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Oxidative stress is a major player in the formation of pathological conditions such as cancer, diabetes, heart disease, accelerated aging, and neurodegeneration. Oxidative stress is when the body encounters an environment of increased free radicals that break down cell membranes and tissues that increase inflammation and the risk of disease.
Anti-oxidant rich foods, herbs, and supplements are used to protect the body from unwanted oxidative stress. Recent research has found a new signaling pathway that plays an enormous role in amplifying the effects of anti-oxidants on the body.
The body adapts to function in a state of homeostasis or balance. When the body is confronted with major stressors the cells must quickly modulate their anti-oxidant capacity to counteract the increased oxidative stress. In order to do this the body is able to activate a massive anti-oxidant effect in a matter of nanoseconds through a specific genetic pathway.
How the Keap1-Nrf2 Pathway Effects Your Health
Nrf2 (NF-E2-related factor 2) is a transcription factor in humans encoded by a specific gene that regulates the expression of a set of antioxidant and detoxifying genes. This pathway is activated under times of oxidative stress to enhance the expression of a multitude of antioxidant and phase II liver detoxification enzymes that restore homeostasis to the ox/redox cycles in the body.1, 2, 3
An enzyme named Keap1, which sits on the cytosol of the cell interacts with Nrf2 and activates it. Keap1 is rich in the amino acid cysteine, and acts as a sensor that is constantly reading the environment for any increase or decrease in oxidative stress. Under times of increased stress, Keap1 activates Nrf2 which then migrates into the cell nucleus and bonds to the DNA to active the Antioxidant Response Element (ARE). ARE then upregulates a variety of powerful antioxidant enzymes and detoxifying proteins.4, 5, 6
This Keap1-Nrf2 pathway regulates over 600 genes involved in cellular protection and anti-oxidant defenses. These various genes act to boost major anti-oxidant and detoxifying enzymes such as glutathione and superoxide dismutase. They also promote anti-inflammatory prostaglandins and enzymes and improve tissue healing and repair. 7, 8
Nrf2 and Cancer Prevention
High levels of oxidative stress damage normal cells, affecting the DNA and inducing cancer causing mutations. Oxidative stress also activates chronic inflammatory pathways that create an optimal environment for cancer development. The Keap1-Nrf2 pathway has been shown to be protective against tumor formation.9, 10
Nrf2 has a dark side in that cancer cells can use a mutated form of this pathway to protect themselves against the body’s immune system and chemotherapeutic agents. Mutations in the Keap1-Nrf2 pathway can lead to fast growing and highly resistant tumor growths. 11, 12
What Are the Top Nrf2 Activators That Can Prevent Cancer?
There are several compounds that can be found in nature and ingested through specific foods and herbs that enhance and coordinate the Keap1-Nrf2 pathway. The most powerful nutrients that support the activation of the anti-oxidant amplifying Nrf2 pathway include curcumin, stilbenes, catechins, and sulforaphane.
You can find these nutrients in turmeric (curcumin), resveratrol in grape skin and berries (stilbenes), green tea and dark chocolate (catechins) and cruciferous veggies (isothiocyanates and sulforaphane). It is highly advisable to consume these compounds every day to keep anti-oxidant systems in balance. This will result in positive adaptations that improve aging, reduce disease formation and improve quality of life.
Turmeric: Curcumin (the active ingredient in turmeric compounds) absorbs best when combined with black pepper
Resveratrol-Stilbenes: Grape skin, red wine, berries
Catechins: Minimally processed dark chocolate, raw cacao, and green tea
Sulforaphane and Isothiocyanates: Cruciferous veggies – broccoli sprouts and fermented cruciferous veggies (sauerkraut and kimchi) have the most
There is also benefit to consuming these ingredients together as they have a synergetic effect that amplifies their effects on the Keap1-Nrf2 pathway. The easiest way this is done is through key supplements that are specifically designed to upregulate this pathway.
From a food and nutritional perspective, you could have steamed Brussel sprouts with grass-fed butter (fat-soluble carrier) or coconut oil melted on top. Add generous amounts of turmeric to the dish, broccoli sprouts (greatest source of sulfuraphane), and a pinch of black pepper to maximize the curcumin absorption.
Consume this with green tea and have some blueberries or organic red wine. Finish with a small bite of minimally processed dark chocolate. This is a great preventative step, but much more needs to be done to boost these pathways in individuals with faster growing cancers.
Strengthen Your Keap1-Nrf2 Pathways:
It is important to strengthen the Keap1-Nrf2 pathways throughout our lives to prevent cancer cell growth. Additionally, we need to constantly work on immune coordination improvement through diet, lifestyle, natural therapies, and supplementation.
In the case of fast growing, chemo-resistant cancers, super high doses of these Nrf2 activators should be used along with other cancer therapy protocols to override the mutated Nrf2 pathways used by the cancer cells.
It is advisable to work with a physician trained in the NrF2 pathway and effective modulation of this Antioxidant Response Element (ARE) if you are looking for maximal protection or you are dealing with a rapidly growing cancer.
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