I have been taking small dose metformin recently 500mg per day and noticed something peculiar, I eat less and move more, but on an involuntary basis. I decided to experiment with metformin because of a tip pointed out by ItsTheWooo and also because I kind of self-diagnosed myself with pre-diabetes.
What I have noticed is I get very satiated on smaller amounts of food now, and I dont feel as lethargic all the time. Whats up with that? Lustig says the amout of energy we burn and how good we feel are the same, so my guess can only be that on metformin, I burn more energy.
But why on earth am I eating less food on metformin? I dont believe in magic. I then remembered that I had found some studies now and then ( but failed to record them on my blog, ) that metformin increased glp-1 secretion ( 1 ). As we know, glp-1 is an anorexiant. Just see the last post to understand how powerful it is.
One of the primary ways metformin works is by decreasing hepatic glucose production. This lowers blood glucose and hyperglycemia symptoms, for example insulin resistance. Increased hepatic glucose production is the classic obese->T2DM->MetSyn pathway that is so common nowadays.
Ok, so what?
Well, I also found this study sometime ago which shows you the problem with high-fat diets. Yes thats right!
HIGH FAT DIETS ARE PROBLEMATIC!
Indeed, high-fat diets seem to be problematic if they are also high carb diets. Just look at the study in the last link, what it shows is that fat ingested alone produces a strong glp-1 response, however, as soon as you add potato to the same meal, the glp-1 response is tiny and insignificant.
Let me say that again,
Eating fat with a potato is less satiating than eating fat alone.
And there in black and white is the study to prove it, and this is the problem with high-fat diets. BTW, a decreased or absent glp-1 response is the sign of T2DM. This study was done on healthy subjects though.
I can understand the confusion here, eating more calories should be more satiating than eating less, right? But that is not what the above study shows us. Neither is it what real life anecdotes tell us, as people often feel more energetic on ketogenic diets while eating less calories.
Ergo, eating more calories does not increase energy expenditure. ( actually I suspect its incretins that increase energy expenditure, not calories per se )
But wait, im not done yet. Whats the reason eating potato with fat produces less glp-1? Well, the authors of the study speculate that it is because of hyperglycemia, i.e. high blood sugar reduces glp-1 response. Ah ha! So now we see why metformin increases glp-1, because metformin lowers blood glucose by lowering hepatic glucose production.
The only way to get out of "starvation mode" where your feeling shit is by increasing the incretin response, the incretin response IS A MAJOR PART of your body can recognising that it is not starving. Eating more calories will only increase fat storage and insulin resistance if the incretin response is still low.
I want to quote this last study to back-up the above paragraph. In this paper the author makes reasoning and links to several other references that show that increasing substrate availability does not increase energy expenditure. One of the studies he links to for proof of this is done with lipid infusion, i.e., calories injected straight into the body, completely by-passing the incretin and gastric system.
Injecting calories into the body is equivalent to eating calories with ZERO incretin response!
We should therefore conclude from this that eating calories with reduced incretin response would be equivalent to injecting calories into the blood, which as shown, only increases fat storage and insulin resistance, not energy expenditure.
We also have the evidence of RYGB surgey people, from a macroscopic perspective, these people are starving, because they eat 300 calories per day. But, they do not display symptoms of starvation by complaining of hunger and moving less, infact, its the exact opposite. And I really do think its becuase RYGB increases incretin response.
P.S. I know I didnt mention leptin or insulin here, ofcourse they are important, but I think the incretin affect is under-appreciated. While insulin and leptin is overemphasized.