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Restless Legs and Caffeine
Caffeine is undoubtedly the most commonly used stimulant. It keeps more than half of the population alert through the day. However, it can also worsen restless leg syndrome. Find out how caffeine consumption affects restless legs and what you can do to overcome it.
by Brad Chase
Caffeine is a bitter, white xanthine alkaloid most commonly known for its stimulant effect.
In nature, it is produced by some plant seeds, leaves and fruits as a pesticide to poison the insects feeding on those plants. In humans, caffeine is a legal psychoactive drug producing its stimulant effect on the central nervous system.
Plant sources of caffeine include tea bush, coffee plant, kola nut, guarana berries and yerba mate. It is also found in teas, soft drinks and energy drinks consumed by many people daily.
Caffeine is toxic in high doses but long-term consumption of normal doses is safe.
Caffeine can have both positive and negative effects and the extent of these effects vary for each individual. For example, while some people complain of sleep disturbance after taking caffeine, others experience only mild sleep disturbance.
While tolerance develops to prolong consumption of caffeine so that most of its effects do not affect some users, it can also cause a kind of dependence deep enough to qualify as addiction.
Caffeine along with other xanthine alkaloids such as theophylline and theobromine are cardiac stimulants found in tea, coffee and even in chocolate (the ones made from cocoa beans) but in much smaller amounts.
Besides drinks, the stimulant effect of caffeine has been exploited to make caffeine tablets to improve mental alertness and reduce fatigue. Caffeine is such a popular stimulant that odd dosage forms have been invented to deliver caffeine including vaporizing the stimulant and caffeinated lip balm.
In plants, caffeine is synthesized from purine nucleotides such as adenosine monophosphate (AMP). One of its precursors is a related alkaloid, theobromine.
Since it is found abundantly in nature, commercially sold caffeine is rarely synthesized in the laboratory.
Caffeine is absorbed into the blood from the small intestine. This takes place within 45 minutes after ingestion and the peak concentration is reached within an hour.
Caffeine is well distributed in the body and the time it takes for the body to eliminate half the ingested dose varies between 5 - 6 hours. The rate of elimination of caffeine depends on various factors including liver function, drugs taken, hormone levels and even pregnancy.
Caffeine is metabolized by the enzyme, cytochrome P450, into 3 metabolites which are then further broken down before they are excreted in the urine.
Caffeine toxicity can occur after the ingestion of a very large dose of caffeine especially when ingested quickly.
A lethal dose of caffeine is estimated at 150 – 200 mg per kilogram of body weight.
Even though caffeine is usually quickly absorbed, the dose required to produce fatality is unlikely to get through. This is because such high doses would cause gastric irritation and trigger vomiting.
However, caffeine toxicity can still occur following the ingestion of 1 g or more of caffeine. Symptoms of caffeine toxicity vary from one individual to another.
These symptoms are usually due to the effect of caffeine on the central nervous system and circulatory system. These symptoms include hyperactivity, insomnia, breathlessness, delirium, diuresis, increased heartbeat, elevated respiratory rates, gastric irritation and vomiting.
Most of the biological effects of caffeine results from antagonizing adenosine.
Adenosine is a natural compound present in high levels in the body. It is found in every part of the body because it is a component of ATP (adenosine triphosphate), the energy molecule for cells.
It is especially found circulating the nervous system where it plays other roles. Adenosine reduces brain activity and it is known to induce the lethargy necessary for some animals to hibernate.
To produce its effects, adenosine (through adenosine receptors) reduces the activities of neurotransmitters such as dopamine, acetylcholine, epinephrine, norepinephrine and serotonin.
Caffeine blocks adenosine receptors in the nervous system. Because it is soluble in both water and lipids, caffeine can cross the blood-brain barrier.
Once it crosses over, it behaves like a non-selective adenosine receptor antagonist.
Because caffeine is structurally similar to adenosine, it can easily bind to adenosine receptors. However, it does not activate them but prevents adenosine from binding to them. In this way, caffeine can increase the levels of the neurotransmitters normally suppressed by adenosine.
Of the different classes of adenosine receptors discovered, the A2A class is the one with some relation to the dopaminergic pathway. These adenosine receptors are found all over the brain but mostly in the basal ganglia.
Furthermore, adenosine is known to be involved in the sleep-wake cycle. More specifically, adenosine has been shown to trigger sleepiness after extended mental activity. It does this by activating specific neurons through the A2A receptors.
Because caffeine blocks all adenosine receptors, it can maintain alertness by preventing adenosine from binding to A2A and causing sleepiness.
By binding those same receptors, it can also interfere with the dopamine system in the brain. This effect may be significant enough to cause changes in the levels of dopamine in the brain.
However, although it is likely that caffeine would increase the level of dopamine in the brain (a positive outcome for treating restless leg syndrome), its ability to also increase other neurotransmitters such as epinephrine and norepinephrine means that it can cause restlessness and hyperactivity (negative outcomes that promote the symptoms of restless leg syndrome).
Because the actions of caffeine on adenosine receptors are non-specific, there is no way to know what the net effect would be for each individual.
The effects of caffeine on the body can either be positive and negative. The table below provides a summary of these effects.
Since caffeine is mostly consumed for its ability to improve alertness and prevent drowsiness and fatigue, its ability to achieve these has been the most studied aspect of the stimulant.
Some of the mechanisms by which caffeine increases mental focus are also the responsible for its ability to trigger the symptoms of restless leg syndrome.
The combination of alcohol and caffeine should be avoided because they do have opposite effects on the central nervous system. While alcohol is a depressant, caffeine is a stimulant.
Avoiding caffeinated foods and drinks is a common lifestyle advice given to restless leg syndrome patients, and in most cases it relieves the symptoms of the syndrome. Such caffeinated products to avoid include teas, coffee, chocolate, soft drinks and energy drinks.
Abruptly stopping caffeine can, however, cause withdrawal symptoms in long-term caffeine drinkers.
Withdrawal symptoms include insomnia, muscle aches, joint pain, reduced mental focus and irritability. All of these symptoms will worsen restless leg syndrome for as long as they last.
Usually, withdrawal symptoms last 2 – 9 days. Therefore, patients getting off caffeine should know that the symptoms of the syndrome may get worse before they get better.
On its own, caffeine increases the arousal of the central nervous system by activating the wake-promoting neurons and increasing the levels of excitatory neurotransmitters. In this way, it prevents patients from sleeping, promotes motor activity and inhibits proper control of fine motor movements.
All of these effects cause heightened sensory awareness, insomnia and shaking of limbs.
Therefore, caffeine can cause the odd sensations, hyperactivity as well as the irresistible urge experienced in the limbs of patients with restless leg syndrome.
Caffeine can also increase energy production in the body and provide the needed energy to enhance performance. It is known to burn fats and triglycerides stored in muscles by increasing the levels of epinephrine.
In addition, through its actions on other neurotransmitters in the brain, it actually lowers neuron activation threshold making it easier for the muscles to burn fat for energy while reducing the perception of exerting the needed effort to achieve this.
This means that caffeine puts the muscles of the limbs on a semi-automatic fat-burning mission to promote movement. This is translated into the irresistible urge to move those limbs.
All the effects of caffeine are not due to the compound but also to its metabolites.
For example, paraxanthine is chiefly responsible for the breakdown of fats and the release of fatty acids to fuel the muscles while theobromine is a vasodilator that helps increase the flow of oxygen and nutrient-rich blood to the muscles and brains to meet the demands of hyperactivity.
Avoiding caffeine usually helps relieve the symptoms of restless leg syndrome for most patients but especially for those who take caffeinated drinks and foods regularly. The relief usually kicks in a few weeks after stopping caffeine.
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