Bioavailability of Vitamin C

[ofonorow]

So, does any one have any idea how our meters can begin registering ascorbic acid (but not sodium ascorbate) within a minute or two on an empty stomach? (Or how Bernstein, a type 1 diabetic (no insulin) reports virtually the same time table for registering glucose? He from minute 3 to minute 40. I am still stumped.

Going back over some email from Dr. Steve Hickey...

?Approx effect of 200 dextrose compared with 150 AA is

A 194 - 118 = 76 compared with 205 for AA
B 200 - 109 = 91 compared with 168 for AA
C? 170 - 127 = 43 compared with 180 for AA
?

Notes.

?Looks like we have an experiment that demonstrates that these meters do indeed measure ascorbic acid.


?The AA is having a larger effect than glucose. So the question is does the meter measure reduction potential or similar (glucose is a reducing sugar)? Check but I think you will find AAs reduction potential is more than twice the magnitude of glucose (as you might expect).

This would explain the measurements and help validate the technique. Have you asked the manufacturer how the measurement is made? They don't need to provide their secrets just give an indication (e.g. tell you it is a redox measurement).

and from another email..

We know rather little about absorption of vit C from the intestines. ?
The researchers are doing a lot of hand-waving and ignoring bowel tolerance.

But ascorbic acid seems to be getting into the blood too rapidly for it to be moving past the stomach.


?You may be right.
You have some direct measurements of the process.
You have a standard mechanism - increased lipid solubility of small organic acids in the stomach.

Hypothesis 1: standard antacid drug that does not form a salt with ascorbic acid (tagamet? or similar) should tend to make the stomach alkaline and block the rapid absorption.
Hypothesis 2: betaine HCl should make an alkaline stomach more acid and increase the amount of quick absorption.
Experiments to test these hypotheses would need a little care in implementation.

?Note ascorbic acid would itself buffer the (more acid) stomach and increase its pH.
Which leads to another question: is self-buffering the reason for the brief period of absorption?

?As always, I hope these comments are useful.?

You are building a case for an interesting and potentially useful finding.

[ofonorow]

This is a draft of the abstract to a paper that was passed to Dr. Steve Hickey for comment

Bioavailability of Vitamin C as Measured by Glucose Meters Sensitive to Ascorbate.

This paper details experiments measuring vitamin C levels in the blood using a standard glucose meter. Both intravenous vitamin C (sodium ascorbate) and oral vitamin C intakes were measured every minute. Vitamin C levels rose unexpectedly as early as minute 3, peaked by minute 20. This rapid uptake of ascorbate into the blood was unexpected and has been missed by previous experiments that waited more than 30 minutes to take the first measurements. Furthermore, our experiments demonstrate that at the rate of 250 mg/minute, both oral (ascorbic acid) and IV/C (sodium ascorbate) availability to the blood stream is equivalent for the first 4000 mg. This quick 'spike' effect on blood concentrations was only observed for ascorbic acid (orally.) The salt form produced lower plasma levels that were as classically expected. An explanation for the absorption is provided with reference to the classical pharmacokinetics of weak acids.

[ofonorow]

Another topic is discussing the "pharmacokenitics" of weak acids, http://www.vitamincfoundation.org/forum/viewtopic.php?f=3&t=12165 This "classical" knowledge would explain the ascorbic acid (a weak acid) entry into the blood stream through the stomach wall. (A corollary is that a weak base is diffused in a high pH (alkaline) environment, such as the small intestine. This would help explain why sodium ascorbate is not absorbed in the acidic stomach, but takes more time to move to the intestine.)

I am considering a protocol to test the weak-acid hypothesis which involves taking the proton-pump blocking drug (now over the counter) Nexium. I only want to do this once! Thoughts, input, advice appreciated.

This is a link on the pharmacokentics of Nexium, but I really don't understand it.
http://www.rxlist.com/nexium-drug/clinical-pharmacology.htm
I am trying to find information on how many Nexium pills I would have to take to substantially increase the pH of the stomach fluids. (A lot of the information in that link is how much Nexium is absorbed into the blood stream, and excreted. Perhaps it works through the blood stream, where it then reaches the stomach Chief cells? i.e. it may not work within the stomach after ingestion?)

I'd like to be able to take one 40 mg Nexium before bed, and then perhaps a pepcid AC in the morning before I repeat the 10 g ultrafine ascorbic acid measurement. (From that link I gather that I may have to take Nexium for 5 days? Johnwen do you concur? Is there a way to measure stomach pH?)

What about taking 10 grams of baking soda, measure for a while, and then taking 10 grams of ascorbic acid? (The problem with this is the variable of producing sodium ascorbate in the stomach).

I want to repeat the experiment with the only difference being reduced stomach acidity.

Added - also found this on the pharmacokentics of Pepsid AC
http://www.rxlist.com/pepcid-drug/clinical-pharmacology.htm

The primary clinically important pharmacologic activity of PEPCID is inhibition of gastric secretion. Both the acid concentration and volume of gastric secretion are suppressed by PEPCID, while changes in pepsin secretion are proportional to volume output.

In normal volunteers and hypersecretors, PEPCID inhibited basal and nocturnal gastric secretion, as well as secretion stimulated by food and pentagastrin. After oral administration, the onset of the antisecretory effect occurred within one hour; the maximum effect was dose-dependent, occurring within one to three hours. Duration of inhibition of secretion by doses of 20 and 40 mg was 10 to 12 hours.

Single evening oral doses of 20 and 40 mg inhibited basal and nocturnal acid secretion in all subjects; mean nocturnal gastric acid secretion was inhibited by 86% and 94%, respectively, for a period of at least 10 hours.

[Johnwen]

First a question???
Do you like Oat Meal??
Why? Because it's probably the only thing you'll be able to keep down after this test. If you eat anything else it'll go thru the intestines like rocks and fast also!!!

Sure stomach acid levels can be tested if you don't mind a tube being stuffed down your throat!! Not a pleasant experience to say the least!!

The day before you do this test go on a liquid diet and fast kind of like getting ready for a colonoscopy without the clean out process! This will allow the stomach acid production to slow to a crawl then adding the esomeprazole should prevent or stop the sudden production of acid that food or nutrients induces.

My thought on the prep part is you'll probably feel pretty good on the onset of it since your body will start using reserves for fuel and you may experience a rise in your sugar levels also. During the test part you probably will experience some discomfort and be wondering why the heck your doing this.
Do not take any more acid blockers!!
Now after it, is when the FUN? Starts! You'll probably be well advised not to eat anything but oat meal or mushy slurry of food for about 8 hours then into the next day eat only light small amounts of food. Do this with plenty of fluids (water) and as they say, 'wait for it!' You'll more then likely experience what could be termed, 'The second phase of the colonoscopy prep!' after that clears things should return to normal. You'll might feel better as you have detoxed your GI system!

Me I'm never happy when I have to prep for a colon check and what your doing is very similar except the addition of a acid blocker and the test your performing. Good Luck!!!
Here's some more info that may help in understanding how the Nexium works etc.

http://www.drugs.com/monograph/esomepra ... esium.html

http://www.drugs.com/pro/esomeprazole-capsules.html

[ofonorow]

Good prep advice. Thank you! Maybe there is another way?

Your links johnwen show that Nexium can be given IV which indicates it does act through the blood stream and the study data indicated it can take days to become totally effective . It may be possible to get the reduced acidity effect with Pepsid AC, which seems to work within an hour and last for about 10 hours. (I remember getting pepsid AC in the hospital after surgery when I wasn't eating with no apparent ill effects.)

The problem of reducing stomach acidity is two-fold.
a) stopping the production of stomach acid
b) reducing the acidity of any acid before doing the experiment.

While Nexium may require days to be effective, apparently Pepsid AC works within one hour and the anti-acid effect (stopping the secretion of stomach acid) can last from 5 to 10 hours.

Please comment on the following protocol.

1. Take 40 mg Pepsid AC before bed.
2. Upon waking, taking another Pepsid AC and also take 1 teaspoon (approx 4g) of baking soda to reduce any acidity in the stomach.
3. Wait sufficient time for the baking soda to leave the stomach. (I am guessing that 2 hours will be long enough?)

Hypothesis is that my stomach acidity would now be around pH 5.

Rerun the 10 grams Ultrafine Ascorbic Acid experiment measuring every minute for 30 minutes.

Results - if the curve looks identical, (high absorption) then the hypothesis about passive diffusion (weak acids) would be refuted.

If the curve looks more like the sodium ascorbate, the hypothesis is strengthened.

Follow-on

At that point I should be able to add stomach acid, i.e., betaine HCL . Rather than waiting for the next day, perhaps a better idea (if the results are more like sodium ascorbate) would be to then take Betaine HCL, (wait how long?) and rerun the experiment?

The idea is to determine whether the increased acidity increases the bioavailability in the second run.

The issue with the follow-on close in time is tissue saturation leading to bowel tolerance/diarrhea.

Comments?

[Johnwen]

This kind of bothered me with your idea of adding Betaine HCL after doing the first phase of the test. When you take Pepcid AC (Famotidine) it basically shuts down the stomach production of all gastric secretions. Which means as it's potency decreases the stomach secretions will rebound. This with one time dosing like your planning. What this means if you add extra acid to the mix within it's effective time range your going to have the rebound acid and the external acid hit a basically unprotected stomach. Which can cause OWEN to be clinching his stomach in the fetal position on the floor.

Action And Clinical Pharmacology: Famotidine is a competitive inhibitor of histamine H2-receptors. The primary clinically important pharmacologic activity of famotidine is inhibition of gastric juice secretion. Famotidine reduces the acid and pepsin content, as well as the volume, of basal, nocturnal, and stimulated gastric secretion.

http://www.rxmed.com/b.main/b2.pharmace ... %20AC.html

I would wait at least 24 hours before trying the elevated acid induced by Betaine HCL to try the elevated acid test!

As far as the Baking soda if you use Pepcid AC it's a GO!

However if you use Nexium or any of the others acid blockers it's a NO!

Because any other acid changing substances cause these drugs to be less effective.

Most if not all of the OTC acid blockers are time release however they reach peak effective value of 40-50% between 1-4 hours even the enteric coated ones.
So taking them before bed and about 2-3 hours before testing should give the acid lowering effect your looking for!

Just remember your basically shutting off your stomachs normal productions and when it comes back on line it does so with vigor meaning extra acid's will be produced so don't do anything that add's to this rebound action!!!
Especially if you ate anything during it's off time!
Hope this helps and remember, 'First do no harm!'

[ofonorow]

Thanks again. So we'll see what happens with pepsid/baking soda and not try the betaine HCL on the same day.

Added.

I will lower the dosage from 10 grams to 5 grams Ultrafine and do the experiment this way.

Day 1 - Take the Betaine HCL and do the standard 40 minute measurements after the 5 gram gulp.

Day 2 - Take Pepsid AC night before, then Pepsid AC and Baking soda upon waking. Run second set of measurments after a 5 gram gulp

This will provide another set of measurements with a lower dosage. Note, if 4000 mg is the most that can be absorbed per the IV simulation, then these numbers should be very similar to the 10 gram gulp.

[ofonorow]

Unexpected results from repeating the experiment with 5,000 mg instead of 10,000 mg of Ultrafine ascorbic acid (and after taking a Betaine HCL tablet). Did not see the expected elevation, so there is no reason at this point to try the baking soda with 5,000. (I will first have to repeat the 10 g w/Betaine HCL and see what happens)

It may very well be that 8 to 10 grams are required to create the early spikes we have measured.

The TrueResult readings are presumably glucose-only - no ascorbate.

Baselines

TrueResult 113
Meter A 135
Meter B 132 Took the 600 mg NOW Foods Betaine HCL tablet, waited 2 minutes
Meter C 132

Consumed 5,000 mg of DSM Quali-C Ultrafine ascorbic acid.

Code: Select all

Meter                 Time                    Reading
A                        1                          158                         (** maybe I read the meter wrong?)
    B                    2                               136
       C                 3                                     137
A                        4                          138
    B                    5                               139
      C                  6                                    135
A                        7                          134
   B                     8                               155
     C                   9                                     141
A                       10                         137
   B                    11                               135
     C                  12                                    145
A                       13                         138
   B                    14                               174      (TrueResult(glucose) 117)
     C                  15                                     148
A                       16                         130
    B                    17                              135
      C                  18                                    139
A                        19                         135
   B                     20                               144
      C                  21                                     141

Notes: One thing I did notice is that the size of the blood bubble from the prick seems to affect the measurement by up to 4 points. The larger the bubble, the higher the score. (Reading 16 was a very small bubble.) The beauty of the FreeStyle Lite is that it requires so little blood to give a reading, but the meter is apparently still sensitive to the amount of blood.

[Johnwen]

That first number anyway you look at it has to be a 138 it would be too far off if in a couple of minutes it jumped from 135 to 158 and then down to 138 and then hung around that number. On lcd display's I noticed myself if you look at them from an angle rather then straight on they can appear to change.
So I set it at 138 for this chart.

[ofonorow]

Thanks again johnwen, (I wonder if there is a way I can get a copy of that graphicing tool!)

Trying to make sense. The last experiment dosage was half as large, but it didn't seem to do much at all. 5 grams like a dud.

Here is the most interesting graph so far - 10 grams IV, 10 grams oral AA and 11.3 grams oral SA



Dr. Hickey guessed that the "moiety" of the Betaine HCL may be the problem, so I will go back to just 5000 mg ultrafine for a baseline, (this should tell us whether 10 grams is required to see the effect) and then figure out how to make my stomach more or less acidic.

Added johnwen if I was going to try to use your graphs in the paper, I need the headings to indicate the dosage of vitamin C (usually 10 grams ascorbate) and the x axis to be labeled minutes and the y axis to be labeled reading mg/dl

[Johnwen]

I just modified the jpg. Image! 'Quick fix!'
What your looking for???
Took longer to get it in Photobucket then to fix!

[ofonorow]

Thank you!

Oppps. Thinking about it though, I believe the above is the graph of taking 250 mg every minutes (to simulate the IV)

And it mixes the sodium ascorbate gulp - with the slower oral/iv introduction of aa/sa.

Here is the graph that matches the top heading (gulp of 10 grams AA)


And this is the comparison of the gulp versus IV.


This would be a good graph to have labeled as it compares gulp of AA and dextrose.


What we are missing and would be interesting.. Average of gulp AA, gulp SA and gulp of Dextrose.

[ofonorow]

Reran the 5 gram gulp of ultrafine ascorbic acid without taking the Betaine HCL. Johnwen, if you can please, the graph of this 5 gram run with the average 10 gram AA gulp would be interesting to see side-by-side.

Baseline
TrueResult 107
Meter A 123
Meter B 124

Code: Select all

Meter              Time            Reading              Running Average (last 3 readings)
A                     1                 158                     
  B                   2                      155   
     C                3                            171          161.33
A                     4                 139
  B                   5                      155
      C               6                            143           145.66
A                     7                 146
   B                  8                      147
      C               9                            157           150
A                    10                130
   B                  11                     154
      C              12                            140          141.33
A                    13                139
   B                  14                     160
       C              15                           149           149.33
A                     16                183
   B                   17                    169                          (TrueResult 115)
      C                18                          164           172
A                      19               148
    B                   20                    156
        C               21                           143         149

Notes.
Question #1 - what made this different than the same run taking Betaine HCL?

Question #2 - Why is there now such separation between the TrueResult (107) and the Abbott meters (123) at baseline? (Could there be residual levels of vitamin C in my blood after all these years that the kidneys are not eliminating. In other words, is my blood level of vitamin C in the morning after waking higher than 1.5 mg/dl?)

Other sources of error are taking the vitamin C by mouth, and then using your tongue to clean the blood on the finger. Should just use a cotton ball to clean the blood.

And johnwen, again the first reading was 158 mg/dl. It makes me think that the first reading the other day was also 158 mg/dl (after one minute) as I would be unlikely to get the first reading wrong. Today, however, the readings increased from there. So again, we have the mystery of how and why the glucose meter measures a blood increase one minute after the gulp?

[Johnwen]

This is the one you just did with 5 Gram Gulp.




This is 5 and 10 Gram Comparison.
The 10 Gram was 7/18/15? Correct??
I reduced the 10 G to the same time's as the 5 G to simplify.
NOTE the times on the bottom their doubled. This is because you can't have two figures in the same column So the numbers are First 5G Second is the 10 gram time.
I could have photoshopped them in but it would have been very clustered because some are pretty close numbers.

[Johnwen]

I believe the following explains why your seeing such differences!
An answers 1 and 2 of your questions.
How about this Horse and cow, Cat and dog their all animals Right?
However they are different! The same as the different type of test strips these meter's use.

True Result!
Enzyme used for glucose testing is glucose dehydrogenase-PQQ!

Read these!

http://www.fda.gov/Safety/MedWatch/Safe ... 177295.htm

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845013/

NOW!
The new FreeStyle Lite test strips do not use the GDH-PQQ enzyme, which can be affected by common non-glucose sugars
The FreeStyle Lite test strips use a GDH-FAD enzyme which is unaffected by common non-glucose sugars, such as maltose or galactose, and minimizes the potential for other interference.

http://www.hmdbio.com/index.php?option= ... &Itemid=61


http://www.bbisolutions.com/news/2013/0 ... nsitivity/

Other sources of error are taking the vitamin C by mouth, and then using your tongue to clean the blood on the finger. Should just use a cotton ball to clean the blood.

Like your parents use to say 'OWEN!!! Keep your fingers out of your Mouth!!'

Take a saucer and put a tiny bit of rubbing alcohol in the bottom and place a 2x2 gause in it and add to saturate it and a small bit extra. Then use this to wipe your finger on and prepare the other one for poking! NOTE: Keep flames and heated objects away from this, rubbing alcohol is Flammable!