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  • 1
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    Chapter 1 A “C Odyssey” (2023)
    Taylor & Francis | Vitamin C | CRC Press
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    Publication Date: 2024-04-01
    Description: The nutritional biochemist Alfred E. Harper was a member of the Food and Nutrition Board of the National Research Council/National Academy of Sciences for many years, and chair of the Food and Nutrition Board from 1978 to 1982. The scientific bases for many Recommended Dietary Allowances (RDA) were prevention of deficiency with a margin of safety, often determined from depletion-repletion studies or balance experiments. As nutritional science has grown, and policy needs have changed, limitations of RDAs were recognized. Fundamental biochemical kinetics concepts can be the foundation for nutrient recommendations. Bioavailability experiments showed plasma and tissue concentrations were tightly controlled with oral administration of ascorbic acid. Reabsorption would be predicted in proximal renal tubules, concurrent with sodium-dependent vitamin C transporter1 localization. Accelerated ascorbic acid utilization in disease states may be a new frontier that can lead to discoveries for roles of ascorbic acid in disease treatment.
    Keywords: acute sepsis; antioxidants; ascorbic acid; cancer treatment; infectious disease; infectious disease treatment; intravenous ascorbate; stem cell transplantation; vitamin c ; thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKG Pharmacology ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences::PSD Molecular biology ; thema EDItEUR::P Mathematics and Science::PS Biology, life sciences
    Language: English
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  • 2
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    High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model (2020)
    National Academy of Sciences
    Details
    Publication Date: 2020-01-07
    Description: Major efforts are underway to identify agents that can potentiate effects of immune checkpoint inhibition. Here, we show that ascorbic acid (AA) treatment caused genomewide demethylation and enhanced expression of endogenous retroviral elements in lymphoma cells. AA also increased 5-hydroxymethylcytosine (5hmC) levels of CD8+ T cells and enhanced their cytotoxic activity in a lymphoma coculture system. High-dose AA treatment synergized with anti-PD1 therapy in a syngeneic lymphoma mouse model, resulting in marked inhibition of tumor growth compared with either agent alone. Analysis of the intratumoral epigenome revealed increased 5hmC with AA treatment, consistent with in vitro findings. Analysis of the tumor immune microenvironment revealed that AA strikingly increased intratumoral infiltration of CD8+ T cells and macrophages, suggesting enhanced tumor immune recognition. The combination treatment markedly enhanced intratumoral infiltration of macrophages and CD8+ T lymphocytes, granzyme B production by cytotoxic cells (cytotoxic T cells and natural killer cells), and interleukin 12 production by antigen-presenting cells compared with single-agent anti-PD1. These data indicate that AA potentiates anti-PD1 checkpoint inhibition through synergistic mechanisms. The study provides compelling rationale for testing combinations of high-dose AA and anti-PD1 agents in patients with aggressive B cell lymphoma as well as in preclinical models of other malignancies.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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