Lecture 7 (2) - Creatine and b-alanine Flashcards
Creatine - background:
- ~95% located in skeletal muscle
- ~1.2% (1-3g) is degraded to creatinine and excreted daily (mainly in urine)
- ~50% of this loss is obtained in diet
- Remainder of requirement is synthesised from arginine, glycine and methionine
- The brain does not store much creatine – although creatine has implications in concussion recovery
The creatine kinase shuttle system:
Oxidative Phosphorylation (Mitochondria):
ATP is produced in the mitochondria via oxidative phosphorylation
mtCK (mitochondrial creatine kinase) catalyzes the transfer of a phosphate group from ATP to Cr, forming PCr.
Adenine nucleotide translocase (ANT) facilitates the exchange of ADP and ATP across the mitochondrial membrane.
Glycolysis (Cytosol):
ATP is also generated in the cytosol through glycolysis
Cytosolic CK isoenzymes (like CK-g) convert ATP into PCr.
Overall Function:
The Creatine-Phosphocreatine Shuttle:
Mitochondria generate ATP, which is then used by mtCK to produce PCr.
PCr acts as a high-energy phosphate reservoir that can rapidly regenerate ATP from ADP in areas of the cell where energy demand is high, using various CK isoenzymes.
How creatine works:
Creatine is involved in the ATP conversion to ADP
ATP is broken down (limited stores in muscle)
PCr can resynthesise ATP
Convert PCr to creatine through several different mechanisms
1) resynthesise ADP back to ATP
- Allows high intensity exercise to continue
2) glycolysis or oxidative phosphorylation to resynthesise creatine.
3) Creatine converted back into PCr at the cost of ATP.
Useful for repeated bouts of HI exercise
Creatine loading: loading skeletal muscle with creatine to get them to their max levels:
- There is variation between people in how much creatine is in the muscle – different starting levels
- How much levels change based on supplementation also varies
- There is an upper limit to how much creatine can be stored in the muscle
- Creatine is an osmotic molecule – holds water within the cell. Too much of it will increase the volume and the weight of the cell
Supplementation protocols:
- 7 days loading (4 x 5 g/day Cr) followed by 2g/day for 28 days (maintenance dose)
- Muscle creatine can be raised up to 140-155mmol/kg dry mass
- You do not need to take a loading dose to increase creatine stores – you can do it slowly via 3g/day
Co-ingestion with carbohydrate:
- Greater muscle creatine concentrations were seen of simple sugars were provided (5 days loading 4 x 5g/day followed 30min later with 93g simple sugars) – glucose spikes insulin to facilitate the uptake of creatine into the muscle
- Similar results possible with carbohydrate-protein mixtures (protein also has an effect on insulin secretion)
The effects of creatine on glycogen:
- You can influence glycogen resynthesis through creatine supplementation
- Muscle glycogen was 2/3rds greater in the creatine supplementation group compared to the placebo – most of this difference was seen after the first 24hours
- We do not know the cause of this – is the muscle able to take on more glucose?
Creatines effect on performance:
- Maximal work – slight elevation with creatine supplementation
- Amount of work that could be done – significant increase in bout 1 and 2 after supplementation
- Having more PCr in the muscle means HI exercise can be maintained for longer
- Strong association between total creatine and total work – this relationship is linear – the biggest the increase in muscle creatine the bigger the increase in work capacity
- Low dose creatine (2.3g.d-1) for 6 weeks enhances resistance to fatigue (5 sets of 30 concentric knee extensions at 180 degrees)
- RCT that shows low doses of creatine can augment repeated resistance exercise
B-alanine:
HI exercise causes a decreased IM pH from ~7.1 to <6.5
Low pH In certain events can cause fatigue
B-alanine buffers the hydrogen ion
H+ buffering in the muscle:
CHO (Carbohydrates) are metabolized to produce lactate and H⁺ ions as by-products, particularly during anaerobic glycolysis (high-intensity exercise).
The accumulation of H⁺ ions leads to a drop in pH (acidosis), which can contribute to muscle fatigue.
To combat this, muscle fibres utilize physico-chemical buffering systems, including:
Phosphate buffers
Bicarbonate buffers
Peptide/protein-bound histidine, which is where beta-alanine becomes relevant.
Dynamic Buffering in Circulation :
Excess lactate and H⁺ ions are transported out of the muscle fibres into the bloodstream to be buffered in the blood.
The bicarbonate buffering system in the blood helps manage this acid load:
CO₂ + H₂O ↔ H₂CO₃ ↔ HCO₃⁻ + H⁺.
Lactate (La⁻) combines with sodium (Na⁺) to form sodium lactate (NaLa), which can further interact with bicarbonate (HCO₃⁻) to buffer additional H⁺.
Creatine and Buffering:
- The creatine kinase (CK) reaction results in the breakdown of PCr and the regeneration of ATP
- Also as part of this process H+ is consumed:
Hydrogen + PCr + ADP↔ Cr+ATP - So PCr breakdown during high-intensity exercise could contribute to intracellular buffering. The hydrogen ion is mopped up when ATP is created
- As such, increasing muscle creatine stores by creatine supplementation might have a small effect on muscle buffering capacity as well as on ATP regeneration
Carnosine synthesis:
Carnosine acts at the muscle as a buffer to absorb hydrogen ions and reduce the drop in pH seen in HI exercise.
To form carnosine we use histidine and b-alanine
B-alanine can be synthesised in the liver and come through the diet but we supplement with b-alanine to augment carnosine in the muscle because its availability in the blood is very low. There is 25x as much histidine as b-alanine in the blood. B-alanine is rate limiting to carnosine synthesis. This acts inside the muscle, working before the hydrogen ions are exported into the blood.
Beta-alanine supplementation:
- When supplementing with low dose b-alanine, high dose b-alanine and carnosine – we saw an Increase in muscle carnosine in low dose, more of an increase in high dose, and the same increase in carnosine (as high dose b-alanine)
- B-alanine is cheaper to manufacture and maintain
- It appears there is no ceiling to what the muscle can absorb
- A short loading dose of b-alanine will not get you enough of the possible effects
High-intensity performance and b-alanine:
- Muscle carnosine significantly elevated from pre-supplementation: 60% after 4 weeks and 80% after 10 weeks
- Total work during CCT110%: increased 13.0% following 4 weeks and increased 16.2% following 10 weeks
- Increase in muscle carnosine content resulted in an increase in work done
- The capacity to do very HI exercise, is directly influenced by muscle carnosine concentration
- Evidence to show hydrogen production is a limiting factor for HI performance
performance durations + b-alanine supplementation:
- No effect on performance <0.5min
Small but significant improvement in performance 0.5-10min after b-alanine supplementation - Tendency for a very small improvement in performance >10min
