Quercetin and Luteolin as Endocrine Disruptors

Patients with MCAS often take the supplements quercetin and/or luteolin, which have been shown to help stabilize mast cells. Quercetin and luteolin are flavonoids, natural compounds found in many different plant foods. I have often used these supplements, favoring the brand Algonot, because it was formulated by the great mast cell researcher Dr. Theo Theoharides.

Quercetin is also gaining popularity for the prevention of COVID-19 and treatment of post-COVID syndrome.

I was unaware of any risks associated with these supplements until I recently came across this article showing that large doses of quercetin and luteolin can act as endocrine disruptors. That means they can alter our hormone levels. The article states that supranatural doses can act to increase estrogen and decrease progesterone, which, among other things, may help prevent some breast cancer, but may increase risk of endometrial cancer. From the conclusion:

“Here our studies reveal that luteolin, a flavone marketed for a variety of therapeutic applications, including pediatric applications, has potent multi-functional endocrine disrupting activity. Luteolin displays estrogen agonist activity that can drive cell growth in estrogen-dependent tissues. Additionally, luteolin can simultaneously act as a progesterone antagonist at physiologically attainable levels. This progestin antagonist activity is beneficial in a breast cancer model, inhibiting the progestin- stimulated increase in a population of cells with stem-like or tumor-initiating properties, but deleterious in an endometrial cancer model, blocking the progestin-mediated brake on estrogen-driven growth. These studies highlight the promise and peril of supplementation with nutraceuticals and suggest caution in supplementing well beyond the intake of a normal, healthy diet.”

So…what does this mean for those of us who benefit from these supplements? How concerned should we be about endocrine disruption from supplements that help our MCAS? I think these are good questions to discuss with our doctors. Some other things to consider include…

1. How dependent am I on quercetin or luteolin to prevent severe MCAS reactions? If they are preventing life-threatening reactions, then a little endocrine disruption may be a small price to pay.
2. How does this fit into the bigger picture of my exposure to endocrine disruptors? According to the Environmenal Working Group, we are exposed in our food, water, dust, food packaging, and personal care products. Here is their list of worst endocrine disruptors and how to avoid them. It makes me wonder if the effect from quercetin and luteolin is significant, and if so, can I offset the effect by being more careful to avoid endocrine disrupters from other sources?
3. Do I have any medical conditions or family history—such as endometrial cancer—that could put me at higher risk from these hormonal effects?
4. Do these supplements make me feel better? It may be worth a test (making any changes very gradually), to make sure. No point taking these supplements if they aren’t helping!
5. What’s my minimum effective dose? It may be worth some experimenting to find out (again, making any changes very gradually, to be on the safe side).
6. Do I need to take these supplements all the time or just occasionally, such as during a flare?
7. Could I achieve the same MCAS control through some other means, like getting an air purifier, following a lower-histamine diet, or doing a better job avoiding some known triggers?

Finally, some studies have found that an anti-inflammatory and vegetable-rich diet may be protective against endometrial cancer. And consumption of a healthy diet (unprocessed, high in fruits and veggies), especially cruciferous vegetables, may help offset any hormone imbalance by reducing excess estrogen. A diet full of sugar and processed foods can contribute to excess estrogen.

My own experience is that I itch like crazy ALL NIGHT LONG without my quercetin and luteolin. That made it an easy decision to keep taking it, although I have no known risk factors for hormone-related cancer, I found a much lower effective dose, and I’m careful to avoid endocrine disrupters from other sources. I also eat a healthy diet, and I like to think my love affair with cauliflower and Brussels sprouts may be protective. But this recent discovery reminds me that supplements always have risks, especially when we’re taking unnaturally high doses of substances that have been extracted from the whole food. It’s not what nature intended, and that can sometimes have consequences.