Nrf2 is a critical pathway to health, as it is the most important pathway to increase our natural and innate antioxidant defense.
Introduction to NRF2
Nuclear factor (erythroid-derived 2)-like 2, also known as NFE2L2 or Nrf2, is a protein (transcription factor).
Nrf2 is found in the highest concentrations (in descending order) in the kidney, muscle, lung, heart, liver, and brain (R).
Antioxidant Defense and Detoxification System Stimulated by Nrf2
Nrf2 stimulates NQO1, which donates electrons and detoxifies a variety of chemicals and drugs. NQO1 is important for phase 2 detox.
I suspect that people sensitive to “everything” have less NQO1 or less of an electron supply.
Nrf2 produces two of the most important rate-limiting steps in glutathione (GSH) production. Glutamate–cysteine ligase, catalytic (Gclc) and glutamate–cysteine ligase, modifier (GCLM) bind together to form glutathione. These are produced by Nrf2.
The glutathione S-transferase (GST) allow glutathione to bind with drugs and toxins, which then allow the body to eliminate potentially harmful and toxic compounds. GSTs are produced by Nrf2 activation and represent an important route of detoxification.
Sulfiredoxin 1 (SRXN1) and Thioredoxin reductase 1 (TXNRD1) give over electrons to peroxiredoxins, proteins important in the detoxification of hydrogen peroxide and peroxynitrite.
Nrf2 stimulates Heme oxygenase-1.
The UDP-glucuronosyltransferase (UGT) family catalyze the conjugation of a glucuronic acid to drugs, chemicals, and toxins, making them more water-soluble and readily excreted. Nrf2 has been shown to induce UGT1A1 and UGT1A6.
Bilirubin and Tylenol are examples of substances that are glucuronidated.
My clients are more likely to have higher bilirubin, and this can come from less of ability to glucuronidation enzymes.
Multidrug resistance-associated proteins (Mrps) are important membrane transporters that eject various compounds from various organs into bile or plasma, with subsequent excretion in the feces or urine, respectively.
Mrps have been shown to be increased by Nrf2 and alteration in their expression can dramatically alter the pharmacokinetics and toxicity of compounds.
People with CIRS or biotoxin related issues usually have a problem excreting toxins in an efficient way, and almost certainly the Nrf2 pathway will help excrete these toxins more easily.
Ideally, you’d want to combine Nrf2 activators with cholestyramine (disclaimer: not for personal use) if you have a biotoxin problem.
The Negatives of Nrf2 Activation
Having low cholesterol might be an indicator of less Nrf2 function (although there are many other pathways that lower cholesterol).
Top Ways to Increase Nrf2
- Exercise (R),
- LLLT (R)
- Fish oil/DHA (R),
- Vitamin D (R)
- Sulforaphane/Broccoli sprouts (R) -and other Isothiocyanates from cruciferous vegetables (R),
- Lipoic Acid
- Butyrate (R),
- Garlic (R),
- Curcumin (R)
- Luteolin (R) – luteolin is ideal because it inhibits Nrf2 in many cancer cells (R),
Other Ways to Activate Nrf2
- PGC-1a (R)
- Calorie Restriction (R)
- Ketosis (R),
- Molecular Hydrogen (Machine) (R),
- Thyroid hormones (R) – make sure your thyroid hormones are up to par.
- Berberine (R) See this post for more on Berberine.
- PQQ (R),
- Cinnamaldehyde/Cinnamon (R),
- Anthocyanins (R, R2, R3)
- Carnitine (R),
- Andrographolide/Andrographis (R, R2),
- Hydroxytyrosol (R),
- Black cumin oil/Thymoquinone (R),
- EGCG (R),
- Astaxanthin (R),
- Lycopene (R),
- Tocopherols and Tocotrienols (Vitamin E) (R),
- Quercetin (R),
- Naringenin (R),
- Resveratrol (R),
- Chlorella (R),
- Cocoa/Chocolate (R),
- Schisandra (R),
- Licorice (R),
- Chinese Skullcap – Has three ingredients that increase Nrf2 – Baicalin (R), Baicalein(R, R2) and Wogonin (R)
- Citrus Flavanoids/Citrus Bioflavonoids (R),
- Withanolide A/Ashwagandha (R),
- Pau Darco (R),
- Ginkgolide B (prevents suppression)/Ginkgo (R),
- Oleanolic acid/Olive Leaf (R)
- Apigenin (R)
- Melatonin (R)
- Ginger (R)
- Pterostilbene (R),
- Hops (R)
- High-dose Vitamin C (R)
- Celastrol found in Thunder God Vine Extract (R)
- Artemisia (R)
- Kaempferol (R),
- Genistein (R), Soy Isoflavones (R),
- Bilirubin (R),
- Betanin/Beets (R),
- Chlorogenic acid (R),
- Carnosic acid/Rosemary (R)
- Grapes (R)
- Propolis (Brazilian green) (R)
- Kiwi Peel (R), Geranium (R),
Inhibitors of Nrf2
NRF2 23andme SNPs
If you want to interpret your genes, you should use SelfDecode.
You need to order 23andme to see your results and plug it into SelfDecode.
The NRF2 gene has some SNPs that can tell you if you’re a high or low producer.
- RS10183914 (NRF2) TT
- RS16865105 (NRF2) AA
- RS1962142 (NRF2) GG
- RS2886161 (NRF2) TT
- RS35652124 (NRF2) TT
- RS6706649 (NRF2) CC
- RS6721961 (NRF2) GG
- RS6726395 (NRF2) AA
- RS7557529 (NRF2) CC
Health Tools I Wish I Had When I Was Sick
At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.
That’s why I decided to create tools that will help others cut down the guesswork:
- Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
- SelfDecode – a software tool that will help you analyze your genetic data from companies such as 23andme and ancestry. You will learn how your health is being impacted by your genes, and how to use this knowledge to your advantage.
- SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
- SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
- Selfhacked Inflammation course – a video course on inflammation and how to bring it down
- Biohacking insomnia – an ebook on how to get great sleep
- Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
- BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
- SelfHacked VIP – an area where you can ask me (Joe) questions about health topics
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