Thursday, May 30, 2024

Protons (72) Humans: 8% LA vs 74% LA by sustained oral ingestion

This study in humans is very different to the previous rat study. People were fed repeated oral fat loads (you could call this Bulletproof Cocoa rather than Bulletproof Coffee), once an hour for 12 hours then every two hours overnight until the start of an hyerglycaemic clamp at 24h, through which the oral fat loading continued. Glucose was infused to a stable 20mmol/l and insulin allowed to respond as best it might. Insulin sensitivity was determined by the glucose infusion rate in the last 30 minutes of the clamp. In some ways this is more physiological than the hyperinsulinaemic euglycaemic clamp, which is considered the gold standard. The oral fat ingestion was slightly above calculated 24h caloric requirements for these subjects.

Differential effects of monounsaturated, polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion, sensitivity and clearance in overweight and obese, non-diabetic humans

Over a 24h period the ingestion of safflower oil, with linoleic acid providing in the region of 70% of total calories, ought to demonstrate the initial Protons predicted insulin sensitising effect, which would only be later replaced by the uncoupling effect if the study had been continued for a week or two. 

Again we can assess insulin sensitivity by how much glucose was needed to be infused during the last 30 minutes of the clamp to maintain an hyperglycaemia of 20mmol/l. This is what happens:

















I don't think I have to make any qualifications here. SFA oral ingestion for 24h causes a very similar degree of insulin resistance to oral ingestion of a minimal calorie supplying control chocolate drink. Tallow rather than palm oil would have accentuated the effect.

Ingesting 70% of your calories as linoleic acid over a 24h period is insulin sensitising compared to ingesting SFA, p less than 0.001. Or ingesting virtually nothing at all, p < 0.05.

Linoelic acid is insulin sensitising.

This is BAD. When fasting you *must* resist even basal insulin or that insulin will lower fasting glucose, lower fasting FFAs and you will be hungry. And raid the fridge at 2am. And get fat.

Protons.

Peter

5 comments:

  1. Golly, I turn away for a day and woosh, look what turns up.
    Look at you!
    Thanks Peter.

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  2. Interesting.Thanks! Which (at least partially) explains why I had to eat every 2 hours while obese and SAD, but fasting after going low carb and veggie oil free, was a breeze... I'm assuming.

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  3. Hi Steve, even high PUFA keto made fasting easy for me, well before low 6. I suspect L6 would make it even easier, but I don't fast much...

    Hi Pass!

    Peter

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  4. This always gets back to the very long half life of LA - even a slightly high intake can bio-accumulate - increasing insulin sensitivity (very hard to loose weight). If someone has the average level of LA in subcutaneous fat - 25% and needs to lower it to what is probably normal - 8% it could take years. Hard to unroll the short vs long-term effects of LA consumption?

    In the progression of T2D - insulin resistance happens first - only later does it appear that the pancreas can't keep up and BG control is lost ( beta-cell exhaustion). I suspect that the first tissue to be damaged is the liver.

    ,.,.

    So if LA + fructose causes NAFLD - which causes insulin resistance in the liver - is it possible for adipose tissue to be still highly sensitive at the same time? So the liver cranks out glucose and lipids while the adipose stores fat? Or another way to say it - adipose is sensitive while the liver is resistant.

    I suppose the LA in the liver tends to form 4-HNE causing insulin resistance and lesions? NAC might help remove 4-HNE...

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  5. karl, and if you generate an obesity model by long term suppression of adipocyte lipolysis you cannot develop the insulin resistance of obesity. A genetic model with the phenotype of permanently effective acipimox...

    Increased Fatty Acid Re-esterification by PEPCK Overexpression in Adipose Tissue Leads to Obesity Without Insulin Resistance
    https://pubmed.ncbi.nlm.nih.gov/11872659/

    Peter

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