CR2: Dale Schoeller - Metabolic Rate and CR

Dale Schoeller (UW) - CR and Metabolic Rate
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Indirect calorimetry - measure iinput and output gases, measure change to
estimate amount of energy burning reactions going on.

Adipose tissue: 3600kcal/lb
Muscle - 500kcal/lb
Glycogen - 500kcal/lb

Body energy stores - 70kg male
  15kg adipose tissue - 17,00kcal
  2kg Glycogen - 2,200kcal
 28kg muscle - 34,000kcal
 22kg viscera - 26,000kcal

Expenditure
  Three components
    RMR - resting metabolic rate
    Thermic effect of meal - TEM
    Energy expenditure of physical activity - EEPA

For most, RMR is largest factor (except elite athletes).

RMR - rate of energy expenditure when subject is lying down, at thermal
neutrality, 12-15h after last meal.  Also called BMR (Basal metabolic rate)
or REE (resting energy expenditure) sleeping metabolic rate (little (1-5%)
lower than RMR).

What tissues account for calorie burn in RMR?
  Adipose - 4kcal/kg/d
  Skelatal muscle - 13kcal/kg/d
  Liver - 200kcal/kg/d
  Brain - 240kca/kg/day
  Kidney&Heart - 440kcal/kg/d

These major organs account for 5% of weight, but 60% of RMR calorie burn.

CR animals have smaller organs, so smaller oxygen requirement.

RMR accounts for 40-60% of Total Energy Expenditure (TEE).

Human typically burn - 1kcal/kg/h

Human equation: RMR equation = 21.6 * FFM + 270kcal/day

RMR decreases by about 200kcal/day during low caloric intake.

Uncoupling protein allows leakage of protons, and thereby decouples energy
intake and metabolic rate. In small mammals, brown adipose tissue (rich in
UCP), can result in doubling of metabolic rate. In people, we don't have as
much BAT

Uncertainty of about 7-10% in human RMR.

Does CR change RMR more than would be predicted by simple drop in body mass?

Thermic effect of meals - increase in metabolic rate above RMR for 6h after
a meal. During this time, it can increase metabolic rate by 30-40%. When
integrated over time, it accounts for 10% of total metabolic rate.

Lots of little meals don't result in bump in metabolic rate - since most of
the energy expenditure is in storage process - if we burn it off as we
ingest it, we don't spend so many extra calories.

High protein results in more thermic effect of food.

After acute bout of intense exercise (running or weight lifting), get 30min
large increase in RMR. But after that, RMR drops back down to be on 3-5%
above RMR for a few hours. So extra calorie burned due to increase in RMR is
about 1/5th that of the amount you actually burn in the exercise itself.
Long term, if you increase fat free mass, obviously you RMR will go up.

On to the topic - the effect of CR on metabolic rate

Minnesota starvation study

Control diet - 3500kcal/day.

6 months 1600kcal/day diet for 6 months - calories adjusted lose about 25%
of body weight

With such a reduction, they couldn't have survived on their reserves.

Absorption of energy doesn't vary with nutritional status - you always
absorb about 95% of calories you eat (by measuring fat grams ingested vs.
fat grams in feces).

Very hard to overload digestive system, even with very large meals.

Diet of Minnesota study:
 Token meat and dairy - protein sufficient
  Lots of turnips & cabbage
  High in potatoes, whole wheat bread & other grains
  Adequate in vitamins and minerals by 1946 standards - maybe low on
antioxidants, but
    other than that - ok.

Lost both fat and (17%) FFM

Measured RMR - 1590kcal/d at start, 960 kcal/d at six months

What accounts for this - drop in FFM or change in underlying metabolism?
Drop in FFM accounts for 220kcal/d, only 600kcal/d.

Thermic effect of food would have been reduced by about 190kcal/day, due to
fewer calories being processed.

Heart size did decrease, but unknown how much this accounts for decrease in
metabolic

Other possibilities:
  Reduced protein turnover
  Reduced thermal regulation
  Reduced organ mass

EEPA not measured. But estimated.
  Dropped from 1720kcal/d to about 910kcal/d

  Reason - hauling less mass around + doing less leisure time activity.

No change in efficiency of walking/running.

65% loss of endurance
30% loss of gripth strength
Developed apathy
Decreased libido
Obsession w/ food.

Women who lost fat, but not FFM, when finally in energy balance, had a 4%
drop in RMR. Pretty small.

Biospherians - 10% drop in sleeping metabolic rate immediately upon exit
(vs. 6 months later), but the significance of this went away when fidgeting
accounted for (CRonies fidgeted less).

Wisconsin Monkeys - Didn't lose much muscle mass, but lost most of fat mass.

Statsticsally significant difference in 24h energy expenditure in CR monkeys
(~15%) - mostly due to drop in nighttime energy expenditure. Small part of
it may be explained by reduced activity at night in CR animals - which has
been observed. Overall, pretty small effect.

Conclusions:

Energy expenditure reduced in CR

More than 50% of reduction due to smaller body size

RMR is reduced in excess of FFM - Could be due to change in organ mass

Human capacity to reduce RMR:
.       smaller than rodents
.       5-10% of RMR, adjusted for FFM

Is excess drop in RMR during weight loss due to temporary thyroid-induced
metabolic changes - which go away when weight stable?  Could be.

Question - Nibbler vs. One meal a day? Healthier to nibble from blood lipid
level for AL fed.

Question - Can you be too lean?  Yes, you don't want to drop below 5% body
fat. If you go below that, your body won't burn fat, and