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). FFA action of hormone- sensitive lipase Body fat TG Increased levels of FFA in the blood allows greater uptake of FFA by muscle cells.
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. -oxidation Acetyl-CoA TCA Cycle inside mitochondria outside mitochondria
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 Caffeine is found in many 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 “caffeine- naive” 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 Sigma- Tau, 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 non- athletes) of all types. Military scientists very active in research on caffeine, especially the development of novel delivery systems (e.g. transdermal patch).