HM Medical Clinic


Pre research packet_1.4

Rev. 1.4 June 2007
Table of Contents

Corporate Philosophy.3
Our Mission.3 Research Philosophy.3 Commitment to Quality .3 Certificate of Analysis .3 Safe and Legal.4
About PreRace Pre-Exercise Supplement .5
Physiological Adaptations .5 Biochemical Processes.5 Citrulline Malate (2:1 Bonded) .6
Stimulates Nitric Oxide .6 Removes Toxins.6 Reduces Lactic Acid and Ammonia .6 L-Taurine.8
Malic Acid .9
Neuro-Stimulant: Metabromine-Caffeine-Catechin-DMAE .9
Caffeine.10 Catechin .12 DMAE.13 Quercetin .14

Corporate Philosophy
Our Mission
Integrate our passion for racing, knowledge of sports nutrition, integrity, and values to provide endurance
athletes with the ultimate, scientifically validated, high-performance racing formulations.
Research Philosophy
Research is the most important value at First Endurance. We are driven by a desire to ensure our products
are proven to enhance endurance performance and have scientific validation. At First Endurance, we refuse
to reduce costs by using "pixie dust" amounts of ingredients just to dress up the label. Our formulations
utilize the same levels (sometimes more) of the active ingredients that were used in the actual human
scientific research. We assure effective products by using the same ingredients used in the human clinical
studies. We are meticulous about research and go out of our way to make sure we have addressed each of
our stringent requirements. All products that First Endurance develops are based on human scientific
Commitment to Quality
First Endurance uses only the finest ingredients and follows stringent quality control. Supplements can be
easily ruined. Even if you buy the right ingredients, they can degrade quickly and lose their efficacy if they
aren't handled under the most stringent controls. We are determined to ensure nothing goes wrong with any
step of the way. PreRace is manufactured under the highest manufacturing guidelines assuring potency
and strict quality control. Not only do our manufacturing facilities not allow banned substances, we take
additional steps to assure complete cleanliness.
Certificate of Analysis
A Certificate of Analysis (C of A) is a document which states every active and inactive substance used to
manufacture a product. A C of A also shows that there are no additional ingredients added to the PreRace
Safe and Legal

First Endurance is committed to developing the most advanced endurance supplements on the market. First
Endurance has taken additional measures to assure that our products are safe legal and stimulant free. First
Endurance supplements are legal to use in any sporting event governed by the World Anti-Doping
Association (WADA), the US Anti-Doping Association (USADA) and by the UCI (Union Cycliste
International). One or more of the aforementioned governing bodies govern all US Cycling, International
Cycling, US Triathlon and International Triathlon and USTF.
Some commonalties among these governing bodies include banned substances which fall into one or more
of the following categories as listed in Section I A-E of the UCI Prohibited Classes of substance and
Prohibited Methods document. A) Stimulants B) Narcotics C) Anabolic agents D) Diuretics and E) Peptide
hormones, mimetics and analogues. This document goes on to list banned substances within each of these
classes. Regulations also ban 'Compounds chemically or pharmacologically related to the products
First Endurance products contain NO ingredients which are explicitly listed under the banned substance
list, and none of the ingredients are related chemically or pharmacologically. First Endurance has also
contacted the USADA and received verbal confirmation that our ingredients are not banned based on their
regulations. Note: USADA, WADA and UCI do not offer any certification or written confirmation.
First Endurance manufactures its formulations to the highest GMP (Good Manufacturing Practice)
standards available. In addition, a proprietary manufacturing method is used for added safety and
All ingredients used in First Endurance formulations come from audited suppliers who do not carry, broker
or supply any banned substances. In addition our manufacturing facility does not allow banned substances
in any products manufactured.
Part XIV Article 7 of the Anti-doping Examination Regulations contains the following warning:
riders must refrain from using any substance, foodstuff or drink of which they do not know the composition.
It must be emphasized that the composition indicated on a product is not always complete. The product
may contain prohibited substances not listed in the composition.

For a complete list of regulations and banned substances please use one of the following links:
UCI Banned Substance List
Use Directions: Mix one heaping scoop into EFS or your favorite pre-exercise drink. Consume 30 to 45 minutes before exercise. Begin use with one half the recommended dose to assess your tolerance. Improper use may be hazardous to a person's health. Supplement Facts
Serving Size: 1 scoop (4800mg) or 1.5 tsp or 6cc or 6ml
Servings per Container: n/a
Supplement Facts
Serving size L-Taurine Citrulline Malate bonded 2:1 Neuro Stimulant Proprietary Blend: DiMethyl Amino Ethanol, Caffeine Anhydrous, Metabromine, Catechin Malic Acid (from Citrulline Malate) *Daily Value Not Established **Percent Daily Values are based on a 2,000 calorie diet.
Provides 200mg Caffeine
About PreRace Pre-Exercise Supplement
PreRace is designed to help endurance athletes improve performance. This revolutionary pre-exercise
supplement is formulated with a mental acuity component comprised of DiMethyl Amino Ethanol
(DMAE), metabromine and catechin, which combine to deliver a clear mental focus prior to exercise.
Citrulline Malate and L-Taurine improve cardiac output, stimulate the nitric oxide (NO) system and clear
lactate. The proprietary formula works synergistically with quercetin (a powerful antioxidant that improves
time to exhaustion in endurance athletes) and 200mg of caffeine. PreRace comes as a flavor-free powder
which can be added to any pre-exercise or during exercise drink, like EFS.
Physiological Adaptations

1) Enhances oxygenation of muscles 2) Increases muscle stamina 3) Increases nutrient absorption by blood 4) Improves time to exhaustion 5) Increases maximal workload 6) Improves oxidative ATP Biochemical Processes
1) Enables significantly enhanced production of nitric oxide 2) Improves cardiac output 3) Augments vasodilation 4) Improves mitochondrial respiration 5) Stimulates removal of metabolic toxins (lactic acid, ammonia)
Citrulline Malate (2:1 Bonded)

CM is a mixture of citrulline, an amino acid involved in the urea cycle, and malate, a tricarboxylic acid cycle intermediate. Circulating levels of citrulline is directly related to endogenous argininie synthesis, possibly to an even greater degree than supplementing with straight argininie. Citrulline malate has been shown to significantly increase aerobic capacity, ATP production and PhosphoCreatine recovery after training, therefore reducing lactate and providing substrate for the aerobic energy production pathway. Early studies have also shown an antiaesthenic (resistance to muscle fatigue) effect. Studies indicate that CM is involved in three physiological roles: 1) stimulates nitric oxide; 2) removes toxins; and 3) reduces lactic acid and ammonia. Therefore, citrulline malate may be useful for all athletes in maintaining energy levels, improving recovery, enhancing exercise performance and fatigue resistance. Stimulates Nitric Oxide
In the body, nitric oxide (NO) serves several roles, mainly involving small blood vessels. Nitric oxide is synthesized from L-arginine and oxygen by various nitric oxide synthase (NOS) enzymes. The compounds are converted to nitric oxide, which in turn dilates the coronary artery thereby increasing its blood supply. Nitric oxide also serves as a neurotransmitter between nerve cells. Unlike most other neurotransmitters that only transmit information from a presynaptic to a postsynaptic neuron, the small nitric oxide molecule can diffuse all over and can thereby act on several nearby neurons, even on those not connected by a synapse. Nitric oxide is an important non-adrenergic, non-cholinergic (NANC) neurotransmitter in various parts of the gastrointestinal tract. In the stomach, it increases the capacity to store food and fluids. The fact that nitric oxide increases blood flow should make it of interest to endurance athletes, as increased blood flow will serve to deliver more nutrients to muscles, thus helping muscles become more resistant to stress. The stimulation of NO has also been found to increase glucose transport in skeletal muscle significantly (Balon et al., 1997). The fact that nitric oxide acts to reduce inflammation should also make it of interest to endurance athletes as it has the potential to reduce the pain associated with subjecting muscles to extreme stress. Removes Toxins
Citrulline acts to remove endotoxins such as lactic acid build up and ammonia by acting as an intermediary
in the urea cycle. These endotoxins impair overall exercise performance and are produced by the body in
response to intense physical exercise, protein metabolism and catabolic states.
Citrulline supplementation rapidly speeds up the removal of lactic acid and ammonia (waste products) from working muscles, resulting in better performance from the working muscle tissue. Ultimately, athletes can train harder and recover faster with each and every workout (Goubel F et al., 1997). Reduces Lactic Acid and Ammonia
Research has demonstrated that citrulline malate has a protective effect against increased blood acidity and protects against ammonia poisoning. This study showed CM significantly increased bicarbonate (an acid buffer that soaks up lactic acid molecules), which allows exercise at a higher level before the negative effects of acidity affect exercise performance (Callis et al., 1991). Further studies showed supplementation with citrulline malate increases the rate of ammonia clearance without affecting ammonia accumulation during bicycle exercise (Vanuxem et al., 1990). This is because citrulline is involved in the urea cycle and therefore plays a role in the detoxification of ammonia. CM positively influences the lactic acid metabolism leading to improved endurance performance. Healthy male subjects participated in a cycle ergometer study designed to determine CM's effect on a) aerobic-anaerobic threshold; b) blood lactate accumulation; and c) 30 minute post-exercise blood lactate recovery. Two maximal cycling tests were performed with one group ingesting CM and another group ingesting a placebo. Aerobic-Anaerobic threshold was significantly higher in the CM group and 27% of subjects were able to achieve a higher maximal workload on the second test. (Janeira MA, 2006). The human study done by Benedahan et al., 2002, demonstrated the great potential of citrulline malate supplementation to enhance aerobic performance. The most important finding of their research was significantly more energy produced aerobically (34% increase). But they also found a significant reduction in the sensations of fatigue and that rate of recovery, as measured by the rate of phospho-creatine recovery, improved by 20%. The researchers concluded that the increased aerobic ATP production, together with a reduced proportion of anaerobic energy supply, may contribute to the lower levels of fatigue experienced by the subjects (Benedahan et al., 2002). Achike FI, Kwan CY. Nitric Oxide, Human Diseases and the Herbal Products That Affect the Nitric Oxide Signalling Pathway. Clin Exp Pharmacol Physiol. 2—3 Sep;30 (9):605-615. Balon TW, Nadler JL. J,. Evidence That Nitric Oxide Increases Glucose Transport in Skeletal Muscle. Appl Physiol. 1997 Jan;82 (1):359-363. Balon TW. Role of Nitric Oxide in Contraction Induced Glucose Transport. Adv Exp Med Biol. 1998;441:87-95 Benedahan, D., Mattei, J. P., Ghattas, B., Confort-Gouny, S., Le Guern, M. E. and Cozzone, P. J. (2002) Citrulline/malate promotes aerobic energy production in human exercising muscle. British Journal of Sports Medicine. 36 (4), 282-289. Briand J, Blehaut H, Calvayrac R, Laval-Martin D. Use of a Microbial Model for the Determination of Drug Effects on Cell Metabolism and Energetics: Study of Citrulline Malate. Biopharm Drug Dispos. 1992 Jan;13(1):1-22. Callis, A., Magnan de Bornier, B., Serrano, J. J., Bellet, H. and Saumade, R. (1991) Activity of citruline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man. Arzneimittelforschung. 41 (6), 660-663. Creff, A. F. (1982) Controlled double-blind clinical-study against stimol placebo in the treatment of asthenia. Gazette Medicale De France. 89, 1926-1929. Goubel F, Vanhoutte C, Allaf O, Verleye M, Gillardin JM. (1997). Citrulline malate limits increase in muscle fatigue induced by bacterial endotoxins. Canadian Journal of Physiology and Pharmacology, 75, 205-207. Janeira MA et al. Citrulline malate effects on the aerobic-anaerobic threshold recovery and in post-exercise blood lactate recovery. Medicine Science Sport and Exercise, 30(5), abstract. 2006. Nitric Oxide in Skeletal Muscle. Kobzik L, Reid MB, Bredt DS, Stamler JS. Nature 1994 Dec 8;372 (6506):546-8. Koh TJ, Tidball JG., Nitric Oxide Synthase Inhibitors Reduce Sarcomere Addition in Rat Skeletal Muscle. J Physiol. 1999 Aug 15;519 Pt 1:189-96. Oknin V, Fedotova AV, Vein AM. Use of Citrulline Malate (Stimol) in Patients with Autonomic Dystonia Associated with Arterial Hypotension. Zh Nevrol Psikhiatr Im S S Korsakova. 1999;99(1):30-3 Vanuxem, D., Duflot, J. C., Prevot, H., et al., (1990) Influence of an anti-asthenia agent, citrulline malate, on serum lactate and ammonia kinetics during a maximum exercise test in sedentary subjects. Seminaire des Hopitaux de Paris. 66, 477-481. Verleye M, Heulard I, Stephens JR, Levy RH, Gillardin JM. Effects of Citrulline Malate on Bacterial
Lipopolysaccharide Induced Endotoxemia in Rats. Arzneimittelforschung. 1995 Jun;45(6):712-715.
Wang MX, Murrell DF, Szabo C, Warren RF, Sarris M, Murrell GA. Nitric Oxide in Skeletal Muscle:
Inhibition of Nitric Oxide Synthase Inhibits Walking Speed in Rats. Nitric Oxide. 2001 Jun;5(3):219-232

Taurine in the pharmaceutical and lab setting is synthesized through a combination of cysteine, methionine
and vitamin E. It is naturally produced in testicles of many mammals. The major pathway for taurine
synthesis occurs in the liver via the cysteine sulfinic acid pathway, which then acts as a metabolic
transmitter, has a detoxifying effect and strengthens cardiac contractility. Taurine is defined as a non-
essential amino acid and is found in high concentrations in the white blood cells, skeletal muscles, central
nervous system as well as the heart muscles. In adults, but not children, this nutrient can be manufactured
from methionine in the body and from cysteine in the liver.
This sulfur-containing amino acid functions with glycine and gamma-aminobutyric acid as a
neuroinhibitory transmitter. At times of extreme physical exertion, the body no longer produces the
required amounts of taurine and a relative deficiency results – essentially, in long exhaustive exercise
taurine concentrations are significantly reduced. These reductions in taurine concentration can lead to
decreased physiological parameters and performance (Manabe et al. 2003).
Through its cardio and oxidative protective roles, oral administration of taurine can improve exercise
performance significantly. Furthermore, pre-exercise taurine administration can reduce muscle damage
caused by endurance training. Researchers also theorize that it is through the cellular protective properties
that taurine attenuates exercise-induced DNA damage and enhances the capacity of exercise.
In a study performed by Zhange et al, 11 healthy-aged men participated in two separate cycle ergometer
tests supplementing orally with taurine prior to exercise. The study results showed significant increases in
VO2max, exercise time to exhaustion and maximal workload. Following exercise, the increase in taurine
concentration correlated positively with exercise time to exhaustion and maximal workload (Zhang et al,
Endurance-trained subjects performed an exhaustive bout of endurance exercise at three different times.
Subjects were placed into three groups: caffeine and taurine, caffeine with no taurine, and a placebo. In
this double-blind placebo-controlled study, the subjects ingesting the caffeine and taurine drink showed
improved cardiovascular stroke volume (Baum M Weiss M, 2001). The authors of this study claim this
was due to a reduced endystolic diameter and volume.
Dawson R J et al. The cytoprotective role of taurine in exercise induced muscle injury.
Baum M, Weiss M. The influence of a taurine containing drink on cardiac parameters before and after
exercise measured by echocardiography. Amino Acids. 2001; 20(1):75-82.
Manabe et al. Decreased blood levels of lactic acid and urinary excretion of 3-methylhistidine after exercise
by chronic taurine treatment in rats. Journal of Nutr Sci Vitaminol (Tokyo) 2003: 49(6):375-80.
Yatabe Y, et. al. Effects of taurine administration in rat skeletal muscles on exercise. J of Orthopedic
Science. 2003: 8(3):415-9.
Zhang M Et al. Role of Taurine supplementation to prevent exercise-induced oxidative stress in healthy
young men. Amino Acids. 2004: 26(2):203-7.
Matsuzaki Y et. al. Decreased taurine concentration in skeletal muscles after exercise for various durations.
Medicine Science Sports Exercise. 2002; 34(5):793-7.

Malic Acid

Malic acid is the only metabolite of the Krebs Cycle which falls in concentration during exhaustive
physical activity. Malic acid is involved in the production of energy in the body under both aerobic and
anaerobic conditions. During anaerobic conditions, malic acid has an ability to remove the accumulation of
reducing equivalents. Human studies have shown that after endurance training, athletes' muscles were
characterized by a 50% increase in the malate-aspartate redox shuttle enzymes. In both animals and
humans, when there is an increased demand for ATP there is an additional demand and utilization of malic
acid. Malic acid stimulates oxygen consumption by increasing mitochondrial uptake of other substrates. It
also stimulates the removal of components that build up under hypoxic conditions and inhibit ATP
production (Wu J et al 2006).
Bobyleva-Guarriero V, Wehbie R, Lardy H. The Role of Malate in Hormone-Induced Enhancement of
Mitochondrial Respiration. Archives of Biochemistry and Biophysics (1986) Vol. 245, No. 2, March: 477-
Bobyleva-Guarriero V, Lardy H. The Role of Malate in Exercise-Induced Enhancement of Mitochondrial
Respiration. Archives of Biochemistry and Biophysics (1986) Vol. 245, No. 2, March: 470-476
Dunaev V, Tishkin N, Milonova N, Belay A, Makarenko S. Farmakol Toksikol Effect of Malic Acid Salts
on Physical Working Capacity and its Restoration After Exhausting Muscular Work. (1988) May-Jun;
Wu J et al. Effects of L-Malate on physical stamina and activities of enzymes related to the malate-
aspartate shuttle in liver of mice. Physiology Res. 2006 Mar 23.
Neuro-Stimulant: Metabromine-Caffeine-Catechin-DMAE

This proprietary combination is designed to enhance performance through a neurological stimulus
improving clarity, focus and concentration. The combination of theobromine, caffeine, and catechin (from
green tea and DMAE) works synergistically to elevate mood and enhance performance.
Metabromine, derived from the seed of the cacao tree (Theobroma cacao), contains procyanidins,
theobromine and caffeine – which are natural methylxanthines. Metabromine's mechanism of action results
from the combination of caffeine, theobromine and procyanidins. The standardized levels of theobromine
and caffeine produce a mild stimulating effect without over-stimulation of the central nervous system.
Theobromine is the primary alkaloid found in cocoa and chocolate, and is one of the causes of chocolate's
mood-elevating effects. Research indicates a possible interaction of the methylxanthines with the
procyanidins which promote a sustained energizing effect.
Theobromine is well documented as a vasodilator as well as having mild stimulant effects (Mumford,
1994). It is extremely well tolerated in humans at doses as high as 0.8 to 1.5 g of the pure compound (IARC
monographs). Theobromine has very different effects than caffeine on the human body; it is a mild, lasting
stimulant with a mood improving effect, whereas caffeine has a strong, immediate effect and increases
awareness. Simultaneous increases in lipid and carbohydrate oxidation is believed to mediate the caffeine-
induced stimulation of energy expenditure (Bracco, et al, 1995). Research has also shown that caffeine
decreases the reliance of glycogen during exercise and increases endurance, possibly by a direct effect on
adipose tissue and active muscle.
Arciero, P.J., et al., Influence of age on the thermic response to caffeine in women. Metabolism 2000 Jan; 49 (1): 101-7. Bracco D, et al., Effects of caffeine on energy metabolism, heart rate and methyl xanthine metabolism in lean and obese women. Am. J. Physiol 1995 Oct; 269: E671-8 Ghonemy, A.M., Wagih, I.M., and Farag, A.A., The effect of pH changes on the precipitating action of tannic acid on alkaloids. J. of Egyptian Med Assoc 57, (11-12) 479-571 1974. IARC Monographs Volume 51 421-441 Mumford, G. K. et al, Discriminative stimulus and subjective effects of theobromine and caffeine in humans. Psychopharmacology (1994) 115: 1-8. Mumford, G., et al., Absorption rate of methylxanthines following capsules, cola and chocolate. Eur J Clin Pharmacol. 1996; 51 (3-4): 319-25. Spencer, J. et al., Decomposition of Cocoa Procyanidins in the Gastric Milieu. Biochem Biophys Res Comm. 272, 236-241 (2000). Yoshida T, Sakane N, Umekawa T, Kondo M. Relationship between basil metabolic rate, thermogenic response to caffeine and body weight loss following combined low calorie and exercise treatment in obese women. Int J Obes Relat Metab Disord 1994 May; 18(5): 345-50. Caffeine
Caffeine stimulates the central nervous system (CNS), increases the release of adrenaline, increases the use
of body fat as fuel and spares glycogen. Adrenaline release is accomplished through caffeine's effect on
epinephrine and nor-epinephrine. Many athletes seek this CNS excitatory response to increase alertness and
to give them the extra ‘energy' needed for their workouts. More importantly, caffeine mobilizes free fatty
acids (FFA) in the blood. Increased FFA in the blood allows the body to use fat as a fuel source. The use of
fat as fuel allows the body to spare glycogen (carbohydrates) for later use in exercise.
Kovacs et al. (1998) studied well-trained cyclists. The results of this study support the use of caffeine
during competition to improve performance. In this study, 15 cyclists ingested different levels of caffeine
in addition to a carbohydrate-electrolyte drink during a time trial. The highest caffeine doses (225 and 320
mg) resulted in a 5% increase in power relative to control trials without caffeine (308 + 9 W and 309 +
10W versus 295 + 9W, respectively). The amount of caffeine ingested during this study was relatively
small, and yielded caffeine concentrations in the urine of less than 5 mg/L for the participants.

Another recent study by Cox et al. (2002) supported the use of caffeine both before and during cycling
performance. This study involved a cycling time trial which occurred after 2 hours of steady state cycling
at 70% of VO2max. Several different patterns of caffeine ingestion were utilized, including different levels
before and during the trial. None of the methods caused an increase in caffeine concentration in the urine to exceed 12ug/ml. These results also demonstrate that ingestion of 1-3 mg/kg of caffeine produced the same level of performance enhancement ( 3%) as did the higher levels of caffeine intake (6 mg/kg). Yeo et al. (2005) published a recent study that looked at the effects of caffeine ingestion on carbohydrate oxidation. Eight male cyclists exercised for 120 minutes on three separate occasions. During exercise, cyclists ingested either a 5.8% glucose solution (Glu; 48 g/h), 5.8% glucose solution with caffeine (Glu+Caf, 48 g/h + 5 mg·kg·h-1), or plain water (Wat). Average exogenous CHO oxidation over the 90- to 120-min period was 26% higher (p < 0.05) in Glu+Caf (0.72 +/- 0.04 g/min) compared with Glu (0.57 +/- 0.04 g/min). Total CHO oxidation rates were higher (p < 0.05) in the CHO ingestion trials compared with Wat, but they were highest when Glu+Caf was ingested (1.21 +/- 0.37, 1.84 +/- 0.14, and 2.47 +/- 0.23 g/min for Wat, Glu, and Glu+Caf, respectively; p < 0.05). There was also a trend (P = 0.082) toward an increased endogenous CHO oxidation with Glu+Caf (1.81 +/- 0.22 g/min vs. 1.27 +/- 0.13 g/min for Glu and 1.12 +/- 0.37 g/min for Wat). In conclusion, compared with glucose alone, 5 mg/kg caffeine (approximately 350mg caffeine for a 150lb athlete) co-ingested with glucose increases exogenous CHO oxidation, possibly as a result of an enhanced intestinal absorption. Doherty et al, (2005) recent meta-analysis of the use of caffeine ingestion on rate of perceived exertion (RPE) supports the use of caffeine as an ergogenic aid. Twenty-one studies were reviewed. In comparison to placebo, caffeine reduced RPE during exercise by 5.6% (95% CI). These values were significantly greater (p<0.05) than RPE obtained at the end of exercise (RPE % change, 0.01%; 95%). In addition, caffeine improved exercise performance by 11.2% (95% CI; 4.6 17.8%). Regression analysis revealed that RPE obtained during exercise could account for 29% of the variance in the improvement in exercise performance. These results demonstrate that caffeine reduces RPE during exercise, which may partly explain the subsequent ergogenic effects of caffeine on performance. In a 2004 study, Doherty et al. investigated the effects of caffeine ingestion on a 'preloaded' protocol that involved cycling for 2 min at a constant rate of 100% maximal power output immediately followed by a 1-min 'all-out' effort. Eleven male cyclists completed a ramp test to measure maximal power output. On two other occasions, the participants ingested caffeine (5 mg·kg) or placebo. Ratings of perceived exertion (RPE; 6-20 Borg scale) were lower in the caffeine trial by approximately 1 RPE point at 30, 60 and 120 s during the constant rate phase of the preloaded test (p <0.05). The mean power output during the all-out effort was increased following caffeine ingestion compared with placebo (794+/-164 vs. 750+/-163 W; p=0.05). Blood lactate concentration 4, 5 and 6 min after exercise was also significantly higher by approximately 1 mmol. in the caffeine trial (p <0.05). These results suggest that high-intensity cycling performance can be increased following moderate caffeine ingestion and that this improvement may be related to a reduction in RPE and an elevation in blood lactate concentration. McClellan and Bell (2004) looked at the ergogenic role of ingesting coffee (COF) prior to the subsequent ingestion of anhydrous caffeine (CAF). Thirteen subjects performed 6 rides to exhaustion at 80 % VO2max 1.5 h after ingesting combinations of COF, decaffeinated coffee (DECOF), CAF, or placebo. Time to exhaustion was significantly greater for all trials with CAF compared to placebo. In conclusion, the prior consumption of COF did not alter the ergogenic effect of the subsequent ingestion of anhydrous CAF. Brinbaum et al. (2004) observed the physiological effects of caffeine on cross-country runners during submaximal exercise. Ten college-age subjects (5 women; 5 men) volunteered to participate in this study. After completing a VO2max test, each subject completed 2 30-minute runs at 70% VO2max on the treadmill, 1 after ingesting caffeine and the other after ingesting a placebo. Tidal volume (TV), alveolar
ventilation (VA), and rating of perceived exertion (RPE) were significantly different (p < 0.05) between
treatment and control groups. The results suggest that the ingestion of caffeine at 7 mg·kg of body weight
prior to submaximal running might provide a modest ergogenic effect via improved respiratory efficiency
and psychological lift.
Birnbaum LJ, Herbst JD. Physiologic effects of caffeine on cross-country runners. J Strength Cond Res.
2004 Aug;18(3):463-5.
Costill DL, Dalsky GP, Fink WJ. Effects of caffeine ingestion on metabolism and exercise performance.
Med Sci Sports Exercise. 1978; 10: 155-158.
Cox GR, Desbrow B, Montgomery PG, Anderson ME, Bruce CR, Macrides TA, Martin DT, Moquin A,
Roberts A, Hawley JA, Burke LM. Effect of different protocols of caffeine intake on metabolism and
endurance performance. J Appl Physiol. 2002; 93(3):990-9.
Doherty, P. M. Effects of caffeine ingestion on rating of perceived exertion during and after exercise: a
meta-analysis. Scandinavian Journal of Medicine & Science in Sports. 2005; 15, 69.
Doherty M, Smith P, Hughes M, Davison R. Caffeine lowers perceptual response and increases power
output during high-intensity cycling. J Sports Sci. 2004 Jul;22(7):637-43. Department of Sport, Exercise
and Biomedical Sciences, University of Luton, Luton LU1 3JU.
Essig D, Costill DL, Van Handel RJ. Effects of caffeine ingestion on utilization of muscle glygogen and lipid during leg ergometer cycling. International Journal of Sports Med. 1980; 1:86-9. Fisher SM, McMurray RG, Berry M, et al. Influence of caffeine on exercise performance in habitual caffeine users. International Journal of Sports Med 1986;7:276-280. Greer F, Friars D, Graham TE; Comparison of caffeine and theophylline ingestion: exercise metabolism and endurance.J Appl Physiol 2000 Nov;89(5):1837-44 Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1. Ivy JL, Costill DL, Fink WJ, et al. Influence of caffeine and carbohydrate feedings on endurance performance Med Science Sports and Exercise. 1979; 11;6-1. Kovacs EMR, Stegen JHCH, Brouns F. Effect of caffeinated drinks on substrate metabolism, caffeine excretion, and performance. J Appl Physiol 1998; 85: 709-715. McLellan TM, Bell DG. The impact of prior coffee consumption on the subsequent ergogenic effect of anhydrous caffeine. Int J Sport Nutr Exerc Metab. 2004 Dec;14(6):698-708. Yeo SE, Jentjens RL, Wallis GA, Jeukendrup AE. Caffeine increases exogenous carbohydrate oxidation during exercise. J Appl Physiol. 2005 Sep;99(3):844-50. Epub 2005 Apr 14. World Anti-Doping Association Caffeine Drug Info: Catechin
Green tea is made up of polyphenols (catechins) and flavonols. The primary catechins found in green tea
with the most potent antioxidant activity are epicatechin (EC), epigallocatechin (EGC), epicatechin gallate
(ECG) and epigallocatechin gallate (EGCG). EGCG makes up 10 - 50% of the total catechin content and
appears to be the most powerful of the catechins. Green tea's antioxidant activity is 25 - 100 times more
potent than vitamins C and E. Green tea is generally standardized to total polyphenol content and/or
EGCG content. For years this extract has been widely studied for its wealth of health benefits including
blood clotting reduction, cholesterol lowering, weight loss and as an anti-carcinogen. Recently green tea
has also shown an ability to improve endurance performance.
A study done on mice investigated the effects of green tea extract (GTE), on endurance capacity, energy,
metabolism, and fat oxidation in mice over a 10-week period. Swimming times to exhaustion for mice fed
0.2-0.5% (wt/wt) GTE were prolonged by 8 - 24%. The effects were dose-dependent and accompanied by
lower respiratory quotients and higher rates of fat oxidation as determined by indirect calorimetry. In
addition, feeding with GTE increased the level of beta-oxidation activity in skeletal muscle. Plasma lactate
concentrations in mice fed GTE were significantly decreased after exercise, concomitant with increases in
free fatty acid concentrations in plasma, suggesting an increased lipid use as an energy source in GTE-fed
mice. Epigallocatechin gallate (EGCG), a major component of tea catechins, also enhanced endurance
capacity, suggesting that the endurance-improving effects of GTE were mediated, at least in part, by
EGCG. The beta-oxidation activity and the level of fatty acid translocase/CD36 mRNA in the muscle was
higher in GTE-fed mice compared with control mice. These results indicate that GTE is beneficial for
improving endurance capacity and support the hypothesis that the stimulation of fatty acid use is a
promising strategy for improving endurance capacity.
In a new Korean study, published on-line in the journal Life Sciences (doi: 10.1016/j.lfs.2005.11.001), the
effect of EGCG on hypoxia-induced apoptosis for human haematoma cells was examined. This study
found Epigallocatechin gallate (EGCG), the main extract from green tea, improves oxygen flow to tissues
deprived of adequate supply.

Hypoxia occurs when oxygen supply to tissue or the whole body is restricted. If cells are denied oxygen for
too long, they die – a process called apoptosis. The most well known form of hypoxia is altitude sickness,
which can occur when travelers go above an altitude of 6,000 – 8,000 feet (1,829 to 2,438 meters). Cells
were exposed to varying concentrations of the tea extract (12.5, 25, 50, 100 micromoles) and the number of
live cells tested. In the control cell culture, 40 per cent of cells died due to lack of oxygen. In the test
groups, although cell death was decreased for all EGCG concentrations, exposure to 12.5 micromoles of
EGCG reduced cell death by 10%. All cells were still alive after exposure to 100 micromoles of EGCG.
The mechanism was theorized to result from green tea preventing the expression of a certain enzyme called
caspase 3, which plays an important role in programmed cell death.
Anderson RA, Polansky MM.; Tea enhances insulin activity. J Agric Food Chem. 2002 Nov
Cooper R, Morre DJ, Morre DM.Medicinal benefits of green tea: part I. Review of noncancer health
benefits.J Altern Complement Med. 2005 Jun;11(3):521-8.
Fujiki H.;Green tea: Health benefits as cancer preventive for humans.
Chem Rec. 2005;5(3):119-32.
Higdon JV, Frei B.;Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions.
Crit Rev Food Sci Nutr. 2003;43(1):89-143. Review.
Katiyar SK.;Skin photoprotection by green tea: antioxidant and immunomodulatory effects.
Curr Drug Targets Immune Endocr Metabol Disord. 2003 Sep;3(3):234-42. Review.
Liao S, Kao YH, Hiipakka RA.;Green tea: biochemical and biological basis for health benefits.
Vitam Horm. 2001;62:1-94. Review.
Murase T; Haramizu S; Shimotoyodome A; Nagasawa A; Tokimitsu., Green tea extract improves
endurance capacity and increases muscle lipid oxidation in mice. Am J Physiol Regul Integr Comp Physiol
2005 Mar; 288(3):R708-5 I Biological Science Laboratories, Kao Corporation, 2606 Akabane, Ichikai-
machi, Haga-gun, Tochigi 321-3497, Japan.
Dimethylaminoethanol (DMAE), related to choline and a biochemical precursor to the neurotransmitter
acetylcholine, is found naturally in fishes like sardines and anchovies. It is reported to have nootropic
effects. DMAE, also known as dimethylethanolamine or Dimethylaminoethanol, can be interpreted to
induce a psychophysiological state of better feeling or well-being on both levels of analysis – mood and
electrical pattern of brain activity.
It is believed that dimethylaminoethanol is methylated to produce choline in the brain. It is known that
dimethylaminoethanol is processed by the liver into choline; however, the choline molecule is charged and
cannot pass the blood-brain barrier. Short term studies show an increase in vigilance and alertness, with a
positive influence on mood. (Pfeiffer, 1957)
Pfeiffer C, et al. Stimulant effect of 2-dimethylaminoethanol; possible precursor of brain acetylcholine.
Science 126(3274):610-611, 1957. [1]
Dimpfel W, Wedekind W, Keplinger I. Efficacy of dimethylaminoethanol (DMAE) containing vitamin-
mineral drug combination on EEG patterns in the presence of different emotional states. European Journal
Medical Research 8(5):183-191, 2003. [2]
Zahniser NR, Chou D, Hanin I. Is 2-dimethylaminoethanol (deanol) indeed a precursor of brain
acetylcholine? A gas chromatographic evaluation. Journal of Pharmacology and Experimental Therapeutics
200(3):545–559, 1977

Quercetin is a flavonoid and, more specifically, a flavonol. It is the aglycone form of a number of other
flavonoid glycosides, such as rutin and quercitrin found in citrus fruit. Quercetin is found to be the most
active of the flavonoids in studies, and many medicinal plants owe much of their activity to their high
quercetin content. Quercetin works to potentiate the effects of both caffeine and nitric oxide.
This flavonol has demonstrated significant anti-inflammatory activity because of direct inhibition of several
initial processes of inflammation. For example, it inhibits both the manufacture and release of histamine
and other allergic/inflammatory mediators. In addition, it exerts potent antioxidant activity and vitamin C-
sparing action. In vitro and animal studies suggest that quercetin inhibits tyrosine kinase and nitric oxide
synthase and that it modulates the activity of the inflammatory mediator, NF-kappaB.
More importantly to endurance athletes, Quercetin acts to potentate the effects of caffeine. Quercetin is
reported to help control cyclo-oxygenase activity. Cyclo-oxygenase activity increases in the body during
periods of high physical stress (Garcia-Mediavilla V et al.). Studies indicate this powerful flavanoid works
synergistically with theobromine and caffeine to further extend the CNS stimulant effects.
MacRae HS, Mefferd KM. Dietary antioxidant supplementation combined with quercetin improves cycling
time trial performance. Int J Sports Nutrition and Exercise Metabolism. 2006 Aug:16(4): 405-19.
Conquer JA, Maiani G, Azzini E, et al. Supplementation with quercetin markedly increases plasma
quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. J Nutr.
1998; 128:593-597.
Hollman PCH, van Trijp JMP, Mengelers MJB, et al. Bioavailability of the dietary antioxidant flavonol
quercetin in man. Cancer Lett. 1997; 114:139-140
Hollman PCH, Gaag MVD, Mengelers MJB, et al. Absorpotion and disposition kinetics of the dietary
antioxidant quercetin in man. Free Red Biol Med. 1996; 21:703-707.
Garcia-Mediavilla V et al,. The anti-inflammatory flavones quercetin and kaempferol cause inhibition of
inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the
nuclear factor kappaB pathway in Chang Liver cells.
Eur J Pharmacol. 2007 Feb 28;557(2-3):221-9. Epub 2006 Nov 15.


Semana Epidemiológica No 31. Manizales, 17 de agosto de 2016 BOLETIN ESPECIAL INFECCIONES RESPIRATORIAS EN CALDAS Contenido Epidemiologia.……………….2 a 5 Caracterización ira en sus cuatro estrategias……….……….6 Iinforme sobre las infecciones respiratorias a semana 31 del año 2016 en el departamento de caldas

Nonparametric bayes modelling of count processes

Nonparametric Bayes modelling of count processes © 2013 by Antonio Canale and David B. Dunson. Any opinions expressed here are those of the authorsand not those of the Collegio Carlo Alberto. Biometrika Advance Access published October 5, 2013 Biometrika (2013), pp. 1–16 Printed in Great Britain Nonparametric Bayes modelling of count processes