Results

The initial search in July 2022 retrieved 1037 citations and after the removal of 481 duplicates, a total of 550 articles were available for title and abstract screening. Following initial screening, 264 articles were eligible for full-text screening. Following full-text screening 19 articles were deemed eligible for inclusion. Two articles were added from email alerts from the databases for a total of 21 included articles. Figure 1 shows the PRISMA Flow Diagram.

Fig. 1. PRISMA Flow Diagram.

Nine studies were conducted in the United States,^{(Reference Sonbol, Jain and Firwana8,Reference Ball, Brown and Das9,Reference Moody, Finlay and Mancuso24–Reference Taggart, Neumann and Alonso30)} three in India,^{(Reference Ramamoorthy, Rubens and Appunni11,Reference Radhakrishnan, Lagudu and Gangopadhyay31,Reference Gupta, Gupta and Meena32)} two in The Netherlands^{(Reference van Dalen, Mank and Leclercq10,Reference van Tiel, Harbers and Terporten33)} and Iran^{(Reference Jalali, Hosseini and Ajami34,Reference Hosseini, Jalali and Ajami35)} and one in Australia,^{(Reference Heng, Barbon Gauro and Yaxley36)} China,^{(Reference Ma, Lu and Liu12)} Germany,^{(Reference Jakob, Classen and Stecher37)} The Philippines^{(Reference Ng and Dujua13)} and Italy.^{(Reference Matteucci, De Pasquale and Pastore14)} Four studies^{(Reference Moody, Finlay and Mancuso24,Reference Taggart, Neumann and Alonso30,Reference Gupta, Gupta and Meena32,Reference Hosseini, Jalali and Ajami35)} included only paediatric participants and nine studies included only adult participants.^{(Reference Matteucci, De Pasquale and Pastore14,Reference DeMille, Deming and Lupinacci25–Reference Lassiter and Schneider28,Reference van Tiel, Harbers and Terporten33,Reference Jalali, Hosseini and Ajami34,Reference Heng, Barbon Gauro and Yaxley36,Reference Jakob, Classen and Stecher37)} Eight studies,^{(Reference Sonbol, Jain and Firwana8–Reference Ng and Dujua13,Reference Moody, Baker and Santizo29,Reference Radhakrishnan, Lagudu and Gangopadhyay31)} including the seven systematic reviews/meta-analysis, included all age groups. Eleven studies were conducted in an inpatient hospital setting, and one in an outpatient setting.^{(Reference DeMille, Deming and Lupinacci25)} Two studies included both inpatients and outpatients^{(Reference Moody, Finlay and Mancuso24,Reference Moody, Baker and Santizo29)} and six of seven systematic reviews/meta-analyses^{(Reference Sonbol, Jain and Firwana8–Reference Ng and Dujua13)} included one or more of the outpatient studies whereas one^{(Reference Matteucci, De Pasquale and Pastore14)} only included studies with an inpatient population. All studies included participants with haematological cancers and four also included participants with oncological cancers^{(Reference Moody, Finlay and Mancuso24,Reference DeMille, Deming and Lupinacci25,Reference Moody, Baker and Santizo29,Reference Gupta, Gupta and Meena32)} however, none analysed results by cancer type. A summary of the characteristics of the included studies are shown in Table 1.

Table 1. Characteristics of Included Studies

ND, neutropenic diet; CD, comparator diet; RCT, randomised control trial; CDN, comparator diet not randomly assigned, ages presented as mean ages or age range.

There are no guidelines for the use of the ND and the diet can vary between hospitals in the foods restricted. This is reflected in the differences between the NDs in the included studies. All included studies restricted most raw fruits and vegetables – some allowed fruits and vegetables with thick skin or that could be hand-peeled.^{(Reference Moody, Finlay and Mancuso24,Reference Lassiter and Schneider28,Reference Moody, Baker and Santizo29,Reference Hosseini, Jalali and Ajami35)} Other restricted foods included raw grains,^{(Reference Trifilio, Helenowski and Giel27,Reference Taggart, Neumann and Alonso30,Reference Jakob, Classen and Stecher37)} raw nuts/nut butters,^{(Reference Moody, Baker and Santizo29,Reference Jakob, Classen and Stecher37)} raw seeds,^{(Reference Trifilio, Helenowski and Giel27)} raw miso,^{(Reference Trifilio, Helenowski and Giel27)} yoghurt,^{(Reference Moody, Baker and Santizo29,Reference Heng, Barbon Gauro and Yaxley36)} dairy from bulk machines (i.e. soft serve ice cream, frozen yoghurt), raw honey,^{(Reference Taggart, Neumann and Alonso30)} dried/raw herbs and spices,^{(Reference DeMille, Deming and Lupinacci25,Reference Trifilio, Helenowski and Giel27,Reference van Tiel, Harbers and Terporten33,Reference Heng, Barbon Gauro and Yaxley36)} yeast,^{(Reference Trifilio, Helenowski and Giel27,Reference Taggart, Neumann and Alonso30)} cold desserts^{(Reference Heng, Barbon Gauro and Yaxley36)} tap/un-boiled water,^{(Reference van Tiel, Harbers and Terporten33–Reference Hosseini, Jalali and Ajami35,Reference Jakob, Classen and Stecher37)} takeaway/fast food,^{(Reference Moody, Finlay and Mancuso24,Reference Moody, Baker and Santizo29,Reference Taggart, Neumann and Alonso30)} buffet/street food,^{(Reference DeMille, Deming and Lupinacci25,Reference Taggart, Neumann and Alonso30)} and sharing food.^{(Reference Taggart, Neumann and Alonso30)}

The major comparator diet in the included studies was the food safety diet, used by nine studies.^{(Reference Moody, Finlay and Mancuso24,Reference Trifilio, Helenowski and Giel27–Reference Gupta, Gupta and Meena32,Reference Heng, Barbon Gauro and Yaxley36,Reference Jakob, Classen and Stecher37)} This diet restricts unpasteurised eggs, dairy, raw/undercooked meat and fish and has regulations on food handling, washing, preparation, and storage.⁽³⁸⁾ One study termed the comparator diet ‘Modified Bone Marrow Transplant Diet’ however restrictions were similar to the food safety diet.^{(Reference Taggart, Neumann and Alonso30)} Two studies^{(Reference Trifilio, Helenowski and Giel27,Reference van Tiel, Harbers and Terporten33)} used a standard hospital diet which followed the food safety diet with some additional restrictions: raw tomatoes, cold smoked fish, raw miso, raw grains/seeds, and brewer’s yeast. One study did not impose any restrictions for the comparator diet,^{(Reference Gardner, Mattiuzzi and Faderl26)} and another included participants in the comparator group if they were non-compliant with the ND.^{(Reference DeMille, Deming and Lupinacci25)}

The incidence of infections was a major outcome in all but two of the 21 included studies. However, the type of infections, grouping of infection types, and the method of reporting varied amongst studies. As shown in Table 2, we report these results as they have been reported in the included studies.

Table 2. Effect of the Neutropenic Diet on Rates of Infection

NA, Not Assessed.

^a During neutropenia.

^b Overall and when neutropenia had resolved.

^c Significant differences not reported however of the six studies 4/6 found no significant difference 1/6 did not include a comparator and 1/6 ND increased infection risk for HSCT transplant recipients only.

^d HSCT recipients and overall.

^e Non-HSCT recipients.

^f Cases of febrile neutropenia.

^g Number of febrile days.

^h HSCT recipients.

ⁱ Non-HSCT recipients and overall.

^j At baseline.

^k Day 15 of study.

− No significant difference between Neutropenic Diet and comparator, ↑Neutropenic Diet increases risk, ↓Neutropenic Diet decreases risk.

Total infection, reported in 13 studies^{(Reference Ball, Brown and Das9,Reference Ramamoorthy, Rubens and Appunni11,Reference Ma, Lu and Liu12,Reference Matteucci, De Pasquale and Pastore14,Reference Moody, Finlay and Mancuso24–Reference Trifilio, Helenowski and Giel27,Reference Moody, Baker and Santizo29,Reference Radhakrishnan, Lagudu and Gangopadhyay31,Reference Gupta, Gupta and Meena32,Reference Heng, Barbon Gauro and Yaxley36,Reference Jakob, Classen and Stecher37)} included infection of any body-site with any bacteria, fungi, or virus. One RCT^{(Reference Gupta, Gupta and Meena32)} reported a significantly higher rate of infection in the ND group with 12 infections (n = 21) compared to nine in the comparator group (n = 21) (P = 0.049).^{(Reference Gupta, Gupta and Meena32)} A retrospective study^{(Reference Trifilio, Helenowski and Giel27)} found a significant difference between the diets for total diagnostically confirmed infections – 135 infections in the ND group compared to 106 in the comparator group (P = 0.03). Infections present when neutropenia had resolved was also significantly higher in the ND group compared to the comparator group (P = 0.01). However, infection during neutropenia was not significantly different (P = 0.22).^{(Reference Trifilio, Helenowski and Giel27)} Ten of the 13 studies which reported on total infection did not find any significant difference between diet groups. Overall, from the included studies the ND either results in no significant difference in infection rates compared to the comparator diet (n = 12 studies) or increases the infection rate (n = 2 studies).

A further three studies reported combined rates of total infection and/or fever.^{(Reference Sonbol, Jain and Firwana8,Reference van Dalen, Mank and Leclercq10,Reference Gardner, Mattiuzzi and Faderl26)} A systematic review/meta-analysis^{(Reference Sonbol, Jain and Firwana8)} found higher rates of infection in the ND group for the total population (RR 1.17, 95% CI (1.04–1.32)). When haematopoietic stem cell transplant (HSCT) recipients following the ND were compared to those following the comparator diet, significantly higher rates of infection in the ND group were demonstrated (RR 1.25, 95% CI (1.02–1.54)). However, no significant difference was seen between diet groups for participants who were not recipients of HSCT.^{(Reference Sonbol, Jain and Firwana8)}

Major infection was assessed in three studies;^{(Reference Sonbol, Jain and Firwana8,Reference Gardner, Mattiuzzi and Faderl26,Reference Radhakrishnan, Lagudu and Gangopadhyay31)} however, as there is no clinical definition of what constitutes a major infection, there were differences in the definition between studies. All three studies included pneumonia, bacteraemia, or fungaemia as major infections,^{(Reference Sonbol, Jain and Firwana8,Reference Gardner, Mattiuzzi and Faderl26,Reference Radhakrishnan, Lagudu and Gangopadhyay31)} whilst one study also included urinary tract infection, meningitis, cellulitis, or diarrhoea.^{(Reference Radhakrishnan, Lagudu and Gangopadhyay31)} A systematic review/meta-analysis reported a significantly higher rate of major infection in the ND group when only assessing participants who were HSCT recipients (RR 1.25, 95% CI (1.02–1.54)). No significant difference was seen in participants who were not transplant recipients or when all participants were assessed together.^{(Reference Sonbol, Jain and Firwana8)}

Minor infection was assessed by two studies;^{(Reference Gardner, Mattiuzzi and Faderl26,Reference Radhakrishnan, Lagudu and Gangopadhyay31)} however, as there is no clinical definition of what constitutes a minor infection, both studies included all other infections not defined as a major infection. Both studies found no significant difference between diet groups.^{(Reference Gardner, Mattiuzzi and Faderl26,Reference Radhakrishnan, Lagudu and Gangopadhyay31)}

Gut colonisation by pathogenic bacteria or yeasts was assessed in two RCTs by faecal analysis.^{(Reference Radhakrishnan, Lagudu and Gangopadhyay31,Reference van Tiel, Harbers and Terporten33)} Radhakrishnan, Lagudu^{(Reference Radhakrishnan, Lagudu and Gangopadhyay31)} reported significantly higher rates of colonisation in the comparator group (n = 40/96) compared to the ND group (n = 29/102) at baseline (P = 0.05). Bacteria isolated from stool included multidrug resistant (MDR) Escherichia coli, MDR E. faecalis, MDR Klebsiella pneumoniae, MDR E. faecium, Vancomycin resistant E. faecium. A positive stool culture at baseline is considered more likely to be reflective of the diet consumed while participants are in the community. At the end of the study (day 15), there were no differences, indicating that the diet did not significantly affect gut colonisation.^{(Reference Radhakrishnan, Lagudu and Gangopadhyay31)} No significant differences were reported in the study by van Tiel, Harbers.^{(Reference van Tiel, Harbers and Terporten33)}

Pneumonia is the inflammation of the lungs caused by bacteria, fungi, or viruses^{(Reference Moeinafshar, Rezaei and Rodriguez-Morales39)} and while there is no evidence linking it to diet, it was assessed in three studies.^{(Reference Gardner, Mattiuzzi and Faderl26,Reference Radhakrishnan, Lagudu and Gangopadhyay31,Reference Gupta, Gupta and Meena32)} Two studies found no significant difference between diet groups^{(Reference Gardner, Mattiuzzi and Faderl26,Reference Radhakrishnan, Lagudu and Gangopadhyay31)} and the third did not analyse statistical significance, however they reported two pneumonia cases in the ND group (n = 21) and one in the comparator group (n = 21).^{(Reference Gupta, Gupta and Meena32)}

Bacteraemia, presence of bacteria in the bloodstream was assessed in seven studies, none of which found a significant difference between diet groups.^{(Reference Ng and Dujua13,Reference Lassiter and Schneider28,Reference Taggart, Neumann and Alonso30,Reference Radhakrishnan, Lagudu and Gangopadhyay31,Reference van Tiel, Harbers and Terporten33,Reference Heng, Barbon Gauro and Yaxley36,Reference Jakob, Classen and Stecher37)} Fungaemia, the presence of fungi in the bloodstream was assessed by one RCT which found no significant difference between diet groups.^{(Reference van Tiel, Harbers and Terporten33)} Combined bacteraemia or fungaemia was assessed in two studies,^{(Reference Sonbol, Jain and Firwana8,Reference Gardner, Mattiuzzi and Faderl26)} a quasi-experimental study found significantly higher rates in the comparator group (n = 17) than the ND (n = 7) (P = 0.03);^{(Reference Gardner, Mattiuzzi and Faderl26)} however, a systematic review/meta-analysis found no significant differences between diet groups.^{(Reference Sonbol, Jain and Firwana8)}

Norovirus, which causes gastrointestinal infection⁽⁴⁰⁾ was assessed in an observational study which reported no significant differences between diet groups.^{(Reference Taggart, Neumann and Alonso30)}

Neutropenic fever or febrile neutropenia is characterised as a high temperature (>38.3°C or >38°C on two occasions).^{(Reference Lingaratnam, Slavin and Koczwara41)} Eight studies assessed fever with five reporting on neutropenic fever,^{(Reference Ng and Dujua13,Reference Moody, Finlay and Mancuso24,Reference Radhakrishnan, Lagudu and Gangopadhyay31,Reference Gupta, Gupta and Meena32,Reference Heng, Barbon Gauro and Yaxley36)} four reported on fever of unknown origin (>38.3°C on multiple occasions for three weeks, with diagnosis unclear after one week^{(Reference Brown and Finnigan42)}),^{(Reference Gardner, Mattiuzzi and Faderl26,Reference Radhakrishnan, Lagudu and Gangopadhyay31,Reference Heng, Barbon Gauro and Yaxley36,Reference Jakob, Classen and Stecher37)} one assessed persistent fever^{(Reference Jakob, Classen and Stecher37)} and one assessed high or low temperature,^{(Reference van Tiel, Harbers and Terporten33)} with none of the eight studies reporting significant differences between diet groups.

Antibiotic use was assessed in two studies with different metrics; length of antibiotic use (the consecutive number of days which an antibiotic is used)^{(Reference Gupta, Gupta and Meena32,Reference van Tiel, Harbers and Terporten33)} and antibiotic duration (the total amount of time in which antibiotics are used).^{(Reference Gupta, Gupta and Meena32)} Neither study found a significant difference between diet groups for use of antibiotics (see Table 3).

Table 3. Effect of the Neutropenic Diet on Clinical Factors

NA, not assessed; NE, neutropenic enterocolitis.

^a Significant difference not reported 3/3 studies included had no significant differences between groups.

^b Only included results from Jakob, Classen.^{(Reference Jakob, Classen and Stecher37)}

− No significant difference between Neutropenic Diet and comparator, ↑Neutropenic Diet increases risk.

Gastrointestinal side effects such as diarrhoea, nausea, and vomiting during cancer treatment may be caused by chemotherapy,^{(Reference Krishnamurthi and Macaron43)} use of antibiotics which causes healthy bacteria of the gut to be destroyed and/or, use of other medications such as opioids.^{(Reference Krishnamurthi and Macaron43)} These symptoms are also commonly attributed to Clostridium difficile infection.^{(Reference Mullish and Williams44)} Diarrhoea was assessed in five studies^{(Reference Matteucci, De Pasquale and Pastore14,Reference Moody, Finlay and Mancuso24,Reference Trifilio, Helenowski and Giel27,Reference Heng, Barbon Gauro and Yaxley36,Reference Jakob, Classen and Stecher37)} and only one study found a significantly higher rate in the ND group (P < 0.001). The remaining studies saw no significant differences. Two studies reported on Clostridium difficile – with both reporting no significant difference between groups – however, no link was made between the incidence of diarrhoea and Clostridium difficile infection.^{(Reference Trifilio, Helenowski and Giel27,Reference Heng, Barbon Gauro and Yaxley36)} Nausea was assessed in two studies, a retrospective study reported a significantly higher rate of nausea in the ND group^{(Reference Jakob, Classen and Stecher37)} and a systematic review included only findings from the retrospective study.^{(Reference Matteucci, De Pasquale and Pastore14)} Vomiting was assessed in one study which reported two of nine participants in the ND group and two of ten in the comparator diet group had instances of vomiting, however, significance was not reported^{(Reference Moody, Finlay and Mancuso24)} (see Table 3).

Neutropenic enterocolitis is the inflammation of the gastrointestinal tract occurring in a neutropenic individual. Two studies^{(Reference Gupta, Gupta and Meena32,Reference Heng, Barbon Gauro and Yaxley36)} assessed neutropenic enterocolitis, one study reported higher rates in the ND group (P = 0.044) and the other reported no significant difference between groups.^{(Reference Heng, Barbon Gauro and Yaxley36)}

Graft vs Host Disease (GvHD) can occur post-stem cell transplant when donor T-cells attack healthy cells of the recipient. Two observational studies assessed GvHD;^{(Reference Trifilio, Helenowski and Giel27,Reference Taggart, Neumann and Alonso30)} however, neither saw a significant difference between diet groups.

Mucositis, defined as, inflammation of the mouth and/or gut, was assessed by one RCT^{(Reference Moody, Baker and Santizo29)} which reported four cases in the ND group and two in the comparator group, however this was not significant.

Mortality was assessed in ten studies;^{(Reference Sonbol, Jain and Firwana8,Reference Ramamoorthy, Rubens and Appunni11,Reference Ma, Lu and Liu12,Reference Matteucci, De Pasquale and Pastore14,Reference Gardner, Mattiuzzi and Faderl26,Reference Trifilio, Helenowski and Giel27,Reference Radhakrishnan, Lagudu and Gangopadhyay31,Reference Gupta, Gupta and Meena32,Reference Heng, Barbon Gauro and Yaxley36,Reference Jakob, Classen and Stecher37)} however, no studies reported any significant differences between groups (see Table 3).

Serum albumin, whilst no longer used as a sole indicator of nutritional status, recent literature suggests decreased levels may be associated with gut dysbiosis.^{(Reference Maslennikov, Ivashkin and Efremova45)} Two RCTs^{(Reference Jalali, Hosseini and Ajami34,Reference Hosseini, Jalali and Ajami35)} assessed serum albumin levels and both found significantly lower levels in ND groups compared to the comparator diets post-intervention (see Table 4). This may indicate a decreased dietary intake or gut dysbiosis. Neither study reported on fluid status, inflammation, microbiome, or other GI related side effects associated with decreased serum albumin levels.

Table 4. Effect of the Neutropenic Diet on Biochemical Factors, Hospitalisation, Nutritional Status, and Well-being

NA, Not Assessed; SNR, Significance Not Reported.

^a Neutropenic Diet significantly decreases serum albumin when compared to diet with additional Vitamin C or olive oil and when compared pre and post intervention.

^b Neutropenic Diet is not significantly different from diet with additional Vitamin C or olive oil pre intervention and diet with additional Vitamin C olive oil is not significantly different pre and post intervention.

^c Neutropenic diet significantly increases risk of weight loss of between 1 and 3 kg.

^d No significant difference between diets for weight loss of greater than 3 kg.

^e Neutropenic diet significantly lower QoL score for PEDS core module.

^f No significant difference between diet groups for PEDS cancer module.

^g only included results from Jakob, Classen.^{(Reference Jakob, Classen and Stecher37)}

↑Neutropenic Diet increases risk, − No significant difference between Neutropenic Diet and comparator.

Four studies assessed hospitalisation by length of stay^{(Reference Trifilio, Helenowski and Giel27,Reference Gupta, Gupta and Meena32,Reference Heng, Barbon Gauro and Yaxley36)} or admissions.^{(Reference DeMille, Deming and Lupinacci25,Reference Gupta, Gupta and Meena32,Reference Heng, Barbon Gauro and Yaxley36)} A retrospective study^{(Reference Trifilio, Helenowski and Giel27)} reported that those in the ND group (n = 363) who underwent HSCT spent, on average, one day longer in hospital than those following the comparator diet (n = 363), but level of significance was not reported.^{(Reference Trifilio, Helenowski and Giel27)} No significant difference was seen in the remaining two studies.^{(Reference Gupta, Gupta and Meena32,Reference Heng, Barbon Gauro and Yaxley36)} None of the three studies which assessed hospital admissions found a significant difference between diet groups^{(Reference DeMille, Deming and Lupinacci25,Reference Gupta, Gupta and Meena32,Reference Heng, Barbon Gauro and Yaxley36)} (see Table 4).

Patient Generated Subjective Global Assessment (PG-SGA) is a common, validated tool used in cancer patients to evaluate nutritional status.^{(Reference Ottery46)} The PG-SGA categorises individuals into three groups: ‘appropriate nutrition’, ‘prone to malnutrition’ or ‘severe malnutrition’. Two RCTs^{(Reference Jalali, Hosseini and Ajami34,Reference Hosseini, Jalali and Ajami35)} reported a significantly higher proportion of the ND group being placed into the ‘prone to malnutrition’ or ‘severe malnutrition’ categories.

Weight change was assessed in four studies.^{(Reference Matteucci, De Pasquale and Pastore14,Reference Jalali, Hosseini and Ajami34,Reference Hosseini, Jalali and Ajami35,Reference Jakob, Classen and Stecher37)} A retrospective study reported a significantly greater proportion of those in the ND group losing between 1 and 3 kg (P = 0.05), however further sub-analysis showed no significance for weight loss greater than 3 kg.^{(Reference Jakob, Classen and Stecher37)} This study only reported absolute weight loss and did not report percentage weight loss, hence making it difficult to determine if this weight loss is clinically significant. Weight loss was an outcome in the systematic review by Matteucci, De Pasquale^{(Reference Matteucci, De Pasquale and Pastore14)} and the only included study for this outcome was Jakob, Classen.^{(Reference Jakob, Classen and Stecher37)} As no further analysis was conducted in the systematic review, results were the same.^{(Reference Matteucci, De Pasquale and Pastore14)}

One study published in 2007^{(Reference van Tiel, Harbers and Terporten33)} assessed the total financial costs as a secondary outcome of the ND contrasted with the comparator diet at different stages of care – including hospital costs, other healthcare costs, and inability to work. The areas in which costs are associated were identified, however the reason for cost differences were not determined. Whilst they reported higher costs for the comparator diet during hospitalisation, in contrast during follow-up and in total, the ND had higher costs, however significance of these results was not reported.^{(Reference van Tiel, Harbers and Terporten33)}

Quality of Life (QoL) is defined by the World Health Organisation as ‘an individual’s perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards, and concerns’.⁽⁴⁷⁾ Two RCTs from the same research group^{(Reference Moody, Finlay and Mancuso24,Reference Moody, Baker and Santizo29)} assessed QoL in paediatric cancer patients (Table 4) using the Paediatric Quality of Life Inventory. These two studies were similar in design and in the outcomes assessed, however the 2017 study^{(Reference Moody, Baker and Santizo29)} had more participants (ND = 77, CD = 73) compared to the 2006 study (24) (ND = 9, CD = 10). In the 2006 study, they found the Core QoL of the ND group was significantly lower (indicating lower overall QoL) than the comparator group (P < 0.05), however, this was not significant for cancer specific QoL.^{(Reference Moody, Finlay and Mancuso24)} In the 2017 study, they did not find a significant difference between diet groups.^{(Reference Moody, Baker and Santizo29)}

Diet acceptability was assessed by three different metrics across three studies^{(Reference van Dalen, Mank and Leclercq10,Reference Moody, Finlay and Mancuso24,Reference Taggart, Neumann and Alonso30)} ; ease of following assigned diet, food not tasting how participants remembered, and inability to consume desired foods. All three RCTs found no significant difference between ND and comparator diet groups for diet acceptability.^{(Reference van Dalen, Mank and Leclercq10,Reference Moody, Finlay and Mancuso24,Reference Taggart, Neumann and Alonso30)}

Diet adherence was measured by two different metrics in two RCTs; number of meals for which participants (n = 19) were following their assigned diet^{(Reference Moody, Finlay and Mancuso24)} and number of weeks participants (n = 42) were following the assigned diet.^{(Reference Gupta, Gupta and Meena32)} Both studies found significantly better adherence in the comparator groups. Participants were reported to have adhered to the ND (n = 9) 94.10% of the time and to the comparator diet (n = 10) 99.99% of the time.^{(Reference Moody, Finlay and Mancuso24)} Participants followed the ND for 93 of the 98 weeks (n = 21) and the comparator 94 of the 98 weeks (n = 21), however, this was not significantly different.^{(Reference Gupta, Gupta and Meena32)}