IUBio

metabolic adaptations during prolonged fasting / starvation

Martin Banschbach, Ph.D. banschbach at vms.ocom.okstate.edu
Mon Aug 12 13:56:55 EST 1996


In article <326963586wnr at concern1.demon.co.uk>, steve collins <steve at concern1.demon.co.uk> writes:
> Marty,
> 
> Thanks for your reply.  I would be very interested to know more about 
> your sources for the changes in the amount of gluconeogenesis in non 
> obese subjects.  Why I am interested is that they seem to be at odds 
> with some other reports of studies of the urinary N excreted 
> during fasting.  

That data came from Basic Medical Biochemistry, Williams and Wilkins, 1996.
The data were for glucose oxidation rates during starvation (after liver 
glycogen is gone, the only source of glucose is going to be 
gluconeogenesis).

> In these studies although urinary N excretion 
> decreases it does so in direct proportion to decreases in BMR.  This 
> leads those investigators to conclude that there is no 
> change in the proportion of fat and protein used i.e. 
> no increased use of ketone bodies by the CNS.  From the figures you 

What you have to do is look at the fuels being burned.  This can be done 
using the respiratory quotent (RQ).  The RQ is 1 for glucose and 0.7 for 
fatty acids.  Protein gives a RQ of 0.8.  Unless you actually measure what 
is being burned, you can't make any conclusions about the relative amounts 
of fat and protein being used to provide energy during starvation (as far 
as I can tell).

>>Gluconeogenesis (the process of converting noncarbohydrate 
>>material to glucose) starts to increase about four hours after the 
>>last meal and it peaks at about 10 grams of glucose produced per hour 
>>about 2-3 days after the last meal is consumed.  Gluconeogenesis then 
>>decreases to about 6 grams of glucose produced per hour until about 12 
>>days after the last meal at which time it increases very slowly upto 
>>40 days (the longest time period that I have) where it's producing 
>>about 8 grams of glucose per hour. 

> it would appear that a 40% decrease in glucose production from 
> gluconeogenesis is not just a reflection of a lowered BMR (this would 
> not decrease by 40% in 12 days) 

Calorie restriction causes about a 12% reduction in BMR so the reduction in 
glucose use is not solely the result of a lowered BMR.  The brain is one 
tissue whose energy requirement does not appear to decrease during 
starvation (as far as I can tell from everything that I've read).  Under 
normal conditions, brain requires about 140 grams of glucose per day.  
Brain use of glucose results in production of CO2 and H20 (complete 
destruction of glucose) and this glucose must be replaced each day.  The 
estimates that I've seen for maximum gluconeogenesis indicate that about 
130 grams of glucose can be produced each day (but this is based on liver 
enzyme activities and levels).  So even here there is a real problem, brain 
needs 140 grams of glucose per day but gluconeogenesis can only produce 130 
grams per day.  

When actual glucose oxidation rates are examined, things get even stranger, 
the maximum glucose oxidation rate is about 240 grams per day (10 grams per 
hour) and even at 6 grams per hour, the 24 hour requirement is 144 grams of 
glucose which is still higher than what gluconeogenesis is supposed to be 
able to produce.  

Unless the brain starts using large amounts of ketone bodies, there is going 
to be a big problem since gluconeogenesis can not apparently produce the 
amount of glucose that the brain normally oxidizes each day.  Just 
about every biochemistry textbook will state that the brain uses mostly 
ketone bodies for energy during starvation but I'm not sure that this has 
ever been proven (it's mostly by inference).  Ketone body levels go up in 
both blood and brain tissue.  Brain mitochondria can't burn fatty acids but 
they can burn ketone bodies so they must be using them to spare glucose 
use.  The drop in glucose use during starvation is always attributed to 
increased ketone body use.  If less glucose is needed, then gluconeogenesis 
must also decrease.

Gluconeogenesis is a very complicated process and it's really not as simple 
as looking at urea production.  Glycerol from fat breakdown in adipose 
tissue can become an important source of glucose and this can spare the use of 
amino acids.  Having brain and muscle both use primarily ketone bodies for 
energy can also help spare some amino acids.

> but does, on the face of it, appear to represent 
> protein sparing.  However could it be that the energy requirement of the CNS is markedly decreased during starvation and that there is not a switch in fuels (glucose to Ketone body) but rather but rather an overall decrease in metabolic rate of the CNS 
> data ? and are there any other estoimates of protein catabolism included such as the urinary N ? 
> If you could send me the names of the references I'd be 
> grateful
> Yours
> -- steve collins

The biochemical dogma is that during starvation, ketone body production 
spares glucose use by brain and muscle and this ends up sparing some muscle 
protein.  Trying to prove this has usually relied on looking at the amount 
of urea produced (if it goes down, then less muscle protein must have been 
broken down).  Saying that the decrease in urea production is simply due to 
a decrease in BMR is interesting (I've not seen this stated in any 
textbook).  The dogma about dietary cholesterol causing heart disease was 
wrong, maybe the dogma about protein sparing during starvation is wrong 
too.
-- 
Marty B.                   "You are what you eat"





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