mg or 5665 IU during 9 to 13 years of age
  • 2.8 mg or 9335 IU during 14 to 18 years of age
  • 3 mg or 10,000 IU after 19 years of age

Vitamin A Toxicity Incidence

About 35 to 50% of adults taking vitamin supplements and are at risk of developing hypervitaminosis or vitamin toxicity. Females use vitamin supplements more frequently than males and are therefore at a higher risk. People consuming large amounts of carrots or animal liver for long are at higher risk of developing retinol or vitamin A toxicity specifically. Cultural and regional factors may therefore play some role in the incidence of vitamin A toxicity depending on groups who have a diet high in vitamin A toxicity.

Vitamin A Toxicity Pathophysiology

Some vitamins are water-soluble, while some are fat-soluble like vitamin A. Water-soluble vitamins are stored only in limited quantities. If a water-soluble vitamin is taken into excess amount, it is usually excreted in the urine. This elimination process decreases the risk of developing vitamin toxicity of a particular water-soluble vitamin.

Conversely, a fat-soluble vitamin is stored in the body in different amounts. It is not as easily eliminated from the system and can build up to very high levels. Therefore when too much of a fat-soluble vitamin is taken, it is more likely to cause toxicity. As a fat-soluble vitamin, vitamin A can accumulate in the body. This makes an overdose of fat-soluble vitamins more dangerous than water-soluble vitamins.

Since retinol is the active form of vitamin A, an overdose with retinol is more likely to result in toxicity symptoms than with beta-carotene. Beta-carotene which is another form of vitamin A is changed into retinol within the body. However, excessive beta-carotene does not lead to vitamin A toxicity. Depending on the period of time over which this occurs, the effects of vitamin A toxicity can vary to some extent.

Vitamin A Toxicity Symptoms

Excess of vitamin A can be of two types:

  • Acute vitamin A toxicity is caused by taking too much vitamin A suddenly or over a short period of time.
  • Chronic vitamin A toxicity occurs when too much of the vitamin is taken for long periods.

Although symptoms of the two types may differ, a headache and skin rash usually develop in both types.

Acute vitamin A toxicity

  • Increase in intracranial (inside the skull) pressure
  • Drowsiness
  • Stomach ache
  • Irritability
  • Nausea, and vomiting
  • Peeling of skin
  • Anorexia
  • Changes in mental state
  • Blurred vision
  • Muscle pain with weakness

Chronic vitamin A toxicity

  • Coarse hair
  • Loss of eye lashes
  • Dry and rough skin
  • Dry eyes
  • Dry and cracked lips
  • Severe headache
  • Weakness
  • Pseudotumor cerebri (false sensation of a tumor, due to pressure of fluid surrounding the brain)
  • Increased risk of fractures (especially in the elderly)
  • Hair loss
  • Fever
  • Sleeplessness
  • Weight loss
  • Tiredness
  • Irritability
  • Diarrhea
  • Anemia
  • Bone and joint pains
  • Irregular menstrual periods
  • Nose bleeds
  • Brittle nails
  • Conjunctivitis
  • Petechiae (pinpoint red dots on the skin)
  • Liver cirrhosis
  • Ataxia (problems in muscle coordination)
  • Swollen optic nerve
  • Double vision
  • Swelling
  • Birth defects of fetus

In children, vitamin A toxicity can cause:

  • Cortical hyperostosis (formation of new bone tissue)
  • Joint pain
  • Itching
  • Anorexia
  • Slow body growth
  • Enlarged liver (hepatomegaly) and spleen (splenomegaly)

In carotenodermia (excess blood carotene), the skin of the palms and soles becomes deep yellow.

Vitamin A Toxicity Causes

The estimated toxic dose of vitamin A is about 25,000 IU/kg.

Acute vitamin A toxicity occurs within hours or days after taking a very large quantity of vitamin A accidentally (usually in children). In adults, eating the liver of certain mammals can result in acute toxicity. These meats contain quite a lot of vitamin A, usually in the million of units.

Chronic vitamin A toxicity occurs after taking 25,000 IU of vitamin A daily for long time. Megavitamin therapy given for acne or other skin disorders can result in chronic vitamin A toxicity. A medication called isotretinoin commonly used for severe acne can cause birth defects in a fetus if used by pregnant women.

The daily intake of vitamin A should not be more than 5000 IU for adults and 8000 IU for pregnant or breastfeeding women. If extremely large amounts of vitamin A are taken, it can cause serious adverse effects which outweighs its potentially beneficial effect.

Vitamin A Toxicity Complications

Deaths from vitamin A toxicity are rare but other complications seen with vitamin A toxicity may include the following:

  • A very high increase in calcium levels, which can result in osteoporosis and kidney damage.
  • Stunted growth in infants.
  • Liver damage.
  • Abnormal development of the fetus.

Vitamin A Toxicity Diagnosis

A preliminary diagnosis may be reached based on the signs ans symptoms indicative of vitamin A toxicity. The history is also important as it may reveal the source of the vitamin A. The following diagnostic methods can be used to diagnose vitamin A overdose or toxicity:

  • Blood tests can be done to check vitamin A levels, but they cannot reveal the extent of toxicity. Fasting serum vitamin A levels may exceed normal values 28 to 86 ug/dL and reach 100 to 2000 ug/dL. Blood calcium levels also rise.
  • X-rays can show bone defects.
  • Liver function tests are also performed if vitamin A toxicity is suspected and it may be abnormal.

Vitamin A Toxicity Treatment

Treatment includes discontinuing intake of vitamin A. Supplements should be stopped immediately while dietary intake of foods high in vitamin A should also be corrected. Except for the cases of birth defects due to vitamin A toxicity, in most of the people complete recovery occurs upon stopping vitamin A intake.

In chronic toxicity, the elimination and utilization of vitamin A takes long periods of time before the levels return to a normal state. However, the symptoms may completely resolve as soon as 1 to 4 weeks. However, birth defects due to vitamin A toxicity are not reversible. In case of severe dehydration, changes in mental status, severe hypercalcemia (high blood calcium levels), and liver toxicity, patients are hospitalized. Patients with high intracranial pressure may need lumbar punctures or further treatment to reduce the pressure.

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