Effect of ketogenic diets on insulin-like growth factor (IGF)-1 in humans: A systematic review and meta-analysis.

BACKGROUND: Insulin-like growth factor (IGF)-1 plays a role in aging and cancer biology, with fasting known to reduce serum IGF-1 levels in human adults. However, the impact of ad libitum ketogenic diets (KDs) on IGF-1 levels remains unclear. METHODS: Adhering to PRISMA guidelines, we conducted a meta-analysis of human trials by systematically searching Ovid, PubMed, Scopus, and CENTRAL Libraries until June 2023. Eligible studies prescribed KDs to adults of any health status, confirmed ketosis, and measured serum IGF-1. Protocols involving prescribed fasting or energy restriction were excluded. Mean differences (MD) and 95 % confidence intervals (CIs) were calculated longitudinally between pre- and post-intervention measurements for the KD groups. RESULTS: Among twelve publications meeting the inclusion criteria, 522 individuals participated, with 236 completing KDs. The intervention duration ranged from 1 to 20 weeks. Pooled results from ten trials showed a significant reduction in serum IGF-1 levels post-intervention (MD: -24.9 ng/mL [95 % CI -31.7 to -18.1]; p<0.0001) with low heterogeneity across studies (I2=27 %, p=0.19). KDs were also associated with significantly decreased fasting insulin (MD: -2.57 mU/L [95 % CI -4.41 to -0.74], p=0.006) and glucose (MD: -7.30 mg/dL [95 % CI -11.62 to -2.98], p=0.0009), although heterogeneity was significant. Subgroup analyses on study design, gender, dietary duration, and oncological status revealed no significant differences. CONCLUSION: Ad libitum KDs (>55 % fat) effectively induce ketosis and can lower serum IGF-1 by 20 %, fasting glucose by 6 % and insulin by 29 %. This clinically notable reduction in IGF-1 can be attained without the need for a prescribed fasting or severe calorie restriction regimen. Further investigation is warranted to explore the impact of KDs on ageing biomarkers and cancer management.

Effects of protein restriction on insulin-like growth factor (IGF)-1 in men with prostate cancer: results from a randomized clinical trial.

BACKGROUND: Insulin-like growth factor (IGF)-1 and its binding proteins are important in cancer growth, especially in prostate cancer. Observational studies suggest that protein restriction can lower IGF-1 levels. However, it is unclear whether an isocaloric protein-restricted diet affects IGF-1 and IGFBPs in men with prostate cancer. METHODS: In this academic, single-center, parallel-group, prospective, randomized, open-label, blinded end-point trial, 38 consenting overweight (BMI 30.5 ± 5.5 kg/m2) men with localized prostate cancer, aged 43-72 years, were randomized (1:1) with permuted blocks to 4-6 weeks of customized isocaloric PR diets (0.8 g protein/kg lean body mass) or their usual diet. Biomarkers influencing cancer biology, including serum IGF-1 and its binding proteins were measured longitudinally. RESULTS: Contrary to our hypothesis, feeding individuals an isocaloric protein-restricted diet did not result in a significant reduction in serum IGF-1. Moreover, there was no observed increase in serum IGFBP-1 or IGFBP-3 concentration. CONCLUSION: These findings demonstrate that protein restriction without calorie restriction does not reduce serum IGF-1 concentration or increase IGFBP-1 and IGFBP-3 in men with localized prostate cancer. Further research is needed to identify dietary interventions for safely and effectively reducing IGF-1 in this patient group.

Microtubule-Targeting Combined with HDAC Inhibition Is a Novel Therapeutic Strategy for Diffuse Intrinsic Pontine Gliomas.

Diffuse intrinsic pontine gliomas (DIPG) are an incurable childhood brain cancer for which novel treatments are needed. DIPGs are characterized by a mutation in the H3 histone (H3K27M), resulting in loss of H3K27 methylation and global gene dysregulation. TRX-E-009-1 is a novel anticancer agent with preclinical activity demonstrated against a range of cancers. We examined the antitumor activity of TRX-E-009-1 against DIPG neurosphere cultures and observed tumor-specific activity with IC50s ranging from 20 to 100 nmol/L, whereas no activity was observed against normal human astrocyte cells. TRX-E-009-1 exerted its anti-proliferative effect through the induction of apoptotic pathways, with marked increases in cleaved caspase 3 and cleaved PARP levels, while also restoring histone H3K27me3 methylation. Co-administration of TRX-E-009-1 and the histone deacetylase (HDAC) inhibitor SAHA extended survival in DIPG orthotopic animal models. This antitumor effect was further enhanced with irradiation. Our findings indicate that TRX-E-009-1, combined with HDAC inhibition, represents a novel, potent therapy for children with DIPG.