Special Interest

A.S.P.E.N. Statement on Aluminum in Parenteral Nutrition

Solutions
The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Aluminum Task Force
Pamela J. Charney, MS, RD, LD, CNSD, Chair

Aluminum is one of the most common elements

found in the soil. Although it has no known functions in the human body, it can be found in small
amounts in most mammalian tissue. Until recently,
little was known of the effects of aluminum accumulation in human tissue. Increased tissue aluminum
levels have now been implicated in some pathologic
conditions in susceptible patient populations.
Exposure to aluminum occurs through a variety
of sources. Aluminum is present in cooking utensils,
aluminum cans, utensils, and containers. Many
medications contain aluminum as a contaminant or
as a component of the raw materials. Skin exposure
to aluminum occurs through aluminum containing
antiperspirants, although it is not known if skin
exposure leads to tissue accumulation. It is estimated that humans ingest 5 to 20 mg of aluminum
per day. Less than 1% of orally consumed aluminum
is absorbed, with 99% of absorbed aluminum lost in
the urine. However, circulating aluminum is highly
protein bound (95%) in plasma. Plasma binding is
saturable so in healthy individuals, urine excretion
increases when intake increases. Therefore, the vast
majority of the population is not at risk for aluminum toxicity from oral or enteral intake.
Certain patient populations may be at risk for
aluminum accumulation in tissue and resulting aluminum toxicity. In the early 1980s, it was noticed
that some patients with end-stage renal disease on
dialysis developed signs and symptoms thought to
be associated with aluminum toxicity, including
encephalopathy and bone pain. It was determined
that aluminum present in dialysate was responsible,
leading to the subsequent removal of aluminum
from dialysis solutions. Accumulation of aluminum
in bone, serum, and tissue of neonates receiving
long-term parenteral nutrition has also been noted.
Tissue accumulation of aluminum would be much
less in infants who receive total parenteral nutrition

for shorter periods. The true significance of tissue

aluminum accumulation is not known at this time.

Current Status
In 1990, the US Food and Drug Administration
(FDA) published an intent to propose regulation of
aluminum content of parenteral solutions. In 2000,
a final rule was published, with a proposed effective
date in 2001. The effective date was postponed, with
the final effective date set for July 26, 2004. Largevolume parenteral solutions will be required to contain 25 g/L of aluminum. Small-volume parenteral solution products will be required to be labeled
with the maximum aluminum content at expiration.
All large- and small-volume parenterals (largevolume parenterals include amino acids, dextrose,
fat emulsions, sterile water for injection, saline, and
electrolyte solutions [IV fluids with added electrolytes]; small volume parenterals include calcium
salts [gluconate, chloride, and gluceptate], potassium salts [acetate, chloride, and phosphates],
sodium salts [acetate, lactate, and phosphates],
magnesium salts [only sulfate was mentioned in the
mandate, not chloride], multiple electrolyte additive
solutions, parenteral multivitamins, trace elements
and single-entity parenteral vitamins) used in parenteral nutrition compounding will contain the following warning in their product literature: WARNING: This product contains aluminum that may be
toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function
is impaired. Premature neonates are particularly at
risk because their kidneys are immature, and they
need large amounts of calcium and phosphate solutions, which contain aluminum. Research indicates
that patients with impaired kidney function, including premature neonates, who receive parenteral
levels of aluminum at 4 to 5 g/kg/day accumulate
aluminum at levels associated with central nervous
system and bone toxicity. Tissue loading may occur
at even lower rates of administration.
The FDA requirements are summarized as follows:
Large-volume parenterals* will be required to
contain 25 g/L of aluminum.

0884-5336/04/1904-0416$03.00/0
Nutrition in Clinical Practice 19:416417, August 2004
Copyright 2004 American Society for Parenteral and Enteral Nutrition

416

August 2004

ALUMINUM IN PARENTERAL NUTRITION SOLUTIONS

Small-volume parenteral solutions will be

required to be labeled with the maximum aluminum content at expiration.
These requirements are meant to encourage
manufacturers to lower the aluminum content
of parenteral solutions.

Recommendations for Practice

Because there is risk of aluminum toxicity in
some patient populations, it is recommended that
aluminum exposure be minimized in all patients
receiving parenteral nutrition. In many patients,
particularly the neonatal population, it may be
impossible to provide 4 5 g/kg aluminum. Patient safety should remain the first and foremost
consideration when compounding parenteral nutrition solutions.
The FDA regulation applies to industry only;
however, those ordering and preparing parenteral nutrition solutions should be aware of the
potential aluminum contaminants present in
the components of these solutions
Compounding pharmacies may desire to
develop a database containing the aluminum
content of products used in parenteral nutrition
solutions.
Clinicians may want to purchase equivalent
products with the lowest aluminum content
when possible and should monitor changes in
the pharmaceutical market that may affect aluminum concentrations.
In addition to products used in preparing parenteral nutrition solutions, clinicians must be aware of
other sources of aluminum:
Heparin
Albumin
Blood products
L-cysteine

417

Conclusions
In light of the potential link between aluminum
contamination of parenteral solutions and morbidity
among patients receiving parenteral nutrition, the
FDA is issuing a rule to regulate aluminum content
and to establish labeling requirements for large and
small volume parenterals used in the compounding
of parenteral nutrition solutions. All healthcare providers involved in the provision of parenteral nutrition should ensure that aluminum exposure is limited when possible in at risk populations. Patient
monitoring for aluminum toxicity may not be possible or reliable in most settings.

Suggested Resources
1. Federal Register, 2000; 65:4103 to 11.
2. Federal Register, 2002; 67:52429 to 31.
3. ASCN/A.S.P.E.N. workgroup on standards for aluminum content of parenteral solutions. Am J Clin Nutr. 1991;53:399
402. Available at: http://www.naspgn.org/sub/position_papers/
aluminum.asp.

*Large volume parenterals include: amino acids,

dextrose, fat emulsions, sterile water for injection,
saline, and electrolyte solutions (IV fluids with
added electrolytes). The FDA regulation applies to
amino acid and dextrose solutions used in compounding parenteral nutrition solutions.
Small volume parenterals include calcium salts
(gluconate, chloride, and gluceptate), potassium
salts (acetate, chloride, and phosphates), sodium
salts (acetate, lactate, and phosphates), magnesium
salts (only sulfate was mentioned in the mandate,
not chloride), multiple electrolyte additive solutions,
parenteral multivitamins, trace elements, and single-entity parenteral vitamins. The FDA regulation
applies to vitamin and electrolyte solutions used in
compounding parenteral nutrition solutions.