What is an Nrf2 activator?

Nrf2 (pronounced 'nerf-too') activators are antioxidant-making powerhouses. More antioxidants usually means less inflammation, less cell damage, and healthier living. So how do we get more antioxidants? Activate your Nrf2! Let’s dive a little deeper and find out how Nrf2 activators affect our bodies.

These days we have so much information at our fingertips, yet finding the truth can be harder than ever. Figuring out how to eat and live healthy is no exception. 

Should I eat whole grains or go gluten-free? Is full-fat plain yogurt better than fat-free fruit yogurt? I’m supposed to get omega-3s from eating fish but don’t vegetarians live longer? It’s hard not to get bogged down in every detail when trying to eat healthy.  

Nrf2 and inflammation

Inflammation is pervasive in modern lifestyles. It plays a major role in many diseases, including in the onset of heart disease, in the incidence of depression, and in the onset of cancer. 

With such widespread inflammation and such powerful negative effects, finding ways of reducing or combating inflammation is of huge importance to medicine today.

Many plants produce active compounds that alleviate inflammation. These phytochemicals can activate antioxidant responses to inflammatory agents such as processed meat, pollution, alcohol, and stress. Phytochemicals (pronounced 'fie-toh-kem-ick-alls') can do this by activating–you guessed it! the Nrf2 pathway.

What this means is in order to reduce systemic inflammation, you can simply change your diet to include lots of inflammation-fighting foods.

Nrf2 and antiviral activity

Viruses are a major component of deaths worldwide. The HIV epidemic of the early 1980s and the current COVID-19 pandemic that we’re all experiencing right now are a grim reminder of what these tiny infections can do.

Research on HIV shows that processes related to the virus stop Nrf2 from being expressed, which leads to damage of healthy tissue in the lungs. However, this study also shows that activating Nrf2 can alleviate some of the damaging effects of the virus on lung tissue.

The research above also shows that even while on anti-retroviral therapy, low levels of the virus still block Nrf2 from activating, stopping antioxidant proteins from being made and increasing oxidative stress. 

Most viruses cause oxidative stress in the body, so helping the body to induce its antioxidant protection could be useful for protecting against toxic oxidants.

In addition to general oxidative stress, some preliminary research shows that COVID-19 can cause pulmonary fibrosis. While the mechanism behind this is still unknown, past research in mice shows that Nrf2 can actually protect against pulmonary fibrosis. That could be one reason why the potent Nrf2 activator sulforaphane has been suggested as a possible COVID-19 therapy.

Similarly, Nrf2-activating supplements using natural ingredients are being proposed as new therapies for COVID-19.

Nrf2 and longevity

There are many theories for why living things age. While we all recognize the symptoms of aging–wrinkles, susceptibility to disease, memory and hearing loss–we don’t know much about what actually causes aging. 

One theory for why we age is the Free Radical Theory of Aging (FRTA), first described in the 1950s. This theory argues that free radicals accumulate in the body, cannot be neutralized, and then cause oxidative damage–also known as aging.

Activating cytoprotective pathways through Nrf2 is known to be protective against diseases including cancer. But Nrf2 is also likely to be a major player in increasing longevity due to its antioxidant power and is even known as the ‘guardian of healthspan.’

Nrf2 and oxidative stress

Think of oxidative stress in your body like rusting on a car. When we don’t take care of our car, exposure to air, water, and salt will cause rusting. Similarly, when we don’t take care of our body by eating healthy, avoiding pollution, and alleviating lifestyle stresses, toxic oxidants build up and cause oxidative stress.

In other words, oxidative stress happens when there are too many damaging oxidants in our system for our body to neutralize. Lots of things can cause oxidative stress: inflammatory foods, lifestyle stress, injury, and simply getting older. 

In today’s world, poor diet choices are a major contributor to oxidative stress. The Standard American Diet (SAD) is full of inflammatory foods such as corn syrup, red meat, candy, processed and pre-packaged foods, high-fat dairy products, processed grains, fried foods, excessive alcohol, and processed meats. 

When we eat these inflammatory foods, our bodies have to produce more antioxidants to neutralize the flood of toxic oxidants.

On the other hand, as we age Nrf2 activation naturally slows down. Yes, even though you need more Nrf2 activation as you age, your body is actually less able to activate it. That means that no matter how healthy you may be and how many antioxidant foods you eat, eventually your body can’t make enough neutralizing antioxidants to prevent oxidative stress. So it’s really important to help your body activate Nrf2 pathways.

So, what does Nrf2 do, exactly? 

Before we get into the nitty-gritty of what Nrf2 is, let’s talk about what it does. Nrf2 is known as the ‘master regulator’ of the body’s antioxidant pathway. 

When you activate your Nrf2 pathway you create more antioxidant proteins. This is essential for battling injury, disease, inflammation, and any kind of cell-level oxidative damage in the body.

Activating the Nrf2 pathway is extremely important, because it regulates the creation of proteins that battle free radicals, also called reactive oxygen species. 

A free radical is any molecule that has free electrons. The free electrons in these molecules make them unstable and reactive. To stabilize, they react with other molecules by stealing an electron–damaging the other molecule in the process.

Nrf2 not only helps to rid the body of damaging free radicals and their toxic byproducts, Nrf2 can even help the body repair after the stressors are gone.

Nrf2 is expressed everywhere throughout the body, but it’s expressed the most in the kidneys, muscles, lungs, heart, liver and brain. 

Nrf2 is a protein

Now that you know why it’s so powerful, what exactly is Nrf2? Nrf2 (nuclear erythroid-related factor 2) is a protein that is encoded by a gene called NFE2L2 in humans. Nrf2 is part of a group of proteins called transcription factors (TF), and there are about 1,600 TFs in humans. 

TFs control which parts of DNA are made into RNA and proteins–in other words, which parts of your DNA blueprint actually get built. Amazingly, Nrf2 controls 3-5% of a human’s cellular proteins. Nrf2 is only one TF of nearly 2,000 yet controls up to 5% of our proteins! This is super important because TFs are in charge of how your body literally builds itself and functions.

Risks of overdoing Nrf2 activators

Some Nrf2-activating supplements need to be treated with caution. There are many sulforaphane-based supplements that say they’re made from broccoli and don’t actually contain any broccoli! 

Similarly, there are some supplements that just contain glucoraphanin–the precursor of sulforaphane–but don’t contain the enzyme needed to make the sulforaphane.

Even though it seems like maxing out Nrf2 activation would always be a good thing, there are risks involved. Research shows that, in people that already have cancer, activating Nrf2 could lead to resistance to chemotherapy. Until cancer researchers know more, Nrf2 is best used as a health-booster instead of a cure for disease.

Additionally, Nrf2 has paradoxically been shown, in mice, to increase plaques in arteries and cholesterol in the liver. However, in these studies, Nrf2 only had this effect in mice fed a high-fat chow diet. 

Until we know for sure how much Nrf2 activation is safe, stick to natural, whole-food sources of Nrf2 activators to stay healthy and prevent disease.

What foods trigger Nrf2 naturally?

While a decade ago pharmaceutical companies created Nrf2-activating medications to combat multiple sclerosis, medications often come with serious side effects. Many researchers began to focus on finding natural, whole-food Nrf2 activators. 

Today, many foods are known to be potent Nrf2 activators. Some of these antioxidant-packed foods are:

• Dark chocolate or cacao nibs
• Vegetables–cruciferous vegetables in particular like cauliflower, bok choy, and broccoli microgreens
• Herbs and spices–especially cloves, ginger, cinnamon, turmeric, yellow mustard, and oregano
• Legumes 
• Red wine–must be red because the grape skin contains most of the antioxidants
• Tea, especially white and green teas

Choose organic foods over conventional, as organic foods are shown to have higher levels of antioxidants.

When we consume antioxidant-rich foods, the antioxidants contained in the foods scavenge free radicals, while at the same time activating our own antioxidant proteins. 

Interestingly, there is research that shows that some foods work synergistically to activate Nrf2. For example, while compounds in ashwagandha, rosemary, and huaihua (Japanese pogoda tree) are known to activate the Nrf2 pathway on their own, the effect is increased when these plants are taken together.

Does anything else activate Nrf2? Research shows that not only can exercise activate Nrf2, consistent exercise helps the body respond better to oxidative stress. 

One human study even found that Nrf2 activation is increased if the subjects exercised more intensely! If you ever needed more motivation to hit the gym or the trail, here it is.

The link between sulforaphane and Nrf2

We already talked about lots of foods and compounds that activate Nrf2, like turmeric and resveratrol. So why do we care about sulforaphane so much?

Sulforaphane, a compound produced in cruciferous vegetables like broccoli, bok choy, and Brussels sprouts, is the most potent known activator of Nrf2. While lots of things activate the Nrf2 pathway, research shows that sulforaphane is the single most powerful agent for doing this. 

Additionally, sulforaphane is much more bioavailable than other Nrf2 activators. Bioavailable means the compounds actually reach the bloodstream so that they can have an effect in the body. 

Think about this: in one study, andrographalides (from Indian echinacea) were about 3% bioavailable, curcumin (from turmeric root) was 1% bioavailable, and sulforaphane (from cruciferous vegetables) was shown to be 80% bioavailable. That’s a huge difference! Sulforaphane was 80 times more bioavailable than the bioactive compounds in turmeric!

So what does that mean? It means that if we want to safely maximize our sulforaphane intake, we definitely need to eat more cruciferous vegetables! That brings us to microgreens.

Do microgreens contain Nrf2 activators?

More than twenty years ago, researchers at Johns Hopkins University were looking for food sources of bioactive compounds that induced phase 2 detoxification enzymes. Inducing phase 2 detox enzymes is important because it is protective against carcinogenesis and free radicals.

They stumbled across broccoli sprouts and found that sprouts contain high levels of bioactive compounds that induce these detoxification enzymes.

Fast-forward fifteen years to the first microgreens nutrition paper. Academic research surrounding microgreens and sulforaphane has exploded, leading to more and more interest in sulforaphane as a potential agent for cancer treatment, reducing inflammation, and other health issues related to Nrf2 activation. 

So are sprouts and microgreens the same thing? No!

The difference between sprouts and microgreens is important. Sprouts are tiny plants that have just germinated, are eaten with the seed, and are grown in water (or in very high humidity). 

Microgreens are baby plants that are grown for 1-3 weeks, have sprouted their first leaves so that they undergo photosynthesis, and are grown hydroponically, or sometimes in soil or other substrates.

Both sprouts and microgreens often have much higher nutrient density than their mature plant counterparts. However, sprouts are grown in high-humidity environments and are frequently associated with foodborne illness, while microgreens are very safe to eat and have more flavor.

How do I activate Nrf2? 

Are you convinced that Nrf2 activation is really important for your health? If so, you’re probably wondering how to get more Nrf2 activators into your diet...without having to eat a huge pile of raw veggies every day.

Besides eating Nrf2-activating foods, there are lots of ways to sneak Nrf2 activators into your daily routine. As discussed above, exercise–especially strenuous exercise–is also known to activate Nrf2.

One of the most convenient ways to activate Nrf2 is to drink Microtea. Microtea combines organic function tea blends with one of nature’s most powerful Nrf2 activators: broccoli microgreens. If you hate vegetables but want the benefits of Nrf2, try drinking a cup of chamomile Relax Microtea before bed.

On the other hand, if you already eat tons of healthy veggies and don’t know how you can fit more Nrf2 activating foods into your diet, try adding a teaspoon of Broccoli Booster to your smoothie or salad. One serving has over 300 microgreens and is absolutely packed with all of the micronutrients and antioxidants your body needs. 

Eating Nrf2 activating foods is a delicious and potent way to increase your body’s ability to make antioxidants. Upping your antioxidants decreases systemic inflammation, and this helps prevent disease and protect your health!

 Carly Anderson Stewart MSc. | Head of Biology and Education