This is a section from Table V of Heinbecker's 1928 paper:
Studies on the Metabolism of Eskimos
This tells us certain very, very interesting things. The subject is a young Eskimo woman. Column 6 gives her RQ and, by day 3.5 of fasting, it is 0.454. Which is clearly impossible. Maybe. It took me a few minutes to realise that the result is probably correct, certainly within the limits of measuring RQ in 1928 in a tent in the Arctic. Let's assume it's ballpark correct.
I've been through this too many times. An RQ below 0.69 suggests the generation of oxygen rich molecules from fatty acids. An RQ of 0.454 suggests a huge amount of (probable) gluconeogenesis from fat is going on.
The other thing which becomes obvious from simple logic is that any oxygen rich molecule generated from fat must NOT be oxidised for it to drop the RQ. If you oxidise stearic acid to CO2 and water you will get the same amount of CO2 per unit O2 consumed whether that process goes via acetyl-CoA (as it usually does) or via ketones, oxaloacetate or glucose.
The girl, Martha, was breast feeding a baby throughout the study:
"Subject II. Nursing female".
She has eaten nothing for 3.5 days, she is excreting both glucose and galactose in her milk. She has used up her glycogen stores. Where is the glucose/galactose for the milk coming from?
The RQ is 0.454, the milk sugars are coming from fat.
Sooooooo. Question:
How much gluconeogenesis is possible from fatty acids?
Answer:
A lot.
How much is a lot? It's not really practical to put a number to this, but enough to drop the RQ to 0.454 or, equally, enough to make a continuous supply of human breast milk. Both seem to be reasonable answers.
Unless you have an agenda.
Peter
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140964/
ReplyDelete"In Silico Evidence for Gluconeogenesis from Fatty Acids in Humans"
OMG, a metabolic "advantage"!!!!!!!!!!!!!!!!!!!!!
ReplyDeletePeter
I thought the size of liver mattered to the amount of gluconeogenesis that a human could do. And that the CPT1A forced Eskimos to have a large liver, because they couldn't use lots of ketones. I have some vague recollection of that controversy :-)
ReplyDeletethere is no metabolic advantage. if anything, it should be called metabolic handicap.
ReplyDeletebuilding on that, I wonder if a researcher could slip it by the censors by coloring the metabolic handicap in a negative light.. "Low carb diets induce a metabolic handicap: more energy is needed to sustain a healthy weight relative to high carb diets"
ReplyDeleteanand, after a period I stopped reading the controversy. There's only so much....
ReplyDeletePurp, Yes! Now you're thinking!!!!
Peter
Excellent post as always - I'm thinking - 1928. There is a trend to discount old science - but I think it is in error. Solid science stands the test of time - at least when money and politics were not in play.
ReplyDeleteI've been a proponent of breast feeding for a very long time - my father was an OBGYN - he would try to explain to his patience, "you know your breasts really aren't for selling cars - they are for feeding babies" .. in his time it was a hard sell - still is. So I tended to track papers on breast milk.
The anti-sat-fat-mantra always seemed rather insane to me - if sat-fat was this terrible poison, why was there globs of it in breast milk? There is another bit - our immune system, appears not well developed in infants - that there are antibiotics in breast milk - that there are time targeted to bugs in the environment strikes me as important. I've wondered if there is a life long effect of being breast fed? (I should point out that in primitive cultures - being breast fed means 2-3 years)..
I also wonder about the use of Infant formula 'milk'
"INGREDIENTS NONFAT MILK, LACTOSE, VEGETABLE OIL (PALM OLEIN,
COCONUT, SOY, AND HIGH OLEIC SUNFLOWER OILS), WHEV PROTEIN
CONCENTRATE, FOLYDEXTROSE', GALACTOOLIGOSACCHARIDES', AND
LESS THAN 1% MORTIERELLA ALPINA OIL", CRVPTHECODINIUM COHNII
OIL'...."
More questions than answers -
They guarantee the linoleic acid content as 800mg/5oz(about 150ml)
I wonder how much linoleic acid was in this Eskimo breast milk? (they probably didn't get any corn-fed chicken or LA coated CIAB )
Sort of a long way from human milk to say the least.
Once the artificial formula feeding is started with out pumping - even a day - can stop natural production. Thus the free samples..
If evolution provided for breast milk production during fasting with as much as RQ of 0.454 thus (probable) gluconeogenesis from fat - seems like breast milk is important evolutionarily - what is the effect of gulps of linoleic acid as an infant?
I had an uncle that was raised on goat-milk as his mother could not provide - was he better or worse off than those raised on this veg-oil monstrosity?
So, glucose intolerance in low carbers could be because they are already producing enough glucose from fat?
ReplyDeleteGreat ?
DeleteI think its been discussed here that glucose intolerance in low carbers mostly stems from the fact if they havent been eating any glucose recently, GLUTS are massively downregulated on all tissues so as to preserve liver derived glucose for the brain. so if youve been eating a zero glucose diet for 3 weeks then suddenly front load your metabolism with 200g of rice your body cant get GLUT's on peripheral tissues fast enough to clear the sudden surge in blood glucose.
ReplyDeleteif you look at the FIRKO mouse you can see GLUT1 drops to tiny levels on adipocytes when no insulin is seen.
IS this fat to carb pahtway highly restricted to milk producing females?
ReplyDeletedid they measure the glucose/galactose content of the woman's milk to confirm it had ordinary levels?
NY,
ReplyDeleteNo, the glucose intolerance is due to down regulation of glucokinase in the pancreas combined with physiological insulin resistance.
Kindke, not measured in this paper.
Peter
Kindke: Here is the start of the next post!
ReplyDelete"Anyone who has read Martha's story and put the narrative together with the folks in Phinney's study will have immediately wondered: How many of Phinney's subjects were lactating? Even just a little bit?"
Peter
(sorry about the typo!)
study idea: feed long term ketogenic dieters labeled fatty acids, take blood samples, maybe find labeled glucose.
ReplyDeletePurp,
ReplyDeleteThe problem would be that glucose is probably not going in to storage but is being oxidised and of course the radio labelled CO2 might or might not have come through glucose. I suspect a lot of the conversion of acetoacetate to glucose occurs within the tissues which need the glucose and all you would see is the CO2. Now, ask for a lactating lady to participate and look in the milk......
Peter
If you feed radio labelled acetone it turns up in sugars and proteins...
ReplyDeleteActually I think it was injected. Don't have the paper to hand.
ReplyDeletehttp://www.ncbi.nlm.nih.gov/pubmed/438326
ReplyDeleteis it this one?
this is quite interesting, 4 to 11% of plasma glucose from acetone.. the testing procedure sounds extremely unpleasant though. acetone dissolved in ice cold saline shortly before injection? I wonder what that feels like.
Probably the one, the numbers seem familiar
ReplyDeletePeter
This was in the news yesterday.
ReplyDeletehttps://www.theguardian.com/australia-news/2016/aug/10/baby-almost-died-after-mother-breastfed-while-on-water-diet-on-naturopaths-advice
Very topical. What a train wreck. Oddly, I can see where the idea came from. I like to compare ketogenic eating to fasting. The relative benefit of ketogenic eating is that it doesn't involve all that inconvenient death stuff which extremely extended fasting ALWAYS produces, if you extend it for long enough.........
ReplyDeletePeter
"So, glucose intolerance in low carbers could be because they are already producing enough glucose from fat?"
ReplyDeleteThere's no such thing as a free lunch.
And to get "Nick-Laneish", there's an energetic cost to maintaining these metabolic pathways. Mother Nature, in all her wisdom, knows that blowing through your energy reserves at an increased rate to maintain a metabolic pathway that isn't used - aside from the occasional birthday cake scenario - is a stupid trade-off.
Peter Attia has recently come out implicating LDL-P as the new villain in heart disease [LDL-C is out]. Thoughts?
ReplyDeleteRattus, people have to blame lipids. Somehow, somewhere, it has to be cholesterol. Personally I KNOW it's Purple Spotted cholesterol which causes CVD. PS-C is sugar coated.
ReplyDeletePeter
Peter, fabulous post! If you want to fall further down this particular rabbit hole I suggest looking into Dairy Science because lactation and ketosis is very well studied and applied. A modern dairy cow post calving can potentially go into such a high state of ketosis (the terminology used in this and for lack of a better term) to convert fat into milk/milk fat that the cow's health is impaired long term.....so its a balancing act to obtain high milk production / milk fat yet not compromise the cow's health to the point the dairyman cannot obtain several more calving/milking cycles from her.....ruminant sciences, particularly dairy science is also a great place to learn a LOT more on the biome and fatty acid synthesis...with the Human Biome all the rage I chuckle to myself because the dairy nutrition science is decades ahead in having a handle on this subject.....have fun and keep posting what you are thinking!
ReplyDelete