Peer Review | Opinion

Neutropenic diet during high-dose

therapy: a risk for patients
Schmidt L+, Erickson NT+, Reudelsterz C, von Grundherr J, Rubin D, Lambeck A, Köpcke U, Arends J,
Hübner J for the German Cancer Society, Working Group Prevention and Integrative Oncology (PRIO);
German Society for Hematology and Medical Oncology, Working Group Nutrition, Metabolism, Exer-
cise; the German Association of Dieticians – German Federal Association; and the Professional Associa-
tion of Oecotrophologists

Background
Statement
• of the German Cancer Society, Working Group Prevention and Integra- In the context of hematologic stem cell trans-
tive Oncology (PRIO) plantation (HSCT), the immune system is se-
• the German Society for Hematology and Medical Oncology, Working verely weakened by chemotherapy [1]. The-
Group Nutrition, Metabolism, Exercise; refore, for more than three decades, patients
• the German Association of Dietitians an the undergoing HSCT have been significantly
• Professional Association of Oecotrophologists restricted in their food choices by a so-called
neutropenic diet [1]. By avoiding numerous
Abstract
foods and special instructions for prepara-
The neutropenic diet has been a dietary regimen prescribed in many centers tion, the risk of food infection is to be reduced
to patients undergoing intensive chemotherapies and/or hematologic stem by the immunosuppressed patients [2]. This
cell transplantation for decades. However, evaluation of the scientific data
seems rational at first, as infections are in-
on the low-germ diet shows that this diet has no benefit but considerable
deed associated with increased morbidity and
risks for patients. Therefore, this form of nutrition is not indicated.
mortality in affected individuals [3]. Nevert-
The undersigned professional societies and working groups therefore call
heless, there is a lack of scientific evidence as to
on all physicians, nurses, nutrition therapists and dieticians to provide com-
whether adherence to a neutropenic diet pre-
prehensive nutritional medical advice to patients undergoing and after in-
tensive chemotherapy. This includes detailed information and training of vents infections [1]. This is relevant because
patients and relatives on hygiene measures in the kitchen and when con- strict limitation of dietary options may affect
suming food. quality of life and compromise body weight
Key words: neutropenic diet, chemotherapy, hematologic stem cell trans- maintenance.
plantation, immunosuppression, malnutrition, hygiene training, cancer, According to the definition of the Robert Koch
nutritional medicine, nutritional therapy Institute (RKI), a neutropenic diet is an "Expli-

+
Both authors share the first authorship

Citation Peer reviewed

Schmidt L, Erickson NT, Reudelsterz C, von Grundherr J, Rubin Opinions and position papers in Ernährungs Umschau, as in
D, Lambeck A, Köpcke U, Arends J, Hübner J for the German many other journals, are not subject to the peer review process
Cancer Society, Working Group Prevention and Integrative On- because these texts have already been evaluated, discussed, and
cology (PRIO); German Society for Hematology and Medical widely agreed upon by experts (peers).
Oncology, Working Group Nutrition, Metabolism, Exercise;
German Association of Dietitians; and the Professional Asso- Corresponding author
ciation of Oecotrophologists: Neutropenic diet during high- Prof. Dr. med. Jutta Hübner
dose therapy: a risk for patients. Ernahrungs Umschau 2022; Universitätsklinikum Jena; Klinik für Innere Medizin II
69(3): 24–9. Am Klinikum 1
The English version of this article is available online: 07747 Jena
DOI: 10.4455/eu.2021.009 [email protected]

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Ernaehrungs Umschau international | 3/2022
 Professional society, year [reference] Opinion
German Cancer Society, 2014 [9] Recommendations are made that can be assigned to a strict neut-
ropenic diet. This involves talking about "bacterial-free" nutrition
in the neutropenia phase and "bacterial-reduced" in the leukocyte
regeneration phase.
German Society for Nutritional Medicine Neutropenic diets are not explicitly mentioned, but "dietary restric-
(DGEM), 2015 [10] tions that limit food intake in patients with (impending) malnutri-
tion can be ... potentially harmful and should be avoided."
German Society for Hematology and The diet of patients with a weakened immune system should be
Medical Oncology (DGHO), 2017 [11]. decided on a more individual basis. In addition, evidence-based
education programs are recommended by all stakeholders.
European Society for Clinical Nutrition and A neutropenic diet is not recommended due to the lack of evidence.
Metabolism (ESPEN), 2021 [12]
Robert Koch Institute, 2021 [4] The strict implementation of a neutropenic diet is explicitly rejected
"because its benefits are unproven and such a diet significantly
impairs patients' quality of life."

Tab. 1: Opinions by several professional societies and the Robert Koch Institute on neutropenic diets

cit avoidance of any food that may cause infections in immuno- a significantly reduced survival prognosis of
compromised patients via contamination with and transmission patients [14].
of facultative pathogenic or opportunistic microorganisms." [4] This is particularly critical as 35% of patients
In practice, this is done in different ways. In 2006, Moody et al suffer from malnutrition after autologous
[5] defined a diet as "low-bacterial" (neutropenic diet) if it excluded HSCT [15] and up to 60% after allogeneic
raw fruits that cannot be peeled and if it did not include raw vege- HSCT [16]. This is due to the side effects of the
tables, aged cheese, cold cuts, fast food, or food prepared away therapy such as nausea, vomiting, diarrhea,
from home. In their study published in 2018 [6], nuts and yogurt and mucositis, which can also lead to reduced
were additionally excluded for this dietary pattern. Van Thiel et al food intake and thus to malnutrition and an-
[7], in a clinical trial published in 2007, investigated a "low bacte- orexia [13, 17, 18]. Another relevant aspect is
rial diet“ without raw vegetables, lettuce, soft cheeses, raw meats, that the changes in the intestinal microbiome
fresh fruits, tap water, and spices that were not heated. In 2012, (dysbiosis) triggered by chemotherapy already
Trifilio et al [8] reported a "low bacterial" diet (neutropenic diet) impair the functionality of the intestinal mu-
that did not include fresh fruits or vegetables, black pepper, raw cosa as a defense barrier [19, 20] and that dra-
or undercooked meat, undercooked cheese products, cold-smoked stic restrictions induce further disturbances in
fish, non-pasteurized dairy products, raw miso products, raw ce- the microbiome [21, 22]. A critical examina-
real products, or brewer's yeast. tion of the evidence on a neutropenic diet and
Due to the restricted selection of foods and the intensive prepara- a clear definition of the patients for whom this
tion, the dietary form of a neutropenic diet can promote malnutri- is necessary is essential in order to minimize
tion [13]. In addition, food prepared according to the regulations the risk of malnutrition.
is not very appetizing and is visually and tastily inadequate, so
that food intake is additionally restricted as a result. These fac-
tors can exacerbate malnutrition. Malnutrition is associated with

While the use of such a low-germ diet has been largely maintained in many transplant centers, the opinions of
relevant professional societies have changed over the past decade and have recently come out against the strict
implementation of a neutropenic diet ( Table 1). In contrast, decisive importance is attached to reliable adherence
to basic hygiene measures in the purchase, storage, and preparation of food (safe food handling). Foods with a high
risk of bacterial contamination by pathogens should be furthermore avoided [4].

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Peer Review | Opinion

Neutropenic diet in criticism Increasing evidence against the use of

neutropenic diet
As early as 2002, there were critical discussions about the neut- Another meta-analysis published in 2019
ropenic diet [23]. Subsequent studies found that it was even asso- from five RCTs with 388 patients undergoing
ciated with a worse disease prognosis. intensive chemotherapy for acute leukemia or
This was confirmed in 2008 by a randomized controlled trial childhood sarcoma confirmed the uniqueness
(RCT) (n = 153) in patients with newly diagnosed acute myeloid of the presented study results. Here, 53.7%
leukemia or high-risk myelodysplastic syndrome (10% to 19% of ND participants (different definition, but
blasts in bone marrow or peripheral blood). Patients consumed exclusion of raw fruits and vegetables) and
either only fresh (but prepared or washed according to Food and 50% in the comparison group (standard hos-
Drug Administration (FDA)-compliant food hygiene) or only ade- pital diet or diet according to FDA food safety
quately cooked fruits and vegetables according to the neutropenic guidelines) suffered an infection, usually de-
diet (ND). In the ND group 29% and in the comparison group fined as pneumonia, bacteremia, and funge-
35% of the participants suffered an infection (major infection), mia (p = 0.10) [31]. A 2019 meta-analysis of
accompanied by pneumonia, bacteremia and/or fungemia. This five RCTs from six included studies also exa-
difference was not significant (p = 0.60). In addition, 51% of par- mined ND in 1116 patients. Within the 69.1%
ticipants in the ND group showed fever of unclear origin compa- HSCT patients, an increased risk of infection
red to 36% in the comparison group (p = 0.07) [24]. was found with adherence to ND (p = 0.03;
In 2012, a retrospective study (n = 726) examined the impact of RR 1.25; 95% CI 1.02–1.54) [32].
ND after HSCT. This showed that 37.2% of ND patients and 29.2%
with a standardized diet (SD) according to the Academy of Nutri- Based on these data, it seems
tion and Dietetics, had a microbiologically confirmed infection (p reasonable that ND after HSCT
< 0.0272) [25]. should not be offered as standard,
In 2014, a pilot RCT (n = 46) examined the difference between a but solely in the context of stu-
ND versus an unrestricted diet in patients undergoing allogeneic dies to clarify possible efficacy.
HSCT. Both groups received an FDA recommendation in safe food
handling, preparation, and storage. There were 28% confirmed The advancing evidence base is now also re-
infections in the ND group and 30% in the comparison group (p flected in the RKI's 2021 recommendation:
= 0.99) [26]. The RKI announcement "Requirements for
An analysis of the pediatric AML-BFM 2004 study published in infection prevention in the medical care of
2016 showed that dietary restriction in the form of ND did not immunocompromised patients" [4] emphasi-
significantly reduce fever of unclear origin, pneumonia, gastroen- zes the importance of patient safety and their
teritis, and bacteremia in 339 children in 37 German hematology quality of life. It is intended to support all me-
centers [27]. dical professional groups to improve the care
In 2018, ND was studied in a pediatric multicenter RCT (n = of immunocompromised patients. This inclu-
150) with various cancers. Again, it showed no advantage over des training of staff, patients and their relati-
FDA food safety guidelines in cancer patients [28]. Only 8.3% of ves, as well as basic hygiene measures in the
participants who followed the FDA guidelines and 10.4% of those facility and out-of-hospital settings.
who additionally followed a ND had developed a microbiologically These must also be observed during nutri-
confirmed infection (p = 0.67). Due to the more difficult imple- tion. In order to ensure adequate nutritional
mentation, adherence to ND was significantly lower at 92.6 (± care during the inpatient stay, individualized
15.3) % compared to FDA at 99.3 (± 4.8) % (p < 0.001) [6]. nutrition may be necessary, especially du-
The key message of the individual studies could be corroborated ring intensive therapy. This is to counteract
in meta-analyses. A 2015 meta-analysis examined three RCTs and complications such as cachexia. Here, the
one observational study with a total of 918 participants with Commission for Hospital Hygiene and Infec-
various malignancies. Both ND and SD patients had a comparable tion Prevention of the Robert Koch-Institute
number of major infections (relative risk [RR] = 1.08, confidence emphasizes that a strict neutropenia diet is not
interval [CI] 0.72–1.61, I2 = 39%) [29]. suitable.
Nevertheless, in a 2018 survey of 90 centers (6 from Germany)
of the European Society for Blood and Marrow Transplantation • Basic hygiene measures in the purchase, sto-
in 23 countries, 93% of participants reported that they recom- rage and preparation of food are essential
mend ND to patients during the neutropenia phase in HSCT. This in order to maintain a low risk of bacterial
is often administered standardized or fortified with high-calorie contamination even in the out-of-hospital
ingredients and nutritional supplements [30]. context [4].
• Intensive education of patients is intended
to sustain compliance with appropriate food
hygiene and preparation.

M136 26  
Ernaehrungs Umschau international | 3/2022
• Accordingly, all-inclusive education begins with purchasing and
ends with consumption [33, 34]. Patients should learn the pro- Conflict of Interest
per selection of intact foods, their refrigeration, transportation, Opinions and position papers reflect the viewpoints and
assessments – including the interests – of the organizati-
and storage. They should be aware of sources of infection such
on(s) named in the author line. The authors declare that
as raw foods (e.g. minced meat, fish, eggs). In this context, cle- there are no further conflicts of interest in connection with
aning of hands, surfaces and kitchen utensils should also be the contents of this publication.
taught to avoid cross-contamination.
• For appropriate food preparation, the importance of washing,
peeling and blanching, as well as the assessment of adequate
Luca Schmidt1
heating and cooling, should be explained. Dr. rer. biol. hum Nicole Tonya Erickson, RD2
The usefulness of these measures as opposed to extensive heating Christine Reudelsterz
was confirmed in a laboratory study. In this, the microbiological Julia von Grundherr MPH, B. Sc. 3
load of one SD and one ND hospital food was examined. Of 36 Prof. Dr. med. Diana Rubin4
Dr. Andrea Lambeck5
samples, two each of the SD and ND were contaminated with B.
Uta Köpcke6
cereus and one of the ND with coagulase-positive Staphylococcus Dr. Jann Arends7
(p = 1.00). Furthermore, this was found in one dish that had Prof. Dr. med. Jutta Hübner1
undergone a cooking process. This emphasizes the importance of [email protected]
hygiene of food and its preparation [35].
1
Universitätsklinikum Jena; Klinik für Innere Medizin II
2
Comprehensive Cancer Center (CCC München LMU),
LMU Klinikum München
3
Universitäres Cancer Center Hamburg (UCCH)
Conclusions Universitätsklinikum Hamburg-Eppendorf
4
Vivantes Klinikum Spandau
5
BerufsVerband Oecotrophologie e. V. (VDOE)
In the context of evidence-based care for patients with intensive 6
Verband der Diätassistenten – Deutscher Bundesverband
chemotherapy regimens, including patients with HSCT, a neutro- e. V.
penic diet is not indicated because it provides no benefit but carries (VDD)
significant risks for patients. 7
Albert-Ludwigs-Universität Freiburg, Universitätsklinikum
The undersigned associations, professional societies and working Freiburg, Klinik für Innere Medizin I
groups therefore call on all physicians, nurses, nutrition thera-
pists and dieticians in hospitals and practices to provide com-
prehensive nutritional advice to patients undergoing and after
intensive chemotherapy. This includes detailed information and
training for patients and relatives on hygiene measures in the kit-
chen and when eating food. Any weight loss must be countered
by appropriate nutritional medical measures. Qualified nutritional
counseling is the first priority here.

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Peer Review | Opinion

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