Turmeric and the MAO Enzymes
Turmeric, and its active compounds of the curcumin family, work some of their magic by binding with and blocking the action of enzymes involved with the catabolism (inactivation) of what are called the catecholamines or monoamines: serotonin, dopamine, and norepinephrine. The enzymes, called monamine oxidazes (MAO A and B for short), maintain the critical balance of neurotransmitters in the brain (and elsewhere) to ensure that there is neither too much or too little. Some of the first anti-depressants designed by pharmacologists inhibited the MAOs (monoamine oxidaze inhibitors – MAOIs) based upon the notion that depression was a result of too little serotonin, dopamine and/or norepinephrine. Consequently, when I was in graduate school, the hottest schizophrenia research suggested mutations in these enzymes (and others like COMT), were linked to the onset of psychosis. Though controversial, the MAO theory remains prominent today. The reduction in enzyme activity was also linked to aggression and violence. These hypotheses were based upon the belief that psychosis was a result of too much dopamine floating around in the brain, while the increased aggression and violence was believed to be loosely associated with excessive serotonin, dopamine and/or norepinenphrine.
Since the 1990s or so, drugs that inhibit MAOs have largely been replaced serotonin reuptake inhibitors or serotonin/norepinepinephrine reuptake inhibitors (SSRI/SNRI) due the myriad of side effects associated with MAOIs. Namely, MAOIs can induce hypertensive crisis, particularly if one consumes foods high in tyramine like cheese, wine, and chocolate. Tyramine blocks MAO-A, further inhibiting an already blocked enzyme.
In addition to their roles in maintaining serotonin, dopamine and norephinephrine balance, the MAO-A and MAO-B enzymes also breakdown and deactivate phenethylamine, benzylamine (MAO-B), tyramine, and tryptamine (MAO-A and B). Phenethylamine is a central nervous system stimulant, close analogs of which form the backbone of many stimulant drugs like amphetamines. The inability to breakdown these compounds, thus, would have serious hyper-stimulatory effects in the brain and in the heart.
Already Deficient in MAO and COMT?
Turmeric is a natural MAOI explaining many of its purported antidepressant effects. While this is viewed a positive effect, in individuals who take MAOIs and/or have mutations in the MAO enzymes, turmeric may be problematic. I am one of those people. I have multiple mutations in the MAOB enzyme and am homozygous in a few. I carry a few homozygous in COMT mutations. I just happen to know this because we did 23andMe testing as a family last Christmas and I am slowly making it through the SNP (single nucleotide polymorphism) analyses. Given my PhD in psychology, finding that I had a propensity towards psychosis was quite the family joke.
I did not know turmeric was an MAOI when I began taking it, nor was I aware that I had these mutations. I had focused solely on its antiflammatory capacity which works by entirely different mechanisms. I suspect many others, including physicians prescribing this compound, are neither aware of its MAOI properties nor aware of the large number of folks who carry mutations in these enzymes. According to Livewello.com, where we ran the SNP analyses, a significant percentage of the population may carry mutations that decrease the activity of one or both of the MAO and/or COMT enzymes (20-50%, depending upon the SNP in question). The mutations are not as rare as we suspected.
What Happens When Someone With MAO Issues Takes Turmeric?
All sorts of things go haywire, according to my experience. Let me preface this by saying, I am 50 years old, healthy and active (competitive powerlifter plus crossfit). I take no medications; haven’t for years. I don’t drink, don’t smoke and I eat well. I have had a lifelong battle with extremely fickle and highly reactive blood pressure (one of the reasons I take no medications) but I have learned how to control it with diet, and except for periodic episodes, haven’t had high blood pressure in years. (With the genetic testing I found out that I also have a bunch of mutations in the renin-angiotensin system – explaining many of my issues with blood pressure and I have always suspected I have this mutation but it isn’t included in the 23andMe analysis, at least that I can tell).
I began taking turmeric, for no real reason other than its anti-inflammatory actions. After taking it regularly for 8 or 9 months, my blood pressure began going up again. I did not know why, as I had not connected the dots yet. Over the course of about 6 weeks, I gained 7lbs with no changes in my diet, suggesting perhaps a new onset insulin resistance. I also began to have hot flashes and night sweats. Overall, my chemistry just seemed off. I assumed I was hitting menopause. I may yet be approaching menopause, but I suspect now these symptoms were related to the turmeric – induced MAO inhibition. Since I already have reduced MAO and COMT capacity, the turmeric, as mild as it is, may have been just enough to send my chemistry into a tailspin. Because the reaction wasn’t immediate, I suspect there was some sort of cumulative effect that ultimately altered enzyme activity or receptor activity, or perhaps, a threshold was met, I am not sure. Nevertheless, the accumulating serotonin would explain the weight gain and potential change insulin sensitivity. The excess dopamine (perhaps via downregulated dopamine receptors and altered renin-angiotensin function), combined with the norepinephrine and phenethylamine would connect to the hypertension I was experiencing. And the entire mess would disturb the autonomic system towards increased sympathetic tone, which would account for the hot flashes/night sweats and general temperature dysregulation.
I stopped taking the turmeric about a month ago and everything has returned to normal. My blood pressure has settled down, no more hot flashes and the weight is gradually coming back off. Again, no changes in diet.
If there is a lesson in this event, it is that no supplement is safe for everyone. I cannot help but wondering what might have happened had I not connected the dots. Would I have progressed into a full blown hypertensive crisis, a serotonin syndrome of sorts or some other equally deleterious event? Perhaps. We’ll never know, because I stopped taking the supplement.
I should note that it was only by happenstance that I connected these dots. I just happened to know that I had these mutations, happened to have studied them in graduate school, and happen to monitor my blood pressure. If any one of these pieces were missing, I doubt I would have considered turmeric as the culprit.
Bottom line – human chemistry is complicated, each of us is a genetic mess, and for as much as we know about genetics and health, we have only scratched the surface. If you are taking a supplement, even if you have been taking it for a while, and weird symptoms arise, consider the possibility that it may not be effective for you.
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