Blood α-Tocopherol, γ-Tocopherol Levels and Risk of Prostate Cancer: A Meta-Analysis of Prospective Studies

Ran Cui., Zhu-Qing Liu., Qing Xu

Background

Epidemiological studies that have examined the association of blood α-tocopherol and γ-tocopherol (the principal bioactive form of vitamin E) levels with the risk of prostate cancer have yielded inconsistent results. In addition, a quantitative assessment of published studies is not available.

Methods and Findings

In this meta-analysis, relevant studies were sought by a search of the PubMed and Embase databases for articles published up to October 2013, with no restrictions. Bibliographies from retrieved articles also were scoured to find further eligible studies. Prospective studies that reported adjusted relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between blood tocopherol levels and the risk of prostate cancer were included. Nine nested case–control studies involving approximately 370,000 participants from several countries were eligible. The pooled RRs of prostate cancer for the highest versus lowest category of blood α-tocopherol levels were 0.79 (95% CI: 0.68–0.91), and those for γ-tocopherol levels were 0.89 (95% CI: 0.71–1.12), respectively. Significant heterogeneity was present among the studies in terms of blood γ-tocopherol levels (p = 0.008) but not in terms of blood α-tocopherol levels (p = 0.33). The risk of prostate cancer decreased by 21% for every 25-mg/L increase in blood α-tocopherol levels (RR: 0.79; 95% CI: 0.69–0.91).

Conclusions

Blood α-tocopherol levels, but not γ-tocopherol levels, were inversely associated with the risk of prostate cancer in this meta-analysis.

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A Phase I Dose-Escalation Study Evaluating the Pharmacokinetics, Safety and Tolerability of Oral Gamma-Delta-Tocotrienol (GDT) in Patients with Castration-Resistant Prostate Cancer (CRPC)

Prof Azad Hassan A. Razack, University of Malaya Medical Centre, Malaysia

Ongoing

Objective:
 In this study, we intend to determine Gamma-Delta Tocotrienol’s (GDT) safety and tolerability in patients with castrate-resistant prostate cancer (CRPC). In addition, GDT’s pharmacokinetic profile in this cohort of patients will be investigated.

Study Type: Interventional

Study Design: Dose-escalation, pharmacokinetics study

Subjects: Castrate-resistant prostate cancer patients

Intervention: Gamma-Delta Tocotrienol (GDT; Davos Life Science Pte Ltd)

Primary Outcome:

  • Safety and tolerability
  • GDT isomer plasma concentration [ time frame: 0, 1, 2, 3, 4, 6, 8, 10, 14, 24 hours ]

Secondary Outcome: Circulating tumor cell (CTC) levels and inflammatory biomarkers (IL-8, MCP-1, MIP-1 alpha, IFN-gamma, IL-1B, IL-4, IL-6, IL-10, IL-12 (p70), IL-17A, Il-23, IL-27, TNF-alpha, MIP-3 alpha, CRP) [time frame: baseline and day 22]

Methodology: During pharmacokinetic evaluation wherein GDT will be taken as a single dose, participants will receive oral GDT for 21 days at 400, 800, 1600, 2400 and 3200 mg/day for 21 days. Pharmakokinetic and safety profiles will be evaluated on the 8th, 15th and 22nd day.