Dehydroascorbic = MUCH higher blood levels of VitC ?

[davids1]

Hi John,

Thank you for the informative post.

Question: Was the manufacturer you contacted in China [and, further, I assume you had to go through several inquiries (beginning with the retailer) before getting the actual manufacturer's contact info]?

Thanks again,

David

[OxC]

[ofonorow]

Backing up a little. Here is a quote from Sherry Lewin's 1976 book Vitamin C: Its Biology and Medical Potential. This was 1976 and I do not remember any discussion of "transporters" in this book! (What is a "transporter" anyway? Does it have atoms? A molecular structure?) Nor do I remember Linus Pauling discussing them much. Aside, We hope to publish Lewin's entire book, which has become rare on our web site.)

Pg 62. 2.4.5 Increased Membrane Permeability

It was concluded by several investigators (e.g. Martin, 1967, Hughs and Maton, 1968) that dehydroascorbic penetrates lipid membranes - such as those of erythrocytes - very much more than does ascorbate. The phenomenon has been attributed to the dehydroascorbic entity possessing a more lipid-like character than ascorbate. However, another way of viewing this phenomenon is to say that because dehydroascorbic possess a much greater power to reduce the interfacial tension, it can correspondingly increase membrane permeability. The implications of the respective formulations are not the same.

(i) An increased lipid-like character would help the DHA to enter the membrane from the aqeuous bulk, but having penetrated the membrane the DHA should prefer to stay in it because of the lipid character of the two. Hence, transfer of DHA from plasma into the inside of the cell would not be promoted, unless the contents of the cell were themselves more lipid-like than the plasma.
(ii) According to the previous explanations any ascorbate present with dehydroascorbic, outside the lipid membrane, need not penetrate the membrane any faster than when dehydroscorbic is absent. According to the view expressed here, the increased membrane permeability on contact with DHA should assist ascorbate penetration. Thus, in a solution containing a mixture of ascorbate and dehydroascorbic the permeability to AA should be higher than that when ascorbate alone is present.

There is also a discussion of the difference in chemistry (over my head) that Lewin uses to explain DHA's greater "lipid permeability."

AA and DHA can be viewed as antagonists, since their activities follow opposing directions. Further, AA, under physiological conditions, displays an ionic character, whereas DHA is more hydrophobic in character. Thus, at neutral pH values ....AA is an anion, while DHA is hardly ionized. Indeed the anhydrous form of DHA displays its relatively non-ionic character by being more lipid-soluble as indicated by the respective ...

[Johnwen]

[OxC]

Backing up a little. Here is a quote from Sherry Lewin's 1976 book Vitamin C: Its Biology and Medical Potential. This was 1976 and I do not remember any discussion of "transporters" in this book! (What is a "transporter" anyway? Does it have atoms? A molecular structure?) Nor do I remember Linus Pauling discussing them much.

The video which is the original subject of this thread http://www.youtube.com/watch?v=YHKBhz7OCB4 includes some general discussion of the trans-membrane types of protein transporters, as well as more specific info about the specific transporters for AA and DHAA. The Wikipedia discussions of "membrane transport proteins" and "ion channels" offer a reasonable overview of these transporters as well (I know, lots of folks criticize Wikipedia as a source of info, but there are many very good and educational discussions with excellent graphics, and I'm not going to get into it with anyone over the absolute accuracy of everything on Wiki).

A lot has happened in the field of vitamin C research since 1976. I'm no "science historian," and wouldn't presume to be able to identify when any particular discovery or knowledge became generally-accepted scientific thought. I can say that in my own collection of literature, it wasn't until the 1980's through the early 1990's that large numbers of reports discussing the transport of DHAA via glucose transporters began to appear. Perhaps a "milestone" in general scientific acceptance of this mechanism could be suggested by a 1993 Nature article entitled "Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid." Realizing that Lewin's book was published in 1976, and that Pauling died in 1994, maybe it is not so surprising that neither of them discussed vitamin C transporters much. That doesn't take away from their respective genius; it would be incredibly improper to criticize scientists from the past for not knowing things that were not generally known in their times, or for not necessarily accepting what may have been considered to be speculative at the time. Isaac Newton is not the only person who has seen further because of his opportunity to stand on the shoulders of giants.

[ofonorow]

[OxC]

A simple list of facts:

• Reduced ascorbate is transported into cells, through the cell membrane, by SVCTs.
• DHAA, formed when reduced ascorbate is oxidized, is transported into cells, through the cell membrane, by certain GLUTs.
• Dietary sources of reduced ascorbate include ascorbic acid (found naturally in foods, also in many dietary supplements), sodium ascorbate, calcium ascorbate, magnesium ascorbate (these salts are found in some dietary supplements, such as "buffered" vitamin C preparations), and even compounds such as ascorbyl palmitate (a fat-soluble compound added to some processed foods as a preservative, but when ingested the palmityl residue can be cleaved by esterase enzymes in the gut, releasing an ascorbate ion, and thus becoming a dietary source of vitamin C). There are others.
• Dietary sources of DHAA include the DHAA found naturally in food, DHAA that is formed when the ascorbate in food becomes oxidized during processing or even chewing food, DHAA that is found in trace amounts in almost all dietary supplements (it is essentially impossible to have a large quantity of ascorbate that is not accompanied by a trace amount of DHAA due to some oxidation of the ascorbate), DHAA that is found in significant quantity in one brand of dietary supplement, and now, as demonstrated in the video http://youtu.be/YHKBhz7OCB4 DHAA that can be found in megadose quantities in a specially-prepared zucchini smoothie.
• When ingested, reduced ascorbate is absorbed and appears in the bloodstream at a particular rate; generally the peak value in the bloodstream occurs about 2 - 3 hours after ingesting it in typical supplemental or megadose quantities. It is clear that the more you eat in a single dose, the higher the peak blood values can get. But it is also clear that after consuming a dose of somewhere around 200 mg, absorption from the gut slows tremendously, and it requires multi-gram increases in dose to only slightly increase the resulting peak blood levels. This phenomenon is currently attributed to characteristics of the SVCT transporters.
• When ingested, DHAA is absorbed and appears in the bloodstream (as reduced ascorbate) more quickly than when reduced ascorbate itself is ingested. The peak levels occurs somewhere around 30 to 90 minutes after ingestion. The peak blood level achieved by ingesting 5 grams DHAA was twice as high as the peak level achieved by the same individual when he ingested 5 grams of reduced ascorbate. More rapid uptake and higher intracellular levels from exposing cells to DHAA as opposed to reduced ascorbate has been demonstrated in many in vitro studies. This phenomenon is currently attributed to characteristics of the GLUT transporters.

Here's some speculation:

• The term "bioavailable" is usually defined (in reference to vitamin C) as the amount of an oral dose that appears in the bloodstream, as compared to the same amount infused directly into the bloodstream. Blood levels are monitored over time to produce curves, and area-under-the-curve analyses are used to compare the estimated total amount of vitamin C in the blood from a single dose given orally versus the same dose given IV. The value is stated as a percent. When 200 mg reduced ascorbate is given orally, such calculations show that this dose is almost 100% bioavailable. When larger doses are given orally (say, 2 grams) such calculations show that this size dose is maybe only 20% bioavailable. The rapid and extremely high blood values achieved by ingesting DHAA suggest that the oral bioavailability of DHAA is much greater, although I'm not aware of any such calculations ever being done. Nevertheless, I speculate that doses of DHAA of 1 or 2 grams, or even 5 grams or more, may be very close to 100% bioavailable.

[ofonorow]

The only fact in your list which seems surprising (at least to me) is this one.

When ingested, DHAA is absorbed and appears in the bloodstream (as reduced ascorbate) more quickly than when reduced ascorbate itself is ingested. The peak levels occurs somewhere around 30 to 90 minutes after ingestion. The peak blood level achieved by ingesting 5 grams DHAA was twice as high as the peak level achieved by the same individual when he ingested 5 grams of reduced ascorbate. More rapid uptake and higher intracellular levels from exposing cells to DHAA as opposed to reduced ascorbate has been demonstrated in many in vitro studies. This phenomenon is currently attributed to characteristics of the GLUT transporters.

Begs the question, where did the electrons come from that "reduced" DHAA back to AA in the blood stream? (From other sources, it appears to be true that the half-life of DHAA is short in the blood (and perhaps the tissues) , but if it isn't reduced, Lewin claimed DHAA soon turns into the Ascorbate Free Radical.

This claim also makes me wonder how a blood test can distinguish between the reduced and oxidized form of vitamin C in the blood?

So the mechanism being described seems to be that DHAA (like glucose) can rapidly enter the blood stream, but the magic is that it has gotten reduced to an antioxidant during this process!?

I asked a biochemist about whether we could use color to check between the D- and L- forms of vitamin C. Here was his response:

Q: can we use color to test between L- and D- ascorbate?
A: No! Absolutely not. The color change occurs by reactions
in successive stages with oxygen. The right or left shape
of the molecular structure has no effect on this.
Q: why do some ascorbate solutions turn yellow quicker
than others?
A: This is a function of pH, temperature and duration.
Lower pH more acidic solutions are protected against
auto-oxidation as hydronium ions stick to and cover up
oxidizable electrons. Higher temperatures speed up collisions
with oxygen and accelerate the reaction rate. Older solutions
had more time to react and turn yellow.

[OxC]

Begs the question, where did the electrons come from that "reduced" DHAA back to AA in the blood stream?

The DHAA was not reduced in the bloodstream. It was reduced in the enterocytes (the cells lining the intestine which absorb DHAA from the intestine). Then the reduced ascorbate was released into the bloodstream by the enterocytes. The electrons came from glutathione or NADH or NADPH as described in the reference I previously posted Vitamin C: Biosynthesis, recycling and degradation in mammals. (We seem to keep going in circles on this point )

There is a peculiar belief among a surprising number of people that vitamin C somehow passes from the gut into the bloodstream without ever entering a cell, and that it is always in "extracellular" compartments in the body until it is finally taken up by some cell that is perceived to be its "destination" or "target" cell. The fact is that the very first step in vitamin C absorption is to be taken "intracellularly" by enterocytes, from which it is then delivered "extracellularly" into the blood plasma. Furthermore, in its travels from the gut to any particular "destination" cell, it often must pass between intracellular and extracellular compartments many times. And finally, it must also pass through membranes that enclose various structures within a particular cell. For example, the mitochondria are enclosed by a membrane, and these intracellular structures are known to contain and utilize a great deal of vitamin C. Interestingly, a number of recent reports (all published since the year 2000) indicate that for vitamin C to pass through the mitochondrial membrane, it is preferred and possibly necessary that the vitamin C be in its oxidized form DHAA.1, 2, 3, 4, 5

This claim also makes me wonder how a blood test can distinguish between the reduced and oxidized form of vitamin C in the blood?

HPLC (high performance liquid chromatography) is the most common method used to measure vitamin C in blood samples. In this method, a sample is pumped through a column containing chromatographic media. The AA and DHAA come out of the column at different times (this is the principle of "chromatography"), and can be measured separately. Not all clinical laboratories report AA and DHAA values separately, in fact most report "total vitamin C" which represents the sum of AA and DHAA, and some only report AA. Generally, the amount of DHAA in blood is so small as to be not detectable.

[Johnwen]

I was just wondering if your chemist is aware of That when one says "D-Ascorbic" he's not only talking a single steroisomer but a whole array of chemical compounds that go by the same name?
Some which don't even mix with water?
Saying "D-Ascorbic" is like going to a Diner and ordering "Food" Good luck at what you'll get!


Perhaps a review of the previous post where we discussed this in detail.


viewtopic.php?f=3&t=11302&start=0

[jimmylesante]

Great topics and knowledge.

[davea0511]

Not to change the subject, because I think the ongoing question is *the* most pertinent one: "Can any of that DHA be converted to useful AA beyond what *normal* cells normally reduce?" (I don't see that it can without an injection of bio-available electrons that AA automatically prepackages), but I must digress to respond to comments about what I said earlier (sorry for the belated reply as I was out)...

I've been wrong about a lot of things and one was thinking that the discoloration was DHA, and I think it must be a fairly common misconception, as I did gain my misunderstanding from Dr. Cathcart who said "this yellow is dehydroascrobate" (see https://www.youtube.com/watch?v=iuRTLoQlSks, at 1:50). I don't mean to be throwing him under the bus as he's probably done as much good rectifying popular misconceptions and hands-on saving lives with IVC than anybody ever (Dr. Hugh Riordan probably is a close second), but if Dr. Cathcart thought this too then correction in this matter is most needed and welcome.

So a thank you to Mr. Kitt for that correction. I'm sure Dr. Cathcart would have also appreciated being directed to those studies.

But as Mr. Kitt seems concerned about my credentials (as if MD's and PhD's are vitamin C experts, and have spent 100's of hours pouring over articles in medline on Vitamin C like I have over the last decade) ... where is Mr. Kitt's peer reviewed study, or even a reproducible experiment demonstrating that AA decomposes in the presence of trace catalyzing metals and oxygen directly to various decomposition derivatives, but *not* to DHA? I'm sure he knows that 35% of AA becomes DHA within 15 minutes of being in tap water, due to mobility of Fe and Cu in that environment (plus added Fe and Cu in tap water) http://www.ncbi.nlm.nih.gov/pubmed/15493459. Is he saying that actually after 15 minute 35% of the AA is neither AA or DHA because that DHA immediately became something else - because that's incredible. Why didn't the tap-water study say that?

Kitt's DHA is reportedly stabilized and with fewer (if any) decomposition derivatives, yes? These are good selling points that makes it worth every penny especially for research purposes. But to suggest that DHA is complicated to create, requiring an enzyme from zucchini, that contradicts the study I just linked. Add that contradicting fact with his presumed selling-point that all that DHA in your cells will undoubtedly become AA (again, where's the evidence of that) ... certainly his message warrants some skepticism. My #1 credential as far as he should be concerned is this: I'm his educated customer with a chip on my shoulder after seeing slick-talking salesmen of supposedly superior vitamin C formulas give this most misunderstood undervalued nutrient a bad name. So I'm a natural skeptic. If he can convert me, then he can convert anyone, but he has to do better than rely on assumptions that he hasn't yet proven nor had validated.

Again, as I did at the first, I still complement his experimental process and results (kudos on using Labcorp, though I'm sure glucose strips would have also worked) as validating the glut-transporter mechanism. The theory was already there but only he was industrious enough to start testing the principle for the sake of health and wellness. That is laudable. Hopefully it will lead to a protocol with improved efficacy over plain old AA, or liposomal AA. I wish him the best in that endeavor. Honestly I hope his DHA is a miracle, and maybe with the right diet and reducing strategy one could get perhaps chemotherapeutic biological concentrations of AA as a result ... but I need more statistical significance and validated proof of in vivo casuality than a laboratory reading of DHA levels before I consider it superior to AA, let alone liposomal C, which he suggests. Especially with respect to taming ROS and boosting metabolic energy, which AA can do while producing DHA, see http://onlinelibrary.wiley.com/doi/10.1 ... 3/abstract.

In short, megadosing pure DHA is uncharted territory: *Nobody* knows what good or *bad* can be done by pumping one's cells with far more DHA than the cells are likely capable of reducing (note that most all studies regarding the GSH ascorbate reducing mechanism is done with tissues where AA is found to be 50x to 100X higher than most places in the body, like brain and eye-lense tissues - so we need to take those studies as representing only those tissues rather than the bulk of tissues in the body). Those megadosing DHA should know they are on the bleeding edge of science and take certain guinea-pig risks, and perhaps it would be in his legal best interest to be the messenger of that fact as a disclaimer.

[OxC]

Dear davea0511,
Thank you for your most recent message. There are many different topics there that I hope I can reply to, but in this message I will select just a few. Let's start here:

But as Mr. Kitt seems concerned about my credentials...

I participate in many forums and try to always be polite. I always live to regret when I fail to do so. I made a "snarky" comment previously. Please accept my apology, and my commitment to communicate with you with the respect you deserve as a well-read and intelligent person. I confess to taking the characterization of DHAA as "orange crap" in a personal way. I hope you understand that I have invested a huge part of my life in this molecule, and sometimes fail to remember that it is not one of my children!

I've been wrong about a lot of things and one was thinking that the discoloration was DHA, and I think it must be a fairly common misconception...

It is a very common misconception. Thank you for giving me the opportunity to clarify it in this thread.

...35% of AA becomes DHA within 15 minutes of being in tap water, due to mobility of Fe and Cu in that environment (plus added Fe and Cu in tap water) http://www.ncbi.nlm.nih.gov/pubmed/15493459 ...to suggest that DHA is complicated to create, requiring an enzyme from zucchini, that contradicts the study I just linked.

Please note this statement from the cited study: "In drinking water samples, contaminated with copper from the pipes and buffered with bicarbonate, 35% of the added vitamin C was oxidized to dehydroascorbic acid within 15?min. After 3?h incubation at room temperature, 93% of the added (2?mM) ascorbic acid had been oxidized." 2mM is a quite dilute solution, 353 mg in one liter. According to this study, after 15 minutes, we could expect 123 mg of AA to be oxidized in the presence of copper ions and buffered with bicarbonate in one liter. Let's assume (incorrectly, as I will explain in a minute) that we recovered all 123 mg as DHAA. It appears that we could consume a 1 gram dose of DHAA by merely drinking about 8 liters, or almost 2 gallons. That's silly of course, but why wouldn't we just cut back on the amount of water? I mean, 353 mg of AA will easily dissolve in 100 mL of water which would be a lot easier to drink in one sitting. The reason is that more concentrated solutions of AA are much more stable to oxidation, even if the solution is made non-acidic and contains copper ions (both being conditions that greatly accelerate AA oxidation). But back to whether or not the product water actually contains very much DHAA:

Is he saying that actually after 15 minute 35% of the AA is neither AA or DHA because that DHA immediately became something else - because that's incredible. Why didn't the tap-water study say that?

Actually, the tap-water study did say that: "The dehydroascorbic acid formed was further decomposed to oxalic acid and threonic acid by the hydrogen peroxide generated from the copper (I) autooxidation in the presence of oxygen." I don't have access to the full-text of this article, the statements I've quoted are from the abstract you supplied as a link. So I don't know the time frame within which the DHAA was "decomposed to oxalic acid and threonic acid" in their study. I also don't know what the actual pH of the solution "buffered with bicarbonate" was, but it isn't uncommon for this to mean neutral or physiological pH. I can cite a reference that says the half-life of DHAA in solution at physiological pH is about 7.5 minutes. So, you see, it is not at all "incredible" that most of the DHAA in that particular solution will become something else almost immediately...it is, in fact, rapidly becoming something else just about as fast as it is being formed. This is the dilemma of trying to create DHAA in useful quantity; the conditions that favor AA oxidation (e.g. non-acidic pH) generally favor DHAA degradation even more. So let me qualify my contention, as you have stated it, that DHAA is complicated to create; it is complicated to create in sufficient quantity and stability for dietary or topical use.

It is late, and I must stop. I hope I can get back soon to reply to some of your other points. I really do appreciate your comments, and look forward to continued amicable discussion.

Best regards,
Doug

[ofonorow]

I don't want to side track this discussion/debate, but it does occur to me that the definition of vitamin C is that it cures scurvy. I wasn't sure if Emil Ginter was alive (see this list of his abstracts! http://www.vitamincfoundation.org/forum/viewtopic.php?f=9&t=152 ) so the following email was a shot in the dark.

Dear Dr. Ginter,



A recent article states that dehydroascorbic acid (DHAA) is a form of vitamin C.



http://www.teatronaturale.com/article/3574.html



Our question, can you give DHAA to guinea pigs and keep them alive?



Thank you.



Owen Fonorow

Vitamin C Foundation.org

His response was interesting.

Yes, you could do it.



Sincerely, Emil Ginter

[davea0511]

Mr. Kitt-

Thank you for your thoughtful reply. I'll do right by your youtube video that I left a comment on ...

I will also look closer at that DHA stabilization study information you just provided. Let's discuss this some more. I think it would be well to see if you could get some resources to help address some of the other items I mentioned. Perhaps I could help ... I'll need to do some thinking on that. I also have been for some time working on stabilization of vitamin C formulations, and like you have some of the same idea of structuring the ip in a way that would keep it out of the hands of those who would abuse it. In fact, I have little interest myself in the stabilization of DHA myself, but there might be some synergy for you with further discussion.

Sounds like we're both busy. I might amend my original comment on this to say that I still think there is enough unknowns to state buyer beware, but if someone was willing to expose themselves the guinea-pig risks then it might be a noble endeavor, but by no means guarantees the results we know will come from tried and tested methods of AA supplementation.