How Genes Influence The Risk For Caffeine-induced Insomnia

Caffeine and Sleep

Caffeine is a central nervous system stimulant, which is widely used for its psychoactive effects. It is commonly used to alleviate behavioral, cognitive, and emotional deficits caused by sleep deprivation.

Regardless of its beneficial effects, caffeine may have adverse sleep-related consequences that might lead to sleep disruption and insomnia symptoms. This is because caffeine consumption is associated with lower levels of 6-sulfatoxymelatonin. 6-sulfatoxymelatonin is a substance produced during the metabolism of melatonin. It is involved in the regulation of circadian rhythm. Lower levels of 6-sulfatoxymelatonin can result in increased alertness (wakefulness).

How Does Genetics Influence The Risk of Caffeine-induced Insomnia?

CYP1A2?encodes cytochrome P-450 group of enzymes. These enzymes influence the absorption and metabolization of caffeine. Caffeine is absorbed rapidly and completely from the gastrointestinal tract. After absorption, the P-450 enzymes help with the metabolization. Variation in the?CYP1A2?activity represents a major source of variability in the pharmacokinetics (drug absorption, distribution, metabolism, and excretion) of caffeine.

While the?CYP1A2?gene is responsible for caffeine metabolism, another gene,?ADORA2A, influences how your sleep is affected by caffeine intake. This gene encodes the adenosine receptor. When an adenosine molecule binds to this receptor, it inhibits all the processes that are associated with wakefulness. Caffeine acts as an adenosine receptor antagonist - it mimics adenosine and goes and binds to the adenosine receptor. This results in increased levels of free adenosine, leading to a boost in neuronal activity and wakefulness.

The adenosine A2A receptor (ADORA2A receptor) plays a role in the effects of caffeine on arousal. Mice lacking functional A2A receptors do not show increased wakefulness in response to caffeine administration, indicating that the A2A receptor mediates the arousal response.

rs5751876 and Caffeine-induced Insomnia

The rs5751876 is a T>C polymorphism located in the?ADORA2A?gene, which modulates the sleep-wake cycle, and contributes to individual sensitivity to caffeine effects on sleep.

Studies have documented that in caffeine consumers (less than 300mg), rs5751876 -?T allele is associated with a decreased risk of sleep complaints and insomnia as compared to the C allele.

Non-genetic Influence on Caffeine-induced Insomnia Risk

1. Regular consumption - Researchers found that the effects of caffeine on sleep are higher in occasional coffee drinkers compared to those who drink coffee regularly.
2. Age and weight - Few studies have reported that older adults are more sensitive to the effects of caffeine compared to younger people. The exposure to caffeine in the body may also differ based on the weight of the person.
3. Time - Consuming caffeine closer to bedtime can disrupt sleep more than when consumed during the day.

Effects of Caffeine-induced Insomnia

If caffeine consumption is not wisely regulated, it could lead to delayed sleep and sleep deprivation. Sleep deprivation is associated with lapses in attention, lowered alertness, and a reduction in cognitive function. Scientific studies have shown that a reduction in sleep time of 90 minutes could reduce objective alertness during the daytime by one-third.

Tips for Regulating Caffeine Consumption

1. Moderate your consumption of caffeine. Do not drink caffeinated beverages post 5:00 pm or 5-6 hours before sleeping, as the effects of caffeine last for up to 6 hours after consumption.
2. Chamomile tea is considered to be a mild tranquilizer or sleep inducer. It contains the antioxidant apigenin, which may promote sleep.

Summary

1. Caffeine, a central nervous system stimulant, may have adverse sleep-related consequences that might lead to sleep disruption and insomnia.
2. Genes like?CYP1A2?and?ADORA2A?influence caffeine-induced insomnia.?CYP1A2 is related to caffeine metabolism while _ADORA2A?influences how your sleep is affected by caffeine intake.
3. The T allele of rs5751876 SNP in the?ADORA2A?gene is associated with a decreased risk of insomnia than the C allele.
4. Age, weight, time of consumption, and frequency of consumption are the non-genetic influences on caffeine-induced insomnia.
5. Moderated caffeine consumption during the day at least 5-6 hours before sleep is recommended to prevent caffeine-induced insomnia. Chamomile tea can also be consumed as it is a sleep inducer.

Reference

• https://pubmed.ncbi.nlm.nih.gov/31817803/
• https://pubmed.ncbi.nlm.nih.gov/15965471/

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