Evidence map›Paper›PMID 23621620›Full record

ReviewAntioxidants & redox signaling2013

Parenteral ascorbate as a cancer therapeutic: a reassessment based on pharmacokinetics.

Nermi L Parrow, Jonathan A Leshin, Mark Levine

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
7.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.

  1. Effect of vitamins C and E on cancer survival; a systematic review.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2022
    Pooled it
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  19. Nuclear and Cytoplasmic Functions of Vitamin C.Chemical research in toxicology · 2020
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Nermi L ParrowMolecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland.
Jonathan A Leshin
Mark Levine
National Institutes of Health · US

Funding

Ascorbic acid as a pharmacologic agent in disease treatmentZIADK053212 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LEVINE, MARK A · 2009 to 2025
$8.5M
Vitamin C (ascorbic acid) recommended dietary ingestionZIADK053211 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LEVINE, MARK A · 2009 to 2025
$7.2M
6 · The paper itself

Abstract

significanceEwan Cameron reported that ascorbate, given orally and intravenously at doses of up to 10 g/day, was effective in the treatment of cancer. Double-blind placebo-controlled clinical trials showed no survival advantage when the same doses of ascorbate were given orally, leading the medical and scientific communities to dismiss the use of ascorbate as a potential cancer treatment. However, the route of administration results in major differences in ascorbate bioavailability. Tissue and plasma concentrations are tightly controlled in response to oral administration, but this can be bypassed by intravenous administration. These data provide a plausible scientific rationale for the absence of a response to orally administered ascorbate in the Mayo clinic trials and indicate the need to reassess ascorbate as a cancer therapeutic. RECENT ADVANCES: High dose ascorbate is selectively cytotoxic to cancer cell lines through the generation of extracellular hydrogen peroxide (H2O2). Murine xenograft models confirm a growth inhibitory effect of pharmacological concentrations. The safety of intravenous ascorbate has been verified in encouraging pilot clinical studies. CRITICAL ISSUES: Neither the selective toxicity of pharmacologic ascorbate against cancer cells nor the mechanism of H2O2-mediated cytotoxicity is fully understood. Despite promising preclinical data, the question of clinical efficacy remains. FUTURE DIRECTIONS: A full delineation of mechanism is of interest because it may indicate susceptible cancer types. Effects of pharmacologic ascorbate used in combination with standard treatments need to be defined. Most importantly, the clinical efficacy of ascorbate needs to be reassessed using proper dosing, route of administration, and controls.

Indexed as

Administration, OralAnimalsAntineoplastic AgentsAscorbic AcidBiological AvailabilityCell DeathDrug InteractionsDrug Screening Assays, AntitumorGene Expression Regulation, NeoplasticHumansNeoplasmsReactive Oxygen SpeciesSignal TransductionAntineoplastic AgentsAscorbic AcidReactive Oxygen Species

Identifiers

PMID23621620
PMCPMC3869468
OpenAlexW2025623273

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.