Ergogenic Aids: Framework and Examples (Part II)

if you were to design a new PED, what 2 big things should you consider?

-What type of athlete is it helping?: endurance, speed, or power athlete?

-What physiological mechanism(s) would be affected that result in better performances?

List of ergogenic target sites

-Muscle mass

-Muscle contraction (nerve, EC coupling like at the NMJ)

-Delay fatigue

-Substrate availability (ex: glycogen, creatine)

-Energy availability (more immediate, fat use, or CHO sparring)

-Control muscle soreness or pain (*pain part of brains evol survival instinct)

-Temperature regulation (*more concerned if hot enviornment bc generate a lot of heat)

-Hydration

-Electrolyte balance

-Oxygen delivery (airway, lungs, capillary vasodilation)

• Blood volume, Hct, Hb (for thermoreg or O₂ delivery), VC, more mito, etc.

Fatigue: Organized around power/speed OR endurance events

Power/Speed events

-muscle mass

-CNS & sympathetic stimulation

-acidosis (*ex: Wingate)

-depletion of PCr

Endurance events

-muscle glycogen depletion

-lactate threshold/accumulation (acidosis)

-low blood [glucose]

-fat oxidation rate

-diminished O₂ delivery

-dehydration

High-intensity exercise effects on muscle metabolites

-Force down

-PCR down

-ATP down (usually constant)

-lactate up

*study: stop blood flow than used electrodes to contract muscles

Endurance training adaptations

-increase VO_2max (~15%)

-increase cardiac output (~15%)

-increase mitochondrial volume (2X) (*in slow twith fibers)

-Lactate threshold shifted to higher intensity

-increase ability to use fats (spares glycogen)

*any compound that could mimic these would help

Designing an Aid based on Physiology example: Increase Muscle Mass

We Know

-Requires stimuli (e.g. >75% 1RM and ~8 reps)

-Need increased protein synthesis

• Involves mTOR signaling (*promotes growth), DNA, RNA, protein translation

-Need decreased protein degradation

Increase stimuli:

-Training (*periodized program)

-Creatine (*so get 1 more rep out, training volume slightly higher; water retained, gain 1-2lb)

Increase protein synthesis

-Protein (*MPS higher w/ meals)

-Anabolic steroids (*target genes boost PS)

-Insulin (weaker) (*increase after meal to store)

-Growth hormone -> IGF-1 (weaker) (*naturally higher and lower; high in morning)

Decrease protein degradation

-Anabolic steroids (*down regulate genes in MPB)

-Insulin (*goal is to store, so limits breakdown)

Designing an Aid based on Physiology example: Delaying Fatigue

-FACT: Metabolic acidosis contributes to fatigue

-QUESTION: If you could prevent acidosis, could you do more? (bicarbonate loading…)

effects of acidosis and bicarbonate loading

Intramuscular effects of acidosis

-lower PFK, phosphorylase

-lower Ca²⁺  sensitivity

-lower cross-bridge force output

-lower ATP turnover

-slows recovery rate

*for all: prod less force

Effects of bicarbonate loading

-higher plasma pH (*which can be transmitted to muscles)

-speeds H⁺ and La^- transport from muscle

*lotion: body can absorb through skin

*CO2 + H20 <-> H+ + HCO3- (*CO2 makes cookies/cake puffy)

Bicarbonate Loading: Dr. P bicycle sprint test results

-Not all studies report performance benefits

-dependent on dosing

-benefits maximal exercise of 1-10 min

-GI distress (*so likely never would be used bc threw up)

*left graph: bicarb group higher levels but drop bicarb as use it up

*right graph: concentration H+ higher if no bicarb; pH higher if on bicarb

Bicarbonate Loading: lotion research

-no improvement in blood buffering capacity or exercise performance if apply topical sodium bicarbonate

Bicarbonate Loading: 40km bicycle time trail test results

*ingested bicarbonate and carbohydrate gels 2 hours before, then did a 40km time trial; aerobic but above lactate threshold; forms gel and enteric coated so through stomach and get to SI (so no GI distress)

-Intro: useful if short time period/less than 10 min

-Purpose: 40km time trials

-Methods: 14 male cyclists, RCT, double blind, everyone got placebo and product

-Results: if consumed bicarb were 1 minute faster, increased buffering, no GI issues

-Ken’s Conclusion: $18/serving (worth the money?)

Designing an Aid based on Physiology example: Increasing O2 Delivery

*doping dif contexts, but usually means illegal; more useful for aerobic activity

-Blood doping via transfusion (self or donor)

• increase RBC concentration (Hct=%blood that is RBC, so higher O2 carrying capacity; iron in center)

• RBC live for 4 months; so test RBC age to see if doping (lot of cells the same age=doping)

-Breathing 100% O₂

-EPO (Epogen, Procrit)

• stimulates RBC production (higher Hct) (*made in red bone marrow)

-Roxadustat:

• Brand name Evrenzo, an anti-anemia medication that is a HIF prolyl-hydroxylase inhibitor that increases endogenous production of EPO (*prod more EPO than normal)

-Altitude + training (increases RBC production)

• live high, train low (*hard to train well at high altitude, so go lower to train hard)

*perception factor in everything; still affect of altitude indoors

Increasing Energy Supply

-Carbohydrate availability: feeding before/during competition

*in any sport can become carb deficient; likely if over 1 hour

-Creatine: important for energy production during power/speed events

Creatine: Background and benefits

Background

•Non-essential, liver makes it, meat eaters get 50% of need

•Naturally occurring in animal products (primarily meat)

•Supplementing increase cellular levels (95% in muscle, rest in brain and nervous tissue)

Benefits

•Increased volume of training

•Increased muscle mass

•Increased repeat sprint performance (*rebuild PCr inbetween intervals)

•May benefit brain health

Stimulants: use and examples

Use

-For cognition (focus, alertness, fatigue resistance/central govener)

-Improved reaction time

-As sympathomimetics

• stimulates SNS (ex: higher HR, mobilized fuels; some golfers/shooters take beta blockers to slow down HR)

Examples

-Amphetamine (inc Adderall)

*for ADHD; going to slow before, match up perception and reality

-Ephedrine(legal)/Pseudoephedrine (not legal; congestion) (Ephedra—Ma Huang: reves up metabolism, like taking meth)

-Methylphenidate (inc Ritalin)

-Cocaine

-Modafinil (aka Provigil)

*ex: Rx for army figther pilots

-Caffeine

Caffeine

-May enhance maximal performance

• if < 5 min or > 30 mins (*very short or longer; not good for a 5k)

-May decrease performance due to side effects

• insomnia, heart palpitations, tremors, anxiety, nervousness, GI distress

-Addiction possible (*tradeoffs)

• Withdrawal symptoms evident (*could periodize)

-Diuretic at higher levels

• Heat stroke a concern

*pure caffeine is a diuretic; otherwise having it w/ fluid

*structure: all things made out of the same stuff

is caffeine legal in sports?

-Urinary concentrations tested

-Intake no longer restricted, except by the NCAA (only)

• 15 mcg/ml of urine (NCAA) (*a lot; for reference ex: 1 soda=50mg; 1 cup coffee=100mg; energy drink=200mg)

• Exceeded with 500 mg dose in some 2 hr prior

-Individual variations in metabolism and excretion

-Ergogenic effects are present when urine levels below limits (*don’t need max)

*caffeine effect HR at rest, but not during exercise

study: caffeine and genotype in endurance performance athletes

*if high intensity and consume caffeine: better reaction time; endurance and caffeine= change perception/RPE (so couple seconds faster each mile)

-Time Trial on own: higher caffeine=more improvement

-Time Trail w/ dif genetics that break down caffeine: CC gene people had worse improvement if took caffeine, most people AA (see improvement) or AC (see no difference)

*shows individual basis

Anabolic Agents: background and examples

Background (*overall=masculine effects)

•Important uses clinically

•Includes FDA approved

•Veterinary products consumed by humans

•Banned in the 1970’s

•Popular in anti-aging circles

•Black market

Examples

•Anabolic steroids (various androgens)

•Selective androgen receptor modulators (SARMs)

*increase # of receptors so more effect

•Growth Hormone (and GNRH)

•Beta-HMB (beta-Hydroxy-beta-MethylButyrate)

*prevents lysine from being broken down as easily

Meldonium

-Latvian drug, does not have FDA approval for US usage

-Placed on world anti-doping agency (WADA) list in Jan 2016

-Used to treat coronary artery disease, anti-ischemic

-A metabolic modulator, probably increases angiogenesis (*growing blood vessels, increase O2 delivery capacity)

-Appears beneficial on cerebral circulation and CNS, too (ex: hand eye coordination)

-Entire U18 Russian ice hockey team; Boxers, middle and long distance runners, wrestlers, judo, cyclists, biathletes all tested positive recently; Majority were Russian/Ukrainian athletes

Therapeutic Use Exceptions

-could use something that is banned if have a Rx for a condition

*ex: asthma and inhaler

Evaluating an Ergogenic Aid: Is there any scientific evidence supporting the ergogenic value?

-Are the studies simply basic research done in animals/clinical populations or have the studies been conducted on athletes?

-Were the studies well controlled?

-Do the studies report statistically significant results or are claims being made on non-significant differences or reported trends?

-Do the results of the studies cited match the claims made about the supplement?

-Were results of the study presented at a reputable scientific meeting and/or published in a peer-reviewed scientific journal?

-Have the research findings been replicated at several different labs?

*Major problem in general! (ex: psychology)

-Were the studies done by the company or independent labs? Who paid for the studies?

is the supplement legal and safe? (questions to ask yourself)

-banned?

-long term safety?

-reproductive toxicology?

-side effects?