Hypervitaminosis A
Encyclopedia
Hypervitaminosis A refers to the effects of excessive vitamin A
(specifically retinoid
) intake.
and vomiting
, headache
, dizziness
, blurred vision
, and loss of muscular
coordination.
s is exceeded. The excess vitamin A enters the circulation causing systemic toxicity. Betacarotene, a precursor
of vitamin A, is selectively converted into retinoids, so it does not cause toxicity.
Although hypervitaminosis A can occur when large amounts of liver (including cod liver oil and other fish oils) are regularly consumed, most cases of vitamin A toxicity result from an excess intake of vitamin A in the form of vitamin supplements. Toxic symptoms can also arise after consuming very large amounts of preformed vitamin A over a short period of time. (See Polar-bear liver below.) The U.S. Institute of Medicine
says that the Lowest Observed Adverse Effect Level (LOAEL) for vitamin A, when taken over an extended period of time is 21,600 IU
. Most multivitamins contain vitamin A doses below 10,000 IU, therefore multi-vitamins are unlikely to cause vitamin A toxicity when taken at their recommended dosages. But in high doses, its central nervous system
toxicity can be enhanced by its lipid solubility because it is readily transported across the blood brain barrier and concentrated in the brain
.
Vitamin A causes cells to swell with fluid; too much vitamin A causes them to rupture in hyposmotic environments, hence the toxicity. Toxicity has been shown to be mitigated through vitamin E
(tocopherol
), cholesterol
, zinc
, taurine, and calcium
. Cholesterol has been shown to prevent retinol induced golgi
fragmentation.
has established Daily Tolerable Upper Levels (UL) of intake for vitamin A from supplements that apply to healthy populations, in order to help prevent the risk of vitamin A toxicity. These levels for preformed vitamin A in microgram
s (µg) and International Unit
s (IU) are
The dose over and above the RDA
is among the narrowest of the vitamins and minerals. Possible pregnancy
, liver disease
, high alcohol
consumption, and smoking
are indications for close monitoring and limitation of vitamin A administration. However, vitamin A has also been repeatedly tested and used therapeutically over several decades in larger amounts. For example, a total dosage of 100,000 - 400,000 IU has been given for treatment of severe pediatric measles
, in areas where vitamin A deficiency may be present, in order to reduce childhood mortality.
of certain animals — including the polar bear
, seal
, walrus
, and husky
— is unsafe to eat because it is extraordinarily high in vitamin A
. This danger has long been known to the Inuit
and has been recognized by Europeans since at least 1597 when Gerrit de Veer
wrote in his diary that, while taking refuge in the winter in Nova Zemlya
, he and his men became severely ill after eating polar bear liver. In 1913, Antarctic explorers Douglas Mawson
and Xavier Mertz
were both poisoned (and Mertz died) from eating the liver of their sled dog
s during the Far Eastern Party
.
Vitamin A
itself was not discovered until 1917.
Pathological changes consistent with hypervitaminosis A have been seen in bones of Homo erectus
, and have also been attributed to consumption of carnivore liver.
The livers of many other animals have lower levels of vitamin A and are commonly eaten
.
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
(specifically retinoid
Retinoid
The retinoids are a class of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth....
) intake.
Presentation
Effects include- Birth defects
- LiverLiverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
problems - Reduced bone mineral density that may result in osteoporosisOsteoporosisOsteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
- Coarse bone growths
- Skin discoloration
- Hair loss
- Excessive skin dryness/peeling (desquamationDesquamationDesquamation , also called skin peeling, is the shedding of the outermost membrane or layer of a tissue, such as the skin.-Skin:Normal, nonpathologic desquamation of the skin occurs when keratinocytes, after moving apically over about 14 days, are individually shed unnoticeably...
) - Angular cheilitisAngular cheilitisAngular cheilitis is an inflammatory lesion at the labial commissure, or corner of the mouth, and often occurs bilaterally. The condition manifests as deep cracks or splits...
- Intracranial hypertension (see Idiopathic intracranial hypertensionIdiopathic intracranial hypertensionIdiopathic intracranial hypertension , sometimes called by the older names benign intracranial hypertension or pseudotumor cerebri , is a neurological disorder that is characterized by increased intracranial pressure in the absence of a tumor or other diseases...
)
Signs
Signs of acute toxicity include nauseaNausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, blurred vision
Visual perception
Visual perception is the ability to interpret information and surroundings from the effects of visible light reaching the eye. The resulting perception is also known as eyesight, sight, or vision...
, and loss of muscular
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
coordination.
Pathophysiology
Hypervitaminosis A occurs when the maximum limit for liver stores of retinoidRetinoid
The retinoids are a class of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth....
s is exceeded. The excess vitamin A enters the circulation causing systemic toxicity. Betacarotene, a precursor
Precursor (chemistry)
In chemistry, a precursor is a compound that participates in the chemical reaction that produces another compound. In biochemistry, the term "precursor" is used more specifically to refer to a chemical compound preceding another in a metabolic pathway....
of vitamin A, is selectively converted into retinoids, so it does not cause toxicity.
Although hypervitaminosis A can occur when large amounts of liver (including cod liver oil and other fish oils) are regularly consumed, most cases of vitamin A toxicity result from an excess intake of vitamin A in the form of vitamin supplements. Toxic symptoms can also arise after consuming very large amounts of preformed vitamin A over a short period of time. (See Polar-bear liver below.) The U.S. Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...
says that the Lowest Observed Adverse Effect Level (LOAEL) for vitamin A, when taken over an extended period of time is 21,600 IU
International unit
In pharmacology, the International Unit is a unit of measurement for the amount of a substance, based on biological activity or effect. It is abbreviated as IU, as UI , or as IE...
. Most multivitamins contain vitamin A doses below 10,000 IU, therefore multi-vitamins are unlikely to cause vitamin A toxicity when taken at their recommended dosages. But in high doses, its central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
toxicity can be enhanced by its lipid solubility because it is readily transported across the blood brain barrier and concentrated in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
.
Vitamin A causes cells to swell with fluid; too much vitamin A causes them to rupture in hyposmotic environments, hence the toxicity. Toxicity has been shown to be mitigated through vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
(tocopherol
Tocopherol
Tocopherols are a class of chemical compounds of which many have vitamin E activity. It is a series of organic compounds consisting of various methylated phenols...
), cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
, zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
, taurine, and calcium
Calcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
. Cholesterol has been shown to prevent retinol induced golgi
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
fragmentation.
Recommended supplement limits
The U.S. Institute of MedicineInstitute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...
has established Daily Tolerable Upper Levels (UL) of intake for vitamin A from supplements that apply to healthy populations, in order to help prevent the risk of vitamin A toxicity. These levels for preformed vitamin A in microgram
Microgram
In the metric system, a microgram is a unit of mass equal to one millionth of a gram , or 1/1000 of a milligram. It is one of the smallest units of mass commonly used...
s (µg) and International Unit
International unit
In pharmacology, the International Unit is a unit of measurement for the amount of a substance, based on biological activity or effect. It is abbreviated as IU, as UI , or as IE...
s (IU) are
- 0–3 years: 600 µg or 2000 IU
- 4–8 years: 900 µg or 3000 IU
- 9–13 years: 1700 µg or 5665 IU
- 14–18 years: 2800 µg or 9335 IU
- 19+ years: 3000 µg or 10,000 IU
The dose over and above the RDA
Dietary Reference Intake
The Dietary Reference Intake is a system of nutrition recommendations from the Institute of Medicine of the U.S. National Academy of Sciences. The DRI system is used by both the United States and Canada and is intended for the general public and health professionals...
is among the narrowest of the vitamins and minerals. Possible pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
, liver disease
Liver disease
Liver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
, high alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
consumption, and smoking
Smoking
Smoking is a practice in which a substance, most commonly tobacco or cannabis, is burned and the smoke is tasted or inhaled. This is primarily practised as a route of administration for recreational drug use, as combustion releases the active substances in drugs such as nicotine and makes them...
are indications for close monitoring and limitation of vitamin A administration. However, vitamin A has also been repeatedly tested and used therapeutically over several decades in larger amounts. For example, a total dosage of 100,000 - 400,000 IU has been given for treatment of severe pediatric measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
, in areas where vitamin A deficiency may be present, in order to reduce childhood mortality.
Toxicity from eating liver
The liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
of certain animals — including the polar bear
Polar Bear
The polar bear is a bear native largely within the Arctic Circle encompassing the Arctic Ocean, its surrounding seas and surrounding land masses. It is the world's largest land carnivore and also the largest bear, together with the omnivorous Kodiak Bear, which is approximately the same size...
, seal
Pinniped
Pinnipeds or fin-footed mammals are a widely distributed and diverse group of semiaquatic marine mammals comprising the families Odobenidae , Otariidae , and Phocidae .-Overview: Pinnipeds are typically sleek-bodied and barrel-shaped...
, walrus
Walrus
The walrus is a large flippered marine mammal with a discontinuous circumpolar distribution in the Arctic Ocean and sub-Arctic seas of the Northern Hemisphere. The walrus is the only living species in the Odobenidae family and Odobenus genus. It is subdivided into three subspecies: the Atlantic...
, and husky
Sled dog
Sled dogs, known also as sleigh man dogs, sledge dogs, or sleddogs, are highly trained types of dogs that are used to pull a dog sled, a wheel-less vehicle on runners also called a sled or sleigh, over snow or ice, by means of harnesses and lines.Sled dogs have become a popular winter recreation...
— is unsafe to eat because it is extraordinarily high in vitamin A
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
. This danger has long been known to the Inuit
Inuit
The Inuit are a group of culturally similar indigenous peoples inhabiting the Arctic regions of Canada , Denmark , Russia and the United States . Inuit means “the people” in the Inuktitut language...
and has been recognized by Europeans since at least 1597 when Gerrit de Veer
Gerrit de Veer
Gerrit de Veer was a Dutch officer on Willem Barentsz' third voyage in search of the Northeast passage. De Veer kept a diary of the voyage and in 1597 was the first person to observe and record the Novaya Zemlya effect, and the first westerner to observe hypervitaminosis A caused by consuming...
wrote in his diary that, while taking refuge in the winter in Nova Zemlya
Novaya Zemlya
Novaya Zemlya , also known in Dutch as Nova Zembla and in Norwegian as , is an archipelago in the Arctic Ocean in the north of Russia and the extreme northeast of Europe, the easternmost point of Europe lying at Cape Flissingsky on the northern island...
, he and his men became severely ill after eating polar bear liver. In 1913, Antarctic explorers Douglas Mawson
Douglas Mawson
Sir Douglas Mawson, OBE, FRS, FAA was an Australian geologist, Antarctic explorer and Academic. Along with Roald Amundsen, Robert Falcon Scott, and Ernest Shackleton, Mawson was a key expedition leader during the Heroic Age of Antarctic Exploration.-Early work:He was appointed geologist to an...
and Xavier Mertz
Xavier Mertz
Xavier Mertz was a Swiss explorer, mountaineer and skier, from Basel. He took part in the Far Eastern Party, a 1912–13 component of the Australasian Antarctic Expedition, which claimed his life...
were both poisoned (and Mertz died) from eating the liver of their sled dog
Sled dog
Sled dogs, known also as sleigh man dogs, sledge dogs, or sleddogs, are highly trained types of dogs that are used to pull a dog sled, a wheel-less vehicle on runners also called a sled or sleigh, over snow or ice, by means of harnesses and lines.Sled dogs have become a popular winter recreation...
s during the Far Eastern Party
Far Eastern Party
The Far Eastern Party was a sledging component of the 1911–14 Australasian Antarctic Expedition, which investigated the previously unexplored coastal regions of Antarctica west of Cape Adare. Led by expedition commander Douglas Mawson, the party aimed to explore the area far to the east of their...
.
Vitamin A
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
itself was not discovered until 1917.
Pathological changes consistent with hypervitaminosis A have been seen in bones of Homo erectus
Homo erectus
Homo erectus is an extinct species of hominid that lived from the end of the Pliocene epoch to the later Pleistocene, about . The species originated in Africa and spread as far as India, China and Java. There is still disagreement on the subject of the classification, ancestry, and progeny of H...
, and have also been attributed to consumption of carnivore liver.
The livers of many other animals have lower levels of vitamin A and are commonly eaten
Liver (food)
The liver of mammals, fowl, and fish are commonly eaten as food by humans. Domestic pig, ox, lamb, calf, chicken, and goose livers are widely available from butchers and supermarkets....
.
See also
- Vitamin poisoningVitamin poisoningVitamin poisoning, hypervitaminosis or vitamin overdose refers to a condition of high storage levels of vitamins, which can lead to toxic symptoms...
- Far Eastern PartyFar Eastern PartyThe Far Eastern Party was a sledging component of the 1911–14 Australasian Antarctic Expedition, which investigated the previously unexplored coastal regions of Antarctica west of Cape Adare. Led by expedition commander Douglas Mawson, the party aimed to explore the area far to the east of their...
- Retinoic acid syndromeRetinoic acid syndromeRetinoic acid syndrome is a potentially life threatening complication observed in patients with acute promyelocytic leukemia and first thought to be specifically associated with all-trans retinoic acid treatment...
- PibloktoPibloktoPiblokto, Pibloktoq or Arctic hysteria is a condition exclusively appearing in Inughuit societies living within the Arctic Circle. Appearing most prevalently in winter, it is considered to be a form of a culture-bound syndrome, although more recent studies question whether it exists at...
External links
- Facts about Vitamin A and Carotenoids, from the National Institutes of HealthNational Institutes of HealthThe National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
's Office of Dietary Supplements.