Vitamin Toxicity – Help From Medscape

What follows are excerpts from the article Vitamin Toxicity, Updated: Dec 26, 2017 Author: Mark Rosenbloom, MD, MBA:

Practice Essentials

Almost 60,000 instances of vitamin toxicity are reported annually to US poison control centers. [12According to National Health and Nutrition Examination Survey (NHANES) data, in 2003–2006 33% of the United States population aged 1 year and older took a multivitamin supplement in a given month. [3In a 2009 survey, 56% of US consumers said they take vitamins or supplements, with 44% saying they take them daily. [4(See Pathophysiology and Etiology.)

Owing to their ability to accumulate in the body, fat-soluble vitamins [K, A, D, E] have a higher potential for toxicity than do water-soluble vitamins. Iron-containing vitamins are the most toxic, especially in pediatric acute ingestions. (See Prognosis, WorkupTreatment, and Medication.)

This link is to general information on each of the following vitamins:

Vitamin A          Vitamin B-1 (thiamine)          Vitamin B-2 (riboflavin)

Vitamin B-3 (niacin)           Vitamin B-6 (pyridoxine)          Vitamin B-12 (cyanocobalamin)

Vitamin C (ascorbic acid)          Vitamin D (cholecalciferol)

Vitamin E:

Vitamin E is any of a group of at least 8 related fat-soluble compounds with similar biological antioxidant activity, particularly alpha-tocopherol but also including other isomers of tocopherol and the related compound tocotrienol.

Folic acid:

Folic acid, which is found in oranges and green, leafy vegetables, decreases the risk of neural tube defects and may reduce serum homocysteine levels (which are a coronary artery disease risk factor). It may also have a therapeutic role as an adjuvant therapy for the treatment of methanol toxicity, since it enhances the elimination of formate.

The following are excerpts from the section of the article, Pathophysiology and Etiology:

Vitamin A:

Being fat-soluble, vitamin A is stored to a variable degree in the body, making it more likely to cause toxicity when taken in excess amounts. [15In contrast, water-soluble vitamins are generally excreted in the urine and stored only to a limited extent; hence, adverse effects occur only when extremely large amounts are taken.

Vitamin A is highly teratogenic in pregnancy, especially in the first 8 weeks with daily intake more than 10,000 IU; however, it is also a cofactor in night vision and bone growth.

Carotenemia is the result of excessive intake of vitamin A precursors in foods, mainly carrots. Other than the cosmetic effect, carotenemia has no adverse consequences, because the conversion of carotenes to retinol is not sufficient to cause toxicity.

Isotretinoin (Accutane), a drug used for the treatment of severe forms of acne, is closely related to the chemical structure of vitamin A, which means that the pharmacology and toxicology of these two compounds are similar. Birth defects (when taken during pregnancy), intracranial hypertension, depression, and suicidal ideation have been reported with isotretinoin. [18A careful drug history to uncover this possibility of isotretinoin use is important in patients presenting with manifestations suggestive of vitamin A intoxication.

Vitamin B-1 (thiamine) and vitamin B-2 (riboflavin) generally are nontoxic.

Vitamin B-3 (niacin)

Vitamin B-3 does not have a toxic dose established for humans. However, adverse effects such as skin flushing can occur at doses of 50 mg/day or greater. While therapeutic doses are considered to typically range from 1,500-6,000 mg/day, these doses carry a risk of liver toxicity, especially if not titrated slowly or in the presence of any preexisting liver disease.

Vitamin B-6 (pyridoxine)

Over time, 300-500 mg/day of vitamin B-6 may be neurotoxic (patients with impaired renal function may be more susceptible). The acute toxic dose has generally not been established.

Vitamin B-12 (cyanocobalamin)

The toxic dose for vitamin B-12 is not established.

Vitamin C (ascorbic acid)

The acute toxic dose for vitamin C has not been determined. The chronic toxic dose is more than 2 g/day.

Vitamin D (cholecalciferol)

The acute toxic dose for vitamin D has not been established. The chronic toxic dose is more than 50,000 IU/day in adults. In infants younger than 6 months, 1,000 IU/day may be considered unsafe. However, a wide variance in potential toxicity exists for vitamin D.

Vitamin E (alpha-tocopherol and others)

Vitamin E can prolong the prothrombin time (PT) in animal models by inhibiting vitamin K–dependent carboxylase, although administration of vitamin K corrects this. High doses of vitamin E increase the vitamin K requirement; coagulopathy can occur in patients who are deficient in vitamin K. [1920(Concomitant use of vitamin E and anticoagulants can also increase the risk of bleeding complications). [1920]

Vitamin E at dosages of 1600 IU/day reduces platelet thromboxane production. Vitamin E supplementation may impair the hematologic response to iron in children with iron-deficiency anemia.

In the Heart Protection Study, a combination of vitamin E (600 IU alpha-tocopherol only), vitamin C, and beta-carotene did not affect mortality.

Although adverse effects usually are observed only at very high dosages of vitamin E, a meta-analysis showed a possible increase in mortality at dosages of 400 IU/d and higher (alpha-tocopherol only). [11]

Most studies using up to 3200 IU/d of vitamin E did not observe significant acute clinical or biochemical adverse effects. [24] Vitamin E supplementation does not seem to significantly increase or decrease cardiovascular events, [25, 26, 27, 28] although it may increase the risk of mortality. [12, 11]

Vitamin E supplementation was shown to increase the risk of prostate cancer in healthy men, in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). [29]

In the Heart Outcomes Prevention Evaluation (HOPE-TOO) study, a randomized trial examining the effects of 400 IU of vitamin E versus those of a placebo in patients with diabetes or vascular disease, vitamin E did not decrease the incidence of cancer deaths or vascular events during follow-up (mean 7.2 y). Evidence indicated, however, that it did increase the incidence of heart failure. [30, 31, 32, 33, 34, 27, 35, 36]

Fatigue and weakness were reported in 2 case series in which vitamin E was administered at dosages of 800 IU/day. The symptoms resolved with removal of the drug.

Transient nausea and gastric distress have been observed in a few patients taking high dosages (2000-2500 IU/day) of vitamin E. Diarrhea and intestinal cramps have been reported at a dosage of 3200 IU/day. Other nonspecific, adverse effects of vitamin E, although reported only rarely, include delayed wound healing and headache.

Vitamin K

A toxic dose amount for vitamin has not been established. However, vitamin K-3 (menadione) supplements have been banned by the US Food and Drug Administration (FDA) because of their high toxicity.

Folic acid

A toxic dose has not been established, but folic acid is generally nontoxic. Intakes more than 5000 mcg/day mask pernicious anemia.


Occurrence in the United States

The Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS) documents the number of exposures for each class of vitamins (eg, adult and pediatric multiple vitamins, individual vitamins), the outcomes, and the fatalities from that ingestion. [12 In 2016, the NPDS reported 54,276 single exposures to vitamins, with 1903 minor adverse outcomes, 193 moderate outcomes, 8 major outcomes (4 of them involving vitamin D), and no deaths.

Regarding vitamin D toxicity, a retrospective analysis of NPDS data from 2000 through June 30, 2014 found that the mean number of exposures, which was 196 per year from 2000 to 2005, increased 1600% between 2005 and 2011 to a new annual mean of 4535 exposures per year. Nevertheless, a decline occurred in the percentage of patients treated in a health care facility and of patients with serious medical outcome, and no deaths were reported. [40]

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