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
http://crystal.res.ku.edu/taksnotes/Bio ... 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