Evidence of rebound effect with ascorbic acid

Tsao, Constance S.; Salimi, Sanam

doi:10.1016/0306-9877(84)90163-4

Cited by 15 publications

(10 citation statements)

References 12 publications

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“…Patients were provided a daily 500 mg oral dose of AA starting the day after the first infusion to avoid a suggested rebound deficiency after high‐dose AA infusions .…”

Section: Methodsmentioning

confidence: 99%

Elimination of Ascorbic Acid After High‐Dose Infusion in Prostate Cancer Patients: A Pharmacokinetic Evaluation

Nielsen

Højgaard

Andersen

et al. 2014

Basic Clin Pharma Tox

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Treatment with high-dose intravenous (IV) ascorbic acid (AA) is used in complementary and alternative medicine for various conditions including cancer. Cytotoxicity to cancer cell lines has been observed with millimolar concentrations of AA. Little is known about the pharmacokinetics of high-dose IV AA. The purpose of this study was to assess the basic kinetic variables in human beings over a relevant AA dosing interval for proper design of future clinical trials. Ten patients with metastatic prostate cancer were treated for 4 weeks with fixed AA doses of 5, 30 and 60 g. AA was measured consecutively in plasma and indicated first-order elimination kinetics throughout the dosing range with supra-physiological concentrations. The target dose of 60 g AA IV produced a peak plasma AA concentration of 20.3 mM. Elimination half-life was 1.87 hr (mean, S.D. AE 0.40), volume of distribution 0.19 L/kg (S.D. AE0.05) and clearance rate 6.02 L/hr (100 mL/min). No differences in pharmacokinetic parameters were observed between weeks/doses. A relatively fast first-order elimination with half-life of about 2 hr makes it impossible to maintain AA concentrations in the potential cytotoxic range after infusion stop in prostate cancer patients with normal kidney function. We propose a regimen with a bolus loading followed by a maintenance infusion based on the calculated clearance.

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“…Patients were provided a daily 500 mg oral dose of AA starting the day after the first infusion to avoid a suggested rebound deficiency after high‐dose AA infusions .…”

Section: Methodsmentioning

confidence: 99%

Elimination of Ascorbic Acid After High‐Dose Infusion in Prostate Cancer Patients: A Pharmacokinetic Evaluation

Nielsen

Højgaard

Andersen

et al. 2014

Basic Clin Pharma Tox

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“…Several groups have reported the existence of a 'conditioning' effect of high intakes of ascorbate in human beings (Cochrane, 1965;Schrauzer & Rhead, 1973;Tsao & Salimi, 1984;Omaye et al 1986). One of these (Cochrane, 1965) refers to an effect on the offspring of pregnant women who had very high intakes, but this is an anecdotal report.…”

mentioning

confidence: 99%

Growth, ascorbic acid and iron contents of tissues of young guinea-pigs whose dams received high or low levels of dietary ascorbic acid or Fe during pregnancy and suckling

1988

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1. Guinea-pig dams were fed on purified diets containing high (5 g/kg diet plus 1 g/l drinking water) or moderate (0.5 g/kg diet) levels of ascorbic acid, in combination with high (1 g/kg diet) or moderate (0.043 g/kg diet) levels of iron, during pregnancy and suckling. Their offsprings' diets contained 0.1 g ascorbic acid/kg and 0.04 g Fe/kg.2. High ascorbic acid intake clearly enhanced both tissue ascorbate and Fe storage in the dams, and high Fe intake increased both the dams' and the pups' tissue Fe stores.3. In the animals receiving high Fe intake, a co-existing high ascorbate intake by the dams reduced the growth rate of the offspring, but only during the early stages of development, not during the later stages of post-weaning growth. All the pups' tissue ascorbate levels fell after weaning, but those born of the dams receiving the high ascorbic acid diets did not fall to levels lower than those of the other pups.4. Thus, although certain disadvantages to the offspring resulting from very-high ascorbic acid intake by pregnant guinea-pig dams were detected, these did not include permanently increased ascorbate requirements, and hence a progression to scurvy as the pups grew and matured.

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“…The trial target dose of 60 g was continued once per week until the initial efficacy evaluation at 12 weeks. Patients were also given a daily oral dose of 500 mg AA from the first infusion, and it was continued for 26 weeks to avoid a hypothetical rebound deficiency following infusion (13). …”

Section: Methodsmentioning

confidence: 99%

Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: a single-arm phase II trial

Nielsen

Højgaard

Andersen

et al. 2017

Transl. Androl. Urol.

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BackgroundAscorbic acid (AA) has in vivo cytotoxic properties at concentrations that can only be achieved through intravenous (IV) administration in humans. Treatment with intravenous AA is widely and increasingly used in complementary medicine despite a lack of clinical evidence for the efficacy of this treatment.MethodsThis non-comparative, single-center, phase II trial included patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC) from an outpatient clinic to evaluate the efficacy and safety of IV AA therapy. Patients received weekly infusions of AA (week 1, 5 g; week 2, 30 g; and weeks 3–12, 60 g) followed by efficacy evaluation at 12 weeks. The primary endpoint for efficacy was a 50% reduction in the prostate-specific antigen (PSA) level. The secondary endpoints included changes in health-related quality of life (HRQoL), biomarkers of bone metabolism, inflammation and bone scans. Clinicaltrials.gov identifier: NCT01080352.ResultsTwenty-three patients were enrolled in this study, and 20 completed the efficacy evaluation at 12 weeks. The mean baseline PSA level was 43 µg/L. No patient achieved a 50% PSA reduction; instead, a median increase in PSA of 17 µg/L was recorded at week 12. Among the secondary endpoints, no signs of disease remission were observed. In total, 53 adverse events (AEs) were recorded. Eleven were graded as “serious”. Three AEs were directly related to AA, and all of which were related to fluid load.ConclusionsInfusion with 60 g of AA did not result in disease remission. This study does not support the use of intravenous AA outside clinical trials.

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Evidence of rebound effect with ascorbic acid

Cited by 15 publications

References 12 publications

Elimination of Ascorbic Acid After High‐Dose Infusion in Prostate Cancer Patients: A Pharmacokinetic Evaluation

Elimination of Ascorbic Acid After High‐Dose Infusion in Prostate Cancer Patients: A Pharmacokinetic Evaluation

Growth, ascorbic acid and iron contents of tissues of young guinea-pigs whose dams received high or low levels of dietary ascorbic acid or Fe during pregnancy and suckling

Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: a single-arm phase II trial

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