Nutritional Counseling During Chemotherapy Treatment: A Systematic Review of Safety, Feasibility, and Efficacy

1. Introduction

There are approximately 20 million new cancer cases every year worldwide [1]. Treatments for cancer and their side effects can significantly impact a person’s quality of life. Fatigue, pain, and other treatment-induced side effects and toxicities lead to dose-reductions of life-saving treatment as well as persistent symptoms that limit daily activities and reduce overall well-being for years after treatment [2].

Dietary interventions may help manage and reduce the side effects of chemotherapy, improve overall quality of life during treatment, and improve tumor response to treatment [3,4]. Furthermore, by making informed choices about their nutrition, patients can actively participate in their cancer care and experience a greater sense of independence [5,6]. Guidelines on nutrition for cancer patients include nutrient quantity and diet composition [3,7,8]. In regard to quantity, clinical practice tends to focus on adequate calorie and protein intake to prevent muscle loss, sarcopenia, and malnutrition, including oral nutrition supplements if nutrient intake is not adequate from food alone [3,7,9]. In regard to dietary composition, guidelines do not recommend specific dietary patterns but encourage a broad range of tolerable foods to meet nutrient needs while discouraging dietary supplements because of their potential to interfere with chemotherapy efficacy [3,8,9,10]. Guidelines also lack more specific recommendations that target specific clinical and supportive care outcomes during chemotherapy. Further, they lack guidance on nutrient timing (e.g., intermittent fasting), a more recent discussion in the nutrition field [11,12].

Translational nutrition research is beginning to show that specific dietary patterns have large effects on tumor development. For example, work from Augenlicht et al. has shown that Western-style diets, which are replete in macro- and micronutrients, promote tumor growth in rodent models [13,14]. In addition, work by Yee et al. showed that omega-3 fatty acid consumption influences breast tissue composition in humans [15,16]. Thus, dietary patterns that are more specific than current recommendations have potential to influence clinical and supportive care outcomes.

Herein, to guide the development of more specific dietary recommendations for various target outcomes, we sought to gain a better understanding of the nutritional interventions that have been tested during chemotherapy treatment. Establishment of feasibility and efficacy for dietary interventions for specific outcomes—weight management, quality of life, etc.—can enhance our understanding of the role of nutrition in cancer care, refine clinical practices, and support the development of targeted interventions that optimize patient outcomes and well-being. The aim of this systematic review is to evaluate the safety, feasibility, and efficacy of dietary interventions on health outcomes in patients undergoing active chemotherapy treatment for cancer.

2. Methods

This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guidelines [17] and the protocol was pre-registered in the PROSPERO database (CRD42023417079). While the pre-registered protocol describes all dietary interventions during chemotherapy and radiation, our preliminary search identified over 88 disparate articles. Thus, we narrowed the focus of this review to only studies among patients undergoing active chemotherapy and excluded dietary interventions that focused on therapeutic diets focused on influencing biomarkers of cancer progression (i.e., intermittent fasting and ketogenic diets). This approach is in accordance with the European Society for Clinical Nutrition and Metabolism guidelines for clinical practice in cancer patients [9]. An ethics approval was not necessary because we were not collecting new data from human participants.

2.1. Eligibility Criteria

Studies were eligible if they matched the following inclusion criteria as specified by population, intervention, study design, and outcomes: (a) population: human participants of any age with any cancer diagnosis undergoing active chemotherapy treatment; (b) intervention: any standardized dietary pattern that modulated nutrient composition or quantity (except ketogenic diet). Studies involving enteral nutrition, dietary supplements, or functional foods were excluded. Interventions that also included physical activity components were included; (c) study design: prospectively assigned randomized controlled trials, cross-over studies, or single-armed studies; (d) outcomes: feasibility/adherence to an intervention, safety, and/or clinical outcomes as presented by the researchers. Only full-text articles published in peer-reviewed journals were included; articles were excluded if they were not published in English, conference abstracts or posters, theses or dissertations, or protocols only.

2.2. Search Strategy

Systematic research was conducted using three databases—EMBASE, Cochrane Library, and SCOPUS—from inception to September 30, 2024. A combination of MeSH (Medical Subject Headings) terms and keywords related to nutritional interventions during chemotherapy was consistently applied for each database search entry (Table S1). Search results from all three databases were imported into EndNote (Clarivate, Philadelphia, PA) and scanned for duplicates. Screening of the titles and abstracts was carried out collaboratively by SJ and AO and independently by AK, followed by a full-text review. Discrepancies in eligibility for full text articles were resolved by all authors responsible for screening (SJ, AO, and AK). The reference lists of identified papers and relevant review articles were manually checked for additional studies fulfilling inclusion criteria.

2.3. Data Extraction and Risk of Bias Assessment

The data extraction procedure followed the PRISMA statement [17]. SJ and AK independently extracted study design; year published; sample size; participants’ demographics (i.e., age, sex); cancer type and chemotherapy treatment regimen; intervention type and frequency of intervention; feasibility in the form of adherence and/or retention; safety in the form of adverse events; and health outcomes as reported in the published studies. Any discrepancies were resolved with discussion. We inductively decided which outcomes to report in the results section; we reported outcomes with the highest frequency among all studies. The two reviewers (SJ and AK) independently assessed risk of bias using Cochrane Risk of Bias 2.0 for randomized controlled trials [18] identifying “high risk,” “some concerns,” and “low risk” of bias for each clinical trial, and differences were resolved with discussion (Figure S1).

3. Results

3.1. Study Design

The systematic search identified 1,295 articles from EMBASE, Cochrane Library, and SCOPUS databases (Figure 1). After the removal of duplicates, evaluation of each article, and review of reference lists from the identified articles and relevant review articles, 38 studies met full inclusion criteria and were included in this review [6,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55].

3.2. Study Characteristics

The included studies were Phase I and Phase II clinical trials; there were no Phase III trials (Table 1) [6,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55]. From the 44 publications, there were 39 trials because some of the studies resulted in more than one manuscript (i.e., Abdollahi et al. [19,28], Bourdel-Marchasson et al. [21,31], Sanft et al. [45,56], Kenkhuis et al. [57,58], and Kleckner et al. [6,52]). On average, the nutritional intervention studies recruited 98 participants, with a range of 15 (Maurer et al. [43]) – 360 (Jacot et al. [42]) individuals. Publications arose from studies conducted all over the world, including the United States (n=9) [6,27,38,40,45,48,52,56,59], China (n=7) [22,26,34,36,55,60,61], the Netherlands (n=6) [33,46,49,50,57,58], France (n=4) [21,31,39,42], Iran (n=3) [19,28,51], Germany (n=2) [29,43], the United Kingdom (n=3) [20,35,37], Brazil (n=2) [23,24], Denmark (n=2) [30,47], India (n=2) [44,53], Italy (n=2) [54], Canada (n=1) [62], Korea (n=1) [25], Taiwan (n=1) and Thailand (n=1) [32]. The most common patient population was breast cancer (n=12/39, 31%) [19,23,24,27,38,39,40,41,42,45,53,54]; mixed cancer types (n=9) [20,21,26,30,32,35,49,50,52]; hematologic cancers (n=4) [29,47,48,51]; head, neck, and/or gastric cancer (n=4) [22,34,37,60]; gynecological cancers (n=3) [43,46,58]; colorectal cancer (n=3) [33,44,62]; pancreatic cancer (n=1) [25]; and lung cancer (n=1) [55]. Six studies recruited patients undergoing concurrent [22,34,35,60] or sequential [39,42] radiation. Only five studies were published before 2010 (i.e., Ollenschläger et al., 1992 [29], Ovensen et al., 1993 [30], Loprinzi et al., 1996 [27], Gardner et al., 2008 [48], and Demark-Wahnefried et al., 2008 [40]).

3.3. Nutritional Interventions

The types of nutritional interventions varied greatly among studies (Table 1). More than half of the 39 total trials examined individualized nutritional counseling (n=30), 19 without [19,20,21,22,23,24,25,26,27,29,30,32,33,34,35,36,60,61,62] and 11 with [37,38,39,40,41,42,43,44,45,46,58] added exercise regimens. All interventions were administered by a registered dietitian, trained coordinator, or unlicensed nutritionist throughout a patient’s cancer treatment, however, the interventions differed in dietary goals and format of counseling (e.g., face-to-face, telephone, video call, or a combination). These studies tended to set recommendations for minimum protein (~0.8-2.0 g/kg body weight) and calorie (~25-50 kcal/kg body weight) intake and/or encourage adherence to published guidelines, such as the European Society for Parenteral and Enteral Nutrition (ESPEN) [23] or the World Cancer Research Foundation (WCRF) [39]. Nine trials examined dietary patterns including a Mediterranean Diet (or a variation, n=3) [51,52,54], a protein-rich home delivery program (n=2) [49,50], high-energy density [47], a neutropenic diet [48], a plant-based high-protein diet [53], or an anti-inflammatory diet [55].

Table 1. Characteristics of the studies included in this systematic review.

Reference (country)	Study design	N =	Eligibility	Intervention Type	Intervention Details	Primary Outcome(s) (not including feasibility)
Nutrition counseling and/or food provision without exercise
Abdollahi et al. 2019 (Iran) [19]	Randomized controlled trial	Randomized N = 150	Female adults (≥18 y) with breast cancer who have received one session of chemotherapy (any type) and have a history of constipation or diarrhea after chemotherapy.	Nutrition counseling	Trial duration: 10-week trial Intervention: Face-to-face nutrition education consisting of a diet with 12–15% calories of protein, 30–35% of fat, and 55–60% of carbohydrates estimated individually based on participant's current age, weight, and height in addition to nutrition recommendations to reduce diarrhea and prevent reflux. Control: Control group had usual care without informational pamphlet, nutritional education and dietary intervention and they were asked not to change their usual diets.	Gastrointestinal side effects - nausea, vomiting, and diarrhea
Baldwin et al. 2011 (United Kingdom) [20]	Randomized controlled trial	Randomized N = 277	Adults with metastatic or locally advanced cancer of the gastrointestinal tract, lung, or mesothelioma; lost weight in the last 3 months; had agreed to undergo and were fit for palliative chemotherapy	Nutrition counseling	Trial duration: 6 weeks with a 52-week follow-up Intervention 1: Advice to increase food intake by 600 kcal (2510 kJ) per day with the intent to increase body weight; booklet contained 150-kcal ideas and were asked to select 4/day. Intervention 2: A 588-kcal (2460-kJ) sachet of nutritional supplement to be prepared in whole milk + a daily multivitamin Control: No dietary intervention	Survival
Bourdel-Marchasson et al. 2014 (France) [21]	Randomized controlled trial	Randomized N = 341	Patients older than 70 y with lymphoma or carcinoma with an indication of chemotherapy (any type); participants must be at risk of malnutrition with a full Mini Nutritional Assessment 17–23.5 points	Nutrition counseling	Trial duration: 3 to 6 months, each participant received 6 visits. Intervention: Aim of achieving an energy intake of 30 kCal/kg body weight/d and 1.2 g protein/kg/d by face-to-face discussion targeting the main nutritional symptoms, compared to usual care. Control: Usual nutritional care given in cancer treatment settings. There were no restrictions for dietary advice or oral supplements.	One-year survival
Cao et al. 2024 (China) [61]	Randomized controlled trial	Randomized N = 92	Adults (≥18 y) diagnosed with head and neck squamous cell carcinoma, planned to receive first round of chemotherapy, and planned to receive cisplatin-based chemotherapy	Nutrition counseling	Trial duration: 24 weeks Intervention: Nurse-led multidomain intervention of chemotherapy-induced nausea and vomiting (CINV) included nurse-led risk assessment, education on prevention and control of CINV, antiemetic treatments following guidelines, dietary strategies (based on the National Comprehensive Cancer Network), relaxation therapy, and follow up. Individualized dietary counseling was provided by the nurse tailored to patients’ specific needs. Control: Usual care of CINV consisting of administration of antiemetics, education about CINV control and dietary recommendations provided by primary nurses.	Incidence of CINV, severity of CINV, influence of CINV on patients’ quality of life
Dai et al. 2022 (China) [22]	Pilot randomized controlled trial	Randomized N = 72	Men and women age 18-75 y, head or neck cancer, concurrent chemoradiation therapy (nedaplatin)	Nutrition counseling	Trial duration: duration of the concurrent chemoradiation therapy Intervention: Face-to-face nutritional counseling at least once every 2 weeks during treatment to achieve calorie and protein requirements determined by the ESPEN guidelines on nutrition in cancer patients. Control: Nutrition treatment plans according to clinical experience.	Body weight
de Lima Bezerra et al. 2023 (Brazil) [23]	Randomized controlled trial	Randomized N = 34	Adult women with breast cancer, indicated for neoadjuvant chemotherapy (any type)	Nutrition counseling	Trial duration: 2 months Intervention: Personalized diet with an individually tailored meal plan based on ESPEN guidelines to address malnutrition [9] (25–30 kcal/kg body weight/day and 1.5 g protein/kg/day). Control: counseling on healthy eating and nutritional information on how to reduce the severity of chemotherapy-induced nausea and vomiting.	Chemotherapy toxicity
de Souza et al. 2021 (Brazil) [24]	Randomized controlled trial	Randomized N = 34	Female adults with breast cancer indicated for neoadjuvant chemotherapy (doxorubicin and cyclophosphamide)	Nutrition counseling	Trial duration: 3 cycles of chemotherapy (21 days/cycle) Intervention: A personalized diet meal plan formulated by dietitian based on age, current weight, and height of each subject, 25–30 kcal/kg/day of energy and 1.5 g/kg/day of protein, based on the ESPEN guidelines [9], including written materials on healthy eating and symptom management Control: Pamphlets with recommendations on healthy eating and to reduce chemotherapy-induced nausea and vomiting	Quality of life
Ford et al. 2024 (Canada) [62]	Randomized controlled pilot trial	Randomized N = 50	Adults (18-85 years) with stage II-IV colorectal cancer	Nutrition counseling	Trial duration: 12 weeks Intervention Groups: Weekly telephone nutrition education with patients to achieve 2.0 g protein/kg body weight/day and meal patterns consistent with those recommended by the Academy of Nutrition and Dietetics. Control: Weekly telephone nutrition education with patients to achieve a protein intake of 1.0 g/kg/day (standard of care). Both: Prescribed diets were translated into an individualized daily meal pattern based on typical dietary intake.	Muscle mass and physical function
Keum et al. 2021 (Korea) [25]	Randomized controlled trial	Randomized N = 40	Males or females aged 20–70 y with pancreatic ductal adenocarcinoma scheduled to receive chemotherapy (any type)	Nutrition counseling via a smartphone app	Trial duration: 12 weeks Intervention: Noom is a mobile app that offers a curriculum and human coaching. It was tailored to the population and included food logging, feedback-based food choices, daily articles for health, and coach-participant messaging with goals to encourage calorie intake and maintain nutritional status. Control: Usual care	Nutritional status and quality of life
Lin et al. 2017 (China) [26]	Randomized controlled trial	Randomized N = 110	Males and females aged ≥18 y with cancer (any type) and were undergoing chemotherapy (any type)	Nutrition counseling	Trial duration: 12 cycles of chemotherapy (duration in days not specified) Intervention: Individual recipes based on estimates of Total Energy Expenditure to achieve or maintain high nutritional status. Participants and their care takers were counseled by experienced nurses, and diets were adjusted as nutritional status changed throughout the intervention. Control: Usual care plus nutrition screening, nutritional guidance, diet mission, and arranged meal times.	Patient weight and serum albumin and prealbumin levels
Loprinzi et al. 1996 (United States) [27]	Randomized controlled trial	Randomized N = 109	Premenopausal women with resected localized breast cancer scheduled to receive adjuvant chemotherapy (any type)	Nutrition counseling	Trial duration: duration of chemotherapy, assessments at 3 and 6 months after initiation of chemotherapy Intervention: Counseling with a dietitian prior to or within 2 weeks of chemotherapy initiation and at 4-to 6-week intervals. Dietitian goals included maintaining on-study body weight or gradual weight reduction toward ideal body weight. Control: Standard care—information on the potential for weight gain and ways to prevent it.	Body weight
Najafi et al. 2019 (Iran) [28]	Same as Abdollahi et al. [19]	Randomized N = 150	Females aged 18–60 y with stage IA-IIIB breast being treated with 3-weekly cycles of doxorubicin, cyclophosphamide, and docetaxel and had experienced vomiting during or after the previous session(s) of chemotherapy	Nutrition counseling	Trial duration: duration of chemotherapy Intervention: Personalized diet and nutrition education before each chemotherapy session. The daily diet was estimated individually and contained 1.2–1.5 g/kg of protein, 30% of energy from fat, and 55–60% of energy from carbohydrate. Control: Usual care	Chemotherapy-induced nausea and vomiting
Ollenschläger et al. (Germany) 1992 [29]	Randomized controlled trial	Enrolled N = 32	Males and females age 17-60 years with acute lymphocytic or nonlymphocytic leukemia; had unintentional weight loss of >5% in the previous 3 months and/or actual body weight below 90% ideal body weight; planned cytostatic treatment	Nutrition counseling	Trial duration: Duration of therapy from induction therapy until planned or premature end of maintenance therapy (4-54 weeks); participants were hospitalized for some of their cancer treatment and some were on an out-patient basis. Intervention: “Intensified oral nutrition program”: ad libitum menu of 1.0-2.0 g protein and 30-50 kcal/kg body weight plus daily visit by a dietitian to assess nutritional status, nutritional behavior, nutrient requirements, symptoms, and well-being. Control: Free choice, ad libitum menu of 1.0-2.0 g protein and 30-50 kcal/kg body weight.	Quality of life
Ovesen et al. 1993 (Denmark) [30]	Randomized controlled trial	Enrolled N = 137	Males and females with small-cell lung cancer, ovarian cancer, or breast cancer	Nutrition counseling	Trial duration: 5 months Intervention: Counseling with a dietitian before chemotherapy and once-twice monthly and as needed; goals to meet the protein and calorie requirements of the Nordic Recommended Allowances (1.5-1.7 × basal energy expenditure as calculated by the Harris-Benedict Equation; 1.0-1.2 g protein/kg body weight) Control: Ad libitum diet Both groups: Advised to supplement diet with one multivitamin tablet that contained the daily recommended allowances of micronutrients	Body weight, quality of life
Regueme et al. 2021 (France) [31]	Same as Bourdel-Marchasson et al. [21]	Randomized N = 283				Health-related quality of life
Sukaraphat et al. 2016 (Thailand) [32]	Randomized controlled study	Enrolled N = 50	Adults (age ≥18 years) with locally advanced unresectable or metastatic cancer	Nutrition counseling	Trial duration: 9-12 weeks (3-4 cycles of chemotherapy) Intervention: Individualized and intensive dietary counseling based on the ESPEN guideline:[3] 30-35 kcal/kg body weight and 0.8-1.2 g protein/kg body weight per day with regular food, supplements used if required Control: Routine care: dietary counseling for general dietary recommendations from a nurse and physician but not a dietitian	Body weight
Tang et al. 2024 (China) [60]	Quasi-experimental study	Randomized N = 60	Adults (≥18 y) with nasopharyngeal carcinoma who have been diagnosed with malnutrition (weight loss ≥5%) and life expectancy of more than 3 months.	Nutrition counseling	Trial duration: 24 weeks Intervention: Face-to-face nutrition education with patients and their families consisting of a diet high in protein, high in calories, high in vitamins and rich in inorganic salts, in addition to nutrition recommendations to avoid dry mouth, oropharyngeal pain, and constipation consistent with guidelines. Control: Routine dietary guidance without nutrition assessment screening.	Nutritional Risk Screening 2002, BMI, and quality of life
van der Werf et al. 2020 (Netherlands) [33]	Randomized controlled trial	Randomized N = 107	Males and females aged >18 y diagnosed with metastatic colorectal cancer, scheduled for first-line chemotherapy with capecitabine and oxaliplatin (CAPOX), infusional 5- fluorouracil and oxaliplatin (FOLFOX) or capecitabine alone, with or without bevacizumab (-B)	Nutrition counseling	Trial duration: During chemotherapy (varied by participant based on regimen) Intervention: Face-to-face counseling (at every chemotherapy infusion) and telephone consultation (between infusions) by a dietitian with the goal of achieving sufficient protein, energy, and micronutrient intake. The protein intake goal was ≥1.2 g protein/kg body weight/day. The dietitian also encouraged moderate-intensity physical activity for ≥30 min per day, five days per week. Control: Access to a dietitian	Skeletal muscle area (primary), quality of life, physical functioning, treatment toxicity, treatment intensity, survival (secondary)
Wang et al. 2023 (China) [34]	Randomized control trial	Randomized N = 53	Males and females aged 50–80 years with esophageal cancer undergoing chemoradiotherapy (cisplatin + paclitaxel or cisplatin + 5-fluorouracil + radiation)	Nutrition counseling	Trial duration: duration of chemoradiotherapy (5-8 weeks) Intervention: individualized nutrition programs with target energy and protein intake (30–35 kcal/kg body weight/day and 1.2–1.5 g protein/kg/day). Nutritional evaluations were conducted by nutrition nurses each day, and nutritional interventions were adjusted based on needs. Control: Usual care	Nutritional status
White et al. 2020 (United Kingdom) [35]	Randomized control trial	Randomized N = 50	Males and females aged >18 y, have cervical or bladder cancer, undergoing chemotherapy and radical pelvic radiotherapy (weekly gemcitabine for bladder cancer or cisplatin for cervical cancer)	Nutrition counseling	Trial duration: not specified, 6-week, 12-week, and 12-month follow-up. Intervention: Individualized dietary counseling using the anthropometric data, patient-reported subjective, global assessment score, malnutrition universal screening tool score, dietician symptom assessment and 3-day food diary to tailor dietary advice and prescription of oral nutritional supplements where necessary. Control: not stated	Feasibility (primary), treatment toxicity (primary clinical outcome)
Xie et al. 2017 (China) [36]	Randomized control trial	Randomized N = 144	Males and females aged ≥18 y with gastric cancer undergoing post-operative chemotherapy (oxaliplatin and capecitabine every 21 days for up to 8 cycles)	Nutrition counseling	Trial duration: duration of chemotherapy Intervention: Intensive individualized nutritional and educational interventions during the entire course of chemotherapy Control: Education on chemotherapy, possible chemotherapy-induced adverse events, basic nutrition guidance, follow-up 2 days after infusion	Nutritional status
Nutrition counseling plus exercise
Allen et al. 2022 (United Kingdom) [37]	Pilot randomized controlled trial	Randomized N = 54	Adults with locally advanced esophagogastric cancer planned for neoadjuvant therapy (any type) plus esophagogastrectomy, or total gastrectomy.	Nutrition counseling and exercise	Trial duration: 15-week trial (preoperative) Intervention: Needs-based, frequent, and tailored to the patient by dietitians to increase total calories and protein where appropriate. This group also received a structured exercise program. Control: Control group got standard care and did not receive nutrition or exercise prehabilitation.	Cardiopulmonary exercise test performance, muscle mass and quality of life
Basen-Engquist et al. 2020 (United States) [38]	Pilot randomized controlled trial	Randomized N = 39	Patients with newly diagnosed stage II or III breast cancer patients within 3 weeks of starting neoadjuvant chemotherapy (any type)	Nutrition counseling and exercise	Trial duration: ~6 month trial (until the end of chemotherapy) Intervention: 20 individualized counseling sessions, 14 in-person and 6 by telephone. Promoted foods with low energy density and consistent with recommendations for survivors. Also, an exercise intervention focused on resistance and flexibility training to maintain or increase fat-free mass. Control: Control group received publicly available written materials on cancer survivorship.	Anthropometrics (to prevent weight gain), quality of life, serum biomarkers
Brouwer et al. 2024 (Netherlands) [57]	Randomized controlled trial	Randomized N = 81	Patients aged >18 years with primary epithelial ovarian cancer who were scheduled for (neo)-adjuvant chemotherapy treatment.	Nutrition counseling and exercise	Trial duration: From first or second chemotherapy cycle until 12 weeks after the last chemotherapy cycle Intervention: Two 1-h sessions per week, supervised by a physical therapist specialized in oncology, including moderate- to high-intensity resistance and aerobic exercise. Dietary counseling was delivered by dietitians specialized in oncology once every 3 weeks during 30–45 min face-to-face sessions in the hospital or by telephone tailored to the nutritional needs of each patient. All participants were advised to follow the dietary guidelines set by the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) and were advised to consume at least 1.2 g of protein/ kg body weight/day and at least 25 g of protein per meal. Control: Usual care during chemotherapy, which could include a referral to a dietitian when malnutrition was detected by the gynecological oncologist.	Relative dose intensity and progression-free survival
Carayol et al. 2019 (France) [39]	Randomized controlled trial	Randomized N = 143	Women aged 18–75 y; non-metastatic breast cancer; enrolled after curative surgery, planned for 6 cycles of adjuvant chemotherapy (epirubicin / cyclophosphamide / 5-fluorouracil for 3 cycles every 3 weeks, followed by docetaxel for 3 cycles every 3 weeks), followed by 6 weeks of radiotherapy	Nutrition counseling and exercise	Trial duration: 26 weeks Intervention: The Adapted Physical Activity and Diet (APAD) intervention consisted of exercise sessions planned thrice-weekly, nine hospital-based and face-to-face nutritional therapeutic education sessions targeting body weight control and feeding behaviors according to WCRF. Specific advice was given to patients for the management of chemotherapy toxicities and side-effects. Control: Usual care; no diet or exercise advice	Cancer-related fatigue
Demark-Wahnefried et al. 2008 (United States) [40]	3-Arm randomized controlled trial	Randomized N = 90	Women with stage I-IIIA breast cancer scheduled for adjuvant chemotherapy (any type)	Calcium-rich diet +/- exercise +/- high fruit and vegetable, low fat	Trial duration: 6 months All groups: 14 contacts of 10-30 minutes each, once weekly for the first month and semiweekly for 5 months Intervention 1 (calcium-rich diet + exercise): calcium-rich intervention + aerobic exercise ≥30 minutes per day, ≥3 times weekly and strength training exercises every other day. Intervention 2 (calcium-rich, low-fat, high fruit and vegetable diet + exercise): Intervention 1 + goals of <20% energy from fat, ≥5 servings fruit+vegetables. Control (calcium-rich diet only): Written and verbal instruction on a calcium-rich diet (1200-1500 mg calcium/day).	Body composition (preservation of lean mass)
Djuric et al. 2011 (United States) [41]	Randomized controlled trial	Randomized N = 40	Females age ≥18 y with stage I-IIIA breast cancer scheduled for or were within two weeks of starting chemotherapy (any type)	Nutrition counseling and exercise	Trial duration: 12 months Intervention: Written educational materials and telephone counseling from a registered dietitian to achieve a high fruit and vegetable and low-fat diet, based on an estimate of Total Energy Expenditure (TEE) Control: “My Pyramid” plan from the United States Department of Agriculture and brochures from the American Cancer Society	Feasibility
Jacot et al. 2020 (France) [42]	Randomized controlled trial	Randomized N = 360 Analyzed in a per-protocol analysis N = 321	Females ≥18 y with early-stage breast cancer, participants were enrolled after undergoing curative surgery and before 6 cycles of chemotherapy then 6 weeks of radiotherapy	Nutrition counseling and exercise	Trial duration: 26 weeks Intervention: The Adapted Physical Activity Diet (APAD2) program: twice weekly exercise sessions and six nutrition sessions, which targeted body weight control and adherence to the WCRF recommendations. Control: Usual care	Cancer-related fatigue
Kenkhuis et al. 2024 (Netherlands) [58]	Same as Brouwer et al. [57]					Body composition, physical functioning, and fatigue
Maurer et al. 2022 (Germany) [43]	Randomized controlled trial	Randomized N = 15 Analyzed N = 11	Females aged ≥18 y with ovarian cancer, tubal cancer or peritoneal cancer, scheduled for adjuvant or neoadjuvant chemotherapy (any type)	Nutrition counseling and exercise	Trial duration: 12 months Intervention: Personalized exercise and nutrition counselling tailored to different phases of patient’s treatment and recovery. The nutrition element included one-on-one sessions with a nutritionist every 3 weeks during chemotherapy with a focus on consuming adequate calories and protein. After chemotherapy, monthly nutrition counselling was focused on the Mediterranean diet. Control: Usual care	Feasibility (primary); secondary: quality of life, cancer-related fatigue, nutritional risk, physical activity, physical performance, body composition
Puklin et al. 2024 (United States) [56]	Randomized controlled trial	Randomized N = 173	Women with stage I-III breast cancer receiving chemotherapy	Nutrition counseling and exercise	Trial duration: Duration of chemotherapy (average 3.3±1.2 months, range 8-24 weeks) Intervention: Goals to meet guidelines according to the Healthy Eating Index-2015 [63] (≥5 fruits and/or vegetables/day, ≥25 g fiber/day, <30 g added sugar/day, ≤18 oz red meat/week, limited consumption of processed foods, ≤1 alcoholic drink/day) and Physical Activity Guidelines (≥150 min/week of moderate- to vigorous-intensity physical activity or 75 min/week of vigorous-intensity physical activity plus twice-weekly resistance training); a mean of 8±3 counseling sessions were offered Control: Usual care; access to a registered dietitian with referrals at the discretion of the treating oncologist	Physical activity and diet quality
Raghunath et al. 2020 (India) [44]	Randomized controlled trial	Randomized N = 120	Males and females 18–65 y with stage II and III adenocarcinoma of the colon and prescribed chemotherapy (8 cycles with oxaliplatin and capecitabine for 14 days then 3 weeks off)	Naturopathy, yoga, and dietary counseling	Trial duration: 18 months Intervention: The dietary intervention included a schedule of foods such as vegetable juice, idlis, korralu, dalia, and milk malt with buttermilk. Also, after the first cycle of chemotherapy, participants underwent a 7-day intensive phase of training in naturopathy and yoga. Control: Psycho-social counselling	Hematological, biochemical, immunological, and psychological variables
Sanft et al. 2023 (United States) [45]	Same as Puklin et al. [56]					Relative dose intensity (measure of chemotherapy completion)
Stelten et al. 2022 (Netherlands) [46]	Randomized controlled trial	Randomized N = 28	Females aged ≥18 y with primary epithelial ovarian cancer scheduled to undergo first-line neoadjuvant chemotherapy	Nutrition counseling and exercise	Trial duration: duration of chemotherapy plus follow-up 3 and 12 weeks after chemotherapy Intervention: The dietary component involved individually tailored diets delivered via face-to-face sessions once every three weeks to achieve/maintain good on nutritional status and dietary intake and to prevent weight loss, guided by the WCRF/AICR (≥1.2 g protein/kg body weight/day evenly distributed throughout meals). The exercise component included two one-hour moderate-to-high intensity resistance and aerobic exercise sessions per week by a physical therapist. Control: Usual care	Body composition, physical function, and fatigue; though only qualitative data are reported in this paper.
Nutrient-specific dietary patterns
Bille et al. 2018 (Denmark) [47] This manuscript also reports two pilot studies (n=5 each) to select meals for the cross-over study. Details from the pilot studies are not described here.	Randomized cross-over controlled trial	Enrolled N = 62	Adults with hematological cancer being treated with chemotherapy (any type)	High-energy density	Trial duration: 30-Day control period followed by a 30-day intervention period. Intervention: Four high-energy-density dishes with protein content of at least 5 g/100 g each eaten once each: chili con carne, chicken in curry, curry soup, and pasta carbonara. Control: Habitual diet	Acceptability of dishes, weight loss
Harvey et al. 2023 (United States) [6]	Same as Kleckner et al. [52]					Qualitative assessment of participants’ experiences
Gardner et al. 2008 (United States) [48]	Randomized controlled trial	Randomized N = 153	Males and females with acute myeloid leukemia receiving remission induction therapy	Neutropenic	Trial duration: length of stay, 24-25 days Intervention: A diet containing no raw fruits or vegetables, only cooked. Control: A diet containing fresh fruit and fresh vegetables with encouraged consumption of at least one/day, with the fruits and vegetables washed with cold water for 30 seconds before eaten.	Infection and death
IJmker-Hemink et al. 2021 (Netherlands) [49]	Randomized controlled trial	Randomized N = 20	Males and females aged ≥18 y with metastatic colorectal or gynecological malignancies starting with 3-weekly scheduled chemotherapy (any type)	Protein-rich home delivery	Intervention duration: 3 weeks (with follow up for 3 months) Intervention: Home-delivered meal service of six protein-rich dishes per day based on the FoodforCare meal service. The meal service provided a morning shake, two lunch meals, a snack, dinner, and dessert for each day (average energy 1553 kcal/day, average protein 60.8 g/day) for 3 weeks. Participants received a leaflet with nutritional advice on protein-rich foods and recommendations for 1.2 g protein/kg body weight/day. Control: Usual care	Quality of life
IJmker-Hemink et al. 2023 (Netherlands) [50]	Randomized controlled trial	Randomized N = 148	Males and females aged ≥18 y with cancer (any type) and receiving chemotherapy on a 2-, 3-, or 4-week cycle (any type)	Protein-rich home delivery	Same as IJmker-Hemink et al. [49]	Quality of life
Jalali et al. 2018 (Iran) [51]	Randomized controlled trial	Randomized N = 50	Males and females with acute myeloid leukemia undergoing chemotherapy	Mediterranean diet	Trial duration: 4 weeks Intervention: Mediterranean Diet with 47% carbohydrate, 15% protein, 38% fat (24% monounsaturated fatty acids mostly from olive oil) including 30 mL olive oil daily. Control: Neutropenic diet: cooked foods and vegetables, except for some raw fruits including banana and orange, boiled water, pasteurized dairy, well cooked meat and eggs -Both diets had a similar calorie count; the Mifflin formula was used to estimate energy needs.	Nutritional status
Kleckner et al. 2022 (United States) [52]	Randomized controlled trial	Randomized N = 33	Males and females aged ≥18 y with cancer (any type) with at least six weeks of chemotherapy remaining (any type)	Mediterranean diet	Trial duration: 8 weeks Intervention: Participants received 12 frozen meals/week delivered to their homes once/week for four weeks and other grocery store items, a custom Mediterranean cookbook, and information describing the MedDiet. Participants had weekly phone-based check-ins with the study team and a one-on-one counseling session with a nutrition scientist during week 3. Control: Usual care	Cancer-related fatigue
Sathiaraj et al. 2023 (India) [53]	Randomized controlled trial	Randomized N = 103	Females aged 18–65 years with nonmetastatic breast cancer and planned to have adjuvant chemotherapy (4 cycles of doxorubicin and cyclophosphamide or docetaxel and cyclophosphamide (1 cycle every 3 weeks)	Plant-based high-protein	Trial duration: Duration of chemotherapy (about 12 weeks) Intervention: A plant-based, high-protein diet (1.2 g protein/kg body weight/day; 25-30% kcal from fat, 55-60% carbohydrate, 10-15% protein) aimed at weight management; advised no meat, included eggs and low-fat dairy, ≥5 servings fruits and vegetables, whole grain and millet, discouraged high-calorie fried food, soda; whey protein supplement (84 kcal, 10 g protein) was given once daily. Participants received educational material and weekly sessions/reviews. Control: Usual care with access to on-demand nutrition appointments with the study team	Cancer-related fatigue (primary), body composition (secondary)
Villarini et al. 2012 (Italy) [54]	Randomized controlled trial	Randomized N = 96	Women of any age, operated for invasive, non-metastatic breast cancer, scheduled for adjuvant chemotherapy (any type)	Diet based on Mediterranean and macrobiotic recipes	Trial duration: Duration of chemotherapy Intervention: Cooking classes and common meals at least twice per week in addition to the recommendations and kitchen course given to the control group; dietary recommendations based on Mediterranean and macrobiotic recipes and on the avoidance of energy dense foods. Protein intake was reduced as meat and cheese consumption was discouraged. Control: Recommendations for the prevention of cancer and a baseline kitchen course on how to reduce gastrointestinal side effects of chemotherapy.	Body weight
Zhang et al. 2023 (China) [55]	Randomized controlled trial	Enrolled N = 106	Patients with lung cancer, body mass index 18.5-30 kg/m2, Brief Fatigue Inventory score of ≥4 points (range 0-10).	Anti-inflammatory diet	Trial duration: 3 months Intervention: The anti-inflammatory diet goals: 2 servings of fruit/day, 5 servings of vegetables/day, 3 servings whole grain cereals/day, ≥3 servings fish/week, 2 servings of nuts or seeds/day, 2 servings olive oil or linseed oil/day, 2 servings probiotic low-fat dairy products/day, ≤2 servings red meat/week, 5 servings white meat per week, encouragement of certain spices and tea, discouragement of refined and processed foods; nutrition education; twice/week phone calls or face-to-face consultations Control: Usual diet; 4 face-to-face visits for regular health education and recommendations based on dietary nutrition prescriptions for patients with cancer in China	Cancer-related fatigue

Abbreviations: AICR, American Institute for Cancer Research; ESPEN, European Society of Parenteral and Enteral Nutrition; mSTF, modified short-term fasting; WCRF, World Cancer Research Foundation; WHO, World Health Organization.

Table 1. Characteristics of the studies included in this systematic review.

Reference (country)	Study design	N =	Eligibility	Intervention Type	Intervention Details	Primary Outcome(s) (not including feasibility)
Nutrition counseling and/or food provision without exercise
Abdollahi et al. 2019 (Iran) [19]	Randomized controlled trial	Randomized N = 150	Female adults (≥18 y) with breast cancer who have received one session of chemotherapy (any type) and have a history of constipation or diarrhea after chemotherapy.	Nutrition counseling	Trial duration: 10-week trial Intervention: Face-to-face nutrition education consisting of a diet with 12–15% calories of protein, 30–35% of fat, and 55–60% of carbohydrates estimated individually based on participant's current age, weight, and height in addition to nutrition recommendations to reduce diarrhea and prevent reflux. Control: Control group had usual care without informational pamphlet, nutritional education and dietary intervention and they were asked not to change their usual diets.	Gastrointestinal side effects - nausea, vomiting, and diarrhea
Baldwin et al. 2011 (United Kingdom) [20]	Randomized controlled trial	Randomized N = 277	Adults with metastatic or locally advanced cancer of the gastrointestinal tract, lung, or mesothelioma; lost weight in the last 3 months; had agreed to undergo and were fit for palliative chemotherapy	Nutrition counseling	Trial duration: 6 weeks with a 52-week follow-up Intervention 1: Advice to increase food intake by 600 kcal (2510 kJ) per day with the intent to increase body weight; booklet contained 150-kcal ideas and were asked to select 4/day. Intervention 2: A 588-kcal (2460-kJ) sachet of nutritional supplement to be prepared in whole milk + a daily multivitamin Control: No dietary intervention	Survival
Bourdel-Marchasson et al. 2014 (France) [21]	Randomized controlled trial	Randomized N = 341	Patients older than 70 y with lymphoma or carcinoma with an indication of chemotherapy (any type); participants must be at risk of malnutrition with a full Mini Nutritional Assessment 17–23.5 points	Nutrition counseling	Trial duration: 3 to 6 months, each participant received 6 visits. Intervention: Aim of achieving an energy intake of 30 kCal/kg body weight/d and 1.2 g protein/kg/d by face-to-face discussion targeting the main nutritional symptoms, compared to usual care. Control: Usual nutritional care given in cancer treatment settings. There were no restrictions for dietary advice or oral supplements.	One-year survival
Cao et al. 2024 (China) [61]	Randomized controlled trial	Randomized N = 92	Adults (≥18 y) diagnosed with head and neck squamous cell carcinoma, planned to receive first round of chemotherapy, and planned to receive cisplatin-based chemotherapy	Nutrition counseling	Trial duration: 24 weeks Intervention: Nurse-led multidomain intervention of chemotherapy-induced nausea and vomiting (CINV) included nurse-led risk assessment, education on prevention and control of CINV, antiemetic treatments following guidelines, dietary strategies (based on the National Comprehensive Cancer Network), relaxation therapy, and follow up. Individualized dietary counseling was provided by the nurse tailored to patients’ specific needs. Control: Usual care of CINV consisting of administration of antiemetics, education about CINV control and dietary recommendations provided by primary nurses.	Incidence of CINV, severity of CINV, influence of CINV on patients’ quality of life
Dai et al. 2022 (China) [22]	Pilot randomized controlled trial	Randomized N = 72	Men and women age 18-75 y, head or neck cancer, concurrent chemoradiation therapy (nedaplatin)	Nutrition counseling	Trial duration: duration of the concurrent chemoradiation therapy Intervention: Face-to-face nutritional counseling at least once every 2 weeks during treatment to achieve calorie and protein requirements determined by the ESPEN guidelines on nutrition in cancer patients. Control: Nutrition treatment plans according to clinical experience.	Body weight
de Lima Bezerra et al. 2023 (Brazil) [23]	Randomized controlled trial	Randomized N = 34	Adult women with breast cancer, indicated for neoadjuvant chemotherapy (any type)	Nutrition counseling	Trial duration: 2 months Intervention: Personalized diet with an individually tailored meal plan based on ESPEN guidelines to address malnutrition [9] (25–30 kcal/kg body weight/day and 1.5 g protein/kg/day). Control: counseling on healthy eating and nutritional information on how to reduce the severity of chemotherapy-induced nausea and vomiting.	Chemotherapy toxicity
de Souza et al. 2021 (Brazil) [24]	Randomized controlled trial	Randomized N = 34	Female adults with breast cancer indicated for neoadjuvant chemotherapy (doxorubicin and cyclophosphamide)	Nutrition counseling	Trial duration: 3 cycles of chemotherapy (21 days/cycle) Intervention: A personalized diet meal plan formulated by dietitian based on age, current weight, and height of each subject, 25–30 kcal/kg/day of energy and 1.5 g/kg/day of protein, based on the ESPEN guidelines [9], including written materials on healthy eating and symptom management Control: Pamphlets with recommendations on healthy eating and to reduce chemotherapy-induced nausea and vomiting	Quality of life
Ford et al. 2024 (Canada) [62]	Randomized controlled pilot trial	Randomized N = 50	Adults (18-85 years) with stage II-IV colorectal cancer	Nutrition counseling	Trial duration: 12 weeks Intervention Groups: Weekly telephone nutrition education with patients to achieve 2.0 g protein/kg body weight/day and meal patterns consistent with those recommended by the Academy of Nutrition and Dietetics. Control: Weekly telephone nutrition education with patients to achieve a protein intake of 1.0 g/kg/day (standard of care). Both: Prescribed diets were translated into an individualized daily meal pattern based on typical dietary intake.	Muscle mass and physical function
Keum et al. 2021 (Korea) [25]	Randomized controlled trial	Randomized N = 40	Males or females aged 20–70 y with pancreatic ductal adenocarcinoma scheduled to receive chemotherapy (any type)	Nutrition counseling via a smartphone app	Trial duration: 12 weeks Intervention: Noom is a mobile app that offers a curriculum and human coaching. It was tailored to the population and included food logging, feedback-based food choices, daily articles for health, and coach-participant messaging with goals to encourage calorie intake and maintain nutritional status. Control: Usual care	Nutritional status and quality of life
Lin et al. 2017 (China) [26]	Randomized controlled trial	Randomized N = 110	Males and females aged ≥18 y with cancer (any type) and were undergoing chemotherapy (any type)	Nutrition counseling	Trial duration: 12 cycles of chemotherapy (duration in days not specified) Intervention: Individual recipes based on estimates of Total Energy Expenditure to achieve or maintain high nutritional status. Participants and their care takers were counseled by experienced nurses, and diets were adjusted as nutritional status changed throughout the intervention. Control: Usual care plus nutrition screening, nutritional guidance, diet mission, and arranged meal times.	Patient weight and serum albumin and prealbumin levels
Loprinzi et al. 1996 (United States) [27]	Randomized controlled trial	Randomized N = 109	Premenopausal women with resected localized breast cancer scheduled to receive adjuvant chemotherapy (any type)	Nutrition counseling	Trial duration: duration of chemotherapy, assessments at 3 and 6 months after initiation of chemotherapy Intervention: Counseling with a dietitian prior to or within 2 weeks of chemotherapy initiation and at 4-to 6-week intervals. Dietitian goals included maintaining on-study body weight or gradual weight reduction toward ideal body weight. Control: Standard care—information on the potential for weight gain and ways to prevent it.	Body weight
Najafi et al. 2019 (Iran) [28]	Same as Abdollahi et al. [19]	Randomized N = 150	Females aged 18–60 y with stage IA-IIIB breast being treated with 3-weekly cycles of doxorubicin, cyclophosphamide, and docetaxel and had experienced vomiting during or after the previous session(s) of chemotherapy	Nutrition counseling	Trial duration: duration of chemotherapy Intervention: Personalized diet and nutrition education before each chemotherapy session. The daily diet was estimated individually and contained 1.2–1.5 g/kg of protein, 30% of energy from fat, and 55–60% of energy from carbohydrate. Control: Usual care	Chemotherapy-induced nausea and vomiting
Ollenschläger et al. (Germany) 1992 [29]	Randomized controlled trial	Enrolled N = 32	Males and females age 17-60 years with acute lymphocytic or nonlymphocytic leukemia; had unintentional weight loss of >5% in the previous 3 months and/or actual body weight below 90% ideal body weight; planned cytostatic treatment	Nutrition counseling	Trial duration: Duration of therapy from induction therapy until planned or premature end of maintenance therapy (4-54 weeks); participants were hospitalized for some of their cancer treatment and some were on an out-patient basis. Intervention: “Intensified oral nutrition program”: ad libitum menu of 1.0-2.0 g protein and 30-50 kcal/kg body weight plus daily visit by a dietitian to assess nutritional status, nutritional behavior, nutrient requirements, symptoms, and well-being. Control: Free choice, ad libitum menu of 1.0-2.0 g protein and 30-50 kcal/kg body weight.	Quality of life
Ovesen et al. 1993 (Denmark) [30]	Randomized controlled trial	Enrolled N = 137	Males and females with small-cell lung cancer, ovarian cancer, or breast cancer	Nutrition counseling	Trial duration: 5 months Intervention: Counseling with a dietitian before chemotherapy and once-twice monthly and as needed; goals to meet the protein and calorie requirements of the Nordic Recommended Allowances (1.5-1.7 × basal energy expenditure as calculated by the Harris-Benedict Equation; 1.0-1.2 g protein/kg body weight) Control: Ad libitum diet Both groups: Advised to supplement diet with one multivitamin tablet that contained the daily recommended allowances of micronutrients	Body weight, quality of life
Regueme et al. 2021 (France) [31]	Same as Bourdel-Marchasson et al. [21]	Randomized N = 283				Health-related quality of life
Sukaraphat et al. 2016 (Thailand) [32]	Randomized controlled study	Enrolled N = 50	Adults (age ≥18 years) with locally advanced unresectable or metastatic cancer	Nutrition counseling	Trial duration: 9-12 weeks (3-4 cycles of chemotherapy) Intervention: Individualized and intensive dietary counseling based on the ESPEN guideline:[3] 30-35 kcal/kg body weight and 0.8-1.2 g protein/kg body weight per day with regular food, supplements used if required Control: Routine care: dietary counseling for general dietary recommendations from a nurse and physician but not a dietitian	Body weight
Tang et al. 2024 (China) [60]	Quasi-experimental study	Randomized N = 60	Adults (≥18 y) with nasopharyngeal carcinoma who have been diagnosed with malnutrition (weight loss ≥5%) and life expectancy of more than 3 months.	Nutrition counseling	Trial duration: 24 weeks Intervention: Face-to-face nutrition education with patients and their families consisting of a diet high in protein, high in calories, high in vitamins and rich in inorganic salts, in addition to nutrition recommendations to avoid dry mouth, oropharyngeal pain, and constipation consistent with guidelines. Control: Routine dietary guidance without nutrition assessment screening.	Nutritional Risk Screening 2002, BMI, and quality of life
van der Werf et al. 2020 (Netherlands) [33]	Randomized controlled trial	Randomized N = 107	Males and females aged >18 y diagnosed with metastatic colorectal cancer, scheduled for first-line chemotherapy with capecitabine and oxaliplatin (CAPOX), infusional 5- fluorouracil and oxaliplatin (FOLFOX) or capecitabine alone, with or without bevacizumab (-B)	Nutrition counseling	Trial duration: During chemotherapy (varied by participant based on regimen) Intervention: Face-to-face counseling (at every chemotherapy infusion) and telephone consultation (between infusions) by a dietitian with the goal of achieving sufficient protein, energy, and micronutrient intake. The protein intake goal was ≥1.2 g protein/kg body weight/day. The dietitian also encouraged moderate-intensity physical activity for ≥30 min per day, five days per week. Control: Access to a dietitian	Skeletal muscle area (primary), quality of life, physical functioning, treatment toxicity, treatment intensity, survival (secondary)
Wang et al. 2023 (China) [34]	Randomized control trial	Randomized N = 53	Males and females aged 50–80 years with esophageal cancer undergoing chemoradiotherapy (cisplatin + paclitaxel or cisplatin + 5-fluorouracil + radiation)	Nutrition counseling	Trial duration: duration of chemoradiotherapy (5-8 weeks) Intervention: individualized nutrition programs with target energy and protein intake (30–35 kcal/kg body weight/day and 1.2–1.5 g protein/kg/day). Nutritional evaluations were conducted by nutrition nurses each day, and nutritional interventions were adjusted based on needs. Control: Usual care	Nutritional status
White et al. 2020 (United Kingdom) [35]	Randomized control trial	Randomized N = 50	Males and females aged >18 y, have cervical or bladder cancer, undergoing chemotherapy and radical pelvic radiotherapy (weekly gemcitabine for bladder cancer or cisplatin for cervical cancer)	Nutrition counseling	Trial duration: not specified, 6-week, 12-week, and 12-month follow-up. Intervention: Individualized dietary counseling using the anthropometric data, patient-reported subjective, global assessment score, malnutrition universal screening tool score, dietician symptom assessment and 3-day food diary to tailor dietary advice and prescription of oral nutritional supplements where necessary. Control: not stated	Feasibility (primary), treatment toxicity (primary clinical outcome)
Xie et al. 2017 (China) [36]	Randomized control trial	Randomized N = 144	Males and females aged ≥18 y with gastric cancer undergoing post-operative chemotherapy (oxaliplatin and capecitabine every 21 days for up to 8 cycles)	Nutrition counseling	Trial duration: duration of chemotherapy Intervention: Intensive individualized nutritional and educational interventions during the entire course of chemotherapy Control: Education on chemotherapy, possible chemotherapy-induced adverse events, basic nutrition guidance, follow-up 2 days after infusion	Nutritional status
Nutrition counseling plus exercise
Allen et al. 2022 (United Kingdom) [37]	Pilot randomized controlled trial	Randomized N = 54	Adults with locally advanced esophagogastric cancer planned for neoadjuvant therapy (any type) plus esophagogastrectomy, or total gastrectomy.	Nutrition counseling and exercise	Trial duration: 15-week trial (preoperative) Intervention: Needs-based, frequent, and tailored to the patient by dietitians to increase total calories and protein where appropriate. This group also received a structured exercise program. Control: Control group got standard care and did not receive nutrition or exercise prehabilitation.	Cardiopulmonary exercise test performance, muscle mass and quality of life
Basen-Engquist et al. 2020 (United States) [38]	Pilot randomized controlled trial	Randomized N = 39	Patients with newly diagnosed stage II or III breast cancer patients within 3 weeks of starting neoadjuvant chemotherapy (any type)	Nutrition counseling and exercise	Trial duration: ~6 month trial (until the end of chemotherapy) Intervention: 20 individualized counseling sessions, 14 in-person and 6 by telephone. Promoted foods with low energy density and consistent with recommendations for survivors. Also, an exercise intervention focused on resistance and flexibility training to maintain or increase fat-free mass. Control: Control group received publicly available written materials on cancer survivorship.	Anthropometrics (to prevent weight gain), quality of life, serum biomarkers
Brouwer et al. 2024 (Netherlands) [57]	Randomized controlled trial	Randomized N = 81	Patients aged >18 years with primary epithelial ovarian cancer who were scheduled for (neo)-adjuvant chemotherapy treatment.	Nutrition counseling and exercise	Trial duration: From first or second chemotherapy cycle until 12 weeks after the last chemotherapy cycle Intervention: Two 1-h sessions per week, supervised by a physical therapist specialized in oncology, including moderate- to high-intensity resistance and aerobic exercise. Dietary counseling was delivered by dietitians specialized in oncology once every 3 weeks during 30–45 min face-to-face sessions in the hospital or by telephone tailored to the nutritional needs of each patient. All participants were advised to follow the dietary guidelines set by the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) and were advised to consume at least 1.2 g of protein/ kg body weight/day and at least 25 g of protein per meal. Control: Usual care during chemotherapy, which could include a referral to a dietitian when malnutrition was detected by the gynecological oncologist.	Relative dose intensity and progression-free survival
Carayol et al. 2019 (France) [39]	Randomized controlled trial	Randomized N = 143	Women aged 18–75 y; non-metastatic breast cancer; enrolled after curative surgery, planned for 6 cycles of adjuvant chemotherapy (epirubicin / cyclophosphamide / 5-fluorouracil for 3 cycles every 3 weeks, followed by docetaxel for 3 cycles every 3 weeks), followed by 6 weeks of radiotherapy	Nutrition counseling and exercise	Trial duration: 26 weeks Intervention: The Adapted Physical Activity and Diet (APAD) intervention consisted of exercise sessions planned thrice-weekly, nine hospital-based and face-to-face nutritional therapeutic education sessions targeting body weight control and feeding behaviors according to WCRF. Specific advice was given to patients for the management of chemotherapy toxicities and side-effects. Control: Usual care; no diet or exercise advice	Cancer-related fatigue
Demark-Wahnefried et al. 2008 (United States) [40]	3-Arm randomized controlled trial	Randomized N = 90	Women with stage I-IIIA breast cancer scheduled for adjuvant chemotherapy (any type)	Calcium-rich diet +/- exercise +/- high fruit and vegetable, low fat	Trial duration: 6 months All groups: 14 contacts of 10-30 minutes each, once weekly for the first month and semiweekly for 5 months Intervention 1 (calcium-rich diet + exercise): calcium-rich intervention + aerobic exercise ≥30 minutes per day, ≥3 times weekly and strength training exercises every other day. Intervention 2 (calcium-rich, low-fat, high fruit and vegetable diet + exercise): Intervention 1 + goals of <20% energy from fat, ≥5 servings fruit+vegetables. Control (calcium-rich diet only): Written and verbal instruction on a calcium-rich diet (1200-1500 mg calcium/day).	Body composition (preservation of lean mass)
Djuric et al. 2011 (United States) [41]	Randomized controlled trial	Randomized N = 40	Females age ≥18 y with stage I-IIIA breast cancer scheduled for or were within two weeks of starting chemotherapy (any type)	Nutrition counseling and exercise	Trial duration: 12 months Intervention: Written educational materials and telephone counseling from a registered dietitian to achieve a high fruit and vegetable and low-fat diet, based on an estimate of Total Energy Expenditure (TEE) Control: “My Pyramid” plan from the United States Department of Agriculture and brochures from the American Cancer Society	Feasibility
Jacot et al. 2020 (France) [42]	Randomized controlled trial	Randomized N = 360 Analyzed in a per-protocol analysis N = 321	Females ≥18 y with early-stage breast cancer, participants were enrolled after undergoing curative surgery and before 6 cycles of chemotherapy then 6 weeks of radiotherapy	Nutrition counseling and exercise	Trial duration: 26 weeks Intervention: The Adapted Physical Activity Diet (APAD2) program: twice weekly exercise sessions and six nutrition sessions, which targeted body weight control and adherence to the WCRF recommendations. Control: Usual care	Cancer-related fatigue
Kenkhuis et al. 2024 (Netherlands) [58]	Same as Brouwer et al. [57]					Body composition, physical functioning, and fatigue
Maurer et al. 2022 (Germany) [43]	Randomized controlled trial	Randomized N = 15 Analyzed N = 11	Females aged ≥18 y with ovarian cancer, tubal cancer or peritoneal cancer, scheduled for adjuvant or neoadjuvant chemotherapy (any type)	Nutrition counseling and exercise	Trial duration: 12 months Intervention: Personalized exercise and nutrition counselling tailored to different phases of patient’s treatment and recovery. The nutrition element included one-on-one sessions with a nutritionist every 3 weeks during chemotherapy with a focus on consuming adequate calories and protein. After chemotherapy, monthly nutrition counselling was focused on the Mediterranean diet. Control: Usual care	Feasibility (primary); secondary: quality of life, cancer-related fatigue, nutritional risk, physical activity, physical performance, body composition
Puklin et al. 2024 (United States) [56]	Randomized controlled trial	Randomized N = 173	Women with stage I-III breast cancer receiving chemotherapy	Nutrition counseling and exercise	Trial duration: Duration of chemotherapy (average 3.3±1.2 months, range 8-24 weeks) Intervention: Goals to meet guidelines according to the Healthy Eating Index-2015 [63] (≥5 fruits and/or vegetables/day, ≥25 g fiber/day, <30 g added sugar/day, ≤18 oz red meat/week, limited consumption of processed foods, ≤1 alcoholic drink/day) and Physical Activity Guidelines (≥150 min/week of moderate- to vigorous-intensity physical activity or 75 min/week of vigorous-intensity physical activity plus twice-weekly resistance training); a mean of 8±3 counseling sessions were offered Control: Usual care; access to a registered dietitian with referrals at the discretion of the treating oncologist	Physical activity and diet quality
Raghunath et al. 2020 (India) [44]	Randomized controlled trial	Randomized N = 120	Males and females 18–65 y with stage II and III adenocarcinoma of the colon and prescribed chemotherapy (8 cycles with oxaliplatin and capecitabine for 14 days then 3 weeks off)	Naturopathy, yoga, and dietary counseling	Trial duration: 18 months Intervention: The dietary intervention included a schedule of foods such as vegetable juice, idlis, korralu, dalia, and milk malt with buttermilk. Also, after the first cycle of chemotherapy, participants underwent a 7-day intensive phase of training in naturopathy and yoga. Control: Psycho-social counselling	Hematological, biochemical, immunological, and psychological variables
Sanft et al. 2023 (United States) [45]	Same as Puklin et al. [56]					Relative dose intensity (measure of chemotherapy completion)
Stelten et al. 2022 (Netherlands) [46]	Randomized controlled trial	Randomized N = 28	Females aged ≥18 y with primary epithelial ovarian cancer scheduled to undergo first-line neoadjuvant chemotherapy	Nutrition counseling and exercise	Trial duration: duration of chemotherapy plus follow-up 3 and 12 weeks after chemotherapy Intervention: The dietary component involved individually tailored diets delivered via face-to-face sessions once every three weeks to achieve/maintain good on nutritional status and dietary intake and to prevent weight loss, guided by the WCRF/AICR (≥1.2 g protein/kg body weight/day evenly distributed throughout meals). The exercise component included two one-hour moderate-to-high intensity resistance and aerobic exercise sessions per week by a physical therapist. Control: Usual care	Body composition, physical function, and fatigue; though only qualitative data are reported in this paper.
Nutrient-specific dietary patterns
Bille et al. 2018 (Denmark) [47] This manuscript also reports two pilot studies (n=5 each) to select meals for the cross-over study. Details from the pilot studies are not described here.	Randomized cross-over controlled trial	Enrolled N = 62	Adults with hematological cancer being treated with chemotherapy (any type)	High-energy density	Trial duration: 30-Day control period followed by a 30-day intervention period. Intervention: Four high-energy-density dishes with protein content of at least 5 g/100 g each eaten once each: chili con carne, chicken in curry, curry soup, and pasta carbonara. Control: Habitual diet	Acceptability of dishes, weight loss
Harvey et al. 2023 (United States) [6]	Same as Kleckner et al. [52]					Qualitative assessment of participants’ experiences
Gardner et al. 2008 (United States) [48]	Randomized controlled trial	Randomized N = 153	Males and females with acute myeloid leukemia receiving remission induction therapy	Neutropenic	Trial duration: length of stay, 24-25 days Intervention: A diet containing no raw fruits or vegetables, only cooked. Control: A diet containing fresh fruit and fresh vegetables with encouraged consumption of at least one/day, with the fruits and vegetables washed with cold water for 30 seconds before eaten.	Infection and death
IJmker-Hemink et al. 2021 (Netherlands) [49]	Randomized controlled trial	Randomized N = 20	Males and females aged ≥18 y with metastatic colorectal or gynecological malignancies starting with 3-weekly scheduled chemotherapy (any type)	Protein-rich home delivery	Intervention duration: 3 weeks (with follow up for 3 months) Intervention: Home-delivered meal service of six protein-rich dishes per day based on the FoodforCare meal service. The meal service provided a morning shake, two lunch meals, a snack, dinner, and dessert for each day (average energy 1553 kcal/day, average protein 60.8 g/day) for 3 weeks. Participants received a leaflet with nutritional advice on protein-rich foods and recommendations for 1.2 g protein/kg body weight/day. Control: Usual care	Quality of life
IJmker-Hemink et al. 2023 (Netherlands) [50]	Randomized controlled trial	Randomized N = 148	Males and females aged ≥18 y with cancer (any type) and receiving chemotherapy on a 2-, 3-, or 4-week cycle (any type)	Protein-rich home delivery	Same as IJmker-Hemink et al. [49]	Quality of life
Jalali et al. 2018 (Iran) [51]	Randomized controlled trial	Randomized N = 50	Males and females with acute myeloid leukemia undergoing chemotherapy	Mediterranean diet	Trial duration: 4 weeks Intervention: Mediterranean Diet with 47% carbohydrate, 15% protein, 38% fat (24% monounsaturated fatty acids mostly from olive oil) including 30 mL olive oil daily. Control: Neutropenic diet: cooked foods and vegetables, except for some raw fruits including banana and orange, boiled water, pasteurized dairy, well cooked meat and eggs -Both diets had a similar calorie count; the Mifflin formula was used to estimate energy needs.	Nutritional status
Kleckner et al. 2022 (United States) [52]	Randomized controlled trial	Randomized N = 33	Males and females aged ≥18 y with cancer (any type) with at least six weeks of chemotherapy remaining (any type)	Mediterranean diet	Trial duration: 8 weeks Intervention: Participants received 12 frozen meals/week delivered to their homes once/week for four weeks and other grocery store items, a custom Mediterranean cookbook, and information describing the MedDiet. Participants had weekly phone-based check-ins with the study team and a one-on-one counseling session with a nutrition scientist during week 3. Control: Usual care	Cancer-related fatigue
Sathiaraj et al. 2023 (India) [53]	Randomized controlled trial	Randomized N = 103	Females aged 18–65 years with nonmetastatic breast cancer and planned to have adjuvant chemotherapy (4 cycles of doxorubicin and cyclophosphamide or docetaxel and cyclophosphamide (1 cycle every 3 weeks)	Plant-based high-protein	Trial duration: Duration of chemotherapy (about 12 weeks) Intervention: A plant-based, high-protein diet (1.2 g protein/kg body weight/day; 25-30% kcal from fat, 55-60% carbohydrate, 10-15% protein) aimed at weight management; advised no meat, included eggs and low-fat dairy, ≥5 servings fruits and vegetables, whole grain and millet, discouraged high-calorie fried food, soda; whey protein supplement (84 kcal, 10 g protein) was given once daily. Participants received educational material and weekly sessions/reviews. Control: Usual care with access to on-demand nutrition appointments with the study team	Cancer-related fatigue (primary), body composition (secondary)
Villarini et al. 2012 (Italy) [54]	Randomized controlled trial	Randomized N = 96	Women of any age, operated for invasive, non-metastatic breast cancer, scheduled for adjuvant chemotherapy (any type)	Diet based on Mediterranean and macrobiotic recipes	Trial duration: Duration of chemotherapy Intervention: Cooking classes and common meals at least twice per week in addition to the recommendations and kitchen course given to the control group; dietary recommendations based on Mediterranean and macrobiotic recipes and on the avoidance of energy dense foods. Protein intake was reduced as meat and cheese consumption was discouraged. Control: Recommendations for the prevention of cancer and a baseline kitchen course on how to reduce gastrointestinal side effects of chemotherapy.	Body weight
Zhang et al. 2023 (China) [55]	Randomized controlled trial	Enrolled N = 106	Patients with lung cancer, body mass index 18.5-30 kg/m2, Brief Fatigue Inventory score of ≥4 points (range 0-10).	Anti-inflammatory diet	Trial duration: 3 months Intervention: The anti-inflammatory diet goals: 2 servings of fruit/day, 5 servings of vegetables/day, 3 servings whole grain cereals/day, ≥3 servings fish/week, 2 servings of nuts or seeds/day, 2 servings olive oil or linseed oil/day, 2 servings probiotic low-fat dairy products/day, ≤2 servings red meat/week, 5 servings white meat per week, encouragement of certain spices and tea, discouragement of refined and processed foods; nutrition education; twice/week phone calls or face-to-face consultations Control: Usual diet; 4 face-to-face visits for regular health education and recommendations based on dietary nutrition prescriptions for patients with cancer in China	Cancer-related fatigue

Abbreviations: AICR, American Institute for Cancer Research; ESPEN, European Society of Parenteral and Enteral Nutrition; mSTF, modified short-term fasting; WCRF, World Cancer Research Foundation; WHO, World Health Organization.

3.4. Feasibility

There was not a standard manner in which studies reported feasibility. For example, some studies measured the percentage of counseling sessions attended (e.g., Bourdel-Marchasson et al. [21]), the number of participants who provided data at all time points (e.g., Keum et al. [25]), number of servings/amount of nutrients consumed from food logs (e.g., Ovesen et al. [30], Gardner et al. [48]), score on a diet composition-related questionnaire (e.g., Kleckner et al. [52]), or serum-based biomarkers (e.g., carotenoids, Djuric et al. [41]). Nutritional counseling resulted in high adherence among the 39 interventions in regard to number of sessions attended and/or compliance with goals, depending on what was reported (Table 2). Retention in the nutritional counseling trials was the lowest for one program with energy and protein goals among patients with esophageal cancer undergoing chemoradiotherapy [34] (67.9%); all others had ≥80% [22,24,25,30,62] or 90% retention [19,20,21,23,26,27,29,32,33,35,36,60,61]. Interventions incorporating exercise in addition to nutritional counseling reported slightly less adherence than nutritional counseling alone and adherence to the exercise components were lower than dietary counseling sessions. Retention for these studies was 70–<80% for 4 studies [38,41,43,58], 80-<90% for 2 studies [42,46], and ≥90% for 6 studies [37,39,40,44,45,55]. Interventions that included counseling sessions [38,40,45,46] reported high attendance (≥80% [38,45,46,58]). In regard to adhering to dietary recommendations, all [19,21,22,28,29,30,31,32,36,40,41,43,45,55,56,61,62] but one [58] of the 18 studies that reported these data demonstrated that participants changed their diets in the direction of the recommendations even if total adherence was not achieved; Kenkhuis et al. [58] was an nutrition and exercise intervention and they noted no within-group or between-group changes in diet quality. Interventions tended to lead to higher calorie and/or protein intake compared to the control group, consistent with goals [21,22,30,32,36,43,50,62], or a decreased energy intake, consistent with goals [29]. Participants also increased fruit and vegetable intake in some [40,41,45,55] but not all [56] studies over time in the intervention group, consistent with recommendations, compared to the control group. Those that tested a Mediterranean diet during treatment saw a within-group increase in Mediterranean Diet Adherence Score or similar measure in the intervention arm and not the control arm [43,52,54].

The trials that tested dietary patterns had high feasibility on average. Retention was >90% in six [48,50,51,52,53,54] of eight [47,48,49,50,51,52,53,54] trials, though in Bille et al. [47] there was a high number of dropouts between consent and initiation of the study; retention was 100% for participants who began the intervention. Studies that utilized a home delivery service to facilitate adherence reported that food provision was indeed a facilitator to adherence [6,49]; in IJmker-Hemink et al. [49] participants reported a median burden level of 2 on a scale from 0 to 10 [49].

3.5. Safety

Adverse events were reported in most studies, but events were primarily attributed to the chemotherapy treatment rather than the intervention itself (Table 2). Nutritional counseling interventions appeared safe, with some studies indicating a lower incidence of chemotherapy-related side effects in the intervention group compared to the control [19,23,24,28,57,64]. Most studies reported no significant differences in side effects between intervention and control groups.

3.6. Primary Health Outcomes Assessed

The primary outcomes of the nutritional intervention clinical trials included feasibility as well as clinical and supportive care outcomes (Table 1). As many of these studies were Phase I or proof-of-concept studies, many declared the primary outcome measure to be feasibility (n=7) [35,38,40,43,52,59,62]; Puklin et al. [56] specifically described changes in physical activity and diet quality attributable to the intervention. Common primary supportive care outcomes (or primary purpose of the manuscript) included quality of life (n=10) [24,25,29,30,31,33,37,38,49,50], body mass and composition (n=15) [22,26,27,30,32,36,38,40,43,46,47,54,58,62], cancer-related fatigue (n=5) [39,42,52,53,55], and nutritional status (n=5) [25,34,36,51,60]. The following primary outcomes were reported by a single study each: clinically relevant decrease in skeletal muscle area [33], anaerobic threshold measured by cardiopulmonary exercise testing (CPET) [37], chemotherapy-induced nausea and vomiting (CINV) [28], gastrointestinal side effects [19], infection [48], one-year survival [21], mortality [20], and relative dose intensity [45].

3.7. Efficacy

The most common clinical outcomes were body weight/body mass index (BMI), nutritional status, quality of life, cancer-related fatigue, chemotherapy toxicity, and chemotherapy responses/survival. These outcomes are summarized here.

3.7.1. Body Weight or Body Composition

Body weight and/or BMI was reported by 25 studies [20,22,23,25,26,27,29,30,32,33,36,38,39,40,41,42,45,47,48,51,52,53,54,58,60]. Nine studies saw no between-group differences in changes in body weight/BMI [20,23,30,32,38,42,45,48,52]. Body weight was higher in the intervention vs. control group for nine studies (weight gain or attenuation in weight loss), consistent with goals [22,25,26,27,33,36,51,58,60] (for the LAM-6 remission induction chemotherapy regimen only in Ollenschläger et al. [29] and for the intervention vs. control periods for Bille et al. [47]). There were four trials that aimed to reduce body weight, specifically fat mass, during chemotherapy and all showed a significant between-group reduction in weight [39,41,53,54]. Demark-Wahnefried et al. [40] noted no significant lean body mass losses in any group over time and no between-group differences except the diet plus exercise arm had a decrease in waist circumference over time. Ford et al. [62] did not report body weight but observed that a greater protein intake was associated with increased muscle mass (as measured using appendicular lean soft tissue index).

3.7.2. Nutritional Status

Nutritional status was measured in nine studies [22,25,26,32,34,36,51,55,60]. Studies monitored nutrition status using albumin levels [22,26,34,36,51,55] the Patient-Generated Subjective Global Assessment (PG-SGA) [25,32,55], and/or the Nutritional Risk Score [60]. Higher nutritional indexes were seen in the intervention vs. control group in eight [22,26,32,34,36,51,55,60] of nine [22,25,26,32,34,36,51,55,60] studies; Keum et al. [25] reported no between-group differences, but observed that participants who used the Noom smartphone application experienced greater improvements in nutritional status.

3.7.3. Quality of Life

Quality of life was measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 [65], a Functional Assessment of Chronic Illness Therapy (FACIT) questionnaire [20,40,41,52], the 36-item Short Form Survey [60] a single-item question [29], the Concise Quality of Life Index [30], the Thai-Modified Function Living Index Cancer Questionnaire [32], the 5-level EuroQual (EQ-5D-5L) questionnaire [35], or the Functional Living Index-Emesis [61] (Table 2). Ten [20,24,25,29,30,31,33,35,60,61] of 11 [20,24,25,29,30,31,33,35,60,61] nutritional counseling studies without added exercise saw no differences between group for quality of life; Najafi et al. [28] reported higher quality of life in the intervention group, though both groups had stable scores over time; Sukaraphat et al. [32] reported greater quality of life in the intervention vs. the control group post-intervention. The exercise plus nutrition interventions were associated with higher quality of life vs. the control group for six [37,38,39,41,43,55] of nine [37,38,39,40,41,42,43,55,58] studies. Both the high protein [50] and the Mediterranean diet [52] interventions led to greater quality of life vs. the control, but the difference did not reach statistical significance.

3.7.4. Cancer-Related Fatigue

Cancer-related fatigue was measured in eight studies [28,39,42,43,52,53,55,58]. These trials used the EORTC QLQ-C30 fatigue scale [28], Multidimensional Fatigue Inventory [39,42,43,58], the Chinese version of the Brief Fatigue Inventory [55], the FACIT-F fatigue subscale [52], or the Fatigue Symptom Inventory [53]. Improvements in fatigue were observed in the intervention vs. control group for six studies [28,39,43,52,53,55] and were similar between groups in two studies of nutrition plus exercise [42,58].

3.7.5. Chemotherapy Tolerance

Eleven studies [21,23,26,32,35,36,37,39,45,53,57] reported tolerability to chemotherapy by means of relative dose intensity or chemotherapy completion rate [35,37,39,45,53,57], chemotherapy interruptions or postponements [21,26,32,36], or dose-limiting toxicities [23]. Despite the broad range of nutritional interventions, there were between-group differences favoring the intervention group or intervention period for six of the studies [23,26,32,35,36,37]; there were no between-group differences for five studies [21,39,45,53,57].

3.7.6. Response to Chemotherapy

Tumor response and/or survival were reported by 13 publications [20,21,23,25,30,32,33,34,37,44,45,48,57]. These outcomes included tumor size or response to treatment [25,30,32,44,45,48], remission status [34,57], and survival or mortality statistics [20,21,23,25,33,37,57]. Between-group differences favoring the intervention group were seen in three studies—one encouraging adequate protein, calories, and micronutrients according to Dutch recommendations [33], one encouraging macronutrients and American food group recommendations [45], and one testing and naturopathy, yoga, and a specific provided Indian diet [44]— with no between-group differences in 10 studies [20,21,23,25,30,32,34,37,48,57]. Keum et al. [25] observed a greater tumor response rate for “above average” Noom smartphone application users vs. non-Noom users.

3.7.7. Other Outcomes

Several other outcomes were not commonly reported but were noteworthy. Abdollahi et al. [19], de Lima Bezzera et al. [23], and White et al. [35] targeted gastrointestinal side effects such as nausea, vomiting, and diarrhea and notable improvements were observed for the nutritional counseling intervention vs. control group. Cao et al. [61] performed a nurse-led multidomain intervention among patients with head and neck cancers and saw significant reduction in the incidence of nausea and rate of vomiting attributable to the intervention. The neutropenic diet intervention, which assessed infection and mortality rates, revealed that the diet did not prevent major infections or death [48].

4. Discussion

The aim of this systematic review was to evaluate the safety, feasibility, and preliminary efficacy of dietary interventions on health outcomes in patients undergoing active chemotherapy treatment for cancer. The results suggest individualized nutritional counseling to meet current nutrition guidelines and/or mitigate chemotherapy-induced side effects can improve patient outcomes while being safe and feasible alone or when combined with exercise interventions. In addition, more specific dietary patterns including an Indian naturopathy dietary pattern [44], Mediterranean Diet [51], and a plant-based high-protein diet [53] were feasible [52]. Nutritional counseling and dietary pattern interventions tended to be effective for managing body weight during treatment, whether it was to (a) increase body weight or attenuate weight loss or (b) minimize increases in fat mass (Table 2). Nutritional counseling interventions consistently improved nutritional status and nutritional indexes. In regard to quality of life, interventions were more effective if exercise was combined with nutrition counseling. Three-quarters (6/8) of nutritional counseling or specific dietary patterns improved cancer-related fatigue. In regard to clinical outcomes, there were between-group differences favoring the intervention group or intervention period for approximately half (6/11) of the studies assessing tolerance to chemotherapy over a broad range of nutritional interventions, and 3/13 interventions favored the intervention group in regard to tumor response and/or survival metrics, with the others showing no between-group differences. None of these trials were Phase III definitive trials, and most of these efficacy measures were not primary outcomes, though these data provide support for future trials testing nutritional interventions during chemotherapy treatment.

The Academy of Nutrition and Dietetics [66], the European Society of Enteral and Parenteral Nutrition (ESPEN) [3,9], and the American Cancer Society [7] publish nutrition guidelines for patients with cancer undergoing chemotherapy, with less formal guidelines for the geriatric oncology population [67,68]. These guidelines aim to detect, treat, and prevent malnutrition, specifically with 25-30 kcal/kg body weight/day and 1.0-1.5 g protein/kg body weight/day with micronutrient needs in accordance with the Recommended Dietary Allowance (RDA) for age [3,7,9]. The Mediterranean diet, a high-protein plant-based diet, and an anti-inflammatory diet support these guidelines and can be tailored to a patient’s preferences (e.g., flavors, protein choices), circumstances (e.g., socioeconomic status, social patterns), and clinical needs. The wide range of energy and protein recommendations among our included studies (e.g., 0.8-1.2 g protein/kg body weight in Sukaraphat et al. [32] and 2.0 g/kg in Ford et al. [62]) may have resulted in the differences in efficacy for some of the reported outcomes such as changes in body weight.

A total of 28 trials tested individualized nutrition counseling programs to promote adherence to established guidelines while mitigating treatment-related side effects and toxicities (Table 1). These studies imply that, despite the existence of general guidelines, directed, personalized education, interpretation, and/or implementation is needed by a dietitian to achieve adherence. This is likely because patients have diverse nutrition needs based on cancer type, pre-treatment body composition, menopausal status, barriers to consuming food, etc. For example, cancers such as head and neck and colorectal cancers more directly interfere with the ability to consume and absorb nutrients; these patients may require modified texture or food types. Some types of cancers are associated with weight gain (e.g., breast cancer) [69] and some are associated with weight loss (e.g., pancreatic cancer), and therefore dietitians may have different priorities for energy needs [3,9]. Furthermore, different symptom profiles such as nausea, mucositis, and diarrhea require individualized nutrition strategies to meet nutrient goals. As nutrition recommendations become more specific, interventions may become contraindicated or require modifications.

This systematic review highlights gaps in the literature. Nutrition in oncology as a field is beginning to move beyond macronutrient recommendations to more specific nutrient recommendations and dietary patterns. More research into the Mediterranean diet [51,52,54], plant-based high-protein diets [53], anti-inflammatory diets [55], and other diets can further guide individualized, structured programs for patients. Overweight status is highly prevalent at large as well as in the oncology population [70]. Studies specifically examining relationships between BMI at presentation and controlled weight change through treatment are needed. In addition, approximately half of patients with cancer are older adults, some who have different metabolic profiles (e.g., decreased anabolic response to protein) and goals of treatment (e.g., minimize dose reductions, maintain independence [71]); nutrition interventions should be tested specifically in older adults with relevant physical and functional outcomes [67]. More research should explore integration of digital platforms to support dietary monitoring and adherence (as the smartphone app in Keum et al. [25] and a web-based program in Chan et al. [72] recruiting men undergoing chemotherapy or radiation). Ketogenic diets and intermittent fasting regiments were beyond the scope of this review, but are an active area of research, mostly as a short-term intervention to improve clinical outcomes [12,73,74,75]. While whole-food plant-based diet tends to meet society guidelines for optimizing nutrition and reducing future chronic disease risk, only a few studies have begun to rigorously test the effects (e.g., Campbell et al. [76]).

There is a plethora of mechanisms by which nutritional interventions can improve outcomes, many of which are active areas of research. First, nutritional counseling and many dietary patterns confer biological and metabolic benefits such as correcting nutritional deficiencies [25,32,55], reducing chronic inflammation [34,55], improving mitochondrial energy metabolism [52], and combating oxidative stress [77]. Indeed, switching from a Western diet to a healthy diet after colorectal cancer initiation improved colon health and symptoms in a mouse model [78]. Future research should look into the ability of dietary interventions during chemotherapy to improve the health of the gut microbiome [79] and regulate circadian rhythms [11]. Second, nutritional interventions can confer psychological benefits including increases in self-efficacy and mood [80], as well as expectancy effects [81]. Third, dietary interventions can result in social benefits by bringing people together, whether it is with friends, family, the clinical care team, or peers in support groups [82,83].

Sex differences in cancer involve variations in the incidence, survival rates, and treatment response between males and females across various cancer types [84,85]. Research suggests that genetic, hormonal, and biological factors contribute to these differences [86]. Sex introduces variations in dietary outcomes attributed to metabolic differences as seen in animal studies [87], as well as organ-specific and hormone-related cancers. We noted a scarcity of research that systematically investigates how these interventions affect males and females differently. Understanding how dietary changes influence cancer outcomes in a sex-specific manner could have profound implications for lifestyle behaviors, treatment strategies, and cancer survivorship.

This work has important clinical implications. There is now clear evidence that individual dietary counseling to meet calorie and protein recommendations can mitigate side effects, maintain weight/fat-free mass, maximize tolerated dose, prevent treatment delays, mitigate reductions in performance status, and improve quality of life during treatment (Table 2) [3,7]. While ensuring that minimum protein and calorie needs are being met should remain the first priority to prevent malnutrition [3,7,9,66], many patients may be in a position to adopt more detailed dietary patterns in regard to macro- and micronutrients, food groups, and nutrient timing. Unfortunately, many cancer treatment centers have inadequate availability of licensed nutrition practitioners [88,89,90]. A clinical workflow that includes dietitians in outpatient cancer care for all patients undergoing chemotherapy, with tools to self-promote adherence, is needed to improve implementation of guidelines and leverage the benefits of optimizing nutrition throughout cancer care.

This review has both strengths and limitations. First, we compiled all interventions conducted during chemotherapy treatment, gathering an all-encompassing understanding of the current state of nutritional interventions in this population. The risk of bias for these studies tended to be low (Suppl. Figure 1), with potential risks being not preregistering the study (especially for older studies), and incomplete description of the randomization process. One limitation of this systematic review is that the interventions, control groups, and outcomes (types and methods of measuring them) exhibited considerable heterogeneity, precluding the ability to conduct a useful meta-analysis. Meta-analyses are instrumental in generating a composite effect size for an intervention in comparison to a control group [17]. However, given the diverse nature of the studies included in this review, combining the data in a meta-analysis would not yield meaningful insights for guiding further intervention development or informing clinical implementation. Second, adherence to interventions was not standardized, and therefore it was not possible to quantitatively assess the relative feasibility of interventions. However, we were able to qualitatively assess feasibility. Third, each cancer type, stage, and process has wildly different implications for baseline patient characteristics and needs, and there are different side effects of the disease process itself. Dietitians individualize recommendations based on these factors in addition to chemotherapy-related side effects and needs. Due to the limited number of studies that tested the same intervention within the same populations, we are not yet at the point where we can make more specific recommendations based on disease type, age, sex, etc. Fourth, our review did not include studies testing oral nutritional supplements, which are common and efficacious for many patients [91]. Finally, some publications that tested nutritional interventions during cancer treatment were not eligible for our review because they recruited patients undergoing chemotherapy or radiation treatment (e.g., Movahed et al. [92], Chan et al. [72]). However, by excluding these we are able to report results for only patients undergoing active chemotherapy.

5. Conclusions

In conclusion, this systematic review shows that dietary interventions that include or go beyond current nutritional guidelines during chemotherapy treatment tend to be feasible, safe, and effective for a multitude of clinical and supportive care outcomes. Further, more definitive research is necessary to establish an evidence base that is strong enough for inclusion in guidelines and incorporation into the clinical infrastructure to improve the outcomes for patients undergoing chemotherapy.