Central Fatigue

1
Central Fatigue

• Lecture 18 Part I

2

• Define fatigue.
• operating definition inability to
• maintain a desired level of intensity.
• We usually think of fatigue during exercise as
• occurring in the muscle e.g. glycogen depletion
  or
• some other limitation decreasing the ability to
• produce ATP at the necessary rate.

3

• Some work suggests other factors are involved.
• Coyle et al. infused glucose into the blood of
  trained
• cyclists (to make sure they were never limited by
  
• availability of carbohydrate) and, though they
  were
• never depleted, they fatigued and stopped cycling.

4

• In 1987, Newsholme et al. proposed a novel
• idea called the central fatigue hypothesis.
• The basis for the idea is that fatigue during
• endurance exercise is related to a buildup
• of serotonin (a neurotransmitter) in the brain.

5

• In 1987, Newsholme et al. proposed a novel
• idea called the central fatigue hypothesis.
• The basis for the idea is that fatigue during
• endurance exercise is related to a buildup
• of serotonin (a neurotransmitter) in the brain.
• It is true that increased levels of serotonin
  causes
• drowsiness and fatigue (many sleeping aids work
  by
• raising levels of serotonin in the brain).
• Tryptophan is an amino acid
• that is converted to 5-
• OH tryptamine and then
• to serotonin in the brain.

6

• In order to get into the
• brain, tryptyophan must
• cross the blood-brain
• barrier via a transporter.
• The transporter is not
• specific for tryptophan,
• it also transports
• branched chain amino
• acids (BCAA),
• so there is a
• competition
• for transport.

7

• During exercise, BCAAs are taken up by muscle
• and oxidized for energy.
• Late in exercise, when muscle glycogen stores are
  
• low, this process is accelerated. Greater uptake
  of
• BCAAs late in exercise leads to lower blood BCAA
• levels and increased ratio of tryptophan/BCAA.
• So more tryptophan gets into the brain
• more serotonin production.
• In addition, as exercise progresses, more free
  fatty
• acids (FFA) are liberated from triglyceride
  stores
• and blood level of FFA goes up.

8

• FFAs and tryptophan are both
• transported in the blood by
• albumen (a common plasma protein).
• As level of FFAs goes up, more tryptophan is
• displaced from binding sites on albumen and the
• free tryptophan concentration rises.
• So, increased BCAA uptake by muscle AND
• decreased binding capacity by albumen greatly
• enhances the transport of tryptophan into the
  brain
• Hypothesis increased tryptophan into brain
  more
• serotonin central fatigue stop exercise.

9
FFA
tryptophan
FFA
albumen
FFA
BCAA
10

• How do you test the central fatigue hypothesis?
• What things do you need to know?
• Does the ratio of tryptophan/BCAA in the blood
• increase during exercise?
• 2. Is there increased entry of tryptophan into
  the brain?
• 3. Does it cause more production of serotonin?
• 4. Does that change in serotonin cause more
• fatigue?

11

• Because supplement industry is driven
• by business and not scientific motives,
• the FIRST studies actually done tested
• the effects of supplements on humans.
• A rational approach would have been
• to supplement with tryptophan and see if it
  caused
• MORE fatigue. But, b/c you cant make money from
• an ergolytic (inhibiting performance) compound,
  the
• first studies tested the efficacy of BCAA
  supplements
• to delay time to fatigue in athletes.
• Complications time to fatigue is easy to
  measure
• in theory but hard to interpret.

12

• In mid-90s, dozens of studies looking at effects
  of
• BCAA (with and w/o CHO) on performance. Most
• showed no effect. Some improved performance but
• studies were usually seriously flawed.
• e.g., Blomstrand et al. in 1991 studied effects
  of
• BCAA ingestion vs. flavored water on marathon
• runners. No effects unless divided group into
  fast
• and slow, saw improvement in the slow
  runners.
• Flaws
• 1. subjects in 2 groups not matched
• 2. did not control energy or CHO intake
• 3. division of runners arbitrary

13

• Finally, in about 2003, a group of investigators
• infused tryptophan into the bloodstream of
  rodents
• and looked at the uptake into the brain and time
  to
• exhaustion. They found that the greatly elevated
• levels of tryptophan in the blood did change the
• BCAA/tryptophan ratio but had no effect at all
  on
• endurance.

14

• Bottom line the evidence to suggest BCAA
• supplements improve endurance performance is
• almost non-existent. The best designed studies
  all
• show negative results.