KEYWORDS: Vitamin C, Oral absorption, Glucose meters, Ascorbic acid, Intravenous absorption, Bioavailability

Unexpected Early Response in Oral Bioavailability of Vitamin C

By Owen R. Fonorow

Copyright Owen R. Fonorow

Introduction

Repeatable and inexpensive experiments have cast doubt on the hypothesis that only 200 mg of vitamin C taken orally can be absorbed. We measured vitamin C blood plasma levels every minute for the first 40 minutes using a novel approach. By contrast to the prevailing paradigm, our results suggest that up to 4,000 mg of ascorbic acid taken by mouth can produce the same rapid increase in plasma concentration as an intravenous infusion. Previous studies did not sample blood levels during this early stage of oral intake. We confirmed that specific glucose meters can provide a reproducible measure of ascorbate concentration. Researchers had previously demonstrated the ability of specific glucose meters to measure high levels of ascorbate during and after intravenous vitamin C (IV/C).¹ Our initial aim was to confirm the adequacy of the method. However, we observed an initial high rate of oral absorption which may add to understanding of the pharmacokinetics of ascorbate and have clinical and nutritional implications.

Methods

In 2012, we observed that the Abbott Laboratories FreeStyle® Lite glucose meter was responding quantitatively to vitamin C in blood plasma. This is consistent with the similarity of glucose and ascorbate molecules. Biologically, this similarity leads to the cellular uptake of dehydroascorbate by GLUT.^2-4 Hence, the sensitivity to ascorbate in certain meters is expected. Initially, the quantitative response was based on direct observations and reports from members of the Vitamin C Foundation. The observations suggested that there is a practical and inexpensive way of estimating in vivo vitamin C levels.

Not every brand or model of glucose meter is sensitive to ascorbate, and the details of the mechanisms are commercially sensitive. We tested several meters that did not provide a robust measure of ascorbate concentration. It is possible that the FDA considers a glucose meter that reacts to vitamin C flawed. For this reason, manufacturers may be forced to upgrade their meters, rendering future versions of the Abbott and other meters unusable for vitamin C measurements. Ideally, a low-cost finger-prick ascorbate (vitamin C) meter will be made available that makes accurate measurements.

We calibrated the Abbott FreeStyle® Lite glucose meters against accurately measured solutions of ascorbic acid equivalent to concentrations in the blood over the range .5 to 1.5 mg/dl.² The meter provided a linearly proportional response to the ascorbate concentrations measured. Here we are concerned with rapid changes in blood plasma relative to baseline. We compared relative blood concentrations between oral and intravenous and different forms of vitamin C.

The subject in these three experiments was a 61-year-old male Type I diabetic who had fasted for at least 8 hours. Lack of insulin production minimized any physiological insulin related response in the control of glucose levels. Plasma glucose levels were expected to be approximately constant over the period of data collection. Data was obtained using three Abbott FreeStyle® Lite glucose meters that were purchased locally between 2013 and 2015. The data estimation was the result of three different meter readings and individual readings or mean values are plotted. Each Abbott device was checked to confirm that it responded linearly and proportionately to ascorbate concentrations in test solutions comparable with the concentrations expected while the subject was undergoing intravenous infusions of vitamin C.

We found that vitamin C in the form of ascorbic acid taken by mouth raised blood levels significantly more than the same amount of oral sodium ascorbate.

In Experiment 1, we measured ascorbate levels during an IV/C directly into the blood stream. For the IV/C, sodium ascorbate was mixed with sterile water. No dextrose or other sugar was delivered in the IV.

Experiment 2 compares the plasma response of oral intake against the IV infusion. Oral doses were given at 250 mg/min to match the rate of infusion. Plasma levels were again measured minute-by-minute over the same duration as the short IV.

Experiment 3 compared a single dose of ascorbic acid by mouth (10 grams) that was equivalent with the amount given IV. Measurement were again taken minute-by-minute over a period of 40 minutes.

Results

Figure 1 shows the results of an infusion of 10 grams of ascorbate (provided as 11.3 grams of sodium ascorbate) introduced at the rate of 250 mg/minute for 40 minutes. The data from the three Abbott meters were highly correlated.

The chart in Figure 1 shows the rapid rising levels of vitamin C measured in the blood and the decline towards the end of the IV session. The IV bag emptied at minute 34, and the line drained and the needle was removed at minute 40. The increase in concentration from the IV is also consistent with our in vitro measurements. The decline at the end of the IV illustrates the short 30-minute half-life of the vitamin. To a first approximation, we take the fasting subject’s glucose levels to be constant over this period.

Figure 1. Measurements at one minute intervals during a 10 gram IV infusion of vitamin C. Three Abbott meters are shown indicating a consistency of measurement.

END FIGURE

Figure 2 compares the response from oral ascorbic acid versus IV administration. The subject was administered vitamin C at the same rate as the infusion, i.e., 250 mg of ascorbic acid by mouth every minute for 40 minutes.

There was little difference in bioavailability of oral ascorbic acid and IV for the first 4,000 mg at the rate of 250 mg/minute. The results are similar for the initial period but diverge after 15 minutes. Indeed, the initial oral measurements appear greater than obtained with the IV suggesting an efficient absorption through the stomach wall.

After this period, the oral blood levels declined. The decline in the rate of absorption may reflect the increase in stomach pH as ascorbic acid buffered the stomach contents (HCl).

Figure 2. Oral versus IV: IV measurements with solid lines, and the oral intake with dashed lines. This plot averages the 3 glucose meters.

END FIGURE

In Figure 3, we measured the blood concentrations after a single oral dose of 10 grams of ascorbic acid, again using all three meters. The blood levels spiked early and profoundly. The maximum levels varied slightly from minute 3 to minute 7. The initial peak had declined back towards baseline by the fifteen minute. This initial high level was consistent with the results in Figure 2 in suggesting a rapid initial absorption of oral ascorbic acid. During the first 12 minutes, blood concentrations of vitamin C were substantially higher than the levels produced by the intravenous infusion.

Oral ascorbic acid can produce transient high blood levels of vitamin C in one subject. These transient high levels would be missed by any experiment with a longer measurement period. Rapid minute-by-minute measurements are required to observe these high values.

Figure 3. Time series following a single oral dose versus IV. All three meters are plotted.

Discussion

The vitamin C absorption findings reported here are now generally practical because some glucose meters are sensitive to and can be used to report ascorbate levels in the blood.¹ This sensitivity appears to give a linear quantitative response and reproducible measurements. While plasma glucose is greater than ascorbate levels, in a fasting individual glucose levels are expected to be approximately constant over the periods considered. In this diabetic subject, there was no physiological change in insulin glucose control. We observed that the meter’s response to ascorbate was greater than that to glucose presumably related to a redox aspect of the measurement. These minute-by-minute measurements are new to the literature, partially because of the practical difficulty in collecting and then storing blood for so many measurements but also, perhaps, reflecting the unexpected nature of the rapid oral response.

While the response was unexpected, it is consistent with known pharmacokinetics of weak acids. A weak acid like ascorbate is in the associated relatively non-polar state in the low pH of the stomach becoming more lipid soluble. Weak acids often absorb rapidly from the stomach. However, if the stomach acid is increased, the weak acid disassociates and the polarity inhibits transfer across cell membranes.

In this preliminary report, we show that during a slow intravenous infusion of 10 grams of vitamin C, three separate meters report a steady increase in measured ascorbate, consistent with the increased concentration of vitamin C in the blood. At the end of the infusion, all three meters showed the decrease in blood levels consistent with ascorbate’s 30 minute half-life and the Dynamic Flow theory of ascorbate.^6,7

We considered our IV/C measurements provided an approximation to a 100% bio-availability baseline. Experiment 2 compared comparable vitamin C intakes orally and by IV at 250 mg every minute. The oral absorption should have been less than or equal to the direct injection concentrations, but the measured plasma levels were comparable.

The minute-by-minute readings comparing the IV infusion for the first 15 minutes (or 4000 mg) lead to the reasonable conclusion that a similar amount of vitamin C entered the blood stream. Some prior research had reported that only about 250 mg can be absorbed before tissue saturation.^8,9 However, measuring vitamin C in the urine or waiting too long to begin blood measurements would have missed the rapid absorption.

In the third experiment, a single dose of 10 grams of vitamin C as ascorbic acid was consumed all at one time. These measurements were compared to the slow intravenous infusion. The surprising finding is that in the first few minutes, the rapid oral absorption of 10 grams of ascorbic acid created higher blood levels than the IV/C.

One objection to these case study data is individual variation in this preliminary study. This reservation is accepted and is common to case studies, which nevertheless can convey interesting observational data. The measurement is direct, using a technique established elsewhere.¹ Moreover, it would appear that some individuals’ large intakes of vitamin C may be rapidly absorbed initially from the oral route. It remains to be established how frequent this phenomenon is in the population. Moreover, if replicated the observations may provide an alternative to IV administration of ascorbate now being trialed in cancer.^10-21 If the process is one of rapid weak acid absorption from the stomach, it may be possible to maintain stomach acidity and promote rapid oral absorption of large doses of vitamin C, at least in some individuals. Consistent with this interpretation we have observed that while ascorbic acid can be rapidly absorbed in to the blood stream, sodium ascorbate raises blood levels more slowly.

Vitamin C blood levels must be measured repeatedly within 30 to 40 minutes to obtain an accurate reading of how much vitamin C enters the blood stream. Cathcart described how people who are sick and under stress can tolerate very high oral intakes of vitamin C.²² The Cathcart bowel tolerance amounts, sometimes as high as 200 grams daily, are difficult to reconcile with the current paradigm if blood plasma saturates at 250 mg. Cathcart also reported that he could only obtain “a clinical ascorbate effect” orally with ascorbic acid, not mineral ascorbates. The rapid early absorption and utilization of ascorbic acid presented here, previously unknown, may help explain the phenomenon.

Acknowledgements

Steven Hickey, PhD, whose advice and counsel was invaluable to this paper.

Thomas Hesselink, MD measured the ascorbate and oversaw the IV.

Forum member johnwen did the initial charts.

Vitamin C Foundation staff member Jerry Nowlin updated the charts.

Feedback from members of the Vitamin C Foundation forum.

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