Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Ask questions, seek advice, or share your experience with vitamin C

Moderators: ofonorow, popnowlin

ofonorow
Ascorbate Wizard
Ascorbate Wizard
Posts: 12886
Joined: Tue Nov 22, 2005 3:16 pm
Location: Lisle, IL
Contact:

Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#1  Post by ofonorow » Fri Jul 06, 2018 9:42 am

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2649700/

This may have been posted/discussed before. It is an excellent discussion of the role of Sodium Vitamin C transporter and the large concentration of ascorbate in the brain.


Although such DHA uptake and reduction can at least transiently generate a trans-plasma membrane gradient of ascorbate [16], several lines of evidence suggest that it is not the major route.

First, DHA concentrations in blood plasma are 2 μM or less, whereas ascorbate concentrations are 40-60 μM [31,32]. Second, glucose will compete in most cells for uptake of this low concentration of DHA on the GLUTs, as has been demonstrated in human leukocytes [33,34]. Third, and perhaps most compelling, ascorbate concentrations are low in cells lacking the SVCT. Two examples highlight this point. First, ascorbate levels are the same in erythrocytes and the plasma from which they were taken [16,35]. This is despite the observations that human erythrocytes express high numbers of GLUT1 [36] and that glucose does not compete well for DHA uptake in this cell type [37]. Key here is that failure to concentrate ascorbate in human erythrocytes corresponds to a lack SVCT proteins [38].

The second example is that knockout of the SVCT2 results in almost undetectable ascorbate concentrations in embryonic brain and pituitary [39]. These observations support the notion that the high trans-plasma membrane ascorbate concentration gradients seen in other non-epithelial cells are due to the SVCT2. Nonetheless, DHA uptake and reduction could well preserve intracellular ascorbate over short time periods in areas of high oxidant stress, where significant amounts of extracellular ascorbate are oxidized
Owen R. Fonorow, Follow #OWENRFONOROW at twitter

tjohnson_nb
Vitamin C Expert
Vitamin C Expert
Posts: 561
Joined: Thu Apr 26, 2012 5:03 am
Location: Canada
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#2  Post by tjohnson_nb » Fri Jul 06, 2018 9:46 am

Yes, it's excellent.
'Always' and 'never' are 2 words you should always remember never to use.

OxC
Vitamin C Master
Vitamin C Master
Posts: 328
Joined: Tue Sep 17, 2013 1:25 pm
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#3  Post by OxC » Sat Jul 07, 2018 8:42 pm

According to the cited article,
The major route by which ascorbate enters the CNS involves transport from plasma to the CSF across the epithelium of the choroid plexus.

But a different study The Influx of Ascorbic Acid into the Rat’s Brain concludes:
The idea, proposed by Spector & Lorenzo (1973), that the choroid plexus plays an important role in the transport of ascorbic acid into the brain must now be reconsidered in the light of our finding that there is a carrier-mediated transport process for this vitamin across the cerebral capillaries…when ascorbic acid in the plasma is within the normal physiological concentration (58 uM), the influx across the brain is approximately 10 times higher than that through the choroid plexus…Another reason for believing that the choroid plexus only plays a small part in the entry of ascorbic acid into the tissue of the brain is that when the ascorbic acid has passed through the choroid plexus into the cerebrospinal fluid (CSF) it has a long pathway to traverse before it reaches the cerebral cells. It must be carried in the CSF from the lateral ventricles, over the convexity of the hemispheres and then alongside the penetrating vessels of the brain into the cerebral tissue. In this study, we have shown that the labelled vitamin was found in the brain tissue within 1 min. The rapidity of this accumulation in the cerebral tissue makes it most unlikely that the choroid plexus is a major route of entry.

And another different study Vitamin C Crosses the Blood–Brain Barrier in the Oxidized Form Through the Glucose Transporters concludes:
We identified the chemical form of vitamin C that readily crosses the blood–brain barrier, and the mechanism of this process. Ascorbic acid was not able to cross the blood–brain barrier in our studies. In contrast, the oxidized form of vitamin C, dehydroascorbic acid (oxidized ascorbic acid), readily entered the brain and was retained in the brain tissue in the form of ascorbic acid…The findings define the transport of dehydroascorbic acid by GLUT1 as a mechanism by which the brain acquires vitamin C, and point to the oxidation of ascorbic acid as a potentially important regulatory step in accumulation of the vitamin by the brain.

So, the form of vitamin C that enters the brain, and the mechanism of its entry into the brain under normal conditions, remains controversial and there is by no means any general agreement or consensus among scientists.

However, it is well-known and agreed that when DHAA is injected into the bloodstream, vitamin C accumulates in the brain at a rate and in an amount many, many times greater than when an equivalent amount of AA is administered. This has been shown in numerous studies. The most recent such study that I’m aware of is this one in which the comparative accumulation is demonstrated with remarkable images of the brain: (11C)Ascorbic and (11C)Dehydroascorbic Acid, An Endogenous Redox Pair for Sensing Reactive Oxygen Species Using Positron Emission Tomography.

Thus for the purpose of pharmacological intervention with exogenous vitamin C for the potential treatment of Alzheimer’s, Parkinson’s, stroke, brain cancers, etc., it seems to me that the choice of DHAA versus AA should be…well, a no-brainer!
Douglas Q. Kitt, founder of ReCverin LLC, sellers of stabilized dehydroascorbic acid solutions.

pamojja
Vitamin C Expert
Vitamin C Expert
Posts: 802
Joined: Sun Jul 26, 2009 7:44 am
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#4  Post by pamojja » Sun Jul 08, 2018 4:23 am

OxC wrote:Thus for the purpose of pharmacological intervention with exogenous vitamin C for the potential treatment of Alzheimer’s, Parkinson’s, stroke, brain cancers, etc., it seems to me that the choice of DHAA versus AA should be…well, a no-brainer!


Since AA is oxidized anyway in the bloodstream into DHAA, why would it be of any advantage to supplement DHAA instead of AA?

Specially considering that many grams of AA each day are readily cheaply available everywhere, which can't be said of DHAA.

BrightSideOfLife
Enthusiast
Enthusiast
Posts: 59
Joined: Wed May 04, 2016 4:27 pm
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#5  Post by BrightSideOfLife » Sun Jul 08, 2018 7:34 am

As I understand it, DHAA needs glutathione in order to reduce it back to a none oxidized state. For some of us there is not a lot spare Glutathione in order to waste in this way. For me DHAA is not a good option.

DIY DHAA using inexpensive ingredients. It does also compare liposomal C and DHAA absorption. Putting it simply, DHAA wins by a big margin.
https://www.youtube.com/watch?v=YHKBhz7OCB4

pamojja
Vitamin C Expert
Vitamin C Expert
Posts: 802
Joined: Sun Jul 26, 2009 7:44 am
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#6  Post by pamojja » Sun Jul 08, 2018 8:30 am

BrightSideOfLife wrote:Putting it simply, DHAA wins by a big margin.


But how do you know that levels in serum inexpensively possible with just 20 g of oral AA a day, would also be possible with self-made DHAA?

Journal of the New Zealand Medical Association, 23-August-2002, Vol 115 No 1160, Glycohaemoglobin and ascorbic acid

Self-reported daily intake varied from 0 to 20 g/day. The plasma AA levels ranged from 11.4 to 517 µmol/L and correlated well with the reported intake.

BrightSideOfLife
Enthusiast
Enthusiast
Posts: 59
Joined: Wed May 04, 2016 4:27 pm
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#7  Post by BrightSideOfLife » Sun Jul 08, 2018 8:58 am

pamojja wrote:
BrightSideOfLife wrote:Putting it simply, DHAA wins by a big margin.


But how do you know that levels in serum inexpensively possible with just 20 g of oral AA a day, would also be possible with self-made DHAA?

Journal of the New Zealand Medical Association, 23-August-2002, Vol 115 No 1160, Glycohaemoglobin and ascorbic acid

Self-reported daily intake varied from 0 to 20 g/day. The plasma AA levels ranged from 11.4 to 517 µmol/L and correlated well with the reported intake.

I am not promoting DHAA's virtues, I do not use it and I am unlikely to do so. I came across that YouTube link while I was looking at videos on liposomal C.

For me it is irrelevant because of the reason that I stated. The less oxidation and requirement for reduction using up valuable Glutathione the better. There are higher priorities and having to reduce DHAA to re-enable it's function immediately after absorption is not wanted. Detox requirements are high enough without adding further burden.

This probably affects you too as I remember your username on another forum (PR) where I go by my Christian name "Carl". I use BSOL on curezone.

pamojja
Vitamin C Expert
Vitamin C Expert
Posts: 802
Joined: Sun Jul 26, 2009 7:44 am
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#8  Post by pamojja » Sun Jul 08, 2018 9:16 am

BrightSideOfLife wrote:Putting it simply, DHAA wins by a big margin.


So simply put, there isn't any evidence that DHAA wins at all.

OxC
Vitamin C Master
Vitamin C Master
Posts: 328
Joined: Tue Sep 17, 2013 1:25 pm
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#9  Post by OxC » Sun Jul 08, 2018 1:58 pm

pamojja wrote:Since AA is oxidized anyway in the bloodstream into DHAA, why would it be of any advantage to supplement DHAA instead of AA?

Apparently there is a limit to the amount of AA that is oxidized in the bloodstream, and/or the amount that is oxidized is rapidly converted back into AA by RBCs at their surface, and/or absorbed by RBCs and other cells (such as neutrophils and macrophages) in the bloodstream, and/or absorbed by the endothelial cells lining the bloodstream. All of these mechanisms have been well described; which of them contribute most isn’t known, but very little DHAA is found in the blood normally. As demonstrated in the article I linked above, injecting just a small amount of DHAA is enough to greatly exceed what occurs normally, or even when plasma levels of AA are increased way above normal. Thus the advantage of directly injecting DHAA is to overcome these mechanisms such that sufficient DHAA is available in the blood supply to the brain. This takes less than 3 minutes to easily detect very significant increases of vitamin C in the brain.

But the concept of increasing the oxidation of AA in vivo is one that has been and is still being researched extensively, and is in actual practice in many cancer centers. I’m referring to simultaneous ascorbate/menadione (vitamin K) treatments. And strangely enough, practioners of chelation therapy are also doing this, albeit unwittingly, and therefore probably not realizing why their treatments are effective in managing the sequelae of diabetes. Most people reading this forum would be very surprised to learn that Linus Pauling himself pioneered some of the work in this field, but he was already in his early 80’s when this article was published in 1983: Enhancement of Antitumor Activity of Ascorbate against Ehrlich Ascites Tumor Cells by the Copper:Glycylglycylhistidine Complex
Douglas Q. Kitt, founder of ReCverin LLC, sellers of stabilized dehydroascorbic acid solutions.

tjohnson_nb
Vitamin C Expert
Vitamin C Expert
Posts: 561
Joined: Thu Apr 26, 2012 5:03 am
Location: Canada
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#10  Post by tjohnson_nb » Mon Jul 09, 2018 3:20 am

In this study, we have shown that the labelled vitamin was found in the brain tissue within 1 min. The rapidity of this accumulation in the cerebral tissue makes it most unlikely that the choroid plexus is a major route of entry.

But this was with a rat's blood and the RBCs are quite different in human blood, are they not? Human RBCs are "designed" to absorb DHAA and so would ingested DHAA make it to the brain like it did with the rat?
'Always' and 'never' are 2 words you should always remember never to use.

pamojja
Vitamin C Expert
Vitamin C Expert
Posts: 802
Joined: Sun Jul 26, 2009 7:44 am
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#11  Post by pamojja » Mon Jul 09, 2018 6:33 am

OxC wrote:
pamojja wrote:Since AA is oxidized anyway in the bloodstream into DHAA, why would it be of any advantage to supplement DHAA instead of AA?

Apparently there is a limit to the amount of AA that is oxidized in the bloodstream, and/or the amount that is oxidized is rapidly converted back into AA by RBCs at their surface, and/or absorbed by RBCs and other cells (such as neutrophils and macrophages) in the bloodstream, and/or absorbed by the endothelial cells lining the bloodstream. All of these mechanisms have been well described; which of them contribute most isn’t known, but very little DHAA is found in the blood normally. As demonstrated in the article I linked above, injecting just a small amount of DHAA is enough to greatly exceed what occurs normally, or even when plasma levels of AA are increased way above normal. Thus the advantage of directly injecting DHAA is to overcome these mechanisms such that sufficient DHAA is available in the blood supply to the brain. This takes less than 3 minutes to easily detect very significant increases of vitamin C in the brain.


The short excerpt of the 'Glycohaemoglobin and ascorbic acid' study is exceptional and the only one in that it didn't only tested serum levels of 1.5-2.5 g AA and further calculated serum levels for remaining doses up to 100 g. But actually tested real life individuals taking up to 20 g throughout the day and consistently reaching above 500 µmol/L. A serum AA level never thought possible reachable by extrapolation of much smaller single doses before. And actually already in a region with anti-cancer effects.

If simply mega-dosing of 20 g/d of AA in serum has otherwise never been tested and such levels thought absolutely impossible, I doubt anyone ever tested DHAA serum levels from such mega-doses of AA. Never mind in the brain. Therefore highly likely in such a case that it also would exceed levels of injected DHAA, if anyone only ever cared to test mega-dosers.

But overall, the fate of DHAA being rapidly converted back etc. would apply to injected just as orally ingested as well. So no difference. Except that 20 g/d of oral throughout the day are so much more convenient and inexpensive to take, than would be daily injections of DHAA. And oral supplementation of DHAA.

tjohnson_nb
Vitamin C Expert
Vitamin C Expert
Posts: 561
Joined: Thu Apr 26, 2012 5:03 am
Location: Canada
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#12  Post by tjohnson_nb » Mon Jul 09, 2018 7:52 am

From Hickey's paper.
However, these preliminary findings suggest that plasma levels of 500–600 mM/L or more could be sustained indefinitely with smaller, but repeated, oral intakes.
'Always' and 'never' are 2 words you should always remember never to use.

OxC
Vitamin C Master
Vitamin C Master
Posts: 328
Joined: Tue Sep 17, 2013 1:25 pm
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#13  Post by OxC » Tue Jul 10, 2018 11:43 am

pamojja wrote:If simply mega-dosing of 20 g/d of AA in serum has otherwise never been tested and such levels thought absolutely impossible, I doubt anyone ever tested DHAA serum levels from such mega-doses of AA.

The "typical pharmacologic doses" used in this study correspond to a range of 17 - 35 grams for a 70 kg human.
Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo
Rats were administered parenteral (i.v. or i.p.) or oral ascorbate in typical human pharmacologic doses (≈0.25–0.5 mg per gram of body weight). After i.v. injection, ascorbate baseline concentrations of 50–100 μM in blood and extracellular fluid increased to peaks of >8 mM. After i.p. injection, peaks approached 3 mM in both fluids. By gavage, the same doses produced ascorbate concentrations of <150 μM in both fluids. In blood, Asc•− concentrations measured by EPR were undetectable with oral administration and always <50 nM with parenteral administration, even when corresponding ascorbate concentrations were >8 mM. After parenteral dosing, Asc•− concentrations in extracellular fluid were 4- to 12-fold higher than those in blood, were as high as 250 nM, and were a function of ascorbate concentrations.
Douglas Q. Kitt, founder of ReCverin LLC, sellers of stabilized dehydroascorbic acid solutions.

pamojja
Vitamin C Expert
Vitamin C Expert
Posts: 802
Joined: Sun Jul 26, 2009 7:44 am
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#14  Post by pamojja » Tue Jul 10, 2018 12:00 pm

OxC wrote:The "typical pharmacologic doses" used in this study correspond to a range of 17 - 35 grams for a 70 kg human.


If already extrapolations/calculations from 1.5-2.5 gram oral vitamins C to higher doses in humans have been shown completely wrong, I don't understand how you could ever place even a jota of confidence in such outlandish calculations from rats to humans? Additionally, rats are still able to produce vitamin C endogenously. Totally different metabolism and animals.

OxC
Vitamin C Master
Vitamin C Master
Posts: 328
Joined: Tue Sep 17, 2013 1:25 pm
Contact:

Re: Vitamin C Function in the Brain: Vital Role of the Ascorbate Transporter (SVCT2)

Post Number:#15  Post by OxC » Tue Jul 10, 2018 5:05 pm

tjohnson_nb wrote:But this was with a rat's blood and the RBCs are quite different in human blood, are they not? Human RBCs are "designed" to absorb DHAA and so would ingested DHAA make it to the brain like it did with the rat?

Yes, there is a difference. Human RBCs take up DHAA 10 – 20 times faster than mouse RBCs. It’s all detailed in this article better than I could ever do: Low Red Blood Cell Vitamin C Concentrations Induce Red Blood Cell Fragility: A Link to Diabetes Via Glucose, Glucose Transporters, and Dehydroascorbic Acid. I assume rat RBCs are similar to mouse RBCs. The bottom line, in my view, is that humans might require DHAA doses 10 – 20 times higher than rats for the same effect. What might that mean in terms of how much DHAA that really is?

In the article I previously cited, where the images were acquired in rats, the actual dose of DHAA injected was about 5 micrograms. If we first calculated the dose for a human based on the weight difference versus a rat, we would need to multiply by a factor of about 280 (heaven forbid pamojja gets wind of this outrageous nonsense! :) ). Then if we increased that by a factor of 20 to compensate for the RBC absorption difference, we get 5 micrograms X 280 X 20 = 28,000 micrograms, or 28 mg.
Last edited by OxC on Thu Jul 12, 2018 7:46 am, edited 1 time in total.
Douglas Q. Kitt, founder of ReCverin LLC, sellers of stabilized dehydroascorbic acid solutions.


Return to “General Discussion Topics and Issues”

Who is online

Users browsing this forum: No registered users and 2 guests