The

Oncologist

Symptom Management and Supportive Care

The Benefit of the Neutropenic Diet: Fact or Fiction?
STEVEN J. JUBELIRER
WVU Charleston Division, CAMC Research Institute, and David Lee Outpatient Center, Charleston,
West Virginia, USA
Key Words. Neutropenic diet Neutropenia Clinical trials Food guidelines
Disclosures: Steven J. Jubelirer: None.
The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from
commercial bias. No financial relationships relevant to the content of this article have been disclosed by the author or independent
peer reviewers.

ABSTRACT
There really should not be a debate about the use of neutropenic diet for cancer patients. Its usefulness has
never been scientifically proven. However, neutropenic
diets remain in place in many institutions even though
their usefulness is controversial. Neutropenic diets were
once thought to be important in protecting patients
from having to succumb to infection from neutropenia
while undergoing chemotherapy. Although food may
contain harmful organisms and research has shown that
bacterial translocation is possible, recent studies have
been unable to obtain significant differences between
placebo and intervention groups. The dietetic chal-

lenges neutropenic patients struggle with include decreased quality of life, malnutrition, gastrointestinal
side effects, food aversion, and impaired cell-mediated
immunity from vitamin deficiency. Unanswered questions in regard to the neutropenic diet include the following: (a) which food should be included; (b) which
food preparation techniques improve patient compliance; (c) which patient populations benefit most; and
(d) when should such a diet be initiated. Without scientific evidence, the best advice for neutropenic patients is
to follow food safety guidelines as indicated by government entities. The Oncologist 2011;16:704 707

INTRODUCTION

ten lethal to patients with prolonged neutropenia, was found

to be isolated from food, water, and ice [4].
The movement of these bacteria from the gastrointestinal tract (GI tract) to other body sites, called bacterial translocation [5], is thought to cause many of the infections in
patients with neutropenia. Deitch et al. [6] demonstrated
that bacteria in the GI tract can travel through the intestinal
mucosa to infect mesenteric lymph nodes and body organs.
Bacterial overgrowth, immunosuppression, physical dis-

Chemotherapy has had a major impact on the survival rates

of patients with cancer, particularly those with hematologic
malignancies. Neutropenia due to chemotherapy is the major risk factor for infection [1]. Several studies [2, 3] reported the isolation of gram-negative organisms such as
Pseudomonas aeruginosa, Escherichia coli, Klebsiella,
and Proteus from a variety of foods, particularly salads,
fresh vegetables, and cold meats. Aspergillus, a fungus of-

Correspondence: Steven Jubelirer, M.D., Clinical Professor of Medicine, WVU Charleston Division, Senior Research Scientist, CAMC
Research Institute, and via mail at David Lee Outpatient Center, Suite 101, 3100 MacCorkle Avenue SE, Charleston, West Virginia
25304, USA. Telephone: 304-388-8380; Fax: 304-388-8395; e-mail: [email protected]; [email protected] Received
January 3, 2011; accepted for publication February 14, 2011; first published online in The Oncologist Express on April 6, 2011. AlphaMed Press 1083-7159/2011/$30.00/0 doi: 10.1634/theoncologist.2011-0001

The Oncologist 2011;16:704 707 www.TheOncologist.com

Jubelirer

ruption of the gut by chemotherapy or radiotherapy, slowed

peristalsis due to narcotics or antidiarrheal agents, trauma,
and endotoxins are factors contributing to bacterial translocation [7]. Theoretically, bacterial translocation can be decreased by reducing sources of pathogenic bacteria from
food and decreasing the bacterial burden of the gut with oral
nonabsorbable antibiotics.
The above studies led to the use of the neutropenic diet.
The neutropenic diet is also called a sterile diet, low microbial diet, or a low bacterial diet (LBD). However, a standardized definition of the neutropenic diet has not been
established [8, 9]. Variations of the neutropenic diet include
an exclusively sterile diet (e.g., all foods that have been
made sterile by canning, baking, autoclaving, or irradiation), a LBD (well-cooked foods only), or a modified house
diet (i.e., a regular diet omitting fresh fruits and vegetables)
[8 11].
The benefit of the neutropenic diet has never been scientifically proven [12]. Despite this, neutropenic diets are
used in many institutions. A descriptive telephone survey
by Todd et al. [11] looked at the use of LBDs for chemotherapy-induced neutropenia among 21 childrens hospitals
and found that (a) 43% of these hospitals used the neutropenic diet for neutropenic non bone marrow transplant patients and (b) 86% of these hospitals used the neutropenic
diet for bone marrow transplant patients. French et al. [13]
surveyed 10 bone marrow transplant centers in Canada and
northwestern United States and reported that 5 of the 7 responding hospitals used a neutropenic diet. However, the
timing of the start of the diet and the food choices that were
allowed varied with each institution. In a national survey,
Poe et al. [14] found that 66% of responding transplant units
enforced some type of modified microbial diet. Smith and
Besser [9] surveyed 400 members of the Association of
Community Cancer Centers (ACCC) and reported that 78%
of the responding hospitals restricted diets of patients with
neutropenia. The most commonly prohibited food items in
these institutions were fresh vegetables and fruits, fresh
juices, and raw eggs. Criteria for dietary restrictions varied
between hospitals. The most common reasons for restricted
diets were documentation of neutropenia defined as a white
cell count 1,000 mm3 and documentation of risk factors
for neutropenia such as recent chemotherapy.

PUBLISHED STUDIES ON THE NEUTROPENIC DIET

AND INCIDENCE OF INFECTION IN
CANCER PATIENTS
The current rationale for recommending the neutropenic
diet is based on prospective cohort or randomized studies
performed in the 1960s and 1970s in which leukemia patients were placed in a total protective environment in the

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hospital setting [10] (i.e., isolation tents, use of oral nonabsorbable antibiotics, laminar air flow, and sterile diet). In
this controlled environment, patients were found to tolerate
higher doses of chemotherapy with less toxicity, including
infections. Although these early studies suggested that protected environments may offer some protection from infection, the independent effect of the neutropenic diet on
infection rates was unclear.
In a more recent study by Moody et al. [15], 19 pediatric
patients receiving myelosuppressive chemotherapy were
randomized to a neutropenic diet or to the Food and Drug
Administrationapproved (FDA-approved) food safety
guidelines diet [16]. Patients randomized to the neutropenic
diet were given dietary restrictions that included not eating
raw fruits (except for those that could be peeled by hand),
raw vegetables, aged cheeses, cold meat cuts, fast food, and
takeout food. For the most part, all patients on the food
safety guideline diet adhered to the diet while adherence
was 94% for the neutropenic diet. There were no statistically significant differences between the two groups with
respect to the degree and duration of neutropenia (absolute
neutrophil count 1,000 mm3), median number of cycles
of chemotherapy, use of postchemotherapy filgastrim, and
comorbidities. Four patients on each diet developed febrile
neutropenia, and the authors concluded that infection rates
between the groups were similar.
Gardner et al. [17] studied 153 newly diagnosed acute
myelocytic leukemia (AML) patients who were admitted to
a high-efficiency particulate air-filtered room to receive induction therapy. With use of their early risk of mortality
(ERM) score for stratification, patients were randomly assigned to a diet with (uncooked n 75) or without (cooked
n 78) fresh fruits and vegetables. Prophylaxis with both
antibacterial and antifungal was used for all patients. No
differences were found between the groups for age, ERM
score, chemotherapy received, or days at risk. The study
outcomes showed no significant difference for time to major infection (p .44) or survival (p .36). The proportion
of those who developed a major infection was 29% for
those in the group without fresh fruits and vegetables and
35% for those allowed to have fresh fruits and vegetables
(p .60). Fevers of unknown origin developed in 51% of
the cooked group and 36% of the raw group (p .07).
DeMille et al. [8] sought to determine whether the use of
the neutropenic diet (no fresh fruits and vegetables) in an
outpatient setting influenced the number of febrile admissions and positive blood cultures. Twenty-three patients
aged 33 67 years completed a 12-week program in which
they were instructed on the neutropenic diet prior to chemotherapy. Study personnel used phone calls to assess adherence at 6 and 12 weeks and reviewed hospital charts at the

Benefit of the Neutropenic Diet

706

end of the study. Sixteen patients were deemed compliant

while seven were noncompliant. Four (25%) from the compliant group had a febrile admission, three of whom had
gram-negative bacteremia, whereas one (14%) of the noncompliant group had a gram-negative febrile admission.
In a study by van Tiel et al. [18], 20 adult patients with
acute leukemia (acute lymphoblastic leukemia [ALL] and
AML) receiving remission-induction chemotherapy were
randomized into two groups: one group to receive antimicrobial prophylaxis (Cipro) and a LBD, and the other group
to receive the same antibacterial prophylaxis and a normal
hospital diet. During chemotherapy cycles, fecal samples
were collected daily to detect gram-negative bacilli or Candida species. There were no differences in the two groups
with respect to mean age, mean weight, total number of chemotherapy cycles, and total number of days within chemotherapy cycles. There were no statistically significant
differences between the treatment groups regarding the incidence of stool colonization by yeasts and gram-negative
bacilli, confirmed and unconfirmed infections, and number
of days of antibiotic use.
There are major limitations of most of these studies.
These include the following: (a) small sample size; (b) the
absence of documentation and/or measurement of other
variables that determine the incidence of neutropenic infection including the degree and duration of neutropenia, exposure to viruses, use of granulocyte colony-stimulating
factors, hematologic versus solid tumors, and extent of mucositis; and (c) potential study bias due to awareness of the
neutropenic diet by patients assigned to the regular diet
arm, resulting in their reluctance to eat fresh fruits or vegetables. Larger randomized studies powered adequately to
compare infection rates between a normal diet and neutropenic diet are needed. Such a study has been initiated by
Moody [19] (Montefiore Hospital, New York) to compare
the FDA-approved food safety diet to the neutropenic diet
with respect to rate of infection during neutropenia in patients aged 121 years receiving chemotherapy for ALL,
AML, sarcoma, and neuroblastoma. The neutropenic diet in
this study emphasizes the avoidance of the following: raw
vegetables and fruits except oranges and bananas; takeout
food and fast foods; aged cheese (blue, Roquefort, and
Brie); deli meats; raw nuts or nuts roasted in shell; well water; and yogurt. An estimated 900 patients will be enrolled.

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ARE THERE PUBLISHED GUIDELINES ON THE USE

NEUTROPENIC DIET?

OF THE

Because there is an absence of evidenced-based studies

supporting the use of the neutropenic diet, there are no official published guidelines on its use. The National Comprehensive Cancer Network (NCCN) 2009 guidelines [20]
on prevention and treatment of infectious complications do
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Nursing Society (ONS) Cancer Chemotherapy guidelines and
Recommendations for Practice [21] state that no recent studies have linked dietary restrictions with a lower risk of infection for neutropenic patients with cancer; however, basic
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and unwashed fruits and vegetables, may be prudent. The
United States Department of Agriculture (USDA) recommendations for food safety for people with cancer [22] include the
following: (a) consumption only of pasteurized juices and
dairy products; (b) washing hands in warm soapy water before
handling, preparing, and eating food; (b) consuming food that
has not passed the expiration date; and (d) storing raw meat,
fish, and chicken carefully in wrapped containers to avoid
spillage of juice onto other foods. Notably there is no recommendation for the restriction of fresh fruits and vegetables.

CONCLUSION
Further research needs to be conducted to better evaluate
the use of neutropenic diet. Research questions to consider
might include the following: (a) Which food choices and foodpreparation techniques would best improve patient compliance? (b) Is there a specific oncology population who benefits
most from the use of neutropenic diet? (c) Is there a role for the
neutropenic diet in neutropenic chemotherapy patients independent of other interventions (i.e., antibiotics, growth factors,
and use of private room) used to prevent infection? (d) Should
the neutropenic diet be initiated at the start of chemotherapy or
only when neutropenia develops?
Until this research is completed, the available evidence
does not support use of the neutropenic diet. In addition,
neutropenic diets are not standardized. Several studies have
emphasized the importance of food in patients quality of
life [10, 15]. Patients receiving chemotherapy undergo
many stressors including body image changes and an uncertain future [8]. Many patients identify appetite and
weight as variables within their control, and food is seen as
a nurturing and comforting area of life [8].

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