Print Friendly, PDF & Email

This gene will make you more tired in the day, but also give you a deeper sleep.

If you want to interpret or analyze your genes, the best tool is SelfDecode.

About Adenosine Deaminase (ADA)

Adenosine deaminase

Adenosine Deaminase or ADA converts adenosine to inosineInosine acts as a competitive inhibitor to adenosine.

Adenosine deaminase is present in places like red blood cells and the vessel wall (R).

There are two 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).

About Adenosine


Adenosine is a chemical that’s a part of ATP and cAMP.  It is believed to sleep promoting and suppresses arousal.

Adenosine can be converted to SAH and AMP (R).

Adenosine inhibits the activity of orexin neurons (by the A1 receptor in the lateral hypothalamus), which causes fatigue and allows for sleep (R).

Orexin A causes wakefulness and the sleep-promoting action of adenosine can be reversed by orexin A (applied to the lateral hypothalamus, perhaps by exciting glutamate input to orexin neurons via the action of orexin receptor 1) (R).

Caffeine’s principal mode of action is as an antagonist of adenosine receptors in the brain (R).

Adenosine increases blood flow to various organs through vasodilation (R).

Adenosine increases insulin sensitivity and glucose uptake in cells, which lowers blood glucose (R).

During instances of cellular stress such as inflammation or hypoxia, adenosine levels increase and (through A2A receptors) produce an overall anti-inflammatory effect (R).

Adenosine receptors are key in opening the blood-brain barrier (BBB). Mice dosed with adenosine have shown increased BBB permeability (R).

Adenosine activates ghrelin/growth hormone secretagogue receptor.  Therefore, it’s able to increase appetite.  However, it is unable to induce the secretion of growth hormone (R).

Adenosine is believed to be an anti-inflammatory agent at the A2A receptor, both internally and topically.  It speeds wound healing (R).

Methotrexate’s anti-inflammatory effect may be due to its stimulation of adenosine release (R).

A reduction in adenosine activity leads to increased activity of dopamine and glutamate (R). 

Adenosine has been shown to promote thickening of hair on people with thinning hair (R).

Adenosine increases slow wave sleep (R).

Adenosine inhibits prolactin and growth hormone secretion in pituitary cells (R).

However, adenosine is an agonist of the Growth Hormone Secretagogue Receptor (R), which means that it probably increases growth hormone release.

ADA, Adenosine, and The Immune System

Adenosine and the Immune system

ADA and adenosine in humans are both involved in the development and maintenance of the immune system (R).

Adenosine and ADA mainly have an immune lowering effect, but also have an immune stimulation effect in some ways.

ADA activates T lymphocytes (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 also inhibits the activity of NK cells (R), which is important to control viral infections.

Adenosine deaminase 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).

The Adenosine Deaminase Gene

Order your 23andme to see what alleles you have.

ADA Gene SNPs:

  1. RS73598374 (ADA) CT

How to Increase Adenosine Deaminase

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 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 play a beneficial role because it’s a PDE inhibitor and also an adenosine antagonist, but caffeine has negatives.


Adenosine deaminase

ADA Inhibitors

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

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

That’s why I decided to create tools that will help others cut down the guesswork:

  • Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
  • SelfDecode – a software tool that will help you analyze your genetic data from companies such as 23andme and ancestry. You will learn how your health is being impacted by your genes, and how to use this knowledge to your advantage.
  • SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
  • SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
  • Selfhacked Inflammation course – a video course on inflammation and how to bring it down
  • Biohacking insomnia – an ebook on how to get great sleep
  • Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
  • BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
  • SelfHacked VIP – an area where you can ask me (Joe) questions about health topics

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.


1 Star2 Stars3 Stars4 Stars5 Stars (7 votes, average: 3.29 out of 5)

Why did you dislike this article?



  • Ben Saini

    If you have the C allele and suffer from insomnia how can you increase Adenosine levels in order to promote restful deep sleep??

  • Mr. Sick

    It’s a shame for people with insomnia that there isn’t a supplement, that decreases ADA. This would do just the right think. I just reduced my coffee consumption (only until 2 pm) to jsut one small cup right after breakfast and the first to days …. damn… that felt kind of normal. Felt real good.
    Unfotunately this effect vanishes and leaves me at least as sleepless as I was before.

    Theoretically, berberine does indeed do the trick ( )

    But it doesn’t work for me somehow. Maybe Berberine has some wakefulness promoting action as well.

    Still not gonna gulp mercury lol

  • Sebastian

    Selfdecode says I have the T allele and I suffer from fatigue, coffee helps, so does zinc. I have borderline low iga igg and igm levels…am I at risk of developing an immune deficiency?

  • Leave a Reply

    Your email address will not be published. Required fields are marked *

    This site uses Akismet to reduce spam. Learn how your comment data is processed.