How to turn on the Nrf2 Pathway and Kick Start the body's main defence system against cell damage that leads to disease, degeneration and cancer, also known as oxidative stress.
What is the Nrf2 Pathway?
It's short for Nuclear Factor Erythoid 2-Related Factor (Nrf2 in the rest of this document). NRF2 is a major transcription factor in detoxing the body and keeping it healthy. It's our main internal defence system that protects us from free radicals and the damage they do to our cells, basically protecting us as we age. By activating this transcription factor it in turn activates the Antioxidant Response Element (ARE) of several hundred identified genes; many of which are related to cellular defence processes. It modulates the expression of genes associated with metabolic cycles, detoxification of harmful substances, anti-inflammation, and antimicrobial capacity, all key components of the upstream cellular defence processes. Diseases known to be affected by oxidative stress are more responsive to cellular defences via Nrf2 activation than by antioxidant supplements.
NRF2 activity is part of the phase II detoxification system which is paramount for taking lipophilic (fat soluble) toxins and getting them ready for excretion. NRF2 activation decreases overall inflammation and oxidation of the body.
To activate NRF2, a threshold of an oxidative response must be met so the body can create an adaptive response, and thus create antioxidants (ie glutathione).
To break it down: Hormetic and Oxidative Stress triggers the NRF2 pathway, then follows the Anti-Oxidant Response. The NRF2 works quickly to balance redox signalling (the balance of oxidant and antioxidant levels in a cell).
What is Hormetic Stress
Hormesis works by adding a small amount of stress on your body. Hormetic stress is the ideal level of exposure to stressors, in that it causes a very mild sort of damage to the body which elicits a much greater therapeutic effect in response. Hormesis, if done properly can produce beneficial reactions in the body: strengthen metabolism, longevity, and wellbeing as well as protect you from chronic illness in general. Before putting your body through Hormesis though, check with your doctor and don’t overdo it. Start out in small amounts and increase a little bit each time. Another good read is our Blog about Biohacking
Ways to Induce Hormetic Stress and Gain Benefits
NRF2 activation : by ingesting 4-day old broccoli sprouts which are the highest forms of sulforaphane. Best eaten raw in a blitzed smoothie or in a salad. Read more about Sulforaphane here.
Diet : ingesting foods rich in flavanoid, polyphenol, or phytochemicals like broccoli sprouts, green tea, turmeric. Read about foods to clean your liver here.
Ketosis : by changing your diet so your body makes a metabolic switch from burning glucose as fuel to burning fat as fuel.
Fasting : Eating with a smaller time frame within the 24 hour day, like 16 hours fasted and 8 hours window to consume calories. Read more about fasting here.
HIST : High intensity strength training which is heavy weighted exercises of 7 minutes every day or 20min every 2-3 days.
Heat : with Sauna or Hot Yoga
Cold : with ice baths or cold showers
Sulforaphane as an Nrf2 Pathway trigger
Sulforaphane is derived in the highest amount from young broccoli sprouts. The Johns Hopkins group found that the 3-day germinated broccoli seed contained 20-50 times more of Sulforaphane than the mature broccoli vegetable. Broccoli-derived Sulforaphane is capable of activating the transcription factor, Nrf2. Of the phytochemicals with Nrf2 inducer capacity, Sulforaphane from 4-day old broccoli sprouts is the most potent, naturally occurring compound, known at this time. It is not only a potent Nrf2 inducer but also highly bioavailable so that modest doses can produce significant clinical responses. The daily Sulforaphane dose found to achieve beneficial outcomes in most of the available clinical trials is around 20-40 mg. That is approximately ½ cup of fresh 4 day old sprouts, easily consumed daily.
Easy, sustainable and bioavailable - you can grow broccoli sprouts easily in your kitchen without soil, just fresh water, seeds and high quality sprouting jars. They're as safe to consume as regular broccoli but with higher benefits. We sprout every week using these kits you can buy in the link below:
Periodic activation of NRF2 can help:
Aging (i.e. Longevity)
Autoimmunity and Overall Inflammation (i.e. Arthritis, Autism)
Cancer and Chemoprotection
Depression and Anxiety
Drug Exposure (Alcohol )
Exercise and Endurance Performance
Gut Disease (i.e. SIBO, Dysbiosis, Ulcerative Colitis)
Kidney Disease (i.e. Acute Kidney Injury, Chronic Kidney Disease, Lupus Nephritis)
Liver Disease (i.e. Alcoholic Liver Disease, Acute Hepatitis, Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, Cirrhosis)
Lung Disease (i.e. Asthma, Fibrosis)
Metabolic And Vascular Disease (i.e. Atherosclerosis, Hypertension, Stroke, Diabetes)
Neurodegeneration (i.e. Alzheimer's, Parkinson's, Huntington's and ALS)
Pain (i.e. Neuropathy)
Skin Disorders (i.e. Psoriasis, UVB/Sun Protection)
Toxin Exposure (Arsenic, Asbestos, Cadmium, Fluoride, Glyphosate, Mercury, Sepsis, Smoke)
Vision (i.e. Bright Light, Sensitivity, Cataracts, Corneal Dystrophy)
4 Top Benefits of the Nrf2 Pathway
1. Protects the body against toxins
NRF2 is an innate trigger that defends cells from outside invaders. It increases multidrug resistance-associated proteins, which improves the body's reaction to medications and toxins (MRPs, proteins which help push chemicals out of the cell). For instance, when cigarette smoke is inhaled, NRF2 is triggered as a mechanism for the lungs to detox. The lungs must also provide defence against allergies, viruses, bacterial endotoxins, hyperoxia, and other environmental contaminants. The lungs lose glutathione due to the persistent stress on this system (such as chronic smoking). Activating NRF2 is a powerful approach to shield the liver against toxins if it isn't inhibited. It can guard the liver against arsenic toxicity. NRF2 safeguards the brain and liver against alcohol use and guards against acetaminophen (Paracetamol) toxicity.
2. Battles Inflammation And Oxidative Stress
NRF2 offers anti-inflammatory protection. For example, NRF2 activation can decrease inflammatory cytokines (such as IL-8) in psoriasis. NRF2 can also lessen arthritis-related inflammation. It can lessen fibrosis and inflammation in the liver, kidney, and lungs (including TGFb1). Allergies can also be helped by NRF2. This is due to NRF2's role in boosting TH2 cytokines while suppressing Th1/Th17 cytokines. Asthma sufferers will benefit from this. Additionally, NRF2 guards against sun-induced UVA/B and blue light cellular damage. One explanation for this is that NRF2 can shield collagen from UV light.
Advanced Glycation End-Products (AGEs) have been found to be important in the progression of a number of diseases, including diabetes, neurodegenerative diseases, and ageing. NRF2 can lessen the oxidative stress that AGEs have on the body. NRF2 can also protect the body against high amounts of heat-based stress (40ºC/104ºF or higher).
3. Improves The Vascular System
Done naturally (with things like sulforaphane), NRF2 activation can protect against heart disease such as high blood pressure (hypertension) and hardening of the arteries (atherosclerosis). This is because NRF2 can improve Acetylcholine's (ACh) relaxing action on the vascular system while lowering cholesterol-induced stress.
4. Combats Neuroinflammation
NRF2 can protect against and help with inflammation of the brain (neuroinflammation). NRF2 can help with a variety of Central Nervous System (CNS) disorders:
Alzheimer’s Disease (AD) - reduces amyloid beta stress on mitochondria
Amyotrophic Lateral Sclerosis (ALS)
Huntington's Disease (HD)
Multiple Sclerosis (MS)
Nerve Regeneration
Parkinson’s disease (PD) - protects dopamine
Spinal Cord Injury (SCI)
Stroke (ischemic and hemorrhagic) - help hypoxia
Traumatic Brain Injury
Growing fresh Broccoli Sprouts
Our favourite way to kick start our defence system is to have young broccoli sprouts in our smoothie.
We grow them on our kitchen bench in a sunny spot. We use plastic free, high quality sprouting jars that we use everyday. You can shop our kits that we have sourced on tried and true equipment we use ourselves. We recommend the Super Saver Kit with 2 x 1000ml jars and 250g of specialty Sprouting Broccoli Seeds.
References for this article
https://mybiohack.com/blog/nrf2-cirs-sensitivities
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924422/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589110/ https://www.ncbi.nlm.nih.gov/pubmed/17668877/ https://www.ncbi.nlm.nih.gov/pubmed/16293230/ inflammation https://www.ncbi.nlm.nih.gov/pubmed/28903401 allergies https://www.ncbi.nlm.nih.gov/pubmed/15322212/ asthma https://www.ncbi.nlm.nih.gov/pubmed/25739561 high blood pressure https://www.ncbi.nlm.nih.gov/pubmed/26490346 acetylcholine https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637098/ https://www.vital-reaction.com/blogs/news/nrf2-explained-in-human-terms