W5 - biochemical basis of dietary supplementation Flashcards

1
Q

What is Pharmacokinetics?

Describe what can be shown:

How long does a supplement usually take to wash out?

A
  • How a drug is absorbed, metabolised, distributed around the body and how much of the medication is excreted
  • Allows us to discover when to take a drug:
  • Peak of supplement - indicates when before the event the supplement must be taken(using the supplement in the most effective way)
  • Usually 4-8hrs to wash out
  • Therapeutic range is beneficial
  • Toxic range can cause adverse response
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2
Q

What is Pharmacodynamics?

A

What a drug does to the body:
-Involving receptors, enzymes, ion channels, physiological systems

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3
Q

What are the 3 types of effects that a drug can cause?

A
  • Additive effect – Where two or more substances produce a response equivalent to the sum of the individual effects (e.g., B + C = A)
  • Synergistic effect – Where two or more substances produce a response greater than the sum of the individual effects (e.g., C + D = A)
  • Antagonistic effect – Where the action of one substance diminishes the effect of another (e.g., A + D = C)
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4
Q

Why is more intake of supplements not always better?

What side effect can over consumption cause?

A
  • An appreciation of the dose response relationship is needed to understand when side effects might outweigh potential for performance enhancement
  • Potential for gastrointestinal sides effects with:
    – Sodium bicarbonate
    – Concentrated carbohydrate solutions
    – High protein
    – High fluid volumes
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5
Q

Why is it important that we understand pharmacokinetics and pharmacodynamics?

A
  1. More likely to give correct dose of a supplement = more increase in performance
    1. Administering the dose at the correct time prior to your assessment
    2. Improve the biological process (e.g., exercise performance) of interest with this supplementation approach - varies depending on the event of the individual (marathon runner)
    3. There are inter-individual differences in the pharmacokinetic and pharmacodynamic responses to a given intervention (personalised supplementation needed?)
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6
Q

Which energy system is most likely to be affected by increased creatine supplementation?

How much creatine would an average 70kg adult have?

Which sporting event does this involve? Why is this the case?

A

Creatine: to boost ATP/PCr system
* Creatine (α-methylguanidinoacetic acid) is a non-essential nitrogenous acid compound
* An average 70 kg adult has a total body creatine pool of ~ 120 g
* Most (~ 95%) of the creatine pool is stored in skeletal muscle [65% as phosphocreatine (PCr)]

Mainly impacts sprinters e.g.: 10-20m
- Type II (fast-twitch) muscle fibres contain more PCr - higher ATPase activity and demand in fast twitch fibres
- Creatine is spontaneously and continuously degraded to creatinine at a rate of ~ 1.6% (~ 2 g) per day
- Continued creatine synthesis is required to sustain the skeletal muscle creatine pool

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7
Q

Why do we not want a marathon runner to take creatine supplements?

A

We do not want this for a marathon runner as creatine causes water retention, which increases the athletes weight causing them to have a lower running economy = longer race time

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8
Q

Where does natural creatine come from?

A
  • Creatine can be provided exogenously through the diet
  • A mixed diet provides ~ 1 g creatine/day
  • Dietary sources of creatine: meat and fish, dairy products
    – Beef (~ 4.5 g creatine/kg) and pork (~ 5 g creatine/kg)
    – Cod (3 g creatine/kg), salmon (4.5 g creatine/kg) and tuna (4 g creatine/kg)
    – Milk (~ 0.1 g creatine/kg)
  • Not feasible to eat enough creatine for performance enhancing effects
  • Vegans need to be more careful to ensure the get the correct quantities
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9
Q

What is the recommended dose of creatine?

Why is it not beneficial to take as daily dose of creatine in one go?

A
  • 4-6 x 5 g doses daily with ~ 4 hours between each dose for the first few days of supplementation is optimal to enhance muscle creatine (facilitates myocyte creatine uptake)
  • Plasma [creatine] increases dose-dependently following oral creatine ingestion - approx. 1hr after

consuming 20g in 1 serving it will not be taken up by skeletal muscle(receptors become saturated) and rest will be excreted(through the kidneys)

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10
Q

How can short term supplementation improve performance?

What was reported by Harris et al., 1992 about creatine supplementation?

A
  • After a few days of creatine supplementation muscle receptors become saturated
  • More of the creatine supplemented is excreted in the urine
  • Harris et al. (1992) reported that during a 3 day supplementation period ingesting 6 x 5 g creatine doses daily
    – 40% was returned in the urine on day 1
    – 61% was returned in the urine on day 2
    – 68% was returned in the urine on day 3
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11
Q

What type of athlete benefits most from creatine supplementation?

Why is there less increase in response to creatine in power athletes?

A
  • The ability to increase muscle total creatine and PCr is linked to pre-supplementation levels of muscle total creatine and PCr
    • Power based athletes will naturally have more creatine in their skeletal muscles - higher baseline
    • More muscle mass which is where creatine is stored
    • Even a 20% increase is beneficial to power athletes as it will still boost their key energy system
  • In the study of Harris et al. (1992) there were 2 non-responders who already had high total muscle [creatine] (> 145 mmol/kg dm)
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12
Q

How can we increase creatine uptake into muscles?

A
  • Muscle creatine uptake is insulin dependent
  • Co-ingestion of creatine and simple carbohydrates increases muscle creatine stores
  • Initial studies suggested that each 5 g creatine dose should be accompanied by 93 g of carbohydrate
  • More recent studies suggest that ingesting 1g carbohydrate/ kg bm twice daily can increase muscle creatine stores
    • Insulin brings receptors to membranes which is useful alongside creatine as it increases amount of creatine brought into the muscle
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13
Q

Once stopping creatine supplementation, do the effects continue?

If we want to keep creatine levels up what is the recommended dose?

A
  • There is a ceiling for muscle creatine stores (150-165 mmol/kg dm) and this is achieved within 3-7 days of supplementation with 20 g/day in 5 g servings(loading phase)
  • After ceasing creatine supplementation muscle creatine stores return to baseline within 5-7 weeks
  • A lower (2 g) maintenance dose of creatine maintains muscle creatine stores - keeping the muscle saturated with creatine
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14
Q

What mechanisms enhance performance from creatine supplementation?

A
  • Increased ATP synthesis through PCr dephosphorylation by CK
  • Increased muscle glycogen and ATP supply through anaerobic glycolysis
  • Increased H+ buffering
  • Decreased ammonia production
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15
Q

Why would injecting glycogen not be beneficial to athletes that use the anaerobic glycolysis system?

A

Severe exercise halved the muscle glycogen roughly
- Muscle pH decreased greatly when they relied highly on anaerobic glycolysis
- Increased muscle acidosis - major cause of fatigue

During continued (≤ 10 min) high-intensity exercise there is still sufficient glycogen available in the muscle at exhaustion
– Carbohydrate supplementation is not consistently beneficial until exercise > 2 hours
* pH declines precipitously and is more likely to limit exercise performance at this exercise intensity

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16
Q

What buffer molecule can lower pH?

A

Sodium Bicarbonate: buffer
- Pulls ions out into blood stream
- Creates water & Co2
intramuscular and extracellular buffers help regulate pH homeostatic during high-intensity exercise

17
Q

Describe the intramuscular buffer carnosine

A
  • Carnosine (β-alanyl-L-histidine) is a dipeptide synthesised from β-alanine and L-histidine
  • carnosine was discovered in muscle with its main food source being meat
  • Skeletal muscle is high in carnosine (~ 20-30 mmol/kg dry muscle in an adult) - buffers hydrogen ions in muscles
  • Type II muscle has a higher carnosine content compared to type I muscle. - as there is more anaerobic glycolysis
  • Carnosine is an important intramuscular buffer to regulate pH homeostasis during high-intensity exercise
18
Q

What is the role of β-alanine?

A

Intramuscular and extracellular buffers help regulate pH homeostasis during high-intensity exercise

19
Q

Why do we supplement β-alanine and not carnosine?

A
  • Compared to histidine, β-alanine concentration in the muscle is low and Km for carnosine synthase is higher than histidine
  • β-alanine is rate limiting for carnosine synthesis in skeletal muscle
    • Not the best way to increase carnosine content in the muscles
20
Q

Are β-alanine permanent?

A
  • The wash-in and wash-out periods for β-alanine supplementation are long
  • A maintenance dose is still required
    • Washes in and washes out quite slowly
    • If 1.2g is taken per day it will keep at a maintenance level
21
Q

How can we improve the effects of β-alanine?

A
  • Recent research suggests that combined supplementation with β-alanine (intramuscular buffer) and sodium bicarbonate(extracellular buffer) = an additive effect which will improve high-intensity exercise performance
  • Ideal for middle distance event improvements
22
Q

What is L-carnitine?

Why could L-carnitine be an issue for nonmeat eaters?

Which type of athletes benefit from carnitine?

A
  • L-carnitine (3-hydroxy-3-N,N,N- trimethyl aminobutyrate) is a quaternary amine
  • Carnitine is found in meat food sources
  • 95% of the body’s carnitine is found within skeletal muscle (~ 25 g in an adult)
  • an estimated ~ 75% of carnitine in the body is attained from dietary intake
  • Non-vegetarians ingest ~1mg/kg body mass of dietary carnitine per day
  • Vegetarians ingest ~0.01mg/kg body mass of dietary carnitine per day

Mainly beneficial for long-distance/endurance athletes

23
Q

How can we increase the amount of carnitine that is taken up by muscles?

How long does it usually take to see the effects of L-carnitine? (Chronic supplementation)

A
  • Plasma carnitine declined when taken with insulin
    • Less carnitine excretion in urine - muscle biopsy to show that carnitine was being taken into the muscle
  • When L-carnitine is infused with insulin muscle carnitine content is increased
  • Chronic supplementation with L-carnitine and simple carbohydrates increased muscle carnitine content.
    • Takes half a year to see significant gains in muscle carnitine
    • Must be coingested with carbohydrates for an insulin spike
24
Q

What type of sports see the largest effect of carnitine supplementation?

Describe Chronic supplementation:

A
  • Useful in endurance exercise
  • This is unlikely to benefit performance short-duration high-intensity exercise
  • Chronic supplementation with L-carnitine and simple carbohydrates can improve endurance performance
    • Less glycogen was used when doing the exercise, switching substrate oxidisation to fats (spares muscle glycogen) - leads to performance enhancement
25
Q

How does L-carnitine supplementation work?

A
  • Promotes the translocation of long-chain fatty acids across the
    mitochondrial membranes for β–oxidation in the mitochondrial matrix
    ➢ Mitochondrial membranes impermeable to long-chain fatty acyl-CoA
    ➢ Mitochondrial membranes not impermeable to long-chain fatty
    acylcarnitine
    ➢ CPT I catalyses the reversible esterification of carnitine with long-chain
    acyl-CoA to form long-chain acylcarnitine
  • CPT I is considered to be the rate limiting enzyme for long-chain fatty acid entry
    into the mitochondria and oxidation
26
Q

How does the end result of b-oxidation occur from L-carnitine supplementation?

A
  • Acylcarnitine is transported into the mitochondrial
    matrix by CACT with a 1:1 exchange with
    intramitochondrial free carnitine
  • Acylcarnitine is transesterfied back to free carnitine
    and long- chain acyl-CoA by CPT II
  • The long-chain acyl-CoA then undergoes β–oxidation
27
Q

What is the upper recommended limit of L-carnitine supplementation per day?

A

2g

28
Q

What are the effects of oral L-carnitine supplementation?

A
  • Chronic L-carnitine supplementation does not increase muscle carnitine
  • Orally administered L-carnitine
    has a poor bioavailability
    (<15% for a 2-6 g dose)
29
Q

What are two ways that L carnitine supplementation results can be maximised?

A
  • When L-carnitine is ingested
    with simple carbohydrates, L-carnitine retention is improved
  • When L-carnitine is infused with insulin muscle carnitine content is increased