Effect of Intermittent versus Chronic Calorie Restriction on Tumor Incidence: A Systematic Review and Meta-Analysis of Animal Studies

Abstract

Both chronic calorie restriction (CCR) and intermittent calorie restriction (ICR) have shown anticancer effects. However, the direct evidence comparing ICR to CCR with respect to cancer prevention is controversial and inconclusive. PubMed and Web of Science were searched on November 25, 2015. The relative risk (RR) [95% confidence interval (CI)] was calculated for tumor incidence, and the standardised mean difference (95% CI) was computed for levels of serum insulin-like growth factor-1 (IGF-1), leptin, and adiponectin using a random-effects meta-analysis. Sixteen studies were identified, including 11 using genetically engineered mouse models (908 animals with 38-76 weeks of follow-up) and 5 using chemically induced rat models (379 animals with 7-18 weeks of follow-up). Compared to CCR, ICR decreased tumor incidence in genetically engineered models (RR = 0.57; 95% CI: 0.37, 0.88) but increased the risk in chemically induced models (RR = 1.53, 95% CI: 1.13, 2.06). It appears that ICR decreases IGF-1 and leptin and increases adiponectin in genetically engineered models. Thus, the evidence suggests that ICR exerts greater anticancer effect in genetically engineered mouse models but weaker cancer prevention benefit in chemically induced rat models as compared to CCR. Further studies are warranted to confirm our findings and elucidate the mechanisms responsible for these effects.

Figure 1. The selection process (PRISMA).

CCR: chronic calorie restriction; ICR: intermittent calorie restriction.

Figure 2. RRs and 95% CIs for tumor incidence in genetically engineered and chemically induced animal models.

The pooled estimates were obtained using a random-effects model. The dots indicate the RRs comparing ICR to CCR. The size of the shaded square is proportional to the weight in each study. The horizontal lines represent the 95% CIs. The diamond data markers indicate the pooled RRs with corresponding 95% CIs. CCR: chronic calorie restriction; CI: confidence interval; ICR: intermittent calorie restriction; RR: relative risk (for tumor incidence).

Figure 3. SMDs and 95% CIs for serum IGF-1 levels in genetically engineered animal models.

The pooled estimates were obtained using a random-effects model. The dots indicate the SMDs comparing ICR-R to CCR. The size of the shaded square is proportional to the weight of each study. The horizontal lines represent the 95% CIs. The diamond data markers indicate the pooled SMDs with corresponding 95% CIs. CCR: chronic calorie restriction; CI: confidence interval; ICR: intermittent calorie restriction; ICR-R: restriction period in ICR group; SMD: standardised mean difference.

Figure 4. SMDs and 95% CIs for serum leptin and adiponectin levels in genetically engineered animal models.

The pooled estimates were obtained using a random-effects model. The dots indicate the SMDs comparing ICR-R to CCR. The size of the shaded square is proportional to the weight of each study. The horizontal lines represent the 95% CIs. The diamond data markers indicate the pooled SMDs with corresponding 95% CIs. CCR: chronic calorie restriction; CI, confidence interval; ICR: intermittent calorie restriction; ICR-R: restriction period in ICR group; SMD: standardised mean difference.