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Physiology of Starvation and Metabolic Changes in Human Body

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Starvation has generally been referred to as the severest form of malnutrition whereby there is a catastrophic lack of energy in form of calories; able for an organisms sustenance.

The human body is sufficiently adapted to survive periods of lack of food intake; through a series of biochemical and hormonal alterations and adaptations to ensure that metabolism continues. There have been reports of people going up to eight months without food, though this was under controlled conditions.

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Despite these adaptations, it is still possible to die of starvation; though most people die as a result of the consequences of starvation such as infection due to diminished immune response, or associated dysrhythmias or cardiac arrest.

Of note is that since starvation is not a sudden event, the response by the body as well is not a sudden but rather goes through various stages or phases as it transitions to save energy and nutrients without causing undue harm to itself. It has generally been agreed that there are five general phases which occur consequently:

First Phase

The first is the gastrointestinal intake of substrate – the gastrointestinal phase(last meal). This refers to the process of absorption of food post ingestion. It involves the complete oxidation of glucose through out the body. Under the influence of the hormone insulin; various organs take up glucose and utilize it. The liver, for example converts glucose to glycogen and a part of it is also converted to pyruvate; which subsequently enters the TCA cycle to provide energy to the liver. The muscles and adipose tissue also take up glucose with the latter also increasing its synthesis of fat.

With meals either low or deficient in carbohydrates, the liver responds by breaking down glycogen to ensure the amount of glucose in the blood is within normal limits while the rest of the body carries on as previously mentioned.

Second Phase

Second phase is glycogenolysis phase. This is largely controlled by glucagon, insulin and the molecule glucose itself. This is a result of their effect on CAMP which regulates the rate of glucose synthesis in the liver.

The levels of absorbed glucose start to diminish and with that the liver stops mopping up the circulating glucose but instead starts making and releasing glucose for use by breaking down glycogen, especially by the central nervous system whose primary source of energy till now is glucose. The muscles also respond by reducing their reliance for glucose as a source of energy but instead use free fatty acids.

Third Phase

Third phase is the gluconeogenesis phase. Metabolic changes are initiated in the liver as a result of a very high glucagon to insulin ratio and high levels of free fatty acids. This results in the liver switching to synthesis of glucose. It acquires some of the substrates from glycerol – a breakdown product of adipose.

The liver utilizes free fatty acids and oxaloacetate. Due to the large amount of free fatty acids available for use; they are dehydrogenated to two Acetyl-CoAs which, due to diminished oxaloacetate, are converted to the ketone bodies – acetoacetate and beta-hydroxybutyrate. This heralds the next stage; the ketone phase.

The muscles and adipose tissue continue to reduce their reliance on glucose by preventing glucose uptake, and its conversion to pyruvate. Any pyruvate is sent back to the liver in the form of alanine via transamination for gluconeogenesis.

Ketone Phase

Occurs from the third day of starvation to about day 14, when it levels out. The brain by this point has switched to ketone bodies as a source of energy; and this is enabled by the gradient provided by the above process.

It is maintained by the extremely high glucagon to insulin ratio due to again low levels of the hormone insulin due to reduced intake.

Final Phase

The final phase is increased ketoacid consumption, with noted reduced gluconeogenesis. This occurs after day 14, when the amount of ketones has leveled out; and the brain is using ketones as a source of fuel. This leads to a preferential sparing of muscle protein with a further reduced need for glucose.

It’s been noted that continual use of free fatty acids brings about a nitrogen sparring effect by reducing the deamination of amino acids such as leucine and valine as reported by Fulks, Li, Goldberg in 1975.

In conclusion, it has been shown through experimental studies that starvation response involves the body switching to fat as a source of fuel; and this has been used clinically in the treatment of obese people who intend of losing weight- with favourable results and few deaths. More research however is required to explain the exact phenomena involved and the interplay of hormones and paradoxical phenomena such as preservation of proteins despite low levels of insulin.

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