ADA

A major reason we use caffeine is because of its wakefulness promoting effects. Caffeine induces these effects through the adenosine receptor ADORA2A. When adenosine binds to ADORA2A pathways promoting sleep are initiated. However, whilst caffeine can also bind to ADORA2A it does not induce these pathways. As the ‘A’ allele of ADA is associated with reduced function, leading to a lack of adenosine clearance by morning. This is associated with feelings of sleepiness and lethargy and so the ADORA2A blocking effects of caffeine may be particularly beneficial.

The ‘A’ allele of ADA G22A demonstrates reduced activity, which may lead to residual adenosine being present upon waking leading to a feeling of sleepiness or lethargy. Caffeine blocks residual adenosine activity promoting a feeling of wakefulness ⁶.

Zinc is a cofactor for ADA and is required for it to function correctly. For those with the ‘A’ allele of ADA G22A which demonstrates reduced activity, which may lead to residual adenosine being present upon waking leading to a feeling of sleepiness or lethargy, ensuring zinc levels are at their optimum should maximize ADA activity and potentially limit the amount of adenosine present on waking ⁷.

Melatonin is a hormone produced by the body in order to regulate sleep patterns. Produced when the body detects a dark environment (receptors in the eyes are especially important for this) it interacts with melatonin receptors throughout the body to slow cell activity and promote the onset of sleep. As well as improving sleep onset melatonin has been shown to improve the feeling of wakefulness and alertness the morning following supplementation, which is especially important in those with the ‘A’ allele of ADA G22A ^8,9.

Magnesium has been shown to improve sleep length and quality by stimulating the complex GABA neurological pathway. It has also been shown to improve the feeling of wakefulness and alertness the morning following supplementation ^10,11. For those with the ‘A’ allele of ADA G22A, which demonstrates reduced activity which may lead to a buildup of adenosine, magnesium may help promote a feeling of wakefulness.

Chamomile has a long history of use, as an aid to improve sleep and act as a general relaxant starting with the Romans, Greeks and Egyptians. The key ingredient of chamomile which promotes sleep is the flavone apigenin. Found in many plants, with chamomile flowers being a particularly rich source, the complex molecule apigenin interacts with the complex neural signaling pathway GABA in order to promote sleep ¹².

The ‘A’ allele of ADA G22A demonstrates reduced activity which may lead to a build up of adenosine in the morning, leading to a feeling of lethargy. Apigenin mediated modulation of GABA may promote a long, better quality nights sleep, meaning ADA has longer to convert adenosine, limiting any feeling of lethargy in the morning.

Passion flowers are a large group of vine growing plants, originally found in tropical regions but now grown much more extensively. They have long been used by Native Americans to make a tea used to treat insomnia; this practice was rapidly adopted by European colonists. The key ingredient of passion flower for promoting sleep has been identified as vitexin, which is derived from apigenin. It is thought to act in a similar fashion to apigenin, promoting good quality, deep sleep and reducing restlessness, by interacting with the complex GABA pathway ^13,14.

The ‘A’ allele of ADA G22A demonstrates reduced activity which may lead to a build up of adenosine, leading to a feeling of lethargy in the morning. Vitexin activation of GABA signaling may promote a longer, better quality nights sleep. Therefore, ADA may have longer to convert adenosine, limiting any feeling of tiredness in the morning.

Adenosine is the native molecule which binds to the ADORA2A receptor to induce a sleep promoting effect. It is released upon the breakdown of ATP, the cells “energy currency”. ADA is the enzyme which breaks down adenosine into inosine, preventing its sleep inducing effect. In those with the ‘A’ allele ADA G22A activity is reduced meaning that residual levels of adenosine are left on waking. This can manifest as a feeling of sleepiness or lethargy in the morning, and so additional adenosine should be avoided ^3,4.