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Home , Hypervitaminosis, Hypervitaminosis A, Overeating, Vitamin D toxicity

International Journal of Health Sciences and Research www.ijhsr.org ISSN: 2249-9571

Review Article

Hypervitaminosis - An Emerging Pathological Condition

J K Roop

PG Department of Zoology, JC DAV College (Affiliated to Panjab University, Chandigarh), Dasuya-144205, District Hoshiarpur, Punjab, India

ABSTRACT

Vitamins are essential organic compounds that are required in small amounts to regulate various metabolic activities in the body. Prolonged and overconsumption of pharmaceutical forms of both water-soluble and fat-soluble may lead to and/or . Hypervitaminosis is an acute emerging pathological condition of the body due to excess accumulation of any of the vitamins. In case of acute with supplements/drugs, emergency assistance is required to detoxify the effects and restore the organization, structure and function of body’s tissues and organs. Sometimes death may occur due to intoxication to , and . So, to manage any type of hypervitaminosis, proper diagnosis is essential to initiate eliminating the cause of its occurrence and accelerate the elimination of the supplement from the body. The present review discusses the symptoms of hypervitaminosis that seems to be a matter of concern today and management strategies to overcome toxicity or hypervitaminosis.

Keywords: Hypervitaminosis, Toxicity, Vitamins, Vitamin pathology, Fat-soluble vitamin, Water- soluble vitamin.

INTRODUCTION body, particularly in the liver. Vitamin are potent organic Complex and vitamin C are water- soluble. compounds present in small concentrations They are dissolved easily in food during in various fruits and vegetables. They cooking and a portion of these vitamins may regulate physiological functions and help in be destroyed by heating. They cannot be maintaining metabolic rate of the body. The stored in body and hence they have to be human body cannot synthesize vitamins on taken daily in foods. Any extra quantity its own. Therefore, it becomes essential to taken in one day is eliminated in urine as obtain right and sufficient vitamins through waste by the body. the in order to maintain healthy Presently, vitamins are made in lifestyle. Imbalanced and poor diet leads to different formulations by various deficiency of vitamins in the body. This pharmaceutical companies in the form of may bring about outburst of various syrups, tablets, pills and powders that are deficiency diseases which if untreated with readily available to be taken as supplements. adequate supplements may lead to death of Therapeutic use of vitamin supplements in an individual. Vitamins are broadly the form of vitamin therapy has helped categorized into, fat-soluble vitamins and people in fighting diseases and managing water-soluble vitamins. Vitamins A, D, E good health. Modern life style has created and K are fat-soluble vitamins. They are not an epidemic of binge drinking, missing lost by cooking and can be stored in the diets, irritability and indigestion. People are

International Journal of Health Sciences & Research (www.ijhsr.org) 280 Vol.8; Issue: 10; October 2018 J K Roop. Hypervitaminosis - An Emerging Pathological Condition trying to integrate healthy habits into HYPERVITAMINOSIS already hectic schedule and to compensate Hypervitaminosis may be acute and for the loss of essential nutrients in the form chronic with very specific and general of vitamins, people have started taking clinical symptoms. Acute hypervitaminosis vitamin supplements daily, believing that in is the result of one time intake of very high case of increased concentration, excess of dose of one or multiple vitamin the vitamins will be lost independently from preparations/supplements. Chronic the body. This misconception and prolonged hypervitaminosis results due to gradual intake of vitamins may cause toxic effects in development of clinical symptoms by a the body or hypervitaminosis, although rare. latent course. Water-soluble and fat-soluble Hypervitaminosis is a condition reported of vitamin toxicity has their own specific having abnormally high storage levels of effects on the body leading to intoxication vitamins leading to toxic symptoms. syndrome. Certain symptoms of intoxication Generally toxicity and hypervitaminosis is syndrome are common to all the forms of caused by a large intake of highly fortified hypervitaminosis like headache, severe foods which leads to accumulation of fat- weakness, dizziness, inability to exercise, soluble vitamins in the liver. Natural foods inability to perform daily routine, nausea, have not been associated with any toxicity. sensations of internal tremor, constipation or [1,2] In the United States, the annual report diarrhoea. Hypervitaminosis due to fat- submitted by control centres reported soluble vitamin groups have a more that more than 60,000 people including pronounced course as these get accumulated children under the age of 6, were subjected in the body tissues and cause severe to life threatening outcomes due to vitamin intoxication. Hypervitaminosis due to . [3-5] The water-soluble vitamins has a less recommendations from the United States pronounced course and does not impose a Department of Agriculture define a threat to the life of a person. Therefore, it “tolerable upper intake level” for most of can be normalized by increasing the urinary the vitamins. [6] output and restricting the intake of such type Most of the natural fruits and of supplements. vegetables are considered to be the potent source of antioxidants instead of the HYPERVITAMINOSIS OF antioxidant supplements in the form of pills DIFFERENT VITAMIN TYPES and tablets. Studies reported that in the well- -- It nourished individuals, prolonged intake of occurs due to prolonged uncontrolled the antioxidant supplements including ingestion of too much of preformed vitamin and may cause increase A from foods (, animal liver and in mortality as a result of unwanted kidney, plant sources like carrots), consequences to the health. [7-9] Whereas, supplements in the form of pills/ tablets/ vitamin D3 supplements have been known powders or prescription . to decrease mortality in elderly people who Dietary vitamin A is available mainly as are living independently or in an preformed vitamin A in western countries institutional care. [10] It has been observed in and as provitamin A carotenoids in trials that regular intake of vitamin C developing countries. Vitamin A in supplements reduce the duration of cold but supplements per capsule is typically 10,000- this was not replicated when therapeutic 50,000 international units (IU). Fish-liver trials were conducted. Regular intake of oils may contain more than 180,000 IU/g. vitamin C supplements have not been The acute toxic dose of vitamin A is 25,000 reported to reduce the incidence of IU/kg, whereas the chronic toxic dose is occurrence of cold in general population. [11] 4000 IU/kg every day for 6-15 months. [12] GENERAL SYMPTOMS OF

International Journal of Health Sciences & Research (www.ijhsr.org) 281 Vol.8; Issue: 10; October 2018 J K Roop. Hypervitaminosis - An Emerging Pathological Condition

Hypervitaminosis A may be acute or intake of beta-carotene in men. [17] This can chronic. An acute form is extremely rare be reversed by discontinuing the intake of and the symptoms may express as headache, beta-carotene. Toxicity due to vitamin vomiting, short-term loss of consciousness, supplements has also been reported in dizziness, irritability, nausea, abdominal children. [18] pain, fever, skin rashes without clear Management is by discontinuation of localization all over the body and visual supplements and taking prescribed disturbances like . The chronic recommended dose. If mental changes are forms are associated with the symptoms like reported, hospitalization is required. Once dry patchy skin, dry fissured lips, hair loss identified, the prognosis is good. Mortality and brittle nails. It affects the osteoarticular is rare. Yellow colour of skin gets reversed apparatus by altering metabolism with time. accompanied by stiffness in movements, HYPERVITAMINOSIS D-- It is caused by pain and swelling of periarticular soft prolonged and/or excessive intake of tissues. It is also accompanied by prescribed medications such as (over eating may result in irreversible health along with . Excessive exposure complications including death), alopecia to sunlight does not result in excessive (baldness), , low grade fever, levels of vitamin D. Today people tend to hepatosplenomegaly, papilloedema (optic stay indoors and this concern about vitamin disc swelling caused by increased D deficiency that has led to the due to any cause), increased/over consumption of various pseudotumor cerebri (caused by increased forms of vitamin D supplements. The acute pressure around the brain).Other features toxic dose for vitamin D has not been include complications like reported. The chronic toxic dose in adults is hypercholesterolemia and atherosclerotic higher than 50,000 IU/day. In infants disease, anemia and thrombocytopenia (in younger than 6 months, 1000 IU/day may be infants), [13] hypocalcaemia, considered unsafe. The tolerable upper and renal stones, benign intracranial intake level (UL) for all groups > 1 year is and increased production of 2000IU/day. [19] Therefore, there is wide mineralocorticoids leading to generalized variation in the potential toxicity for vitamin edematous syndrome, depression and D. Toxicity is much more likely to occur suicidal tendencies (particularly with from high intakes of dietary supplements ). [14,15] In pregnant women, long- containing vitamin D. Long term intakes term use may cause severe teratogenic above UL increases the risk of adverse side effects in fetus including malformations of effects. [20] Hypervitaminosis D is eyes, skull, and heart. [15] In elderly occasionally associated with increased persons the symptoms may manifest in the production of as in form of worsening of all the pathological hyperparathyroidism. Secondary conditions, decreased vision, imbalance of is noticed with increased lipidogram indices, arrhythmia (irregular and hypercalciuria along heartbeat), common arthralgia (pain in with , polydipsia, vomiting, joints),chronic hepatic and renal failure. dehydration, constipation, anorexia and Hypervitaminosis A affects skin lethargy, hypertension, tetany and seizures predominantly. [16] that may be fatal. [21] No toxicity has been associated with In adults, hypervitaminosis D the use of large doses of supplements of results in muscle weakness, frequent and beta-carotene as compared with preformed rapid fatigue, functional dyspepsia vitamin A. But carotenodermia (harmless (indigestion), sub febrile type of fever, with condition in which skin turns yellow- progressive weight loss, constant headaches orange) has been reported by long term without clear localization, hypertensive

International Journal of Health Sciences & Research (www.ijhsr.org) 282 Vol.8; Issue: 10; October 2018 J K Roop. Hypervitaminosis - An Emerging Pathological Condition crises leading to stroke, development of can be taken to reduce the absorption of various forms of cardiomyopathies [22] vitamin D and other fat-soluble vitamins. accompanied with bradyarrhythmic [28,29] Short term toxicity can be ameliorated disorders of cardiac activity and generalized by administration of vitamins A and K. [26] icterus of the skin and mucous membranes. The modulation of toxic effects of vitamin Signs of acute poisoning include tremors of D3 by administering may be due distal parts of the extremities, a sharp pain to biological activity of vitamin K syndrome in the muscles of back and dependent proteins that are synthesized in extremities, general dehydration of the body the liver and secreted into blood where they and subcutaneous hemorrhages of various depend on the normal complement of forms and to different extent. The uses of Glaresidues that are efficient chelators of supplements of both calcium and vitamin D calcium ions and counteract hypercalcemia. by post-menopausal women have known to [30] The protective effect of vitamin A in cause risk of kidney stones. [23] In pregnant hypervitaminosis D3 is its ability to women, there is the risk for the development downregulate matrix Gla proteins in the soft of bone structure anomalies. Certain tissues and prevents in renal nonspecific symptoms have been associated tissue. [31] with such as weight loss, HYPERVITAMINOSIS E-- Naturally anorexia, polyuria, heart arrhythmias, raised vitamin E is present in vegetable oils, blood calcium leading to stones in urinary unprocessed cereal grains, nuts and seeds. tract, vascular and tissue calcification that No adverse side effects have been reported may cause damage to the heart. Long-term after consuming vitamin E in natural foods. high-dose supplement intake may result in Today, people have started taking vitamin E adverse health effects, increase in mortality, supplements on a regular basis, because of greater risk of pancreatic cancer, its known antioxidant, [32] antiatherogenic, cardiovascular events, more falls and [33] fertility promoting (anti-sterility) [34] and fractures in elderly. Hypervitaminosis has anti-ageing [35] properties. The also been recognized as a cause of recommended daily dose is 3- 25 mg/day depression. [24] In children it has been and the side effects are observed at doses associated with dental enamel hypoplasia above 1g/kg. Physicians have reported few and focal pulp calcification. [25] cases of cerebral haemorrhage due to Complications may arise due to increase in prolonged intake of vitamin E at a dose of serum calcium levels, cardiac enzyme 50 mg/day. Healthy individuals taking elevations, disturbances in renal function vitamin E daily at a dose of 100mg or more tests leading to chronic kidney disease, for prolonged duration (one year) are likely nephrolithiasis, , calcinosis to exhibit hypervitaminosis E. High daily of the joints and periarticular tissues. [26] dose @ 150-200 mg/ kg body weight / day Management is by discontinuing the may result in cystic fibrosis supplements and treats the cause. In case of abetalipoproteinemia. The number and severe vitamin D intoxication, severity of side effects are directly glucocorticoids are occasionally used for a proportional to the dose and duration of short while. Bisphosphonates like vitamin E intake. Increases in all-cause pamidronate may be used to treat mortality have been reported after hypercalcaemia. Phenobarbital and consuming large overdose of vitamin E phenytoin are used to prevent and control supplements. [9,10,36] High doses of alpha- epileptic seizures, increase the hepatic tocopherol supplements can affect blood metabolism of vitamin D to inactive clotting by inhibiting vitamin K-dependent compounds and reduce calcium absorption. carboxylase and thus leads to increased [27] Both weight-loss drug orlistat and bleeding, inhibit platelet aggregation by cholesterol-lowering drug cholestyramine reducing the platelet thromboxane

International Journal of Health Sciences & Research (www.ijhsr.org) 283 Vol.8; Issue: 10; October 2018 J K Roop. Hypervitaminosis - An Emerging Pathological Condition production, cause haemorrhage and can rupture of RBC membrane due to oxidative impair immune system by decreasing stress and thus lead to haemolytic anemia, phagocyte activity of leucocytes, leading to jaundice and liver damage. This is rarely necrotic enter-colitis, neuromuscular and observed in adults and is mostly seen in endocrine disturbances. [37,38] The infants. People taking blood thinning drugs cardiovascular effects associated with or anticoagulants should limit their intake of hypervitaminosis E are aggravation of foods with vitamin K, as excess vitamin K angina, hypertension, acceleration of can alter blood clotting times. [40, 41] atherogenesis, and restenosis process and HYPERVITAMINOSIS C-- The acute toxic reduction of cerebral blood flow leading to dose for vitamin C has not been determined. stroke. [36, 39] Certain dermatological, renal The chronic toxic dose is more than 2 g/day. and gynecological side effects have also The maximum dose for adults should not been reported, like ecchymosis and exceed 90 mg/day. The symptoms of chapping of lips, creatinuria and hypervitaminosis C in adults are manifested creatinaemia, irregular vaginal bleeding, in general as feeling of weakness, dizziness, gynaecomastia, breast cancer and diarrhoea, nausea and vomiting, insomnia, disturbances in reproduction. [38] Fatigue, strong headache, allergic reactions to skin, weakness, headache and gastrointestinal heartburn and stomach ache. Overdose of disturbance, diarrhoea, intestinal cramps and ascorbic acid have been reported to be delayed wound healing have also been associated with increased nervous associated with vitamin E toxicity. excitability, unmotivated aggression, itching Management is by discontinuing the and rashes on the skin in children. Various supplements and treats the cause. Try to serious consequences have also been consume daily recommended dose only. reported with prolonged overdose of the HYPERVITAMINOSIS K-- Vitamin KI supplement like kidney disease, gastritis and and vitamin K2 are the two common forms stomach ulcer, deficiency of vitamin B of vitamin K. Vitamin K1 is produced in complex, disturbance of pancreas, increased green leafy vegetables like turnip, spinach, blood pressure, clotting disorder, cauliflower, cabbage, broccoli and Brussels progressive deterioration of vision, sprouts and also found in cow’s milk, soy disturbance in menstrual cycle oil, cottonseed oil, canola oil and olive oil. (dysmenorrhea), change in morphological Vitamin K2 is synthesized by intestinal composition of the blood with the decrease bacteria in the body. Both the forms are in the number of leucocytes and hormonal likely safe for most people when taken by disorders. Excessive amount of vitamin C in mouth or injected into the vein. Side effects the body stimulates the accumulation of are negligible in most people who prefer oxalates and their deposition in the renal physician’s recommended amount each day. tissue and gall bladder. [42] An overdose of There isn’t enough scientific information to vitamin C during can cause determine recommended dietary allowances severe disorders in the metabolism of the for vitamin K. It has been reported that if foetus. So, with extreme caution, ascorbic one is suffering from diabetes, monitoring acid should be taken during pregnancy, of blood sugar level becomes necessary as diabetes, and impaired renal vitamin K1 might lower blood sugar level. activity. High doses of vitamin K can worsen the Management is by discontinuing the clotting problems caused by severe liver supplement use and increasing the urinary disease. Vitamin K toxicity can occur only output. with type K3 that leads to haemolytic HYPERVITAMINOSIS B COMPLEX-- anemia by inhibiting the glutathione Hypervitaminosis of group vitamin B function that may lead to accumulation of complex has combined characters and the reactive oxygen species. This may cause symptoms appear in the form of generalized

International Journal of Health Sciences & Research (www.ijhsr.org) 284 Vol.8; Issue: 10; October 2018 J K Roop. Hypervitaminosis - An Emerging Pathological Condition hyperemia and hypersensitivity of skin, adverse effects such as skin flushing have headache of varying degrees of intensity been reported at a dose of 50 mg/day or without limited localization, intestinal greater. The therapeutic doses are ulcers, occurrence of sleep disorders, considered to range from 1,500-1,600 increased convulsive readiness, fatty liver, mg/day. Prolonged usage at a dose of 3 hyperglycemia, hyperuricaemia, nausea and gm/day may be associated with risk for liver indigestion are found. [42] toxicity, low blood pressure, light Hypervitaminosis B12 occurs in the headedness, insomnia, peptic ulcer, skin elderly who take it in the parenteral dosage rash, hyperemia of skin, pruritus, for more orally for treating malignant gastrointestinal disturbances, aggravation of anemia. Overdose may lead to various types bronchial asthma, gout and fasting of allergic reactions, congestive heart hyperglycemia. Hypervitaminosis B2 failure, pulmonary oedema, reduction in the () may result in liver dysfunction, size of vascular controlled reflexes, photophobia, zaeda in the corners of mouth palpitation, tingling sensation and numbness and cardiomyopathies, vomiting, itching, of limbs. The toxic dose for vitamin B12 numbness, burning or prickling sensation, has not been specified. The symptoms of hypotension, fatigue and production of hypervitaminosis B9 (folic acid) are bright yellow urine. Overdose of Thiamine specified by tonic convulsions in the (B1) blocks nerve transmission, cause gastrocnemius muscles that may occur at paralysis, restlessness, convulsions, any time of the day and inhibition of the respiratory paralysis and cardiac failure. It function of hepatic dehydrogenase. also interferes with other B vitamins, insulin Sleep, stomach and skin problems are also and thyroid functions. [42] associated with overdose. Side effects from an overdose of biotin (vitamin H/B7) are DISCUSSION rare, as it is easily excreted in urine and Due to stress and hectic life style, faeces. Sometimes overdose may cause the city dwellers are more prone to hyperkeratosis of superficial follicular overeating or no eating at all. This has led to epithelium. Hypervitaminosis B6 the loss or deficiency of vitamins in the (Pyridoxine) is extremely rare. For its body. To compensate for the imbalance or development the dose of the drug should deficiency of essential vitamins needed for exceed 1000times.Prolonged use of maintaining the basal metabolic activities, supplements at a dose of 300-500mg/day people have now-a-days started taking can cause severe and progressive sensory various vitamin supplements in the form of neuropathy with ataxia, painful skin rashes, powders, syrups, tablets and pills without photosensitivity, nausea and heartburn. [9, 10, consulting and proper monitoring by the 43] The severity of symptoms is dose nutritionists and dieticians. This has led to dependent. Excessive doses cause damage accumulation of vitamins in the body tissues to sensory neurons resulting in paraesthesia and fluids that cause toxicity/ in the hands and feet, difficulty in walking, hypervitaminosis in the body. Toxicity/ tiredness, and reduced sensation to touch, hypervitaminosis due to water soluble temperature and vibration. Discontinuing vitamins do not impose threat to the life of a the usage of may resolve person. Whereas, accumulation of fat symptoms unless irreversible damage has soluble vitamins A,D,E and K may cause occurred to neurons. Overdose of intoxication syndrome resulting in certain hypervitaminosis B5 (Pantothenic acid) may common symptoms like headache, inability cause diarrhoea, gastrointestinal problems, to exercise and perform daily routine and water retention leading to oedema. activities, diarrhoea, vomiting, constipation, Hypervitaminosis B3 (Niacin) have not irritability, nausea, weakness and dizziness. been established. However, some of the Hypervitaminosis can be normalized by

International Journal of Health Sciences & Research (www.ijhsr.org) 285 Vol.8; Issue: 10; October 2018 J K Roop. Hypervitaminosis - An Emerging Pathological Condition increasing the urinary output and limiting 7. Bjelakovic G, Nikolova D, Gluud LL, the intake of vitamin supplements. It is et al. Antioxidant supplements recommended to take the advice of the forprevention of mortality in healthy physician/nutritionist before taking vitamin participants and patients with various supplements in different forms. diseases. Cochrane Database of Syst Rev. 2008; Issue2. Art. No.: CONCLUSION CD007176. To avoid the signs of toxicity and/or 8. Bjelakovic G, Nikolova D, Gluud LL, hypervitaminosis, experts recommend et al. Antioxidant supplements for restricting the use of pharmaceutical form of prevention of mortality in healthy participants and patients with various vitamins without consulting dieticians and diseases. Cochrane Database Syst gastroenterologists. Rev. 2012; 14(3):CD007176.

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How to cite this article: Roop JK. Hypervitaminosis - an emerging pathological condition. Int J Health Sci Res. 2018; 8(10):280-288.

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