Mitochondrial Damage And Fatty Acid Buildup, Not Glucose, May Drive Diabetes

haidut

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Finally some common sense is coming out of mainstream medicine. The study below demonstrates that it is the buildup of fatty acid metabolites and mitochondrial damage that drives the chronic inflammation now known to be a major causative factor for diabetes II (T2DM), as well as virtually all other chronic diseases. Aside from corroborating the role of fat in diabetes, as well as exonerating glucose, the study calls into question virtually all current therapies for diabetes II (T2DM). Those therapies focus mainly on lowering blood glucose (HbA1C), but the study's findings question the effectiveness of this approach since it does not address the fatty acid buildup or the mitochondrial damage. As such, targeting glucose is at best misguided and at worst contributing to the diabetes pathology. This may explain why drugs that try to selectively lower HbA1C increase all-cause mortality.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61969-3/fulltext
Study claims low HbA1c increases mortality risk

Combined with the recent study showing the causative role of drugs like metformin in the "cancerization" process I think it is way overdue for the medical industry to re-evaluate its relationship with glucose as well as its overall approach to treating diabetes. There are multiple studies showing niacinamide and aspirin being therapeutic for diabetes, and unlike the HbA1C lowering drugs the former two chemicals are rather benign, not to mention dirt cheap compared to pharma darlings like Jardiance, Glyxambi, sulfa drugs, etc.

https://www.sciencedirect.com/science/article/abs/pii/S1550413119303778?via=ihub

"...Our results effectively dismiss the oversimplified notion that glycolysis drives inflammation as in other diseases (Cham and Gajewski, 2005; Peng et al., 2016; Yin et al., 2015) by showing instead that glycolysis, which does not strictly result from hyperglycemia/insulinemia of T2D, parallels rather than promotes T2D inflammation. Because better glycemic control is generally the goal of classical T2D interventions, the demonstration that glucose is not the dominant activator of Th17-mediated inflammation in T2D raises clinical concerns that fatty acid metabolites will continue to drive systemic and/or tissue inflammation even after glycemic control is optimized. The newly appreciated disconnect between glucose as a fuel and T2D inflammation may also explain in part the modest impacts of anti-inflammatory drugs on glycemic control in T2D clinical trials: our data show the two characteristics of T2D are only secondarily linked."

Mitochondria, not glucose, could be driving inflammation in type 2 diabetes

"...A breakthrough discovery has cast doubt on previous assumptions that glucose is the main driving force behind chronic inflammation within type 2 diabetes. University of Kentucky researchers carried out a study to test whether glucose is the cause of chronic inflammation - previously it has been assumed that raised blood glucose levelsis the cause. Their investigations indicate that an interaction between certain lipids (blood fats) and mitochondria (the powerhouse of cells in the body) appeared to be the problem. Blood glucose control is still important for managing type 2 diabetes, but the researchers state it may not be the key factor in the development of problems related to inflammation such as heart and kidney disease. Originally the researchers had set out to prove another theory: that immune cells from people with type 2 diabetes would produce energy by burning glucose. "We were wrong," said Barbara Nikolajczyk, from the UK Barnstable Brown Diabetes Center, Department of Pharmacology and Nutritional Sciences, who co-led the study. The researchers found instead that energy from glucose was not driving chronic inflammation, but rather it was a combination of defects in mitochondria and an increase in fat derivatives that were responsible. "Our data provide an explanation for why people with tight glucose control can nonetheless have disease progression."

https://www.medicalnewstoday.com/articles/326143.php

"...Chronic inflammation is the root cause of many of diabetes' complications, including cardiovascular and kidney disease. Until now, the scientific consensus has been that glucose drives inflammation in type 2 diabetes. But new research counters this popular notion and points instead to high levels of lipids and defects in mitochondria — the tiny energy-reducing organelles inside cells."
 

Collden

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Oct 6, 2012
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@haidut What defects in the mitochondria and is there a way to fix this? Thanks
"In the resting state, muscles consume mainly fats, so maintaining relatively large muscles is important for preventing the accumulation of fats" - Peat

Resistance exercise is also helpful for mitochondrial function.
 

rob

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@contact interesting post.

As for what to do, the research speaks of a low CACT:CAPT1 ratio in the immune cells. So, effectively, carnitine has problems in transporting long-chain fatty acids into the mitochondrial matrix for energy production causing a cellular build up of metabolites.

Logically, this would suggest a diet very low in long-chain fats and high in carbs - with, maybe, some mediuum-chain fats if tolerated. Equally, regular eating and certainly avoidance of fasting would look advisable. Also, I think you would have to be very careful around exercise and ensuring you are well fuelled.
 

Cirion

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My latest strategies myself to fix my own disorder is avoid ALL fats (even coconut oil) and some days I may be as low as 5 gram total fat (and 1 gram or less of PUFA) while also eating ample sugar/carbs and also playing with lipolysis/FAO blockers. Still waiting for my pyrucet which annoyingly seems lost in the mail (Thanks Haidut btw for replying quickly to my request as to what the deal is with it, I think maybe the delay is due to the hurricane as I did see a notice on the USPS website about that) so I can really kick my FAO blocking into high gear. In regards to exercise, I definitely want to incorporate some resistance exercise once I get a little more energy. I've finally managed to drop around 10 lb in 2 weeks doing this--eating very high sugar which blocks FAO quite handily. I'm still heavily obese, but I'll take any progress I can get at this point. Every lb I drop reduces endotoxin/serotonin/FAO/lipolysis and should start setting me on a positive spiral path.

I've more than proven to myself that sugar doesn't cause diabetes, it cures it, in fact it is my latest fruit juice / syrup diet that made me shed 10 lbs quickly.

Was interesting to read that a high fat diet can result in FFA's / FAO that is literally triple that of a low fat diet. I sure believe it, a high fat diet quickly sends me into Serotonin City.
 
Last edited:

lampofred

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My latest strategies myself to fix my own disorder is avoid ALL fats (even coconut oil) and some days I may be as low as 5 gram total fat (and 1 gram or less of PUFA) while also eating ample sugar/carbs and also playing with lipolysis/FAO blockers. Still waiting for my pyrucet which annoyingly seems lost in the mail (Thanks Haidut btw for replying quickly to my request as to what the deal is with it, I think maybe the delay is due to the hurricane as I did see a notice on the USPS website about that) so I can really kick my FAO blocking into high gear. In regards to exercise, I definitely want to incorporate some resistance exercise once I get a little more energy. I've finally managed to drop around 10 lb in 2 weeks doing this--eating very high sugar which blocks FAO quite handily. I'm still heavily obese, but I'll take any progress I can get at this point. Every lb I drop reduces endotoxin/serotonin/FAO/lipolysis and should start setting me on a positive spiral path.

I've more than proven to myself that sugar doesn't cause diabetes, it cures it, in fact it is my latest fruit juice / syrup diet that made me shed 10 lbs quickly.

Was interesting to read that a high fat diet can result in FFA's / FAO that is literally triple that of a low fat diet. I sure believe it, a high fat diet quickly sends me into Serotonin City.

Hydrogenated CO is amazing. Butter, ghee, ordinary CO don't compare.
 

Kingpinguin

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Joined
Aug 14, 2019
Messages
586
Finally some common sense is coming out of mainstream medicine. The study below demonstrates that it is the buildup of fatty acid metabolites and mitochondrial damage that drives the chronic inflammation now known to be a major causative factor for diabetes II (T2DM), as well as virtually all other chronic diseases. Aside from corroborating the role of fat in diabetes, as well as exonerating glucose, the study calls into question virtually all current therapies for diabetes II (T2DM). Those therapies focus mainly on lowering blood glucose (HbA1C), but the study's findings question the effectiveness of this approach since it does not address the fatty acid buildup or the mitochondrial damage. As such, targeting glucose is at best misguided and at worst contributing to the diabetes pathology. This may explain why drugs that try to selectively lower HbA1C increase all-cause mortality.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61969-3/fulltext
Study claims low HbA1c increases mortality risk

Combined with the recent study showing the causative role of drugs like metformin in the "cancerization" process I think it is way overdue for the medical industry to re-evaluate its relationship with glucose as well as its overall approach to treating diabetes. There are multiple studies showing niacinamide and aspirin being therapeutic for diabetes, and unlike the HbA1C lowering drugs the former two chemicals are rather benign, not to mention dirt cheap compared to pharma darlings like Jardiance, Glyxambi, sulfa drugs, etc.

https://www.sciencedirect.com/science/article/abs/pii/S1550413119303778?via=ihub

"...Our results effectively dismiss the oversimplified notion that glycolysis drives inflammation as in other diseases (Cham and Gajewski, 2005; Peng et al., 2016; Yin et al., 2015) by showing instead that glycolysis, which does not strictly result from hyperglycemia/insulinemia of T2D, parallels rather than promotes T2D inflammation. Because better glycemic control is generally the goal of classical T2D interventions, the demonstration that glucose is not the dominant activator of Th17-mediated inflammation in T2D raises clinical concerns that fatty acid metabolites will continue to drive systemic and/or tissue inflammation even after glycemic control is optimized. The newly appreciated disconnect between glucose as a fuel and T2D inflammation may also explain in part the modest impacts of anti-inflammatory drugs on glycemic control in T2D clinical trials: our data show the two characteristics of T2D are only secondarily linked."

Mitochondria, not glucose, could be driving inflammation in type 2 diabetes

"...A breakthrough discovery has cast doubt on previous assumptions that glucose is the main driving force behind chronic inflammation within type 2 diabetes. University of Kentucky researchers carried out a study to test whether glucose is the cause of chronic inflammation - previously it has been assumed that raised blood glucose levelsis the cause. Their investigations indicate that an interaction between certain lipids (blood fats) and mitochondria (the powerhouse of cells in the body) appeared to be the problem. Blood glucose control is still important for managing type 2 diabetes, but the researchers state it may not be the key factor in the development of problems related to inflammation such as heart and kidney disease. Originally the researchers had set out to prove another theory: that immune cells from people with type 2 diabetes would produce energy by burning glucose. "We were wrong," said Barbara Nikolajczyk, from the UK Barnstable Brown Diabetes Center, Department of Pharmacology and Nutritional Sciences, who co-led the study. The researchers found instead that energy from glucose was not driving chronic inflammation, but rather it was a combination of defects in mitochondria and an increase in fat derivatives that were responsible. "Our data provide an explanation for why people with tight glucose control can nonetheless have disease progression."

Inflammation in type 2 diabetes: Study overturns previous notions

"...Chronic inflammation is the root cause of many of diabetes' complications, including cardiovascular and kidney disease. Until now, the scientific consensus has been that glucose drives inflammation in type 2 diabetes. But new research counters this popular notion and points instead to high levels of lipids and defects in mitochondria — the tiny energy-reducing organelles inside cells."

This is awesome
 

Cirion

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Hydrogenated CO is amazing. Butter, ghee, ordinary CO don't compare.

I tried HCO for a while with some success but abandoned it due to really painful bowel movements w/ blood in bowels (sorry if tmi).

However, I am thinking this was now actually due to the blood thinning effects of aspirin and not HCO because the last few days the pain has come back and I recently brought back aspirin.

Maybe I'll try it again, I have a lot of leftover HCO.
 

lampofred

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I tried HCO for a while with some success but abandoned it due to really painful bowel movements w/ blood in bowels (sorry if tmi).

However, I am thinking this was now actually due to the blood thinning effects of aspirin and not HCO because the last few days the pain has come back and I recently brought back aspirin.

Maybe I'll try it again, I have a lot of leftover HCO.

It might have been due to both. They raise metabolism pretty strongly if you are full of PUFA and will exacerbate a glycine deficiency, which everyone in this country has thanks to Monsnto. And glycine is essential for the gut.
 

yerrag

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Not so fast.

Long chain fatty acids have their uses. I'd avoid the PUFAs, but SFAs are fine. For one, these fats spur production of bile, and these fats go into circulation enclosed in chylomicrons. Bile is needed for fecal extraction. Chylomicrons also carry endotoxins to the liver, where endotoxins are prepared for excretion. If you're avoiding these fats, then you're also going to have a harder time excreting endotoxins, and you're also losing out on the benefit of bile production facilitating bowel movement.
 

Cirion

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Not so fast.

Long chain fatty acids have their uses. I'd avoid the PUFAs, but SFAs are fine. For one, these fats spur production of bile, and these fats go into circulation enclosed in chylomicrons. Bile is needed for fecal extraction. Chylomicrons also carry endotoxins to the liver, where endotoxins are prepared for excretion. If you're avoiding these fats, then you're also going to have a harder time excreting endotoxins, and you're also losing out on the benefit of bile production facilitating bowel movement.

That's true in theory but not in practice, at least not for me. I know some here have seen success on dietary fats so I certainly can't discount their experiences, but I don't know a single obese person who has done well. All of the people who did well weren't nearly as overweight as me and already overloaded with FFA's. Intaking dietary fat, yes even SFA's, can increase FFA's, which is a disaster in some cases. The goal should be to reduce, not increase, fatty acid oxidation (FAO) and haidut has threads on this subject.

That said ----- @lampofred may be on to something with Hydrogenated coconut oil because it has ZERO pufa and zero mufa. I think I will try it again and see what happens. The last time I tried HCO I was still drinking milk and eating cheese both of which I realize now reduce my metabolic rate, so HCO in the context of my current eating pattern may indeed be useful. We shall see.

Keep in mind that ALL saturated fats come with PUFA with the exception of HCO. So it could be that I'm so hypersensitive to PUFA, that even the tiny trace amounts in various foods affect me more than the SFA's that come with it help me.
 

yerrag

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That's true in theory but not in practice, at least not for me. I know some here have seen success on dietary fats so I certainly can't discount their experiences, but I don't know a single obese person who has done well. All of the people who did well weren't nearly as overweight as me and already overloaded with FFA's. Intaking dietary fat, yes even SFA's, can increase FFA's, which is a disaster in some cases. The goal should be to reduce, not increase, fatty acid oxidation (FAO) and haidut has threads on this subject.

I'm not one to take too much fats as we want to be supplied with energy from glucose metabolism.

Just this week, I began to put about 20g of cocoa butter in my morning coffee. I intended to stimulate both bile and chylomicron production, as they both are needed to clear endotoxins through the fecal route. The high amount of long-chain SFAs and MUFAs would increase chylomicrons, as the nature of their being long-chains mean the fats don't go directly to the liver to be metabolized, and when the route to be taken isn't a direct one to the liver, chylomicrons are needed to transport these fats.

I'm not sure yet if they're doing the job I expected of them, but the intake of cocoa butter certainly made me have better and more frequent bowel movement. This wasn't expected, but I suppose if more bile is produced, bowel movement would also be facilitated.

I've not been up to speed with your blog. All I know is that you've struggled with obesity. I know you had focused once on increasing your metabolism and temperature. And to that end you have a high caloric intake. I could be wrong, and you may have shifted your approach.

I've lately put on some weight, and this is even before I started adding cocoa butter to my coffee. I felt sluggish even after meals, and this wasn't typical of me. It took a while for me to notice my lack of energy. It would turn out that I'm low on thiamine, and it was because I have for two months been urinating a lot. And with that, thiamine and potassium stores are lowered. All it took was for me to take more thiamine and my energy level was restored after meals.

I have a blood glucose meter, and I'd normally be stable at around 85 during the day. But during this episode of lack of energy, my blood sugar was high at 103. It was the thiamine deficiency.

Doing self-help on health is a tough task for all of us. I started out and continue to work at lowering my blood pressure. I made the wrong combination and dosage of enzymes and antibiotics, and I ended up with an endotoxin storm, only to see my blood pressure go higher. It's frustrating and confounding. It was what caused my frequent urination, and this led to thiamine and potassium deficiency. Late to catch on, I finally stumbled upon the cause. During this time, I had added weight, and my waistline got bigger. I had to go shopping for new pants.

I think though that taking some long-chain SFAs isn't going to cause obesity. It's often the case that we argue the merits of MCTs and we've heard of the benefits of MCTs in helping people lose weight, and I would hear little of the benefits of taking long-chain saturated fats. I like VCO because it has plenty of lauric acid, which helps with increasing cholesterol production, and I like the long chain SFAs as well, because it spurs bile and chylomicron production, and they have their beneficial uses. I won't take them as a replacement to carbohydrates, but I won't stay away from them either. There's good in them and I should employ their help, especially when I have issues they can help me with.
 
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