Vitamin A is a fat-soluble vitamin naturally found in certain foods, such as meat and dairy products. It can also be consumed as a dietary supplement. This vitamin is stored in the liver. Hypervitaminosis A (HA) refers to the excessive consumption of vitamin A which leads to acute or chronic toxicity.

Usually, HA is caused by taking excessive amounts of vitamin A supplements, or the accidental ingestion of its topical forms, such as retinol. Acutely, patients may present with non-specific manifestations that include nausea, vomiting, and anorexia. Children may exhibit features such as failure to thrive, bulging of the fontanelles, visual disturbances, and premature closure of epiphyses. Similarly, visual changes and ocular signs occur in adults, and these may involve blurry vision, photophobia, and conjunctivitis.

Central nervous system (CNS) effects include a decreased level of consciousness, lethargy, ataxia, dizziness, headache, and irritability. Some of the CNS manifestations, namely papilledema and bulging of the fontanelles in infants, are due to raised intracranial pressure precipitated by HA.

HA also promotes an abnormal breakdown of bone tissue, which may lead to hypercalcemia and osteoporosis [1] [2] [3]. Further systemic consequences of HA are hepatotoxicity, hepatomegaly, splenomegaly, ascites, migratory arthritis, and hepatic hydrothorax [4] [5].

Chronic HA affects multiple systems, with features such as arthralgia, bone pain, hair loss, desquamation of skin, eczematous lesions, photosensitivity, and petechiae. Other cutaneous manifestations of HA include angular stomatitis, cheilitis, and brittle nails. Last but not least, hypervitaminosis A has teratogenic effects on the developing fetus.

• Splenomegaly

  Further systemic consequences of HA are hepatotoxicity, hepatomegaly, splenomegaly, ascites, migratory arthritis, and hepatic hydrothorax. [symptoma.com]

  Splenomegaly. Raised intracranial pressure. Stupor. Limited body movement. Cirrhosis of liver. Young children with acute hypervitaminosis A may show papilloedema and symptoms suggestive of pseudo-tumour cerebri. [nhp.gov.in]

• Fatigue

  Upon further questioning, her mother reported that she seemed more fatigued for a few weeks, had abdominal pain, and was urinating more frequently. [ncbi.nlm.nih.gov]

  Weight loss Later symptoms may be of an underactive thyroid ( hypothyroidism ), including fatigue and cold intolerance, until the thyroid recovers. [mclaren.org]

  At first I thought these things were due to pregnancy & post-partum hormones as well as chronic fatigue that I have battled for 12 years; but after reading about vitamin A toxicity I realized most of these symptoms occurred after I had been taking cod [easy-immune-health.com]

  Some studies have also reported fatigue, weakness, headache and gastrointestinal upset. Impaired immunity with secondary necrotising enterocolitis has been observed in premature infants given vitamin E to prevent retrolental fibroplasia. [patient.info]

  The patient reported unintentional weight loss of 70 pounds in the last two years, hair loss, generalized fatigue and constipation. [caribbean.scielo.org]

• Nausea

  Clinical findings Bone pain, dry skin, gastrointestinal complaints (nausea, vomiting, constipation, diarrhoea), increased intracranial pressure, poor growth in children; affected infants may develop bulging fontanelles, craniotabes (softening of skull [medical-dictionary.thefreedictionary.com]

  More sustained intake of excess vitamin A leads to increased intracranial pressure (pseudotumour cerebri), dizziness, nausea, headaches, skin irritation, pain in joints and bones, coma, and even death. [patient.info]

  Acutely, patients may present with non-specific manifestations that include nausea, vomiting, and anorexia. Children may exhibit features such as failure to thrive, bulging of the fontanelles, visual disturbances, and premature closure of epiphyses. [symptoma.com]

  Symptoms of acute vitamin A toxicity include: drowsiness irritability abdominal pain nausea vomiting increased pressure on the brain Symptoms of chronic vitamin A toxicity include: blurry vision or other vision changes swelling of the bones bone pain [healthline.com]

  […] infants and children) Blurred vision Bone pain or swelling Bulging fontanelle (infants) Changes in consciousness Decreased appetite Dizziness Double vision (young children) Drowsiness Headache Increased intracranial pressure Irritability Liver damage Nausea [coordinatedhealth.com]

• Vomiting

  Serum electrolytes: Vomiting and diarrhea may lead to derangements. High-performance liquid chromatography (HPLC). Lumbar puncture. Other useful tests include: X-rays: These may show abnormal bone calcification. Electrocardiography. [symptoma.com]

  Vomiting. Drowsiness. Less commonly, there may be diplopia, cranial nerve palsies, and symptoms suggestive of pseudo-tumour cerebri. [nhp.gov.in]

  Features of hypercalcaemia include polyuria, polydypsia, vomiting, anorexia, lethargy, dehydration, constipation, hypertension, tetany and seizures. The traditional description of hypercalcaemia is stones, bones and groans. [patient.info]

  Symptoms of acute vitamin A toxicity include: drowsiness irritability abdominal pain nausea vomiting increased pressure on the brain Symptoms of chronic vitamin A toxicity include: blurry vision or other vision changes swelling of the bones bone pain [healthline.com]

  Clinical findings Bone pain, dry skin, gastrointestinal complaints (nausea, vomiting, constipation, diarrhoea), increased intracranial pressure, poor growth in children; affected infants may develop bulging fontanelles, craniotabes (softening of skull [medical-dictionary.thefreedictionary.com]

• Abdominal Pain

  Upon further questioning, her mother reported that she seemed more fatigued for a few weeks, had abdominal pain, and was urinating more frequently. [ncbi.nlm.nih.gov]

  My youngest son (almost 4) had extremely yellow skin & abdominal pains last year for a couple of weeks & returned again a couple of weeks ago when we started on the cod liver oil after a 2 month abstinence. [easy-immune-health.com]

  Symptoms of acute vitamin A toxicity include: drowsiness irritability abdominal pain nausea vomiting increased pressure on the brain Symptoms of chronic vitamin A toxicity include: blurry vision or other vision changes swelling of the bones bone pain [healthline.com]

  Acute hypervitaminosis A Abdominal pain Sleepiness Irritable mood Dizziness Chronic hypervitaminosis A Bone abnormalities and joint pain Jaundice Visual disturbances Loss of appetite Dizziness, confusion Loss of hair or alopecia Peeling, oily or itching [news-medical.net]

  Symptoms include: Headache Abdominal pain Nausea or vomiting Lethargy Visual changes Impaired consciousness Other features suggestive of raised intracranial pressure, such as bulging fontanelle (in an infant), papilloedema and diplopia, may also occur [patient.info]

• Loss of Appetite

  […] softened skull; increased intracranial pressure in the brain may be observed Chronic Hypervitaminosis A: Loss of appetite, weakness, drowsiness, irritability Anemia, weight loss Bone and joint problems, which include pain, fracture Hair loss, skin abnormalities [dovemed.com]

  Acute hypervitaminosis A Abdominal pain Sleepiness Irritable mood Dizziness Chronic hypervitaminosis A Bone abnormalities and joint pain Jaundice Visual disturbances Loss of appetite Dizziness, confusion Loss of hair or alopecia Peeling, oily or itching [news-medical.net]

  Other symptoms can be quite nonspecific: Scaly seborrhoeic eczema Patchy hair loss Stomatitis Loss of appetite Nausea Vomiting Malaise Hepatosplenomegaly Liver failure Raised intracranial pressure Children can present with craniotabes, irritability, failure [patient.info]

  Chronic Toxicity of Vitamin A long-term megadose; possible permanentdamage Bone and muscle pain Loss of appetite Skin disorders Headache Dry skin Hair loss Increased liver size [email protected] 32. [slideshare.net]

• Cracked Lips

  My oldest daughter (11yrs old) has had bone pain every once in a while, seborrhea, cracked lips in the winter, & in the last 2 years had needed glasses for farsightedness (she hardly ever gets sun). [easy-immune-health.com]

• Hepatomegaly

  This article describes the common symptomatology of vitamin A toxicity, including hypercalcemia, hepatomegaly, and dermatological and neurological effects. Retinol supplements, but not carotene supplements, become toxic when free retinol circulates. [journals.lww.com]

  Further systemic consequences of HA are hepatotoxicity, hepatomegaly, splenomegaly, ascites, migratory arthritis, and hepatic hydrothorax. [symptoma.com]

  Hepatomegaly. Splenomegaly. Raised intracranial pressure. Stupor. Limited body movement. Cirrhosis of liver. Young children with acute hypervitaminosis A may show papilloedema and symptoms suggestive of pseudo-tumour cerebri. [nhp.gov.in]

  ChronicIntoxication Results when >50,000 IU/day ingested for several wksor more Signs & symptoms in infants: Early are anorexia, pruritus, irritability, tenderswollen bones w/motion limitation Alopecia, seborrhea, cheilosis & peeling of palms &soles Hepatomegaly [slideshare.net]

  Symptoms and signs of toxicity include dry skin, nausea, headache, fatigue, irritability, anorexia, liver disease and hepatomegaly, hair loss and alopecia, hyperostosis, high cholesterol and increased cerebrospinal fluid pressure [pseudotumour cerebri [caribbean.scielo.org]

• Hepatosplenomegaly

  Acute pseudotumour cerebri Chronic pruritus, dry skin, dry lips soft tissue nodules diffuse symmetric periostitis (scintigraphy may allow earlier detection 2 ) may cause premature fusion of ossification centers separation of cranial sutures hepatosplenomegaly [radiopaedia.org]

  Other signs and symptoms include anorexia, hepatosplenomegaly, irritability, scaly dermatitis, patchy hair loss, bone pain and hyperostosis. The lowest intake required to produce toxic symptoms is not known. [gpnotebook.co.uk]

  Abdominal ultrasound was normal except for hepatosplenomegaly. Fig. 1. Bone marrow appearance on admission. Marked decrease of nucleated erythroid cells with binucleate erythroblasts, absence of megakaryocyte, and normal myeloid cells. [bloodjournal.org]

  Other symptoms can be quite nonspecific: Scaly seborrhoeic eczema Patchy hair loss Stomatitis Loss of appetite Nausea Vomiting Malaise Hepatosplenomegaly Liver failure Raised intracranial pressure Children can present with craniotabes, irritability, failure [patient.info]

• Hypertension

  Hypervitaminosis A may be associated with benign intracranial hypertension. So far, the explanation for this phenomenon has remained obscure. [ncbi.nlm.nih.gov]

  Wall M: The headache profile of idiopathic intracranial hypertension. Cephalalgia 1990, 10: 331–335. PubMed CrossRef Google Scholar 13. Friedman DI, Rausch EA: Headache diagnoses in patients with treated idiopathic intracranial hypertension. [doi.org]

• Diplopia

  Less commonly, there may be diplopia, cranial nerve palsies, and symptoms suggestive of pseudo-tumour cerebri. [nhp.gov.in]

  Patients present with daily headache, pulse-synchronous tinnitus, transient visual obscurations, papilledema with its associated visual loss, and diplopia from sixth nerve paresis. [doi.org]

  Symptoms include: Headache Abdominal pain Nausea or vomiting Lethargy Visual changes Impaired consciousness Other features suggestive of raised intracranial pressure, such as bulging fontanelle (in an infant), papilloedema and diplopia, may also occur [patient.info]

• Bone Pain

  The clinical features included irritability, xerosis of the skin and mucous membranes, pruritus, bone pain, and loss of ambulation. The bone scan showed involvement of more bones than was apparent on the roentgenograms. [ncbi.nlm.nih.gov]

  Other signs and symptoms include anorexia, hepatosplenomegaly, irritability, scaly dermatitis, patchy hair loss, bone pain and hyperostosis. The lowest intake required to produce toxic symptoms is not known. [gpnotebook.co.uk]

  Chronic HA affects multiple systems, with features such as arthralgia, bone pain, hair loss, desquamation of skin, eczematous lesions, photosensitivity, and petechiae. [symptoma.com]

  Symptoms of acute vitamin A toxicity include: drowsiness irritability abdominal pain nausea vomiting increased pressure on the brain Symptoms of chronic vitamin A toxicity include: blurry vision or other vision changes swelling of the bones bone pain [healthline.com]

  Clinical findings Bone pain, dry skin, gastrointestinal complaints (nausea, vomiting, constipation, diarrhoea), increased intracranial pressure, poor growth in children; affected infants may develop bulging fontanelles, craniotabes (softening of skull [medical-dictionary.thefreedictionary.com]

• Arthralgia

  Chronic HA affects multiple systems, with features such as arthralgia, bone pain, hair loss, desquamation of skin, eczematous lesions, photosensitivity, and petechiae. [symptoma.com]

  Role in Dengue Hemorrhagic Fever interactions between dengue viruses and retinoids in the liver, triggering viral replication and disease pathogenesis, and that disease manifestations (e.g., fever, severe arthralgia, bone pain, plasma leakage, thrombocytopenia [flipper.diff.org]

• Alopecia

  A case of chronic hypervitaminosis A is reported in a 57-year-old woman who took vitamin preparations for alopecia. [ncbi.nlm.nih.gov]

  Alopecia. Swelling of bones. Diplopia (double vision). Irritability. Young children may have Lack of gain in weight. Pruritus (itching). Bulging fontanelles. [nhp.gov.in]

  Acute hypervitaminosis A Abdominal pain Sleepiness Irritable mood Dizziness Chronic hypervitaminosis A Bone abnormalities and joint pain Jaundice Visual disturbances Loss of appetite Dizziness, confusion Loss of hair or alopecia Peeling, oily or itching [news-medical.net]

  Herein we present the case of a 60‐year‐old male with symptoms of muscle soreness, alopecia, nail dystrophy, and ascites. [doi.org]

  Summary A case of chronic hypervitaminosis A is reported in a 57-year-old woman who took vitamin preparations for alopecia. [link.springer.com]

• Pruritus

  The clinical features included irritability, xerosis of the skin and mucous membranes, pruritus, bone pain, and loss of ambulation. The bone scan showed involvement of more bones than was apparent on the roentgenograms. [ncbi.nlm.nih.gov]

  Acute pseudotumour cerebri Chronic pruritus, dry skin, dry lips soft tissue nodules diffuse symmetric periostitis (scintigraphy may allow earlier detection 2 ) may cause premature fusion of ossification centers separation of cranial sutures hepatosplenomegaly [radiopaedia.org]

  Pruritus (itching). Bulging fontanelles. Acute hypervitaminosis A (such as consumption of a single large dose of 30- 60 mg of vitamin A) may lead to Nausea. Vomiting. Drowsiness. [nhp.gov.in]

  Scaly seborrhoeic eczema Patchy hair loss Stomatitis Loss of appetite Nausea Vomiting Malaise Hepatosplenomegaly Liver failure Raised intracranial pressure Children can present with craniotabes, irritability, failure to thrive, decreased appetite and pruritus [patient.info]

  ChronicIntoxication Results when >50,000 IU/day ingested for several wksor more Signs & symptoms in infants: Early are anorexia, pruritus, irritability, tenderswollen bones w/motion limitation Alopecia, seborrhea, cheilosis & peeling of palms &soles [slideshare.net]

• Yellow Discoloration of the Skin

  […] and hair changes Cracking at corners of the mouth Hair loss Higher sensitivity to sunlight Oily skin and hair ( seborrhea ) Skin peeling, itching Yellow discoloration of the skin Vision changes Vomiting Signs and tests Bone x-rays Blood calcium test [coordinatedhealth.com]

  […] and hair changes Cracking at corners of the mouth Hair loss Higher sensitivity to sunlight Oily skin and hair ( seborrhea ) Skin peeling, itching Yellow discoloration of the skin Vision changes Vomiting Exams and Tests Bone x-rays Blood calcium test [healthmedicinet.com]

• Headache

  Findings included headache, confusion, skin desquamation, and hypercalcemia. Prior to developing hepatitis, he had ingested supplemental vitamin A without recognized ill effect. Liver and serum vitamin A without recognized ill effect. [ncbi.nlm.nih.gov]

  Manifestations include bone fragility, xeroderma, nausea, headache, and loss of hair. hypervitaminosis a condition produced by ingestion or injection of excessive amounts of vitamins; symptom complexes are associated with excessive intake of vitamins [medical-dictionary.thefreedictionary.com]

  The condition was first described in Arctic explorers who developed headache, diarrhoea and dizziness after eating polar bear liver. [gpnotebook.co.uk]

  Central nervous system (CNS) effects include a decreased level of consciousness, lethargy, ataxia, dizziness, headache, and irritability. [symptoma.com]

  More sustained intake of excess vitamin A leads to increased intracranial pressure (pseudotumour cerebri), dizziness, nausea, headaches, skin irritation, pain in joints and bones, coma, and even death. [patient.info]

• Irritability

  The clinical features included irritability, xerosis of the skin and mucous membranes, pruritus, bone pain, and loss of ambulation. The bone scan showed involvement of more bones than was apparent on the roentgenograms. [ncbi.nlm.nih.gov]

  There is also hyperesthesia, irritability, anorexia, weight loss, and sometimes neurological deficits. [medical-dictionary.thefreedictionary.com]

  Other signs and symptoms include anorexia, hepatosplenomegaly, irritability, scaly dermatitis, patchy hair loss, bone pain and hyperostosis. The lowest intake required to produce toxic symptoms is not known. [gpnotebook.co.uk]

  Central nervous system (CNS) effects include a decreased level of consciousness, lethargy, ataxia, dizziness, headache, and irritability. [symptoma.com]

  HypervitaminosisAAcute Intoxication: Results when excessively large single doses>300,000 IU ingested Infants: n/v, drowsiness or irritability w/signsof increased ICP Adults: drowsiness, irritability, headache &vomiting Serum vitamin A values = 200 [slideshare.net]

• Lethargy

  Central nervous system (CNS) effects include a decreased level of consciousness, lethargy, ataxia, dizziness, headache, and irritability. [symptoma.com]

  Signs : anorexia, weight loss, lethargy, neck stiffness, lameness, progressive ankylosis → characteristic 'kangaroo' stance. Diagnosis : radiology demonstrating cervical ankylosis and subperiosteal new bone; serology. [vetstream.com]

  Features of hypercalcaemia include polyuria, polydypsia, vomiting, anorexia, lethargy, dehydration, constipation, hypertension, tetany and seizures. The traditional description of hypercalcaemia is stones, bones and groans. [patient.info]

When HA is suspected, there are several biochemical tests and radiological modalities available to confirm the diagnosis and assess effects of the disease. The biochemical tests include:

• Serum vitamin A levels: The normal range is 20-60 micrograms per deciliter. In patients with HA, vitamin A levels will be above 60-100 micrograms per deciliter.
• Serum calcium levels: These may be elevated [6].
• Random blood glucose test.
• Complete blood count: This is requested to rule out anemia, leukopenia, or thrombocytopenia.
• Serum cholesterol levels.
• Liver function tests.
• Serum electrolytes: Vomiting and diarrhea may lead to derangements.
• High-performance liquid chromatography (HPLC).
• Lumbar puncture.

Other useful tests include:

• X-rays: These may show abnormal bone calcification.
• Electrocardiography.
• Bone mineral density: Chronic toxicity causes reduced bone density [7].

It is advised that drug levels of aspirin and paracetamol also be checked.

• HLA-B27

  Tests were negative for the HLA-B27 antigen in all 3 patients. Serum vitamin A levels were high, ranging from 894 to 1123 microg/L (normal, 489-720). None of the patients reported taking retinoids or having unusual eating habits. [ncbi.nlm.nih.gov]

The ingestion of vitamin A, which is often prescribed for the treatment of acne, may lead to hypervitaminosis A. [ncbi.nlm.nih.gov]

Although each new retinoid is developed with the aim of maximizing specific therapeutic effects and minimizing toxicity, the fact remains that the major side effects of retinoid treatment are those of hypervitaminosis A syndrome. [experts.umich.edu]

Problems in the diagnosis and treatment of pseudotumor cerebri. Can J Neurol Sci 1983, 10: 221–229. PubMed Google Scholar 42. [doi.org]

Prognosis Mortality is rare. Once identified, the prognosis is good. The yellow coloration of skin will reverse with time. [patient.info]

Expectations (prognosis) Most people fully recover. [coordinatedhealth.com]

The prognosis is excellent, if the condition is recognized early and treated appropriately Individuals with severe conditions of Hypervitaminosis A may require hospitalization with extended treatment. [dovemed.com]

Outlook (Prognosis) Most people fully recover. [nicklauschildrens.org]

Prognosis : depends on degree of exostosis and ankylosis. Use the interactive tool from ROYAL CANIN® UK to explain cat anatomy and disease conditions to your client. Visit ROYAL CANIN Natom Explorer to find out more. [vetstream.com]

This study hypothesizes the possible implication of vitamin intoxication, namely, hypervitaminosis A, in the etiology of some cases of pibloktoq. [ncbi.nlm.nih.gov]

This is especially true when the etiology is unknown or there is no established therapy for the cause of the chronic injury. [doi.org]

Pathogenesis Etiology Diet exclusive, or high in, liver. Supplementation with vitamin A. Dietary intake exceeding 60,000 IU/kg bodyweight/day (normal dietary allowance 300 IU/ kg bodyweight). Specific Liver diet. Vitamin A supplementation. [vetstream.com]

Recent epidemiological studies have suggested, but not proven, that intake of high levels of vitamin A during early pregnancy may pose a teratogenic risk. [ucdavis.pure.elsevier.com]

Giovanni Corrao, Pierfederico Torchio, Antonella Zambon, Amleto D'Amicis, Anna Raffaella Lepore and Ferdinando Di Orio, Alcohol Consumption and Micronutrient Intake as Risk Factors for Liver Cirrhosis: A Case-Control Study, Annals of Epidemiology, 8, [doi.org]

The present findings suggest that sinusoidal barrier abnormalities might constitute a major event in the pathophysiology of vitamin A-induced liver injury as well as of peliosis hepatis. [ncbi.nlm.nih.gov]

Pathophysiology Excess dietary vitamin A → formation of bony exostoses around joints. Cervical vertebrae (particularly), elbow, hip and stifle joints affected. Timecourse Months. [vetstream.com]

[…] in 2003–2006 33% of the United States population aged 1 year and older took a multivitamin supplement in a given month. [3] In a 2009 survey, 56% of US consumers said they take vitamins or supplements, with 44% saying they take them daily. [4] (See Pathophysiology [emedicine.com]

Hypervitaminosis A has been described as resulting from excess ingestion of vitamin A for prevention of sunburn and treatment of minimal brain dysfunction. [ncbi.nlm.nih.gov]

Thus, prevention plays an important role in avoiding toxicity. [nhp.gov.in]

[…] has been described in at least 17 infants and young children since Josephs' original article in 1944. 1, 2 Sulzberger and Lazar 3 described similar toxic symptoms which occurred in an adult female who took large amounts of vitamin A in an attempt to prevent [annals.org]

Prevention Hypervitaminosis A can be prevented by not ingesting more than the Tolerable Upper Level of intake for Vitamin A. This level is for synthetic and natural retinol ester forms of vitamin A. Carotene forms from dietarysources are nottoxic. [flipper.diff.org]

1. Scheven BAA, Hamilton NJ. Retinoic acid and 1,25-dihydroxyvitamin D3 stimulate osteoclast formation by different mechanisms. Bone. 1990;11(1):53-59.
2. National Institutes of Health Office of Dietary Supplements. Vitamin A Fact Sheet for Health Professionals. National Institutes of Health. http://ods.od.nih.gov/factsheets/vitamina.asp. Accessed September 15, 2017.
3. Ribaya-Mercado JD, Blumberg JB. Vitamin A: is it a risk factor for osteoporosis and bone fracture? Nutr Rev. 2007;65(10):425-438.
4. Miksad R, de Lédinghen V, McDougall C, Fiel I, Rosenberg H. Hepatic hydrothorax associated with vitamin a toxicity. J Clin Gastroenterol. 2002;34(3):275-279.
5. Hathcock JN, Hattan DG, Jenkins MY, McDonald JT, Sundaresan PR, Wilkening VL. Evaluation of vitamin A toxicity. Am J Clin Nutr. 1990;52(2):183-202.
6. Bhalla K, Ennis DM, Ennis ED. Hypercalcemia caused by iatrogenic hypervitaminosis A. J Am Diet Assoc. 2005;105(1):119-121.
7. Barker ME, Blumsohn A. Is vitamin A consumption a risk factor for osteoporotic fracture? Proc Nutr Soc. 2003;62(4):845-850.