With up to 2.5 g this is neither a "low-dose" study, nor does this or several other studies showing a similar plasma-dose curve allow for any other extrapolation.
...If you really think that those studies are not conclusive, you obviously have an irrational affection with vitamin C.
1.25 g single Vitamin C doses 2 times a day are low compared to the up to 9 g single doses 3 times a day regularly taken by me.
Those couple of higher dose case studies by Hickey or Copplestone, where plasma levels were repeatedly meassured above the usually maximum possible 220 µmol/L - even if not published in a pharma-sponsored journal - should raise the concern that further investigations would have to be done before taking assumptions, in the face of however feeble opposing evidence, as conclusive.
My personal beneficial experiences with mega-dosing Vitamin C is related in this post already:
- Vitamin C (after a PAD diagnosis almost 5 years ago, together with lysine and all other nutrients recommended by Linus Pauling) - pain-free walking distance improved from mere 3-400 meters up to 2 hours. But only once I exceeded the in his view minimal therapeutic dose of 6g/d. Side-benefits: a since 2 years persistent skin-rush cleared up, hay-fewer symptoms recurring every spring since 12 years got alleviated (though this year it took 30 g/d; in avg. about 20 g/d for 5 years). HbA1c stayed unproportionally low, compared to rising blood glucose. Truly addictive stuff for someone with my health-issues. Only negative side-effect: flatulence.
- ...
I wouldn't recommend large doses of vitamin C for generally healthy people.
... Hence, we have evolved a tight regulation for exogenous ascorbate, keeping the plasma level at a maximum of ~100mcg/ml, much less than that of most ascorbate synthesizing species (a discrepancy which mislead Linus Pauling into his megadosing theory).
That said, of course it would be possible to continuously overload the kidneys with periodic mega-dosing. That would be an option for severe illnesses where supraphysiological plasma levels have shown promise (e.g. cancer) and IV dosing is impractical. However, as I said before, I think that healthy people want to avoid such plasma levels. We have to assume that there is a good evolutionary reason for this regulatory mechanism.
That's where, I think, our different approaches come from. Where I can't but have to consider the beneficial effects I experienced from mega-dosing with severe illness (where the extrapolated ~100mcg/ml saturation levels just wouldn't make any sense) - healthy people wouldn't experience that many benefits, at least in the short term.
So according to your last post Pauling wasn't that mislead about mega-dosing with severe illness? How you reconcile that with the discrepancy of low-dose saturation you're still maintaining?
Therefore, I think it is advisable to keep the plasma level saturated by insuring a total intake of at least 400mg (agreeing with the LPI's recommendations), ..
The Difference Between Dr. Linus Pauling's Recommendations and the Linus Pauling Institute's Recommendation for Vitamin CIntake
In this context, it is important to note that data from the National Institutes of Health (NIH) have indicated that vitamin C levels in plasma and circulating cells become fully saturated at intakes of about 400 mg/day in young, healthy nonsmokers. These observations are consistent with other data that intakes of about 400 mg/day are associated with reduced risk of heart disease. While these NIH studies are the best we currently have regarding the pharmacokinetics of vitamin C in the human body, they have numerous limitations, including the fact that they are based on a small number of young, healthy men and women. We currently do not know how much vitamin C is required to achieve saturation of cells and tissues in children, older adults, and diseased or stressed individuals. A recent meta-analysis of 36 studies on the relationship between vitamin C intake and plasma concentrations found that the elderly require a substantially higher daily intake of vitamin C to attain plasma concentrations that younger adults achieve at a lower intake. Additionally, work by Linus Pauling Institute investigators has shown that cellular uptake of vitamin C declines with age, supporting the notion that vitamin C requirements are increased in the elderly.
About the
safety of Vitamin C mega-dosing:
Safety, Toxicity
A number of possible problems with very large doses of vitamin C have been suggested, mainly based on in vitro experiments or isolated case reports, including genetic mutations, birth defects, cancer, atherosclerosis, kidney stones, "rebound scurvy," increased oxidative stress, excess iron absorption, vitamin B12 deficiency, and erosion of dental enamel. However, none of these alleged adverse health effects have been confirmed in subsequent studies, and there is no reliable scientific evidence that large amounts of vitamin C (up to 10 grams/day in adults) are toxic or detrimental to health.
And further their response about a Vitamin C UL:
With respect to the UL, we agree with the Panel that there is no scientific evidence that even very large amounts of vitamin C are toxic or exert adverse health effects. Specifically, in healthy individuals vitamin C does not cause mutations, cancer, birth defects, hardening of the arteries (atherosclerosis), kidney stones, pro-oxidant effects, "rebound scurvy," excess iron absorption, vitamin B12 deficiency, allergic response, or erosion of dental enamel. The Panel used osmotic diarrhea and gastrointestinal disturbances as criteria to determine the UL for vitamin C and arrived at a level of 2 grams/day. We disagree with this conclusion because it is based primarily on data from uncontrolled case reports. Some studies have reported no gastrointestinal disturbances or diarrhea at up to 6 grams/day of vitamin C, and gastrointestinal disturbances have been observed at widely differing threshold levels (from 3 grams/day up to 10 grams/day). More importantly, we believe that diarrhea and gastrointestinal disturbances are not toxic or severe enough effects to justify a UL based on these criteria. Thus, the side effects of vitamin C are generally not serious, and individuals experiencing these effects may easily eliminate them by reducing vitamin C intakes.
Based on our review of the literature, we conclude that the RDA for vitamin C should be 120 mg/day for optimum risk reduction of heart disease, stroke, and cancer in healthy individuals. Special populations, such as older adults and individuals with disease, may require substantially larger amounts of vitamin C to achieve optimum body levels and derive therapeutic benefits. Furthermore, we conclude that there is currently no consistent and compelling data for serious adverse effects of vitamin C in humans, and a UL can therefore not be established.