haidut

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At least in diabetes, according to the study below. Peat mentioned in several of his articles and interviews that the kidney damage so commonly seen in both type I and II diabetes patients is due to increased PUFA oxidation and decreased glucose oxidation. He also said that the same mechanism applies to kidney damage of "unknown etiology" as medicine likes to call the cases where diabetes is not present or the reason is iatrogenic. I have had multiple arguments with doctors over this and the ruling dogma in endocrinology right now is that diabetes is due to decreased fat oxidation and promoting that oxidation in any way is actually therapeutic. One of the main mechanisms of action of metformin is precisely such increase in fatty acid oxidation, yet the rates of kidney damage in patients on metformin is often higher than in people not using any diabetes drugs.
The study below provides direct evidence for the increased beta-oxidation and decreased pyruvate dehydrogenase (PDH) activity in diabetic patients, and that this increase in fat oxidation is what drives the proximal tubule damage seen in the kidneys. As such, substances like niacinamide, thiamine (for PDH as per the study), aspirin, vitamin E, progesterone, etc are much more likely to be therapeutic than the various poisons sold by Big Pharma that try to lower blood glucose at all costs.

http://diabetes.diabetesjournals.org/content/diabetes/early/2012/05/08/db11-1437.full.pdf
"...Mitochondrial reactive oxygen species (ROS) cause kidney damage in diabetes. We investigated the source and site of ROS production by kidney cortical tubule mitochondria in streptozotocininduced type 1 diabetes in rats. In diabetic mitochondria, the increased amounts and activities of selective fatty acid oxidation enzymes is associated with increased oxidative phosphorylation and net ROS production with fatty acid substrates (by 40% and 30%, respectively), whereas pyruvate oxidation is decreased and pyruvate-supported ROS production is unchanged. Oxidation of substrates that donate electrons at specific sites in the electron transport chain (ETC) is unchanged. The increased maximal production of ROS with fatty acid oxidation is not affected by limiting the electron flow from complex I into complex III. The maximal capacity of the ubiquinol oxidation site in complex III in generating ROS does not differ between the control and diabetic mitochondria. In conclusion, the mitochondrial ETC is neither the target nor the site of ROS production in kidney tubule mitochondria in short-term diabetes. Mitochondrial fatty acid oxidation is the source of the increased net ROS production, and the site of electron leakage is located proximal to coenzyme Q at the electron transfer flavoprotein that shuttles electrons from acyl-CoA dehydrogenases to coenzyme Q."

"...This study shows that 8- to 9-week type 1 diabetes induces an increase in mitochondrial FA b-oxidation without defects in the electron transport and identifies oxidation of FA rather than glycolysis-derived substrate (pyruvate) oxidation as the source of mitochondrial ROS in diabetic tubules. Because more than 90% of kidney cortex consists of proximal tubules, our results can be attributed to proximal tubule mitochondria. These changes in mitochondria coexist with renal structural and functional modifications consistent with the early stage of DN (35,36). Diabetic cortical tubule mitochondria reach maximal respiratory rates with glutamate when oxidation is coupled with and depends on phosphorylation of ADP, and do not further increase when the control of oxidation by phosphorylation is eliminated by the uncoupler. These data show that the control site of oxidative phosphorylation is located at the level of glutamate oxidation to form NADH or electron transport rather than at the level of the phosphorylation system. When substrates that donate electrons at specific sites in the ETC were used, no change in respiratory rates was detected, showing that the formation of NADH from glutamate (glutamate transporter or dehydrogenase) rather than the electron transport is increased in diabetes. The decrease in pyruvate + malate oxidation in diabetic tubule mitochondria suggests a decrease in either pyruvate transporter or pyruvate dehydrogenase that was reported inhibited in the diabetic kidney (15,37). However, the oxidation of pyruvate in isolated tubule mitochondria was performed with a concentration of pyruvate (10 mmol/L) that keeps pyruvate dehydrogenase in its active form by inhibiting pyruvate kinase (38). Therefore, pyruvate transporter rather than pyruvate dehydrogenase seems to be responsible for the decrease in pyruvate oxidation in diabetic tubule mitochondria."

"...In conclusion, mitochondrial ETC is neither the target nor the ROS-generating site in short-term diabetes. This study identifies FA as the source of reducing equivalents responsible for increased ROS production by kidney tubule mitochondria in diabetes and shows that ETF is the major site of electron leakage. A future time course study will help to link the increase in ROS production originating from mitochondrial FA oxidation pathway with the ETC damage and the progression to advanced stages of diabetic kidney disease."
 
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Vinero

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So increasing Pyruvate Dehydrogenase is very protective for the kidneys. That confirms Peat recommending eating a high calcium diet, since dietary calcium stimulates Pyruvate Dehydrogenase. It also means that Thiamin (B1) is good for the kidneys, as it also stimulates PDH.
 

haidut

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So increasing Pyruvate Dehydrogenase is very protective for the kidneys. That confirms Peat recommending eating a high calcium diet, since dietary calcium stimulates Pyruvate Dehydrogenase. It also means that Thiamin (B1) is good for the kidneys, as it also stimulates PDH.

Yep, and thiamine has already been found to help with CKD in humans even though the official mechanism of action is "unknown".
Thiamine Reverses Diabetic Kidney Damage In Humans
 

Kartoffel

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So increasing Pyruvate Dehydrogenase is very protective for the kidneys. That confirms Peat recommending eating a high calcium diet, since dietary calcium stimulates Pyruvate Dehydrogenase. It also means that Thiamin (B1) is good for the kidneys, as it also stimulates PDH.

It does?
 

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https://www.sciencedirect.com/science/article/pii/S0005272809000127
Studies in Bristol in the 1960s and 1970s, led to the recognition that four mitochondrial dehydrogenases are activated by calcium ions. These are FAD-glycerol phosphate dehydrogenase, pyruvate dehydrogenase, NAD-isocitrate dehydrogenase and oxoglutarate dehydrogenase.
These and subsequent studies on purified enzymes, mitochondria and intact cell preparations have led to the widely accepted view that the activation of these enzymes is important in the stimulation of the respiratory chain and hence ATP supply under conditions of increased ATP demand in many stimulated mammalian cells.
 

S-VV

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Pyruvate dehydrogenase is activated by intracellular Calcium ions. The concentration of which is thightly regulated by the cells, and to a great extent doesn't reflect calcium intake.

The reason PDH is activated by calcium ions is that muscular contraction( which requires high ATP) is initiated by a release of calcium ions from the sarcoplasmic reticulum to the cytoplasm.

So it makes sense for the body to "anticipate" the ATP need and increase oxphos.

That being said, a high calcium intake has lots of benefits like Ray says, like suppressing PTH.
 

Kartoffel

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Another link: Pyruvate dehydrogenase and the citric acid cycle
One more interesting detail is that the PDH phosphatase is activated by calcium ions. Calcium ions also trigger the contraction of muscle cells. Concomitant activation of PDH anticipates the need to replace the ATP that will be consumed in the contraction.

Well, ok but this doesn't show that a high-calcium diet leads to increased activation of PDH by Ca+ ions.
 
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