Curcumin and the MAO Inhibitor “Cheese Effect” from Tyramine Triggered Hypertension

Curcumin is a widely consumed component of the spice tumeric, commonly used in India and other parts of Asia. One of its important properties is functioning as MAO-A (Monoamine oxidase A) inhibitor that may help with certain neurotransmitter imbalance conditions that often manifest in a diagnosis such as depression. Some research shows that MAO-A levels in the brain are higher in many people with major depression and sleep disorders. This is probably why MAO inhibitor drugs have often been helpful for such conditions.

As an inhibitor, curcumin can lower MAO-A levels. Curcumin also helps boost serotonin and dopamine levels and that may be another part of why it helps depressed people.

A reader recently wrote to me wondering if curcumin could cause the deadly “cheese effect” known as the tyramine hypertensive crisis. This is a massive spike in blood pressure that is precipitated by MAO inhibitors when consumed with many common foods, particularly cheese but also chocolate, alcohol, yogurt, tofu, soy sauce, and also many meat products such as liver, pickled meats, and pork. The full list of foods containing substantial tyramine is very long. So the question is a good one as a tyramine crisis could kill you and it is very hard to avoid tyramine in food.

I’ll approach this question from two angles. The first is the theoretical basis of why curcumin is unlikely to cause a tyramine crisis. The second is my personal experience using curcumin. But first, let me explain the tyramine crisis.

Tyramine Crisis

Tyramine is a normal breakdown product of the amino acid tyrosine. The MAO-A and MAO-B enzymes are involved in breaking down tyramine so its levels do not build up too high. When tyramine levels get too high, stored monoamines such as dopamine, norepinephrine, and epinephrine are released to an unhealthy degree. This can send blood pressure skyrocketing. Often the first symptom is a headache. When it’s really severe, it can cause organ damage such as lethal brain hemorrhaging.

There’s also a theory that tyramine itself may be a neurotransmitter as receptors with high affinity for tyramine have been found on cell membranes in the brain and kidney. So it may be that tyramine has a direct impact on blood pressure, also, but most explanations focus on the jacked up release of neurotransmitters already well known for boosting blood pressure.

The “cheese effect” got its name when a doctor whose wife was eating cheese got severe headaches. He figured out that the MAO inhibitor drug she was taking interacted with the contents of the cheese.

Some cheeses, particularly aged cheeses, contain high levels of tyramine. (Interestingly, some such as cottage cheese have little tyramine.) People who are prescribed MAO inhibitor drugs are often told that they must avoid many common foods containing tyramine as a safety precaution. For most people, cutting common and enjoyable foods such as cheese, chocolate, tofu, and yogurt, out of their diets is going to be a problem. So often the question becomes one of whether the benefits of the MAOI drug outweigh the drawbacks.

Curcumin Is A Reversible MAO Inhibitor

The problems with the MAO inhibitor drugs in their early years (1960’s) were severe because almost nobody understood the reaction at first. There were many hospitalizations and deaths from the tyramine hypertensive crisis occuring in people using MAO inhibitor drugs that were irreversible inhibitors.

An irreversible inhibitor binds to the inhibited enzyme such that it cannot be unbound, at least not through normal biological processes. Many of the MAOI drugs on the market fall into this category.

Curcumin, however, is a reversible inhibitor. This means that when curcumin binds to the MAO enzyme molecules, it can later be unbound. This typically happens when there is a competing compound with affinity for the MAO enzyme. Tyramine is a good example. If you take curcumin and it binds to some of the MAO enzymes in your body, this binding can and will be reversed to at least a significant degree if you eat a lot of tyramine in your diet. This keeps the tyramine levels from building up dangerously.

Also, you may notice that any discussion of MAO drugs usually includes mention of both the MAO-A and MAO-B enzyme variants. These are slightly different enzymes that can both break down tyramine. It appears you can inhibit MAO-A but if you do not also inhibit MAO-B then the body can still break down some tyramine to help avoid the tyramine hypertensive crisis. MAO-A and MAO-B inhibitors also affect a somewhat different set of neurotransmitters, so there are reasons why one may be better than another for particular conditions.

But you may notice that in some writings curcumin is listed as inhibiting both MAO-A and MAO-B. So why doesn’t curcumin cause a problem? One common belief is that the MAO-B inhibitory effect is weak compared to the MAO-A inhibitory effect so you could call it “partially selective”. But I think the reversible inhibitor explanation is probably more responsible for the relatively low risk of curcumin compared to many MAO inhibitor drugs that are irreversible inhibitors.

Many MAOI drugs are prone to problems with the “cheese effect” because they inhibit both MAO-A and MAO-B enzymes and are irreversible meaning their inhibitory effect does not naturally decay and the enzymes already inhibited will never be restored to function. They leave a person’s body with little ability to break down tyramine and that’s why diet is so important when taking such drugs.

There are some newer MAO inhibitor drugs that are reversible and/or selective, meaning that either MAO-A or MAO-B reduction can be attempted without much affect on the other MAO variant. These drugs are likely to be much safer than the early MAO inhibitors.

My Own Experience With Curcumin

I’ve used curcumin myself for years, generally one or two capsules daily. I take them at least several hours apart along with meals containing some fat and fatty supplements (fish oil, borage oil, lecithin, etc.). Initially I started taking tumeric, but long ago switched to Life Extension’s BCM-95 Super Bio-Curcumin product.

I have never noticed any interaction with cheese or other tyramine containing foods such as tofu, soy sauce, and yogurt. I eat all those foods fairly often. I also do check my blood pressure and it is healthy, not high, so from my personal experience I think curcumin alone is not likely to cause a tyramine crisis with skyrocketing blood pressure even if you take it regularly and do not try to avoid tyramine in your diet.

If you examine the “List of MAOIs” section in Wikipedia’s article on MAO inhibitors, you will see a lot of common supplements and food compounds listed including reseveratrol, curcumin, tumeric, gingko biloba, rhodiola rosea, anthocyanins, proanthocyanidins, licorice, eleuthero (Siberian ginseng), piperine (often mixed with curcumin to enhance bioavailability), coffee, etc. I consume many of these each day, as do many other people. Yet I don’t have the tyramine reaction and I have not personally heard or read of anybody having a severe life-threatening tyramine reaction from such a practice. Tyramine triggered severe hypertension seems to be in practice exclusively a problem for MAOI drugs, not herbals and foods.

Tyramine is a breakdown product of tyrosine, an important amino acid for thyroid function. A lot of people with poor thyroid function probably have too little tyrosine and/or phenylalanine in their diets. The body can make tyrosine from phenylalanine, so if you have enough of it you’re less likely to end up with a tyrosine deficiency. But if you’re taking a MAOI drug that irreversibly inhibits both A and B then tyrosine supplements could in theory be a problem as they could cause the buildup of tyramine that does not breakd down due to the MAOI drugs.

I think you are extremely unlikely to have a severe tyramine reaction from any reasonable combination of the common supplements listed above, particularly if you spread them out over the day so you are not taking everything at once. Both the theory and my personal experience and that of others bear this out.

The main adverse reactions I’ve seen reported involving curcumin and symptoms of elevated tyramine are headaches. But there are also plenty of reports of people taking curcumin and having their headaches disappear. Headaches are among the most common complaint in people and unfortunately as a single symptom really can’t tell you much because almost everybody has them sometimes and the causes are all over the map.

After decades of intensive research trying to connect migraine-prone people’s headaches to a cause, there is some evidence that in some people tyramine could be the culprit. It’s particularly true for those who get a headache shortly after eating a particular kind of food. But then you’ve got people advising curcumin for migraine headaches and others swearing it worked great for relieving their chronic headaches:

Quoted from Margaret’s curcumin PROTOCOL:

A listserv friend, who plans to start taking curcumin soon, wrote about having chronic pain and headaches. I don’t recall if I have written anything about headaches on my blog, but this is what happened to me. I used to have horrendous headaches almost daily. I think they might have been caused by my very high blood viscosity (that seems to be one of my main MM symptoms), which essentially means that I have thick blood. Well, curcumin is a natural blood-thinner. Not long after I began taking curcumin, my headaches stopped. Gone. Poof! Just like that. I still get occasional mild headaches, probably because my blood viscosity is still on the high side, but nothing like those terribly painful pre-curcumin ones. I hope curcumin will take care of my friend’s headaches, too.

The odds are there are multiple factors involved in most headaches. Tyramine isn’t the only factor to be considered and hence the MAOI effects of curcumin may or may not be relevant to any particular headache sufferer. And there’s always the chance that the anti-inflammatory and blood flow improving effects of curcumin will lower blood pressure more than any tyramine-buildup effect might raise it. There’s no way to know without trying it or perhaps in the future some combination of extensive (and likely expensive) testing to predict what the effect might be.

Any time you use a new supplement, you should be cautious and watch for both the intended effect and any unexpected side effects. So with curcumin, that means you should start with a low dosage and monitor for effect. If you do not detect any side effects, then raise the dosage gradually until you get the effect you desire or reach a recommended or prescribed dosage.

A lot of people take curcumin for its general preventive effects at blocking inflammation, cancer, beta amyloid plaque buildup, etc. and so they may have trouble determining if the intended effect is ever obtained because they are not treating a symptom that can be readily monitored. So for them, I’d say stick with the recommended dosage on the product unless you get compelling informed advice otherwise.

This is really what you should be doing with pretty much any supplement or medication. Interactions are always a potential problem, but if you start low and ramp up gradually to a reasonable dosage then you are not likely to have a problem that gets so bad that it is a major threat to your health before you can easily do something about it. This is also why it is best to introduce only one supplement (or a few if they have little chance of interaction) at a time and give them some time (at least a week, preferably a month) to have an effect before you introduce yet another supplement.

I realize that this may mean it could take over a year to get going to a comprehensive supplementation program for somebody who is extensively using dozens of supplements. The best advice here is to look for groups of supplements that have no documented adverse interactions and then try spacing their introductions more closely together. For instance, it’s reasonably safe to start taking both niacin and plant sterols at the same time if your cholesterol levels are high as both will tend to lower cholesterol mildly and therefore are unlikely to lower it to a dangerously low level. But you probably should not start statins or other HMG CoA reductase inhibitors at the same time as niacin and plant sterols as they are more likely to drastically drop cholesterol levels. (Frankly my advice would be to avoid statins entirely except as a measure of last resort and then to only take them if you also get your CoQ10 levels tested regularly and supplement with CoQ10 to keep the levels in the upper half of the reference range.)

Final Thoughts

Curcumin is a great supplement with a lot of promising effects and very low reported incidence of serious side effects. Beyond the reasons I listed above, consider that it has been widely consumed for thousands of years in some parts of Asia where tofu and other fermented foods high in tyramine are also widely consumed. If there was likely to be a severe problem with curcumin triggering a dangerous tyramine hypertensive reaction, it’s likely that this problem would be fairly well known. But there is no mention of this.

So all things considered, I personally am not worried about curcumin consumption being a major risk factor that could precipitate a tyramine hypertensive crisis. Moreover, I believe that if you can use curcumin to get relief from symptoms that MAOI drugs are often used to treat, you are probably safer doing so because there have been vastly more harmful reactions to MAOI drugs than to curcumin.

Related Articles

Further Reading

Elevated Monoamine Oxidase A Levels in the Brain: An Explanation for the Monoamine Imbalance of Major Depression

Inhibition of monoamine oxidase-B by the polyphenolic compound, curcumin and its metabolite tetrahydrocurcumin, in a model of Parkinson’s disease induced by MPTP neurodegeneration in mice

Food constituents attenuate monoamine oxidase activity and peroxide levels in C6 astrocyte cells

Turmeric, Curcumin…Alzheimer’s & Migraine Pain Relief

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