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Over the past several months it has come to FDA’s attention that there is an increase in the number of liquid vitamin D dietary supplements being marketed that could lead to infants receiving an unsafe amount of vitamin D. As a result, FDA believes industry should provide the necessary safeguards to ensure that infants using these products would not receive an unsafe amount of vitamin D.
Most liquid vitamin D products marketed today use a dropper to measure and deliver the vitamin D. FDA has concerns regarding any liquid vitamin D products that could deliver a significantly excessive amount of vitamin D. The concern is that the droppers can hold a considerably greater amount of liquid vitamin D than an infant should receive. This could lead to a parent inadvertently or mistakenly giving an unsafe amount of vitamin D to an infant.
To reduce the likelihood of dosing errors, FDA recommends that 400 units be clearly and accurately marked on the dropper accompanying your product. In addition, for products intended for infants, FDA recommends that the dropper hold no more than 400 units.
We are providing the following additional information to industry on Vitamin D and its safety:
Vitamin D is a generic term that is used to refer to the secosterols, ergocalciferol or Vitamin D2, and cholecalciferol or Vitamin D3 and their metabolites and analogues. Vitamin D is normally produced in the skin from a pro-vitamin using ultraviolet B (UV-B), and with adequate sun exposure, Vitamin D is not required in daily dietary intake. Vitamin D is the principal regulator of calcium, and is therefore important for skeletal development, bone mineralization and bone homeostasis, among other functions.
The Institute of Medicine’s (IOM) recommended Upper Limit (UL) for chronic Vitamin D intake for infants (children less than 1 year of age) is 25 mcg/day (1,000 IU/d), and for children age 1 year and older the recommended UL is 50 mcg/day (2,000 IU/d), based upon the specific vitamin D molecule being D3 from naturally occurring substances, such as fatty fish and fish liver oils. The UL for pregnancy and lactation is the same as for non-pregnant adults at 50 mcg/day (2000 IU/d). The UL value for adults ages 18 and older was based on a safety factor of 1.2 applied to a no adverse effect level (NOAEL) of 60 mcg/d. The lowest adverse effect level (LOAEL) in the IOM analysis was 95 mcg/d. The adverse effect used in the risk assessment was hypercalcemia, serum calcium elevated above the normal range, specified as above 2.75 mmol/liter (11 mg/dL)1.
In 2008 the American Academy of Pediatrics (AAP) recommended that all breast-fed and partially breast-fed infants (beginning in the first 2 months after birth) consume 400 IU/day of Vitamin D . Initial symptoms of Vitamin D toxicity are usually associated with resultant high serum calcium and include weakness, fatigue, lassitude, headache, nausea, vomiting, and diarrhea; mental status changes and coma may also develop. Renal function may be affected early. Cardiac arrhythmias may also ensue. Prolonged hypercalcemia can lead to soft tissue deposition of calcium; favored areas include the kidney, resulting in other associated problems such as hypertension. Additionally, other soft tissues that are affected include blood vessels, heart, lungs, and skin. Osteomalacia may also occur. Blood chemistry changes include elevated calcium and urea, with inconsistent elevation of phosphorus. If the problem is caught early, treatment may completely reverse the symptoms. Residual sequelae may include permanent renal impairment, and osteoporosis, among others2.
FDA appreciates your attention to this matter. If you have any questions, please contact Lesley Maloney, Pharm.D., Senior Advisor for Business and Industry Relations, in FDA’s Office of External Relations. Her email address is Lesley.Maloney@fda.hhs.gov, and her telephone number is 301-796-8236.
Joshua M. Sharfstein, M.D.
Principal Deputy Commissioner
of Food and Drugs
2Daniel D. Federman, M.D., Elizabeth G. Nabel, MD, eds. 2010. ACP Medicine. New York, NY. BC Decker Inc. ISBN 0-9703902-9-7. ISSN 1548-9345. STAT!Ref Online Electronic Medical Library. http://online.statref.com/document.aspx?fxid=48&docid=630. 4/9/2010 12:41:40 PM CDT (UTC -05:00).