Hypervitaminosis A refers to high storage levels of vitamin A in the body that can lead to toxic symptoms. There are four major adverse effects of hypervitaminosis A: birth defects, liver abnormalities, reduced bone mineral density that may result in osteoporosis (see the previous section), and central nervous system disorders.1 2 3

Toxic symptoms can also arise after consuming very large amounts of preformed vitamin A over a short period of time. Signs of acute toxicity include nausea and vomiting, headache, dizziness, blurred vision, and muscular uncoordination.4 5 6 Although hypervitaminosis A can occur when large amounts of liver are regularly consumed, most cases result from taking excess amounts of the nutrient in supplements.

The IOM has established Tolerable Upper Intake Levels (ULs) for vitamin A that apply to healthy populations.7 The UL was established to help prevent the risk of vitamin A toxicity. The risk of adverse health effects increases at intakes greater than the UL. The UL does not apply to malnourished individuals receiving vitamin A either periodically or through fortification programs as a means of preventing vitamin A deficiency. It also does not apply to individuals being treated with vitamin A by medical doctors for diseases such as retinitis pigmentosa.

Table 5: Tolerable Upper Intake Levels (ULs) for retinol

Age
(years)		 Children
(mcg)		 Males
(mcg)		 Females
(mcg)		 Pregnancy
(mcg)		 Lactation
(mcg)
0-1 600
(2,000 IU)
1-3 600
(2,000 IU)
4-8 900
(3,000 IU)
9-13 1,700 (5610 IU)
14-18 2,800 (9,240 IU) 2,800 (9,240 IU) 2,800 (9,240 IU) 2,800 (9,240 IU)
19+ 3,000 (10,000 IU) 3,000 (10,000 IU) 3,000 (10,000 IU) 3,000 (10,000 IU)

Retinoids are compounds that are chemically similar to vitamin A. Over the past 15 years, synthetic retinoids have been prescribed for acne, psoriasis, and other skin disorders.8 Isotretinoin (Roaccutane® or Accutane®) is considered an effective anti-acne therapy. At very high doses, however, it can be toxic, which is why this medication is usually saved for the most severe forms of acne.9 10 11 The most serious consequence of this medication is birth defects. It is extremely important for sexually active females who may become pregnant and who take these medications to use an effective method of birth control. Women of childbearing age who take these medications are advised to undergo monthly pregnancy tests to make sure they are not pregnant.

Provitamin A carotenoids such as beta-carotene are generally considered safe because they are not associated with specific adverse health effects. Their conversion to vitamin A decreases when body stores are full. A high intake of provitamin A carotenoids can turn the skin yellow, but this is not considered dangerous to health.

Clinical trials that associated beta-carotene supplements with a greater incidence of lung cancer and death in current smokers raise concerns about the effects of beta-carotene supplements on long-term health; however, conflicting studies make it difficult to interpret the health risk.

For example, the Physicians Health Study compared the effects of taking 50 mg beta-carotene every other day to a placebo in over 22,000 male physicians and found no adverse health effects.12

Also, a trial that tested the ability of four different nutrient combinations to help prevent the development of esophageal and gastric cancers in 30,000 men and women in China suggested that after five years those participants who took a combination of beta-carotene, selenium, and vitamin E had a 13% reduction in cancer deaths.13

In one lung cancer trial, men who consumed more than 11 grams/day of alcohol (approximately one drink per day) were more likely to show an adverse response to beta-carotene supplements.14 which may suggest a potential relationship between alcohol and beta-carotene. The IOM did not set ULs for carotene or other carotenoids. Instead, it concluded that beta-carotene supplements are not advisable for the general population. As stated earlier, however, they may be appropriate as a provitamin A source for the prevention of vitamin A deficiency in specific populations.15


Disclaimer
Reasonable care has been taken in preparing this document and the information provided herein is believed to be accurate. However, this information is not intended to constitute an "authoritative statement" under Food and Drug Administration rules and regulations.

About Source: ODS

The mission of the Office of Dietary Supplements (ODS) is to strengthen knowledge and understanding of dietary supplements by evaluating scientific information, stimulating and supporting research, disseminating research results, and educating the public to foster an enhanced quality of life and health for the U.S. population.

General Safety Advisory

Health professionals and consumers need credible information to make thoughtful decisions about eating a healthful diet and using vitamin and mineral supplements. These Fact Sheets provide responsible information about the role of vitamins and minerals in health and disease. Each Fact Sheet in this series received extensive review by recognized experts from the academic and research communities.

The information is not intended to be a substitute for professional medical advice. It is important to seek the advice of a physician about any medical condition or symptom. It is also important to seek the advice of a physician, registered dietitian, pharmacist, or other qualified health professional about the appropriateness of taking dietary supplements and their potential interactions with medications.

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Footnotes

  1. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001. [↩]
  2. Bendich A, Langseth L. Safety of vitamin A. Am J Clin Nutr 1989;49:358-71. PubMed abstract [↩]
  3. Udall JN, Greene HL. Vitamin update. Pediatr Rev 1992;13:185-94. PubMed abstract [↩]
  4. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001. [↩]
  5. Bendich A, Langseth L. Safety of vitamin A. Am J Clin Nutr 1989;49:358-71. PubMed abstract [↩]
  6. Udall JN, Greene HL. Vitamin update. Pediatr Rev 1992;13:185-94. PubMed abstract [↩]
  7. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001. [↩]
  8. Soprano DR, Soprano KJ. Retinoids as teratogens. Annu Rev Nutr 1995;15:111-32. PubMed abstract [↩]
  9. Orafanos CE, Zouboulis CC, Almond-Roesler B, Geilen CC. Current use and future potential role of retinoids in dermatology. Drugs 1997;53:358-88. PubMed abstract [↩]
  10. Meigel WN. How safe is oral isotretinoin? Dermatology 1997;195:22-28, 38-40. PubMed abstract [↩]
  11. Hathcock JN. Vitamin and Mineral Safety. Council for Responsible Nutrition, Washington, DC, 1997, pp. 26-27. [↩]
  12. Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, Belanger C, LaMotte F, Gaziano JM, Ridker PM, Willett W, Peto R. Lack of effect of long-term supplementation with beta-carotene on the incidence of malignant neoplasm and cardiovascular disease. N Eng J Med 1996;334:1145-9. PubMed abstract [↩]
  13. Blot WJ, Li J-Y, Taylor PR, Guo W, Dawsey S, Wang G-Q, Yang CS, Zheng S-F, Gail M, Li G-Y, Yu Y, Liu B-Q, Tangrea J, Sun Y-H, Liu F, Fraumeni JF, Zhang Y-H, Li B. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 1993;85:1483-92. PubMed abstract [↩]
  14. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001. [↩]
  15. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press, Washington, DC, 2001. [↩]

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