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Supplements for
Endurance
Lecture 15
body fat
 
free fatty acids
 
mitochondria

beta-oxidation

acetyl-CoA

NADH, FADH

electron transport system
 
ATP
As we discussed,
any intervention
that can shift energy
production toward a
greater use of fat can
enhance endurance
exercise performance.
There are 3 potential
places where a
substance could be
effective.
In response to the action of epinephrine and
norepinephrine (secreted in large quantities during
exercise) hormone-sensitive lipase, an enzyme
located in adipose tissue (body fat) and muscle,
breaks down triglycerides to free fatty acids (FFA).
Body fat
Increased levels of FFA in the
blood allows greater uptake of
FFA by muscle cells.
TG
FFA
Fatty acids are converted to Acetyl-CoA. Before this
can take place, the fatty acid must get into the
mitochondria. An enzyme called carnitine
acyltransferase (CAT 1), located on the
mitochondrial membrane, is the “door” that allows the
fatty acids to enter the mitochondria. This process is
the rate-limiting step in fatty acid oxidation.
outside mitochondria
inside mitochondria
 -oxidation
Acetyl-CoA
TCA Cycle
The NADH and FADH2 produced in the TCA cycle
are sent to the Electron Transport System and used
to create a proton gradient across the membrane of
the mitochondria – this potential energy provides the
energy to convert ADP to ATP. 90% of ATP
synthesis happens during electron transport.
The “mobile”
part of the ETS
is a lipid-soluble
compound called
Coenzyme Q10
Q10
body fat
  CAFFEINE
free fatty acids
  CARNITINE
mitochondria

beta-oxidation

acetyl-CoA

NADH, FADH

electron transport system
  CoQ10
ATP
As we discussed,
any intervention
that can shift energy
production toward a
greater use of fat can
enhance endurance
exercise performance.
There are 3 potential
places where a
substance could be
effective.
Caffeine is found in many Caffeine
common products. It is in
highest concentration in
coffee at about 175 mg
per 5 oz. Since modern
coffee places sell coffee in
12-20 oz. servings, you
get 420-700 mg/cup at a
place like Rao’s or
Starbucks.
Caffeine is also a listed
(and unlisted) component
of MANY supplements
Caffeine increases the breakdown of TG
to FFA
blood
Increase in blood FFA
allows muscle more access
and can increase the
uptake of FFA into
muscle.
Increased fat oxidation
= less CHO oxidation.
Thong et al (2002)
Less CHO oxidation can spare muscle and/or
liver glycogen: exercise longer at same intensity
or at a higher intensity for the same distance.
Fat use DOES increase when subjects are treated
with caffeine BUT effect is much smaller in frequent
users. Desensitization reduces lipolytic effect.
In many studies, caffeine (> 300 mg) does enhance
endurance performance. Effect greater in “caffeinenaive” individuals.
Surprisingly, several studies show no rise in fat use
but performance is enhanced. Other studies
show higher fat use but performance not enhanced.
Side effects of caffeine include:
1. blood levels consistent with ingesting 4-5 small
cups of coffee can result in a positive drug test (urine
levels greater than 12 ug/ml).
2. caffeine is a diuretic: increased water loss; greater
likelihood of dehydration.
3. in large quantities can cause cardiac arrhythmia,
tachycardia. Also may result in mental confusion.
Caffeine also enhances performance of short
exercise tasks requiring power/speed.
Improves mental performance (recall, reflexes, etc.).
Can improvements on these types of tasks be
explained by increased availability of FFA?
Probably not, time frame too short for physiologically
relevant contribution of fat to energy production.
More likely related to action of
caffeine as general CNS stimulant.
Caffeine Doping Extra Info
• The International Olympic Committee took caffeine off
the banned list in January 2004. Urinary levels up to a
concentration of 12 mg/liter were acceptable,
representing casual use. Levels above this are viewed
as achieved through a deliberate attempt at doping by
the athlete. Approximately 1000mg of caffeine (about 8
cups of coffee) would be required to exceed the current
IOC limit, but it is very important to note that people can
metabolize caffeine at very different rates. Differences in
metabolism, medications, and certain diseases may
significantly alter the rate in which caffeine is cleared
from the body. Some athletes came close to flunking the
drug test after ingesting only 350mg.
Carnitine is an amino acid-like molecule that is
found in meat products (muscle). It can
also be synthesized. Vegetarians usually have
normal levels of muscle carnitine.
Carnitine functions as part of the carnitine acyl
transferase enzymes (CAT-I and CPT-II) that
regulate entry of long chain fatty acids from the
cytosol to the mitochondria.
IF transport through CAT-1 is the rate-limiting step in
the ability to oxidize FFA for energy, increasing the
quantity of carnitine may benefit performance.
More carnitine = greater transport of fatty acids into
mitochondria = more fat oxidation= less
carbohydrate oxidation = spare glycogen use
and enhance endurance performance.
glycogen
triglyceride


glucose
free fatty acid


pyruvate
fatty acyl CoA


acetyl-CoA
TCA cycle
Studies: about 20 different studies
done looking at the impact of
carnitine supplementation on some
aspect of human performance.
Some show + benefits, some show no effect
Common theme in + studies: they were
generally done in Italy and funded by SigmaTau, an Italian pharmaceutical company that
produces/sells carnitine.
Studies: about 20 different studies
done looking at the impact of
carnitine supplementation on some
aspect of human performance.
Some show + benefits, some show no effect
Most well-controlled, double-blind studies
show no positive effects of carnitine on
performance.
Research
• Long-term oral treatment of healthy adults
with L-carnitine is not associated with a
significant increase in the muscle carnitine
content, mitochondrial proliferation, or
physical performance. (Wachter 02)
If it were possible, increasing levels of CAT-1 would be
more effective. Despite lack of evidence showing
efficacy, carnitine remains very popular as both a
supplement for athletic performance and for weight
maintenance, overall health and longevity.
Coenzyme Q10 (CoQ10) is found in many animal
products and synthesized by the body. Consists of a
polar “head” and a very long hydrocarbon “tail”.
Carries electrons among enzyme
complexes in the ETS
As a part of the system that is mobile, some
scientists believe that CoQ10 levels limit the rate at
which energy can be produced in the ETS.
If true, raising levels of CoQ10 could increase ability
to produce energy oxidatively
Does not translate directly into more fat use but
greater ability to oxidize the NADH and FADH
produced in the TCA cycle means less need to
produce energy by glycolysis = less glycogen use
Blood levels of CoQ10 tend to be lower in very
active individuals. Used as evidence that
athletes are relatively CoQ10-deficient.
Many studies on CoQ10 and performance: all show
increase in blood levels of CoQ10 but very few
show a positive effect.
Likely that blood levels of CoQ10 do not reflect what
is happening inside muscle mitochondria.
• It was speculated that the non-significant
effects of supplementation in healthy, non
CoQ(10)-deficient men could be due to
either that the mitochondrial membrane is
normally saturated with CoQ(10) (Zhou
05)
In addition to its use by
athletes, Coenzyme Q10
is an extremely popular
supplement for everything
from impotence to
longevity. It is widely
used during open heart
surgery to prevent free
radical damage to the
heart when blood flow is
restarted.
Of the 3 C’s (caffeine, carnitine, CoQ10),
only caffeine has been reliably shown to
benefit athletic performance.
Side-effects and de-sensitization with repeated use.
Still remains very popular among athletes (and nonathletes) of all types.
Military scientists very active in research on caffeine,
especially the development of novel delivery
systems (e.g. transdermal patch).