Posted by Larry Hoover on February 21, 2009, at 15:13:28
In reply to Re: Start Questioning Vitamins?, posted by desolationrower on February 20, 2009, at 2:06:31
> > d/r wow I take 2grams of extended release C with rose hips what's the consequences should I cut down? Thanks Phillipa
>
> oh, 2g is ok. i get about a gram supp and food... it can affect insulin activity, kidney stones, affects histamine, dopamine, probably some other stuff i'm forgetting...could interfere with excercise benefits...its just an unpredictable chemical, easily switches antioxidant/proxidant, involved in many things, taking excess is a bad idea
>
> -d/rI have a very different opinion about vitamin C than have you.
I've been following the "vitamin C becoming a pro-oxidant" argument quite closely, and I don't know of a case where it has been scientifically shown to occur in vivo, i.e. in a living human. There are numerous studies showing that it can happen in vitro, in a lab dish, but if and only if non-physiological conditions are present. Most commonly, that would be free metal cations, such as iron++, copper++, or zinc++. The second condition, generally, is a complete absence of other free radical quenchers (anti-oxidants). Only under these artificial circumstances can we find meta-stable ascorbate radicals. Metal ions are virtually never freely dissolved in blood. Instead, they are transported by specialized globular proteins called metalothionines. When they get where they're going, they are incorporated into the protein structure of enzymes. They cannot produce this kind of havoc, in vivo.
One thing is true of all antioxidants....when they quench a reactive oxygen species (ROS), they themselves become oxidants. That's true of curcumin, glutathione, vitamin E.....they all become oxidants, but very much weaker than the ROS that they quenched.
Many common antioxidants in human physiology have significant interactions. For example, one of the primary functions of vitamin C is to reduce spent tocopherol (vitamin E) after it has been oxidized. That restores it to its active form again. In turn, glutathione can restore oxidized vitamin C back to its antioxidant form. And cysteine reduces glutathione back to its antioxidant form. However, none of them is dangerous when in the oxidized state, despite being technically pro-oxidant in structure.
Vitamin C uptake into some tissues even requires that it be in the oxidized form, the pro-oxidant form, for it to even get across the cell membrane. That's because the oxidized form, called dehydroascorbic acid (DHAA) utilizes the glucose transporter to enter tissues that do not have dedicated sodium-dependent ascorbic acid transporters. Now, the glucose transporter is insulin dependent, so your mention of insulin responsivity is well-founded. However, vitamin C improves insulin sensitivity, and moderates blood glucose levels, in both Type 1 and 2 diabetics. There is a complex interaction which is hard to simplify to a sound-bite statement. Diabetics develop tissue-specific scurvy because their glucose transporters don't work efficiently. This leads to complications of diabetes such as cataracts, and retinal deterioration.....due to local vitamin C deficiency. Diabetics typically have very low vitamin C levels, and supplementation is usually recommended.
The kidney stone thing was a hypothesis that was never demonstrated. It just took on a life of its own. I've seen one study that linked actual calcium oxalate stones to higher vitamin C intake, but I've seen many other and larger studies that found no such correlation. Far more important in CO stones is low calcium intake, which is totally counter-intuitive. Normal healthy people do not have any reason to fear kidney stones from vitamin C. On a risk/benefit basis, the benefits truly outweigh this unproven risk.
And yes, histamine is affected. Vitamin C is an anti-histamine. And by suppressing circulating histamine levels, the immune system activity is enhanced.
Now, as to dopamine.....There are a number of dopamine receptors whose activity is dependent on not only dopamine concentration, but also local vitamin C concentration. The mechanism has not been explained, but e.g. the pituitary dopamine receptor that induces release of prolactin is inhibited by vitamin C. I'm sure vitamin C has many other effects that a closer look at biochemistry might reveal. One neurotransmitter related synthesis is entirely dependent on vitamin C: It takes one molecule of vitamin C to produce one molecule of norepinephrine from dopamine.
Vitamin C is the dominant anti-oxidant in mitochondria, the energy factories for the body. Vitamin C is essential for collagen synthesis. Vitamin C is essential for the synthesis of carnitine.
The evidence for how much is an optimal intake is not yet sufficient for the "experts" to reach a consensus. However, here are pieces of evidence that I consider useful to consider.
In primates which like ourselves have lost the ability to produce ascorbic acid from glucose, circulating blood concentrations would suggest that humans would require daily intake of about 2500 mg to maintain similar concentrations. Unless we're unique among primates, that's one predictor.
In mammals which possess the genes to synthesize their own vitamin C, adjusted for body mass, we'd be looking at perhaps 18-30 grams (18,000 to 30,000 mg) per day. And those levels have been shown to increase 10-fold or more when the animal is stressed, as by a flesh wound or psychological factors.
It's quite likely that we've evolved some ways of minimizing our dependency on vitamin C, but I doubt that we can forego the enhanced demand that occurs during stress. However, we're limited on the uptake side. But even that might be conditional.
When they've done vitamin C uptake studies, blood concentrations tend to plateau despite increasing doses into the multiple gram range of intake. That indicates that the gut transporters are saturable, i.e. they can't transport more than some maximum level. What I have not seen done is any test to see if that transporter system upregulates in reponse to increased intake. It doesn't make sense from an energy efficiency perspective for the gut to have a greater number of transporters at the ready than would likely be required to transport amounts of vitamin C above what it typically sees. So, this maximum uptake level might well increase with supplementation. That's my conjecture.
Recent work has begun to revisit vitamin C as a cancer therapy. The problem that took many years to overcome was that fifty years ago, vitamin C debunkers used oral vitamin C in cancer treatment, whereas proponents had shown some success using IV treatment. Because of the uptake-limiting pump capacity issue, oral loading could only produce maximum blood concentrations far below those being produced via IV infusions. Vitamin C was said to have failed clinical trials, when it was instead a method failure, by the Mayo Clinic. Some have claimed they did it on purpose. Anyway, they're now giving IV vitamin C to terminal cancer patients at doses up to 1.5g/kg body weight, thrice weekly. That's 105 grams (105,000 mg) in one dose, based on a typical 70 kg person. No adverse effects have been noted, but these people are quite ill to begin with. Quality of life measures have been significantly increased, though.
On a risk/benefit analysis basis, I think there are a lot of potential benefits, and no clearly identified risks from vitamin C supplements.
Uptake is optimized if smaller doses are taken more frequently, or a timed-release formula is used. Honestly, I think we're going to see the recommended daily intake for this vitamin increase substantially, just as we saw with vitamin D. That's what I think, anyway.
Lar
poster:Larry Hoover
thread:880621
URL: http://www.dr-bob.org/babble/20090213/msgs/881536.html