The Randle Cycle Revisited. It Could Be Extended To Lactate

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The Randle cycle revisited: a new head for an old hat

Inhibition of glucose utilization by fatty acids was originally demonstrated in heart (142). It was later also found in liver (13, 84) and in the β-cells of the pancreas, where a permissive effect of fatty acids on glucose-induced insulin secretion has been established (146). Interestingly, the cycle can be extended to lactate in heart and liver (36, 37, 39, 74, 169, 182), two lactate-consuming organs. Here, lactate inhibits the oxidation of both glucose and fatty acids. Much experimental evidence accumulated thus far confirms that the Randle cycle is actually working in whole animals as well as in humans (63, 64, 146).

This makes sense for me. Inability to oxidase both FA and glucose, this what creates failed energy utilization, some kind of lactate induced metabolic "bottleneck" creating vicious cycle. Does it mean that lactate issues should be the first target in restoring metabolic health?

@haidut Can I hear your opinion please?
 
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Very good fine. Dr. peat is constantly talking about how low metabolism causes lactate buildup which interferes with oxidative phosphorylation.
 

milkboi

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Can I conclude that Lactate buildup isn't a problem for me because high dose Thiamin HCL (1,5g) does nothing (noticeable) for me?
 

milkboi

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Maybe you need to take it for a longer duration?

I took it for a few weeks... For now, I'm sticking with just 100mg or so. Gonna experiment with higher doses again soon, combined with a few mgs MB and Mag carbonate. If that doesn't make a noticeable difference I'll direct my attention otherwhere.
 

haidut

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The Randle cycle revisited: a new head for an old hat

Inhibition of glucose utilization by fatty acids was originally demonstrated in heart (142). It was later also found in liver (13, 84) and in the β-cells of the pancreas, where a permissive effect of fatty acids on glucose-induced insulin secretion has been established (146). Interestingly, the cycle can be extended to lactate in heart and liver (36, 37, 39, 74, 169, 182), two lactate-consuming organs. Here, lactate inhibits the oxidation of both glucose and fatty acids. Much experimental evidence accumulated thus far confirms that the Randle cycle is actually working in whole animals as well as in humans (63, 64, 146).

This makes sense for me. Inability to oxidase both FA and glucose, this what creates failed energy utilization, some kind of lactate induced metabolic "bottleneck" creating vicious cycle. Does it mean that lactate issues should be the first target in restoring metabolic health?

@haidut Can I hear your opinion please?

Great find, and easily explainable. When lactate is high, the mitochondrial (but not cytosol) NAD/NADH ratio is low and as a result both PDH and beta oxidation are downregulated as they both depend on the NAD/NADH ratio.
 
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Great find, and easily explainable. When lactate is high, the mitochondrial (but not cytosol) NAD/NADH ratio is low and as a result both PDH and beta oxidation are downregulated as they both depend on the NAD/NADH ratio.

If both are downregulated, how is the cell getting energy @haidut

Thank you!
 

haidut

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haidut

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Does niacinamide lower lactate or just FFAs?

Both. Anything that raises NAD/NADH ratio allows for proper pyruvate processing by PDH and as such there is little leftover pyruvate to generate lactate.
 

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