Glucose Modulates Vitamin C Transport

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Glucose Modulates Vitamin C Transport

Post Number:#1  Post by majkinetor » Tue Apr 17, 2012 1:16 am

Well, we knew that glucose competes with DHAA, but not with AA.

It looks like we were wrong. It competes with DHAA and directly inhibits SVCT transporter "from inside" :)

http://jn.nutrition.org/content/130/1/6 ... nsion.html

Low Carb Diet anyone ?

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Re: Glucose Modulates Vitamin C Transport

Post Number:#2  Post by VanCanada » Tue Apr 17, 2012 9:08 am

Do you think the competition works both ways?
A low(er) carb diet would be best for most of us, obviously, but to what extent do you think megadosing vitamin C could compensate for the deleterious health effects of a diet as high in simple carbohydrates as the Standard American Diet? If my memory is right I think the SAD is up to a daily average intake of 150 grams of sugar?? Linus Pauling recommended a maxiumum daily intake of 50 grams of sugar.

I'm thinking of this as a thought experiment for those hypothetical people willing to megadose vitamin C but not willing to change their typical SAD consumption of Frosted Flakes and Slurpees...a rare breed of person indeed, but perhaps useful for exploring these concepts more fully.

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Re: Glucose Modulates Vitamin C Transport

Post Number:#3  Post by majkinetor » Tue Apr 17, 2012 9:47 pm

Yes, I think it works both ways in some extent based on some studies.

Naylor et al (1985) showed that only by adding 3x1g of C in the ad libitum diet weight loss is achieved in women. They say:

Though the use of ascorbic acid in obesity was first suggested because it may possibly indirectly affect the activity of the sodium pump, its mechanism of action is, of course, purely speculative and other explanations are equally possible, e.g. that 3g per day of ascorbic acid interferes with absorption of food.


In the paper I provided in the first post (Malo & Wilson, 2000) they say that AA doesn't affect SGLT so first speculation is probably wrong. Bold part might be right because GI has high levels of DHAA (because of extensive presence of immune cells) which compete with glucose over GLUT receptors.

Next, Garcia-Diaz et al (2010) showed that "VC dose dependently inhibited glucose uptake" in isolated rat adipocytes. They observe its because of GLUT competition also:

The glucose uptake inhi-bition observed in adipocytes without insulin treatment, and especially in adipocytes under insulin treatment, could be partially explained by the fact that dehydroascorbic acid (DHA; the oxidized form of VC that is transported inside cells) possibly competes with glucose for GLUT1 (SLC2A1) and GLUT3 (SLC2A3; Arrigoni & De Tullio 2002), and for GLUT4 (SLC2A4; Vera et al . 1993 ) transporters respectively.


Also, Patel et al. (2001) described interactions of AA, DHAA and Glu in neuronal cells in vitro and concluded that "ascorbate, at concentrations generally thought to be supraphysiological, has the potential for disrupting glucose transport". Supraphysiological concentrations may be achieved in the gut for people on megadoses although I don't know any paper looking into that. From mechanical point of view and properties of SVCT1 receptor it looks possible to me. Keep in mind that I extrapolated from findings in neuronal cells to enterocites but all explanations given for that effect of ascorbate didn't seem context sensitive to me.


So, yes, I think that there is both theoretical and experimental background on this phenomena and that it is highly likely. I don't have time now to list everything, there are number of papers I could include.

I have one reservation tho - if AA and DHAA block glucose transport by all means they should be diabetogenic (Patterson, 1950) yet it doesn't happen for some reason (Afkhami-Ardekani, 2007 for instance) although there are a number of studies showing that effect. There is probability that this functions just like this: C blocks it for a short time, cells upregulate GLUT receptors, C is used and hence original GLUT receptors unblock and finally we have increased GLUT number in non-insulin dependent way and better glucose clearance.


Naylor, G J, L Grant, and C Smith. “A Double Blind Placebo Controlled Trial of Ascorbic Acid in Obesity.” Nutrition and Health 4, no. 1 (1985): 25–28.

Garcia-Diaz, D F, J Campion, F I Milagro, N Boque, M J Moreno-Aliaga, and J A Martinez. “Vitamin C Inhibits Leptin Secretion and Some Glucose/lipid Metabolic Pathways in Primary Rat Adipocytes.” Journal of Molecular Endocrinology 45, no. 1 (July 2010): 33–43.

Patel, M, L McIntosh, T Bliss, D Ho, and R Sapolsky. “Interactions Among Ascorbate, Dehydroascorbate and Glucose Transport in Cultured Hippocampal Neurons and Glia.” Brain Research 916, no. 1–2 (October 19, 2001): 127–135.

Afkhami-Ardekani, Mohammad, and Ahmad Shojaoddiny-Ardekani. “Effect of Vitamin C on Blood Glucose, Serum Lipids & Serum Insulin in Type 2 Diabetes Patients.” The Indian Journal of Medical Research 126, no. 5 (November 2007): 471–474.

Patterson, J.W., and others. “The Diabetogenic Effect of Dehydroascorbic and Dehydroisoascorbic Acids.” Journal of Biological Chemistry 188 (1950): 81–88.

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Re: Glucose Modulates Vitamin C Transport

Post Number:#4  Post by majkinetor » Thu Apr 19, 2012 12:13 am

Actually, I found reference for higher concentration of AA in the gut (is it supraphisiological, I don't know):

http://www.sciencedirect.com/science/ar ... 299090727A

1. Concentration of ascorbic acid present in the gastric or intestinal secretion of fish, dogs and humans is several times higher than in plasma.

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Re: Glucose Modulates Vitamin C Transport

Post Number:#5  Post by ofonorow » Thu Apr 19, 2012 2:46 am

I'm lost
if AA and DHAA block glucose transport by all means they should be diabetogenic


Who is claiming this? How can 1/10 the volume in the blood (15 mg/dl versus 100 mg/dl) block out the higher concentration?

According to Dr. Ely, probably due to the fight-or-flight evolutionary response, the transports favor glucose. Glucose no doubt crowds out vitamin C, not the other way!? (I am learning that much of this F-o-F response is due to cortisol release, which rapidly elevates blood sugars.)
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Re: Glucose Modulates Vitamin C Transport

Post Number:#6  Post by majkinetor » Thu Apr 19, 2012 4:46 am

But continuous infusion could do it, perhaps.
But generally you are right. Nobody claims that, I provided research above from 1950. Also, there is higher concentration of C near the pancreas which delays insulin secretion (there are few studies about it) so glucose hang out more in the blood.

But I guess its not that important.

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Re: Glucose Modulates Vitamin C Transport

Post Number:#7  Post by jaamzg » Thu Jun 07, 2012 5:03 am

Here's a question. Would taking chromium (gtf) along with VC help in getting it into the cells, along with the glucose? We know it's first on the list to help transport glucose into the cell, but since the chemical structure of VC is similar, would it help transport it into the cells, also?

This also led me to think a little bit about the lypo-c which is theoretically helping by getting the VC into the cell via contact with the cell membrane. What if someone who was ill (not necessarily diabetic, flu for example) were to take AA along with Chromium, would that maybe produce better results by helping provide a bridge for the AA into the cells?

I wonder if taking chromium would raise titration levels as the body might be able to push more AA into the cells?

What do you all think?

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Re: Glucose Modulates Vitamin C Transport

Post Number:#8  Post by VanCanada » Thu Jun 07, 2012 6:55 am

There seem to be two elements to this experiment.

1. Does bowel tolerance (BT) increase for healthy individuals? (BT is expected to increase for those with the flu, etc., therefore testing this element with sick individuals quickly becomes too complicated for us amateurs.)

2. Are flu symptoms ameliorated more at a given level of vitamin C supplementation when chromium is co-administered?


And to take this line of thought into other related tangents, I have two other questions.

Would chromium work like vitamin K3 in helping vitamin C to induce apoptosis in cancer cells?

Would the serum levels of vitamin C be predicted to increase or decrease (compared to the same AA supplementation without any co-administered chromium) if chromium acts like you are saying it might?

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Re: Glucose Modulates Vitamin C Transport

Post Number:#9  Post by jaamzg » Thu Jun 07, 2012 9:57 am

Here would be my thoughts on this from a purely theoretical basis.

1) AA bowel tolerance, we assume, is a function of AA plasma levels and the osmotic pressure differential in the GI moves the AA into the body and halts further absorption until the AA gets utilized. If Chromium were to help move the AA into the cells from the plasma, I would assume that the plasma levels would drop and allow for greater bowel tolerance levels in a healthy individual.

2) On the flu symptoms, that would be the experiment. But if we are to work off the assumption given by Levy for the increased efficacy of Lypo-C being from being able to get the AA (SA for Lypo-c) INTO the cells instead of just bathing the cells, then another mechanism that assists in AA delivery into the cell may produce enhanced efficacy over AA alone. Chromium being that supplement that helps in glucose transfer maybe can also assist in AA transfer?

I have some chromium, I may try it one of these days soon to see if there is an increase in bowel tolerance. It would be interesting to also test it with homemade lypo-c, being that if it works as theorized, the undissolved VC in the homemade solution could still be transported into the cells and increase the bt levels. It might provide a double effect?

On the cancer cell apoptosis, my understanding was that cancer cells have a ravenous appetite for glucose and would uptake the VC due to it's similar chemical structure. The k3 is somewhat of a "booster" in the internal cell reaction bringing about a greater percentage of apoptostic cells. I'm not sure how chromium would affect a cancerous cell.

As the the prediction, as I stated in 1), my assumption would be serum levels would decrease more rapidly with the chromium/AA combo, as the AA is transported into the cells, over the same given period of time for AA alone.

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Re: Glucose Modulates Vitamin C Transport

Post Number:#10  Post by majkinetor » Thu Jun 07, 2012 10:31 pm

jaamzg wrote:If Chromium were to help move the AA into the cells from the plasma, I would assume that the plasma levels would drop and allow for greater bowel tolerance levels in a healthy individual.


This is not right. More C in cells means more C in plasma because cells release C back into the plasma.

I must admit that chromium + C is excelent idea. I researched it some more using the query on Google schoolar given bellow:

Code: Select all

intitle:chromium intitle:"ascorbic acid" | intitle:"vitamin c"

There are not that many studies, only 1 in humans with diabetes testing Cr + C + E. Others are in chickens, cows, guinea pigs, rats, etc. There are studies looking into effects on other nutrients, on tissue saturation of Cr and AA and urinary excretion. The only potential negative effect is reduction in Cu absorption (again, known side effect of AA which might be problematic for some people in the context of Cu deficient diet for longer time).

My quick scan showed that they all show positive effects and additive effect of combination. This is reasonable: Cr brings blood glucose down (good for C) although it also brings insulin down (which is not good for C absorption) however this is due to increased insulin sensitivity so that lower amounts of insulin can bring the same effects as higher amounts before Cr supplementation , so all in all, this looks like good for C bioavailability.

It also looks like AA promotes Cr absorption. Also, toxicity of Cr-6 is known in dermatology and AA is used to reduce it to Cr-3 and prevent toxicity. This might be important in some scenarios.

They seem to have aditional additive effects, for instance reduction of cholesterol or even improvement in osteoporosis.

References:

apellmann, M., and Bolt, H. (1992). Chromium (VI) reducing capacity of ascorbic acid and of human plasma in vitro. Archives of Toxicology 66, 45–50.


Chatterjee, G.C., Roy, R.K., Sasmal, N., Banerjee, S.K., and Majumder, P.K. (1973). Effect of chromium and tungsten on L-ascorbic acid metabolism in rats and chicks. J. Nutr. 103, 509–514.

Lai, M.-H. (2008). Antioxidant effects and insulin resistance improvement of chromium combined with vitamin C and e supplementation for type 2 diabetes mellitus. J Clin Biochem Nutr 43, 191–198.

Lee1a, H.G., Yina, J.L., Xu, C.X., Hong, Z.S., Lee, Z.H., Jin, Y.C., Choi, C.W., Lee, D.H., Kim, K.H., and Choi, Y.J. (2011). Effects of the Combination of Glucose, Chromium Picolinate, and Vitamin C on Lipid Metabolism in Steers.

Sahin, K., Onderci, M., Sahin, N., and Aydin, S. (2002a). Effects of dietary chromium picolinate and ascorbic acid supplementation on egg production, egg quality and some serum metabolites of laying hens reared under a low ambient temperature (6 degrees C). Arch Tierernahr 56, 41–49.

Sahin, K., Sahin, N., and Kucuk, O. (2002b). Effects of dietary chromium and ascorbic acid supplementation on digestion of nutrients, serum antioxidant status, and mineral concentrations in laying hens reared at a low ambient temperature. Biological Trace Element Research 87, 113–124.

Sahin, K., Sahin, N., and Kucuk, O. (2003). Effects of chromium, and ascorbic acid supplementation on growth, carcass traits, serum metabolites, and antioxidant status of broiler chickens reared at a high ambient temperature (32°C). Nutrition Research 23, 225–238.

Seaborn, C.D. (1990). Chromium-nutrient interactions affecting tissue chromium, vitamin C metabolism, and cholesterol synthesis.
Seaborn, C.D., Cheng, N., Adeleye, B., Owens, F., and Stoecker, B.J. (1994). Chromium and chronic ascorbic acid depletion effects on tissue ascorbate, manganese, and 14C retention from 14C-ascorbate in guinea pigs. Biol Trace Elem Res 41, 279–294.

Seaborn, C.D., and Stoecker, B.J. (1990). Effects of antacid or ascorbic acid on tissue accumulation and urinary excretion of 51chromium. Nutrition Research 10, 1401–1407.
Last edited by majkinetor on Fri Jun 08, 2012 4:39 am, edited 1 time in total.

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Re: Glucose Modulates Vitamin C Transport

Post Number:#11  Post by jaamzg » Fri Jun 08, 2012 1:11 am

Quite a list of references, Majk! I'll have to spend some time going over it. Since I'm not really up to speed on the uptake and release of C into cells, maybe you can explain it a little more. I think I had read on another post that DHA and AA were taken into cells by different pathways. Once the C is used in the cell, does it just release DHA or is it releasing AA also? If all cells re-release the AA after uptake thereby keeping the plasma level elevated, where does the all the AA get used, since we know there has to be a constant supply to keep plasma levels elevated?

My thinking was that if it were going into the cells, as the lypo-c is supposed to do, then you raise your bowel tolerance level, just like you can do with the homemade lypo (unless the theory is wrong and it's just that the lipids being consume reduce the GI distress). If it is true that the C is getting into the cells, then I would assume a lower circulating plasma level, but that would depend, as you say, on it not being re-released.

I'm feeling another group self-experimentation coming on like when we stated the homemade lypo-c thread :lol:

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Re: Glucose Modulates Vitamin C Transport

Post Number:#12  Post by ofonorow » Fri Jun 08, 2012 3:30 am

I apologize, for the injection, I have not had time to digest all the arguments above, but I did notice:
jaamzg wrote:then you raise your bowel tolerance level, just like you can do with the homemade lypo

Is this well known? Raise means you still hit bowel tolerance.

It is very hard to hit it with Lypo-C.

If this observation were generally true, it may confirm the notion that homemade lipos are just emulsifying C (and protecting the vitamin like kiwi or aloe vera gel would) and not creating sustainable liposomes such as those that are in Lypo-C.
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Re: Glucose Modulates Vitamin C Transport

Post Number:#13  Post by majkinetor » Fri Jun 08, 2012 4:36 am

I think I had read on another post that DHA and AA were taken into cells by different pathways.

GLUT transporters are bidirectional so DHA will go up and down. AA that is oxidized inside the cell can also get out via this mechanism. Currently it is not known how cells exactly push AA out of itself and this is subject of resarch AFAIK. I know Levy said similar thing in our lypo c thread related this route.

BTW, lipo c has higher BT not because it is absorbed more, but because it has different digestion route and is 100% absorbed in small intestines via lymphatic channels as chylomicron.


Should it bring higher BT ? I don't know, it doesn't seem very likely to me. I am not even sure how BT functions since I observed that many people who can't initially tolerate high doses (like 1,2g) can after some time tolerate 10x higher dose. This is inline to what Pauling speculated about enzimatic reactions that turn on once there is enough C, so body pushes more from GI tract after that (thats why you get rebound scurvy when you stop supplementation).

The only true way to test it is via biopsy I guess.
BTW, I accidentally doubled the references - I fixed it now.

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Re: Glucose Modulates Vitamin C Transport

Post Number:#14  Post by jaamzg » Fri Jun 08, 2012 6:54 am

Is this well known? Raise means you still hit bowel tolerance.


I would say that anything having to do with homemade lypo is not well known. From personal experience, in a healthy state, I am able to raise BT from around 3grams to around 8 grams with homemade lypo. I suspect it's due to lack of full encapsulation and that is why there is still a BT level that's hit. Maybe there really isn't a BT level with commercial Lypo since it's pure lypo without the extra unencapsulated VC floating around. But, at least for me, there is a BT limit on the homemade stuff. If I remember correctly, when running the tests on the homemade lypo c, I had created a batch and divided the emulsified solution, sonfied one half and not the other. There was less gas produced when mixing the baking soda in with the homemade lypo c than than there was when mixing it with the emulsified (non sonified) solution, but even the sonified solution produced some gas.

I know Levy said similar thing in our lypo c thread related this route.


Do you have a link to that thread, please?

I'll need someone to explain that powerpoint slide to me. Why would the cell be taking up DHA, reducing it, then sending the AA out? Doesn't that just negate the whole point of taking up AA for that electron? Why would it be using up energy to make AA and then get rid of it? And if the cells did this, then why not just take DHA and let the cells create AA for us? I'm missing something somewhere. I totally get that there may be a competition between glucose and AA if they have similar molecular structures and are using the same pathways but reducing the DHA to send on it's way just seems odd to me.

I'll probably give the chromium a try this next week and report back on any perceived changes in BT levels.

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Re: Glucose Modulates Vitamin C Transport

Post Number:#15  Post by majkinetor » Fri Jun 08, 2012 8:10 am

As far as I know DHA is excreted. So cell can take AA via SVCT, it gets oxidised to DHA which then gets excreted out via GLUT.

See this pic
http://www.biocarta.com/pathfiles/m_vitcbpathway.asp

However, some cells (all ?) must have mechanism to push out AA - at least liver, kidney and adrenals - to the blood. As I said its still new topic and not much is known so who knows if maybe all cells can do that. Why would cells do that? Who knows; there are reports that AA could serve as paracrine agent for instance.

Here is the page you requested:
viewtopic.php?p=23712#p23712


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