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Nrf2 and Detox Support

Key Topics: Inflammation
March 6, 2021 • 4 min read

A Toxic World

The modern world exposes the human body to a daily multitude of metabolic toxins including heavy metals, pesticides, and herbicides. It has been estimated that there are between 25,000 and 84,000 chemicals currently in commerce in the United States, and biomonitoring has shown that hundreds of circulating synthetic chemicals make their way from the environment into the human body.1 Such a high chemical burden can put pressure on the body’s natural metabolic detoxification capacity, and toxicant exposure and bioaccumulation of xenobiotics may be a significant contributor to the increasing prevalence of chronic disease observed within the past several decades.2,3 Some conditions for which the improper clearance of toxins has been associated with include:

  • Weight gain4
  • Cardiovascular disease5
  • Chemical sensitivity and intolerance
  • Neurocognitive concerns (e.g. attention deficit/hyperactivity disorder6,7
  • Immune dysfunctions, such as autoimmune disease8
  • Reproductive and developmental concerns9,10

Reducing toxic exposure and enhancing the metabolism and excretion of toxicants appears to be crucial toward controlling oxidative stress and inflammation and in the prevention of disease. Thankfully, cells possess a broad range of sophisticated antioxidant mechanisms to help protect against environmental stressors such as exposure to toxins, and these pathways can be activated by phytochemicals found within foods. The ability for plants to prevent disease is possible in part through the activation of genetic transcriptional factors such as nuclear factor erythroid 2-related factor 2 (Nrf2), which has significant health-promoting properties and allows the body to better cope with harmful biochemical stressors.

Nrf2 & Detoxification

Within the last few decades, awareness around the importance of Nrf2 as a genetic transcriptional factor that regulates the body’s cellular resistance to oxidative stress has been increasing. By regulating oxidant levels, Nrf2 participates in the control of several important cell functions such as autophagy, inflammasome signaling, apoptosis, mitochondrial biogenesis, and stem cell regulation.11 Once activated, Nrf2 can:

  • Control and induce the expression of antioxidant response element (ARE) dependent genes, which regulate antioxidant defenses and the pathophysiological outcomes of oxidant exposure
  • Enhance the detoxification and elimination of numerous exogenous chemicals by mediating the induction of enzymes involved in phase one and two detoxification mechanisms including important phase two conjugation enzymes such as glutathione S-transferase (GST)12

As the production of most phase two detoxification enzymes is controlled by Nrf2, its activity and ability to protect cells against free radical damage and xenobiotics has been implicated in a range of characteristic chronic diseases typically associated with oxidative stress and exposure to harmful chemical exposures.13

Understanding the Terms
Autophagy A cellular regulation process where unneeded or dysfunctional cell parts are broken down and recycled
Inflammasome A bundle of proteins of the innate immune system linked to inflammation activation
Apoptosis Self-activated programmed cell death
Mitochondrial biogenesis The process by which mitochondria, energy-producing cell organelles, expand in number
Stem cell Undifferentiated cells with diverse cell type potential

NrF2 Activators: The Brassicas

Consuming a higher intake of brassica vegetables has been associated with a decreased risk of chronic disease and the potential to reduce cancer risk through Nrf2 activation.1,2 Key phytochemicals in these plants are able to bind to Nrf2 and have been referred to as “Nrf2 activators.” They have been shown to protect against oxidative stress, exert cytoprotective and neuroprotective effects, and induce phase two detoxification enzymes when consumed through the diet.3-5 Though many phytochemicals have been identified as activators of Nrf2-signaling mechanisms, those which have been studied the most extensively include curcumin from turmeric (Curcuma longa), and sulforaphane from the Brassicaceae family of plants and – in particular – from broccoli.

Phytonutrient profiles unique to brassicas include compounds called glucosinolates, which are sulfur-containing molecules that exist almost exclusively in cruciferous plants and are responsible for the bitterness and pungency of many edibles such as mustard, cabbage, broccoli, Brussels sprouts, and radish. The breakdown products from chewing these foods imparts their distinctive taste and is responsible for converting glucosinolates such as glucoraphanin into isothiocyanates such as sulforaphane via myrosinase, an enzyme. Myrosinase is activated within the plant once it becomes damaged, and in this way the glucosinolates become hydrolyzed into potent Nrf2 activators through chewing, in part by the bacterial microbiota of the gastrointestinal tract. In vitro and in vivo studies suggest a chemopreventive activity of isothiocyanates through Nrf2 activation, and studies in humans support anti-inflammatory effects and the potential to regulate epigenetic pathways.6 Of the phytochemicals with Nrf2 inducer capacity, brassica-derived sulforaphane is thought to be the most potent naturally occurring biomolecule known at this time.7

Obtaining Sufficient Sulforaphane

As a generation under significant toxic burden, encouraging the mobilization and excretion of toxins while simultaneously enhancing antioxidant effects through upregulating Nrf2 pathways is a sensible way to prevent and mitigate the risk of chronic and inflammatory conditions. Consuming a brassica-rich diet over time appears to result in a range of clinically significant health benefits; however, achieving a therapeutic dose of sulforaphane solely through dietary intake has its challenges. Many individuals already struggle to consume their recommended daily number of vegetables, and in most cases when they do, preparation includes using heat. Raw brassicas are known to be a much better source of glucosinolates (and therefore sulforaphane) compared to those that are cooked as the cooking process inactivates myrosinase, producing an estimated three to four times less sulforaphane in the body.8,9 Moreover, glucoraphanin levels in plants can vary greatly dependent on their quality (i.e. growing and storage conditions) and genotype, making it difficult to achieve consistent levels through food.10 In these cases, high quality sulforaphane supplementation may be a useful consideration to help reduce the body’s toxic burden and leading to improved health outcomes for a wide range of clinical presentations.

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