Metabolism During Extreme Caloric Restriction


This lecture is all about how the body responds to very low food intake, or complete starvation. These lessons will prove useful when thinking about how the body adapts during large calorie deficits during dieting.

We will explore how the body’s fuel source changes over time during caloric restriction, from the use of glucose, to fatty acids, to protein, to ketones

From there, we’ll explore the major hormonal changes that occur, and specifically discuss the hormone leptin and how it regulates hunger and movement. We’ll also talk about thyroid hormone, how it changes during starvation and how it interacts with the hormone leptin.

Key Results

At the end of this lecture, you should be able to:

  • Understand how the body changes its primary energy source over an extended period of calorie restriction
  • Understand WHY the body makes these changes
  • Understand the major role of leptin in controlling hunger/appetite
  • Understand thyroid biology and how it controls metabolism at a high level

Key terms we will cover:

Extreme Caloric Restriction

  • The body needs to mobilize fuel sources
  • The brain and RBC continue to need glucose
  • Other tissues reduce their consumption of glucose; insulin levels fall
  • Liver glycogen is depleted and gluconeogenesis is intensified


  • adipose tissue releases fatty acids and glycerol
  • ketosis begins
  • leptin levels drop
  • thyroid hormone concentration drops — cells work at a slower rate

Phase 1 - the post absorptive phase

  • subtle decrease in blood glucose alters the insulin: glucagon ratio
    • stimulates hepatic glycogenolysis
    • early liberation of fatty acids from adipose tissue
    • Muscle begins to use lipids as a major fuel source

Muscles will use whatever is most abundant in the blood stream

Phase 2 and 3 - The gluconeogenic phase

Phase 2

  • glycogen breakdown increases dramatically
    • liver stores are depleted within 24 hours

Phase 3

  • Gluconeogenesis takes over as the primary driver of glucose formation

Phase 4: Muscle sparing adaptations

  • ~1.75g of muscle protein must be broken down to provide 1 gram of glucose
  • the brain requires 100120g of glucose per day We’d need to break down a lot of protein…

Metabolic Adaptions in “Starvation”

  • lactate recycling increases
  • glycerol usage increases due to lipolysis
  • ketogenesis increases
    • uses ketone bodies, reducing the reliance upon glucose
  • ketone bodies exert a restraint on muscle protein
  • muscles operate primarily off of fatty acids
  • thyroid concentrations drop

hormonal changes during

  • insulin decreases as because of slowly decreasing blood glucose
  • glucagon concentrations rise
  • leptin concentrations drop as a result of decreasing adipose tissue
  • T3 levels begin to decrease

Leptin biology

leptin stimulates corticotrophin releasing hormone appetite👇 Movement👆 -> decreased body fat, less leptin -> less corticotrophin appetite👆 Movement👇

Thyroid biology

Hypothalamus produces TRH Pituitary produces TSH travels to Thyroid -> produces T3 and T4

T3 induces optimal function of every cell

Liver converts T4 to T3

starvation reduces in less TRH -> less T3

Under caloric restriction.. liver converts T4 into reverse T3

Hormone Summary

  • Leptin concentrations drop, reducing activity and increasing hunger
  • Leptin is also responsible for signaling the Hypothalamus to stimulate the Thyroid Pathway
  • T3 levels drop rapidly, and reverse T3 levels rise
  • In sum, this slows down metabolism dramatically, sparing muscle tissue
    • The metabolism of the brain does not change dramatically however

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