Dr. Ron’s Research Review – September 27, 2017

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This week’s research review focuses on IV vitamin C reduces fatigue.

A double-blind randomized controlled trial found that intravenous vitamin C administration reduces fatigue in office workers. (Suh et al., 2012)
A group of 141 healthy volunteers; the treatment group (n=73) received 10 grams of vitamin C with normal saline intravenously, while the placebo group  (n=74) received normal saline only.
The fatigue scores measured at two hours after intervention and one day after intervention were significantly different between the two groups (p = 0.004); fatigue scores decreased in the vitamin C group after two hours and remained lower for one day.
Trial also led to higher plasma vitamin C levels and lower oxidative stress compared to the placebo group (p < 0.001, p < 0.001, respectively).
The effect of vitamin C injection was evident in subjects with an initially lower vitamin C level and not in subjects with initially higher levels. Fatigue was reduced in the lower baseline vitamin C level group after two hours and after one day (p = 0.004). The same did not hold for the higher baseline group (p = 0.206). 
Thus, intravenous vitamin C reduced fatigue at two hours, and the effect persisted for one day.

Until recently, oral and intravenous vitamin C were considered equivalent, but recent data has shown different pharmacokinetic characteristics. Plasma concentrations of vitamin C following oral administration are not dose-dependent, and are instead subject to a plateau. Vitamin C distribution after oral delivery is tightly controlled by intestinal absorption, transport to tissues, and renal reabsorption and excretion. Intravenous administration could achieve 70-fold higher blood levels of vitamin C compared to the highest tolerated oral dose.

 

Dr. Ron


 

Articles

Vitamin C pharmacokinetics: implications for oral and intravenous use.
            (Padayatty et al., 2004) Download
BACKGROUND:  Vitamin C at high concentrations is toxic to cancer cells in vitro. Early clinical studies of vitamin C in patients with terminal cancer suggested clinical benefit, but 2 double-blind, placebo-controlled trials showed none. However, these studies used different routes of administration. OBJECTIVE:  To determine whether plasma vitamin C concentrations vary substantially with the route of administration. DESIGN:  Dose concentration studies and pharmacokinetic modeling. SETTING:  Academic medical center. PARTICIPANTS:  17 healthy hospitalized volunteers. MEASUREMENTS:  Vitamin C plasma and urine concentrations were measured after administration of oral and intravenous doses at a dose range of 0.015 to 1.25 g, and plasma concentrations were calculated for a dose range of 1 to 100 g. RESULTS:  Peak plasma vitamin C concentrations were higher after administration of intravenous doses than after administration of oral doses (P < 0.001), and the difference increased according to dose. Vitamin C at a dose of 1.25 g administered orally produced mean (+/-sd) peak plasma concentrations of 134.8 +/- 20.6 micromol/L compared with 885 +/- 201.2 micromol/L for intravenous administration. For the maximum tolerated oral dose of 3 g every 4 hours, pharmacokinetic modeling predicted peak plasma vitamin C concentrations of 220 micromol/L and 13 400 micromol/L for a 50-g intravenous dose. Peak predicted urine concentrations of vitamin C from intravenous administration were 140-fold higher than those from maximum oral doses. LIMITATIONS:  Patient data are not available to confirm pharmacokinetic modeling at high doses and in patients with cancer. CONCLUSIONS:  Oral vitamin C produces plasma concentrations that are tightly controlled. Only intravenous administration of vitamin C produces high plasma and urine concentrations that might have antitumor activity. Because efficacy of vitamin C treatment cannot be judged from clinical trials that use only oral dosing, the role of vitamin C in cancer treatment should be reevaluated.

Summaries for patients. How vitamin C is administered affects how much reaches the bloodstream and may affect the results of studies of its potential effect on cancer.
            (Padayatty, 2004) Download


 

Intravenous vitamin C administration reduces fatigue in office workers: a double-blind randomized controlled trial.
            (Suh et al., 2012) Download
BACKGROUND:  Studies of the efficacy of vitamin C treatment for fatigue have yielded inconsistent results. One of the reasons for this inconsistency could be the difference in delivery routes. Therefore, we planned a clinical trial with intravenous vitamin C administration. METHODS:  We evaluated the effect of intravenous vitamin C on fatigue in office workers. A group of 141 healthy volunteers, aged 20 to 49 years participated in this randomized, double-blind, controlled clinical trial. The trial group received 10 grams of vitamin C with normal saline intravenously, while the placebo group received normal saline only. Since vitamin C is a well-known antioxidant, oxidative stress was measured. Fatigue score, oxidative stress, and plasma vitamin C levels were measured before intervention, and again two hours and one day after intervention. Adverse events were monitored. RESULTS:  The fatigue scores measured at two hours after intervention and one day after intervention were significantly different between the two groups (p = 0.004); fatigue scores decreased in the vitamin C group after two hours and remained lower for one day. Trial also led to higher plasma vitamin C levels and lower oxidative stress compared to the placebo group (p < 0.001, p < 0.001, respectively). When data analysis was refined by dividing each group into high-baseline and low-baseline subgroups, it was observed that fatigue was reduced in the lower baseline vitamin C level group after two hours and after one day (p = 0.004). The same did not hold for the higher baseline group (p = 0.206). CONCLUSION:  Thus, intravenous vitamin C reduced fatigue at two hours, and the effect persisted for one day. There were no significant differences in adverse events between two groups. High dose intravenous vitamin C proved to be safe and effective against fatigue in this study. TRIAL REGISTRATION:  The clinical trial registration of this trial is http://ClinicalTrials.govNCT00633581.

 

 

References

Padayatty, SJ (2004), ‘Summaries for patients. How vitamin C is administered affects how much reaches the bloodstream and may affect the results of studies of its potential effect on cancer.’, Ann Intern Med, 140 (7), I61. PubMed: 15069006
Padayatty, SJ, et al. (2004), ‘Vitamin C pharmacokinetics: implications for oral and intravenous use.’, Ann Intern Med, 140 (7), 533-37. PubMed: 15068981
Suh, SY, et al. (2012), ‘Intravenous vitamin C administration reduces fatigue in office workers: a double-blind randomized controlled trial.’, Nutr J, 11 7. PubMed: 22264303