Adenosine Deaminase or ADA converts adenosine to inosine.  Inosine acts as a competitive inhibitor to adenosine. So higher ADA will reduce adenosine and increase inosine. Lower ADA will increase adenosine and lower inosine.

The ADA gene provides instructions for producing the enzyme adenosine deaminase. This enzyme is produced in all cells, but the highest levels of adenosine deaminase occur in immune system cells called lymphocytes, which develop in lymphoid tissues. These lymphoid tissues include the thymus, which is a gland located behind the breastbone, and lymph nodes, which are found throughout the body. Lymphocytes form the immune system, which defends the body against potentially harmful invaders, such as viruses or bacteria.

The function of the adenosine deaminase enzyme is to eliminate a molecule called deoxyadenosine, which is generated when DNA is broken down. Adenosine deaminase converts deoxyadenosine, which is toxic to lymphocytes, to another molecule called deoxyinosine, which is not harmful.

Read: About Adenosine and The Adenosine Deaminase Gene: Rs73598374.

Adenosine Deaminase or ADA converts adenosine to inosine. Inosine acts as a competitive inhibitor to adenosine. So higher ADA will reduce adenosine and increase inosine.

Lower ADA will increase adenosine and lower inosine. ————————————————————————————– Adenosine has a bunch of effects on the body:

• Adenosine is sleep promoting.
• Adenosine increases blood flow to various organs through vasodilation (R).
• Adenosine increases insulin sensitivity and glucose uptake in cells, which lowers blood glucose (R).
• Adenosine is overall anti-inflammatory and speeds wound healing (R).
• Adenosine opens the blood-brain barrier (BBB) (R).
• Adenosine activates ghrelin/growth hormone secretagogue receptor, which increases appetite (R).
• Adenosine generally decreases the activity of dopamine and glutamate (R).
• Adenosine promotes thickening of hair for people with thinning hair (R).
• Adenosine increases slow wave sleep (R).
• Adenosine stimulates the immune system by triggering the release of IL-6 and IL-1b (R).
• Adenosine inhibits the immune system by decreasing TNF, which is an inflammatory cytokine.
• Adenosine inhibits the activity of NK cells (R), which is important to control viral infections.

Adenosine deaminase is present in places like red blood cells and the vessel wall (R). There are 2 forms of ADA: ADA1 and ADA2. ADA2 is the predominant form present in blood and is increased in many diseases, particularly those associated with the immune system: for example most cancers, rheumatoid arthritis, psoriasis and sarcoidosis (R).

In addition to adenosine breakdown, ADA is believed to stimulate the release of excitatory amino acids (R). ADA is also necessary for the adenosine A1 receptors to work properly.  A₁ receptors are implicated in sleep promotion by inhibiting wake-promoting cholinergic neurons in the basal forebrain.  

Caffeine blocks these receptors (R). Levels of ADA correlate with blood glucose (HbA1C) because adenosine increases insulin sensitivity – and higher ADA will lower adenosine (R).

The A1 receptors decrease cAMP (R). Stimulation of the A₁ receptor results in a decrease in heart rate (R). ADA causes reduced telomerase activity (R).

ADA is involved in the development and maintenance of the immune system (R). ADA activates T lymphocytes (R). ADA deficiency is a known cause of immunodeficiency (R).

ADA deficiency increases thymus cell death (R), which will cause lower immune function as you age. ADA inhibition causes a quicker depletion of CD8+ T lymphocytes as people age (R).

ADA causes less IL-2 production (R). Deficient levels of ADA have also been associated with lung inflammation, thymus cell death, and defective T-cell receptor signaling (R).

What To Do If You Have The T Allele

If you have low ADA, you especially want to make sure you’re getting enough Zinc.

• Zinc is the only cofactor necessary for ADA activity, so adequate zinc is needed in order for the enzyme to work well (R).
• Estradiol is one of the few inducers of adenosine deaminase (R).
• IGF-1 is another inducer of adenosine deaminase (R).
• Simvastatin (and probably other statins) increases ADA production when it’s suppressed by IL-13 (R).
• Since low ADA will also lead to lower inosine, I recommend supplementing with 250-500mg inosine. Inosine will also compete with adenosine and balance you out more.
• Caffeine can really play a beneficial role because it’s a PDE inhibitor and also an adenosine antagonist, but caffeine has negatives.

ADA Inhibitors

If you have the T allele, you want to be aware of ADA inhibitors.

• Progesterone (R)
• IL-13 (R)
• DPP4 inhibitors, one of which is berberine (R).
• Mercury (R)
• Curcumin inhibits ADA in rats exposed to cadmium (R).
• Nettle inhibits ADA in prostate cancer tissue (R).