Sports nutrition and metabolism Flashcards

(284 cards)

1
Q

Key principle of food first?

A

Nutrient dense foods can supply balanced mix of micro- and macro-nutrients

Work synergistically to support absorption

Bioactive compounds present in foods - fibre, polyphenols, vitamins

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2
Q

Rationale for ergogenic aids or supplements?

A

To correct a deficiency Convenience Performance enhancing

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3
Q

Gene doping?

A

CRISPR technology can edit genes

Not a risk right now, takes a lot of genes to make musculature change

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4
Q

Issues to consider when prescribing a supplement?

A

Legality - WADA

Safety - toxicity, more not always better, special populations

Contamination of supplements

Consider what their performance/health goals are

How to monitor it through biomarkers

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5
Q

Performance factors to consider?

A

Type of sport - endurance, team, strengthpower, weight classification/aesthetic

Factors limiting performance

Athlete characteristics

Periodised phase of programme

Environmental conditions

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6
Q

Australian institute of sport - ABCD model?

A

Supported for use in specific situations using evidence based protocol - A
Deserving of further research and could be considered for provision to athletes under a research protocol or case-managed monitoring situation - B
Have little meaningful proof of beneficial effects - C
Banned or at high risk of contamination with substances that could lead to a positive drug test - D

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7
Q

Class A performance supplements?

A

Macronutrients Carbohydrate
Protein

 Electrolytes
 Glycerol  Creatine  Nitrate

 Buffers
 β-alanine (β-alanyl-L-histidine)  Sodium bicarbonate

 Stimulants  Caffeine

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8
Q

What is cannabidiol?

A

One of the many cannabinoids in marijuana or hemp = CBD

Its not THC

Claims (effects) - anti-inflammatory, neuroprotective, analgesic, anxiolytic

Claims (application) - concussion/ sub-concussive injury, performance enhancing (less pain, pacing), sleep enhancing, recovery enhancing

Risk of doping infringement, CBD can be contaminated by THC or other banned cannabinoids

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9
Q

CBD use in rugby?

A

26% of players using, more older players were using it

Goals were to improve recovery/pain or sleep

Only 14% saw an improvement

Unpublished data also shown that 20mg on CBD had no effect on acute or chronic muscle soreness in rugby players

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10
Q

Conclusions on CBD?

A

Significant risk of doping charge

Limited evidence of efficacy

Plausible mechanisms of action

More research is needed

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11
Q

How is vitamin D made?

A

In our skin by converting UVB light, 30 mins per day is enough

Can also be found in lots of food

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12
Q

Cellular effects of vitamin D?

A

Classical actions -
Calcium homeostasis
Bone metabolism
Neuromuscular function

Non-classical actions - 
Immune function
Cardiovascular function
Mitochondrial function
Cellular proliferation and differentitation
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13
Q

Is vitamin D deficiency common in athletes?

A

yes, studies shown especially in indoor athletes

This is also affected by seasonal changes

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14
Q

Roles of vitamin D?

A

Bone health:
Increases calcium and phosphate absorption
Bone mineral density increases with vitamin D

Muscle function:
Calcium kinetics
myoblast differentiation - muscle regeneration
Muscle weakness evident with vitamins D deficiency

Immune function:
Improved macrophage and monocyte function
Increased upper respiratory tract infection (URTI) rate with a poor fit D status

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15
Q

What is measured as a biomarker to indicate levels of vitamin D within the blood?

A

25(OH)D

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16
Q

Vitamin D conclusions?

A

Deficiency or inadequacy is prevalent amongst athletes

Poor vitamin D status is associated with impaired bone health, exercise performance and immune function

Not sure if casual

Vit D3 supplementation may be helpful for those who are deficient, reaching a target serum of 75nmol.L^-1 which is done by having 4000 IU per day

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17
Q

Blood glucose mass (kg), Energy (kJ) and exercise time (min)?

A

0.01 kg

160 kJ

2 min

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18
Q

Liver glycogen mass (kg), Energy (kJ) and exercise time (min)?

A

0.08 kg

1280 kJ

16 min

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19
Q

Muscle glycogen?

A

0.40 kg

6400 kJ

80 min

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20
Q

Fat mass (kg), Energy (kJ) and exercise time (min)?

A

10.5 kg

388500 kj

4856 min

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21
Q

Protein mass (kg), Energy (kJ) and exercise time (min)?

A

12 kg

204000 kj

2550 min

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22
Q

Carbohydrate digestion?

A

In mouth broken down by salivary amylase

Down the oesophagus into the stomach

High levels of acid stop amylase action - no carb breakdown

Move to small intestine where there is pancreatic amylase which breaks carbs down into disaccharides

Sucrase, Lactase and Maltase then break the carbs down into monosaccharides

Monosaccharides transported into the blood and the liver

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23
Q

Monosaccharide absorption for glucose and galactose?

A

Co transported with Na+ from the intestinal lumen via SGLT 1, through the intestinal wall and into the blood via GLUT 2

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24
Q

Monosaccharide absorption for fructose?

A

Intestinal lumen through the intestinal wall via GLUT 5, then into the blood via GLUT 2

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25
What does adipose tissue store?
Triglycerides
26
What does liver store?
80-100g of glycogen but can break this down into glucose and transport in to the blood This is down by glucose - 6 -phosphatase
27
What does the blood store in terms of carbohydrates?
4-5mmol/l (20g) Can be transported into muscle
28
Muscle carbohydrate storage?
Muscle has 300-400g of glycogen, in athletes can go up to 900 g
29
Make notes on glycolysis, TCA and ETC for exam most likely?
ok
30
Is muscle glycogen essential for endurance capacity and obtained from a high carb diet, and features of this?
yes It also depletes quicker with more intense exercise Same with liver glycogen Therefore muscle glycogen is essential for short duration exercise, gets used up so not utilised in longer bouts of exercise
31
Classical super compensation protocol?
Week before a race you would do one hard bout of training, followed by no training at all and 3 days of low CHO intake, then 3 days of high CHO intake before race day Problems: Hypoglycaemia in low CHO = low blood blood sugar Difficult to find food with no carbs GI distress Poor recovery Poor mental state from no training
32
Moderate super compensation protocol?
Slowly decrease training, whilst slowly increasing CHO intake No difference compared to the classical after 60 minutes of exercise
33
Carb loading prior to squash?
Diet high in CHO resulted in Increased CHO oxidation Maintains higher blood glucose Improves physical performance
34
Is carb loading worth it?
Yes for: Repeated sprints Intermittent sports lasting greater than an hour Exercise lasting more than 90 minutes No for: Short and explosive Kess apparent if ingesting CHO during exercise
35
Practical guidelines for carb loading?
Start exercise with sufficient muscle glycogen, don't need way more Eating CHO rich for 2 days prior to a race decrease training EE reduced so not just ear more A carbohydrate intake of 5-7 g/kg per day seems to be sufficient in the majority of cases (with low EE) GI athletes need to be careful
36
CHO intake hours pre exercise?
Maximise glycogen in liver and muscle Improves performance CHO are most important 1-4g/kgBM - lower if very close to the event Avoid low GI and avoid fat, need to get all food out of stomach before running to avoid runners trots Practice the routine
37
Physiological effects of CHO intake hours pre exercise?
Transient fall in plamsa glucose at exercise onset Increased CHO oxidation and accelerated glycogen breakdown Blunting of Fatty acid mobilisation and fat oxidation - good for short exercise as want to prioritise carbs Important if cannot take CHO in during exercise
38
Physiological effects of CHO intake 30-60 min pre exercise?
Causes large rise in plasma glucose and insulin Which may then lead to hypoglycaemia during exercise This is due to large rise in plasma glucose and insulin, which can then lead to reactive/rebound hypoglycaemia during exercise Can manipulate of ingested CHO to help tis (lower are better), also low GI food and just don't eat This is hypothetical and performance should be fine
39
Goals and considerations when taking in CHO during exercise?
Prevention of the depletion of blood glucose, and muscle and liver glycogen Maintain hydration Duration of event? How much CHO? (duration, intensity, GI ability) Type and form of CHO? (gel /solid/ monosachharide
40
When you have low carbs do you have to rely on free fatty acids and glycerol more?
yes
41
Is it possible to have performance benefits from in exercise CHO intake but not see an increase in CHO levels in plasma?
Yes will find out why in a few videos time
42
Exogenous galactose versus oxidation during exercise?
Higher levels of oxidation of glucose than oxidation
43
Oxidation of ingested carbohydrate?
It doesn't keep on getting bigger the more carbs you eat, maxes out round 1g/min can't digest it quick enough, or absorb it ``` Rapidly oxidised: (up to 1g/min) - Glucose Sucrose Maltose Maltodextrins Amylopectin ``` Oxidised at lower rates (up to 0.5g/min) ``` Fructose (liver) Galactose (liver) AMyose Isomalutose Trehalose ```
44
What can be done to increase ingested carb oxidation rate?
Combined ingestion - means that different transporters are utilised
45
This means there is now very rapidly oxidised carbohydrate mixes ( >1g/min) which are?
Glucose and fructose (>60g/h glucose) Maltodextrin and fructose (>60g/h maltodextrin) Glucose, sucrose and fructose (>60g/h glucose and sucrose) If you can tolerate higher levels of carbs (120g/h) then during hard exercise can reduce exercise induced muscle damage markers such as creatine kinase, lactate dehydrogenase, GOT Also performance is enhanced by using combinations
46
Does the infusion of CHO increase exercise performance?
no
47
Features of brain imaging when glucose compared to a sweetener is used as a mouth rinse, and does glucose increase cycling time?
Glucose activates parts of the brain which improves performance LAB REPORT IMPORTANT Glucose increases power and TT time when cycling, works better when you are in a fasted state
48
Practical application of CHO during exercise?
``` Mix and match of: Water CHO drinks Gels Bars FOod ``` Low in fat and fibre Protein if over 4 hours long Absolute amount not per bodyweight - it's about how quickly you can get it in 200ml every 20 min = better than 50ml every 5 min, makes a balance between stomach too full and just right Practice is most important
49
Conclusions on CHO use on exercise performance?
CHO can improve endurance capacity over 2 hours, but also high intensity exercise lasting around 75 min CHO ingested during exercise will spare liver glycogen and can completely block hepatic glucose output Exogenous CHO oxidation rates of a single CHO peaks at 1-1.1 g.min^-1 Ingestion of multiple transportable CHO can increase exogenous carbohydrate oxidation rates by 20-50%
50
Features of triglycerides?
Major storage from of fats in the body 3 fatty acids react with one glycerol molecule to produce a triglyceride molecule This is done via a condensation reaction = esterification (water is removed)
51
Features of carbon chain length?
Fatty acids vary in (carbon chain) length and can be classified as short (4 or less) (SCFA), medium (6-12) (MCFA) or long (>14) (LCFA) The longer the chain length, the more solid and less liquid a fatty acid becomes at room temperature More we eat is long chain fatty acids
52
Saturated vs unsaturated fatty acids?
saturated = all hydrogen bonds Unsaturated = missing hydrogen bonds (has double carb bonds)
53
What are trans fats?
In nature they are cis Trans form due to processing e.g. heat and light
54
Essential/non-essential fatty acids?
Essential = can't be made in the body so has to be obtained by the diet Non-essential = can synthesis in the body from specific precursors Omega end = the end away from the Carboxyl complex Omega number = number of carbons away from the omega end in which the closest double bond occurs
55
n-3 and n-6 polyunsaturated fatty acids are incorporated into cell membranes, what effect does this have on cell function?
The ratio of n-3/n-6 PUFA in cell membranes leads to different set of intracellular mediators produced Higher n-3 leads to less inflammatory mediators produced Studies in illness, disease in human and animal confirm this effect, which is modulated by dietary intake
56
Features of adipose tissue?
Provides a basically infinite store of energy during exercise
57
Features of lipoproteins?
Fat has to be transported in aqueous solution (blood) Done via chylomicrons You have very low, low and high density lipoproteins
58
Should learn all of first year cards
ok
59
Can you generate ATP from fat anaerobically?
NO Fat must go through complex set of regulatory reactions to get into the mitochondria, then can enter the TCA cycle to produce ATP So its slower than producing energy from carbs
60
Describe long chain fatty acids getting into the mitochondria and therefore being able to produce ATP?
Fatty acid translocase/CD36 and fatty acid binding protein take the long chain fatty acids from circulation into the cytosol Join a pool from the intramuscular triglyceride store as well The long chain fatty acids are very inert so become activated by Co enzyme A (CoASH), forming Acyl-CoA This can now enter the mitochondria through the carnitine shuttle, achieved through the CPT1, CACT, and CPT2 enzymes Ready to undergo beta oxidation to make ATP This is why fat can't sustain contractions at 75% VO2 max, it is too sluggish
61
The athletes paradox?
As we exercise we reduce the amount of adipose tissue we have Oxidative capacity and insulin sensitivity are markers of good metabolic health as we exercised more, restricted calories, are metabolic health increases, and if we are inactive, obese and on high fat diets it would decrease The more fat we get the more is stored as intra myocellular lipids as expected at one end of the scale As you get leaner the intra myocellular lipids levels drops, but when you keep on training on the scale of athlete they increase above what someone who is obese or type 2 diabetic
62
In athletes how is the intra myocellular lipids stored in the muscle compared to that of an obese person?
In athletes stored directly proximal to the mitochondria Also in athlete normally in smaller droplets = larger SA to volume ratio so can be used quicker Therefore most readily available fat store in the body Obese individual harder to access the fat and use it effectively
63
Different types of fat as fuel?
Plasma fatty acid - 0.004kg, 16KJ Plasma triacylglycerol, 0.004kg, 160 KJ Adipose tissue - 12kg, 40,400KJ Intramuscular triacylglycerol - 0.3kg, 10,800 KJ
64
What happens when you go over 65%-80% of VO2 max?
Before that use carbs and fats equally After that fats drops massively and carbs is increased
65
What are the possible limitations to fat oxidation during exercise?
Want fatty acids that can be transported to the muscle for fuel These are made from lipoprotein lipase breaking triglycerides, or Adrenaline released by exercise causing lipolysis through hormone sensitive lipase causing triglycerides to turn into fatty acids Increase in insulin (released after a meal) causes lipogenesis, fatty acids turned into triglycerides Problem is actually that fewer fats actually being able to get into the muscle cell - even though the supply of fats is enough The ability of the cell to take them up is not actually impaired, so the decline must be intracellular Co enzyme A exists in small amounts in the cytosol and mitochondria to form Acyl-CoA, but it is also needed for beta oxidation of Acyl-CoA to Acetyl-CoA Co enzyme A also needed in the carbohydrate pathway, when this increases so does this demand Same problem with Carnitine which takes Acyl-CoA across the mitochondrial membrane, it is also required on the carbohydrate side to form acetlycarnitine
66
The more trained we get do we utilise fat more?
yes. it enhances fat oxidation
67
What is Fatmax?
Where fat oxidation peaks Around 50-65% achten et al 2002
68
Does fat oxidation increase with exercise duration (fasted state)?
yes
69
What can a nutritionist potentially do?
Increase endogenous fat availability, increasing fat oxidation and spare carbohydrate - good for performance Can we increase this in the diet and should we?
70
What happens when pre exercise fat feeding (+heparin which helps them to be converted to fatty free acids) occurs?
Increases fat oxidation, and spares muscle glycogen use Without heparin does not help, as only triglyceride levels have increased as not being converted quickly to fatty free acids Overall pre exercise fat feeding does not help exercise performance
71
Take home points on acute fat feeding?
It's not easy to increase fatty acid availability When increased you do increase fatty acid oxidation This doesn't help with exercise performance Regardless of the length of chain of fat feeding Why doesn't it help? and if supplementing is not possible can chronic feeding be used as a practical strategy
72
3 day high fat diet on cyclists has what effect?
Favourable changes in substrate use with high fat diet They have adapted to be able to utilise fat more effectively
73
Does more fat in diet result in more optimal storage of intramuscular triglyceride stores and glycogen stores?
No, need a set amount in the diet to maintain IMTG stores, and too much and impair glycogen storage
74
Does a low fat diet result in more glycogen utilisation?
yes
75
Over 7 weeks what improved cycling performance more, the high carb or high fat diet?
High carb by far.
76
Baseline knowledge on low fat intake and high fat intake?
If too low: There is progressive depletion of IMTG Minimum fat intake is required to maintain IMTG stores ( a key energy source for endurance performance) If too high: Results in greater fat oxidation Also results in lower muscle glycogen storage This reduces performance, particularly during higher intensity events which rely on carbohydrate oxidation This could also be due to a decrease in the efficiency of CHO use during more intense exercise
77
A theory on how to get the best out of both high CHO diet and high Fat diet?
Have people of high fat diet in weeks leading up to performance so adapt to be able to perform more fat oxidation Then before performance have a high CHO diet to replenish glycogen stores Because: Potentially elevated ketones are shown that they increase RPE High fat diet make it difficult to reach a 'top gear', as their ability to move carbohydrate through the rate limiting step of pyruvate dehydrogenase is reduced The high fat diet has deprimed the carbohydrate adaptations the body has
78
Conclusions on should you have a high fat diet or high carb diet?
High carb is better, good endurance exercise is also normally performed higher than 75% VO2 max as this is strongly CHO dependant So under most conditions Fat adaptation is not useful for exercise performance
79
Caffeine mechanisms to improve exercise performance?
Blood: Increased free fatty acids, means less carbohydrate stores used Muscle: Altered {K+} Blood lactate concentration Increasing Ca handling = increasing the power of muscle contractions Brain: Increased motor unit recruitment Adenosone antagonism = decreased rpe and pain Increases reaction time, alertness and mood = anti fatigue effects
80
What are the factors that limit repeated sprint performance?
Phosphocreatine supply Low muscle pH - acidosis Extracellular potassium accumulation - altered excitability Central fatigue
81
How much ATP do we produce a day?
Our body weight If very active can double;e or triple
82
Why do we care about the integration of fuel metabolism?
The integration of fuel metabolism is crucial to generating large amounts of ATP Important in the current day
83
What do we mean by the intergration of fuel metabolism?
At any time point the energy required by the cells of our body (metabolic rate) is almost always provided by both fat and CHO utilisation Different circumstances can require different amounts of energy At any given energy expenditure there can be a different contribution of dat and CHO to this energy expenditure
84
Importance of skeletal muscle in fuel metabolism?
Skeletal muscle is 40-50@ of body mass Responsible for 20-30% of resting oxygen consumption Mediates over 75% of all insulin mediated glucose disposal under normal physiological conditions Primary depot for this disposal of nutrients
85
What's the Randle cycle?
Fat is boss in the integration of fuel metabolism - under most conditions it's what regulates metabolism over carbohydrates Fatty-acid pathway can inhibit the glucose pathway The acceleration of fat metabolism happens over carbs when we are fasting End product inhibition, fatty acid cycle produces Acetyl-CoA, which is also the end product of glucose metabolism, so if the glucose pathway isn't even working hard there is an imbalance between pyruvate which should be converted into the abundant acetyl-CoA which has now been made harder Acetyl-CoA also enters the TCA cycle and one of the products it produces is Citrate, which in excess diffuses across the mitochondrial membrane into the cytosol, where it inhibits phospofructokinsase, and essential enzyme is glycolysis This results in a build up of glucose-6-phosphate, which inhibits hexokinase which is required to activate the glucose molecule Empirical data supports all of this
86
Empirical evidence supporting the randle cycle?
Increasing plasma FFA (via lipid and heparin infusion): ž (Odland et al, 1998, 2000). • Suggests regulation at PFK. ž 33% ↓ thigh glucose uptake during moderate intensity knee extensor exercise (Hargreaves et al, 1991). • Suggests regulation at GLUT4. ž ↑ fat oxidation by 15% and ↓glycogenolysis by 50% at >80% VO2max. ↔ PDC activity and muscle contents of acetyl-CoA, citrate, and G-6-P. ↓ free ADP and AMP. (Dyck et al, 1993, 1996; Romijn et al, 1995). • Suggests regulation at Glycogen phosphorylase.
87
Insulin stimulated glucose uptake?
Eat carbs meal Carbs digested and absorbed as glucose which is distributed in circulation As glucose passes by the pancreas, pancreatic beta cells release insulin Glucose is impermeable so needs an active transporter (insulin) More simple carbs = quick insulin peak (easier to breakdown) More complex carbs = more prolonged peak (harder to breakdown) Insulin attached to insulin receptor on cell membrane Phosphorylation and therefore activation of IRS-1 IRS-1 stimulates PI3kinase, this stimulates GLUT4 (a muscle specific transporter) to go from vesicles within the cell into the cell membrane PI3kinase also stimulates the protein AKt, which stimulates GLUT4 as well GLUT4 makes the cell membrane essentially permeable to glucose Akt also directly regulates the pyruvatedehydrogenase complex
88
3 routes the initial glucose molecule can take?
Aerobically converted from pyruvate into acetyl-CoA Anaerobically converted from Pyruvate into lactate Stored as glycogen
89
Does the feeding of glucose ( so not being in a fasted state) disrupt the randle cycle?
Yes, it helps to reverse the randle cycle But it only impairs oxidation of long chain fatty acids, not medium chain This switch is controlled by CPT1
90
Molecular mechanism how the fed state reverses the randle cycle?
Rise in glucose results in an increase Acetyl-CoA Produced in excess to what the TCA cycle can handle So it is converted by the ACC enzyme into Malonyl-CoA which inhibits CPT1
91
Data saying that malonyl-CoA is not involved?
>2fold ↑ in fat oxidation (due to depleted pre-exercise muscle glycogen content) during exercise at 65% VO2,peak. ↔ muscle malonyl-CoA compared to control. (Roepstorff et al, 2005) ž No association between muscle malonyl-CoA content and fat oxidation rates during prolonged moderate-intensity exercise or graded-intensity exercise. (Odland et al, 1996, 1998; Dean et al, 2000) so doesn't work in humans
92
Free carnitine hypothesis?
Acetyl-CoA converted into acetylcarnitine and moved into the cytosol by CAT and CACT reacting acetyl-CoA and Carnitine Acetyl-CoA can act as a metabolic sink CoA is also produced which can be used by the mitochondria This overall causes a decrease in free Carnitine, so can't act as a cofactor for CPT1 to shuttle fatty acids (acetyl-CoA) into the mitochondria -this is the limiting step everyone believes right now
93
Claims around carnitine supplementation?
Broad et al. (2005) found no effect of oral L-carnitine supplementation for 4 weeks (3g/day) on carbohydrate and fat metabolism or on exercise performance Vukovich et al. (1994) reported no significant effects on fat or carbohydrate metabolism during exercise at 70% VO2max after 14 days (6g/day) supplementation of L-carnitine. Wächter et al. (2002) also concluded that oral L-carnitine supplementation for 3 months (4g/day) did not affect exercise performance. Importantly, Wächter et al. (2002) and Vukovich et al. (1994) reported that L- carnitine supplementation did not alter muscle carnitine content. Does not work from these studies, it works basically only in the muscle, so when you digest it there is an unfavourable concentration to get more in the muscle So you need molecules that bring the carnitine into the muscle, can use carbohydrates to do this Ben wall and colleagues shows it can work when it is up taken, can alter fat and carb oxidation, and can increase exercise performance by saving glycogen stores through driving fat oxidation (only lower intensities), but at higher % of Vo2 max where carnitine is a limiting factor for fat oxidation, it didn't actually help, what it did was reduce lactate accumulation What carnitine did was change its role from being used in CPT1 translation to the mitochondria, or it's role as a acetyl buffer depending on glycolytic flux So higher glycolytic flux (higher work intensity) drove carnitine to help form a metabolic sink for acetyl coA, more of it means it can be done in larger quantities, reducing pyruvate quantities and therefore lactate accumulation
94
What is insulin resistance?
The reduced responsiveness of skeletal muscle glucose uptake to normal circulating levels of insulin Can also be viewed as... Impaired ability of insulin to stimulate glucose oxidation (via PDC) Impaired ability of insulin to stimulate microvascular perfusion Impaired ability of insulin to stimulate amino acid uptake into muscle cells Impaired ability of insulin to inhibit muscle protein breakdown. Makes it harder to get glucose into the cell, therefore results in it being harder to use it to generate energy
95
Some techniques at measuring insulin resistance?
Single blood sample Ratio of insulin to glucose in your blood using an equation Healthy in fasted = low in both Diabetes type 2 = high insulin and high glucose as it just isn't enough to get the glucose in the cell Or high glucose low insulin, as the pancreas has been stimulated so much it can't release much anymore One technique is looking at glucose disposal rate Gold standard is hyperinsulianemic clamp technique
96
Measuring insulin resistance, the hyperinsulianemic clamp technique?
Induce artificial high levels of insulin pumped into the body Glucose chased away into peripheral cells, so you inject glucose as well and look at the rate in which it gets put into cells Athlete will have fast rate Obese will have slow rate
97
Features of type 2 diabetes and insulin resistance?
Insulin resistance is usually brought about by increased energy intake, physical inactivity and/or the development of being overweight and/or obese. ž Insulin resistance is the direct precursor to frank type 2 diabetes. ž Type 2 diabetes is defined as resulting from a defect in both insulin sensitivity and ž 80% of type 2 diabetics are obese ž 2.75 million people in the UK now have diabetes, 2 million of which have type 2 diabetes. The total is forecast to climb to four million by 2025. ž Diabetes accounts for approximately a tenth of NHS budget each year, a total exceeding £9 billion. ž The complications of diabetes are numerous and include amputation, heart disease, kidney failure and blindness.
98
What is metabolic inflexibility?
Obese people suffer from it From fasting to insulin stimulated they can't oxidise the glucose they have digested Can't switch between fat and carb oxidation
99
Lipid overspill theory (following on from Randle cycle)?
Big lipid droplets form in muscle Broken down to acyl-CoA Athlete can turn these over Obese can't, resulting in an accumulation of fatty acid intermediates, such as Ceramide and Diacylglycerol These stimulate the JNK pathway which can directly inhibit the IRS-1 which is needed for to pathway of insulin creating an effect within the muscle cell The IkKB and PKC pathways do the same to IRS-1 Overall this exacerbates the cycle build up of lipids
100
What's the inflammation theory?
Excess lipid and adipose tissue release Il-6 and TNF-a cytokines can interfere with insulin signalling Interacts with JNK pathway as well
101
What can't obese individuals oxidise?
Muscle and plasma triglyceride Can do endogenous carbohydrate and plasma FFA
102
When we do exercise without insulin being present (haven't just had a meal) is glucose still used?
yes, so it is contraction stimulated glucose uptake Contraction increases concentration of Ca2+ and turns ATP broken down into AMP and ADP, this changes the charge of the cell, this ratio tells AMPK what to do AMP accumulates, AMPK tells the cell to breakdown Glycogen to provide ATP AMPK also tells GLUT4 to go to the membrane, and stimulates CPT1 to shuttle fats into the mitochondria Ca2+ increase stimulates PDC increase activity, as well as the enzyme CaMK which increases GLUT4 translocation the cell membrane
103
Does exercise increase insulin sensitivity in obese individuals?
yes
104
Type 2 diabetes pharmacological approaches?
Secretagogoues: Sulphonylureas Meglinitinides Exogenous insulin Sensitisers: Biguanides Thiazoliddinediones AICAR Peptide analogous/agonists Exenatide These work at the metabolic level to increase metabolism
105
What are proteins?
Chain (polymer) of amino acids Arranged into primary, secondary and tertiary (and quaternary) structures Contain Nitrogen
106
How are proteins made?
Transcription Translation (initiation, elongation, termination) Post translational modification
107
What do proteins do?
``` Provide structure Hormones Antibodies Transporters Enzymes Movement ```
108
(muscle) protein synthesis?
The creation of new proteins from amino acids (as a result of initial transcription of the DNA)
109
(muscle) protein breakdown?
The degradation of whole proteins back to constituent amino acids
110
(Muscle) protein balance?
The net result of muscle protein synthesis and muscle protein breakdown (synthesis -breakdown)
111
Amino acid oxidation?
The breakdown of intracellular amino acids for energy production If oxidised not available for protein synthesis
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Amino acid uptake?
The rate of transport of amino acids from one pool (eg. the plasma) to antlers (e.g. the muscle cell)
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Amino acid utilization?
The amount of dietary amino acids (obtained from dietary protein) that is used by the tissue and organs of the body for the above processes
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The central dogma?
DNA to RNA = transcription RNA to Protein = Translation Results in a trait
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Essential amino acids? (essential means have to come from the diet, can't synthesis them)
``` Valine Isoleucine Leucine Lysine Methionine Phenylalanine Threonine Tryptophan Histidine ```
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Conditionally essential? (clinical situations where an amino acid can't be synthesised, extreme exercise can result in this as well)
``` Glycine Arginine Glutamine Proline Cysteine Tyrosine Serine Asparagine ```
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Non essential (can synthesise them)?
Glutamic acid Alanine Selenocysteine Aspartic acid
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Primary through to quaternary?
Primary = polypeptide chain order of amino acids, held together by peptide bonds that are made during the process of protein biosynthesis Secondary = B pleated sheet or alpha helix, hydrogen bonds Tertiary = The tertiary structure of a protein refers to the overall three-dimensional arrangement of its polypeptide chain in space. It is generally stabilized by outside polar hydrophilic hydrogen and ionic bond interactions, and internal hydrophobic interactions between nonpolar amino acid side chains quaternary = The quaternary structure of a protein is the association of several protein chains or subunits into a closely packed arrangement
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Amino acid structure?
Carbon skeleton Top of skeleton = COOH On the right = NH2 On the left = H On the bottom = R chain, this characterises it
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What happens to the amine group when it gets oxidised?
It's removed by urea synthesis in the liver, then excreted as urine So the amino acid can actually be oxidised
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Leucine oxidation?
The enzyme KIC via transamination and decarboxylation turns Leucine into isovaleryl - CoA with the byproducts glutamate and Co2 This then turns into Acetyl CoA or Acetoacetate
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Protein turnover described?
Intake protein through diet (50-100g a day) which forms plasma amino acid pool via digestion and absorption These amino acids are uptake by cells forming an intracellular amino acid pool This is when protein synthesis now occurs, (350g/day) Protein breakdown is also occurring going into the intracellular amino acid pool
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Inter-organ nitrogen transfer?
Amino acids and ammonia go from the GI tract to the liver Amino acids go from the GI tract to skeletal muscle, breakdown of proteins here produces alanine which turns into glutamine and goes to the kidneys where glujconeogeneis occurs and glucose is formed which goes to the liver Liver excretes urea, glucose, triglycerides, and proteins
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What percent of proteins never reach circulation because use to synthesis proteins in the GI tract
40-50%
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2 major methods to look at protein metabolism?
Nitrogen balance: Nitrogen excretion = nitrogen intake Need to know exactly what's being eaten, and what is being excreted (Sweat, urine, faecaes) You don't know what tissues storage is occurring in or what time Stables isotopes: Label a specific amino acid can trace where it is in the body eg. 13C-Leucine Can see how much is uptake from plasma amino acid pool into the intracellular amino acid pool Can see how much undergoes oxidation Can see how much incorporated into muscle protein through synthesis Can also see how much of this protein is then broke down
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Factors influencing protein turnover?
``` Habitual diet Protein intake Energy intake Hormones - insulin, steroids such as testosterone Exercise ```
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Potential roles of dietary protein in sports and exercise?
``` Muscle hypertrophy žMuscle strength žImmune function žCentral fatigue žGlycogen re-synthesis žAdditional energy during exercise žSpecific function of individual amino acids žEffects on muscle damage žOxidative damage žIncreasing the synthesis of specific proteins? Mitochondrial/oxidative proteins? ```
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What percent of muscle protein is turnover every day?
1-2% per day (300g-600g muscle tissue)
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What does endurance exercise do to muscle protein metabolism?
During exercise amino acid metabolism increases (still low compared to carb and fat metabolism, it's 1-10%) to produce energy, it's lower pre and post exercise Therefore whole body protein synthesis is higher pre and post exercise When we begin endurance exercise the priority of the tissue is to produce energy = catabolic state Same showed on a training day in which nitrogen balance goes negative
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Effect of endurance exercise and CHO/Protein feeding during exercise?
8 physically active overnight fasted young men 2 trials one with and one without protein (both have carbs) 2h rest, 3h exercise at 60% VO2 max, 3h recovery Leg phenylalanine kinetics, fractional synthetic rate looked at No decline seen in protein synthesis as both were fed with carbs, but protein showed far larger protein synthesis. Exercise makes protein synthesis increase when having protein, but the breakdown from exercise is still too much that it's still net negative Protein breakdown was the same on all conditions
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When protein synthesis is high does that mean that the net result is positive?
Not necessarily, have to look at breakdown as well
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What is the relevance of improving muscle protein balance for the endurance athlete?
Adaptation to the mitochondria within the muscle = improved oxidative capacity More mitochondria/ better functioning mitochondria Oxidative enzymes in higher concentrations in endurance athletes compared to resistance trained
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What did the study looking at acute and chronic effect of resistance and endurance training?
Training one leg to do endurance work compared to the other which is doing resistance will increase the endurance one endurance capacity and not the other sa as much
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What does endurance training cause and what does resistance training cause?
Endurance = increase in mitochondria Resistance = increase in myofibrillar proteins
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Effect of CHO/Protein during recovery from endurance exercise? (Breen et al, 2011)
Was found that protein increases myofibrillar but not mitochondrial protein synthesis - so not as good for the endurance athlete This evidence is not that researched however, seems still essential to not spend days in negative protein balance, Overall the findings in meta analysis are conflicting
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Does endurance exercise generate negative net protein balance?
yes
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IN THE EXAM??? What is the relevance of protein balance during exercise for the ultra-endurance athlete
ok
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What is central fatigue their?
Theory on how protein improves endurance exercise performance Its that fatigue may be associated with inadequate central nervous system drive to the working muscle Main theory is Serotonin Central Fatigue Hypothesis: Increased brain 5-hydroxytryptamine (5-HT) (Serotonin) concentration causes a deterioration in performance Serotonin synthesised in the brain from the amino acid tryptophan
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Mechanism of Serotonin Central Fatigue Hypothesis? (in reverse)
Serotonin interferes neural drive - causing impaired CNS function, reducing exercise performance Serotonin is directly affected by Tryptophan (it's amino acid pre cursor) that arrives at the brain through the blood Brain barrier using a selective transporter This selective transporter is not very specific, and also allows other amino acid chains to cross the barrier, therefore there is competitive inhibition So less free tryptophan will get across the blood brain barrier if there are branch chain amino acids present Tryptophan circulates the body bound to Albumin and free fatty acids BCAA concentration depends on dietary protein intake and exercise Exercise causes more FFA to be released from the adipose tissue which binds onto Albumin increases the ratio in favour of tryptophan We are using the BCAA for exercise, so that makes the ratio worse BCAA's again
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Can you use BCCA for improved exercise performance?
Blomstand et al 1991 Looked runners, only improved slower runners performance, but these slower runs all had lower rates of CHO ingestion as well
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What did VAN HALL ET AL 1995 show?
That placebo, tryptophan, and BCAA supplementation all had the same to time to exhaustion during cycling
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So does protein help during exercise?
Only if you have insufficient energy from food, and carbohydrate is better and easy to supplement with during exercise
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Is lean body mass conserved with increased protein take when in a calorie deficit?
In control body mass, fat mass, and leanness all decreased With increased protein, body mass reduced less, fat mass reduced the same, and lean mass decreased far less
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What did the study "Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss"?
You can be in calorie deficit and gain muscle 4 weeks of 40% hypolcaloric diet to induce weight loss 1.2 g protein per kg bw vs 2.4g protein per kg bw Resistance and HIIT training 6 days pre week In both Fat mass and Body mass dropped Protein high diet increased lean mass, the normal protein maintained lean mass
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So do endurance athletes require increased protein?
Meredith et al, 1989 Looked at 0.6, 0.9, or 1.2g protein/kg/d in endurance trained athletes Only when you got to 1.2g per day they were really in a nitrogen positive balance, showing could be making the adaptations Most endurance athletes surpass this from their diet anyways, so it's not normally a concern ``` So RDI = 1.2-2.0 g/kg Dependent on: Mode/intensity/duration of training Protein quality Likely that adequate energy in the diet = adequate protein, without supplementation ``` Timing relative to exercise is important: Protein ingestion in close proximity to exercise may facilitate muscle reconditioning Protein feeding during exercise does not appear to enhance exercise performance assuming adequate CHO is consumed To lose weight without losing muscle should have higher protein diets
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Tarnopolsky et al 1992 said what RDA protein for strength trained athletes?
1.76/g/kg/d for optimal adaptations
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What are the building blocks and anabolic signal for muscle to be built?
Amino acids Eating high protein meal will increase protein synthesis for up to 5 hours
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Describe regulation of skeletal muscle mass?
You eat a meal Muscle protein synthesis goes up Insulin released which inhibits muscle protein breakdown Over time this will drop and your fed gains reduces This goes up and down resulting in a balance that is stable overall in a normal individual (oscillation) So there is mild anabolism and catabolism
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Normal turnover of protein every day and then compared to resistance trained?
Normal = 1-2% per day = 300-600g muscle tissue Following resistance training = 2-3% per day (600g-900g) But nutrition allows a positive balance and this net muscle protein accretion (hypertrophy)
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What happens to muscle protein synthesis after exercise?
Decreases during exercise Then after exercise increases above basal Exercise also increases breakdown levels over the next few days (adaptations taking place)
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Without nutrition what does exercise do?
Cant ever be in a positive protein balance no matter how hard you train
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The synergistic effects of exercise and nutrition?
If you only train one arm, there will still be positive muscle protein synthesis in your other arm
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Does presleep ingestion compromise the muscle protein synthesis response to protein ingested the following morning?
no More of what protein you eat after exercise will always become more muscle than normal
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Meta analysis on does protein favour muscle mass and strength when resistance training?
Yes it does, small but significant
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Questions to ask when looking how do we maximise the post exercise muscle protein synthetic response?
Amount? Type? Other macronutrients? Food? Timing?
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Post exercise dose response study no how much protein you need for it to not be a rate limiting step?
Around 20g, going up to 40g only increases it a little bit more, this 40g will become more needed when doing a whole body workout Therefore its more about the muscle you activate, rather than the amount of muscle you have
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Does carbohydrate assist with anabolism?
Insulin release, increases perfusion to the muscle (amino acid amount getting delivery to the cell and into the cell), Depends if they are rate dependent steps However in reality they don't help, the already modest insulin response from protein is enough to stimulate maximal muscle protein synthesis
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Does fat assist with anabolism?
No, it just slows down the digestion and absorption of amino acids
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4 factors that will allow for an anabolic response to dietary protein?
Postprandial insulin response (carbs isn't need to make it valid) Bioavailability Digestion and absorption kinetics Amino acid composition
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Proteins in milk?
Casein (80%) Whey (20%) Whey quickly absorbed Casein very slow absorbed Hydrolysed casein = meaning its been pre digested, it's still not as fast as whey so something else is happening This difference is due to the peak (richness) of essential amino acids, especially Leucine
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Do plant based proteins tend to have lower essential amino acid content compared to animal protein?
yes, tends to have a better response in protein synthesis rates and adaptation over a longer period
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How does mycoprotein (from fungus so its an actual food containing carbs and fat and micronutrients) compare to milk protein?
In rested and exercise fasted milk was slightly better In rested fed and exercise fed mycoprotein was better (higher protein synthesis rate) So whole food is most likely more anabolic than isolated proteins
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Vegan diets to support training adaptations?
Strength and hypertrophy changes are very similar if not in favour on the vegan diet But needs more data
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Does protein timing and distribution influence daily muscle protein synthetic rates?
Looked at 12h recovery from resistance exercise 80g fed to all volunteers as 1) 8 x 10g every 1.5h (pulse) 2) 4 x 20g every 3h (intermediate) 3) 2 x 40g every 6 (bolus) Intermediate resulted in most protein synthesis
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Does having a protein shake during the night increase muscle protein synthesis?
yes, also helps before sleep
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Dietary recommendations of protein for athletic populations?
Maximal anabolic response with 25-30g protein 5-6 meals per day 1.6-2.2g per kg body mass / day
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Summary on protein diet advice?
Exercise sensitises the muscle tissue to the anabolic properties of nutrition during each and every meal for at least a 24h period 20-30g per post exercise meal will induce an optimal anabolic response We can look at the types of protein that would be most effective, select optimal sources or fortify those sub optimal sources Ideally each protein meal would be rapidly digestible, rich in essential amino acids, and leucine in particular (2.5-3 g of leucine) Protein is the only fundamentally anabolic nutrient, as such additional energy from other macronutrients from an anabolism perspective, but clearly being part of real food has benefits Protein meals should be adequately spaced apart to gain the most anabolism from each meal Presleep protein ingestion offers a unique timing opportunity to improve overnight muscle protein accretion
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Majority of the bacteria in the microbiome are from the phylum?
Firmicutes and Bacteridetes There are also fungi, archaea, viruses and parasites within the gut
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Functions of gut microbiome? (Amon and Sanderson, 2017)
Protection against pathogens Synthesis of vitamins Immune system Promotion of intestinal angiogenesis Adipocyte function Short Chain Fatty Acid production by fermentation of dietary fibre Modulation of central nervous system
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Healthy gut micrombime relies on?
Increase in diversity and SCFAs+, and decrease in gut permeability If these are all reversed bad things happen: Dysbiosis - reduction in protection against autoimmunity Increased cytokine production eg. IFN-y, meaning a reduction in Tree cell production Increase in inflammation
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A good microbiome supports homeostasis in what ways?
Immune function Appetite regulation Mood Metabolism Vascular function
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Factors that affect the gut microbiome?
Birthing process - c section or not Infant feeding method Stress (exercise, metabolic, psychological) Diet Pharmaceuticals geography Lifecycle stages
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What does exercise do the gut microbiome?
Increased microbial diversity and increased SCFA
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How do we know about factors of the gut microbiome?
Fecal samples Then: DNA-Based approaches = metagenomics RNA-based approaches = metetranscriptomics Protein based approaches = metaproteomics Metabolite based approaches = metabolomics
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How does exercise performance and gut microbiota help each other?
Exercise performance results in: Higher microbial resistance Higher abundance of beneficial Akkermansia, Veillonelaa, Prevotella Selection advantage for lactate utilising bacteria Benefits of a good microbiota for the athlete: Production of bioactive metabolites (SCFA and neurotransmitters) Maintenance of intestinal barrier function Modulation of immune system Improved energy harvest and utilisation Regulation of muscle metabolism
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However what bad thing can exercise cause?
GI distress, as there is a reduction of blood flow to the gut
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What are pre biotic?
Food for bacterial growth Can only be metabolised by the gut bacteria and not the human host
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What are probiotics?
Live bacterial cultures
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What syn-biotics?
Mixture between pre and pro biotics
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What do Bifdobacteria do?
The various strains help to relegate the levels of other bacteria in the gut Modulate immune responses to invading pathogens Prevent humour formation Produce vitamins
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What do Escherichia Coli do?
Several type inhabit the human gut Involved in the production of vitamin K2 (essential for blood clotting) and help to keep bad bacteria in check Some strains can lead to illness
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What do lactobacilli do?
Beneficial varieties produce vitamins nutrients, boost immunity and protect against carcinogens
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What do Campylbacter do?
C Jejuni and C coli are the strains most commonly associated with human disease. Infection usually occurs through the ingestion of contaminated food
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What do Enterococcus Faecalis do?
Common cause of post surgical infection
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What do Clostridium difficile do?
Most harmful following a course of antibiotics when it is able to proliferate
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Stimulant definition?
Stimulate the central nervous system with a marked effect on: Mental function and behaviour Producing excitement and euphoria Reduced sensation of fatigue Increase in motor activity
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What is caffeine?
1,3,7 - trimethlyxanthine Takes an hour to have maximal ergogenic effect Half life of 5 hours Metabolism affected by: Hepatic dysfunction Habituation Removed from banned list in 2004
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Caffeine mechanisms?
Central effects - stimulant: Binds to adenosine receptors in the brain, displacing adenosine which has a stimulant effect ``` Increased lipolysis (sympathetic activation): Increased availability of fatty acids through the sympathetic system being activated, so more carb sparing so improved performance: ``` Reduced extracellular potassium Sarcoplasmic Reticulum Ca2+ release: Improving calcium handling (binds to troponin, allowing myosin to be bound and cross bridge cycling can occur - release and uptake of calcium into the sarcoplasmic reticulum, improving contractility, faster time to peak force Caffeine preserves the resting membrane potential of the nerve impulse in the muscle, meaning even after being stimulated a lot from exercise can still generate action potentials
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Will most likely have to have references to answers
ok
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Technique to look at neuromuscular function in the muscle?
Transcranial magnetic simtulation, causes a contraction in a specific area of the motor cortex, which makes a specific muscle contract Used to look at how caffeine affects muscle
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What is the femoral nerve technique?
Stimulate it and it causes the knee reflex action so stimulates muscle so stimulates the knee extensor muscles so can look at their function with caffeine or not
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What does a voluntary max contraction force being lower than an involuntary max contraction force mean?
There is room for a stimulant to increase this max voluntary contraction Can also link at the time for the contraction to occur
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What did Bowtell and colleagues 2018 find through "Caffeine supplementation and fatigue during repeated maximal contractions?
Received 6 mg caffeine . kg^-1 or placebo 1 hour prior to performing exercise 5 bouts of single leg knee extensor exercises to fatigue Time to fatigue was recorded and they had 5 mins each time to recover Caffeine made exercise capacity far better, but you also see an increase in blood lactate (from doing more work) Muscle metabolites: Sets 2-5 is Per conc is far lower in caffeine condition, Muscle pH goes more acidic in caffeine condition, showing they are doing more work Overall benefit was from an increased voluntary activation ``` This is from: Increased contractility Increased relaxation rate Increased excitability Increased wave amplitude ``` ``` Conclusions: Increases in exercise capacity Delays fatigue Inceazed contractility? Increased voluntary activation Helpful where central fatigue is a key cause of poor performance ```
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Metabolic effects of caffeine (Graham et al, 2000) features of the study?
10 healthy untrained subjects Caffeine (6 mg.kg^-1) vs placebo Complete1h at 70% VO2max, 1h after ingestion of supplement Arterial fatty acid conc higher in caffeine, especially at the beginning of exercise Increased adrenaline due to caffeine Reduced extracellular potassium Sarcoplasmic Reticulum Ca2+ release: RER is the same, so no difference in fat and carbo oxidation Conclusions: Caffeine stimulates lipolysis at rest Appears to stimulate sympathetic nervous system activity No metabolic effects Lowers plasma potassium
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Endurance performance (Hulston and Jeukendrup, 2008) what did they do and find?
10 subjects 3 trials 105 min @ 60%VO2max + time trial (calculated what work would have been done at 70% VO2max over 45 mins, then had to complete it as fast as possible) Placebo Cho (0.7g/min) Cho + caff (5mg/kg) No carb sparing shown, as affects of caffeine overwhelmed by carb dosing Caffeine + CHO = better performance (4.6% better performance)
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Does caffeine reduce rate of perceived exertion?
yes
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Sytemic review of effects on endurance performance (gain et al, 2009) showed?
Caffeine only prior to exercise (2.3% increase in performance) Caffeine ingestion before and during exercise (4.3% increase in performance)
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Conclusions on 2019 caffeine meta analysis? (Shen et al)
3% increase in performance Magnitude of effects not influenced by Sex, age, VO2max, event, or timing prior to competition Performance benefits are greater for longer duration events Not effective for 800m performance and impaired subsequent sleep quality (Ramos-Campo et al, 2019.). (one study)
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Schneiker et al 2006, caffeine improves intermittent sprint performance?
10 male amateur team sport players Repeated cyclic sprints to mimic team sports 2 x 36min halves - 18 x 4 sprints 5 mg.kg^-1 caffeine or placebo Caffeine showed increased world done and power output Faster reaction time
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Team sport performance saline et al 2019 showed that caffeine did what?
Increased small benefit to repeated and single jumping Same in single and repeated sprint Bit larger improvement to agility Improved running distance All these factors are cumulative
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Grgic et ak 2019 showed what about caffeine and exercise performance?
Improved muscular endurance, MVC strength, 1RM strength, isokinetic strength
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Sex differences in ergogenic effects of caffeine for endurance performance (skinner et al 2019)?
Endurance trained participants: 11 female on oral contraception 16 male Randomised, double blind, placebo-controlled crossover trial Incremental test, 2 x familiarisation, 2 x performance trials (test were how fast can you do your 75% vo2max distance for an hour ) 3mg.kg^-1 90 min per exercise No sex differences found
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Does caffeine work the same even at different points in the menstural cycle (Lara et al 2019)?
13 well trained eumenorrheic triathletes no on oral contraception Randomised, double blind, crossover trial Placebo and caffeine (3mg.kg^-1) trials in: Early follicular Pre-ovulation Mid-luteal Found to have no effect
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What did paton et al in 2015 show about caffeinated chewing gum?
Improved cycling performance - more details on slides Peaks faster than a pill as well (peaks at 10 mins) 5 mins chewing gets 80% of caffeine out
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Lara et al 2019 showed what caffeine habituation?
that it gets less effective the more you take over a period of time so you would need a higher dose
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When is caffeine toxic?
over 12mg per kg body weight
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Is caffeine a diuretic?
yes at rest, not doing exercise, females more susceptible But caffeine does cause poor sleep quality
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Types of radicals?
Reactive oxygen species (Radical and non radicals) Reactive Nitrogen species (Radicals and non radicals)
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Sources of oxidants?
``` Environmental: Ultraviolet radiation Pollution Smoking Burnt food ``` Cellular processes: Oxidase enzymes Mitochdonrial respiration
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Good Important roles of ROS and RNS?
``` Cell communication: SR Ca2+ release Glut 4 translocation Increased protein synthesis Metabolic regulation ``` Vasodilation Immune function
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Consequences if reactive species exposure exceeds antioxidant defences?
Oxidative damage: Damaging lipids: Peroxidation Cells membranes damaged - dysfunctional cells Reduced NO bioavailability - impaired blood vessel function Damage to body proteins: Oxidative modification - carbonisation, nitrosylation Altered function - aging DNA damage: Aging Cancer Triggers inflammation
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Types of endogenous antioxidants?
Enzymes Non-enzymatic Nutritional: Vitmains Minerals Polyphenols
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Polyphenol classification?
``` Flavonoids: Anthocyanidins = cyadnidin, peargonidin, peoonidin, delphinidin, perunidin, malvidin Falvonols Flavonones Isoflavones Flavanols ``` Lignans Other polyphenols Phenolic acids Stilbenes
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Direct antioxidant properties?
Radical scavengers Only about 5-10% of dietary polyphenols go into circulation, rest are digested by microbiome which then can be used Due to his poor bioavailability, they are converted to prooxidants such as Semiquinones and quinones These then trigger increased synthesis of endogenous antioxidants by cells Also the actual antioxidants can inhibit ROS production
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Effect of exercise on ROS generation?
NADPH oxidase creates O2- radicals which with the product of the mitochondria produced H2O2 intracellularly Extracellularly NADPH oxidase and XO form O2- radicals which forms H2O2 When exercise occurs both their concentrations increase
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How do we look for evidence of increased reactive species generation during exercise as their half life is so small?
``` Markets of oxidative damage (indirect): Protein carbonyl and nitrotyrosine F2 - isopostanes TBARS - thionbabituric acid reactive substances MDA- malondialehyde ``` Electron paramagnetic spin resonance (direct) Spin traps for specific radicals
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Optimal level of oxidation and reduction for exercise?
In the middle, balance of cellular redox state
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Process of fatigue?
``` Ioninc gradients E-C coupling Central drive Substrate depletion By-product accumulation Muscle perfusion ``` ROS and RNS can contribute to these processes, so does antioxidant supplementation improve performance
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ROS expose can trigger what?
Increased production of antioxidant enzymes For example ROS and RNS allows Nrf2 to unbind with Keap1, NRF2 then can fit into the cell and cause a antioxidant response element So exercise training increases antioxidant defences So does antioxidant supplementation block training adaptation
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Antioxidant relevance to exercise recovery?
ROS and RNS can result in: Damaged cell membranes - leaky- impaired permeability Damaged proteins - altered function - transporters, enzymes, contractile proteins Inflammation - soreness, pain Can lead to injury which worsens inflammation and the immune response, which increases the ROS and RNS concs So can antioxidant supplementation improve recovery
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Features of N-acetylcysteine?
Direct oxidant scavenger Cysteine donor to support glutathione function So acts as a radical scavenger as well as supporting gluthathione function
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Effect of N-acetlycysteine supplementation on cycling performance?
10 male triathletes Double blind crossover study 1200mg.d^-1 dor 9d (NAC (antioxidant in last flashcard) or placebo) Improved 5s, 10s and 15s sprint performance Conclusions: Favourable effects on oxidant balance Improved cycling sprint performance Better tolerance of increased training intensity Other studies suggest NAC better for endurance rather than sprint performance
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Whats quercetin?
Polyphenol Falvonol from the flavonoid family Widespread presence in fruits and vegetables Habitual intake = 5-13mg.d^-1 ``` Purpoted properties: Antiooxidant Anticarcinogenic Cardioprotective Ergogenic ``` 500-1000 mg quercetin per day resulted in 2.8% increase in endurance performance
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Morgan et al 2019 study using cherry supplementation?
257mg anthocyanin and 456mg total phenolics Saw higher blood lactate concentration in cherry when exercise was occurring, due to higher tissue saturation (better perfusion) meaning better removal of lactate from the muscle and into the blood 4.6% increase in performance with cherry Might be because of better cognitive function
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In 4th lecture good example of a summary table I need for my lab report
ok
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Effect of antioxidant vitamins on recovery from muscle damage?
38 active healthy mean Randomised to 6 week nutritional supplementation, twice per day Placebo or Vit C (400mg) and E (268mg a-tocopherol) 90 min intermittent shuttle running Bloods and muscle function tests Found no significant effects of antioxidant vitamin supplementation, some studies find it, some don't but mostly likely doesn't help recovery. Also they might stop adaptations to training
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Features of montmorency cherry concentrate improves muscle recovery (bowtell et al., 2011) found what?
Found improved functional recovery Reduced amount of protein carbonyls and creatine kinase Mediated via reduced exposure to reactive oxygen species
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Conclusions on polyphenols?
Enhance functional recovery: Reduced oxidative damae Reduced inflammation Consume 1000mg.d^-1 for 3 days minimum prior to exercise Optimal mix, dose and timing still not known
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How do muscles move?
Acetlycholine released from the axon terminal binds to receptors on the sarcolemma An action potential is generated and travels down the T tubule Ca2+ is released from the sarcoplasmic reticulum in response to the change in voltage Ca2+ binds troponin: cross bridges form between actin and myosin Acetlycholinesterase removes acetylcholine from the synaptic cleft Ca2+ is transported back into the sarcoplasmic reticulum Tropomyosin binds active sites actin causing the criss-bridge to detach
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Why is there fatigue in repeated sprints?
Glycogen depletion (can help with carb loading, but glycogen depletion isn't that important) Phosphocreatine depletion (can creatine load) Muscle acidosis (Can increase buffering capacity loading) - delaying the effect of acidosis (pH below 7, caused by the hydrogen ions associated with lactate)
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Products of glycolysis that causes glycolysis, and what transporters are there to get rid of the it?
Produces Hydrogen ions Monocarboylase enzymes can remove H+ and Lactate from the muscle Sodium hydrogen transporter, can take hydrogen out and put sodium into the muscle Sodium bicarbonate takes sodium out, and puts in bicarbonate (alkali) in The bicarbonate binds with hydrogen forming carbonic acid which can dissociate into carbon dioxide and water, which is better for the body to cope with So the alkali is neutralising the hydrogen ions
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Resting membrane potential?
Potassium is important for membrane potential 2 sodium out, 2 potassium in Accumulate potassium out of cell Change with AP much smaller (now -55mv to 30mv, instead of -70mv to 30mv) Causes an issue with ability to generate force
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Effects of extracellular potassium on peak force?
As extracellular potassium increases, peak force decreases Same as extracellular potassium increases resting membrane potential increases When the membrane increases past -65mv there is a critical drop in the peak power that can be generated
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Alkalosis may attenuate the increase in potassium
When sodium biacarobonate was given as a supplement Arteries (what's going to the muscle): Hydrogen ions dropped Lactate stayed the same K+ ions decreased Veins (what's leaving the muscle): Lower hydrogen ions Higher lactate concentration (they exercised longer due to the supplement so lactate was allowed to increase further) Lower potassium concentration Exercised 25% longer
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Features of sodium bicarbonate?
Extracellular anion Biocarbonate loading results in increases in blood bicarbonate pools Muscles become buffered Helps in events in which a low pH is a limiting factor (banned in horse racing)
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Sodium bicarbonate effect on high intensity endurance performance (egger et al 2014)?
0.4/kgBM, 30min at individual anaerobic threshold Time to exhaustion increased by 10%
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Acidosis following sprints (Bishop et al 2004)?
5 x 65 sprint No difference in placebo compared to sodium bicarbonate in muscle H+ concentration But post workout increased muscle lactate concentration in sodium bicarbonate compared to placebo (so you have worked longer, so more lactate but your hydrogen ions haven't increased as they have been buffered) Performance improved in sodium bicarbonate condition
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Why is there a far larger increase in sodium bicarbonate supplementation improving performance in untrained compared to trained?
Trained already have adaptations that increase monocarboxylase transporters so already have an improved buffering capacity This effect is less in longer duration, quite similar
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Douroudos et al 2006 showed what looking at chronic sodium bicarbonate supplementation (5 days before)
Placebo, medium 0.3g/kg, high 0/5g/kg Pre workout there was an increase in pH (more alkali), sodium incarnate conc, but no change in potassium conc from supplementation After exercise pH dropped less in supplementation, same with bicarbonate concentration Smaller elevation in potassium concentration in supplementation Greater average power in Wingate in high supplementation
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Sodium bicarbonate as a training aid, (Edge et al 2006)?
8 week training: Both increased buffering capacity, VO2 peak, Lactate threshold But with sodium bicarbonate there was more of an increase in Lactate threshold and time to fatigue Better trained showed less of an effect
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Side effects of sodium carbonate (Potentially)?
Nausea, vomiting, GI distress Better to take with capsules Have with fluid and light meal, spread dose, specific profiling
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Bicarbonate conclusions?
0.3-0.5g/kgBM 90-120 min per exercise Exercise where pH is limiting Individual variation
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Features of the intracellular buffer carnosine?
Dipeptide present in animal flesh L-histidie (EAA) Beta alanine (AA) Buffers hydrogen ions, when you exercise there is an increase in lactic acid which dissociates into lactate and hydrogen ions, carnosine prevents this accumulation Carnosine also acts as a antioxidant protecting against oxygen radicals Glycation and carbonisation prevention - stop glucose and protein sticking Carnitine is made in the body, but beta alanine is rate limiting in it's production 15% of our muscle buffering ability comes from carnosine More carnosine in type 2 muscles, this makes sense as explosive contractions are more likely to result in increased lactate concentration Aging decreases carnosine Males have more If you eat more beta alanine, you will have more carnosine
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Carnosine synthesis?
You can't absorb it whole You eat it and splits into L-histidie and beta alanine Dietary carnosine is absorbed into hepatic portal veins and splits into its parts Beta-alanine shares transport with taurine so need to make sure don't have too much in which taurine uptake is decreased Carnosine synthesase puts them back together Supplementation does just with Beta alanine supplementation
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For a desired increase of 50% in muscle Carnosine what do you have to do?
A total of 200g of BA must be taken 6 weeks at 4.8d/day, 9 weeks at 3.2g/day or 18 weeks at 1.6g/day
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Hill et al (2007) showed what about 10 week of beta alanine supplementation?
Training was done on weeks 0, 4, and 10. no additional training was done No changes in placebo More work done, and more carnosine in muscle done in beta alanine supplementation
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Baguet, 2010 showed what on carnosine?
Baseline carnosine correlates to performance Supplementation increased performance
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Meta analysis looking at different times on carnosine effect?
Under 60 secs = no improvement 50-240 secs = biggest impact Over 240 secs = some impact
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Beta Alanine and HIIT training?
Placebo and beta alanine Both increased VO2 max at 3 weeks, further increase at 6 weeks in BA Both increased time to exhaustion at 3 weeks, further increase in BA at 6 weeks BA allowed the training to be at a higher intensity
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Beta alanine washout?
Long washout Stable protein, so 2% per week
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Side effects of beta alanine?
Parathesia Double vision Weight gain Hypertension Decrease in performance So can take slow release tablets
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Artioloi et al 2010 has good diagram on summary on carnosine
ok
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Sale et al 2011 looked at beta alanine and carnosine supplementation what did they find?
Taking beta alanine was the most important, but taken with sodium bicarbonate helped but wasn't significant (only 70% chance it was helping)
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Danaher et al 2014 showed?
Beta alanine was more effective, and with sodium bicarbonate didn't help anymore
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Why is BA more important than sodium bicarbonate?
It is in the muscle, while sodium biacrobate is extracellular so its in the blood, so has to go into the muscle to work So the beta alanine is in the muscle already so can buffer straight away
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Mero et al 2013 showed what about swimming performance and BA and sodium bicarbonate supplementation?
Found that sodium bicarbonate group only was the most effective Difference was it was less duration, and was how fast you can do something not for how long
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2 phases of muscle glycogen resynthesis?
During exercise muscle glycogen drops During exercise GLUT4 is at membrane to take up glucose thanks to calcium and adrenaline Once exercise stops consume CHO which means the pancreas releases insulin GLUT4 to cell membrane which takes up more glucose, so there is a large amount of GLUT4 at the membrane at this point So there is a rapid rise in glycogen resynthesis (first phase, which slows down after this initial rise (second phase)
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How does glycogen synthesis actually occur and exercises influence?
Glycogen synthase goes to it's active form when there is increase Insulin, Glucose, and Glucose-6-phosphate which makes Protein phosphatase which activates glycogen synthase However exercise increases the amount of calcium ions, glucagon, and adrenaline which increases protein kinase A, which converts glycogen synthase into it's inactive form
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Betts and William 2010 showed what about carb ingestion?
max rate of 1.2g/kg/h results in max muscle glycogen re synthesis rate
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Rabinowitz 1966 showed what about the insulin repose to beef and CHO?
Beef = lowest insulin response Just glucose = medium response Both = best response Which increases glycogen synthase and increase glucose uptake which repsults in increased muscle glycogen synthesis
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Zawadkzi 1992 showed what about CHO and protein on glycogen resynthesis?
Same as previous study, there was the greatest increase in muscle glycogen storage
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Bowtell 1999 showed what about glutamine?
Glutamine alone doesn't really increase insulin But greatest rise came from glutamine with glucose polymer Glutamine alone provide the smallest muscle glycogen concentration Glutamine and glucose polymer provided medium response Glucose polymer alone provided largest muscle glycogen concentration Glutamine + glucose also resulted in largest non oxidative CHO disposal, so wasn't being used, but also wasn't being stored in the muscle, but the liver
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What did Van loon 2000, and Jentjens 2001 show?
That with sufficient CHO there is no need to add protein for muscle glycogen resynthesis Most likely protein only helps when Cho is suboptimal (under 1,2g/kg/h)
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Caffeine mechanism on adenosine?
Adenosine normally binds to and adenosine receptor, and this makes you feel tired Caffeine blocks this and binds to the receptor itself , pituarity gland sees this as an issue and increases adrenaline Adrenaline stimulates hepatic glucose output, and promotes intestinal absorption More glucose in blood More glucose taken up by muscle Greater muscle glycogen synthesis
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Pedersen 2006 showed what?
Carb or Carb + caffeine Not much caffeine ingested as only 71kg so reduced amount (only 1g/kg/bm) Higher glucose seen with caffeine Higher insulin AUC with caffeine So caffeine stimulates glycogen resynthesis But Beelen 2012 showed that adding caffeine or protein only works when carbs are not optimal There are also no differences in the muscle fibre types
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Dosing for maximal glycogen resynthesis in muscle?
Small regular feeding better than few large doses No difference if solid or liquid CHO but liquid might help rehydrate, and easier to consume when appetite is reduce You want glucose/sucrose as fructose increases it in the liver to be able to converted into glucose
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Factors influencing hydration?
Gastric emptying - maximise Depends on volume / energy content / osmolality / temperature / exercise / dehydration Intestinal absorption - electrolyte content Palatability - flavour / temp / electrolyte content
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How can we favour hydration?
Fluid volume topped up (not too high) enhances gastric emptying Energy content. not too high (6% CHO) - higher will slow gastric emptying Same as above for osmolality Temp - no effect on gastric emptying but tastes better Dehydration - avoid below 2% weight loss - reduced splanchnic blood flow Flavour - tasty - drink more Electrolyte - tasty levels - maintains Na+ conc and thirst
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Shirreffs, 1996 showed what about sodium content and rehydration?
Known that for whatever body weigh you lose from dehydration as to drink 1.5 x that weight in water Lower the urine output, the more water has stayed in the body - 100mml was the best but would have been disgusting - it also showed the best net fluid balance, they were the only ones who remained in the positive state after 6 hours 25 mmol only one you cn drink normally - 100mmol also caused issues with the potassium balance We can try get this salt from food instead
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What did Watson 2008 show?
Protein can aid fluid retention But this not effect time to exhaustion trial
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Beer in recovery?
Hydration index for larger is slightly lower than water but not significant Beer will not complete restore fluid balance Add some sodium to the beet and its more effective Lower alcohol is better Going over 4% is problematic Claims of micronutrients - caution Not great source of calories - alcohol calories not good for muscle (can't use it)
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Why would protein help recovery from eccentric training? IN THE EXAM
Following EE there is increased muscle protein synthesis, muscle damage and loss of contractile function Protein increases muscle protein synthesis - inhibiting mTOR delays the recovery of muscle function Protein shown to enhance recovery - but not through increasing muscle protein synthesis (Pavis et al., 2020) in the exam
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What did Jackman 2010 show about BCAAs?
They attenuate muscle soreness - specifically 48-72hrs after eccentric exercise However no functional effect No change in Creatine kinase or myoglobin in blood Whey protein, had slight functional effect at early time points, had no effect on creatine kinase, no effect on IL6 (inflammation marker), Had an early effect on muscle soreness
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Pavis et al 2020 showed?
Effect of protein with polyphenols after 300 eccentrics Soreness reduced with protein, and function recovered quicker Early on there are hue signalling changes driven by nutritional intervention - perhaps the real rational for protein being effective Don't forget polyphenols and antioxidant lecture and how they effect recovery
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Bergstrom and Hultman 1967 showed what about about glycogen stores?
Exercise depletes them, eating CHO helps replenish Deplete carb then replenish helps performance
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Glucose adaptation revision?
Glucose gets dragged into the cell during exercise to provide ATP After exercise is in the cell to replenish glycogen stores (insulin stimulated glucose uptake)
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For adaptation do we want homeostasis?
For performance we want a nutritional intervention if we are going to be performing later that day, ie carbohydrate after an endurance bout to replenish glycogen stores We want homeostasis to result in adaptation Theory on exercising in the low glycogen state to disrupt homeostasis more to result in a larger adaptation Pilegaard et al 2002 showed that there was more activation of PDK4 (means less PDC which means less glucose oxidation = harsher conditions) that result in adaptation in the low glycogen state compared to the normal following exercise, there was also more expression of UCP3 in low muscle glycogen indicating more mitochondrial expression The low glycogen state was achieved by working out only 1 leg, and not providing CHO so glycogen not restored in that leg, but the other is fine as it didn't do the workout Same in LPL, so more efficient utilising lipids Take home message is avoid carbs after training to drive larger adaptation as glycogen is not replenished Different study looked also at PGC-1 which is believed to be main determinant on mitochondria biogenesis, and low carb diet enhances this
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Skeletal muscle adaptation training twice every second day vs training once daily show about the low glycogen state?
In low state (Training twice every second day, so second session is in the glycogen depleted state) had higher muscle glycogen content by the end of the study, compared to training once every day (never in the glycogen depleted state and overall do the same amount of work) Better muscle oxidative capacity seen as well, as well an improvement in exercise performance But under tightly controlled laboratory conditions - not allowing for any alteration in training load dependent on nutritional status) Best nutritionists working with runners, chose specific times of year (off season) to work in low carb state to get maximal adaptation
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Glycogen availability and training adaptation YEO et al, 2008 showed what?
Compared does having carbs allow you to do more work which outweighs the better adaptations you get from being in the low carb state High group performed better in the maximal hit sessions Low carb training group still had far better adaptations even though they did less work in the maximal hit class However there was no statistical benefit in exercise performance in low carb group Ben Wall says its due to difficulty to find top gear, they are in less of a good position to do it as they aren't use to going max out
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Practical approach to going low carb diet?
Chonric low CHO diet Twice per day training Train after overnight fast Withhold CHO in early recovery Sleep low/ train low Issues: Poor training quality Immunosuppression Muscle protein loss
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Creatine supplementation?
Synthesised from the amino acids arginine and glycine Synthesised in liver and kidney Muscle concentration < 160mmol.kg^-1, 60% in the phosphorylated state Meeting ATp demand during sprint exercise: PCR (increased by supplementation) + ADP + H+ with creatine kinase goes to ATP + Cr, which then the ATP is used for energy by ATPases resulting ADP + Pi + H+ In resting state = PCr, after exercise is Cr Glycogen + 3ADP + Pi via glycolysis creates 3ATP + 2 lactate + 2H+, the ATP is used by the ATPases
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Possible effects of creatine
Increased {PCr} Increase capacity to perform high intensity contraction within a bout (anaerobic performance) Increased rate of PCr resyntehsis Increased capacity to perform multiple bouts of high intensity contractions Increased training adaptations as result of training load Glycogen resynthesis Aerobic permanence? H+ buffering Improved diffusion of ATP through the muscle Activation of glycolytic enzymes Main way it works is that it allows you to do more reps
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Supplementation protocol forcreatine monohydrate?
20g or 0.3kg^-1 for 5 days Maintenance dose 2g or 0.03g.kg^-1 CHO coingestion - helps to alleviate non responders issue Good safety - don't need to cycle it Side effects - increase in water weight or body weight
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What did Trappe et al 2002 show?
Ibuprofen and paracetamol block MPS following exercise in young men In 2011 did not block hypertrophy in older individuals in older adults