Transcript Slide 1
Central Fatigue Lecture 18 Part I 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. 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. 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. 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 5OH tryptamine and then to serotonin in the brain. In order to get into the brain, tryptyophan must Blood Vessel cross the blood-brain barrier via a transporter. Brain The transporter is not specific for tryptophan, it also transports branched chain amino acids (BCAA), so there is a “competition” for transport. Transporter During exercise, BCAA’s 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. FFA’s and tryptophan are both transported in the blood by albumen (a common plasma protein). As level of FFA’s 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. FFA FFA tryptophan albumen FFA BCAA How do you test the central fatigue hypothesis? What things do you need to know? 1. 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? 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 can’t 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. In mid-90’s, 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 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. Bottom line: the evidence to suggest BCAA supplements improve endurance performance is almost non-existent. The best designed studies all show negative results.