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Journal of Parenteral and Enteral
Nutrition
http://pen.sagepub.com/
Micronutrient Supplementation in Adult Nutrition Therapy: Practical Considerations
Krishnan Sriram and Vassyl A. Lonchyna
JPEN J Parenter Enteral Nutr 2009 33: 548 originally published online 19 May 2009
DOI: 10.1177/0148607108328470
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Review Journal of Parenteral and
Enteral Nutrition
Volume 33 Number 5
Micronutrient Supplementation in September/October 2009 548-562
© 2009 American Society for
Parenteral and Enteral Nutrition
Adult Nutrition Therapy: 10.1177/0148607108328470
http://jpen.sagepub.com
Practical Considerations hosted at
http://online.sagepub.com
1 2
Krishnan Sriram, MD, FRCS(C) FACS ; and Vassyl A. Lonchyna, MD, FACS
Financial disclosure: none declared.
Preexisting micronutrient (vitamins and trace elements) defi- for selenium (Se) and zinc (Zn). In practice, a multivitamin
ciencies are often present in hospitalized patients. Deficiencies preparation and a multiple trace element admixture (containing
occur due to inadequate or inappropriate administration, Zn, Se, copper, chromium, and manganese) are added to par-
increased or altered requirements, and increased losses, affect- enteral nutrition formulations. Most enteral nutrition prepara-
ing various biochemical processes and resulting in organ dys- tions also contain adequate amounts of vitamins and trace
function, poor wound healing, and altered immune status with elements, although bioavailability may be an issue. Detailed
deleterious sequelae. Guidelines for the 13 essential vitamins information about individual micronutrient use specifically in
and 10 essential trace elements have been established. These hospitalized adult patients receiving nutrition therapy will be
recommendations, however, are applicable to healthy adults and discussed, emphasizing the practical and clinical aspects.
not to critically ill patients, in whom decreased serum levels Clinicians are encouraged to think of micronutrients not as
may indicate actual deficiencies or a deficiency due to redistri- nutritional supplements alone but also as therapeutic agents
bution. Benefits of supplementation over and above the daily and nutraceuticals. (JPEN J Parenter Enteral Nutr. 2009;33:
requirements, which may not result in increased serum levels, 548-562)
are also unclear and may, in fact, be detrimental. Vitamin
requirements are increased in disease states, but a similar rec-
ommendation for trace elements has not been initiated except Keywords: micronutrients; trace elements; vitamins
he purpose of this review is to highlight practical Preexisting micronutrient deficiencies, especially zinc
considerations in the use of micronutrient supple- (Zn), iron (Fe), selenium (Se), and vitamins A, B, and C,
Tmentation as part of short-term nutrition therapy are often present in critically ill patients.1 In addition, defi-
in adults. The term micronutrient includes vitamins and ciencies may occur due to the inadequate or inappropriate
trace elements. Vitamins are organic substances not syn- administration of micronutrients during nutrition therapy
thesized by the body and necessary for normal metabo- or because of increased requirements or increased bodily
lism. They are divided into water soluble or fat soluble losses.2,3 These deficiencies can be expected to deleteri-
and those with or without coenzyme function. Trace ele- ously affect various biochemical processes and enzyme
ments are metals present in very minute quantities in the functions, leading to organ dysfunction, muscle weakness,
body; they are essential for normal metabolic functions poor wound healing, and altered immune status.
and are cofactors of enzymes or form an integral part of The U.S. Food and Nutrition Board first prepared the
the structure of specific enzymes. daily nutrient requirements more than a half century ago
and established the Recommended Dietary Allowance
(RDA). The RDA has since been modified numerous
times and now includes the 13 essential vitamins (4 fat
1 4
From the Division of Surgical Critical Care, Department of soluble and 9 water soluble) and the following trace ele-
Surgery, John H. Stroger Jr. Hospital of Cook County, and ments: copper (Cu), chromium (Cr), cobalt (Co), Fe, flu-
2Department of General Surgery, Rush University Medical
Center, Chicago, Illinois. oride (Fl), iodine (I), molybdenum (Mo), manganese
(Mn), Se, and Zn.5 These recommendations, supported by
Received for publication February 25, 2008; accepted for pub- publications from several organizations, are typically
lication July 9, 2008. applicable to the general healthy population.
Address correspondence to: Krishnan Sriram, MD, FRCS(C), Over the past decade, the Institute of Medicine has
FACS, Stroger Hospital of Cook County, Surgical Critical developed a new set of dietary requirements known as
Care/Dept of Surgery, Chicago, IL 60612; e-mail: ksri-
ram41@hotmail.com. 6
the Dietary Reference Intake (DRI). Table 1, based on
548
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Micronutrients in Adults / Sriram, Lonchyna 549
6
Table 1. Dietary Reference Intakes
EAR RDA AI UL
Fat-soluble vitamins
A 300-625 µg RAE 700-900 µg RAE 3000 µg RAE
D 5-10 µg 50 µg
E 12 mg 15 mg 1000 mg
K 90-120 µg
Water-soluble vitamins
C (ascorbic acid) 60-75 mg 75-90 mg 2000 mg
B (folate) 320 µga 400 µg 1000 µg
Niacin 11-12 mgb 14-16 mg 35 mg
B2 (riboflavin) 0.9-1.1 mg 1.1-1.3 mg
B (thiamine) 0.9-1.0 mg 1.1-1.2 mg
1
B (pyridoxine) 1.1-1.4 mg 1.3-1.7 mg 100 mg
6
B (cobalamin) 2.0 µg 2.4 µg
12
Pantothenic acid 5 mg
Biotin 30 µg
Trace elements
Zinc 6.8-9.4 mg 8-11 mg 40 mg
Selenium 45 µg 55 µg 400 µg
Copper 700 µg 900 µg 10 000 µg
Chromium 20-35 µg
Manganese 1.8-2.3 mg
Cells are left blank where no data are available. EAR, Estimated Average Requirement (the nutrient needs of 50% of the population
[age and gender specific]); RDA, Recommended Dietary Allowance (the nutrient needs of 98% of the population; RDA = EAR + 2
standard deviations); AI, Adequate Intake (the recommended daily nutrient intake); UL, tolerable Upper Limit (the highest average
daily nutrient intake level above which side effects occur); RAE, retinol activity equivalent (1 µg RAE = 1 µg retinol, 12 µg
β-carotene, or 24 µg α-carotene). 1 IU of vitamin A = 0. 344 µg.
aAs dietary folate equivalent (DFE). 1 DFE = 1 µg food folate = 0.6 µg of folic acid.
b
As niacin equivalent (NE). 1 g of niacin + 60 mg of tryptophan.
information obtained from this 2006 publication, provides mandated by the USFDA. The American Society for
the DRI for the micronutrients discussed in this review. Parenteral and Enteral Nutrition (A.S.P.E.N.) has estab-
DRIs are further categorized as Estimated Average lished guidelines for the administration of parenteral
11
Requirement (EAR), RDA, Adequate Intake (AI), and tol- trace element additives. Tables 2 and 3 summarize
erable Upper Limit (UL) and are explained in the caption the current recommendations for administration of vita-
to Table 1. These figures serve to provide us with reference mins and trace elements to patients requiring nutrition
ranges but are applicable only to enteral intake and to sta- support.
ble patients. In practice, a multivitamin preparation (including vita-
Micronutrient requirements in critically ill patients min K) and a multiple trace element admixture (containing
are unknown.7 Decreased serum levels may not indicate Zn, Se, Cu, Cr, and Mn) are added to parenteral nutrition
actual deficiencies but just redistribution. The decrease (PN) formulations. Most standard commercially available
in serum levels may actually be a beneficial and adaptive enteral nutrition (EN) preparations already contain the RDA
response,8 as some vitamins at high doses function as of vitamins. Table 4 lists the recommendations for vitamins
pro-oxidants. Benefits of supplementation, which may and trace elements of interest in critical care practice.12
not result in increased serum levels, are also unclear.9 However, the composition of commercially available
However, the United States Food and Drug Admini- trace element preparations in the United States is far from
stration (FDA), as early as 1984, recognizing that par- ideal, especially for long-term use, as shown in a recent study
enteral vitamins are a requirement for the maintenance of on autopsy specimens obtained from patients with short
13
the body’s reparative and defensive processes, wrote into bowel on long-term PN. Tissue levels of Cu, Mn, and Cr
law the content and dosage of a parenteral multivitamin were elevated, suggesting that better trace element admix-
supplement. In 2000, the doses of vitamins B , B , C, and tures, available in several other countries, should be approved
1 6
folic acid were increased, and vitamin K was added to the and made available in the United States. This study also
formulations (for a total of 13 vitamins).10 However, a recommended that the daily Mn dose should be decreased to
similar recommendation for trace elements has not been 30-60 µg and that the daily Cr dose should be decreased to
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550 Journal of Parenteral and Enteral Nutrition / Vol. 33, No. 5, September/October 2009
Table 2. Suggested Composition of Parenteral Table 3. Suggested Composition of Parenteral Trace
10,11 10,11,122
Multivitamin Products for Adults Element Products for Adults
Amount Per Ingredient Amount Per Unit Dose
Ingredient Unit Dose
Zinc 2.5-5.0 mg
Fat-soluble vitamins Selenium 20-60 µg
A (retinol) 1 mg Copper 0.3-0.5 mg
a
D (ergocalciferol or cholecalciferol) 5 µg Chromium 10-15 µg
E (α-tocopherol) 10 mg Manganese 60-100 µg
K (phylloquinone) 150 µg
Water-soluble vitamins
C (ascorbic acid) 200 mg
Folic acid 600 µg
Niacin 40 mg
B (riboflavin) 3.6 mg
2
B1 (thiamine) 6.0 mg Absorption and Interactions
B (pyridoxine) 6.0 mg
6
B12 (cyanocobalamin) 5 µg Most water-soluble vitamins are absorbed easily from the prox-
Pantothenic acid 15 mg imal gastrointestinal (GI) tract. Fat-soluble vitamins are
Biotin 60 µg absorbed in the mid- and distal ileum as digestion of fat by
aEquivalent to 200 IU. bile and pancreatic lipase is required. In conditions where
fat malabsorption can occur, such as pancreatic insufficiency
and bile loss, deficiency of fat-soluble vitamins is common.
Deficiencies may occur with losses that occur with high-
output GI fistulas or with excessive diarrhea, as seen in
patients with inflammatory bowel disease. Reinstillation of
5-10 µg. A higher dose of Se (60-100 µg), especially in indi- upper GI secretions into the jejunum, either via a nasojejunal
14 21
viduals younger than age 40 years, was also suggested. tube or jejunostomy, will facilitate absorption of fat-soluble
In this review, we summarize the currently available vitamins that require bile and pancreatic secretions for optimal
information on the use of vitamins and trace elements as absorption; in addition, loss of trace elements is avoided.
an important component of nutrition therapy, especially Food needs to be digested first before trace elements
in the critically ill adult patient, emphasizing practical become bioavailable. Absorption of trace elements is dif-
and clinical aspects. Publications on nutrition support ficult to study, and the information available is limited. Zn
often emphasize macronutrient administration with an and Se are absorbed mainly in the duodenum and
emphasis on proteins, fats, and carbohydrates. We expect jejunum. Fe is absorbed in the duodenum and proximal
that this review will help the clinician to appreciate the jejunum, whereas Cr and Cu are absorbed in the ileum.
important role of micronutrients in the metabolic support Interactions between various vitamins are very com-
of patients. Information about the risks and clinical man- 22
plex. For example, vitamins E and C are synergistic.
ifestations of deficiency, recommended dosages, and pos- Vitamin C recycles vitamin E; thus, vitamin C deficiency
sible adverse effects for each micronutrient is presented. decreases function of the latter. Vitamin A function is
The use of PN has become easier in many parts of the antagonized by an excess of vitamin E. Requirements for
world with the ready availability of multicompartment niacin are increased in pyridoxine (vitamin B ) and
6
bags, often marketed as “total nutrient admixtures.” riboflavin (vitamin B ) deficiencies.
2
However, if improperly administered without micronutri- Numerous interactions exist between the different
ents, serious consequences may occur.15 trace elements affecting absorption via the GI tract.
The role of micronutrients in the general population, Factors affecting bioavailability of trace elements include
in epidemiologic studies, and in specific disease states will the actual chemical form of the nutrient (eg, organic form
not be presented and can be obtained from other of Cr is better absorbed than the ionic form), antagonis-
reviews.16,17 Reviews on the use of micronutrient supple- tic ligands (eg, Zn absorption is decreased by phytate and
mentation in critical illness18 and human immunodefi- fiber; Fe absorption is decreased by fiber), facilitatory lig-
ciency virus (HIV) infections19 provide more detailed ands (eg, Zn absorption is aided by citric acid), and com-
information. We will also not discuss in detail the individ- petitive interactions (eg, Fe depresses the absorption of
ual and combined antioxidant roles for several micronutri- Cu and Zn; Zn depresses Cu absorption and vice versa).
ents, as these have also been reviewed recently.20 The main Administration of ferrous sulfate with EN can result in
focus will be nutrition therapy of the hospitalized patients, zinc deficiency.23
usually short-term rather than long-term home support. Vitamins and most trace elements are stored in the liver.
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