Effect of Ketogenic Diets on Cardio-Metabolic Outcomes in Cancer Patients: A Systematic Review and Meta-Analysis of Controlled Clinical Trials

Abstract

In this systematic review and meta-analysis of clinical controlled trials (CCTs) we aimed to investigate the efficacy of KDs as an adjuvant therapy on cardiometabolic outcomes in patient with cancer compared to conventional non-ketogenic diets. Only CCTs involving cancer patients that were assigned to either a KD or a standard diet control group were selected. Two reviewers independently extracted the data, and a meta-analysis was performed using a random effects model to estimate weighted mean differences (WMDs) and confidence intervals (CIs) in body composition, metabolite, lipid profile, liver and kidney function parameters and quality of life. This meta-analysis showed a significant reduction in body weight (WMD= −2.99 kg; 95% CI: −4.67, −1.31; and P < 0.001), BMI (WMD= −1.08 kg/m²; 95% CI: −1.81, −0.34; P ≤ 0.002) and fat mass (WMD= −1.48 kg; 95% CI: −2.56, −0.40; and P = 0.007) by a KD. KDs significantly decreased glucose (WMD= −5.22 mg/dl; 95% CI: −9.0, −1.44; and P = 0.007), IGF-1 (WMD= −17.52 ng/ml; 95% CI: −20.24, −14.8; and P ˂0.001) and triglyceride (WMD= −24.46 mg/dl; 95% CI: −43.96, −4.95; and P = 0.014) levels. Furthermore, KDs induced ketosis by increasing β-hydroxybutyrate (WMD= 0.56 mmol/l; 95% CI: 0.37, 0.75; and P < 0.001). There were non-significant pooled effects of KDs on improving insulin, C-reactive protein and cholesterol levels and kidney and liver function. Emotional functioning was even increased significantly in the KD compared to the SD groups. In summary we found that KDs result in a greater reduction in glucose, IGF-1, triglycerides, body weight, BMI, and fat mass in cancer patients compared to traditional non-ketogenic diets and improved emotional functioning. The quality of evidence in the meta-analysis was moderate according to the Nutrigrade assessment.

Acknowledgment

This paper was derived from the research project approved and financed by Student Research Committee, Kerman University of Medical Sciences, under no 400000289.

Author Contributions

The authors’ responsibilities were as follows A. Khodabakhshi designed the study; A. Khodabakhshi, M. Khazdouz and M. Malekahmadi screened and selected the trials; A. Amanollahi and M. Malekahmadi M extracted the data; A. Amanollahi analysed the data; A. Amanollahi and M. Malekahmadi assessed the risk of bias; M. Malekahmadi assessed the Nutrigrade; A. Khodabakhshi, M. Khazdouz, D. Lee, M. Malekahmadi, A. Amanollahi and R.J. Klement drafted the manuscript; all authors read and approved the final manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

Data Availability Statement

All data generated or analyzed during this study are available from the corresponding author on reasonable request

Identification number in PROSPERO: CRD42021269692 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=269692)

Notes

1 Bayes factors (or likelihood ratios in case of simple hypotheses) measure the strength of evidence between two competing hypotheses (99). In exploratory analyses, a p-value of 0.01 corresponds to a minimum Bayes factor of 1/6.5, providing moderate-to-strong evidence against the null hypothesis .