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Vitamin C Potent Anti-AGE

glycation

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10 replies to this topic

#1 Sillewater

  • Location:Canada

Posted 23 December 2011 - 10:01 PM


Joe A. Vinson, Thomas B. Howard III, Inhibition of protein glycation and advanced glycation end products by ascorbic acid and other vitamins and nutrients, The Journal of Nutritional Biochemistry, Volume 7, Issue 12, December 1996, Pages 659-663, ISSN 0955-2863, 10.1016/S0955-2863(96)00128-3. (http://www.sciencedi...955286396001283) Keywords: glycation; advanced glycation end products; vitamins; nutrients; ascorbic acid




The present Vitamin C supplementation study (in a bio-
flavonoid mixture) demonstrated an average decrease of
46.8% in protein glycation in normoglycemic subjects in
good agreement with Davie.30 He showed a 33% decrease
in glycated albumin after 3 months with 1 g/day of ascor-
bate and an 18% reduction in GHb. Stolba also found a
significant decrease in fructosamine in insulin-dependent
diabetics given 1.5 g of ascorbate/day.36 The glycation-
lowering effect in the supplement could be due to both the
ascorbate and flavonoids in the mixture. Odetti found that
the flavonoid rutin decreased collagen-linked AGE fluores-
cence in diabetic rats.37

Epidemiological studies have recently found a negative
correlation between vitamin C intake and GHb in normal
subjects.38 Ascorbate either alone or in the form of a citrus
extract has also been found to be an effective agent in low-
ering red blood cell sorbitol in human diabetic subjects at 2
g/day, 39 1 glday,40 and 100 mg/day.41 Vitamin C thus ben-
eficially influences the two mechanisms of diabetic compli-
cations; glycation and the sorbitol pathway.



Seems like 1g/day may be pretty effective. Taken away from exercise and maybe with food. The subjects were 7 college students and 11 middle-aged folks.

The referenced study (30) is this one:


Diabetes. 1992 Feb;41(2):167-73.Effect of vitamin C on glycosylation of proteins.Davie SJ, Gould BJ, Yudkin JS.


In the above study they used a product called Re-natured C which contains bioflavanoids, while I do not have access to the second study so unsure what product they used, however the results are fairly simliar. Both healthy groups too (as per the description, no detailed descriptive data).
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#2 niner Re: Vitamin C Potent Anti-AGE

  • Location:Philadelphia

Posted 23 December 2011 - 10:40 PM

Wow, that's a pretty huge result. From the nineties, too.. Where has this been hiding? Ascorbate hasn't popped up when we've talked about glycation inhibitors in the past. I wonder why? I suppose we should split doses to coincide with meals, or whenever the biggest glucose challenge would occur. Would it be better to take it after a meal in order to cover the post-prandial glucose spike? It seems like with ascorbate or carnosine, or any glycation inhibitor with fast kinetics, you'd want to take some pains to match the Cmax of the drug with the peak of the glucose spike, if you're trying to optimize things.
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#3 Sillewater Re: Vitamin C Potent Anti-AGE

  • Location:Canada

Posted 24 December 2011 - 01:14 AM

There's all this talk about aldose reductase pathway inhibitors and sorbitol is a biomarker for this (I think), and here we have a pretty cheap and effective agent for diabetics.

J Am Coll Nutr. 1994 Aug;13(4):344-50.


Vitamin C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus.

Cunningham JJ, Mearkle PL, Brown RG.



The product re-natured can be found here: http://www.grownbynature.com/#!vstc2=vitamin-c-plus. They have some studies too.
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#4 Sillewater Re: Vitamin C Potent Anti-AGE

  • Location:Canada

Posted 24 December 2011 - 02:40 AM

Also Epalrestat is an inhibitor. I posted about it before: http://www.longecity...at-heard-of-it/

I've never heard of it being used in practice though.
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#5 Sillewater Re: Vitamin C Potent Anti-AGE

  • Location:Canada

Posted 24 December 2011 - 04:33 AM

Carbohydr Res. 2004 Feb 25;339(3):483-91.


Characterization and detection of lysine-arginine cross-links derived from dehydroascorbic acid.

Reihl O, Lederer MO, Schwack W.



Source

Institut für Lebensmittelchemie (170), Universität Hohenheim, Garbenstr 28, D-70593 Stuttgart, Germany. oreihl@uni-hohenheim.de



Abstract

Covalently cross-linked proteins are among the major modifications caused by the advanced Maillard reaction. So far, the chemical nature of these aggregates is largely unknown. L-dehydroascorbic acid (DHA, 5), the oxidation product of L-ascorbic acid (vitamin C), is known as a potent glycation agent. Identification is reported for the lysine-arginine cross-links N6-[2-[(4-amino-4-carboxybutyl)amino]-5-(2-hydroxyethyl)-3,5-dihydro-4H-imidazol-4-ylidene]-L-lysine (9), N6-[2-[(4-amino-4-carboxybutyl)amino]-5-(1,2-dihydroxyethyl)-3,5-dihydro-4H-imidazol-4-ylidene]-L-lysine (11), and N6-[2-[(4-amino-4-carboxybutyl)amino]-5-[(1S,2S)-1,2,3-trihydroxypropyl]-3,5-dihydro-4H-imidazol-4-ylidene]-L-lysine (13). The formation pathways could be established starting from dehydroascorbic acid (5), the degradation products 1,3,4-trihydroxybutan-2-one (7, L-erythrulose), 3,4-dihydroxy-2-oxobutanal (10, L-threosone), and L-threo-pentos-2-ulose (12, L-xylosone) were proven as precursors of the lysine-arginine cross-links 9, 11, and 13. Products 9 and 11 were synthesized starting from DHA 5, compound N6-[2-[(4-amino-4-carboxybutyl)amino]-5-[(1S,2R)-1,2,3-trihydroxypropyl]-3,5-dihydro-4H-imidazol-4-ylidene]-L-lysine (16) via the precursor D-erythro-pentos-2-ulose (15). The present study revealed that the modification of lysine and arginine side chains by DHA 5 is a complex process and could involve a number of reactive carbonyl species.





Maybe Vitamin C ain't so good. Will have to do some epidemiological studying and intervention studies for cataracts and Vitamin C before deciding to supplement.
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#6 niner Re: Vitamin C Potent Anti-AGE

  • Location:Philadelphia

Posted 24 December 2011 - 04:41 AM

Hmm. I wonder if that's why the mixture of vitamins E and C was better than either by themselves, as reported in the paper on the Grown by Nature site that you posted above. (Why do they not have Supplement Facts labels? or even tell us the dose?)
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#7 JChief Re: Vitamin C Potent Anti-AGE

  • Location:US of A

Posted 24 December 2011 - 04:27 PM

Wow, that's a pretty huge result. From the nineties, too.. Where has this been hiding? Ascorbate hasn't popped up when we've talked about glycation inhibitors in the past. I wonder why? I suppose we should split doses to coincide with meals, or whenever the biggest glucose challenge would occur. Would it be better to take it after a meal in order to cover the post-prandial glucose spike? It seems like with ascorbate or carnosine, or any glycation inhibitor with fast kinetics, you'd want to take some pains to match the Cmax of the drug with the peak of the glucose spike, if you're trying to optimize things.


This may have been partly why Raymond Francis considers Vitamin C a "cornerstone of health" heh. I did a quick search on just what glycation was and read the following from WiseGeek:

glycation disrupts normal metabolic pathways and advances the circulation of AGEs, it can promote certain health risks. Glycation also occurs outside the body. In fact, exogenous glycations are responsible for allowing foods to brown during cooking. This type of glycation is dubbed the Maillard reaction, in honor of the early 20th century French chemist that first observed how sugars react with fats or proteins while exposed to high temperatures. While crisp French fries and grilled meats may be tasty, the reaction that produces them also creates 2-propenamide, a suspected carcinogen that comes with the meal. In addition, exogenous AGEs are sometimes added to certain foods to enhance color and flavor, including baked goods, dark colas, and coffee.


Another reason why I think keeping cooked meats to less than 10% of the overall diet is a sound decision.

Clearly, AGEs age the human body faster than nature intended. However, in addition to limiting consumption of baked goods, fried foods, and other high content AGE-containing foods, studies have shown that certain nutrients may serve as glycation inhibitors. For instance, calcium pyruvate and carnosine not only appear to help prevent this reaction, but also stimulate proteolysis, or the degradation of glycated proteins. Certain plant extracts have also been studied for their potential to prevent glycation, at least in vitro. Among those that have shown promising results are cinnamon, black pepper, ginger, cumin, and green tea.


Now looks like we can add Vitamin C to the list. Nice.

Edited by JChief, 24 December 2011 - 04:36 PM.

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#8 brunotto Re: Vitamin C Potent Anti-AGE

  • Location:Italy

Posted 16 February 2012 - 02:04 PM

Now looks like we can add Vitamin C to the list. Nice.


Not so sure... it looks like Vitamin C should be taken with a lot of other long lasting antioxidant like Asthaxantin, alpha/gamma tocopherol that prevent its massive and quick oxidation...

Vitamin C mediates chemical aging of lens crystallins by the Maillard reaction in a humanized mouse model...

http://www.ncbi.nlm....les/PMC1636553/

This is another reason becouse Vitamin C should not be taken with meals rich in transition metal ions (Cu, Fe)...

Oxidative modification of LDL in vitro, either induced by Cu2+ or mediated by cultured arterial wall cells in media containing trace amounts of transition metal ions, is strongly inhibited by vitamin C (L-ascorbic acid (AA)). AA, however, is known to act as a prooxidant rather than an antioxidant in the presence of transition metal ions.

http://www.jbc.org/c...2/1304.abstract

I suspect its better taking "vitamin c" (buffered) on empty stomac, maybe before sleeping and/or early in the morning with a lot of other antioxidant specially ultimate (suicidial) antoxidant like asthanxanthin (or melatonin)....

Edited by brunotto, 16 February 2012 - 02:56 PM.

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#9 niner Re: Vitamin C Potent Anti-AGE

  • Location:Philadelphia

Posted 16 February 2012 - 02:56 PM

Not so sure... it looks like Vitamin C should be taken with a lot of other long lasting antioxidant like Asthaxantin, alpha/gamma tocopherol etc and better in a low sugar (not after meals)...

Vitamin C mediates chemical aging of lens crystallins by the Maillard reaction in a humanized mouse model...


I don't think all of that follows from the paper. To put this in perspective, in this paper, they genetically added a vitamin C transporter to the mouse lens that increased its vitamin C concentration by a factor of 5-15. This resulted in a much more rapid aging of the lens. However, they note:

What are the implications of our findings concerning vitamin C supplementation, lenticular aging, and cataractogenesis? On one hand, the vanishing low vitamin C levels in the mouse lens imply that millimolar concentrations of the vitamin are not necessary for maintaining lens clarity. On the other hand, low serum levels of the vitamin have been associated with increased risk of cataractogenesis in the human (29), and various studies suggest that supplementation of the vitamin is beneficial for decreasing the risk of cataractogenesis (30), in particular under conditions that favor oxidant stress (31). Proposed mechanisms include the scavenging of free radicals by the vitamin itself or in conjunction with glutathione that is present in millimolar concentrations in rodent lenses. Thus, vitamin C joins the ranks of those metabolites that are essential for life, such as glucose, fatty acids, and oxygen, but can inflict damage when the cell's defenses are weakened by diabetes, end-stage renal disease, poor nutrition, exposure to UV light, or old age itself.


Taking vitamin C with other longer-lasting antioxidants isn't a bad idea, but I don't see the point of taking vitamin C away from meals. The post-prandial period is when most of the glycation damage happens, (at least in non-diabetics) because that's when blood sugar is highest. It seem to me that this would be exactly when you would want the vitamin C around, since it reduces glycation on balance.
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#10 brunotto Re: Vitamin C Potent Anti-AGE

  • Location:Italy

Posted 16 February 2012 - 03:00 PM

Long digestion (hours) in the presence of copper or iron ions can oxidize ascorbic acid (and reduce Fe and Cu ions) before they enters in the blood stream... we have also to consider that animals who produce their own vitamin c dosent have to digest it !!!

Edited by brunotto, 16 February 2012 - 03:22 PM.

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#11 brunotto Re: Vitamin C Potent Anti-AGE

  • Location:Italy

Posted 16 February 2012 - 03:06 PM

There persists in medical literature the idea that vitamin C, acting as a reducing agent, causes reactions with iron (and other metals) that generate damaging free radicals.


These free radicals then go on to produce oxidative damage to cells and molecules, the products of which can

be measured in blood tests. The idea goes that vitamin C is a powerful reducing agent which reduces Fe (III) to Fe (II), the reduced iron then participates in the Fenton

reaction which produces hydroxyl radicals. A considerable amount of literature can be found that links these ideas together, and the obvious conclusion reached

by most of these researchers is a warning not to take vitamin C with metals and not to take vitamin C in iron overloaded conditions (e.g. haemochromatosis).


http://www.orthomed....DF/BW_iron.pdf

It think the safest (and most usefull) is to take the vitamin c something like 3/4 or 1/2 hour before eating so its already in the blood as glucose comes and has not to stay long in the stomac toghether with metal ions (also not a good idea to take multimineral supps toghether with ascorbic)...

Edited by brunotto, 16 February 2012 - 03:27 PM.

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