Dehydroascorbic = MUCH higher blood levels of VitC ?

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Re: Dehydroascorbic = MUCH higher blood levels of VitC ?

Post Number:#31  Post by OxC » Mon Oct 06, 2014 6:44 pm

I'm always excited when I see brand new, peer-reviewed scientific articles concerning DHAA that are open source, meaning you can read the full text without having to subscribe to the journal. Here's a link to one just published in May 2014. It is focused on vitamin C uptake and recycling in the brain. An understanding of these mechanisms helps in understanding why DHAA has been investigated as a potential therapy for stroke and Alzheimers.
Douglas Q. Kitt, founder of ReCverin LLC, sellers of stabilized dehydroascorbic acid solutions.

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Re: Dehydroascorbic = MUCH higher blood levels of VitC ?

Post Number:#32  Post by ofonorow » Wed Oct 08, 2014 2:29 pm

I finally watched the entire video, and while interesting, I came away wondering what evidence there was or is that DHAA provides health benefits. (When iron oxidizes, we get rust. When an apple oxidizes, it turns brown.) I don't understand why I would want an oxidant to enter my blood stream, even or especially at high levels, unless I was fighting a disease - such as Lyme?

The assumption in the video seems to be that because it is a form of vitamin C, that DHAA has all the same benefits of reduced ascorbate. The other assumption based on a single experiment is that the blood measurement (in red) was a) not an anomaly, and b) was reduced ascorbate in the blood.

So before going on lets review some of the proposed "facts" presented previously.

OxC wrote:A simple list of facts:
  • Reduced ascorbate is transported into cells, through the cell membrane, by SVCTs.

Even if we accept this, it does not explain how liposomal vitamin C, or even ordinary ascorbate reaches the blood stream. The claim is that ascorbate actually enters (and exits) intestinal cells called Enterocyte. (And since wikipedia was often cited, please note that there is no mention of ascorbate entering these cells in the enterocyte wiki discussion.) My training was that most nutrient transport is via intestinal villus Little tubules that move nutrients from the intestines to the blood stream. So while the SVCT may transport AA through membranes, I do not think it is accepted that all ascorbate moves into and out of any cell prior to reaching the blood stream.

Furthermore, the Hickey/Roberts book RIDICULOUS DIETARY ALLOWANCE reveals that some (all, most?) of the ascorbic acid taken by mouth NEVER REACHES THE INTESTINES (if the stomach acid pH is low enough) because it is "assimilated" through the stomach wall into the blood stream

  • 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 DHAA that can be found in megadose quantities in a specially-prepared zucchini smoothie.

  • This is interesting and not something we usually think about, but as the video author points out, the ratio of AA to DHAA "in nature" is about 5 to 1."

  • 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.

  • From our crude glucose meter measurements, this does sound like an alkaline ascorbate that has reached the intestines. High dose (5 grams) of Ascorbic Acid peaks around 20 minutes, which seems to confirm the Hickey/Roberts stomach entry mechanism. See:

    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.

    There are multiple factors determining blood levels. Rate of absorption into the blood, and high dosages are immediately lowered by the kidneys (30 minutes half life). The idea of 200 mg is tied to the ascorbate absorption (per your model) into white blood cells, but has little to say about general blood levels. Again refer to RIDICULOUS DIETARY ALLOWANCE

  • When ingested, DHAA is absorbed and appears in the bloodstream (as reduced ascorbate) more quickly than when reduced ascorbate itself is ingested.

  • This would be amazing if true, but assuming the model presented is accurate then those poor enterocyte cells are undergoing severe oxidative stress! (If the C is being reduced in these cells, then other parts of these cells are oxidizing. The only way to provide the necessary electrons to reduce the oxidative stress is by an antioxidant.)

    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.

    The one fact that supports the idea is the very short half-life of DHAA.

    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.

    What about a 200,000 mg daily "bowel tolerance" dosage for mono or other high-powered virus? How would this dose pass through the enterocytes? The Cathcart theory is that any ascorbate which is not absorbed into the blood stream reaches the rectum causing diarrhea. See So where did the 200 grams of ascorbate go, if not into the blood and immediately into the ascorbate depleted tissues?

    And Cathcart's theory is that at these dosages, we are no longer dealing with the "vitamin" property of ascorbate - the ability to make collagen and avoid scurvy - instead, we are using the antioxidant property to quench free radical fires caused by the virus.

    That is not to say there couldn't be significant beneficial properties to the oxidant DHAA.

    A forum poster wrote and article published in the Townsend Letter providing evidence that it is DHAA that is ultimately responsible for ascorbate's anti-viral properties. (At these 200,000 mg levels, probably 20% breaks down to DHAA and that may be what creates much of the benefit).

    I know doctors who use the anti-malaria oxidant MMS to treat diseases like Lyme. They use the oxidant property on purpose. I do not want to rust myself, so I will not take 5 grams of DHAA to merely repeat the blood measurement shown in the video, but if I had Lyme disease, that would be a different matter, and I would then be willing to try high doses of DHAA. (With something like 5 times the amount of AA - later)
    Owen R. Fonorow, Orthomolecular Naturopath
    My statements have not been evaluated by the Food and Drug Administration. Any product mentioned is not intended to diagnose, treat, cure or prevent any disease.”

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    Re: Dehydroascorbic = MUCH higher blood levels of VitC ?

    Post Number:#33  Post by OxC » Thu Oct 09, 2014 10:48 am

    ofonorow wrote:A forum poster wrote an article published in the Townsend Letter providing evidence that it is DHAA that is ultimately responsible for ascorbate's anti-viral properties. (At these 200,000 mg levels, probably 20% breaks down to DHAA and that may be what creates much of the benefit).
    I'm not sure there is any evidence to support an assumption that "probably 20%" of a 200 gram dose of AA is converted to DHAA, but maybe it is true. Maybe, for that matter, the conversion of AA to DHAA is responsible for most of the perceived benefits of taking megadoses of AA. As you have pointed out, there remains a great deal that is unknown as to the fate or function of large doses of AA.
    Douglas Q. Kitt, founder of ReCverin LLC, sellers of stabilized dehydroascorbic acid solutions.

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    Re: Dehydroascorbic = MUCH higher blood levels of VitC ?

    Post Number:#34  Post by OxC » Thu Oct 16, 2014 4:33 pm

    Hello davea0511,
    It’s been a while since I’ve had time to come back to this thread and comment on some of things you’ve posted. Today I’d like to address the concept of vitamin C utilization as a source of energy, and some comments you have made in this regard:
    davea0511 wrote:AA, which is 99% of what you are using when you buy a bottle of regular vitamin C ... this form donates a bioavailable electron at the cellular level and provides an alternate pathway for aerobic ADP -> ATP synthesis (see ... chp_17.pdf, pages 9-11), which is the main reason why vitamin C gives you energy.

    The utilization of vitamin C for aerobic ATP synthesis is perhaps its most valuable asset…

    ...going from AA to DHA imparts energy to synthesize ATP ... the molecule responsible for energizing all cellular activity. So, again, consuming DHA is kind of like breathing in CO2, imnsho. Not doing you a whole lot of good filling your cells with spent fuel.

    The reference you cited shows an experiment under the heading Electron-transport chain has been elucidated through the use of inhibitors. This is a famous experiment, taught in many physiological chemistry courses, but it is important to understand what this experiment is intended to demonstrate, and what it is not intended to demonstrate. If you read the details closely, you will see that a number of chemicals were added sequentially to isolated mitochondria, including: rotenone (a pesticide), amytal (a barbiturate drug), antimycin A (an antibiotic), b-hydroxybutyrate, TMPD (a synthetic indicator and reducing agent), ascorbic acid, succinate, and cyanide ion. Here is the summary of the experiment copied from the citation:
    Summary of experiment:
    1. Add β-hydroxybutyrate into the reaction cell → O2 consumption is increased.
    2. Add rotenone or amytal into the reaction cell → O2 consumption is stopped (Complex I is inhibited).
    3. Add succinate into the reaction cell → O2 consumption is resumed.
    4. Add antimycin A into the reaction cell → O2 consumption is stopped (Complex III is inhibited).
    5. Add TMPD + ascorbic acid into the reaction cell → O2 consumption is resumed.
    6. Add CN- into the reaction cell → O2 consumption is stopped (Complex IV is inhibited).

    Each of these reagents have a specific effect in the electron-transport chain, and are therefore useful in demonstrating the steps involved. But I think most people will recognize that substances like rotenone, amytal, cyanide, and antimycin A are poisons and/or drugs, and therefore that this experiment was not intended to suggest that these chemicals participate in the electron-transport process under normal circumstances. Likewise, ascorbic acid plus TMPD were used as reagents. The AA was artificially oxidized by TMPD to yield electrons, said electrons being injected into a pathway that had previously been poisoned by an agent that prevented electron transport. The artificially supplied electrons “restarted” transport in the next step, and so a particular step was “elucidated.” But this experiment does not suggest or imply that this is a normal or likely pathway of ascorbic acid metabolism in the human body.

    On the other hand, this experiment does not exclude that possibility. It may be that AA is utilized in the mitochondria for energy production by this mechanism, with each AA molecule offering two electrons and therefore being able to produce one ATP molecule (“one ATP is synthesized when the two electrons pass through every Complex I, Complex III, and Complex IV”). This could explain your observation that, “…for some people (self included) megadosing at night will make them sleepless.” My point here is that this mechanism is not a proven pathway of ascorbic acid metabolism; it is a hypothesis. And furthermore, it is not the only reasonable hypothesis that can be put forth.

    So I would ask you to consider another possibility; that both AA and DHAA can be diverted into energy production by aerobic utilization in the citric acid cycle. And before presenting any evidence in that regard, I would ask you to consider the implications of such a possibility:

    • If a molecule of AA or DHAA could be enzymatically converted to a metabolizable sugar, then utilization of that sugar for energy production through the citric acid cycle could produce a net gain of not just one but many ATP molecules. For example, it is known that the utilization of a glucose molecule can produce a net gain of about 30 ATP molecules. Even if a degradation product of AA or DHAA were to yield a single moiety that could be utilized in the citric acid cycle (rather than the two moieties that glucose provides), the net gain could easily be 10 ATPs. Thus the sleepless nights from megadosing vitamin C would be even more readily explained by one of these mechanisms.
    • The bioavailable electrons derived in the citric acid cycle are not always utilized for ATP production; in fact, most of these electrons are first transferred to NAD to produce NADH. A glucose molecule produces 24 bioavailable electrons in this cycle, most of which are first transferred to NADH. As I’ve pointed out in previous messages in this thread, it is this NADH that is the ultimate source of bioavailable electrons for the recycling of DHAA to AA. Thus, in the case of ingesting a megadose of DHAA, metabolism of only a fraction of it for energy production could easily supply the bioavailable electrons needed to recycle the remainder to AA.

    So what evidence is there that both AA and DHAA might be utilized for aerobic energy production?
    ”Hepatocytes prepared from 48 h starved animals are glycogen depleted, therefore the source of their glucose production is gluconeogenesis. Cells were incubated in the presence of various concentrations of ascorbate or dehydroascorbate for 30 min and their glucose production was measured. For comparison gluconeogenesis from alanine was also detected. Significant glucose formation from ascorbate was observed, which reached saturation at relatively low ascorbate concentrations. Dehydroascorbate-fueled glucose production showed a greater rate and saturation was reached at higher substrate concentrations. Gluconeogenesis from both substrates was surprisingly effective, its rate being comparable to that from alanine.”
    Gluconeogenesis from Ascorbic Acid: Ascorbate Recycling in Isolated Murine Hepatocytes (1996)

    So we see that both AA and DHAA can be converted to metabolizable sugars in the liver of at least one mammal, in this case a mouse. There are many references that speculate or provide indirect evidence of this pathway in other mammals, but I have found none that either strongly support or refute this capacity in humans.
    “The major pathway of catabolism of ascorbic acid in the guinea pig is the oxidation of its lactone carbonyl carbon to CO2 with subsequent oxidation of the entire carbon chain to CO2.”

    “The guinea pigs fed the massive amounts of ascorbic acid catabolized the vitamin at a faster rate than those animals fed the control amount. The total amount of radioactivity excreted by the experimental groups was significantly greater than the amount excreted by the control group… This was due to greater CO2 excretion in the experimental group.”

    Catabolism and Tissue Levels of Ascorbic Acid Following Long-term Massive Doses in the Guinea Pig (1974)

    The appearance in the breath as CO2 of carbon atoms derived from any particular nutrient has often been taken as strong evidence that the nutrient in question has been catabolized aerobically to produce electrons or energy in the citric acid cycle. This is because the vast majority of expired CO2 comes from this source. I admit that this is not definitive evidence, because there are other ways that CO2 can appear in the breath. (Just as an aside, the mechanism you propose, wherein electrons from AA might be injected directly into the electron-transport chain towards ATP production, would not result in production of CO2).

    This reference I’ve cited is only one of many demonstrating that various mammals, including mice, rats, guinea pigs, and monkeys, all produce significant amounts of CO2 from ingested AA, even when only small amounts are ingested. Most studies have been conducted with small doses of vitamin C, such as would be found in a meal of common food. Only a few have explored what happens when megadose amounts are consumed. I cited this particular reference because of the further demonstration that larger doses result in a larger percentage of CO2 being expired.

    Interestingly, when small doses are given to humans, literally none of the vitamin C appears to be utilized for energy production, because very few of the carbon atoms derived from vitamin C appear in the breath as CO2. Apparently we humans are more stingy about “wasting” precious vitamin C on energy production, even as compared to other species that can’t synthesize vitamin C. Maybe we’ve evolved this way because our diets don’t contain as high a proportion of vitamin C as guinea pigs and monkeys. In any event, this appears to be the case when we eat these small amounts. But what happens when we take larger doses?
    ” Volunteers were given a steady intake of various individually different daily dosages of ascorbic acid. After 3 weeks 1-14C-labelled ascorbate was given together with various amounts of unlabelled ascorbic acid (90-1000 mg). Regardless of the total daily dose, in cases where the carrier dose amounted to 180 mg or more, carbon dioxide was recovered from the breath. The amount recovered ranged from 1 to more than 30% of the given dose. The larger the amount of carrier the larger was the amount of label recovered as carbon dioxide.”
    Formation of Carbon Dioxide from Ascorbate in Man (1985)

    So in humans, although small doses of AA don’t appear in the breath as CO2, it appears that larger doses do; and it also appears that the larger the dose, the more AA is catabolized to CO2.

    And finally, if AA and DHAA cannot be converted to metabolizable sugars in humans, is there any other way that they might be utilized in the citric acid cycle?
    "1. Evidence is presented showing that progressive degradative changes occur in L-ascorbic acid dissolved in water and kept at 25°C for a 72-hour period. 2. When a human subject received 20 μc of freshly dissolved L-ascorbic-1-C14 acid solution, little or no C14 appears in his respiratory CO2. 3. Men who were given similar samples of L-ascorbic-1-C14 acid aged for 36 and 72 hours, respectively, excreted 30.6% of the ingested C14 as respiratory CO2."
    Respiratory Catabolism in Man of the Degradative Intermediates of L-ascorbic-1-C-14 Acid (1963)

    So degraded solutions of AA contain significant amounts of “something” that appears to be utilized in aerobic energy production. That “something” could be DHAA formed from oxidation of AA, but as I’ve pointed out previously, DHAA has a very short half-life in aqueous solutions, so the “something” (which represents 30% of the original AA in this experiment) may also be or include one or more degradation products such as DKG. The point is that, even if AA and DHAA are never converted to metabolizable sugar in man, when AA becomes DHAA or is further degraded in our bodies, the DHAA or further degradation products appear to be substrates for aerobic energy production.

    I freely admit that the mechanism(s) I hypothesize here are just that: hypotheses. But I also contend that my hypotheses are as well-supported by the evidence that I provide as is your hypothesis by the citation that you provide. A big difference, in regard to the original topic of this thread, is that your hypothesis suggests that only AA, and not DHAA, can be utilized for energy production, and this leads you to the conclusion that DHAA is “spent fuel,” and “consuming DHA is kind of like breathing in CO2.” My hypotheses suggest that both AA and DHAA can be utilized for energy production.

    Best regards,
    Doug Kitt

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