The Nrf2 pathway has been referred to as the “master regulator of antioxidant, detoxification and cell defense gene expression” - that's quite a gig, right!
Your Nrf2 pathway is so important that so much research has been carried out trying to explore how activating this life-sustaining pathway may help us to achieve optimal health and longevity. Particularly in today's world where we are exposed to more toxins and free radicals than our grandparents.
What is the BIG deal by oxidative stress?
Most compounds and molecules in your body are stable, this is why you need enzymes (encoded by your genes) to break them down or turn them into other more useful molecules.
However, some reactions in your body lead to the formation of molecules called free radicals, particularly during energy generation within each of your cells. Put another way, the byproduct of energy metabolism are damaging free radicals.
This is where antioxidants step in, it’s their function to 'mop up' these highly reactive elements making sure they don’t interact with any of the important molecules in a cell. This mopping up process occurs constantly in your body, however, when the antioxidant function in the body becomes overwhelmed by free radicals, oxidative stress can occur. If you carry medium to high impact genetic variations in the key oxidative stress genes (namely MnSOD/SOD, GSTM1, GSTP1and GPX) and/or are a poor phase 1 and phase 2 detoxifier, then you are more likely to be predisposed to free radical damage. If this is the case, then you should be focusing on activating your NrF2 pathway. This is an awesome and easy biohack!
Chronic oxidative stress is associated with accelerated ageing and several chronic diseases including Parkinson’s disease, Alzheimer’s disease, cardiovascular disease, and several cancers.
Oxidative stress triggers in your environment
It's important for us to be aware of what else can trigger oxidative stress and cell damage in our bodies. Some of these are easy to avoid while others, like air pollution, are more difficult to escape. By 'swapping out' these for better, more healthy choices daily can definitely provide additional antioxidant support.
| Oxidative stress triggers | Antioxidant support |
| Alcohol | Drink 1-2 units weekly. Red wine. |
| Medications and drugs | Add in an antioxidant supplement to circumvent the toxic effects |
| Smoking | Try to quit! Avoid being exposed to second-degree smoke |
| Burnt red-meat | Fish, baked |
| Chemicals in personal care products | Swap out for better, non-toxic, chemical-free options |
| Pesticides & herbicides | Swap out for organic, chemical-free options |
Is there an Nrf2 genotype?
Nrf2 regulates more than 600 genes. Over 100 of these are encoded for cytoprotective proteins, which increase toxin metabolism and removal, lower oxidative stress and maintain cellular homeostasis. However, if you carry medium to high impact genetic variations in these genes, you're going to be more predisposed to oxidative stress. Having this type of information about your body is truely amazing as you can start to personalise your health choices based on your own scientific data.
| NrF2 genes | Action | Test |
| NRF2 |NFE2L2 | Encodes is a basic leucine zipper protein that regulates the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation. | |
| KEAP1 | Balances and regulates the activation of Nrf2 | Whole Exome Testing |
| NQO1 | Involved in the detoxification. NQO1 also protects cells from oxidative stress by maintaining your antioxidant levels | |
| GST superfamily | Phase 2 liver detox and antioxidant protection | |
| AKR superfamily | Play a protective role in liver protection | Whole Exome Testing |
| SULF superfamily | Encodes for the sulfation of toxins | Whole Exome Testing |
| UGT | Phase 2 liver detox to phase 3 bile | VITAFEM |
| UGT | Phase 2 liver detox to phase 3 bile | VITAFEM |
| CYPs | Play a role in phase 1 detox in the liver | |
| GPX | Encodes a member of the glutathione peroxidase family, which contains important antioxidant enzymes and helps detoxify hydrogen peroxide with glutathione, and thereby protect cells against oxidative damage. | |
| MnSOD | SOD | Vital for antioxidant activity within the cell, especially within the mitochondria. |
Supporting your Nrf2 pathway with Nrf2 activators
Recent research has identified certain processes to be very effective at stimulating your body’s natural mechanisms for creating antioxidants through a process called NrF2 activation.
Eating foods and supplementing with Nrf2 activators is believed to offer a number of remarkable health benefits, from reducing inflammation and pain to protection against diabetes (reducing insulin resistance) and protection against a variety of degenerative and immune-based diseases.
The following is a list of common NRF2 activators:
| NrF2 Activators | Source | Supplement |
| Curcumin | Turmeric | Bio-Curcumin in bioavailable form |
| Resveratrol | Red grapes | Phytomulti |
| Pterostilbene | Blueberries, cranberries and red grapes | |
| Silybin | Milk thistle | Axis Endo |
| Sulforaphane | Broccoli, Brussel sprouts, cabbage, cauliflower, kale | Bio-Sulforaphane in bioavailable form |
| Alpha Lipoic Acid | Red meat, organ meat | Alpha Lipoic Acid |
| Vitamin D | Egg yolks, saltwater fish, liver, milk and dairy products | D3 1000 |
| Intermittent fasting & caloric restriction | No eating for 3 hours between dinner & bed, plus 10 hours overnight | Functional Medicine Health Coaching |
| Exercise | Daily, 30 mins | Rebounder |
Testing Nrf2 levels?
You can measure and track your glutathione levels and oxidative stress damage by ordering the DUTCH COMPLETE test online. By determining your current levels, you will be empowered to make better choices, deep inside your biochemistry way before an actual oxidative stress-related, chronic disease can manifest. This is powerful, preventative and personalised health!
Take-home message on Nrf2
Nrf2 is a potent modulator of antioxidant response and can rapidly target oxidative stressors. While Nrf2 responds to oxidative stress directly, certain key nutrients can improve this effect, the exact source of these nutrients varies widely but dark green and leafy vegetables (think spinach, kale, and broccoli, especially the seed extract), or reddy vegetables and spices (saffron, Tumeric or paprika) are a particularly rich source. Importantly these foods are also typically rich indirect antioxidants and display numerous other health benefits, so they are a great way to become healthier and improve your healthspan. And it's not bad for the skin too!
If you would like to learn more about your ability to fight oxidative stress and how to enhance the power of your NrF2 pathway, book a Functional Medicine Health Coaching session online.
Written by:
Marguerite Doig-Gander
CEO of MY DNA CHOICES
BA (Speech, Hearing & Lang Therapy) Hons | FMCHC | ReCODE Coach | HMX Genomics & Biochemistry (Candidate)
