42 replies to this topic

[niner]

I am surprised more diabetics are not documenting similar benefits and would urge diabetics to do so.

Non insulin dependent Type II pre-diabetic on metformin for 2.5 years. Been taking resveratrol about 4 months now. Started at 600mg 50%, then went to 500mg 99%, and now on 250mg micronized 99% w/ polysorbate 80. Fasting sugar went from 105-115mg/dl before to 95-105mg/dl now. Nothing spectacular but I'll take it.

Fasting glucose still @ 95-105mg/dl but A1C went from 5.5% to 5.6%. No worries. I'm not stopping.

That's probably the same number within the accuracy of the test. You might have expected it to go down with the improvement in fasting glucose, but the A1C might be dominated by post-prandial glucose. Could that be higher for any reason?

[fatboy]

That's probably the same number within the accuracy of the test. You might have expected it to go down with the improvement in fasting glucose, but the A1C might be dominated by post-prandial glucose. Could that be higher for any reason?

It looks like the lower the A1C the more influence from post-prandials and the higher the A1C the more contribution from fasting sugars. Figure 3 here: Contributions of Fasting and Postprandial Plasma Glucose Increments to the Overall Diurnal Hyperglycemia of Type 2 Diabetic Patients

And yeah, I went from eating 3 squares to 6 smaller ones throughout the day. That might be able to explain it. But it is likely to just be within the accuracy of the test as well.

Edited by fatboy, 18 September 2009 - 06:14 PM.

[niner]

That's probably the same number within the accuracy of the test. You might have expected it to go down with the improvement in fasting glucose, but the A1C might be dominated by post-prandial glucose. Could that be higher for any reason?

It looks like the lower the A1C the more influence from post-prandials and the higher the A1C the more contribution from fasting sugars. Figure 3 here: Contributions of Fasting and Postprandial Plasma Glucose Increments to the Overall Diurnal Hyperglycemia of Type 2 Diabetic Patients

And yeah, I went from eating 3 squares to 6 smaller ones throughout the day. That might be able to explain it. But it is likely to just be within the accuracy of the test as well.

Thanks for that ref. It looks like at your (and my) level of HbA1C, a large majority of it is from post-prandial glucose. That's good to know. I guess one way to push it down is to focus on getting a lower glycemic load in our meals. I don't know what the consequence of going to more, smaller meals would be on this.

[kismet]

Nice ref! I was thinking that something along the lines must be true. That explains why Hb1ac shows a somewhat weak, but linear relationship to CVD mortality (at lower levels it should reflect postprandial glucose levels and not blood sugar; thus better reflecting overall [CVD] health), while blood sugar per se is not protective over the whole range and shows a J-shaped response curve (much lower then 90mg/dl is not necessarily protective). At least at first glance that's my take, although, their reference Hb1Ac values are pretty high to be jumping to conclusions for 3-4% levels.

Edited by kismet, 18 September 2009 - 07:07 PM.

[Blue]

Resveratrol is a potent inhibitor of α-glucosidase activity. So what you are reporting could be an effect similar to that from acarbose which looks to be a very good drug for type II diabetes. Would be ironic if the only human study finding beneficial effects from Reseveratrol, that is reducing posprandial glucose in type II diabetes, is actually due a mechanism that is not due to SIRT activation.
http://pubs.acs.org/....1021/jf052436+

[niner]

Resveratrol is a potent inhibitor of α-glucosidase activity. So what you are reporting could be an effect similar to that from acarbose which looks to be a very good drug for type II diabetes. Would be ironic if the only human study finding beneficial effects from Reseveratrol, that is reducing posprandial glucose in type II diabetes, is actually due a mechanism that is not due to SIRT activation.
http://pubs.acs.org/....1021/jf052436+

It's good compared to acarbose, but if the abstract was printed and rendered correctly, then the IC50 of near 100 uM is not obtainable in humans. They described the IC50 of resveratrol against α-glucosidase as <0.1 mM. "m" is the conventional abbreviation for "milli", while "micro" is often abbreviated with the lowercase Greek mu, sometimes "u", which kind of looks like mu, and sometimes "mc" is used as the abbreviation. It's possible that somewhere along the line, a mu got changed to an m...

[Blue]

Resveratrol is a potent inhibitor of α-glucosidase activity. So what you are reporting could be an effect similar to that from acarbose which looks to be a very good drug for type II diabetes. Would be ironic if the only human study finding beneficial effects from Reseveratrol, that is reducing posprandial glucose in type II diabetes, is actually due a mechanism that is not due to SIRT activation.
http://pubs.acs.org/....1021/jf052436+

It's good compared to acarbose, but if the abstract was printed and rendered correctly, then the IC50 of near 100 uM is not obtainable in humans. They described the IC50 of resveratrol against α-glucosidase as <0.1 mM. "m" is the conventional abbreviation for "milli", while "micro" is often abbreviated with the lowercase Greek mu, sometimes "u", which kind of looks like mu, and sometimes "mc" is used as the abbreviation. It's possible that somewhere along the line, a mu got changed to an m...

You are considering we are talking about the intestine and not blood or inside a cell? I wonder how many of Reseveratrol's effects can be explained by this and not sirt activation? Acarbose seems very beneficial for rodents and type II diabetics regarding CVD and many other things. Can the "French Paradox" be explained by reseveratrol as an α-glucosidase inhibitor? The GI side effects are often blamed on emodin from non-pure preparations but may reseveratrol itself be partially responsible since such effects are the main seen from acarbose?

Edited by Blue, 19 September 2009 - 01:42 AM.

[maxwatt]

Resveratrol is a potent inhibitor of α-glucosidase activity. So what you are reporting could be an effect similar to that from acarbose which looks to be a very good drug for type II diabetes. Would be ironic if the only human study finding beneficial effects from Reseveratrol, that is reducing posprandial glucose in type II diabetes, is actually due a mechanism that is not due to SIRT activation.
http://pubs.acs.org/....1021/jf052436+

It's good compared to acarbose, but if the abstract was printed and rendered correctly, then the IC50 of near 100 uM is not obtainable in humans. They described the IC50 of resveratrol against α-glucosidase as <0.1 mM. "m" is the conventional abbreviation for "milli", while "micro" is often abbreviated with the lowercase Greek mu, sometimes "u", which kind of looks like mu, and sometimes "mc" is used as the abbreviation. It's possible that somewhere along the line, a mu got changed to an m...

You are considering we are talking about the intestine and not blood or inside a cell? I wonder how many of Reseveratrol's effects can be explained by this and not sirt activation? Acarbose seems very beneficial for rodents and type II diabetics regarding CVD and many other things. Can the "French Paradox" be explained by reseveratrol as an α-glucosidase inhibitor? The GI side effects are often blamed on emodin from non-pure preparations but may reseveratrol itself be partially responsible since such effects are the main seen from acarbose?

Some of resveratrol's effects could well be due to α-glucosidase inhibition in the intestines, but not all, I think. Mitochondrial biogeneses, well documented at moderate to high doses in rodents, cannot be explained this way. People have posted about measuring improved athletic performance, consistent with the effect on rodents, so more is going on. The abstract below (1) shows an effect on insulin secreting cells at 50 microMconcentration, so the effects may be systemic.

Reveratrol has been shown to induce chloride secretion in the small intestine, which gives a laxative effect to which people show various degrees of susceptibility. (2)


(1)

Cell Physiol Biochem. 2008;22(5-6):567-78. Epub 2008 Dec 9.
Resveratrol inhibits electrical activity and insulin release from insulinoma cells by block of voltage-gated Ca+ channels and swelling-dependent Cl- currents.

Jakab M, Lach S, Bacová Z, Langelüddecke C, Strbák V, Schmidt S, Iglseder E, Paulmichl M, Geibel J, Ritter M.
Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria.
The phytostilbene resveratrol (RV) improves the metabolic state in animal models by increasing the insulin responsiveness of tissues and there is evidence that RV affects insulin secretion from native beta-cells and insulinoma cells. In whole cell patch clamp experiments on clonal rat INS-1E cells we used high extracellular glucose (20 mM), extracellular hypotonicity (30%) or tolbutamide (100 microM) to elicit membrane depolarizations and electrical activity. Application of RV (50 microM) repolarized the cells, terminated electrical activity and prevented the hypotonicity-induced depolarization. These effects were fully reversible and intermittent application of RV restored tolbutamide-induced electrical activity after desensitization. Glucose-induced depolarization was counteracted by RV in presence of iberiotoxin (50 nM), showing that the RV effect does not depend on BK(Ca) channel activation. RV dose-dependently inhibited K(ATP) currents, L- and T-type Ca(2+) currents and swelling-dependent Cl(-) currents evoked by either hypotonicity or high extracellular glucose--ion conductances crucially involved in regulating the electrical activity of insulin secreting cells. We further show that RV blunts glucose-induced, but not basal insulin release. Our results indicate that RV counteracts/prevents stimulus-induced cell membrane depolarization and electrical activity by blocking voltage-gated Ca(2+)- and swelling-dependent Cl(-) currents despite the inhibition of K(ATP) currents. Copyright 2008 S. Karger AG, Basel.
PMID: 19088439

(2)

Clin Cancer Res. 2005 Aug 1;11(15):5651-6.
The chemopreventive agent resveratrol stimulates cyclic AMP-dependent chloride secretion in vitro.

Blumenstein I, Keserü B, Wolter F, Stein J.
Division of Gastroenterology and Clinical Nutrition, 1 Department of Medicine, ZAFES, J.W. Goethe-Universität, Theodor-Stern-Kai 7, Frankfort on the Main, Germany.
Resveratrol and its analogs are promising cancer chemoprevention agents, currently under investigation in clinical trials. However, patients administered other plant polyphenols experienced severe diarrhea, likely due to an increase in intracellular cyclic AMP (cAMP). Resveratrol itself raises intracellular cAMP levels in breast cancer cells in vitro. Its future use as a cancer chemopreventive agent could therefore be compromised by its severe side effects. The aim of the study was (a) to define the influence of resveratrol on intestinal Cl(-) secretion and (b) to elucidate possible intracellular transduction pathways involved. Resveratrol caused a dose- and time-dependent increase in DeltaIsc in T(84) cells. The specificity of resveratrol was confirmed by using piceatannol 100 mumol/L, the hydroxylated resveratrol analog, which did not alter DeltaIsc. A significant elevation of [cAMP](i) by resveratrol was assessed in T(84) cells. In mouse jejunum, resveratrol induced a time- and dose-dependent increase in DeltaIsc as well. In bilateral Cl(-)-free medium, as well as after inhibition of protein kinase A, resveratrol-induced DeltaIsc was reduced significantly. Preincubation of T(84) cells with butyrate 2 mmol/L (24 and 48 hours) significantly inhibited resveratrol as well as forskolin-induced Cl(-) secretion. In summary, the main mechanism of action of resveratrol in intestinal epithelia is cAMP-induced chloride secretion which can be suppressed by butyrate. It can therefore be suggested that in cancer chemoprevention, both agents should be combined to reduce an undesired side effect such as diarrhea and to benefit from the known agonistic effect of both agents on differentiation of colon cancer cells.
PMID: 16061885

[Blue]

There is a surprising number of beneficial plants substances that are α-glucosidase inhibitiors: green tea, pine bark extract, ellagic acid, anthocyanidins, genistein, curcumin.

If you are aiming for α-glucosidase inhibition it may be better to dose such substances similarly to acarbose. Immediately before every major meal.

Edited by Blue, 19 September 2009 - 07:30 PM.

[fatboy]

... I guess one way to push it down is to focus on getting a lower glycemic load in our meals. I don't know what the consequence of going to more, smaller meals would be on this.

Since even on 3 meals/day, I didn't eat anything (more than once) which caused my 2 hour post-prandials to go above 120, my thinking is that smaller, more frequent meals could explain an increase in A1C. I probably have more stable sugars this way, but they might not have a chance to drop to lower levels like they would if I waited 4-5 hours between eating. That's my thinking anyways.

But I also think the difference in my A1C is within the margin of error of the test. And so this reasoning is merely academic.

Edited by fatboy, 20 September 2009 - 12:59 AM.

[niner]

Resveratrol is a potent inhibitor of α-glucosidase activity. So what you are reporting could be an effect similar to that from acarbose which looks to be a very good drug for type II diabetes. Would be ironic if the only human study finding beneficial effects from Reseveratrol, that is reducing posprandial glucose in type II diabetes, is actually due a mechanism that is not due to SIRT activation.
http://pubs.acs.org/....1021/jf052436+

It's good compared to acarbose, but if the abstract was printed and rendered correctly, then the IC50 of near 100 uM is not obtainable in humans. They described the IC50 of resveratrol against α-glucosidase as <0.1 mM. "m" is the conventional abbreviation for "milli", while "micro" is often abbreviated with the lowercase Greek mu, sometimes "u", which kind of looks like mu, and sometimes "mc" is used as the abbreviation. It's possible that somewhere along the line, a mu got changed to an m...

You are considering we are talking about the intestine and not blood or inside a cell? I wonder how many of Reseveratrol's effects can be explained by this and not sirt activation? Acarbose seems very beneficial for rodents and type II diabetics regarding CVD and many other things. Can the "French Paradox" be explained by reseveratrol as an α-glucosidase inhibitor? The GI side effects are often blamed on emodin from non-pure preparations but may reseveratrol itself be partially responsible since such effects are the main seen from acarbose?

There must be a couple liters of water in the GI tract, and resveratrol's solubity in water is very low. Cayman Chemical reports it to be ca. 100 ug/ml in a pH 7.2 buffer solution. So, that's in the ballpark. Perhaps intestinal glucosidase inhibition is occurring with resveratrol. There's a lot more to resveratrol than that, however, as maxwatt points out. I don't think there's enough resveratrol in wine to explain the French paradox, (which is probably not a paradox), through whatever mechanism.

[Gerald W. Gaston]

Since even on 3 meals/day, I didn't eat anything (more than once) which caused my 2 hour post-prandials to go above 120, my thinking is that smaller, more frequent meals could explain an increase in A1C. I probably have more stable sugars this way, but they might not have a chance to drop to lower levels like they would if I waited 4-5 hours between eating. That's my thinking anyways.

But I also think the difference in my A1C is within the margin of error of the test. And so this reasoning is merely academic.

My fasting is usually 95-110. But my last A1C was 4.9, twice before that was 5.0 also. I eat 2-3 meals per day and likely I'm going slightly hypo at times. Spreading out to 5-6 meals (as long as you just spread out and not increase consumption) would hopefully be less BG and subsequent insulin spikes... and less change of hypo as with a long interval between meals. I'm switching to 4-5 meals next week and will check the results in 3 months. At least working out of my house makes it a little easier to eat when I want to now.

[pycnogenol]

My fasting is usually 95-110. But my last A1C was 4.9, twice before that was 5.0 also.

Those are pretty good numbers; I just got re-tested last Friday and my A1c is 5.5 which is not bad considering I have a strong family history of type 2.

Frankbuzin -- How much Resveratrol do you take? I'm currently taking 250 mg but will be bumping it up to 500 mg next month.

Edited by pycnogenol, 20 September 2009 - 02:04 PM.