Bioavailability of Vitamin C

[ofonorow]

Then by all means, please keep posting the graphs! Thank you.

For the next experiments, I want to keep all conditions the same as the IV baseline. (Per water discussion, we know a) the meter can read vitamin C without glucose, and b) I did discover that even having a cup of coffee about an hour later had no effect on the 165 mg/dl reading afterwards.)

After these experiments, I am willing to investigate whether taking Lantus changes the readings. And I do want to try the 2 to 4 hours out investigations, especially with liposomal. (Although that is a long time without coffee in the morning!)

Added - just noticed the post previous to your last post johnwen. And the thought occurs that the reason for the 2 to 4 hour spike may not be related to the kidney, rather the oral vitamin C that is traveling down the intestines - and finally reaches the blood stream. (From a Levy book I learned that generally carbs leave the stomach in 2 hours, proteins in 4 hours and fats in 6 hours.)

[ofonorow]

Measurements of 10 gram UltraFINE ascorbic acid powder in one gulp (4 oz of water).

Due to some stress, I consider these numbers a practice or dry run as my own cortisol may have spiked! (One meter (b) read over 400 during the baseline, so we switched to a new meter, so B in the previous reading is new). My initial baselines were about 10 points higher than last week, we started earlier (didn't have to drive to doctors). Even if not perfect, the numbers do illustrate that if you are not looking early (first minute!?) you miss a lot of the action from taking ascorbic acid by mouth.

Code: Select all

Baselines
A.    134 mg/dl
B.    140 mg/dl  (new B)   after old meter > 400
C     135  mg/dl

Minute 0 - gulped 10 grams ascorbic acid in 4 oz water.

Code: Select all

Meter             Minute               Reading

A                    +1                  247
   B+               +2                         304
       C             +3                                 163
A                    +4                 147
   B+               +5                         259
        C            +6                                 280
A                    +7                  202
   B+               +8                         215
       C             +9                                255
 A                  +10                  207
    B+             +11                        170
       C            +12                               169
 A                  +13                164
   B+              +14                       140
      C             +15                              142
 A                  +16                159
   B+              +17                        157
       C            +18                              200
A                    +19               196
   B+               +20                      167
       C             +21                            188
A                    +22                145
   B+               +23                       149
       C             +24                             152
A                    +25                141
   B+               +26                       145
       C             +27                             156
A                    +28                146
   B+               +29                        148
       C             +30                               140
A                    +31                 176
   B+               +32                         160
       C             +33                                140
A                    +34                  161
   B+               +35                          185
       C             +36                                 147
A                    +37                 147
   B+               +38                          150
       C             +39                                  142
A                    +40                159
   B+               +41                          143

Paused measurements

       
A                    +45                 145
 
   B+               +50                  142

Notes: Remember this is not a slow IV drip into the vein, there are probably multiple pathways for ascorbate to enter the blood stream, which may explain some of the small spikes.

But the question remains - how in the heck does so much reach the blood stream in the first minute!

Part of the plan is to compute the deltas from baseline for 40 minutes - IV and oral - and add them up as a simple comparison of bioavailability.

[Johnwen]

[ofonorow]

That was quick johnwen! Thank you. (Added the old chart so we can see them together.) Sort of opposite tracks as you might expect. And I wonder if there is some kind of insulin response for the rapid decline in the oral measurements.

My first thought was to measure the delta between the baseline (or better, the last measurement) - which seems show how much vitamin C entered the blood. But this is more difficult in the oral case, because not all may get into the blood stream right away, so there is both an into the blood flow and out flow? at the same time.

Added - didn't check all numbers but noticed the 304 (B+) for minute 2 was missing.

More - some other observations.

Peak of the IV when the 10 grams ran out of the bag was 210 (or 90 above) baseline. Rate approximately 22.5 point increase every 10 minutes if the IV had been continued. So next gram (4 minutes) in bag should have reached oral peak.

Oral immediately reached 233 (average of first six measurements). One could argue for the amount up to 10 grams, that oral is more bioavailable than IV - up to probably 11 grams.

In theory, if a larger IV increases at the same rate, then 50 gram (or 200 gram) IV/Cs should raise the blood levels to the heights that some researchers report - over time

And 10 grams is probably close to the max one-time oral intake. (However, we may be seeing why a 8-10 gram dose, every 20 minutes, for 2 hours, cures the common cold

[Johnwen]

Here I combined the Oral & IV graphs together. It got kind of crowded so I Thickened the IV Lines for contrast!!





This is a comparison of Oral & IV on Meter A




This is a comparison of Oral & IV on Meter B



This is a comparison of Oral & IV on Meter C





Just having Fun on a rainy Saturday!

[pamojja]

Just having Fun on a rainy Saturday!

Also interesting area under the curve!

[ofonorow]

Thank you johnwen. Very nice. We may be close to being able to rest our case

Me thinks we have illustrated the point that oral ascorbic acid makes it into the blood stream, in my case, without much loss compared with IV/C.

And we have shown that any measurements of oral vitamin C which ignored the first fifteen minutes would have missed all this action.

And again, other than possibly the Hickey/Roberts "weak acid through the stomach wall" explanation, we are at a loss to explain how in one minute, so much"glucose" (vitamin C) is detected in the fingers!?

Have to reorder more test strips, so we have time to consider the next experiment...

1) 250 mg orally every minute experiment for the direct comparison with IV/C.

2) For completeness, 11.3 grams of sodium ascorbate orally. Might as well gulp because if previous experiments were valid, this will be a much lower curve (more like time release)

3) We have never measured liposomal in the blood this way, but the reason is probably that we didn't wait long enough.. (3 or 4 hours without coffee doesn't sound like fun though.)

4) Not sure I want to take 10 grams of sugar (or glucose) all at once, but I am curious if the blood sugar would spike in the first 10 minutes like the vitamin C did? If so, we could speculate that glucose/ascorbate share the same pathway quickly into the blood stream.

And here is a conversion of the numbers from mg/dl to umol/l - to compare the numbers with recent studies and Hickey.

From this wiki (and a check of the numbers given the atomic weight of ascorbic acid (C6H8O6) with a molar mass of 176.12) the kidney threshold I am familiar with is 1.5 mg/dl which is 85 umol/l. See vitamin C (ascorbic acid) down the pagehttps://en.wikipedia.org/wiki/Reference_ranges_for_blood_tests The conversion factor for ascorbic acid is 56.78, so you multiply the mg/dl by 56.78 to get the umol/l number. Checking 1.5 mg/dl * 56.78 = 85.17 umol/l

The highest IV was 210 mg/dl 11,923.800000000001 umol/l
The highest oral was 304 mg/dl 17,261.12 umol/l

The problem is the glucose reader thinks its measuring glucose with a molar mass of 180.16, so the actual numbers are a few percent less.

And we need to deduct the glucose (approximately 130 mg/dl) for the vitamin C part... later

Here is a web conversion tool. http://www.endmemo.com/medical/unitconvert/Vitamin_C.php with a batch mode..

For the record, here is the conversion of the first 40 minutes of raw IV data.

Code: Select all

147,143,143,152,146,152,159,150,162,159,164,159,168,164,174,162,167,173,179,174,178,175,187,189,187,199,191,211,207,200,207,198,210,210,199,200,197,191,194,184

8346.66
8119.54
8119.54
8630.56
8289.880000000001
8630.56
9028.02
8517
9198.36
9028.02
9311.92
9028.02
9539.04
9311.92
9879.72
9198.36
9482.26
9822.94
10163.62
9879.72
10106.84
9936.5
10617.86
10731.42
10617.86
11299.22
10844.98
11980.58
11753.460000000001
11356
11753.460000000001
11242.44
11923.800000000001
11923.800000000001
11299.22
11356
11185.66
10844.98
11015.32
10447.52

here is the conversion of the first 40 minutes of oral data.

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247,304,163,147,259,280,202,215,255,207,170,169,164,140,142,159,157,200,196,167,188,145,149,152,141,145,156,146,148,140,176,160,140,161,185,147,147,150,142,159

14024.66
17261.12
9255.14
8346.66
14706.02
15898.4
11469.56
12207.7
14478.9
11753.460000000001
9652.6
9595.82
9311.92
7949.2
8062.76
9028.02
8914.460000000001
11356
11128.880000000001
9482.26
10674.64
8233.1
8460.22
8630.56
8005.9800000000005
8233.1
8857.68
8289.880000000001
8403.44
7949.2
9993.28
9084.8
7949.2
9141.58
10504.300000000001
8346.66
8346.66
8517
8062.76
9028.02

And finally for my last trick, lets look at the vitamin C portion of the highest measurements

Code: Select all

IV/C   210  -  124 (glucose baseline) =  86 mg/dl    ==>   approximately   4,883.08  umol/l
Oral   304  -   134 (glucose baseline) =   170 mg/dl   ==>   approximately   9,652.6   umol/l

What did the NIH say was the highest oral concentration achievable

Added, this from Hickey
Pharmacokinetics of Oral Vitamin C
http://www.livonlabs.com/proof/Dr_Hickey_Clinical_Study_Published.pdf

Of the 15 000 measurements, the highest recorded serum value in a subject not receiving intravenous vitamin C was 220 umol/L . This is consistent with the published maximum value. With intravenous administration, Biolab have recorded plasma values in excess of 5000 umol/l, in subjects under ascorbate treatment for osteosarcoma

[Johnwen]

[ofonorow]

Good idea on the glucose (only) 10 grams johnwen. But will probably do glucose last as each test is probably $40 in test strips

I shared your combined graph with Dr. Hickey and this was his early response:

Hi Owen,

It would be very interesting indeed if a proportion of vit C is absorbed quickly.

The first question you are likely to be asked is: how have you calibrated the measuring device?

This may be me asking granny to suck eggs but I have experience of specialist labs badly messing up vitamin C measurements...

Do you have a response curve for ascorbic acid in distilled water?
Do you have a response curve for glucose in distilled water?
Then you need response??
s obtained by adding ascorbic acid to different physiological concentrations of glucose.

You may have all of these but I am particularly short of time for the next few days and unable to search through your forum properly.

Note in the discussion of pharmacokinetics to always remember Cathcart's bowel tolerance.
The dominant data is for healthy individuals and the experimenters ignore Cathcart.
Ignoring bowel tolerance is nuts but there are (of course) political and financial reasons for the data being restricted in this way.

Keep experimenting

Steve

[OxC]

[ofonorow]

Thank you OxC for the professional calibration technique, which I may try if I can obtain the whole blood. (Not sure why the EDTA should be added as this is not the condition in our blood streams?)

At this point, the reason we call these measurements "crude", are because the precise numbers are not material to the argument that ascorbic acid (if it is indeed being measured) enters the blood stream much more rapidly than has been so far reported.

There may be a way to calibrate based on the 10 gram IV/C numbers to help determine the approximate meter readings. (sanity check) 10 grams was infused over 40 minutes, or 2.5 grams every 10 minutes, or 250 mg every minute.

For example, the baseline reading for the IV was 124 mg/dl (assuming 1.5 mg/dl vitamin C)

After 10 minutes the readings were approximately 160 mg/dl - about 35 mg/dl higher after approximately 2.5 grams infused. Final numbers depend on the blood volume

5 liters
In an average healthy adult, the volume of blood is about one-eleventh of the body weight. Most sources state the volume of blood in an average human adult, who is between 150 to 160 pounds, as between 4.7 and 5 liters, although the more recent sources state the volume of blood in an average adult as 4.7 liters

2.5 grams is 2500 mg, so we are adding 2500mg/50 DL (5 liters) which reduces to 50 mg/dl as a rough approximation. (35 mg/dl measured increase versus 50 mg/dl predicted, although I am unfortunately larger than the typical male.)

[OxC]

(Not sure why the EDTA should be added as this is not the condition in our blood streams?)

It's just that whole blood without anticoagulant will clot (coagulate) in about 5 or 10 minutes, so there isn't time to make dilutions and perform the tests before the blood turns into a lump instead of a fluid.

At this point, the reason we call these measurements "crude", are because the precise numbers are not material to the argument that ascorbic acid (if it is indeed being measured) enters the blood stream much more rapidly than has been so far reported.

"...ascorbic acid (if it is indeed being measured)" is one question that this procedure will answer.

[ofonorow]

Measurement #3 - 11.3 grams sodium ascorbate in 4 oz water by mouth (gulp)

Baselines
A 99 mg/dl
B 112 mg/dl
C 112 mg/dl

Time 0 - gulped the 11.3 grams sodium ascorbate.

Code: Select all

Meter                  Time                      Reading
A                          +1                          117
  B                        +2                               116
    C                      +3                                    142
A                          +4                         128
  B                        +5                                140
    C                      +6                                      138
A                          +7                          129
  B                        +8                                 137
    C                      +9                                       113
A                         +10                          134
  B                       +11                                124
    C                     +12                                      128
A                         +13                         131
  B                       +14                                 198         ** felt like a bad reading - meter took too long to report
    C                     +15                                       128
A                         +16                         127
  B                       +17                                 130
    C                     +18                                       145
A                         +19                          135
  B                       +20                                 120
    C                     +21                                        129
A                         +22                           131
  B                       +23                                 127
    C                     +24                                        128
A                         +25                           147
  B                       +26                                 130
    C                     +27                                        120
A                         +28                           123
  B                       +29                                 125
     C                    +30                                        136
A                         +31                           132
  B                       +32                                  129
    C                     +33                                        131
A                         +34                            129
  B                       +35                                  128
    C                     +36                                        138
A                         +37                           132
   B                      +38                                  129
      C                   +39                                         129
A                         +40                           134

Observations.

#1. No matter what we are measuring (my theory is we are measuring ascorbate, rather than glucose, although not necessarily the numbers shown on the meter) this experiment illustrates the difference between the oral consumption of ascorbic acid and sodium ascorbate.

Brings us back to the mystery: Why does so much more ascorbic acid get absorbed into the blood stream so rapidly?

#2 Even sodium ascorbate raises blood levels in the first few minutes.

#3 My guess is that sodium ascorbate absorption generally follows the traditional thinking and has to travel down the gut so that the absorption is spread out over time.

[tjohnson_nb]

Personally, I can feel the effect of ascorbate in the first few minutes after a tsp. It's a sort of increase in energy and more positive outlook. It does seem to be short-lived though I'm sure I still get all the other benefits. That sort of matches your numbers.

[Johnwen]

Ya think??? you can find the answer to your question in this quote??
What does V-C look like Chemically???

THEN, you are asked to drink a liquid of pure glucose and water,
Then, We take more glucose readings over the next 1-4 hours.

These readings allows us to draw a GRAPH, showing your body's response to glucose.
In ALL cases, you body will show a sudden "spike" in the blood sugar level almost immediately after you drink the fluid.