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Topic: Gluconeogenesis in prolonged fasting  (Read 5004 times)

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Offline writer

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Gluconeogenesis in prolonged fasting
« on: April 01, 2017, 09:31:54 AM »
Does gluconeogenesis from glycerol (from triglycerides) provide sufficient amount of glucose to meet the demand of brain for glucose during prolonged water fast?

The article from Wikipedia: Starvation Response says that some glucose can come from gluconeogenesis from glycerol from fats, but 10% of the brain glucose requirement still needs to come from gluconeogenesis from amino acids from muscle protein. This means that the muscle wasting would limit the duration of fast even when fat stores are still available.
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After 2 or 3 days of fasting, the liver begins to synthesize ketone bodies from precursors obtained from fatty acid breakdown. The brain uses these ketone bodies as fuel, thus cutting its requirement for glucose. After fasting for 3 days, the brain gets 30% of its energy from ketone bodies. After 4 days, this goes up to 75%.[5]

Thus, the production of ketone bodies cuts the brain's glucose requirement from 80 g per day to about 30 g per day. Of the remaining 30 g requirement, 20 g per day can be produced by the liver from glycerol (itself a product of fat breakdown). But this still leaves a deficit of about 10 g of glucose per day that must be supplied from some other source. This other source will be the body's own proteins

In this article it is said that after keto-adaptation, the brain still needs 44 grams of glucose, which comes from...
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...stored triacylglycerols (15g), amino acids taken from muscle tissue and to a lesser extent other tissues (20g), and pyruvate / lactate (14g)

But...in this article in Postgraduate Medical Journal from 1973, it is mentioned that a man weighing 207 kg was fasting for 382 days (!), while consuming only water and some yeast, vitamin and mineral supplements. On the end he weighed 82 kg.
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A 27-year-old male patient fasted under supervision for 382 days and has subsequently maintained his normal weight.

Is this theoretically possible?
« Last Edit: April 01, 2017, 12:07:34 PM by writer »

Offline Babcock_Hall

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Re: Gluconeogenesis in prolonged fasting
« Reply #1 on: April 01, 2017, 01:19:42 PM »
I seem to recall reading that a moderately obese individual has enough metabolic energy stored as triacylglycerols to last for several months, and hibernating bears may do so for as long as seven months.  So empirically we know that a long fast is possible.  Your question is very quantitative with respect to the source of glucose and its consumption, and I do not know the answer.  I would point out a couple of things.  One (as you indicated) the brain can run on a mixture of glucose and ketone bodies during starvation.  If the presumed ratio of the two is incorrect, then the calculation of how much glucose the brain needs will also be incorrect.  Ditto for the mass of TAGs broken down per day.  It would be interesting to know how much protein the individual in question broke down per day.  Perhaps they were monitoring how much urea he excreted.

Offline writer

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Re: Gluconeogenesis in prolonged fasting
« Reply #2 on: April 01, 2017, 02:00:25 PM »
My question is quantitative because one of the longest reported times someone has lived (and then died) after a hunger strike is 94 days.

On the other hand, apart from those 382 days, this 1982 article in PubMed Central mentions another 6 cases of people who fasted (to lose weight) from 117 to 350 days and survived. They lost 3-6 grams of protein per day. If I say 5 g/day, this is 1780 g/year, which is not that much after all. 
« Last Edit: April 01, 2017, 04:49:33 PM by writer »

Offline Arkcon

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Re: Gluconeogenesis in prolonged fasting
« Reply #3 on: April 02, 2017, 09:45:45 AM »
You have two data points:  94 days, and 382 days.  You're applying them two two biological organisms, and living things have variability.  I expect you're going to be disappointed if you're expecting a conclusive answer.  Yes, you're quoting peer-reviewed sources.  But ... still ... I'm half expecting a multi page thread of ... yeah ... but ...

Um ... let me start with the loaded question.  Hunger strike?  Really?  That's a quantitative, scientific data point?  We're sure the subject wasn't adversely stressed before and during the process?

You have another experiment on 6 people.  That's a better source.  It gives a range, which is also good.  Here's a thought ... how far outside the confidence interval, is the 94 day data point, with respect to the other data?
Hey, I'm not judging.  I just like to shoot straight.  I'm a man of science.

Offline writer

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Re: Gluconeogenesis in prolonged fasting
« Reply #4 on: April 03, 2017, 05:08:20 AM »
Newspaper reports about how long someone has lived during a hunger strike are just - reports, but then, a study saying someone has lived for 382 days is also just a report, because the study has been performed in a free-living person, not monitored every minute for eventual food intake. So, I was wondering if it is theoretically possible to survive 382 days. The main limiting factor (besides the fat stores available) seems to be the rate of protein (muscle) breakdown. I was searching further and one article I linked above, mentioned 3-6 grams of protein loss per day, which is compatible with 382 days survival.

Offline Babcock_Hall

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Re: Gluconeogenesis in prolonged fasting
« Reply #5 on: April 03, 2017, 10:09:53 AM »
IMO a key difference may be in the level of medical supervision.  An obese man who is fasting to get back to a normal body mass with a doctor's supervision is one thing.  He took vitamins, for example.  A fasting prisoner may be a different matter altogether, and it may depend on the laws of the country in question.  Who monitored him, and did he get vitamin supplements?  Don't take anything I say as being medical advice, but I would wonder about his electrolyte balance, for example.
ETA
Also newspapers reports have to go through an editor, but a journal article has to go through peer review.  In general, the latter are expected to have fewer mistakes for this reason among others.
« Last Edit: April 03, 2017, 12:31:10 PM by Babcock_Hall »

Offline Babcock_Hall

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Re: Gluconeogenesis in prolonged fasting
« Reply #6 on: April 03, 2017, 12:37:01 PM »
"There now appears to be crosstalk between adipose tissue and muscle tissue [38]. The amount of muscle protein that is lost during the initial hours of starvation is inversely related to the amount of total body fat within an individual. In obese patients who are losing weight, the total amount of muscle proteolysis is lower than in lean patients [39]. Whether or not this decreased proteolysis in obese people simply reflects their required increased exercise in daily movements remains to be established."

Nutrition. 2006 Jul-Aug;22(7-8):830-44. "Proteolytic and lipolytic responses to starvation."  Finn PF, Dice JF.
abstract:  https://www.ncbi.nlm.nih.gov/pubmed/16815497

This passage seems to apply only to events early in starvation, but it illustrates how complex the process is.

Offline pyrophoric

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Re: Gluconeogenesis in prolonged fasting
« Reply #7 on: July 31, 2017, 10:42:13 AM »
From what I remember about studying metabolism, only odd-chain fatty acids are broken down in a way where they can enter gluconeogenesis to make glucose.  However, when blood glucose is low the body makes ketones from fats to replace it but this is not meant to be a long term solution.  It puts the body under a lot of stress due to ketoacidosis.  You need 160g of sugar per day to function, ketones from fats are not enough. 

Offline Babcock_Hall

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Re: Gluconeogenesis in prolonged fasting
« Reply #8 on: August 05, 2017, 01:32:36 PM »
If a fatty acid has an odd number of carbons, it will be metabolized into propionyl CoA, which can be made into oxaloacetate, which can be converted into glucose.  Some amino acids also produce propionyl CoA upon catabolism.

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