20. Starvation

Question 1

What stores of energy does a 70 kg male possess?

Answer 1

Energy is stored as carbohydrate, protein and fat.

> 1600 kcal as glycogen

> 24 000 kcal in mobilisable protein

> 135 000 kcal in triacylglycerols

[kcal is an abbreviation for kilocalorie,
which is equivalent to 1 large calorie
(1c), or 1000 small calories (1000 c),
or about 4.185 kJ (kilojoules)]

Question 2

What are the 24-hour energy requirements of a 70 kg male at rest?

If there is no energy intake, how
does the body adapt?

Answer 2

1600–2000 kcal per 24 hours
(this may rise to 6000 kcal with stress).

Carbohydrate reserves (glycogen) only
last approximately 24 hours,
and less if the subject is exercising.

Despite the exhaustion of glycogen,
blood glucose levels are maintained.

The brain cannot tolerate low blood glucose
for even short periods

and so the first priority of metabolism
in starvation is to
provide sufficient glucose

to
both the brain
and
red blood cells,

both of which are absolutely
dependent on this fuel source.

A lot of energy is stored in triacylglycerols;
however, fatty acids cannot be converted

into glucose to supply the brain
or
red cells

because acetyl-CoA cannot
be converted into pyruvate.

The only other source of glucose
available is amino acids derived

from protein breakdown
(i.e. muscle breakdown);

however, survival depends on
maintaining protein and muscle mass

and,

therefore, the second priority
of metabolism in starvation is to
preserve protein.

Consequently, the body shifts
its primary fuel source from
glucose to fatty acids and ketones

Question 3

What adaptations occur during the first 24 hours of starvation?

Answer 3

As blood glucose levels begin to fall,

insulin secretion is reduced

and its counter-regulatory hormone,

glucagon, is secreted,
leading to mobilisation of triacylglycerols
in fat and gluconeogenesis by the liver.

Concentrations of acetyl-CoA
and citrate rise, which reduces glycolysis.

Muscle uptake of glucose
reduces secondary to the
lack of insulin and, therefore,

muscle also shifts to using
fatty acid as fuel.

Pyruvate is no longer converted 
into acetyl-CoA 
and 
therefore 
pyruvate,
lactate and 
alanine are exported to the 
liver for conversion into glucose

Question 4

What adaptations occur after

72 hours of starvation?

Answer 4

The most important metabolic change
is the hepatic production of

large amounts of ketone bodies
(acetoacetate and 3-hydroxybutarate)

from acetyl-CoA.

This occurs because gluconeogenesis
depletes the supply of oxaloacetate,

which is essential for acetyl-CoA
to enter the Krebs cycle.

Instead, the acetyl-CoA is
used for ketogenesis.

The brain now begins to use acetoacetate
(ketone body) for 30% of its
energy requirements,

i.e. adaptation has occurred.

The heart is also able to use ketones as an energy source.

Question 5

What adaptations occur several weeks into starvation?

Answer 5

Ketones now become the
major fuel source for the brain (>70%).

The effective conversion of
fatty acids into ketones
by the liver and

their subsequent use by the brain
markedly diminishes the
need for glucose and,
therefore, reduces muscle breakdown.

The duration of starvation compatible
with life is determined by the size of
the triacylglycerol stores.

Early starvation – 
reduction in energy expenditure, 
glycogen stores used
within 24 hours, 
use of alternative fuels such as 
ketones to minimise protein wasting.

Late starvation –
fatty acids,
ketones and
glycerol provide all of the energy

requirements for the body, except for the
brain and red blood cells, which
still require a glucose source.