Bioavailability of Vitamin C

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Bioavailability of Vitamin C

Post Number:#1  Post by ofonorow » Mon Jun 15, 2015 1:47 pm

During another discussion with an MD, http://www.vitamincfoundation.org/forum/viewtopic.php?f=11&t=11923

he cited this reference


http://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/

Oral vitamin C produces tissue and plasma concentrations that the body tightly controls. Approximately 70%–90% of vitamin C is absorbed at moderate intakes of 30–180 mg/day. However, at doses above 1 g/day, absorption falls to less than 50% and absorbed, unmetabolized ascorbic acid is excreted in the urine [4]. Results from pharmacokinetic studies indicate that oral doses of 1.25 g/day ascorbic acid produce mean peak plasma vitamin C concentrations of 135 micromol/L, which are about two times higher than those produced by consuming 200–300 mg/day ascorbic acid from vitamin C-rich foods [10]. Pharmacokinetic modeling predicts that even doses as high as 3 g ascorbic acid taken every 4 hours would produce peak plasma concentrations of only 220 micromol/L [10].


Question: What is "unmetabolized" ascorbic acid - and how does it reach the urine (if it doesn't enter the blood stream?)

Question: Re: "absorption falls to less than 50% " What is the definition of "asbsorbed?" Into the blood stream? From the blood into cells? To me, this implies that fully half of dosage of one gram (or 500 mg) is not absorbed into the blood stream, but I want to understand if this is what they are saying.
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Re: Bioavailability of Vitamin C

Post Number:#2  Post by Johnwen » Mon Jun 15, 2015 4:19 pm

Owen;

Take a few minutes of quiet time and read the Hickey, Roberts and Miller PDF I posted in the other discussion you mentioned. They do a real good job of showing what happens with different doses and types of VC in the body.

You already have questions but here’s a way I found helps in understanding these study presentations. It’s kind of simple but makes for better understanding.

When you get the study in front of you zoom down and read the conclusion first, don’t bother reading the abstract or anything else first. You already read the title that’s why your reading it!!

Now you have a bunch of questions in your mind to be answered.

Again skip the abstract and go to the introduction and start reading. Your questions will start to get answers. Now you got answers and a good idea of what is going on here.
Read the abstract and see if it will confirm what your answers are.

I found that just reading the conclusion first also is a good way to go thru a lot of studies to see which one have any relevance to what your looking for in a study.

This way your also avoiding making a judgment from a study before you seen what they did to get to the point where it might not be what one would expect it to be. Then if it’s not you can search on to see if they made the mistake or the mistake was in something you read before. YEP! Their not all perfectly accurate!!!

Unmetabolized;
Means unused Ie; None of the cells used it. It made it into the blood but no one was hungry! Or wasn’t attached to a transport to escort it into the cells.
Example, Glucose in the blood is unmetabolized glucose! It needs insulin to enter the cells Ie; to get metabolized by the cells.

Absorbed;
Made it through the digestive process and has made it into the blood.
Injections are absorbed thru the venial system in the muscles and into the blood stream

From the blood into cells!
This is metabolized product! Being brought into the cells and used by the cell. This done by changing it’s character or attached to a transport molecule.
With VC depending on what state it’s in (DHA,AA or 2,3-diketo-l-gulonic acid) will be brought into the different types of cells by either GLUT1, GLUT2, GLUT4, SVCT1 or SVCT2 ..

Hope this all helps!!!

http://www.encognitive.com/files/Pharma ... in%20C.pdf
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Re: Bioavailability of Vitamin C

Post Number:#3  Post by ofonorow » Thu Jun 18, 2015 10:29 am

First, thank you. It was a good idea to review those papers. (Aside, why change vitamin C units from mg/dl to umol/l ?? I can understand doing this when it makes more sense to "count particles." However, the new units makes it hard to use relate these numbers based on what Pauling and others have written. Maybe that was the intention?

Anyway, I take it 1.5 mg/dl is roughly equivalent to 70 umol/l
.)

http://www.encognitive.com/files/Pharmacokinetics%20of%20oral%20vitamin%20C.pdf%20%20Seems%20to%20challenge%20the%20assertion%20of%20a%20maximum

Good paper and indicates that we can raise and sustain blood levels around 440 umol/l, or about double what the NIH predicted, enough to have a possible therapeutic effect on some cancers, and provides an argument for the sustained and continual intake of vitamin C throughout the day.

I found the second paper difficult to read and tried your trick - read conclusion first.
http://prhsj.rcm.upr.edu/index.php/prhs ... view/13/11

In general, the metabolism of ascorbate has been reported to be saturable. This conclusion comes from the observation of an upper limit to the rate of excretion of ascorbate metabolites as the oral dose of vitamin C is increased. However, re-analysis of the relation between the metabolite excretion rate and plasma ascorbate concentration indicates that this ratio remains essentially constant and that there is no saturation of ascorbate metabolism (47)


http://injectablevitaminc.com/images/Ch33.pdf
This 2004 paper seems diametrically opposed to the first, and second, and seems to be what the people doing the studies at Kansas believe - that oral intakes are tightly controlled. Only IV/C can raise blood levels, etc.

http://advances.nutrition.org/content/2/2/78.full.pdf
Again the idea seems to be IV over oral.

I am trying to figure out what happens to 9000 mg of ascorbic acid if I take it all at once by mouth.

I have been assuming that because I personally do not suffer runs, gas or diarrhea at this dose, that most (if not all) of the AA has been absorbed into the blood stream.

And I wonder if there is any delay or timed release action, say over several hours, that makes oralmore optimal than a high dose IV (bolus?) The IV quickly shoots its wad, but then the high blood levels are quickly excreted by the kidneys? Might not the slower oral dosage, in fact, be more "available" to tissues?

Knowing how much blood volume there is typically in the human body, and with our ability to crudely measure AA levels (above glucose), might we be able to predict what the glucose readings should be if 9000 mg of AA is taken orally? (One thought is to measure 9000 mg IV as the reference point)
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Re: Bioavailability of Vitamin C

Post Number:#4  Post by pamojja » Thu Jun 18, 2015 2:10 pm

ofonorow wrote:.. might we be able to predict what the glucose readings should be if 9000 mg of AA is taken orally? (One thought is to measure 9000 mg IV as the reference point)


Last fall I tested my serum Vitamin C.

My GP always sends me to a lab to test homocysteine because he doesn't do centrifugation himself. So I fasted from dinner and took 4x 9 gram in the 12 hours before the blood draw, the last time 10 minutes before arriving at the lab:

23,4 mg/dl (5 - 15)

if I calculate it right, that should be about 133 µmol/L (and yes, actually wanted to see it above 400).

Thinking about it.. now I understand why the resulting homocysteine was my erstwhile highest at 14,1 µmol/L, before always closer around 10. Since 36 g of vitamin C isn't exactly fasted anymore :roll:
Last edited by pamojja on Fri Jun 19, 2015 4:55 am, edited 1 time in total.

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Re: Bioavailability of Vitamin C

Post Number:#5  Post by OxC » Thu Jun 18, 2015 4:20 pm

ofonorow wrote:I am trying to figure out what happens to 9000 mg of ascorbic acid if I take it all at once by mouth.

Hornig D, Vuilleumier JP, Hartmann D. Absorption of large, single, oral intakes of ascorbic acid. Int J Vitam Nutr Res. 1980;50(3):309-14.
Abstract:
"A male non-smoking volunteer increased his daily intake of ascorbic acid continuously by ingesting in a single, oral dose 1, 2, 3, 4 and 5 g crystalline ascorbic acid. The dose was always kept constant for 2 days and was taken with breakfast. During the regimen of ascorbic acid ingestion blood samples were taken and all urine was collected. Then, with a 5 g dose of ascorbic acid 8.17 micro Ci (170 microgram) (1-14C)ascorbic acid was ingested. Following the labelled dose radioactivity was determined in plasma, urine, and faeces. Daily ingestion of 5 g ascorbic acid was continued for 10 days. During the whole experiment the ascorbic acid concentrations in plasma and in urine were determined. The urinary excretion of unmetabolized unlabelled ascorbic acid per day was taken as index for the absorption of ascorbic acid. It decreased from 75% (1 g), 44.0% (2 g), 39%, (3g), 28% (4 g) to 20% (5 g) of the ingested ascorbic acid. The linearisation of the relationship between ingested dose and the excreted amount in urine yielded a maximum amount of 1160 mg ascorbic acid which can be absorbed in 24 h under the conditions of the experiment. The experiment with (1-14C)ascorbic acid revealed that a single oral dose of 5 g ascorbic acid is absorbed to 22.2%, in the faeces collected up to 117 h following ingestion of label only 2.8% of the radioactivity could be recovered. Several possibilities are discussed regarding the fate of the remaining unabsorbed (1-14C)ascorbic acid."


I have never been able to get a copy of this article's full text, so I don't know what these authors suggested concerning the fate of the remaining unabsorbed AA. Some other studies seem to suggest that AA that is not absorbed into the bloodstream as vitamin C may be metabolized by the bacteria in the large intestine. This would be consistent with the fact that when large doses of (1-14C)ascorbic acid are taken orally by humans, a large proportion of the radioactive carbon appears in the breath as carbon dioxide. This would also help explain why, in this study, even though only about 20% of a 5 gram dose appeared in the blood and then the urine, very little of the radioactive carbon was found in the feces.

(BTW, if anyone has the full text of the above article, I would greatly appreciate a copy!)
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Re: Bioavailability of Vitamin C

Post Number:#6  Post by ofonorow » Fri Jun 19, 2015 10:24 am

First, OxC, I hope you don't mind but I edited your post, and put the abstract in quotes to make it clearer which words were yours. (and pamojja - your post lost me. Sorry. Can't follow the numbers. Are you saying that there was a vitamin C measurement in there?)

OxC, I would appreciate your interpretation of the study/abstract. They were trying to measure what, in your opinion? (I think I can understand following radioactive dyes, say in a thallium stress test - they light up the heart and show where the blood is circulating)

Even if accurate, I am trying to follow what they are trying to measure (and the thought of introducing radioactive ascorbate into cells is disconcerting.)

Longer telomeres are not making me smarter :oops:

I'd appreciate your (or anyone's) thoughts on my idea to measure vitamin C levels, lets say after a 5 gram and 10 gram IV - perhaps for two hours after the IV. While every 5 minutes is more illuminating, for the sake of my fingers, I'll probably take the reading every 10 minutes. Maybe every 5 minutes during the first hour.

In theory this provides a reference point for "100% absorption" -- directly into the vein.

From that point, I can experiment with oral intake, and compare it - over time - with the IV area under the curve.
Owen R. Fonorow, Orthomolecular Naturopath
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Re: Bioavailability of Vitamin C

Post Number:#7  Post by OxC » Fri Jun 19, 2015 3:05 pm

ofonorow wrote:OxC, I would appreciate your interpretation of the study/abstract. They were trying to measure what, in your opinion? (I think I can understand following radioactive dyes, say in a thallium stress test - they light up the heart and show where the blood is circulating) Even if accurate, I am trying to follow what they are trying to measure (and the thought of introducing radioactive ascorbate into cells is disconcerting.)

They measured the bioavailability of oral AA doses of 1,2,3 4 and 5 grams. Consistent with many other studies, they found that large doses have limited bioavailability...in this case, for example, that a 5 gram oral dose was about 20% bioavailable. This study offers something in addition; because they also used radiolabeled AA, it gives some insight into the fate of the 80% that was not absorbed into the bloodstream as ascorbate. The limited bioavailability of oral AA is well-known and has been tested many times, but I have found only a few studies that attempt to discern what happens to the AA that you swallow but doesn't appear in the blood.
ofonorow wrote:I'd appreciate your (or anyone's) thoughts on my idea to measure vitamin C levels, lets say after a 5 gram and 10 gram IV - perhaps for two hours after the IV. While every 5 minutes is more illuminating, for the sake of my fingers, I'll probably take the reading every 10 minutes. Maybe every 5 minutes during the first hour. In theory this provides a reference point for "100% absorption" -- directly into the vein. From that point, I can experiment with oral intake, and compare it - over time - with the IV area under the curve.

Two thoughts:
  • You are describing a classic bioavailability test, using blood ascorbate levels to compare the amount absorbed from an oral dose versus the amount from a comparable IV dose. There's certainly no problem with that, but it has been done so many times before with AA that I'm not sure why you want to do it.
  • What is a problem is that you are proposing to do your study with an unreliable measurement method. You can't get accurate blood ascorbate measurements with a glucose meter. If you're going to go to all the trouble to conduct such a study, I'd suggest you have the blood samples tested by a method which was designed, intended, and validated to measure ascorbate. When I did this, I purchased the blood tests through Life Extension and the samples were sent to a certified lab (LabCorp) for analysis.
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Re: Bioavailability of Vitamin C

Post Number:#8  Post by Johnwen » Fri Jun 19, 2015 9:53 pm

Here’s a calculator to help determine mg/dl to umol/L and vice a verse a of ascorbic acid! It’ll kind of help clear up some of the figures.

http://www.endmemo.com/medical/unitconv ... amin_C.php


Also:
Owen you do know about the voluptuous girl on your finger tip don’t you?
Look at your finger tip and picture this drawn on the top section (from the tip down to the first joint “ ) ( “ about 7mm in the waist section. Now when you poke yourself you do it outside the girly marks “ >| x) (x |< “ Why there’s no nerves there! = No Pain! Plenty of Blood.
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Re: Bioavailability of Vitamin C

Post Number:#9  Post by pamojja » Sat Jun 20, 2015 7:43 am

ofonorow wrote: (and pamojja - your post lost me. Sorry. Can't follow the numbers. Are you saying that there was a vitamin C measurement in there?)


Yes, that's the serum ascorbate value after taking a 9 gram ascorbic acid dose each at about 11 PM, 3, 7 and 10 AM. Therefore 36 gram in total of vitamin C in roughly a 12 hour period before the blood draw:

pamojja wrote:23,4 mg/dl (5 - 15)

if I calculate it right, that should be about 133 µmol/L


Johnwen wrote:Here’s a calculator to help determine mg/dl to umol/L and vice a verse a of ascorbic acid! It’ll kind of help clear up some of the figures.


My goodness, your calculator would give me a whooping 1323 µmol/L !!!!

ofonorow wrote:
Longer telomeres are not making me smarter :oops:


Shorter telomeres aren't making me smarter either: :oops:

I used the same conversion factor. However, just checked the original lab report and it gives the 23,4 as mg/L = 2,3 mg/dl.

But still calculated with the adjusted conversion factor. So still 132 µmol/L only. Thanks for making me check my numbers again, Johnwen.

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Re: Bioavailability of Vitamin C

Post Number:#10  Post by OxC » Wed Jun 24, 2015 12:49 am

pamojja wrote:So still 132 µmol/L only.

A blood plasma level of only 132 uM after eating 36 grams of ascorbic acid in the previous 12 hours would seem incredibly low to some believers in megadosing AA, but should not surprise anyone given the many studies that demonstrate the low bioavailability of large doses of AA. Thank you for sharing your experience including your actual blood plasma measurement! By comparison, 5 grams of DHAA raised my blood level to over 400 uM in 30 minutes.
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Re: Bioavailability of Vitamin C

Post Number:#11  Post by ofonorow » Wed Jun 24, 2015 5:10 am

I am confused - if pam's blood was mg/dl then the amount shown was at least double normal (1.5 mg/dl) or more than 220 m/l and probably close to the 400 number Oxc mentions??

And given the 30 minute vitamin C half-life in the blood, our crude measurements have shown that these very high blood concentrations are only visible from minutes 5 to 25 after oral ingestion, and only with ascorbic acid (not sodium ascorbate).

OxC I would not call what I am proposing a "study", just a way to crudely illustrate that more than 20% of what I take orally at 9000 mg is absorbed into the blood. (Either it will be, or it won't. I'll bet a quarter that about 1/2 makes it into the blood, or 50%, and because it is ascorbic acid, under Cathcart's theory, it would approximate the therapeutic effectiveness of the IV - a vitamin C IU if you will - because the IV is sodium ascorbate.)

I wouldn't be surprised if 90% makes it to the blood in my case.

First, we notice from Hickey's (and other) studies of liposomal, that the vitamin C doesn't peak for two hours after oral intake.

One benefit of our crude measurements was showing the difference between AA (ultrafine powder) and Sodium Ascorbate. Sodium ascorbate was either delayed or not absorbed (as we didn't measure longer than one hour) And thanks johnwen for the pin prick location advice!

But the AA was noticed by our meter at minute five and if memory serves, peaked around minutes 20 to 25. So any test that is not measuring this soon and this often is going to MISS a lot of vitamin C (as ascorbic acid) entering the blood stream

And this observation has increased my confidence in the Hickey/Roberts theories and writing. Their book RIDICULOUSE DIETARY ALLOWANCE is where we learn that ascorbic acid can enter the blood stream through the stomach lining (at the proper low pH).
For AA to reach the blood this quickly (5 minutes!) something like this MUST be happening, and as I mentioned, we did not observe the same thing measuring sodium ascorbate.
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Re: Bioavailability of Vitamin C

Post Number:#12  Post by pamojja » Wed Jun 24, 2015 5:14 am

OxC wrote:
pamojja wrote:So still 132 µmol/L only.

A blood plasma level of only 132 uM after eating 36 grams of ascorbic acid in the previous 12 hours would seem incredibly low to some believers in megadosing AA, but should not surprise anyone given the many studies that demonstrate the low bioavailability of large doses of AA. Thank you for sharing your experience including your actual blood plasma measurement! By comparison, 5 grams of DHAA raised my blood level to over 400 uM in 30 minutes.


Thanks for the response. As already said, I expected it higher since I seen a study which measured gradually higher serum levels which correlated to the dose in different subject. Up to slightly above 400 µmol/L with 20 g ascorbic acid per day in one subjuect.

So I think it's a little bit comparing apples to oranges if you compare your serum levels with mine. Do you have a comparable serum test with 5 grams of ascorbic acid?

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Re: Bioavailability of Vitamin C

Post Number:#13  Post by pamojja » Wed Jun 24, 2015 5:19 am

ofonorow wrote:For AA to reach the blood this quickly (5 minutes!) something like this MUST be happening, and as I mentioned, we did not observe the same thing measuring sodium ascorbate.


Absolutely. Whenever I get sneezes from my hay-fever and take a glass of water with 2 tea-spoons of vitamin C, within 3 minutes it eases it already.

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Re: Bioavailability of Vitamin C

Post Number:#14  Post by OxC » Wed Jun 24, 2015 11:06 am

pamojja wrote:So I think it's a little bit comparing apples to oranges if you compare your serum levels with mine. Do you have a comparable serum test with 5 grams of ascorbic acid?

Yes.
Image
If the image doesn't show, here's the link:
http://1drv.ms/1J5H6xB
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Re: Bioavailability of Vitamin C

Post Number:#15  Post by pamojja » Wed Jun 24, 2015 11:50 am

So you tested each 3 times: at 30, 60 and 120 minutes after a 5g dose of AA or DHAA.

Thanks for sharing.


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