by Thomas Incledon, PhD(c), RD, LD/LN, RPT, NSCA-CPT, CSCS
Background Neurotransmitters are responsible for communicating signals between neurons and other cells. Stress can deplete both catecholaminergic neurotransmitters like norepinephrine and dopamine and cholinergic neurotransmitters like acetylcholine in the brain. When this happens, mental and physical performance can be hindered. Certain amino acids and other compounds can be used to produce new neurotransmitters. These neurotransmitter precursors can help maintain normal levels of neurotransmitters and stimulate different regions of the brain resulting in altered hormonal responses and improved function of the central nervous system. Researchers have investigated a number of these precursors. This article will summarize the evidence behind each agent and discuss the role each may have in improving exercise performance.
Acetyl-L-Carnitine (ALC) While it’s always nice to have human research when talking about enhancing human performance, we also have to take into account that for some techniques, it just isn’t appropriate to use people. Take for example when researchers wanted to see how ALC affected different brain regions [1]. They had to dice and slice the brain to look at the concentration of different amino acids and neurotransmitters. Since human volunteers for this type of work is difficult to find, rats make a much better alternative. They found that ALC elevated both acetylcholine and dopamine in specific regions of the brain. Another group also found that apart from stimulating acetylcholine release, ALC may also be converted into acetylcholine [2]. The importance of these Trivial Pursuit-type facts is that they may explain why ALC has some utility in slowing the decline of Alzheimer’s Disease [3]. Some progressive researchers feel that ALC is useful for maintaining mitochondrial health in brain cells and other cell types. They believe this may prevent some of the diseases that we see associated with aging. It is too early to say if this is true or not as preventative research is lacking. However it was also found that ALC treatment prevents changes in the neuromuscular junction (the region where neurons stimulate muscle fibers) that occur with aging [4]. Normally as people age, they lose their ability to recruit fast-twitch muscle fibers and as a result the fibers atrophy and wither away. This leaves primarily Type I muscle fibers remaining. In rats treated with 150 mg of ALC per kg of body weight for six months, the decrease in Type II fibers was attenuated. The equivalent body weight dose for a 154-pound guy working out would be 10.5 grams, however pharmacologists would usually say one to two grams should work in humans. There are no exercise performance studies on human using ALC. Anecdotally, athletes report an increase in speed when ingesting about 10 grams per day. My lab has found that doses of two grams and higher can increase testosterone. It is too early to say if the endocrine responses we have observed will materialize into strength or performance gains.
Choline Research on runners has shown that after a marathon, choline levels may decrease by as much as 40% [5]. They speculated that if choline levels were depleted enough during exercise, acetylcholine levels would be affected and this would lead to a decrease in performance. However, studies administering either choline citrate [6] or choline bitartrate [7] demonstrated no effects on physical performance. So far the overall evidence for most choline-containing compounds to improve physical performance is weak. However there appears to be sufficient evidence on alpha-glycerylphosphorylcholine to warrant further investigation into its potential ergogenic value.
Alpha Glycerophosphcholine (alpha-GPC) Alpha-glycerylphosphorylcholine is a choline-containing compound that is believed to serve as a precursor for acetylcholine and/or membrane phospholipids. Animal studies indicate that it improves both learning and memory in a dose dependent fashion[8-10]. Studies on humans indicate that it can prevent drug-induced memory deficits [11] and offer therapeutic application for protecting the brain and other neural tissues [12]. Recent interest in alpha-GPC has focused on its ability to augment growth hormone release when combined with other stimuli. Administration of alpha-GPC and growth hormone releasing hormone results in significantly greater growth hormone release [13]. An abstract presented at the American Society of Exercise Physiologists’ Annual Meeting lends additional support to the previous findings. A product containing 100 mg of alpha-GPC stimulated a greater increase in exercise-induced growth hormone release compared to placebo [14]. Clinical studies have generally used doses between 400 and 1200 mg per day. Most products on the market offer substantially less than this (ie 100 mg or less). I am currently working on dose response studies using alpha-GPC to determine the most efficacious dose.
Tyrosine Various forms of stress can induce depletion of brain catecholamines, especially epinephrine. Animal studies indicate that reduced brain epinephrine levels are closely related to stress-induced performance decrements. Tyrosine administration minimizes or reverses stress-induced performance decrements by increasing brain epinephrine levels. Studies on humans indicate that tyrosine can improve cognitive performance during stressful conditions [15] and reduce the effects of environmental stress. [16-19]. Products marketed towards increasing neurotransmitter levels often provide less than 3000 mg of tyrosine. The actual doses used in studies varies from two gram doses ingested five times per day (a total of 10 grams ingested), to single servings providing up to 15 grams in one dose. Most studies showing a benefit of tyrosine use 100 mg/kg for a single dose. For tyrosine to work it needs to be taken on an empty stomach so that competition with other amino acids is minimized. It is not recommended for people taking MAOIs or who have high blood cholesterol.
A Sample Strategy It’s not uncommon for athletes to want to take everything at once, with the thought process that if one thing works, then taking everything should really boost performance. Unfortunately, this is seldom the case and even if it were true, it would still not be the ideal strategy. In order to evaluate the effectiveness of a given supplement, it has to be administered in a controlled fashion. A prudent strategy first involves determining if the individual is following the right diet. A poor diet with lots of supplements is still a poor diet. Rather than using supplementation to mask dietary weakness, it would be better to use supplementation to augment a sound diet. You should establish baseline values while following a diet for four-to-eight weeks. Then introduce each supplement one at a time with an appropriate evaluation period. Using this systematic approach, an individualized and unique diet and supplement strategy is developed. Assuming this process has taken place, a sample strategy would look like:
7:00 AM Meal 1 10:00 AM Meal 2 1:00 PM Meal 3 3:30 PM Pre-Workout Drink #1: 100 mg/kg tyrosine mixed in carbohydrate beverage like CeraSport or Gatorade. (Ingested about 30-45 minutes before training) 4:10 PM Pre-Workout Drink #2: Six grams of essential amino acids, 35 grams of sucrose. (Ingested immediately before training) 5:30 PM Post-Workout Drink: Six grams of essential amino acids, 35 grams of sucrose and five grams of creatine. 7:00 PM Meal 4 10:00 PM Meal 5
This strategy can be applied to both the athlete desiring to lose weight as well as the athlete desiring to gain weight, providing the appropriate calorie and macronutrient adjustments are made. It should not be mistaken for a template to copy and hand out to everyone. Rather it is simply an example of one possible strategy that can be developed utilizing the latest research on supplementation with an emphasis on improving performance. While this article certainly doesn’t cover all the supplements currently on the market, it hopefully offers some insight to the potential use of some products.
References 1. Toth, E., et al., Effect of acetyl-L-carnitine on extracellular amino acid levels in vivo in rat brain regions. Neurochemical Research, 1993. 18(5): p. 573-8. 2. White, H.L. and P.W. Scates, Acetyl-L-carnitine as a precursor of acetylcholine. Neurochemical Research, 1990. 15(6): p. 597-601. 3. Brooks, I.J., et al., Acetyl L-carnitine slows decline in younger patients with Alzheimer’s disease: A reanalysis of a double-blind, placebo-controlled study using the trilinear approach. International Psychogeriatrics, 1998. 10(2): p. 193-203. 4. De Angelis, C., et al., Age- and trauma-dependent modifications of neuromuscular junction and skeletal muscle structure in the rat. Effects of long-term treatment with Acetyl-L-Carnitine. Mechanisms of Ageing & Development, 1995. 85(1): p. 37-53. 5. Conlay, L.A., L.A. Sabounjian, and R.J. Wurtman, Exercise and neuromodulators: Choline and acetylcholine in marathon runners. International Journal of Sports Medicine, 1992. 13(Suppl 1): p. S141-S42. 6. Spector, S.A., et al., Effect of choline supplementation on fatigue in trained cyclists. Medicine & Science in Sports & Exercise, 1995. 27(5): p. 668-673. 7. Warber, J.P., et al., The effects of choline supplementation on physical performance. International Journal of Sport Nutrition & Exercise Metabolism, 2000. 10(2): p. 170-81. 8. Lopez, C.M., et al., Effect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholine. Pharmacology, Biochemistry & Behavior, 1991. 39(4): p. 835-40. 9. Drago, F., V. D’Agata, and G. Guidi, Effects of L-alpha-glycerylphosphorylcholine on drug-induced behavioral alterations in rats. Dementia, 1992. 3(1): p. 7-9. 10. Drago, F., et al., Behavioral effects of L-alpha-glycerylphosphorylcholine: influence on cognitive mechanisms in the rat. Pharmacology, Biochemistry & Behavior, 1992. 41(2): p. 445-8. 11. Canal, N., et al., Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine. International Journal of Clinical Pharmacology, Therapy, & Toxicology, 1991. 29(3): p. 103-7. 12. Barbagallo Sangiorgi, G., et al., alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks: An Italian multicenter clinical trial. Annals of the New York Academy of Sciences, 1994. 717(pp 253-269). 13. Ceda, G.P., et al., alpha-Glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects. Hormone & Metabolic Research, 1992. 24(3): p. 119-21. 14. Ziegenfuss, T.N. and R.W. Mendel. Acute Hormonal Responses to a Novel Botanical Compound. in American Society of Exercise Physiologists 4th ASEP National Meeting. 2001. Memphis, TN: American Society of Exercise Physiologists. 15. Thomas, J.R., et al., Tyrosine improves working memory in a multitasking environment. Pharmacology, Biochemistry & Behavior, 1999. 64(3): p. 495-500. 16. Deijen, J.B., et al., Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course. Brain Research Bulletin, 1999. 48(2): p. 203-9. 17. Owasoyo, J.O., D.F. Neri, and J.G. Lamberth, Tyrosine and its potential use as a countermeasure to performance decrement in military sustained operations. Aviation Space & Environmental Medicine, 1992. 63(5): p. 364-9. 18. Banderet, L.E. and H.R. Lieberman, Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Research Bulletin, 1989. 22(4): p. 759-62. 19. Salter, C.A., Dietary tyrosine as an aid to stress resistance among troops. Military Medicine, 1989. 154(3): p. 144-6.
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