oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Vitamins are readily available and sold in many different formulations and a wide variety of retail outlets. The food industry occasionally supplements foods with vitamins. It is perhaps understandable that there is a widely held perception that vitamin deficiency is the only concern. In fact, vitamins can be taken in excess and we should be aware of the problems from hypervitaminosis which, although uncommon, do occur.
The belief that megadosage vitamin C is beneficial for the common cold was given credence by the American scientist Linus Pauling (1901-1994). This view is not supported by medical evidence. However, this belief is still propagated and given tacit support by, for example, the inclusion of vitamin C in cold remedies. The use of vitamin supplements in 'sweet-like' formulations is not without hazards.
Generally speaking, any excess of water-soluble vitamins is excreted in the urine. However, fat-soluble vitamins can be toxic in excess. Hypervitaminosis can result from unusual dietary factors or from excessive supplementation.
Vitamin A is present as fatty-acid esters in food sources such as liver, kidney, and milk, and as provitamin A carotenoids in plants usually as beta-carotene. High intake of beta-carotene (hypercarotenaemia) can colour the skin yellow, sparing the eyes (in contrast to jaundice where the sclera are also yellow).
Vitamin A toxicity can be acute or chronic. It is well absorbed and there is no effective mechanism for removing or metabolising large quantities. Adults require 500 μg retinol equivalents/day, children 250-350 μg/day. Pregnant women should not exceed their recommended intake of 600 μg/day. High doses of vitamin A can be teratogenic. Toxicity from vitamin supplements has been reported in children.
Acute hypervitaminosis A
This occurs after large overdosage of the vitamin. This can occur with unusual dietary intake such as, for example, ingestion of polar bear liver, which has a very high vitamin A content. Symptoms include:
- Abdominal pain
- Nausea or vomiting
- Visual changes
- Impaired consciousness
Other features suggestive of raised intracranial pressure, such as bulging fontanelle (in an infant), papilloedema and diplopia, may also occur. Anaemia and thrombocytopenia have also been described.
Chronic hypervitaminosis A
This requires in excess of 50,000 units/day for more than 3 months. Symptoms often include bone pain and bony swelling due to increased bone resorption and periosteal bone formation, often associated with hypercalcaemia. Other symptoms can be quite nonspecific:
- Scaly seborrhoeic eczema
- Patchy hair loss
- Loss of appetite
- Liver failure
- Raised intracranial pressure
Children can present with craniotabes, irritability, failure to thrive, decreased appetite and pruritus. Craniotabes is abnormally soft bones of the skull and is unrelated to tabes dorsalis. Complications include:
- Hypercalciuria and renal stones.
- Benign intracranial hypertension.
- Increased bone fragility with increased risk of fractures.
- U&E, especially if there is vomiting.
- Dual energy X-ray absorptiometry (DEXA) scan for bone density in chronic intoxication.
Stop the supplements. If there are changes in mental state, admission to hospital is required.
Mortality is rare. Once identified, the prognosis is good. The yellow coloration of skin will reverse with time.
Usually this is caused by excessive ingestion or overprescription of prescribed medications such as calcium with vitamin D. Occasionally there is increased calcitriol production as in hyperparathyroidism or malignancy including some renal adenomas, sarcomas and lymphomas. In sarcoidosis there is a hypersensitivity to vitamin D. Excessive levels of vitamin D do not result from excessive exposure to sunlight because of further breakdown of D3 into products which have no effect on calcium metabolism. Recent concerns about vitamin D deficiency have led to increased use of supplements.
Most symptoms occur because of secondary hypercalcaemia with increased bone resorption and hypercalciuria. They include:
- Seizures - can be fatal
The traditional description of hypercalcaemia is stones, bones and groans. Hypervitaminosis D is also recognised as a cause of depression. In children it can result in dental enamel hypoplasia and focal pulp calcification.
Serum calcium and phosphate and 25 hydroxy-vitamin D and 1,25 dihydroxy-vitamin D levels.
Stop the supplements and treat the cause. Bisphosphonates such as pamidronate may be used to treat hypercalcaemia. Glucocorticoids are occasionally used for a short while in severe cases of vitamin D intoxication.
These may include:
- Nephrocalcinosis (calcium oxalate and calcium phosphate are radio-opaque stones).
- Calcinosis of the joints and periarticular tissues.
- Ultimately, chronic renal failure.
Renal disease is usually reversible if recognised early.
Vitamin E is present in a great many foods and 3 or 4 decades ago it appeared to be 'a vitamin in search of a deficiency'. Its importance had been demonstrated only for reproductive efficacy in rats. Vitamin E (alpha tocopherol) is a fat-soluble vitamin which acts as an antioxidant and disposes of free radicals. Problems only usually occur after a very large overdose. The recommended daily dose is 30 mg per day, and side-effects are usually experienced at doses above 1 g/kg.
Bruising and bleeding with increased prothrombin time is mediated by the inhibition of vitamin K-dependent carboxylase, and reversed by administering vitamin K. Platelet thromboxane production is also reduced. 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.
- Clotting screen
- Alpha-tocopherol serum levels
Stop the supplements. Consider vitamin K if prothrombin time is prolonged.
Vitamin B6 is a water-soluble vitamin and one of eight B vitamins. As such, it might be considered safe but at doses over 200 micrograms per day it can cause neurological disorders when taken over a prolonged period. It used to be prescribed extensively for carpal tunnel syndrome and premenstrual tension.
Excessive doses damage sensory nerves. This can cause:
- Paraesthesia in the hands and feet.
- Difficulty walking (poor co-ordination, 'staggering').
- Reduced sensation to touch, temperature, and to vibration.
Stopping the vitamin B6 resolves symptoms in all cases. Failure to do so suggests another cause for symptoms.
Toxicity from excess of vitamins A and D and, exceptionally, vitamin E, can occur but it is important not to exaggerate the risk . However, the belief that vitamins are good, therefore lots of vitamins are even better is inaccurate and simplistic. There has been an explosion of interest in vitamin supplementation and a great deal of interest in nutritional medicine. This may help to inform on better diets and better dietary supplementation. It is important for doctors to be informed and to be able to identify misinformation, harmful diets and potentially harmful misuse of vitamin supplements.
The 1597, Gerrit de Veer wrote in his diary about taking refuge through the winter, in Nova Zembla, during an attempt to reach Indonesia by the northern passage. He and his men became gravely ill after eating polar-bear liver. They feared for their lives but ultimately recovered. De Veer's diary also notes widespread and striking desquamation during recovery. They were the first Westerners to observe the effects of hypervitaminosis A.
Further reading & references
- Eledisri MS et al, Vitamin A toxicity, eMedicine, Sep 2009
- Gentili A et al, Vitamin E toxicity, eMedicine, Aug 2008
- Vitamin D Toxicity, The Merck Manual
- Prakash R; The acute and chronic toxic effects of vitamin A. Am J Clin Nutr. 2006 Aug;84(2):462; author reply 462-3.
- Brown CT; Vitamin A and Sir Douglas Mawson. Br Med J. 1978 Mar 11;1(6113):650.
- Update on Vitamin D, Scientific Advisory Committee on Nutrition, February 2007
- Lam HS, Chow CM, Poon WT, et al; Risk of vitamin A toxicity from candy-like chewable vitamin supplements for children. Pediatrics. 2006 Aug;118(2):820-4.
- Collins MD, Mao GE; Teratology of retinoids. Annu Rev Pharmacol Toxicol. 1999;39:399-430.
- Perrotta S, Nobili B, Rossi F, et al; Infant hypervitaminosis A causes severe anemia and thrombocytopenia: evidence of a retinol-dependent bone marrow cell growth inhibition. Blood. 2002 Mar 15;99(6):2017-22.
- Cheruvattath R, Orrego M, Gautam M, et al; Vitamin A toxicity: when one a day doesn't keep the doctor away. Liver Transpl. 2006 Dec;12(12):1888-91.
- Michaelsson K, Lithell H, Vessby B, et al; Serum retinol levels and the risk of fracture. N Engl J Med. 2003 Jan 23;348(4):287-94.
- Blank S, Scanlon KS, Sinks TH, et al; An outbreak of hypervitaminosis D associated with the overfortification of milk from a home-delivery dairy. Am J Public Health. 1995 May;85(5):656-9.
- Holick MF; Sunlight and vitamin D for bone health and prevention of autoimmune diseases, Am J Clin Nutr. 2004 Dec;80(6 Suppl):1678S-88S.
- Keddie KM; Severe depressive illness in the context of hypervitaminosis D. Br J Psychiatry. 1987 Mar;150:394-6.
- Giunta JL; Dental changes in hypervitaminosis D. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998 Apr;85(4):410-3.
- Sharma OP; Vitamin D, calcium, and sarcoidosis. Chest. 1996 Feb;109(2):535-9.
- Kappus H, Diplock AT; Tolerance and safety of vitamin E: a toxicological position report. Free Radic Biol Med. 1992;13(1):55-74.
- Schaumburg H, Kaplan J, Windebank A, et al; Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med. 1983 Aug 25;309(8):445-8.
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Dr Richard Draper
Dr Richard Draper