RESEARCH
Perspectives in Practice
An Evidence-Based Approach for Dietitian
Prescription of Multiple Vitamins with Minerals
DEBORAH E. WILDISH, MA, RD
ABSTRACT
Dietitians working in hospitals are routinely involved in
assessing energy and macronutrient (ie, protein, fat, car-
bohydrate) requirements of patients. However, complete
nutritional therapy requires a comprehensive review of
vitamin and mineral requirements. Scientific evidence for
vitamin and mineral supplementation is primarily based
on healthy, free-living people. This raises clinical chal-
lenges for dietitians working with patients whose vitamin
and mineral requirements are impacted by various dis-
eases, conditions, and medical treatment. Dietitians are
the best-positioned health professionals to lead an evi-
dence-based approach toward recommending vitamin
and mineral supplements. The dietitians at the Toronto
Rehabilitation Institute were authorized through a med-
ical directive to prescribe multiple vitamins with miner-
als and to discontinue orders for unnecessary vitamin
supplements. This is an ongoing, advanced practice ini-
tiative that focuses on the clinical efficacy for and safety
of supplementation with multiple vitamins with miner-
als. It involves assessing the strength of evidence as it
emerges in the literature, determining its relevance to
specific patient populations in the practice setting and
reevaluating clinical practices for potential applications.
When dietitians assume advanced practice initiatives,
they are better equipped to deliver high-quality patient
care. Simultaneously, state-of-the-art dietetic practice
heightens dietitian recognition as a valuable member of
the health care team.
J Am Diet Assoc. 2004;104:779-786.
C
linical questions arise from various sources; an evi-
dence-based approach begins with refining ques-
tions in a way that is meaningful and relevant to
practice.
Collectively, the dietitians at the Toronto Rehabilita-
tion Institute had many treatment questions pertaining
D. E. Wildish is the manager of clinical nutrition and
corporate professional leader, dietetics, ARAMARK Can-
ada Ltd, Toronto Rehabilitation Institute, Toronto, On-
tario, Canada.
Address correspondence to: Deborah E. Wildish, MA,
RD, c/o Nutrition Services, University Centre, Toronto
Rehabilitation Institute, 550 University Ave, Toronto,
Ontario, Canada M5G 2A2. E-mail: wildish.debora@
torontorehab.on.ca
Copyright © 2004 by the American Dietetic
Association.
0002-8223/04/10405-0001$30.00/0
doi: 10.1016/j.jada.2004.02.022
© 2004 by the American Dietetic Association
to vitamins and minerals. Before investing significant
time and committing to this advanced practice initiative,
the dietitian team carefully weighed the potential bene-
fits to patient care. This process began by posing broad
clinical questions, in the form of assumptions, tested
through an initial literature review. An immense volume
of literature relevant to vitamins and minerals necessi-
tated streamlining the scope of this initiative to render it
feasible. To maintain the project focus, boundaries were
defined to provide limits for the clinical questions that
would be entertained: To focus on the clinical efficacy for
and safety of supplementation with multiple vitamins
with minerals (MVWMs) in patient populations repre-
sented at the Toronto Rehabilitation Institute, and to
defer evaluating literature related to supplementing with
individual vitamins or minerals, including megadoses, to
cure deficiencies, correct drug-nutrient interactions, pre-
vent disease, or improve immunity.
RESISTING THE URGE TO SHORTCUT AN EVIDENCE-BASED
APPROACH
A series of comprehensive literature reviews was con-
ducted with librarian assistance. Using an Ovid inter-
face, hundreds of full abstracts were reviewed from MED-
LINE, EMBASE, CINAHL, and the Best Evidence
database. The initial search strategy was similar to that
of Avenell and colleagues (1) and included both subject
headings and text words for every form of vitamin and
mineral. This was a timely initiative because it coincided
with the release of scientific reports and position papers
that provide additional evidence and direction for supple-
mentation with MVWMs (2-11).
After the literature review, the strength of the evidence
was graded for each journal article, with the letter grades
A through D representing the best and worst evidence,
respectively (12-15). Grade A evidence to support a treat-
ment decision, such as prescribing MVWMs, primarily
includes systematic reviews of randomized controlled tri-
als and individual randomized controlled trials with nar-
row confidence intervals (12-15). A conservative approach
was applied; a grade A rating was reserved for high-
quality original research and review articles consistently
supported by grade A evidence. Grade B evidence is a
broad category including both individual studies and
systematic reviews of homogeneous cohort studies or
case-control studies, lower-quality randomized controlled
trials, and outcomes research. Grade C evidence encom-
passes case series without control groups and lower-
quality cohort or case-control studies. Grade D evidence
is based on expert opinion, such as commentaries, lacking
explicit critical appraisal or cited research to support
statements or conclusions.
Journal of THE AMERICAN DIETETIC ASSOCIATION 779
 A decision was made to reflect the grade range of avail-
able evidence, rather than to exclude findings from arti-
cles with a lower grade of evidence. The rationale was to
provide a balanced and transparent perspective. Review
articles may be thorough yet weakened by the lack of
existing evidence. Grade D resources were used primarily
for generating questions or locating other references.
TESTING THE WATERS BEFORE DIVING IN
An initial literature review confirmed the assumptions,
providing support for undertaking this initiative, as indi-
cated by the following three points.
● The majority of research and recommendations for vi-
tamins and minerals has focused on healthy, free-living
populations. Fourteen grade A studies were found rel-
evant to vitamin and mineral research in free-living
adults (16-29). Only three grade A studies were located
relevant to hospitalized or institutionalized adults,
none of which studied the use of complete MVWMs
(30-32).
● Vitamin and mineral requirements and the efficacy of
supplementation with MVWMs may vary from a
healthy population to an individual who presents with
a complex medical history. There is a consensus that
nutritional requirements may be impacted by chronic
disease; however, this has not been thoroughly studied
and fully elucidated (4,21,33-36).
● Supplementation with MVWMs can improve vitamin
and mineral status of adults identified as at nutritional
risk. Twelve grade A studies showed that supplemen-
tation with vitamins or minerals improved biochemical
markers for nutritional status in free-living or institu-
tionalized adults (17-20,25-32).
Therefore, strong evidence exists that MVWMs can
maintain or improve nutritional status. However, the
literature provides poor direction regarding the efficacy
and safety of MVWMs for adults with medical conditions
despite the high prevalence of supplement usage to pre-
vent or treat chronic disease (37). The dietitian’s role in
recommending MVWMs to improve nourishment (9) is
challenged by the absence of rigorous criteria that iden-
tify potential benefits and adverse effects (4,33). There-
fore, the dietitians at this institute were determined to
reconcile when patients should and should not receive
MVWMs.
ESTABLISHING THE INDICATIONS AND CONTRAINDICATIONS
FOR MVWMS
The formal approach described by Gray and Gray (12)
was used to develop broad and more specific clinical ques-
tions. These questions focused on treatment with
MVWMs in patient populations represented at this insti-
tute. Several subsequent literature reviews were con-
ducted, applying broad search terms such as “diet” and
“nutrition” with a number of key terms relevant to each
individual question. This approach located articles not
indexed under vitamins or minerals, including many gen-
eral review articles for clinical nutrition therapy.
Table 1 summarizes the indications for MVWMs that
were studied across five in-patient programs: neuroreha-
780 May 2004 Volume 104 Number 5
bilitation, musculoskeletal rehabilitation, spinal cord re-
habilitation, geriatric rehabilitation, and complex con-
tinuing care, and also an in-patient hemodialysis clinic.
Despite the array of nonprescription vitamin and min-
eral supplements, adverse reactions to supplements have
not been sufficiently reported or studied (69). Adminis-
tering high-potency or more than one vitamin/mineral
supplement may be contraindicated if the total dose of a
given nutrient exceeds the tolerable upper intake level
(4,9,10,40). Vitamin and mineral toxicities are usually
caused by supplements, not by dietary intake (9,10). One
individual case study reported the onset of acute hepati-
tis in an elderly patient residing in a long-term care
facility who received megadoses of MVWMs (70). Another
grade B study reported that many supplement users ex-
ceed the tolerable upper intake level for safety (40).
Additional literature reviews were conducted to deter-
mine whether specific patient groups represented at this
institute might have adverse reactions to supplementa-
tion with MVWMs based on age, disease state, or medical
treatment as summarized in Table 2.
Finally, defining the indications and contraindications
for MVWMs prompted teamwork with pharmacists to
obtain the ideal formulation of MVWMs for the hospital
medication formulary. The desired supplement would
need to provide a low dose of MVWMs (10) while meeting
the recommended dietary allowance (RDA) of different
adult age and sex groupings. The major challenge was to
find supplements with appropriate levels of nutrients.
Special considerations are listed in Table 3.
IMPLEMENTATION OF NEW EVIDENCE INTO PRACTICE
The evidence-based answers to the focused clinical ques-
tions became the framework that enabled dietitians to
prescribe MVWMs. Although there are differences in re-
gional health care law within and between countries, the
physician usually oversees the medical treatment of pa-
tients. Various written mechanisms can enable a physi-
cian to transfer the authority to perform a specific proce-
dure to another professional who is not authorized to
perform it. The development of medical directives in Can-
ada (89) and clinical privileges in the United States
(90,91) is an evolving topic that has sparked dietitian
interest. Dietitian practice is shaped by legislation and
the governing body of individual hospitals.
At the Toronto Rehabilitation Institute, the framework
for dietitian prescription of MVWMs was written into a
medical directive that was endorsed by both the Clinical
Practice Committee and the Pharmacy and Therapeutics
Committee before approval by the Medical Advisory Com-
mittee. On February 14, 2002, in-patient dietitians at
this institute were authorized to prescribe MVWMs.
THERAPEUTIC VS NONTHERAPEUTIC SUPPLEMENTS
To safely prescribe MVWMs, dietitians must thoroughly
review existing orders for both therapeutic and nonthera-
peutic doses of individual vitamins and minerals. The
dietitians at this institute deliberated their proposed role.
Therapeutic doses were defined as the prescription of
individual vitamins or minerals to cure nutrient deficien-
cies or to treat a medical condition (10). Common thera-
Table 1. Indications for prescribing multiple vitamins with minerals
Identified criteria Evidence References

Moderate to high risk for malnutrition Grade B 4,9,10

Grade C 38 to 40
Poor nutrient quality of dietary intake resulting from exclusion of one or more food groups Knowna ...
Inadequate quantity of oral intake because of poor intake or strict reducing diets (eg, less than Grade B 9
1,200 kcal/d)
Moderate or severe weight loss Grade C 41
Chronic malabsorption, diarrhea, or vomiting resulting from gastrointestinal diseases, surgery, or Knowna ...
medical treatment
Tube-feeding regimens providing less than 90% recommended dietary allowance Calculatedb ...
c
Chronic wounds at more advanced ulcer stages or resistant to healing Grade A 42
Grade B 51,52
Grade C 43-50,53
Multiple traumas characterized by significant weight loss and subclinical deficienciesd Grade B 52,55,56
Grade C 34,53,54,57
Elderly patients require individual assessment to determine need for supplementatione Grade A 18,19,22,24,28,30,31,59
Grade C 35,36,39,58,60-68
a
This is a well-established fact in clinical dietetic practice.
b
Patients in the complex continuing care program often have low energy requirements (eg, less than 1,000 kcal, to maintain weight within their reference range). March 2003 calculations
determined that 38 of 78 patients requiring tube feeding received less than 100% nutrient requirements. It is not feasible to supplement all patients who might fall short of 100% of
the recommended dietary allowance. Ninety percent of the recommended dietary allowance was considered an acceptable target, which required that 18 patients receive
supplementation with multiple vitamins with minerals.
c
Chronic wounds include diabetic ulcers, venous stasis and arterial ulcers, and pressure sores. The literature failed to provide specific direction for supplementation with multiple vitamins
with minerals or relevant evidence was weak (43,53). Multiple vitamins with minerals may be beneficial for ulcer stages III and IV or for ulcers that do not decrease in size within 2
weeks (44). Clinical judgment must be applied for each patient case.
d
At this institute, patients often present with multiple traumas secondary to motor vehicle accidents. Multiple traumas result in substantial tissue, blood, and other body fluid losses,
resulting in subclinical deficiencies not easily measured by standard biochemical methods and complicated by inflammatory processes (56). Increased metabolic requirements continue
into the recovery phase while anabolism is under way (34).
e
Elderly patients have lower energy requirements, necessitating a nutrient-dense diet (39,58). Consistent grade A and C evidence suggests the elderly are at risk for subclinical vitamin
and mineral deficiencies. Only grade C evidence exists for supplementing all hospitalized elderly patients (35,58). Existing guidelines recommend an individualized nutritional assessment
before considering treatment with multiple vitamins with minerals (9,10,66).

Table 2. Contraindications for prescribing multiple vitamins with minerals

Identified risk factors Evidence References
a
Receiving enteral nutritional supplements fortified with vitamins and minerals Calculated ...
Elderly patients may be at risk for vitamin A toxicityb Grade A 16,59
Grade B 71,72,74,75
Grade C 66,73
Pregnant womenc Grade B 10
End-stage renal diseasec Grade C 76 to 80
Oncology patients undergoing active treatment require individual review for appropriate supplementationd Grade C 81 to 88
a
Calculations will confirm whether a given patient’s total nutritional intake of vitamins and minerals is sufficient to meet recommended dietary allowances without supplementation with
multiple vitamins with minerals.
b
In the elderly, vitamin A absorption may be increased and hepatic retinyl ester clearance decreased (66,71,72). Consistent findings of four grade B studies reported no deleterious effects
on liver function or skeletal turnover with vitamin A supplementation at 1,500 ␮g retinol per day (71,72,74,75). Therefore, one-half the upper limit was deemed a conservative limit
for the elderly.
c
Pregnant women and patients with end-stage renal disease are two distinct groups requiring specially formulated multiple vitamin and mineral supplements.
d
Conflicting and low-grade evidence exists regarding whether antioxidants may reduce (81-83) or enhance (84-87) the effectiveness of and tolerance to radiation or chemotherapy.
High-quality studies are needed that directly link cancer treatment successes or failures with antioxidant intake (83). Because there is a high prevalence of vitamin and mineral usage
by patients during cancer treatment, the dietitian plays an instrumental role in reviewing and recommending appropriate supplements (88). The goal is to maintain nutrient intake within
the dietary reference intakes.

Journal of THE AMERICAN DIETETIC ASSOCIATION 781


Table 3. Desired formulation of supplement containing multiple
vitamins with minerals
Specific nutrient Target level References
All nutrients 50% to 200% RDAab 4 process and share responsibility for maintaining current
Iron 8 mgc 10,66
Vitamin A 1,500 ␮g per dayd 10,71,72,74,75
Calcium Limited by supplemente 5 undertaking vitamin and mineral projects in focused
Zinc, copper, selenium, Within RDA levels 5,7,8
magnesium,
manganese,
chromium,
molybdenum,
and iodinef
a
RDA⫽recommended dietary allowance.
b
Many supplements provide nutrients above the RDA, especially for B vitamins,
antioxidants, and trace minerals.
c
The RDA for women younger than 51 years is 18 mg, and the RDA for men 19 years
and older is 8 mg. Additional iron may be detrimental for adult men or postmenopausal
women. Many adults have the genetic tendency for hemochromatosis, which leads to
high iron stores and subsequent disease risk (10). Adults with iron deficiency should
receive additional supplementation by physician order.
d
Safe level of retinol intake is one-half the upper limit to prevent potential toxicity in
the elderly and to provide a cautionary intake for women of child-bearing age to
prevent potential teratogenic effects (10).
e
The calcium content of available supplements containing multiple vitamins with
minerals is often below the RDA. If individuals do not consume adequate milk products,
they may require additional calcium supplementation.
f
Trace element content is often neglected and should be included to promote optimal
health.
peutic doses of a given nutrient may exceed the tolerable
upper intake level (40). Therefore in this situation, it is
prudent not to exceed the original therapeutic dose. The
dietitians decided not to initiate or change orders for
therapeutic doses. However, if the patient would benefit
from MVWMs, the dietitian will calculate the total dose of
each nutrient from all supplements to ensure that it falls
within the tolerable upper intake level or within the
original therapeutic dose ordered. If any changes are
required, the dietitian will alert the physician and re-
quest an adjustment to the therapeutic dose.
Nontherapeutic doses of individual or multiple vitamin
supplements were defined as supplements used for pro-
phylaxis, to prevent disease, or to maintain health. Such
supplements may be prescribed by the physician on re-
quest of a patient or substitute decision maker. The im-
plementation plan required that each dietitian work in
coordination with the physician. It was agreed that die-
titians may discontinue nontherapeutic doses if there is
no efficacy for a supplement in combination with MVWMs
or when the tolerable upper intake level is approached.
The dietitians must obtain patient or substitute decision
maker consent before discontinuing orders for nonthera-
peutic supplements.
APPROACH TO EDUCATION
The hospital medication formulary was used to develop
customized tables detailing the availability of individual
and combination vitamin and mineral supplements, their
782 May 2004 Volume 104 Number 5
nutrient content, and common indications for therapeutic
doses. This information was compared against the di-
etary reference intakes (DRIs) for each vitamin and min-
eral to provide dietitians with practice tools (5-8,11).
All members of the dietitian team contributed to the
best practice in the provision of MVWMs. It is envisioned
that dietetics interns will participate in future initiatives,
areas.
Whenever a dietitian prescribes MVWMs, the dietitian
becomes accountable for nutritional follow-up and must
reassess the continuing need for MVWMs. It is neither
economical nor practical to monitor biochemistry to de-
termine whether nutrient deficiencies exist or have been
corrected (17,20,64,65,67). Several grade A studies indi-
cate the duration of supplementation required to improve
biochemical markers of vitamin and mineral status. The
effectiveness of supplementation may begin to be shown
within 2 (19,28) or 3 months (24). However, the most
significant and complete effects were reported after 6
months of supplementation (20,30-32).
If the indications for MVWMs are no longer applicable,
the dietitian must write an order to discontinue MVWMs.
However, if MVWMs are recommended postdischarge,
the dietitian must provide instructions. A teaching tool
was developed to help patients understand why they
would benefit from MVWMs. The duration of supplemen-
tation is specified and special instructions for administer-
ing MVWMs are provided when the patient has dyspha-
gia or receives all medications via a feeding tube.
The dietitians submit monthly quality monitoring sta-
tistics for all dietitian-written orders on a combination
tracking form. This information is compiled for feed-
back to the dietitian team and the Medical Advisory
Committee.
DISCUSSION
Applying an evidence-based approach presented many
challenges. The final test of the evidence is its relevance
to the clinical questions posed and the patient popula-
tions under study. The ideal evidence to support a treat-
ment decision, such as prescribing MVWMs, would have
been a systematic review of randomized controlled trials.
However, no randomized controlled trials were found to
support the clinical efficacy for and safety of supplemen-
tation with MVWMs in patient populations represented
at the Toronto Rehabilitation Institute.
There is a tendency to base clinical practice on review
articles that offer the convenience of summarizing many
nutrition topics. However, most review articles located
for this initiative provided grade C or lower evidence. It is
common for investigators to provide expert opinion when
research is lacking. Furthermore, evidence in review ar-
ticles was often difficult to grade because of extensive
topic areas with varying levels of evidence. For example,
a review article may be assigned an overall grade of B yet
may present some topic areas with higher or lower levels
of evidence. Furthermore, each grade has a hierarchy of
evidence; some studies or review articles meeting grade B
criteria may be closer to grade A or to grade C (12-15).
There is a definitive need for randomized controlled
trials that define specific clinical endpoints for optimal
vitamin and mineral provision in various disease states,
severely injured patients, and institutionalized adults,
including the elderly (4,21,33-36). There is mounting ev-
idence from grade A studies that suggests that MVWMs,
antioxidants, or trace elements may improve immunity in
the elderly (18,20-23,29-31,59). Other grade A studies
suggest benefits of supplementing patients with type 2
diabetes to improve immunity (22) and restore magne-
sium (92) or zinc and chromium levels (25).
Further research is needed to evaluate the efficacy of
vitamin and mineral supplements for long-term health
promotion and reduction of chronic disease risk
(4,10,38,63). One grade A, 8-year primary prevention
trial is under way to determine whether nutritional doses
of antioxidants decrease the risk of cardiovascular dis-
ease and cancer (26). Other grade A (17) and grade C
(60,62,63,93-95) studies have focused on the use of
MVWMs or antioxidants to improve cognition or protect
against Alzheimer disease.
The final test of the evidence is its
relevance to the clinical questions
posed and the patient populations
under study.
The success of this initiative required collaboration
with medicine, pharmacy, and nursing staff who have
overlapping professional scopes of practice and roles. It
was a rigorous process that tied professional practice to
scientific evidence. The commitment to this initiative is
ongoing, requiring weekly literature reviews through
Ovid updates.
Dietitian prescription of MVWMs has expedited pa-
tient care. In the past, dietitians did not recommend
MVWMs for all patients who might benefit from supple-
mentation because the indications were ambiguous and
the process was cumbersome. Physicians are not always
present, nor do they routinely read the dietitian’s recom-
mendations in the patient health record. Furthermore,
contacting a physician for the purpose of ordering
MVWMs ranked lower on the list of medical priorities.
During the first year that the medical directive was ap-
proved, approximately three dietitians wrote 65 prescrip-
tions for MVWMs and three orders to discontinue unnec-
essary vitamin supplements. Dietitians consistently
document the rationale for MVWMs in the patient health
record, including the patient’s or substitute decision mak-
er’s consent to or refusal of treatment with MVWMs.
The fragmentation of patient care has been reduced. In
1999, the dietitians at the Toronto Rehabilitation Insti-
tute were authorized through a medical directive to write
diet and tube feeding orders (89). Now that the dietitians
can prescribe MVWMs, they can order complete nutri-
tional therapy. State-of-the-art dietetic practice height-
ens recognition of dietitians as valuable members of the
health care team.
CONCLUSIONS
● Dietitian prescription of MVWMs is an advanced prac-
tice initiative, requiring an ongoing commitment to an
evidence-based approach.
● Before dietitians recommend or prescribe MVWMs,
specific clinical questions must address both indica-
tions and contraindications relevant to the patient pop-
ulations in their practice setting. Rigorous literature
searches are required, and librarian assistance is ben-
eficial. The evidence needs to be graded using evidence-
based medicine protocols to evaluate the literature.
When faced with inadequate knowledge or conflicting
evidence, good clinical judgment must be applied.
● Vitamin and mineral requirements and the efficacy for
MVWMs may vary between healthy populations and an
individual patient who presents with a complex medi-
cal history. Further research is needed to address the
efficacy for individual vitamins and minerals for each
complex patient case.
● In the future, the dietitian’s role may evolve to include
prescription of therapeutic doses of individual vitamin
and mineral supplements to cure and prevent disease.
In preparation for expanding roles, an evidence-based
approach must be embraced. Dietitians would then be
accountable for ensuring that high doses of single nu-
trients would not cause relative deficiencies of other
nutrients, medication interactions, or other negative
impacts on health status (4,9).
● Advanced practice roles may require academic prepa-
ration and must be consistent with the scope of practice
limitations, licensing regulations, and health care leg-
islation. Support from physicians is required to cham-
pion the delegation of writing vitamin and mineral
prescriptions to dietitians, formally approved through a
written mechanism such as a medical directive (89).
The author thanks Pat Gottschalk, RD, ARAMARK Can-
ada Ltd, at the Toronto Rehabilitation Institute. She
contributed to the article by assisting in the review and
grading of evidence in various topic areas.
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