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One of the best parts of researching methylation is meeting people who ask very good questions.  One very good question came up the other day about MAO-A and whether or not it was sped up or slowed down.  This question is important considering how much impact the MAO system has on how we handle stress and neurotransmitter balance.  Taking this idea further, because MAO enzyme degrade catecholamines (and histamine BTW!) we NEED to know if MAO-A and -B are going FASTER or SLOWER.  This is the question that I was asked and I have found the research that answers this for us. 

MAO-A comes in two different flavors – low activity or high activity.  The gene that is tested for on Sterling’s App is the rs6323 variant.  As I poured through my research looking for the answer to whether or not MAO-A was sped up or down, I found this research nugget:

“We examined polymorphisms in genes encoding the catabolic enzymes catechol-O-methyltransferase and monoamine oxidase A. Subjects with monoamine oxidase A G/T polymorphisms (rs6323) coding for the highest activity form of the enzyme (G or G/G) had a significantly lower magnitude of placebo response than those with other genotypes.” – J Clin Psychopharmacol. 2009 Aug;29(4):372-7. PMID: 19593178

This was a huge find!  It basically proves that anyone with MAO-A rs6323 +/- or +/+ for the T allele has slowed activity of the enzyme (if you don’t have a G allele, then your MAO-A is slowed down).  This means conversely that those with MAO-A rs6323 -/- on the variant report have the high activity enzyme – aka the normal enzyme and the G/G genotype.  MAO systems exists outside the brain in cells like RBCs and thrombocytes.  But in the brain the MAO system is inducible.  Anything that injure mitochondria such as oxidative stress, toxin exposure, and the aging process in general will cause an increase in MAO activity regardless of genetics.  That is what inducible means, it can increase due to environmental signals regardless of the genetics – a key point to remember!

Aging is equivalent to DNA damage and as mitochondria are destroyed int the brain from toxins/stress/malnutrition then we are effectively aging faster. These effects plus SNPs cause increases in enzyme speed of the MAO system, esp. MAO-B (less clarity when it comes to MAO-A but likely same pattern since molecularly almost identical). Repeat: aging, inflammation, toxins or anything else that hurts the mitochondria will INCREASE the speed of both MAO-A and MAO-B. MAO-B is found mostly in the brain and therefore is more important with neurological issues like Parkinson’s disease, where it has long been known that MAO-B is sped up!  The take away is that its all about MAO system going too fast and causing problems.

This doesn’t mean that people with MAO-A rs6323 -/- will never have the same issues as those with MAO rs6323 +/+.  It simply means for people with MAO-A ++ or +- one of the main enzymes responsible for breaking down catecholamines is going slower genetically.  If you don’t know which version of MAO-A you have, all you need to do is get your 23andme report and run it through’s variant report.  This will tell you whether MAO-A is sped up or slowed down.

Yours in Health,

Dr. Rostenberg

By studying the current peer-reviewed research, Dr. Rostenberg has discovered powerful, natural strategies to balance your methylation pathways and heal your body.  He can help you uncover the genetic or root causes of your health problem and find a natural solution!  If you would like help with your methylation genetics to improve your gut function and reduce/eliminate your symptoms, please contact Dr. Rostenberg at Red Mountain Natural Medicine today. Phone 208-322-7755. Email Website