When is vitamin a toxic

In excessive amounts, however, it can accumulate in the liver and cause a wide array of symptoms. Toxicity is classified as either acute or chronic. The most common cause of acute vitamin A toxicity is the ingestion generally accidental of over , IU of vitamin A.

The most common cause of chronic vitamin A toxicity is the regular ingestion of over , IU daily, which is sometimes prescribed for dermatological conditions such as acne. It is also important to note that vitamin A is highly teratogenic if taken during pregnancy especially in the first 8 weeks if intake exceeds 10, IU daily.

Birth defects can also be caused by isotretinoin or other oral retinoids , if taken while pregnant. Excessive intake of Vitamin A during pregnancy has been associated with the following birth defects, collectively known as retinoic acid syndrome :.

Diagnosis of vitamin A toxicity is based on signs and symptoms, patient history, lifestyle habits and use of supplements.

Unless birth defects are present, adjusting the dose almost always leads to complete recovery. Vitamin A helps maintain epithelial tissues and is important for lysosome stability and glycoprotein synthesis.

Dietary sources of preformed vitamin A include fish liver oils, liver, egg yolks, butter, and vitamin A—fortified dairy products. To use vitamin A , the body releases it into the circulation bound to prealbumin transthyretin and retinol-binding protein. Beta-carotene and other provitamin carotenoids, contained in green leafy and yellow vegetables, carrots, and deep- or bright-colored fruits, are converted to vitamin A.

Carotenoids are absorbed better from vegetables when they are cooked or homogenized and served with some fat eg, oils. Synthetic vitamin analogs retinoids are being used increasingly in dermatology. The possible protective role of beta-carotene, retinol, and retinoids against some epithelial cancers is under study. However, risk of certain cancers may be increased after beta-carotene supplementation.

In adults, acute toxicity has occurred when arctic explorers ingested polar bear or seal livers, which contain several million units of vitamin A. Megavitamin therapy is a possible cause, as are massive daily doses , to , units [50, to , RAE] of vitamin A or its metabolites, which are sometimes given for nodular acne or other skin disorders. Such megadoses can cause liver toxicity. Birth defects occur in children of women receiving isotretinoin which is related to vitamin A for acne treatment during pregnancy.

Megadoses of vitamin A can cause liver toxicity. Although carotene is converted to vitamin A in the body, excessive ingestion of carotene causes carotenemia, not vitamin A toxicity. Carotenemia is usually asymptomatic but may lead to carotenosis, in which the skin becomes yellow. However, the vitamin A status of the treatment group was significantly lower than that of the placebo group at baseline, despite randomization, and this may have resulted in larger treatment effects. The elevation of vitamin A in the breast milk of the supplemented group at 1 mo 1.

Treatment effect was still observed at 3 and 6 mo and amounted to a difference of 0. It is interesting that breast-milk vitamin A at 9 mo was significantly lower in the supplemented than in the control group. More recently, Bahl et al measured the effect of IU vitamin A as retinyl palmitate , given 21—42 d after delivery, on the breast milk of women from Peru, India, and Ghana. At 2 mo after delivery, supplementation increased breast-milk vitamin A, but the effect was not sustained at 6 and 9 mo.

There were site-specific effects that suggest a highly variable response. Breast-milk vitamin A concentrations did not differ between the women in Ghana and Peru, which showed that the effect was due solely to the breast milk of the women in India. Moreover, breast-milk vitamin A concentrations were significantly lower in the supplemented women than in the control subjects at all 3 sites 9 mo after delivery.

The lack of a consistent and sustained effect on breast-milk vitamin A concentrations in these studies has prompted some researchers to suggest that IU vitamin A is too low , even though few studies of the effect of a higher dose have been conducted.

Research by Ayah et al in Kenya suggested that an increase to IU vitamin A would not be a solution, because a consistent effect beyond 4 wk was not observed when breast-milk vitamin A was corrected for fat content. Furthermore, no data on the metabolism of vitamin A in mammary tissue after a large dose of preformed vitamin A have been published.

Such data would be important to ensure that high doses of vitamin A do not result in an increase in retinoic acid concentrations in the breast milk. One report has documented the excretion of acitretin, as well as its cis metabolite, into the breast milk of a woman who received oral acitretin therapy for a skin disorder It is possible that, as in plasma, milk retinoic acid concentrations rise after a large dose of preformed vitamin A. A lactating sow—nursing piglet model was used to better define the effects of acute large vitamin A doses on both maternal and infant vitamin A status.

High doses of preformed vitamin A were given to lactating sows to emulate doses administered to lactating women in developing countries 32 , , The circulation of serum retinyl esters increased after the dose 32 ; however, sow milk concentrations did not differ significantly between dose groups On the basis of a theory that the benefit to infants may not differ between and IU when vitamin A is given as a single bolus , a separate study was performed in which piglets were killed at 2 time points after the administration of the same doses to sows.

As predicted, piglet liver vitamin A reserves did not differ between the high- and low-dose treatment groups Moreover, less-toxic metabolites of retinol and retinoic acid were elevated in the sows after high-dose supplementation Figure 1. From this series of studies, it appears that higher doses given to human mothers may not be more beneficial than are lower doses for their infants when given as a single bolus , and the higher doses may result in the formation of a greater amount of detoxifying metabolites in the mothers Given the above results, it would appear that a single large dose of preformed vitamin A may not be as beneficial as a long-term food-based strategy or low-dose vitamin A supplements given for a longer period of time.

Research in rats suggests that sustained chylomicron delivery may be the most important means by which vitamin A is delivered to mammary tissue Moreover, the large doses of vitamin A may be toxic or teratogenic or both , and, therefore, the timing of the dose is critical. Vitamin A supplementation efforts were initiated as an immediate action to control vitamin A deficiency while other more long-term, sustainable interventions could be developed and implemented.

Examples of the latter include food fortification, diet diversification, and biofortification. Sugar-fortification programs are in place in a number of countries, including Zambia, El Salvador, Guatemala, Honduras, and Nicaragua.

A recent evaluation of the program in Nicaragua suggested a positive effect, but continued monitoring of the program will be necessary to ensure that sustained greater intakes of preformed vitamin A from sugar pose no risk of adverse health effects Because diet diversification and biofortification typically provide provitamin A carotenoid sources, toxicity will not occur.

Moreover, carotenoid sources of vitamin A, which have antioxidant capacity, may confer to the nursing infant other benefits that are not available with preformed vitamin A. Vitamin A is an essential nutrient and is added to a variety of foods in the developed world and to specific foods in developing countries. Ideally, vitamin A status is monitored as part of public health programs to prevent the occurrence of both subclinical deficiency and toxicity.

The deleterious effects of vitamin A deficiency are known, but further research is needed to ascertain whether subclinical toxicity exists and, if so, what are its effects on overall health and well-being. The authors thank Penny Nestel for her insightful comments on and edits to a draft of this manuscript.

The authors also thank Julie Howe, laboratory research associate, for constructing the figure. KLP performed the literature review and wrote the first draft of the manuscript. SAT secured funding and revised the manuscript. None of the authors had a personal or financial conflict of interest.

This review was prepared in partial fulfillment of requirements for the doctoral dissertation of KLP. Supported by grant no. Mehta NJ. Dietary intervention with dark green leafy vegetables-spinach Spinacia oleracea to combat subclinical vitamin A deficiency SVAD in slum children of Dharavi, Mumkbai, India.

Sight Life Newslett ; 4 : 32 — Google Scholar. Olson JA. Vitamin A. Present knowledge in nutrition. Google Preview. Gerster H. Vitamin A—functions, dietary requirements and safety in humans. Int J Vitam Nutr Res ; 67 : 71 — Tanumihardjo SA. Factors influencing the conversion of carotenoids to retinol: bioavailability to bioconversion to bioefficacy. Int J Vitam Nutr Res ; 72 : 40 — 5. Transport and storage of vitamin A.

Science ; : — Vitamin A concentration in human tissues collected from five areas in the United States. Am J Clin Nutr ; 25 : — 6. Vitamin A metabolism: new perspectives on absorption, transport, and storage. Physiol Rev ; 71 : — Am J Clin Nutr ; 49 : — Furr HC. Analysis of retinoids and carotenoids: problems resolved and unsolved. J Nutr ; : S — 5S. Effects of dietary vitamin A deficiency, retinoic acid and protein quantity and quality on serially obtained plasma and liver levels of vitamin A in rats.

J Nutr ; : — Nau H. Teratogenicity of isotretinoin revisited: species variation and the role of all- trans -retinoic acid. Safety of vitamin A: recent results. Int J Vitam Nutr Res ; 68 : — 6. Teratology of retinoids. Annu Rev Pharmacol Toxicol ; 39 : — Pharmacokinetics of 9- cis -retinoic acid in the rhesus monkey. Cancer Res ; 55 : — 5. A lethal hypervitaminosis A syndrome in young monkeys Macacus fascicularis following a single intramuscular dose of a water-miscible preparation containing vitamins A, D 2 and E.

Int J Vitam Nutr Res ; 51 : — Allen LH , Haskell M. Estimating the potential for vitamin A toxicity in women and young children. J Nutr ; : S — 19S. A possible case of hypervitaminosis A in Homo erectus. Nature ; : — Zimmerman MR. The paleopathology of the liver. Ann Clin Lab Sci ; 20 : — 6. Bendich A , Langseth L. Safety of vitamin A. Evaluation of vitamin A toxicity.

Am J Clin Nutr ; 52 : — Preclinical and clinical toxicology of selected retinoids. The retinoids. Volume 2. Orlando, FL : Academic Press , : — Hypercalcemia and skeletal effects in chronic hypervitaminosis A.

Ann Intern Med ; 80 : 44 — 8. Increased risk for vitamin A toxicity in severe hypertriglyceridemia. Ann Intern Med ; : — 9.

Hepatic hyper-vitaminosis A: importance of retinyl ester level determination. Eur J Gastroenterol Hepatol ; 12 : — 4. A longitudinal study of the relationship between vitamin A supplementation and plasma retinol, retinyl esters, and liver enzyme activities in a healthy elderly population. Am J Clin Nutr ; 54 : — Determination of retinyl esters and retinol in serum or plasma by normal-phase liquid chromatography: method and applications. Clin Chem ; 32 : 35 — Water-miscible, emulsified, and solid forms of retinol supplements are more toxic than oil-based preparations.

Am J Clin Nutr ; 78 : — 9. Amounts and types of fatty acids in meals affect the pattern of retinoids secreted in human chylomicrons after a high-dose preformed vitamin A intake. Metabolism ; 52 : — 9. Postprandial plasma retinyl ester response is greater in older subjects compared with younger subjects. J Clin Invest ; 85 : — Porcine intestinal metabolism of excess vitamin A differs following vitamin A supplementation and liver consumption.

Arch Biochem Biophys ; : — Am J Clin Nutr ; 81 : — 8. Toxicol Appl Pharmacol ; : — Napoli JL. Interactions of retinoid binding proteins and enzymes in retinoid metabolism. Biochim Biophys Acta ; : — Eckhoff C , Nau H. Vitamin A supplementation increases levels of retinoic acid compounds in human plasma: possible implications for teratogenesis. Arch Toxicol ; 64 : — 3.

Institute of Medicine, Food and Nutrition Board. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, molybdenum, nickel, silicon, vanadium, and zinc.

The teratogenic metabolites of vitamin A in women following supplements and liver. Hum Exp Toxicol ; 13 : 33 — Retinoic acid metabolites in plasma are higher after intake of liver paste compared with a vitamin A supplement in women. Identification of 9- cis -retinoic acid, 9,di- cis -retinoic acid, and hydroxy-4, retro -retinol in human plasma after liver consumption.

Pharmacol Lett ; 59 : — Reduction of serum retinol levels following a single oral dose of all- trans retinoic acid in humans. Int J Vitam Nutr Res ; 67 : — 6. Am J Clin Nutr ; 43 : — 5. Severe hypervitaminosis A in siblings: evidence of variable tolerance to retinol intake. J Pediatr ; : — Coghlan D , Cranswick NE. Complementary medicine and vitamin A toxicity in children.

Med J Aust ; : — 4. Russell RM. New views on the RDAs for older adults. J Am Diet Assoc ; 97 : — 8. Here are some of the common symptoms you may experience if you have vitamin A toxicity, according to Childress. Eating excessive amounts of beta-carotene — a form of vitamin A that is found in fruits and vegetables — can cause skin discoloration and give your skin a yellow-orange tint. This symptom is not harmful, though it may be a sign of developing toxicity.

It may take up to months for your skin to return to its natural hue. Pregnant women should be especially careful to avoid taking too much vitamin A, as it can cause birth defects.

For example, the common acne drug isotretinoin — commonly known as Accutane — is a vitamin A derivative, meaning it acts like an extremely potent form of vitamin A. This drug is known to cause birth defects, which include cleft lips as well as ear, eye, and mental defects.

She also says if you could become pregnant you should stop taking the drug as soon as possible. Long-term complications of vitamin A toxicity include:.

Vitamin A is a fat-soluble vitamin, which means it is stored in your fat tissues and liver. If your liver is not functioning correctly, your body won't be able to properly absorb vitamin A, which can lead to toxicity. Getting vitamin A from your diet — from fruits, meats, and dairy products — rarely leads to toxicity.

Vitamin A toxicity occurs most commonly in people that take vitamin A dietary supplements. Most people shouldn't take vitamin A supplements unless directed by their doctors.