60 replies to this topic

[Chupo]

These are about methylglyoxal: 

 

http://www.ncbi.nlm....pubmed/18533369

 

http://www.ncbi.nlm....pubmed/23333621

[niner]

Basically, methylglyoxal is like a chemotherapy agent.  Very toxic, but because it induces cell cycle arrest and apoptosis, it acts as an anti-cancer drug when given in some (probably fairly large) dose and formulation.   To quote the first abstract, "recent literature abounds with the toxic effects of methylglyoxal".  Maybe good at some dose if you have cancer, not so hot if you're healthy.

[Chupo]

Also to quote the first abstract: "the beneficial effects of methylglyoxal outweigh its toxic effects"

[niner]

Also to quote the first abstract: "the beneficial effects of methylglyoxal outweigh its toxic effects"

 

If you have cancer.  That's also true for Cisplatin...

[Hebbeh]

http://www.scienceda...40901090341.htm

 

Sugar substance 'kills' good HDL cholesterol

 

Date: September 1, 2014

Source: University of Warwick

 

Scientists at the University of Warwick have discovered that 'good' cholesterol is turned 'bad' by a sugar-derived substance.

The substance, methylglyoxal -- MG, was found to damage 'good' HDL cholesterol, which removes excess levels of bad cholesterol from the body.

 

Low levels of HDL, High Density Lipoprotein, are closely linked to heart disease, with increased levels of MG being common in the elderly and those with diabetes or kidney problems.

 

Supported by funding from the British Heart Foundation (BHF) and published in Nutrition and Diabetes, the researchers discovered that MG destabilises HDL and causes it to lose the properties which protect against heart disease.

 

HDL damaged by MG is rapidly cleared from the blood, reducing its HDL content, or remains in plasma having lost its beneficial function.

 

Lead researcher Dr Naila Rabbani, of the Warwick Medical School, says that: "MG damage to HDL is a new and likely important cause of low and dysfunctional HDL, and could count for up to a 10% risk of heart disease."

 

There are currently no drugs that can reverse low levels of HDL, but the Warwick researchers argue that by discovering how MG damages HDL has provided new potential strategies for reducing MG levels.

 

Commenting on the research's implications Dr Rabbani said:

 

"By understanding how MG damages HDL we can now focus on developing drugs that reduce the concentration of MG in the blood, but it not only be drugs that can help.

 

"We could now develop new food supplements that decrease MG by increasing the amount of a protein called glyoxalase 1, or Glo 1, which converts MG to harmless substances.

 

"This means that in future we have both new drugs and new foods that can help prevent and correct low HDL, all through the control of MG."

 

A potentially damaging substance, MG is formed from glucose in the body. It is 40,000 times more reactive than glucose it damages arginine residue (amino acid) in HDL at functionally important site causing the particle to become unstable.

 

Glo1 converts MG to harmless substances and protects us. MG levels are normally kept low in the body to maintain good health but they slowly increase with aging as Glo1 slowly becomes worn out and is only slowly replaced.

 

Dr Rabbani says: "We call abnormally high levels of MG 'dicarbonyl stress'. This occurs in some diseases -- particularly diabetes, kidney dialysis, heart disease and obesity. We need sufficient Glo1 to keep MG low and keep us in good health."

 

Story Source:

The above story is based on materials provided by University of Warwick. Note: Materials may be edited for content and length.

Journal Reference:

1. L Godfrey, N Yamada-Fowler, J Smith, P J Thornalley, N Rabbani. Arginine-directed glycation and decreased HDL plasma concentration and functionality. Nutrition & Diabetes, 2014; 4 (9): e134 DOI: 10.1038/nutd.2014.31

 

Edited by Hebbeh, 02 September 2014 - 11:01 PM.

[kramer91]

Apparently the method (immunoassays) to determine the amounts of AGEs in foods in the charts referenced earlier in this thread is very inaccurate.

 

Mass spectrometry is much more accurate: http://www.ncbi.nlm....pubmed/18389168

 

Very different results! Thoughts?

[InquilineKea]

At any rate, animals on diets that are high in exogenous AGEs but otherwise identical to controls (done by using the same diets, but heating one of them) are less healthy and die a lot sooner.

 

How strong are the effects - and how much are the oils heated? Asians stir-fry all their vegetables, and I'm not sure how much this hurts them. Certainly, I'd take rice out of my diet well before I'd take vegetables stir-fried in MUFAs.

 

I wish I could convince my parents to not stir-fry their vegetables (I've already convinced them to serve me almost zero rice, and I'm already significantly reducing my intake of other forms of fried food), but this could be a losing battle. At least I've told them to just fry them in olive oil. I feel that the benefits of eating vegetables are already so high that the extra load of exogenous AGEs might not be *that* bad, but I don't know.

 

==

 

BTW, couldn't low levels of methylglyoxal help promote hormesis? I know that low-levels of 9-HNE does that.

 

Also, if MG was so harmful, then wouldn't this show in people who practice low-carb diets? Maybe it's possible that the harmful effects of MG are especially pernicious in those who are metabolically compromised. But in those who aren't metabolically compromised (esp those on low-carb diets), could it not be as bad?

 

Anyways, given that the bulk of MG is produced through glycolysis, I'd think that low-carb diets would decrease it, rather than increase it.

Edited by InquilineKea, 07 October 2014 - 09:45 PM.

[InquilineKea]

Wow, this is scary:

 

Olive oil, heated at 100°C for 5 min (Colavita, Linden, NJ) 9,700 6,295

 

The order of magnitude is on the same level as that of many processed foods (and meats), but most people who stir-fry this stuff usually do it for longer than 5 minutes... and the temperature is higher than 100C...

 

But if oil is just oil... then where does all the lysine to be oxidized come from?

 

==

 

Also - regarding all the research that measures AGEs in vegetarians, or blood levels of AGEs (including http://www.scienceda...70424155559.htm ) - I'm not sure if they measure intracellular AGEs. I suspect that it's the intracellular AGEs that matter the most, not the extracellular ones (although extracellular still matters a bit).

 

In the end - we'll probably be able to grow replacement organs for everything except the brain in 30 years anyways. The most important question is whether or not dietary AGEs pass the blood-brain barrier. Methylglyoxal looks too polar to do so (though it's a small molecule and anything could be possible)

Edited by InquilineKea, 07 October 2014 - 10:33 PM.

[Kalliste]

Did I get this right, according to this theory coffee is something to be worried about? That does not seem to go in line with all the positive stuff about coffee that has been coming out in recent years. What's up with that?

[Invariant]

Did I get this right, according to this theory coffee is something to be worried about? That does not seem to go in line with all the positive stuff about coffee that has been coming out in recent years. What's up with that?

 

Coffee having certain positive effects is not at all informative about whether or not it has negative effects as well.

 

Most likely, coffee will have both positive and negative effects, and the question becomes which one outweighs the other for a particular individual. Epidemiological studies seem to suggest that at the population level, coffee is a net positive except for hypertensive individuals, but theoretically it could be that for the health-hyperoptimizers of this board, the negatives will outweigh the positives. I doubt it though.

[Kalliste]

I guess that is the case. That was what Spindler found too. I'm far from optimal though, as I consume sugar and occasionally smoke. I'm going to stick with the odd cup or two a day.

[ikon2]

 

Any comment on why vegetarians may have higher AGEs in plasma?

 

 

 

Many vegetarians like to eat a diet high in polyunsaturated-fat, like nuts, seeds, avocadoes, oil and fried-vegetables. The number one cause of free-radicals is the intake of polyunsaturated-fats.
 

 

 

Are avocados not mono unsaturated fats?

[ikon2]

When we are talking about olive oil here, is it heated or even uncooked olive oil?  Also, how effective would high dose carnosine be at combatting the AGE (or ALE)'s from the goodies like olive oil and coffee if one was not ready to kick them out of their diet (which it seems most here are not)?

 

This is all very worrisome in that, if you take this along side this great discussion started by niner here http://www.longecity...ing-hypothesis/ , it seems we cannot ingest mono or PUFA.

 

I'm having a lot of trouble reconciling all of this and coming up with a suitable diet.

[ikon2]

misterE, am I taking your post incorrectly?  When you say avocados and PUFA's, did you simply mean that vegetarians eat various things that end up in a high net PUFA diet or were you specifically suggesting avocados were high in PUFA?  AFAIK avocados are MUFA.  I eat lots of avocados.  Is there some danger here I am unaware of?

 

 

 

 

Any comment on why vegetarians may have higher AGEs in plasma?

 

 

 

Many vegetarians like to eat a diet high in polyunsaturated-fat, like nuts, seeds, avocadoes, oil and fried-vegetables. The number one cause of free-radicals is the intake of polyunsaturated-fats.
 

 

 

Are avocados not mono unsaturated fats?

 

 

[misterE]

 

misterE, am I taking your post incorrectly?  When you say avocados and PUFA's, did you simply mean that vegetarians eat various things that end up in a high net PUFA diet or were you specifically suggesting avocados were high in PUFA?  

 

 

Yes, vegetarians seems to eat foods that give them an overall high PUFA intake. For instance two avocadoes (at 645 calories) provides 7.5 grams of PUFA. To obtain 7.5 grams of PUFA from grains... let's use barley as an example: you would need to eat over 6.5 cups of raw barley (at 4650 calories).

 

Avocadoes (645 calories)   = 7.5 grams of PUFA

Barley         (4650 calories) =7.5 grams of PUFA

 

 

Many vegetarian friends of mine get their fuel from nuts, peanut-butter, soy, tofu, avocados, seeds, etc. instead of grains. They are taking in healthy whole-foods but they are also eating quite a bit of PUFA compared to a person eating mostly starches. I tell them this, but they would rather continue eating their calorie-dense nuts and butters because they enjoy eating them over starches, but I don't think it is a good idea. 

[ikon2]

 

 

misterE, am I taking your post incorrectly?  When you say avocados and PUFA's, did you simply mean that vegetarians eat various things that end up in a high net PUFA diet or were you specifically suggesting avocados were high in PUFA?  

 

 

Yes, vegetarians seems to eat foods that give them an overall high PUFA intake. For instance two avocadoes (at 645 calories) provides 7.5 grams of PUFA. To obtain 7.5 grams of PUFA from grains... let's use barley as an example: you would need to eat over 6.5 cups of raw barley (at 4650 calories).

 

Avocadoes (645 calories)   = 7.5 grams of PUFA

Barley         (4650 calories) =7.5 grams of PUFA

 

 

Many vegetarian friends of mine get their fuel from nuts, peanut-butter, soy, tofu, avocados, seeds, etc. instead of grains. They are taking in healthy whole-foods but they are also eating quite a bit of PUFA compared to a person eating mostly starches. I tell them this, but they would rather continue eating their calorie-dense nuts and butters because they enjoy eating them over starches, but I don't think it is a good idea. 

 

 

Thank you for the feedback.  From this perspective, grains seem like a good idea but does the gluten not concern you?  Would say, sweet potatoes and plant proteins not be better options?  Or gelatin (zero PUFA and also super no methionine either) protein and legumes?

[misterE]

 

 

From this perspective, grains seem like a good idea but does the gluten not concern you?  Would say, sweet potatoes and plant proteins not be better options?  Or gelatin (zero PUFA and also super no methionine either) protein and legumes?

 

 

Gluten does not concern me because I don't have celiac-disease. All large populations of people have always ate a grain-based diet. Even in America in 1909 most of the calories Americans ate came from beans, grains and potatoes.

 

The American diet in 1909 consisted of animal-fat, starch and plant-protein. Currently in America the diet consists of vegetable-oil, sugar and animal-protein. Another way of looking at it is this: The 1909 American diet was low in essential-fatty-acids and essential-amino-acids; opposite of today.

Edited by misterE, 12 November 2014 - 11:55 PM.

[niner]

Gluten does not concern me because I don't have celiac-disease. All large populations of people have always ate a grain-based diet. Even in America in 1909 most of the calories Americans ate came from beans, grains and potatoes.

 

"Always", meaning for the last ten - twelve thousand years.  That is certainly long enough to push the level of celiac disease down to a very low level, but it probably isn't long enough to evolve out every trace of gluten sensitivity.  If gluten makes you feel kind of lousy, but you're still functional, it's a fair trade-off against occasional starvation.  There's also the issue of how bread and other grain products are manufactured in today's factory farming world, compared to the foods we evolved with over the past 5-600 generations.  We've had 3 or four generations eating the new factory food, and today we are likely eating a hell of a lot more than we ever did in the past.  These are the counter-arguments against the claim that today's rash of gluten-paranoia is insanity.  I would say that it's not insanity, but that it is very much overdone of late.  A lot of people who are trying to avoid gluten probably don't need to worry about it.  Some of them might be sensitive to FODMAPs or something else that correlates with gluten foods, and feel better when they avoid gluten foods, but not for the reason they think they do.

[misterE]

 

 

 

"Always", meaning for the last ten - twelve thousand years. 

 

 

 

Humans have been eating grains for over 105,000 years niner:

 

 

Science. 2009 Dec 18;326(5960):1680-3. doi: 10.1126/science.1173966.

 

Mozambican grass seed consumption during the Middle Stone Age.

Mercader J.

 

Abstract

 

The role of starchy plants in early hominin diets and when the culinary processing of starches began have been difficult to track archaeologically. Seed collecting is conventionally perceived to have been an irrelevant activity among the Pleistocene foragers of southern Africa, on the grounds of both technological difficulty in the processing of grains and the belief that roots, fruits, and nuts, not cereals, were the basis for subsistence for the past 100,000 years and further back in time. A large assemblage of starch granules has been retrieved from the surfaces of Middle Stone Age stone tools from Mozambique, showing that early Homo sapiens relied on grass seeds starting at least 105,000 years ago, including those of sorghum grasses.

 

 

 

Edited by misterE, 13 November 2014 - 06:16 PM.

[Kalliste]

The grains they ate are completely different, in composition and in production and treatment, from the ones the average pig slobs down today.

[misterE]

The grains they ate are completely different, in composition and in production and treatment, from the ones the average pig slobs down today.

 

 

The only difference, is that people 105,000 years ago probably couldn't refine the grain or make flour out of it, but the point is that humans are VERY well adapted to grains. So much so, that the main digestive enzyme in the body (amylase) is made for digesting starch.
 

[Kalliste]

That is no small difference! We know that white flour is a poison in the copious amounts people consume it today. I suspect that even a diet with only whole grains of fine quality is going to be bad put in comparison to a diet of steamed vegetables and fish.

Our specie is old, millions of years. I see a pattern in diet where those components who are the oldest companions of us seems to be the best ones. Nuts, fish, shrimps, onions, berries.

Grains on the other hands are new friends, we are adapted to them to some extent but not well enough to make me comfortable.

Some people, blacks for instance, seem to be less well adatped to starch diets and are easily hit by diabetes and cancer.

In the end we need to be able to repair broken humans, I suspect that will happen well before we can mind control the planetary population into eating healthy stuff.

[misterE]

{1} That is no small difference!

 

 

{2} We know that white flour is a poison in the copious amounts people consume it today.

 

 

{3} I suspect that even a diet with only whole grains of fine quality is going to be bad put in comparison to a diet of steamed vegetables and fish.

 

 

{4} Grains on the other hands are new friends, we are adapted to them to some extent but not well enough to make me comfortable.

 

 

{5} Some people, blacks for instance, seem to be less well adatped to starch diets and are easily hit by diabetes and cancer.

 

 

 

 

{1} Sure it is. Turning a whole-grain into a refined flour is a massive difference and has different metabolic-effects.

 

{2} I don't think so. Americans ate much more flour back in 1909 than we do today. It's the oil that is the culprit.

 

{3} A diet of steamed vegetables and fish is lacking in carbohydrates, which will decrease your physical activity and increase glucocorticoids (like cortisol), which increase the risk of diabetes.

 

{4} 105,000 years is a long time. Long enough to change our digestive-enzymes to prefer digesting starch.

 

{5} Well if you are familiar with the works of Denis Burkitt, who studied the traditional-diets of Africans, he found that cultures that eat lots of fiber and starch are immune to cancer, diabetes and heart-disease, yet when these cultures migrate to the United-States or change their diet in the homeland, to less fiber and starch and more fat and protein, their disease rates increase substantially. This is also well established with the Asian population who's dietary-staple in polished white-rice.

[niner]

Just because someone found a small group in Mozambique that ate some amount, likely small, of grass seed 100,000 years ago doesn't mean that wheat production was widespread.  The Mozambique tribe wasn't farming, were they?   Probably no "Amber Waves of Grain" there, nor half million dollar combines.

[Chupo]

Starch from the bulbs of grasses such as sedges or tiger nuts would have been much more abundant than their tiny, seasonal seeds.  It would also account for the high C4 content of our ancestors' bones. This C4 content is what initially led researchers to the conclusion that grains were eaten.  They either didn't know about or didn't consider the other edible parts of the grasses.

[misterE]

Just because someone found a small group in Mozambique that ate some amount, likely small, of grass seed 100,000 years ago doesn't mean that wheat production was widespread.  The Mozambique tribe wasn't farming, were they?   Probably no "Amber Waves of Grain" there, nor half million dollar combines.

 

They probably weren't farming on a scale you would see in the agricultural-revolution, but the fact remains that humans have been eating grains for much longer than previously thought. The agricultural-revolution was a landmark event in human evolution and gave us a huge advantage over other species. We were able to transition to a grain-based diet without much consequence because of our long previous (105,000) history of eating grass-seed (grains).

 

It's the transition away from the grain-based diet to a diet based on meat, oil and sugar, that is so damn problematic. This is clearly shown in studies in India, Japan and China, where you have a large population of people who traditionally ate a primarily vegetarian-diet based on grains and beans. But currently those nations are industrializing and are eating less grains and beans and more meat, fat and sugar and are developing metabolic-syndrome at a ramped rate! It is so obvious...  

[blood]

http://www.scienceda...40901090341.htm
 
Sugar substance 'kills' good HDL cholesterol
 
... methylglyoxal -- MG, was found to damage 'good' HDL cholesterol, which removes excess levels of bad cholesterol from the body...

 
HDL damaged by MG is rapidly cleared from the blood, reducing its HDL content, or remains in plasma having lost its beneficial function...
 
"We could now develop new food supplements that decrease MG by increasing the amount of a protein called glyoxalase 1, or Glo 1, which converts MG to harmless substances...
 
Glo1 converts MG to harmless substances and protects us. MG levels are normally kept low in the body to maintain good health but they slowly increase with aging as Glo1 slowly becomes worn out and is only slowly replaced.
 
Dr Rabbani says: "We call abnormally high levels of MG 'dicarbonyl stress'. This occurs in some diseases -- particularly diabetes, kidney dialysis, heart disease and obesity. We need sufficient Glo1 to keep MG low and keep us in good health"...

 
Pamela Maher found that fisetin up-regulates glyoxalase 1 in mice (at doses that would be 'doable' in people):
 
 

ScienceDaily
 
... Maher and colleagues ... evaluated effects of fisetin supplementation in Akita mice, a very robust model of type 1 diabetes, also called childhood onset diabetes.

Akita mice exhibit increased blood sugar typical of type 1 diabetes and display pathologies seen in serious human complications of both type 1 and 2 diabetes. Those include diabetic nephropathy or kidney disease, retinopathy, and neuropathies in which patients lose touch or heat sensations.
 
Mice fed a fisetin-enriched diet remained diabetic, but acute kidney enlargement-or hypertrophy-seen in untreated mice was reversed, and high urine protein levels, a sure sign of kidney disease, fell. Moreover, fisetin ingestion ameliorated anxiety-related behaviors seen in diabetic mice. "Most mice put in a large area become exploratory," says Maher. "But anxious mice tend not to move around. Akita mice showed enhanced anxiety behavior, but fisetin feeding restored their locomotion to more normal levels."
 
The study also defines a likely molecular mechanism underlying these effects. Researchers observed that blood and brain levels of sugars affixed to proteins known as advanced glycation end-products-or AGEs-were reduced in fisetin-treated compared to untreated Akita mice. These decreases were accompanied by increased activity of the enzyme glyoxalase 1, which promotes removal of toxic AGE precursors.
 
The discovery of an AGE-antagonizing enzyme upregulated by fisetin is very intriguing, because substantial evidence implicates high blood AGE levels with many if not most diabetic complications. "We know that fisetin increases activity of the glyoxalase enzyme and may increase its expression," says Maher. "But what is important is that ours is the first report that any compound can enhance glyoxalase 1 activity."
 
Interestingly, excessively high AGE levels also correlate with inflammatory activity thought to promote some cancers. In fact, studies published by others confirm that fisetin decreases tumorigenicity of prostate cancer cells both in culture and in animal models, which if supported would represent a major added incentive to eat your strawberries.
 
To ingest fisetin levels equivalent to those fed Akita mice, Maher estimates that humans would have to eat 37 strawberries a day, assuming that strawberry fisetin is as readily metabolizable by humans as fisetin-spiked lab chow is by mice. Rather than through diet, Maher envisions that fisetin-like drugs could be taken as a supplement.

Fisetin Lowers Methylglyoxal Dependent Protein Glycation and Limits the Complications of Diabetes (full text)

Abstract

The elevated glycation of macromolecules by the reactive dicarbonyl and α-oxoaldehyde methylglyoxal (MG) has been associated with diabetes and its complications. We have identified a rare flavone, fisetin, which increases the level and activity of glyoxalase 1, the enzyme required for the removal of MG, as well as the synthesis of its essential co-factor, glutathione. It is shown that fisetin reduces two major complications of diabetes in Akita mice, a model of type 1 diabetes. Although fisetin had no effect on the elevation of blood sugar, it reduced kidney hypertrophy and albuminuria and maintained normal levels of locomotion in the open field test. This correlated with a reduction in proteins glycated by MG in the blood, kidney and brain of fisetin-treated animals along with an increase in glyoxalase 1 enzyme activity and an elevation in the expression of the rate-limiting enzyme for the synthesis of glutathione, a co-factor for glyoxalase 1. The expression of the receptor for advanced glycation end products (RAGE), serum amyloid A and serum C-reactive protein, markers of protein oxidation, glycation and inflammation, were also increased in diabetic Akita mice and reduced by fisetin. It is concluded that fisetin lowers the elevation of MG-protein glycation that is associated with diabetes and ameliorates multiple complications of the disease. Therefore, fisetin or a synthetic derivative may have potential therapeutic use for the treatment of diabetic complications.

[ikon2]

 

http://www.scienceda...40901090341.htm
 
Sugar substance 'kills' good HDL cholesterol
 
... methylglyoxal -- MG, was found to damage 'good' HDL cholesterol, which removes excess levels of bad cholesterol from the body...

 
HDL damaged by MG is rapidly cleared from the blood, reducing its HDL content, or remains in plasma having lost its beneficial function...
 
"We could now develop new food supplements that decrease MG by increasing the amount of a protein called glyoxalase 1, or Glo 1, which converts MG to harmless substances...
 
Glo1 converts MG to harmless substances and protects us. MG levels are normally kept low in the body to maintain good health but they slowly increase with aging as Glo1 slowly becomes worn out and is only slowly replaced.
 
Dr Rabbani says: "We call abnormally high levels of MG 'dicarbonyl stress'. This occurs in some diseases -- particularly diabetes, kidney dialysis, heart disease and obesity. We need sufficient Glo1 to keep MG low and keep us in good health"...

 
Pamela Maher found that fisetin up-regulates glyoxalase 1 in mice (at doses that would be 'doable' in people):
 
 

ScienceDaily
 
... Maher and colleagues ... evaluated effects of fisetin supplementation in Akita mice, a very robust model of type 1 diabetes, also called childhood onset diabetes.

Akita mice exhibit increased blood sugar typical of type 1 diabetes and display pathologies seen in serious human complications of both type 1 and 2 diabetes. Those include diabetic nephropathy or kidney disease, retinopathy, and neuropathies in which patients lose touch or heat sensations.
 
Mice fed a fisetin-enriched diet remained diabetic, but acute kidney enlargement-or hypertrophy-seen in untreated mice was reversed, and high urine protein levels, a sure sign of kidney disease, fell. Moreover, fisetin ingestion ameliorated anxiety-related behaviors seen in diabetic mice. "Most mice put in a large area become exploratory," says Maher. "But anxious mice tend not to move around. Akita mice showed enhanced anxiety behavior, but fisetin feeding restored their locomotion to more normal levels."
 
The study also defines a likely molecular mechanism underlying these effects. Researchers observed that blood and brain levels of sugars affixed to proteins known as advanced glycation end-products-or AGEs-were reduced in fisetin-treated compared to untreated Akita mice. These decreases were accompanied by increased activity of the enzyme glyoxalase 1, which promotes removal of toxic AGE precursors.
 
The discovery of an AGE-antagonizing enzyme upregulated by fisetin is very intriguing, because substantial evidence implicates high blood AGE levels with many if not most diabetic complications. "We know that fisetin increases activity of the glyoxalase enzyme and may increase its expression," says Maher. "But what is important is that ours is the first report that any compound can enhance glyoxalase 1 activity."
 
Interestingly, excessively high AGE levels also correlate with inflammatory activity thought to promote some cancers. In fact, studies published by others confirm that fisetin decreases tumorigenicity of prostate cancer cells both in culture and in animal models, which if supported would represent a major added incentive to eat your strawberries.
 
To ingest fisetin levels equivalent to those fed Akita mice, Maher estimates that humans would have to eat 37 strawberries a day, assuming that strawberry fisetin is as readily metabolizable by humans as fisetin-spiked lab chow is by mice. Rather than through diet, Maher envisions that fisetin-like drugs could be taken as a supplement.

Fisetin Lowers Methylglyoxal Dependent Protein Glycation and Limits the Complications of Diabetes (full text)

Abstract

The elevated glycation of macromolecules by the reactive dicarbonyl and α-oxoaldehyde methylglyoxal (MG) has been associated with diabetes and its complications. We have identified a rare flavone, fisetin, which increases the level and activity of glyoxalase 1, the enzyme required for the removal of MG, as well as the synthesis of its essential co-factor, glutathione. It is shown that fisetin reduces two major complications of diabetes in Akita mice, a model of type 1 diabetes. Although fisetin had no effect on the elevation of blood sugar, it reduced kidney hypertrophy and albuminuria and maintained normal levels of locomotion in the open field test. This correlated with a reduction in proteins glycated by MG in the blood, kidney and brain of fisetin-treated animals along with an increase in glyoxalase 1 enzyme activity and an elevation in the expression of the rate-limiting enzyme for the synthesis of glutathione, a co-factor for glyoxalase 1. The expression of the receptor for advanced glycation end products (RAGE), serum amyloid A and serum C-reactive protein, markers of protein oxidation, glycation and inflammation, were also increased in diabetic Akita mice and reduced by fisetin. It is concluded that fisetin lowers the elevation of MG-protein glycation that is associated with diabetes and ameliorates multiple complications of the disease. Therefore, fisetin or a synthetic derivative may have potential therapeutic use for the treatment of diabetic complications.

 

 

Fisetin looks intruiging.  Any ideas on dosages?  It seems there are Swanson products and Doctor's Best.  The DB seems to have two different products though, both Fisetin at 100mg/pill but one is called "Novusetin" and the other is called "Cognisetin".  Any idea what the difference is?

 

http://www.drbvitami...h.TVLo70tr.dpbs

 

http://www.vitacost....0-veggie-caps-2

[ikon2]

 

To kramer91's point, it is, indeed, a very confusing area.  Now all the positives i had held toward avocados are questioned. I know too much PUFAs aren't advisable under this category. What fat sources should I keep, or include, in my diet? These are some I've had on and off over the months:

 

Pumpkin seeds

Avocados

Thought of trying nut butters, like almond

 

Obviously I go easy on these, and try to be very careful with them. At most, in a day, I have a tsp of Olive oil and a tsp of pumpkin seed, along with no more than 1 avocado, and that's it. Lion's share comes mostly from vegetables, leafy greens, berries, and the occasional few fruits depending on the season. 

 

As Logic noted, vinegar and citric acid as cooking sources sound very interesting and worth trying.   

 

 

Twinky, I too have the same question.  This is a confusing (or rather difficult to reconcile with other dietary warning categories) area.  It also seems to align with the "DHA Accelerated Aging Hypothesis", started by Niner.  I posted a similar question on that thread to you here:

 

http://www.longecity...e-2#entry699849

 

ikon2, on 20 Nov 2014 - 07:37 AM, said:

Forgive my idiocy, but what is the net/net here (assuming one subscribes to this theory,which I for one am becoming increasingly convinced of given the continued studies supporting it)?

 

Would a good approach be to make 30% of one's diet fats and within that percentage make:

 

33% LA (coconut oil, macadamia nuts)

 

33% ALA (Flax)

 

33% MUFA (olive oil, avocado)

 

Would this approach satisfy realizing the benefits of MUFA's, realize the benefits of keeping n-3 to n-6 at approx 1:1 and also keep the DHA intake to a minimum and let the body convert what it needs?  And am I correct to assume that Flax, although a PUFA is the type one would want?

 

Am I missing anything here or are any of my foods/fat sources or ratios off?  Is Olive oil considered a HUFA?

 

Also, how does one know if a PUFA (when reading a nutrition label) know if it is a short chain or long chain?

 

And not too much talk about MUFA's in this thread.  Are these good or bad in terms of this theory?

[blood]

Fisetin looks intruiging.  Any ideas on dosages?  It seems there are Swanson products and Doctor's Best.  The DB seems to have two different products though, both Fisetin at 100mg/pill but one is called "Novusetin" and the other is called "Cognisetin".  Any idea what the difference is?

On doses:
 

... Based on average weekly food consumption and body weight, the wild type mice received ~25 mg/kg fisetin/day while the diabetic mice ate more food and received ~40 mg/kg/day...
...

A human equivalent dose (using body surface area normalisation method) could be ~ 2 - 3.2 mg/kg/day. For a 70 kg human, that would be ~ 140 - 224 mg/day. It's anyone's guess if these kinds of doses would be of benefit in humans (we won't know until someone does a study).

Novusetin and Cognisetan are just trade names for plant extracts which have high amounts of fisetin. They're both derived from the same plant. I doubt there is any difference worth worrying about (so go with the most economical).

Edited by blood, 01 December 2014 - 08:07 AM.