Chapter 11: Water and the Major Minerals

1
9 Outline for today

• Fasting
• Set Point Theory
• Obesity
• Weight loss diets
• Next time
• Anorexia, bulimia etc.
• How to determine if what you read and hear is
  credible

2
Recap of last lecture

• CJD
• Central role of pyruvate, acetyl-CoA and
  oxaloacetate
• Ketosis

3
Minimum amount of carbohydrates to avoid ketosis

• Literature reports range from 50 130g /day.
• The latter is the DRI value
• The value varies from one person to another
• There is no specific amount, because some
  ketogenesis is always present.
• Best definition is probably the amount that
  prevents detectable ketosis.
• (possible experiment?)

4

• Although the 3500 kcal/lb fat figure has been
  around a long time, the current thinking is that
  a figure of 2700 kcals per pound is a more
  accurate one to use, because there is always loss
  of muscle tissue ("lean" tissue) along with the
  loss of the fat. This works out to about 400
  kcals per day for a week to correspond to one
  pound.

5
Fasting

• The only difference between a true fast and
  starvation is that one is voluntary, the other
  not.
• What most of you consider fasting, i.e. the
  "juice fast" is not really a true fast because
  you are in fact taking in considerable amounts of
  nutrients, including a significant amount of
  energy (typical juice fasts involve about 1000
  kcals).

6
Fasting

• Fruit juice contains sugars which provide
  significant Cals. Typically eight ounces of juice
  has about 30 g carbohydrate, i. e. about 120
  cals.
• There is no nutritional value to fasting.
• If you are a healthy adult without diabetes,
  there is probably little associated risk to fast
  for one day as long as you include water to
  prevent dehydration.

7
Contd

• During a fast, your body still burns calories,
  initially mostly from blood glucose or glycogen
  stored in muscles.
• Once that approx. 1500-calorie supply of glycogen
  is exhausted, the body has to use protein to
  generate glucose.
• Various fad diets have advocated periodic fasting
  to supposedly shock metabolism or rid the body
  of toxins. Neither has been substantiated by
  research.

8
Toxins

• Actually, its ironic, because the fat
  mobilization that occurs in fasting releases
  toxic compounds stored in fat e. g. DDT, PCBs

9
Fasting the bodys response

• No incoming nutrients
• So the body begins to break itself down to supply
  energy, especially for the brain, CNS, liver and
  kidneys.
• The energy comes from stored fat and from
  breakdown of proteins.
• The brain requires glucose, obtained from some of
  the amino acids and from glycerol from the
  breakdown of TG's.

10
The bodys response contd

• The absence of incoming sugars leads to a
  relative decrease in the amount of pyruvate and
  oxaloacetate relative to acetyl-CoA and this
  leads to ketosis. Prolonged lack of food intake
  causes the body to undergo major metabolic
  changes.
• Note that we always get some of our energy
  from fats, but generally glucose is preferred

11
Fasting - Energy "reserves"

• Consider the following table for a normal and
  obese male. Assume BMR (basic metabolic rate) is
  1800 kcal/day
• No. of gms Normal Obese
• (70kg)(154 lb.) (135
  kg)(300lb.)
• Adipose tissue (fat) 15,000 141,000 kcals
  752,000 kcals
• Protein (mostly muscle) 6,000
  24,000 32,000
• Glycogen (muscle liver) 120 70
  900 920
• Circulating glucose fat 20 100 110
• Total 166,000 785,000 kcals
• Estimated survival time 2-3 months ?8
  months

12
Fasting metabolic adaptation

• The major changes during fasting are a change to
  using fat and protein as energy sources.
• Typically it takes about 4 weeks to adapt to a
  lack of food.
• During this time the blood sugar level remains
  relatively constant around the normal value of 80
  mg/dl.
• However the blood levels of free fatty acids and
  ketones increases significantly, as does the
  excretion of N in urea in urine, due to amino
  acid breakdown and conversion to glucose to
  "feed" the brain.

13
Fasting metabolic adaptation

• The brain requires about 20 of the energy
  consumed at rest, in the form of 140 g
  glucose/day.
• Low blood sugar (hypoglycemia) leads to impaired
  mental and nerve functioning.
• After the glycogen stores are used up (about 1
  day) the main source of glucose is amino acids
  from the breakdown of protein and a small amount
  from glycerol from TG breakdown.
• The aa's are deaminated, the N excreted as urea,
  and the C skeleton yields 57g glucose per 100g
  body protein.

14
Fasting changes in blood composition

• Blood concentrations (mM)
• Glucose FFA's Ketones Amino
  acids
• Normal 4.5 - 4.8 0.5 0.02 4.5
• Fasting 3.8 1.5 5.0 4.5
• 1 wk
• Fasting 3.6 2.0 7.8 3.1
• 5 wks

15
Fasting- Order of loss of body protein

• 1. Digestive enzymes
• 2. Liver enzymes processing incoming nutrients
  
• 3. Muscle protein
• For the first week protein is lost at the rate of
  100g/day (obviously couldn't go on for long at
  this rate).
• After 4-6 weeks its down to 12-15g/day.
• In addition after this period the brain has made
  a major adaptation and has begun to use ketones
  as an energy source.

16
Contd

• Lower body temperature, lower blood pressure,
  lower BMR. Lethargy, signs of mild vitamin
  deficiencies, increased susceptibility to
  disease, infection, poor health due to nutrient
  deficiencies.
• Eventually the organs break down and fail,
  resulting in death

17
Fasting- Order of loss of body protein

• Once all the fat is used up the person will die
  rapidly.
• Since children normally have rather limited
  stores of fat they cannot survive too long.
• The body's first priority is to get glucose for
  the brain. The second is to conserve protein by
  having the liver and muscles use fatty acids and
  ketones as energy sources.

18
Contd

• During fasting the BMR decreases and the body
  decreases its physical activity to conserve
  energy. Naturally fasting or starvation is
  accompanied by weight loss
• The initial weight loss is due mostly to water,
  due to the excretion of electrolytes (minerals)
  such as Na, K, Ca, Mg, and also the increased
  amount of urea.
• It has been shown that if a pregnant woman fasts,
  especially during the first trimester, it has
  very severe effects on the fetus.

19
How fast can you lose weight due to fat?

• Seen those ads for losing 25 lbs in one week -
  sound to be too good to be true? 25 lbs of
  adipose fat corresponds to 87,500 kcals, or
  12,500 kcals per day. To burn that many calories
  the person would have to ride the equivalent of a
  tough Tour de France bike race for most of the 24
  hours each day!!

20
Do our bodies control our weight?

21
Do our bodies control our weight?

• Yes
• We normally keep our body weight constant ? 1
  over periods of many years, in spite of
  fluctuating food intake and physical activity.
• It is believed that total fat mass is sensed by a
  feedback system. The hypothalamus is the main
  control center damage leads to obesity and
  stimulation leads to increased energy expenditure
  and reduced eating.

22
Set-point theory

• This is the best available theory at present.
• It postulates that each individual has some
  particular body weight, which the body maintains
  by regulation and control of a number of things.
• The key feature, however, is that the body can
  alter its metabolism to make it more or less
  efficient, e. g. by converting more or less
  energy into heat.
• By converting more energy into heat, rather than
  fat, the body weight can be controlled.
• Obesity then results either from a high
  set-point, or a malfunction in the control
  system.

23
Set Point Theory key features

• Weight is closely regulated by the body
• Genetically predetermined body weight
• Body resists weight change
• Leptin and thyroid hormone assist in weight
  regulation
• Weight returns after weight loss
• Reduction in energy intake results in lower
  metabolic rate
• the set point weight can shift

24
Set-point theory contd

• There is growing evidence to support the idea
  that the body regulates its weight in the same
  manner that it regulates its temperature, but
  with one difference
• the controlled body weight differs substantially
  from one person to the next
• however, for that person the body will try to
  maintain that particular weight (now usually
  called the set-point).
• It is apparent that if, for some reason, a person
  becomes obese, the set-point is often reset to a
  much higher value.

25
Support for the set-point theory

• Normally our daily caloric input varies
  significantly. On average we tend to err on the
  side of taking in more than we need. Thus, if we
  took in an extra 500 kcals a week, at the end of
  a decade this would mean we should weigh 10 x 500
  x 52 /3500 75 lbs more.
• It has long been known that animals seem to have
  their own stable weights. If they are force-fed
  they will become fatter, but as soon as the force
  feeding is stopped they revert to their earlier
  levels. If they are semi-starved they lose
  weight, but on returning to a normal diet their
  weight returns to its earlier level.

26
Contd

• Humans who were formerly grossly obese and have
  lost weight respond as if they were fasting the
  fat cells are tiny, the women do not menstruate,
  their thyroid hormone levels are low, they ingest
  25 fewer kcals then would be expected, based on
  their weights and heights.
• Furthermore the triglycerides in adipose cells
  are always turning over, in normal cases 50 of
  the fatty acids are reconverted into TG's in the
  cell, during fasting only 10. In obese subjects
  the rates are 50, however when they had lost
  weight the levels were only 10.
• In other words these people's bodies were
  responding as if they were fasting, and that the
  obese state was the "normal" one for them.

27
Contd

• In an interesting study with a small set (12) of
  identical twins forced to eat an extra 1000 kcals
  a day for 100 days it was found that some gained
  only 9 lbs, whereas others gained 29 lbs (also
  each twin in a pair gained about the same
  amount!). (From 3500 kcals equivalent to 1 lb.
  fat one would have expected 28.6 lb. gain.) This
  is only one of several studies which indicate
  that different individuals respond to excess
  calories in different ways.

28
Set-point theory

• Both rats and humans, if forced to eat more than
  they want, put on weight, but after being allowed
  to eat what they want, lose the excess. If a
  substantial mass of fat is removed, it is
  followed by excess eating and an increase in the
  remaining fat stores! If an obese mouse (due to
  the ob gene mutation) is surgically joined to a
  normal mouse the former will lose weight,
  presumably due to transfer of the hormone from
  the normal mouse to the blood of the obese one.

29
Contd

• One well-documented metabolic change on
  weight-loss through dieting is a substantial
  decrease in the resting metabolic rate - this may
  be decreased by as much as 50 - and is thought
  to reflect the body's going into "starvation"
  mode. As a result weight loss drops off
  dramatically since the body is using many fewer
  calories - this is a very strong argument against
  using very low calorie diets (

30
Set-point theory contd

• The set point theory also explains the
  observation that some people eat relatively
  little and become overweight, whereas others can
  eat almost unlimited amounts and not become
  obese. The former have very efficient metabolism,
  the latter inefficient, that is they convert a
  lot of energy into heat, rather than storing it
  as fat. The thyroid is one of the factors that
  controls the rate of metabolism. However, things
  appear to be considerably more complicated.

31
Set-point theory contd

• For example, some types of adipose tissue are
  known as brown fat, due to its color. The color
  is imparted by cells which are very rich in
  mitochondria. Its main function seems to be to
  produce heat. Hibernating animals have large
  amounts. In studies with rats, overfeeding leads
  to increased amounts of brown fat and increased
  heat production.
• For example rats fed 80 excess kcals over
  controls put on only 27 more weight, but
  increased their energy production by a factor of
  two as measured by oxygen consumption.
• Obese rats don't adjust.

32
Is this you?

• Much of our eating and drinking is determined by
  social settings and customs, e. g. the stereotype
  of sitting down to watch TV with a bag of chips
  and a bottle of beer (lots of calories - 5 kcals
  per chip, 150 kcals for the beer (180 for a
  typical slice of pizza)).