Gluconeogenesis: I keep hearing that it's only demand driven, can that be right?

(Chris) #24

It’ll come from your lean tissue if not. The glucose your body wants must come from somewhere.

(Brian) #25

I don’t do protein shakes but do occasionally use some whey protein powder in a keto dessert. I tend to be cautious about it and don’t want to use it as a staple of my diet mostly because of it’s reputation as a spiker of insulin. I’m not “afraid” of it. I just use lightly and only occasionally.

Probably a bit off topic but just something that came to mind.

(Diane) #26



I don’t seem to have much reaction to whey but for those who do have you tried casein? Apparently it absorbs more slowly and is more satiating. I have some casein powder and taste-wise it’s good but it’s grainier than most whey I’ve had.

(Steve Stephenson) #28

An amazing blog post by! Near the end there’s this:

I recommend this video for an absolutely frikkin’ fascinating lecture on glucagon, and the importance of glucagon and insulin working in concert to regulate BG. I had my mind blown several times while watching. Well worth your time if you want to understand this stuff.

The video title is, “A New Biology For Diabetes”, the Rolf Luft Award 2014, Prize Lecture by Professor Roger Unger, University of Texas.

(Banting & Yudkin & Atkins & Eadeses & Cordain & Taubes & Volek & Naiman & Bikman ) #29

All of Rosedale’s citations on the deleterious effect of mTOR ignore two crucial facts:
AMPK is upstream from mTOR… it can regulate mTOR expression
LCHF/Keto/Fasting stimulates AMPK phosphorylation, thus downregulating mTOR.

I would go with Fung’s theory of protein stimulating insulin, except that Bikman smacked that with context dependency like he was the average sized, white Mutumbo.

It’s all very context specific. If your fasting glucose/insulin is in good shape, and you are LC, protein is your body’s buddy. If your fasting insulin is T2D, I think Fung is your guy.

Rosedale is so focused on mTOR that he’s not seeing the importance of context. That’s why there’s been very few outbursts from him since the 2017 LC Breckenridge.

GNG, protein and blood glucose re-visited
(Jason Jodway) #30

To say GNG is demand driven is misleading as that implies the explicit need for glucose is why it happens and that is simply not true. It is signalling driven. Certain substrates will always drive GNG but we don’t eat these directly really and it amounts to a meaningless amount. Otherwise, it is the combination of hormonal levels, FFA levels, and availability of amino acids that dictates GNG. T1 and T2 in high glucagon/FFA states will have more GNG despite a high glucose state.

“surplus protein” is in of itself misleading. The fate of amino acids is vast. They can be used for their primary purpose as components of protein structures, cross converted into other amino acids for the same purpose, incorporated into the urea cycle, deaminated to carbon skeletons and used as intermediates in the TCA cycle, or, yes, have the carbon skeleton used as a substrate for glucose production. The key here being there is no requirement for amino acids to become glucose to be used as a metabolic substrate. They can also simply be lost in urine.

The most primary concern about very high protein consumption is that the oxidation of amino acids for metabolic fuel produces ammonia which is toxic. Each individual person will have their own maximal rate of binding this ammonia as urea and excreting it.

(Banting & Yudkin & Atkins & Eadeses & Cordain & Taubes & Volek & Naiman & Bikman ) #31

A thing that only really happens on LCLF or in more caloric restricted versions of LC. Amino acids are, to my understanding, the last choice for energy.

(Jason Jodway) #32

They certainly aren’t prioritized to be oxidized as that destroys them as amino acids which are essential structural components, but it is one of the potential ultimate fates of amino acids.

(Jason Jodway) #34

This is extremely inaccurate. There is literally never a time you aren’t oxidizing some amino acids.

(Brian) #35

I haven’t actually noticed anything negative by using what I have but then again, it’s pretty small amounts of it. It’s mostly just the chatter online that gives me cause to be a little mindful at least.

Had a week of “indulging” with the keto sweets as we had company most of last week. Hit a new weight low yesterday so it’s obviously not pushing the scale higher. (?)

I am guessing that most people that use whey protein powder are probably using it in conjunction with weightlifting or bodybuilding of some other heavy exercise routine and in considerably larger amounts than I would. I don’t “work out” but I do work outside a lot of days, not sure if that counts. :wink: But I also just use it as an ingredient in the occasional baked treat, mostly as a conditioner of sorts to help with texture that’s just not there with the gluten we’d have if we were using wheat flour.

Thanks for the suggestion of casein, though.


(Bacon is a many-splendoured thing) #36

Here’s where I learned about it:

I’m certainly not going to argue with Richard!

Everybody’s a comedian! :grin:

(Bacon is a many-splendoured thing) #37

Huh. Interesting!

Well, then, that’s probably why Bikman and he seem so far apart. Do you have a reference I could check out? Preferably one for the easily-confused? I really need to learn more about this stuff, and I’d prefer not to have to follow Richard back to university, lol! :smiley:

(mole person) #38

I’ve done a bunch of reading over the last couple of days and I think the answer is that gluconeogenesis IS demand driven AND that eating more protein drives that demand via increased glucagon leading to GNG. Further there are other processes that convert protein consumed into non glucose metabolic fuels. Although this is all different than saying “too much protein is like stuffing your face with candy” it’s still a fact that too much protein will inhibit both ketosis and lipolysis which is what most of us are aiming for.

(mole person) #39

Thank you, I love that you tested it out. To me it only makes sense too. If your getting more protein than your body can use, and the body’s ability to store amino acids is small, I only see two options 1) convert to fuel or 2) somehow excrete it. But why would the body excrete it when it could convert and store it? Without a reason why this would happen, or evidence that it is happening, I’ll assume 1) since storage of fuel for future use seems to be what our bodies love to do

(Banting & Yudkin & Atkins & Eadeses & Cordain & Taubes & Volek & Naiman & Bikman ) #40

Over in my accountability thread, I did the research and broke it down. Search LeChef Midlife AMPK and that should get ya there.

(mole person) #41

Thank you. That post was very helpful and informative. I have a few questions though.

You wrote:

“Otherwise, it is the combination of hormonal levels, FFA levels, and availability of amino acids that dictates GNG.”

Could you expand on this? how do each of these influence GNG.

Do we know that this increases with overconsumption of protein? As opposed to just a regular amount of waste amino acids, for example.

(Bacon is a many-splendoured thing) #42

On the other hand, Dr. Bikman makes it sound that if you are already ketotic, you don’t need to worry about gluconeogenesis above the body’s actual need for it:

Though it’s always possible I misunderstood what he said.

(Diane) #43

I agree with your understanding though it’s always possible there is a difference for those eating ketogenically with high insulin resistance vs those who are sensitive to insulin.

(Jason Jodway) #44

Glucagon, cortisol, other catecholimines promote GNG. Insulin inhibits GNG. Leptin, T4, T3, Adiponectin influence the sensitivity to these signals not necessarily in a linear way. GH, IGF I’m sure play some part. There are potentially other unknown hormones, cytokines that have an effect. There are all sorts of signaling molecules we have little solid knowledge about so far.
FFA are relevant (somewhat speculative) because GNG is an energy consuming process so you have to have enough fuel for the liver plus extra and intrahepatic FA levels will reduce insulin action which is normally inhibitory of GNG.

Availability of amino acids is mostly to the extent that some are purely gluconeogenic, some are purely ketogenic, and some can be either, and that availability plus ratio drives the relative amount of glucose production versus ketone production. Less AA available means greater ketones, less glucose guaranteed.

As for how much is lost in urine, I’ve never seen any study data so I could only speculate. While typically elevated protein in urine makes one think of kidney failure, it is the typical trend that the more of something you consume in your diet, the more will be lost in urine as well. The reality is that the kidneys are not perfect and do lose useful nutrition over time.