Nrf2 Pathway: Increasing the body’s ability to get rid of toxins

This is part of an ongoing series on the genes involved in detoxification.

The Nrf2 signaling pathway regulates the expression of antioxidants and phase II detoxification enzymes. I think of it as flipping the switch to call up the phase II enzymes to take out the trash produced in phase I detox.

The phase II enzymes then further break down the metabolites from phase I detoxification, making them into something that can be excreted by the body. Specifically, the Nrf2 signaling pathway is involved in GSTs, NQO1, UGTs, and SULTs.

Genetic Variants:

Variants in the NFE2L2 (Nrf2 pathway) gene are fairly common, with some variants increasing Nrf2 pathway signaling and some diminishing it. Some of these are being studied in relation to cancer prognosis, lung volume in smokers, and Parkinson’s disease.

Genetic variants that increase Nrf2:

Check your 23andMe results for rs6726395 (v.4):

GG: greater lung volume in smokers [ref], decreased risk of AMD [ref]
AG: somewhat greater lung volume in smokers
AA: normal

Check your 23andMe results for rs13001694 (v5):

GG: reduced risk of all-cause mortality, especially in smokers [study]
AG: reduced risk of all-cause mortality, especially in smokers
AA: normal

23andMe results for rs1806649 (v4):

CC: normal
CT: significantly reduced risk of death from COPD
TT: significantly reduced risk of death from COPD (70% reduction) [ref]

Genetic variant that reduces Nrf2 expression:

Check your 23andMe results for rs6721961 (v.4):

GG: normal
TT: significantly diminished Nrf2 expression, increased risk of lung cancer [ref]

Lifehacks:

Sulforaphane, a natural substance found in broccoli sprouts, Brussels sprouts, cabbage, cauliflower, activates the Nrf2 pathway. [study][study] Broccoli sprouts are supposed to be one of the best sources of sulforaphane that you can eat. There are also sulforaphane supplements available. Be sure to get one that includes the myrosinase enzyme such as this one from Jarrow.