The Effect of a Ketogenic Diet on Cancer: Evidence From Systematic Reviews and Meta-Analyzes

Abstract

Background:

Emerging evidence suggests that the ketogenic diet (KD) may support cancer treatment by improving metabolic parameters and reducing treatment-related side effects. This review aimed to synthesize evidence from systematic reviews and meta-analyses on the effects of ketogenic diets in cancer, focusing on metabolic outcomes, body composition, quality of life, and tumor progression. Treatment-related complications were considered as exploratory outcomes.

Methods:

A comprehensive review of meta-analyses were conducted following PRISMA guidelines. Databases including PubMed, Scopus, and Web of Science were searched for systematic reviews and meta-analyses exploring the effects of KD on cancer and treatment side effects. After screening 615 articles, 24 eligible reviews were examined to explore the effects of ketogenic diets on metabolism, quality of life, body composition, and cancer progression.

Results:

KD improved metabolic markers such as glucose and triglycerides, and showed benefits in body composition and quality of life. Evidence on treatment-related complications, including radiotherapy side effects, was limited and heterogeneous.

Conclusions:

KD shows promise as a safe and effective adjunctive therapy in cancer management. More evidence is needed to draw firm conclusions.

Introduction

Cancer is the second leading cause of death from non-communicable diseases in the world. Globally, more than 20 million new cancer cases were diagnosed in 2022, and over 9.7 million people died from the disease. Despite this burden, access to treatment has expanded substantially, with millions of patients now receiving chemotherapy, radiotherapy, surgery, or targeted therapies; However, notable differences in care continue across regions. ¹ This continuing rise in incidence and mortality highlights the urgent need for coordinated global strategies to reduce the cancer burden and to ensure equitable access to effective treatments across populations. ²

Standard cancer treatments such as chemotherapy, radiotherapy, and surgery remain the cornerstone of care worldwide. ³ However, these modalities are frequently associated with adverse effects including fatigue, nausea, gastrointestinal disturbances, and treatment-induced malnutrition, which can strongly affect patients’ quality of life (QoL) and limit adherence to therapy. ⁴ Optimal nutritional support plays a critical role in enhancing treatment tolerance, mitigating adverse effects such as fatigue, nausea, and malnutrition, and ultimately improving the overall QoL and clinical outcomes in cancer patients. ⁵

The ketogenic diet (KD) is a low-carb, high-fat diet that has been associated with various health benefits. KD encompass various forms, including classical KD, modified Atkins, and low glycemic index therapies, all of which typically consist of 70% to 80% fat, 10% to 20% protein, and 5% to 10% carbohydrates. KD involves consuming a very low amount of carbohydrates and replacing them with fat, which puts the body into a metabolic state called ketosis. ⁶ This diet is reported to be effective for weight loss and may also have benefits against diabetes, epilepsy, Alzheimer’s disease, and cancer.^{7 -11}

Several studies have examined the effect of a KD on the body composition of patients with cancer. For example, the KETOCOMP study, a controlled trial conducted to study the impact of a KD on breast patients with cancer undergoing RT, found that a KD during RT may improve body composition. ¹² Also, another study on head and neck cancer patients confirmed that a KD has a positive impact on body composition. ¹³

Studies investigating the effects of a ketogenic diet in patients with cancer are valuable, as they may provide important evidence regarding its potential therapeutic benefits and impact on treatment outcomes. However, conflicting results have been reported regarding the impact of KD on the health outcomes of patient with cancer. The aim of this review was to evaluate the effects of ketogenic diets on cancer-related outcomes, including metabolic indices, body composition, QoL, and tumor progression. Treatment complications were explored when reported.

Methods

Study Selection and Search Strategy

This review was conducted in accordance with PRISMA guidelines to ensure methodological transparency and rigor. A comprehensive literature search was performed across 3 major databases including Web of Science, Scopus, and PubMed to cover publications up to April 2025. Predefined outcomes included body composition, QoL, metabolic indices, and tumor progression. Treatment-related complications (eg, fatigue, gastrointestinal symptoms, radiotherapy toxicity) were considered secondary outcomes when available. A total of 615 records were retrieved: 368 from Web of Science, 182 from Scopus, and 65 from PubMed. Duplicate records (n = 60) were removed using EndNote software, resulting in 555 unique articles for screening.

During title and abstract screening, 430 articles were excluded (201 based on title and 229 based on abstract). The full texts of 125 articles were then assessed for eligibility. Of these, 101 were excluded due to irrelevance to ketogenic diets or cancer, non-systematic formats (eg, editorials, commentaries, letters), language restrictions, or lack of extractable outcomes. Ultimately, 24 systematic reviews and meta-analyses met the inclusion criteria and were incorporated into the final synthesis. This review was not registered in PROSPERO or any other registry for systematic reviews. The detailed selection process is presented in the PRISMA flowchart (Figure 1).

Figure 1.

PRISMA flow diagram of study selection process. This figure illustrates the systematic screening and selection process for this review, following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines.

Outcomes and Data Extraction

In this review, predefined outcome domains included body composition, QoL, metabolic indices, and tumor progression. Body composition was assessed through parameters such as changes in weight, fat mass, lean mass, and body mass index (BMI). QoL outcomes were extracted based on validated instruments such as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30) and short Form Health Survey, 36 items (SF-36). Metabolic indices encompassed serum levels of glucose, triglycerides, insulin, insulin-like growth factor 1 (IGF-1), cholesterol, and inflammatory markers such as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α). Tumor progression was evaluated using clinical endpoints including tumor size, progression-free survival (PFS), and overall survival (OS).

For each included systematic review or meta-analysis, all reported results compatible with the predefined outcome domains were sought. This included data across all relevant measures, time points, and analytical approaches, such as subgroup and sensitivity analyses. In cases where multiple outcomes or time points were presented, data selection was guided by relevance to ketogenic diet interventions in oncology, completeness of reporting, and consistency across studies. When outcome definitions varied, the original definitions provided by the authors were retained, and any discrepancies were documented during synthesis. Data extraction was conducted independently by 2 reviewers, with disagreements resolved through discussion or consultation with a third reviewer to ensure methodological rigor and minimize bias.

Results

Ketogenic Diet and All Cancers

Among the included studies, 12 systematic reviews or meta-analyses explored the impact of KD on cardiometabolic parameters and QoL across various cancer types (Table 1).^{14 -25} A systematic review and meta-analysis based on 18 controlled clinical trials by Amanollahi et al ¹⁴ indicated that KD may contribute to reductions in triglycerides, IGF-1, and glucose levels, alongside improvements in emotional well-being, body composition, and overall QoL. However, adherence rates showed large differences, with some studies reporting rates as low as 49%, highlighting a potential barrier to clinical implementation. KD did not result in better improvements than control diets in cholesterol levels, insulin, C-reactive protein, or liver and kidney function.

Table 1.

Summary of the Studies.

First author	Intervention	Sample	Study design	Main outcome	Key findings	Implications and conclusion	Study type
Nagy et al 18	MD, KD, plant-based	23 studies (MD = 15, KD = 4, plant-based = 4)	Systematic review	Cancer	MD, KD, and plant-based diets lowered cancer development	Dietary interventions may reduce incidence/progression	Mixed
Taftian et al 23	KD	8 studies	Systematic review & meta-analysis	Cancer	KD was associated with body weight reduction, and this effect was also observed in patients with breast cancer >10-week trials	KD might result in weight loss in adults with cancer	RCTs
Chelikam et al 15	KD, IF, SD	10 studies	Systematic review	Cancer	KD adjunct improved QoL, survival, safety; may enhance chemo/RT	More prospective studies needed	Clinical
Amanollahi et al 14	KD	8 studies	Systematic review & meta-analysis	Cancer	KD reduced weight, glucose, fat mass; improved emotional functioning	KD improves metabolic outcomes and emotional functioning	RCTs
Yang et al 24	LCKD vs non-KD	6 studies	Systematic review & meta-analysis	Cancer	Limited overall effects; changes observed in PSA, ketosis, and patient satisfaction.	Inadequate evidence for LCKD on antitumor therapy	RCTs
Römer et al 20	KD	45 studies	Systematic review	Cancer	Majority had weight loss and mild/moderate side effects	Evidence for survival/anti-tumor/side effect reduction lacking	Clinical
Rinninella et al 37	Dietary patterns	29 studies	Systematic review of cohorts	Cancer	Western diet harmful, fiber protective	Conclusions based only on KD arms; diet quality matters	Observational
Klement and Sweeney 13	KD	13 studies	Systematic review	Cancer	KD beneficial for body composition	KD helpful in overweight/frail patients	Clinical
Shingler et al 21	KD, fasting, protein restriction	23 studies	Scoping review	Cancer	Biomarker changes (ketones ↑, IGFs ↓; glucose not reduced)	Future research with adequately powered studies is required	Mixed
Sremanakova et al 22	KD	11 studies	Systematic review	Cancer	Evidence inconclusive; mixed blood/tumor/QoL; adherence low	High-quality evidence lacking; heterogeneity/adherence issues	Clinical
Zhao et al 25	KD	10 studies	Systematic review & meta-analysis	Cancer	KD reduced weight and fat mass; limited metabolic changes	KD is safe, reduces weight/fat mass, may improve QoL	RCTs
Erickson et al 16	Isocaloric KD	15 studies	Systematic review	Cancer	Weight loss observed	Stronger evidence needed	Clinical
Pahwa et al 28	KD	22 studies	Systematic review	Glioma	No clear difference in survival was observed	More human subjects needed	Clinical
Sargaço et al 30	KD	9 studies	Systematic review	Gliomas	Mean OS ≈ 15.9 mo	KD may increase survival	Clinical
Pangal et al 29	CAM incl. KD	22 studies	Scoping review	Gliomas	Tumor response improved	KD appears safe/tolerated	Clinical
Montemurro et al 26	KD	29 studies	Review	Glioblastoma	KD may act via multiple mechanisms	Further studies needed	Narrative
Noorlag et al 27	KD/CR	24 studies	Systematic review	Gliomas	Preclinical growth reduction; limited survival benefit	Positive preclinical effects	Preclinical
Winter et al 31	KD	16 studies	Systematic review	Glioma	KD may reduce growth, improve QoL	—	Mixed
Noura et al 35	KD	5 studies	Systematic review	Breast cancer	KD improved QoL, metabolic biomarkers	KD beneficial long-term	Clinical
Jemal et al 32	KD	7 studies	Systematic review	Breast cancer	Mechanistic shifts, host milieu improved	KD potential for PFS/OS	Mixed
Weigl et al 34	Low-carb/KD/veg	3 studies	Systematic review	Breast cancer	No beneficial effect	No evidence of an association was observed	Observational
Martin-McGill et al 33	Multiple diets incl. KD	39 studies	Systematic review	Breast cancer	Limited evidence for KD; some negative correlations	High-quality diets beneficial	Mixed
Mikolaskova 36	LCKD + nutraceuticals	28 studies (LCKD = 9; natural products = 9)	Systematic review	Pancreatic cancer	LCKD improved parameters	Reduced risk/progression	Mixed
Rinninella et al 37	KD + other interventions	14 studies	Systematic review of RCTs	Ovarian cancer	KD reduced fat mass versus ACS diet	KD interventions in ovarian cancer reduced fat mass and improved metabolic parameters, but evidence remains heterogeneous; larger RCTs with survival endpoints are needed	RCTs

Four meta-analyses of randomized controlled trials (RCTs)^16,17,20,23 were associated with weight loss and better body composition compared with control diets. In a meta-analysis of 10 RCTs, Zhao et al ²⁵ confirmed these effects on body weight and fat mass, but did not observe meaningful changes in lipid profiles (except triglycerides), TNF levels, or measures of blood glucose control. Shingler et al similarly reported that KD did not meaningfully affect glycemic statuy. ²¹ After the low-carbohydrate ketogenic diet (LCKD) intervention, the study conducted by Yang et al ²⁴ observed improvement in metabolic risk factors such as glycemic index, lipid profile, body composition, tumor markers, and QoL. In a study by Chelikam et al, ¹⁵ KD improved QoL, tolerability, survival, and demonstrate an acceptable safety profile. They also found that KD may enhance the anti-tumor effects of classical chemotherapy and RT. Nonetheless, the heterogeneity in outcomes and adherence underscores the need for cautious interpretation and further investigation.

Ketogenic Diet and Glioma

Six studies assessed the effect of KDs on the management of gliomas.^{26 -31} Noorlag et al ²⁷ reviewed 32 preclinical and clinical studies and found that KD reduced tumor growth, but only a minority of the in vivo studies found improved survival. KDs was also reported to affect several molecular biological pathways, including the PTEN/Akt/TSC2 and NF-kB pathways. Clinical data remain insufficient to draw firm conclusions regarding efficacy; however, available studies suggest that ketogenic diets may be effective and suitable for use in patients with glioma. Other studies have shown that KDs are safe and well tolerated by patients with glioma and may increase the QoL, progression-free survival, and overall survival.^{28 -30} Winter et al ³¹ also found in preclinical and clinical literature that KDs have safety and efficacy in malignant glioma model systems.

Ketogenic Diet and Breast Cancer

Four systematic reviews or meta-analyses investigated the efficiency of KD on breast cancer.^{32 -35} Two systematic reviews concluded that adherence to KD may have beneficial effects on tumor characteristics, QoL, and some metabolic parameters. ³² For example, Noura et al ³⁵ found that long-term adherence to KD can lead to improved body composition, enhanced QoL, reduced inflammatory biomarkers, serum lipid profile disorders, insulin resistance, and tumor size in breast cancer patients. In a study conducted by Jemal et al, ³² it was found that KDs reduce the body’s reliance on glucose and insulin for energy. This includes an increase in fatty acid oxidation and a decrease in glucose flux, which may potentially serve as a therapeutic mechanism in the treatment of breast cancer. KDs also restore the hormonal and inflammatory environment of the host, which is thought to inhibit tumor growth. However, 2 other reviews did not find any evidence that use of KD predicted lower breast cancer morbidity and mortality.^33,34

Ketogenic Diet and Other Cancers

Two systematic reviews assessed the beneficial impact of KD on clinical outcomes in pancreatic ³⁶ and ovarian cancer. ³⁷ Mikolaskova et al ³⁶ conducted a systematic review of 28 studies and reported that a low-carbohydrate KD, when combined with standard therapies, may improve the management of type 2 diabetes and reduce the risk of pancreatic ductal adenocarcinoma (PDAC) development and progression. However, this review primarily addressed nutraceuticals and ketogenic diets in the context of diabetes and PDAC, with much of the evidence being preclinical or prevention-oriented with only limited direct clinical data in pancreatic cancer patients. Accordingly, the study was included for completeness, but its findings should be interpreted as supportive or mechanistic rather than as evidence of clinical outcomes in PDAC.

Only 2 of the studies included in the systematic review specifically looked at the effects of a ketogenic diet in ovarian cancer patients. One study found that patients on a ketogenic diet had lower total and abdominal fat compared with those who follow the standard diet recommended by the American Cancer Society. In another study, ketogenic diet improved patients’ physical function and reduced cravings for starchy and high-fat fast foods. In conclusion, ketogenic diet has several benefit for ovarian cancer patients, such as selective fat loss without losing lean mass, better physical function, and improved quality of life. ³⁷

Ketogenic Diet and Treatment Complications

Only 2 reviews explicitly reported treatment-related complications.^15,20 These included reduced fatigue and inflammation, but inconsistent findings on nausea, constipation, and anorexia. Evidence on radiotherapy-specific toxicity was scarce.

Discussion

To our knowledge, this is the first review to comprehensively evaluate the effects of ketogenic diets on cancer outcomes and treatment-related side effects. A total of 24 systematic reviews and meta-analyses were included, encompassing a wide range of cancer types and therapeutic contexts.

Regarding tolerability and adherence, KD was generally well tolerated among cancer patients, with most studies reporting successful short-term adherence during chemotherapy and radiotherapy. Of the 12 studies that assessed tolerability, 9 reported that patients were able to maintain ketosis during treatment. However, long-term adherence showed large differences, with dropout rates ranging from 20% to over 50% in some trials. Factors contributing to non-adherence to ketogenic diets included taste fatigue, gastrointestinal symptoms such as nausea and constipation, and the restrictive nature of dietary protocols. Chelikam et al ¹⁵ and Noura et al ³⁵ emphasized that patient education and individualized support may improve adherence and tolerability.

Concerning treatment-related complications, KD appeared to influence several treatment-related complications. Eight reviews reported improvements in body composition, including reductions in fat mass and preservation of lean mass, which are critical in oncology settings.^{14,16,17,20,22 -25} For example, Zhao et al ²⁵ and Amanollahi et al ¹⁴ found clear reductions in weight and fat mass across more than 1000 patients. Yang et al ²⁴ observed decreased fatigue and inflammation, while nausea, vomiting, and cachexia were less frequently reported. However, only 3 studies explicitly quantified these symptoms, limiting generalizability.^14,23,25

The effects of ketogenic dietary interventions on weight and body composition varied by cancer type and clinical setting. Weight loss was reported across breast, head and neck, and mixed solid tumor populations, with magnitudes influenced by energy prescription, adherence, and treatment stage. Three meta-analyses measured body composition directly and showed reductions in fat mass, with lean mass preserved in some clinical contexts.^14,23,25 Additional systematic reviews reported weight change, with heterogeneous and partially reported body composition assessments.^{16,17,20,22,24} These changes were observed during radiotherapy and in peri-treatment outpatient settings, with more favorable lean mass preservation in isocaloric protocols and programs with nutrition support.

The implications of weight and fat mass reduction varied by cancer type and stage. In overweight patients with early stage breast cancer, reductions in weight and fat mass were generally interpreted as beneficial metabolic effects. In contrast, in late stage pancreatic and lung cancer patients, where cachexia is a concern, weight loss may reflect undesirable loss of lean mass. Only 3 meta-analyses explicitly quantified body composition,^14,23,25 showing reductions in fat mass with context-dependent preservation of lean mass. Other reviews reported weight change without clear distinction between fat and lean mass, making it difficult to determine whether ketogenic dietary interventions primarily affect adiposity or contribute to cachexia in advanced disease settings.

With respect to laboratory biomarkers and metabolic indices, 10 studies evaluated the impact of KD on laboratory biomarkers. Consistent reductions in glucose and insulin-like growth factor-1 (IGF-1) were reported in at least 6 reviews, including Amanollahi et al ¹⁴ and Shingler et al, ²¹ involving over 800 patients. Chelikam et al ¹⁵ and Jemal et al ³² suggested that KD may enhance the efficacy of chemotherapy and radiotherapy by altering metabolic pathways, including reduced reliance on the glucose/insulin axis and increased fatty acid oxidation. Triglyceride levels also decreased in most studies, while effects on cholesterol, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) were mixed. Only 4 reviews assessed inflammatory markers directly, and results varied depending on cancer type and KD protocol. These findings suggest potential metabolic benefits, though further standardized trials are needed to confirm clinical relevance.

In terms of tumor growth and survival outcomes, KD’s impact on tumor progression and survival was assessed in 11 reviews. In glioma and breast cancer, KD was associated with reduced tumor growth and improved progression-free survival (PFS) in preclinical and early-phase clinical studies. For example, Noorlag et al ²⁷ reviewed 32 studies and found tumor suppression in most animal models, though survival benefits were limited. However, Shingler et al and 2 other reviews^33,34 found no evidence of improved overall survival or reduced breast cancer mortality. Assessment methods varied widely, including imaging, biomarker tracking, and clinical endpoints, limiting comparability across studies.

Limitations and Future Directions

This review has several limitations. First, it was not registered in PROSPERO or any other registry, and the absence of prospective registration is acknowledged as a limitation, as registration enhances transparency and methodological rigor. Second, the review did not include formal assessments of methodological quality using AMSTAR-2, evaluations of the certainty of evidence with the GRADE framework, or an assessment of study overlap across systematic reviews. These omissions are recognized as limitations, since such assessments are key features of high-quality umbrella reviews. Third, definitions of ketogenic diets varied considerably across studies, which affected the comparability of outcomes. QoL improvements were frequently reported, but measurement tools such as the EORTC QLQ-C30 and SF-36 were applied inconsistently. Moreover, heterogeneity in outcome definitions, measurement instruments, and reporting formats across the included meta-analyzes made a unified statistical synthesis infeasible. In addition, the diversity of cancer types and treatment protocols limits the generalizability of the findings. Finally, evidence on treatment-related complications is limited and heterogeneous. While some reviews suggested improvements in fatigue and inflammation, systematic data on radiotherapy-related toxicity are lacking. Future trials should adopt standardized KD protocols, include patient-reported outcomes, and evaluate long-term adherence and safety. Longitudinal studies with robust designs are essential to clarify KD’s role in cancer management and its interaction with treatment side effects.

Conclusion

In summary, this review suggests that KD may serve as a promising adjunctive approach in cancer management. Evidence across systematic reviews and meta-analyses indicates consistent benefits in improving metabolic parameters such as glucose and triglycerides, enhancing body composition by reducing fat mass and preserving lean mass, and supporting QoL in selected patient populations. Preliminary data also suggest potential tumor-suppressive effects in glioma and breast cancer, although survival outcomes remain inconclusive. Importantly, evidence on treatment-related complications, including radiotherapy-associated toxicity, is scarce and heterogeneous, underscoring the need for more rigorous trials with standardized patient-reported outcomes. Long-term adherence to KD remains a major challenge, with dropout rates influenced by dietary restrictiveness and gastrointestinal symptoms. Future research should prioritize well-designed randomized controlled trials with harmonized KD protocols, robust monitoring of metabolic and clinical endpoints, and evaluation of long-term safety. Overall, while KD cannot yet be recommended as a standard therapy, it holds potential as a safe and feasible supportive strategy to improve metabolic health, body composition, and possibly treatment tolerance in cancer patients.