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Starvation

Oliver E. Owen, Karl J. Smalley, Robert L. Jungas

10.1002/cphy.cp070239

Source: Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism

Originally published: 2001

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Fundamental Principles and Observations of Bioenergetics
2 Epidemiology
3 Weight Loss, Body Composition and Energy Requirements During Food Deprivation
4 Urinary Excretory Products During Total Starvation
5 General Metabolism During Starvation
5.1 Anaplerosis and Cataplerosis
5.2 Gluconeogenesis, Ketogenesis, Ureagenesis, Ammoniagenesis and Acid‐Base Balance
5.3 Minimum Protein, Fat and Glucose Requirements
6 Endocrine Signals
6.1 Insulin
6.2 Glucagon
6.3 Catecholamines
6.4 lodothyronines
6.5 Growth Hormone, Insulin‐like Growth Factor and Cortisol
6.6 Leptin and Neuroendocrine Factors
7 Clinical Observations
Figure 1. Figure 1.

Weight and resting metabolic rate of 135 women and men, 32 of whom are dwarfs, mostly achondroplastic. Regression lines include dwarfs and average‐stature lean and obese human beings. Caloric requirements for women and men per kg body weight are shown (top). Data for hypochondroplastic (H), pseudo‐achondroplastic (P) and Dyggve‐Melchior‐Clausen (D) dwarfs are lettered.

(From Owen et al. 98.)
Figure 2. Figure 2.

Resting metabolic rate (RMR kcal/24 hr) is contrasted against body weight of 44 women and 60 men. Slopes of regression lines for women and men are statistically significantly different. When RMR is plotted against fat‐free mass determined by densitometry (FFMD), RMR is indistinguishable for women and men. Shaded area above or below regression lines represents the 95% confidence limits for predicted RMRs.

(From Owen et al. 83.)
Figure 3. Figure 3.

Relationships among total body mass, fat‐free mass and fat mass in lean and obese women and men. Regression lines for fat‐free masses of women and men are statistically different. P <0.001.
Figure 4. Figure 4.

Sketched outline of a morbidly obese woman with grossly excessive adipose tissue primarily overlying trunkal regions of the body. She suffers from diabetes mellitus and malignant hypertension. Caloric value of the adipose tissue is in great excess to the caloric value of her lean body tissue.
Figure 5. Figure 5.

Weight loss of five obese women and five obese men who starved for a minimum of 36 days. Oral intake consisted of only water, salt and vitamins. Men lost significantly more weight (P <0.0001) than women during prolonged total starvation (Part A). When weight loss is expressed as percent of initial weight, the loss of body mass by gender is indistinguishable (Part B).
Figure 6. Figure 6.

Body compositional changes measured by body densitometry are expressed as fat mass (FATMD) and fat‐free mass (FFMD) near the beginning of starvation at about day 0 and after about 21 days of fasting. Weight losses in these compartments decreased in parallel 97.
Figure 7. Figure 7.

Body weight, O2 consumption and CO2 production by five obese volunteers who were studied during a 21‐day fast. Carbon dioxide production decreased out of proportion to O2 consumption, creating a mysterious nonaminogenic (nonprotein) respiratory quotient (naRQ) and a disparity in RMR via O2 and CO2. Some symbols are slightly misaligned so they can be distinguishable from each other.
Figure 8. Figure 8.

Resting metabolic rate (RMR) calculated from O2 and CO2 and corrected for fatty acid desaturation for five obese volunteers who were studied during a 21‐day fast. The gap in the nonaminogenic (nonprotein) RMR between O2 consumption and CO2 production was practically eliminated by correcting for assumed fatty acid desaturation during starvation. SD for weight and RMR by O2 and CO2 were omitted to avoid clutter 97.
Figure 9. Figure 9.

Mean ± SD nonaminogenic (nonprotein) respiratory quotient (naRQ) in obese volunteers undergoing 21 days of starvation.
Figure 10. Figure 10.

Total urinary nitrogen excretion of five obese women and five obese men during prolonged starvation. Part A shows men excrete significantly more nitrogen than women (P <0.0004). Part B shows that loss of urinary nitrogen between women and men persists and is significantly different (P <0.0004) even when expressed per kg body weight.
Figure 11. Figure 11.

Quantities of urinary total (TUN), urea N, NH4+ N, creatinine N, and uric acid N excreted daily by five obese women and five obese men who starved for a minimum of 36 days. Quantities of nitrogenous components excreted have been “stacked” so their sum can be compared to total urinary nitrogen excretion. Shaded area represents urea nitrogen. Clear area between urea and total urinary nitrogen represents unmeasured urinary nitrogenous compounds.
Figure 12. Figure 12.

Data of Figure 11 have been replotted “unstacked” to permit their analysis by exponential regression. The least squares best fit regression equation of each nitrogenous component is shown, in each case using data only after the initial transients have relaxed. Note the time‐dependent reciprocal relationship between quantities of urea and ammonium nitrogen excretion during starvation, with a crossover at 16–18 days. Time constants for excretion of urea and uric acid nitrogen are the same, both decaying more rapidly than either total or ammonium nitrogen excretion.
Figure 13. Figure 13.

Interrelationships among gluconeogenesis, ketogenesis, ureagenesis and ammoniagenesis during starvation. A perturbation that modifies one of these metabolic processes has a demonstrable impact on related metabolic processes involved in maintaining fuel homeostasis during starvation. For simplicity, it is indicated that gluconeogenesis “uses ATP,” and while this is certainly true when lactate/pyruvate or glycerol/acetone is the precursor, conversion of a physiological mixture of amino acids to glucose is energetically self‐sufficient. Similarly, ammoniagenesis from glutamine does not require ATP support from other fuels.
Figure 14. Figure 14.

Composition of urine derived from five obese human beings undergoing prolonged starvation 97. Trend lines were fitted by eye. Day 0 data were based on creatinine excretion from days 1–3.
Figure 15. Figure 15.

Schematic presentation of cellular anaplerosis (replenish) and cataplerosis (drain). Substrates are continuously and simultaneously being added to and withdrawn from the citric acid cycle. Although, for simplicity, isoleucine and valine are shown together with the other anaplerotic amino acids (left), in fact the branched chain amino acids are metabolized mainly in skeletal muscle while the other amino acids are processed mainly in the liver.
Figure 16. Figure 16.

Interorgan flux of fuels highlighted by glucose and glutamine, to support anaplerosis and cataplerosis so fuel homeostasis can be maintained. Purine nucleotide cycle is abbreviated as PNC.

(From Owen et al. 97.)


Figure 1.

Weight and resting metabolic rate of 135 women and men, 32 of whom are dwarfs, mostly achondroplastic. Regression lines include dwarfs and average‐stature lean and obese human beings. Caloric requirements for women and men per kg body weight are shown (top). Data for hypochondroplastic (H), pseudo‐achondroplastic (P) and Dyggve‐Melchior‐Clausen (D) dwarfs are lettered.

(From Owen et al. 98.)


Figure 2.

Resting metabolic rate (RMR kcal/24 hr) is contrasted against body weight of 44 women and 60 men. Slopes of regression lines for women and men are statistically significantly different. When RMR is plotted against fat‐free mass determined by densitometry (FFMD), RMR is indistinguishable for women and men. Shaded area above or below regression lines represents the 95% confidence limits for predicted RMRs.

(From Owen et al. 83.)


Figure 3.

Relationships among total body mass, fat‐free mass and fat mass in lean and obese women and men. Regression lines for fat‐free masses of women and men are statistically different. P <0.001.



Figure 4.

Sketched outline of a morbidly obese woman with grossly excessive adipose tissue primarily overlying trunkal regions of the body. She suffers from diabetes mellitus and malignant hypertension. Caloric value of the adipose tissue is in great excess to the caloric value of her lean body tissue.



Figure 5.

Weight loss of five obese women and five obese men who starved for a minimum of 36 days. Oral intake consisted of only water, salt and vitamins. Men lost significantly more weight (P <0.0001) than women during prolonged total starvation (Part A). When weight loss is expressed as percent of initial weight, the loss of body mass by gender is indistinguishable (Part B).



Figure 6.

Body compositional changes measured by body densitometry are expressed as fat mass (FATMD) and fat‐free mass (FFMD) near the beginning of starvation at about day 0 and after about 21 days of fasting. Weight losses in these compartments decreased in parallel 97.



Figure 7.

Body weight, O2 consumption and CO2 production by five obese volunteers who were studied during a 21‐day fast. Carbon dioxide production decreased out of proportion to O2 consumption, creating a mysterious nonaminogenic (nonprotein) respiratory quotient (naRQ) and a disparity in RMR via O2 and CO2. Some symbols are slightly misaligned so they can be distinguishable from each other.



Figure 8.

Resting metabolic rate (RMR) calculated from O2 and CO2 and corrected for fatty acid desaturation for five obese volunteers who were studied during a 21‐day fast. The gap in the nonaminogenic (nonprotein) RMR between O2 consumption and CO2 production was practically eliminated by correcting for assumed fatty acid desaturation during starvation. SD for weight and RMR by O2 and CO2 were omitted to avoid clutter 97.



Figure 9.

Mean ± SD nonaminogenic (nonprotein) respiratory quotient (naRQ) in obese volunteers undergoing 21 days of starvation.



Figure 10.

Total urinary nitrogen excretion of five obese women and five obese men during prolonged starvation. Part A shows men excrete significantly more nitrogen than women (P <0.0004). Part B shows that loss of urinary nitrogen between women and men persists and is significantly different (P <0.0004) even when expressed per kg body weight.



Figure 11.

Quantities of urinary total (TUN), urea N, NH4+ N, creatinine N, and uric acid N excreted daily by five obese women and five obese men who starved for a minimum of 36 days. Quantities of nitrogenous components excreted have been “stacked” so their sum can be compared to total urinary nitrogen excretion. Shaded area represents urea nitrogen. Clear area between urea and total urinary nitrogen represents unmeasured urinary nitrogenous compounds.



Figure 12.

Data of Figure 11 have been replotted “unstacked” to permit their analysis by exponential regression. The least squares best fit regression equation of each nitrogenous component is shown, in each case using data only after the initial transients have relaxed. Note the time‐dependent reciprocal relationship between quantities of urea and ammonium nitrogen excretion during starvation, with a crossover at 16–18 days. Time constants for excretion of urea and uric acid nitrogen are the same, both decaying more rapidly than either total or ammonium nitrogen excretion.



Figure 13.

Interrelationships among gluconeogenesis, ketogenesis, ureagenesis and ammoniagenesis during starvation. A perturbation that modifies one of these metabolic processes has a demonstrable impact on related metabolic processes involved in maintaining fuel homeostasis during starvation. For simplicity, it is indicated that gluconeogenesis “uses ATP,” and while this is certainly true when lactate/pyruvate or glycerol/acetone is the precursor, conversion of a physiological mixture of amino acids to glucose is energetically self‐sufficient. Similarly, ammoniagenesis from glutamine does not require ATP support from other fuels.



Figure 14.

Composition of urine derived from five obese human beings undergoing prolonged starvation 97. Trend lines were fitted by eye. Day 0 data were based on creatinine excretion from days 1–3.



Figure 15.

Schematic presentation of cellular anaplerosis (replenish) and cataplerosis (drain). Substrates are continuously and simultaneously being added to and withdrawn from the citric acid cycle. Although, for simplicity, isoleucine and valine are shown together with the other anaplerotic amino acids (left), in fact the branched chain amino acids are metabolized mainly in skeletal muscle while the other amino acids are processed mainly in the liver.



Figure 16.

Interorgan flux of fuels highlighted by glucose and glutamine, to support anaplerosis and cataplerosis so fuel homeostasis can be maintained. Purine nucleotide cycle is abbreviated as PNC.

(From Owen et al. 97.)
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Article Title: Starvation
 

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Oliver E. Owen, Karl J. Smalley, Robert L. Jungas. Starvation. Compr Physiol 2011, Supplement 21: Handbook of Physiology, The Endocrine System, The Endocrine Pancreas and Regulation of Metabolism: 1199-1225. First published in print 2001. doi: 10.1002/cphy.cp070239