So how can we manipulate RQ values?
This is a graph taken from that nice paper on ketogenic diets for rats. The black line is the RQ of the chow fed rats. They are on 17% or so calories from fat, 64% of calories from starch and the rest is protein. Grey zones are night, white zones are daytime. Ratties are nocturnal, they eat their high carbohydrate diet at night. While they are eating they run their metabolism on glucose. This should give an RQ of 1.0 but we can see the RQ is greater than 1.0 during the times at which the rats are feeding:
We've seen this before during an OGTT in massively weight reduced people. Show them some glucose and they will immediately convert it to lipid and store it. After a mere 75g of glucose during an OGTT, these post obese ladies will develop an RQ over 1.0, see the top dashed line:
This is de novo lipogenesis, either routine in the rats on a 64% carbohydrate or pathological in the post obese ladies. Glucose arrives as an oxygen rich molecule. During the reorganisation to a very oxygen poor molecule oxygen is provided without it needing to be taken up through the lungs. Smaller oxygen flux per unit CO2 produced gives an RQ greater than 1.0.
So it's pretty easy to get a RQ above 1.0. How easy is it to get an RQ below 0.69?
As we all know, acetoacetate is unstable, spontaneously decarboxylating to acetone and CO2. On its own this isn't fast enough to be useful so we have acetoacetate decarboxylase to speed the process up. You find it in the liver and in the brain, mostly. The sorts of places where glucose might be useful.
Apart from being exhaled, what is the fate of acetone in the body? I can't imagine that we are deliberately forming the stuff enzymatically just to breathe it out... Well, here's a pathway I cribbed earlier, can't remember from which paper but one on basic acetone metabolism:
Soooo theoretically ketone bodies, via acetone and oxaloacetate , are glucose precursors. If you radio label acetone with (14)C, where does it end up?
"Radioactivity from (14)C acetone was not detected in plasma free fatty acids, acetoacetate, beta-hydroxybutyrate, or other anionic compounds, but was present in plasma glucose, lipids, and proteins".
Ketones to glucose. How much?
“On the basis of our specific activity data, we have calculated that 4-11% of plasma glucose production could theoretically be derived from acetone”.
The 11% was calculated for 21 day starved humans.
The most logical explanation for an RQ of 0.62 is that the person is performing a significant conversion of fat to glucose. This is completely plausible via acetoacetate, acetone and oxaloacetate. The exact steps are unimportant. What matters is that there will be an increased consumption of oxygen per unit CO2 produced. The RQ is just a ratio so increasing oxygen use will make it drop, possibly below that 0.69 of saturated fat oxidation.
Summary: We already know that total O2 consumption must and did drop on fat adaptation. We know from simple arythmetic that CO2 production drops even more that O2 usage when fat (vs glucose) is oxidised, to give us that normal RQ of 0.69.
If there is a further usage of O2 in the process of converting ketones derived from fat in to glucose, this would explain an RQ of 0.62.
Despite this "waste" of oxygen you still use less O2 per ATP from fat oxidation, even if doing some gluconeogenesis. We know this from the absolute VO2 measurements combined with the RQ values in Phinney's Table II and my back of envelope calculations.
I sit in awe of fat oxidation. We carry fat as long term energy storage for use in times of need. Under those conditions of privation this long term energy store allows very efficient ATP generation per unit oxygen, at the same time as reducing CO2 production, at the same time as generating a significant amount of glucose. Fatty acids and beta oxidation, with ketones thrown in, are just awesome.
I'm also hugely impressed by how far ahead of its time Stephen Phinney's paper was and how well it still stacks up against modern papers.