Nrf2 pathway is a major target for sulforaphane. www.sciencedirect.com

Nutrition Sulforaphane Glutathione NRF2
Nrf2 (nuclear factor erythroid 2-related factor 2) is a cellular protein that regulates the expression of antioxidant and stress response proteins. It participates in the Keap1/Nrf2/ARE biological pathway – the primary mechanism by which sulforaphane exerts its beneficial effects. A 2017 review describes the role of sulforaphane in the Keap1/Nrf2/ARE pathway and summarizes the beneficial health effects associated with the compound.

The Keap1/Nrf2/ARE pathway is a key mediator of cytoprotective responses to oxidative and electrophilic stressors. Under normal cellular conditions, Keap1 tethers Nrf2 in the cytoplasm (the region of the cell outside the nucleus), where it can be tagged and delivered for degradation. However, following exposure to stressors, Keap1 undergoes modifications that impair its ability to bind to and target Nrf2 for degradation. As a result, Nrf2 is free to travel to the nucleus, where it binds to antioxidant response elements (AREs) of DNA. AREs are sequences in the regulatory regions of genes that activate transcription of a diverse group of cytoprotective enzymes.

Isothiocyanates react with certain regions on Keap1, eliminating Keap1’s ability to target Nrf2 for degradation – effectively serving the role of stressor. Sulforaphane, an isothiocyanate derived from broccoli and broccoli sprouts, is the most potent naturally occurring inducer of Nrf2.

The authors of the review presented evidence that sulforaphane protects against carcinogenesis in models of skin, oral, stomach, colon, lung, prostate, and bladder cancer. They also reported that feeding studies involving humans and consumption of isothiocyanate-rich cruciferous vegetables have demonstrated measurable Nrf2 activity, reflected in increased levels antioxidant proteins and enzymes, including glutathione S-transferase and NQO1. Future research will inform optimal dosages and formulations for clinical trials.

Watch this clip in which Dr. Jed Fahey describes the early co-discoveries of sulforaphane and Nrf2 and describes the importance of the Nrf2 pathway.
- Link to full review.
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Fish oil supplementation provides protection against fine particulate air pollution www.onlinejacc.org

Omega-3 Glutathione Protein Dairy
An estimated 4.2 million deaths each year, many of which are cardiovascular disease-related, are associated with exposure to air pollution. The mechanisms that drive this association include systemic inflammation, endothelial dysfunction, oxidative stress, hypertension, and metabolic dysfunction. Findings from a recent study suggest that supplemental omega-3 fatty acids may reduce the risk of cardiovascular disease-related death associated with exposure to particulate air pollutants.

Particulate matter in air pollution is a mixture of solid particles and liquid droplets. It is present in fine inhalable particles, with diameters that are generally 2.5 micrograms (PM2.5) or less. The daily standard for PM2.5 in the United States is 35 micrograms per cubic millimeter per day, as long as the average annual exposure is less than 12 micrograms per cubic millimeter daily.

Omega-3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are derived from marine sources, elicit a wide array of health benefits. The American Heart Association recommends that people who have coronary heart disease consume approximately 1 gram of DHA and EPA daily in foods or supplemental form.

The randomized, double-blind study involved 65 healthy students attending Fudan University in Shanghai, China. Participants received either a 2.5-gram EPA- and DHA-rich fish oil supplement or a placebo daily for a period of four months. The authors of the study measured PM2.5 levels throughout the study. They also collected blood samples from the participants to assess levels of 18 cardiovascular disease-related biomarkers.

The average PM2.5 level during the study period was 38 micrograms per cubic millimeter. Whereas the participants who took the fish oil supplement had biomarker profiles that were cardioprotective, the participants who took the placebo had biomarker profiles associated with inflammation and cardiovascular disease. In particular, taking the fish oil supplement was associated with having higher levels of glutathione peroxidase (an enzyme that protects against oxidative stress) but the supplement was associated with having higher levels of C-reactive protein (a driver of inflammation).

These findings suggest that the intake of fish oil supplements rich in EPA and DHA may provide cardiovascular protection to people living in areas of high air pollution.
- Link to study abstract.
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