Schedule Dependence in Cancer Therapy: Intravenous Vitamin C and the Systemic Saturation Hypothesis.

Michael J Gonzalez, Jorge R Miranda Massari, Jorge Duconge, Neil H Riordan, Thomas Ichim
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Abstract

Despite the significant number of in vitro and in vivo studies to assess vitamin C effects on cancer following the application of large doses and its extensive use by alternative medicine practitioners in the USA; the precise schedule for successful cancer therapy is still unknown. Based on interpretation of the available data, we postulate that the relationship between Vitamin C doses and plasma concentration x time, the capability of tissue stores upon distribution, and the saturable mechanism of urinary excretion are all important determinants to understand the physiology of high intravenous vitamin C dose administration and its effect on cancer. Practitioners should pay more attention to the cumulative vitamin C effect instead of the vitamin C concentrations to account for observed discrepancy in antitumor response. We suggest that multiple, intermittent, short-term intravenous infusions of vitamin C over a longer time period will correlate with greater antitumor effects than do single continuous IV doses of the same total exposure. This approach would be expected to minimize saturation of renal reabsorption, providing a continuous "dynamic flow" of vitamin C in the body for optimal systemic exposure and clinical outcomes. This prevents the "systemic saturation" phenomena, which may recycle vitamin C and render it less effective as an anticancer agent. Nonetheless, more pharmacokinetic and pharmacodynamic studies are needed to fully understand this schedule-dependence phenomenon.

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癌症治疗中的时间表依赖性:静脉注射维生素 C 和全身饱和假说
尽管有大量的体外和体内研究来评估维生素 C 大剂量应用后对癌症的影响,而且美国的替代医学从业者也广泛使用维生素 C,但成功治疗癌症的精确时间表仍然未知。根据对现有数据的解读,我们推测维生素 C 剂量与血浆浓度 x 时间之间的关系、分布时组织储存的能力以及尿液排泄的饱和机制都是了解大剂量静脉注射维生素 C 的生理学及其对癌症影响的重要决定因素。从业人员应更多地关注维生素 C 的累积效应,而不是维生素 C 的浓度,以解释所观察到的抗肿瘤反应差异。我们建议,在较长时间内多次、间歇、短期静脉注射维生素 C,其抗肿瘤效果会比连续静脉注射单次相同总剂量的维生素 C 抗肿瘤效果更好。这种方法有望最大限度地降低肾脏重吸收的饱和度,为体内维生素 C 提供持续的 "动态流",以达到最佳的全身暴露和临床效果。这可以防止出现 "全身饱和 "现象,因为这种现象可能会使维生素 C 回收,从而降低其作为抗癌剂的效果。不过,还需要进行更多的药代动力学和药效学研究,以充分了解这种时间表依赖现象。
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