Lec 10 & 11- Caffeine

Question 1

what is pure caffeine known as?

Answer 1

1,3,7-trimethylxanthine

Question 2

how much caffeine is consumed a day?

Answer 2

Around 6 billion caffeine-containing drinks are consumed worldwide every day

About 30,000 kg of caffeine per day

Question 3

how much caffeine is in coke, tea, chocolate and coffee?

Answer 3

coke = 33
tea = 50
choc =12
coffee = 80-120

Question 4

what are the sources of caffeine?

Answer 4

Tea, coffee, mate, cocoa, cola nut and guarana

Question 5

how many cups of tea are drunk daily in the UK?

Answer 5

165 million

Question 6

in terms of monetary value traded worldwide, where does coffee rank?

Answer 6

second after oil

Question 7

physiology of caffeine

Answer 7

It is an adenosine A1 and A2A receptor antagonist
=The effects of caffeine on human physiology and behaviour occur primarily because caffeine antagonises (blocks) the action of endogenous adenosine (i.e., adenosine produced, as a result of metabolic activity, in the body) at adenosine A1 and A2a receptors

Question 8

Difference between caffeine and adenosine

how does adenosine work

Answer 8

Caffeine has opposing effects, for example, adenosine causes vasodilation (the dilatation of blood vessels, which decreases blood pressure) and caffeine cause vasoconstriction (the constriction of blood vessels, which increases blood pressure).

Adenosine modulates neural activity=
Activation of adenosine postsynaptic receptors by endogenous adenosine slows neural activity
Caffeine prevents activation of adenosine receptors by adenosine, thus removing this brake on neural activity

Question 9

define tolerance to caffeine..

how do we become tolerant?

Answer 9

Prolonged exposure to caffeine leads to changes in adenosine signalling that oppose the effects of caffeine (tolerance)
With prolonged exposure to caffeine, the body attempts to restore normal performance through alterations in the endogenous system – eg through changes in concentrations. The adenosine system then becomes more sensitive and we become partially tolerant to effects of caffeine.

Question 10

metabolism of caffeine

Answer 10

After consuming a caffeine-containing drink or food, caffeine is rapidly absorbed from the gastrointestinal tract into the bloodstream, and peak concentration in blood is reached after about 30 to 60 minutes. It is then distributed throughout the entire body including the brain. It takes about 15 minutes to reach the brain and is detectable in saliva soon after consumption.

Caffeine does not accumulate in the body, however, because it and its metabolites are efficiently excreted. For adults, the elimination half-life of caffeine is around 3 to 7 hours

Question 11

Who was the first person to investigate caffeine? and what did he find?

Answer 11

Hollingworth 1912
compared pp who swallowed caffeine in a capsule in doses between 1 and 6 grains versus placebo capsule which contained ‘sugar of milk’
= Caffeine appears to speed up performance on simple motor tasks like tapping. This is not the pp motivation but a physiological response of caffeine.
=large doses of caffeine (390 which is about 3 or 4 cups of coffee) disrupts performance on hand steadiness task and causes shakiness.

He concludes that caffeine can have some positive effects by increasing motor performance

Question 12

Smit and Rogers 2000 study

Answer 12

demonstrate that we are sensitive to caffeine at levels that not only occur in coffee and tea, but also in chocolate and cola beverages (levels 0, 12.5, 25, 50 and 100)
=Caffeine has effect on RT and people are faster with caffeine than placebo
=Relative to placebo, performance is also better with caffeine on rapid number search task.
=One strange finding was that low doses of caffeine produce similar effects to higher dose
the effects on performance were more marked in individuals with a higher level of habitual caffeine intake,
BUT vast majority of literature look at caffeine consumers and will stop them consuming caffeine before the test, this may effect the interpretation of data. .. therefore perhaps is effect of caffeine withdrawal, not that caffeine speeds up reaction time but that placebo slows down reaction time

Question 13

what is the withdrawal reversal hypothesis?

Answer 13

• Acute (e.g., overnight) caffeine withdrawal lowers alertness and degrades mental performance
• Caffeine restores alertness and mental performance to, but not above, baseline (normal) levels

Question 14

Goldstein 1969 study

Answer 14

3 main findings:
1- caffeine consumers rated themselves as feeling less alert before administration of the treatments (caffeine or placebo) than did the non-consumers.
2- Second, over the next 2 h, caffeine versus placebo increased alertness in consumers; however, even after the highest caffeine dose, their alertness increased only to the level of alertness rated by non-consumers when they received placebo. Therefore caffeine only increased alertness to the (baseline) level
3- Third, caffeine barely affected alertness in non-consumers despite there being a considerable room for an increase in scores

=also found that high caffeine had little effect on regular drinkers but large effect in non-drinkers, these people reacted negatively to caffeine; principal complaints were jitteriness, nervousness, and “upset stomach.”

Question 15

how can we avoid the self-selection bias

Answer 15

Randomise caffeine consumers to short-term versus long-term caffeine abstinence. Take people who are caffeine consumers and ask them to become abstain for a period of time and ask other consumers to carry on as normal and then compare. For the people who abstain, their withdrawal symptoms begin to decrease and eventually disappear. Their systems have therefore adjusted to life without caffeine and tolerance is lost. Can compare them to people who are withdrawn just overnight

Question 16

what is Phenylketonuria (PKU)

Answer 16

PKU is an inherited metabolic disorder in which people are born with inability to metabolise PKU, therefore it builds up and results in elevated levels and cog impairments.

• High neonatal blood level of phenylalanine (1 in 10,000 in UK) and metabolites in urine, including phenylpyruvate (phenylketone)
• Deficiency of phenylalanine hydroxylase (PAH) activity due to mutation in gene coding for PAH (300 PAH mutations identified)

=tyrosine deficiency leads to dopamine deficiency =
=elevated phenylalanine leads to impaired myelin production and maintenance

Question 17

Rogers et al 1995 study

Answer 17

They investigated caffeine reinforcement by assessing changes in preference for a novel flavoured fruit juice drink consumed with or without caffeine (70 mg). The drinks were consumed at breakfast on 10 consecutive weekdays. Changes in preference for the target drink during conditioning were examined by subtracting subjects’ ranked preference for the target drink on day 0 from their ranked preference for this same drink on day 10. Mood was assessed on each of the conditioning trials 1 h after the drink was consumed.
Based on their caffeine intake, subjects were divided into low and moderate users

= low users showed, overall, an increase in preference for the target drink relative to the other drinks. This change in preference was not significantly affected by the caffeine content of the target drink.

=In contrast, subjects who were habitually consuming caffeine at the higher level developed a relative dislike for the target drink if it lacked caffeine, and showed an increase in preference for the drink if it was caffeinated.

=Mood in the low caffeine consumers was largely unaffected by the ingestion of caffeine, but tended to be lowered in regular users who received the noncaffeinated drink. They felt less clearheaded, less energetic and less lively, and more tired than the moderate users who received caffeine.

Question 18

Yeomans et al 1998 -

Answer 18

This study examined whether 100 mg caffeine could reinforce preference for the flavour of a novel herbal tea drink in moderate caffeine users, both after overnight caffeine abstinence and 2 h after receiving 100 mg
= Liking for the tea increased significantly over four days for subjects receiving caffeine, and decreased significantly in those without caffeine.

Question 19

Rogers et al 2013 study

Answer 19

-caffeine withdrawal at 10:30am associated with some detrimental effects including slower RT times
-caffeine withdrawal also associated with greater sleepiness, lower self reported mental altertness and poorer cog performance - all of which are reveresed by caffeine
In contrast to medium-high caffeine consumers, (non-tolerant) non-low consumers experience an increase in anxiety/jitteriness after caffeine which offsets any benefit for mental alertness and mental performance arising from reduced sleepiness.

Tolerance in consumers develops to anxiety (Rogers 2010) but not to the effects on sleepiness as the beneifits in mental alertness and mental performance only return levels to a normal state of affairs.

anxiety and jitteriness have neg effects on performance- Eysenck 2007 - anxiety reduces attentional control and increases threat stimuli processing.

an important dissociaiton in this study was between sleepiness/wakefulness and mental alertness, which previously were measured as lying on continuum Rogers 2010).

Question 20

what is the difference between addiction and dependence

Answer 20

• ‘Addiction is restricted to the extreme or psychopathological state where control over drug use is lost.’ – loss of control is key.
• ‘Dependence refers to the state of needing a drug to function within normal limits; it is often associated with tolerance and withdrawal (symptoms), and with addiction as defined above.’

Question 21

what is the underlying mechanism for cognitve decline and diet?

Answer 21

vasuclar disease which leads to cerebral ischaemia.

Question 22

what is Atherosclerosis?

Answer 22

a disease in which fatty plaques develop on the inner wall of arteries, resulting in obstruction of blood flow

Question 23

what are the fatty acids that have beneficial effects in relation to atherosclerosis and associated effects

Answer 23

n-3 fatty acids (alpha-linolenic acid, DHA and EPA)

Question 24

what is ischemia and how is it effected by caffeine?

Answer 24

ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus to the death of brain tissue or cerebral infarction / ischemic stroke

When someone suffers from ischemia, adenosine is released, this feeds back to reduce the adverse effects of ischemia. Through chronic exposure to caffeine, and caffeine’s effect of adenosine, it sensitises this and creates adenosines protective response to ischaemia

Question 25

Jarvis 1993 study

Answer 25

The relationship between habitual coffee and tea consumption and cognitive performance was examined using data from a cross-sectional survey of a representative sample of over 7000 British adults. Subjects completed tests of simple reaction time, choice reaction time, incidental verbal memory, and visuo-spatial reasoning.

= The relationship between consumption and performance is only clear in older people within the study. It is not present in younger people. One argument could be that this is a different effect of caffeine, these are effects that have accumulated over time and causing improved cognitive health in older people. Perhaps younger people have not had enough exposure to caffeine.

=Rather than an acute effect of increased alertness, Jarvis’s results represent a chronic protective effects of coffee/tea/caffeine on cognitive function

Question 26

what are the 6 protective mechanisms in diet?

Answer 26

1) n3 fatty acids,
(alpha-linolenic acid, DHA and EPA) have a variety of beneficial effects in relation to atherosclerosis and associated effects
blood triglyceride levels, inflammatory reactions, and formation and removal of blood clots

2) Diet low in saturated fat, relative to polyunsaturated fatty acids

3) Antioxidants (e.g., vitamin C, vitamin E, beta carotene) are protective
Oxidative modification of cholesterol plays a major role in the pathogenesis of atherosclerosis

4) Vitamin B9 (folate/folic acid), vitamin B6 and vitamin B12
An elevated blood level of homocysteine is an independent risk factor for coronary, cerebral and peripheral vascular disease

5) Alcohol

6) Tea and Coffee
Neuroprotective role of adenosine during brain ischaemia.
Polyphenols and other compounds in tea and coffee may protect against vascular disease

Question 27

who should you cite when discussing adenosine A1 and a2a recpetors?

Answer 27

Fredholm et al., 1999).

Question 28

who argues that caffeine has no beneficial effects per se, but merely removes negative effects produced by caffeine withdrawal ?

Answer 28

James 1994

Question 29

Warbuton 1995

Answer 29

measured the effects of caffeine given to frequent caffeine consumers while they are in a nonwithdrawn state.
=They showed that performance and mood effects can be obtained with doses as low as 75 mg when the participants had only been minimally deprived of caffeine and had received 75 mg caffeine 1 h before the laboratory testing.
Thus, the mood and performance-enhancing effects of caffeine were argued to not represent alleviation of deficits induced by caffeine abstinence, but rather as absolute improvements. They therefore contradict findings that suggest that caffeine only produces improvements because it is reversing the effects of caffeine withdrawal.

Question 30

evidence against Warbuton 1995

Answer 30

As Rogers 2014 points out, it does not refute withdrawal reversal. First, the logic is flawed because without a comparison group of non-consumers or long-term withdrawn frequent consumers, there is nothing to verify the claim that the 75 mg ‘‘predose’’ fully reversed withdrawal. It is possible that this was sufficient to only partially remove withdrawal, leaving the caffeine given in the laboratory to remove more of it.

Second, the procedure leaves open the possibility that failure to comply with the instruction to consume (rather than to not consume) caffeine shortly before arriving for testing can account for the observed effects of the caffeine administered in the laboratory. Evidence supporting the latter explanation comes from a study in which Yeomans et al 2002 replicated and extended Warburton’s procedure but ensured that participants consumed the predose by observing them taking it (in the laboratory).In doing this, they did not replicate his results.

Question 31

James and Rogers 2005 – review.

Answer 31

Three main experimental approaches were employed: studies that compare consumers and low/non-consumers, pre-treatment and ad lib consumption studies, and long-term withdrawal studies.
=Of the three approaches, only long-term withdrawal studies are capable of unambiguously revealing the net effects of caffeine. Overall, there is little evidence of caffeine having beneficial effects on performance or mood under conditions of long-term caffeine use vs abstinence. Although modest acute effects may occur following initial use, tolerance to these effects appears to develop in the context of habitual use.

Question 32

Caffeine is generally accepted to be the most widely consumed drug in the world … cite?

Answer 32

Gilbert 1984

Question 33

Elimination half-life of caffeine in pregnancy and smokers

Answer 33

Elimination half-life of caffeine is longer during pregnancy and shorter in smokers - Rogers 2008

Question 34

evidence for stimulant effects of caffeine come from..

Answer 34

Hollingworth 1912
Smith 2006
Childs 2006
Warbuton 1995

Question 35

Elevated blood pressure in mid-life is associated with ..

Answer 35

increased risk of dementia 15-20 years later

Question 36

there is a Strong association between atherosclerosis and

Answer 36

dementia

Question 37

Obesity is a risk factor for which 3 things?

Answer 37

atherosclerosis, hypertension and Type 2 diabetes