Nrf2: The Master Switch That Calms Inflammation and Protects Your Brain

In this blog, I'll review a recent paper that caught my attention: “Nrf2-Activating Natural Compounds in Neurodegenerative Diseases: Targeting Oxidative Stress and Protein Aggregation.”⁽¹⁾ I'll explain what the Nrf2 pathway is and how it contributes to overall health, as well as the drugs that were developed to stimulate it, the disease states pharmaceutical companies are investigating, and how you can activate Nrf2 without a prescription.

What Is The Nrf2 Pathway?

The Nrf2 pathway (nuclear factor erythroid 2-related factor 2) is one of the most important regulatory systems in your cells. When activated, it protects cells from excessive oxidative stress, chronic inflammation, and toxin damage — largely by switching "on" more than 250 genes involved in resolving inflammation and improving your body's detoxification processes.⁽¹⁾

What Nrf2 Does in Our Cells

Nrf2 activation triggers several important protective responses:

It increases the production of glutathione — your body's master antioxidant — within the cell itself, which helps quench excessive oxidative stress and protect the mitochondria.

It inhibits NF-κB (nuclear factor kappa B), a key driver of the chronic, excessive inflammation associated with autoimmune conditions, cognitive decline, Parkinson's, Alzheimer's, and mental health issues like anxiety and depression.

It also boosts the production of phase 2 detoxification enzymes, which help your body clear toxic compounds more efficiently.

Drugs That Stimulate Nrf2 To Treat Disease

Tecfidera® (dimethyl fumarate) was developed to stimulate Nrf2 and has FDA approval to treat relapsing remitting multiple sclerosis,^{(2, 3)} clinically isolate syndrome (first neurologic event with evidence of demyelination on brain imaging)^{(2, 3)}, and psoriasis.⁽⁴⁾ It is used off-label for pediatric-onset multiple sclerosis.⁽⁵⁾

Tecfidera® was one of the earliest disease-modifying MS drugs available in pill form and has a relatively favorable side effect profile.

The Future of Nrf2-Based Treatments

Research into Nrf2-based therapies is expanding rapidly — and for good reason. Oxidative stress and chronic excessive inflammation are at the root of many conditions that are increasing in both children and adults: autoimmunity, neurodegeneration, heart disease, obesity, pre-diabetes, and type 2 diabetes.

Nrf2-stimulating therapies are currently being studied for neurodegeneration (including Parkinson's disease, Alzheimer's, and other dementias), heart disease, liver disease, pulmonary disease, and diabetes and metabolic syndrome.^(1,6,7) More studies are underway to understand how drugs like Tecfidera® might be used across a wider range of chronic diseases.

How to Stimulate Nrf2 Pathways With Food And Supplements

It will be several more years before Tecfidera® is approved to treat the many conditions currently being studied. In the meantime, there is a lot you can do to optimize your Nrf2 activation.

Start with food. Reduce or eliminate sugar-sweetened beverages and white flour-based foods. Eat more non-starchy vegetables and berries. Drink green tea. Add culinary spices like turmeric and ginger to your meals. I recommend having a family conversation about what changes feel doable together — it's much easier when everyone is on board.

Next, consider adding targeted supplements to support your Nrf2 pathways. Several natural compounds have demonstrated the ability to activate Nrf2 pathways and may be particularly helpful for brain-related conditions:

Pterostilbene activates Nrf2 pathways and is present in berries.⁽⁸⁾ Epigallocatechin gallate (EGCG), found in green tea, also activates Nrf2 pathways. Curcumin (found in turmeric) is yet another Nrf2 activator.⁽⁹⁾ And glucoraphanin — which is metabolized in the body to produce sulforaphane — is one of the most potent natural stimulators of the Nrf2 pathway.⁽¹⁰⁾

I have combined these compounds into Cytokine Modulator to help support Nrf2 activation and reduce excessive oxidative stress and chronic inflammation.

Closing Thoughts

The pharmaceutical industry's growing interest in the Nrf2 pathway reflects how central it is to so many chronic diseases. While Tecfidera® is well-tolerated and effective, it will be years before it's approved for additional conditions.

In the meantime, you can begin supporting your Nrf2 pathways today — through a nutrient-dense diet and targeted supplementation. Cytokine Modulator can further enhance this activation to help lower oxidative stress and calm chronic excessive inflammation.

Citations

1. Chico L, Schirinzi E, Balestrini L, Polzella M, Siciliano G. Nrf2-Activating Natural Compounds in Neurodegenerative Diseases: Targeting Oxidative Stress and Protein Aggregation. Int J Mol Sci. 2026;27(3).
2. Yadav SK, Soin D, Ito K, Dhib-Jalbut S. Insight into the mechanism of action of dimethyl fumarate in multiple sclerosis. J Mol Med (Berl). 2019;97(4):463-72.
3. Zingkou E, Medoro A, Davinelli S, Saso L, Sotiropoulou G, Pampalakis G. Dimethyl fumarate as a versatile therapeutic agent: molecular mechanisms and potential clinical applications. Mol Biol Rep. 2026;53(1):344.
4. Gesser B, Rasmussen MK, Iversen L. Dimethyl Fumarate Targets MSK1, RSK1, 2 and IKKalpha/beta Kinases and Regulates NF-kappaB /p65 Activation in Psoriasis: A Demonstration of the Effect on Peripheral Blood Mononuclear Cells, Drawn from Two Patients with Severe Psoriasis Before and After Treatment with Dimethyl Fumarate. Psoriasis (Auckl). 2020;10:1-11.
5. Craiu D, Dica AD, Pomeran C, Pescaru G, Menascu S, Simu M. Disease-Modifying Treatment Options in Very Early Onset Multiple Sclerosis-What Choices Are There for Onset Under 5 Years of Age? A Systematic Review. J Clin Med. 2025;14(22).
6. Hadinata E, Harbuwono DS, Soegondo S, Prajitno JH, Mudjanarko SW, Taslim NA, et al. Marine nutraceuticals as a source of SIRT1 and NRF2 activators for diabetes and aging-related metabolic disorders. Diabetol Metab Syndr. 2025;17(1):394.
7. Rosito M, Testi C, Parisi G, Cortese B, Baiocco P, Di Angelantonio S. Exploring the Use of Dimethyl Fumarate as Microglia Modulator for Neurodegenerative Diseases Treatment. Antioxidants (Basel). 2020;9(8).
8. Cui C, Zheng J, Zhang H, Xing Z. Pterostilbene ameliorates oxidative stress and neuronal apoptosis after intracerebral hemorrhage via the sirtuin 1-mediated Nrf2 pathway in vivo and in vitro. J Stroke Cerebrovasc Dis. 2024;33(11):107950.
9. Smith RE, Tran K, Smith CC, McDonald M, Shejwalkar P, Hara K. The Role of the Nrf2/ARE Antioxidant System in Preventing Cardiovascular Diseases. Diseases. 2016;4(4).
10. Tarozzi A, Angeloni C, Malaguti M, Morroni F, Hrelia S, Hrelia P. Sulforaphane as a potential protective phytochemical against neurodegenerative diseases. Oxid Med Cell Longev. 2013;2013:415078.