Synthesis of opposing views: a syncretic view of the many contradictions re vitamin C

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A model that makes sense of opposing views about vitamin C has the following “tenets” (by definition, tenets are tentatively held ideas, modifiable with every piece of data that does not fit the model):

  1. Pauling focused on the high rate of synthesis of vitamin C in animals that make it. He focused on the fact that if we ingest grams of vitamin C, we absorb grams of vitamin C. He noted that we absorb even more vitamin C when we are ill. Pauling focused on the proven utility of high dose vitamin C in the work of Dr. Frederick Klenner. He more or less ignored the high rate of urinary excretion of vitamin C.
  2. The US government focused on the high rate of urinary excretion and the fact that total body pools of vitamin C cannot be increased stably beyond about 1500-3000 mg. The government scientists ignored the fact that animals of our size make 200 times our RDA and that we absorb grams of vitamin C before we excrete all but about 100 mg of it per day and that we absorb more vitamin C when we are sick.
  3. As a rule, animals make about what they need of various nutrients. Exception: we make less choline than we need. As a consequence, animals do not make 200 times what they need.
  4. Both Pauling and the government scientists are making valid points. What is the explanation of these contradictory viewpoints?
  5. A possible explanation of the paradox is that vitamin C is accidentally absorbed (for example, oxidized vitamin C is absorbed by a glucose receptor) and deliberately excreted. This fails to explain why vitamin C is absorbed better when we are ill.
  6. Optimal tissue levels of vitamin C are at or near SL (saturating or near saturating levels). This explains why goats make 13 grams of vitamin C a day and why we absorb grams per day even though we need but 100 mg or so to replace losses of vitamin C (at 2-4% loss per day with a total body pool size of 1500-3000 mg).
  7. Supersaturating levels in serum and tissues occur for a short period of time following injection with high levels of sodium ascorbate.
  8. Chosen properly, an injection that achieves a therapeutic window of proper supersaturating levels of serum and tissue vitamin C, which I will call SSL1 (supersaturating level 1), avoids most of the toxicity and allows some antitumor, antiviral, antibacterial, and antifungal action, as well as some high level chelating of heavy metals. This explains the effectiveness of the use of injectable vitamin C as an adjunct cancer therapy and the many anecdotal results (more than 30 diseases treated) of Dr. Frederick Klenner re injection of high doses of vitamin C followed by high oral doses. Before even getting a diagnosis, Dr. Klenner treated everyone prophylactically with a high dose of injectable vitamin C, followed by multiple oral high dose vitamin C. When they came back for their diagnosis and treatment, they were in many cases on the road to recovery.
  9. Chosen improperly, there is a level of serum and tissue super-saturation, SSL2 (supersaturating level 2), at which there could be heavy damage to normal cells, especially if the kidneys are compromised. Possible mechanism: a catalytic cycle in which vitamin C binds regions in the genome in which copper is bound to cellular DNA, and creates single and double stand breaks. Vitamin C can be regenerated by various cellular antioxidants like glutathione (at 5-10 mM, glutathione is many times higher in concentration than cellular vitamin C), making this a highly destructive catalytic event.
  10. This toxic reaction or something like it or both explains why evolution has favored those animals whose kidneys excrete vitamin C so well and so rapidly, and this rapid excretion explains why vitamin C cannot ordinarily be driven to still higher concentrations in tissues (>=SSL2), given reasonably healthy kidney function.
  11. This explains the US government’s position – why take more than about 100 mg a day if it is all going to be excreted? Well yes, after tissue saturation has been achieved. I doubt that 100 mg a day can always maintain saturation in all tissues. When we are sick we absorb more vitamin C (as evidenced by higher bowel tolerance) and we consume more vitamin C when we are sick. When goats are sick they make twice as much vitamin C as when they are healthy.
  12. Nature’s program is to overdose the vitamin, thus achieving tissue saturation, and then excrete the excess as rapidly as possible to sidestep the toxic side reaction(s).
  13. Because of the toxic reaction(s) at SSL2, at inappropriately high supersaturating concentrations of vitamin C, no one with impaired kidney function should take Pauling type doses (18 grams a day).
  14. Re the government’s position: I would argue that vitamin C passing through the bowel may be doing us a world of good in keeping stools somewhat looser rather than too hard. I would also argue that vitamin C in urine is definitely doing us a world of good. First, in solubilizing substances like calcium (calcium oxalate and calcium phosphate stones are much less likely in someone taking high dose vitamin C). Second, and this is more speculative, in reducing the likelihood of UTI – the acidity of urine with lots of vitamin C likely makes it very uncomfortable for fimbriated bacteria trying to colonize the urinary tract.
  15. Also, re the government’s position: the total requirement for vitamin C cannot be deduced merely from mass balance studies. Two reasons – vitamin C is likely a member in a number of other nutrients’ ADME networks, and it will have an optimal dose for functioning there that is in addition to its own optimal dose (since a vitamin C molecule cannot be in two places at once). In addition, we need to write the total requirement of any nutrient as the sum of at least 4 independent parts: 1. the requirements of the entire gut. 2. the requirements of the blood stream and lymphatic systems. 3. the sum of the requirements of all tissues. 4. the requirements of the urinary system.

How general is this model? Might the same not be true of selenium and other nutrients in which the therapeutic window is rather narrow?

Nature plays with fire – it has to; life would never have come to be without doing so – and avoids getting burned most of the time thanks to many rounds of selective pressure that was at times so great that scientists estimate that ~90% of all species were extinguished. That is how nature comes up with such nearly flawless solutions to working with substances that can be as beneficial at one set of doses, between SL and SSL1, and so harmful at another set of doses, that is, >=SSL2.

Optimal vitamin C levels in the body

The body does not allow vitamin C pools to expand beyond about 3 grams. Probably because there is a toxic side reaction associated with higher bodily pools. Possibly the double strand breaks in DNA that vitamin C plus copper would catalyze wherever copper is already bound to DNA.

How much more than 3 grams would be toxic? If it is 4 grams, then 3 grams may be way too much. If it is 10-30 grams, 3 grams might be optimal. It all depends when the putative toxic side reaction kicks in.

Degeneration of normal probability distributions into bimodal distributions

I wonder if this could be generally true.

A natural process working properly has a normal distribution of outcomes. Given aging or any other form of degeneration, the normal distribution breaks down and begins to look bimodal, trimodal, etc.

The normal distribution was due to an appropriate balance among the bimodal competing tendencies (really two normal distributions that overlap and coalesce to make the resulting normal distribution). That normal distribution breaks down and one begins to see the bimodal emerge.

When three or more competing processes equilibrate to make a single normal distribution, breakdown can lead to bimodality, trimodality, etc.

Can the rate and extent of breakdown of normality toward bimodality in reference processes be used to age an organism, or at least to assign relative ages?

An example of what I am talking about – consider the difference between normal stool in healthy individuals in which nature finds the balance of water, solids, and motility to produce something that moves easily and almost effortlessly through the bowels, while maintaining enough hydration for the rest of the body and the kidneys to function well also. Consider what happens with inflammatory bowel diseases, in which there are periods of diarrhea and periods of constipation -often roughly equal in numbers and durations – and few “normal” days as far as stool is concerned.

Backpedaling

In describing nature, whenever we use absolute language, and we do that a lot, we have to backpedal or face clear deficiencies in our descriptions and contradictory data.

Karl Jaspers said that one has not understood what Nietzsche wrote until one also finds the contradiction. Is this unique to Nietzsche? I doubt it.

In the popular picture of Hegel’s thought, thinking correctly moves from thesis to antithesis to (Hegelian) synthesis. Indeed, if one proposes an absolute thesis, one has to deal with contradiction. Hegel’s way was a type of syncretism.

How does one say something meaningful without having to backpedal? Answer: by eliminating all absolute words and terms and any words or terms that can be confused with such. We need a computer program that does this and suggests properly worded alternatives. The goal is no backpedaling. Clarity is truthful descriptiveness of nature and that implies no backpedaling.

Another useful program: one that extracts contradictions and puts contradictions and absolute statements on facing pages. I would love to write this program to highlight the backpedaling that so many people ignore – and to catch my own before I have to backpedal.

Oxygen – can’t live with it; can’t live without it

With our present genome and its limited investment in self-preservation, we cannot live for more than about 120 years while dealing with the damage done by oxygen (with help from iron and copper, mainly), and we cannot live more than about 10 minutes without any oxygen. Between those extremes, most Americans live about 75 years with so/so oxygenation of their tissues and mediocre oxidative defenses.

A distinct possibility

Every enzyme in the body may be misnamed.

Every enzyme carries out more reactions and side reactions than its eponym indicates.

For example, NOS, nitric oxide synthase, of which there are at least 3 forms. However, all of them could be named

“nitric oxide superoxide synthase,” as all of them can produce at least nitric oxide and superoxide, and the relative amounts of nitric oxide production and superoxide production depend entirely on the local conditions. How much of important structure stabilizers (such as potassium?, taurine?), BH4 (an important structure stabilizer for NOS), how much arginine, how much asymmetric dimethyl-arginine, how much agmatine, how much zinc (an important structure stabilizer for NOS), how much the enzyme has been genetically modified in different ways in different cells, how much the enzyme has been chemically modified (in part by other things, in part by its own byproduct, superoxide, and in part by the product, peroxynitrite, of its product, NO, and its byproduct, superoxide; peroxynitrite does a lot of damage to a lot of things, including converting BH4 into quinoid BH2), where the enzyme has been chemically modified (e.g. there are serines that if phosphorylated, activate it, and there is a threonine that if phosphorylated, inhibits it), how much enzyme is bound to various competing cofactors like Ca2+-calmodulin, hsp90, caveolin-1, etc. etc.

Incredibly complicated, and this is just the tip of that complicated iceberg. At any rate, the enzyme, like most or all others, is misnamed or shall we say “under-named”?

What’s killing us

One thing: our terribly imperfect human genome. It seems that in evolution slow breeding, longer-lived species almost inevitably lose out in competition with faster breeding, shorter lived species. And as a result of evolutionary selective pressures, we suffer the consequences of aging and death, and we note the contradictory importance of two more things that would spell our demise even if our genome were quite a bit improved with respect to maintenance/repair: oxidation and lack of oxidation. The former is the penalty we must suffer just to have abundant energy from mitochondrial respiration and the latter is the penalty we suffer when we don’t do enough mitochondrial respiration, and we lose measurable respiration capacity with each passing decade of life.